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, Manetti Alice Chiara, Maiese Aniello, Scopetti Matteo, Di Paolo Marco
Journal of Clinical Nephrology, Volume 5, pp 008-009; https://doi.org/10.29328/journal.jcn.1001066

Published: 15 December 2020
Journal of Clinical Nursing; https://doi.org/10.1111/jocn.15605

Abstract:
It is with a sense of honour and humility that I assume the role of Editor‐in‐Chief of the Journal of Clinical Nursing (JCN) – the largest nursing journal in the world. A journal that truly is the International Voice of Nursing Research, Theory and Practice. I am acutely conscious that I follow two of the most globally eminent nursing leaders and researchers – Professors Debra Jackson and Roger Watson – into this role.
Published: 5 December 2020
Reactions Weekly, Volume 1833, pp 355-355; https://doi.org/10.1007/s40278-020-87173-4

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Published: 17 October 2020
Reactions Weekly, Volume 1826, pp 279-279; https://doi.org/10.1007/s40278-020-84726-6

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Published: 26 September 2020
Reactions Weekly, Volume 1823, pp 107-107; https://doi.org/10.1007/s40278-020-83735-8

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Published: 12 September 2020
Reactions Weekly, Volume 1821, pp 210-210; https://doi.org/10.1007/s40278-020-83330-3

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Published: 15 August 2020
Reactions Weekly, Volume 1817, pp 102-102; https://doi.org/10.1007/s40278-020-82061-9

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Matthew Krinock, Deepak Goyal, ,
Published: 14 August 2020
Journal of Human Hypertension, Volume 34, pp 741-744; https://doi.org/10.1038/s41371-020-00399-y

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Stefano Gelibter, Lucia Moiola, Stefano Carlo Previtali,
Published: 9 July 2020
Journal of Neurology, Volume 267, pp 2744-2746; https://doi.org/10.1007/s00415-020-10049-5

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Published: 16 May 2020
Reactions Weekly, Volume 1804, pp 220-220; https://doi.org/10.1007/s40278-020-78646-y

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Journal of Communications and Networks, Volume 22, pp 162-168; https://doi.org/10.1109/jcn.2020.100012

Abstract:
Journal of Communications and Networks (JCN) was launched in March 1999. It is published six times per year, and is committed to publishing high quality papers that advance the state-of-the-art and practical applications of communications and information networks. Theoretical research contributions presenting new techniques, concepts, or analyses, applied contributions reporting on experiences and experiments, and tutorial expositions of permanent reference value are welcome. The subjects covered by this journal include all topics in communication theory and techniques, communication systems, and information networks. JCN is indexed in Science Citation Index Expanded (SCIE), Engineering Village and Scopus. The official title is Journal of Communications and Networks (JCN) and the abbreviate title is ‘J.Commn.Net’.
Published: 25 April 2020
Reactions Weekly, Volume 1801, pp 219-219; https://doi.org/10.1007/s40278-020-77879-7

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Published: 4 January 2020
Reactions Weekly, Volume 1785, pp 372-372; https://doi.org/10.1007/s40278-020-73353-5

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Sergi Roig Puiggros, , , Nadia I. Bocai, , , Gimena Gomez, Sara Grassi, , , et al.
Published: 20 October 2019
Journal of Neurochemistry, Volume 153, pp 10-32; https://doi.org/10.1111/jnc.14900

Abstract:
Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.
Untung Sujianto, Andrew Johan
Published: 9 October 2019
KnE Life Sciences pp 162–175-162–175; https://doi.org/10.18502/kls.v4i13.5237

Abstract:
[1] Therapies, C. (2014). Complementary, Alternative, and Traditional Therapies, 34(6), 50–56. [2] Gronowicz,G.,Secor,E.,Flynn,J.,Jellison,E.,&Kuhn,L.(2015).TherapeuticTouchhassignificanteffects onmouseBreastCancermetastasisandImmuneresponsesbutnotprimarytumorsize.Evidence-Based Complementary and Alternative Medicine, 2015, 1–10. https://doi.org/10.1155/2015/926565 [3] Ross, S., & Grande, R. (2017). A Practice-Based Theory of Healing Through Therapeutic Touch, 1–13 [4] Gregory,S.,&Verdouw,J.(2005).Therapeutictouch:Itsapplicationforresidentsinagedcare.Australian Nursing Journal (July 1993), 12(7), 23–25. Retrieved from http://www.healthyoutlook.com.au/images/ 0502_clin_update.pdf [5] JeanSayre-AdamsStephenWright.(2001).TherapeuticTouch(2ndEditio).Livingstone:ElsevierMosby Publications [6] Robinson, J., Fc, B., & Dolk, H. (2009). Therapeutic touch for anxiety disorders (Review), (3). [7] Myers,C.D.,Walton,T.,Bratsman,L.,Wilson,J.,&Small,B.(2008).MassageModalitiesandSymptoms Reported by Cancer Patients: Narrative Review, 6(1), 19–28. https://doi.org/10.2310/7200.2008.0005 [8] Study,A.Q.(2015).EffectsofTherapeuticTouchonAnxiety,VitalAmericanHolisticNursesAssociation Volume30Number 4 Signs,and CardiacDysrhythmiain a Sample ofDecember2012 225-234© The Author(s) 2012 Iranian Women Undergoing Cardiac 10.1177/0898010112453325 http:, 225–234. [9] Jung,M., Jonides,J., Northouse,L., Berman,M. G., Koelling,T.M.,& Pressler,S. J.(2017).Randomized Crossover Study of the Natural Restorative Environment Intervention to Improve Attention and Mood in Heart Failure. Journal of Cardiovascular Nursing, 32(5), 464–479. https://doi.org/10.1097/JCN. 0000000000000368 [10] Taylor,A.F.,Kuo,F.E.,&Sullivan,W.C.(2002).Viewsofnatureandself-discipline:Evidencefrominner city children. Journal of Environmental Psychology, 22(1–2), 49–63. https://doi.org/10.1006/jevp.2001. 0241 [11] Alaaeddine, N., Okais, J., Ballane, L., & Baddoura, R. M. (2012). Use of complementary and alternative therapy among patients with rheumatoid arthritis and osteoarthritis, 1–7. https://doi.org/10.1111/j.13652702.2012.04169.x [12] Unit, D., Diego, S., Awdishu, L., & Diego, S. (2018). Copyright of Nephrology Nursing Journal is the property of American Nephrology Nurses ’ Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder ’ s express written permission. However, users may print, download, or email articles for individual use., 45(2). [13] Aghabati, N., Mohammadi, E., & Esmaiel, Z. P. (2010). The Effect of Therapeutic Touch on Pain and Fatigue of Cancer Patients Undergoing Chemotherapy, 7(February 2008), 375–381. https://doi.org/10. 1093/ecam/nen006. [14] Article, O., Sancar, B., Yalcin, A. S., & Acikgoz, I. (2018). An examination of anxiety levels of nursing students caring for patients in terminal period, 34(1), 94–99. [15] Moeini, M., Zare, Z., Hazrati, M., & Saghaei, M. (2008). Original Article Effect of therapeutic touch on patients’ anxiety before coronary artery bypass graft surgery, 13(2), 47–51. [16] Tabatabaee, A., Tafreshi, M., Rassouli, M., Aledavood, S., Majd, H., & Farahmand, and. (2016a). Effect of Therapeutic Touch in Patients with Cancer: a Literature Review. Medical Archives, 70(2), 142. https: //doi.org/10.5455/medarh.2016.70.142-147 [17] Tabatabaee, A., Tafreshi, M., Rassouli, M., Aledavood, S., Majd, H., & Farahmand, and. (2016b). Effect of Therapeutic Touch in Patients with Cancer: a Literature Review. Medical Archives, 70(2), 142. https: //doi.org/10.5455/medarh.2016.70.142-147 [18] Karagozoglu, S., & Kahve, E. (2013). Effects of back massage on chemotherapy-related fatigue and anxiety: Supportive care and therapeutic touch in cancer nursing. Applied Nursing Research, 26(4), 210–217. https://doi.org/10.1016/j.apnr.2013.07.002
Journal of Christian Nursing, Volume 36, pp 70-71; https://doi.org/10.1097/cnj.0000000000000600

Abstract:
“It's about relationship with each other” is how Christy Secor, DNP, RN, CDWF, summarizes why NCF nurse groups are so beneficial. As NCF's Professional Ministries Director, Christy supports and helps develop these groups across the United States. “One of the best ways we have to relate to each other as professional nurses is through NCF nurse groups,” Christy says. Nurse groups, which can meet at a workplace, an individual's home, a coffee shop, or nearly anywhere, provide a gathering opportunity for prayer, Bible study, and personal support. For examples of how nurse groups are building relationships, read on the NCF blog (ncf.-jcn.org/blog) about groups in Delaware and Northern California. If you don't have a group near where you live or work, email [email protected] so NCF staff can work with you to find or start a group. NCF is unique! As a ministry and professional organization, NCF serves nursing students, nurse educators, and practicing nurses—the only organization of its kind. As a ministry organization, NCF brings faith to students in the struggle of nursing school and to nurses in the challenges of practice or academia. As a professional organization, we bring expert nursing knowledge to every member through the Journal of Christian Nursing, ANCC-certified continuing education, and more. Why join NCF? Your membership indicates your commitment to faith and the profession on your résumé and to your employer. Membership in NCF is economical—less than other nursing organizations. Your membership helps support the growth of NCF chapters in nursing schools and NCF nurse groups throughout the country. Another reason to join NCF? The benefits! Members receive the award-winning JCN, free and discounted CE in numerous clinical areas, including pharmacology hours for advanced practice nurses, discounts from LWW and InterVarsity publishers, a network of fellow Christian nurses throughout the country, and more. Join NCF today at http://ncf-jcn.org/membership. Already a member? Watch your inbox for your next renewal notice. Remembering Our Purpose Have you ever asked God, Why? Why am I here? Am I making a difference? What do you want of me? There is not enough of me to get through this day...this shift...this semester. It's too easy within the chaos of life and work to lose our sense of purpose in who we are as individuals and as professionals. Sometimes we lose hope. As NCF's Professional Ministries Director, I speak with nursing students, educators, and nurses in practice about the challenges they face. The demands are real. Long hours, doing more with less, not having time for our patients, a lack of teamwork, insecurities about pay, caring for our loved ones, as well as coping with the loss and grief we experience. It is into this space Nurses Christian Fellowship is called. It is into this space we as nurses are called. The mission statement for NCF reads: The purpose of Nurses Christian Fellowship ... is to establish and advance in nursing, within education and practice, witnessing communities of nursing students and nurses who follow Jesus as Savior and Lord: growing in love for God, God's Word, God's people of every ethnicity and culture, and God's purposes in the world. Our purpose is always found in God. It isn't one more thing for us to do. It is who we are. The beauty of God's design is this ... our purpose is lived in relationship with him and with each other.
Journal of Christian Nursing, Volume 36, pp 73-73; https://doi.org/10.1097/cnj.0000000000000597

Abstract:
Have you discovered What's Vital yet? This new, regular JCN column probes a Scripture portion, considering the cultural facet and biblical context. Author Jan Wilson writes the content and applies a nursing perspective by concluding the column with questions for nurses to consider. The first column addressed crossing racial, ethnic, religious, and social barriers to communicate with others different from ourselves. In this issue, Wilson considers how rest—frequently a commodity in short supply—may be experienced in unexpected places. This addition to JCN can also be useful as a discussion topic or Bible study focus for nurses' groups. Let us know your opinion of this new column and how you're using it. As the only nursing journal focused on practicing from a biblically-based, Christian perspective, JCN welcomes new and returning authors to submit manuscripts. The instructions for authors detail the types of articles published, how to submit your article, and the appropriate writing style. All articles are submitted online; a tutorial at the JCN editorial manager site walks first-time authors through this process. Authors are encouraged to submit articles for columns, as well as longer manuscripts related to faith community nursing, healthcare missions, clinical topics for practicing nurses and educators, original research, and professional issues. Substantive, referenced teaching articles can be selected for the issue's CE feature; the publisher produces the CE test. Articles typically are published 9 to 12 months after acceptance; revision may be needed, and editorial staff provide guidance with this process. All editing changes of accepted manuscripts are submitted for author approval prior to publication, whether in print or online. To access the instructions for authors and other detailed information about the types of articles published in JCN, go to https://www.editorialmanager.com/ncf-jcn/default.aspx. Encouragement, ideas, successes, pertinent input from the Bible. These are all found on the NCF blog at ncf-jcn.org. This smorgasbord of articles, devotionals, news, and interviews brings into focus local nurse groups that are impacting peers and their communities; student groups and faculty advisors leaping out in faith; and interviews with NCF staff. Scripture-based content and guest posts from NCFI, our international sister organization, are served, along with thoughtful content from JCN authors. Recently a candid, personal post by JCN contributing editor Kris Mauk on what she gained through physical pain brought this response from a reader: I echo praise to God for teaching me gratitude for the simple things of life, like taking walks and picking flowers, after years of limitations due to severe back pain and numerous surgeries. His grace has turned loss into gain. Chronic pain continues to teach me to be grateful for times of relief and helps me be sensitive to the needs of others. You can subscribe by email to the blog feed using the button on the blog page. Posts release every 6 to 10 days. Visit the ncf-jcn.org website and see what you think. International Westberg Symposium, “In These Times: Serving Through Adversity” is April 8-10, 2019, at First Baptist Broad Church in Memphis, Tennessee. Find details here: https://westberginstitute.org/symposium2019/. Trinity Western University School of Nursing Faith & Nursing Symposium, “Inspiring Person-Centeredness: A Call to Action,” May 8-10, 2019, held at TWU, near Vancouver, British Columbia, Canada. Get more information at: https://www.twu.ca/inspiring-person-centredness-call-action.
Published: 11 January 2019
Frontiers in Neuroscience, Volume 12; https://doi.org/10.3389/fnins.2018.01032

Abstract:
Editorial on the Research TopicNeurocardiovascular Diseases: New Aspects of the Old Issues Concept of neuro-cardiovascular diseases (NCVD) is one fruitful approach that enables the comprehension of the pathological processes raising along the brain-heart & blood vessel axes from the integrative prospective. That is the reason why multidisciplinary and interdisciplinary approaches result in novel insights into pathophysiological processes bringing new directions for therapeutic development, both at the laboratory bench and at the clinical bedside. NCVD comprises the group of pathologies that have as a primary pathological substrate the changes in neurochemical, neurophysiological and neuroanatomical levels of the autonomic nervous system (ANS) and its regulated organs (e.g., heart, blood vessels). A striking fact is that “cardiovascular disease is the leading cause of death in the world today and will remain so by the year 2020” (The WHO MONICA Project, Investigators, 1988) strongly supports the need for new insights into cardiovascular regulatory mechanisms (Bojić, 2003). A picture of the classical cardiovascular risk factors from the prospective of neural cardiovascular control, links these factors with stress. The central topic of NCV physiology is related to stress-induced disfunction (e.g., hypertension, Du et al., 2017), emotional stress coping-cigarette smoking, obesity, Strickland et al., 2007) and stress-releasing strategies (exercise, Acevedo et al., 2006; Webb et al., 2017). Central questions of neurophysiology of stress is: a. Identification of different brain networks activated during stress b. Spacial and temporal patterns of their activation c. Identification of neuronal hubs coupling cognitive-emotional neural networks with body effectors, like the hypothalamus-pituitary-adrenal (HPA) and the sympathetic-adrenomedullary axis (SAM) (Ulrich-Lai and Herman, 2009; Godoy et al., 2018). The interaction of the heart and vessels with the central and peripheral nervous systems represents the major topic of the basic neuro-cardiovascular research, with the current aim of the field being to highlight the mechanisms of devastating effects of stress upon the cardiovascular system. In the review of Dampney the focus was on anatomical basis and functional role of the dorsolateral periaqueductal gray (dlPAG) in generating behavioral and autonomic responses to real and perceived emotional stressors. Central position and integratory function of this structure, between higher cortical regions (auditory, secondary visual, olphactory; medial prefrontal cortex -MPC, hypothalamus and lower brainstem structures), qualifies it as a crucial, emotional stress mediator neural hub. Though the review reports, parallel and comparative results obtained in different species, the guiding theme is the enlightening of the understanding of the morpho-functional substrate affiliated with emotional stress response in humans. Crucial for understanding of the behavioral response to the perceived emotional stress are the inputs from the MPC to the dlPAG. The species-specific MPC subregion of the primate brain, the area 10 m, has the largest volume in humans with respect to other primate species. Allman and collaborates (Allman et al., 2002) describe this structure as a comparator of current and memorized behavioral states, and as a consequent decision-maker about future, potentially advantageous behavior. Its high activation and direct interface with dlPAG points to its special role in complex emotional responses, resulting from such comparisons. In conclusion, dlPAG is presented as integrator of the reactions of both the conscious and the unconscious to threatening stimuli with dependent autonomic networks (i.e., cardiorespiratory network) which support the behavioral response to stress and threatening stimuli. Future studies need to address the questions of chemical phenotyping of the dlPAG and other extensive stress mediating brain networks; the question of morpho-functional plasticity with respect to timing and duration of stress exposure; association of stress-induced morpho-functional changes of critical brain networks associated with different cardiovascular pathologies, as well as the question of genetic predisposition to developing of specific pathological entities like NCVD on the order of short or long time scales. The impact of peripheral information on neural mediation of the cardiovascular (CVS) response can be crucial to the development of pathologies initiated by physical stressors like injury. When a physical stressor is recognized by the brainstem through pain, inflammation and other signals, both fast SAM and sluggish HPA responses are activated (Godoy et al., 2018). Up to the present it is not known what the role of pre-stimulus of the ANS regime is for development of the compartment syndrome. In this line, the study that investigated the effect of peripheral neural input to the heart rate regulating network by Watanabe and Hotta for the first time examined the specific cardiac autonomic changes induced by the bio-mechanical pressure stimulation of skeletal muscle. The authors identified sympathetic nervous system as the effector of changes in heart rate and blood pressure. In addition, it was demonstrated that the tonic level of pre-stimulus sympathetic neural activity determines the direction of induced heart rate changes and changes to blood pressure. This data could be of particular importance for understanding the compartment syndrome, the condition of muscle ischemic necrosis due to excessive intramuscular pressure and blood hypoperfusion. Future studies are necessary for revealing the site of the interaction of peripheral muscle pressure, stretching and contraction stimulus of the CVS neural networks (spinal or brainstem), and chemical phenotyping for the purpose of pharmacological intervention, and the role of tonic pre-stimulus sympathetic neural activity, for the development of the hemodynamic profiles that are susceptible to progression of the compartment syndrome. Drug targeting of spinal and brainstem autonomic neural circuits causally involved in the genesis of different NCVD could result with long-awaited pharmacological solutions (Pierce et al., 2010; Zimmerman, 2011) for unexpected groups of pathophysiological entities, like compartment syndrome and neurogenic hypertension. Neurogenic hypertension (NH) and vasovagal syncope (VVS) are NCV entities representing an unsolved pathophysiological puzzle. Novel data exists about the central molecular mechanisms regulating the tonic activity of preganglionic sympathetic neurons (Zimmerman, 2011), with antagonizing effects of the angiotensin II receptor and the MAS1 receptor mediated cascade offer a promising perspective for in silico strategies for investigation of NH. The Information Spectrum Method (ISM), a virtual spectroscopy method for studying the long-range interactions between biological macromolecules (Veljković et al., 1985), was previously successfully applied in study of HIV (Veljković et al., 2007), anthrax (Doliana et al., 2008) and the influenza virus (Perović et al., 2013). This widely accepted method (Veljković et al., 2011) was applied for the first time by Bojić et al. for the investigation of molecular targets of NH and VVS. As the result of this study, there have been proposed three novel therapeutic candidates for treatment of NH (apelin-28, apelin-31 and apelin-36) and also 12 repurposed antimuscarinic drugs potentially could be efficient in VVS treatment. Follow up with in vitro and in vivo studies will test the therapeutic capacities of drug candidates identified by ISM. Baroreflex sensitivity (BRS) represents one of the central research topics of NCV physiology in the last few decades (Bojić, 2003; Silvani et al., 2003, 2005; Zoccoli et al., 2005; Bajić et al., 2010; Kapidžić et al., 2014; Platiša et al.) and pathophysiology (Parati et al., 2004; Glišić et al., 2016). BRS has been recognized as valuable prognostic factor for the outcome of different NCVD like myocardial infarction (La Rovere et al., 1998), heart failure (Libbus et al., 2016) and hypertension (Subha et al., 2016). The methodology of BRS estimation evolved from the classical methods of BRS estimation based on induced blood pressure changes (mechanical, pharmacological, etc.) with the related research activity achieving considerable levels since the late 1950's (Ernsting and Parry, 1957; Lamberti et al., 1968; Kirchheim, 1976), up to the BRS techniques for analysis of blood pressure and HP spontaneous fluctuations, which were introduced during the late 1980's (Fritsch et al., 1986; Bojić, 2003). Major advantages of spontaneous fluctuations method are: 1. There is no administration of vasoactive compounds or external appliances that could influence the baroreceptor reflex by a direct action on receptor or effector sites (Coleman, 1980). 2. BRS is measured within physiological ABP ranges, allowing the computation of the gain at ABP close to the operating set point value, with minimal nonspecific effects from other efferent nerves. 3. The method does not arouse subjects or animals, thereby reducing stress induced effects. 4. In contrast with pharmacological or mechanical methods, they are suitable to assess the BRS over prolonged periods of time (Mancia and Mark, 1983; Oosting et al., 1997). Still, time and frequency domain analysis of ANS activity in cardiovascular signals require certain conditions, with a stable baseline as one of the most important and most difficult states to obtain on long data segments. Li et al. propose a Multiple Trigonometric Regressive Spectral Analysis as a novel method for baroreflex sensibility (BRS) estimation for short (20–30's) time segments. The proposed method uses the oscillations of ABP and HP instead of their original values. The method provides reliable estimates of BRS without regard to posture change during the short data segments of 20–30 s in length. The proposed method solves several shortcomings of the sequence method by increasing the accuracy and validity of BRS estimation (Ziemssen et al., 2013), by providing a pure physiological spectrum of ABP and HP fluctuations and by reducing the influence of non-baroreflex drives. Further studies are necessary for evaluation of this promising method for studying BRS and other CVS indexes during the dynamic processes of daily life. Atrial fibrillation (AF) presents NCVD events typically triggered by sympathovagal discharge (Goldstein, 2001), resulting in a dysfunctional atrial rhythm possessing as a consequence stroke, heart failure and risk of dementia. The electrical instability of atria, both focal and re-entrant activity, are progressive, self-feedback processes that evolve paroxysmal AF toward its persistent form. These classical experimental and clinical observations were without clear evidence-based pathophysiological explanation (Schotten et al., 2011). Ashton et al. propose the morpho-functional remodeling of ANS, both of its extrinsic (pre and post-ganglionic neurons) and intrinsic components (ganglionated plexus) that innervate the heart, as fundamentally contributing to positive feedback mechanism of AF. The ganglionated plexus, is the network of acetylcholine and other neurochemically distinct neurons, which play an important role in the modulation of cholinergic transmission and can be the site of maladaptive changes including arrhythmogenesis. These maladaptive changes could be based on both short-term and long-term plasticity mechanisms, with engagement of 5HT3 receptors, acetylcholine release and NO signaling in sympathetic neurons, and nicotinic expression, NO-cGMP signaling and NMDA receptor expression in vagal neurons. The neurochemical profile of synaptic plasticity of both sympathetic and vagal ganglionic transmission is promising target for future pharmacological studies aiming to intervene in AF that is morpho-functionally stabile as its persistent form. Traditional ECG and HRV linear and nonlinear indexes (Kikillus et al., 2007) could not give the answers about regulatory mechanisms of longer time scales and their differences between healthy and AF patients. Differences in nonlinear HP functional patterns between healthy and AF patients could be of major importance for the diagnosis and consequent therapy of AF forms that are of central neural origin (Andrade et al., 2014). This was the focus of the research of Platiša et al., where novel Generalized Poincaré Plot (GPP) analysis of RR interval was proposed as a sensible method for distinction of AF from healthy subjects. GPP revealed for the first-time different system dynamics for large time scales in AF and healthy subjects. In the special case when GPP analysis was performed between 100 preceding and 100 following RR intervals, distinct regimes could be observed in healthy subjects, reflecting hypothetical different set-points of the blood pressure-heart rate baroreflex loop. In AF patients the GPP profile of RR intervals were scattered. This result suggests that AF patients have smaller adaptive capacity to internal and external perturbations. Four cluster profile of correlation maxima and their absolute values for different correlation scales were also different in healthy and AF patients. These results supported the hypothesis that regulatory regimes in healthy subjects operate in fine tuned superimposed regimes acting on different time scales-parasympathetic, sympathetic and slow regulatory mechanisms like thermoregulation, rennin-angiotensin-aldosterone-sodium system, hormones etc. The AF cluster pattern was highly distorted, shifted toward higher frequencies and with increased randomness. The new GPP methodological approach for detection and profiling cardiovascular regimes need future pharmacological evaluation and potential translatory development as a diagnostic tool for AF and other NCVD. ANS is coupled directly to the cardiovascular system, but also through the interface of an energy regulating system. This is why an imbalance of energy regulation, as it is the case in obesity, often represents the first step, or the initial trigger of a neurally and metabolically mediated cascade of cardiovascular complications (hypertension, generalized atherosclerotic diathesis, dyslipidemia, diabetes mellitus type II). Digestion, absorption and neuroendocrine activity associated with the adoption of food has a direct effect on cardiovascular regulating centers (de Lartigue, 2014), pointing to the vagal subsystem as the potential target for neuromodulatory and pharmacological interventions in treatment of obesity, and, consequently, obesity related diseases. This important aspect of NCVD was reviewed by Guarino et al. Even though this comprehensive overview emphasizes the potential vagal route for neuromodulation and pharmacological intervention, the sympathetic route was also evaluated. This, more complex and differently structured subsystem presents itself as less understood and consequently is a significantly diminished path for obesity and related NCVD treatment. Its anatomical characteristics, i.e., approachability by external manipulations imply that the pharmacological approach should be investigated in the future, while the vagal route offers a good basis for both neuromodulatory and pharmacological strategies. Vagal modulation, in specific transcutaneous auricular vagus nerve stimulation is a promising method for body weight reduction in obese patients, also resulting with significant improvements of cardiometabolic profile. Sympathetic modulation, with inconsistent results on body weight reduction and partial cardiometabolic effects, from a results prospective, is a less promising strategy. Hyperadrenergic state is the classical hallmark of heart failure (HF), the clinical endpoint of the number of CVD (Marwick, 2018). Toschi-Dias et al. details elaborates the neurohumoral responses to hemodynamic stress, the common initial event of the HF hyperadrenergic state. The HF hyperadrenergic state, associated with different reductions of left ventricular ejection fraction (LVEF: preserved-p, mid-range-mr, reduced-r) is also associated with different morpho-functional remodeling of left ventricle, specific for its ejection functioning. This interesting association, widely recognized as a valuable prognostic and diagnostic parameter (Marwick, 2018) seeks for a deeper genetic and/or environmental influence studies, due to the hypothesis that different pathophysiological patterns might sculpture different EF phenotypes in HF. Vascular remodeling in HF further complicates an ANS functional profile, pushing it toward the maintenance and/or enhancement of hyperadrenergic state. Arterial baroreceptor (ABR) dysfunction, mostly due to the decrease of large vessel elasticity following chronic hypertension, distinguishes itself as an important factor in generation of cardiac diastolic dysfunction. ABR seem to play dominant role in sustaining hyperadrenergic state both in HFrEF (low stroke volume) and HFpEF (increased vascular stiffness), by different mechanisms. This issue necessitates future investigations of the hierarchical (in sense of absolute and relative quantitative contribution to the hyperadrenergic state) and temporal order of cardiovascular reflexes engaged in HFmrEF and HFpEF. It is reasonable to hypothesize that different quantitative and temporal patterns of cardiovascular reflex response result with different HFEF phenotypes. Cardiopulmonary reflex (CPR) regulates the state of systemic blood volume by (a) sympathetic modulation (low intensity changes), (b) release of atrial Na-uretic peptide, and (c) by strengthening and enhancing ABR action at high intensity changes. In HFrEF patients, no reduction of sympathetic outflow is obtained by CPR unloading. Participation of cardiac sympathetic afferent reflex and arterial chemoreflex was thoroughly evidenced in the hyperadrenergic state of HFrEF, while their role in HFpEF and HFmrEF needs future evaluation. A number of surgical and pharmacological interventions manifest NCV disturbances as an important caveat. For that reason, detailed and comprehensive NCV evaluation becomes a constituent part of pre-interventional evaluation of the patient and postintervention follow up. Coronary artery bypass graft (CABG) surgery can induce disbalance of sympathovagal ratio and, consequently respiratory depression, approximately 5 days after the surgery (Aronson et al., 2011; Pantoni et al., 2014; Patron et al., 2014; Ksela et al., 2015). In order to identify a prognostic marker, Costa et al. studied the prognostic significance of perioperative arterial blood pressure (ABP) variability for the occurrence of respiratory depression following CABG. The finding of Costa et al. that ABP variability parameters have prognostic value for respiratory depression has both pathophysiological and clinical significance. Deep brain stimulation (DBS) represents an invasive, frequent and developing intervention for the treatment of a spectrum of neurological diseases, with Parkinson's disease (PD) as the most common. As reported by Chowdhury et al., hemodynamic perturbations, like hypertension, hypotension, bradycardia, tachycardia and arrhythmia are frequent side-effects of this procedure in PD patients. They can be the consequence of (a) the independent or accompanying autonomic co-morbidity of the main PD pathological process, (b) the procedures associated to the surgery (semi-sitting position, anesthetics, sedation, stress, electrode battery placement and the stimulation of brain nuclei itself). Significant predictor potential has only pre-operative ABP, with diastolic BP as the marker most associated with hemodynamic event. Hypertension, predisposing factor of cerebral hemorrhage was noted during electrode placement and nuclei stimulation. A prospective study is needed for detailed hemodynamic evaluation (a) during the DBS surgery and the estimation of (b) pre- and (c) post-operative autonomic status of the PD patients. This approach would potentially change protocols of presurgical evaluation and postsurgical treatment of PD patients subjected to DBS. After heart transplantation, the autonomic reinnervation of the transplanted heart has important consequences on its reactivity and hemodynamical adaptability (exercise capacity, coronary blood flow regulation (Grupper et al., 2018). Wdowczyk et al. present a novel tool, Transition Networks, in the case report that has potential for distinguishing HRV increase due to reinnervation. Further stratified longitudinal clinical studies are needed for evaluation of this method. However, the capacity of the method to offer an insight into dynamical inter-beat dependences of RR intervals enounce better comprehension of the transplant functional adoption into CVS neural network. Pharmacological interventions in neuropsychiatric patients often disturb autonomic balance. Li et.al. applied their method (long-term Multiple Trigonometric Spectral Analysis, Li et al.) combined with conventional liner parameters of HRV as a tool for predicting fingolimod-induced bradycardia in patients with multiple sclerosis (MS). On the basis of their analysis they report an increased pre medication parasympathetic activity as the predisposing factor for fingolimod induced bradycardia, with pretreatment HR as the only predicting factor. Yuen et al. performed the meta-analysis on clozapine induced autonomic dysfunction in patients with schizophrenia. They conclude that the most frequent complications were myocarditis, orthostatic hypotension and tachycardia, prevalently due to sympathetic overactivity. This report emphasizes the need for introduction of post-medication NCV evaluation autonomic tests for prevention and therapeutic coping with clozapine-induced side-effects. In accordance with Li et al., an intuitive direction for future investigations would be the identification of NCV predicting parameters for clozapine induced autonomic side effects. Cerebral blood flow (CBF) is an issue of the upmost importance for understanding the NCVD, from two aspects: a. A growing corpus of data supports the standpoint that besides the cerebral autoregulation (Silvani et al., 2004; Zoccoli et al., 2005), sympathetic (Cassaglia et al., 2008; ter Laan et al., 2013; Frederiksen et al., 2017), parasympathetic (Purkayastha et al., 2018) and sensory innervations (Branston et al., 1995) functionally participate in the regulation of CBF. b. Compromise of CBF, especially in the neonates, can cause serious, life threatening autonomic dysfunctions (Silvani et al., 2004; Metzler et al., 2017; Campbell et al., 2018). Glutamate is considered to be the neurochemical initiator and executor of brain injury in hypoxic-ischemic brain disorder (HIBD). Dang et al. report “two phase” change of basal ganglia glutamate level after HIBD, that is significantly and negatively correlated to the brain perfusion fraction. Even though this association is suggestive for negative electrochemical coupling of cerebral activity (glutamate) and brain perfusion in HIBD, further investigations are necessary for elucidating the mechanism(s) of brain activity-blood flow coupling in HIBD. Special emphasis should be on the role of sympathetic nervous system in cerebral activity-blood flow regulation in HIBD (Ainslie, 2008; Cassaglia et al., 2008; Edvinsson, 2008; Immink and Passier, 2008; Levine and Zhang, 2008; Ogoh, 2008; Paulson and Knudsen, 2008; Prakash, 2008; Visocchi, 2008; Yildiz, 2008; ter Laan et al., 2013). An important protective effect of artesunate against necrosis in cerebral infarction was reported by Shao et al., suggesting an autophagy as the most probable mechanism. Potential treatment by artesunate could have beneficiary effect for autonomic dysfunction, an important caveat of neonatal hypoxic-ischemic encephalopathy (Metzler et al., 2017; Campbell et al., 2018). In conclusion, the presented physiological, methodological and pathophysiological aspects of NCVD point to the importance of consideration of NCVD from integrative point of view and as a constitutive part of different pathophysiological entities. Application of novel mathematical methods for molecular targeting and systemic characterizing of NCVD enounce promising lines of future research in the translational science. Neurocardiovascular side-effects of surgical and pharmacological interventions emphasize the importance of ANS evaluation before and after the intervention as the routine procedure in the clinical work. 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No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Tijana Bojić, [email protected]; [email protected]
Journal of Communications and Networks, Volume 20, pp 1-1; https://doi.org/10.1109/jcn.2018.000065

Abstract:
Presents the aim and scope of this publication. Also includes information for authors.
Tanya Zilberter, Yuri Zilberter
Published: 30 August 2018
Frontiers in Nutrition, Volume 5; https://doi.org/10.3389/fnut.2018.00075

Abstract:
Thomas Seyfried remarked in his book [(1), page 6]: “The definition of ketogenic diet allows for considerable leeway in food choices as long as the individual has reduced blood glucose and is producing ketones.” Unfortunately, these parameters are lacking in many if not most of studies into metabolic effects of macronutrients. Meanwhile, there is a precise way to predict whether or not a diet will induce ketosis and the aim of this opinion article is to advocate a broader usage of this way. Why is this so important? Excess of carbohydrate intake typical for consumers of the Western diet may cause detrimental effects on metabolism and increase risks of the onset and progression of many neurodegenerative diseases (2–4). On the other hand, diets high in fat and low in carbohydrates decrease appetite, probabilities of food addiction and obesity, and are neuroprotective (5, 6). Carbohydrate restriction induces physiological changes which are very similar to the well documented beneficial effects of calorie restriction (7, 8). Conversely, the hallmark of high-carbohydrate diets is homeostatic inadequacy (9), an overproduction of reactive oxygen species and advanced glycation products, both of which are implicated in neuroinflammation and neurodegeneration (10–12). However, the meaning of “high” or “low” in diets' definition has been drifting away from the previously established quantitative criterion known as ketogenic ratio. Almost a century ago, Woodyatt (13) wrote: “antiketogenesis is an effect due to certain products which occur in the oxidation of glucose, an interaction between these products on the one hand and one or more of the acetone bodies on the other.” The ketogenic ratio (KR), as proposed by Shaffer (14), is a ratio of the sum of ketogenic factors to the sum of antiketogenic factors: KR = K/AK. The antiketogenic part of the equation invariably equals 1 so the KRs are always expressed as 2:1, 4:1, etc. For the sake of economy of reading, we leaved out the repeating part not bearing any information and mention only the informative digit. Shaffer concluded that the maximal ratio compatible with the oxidation of the “ketogenic” molecules becomes possible at the KR = 1, making KRs below 1 antiketogenic and KRs above 2 ketogenic. Wilder and Winter (15) described the KR of a food in terms of times the fat content exceeds the amount of carbohydrate and protein combined, roughly. The reasoning was based on their own experimental observation that fats are predominantly ketogenic (90%), carbohydrates are almost 100% anti-ketogenic, and protein is both ketogenic and antiketogenic, 46–58% respectively. They arrived, along with Woodyatt and Sansum (13), at the conclusion that KR for induction of ketogenesis should be 2 or higher while the upper limit of antiketogenesis is 1. In 1980, Withrow (16) modified the equation and since that time, the equation looked like this: KR = (0.9 F + 0.46 P): (C + 0.58 P + 0.1 F) where F is grams of fat; P is grams of protein and C is grams of carbohydrate. Currently, this equation is rarely used in nutrition research and less so in dietetic practice, which is regrettable since properly calculated KRs reveals interesting patterns of diet effects. Previously (9), using the Withrow's equation, we calculated KRs in a number of diets and came to conclusion that the watershed in the group of effects occurs at KR of about 1.7. Above this value, metabolic features of diets were characteristic for ketogenesis, while below this value, they were characteristic for the obesogenic high-fat diet (oHFD), which, in contrast to the diet resulting in ketosis (KD), is high in fat but also in carbohydrates. Here, we analyzed three groups of diets in order to compare our observation regarding the watershed with the classification of diets made by the authors of 62 studies, in which it was possible to calculate KRs. We can see that there is no common criteria in choosing diet compositions for the “normal control” group to start with (Figure 1A). The vast majority of “normal control” diets are clearly anti-ketogenic (KRs below or equal 1). The oHFD group of diets had broader spectrum of KRs ranging from the anti-ketogenic 0.456 to clearly ketogenic 2.994. The KRs of diets, which were considered ketogenic by the authors, ranged especially broadly: from 0.36 to above 6. The macronutrient compositions of oHFD diets and KDs overlap although the obesogenic oHFD is discussed in literature as diametrically different from the KD. The metabo- and neuroprotective effects of KD are experimentally and clinically confirmed, however, the low compliance rate of the strict KD caused mass attempts to reduce the KR below KR = 2, which for a century used to be the minimal accepted value to consider a diet ketogenic. Figure 1. (A) Green line, theoretical threshold of ketogenesis; dashed green line, empirical threshold of ketogenesis. Red line, theoretical threshold of anti-ketogenesis; dashed red line KR = 0.5. Vertical axis, ketogenic ratios. Horizontal axix, original studies, first author and year (17–50). (B) Ketogenic ratios of diets below the ketogenic threshold. Calculated basing on data extracting from the studies (25, 51–54). Gray curves in (B,C) trendlines. (C) Body-mass loss on diets below the ketogenic threshold. VLCD, very low carbohydrate diet; MAD, modified Atkins diet; Zone, the Zone diet; KLC, ketogenic low carbohydrate diet; WW, Weight Watchers diet; VLFD, very low fat diet; NLC, non-ketogenic low carbohydrate diet. An example is the Modified Atkins Diet (MAD) first tried at The Johns Hopkins Hospital. It is a protocol replicating the induction phase of the original Atkins diet. MAD is composed of approximately 10% energy from carbohydrates, 30% from protein, and 60% from fat, no calorie restriction (55–58). The MAD became an intervention for treating a number of diseases, first of all in cases of intractable childhood epilepsy but also in pharmacoresistant epilepsy in adults and in pathologies of glucose utilization (58). MAD is labeled “ketogenic” while its KR = 1.3 (calculated basing on 11). However, its efficiency is limited: although 70% of epilepsy patients on MAD experienced a 50% reduction in seizures, after switching to the strict clinical KD (KR = 4) the patients benefited from an additional 37% improvement and 18.5% became seizure-free (13, 59, 60) indicating that the KR is indeed an important predictor of diet effectiveness. Basing on our review of KR-dependent effects of diets (6), here we compiled a brief overview in order to demonstrate the critical differences between KD and oHFD. 1. The risks of pathologies caused by brain hypometabolism (e.g., due to hypoxia, hypoglycemia, brain trauma) is reduced in diets capable of inducing ketogenesis; the opposite is shown for the oHFD diets (39, 61–69). 2. Inflammation, e.g., neuroinflammation is shown to be induced by oHFD but decreased by KD (70–78) among other things resulting in improved or impaired cognitive function (76, 78–82). 3. Neuronal hyperactivity and epilepsy is attenuated by KD but exacerbated by oHFD (75, 83–85, 85–88). 4. Inhibition of growth of tumor and metastasis as well as tumor neo-angiogenesis is demonstrated for KD while oHFD increases the risk of cancerogenesis (8, 89–92). 5. KD decreased cardiovascular risks while oHFD increases them (93, 94). 6. KD lowered the type 2 diabetes risks, improves management of complications and glucose control while oHFD increases the risks, exacerbates complications and induced glucose intolerance (95–99). In the ragne of KRs between 1 and 2 lays the area of metabolic uncertainty where the effects are poorly predictable, the definitions are vague and outcomes even more so. The most critical value in this area is 1.5, the experimentally reached threshold of anti-ketogenesis (100). Here we report the result of our analysis of non-ketogenic diets (Figures 1B,C) using data extracted from the studies: • Very low carbohydrate diet [VLCD, (51)]; • The Atkins diet - induction and maintaining phases, the Zone diet and very low fat diet, [VLFD, (52, 53)]; • MAD, Zone, Weight Watchers diet (WW) and VLFD (54); • Ketogenic low carbohydrate diet (KLC) and non-ketogenic low carbohydrate diet (NLC) (25). The common feature of these diets was that none of them reached the threshold of ketogenesis defined as KR = 1.5 (100). The diets were roughly isocaloric (1,412 ± 35.5 Kcal/day; caloric intake of WW varied averaging 1,400 Kcal), with main outcome a body-mass loss. Beyond the strictly utilitarian standpoint, body-mass loss is an indicator of lipolysis and thus of ketogenesis likelihood. In diets ranging from KR = 1.413 to KR = 0.06 (Figure 1B), the metabolic outcome did not depend on KR as directly as it does above the ketogenic threshold (Figure 1C) indicating that mechanisms other than the ketogenesis-glycolysis counterbalancing seem to be predominant. Indeed, in the study of Johnston et al. (25) the inverse relationship has been observed: the KLC diet having six times higher KR than NLC (0.35 vs. 0.06) had almost twice lower effect (4 vs. 7 kg) leading the authors to conclusion they even used as the article title: “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets”—although both diets were undoubtedly anti-ketogenic. It has been shown before (26) that the prevalence of carbohydrates in an otherwise equally high-protein diets increased energy intake in the ad libitum consumption mode initiating the vicious cycle of non-homeostatic processes, including reward seeking and food addiction (101) and the prevalence of energy-conserving metabolic mode over the homeostatically balanced mode (9). Theoretically, below the KR = 1.5, glucocentric metabolic mode prevails while above KR = 1.5 the dominant metabolic mode is adipocentric with the important consequence being initiation of lipolysis (102). This is why the body-mass loss of diets is a convenient parameter indirectly indicating that lipolytic processes take place. It has been measured empirically (100) that ketosis is not observed in KRs below 1.5—however, the “ketogenic” label has been assigned to MAD (KR = 1.021) and even to KLC (KR = 0.36). There is a turning point in the KR-effect interaction curve at KR = 0.5 (Figure 1C), the diet nearest to this point being at KR = 0.438 [the Zone diet, (52–54)]. Further decrease of KRs up to the value of 0.06 resulted in an inverted U-shaped dose-response relationship under the threshold of ketogenesis. Currently the classification of diets is rather unsatisfactory and diet labels offered by the authors (quite arbitrarily) “normal”, “oHFD,” or “ketogenic” oftentimes do not correspond to their respective diets' macronutrient compositions. Description based on percentages of energy from each of the macronutrients does not make it easy to qualify diet type and unify the categorization. The macronutrient ratio in terms of ketogenicity is often ignored in qualification of metabolic effects. The most striking example of this is the oHFD diet, which in fact is also high in carbohydrates. As we briefly discussed above, its effects are diametrically opposing those of the ketogenic diet which is also high in fat but low in carbohydrates, resulting in striking differences in diets' physiological effects (see Effects of KD vs. oHFD). The ad libitum access to food is the standard protocol in animal experiments although the validity of it is rightfully questioned since the subjects become “sedentary, obese, glucose intolerant, and on a trajectory to premature death” [(103), page 6,127]. On the other hand, the low-carbohydrate diets that are high in fat have a number of metabolic advantages: for instance, they facilitate increase energy expenditure by increasing thermogenic effects and excretion of ketone bodies (104). Greater carbohydrate intake was associated with poorer performance in patients with Alzheimer's disease (105), while KD improved cognition independent of weight loss in healthy human subjects (80). KD improved verbal vocabulary and reaction time in children with epilepsy and attention (4), concentration, and memory in adults with multiple sclerosis (106). Diets limiting carbohydrate intake mimic the effects of fasting or caloric restriction (102). In fact, calorie restriction is not even required on a very low carbohydrate diet to achieve the desired goals, while on a low-fat, high-carbohydrate diet calorie restriction is the principal requirement (107). The metabolic effects of dietary fat on energy homeostasis differs from the effects of carbohydrates in two key features. One is the ability to store energy in depots - fat is exceptionally good at it, but carbohydrates are limited in this ability. The other is the ability to increase the drive to consume energy. Carbohydrates have a characteristic ability to elicit positive reward and thus addiction (5, 101, 108–110) while significant carbohydrate restriction in VLCD caused not only energy intake decrease but also energy expenditure increase in both resting and active states (51). In spite of these non-homeostatic features, these mechanisms are evolutionarily appropriate in wild nature, but as soon as the living conditions change the hard-wired pursuit to maximize the energy store becomes a metabolic trap (9s), resulting in non-homeostatic overconsumption and all the negative metabolic consequences it causes. To conclude, the current classification of diets results in terminological confusion. We suggest that rethinking the existing descriptive approach and reanimating the century-old qualitative and clear-cut criterion may facilitate the use of common language and substantive discussion in nutrition and metabolism. 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Edited by: Reviewed by: Copyright © 2018 Zilberter and Zilberter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Yuri Zilberter, [email protected]
, Ronald W. Davis
Published: 2 August 2018
Frontiers in Physiology, Volume 9; https://doi.org/10.3389/fphys.2018.01040

Abstract:
Parkinson's disease (PD) is a neurodegenerative disease caused by a reduction in dopaminergic neurons in the substantia nigra (Dexter and Jenner, 2013). Individuals can exhibit muscle tremors, rigidity, and bradykinesia, leading to posture and gait abnormalities (Dexter and Jenner, 2013). Although the incidence ratio of males to females is ~1.46 (Taylor et al., 2007), the prevalence of PD among men is doubled when compared to women (Elbaz et al., 2002). A lower mortality rate has traditionally been associated with PD in women due to the overall longer life expectancy when compared to men in the general population (Xu et al., 2014; Pinter et al., 2015). However, a diagnosis of PD was found to be associated with a two-fold increased risk for all-cause mortality in a recent study with 396 older women (Winter et al., 2016). This value is similar to that reported among older men (Xu et al., 2014). Males may have a greater predisposition to develop PD (Gillies et al., 2014). This bias may be due to the molecular pathology of PD. Gene expression profiles in dopaminergic neurons are sex-specific, and the survivability of these neurons are dependent on molecular pathways that are very different in men and women (Gillies et al., 2014). In healthy brain tissue, genes involved in signal transduction and neuronal growth are up-regulated more in women (Cantuti-Castelvetri et al., 2007). In men, genes with specific mutations (e.g., α-synuclein, PINK-1) that may contribute to the pathogenesis of PD are upregulated more often (Simunovic et al., 2010). A downregulation of genes that provide for oxidative phosphorylation, and synaptic and nerve impulse transmission, is also more prevalent in older males (Simunovic et al., 2010). Therefore, women are thought to have greater protection from PD when compared to men, which may also be due to estrogen concentrations (Gillies et al., 2014). Estrogen influences dopamine synthesis and release while inhibiting dopamine uptake (Shulman, 2007). The higher concentrations of estrogen are a possible reason for the more benign phenotype in women when compared to men, particularly before a course of medication has begun (Haaxma et al., 2007; Miller and Cronin-Golomb, 2011; Cereda et al., 2013). Estrogen may play a role in preventing toxins from possibly degrading neurons in the substantia nigra (Shulman, 2007). Exogenous or endogenous estrogen administration may therefore play a crucial role in the pathogenesis of PD (Lv et al., 2017). There are several factors, including medicinal options, surgical interventions, dietary strategies, and lifestyle habits that may alter estrogen levels in women with PD. Oral contraceptive (OC) use may increase the risk of PD among women (Nicoletti et al., 2011), with a 20% increased risk of developing PD for every five years of OC use (Simon et al., 2009). However, the use of OCs has been also been shown to be inversely associated with PD risk (Greene et al., 2014), with continuous use for more than 10 years determined to even be a protective mechanism against developing PD (Liu et al., 2014). Following an ovariectomy, a decrease in the concentration of estrogen receptor-α and an increase in angiotensin, NADPH-oxidase activity, and the expression of neuroinflammatory markers was observed in the substantia nigra of menopausal rats (Rodriguez-Perez et al., 2015). Smoking may increase levels of estrogen and serum sex hormone-binding globulin, and may also be protective against PD, as an inverse correlation between smoking and PD risk has been shown (Ritz et al., 2007; Breckenridge et al., 2016). Proper intake of vitamin D may increase glial derived neurotrophic factor (Smith et al., 2006) and reduce activated microglial cells (Kim et al., 2006), therefore acting as a neuroprotectant with estrogen and reducing inflammation. The protective effect of estrogen is not always evident, particularly in women who report a more rapid onset of motor symptoms upon diagnosis (Sato et al., 2006; Colombo et al., 2015; Bjornestad et al., 2016). With regard to motor symptoms, women typically present more with tremors and bradykinesia, but not rigidity, when compared to men (Haaxma et al., 2007; Martinez-Martin et al., 2012). Non-motor symptoms, such as constipation, restless legs, pain, nervousness, anxiety, and sadness, are more prevalent in women (Martinez-Martin et al., 2012; Solla et al., 2012; Picillo et al., 2013; Szewczyk-Krolikowski et al., 2014). A reduction in visuospatial cognition also occurs more frequently in women (Miller and Cronin-Golomb, 2011). To treat the motor and non-motor symptoms of PD, individuals are often presented with a variety of options. Medications and surgical procedures are available but are often unsuccessful at treating all symptoms of PD, can be expensive and invasive, and may lead to unwanted side effects (Bloem et al., 2004). Exercise may therefore be an inexpensive and complementary option to other interventions to treat symptoms of PD. Performing regular exercise may improve numerous functional outcome measures and quality-of-life, particularly in higher-functioning individuals diagnosed with neurodegenerative diseases, including PD, multiple sclerosis, and dementia (Dodd et al., 2011; Brienesse and Emerson, 2013; Morley et al., 2015). Gait speed is slower in older women, possibly due to observed increases in muscle strength and standing balance ability in men (Bohannon, 1997). When compared to men with PD, women with PD exhibit increased cadence and decreased stride length and frequency (Kokko et al., 1997; Pedersen et al., 1997). To improve gait, motor performance, and quality-of-life, aerobic exercise on a motorized treadmill may be effective intervention for those with PD (Herman et al., 2007). Treadmill exercise can improve motor function, stride and swing time variability, and gait speed in adults with mild to moderate PD (Herman et al., 2007). This in turn may allow for greater mobility during activities of daily living (ADLs) and a reduced incidence of falls (Cakit et al., 2007; Herman et al., 2007). Performance during ADLs may be enhanced more with the use of external sensory cues during exercise (Cassimatis et al., 2016). These auditory, visual, or tactile cues bypass the basal ganglia using alternative pathways (e.g., cortical, parietopremotor) when processed, thus creating an additive improvement in ADL performance (Kones, 2010). Resistance and flexibility exercises are also recommended for individuals diagnosed with PD. Resistance exercise training can improve muscle strength, muscular endurance, fat-free mass, balance and mobility, and walking economy in adults with PD (Brienesse and Emerson, 2013). When assessing lower limb strength, Pääsuke et al. (2002) found that reaction times and maximum isometric force values were different between legs in women with PD. This may be due to the postural and balance impairments that are prevalent with a diagnosis of PD. Using regression analysis, Schenkman et al. (1998) found a greater correlation between women with PD and poor spinal flexibility and balance when compared to men with PD. Alternative modalities of exercise, including Nordic walking (Cugusi et al., 2017), tai chi (Hackney and Earhart, 2008), and tango dancing (Hackney et al., 2007), may also elicit improvements in balance and mobility in those with PD. Virtual reality (VR) is a newer technology that may be integrated into a rehabilitative program for those with PD. By allowing for repetitive movement that targets both motor and cognitive performance, VR may allow for the learning or re-learning of motor strategies that have been lost due to the progression of PD (Goble et al., 2014). Traditional aerobic and resistance exercise should be prescribed differently to women diagnosed with PD due to the possible inherent sex differences in this population. Current exercise guidelines for adults with PD and proposed guidelines for women with PD are found in Table 1. As PD is a risk factor for osteoporosis, appropriate aerobic modalities should be chosen for women with PD. Short, supervised walks on a level surface with occasional turns (e.g., an athletic track), to add variation to the direction of loads, may be the best aerobic exercise modality that can be prescribed to women with PD. If not ambulatory, leg ergometry may be a suitable option, with a focus on resistance rather than speed. Intensity should be prescribed using VO2 reserve (if available) or rate of perceived exertion (RPE). Prescribing intensity using heart rate responses should not be recommended, as many individuals with PD exhibit autonomic nervous system (ANS) dysfunction (e.g., sympathetic denervation) and are prescribed medications that can interfere with heart rate responses and heart rate variability (Ziemssen and Reichmann, 2010; Moore et al., 2016). This ANS dysfunction is thought to contribute to fatigue in those with PD (Nakamura et al., 2011). Session duration and frequency, particularly at the start of an exercise program, should therefore be limited. Table 1. Exercise guidelines for adults diagnosed with Parkinson's disease. Squats using only body weight or with additional weight may be the most appropriate resistance exercise modality for women with PD. Squats are closed-chain kinetic exercises, which may be a more suitable exercise due to the abnormal coordination between limbs caused by a greater prevalence of tremors at rest in women with PD (Ehrman et al., 2013). The strength of the quadriceps, the prime movers during the upward phase of a squat, is correlated with functional abilities and performance during ADLs (Moore et al., 2016). Targeting the quadriceps musculature during exercise is beneficial because the extensors typically exhibit more muscle weakness than the flexors, and there is evidence that proximal muscles are weaker than distal muscles in those with PD (Inkster et al., 2003; Cano-de-la-Cuerda et al., 2010). The induced compression during the exercise may also improve bone mineral density (BMD) at the hip. Machine weights may be an added supplement to resistance training once increases in volume and frequency can be tolerated. Flexibility training needs to be incorporated into an exercise program for those with PD. A combination of stretching and resistance exercise can improve muscle strength and gait speed in this population (Shulman et al., 2013). As women with PD typically exhibit more frequent episodes of bradykinesia, increasing the strength of skeletal muscles (particularly lower body) and gait parameters is crucial (Haaxma et al., 2007). The Office of Research on Women's Health (ORWH) within the National Institutes of Health (NIH) has called for research scientists to consider sex when designing study protocols to allow for both men and women to receive the full benefit of medical research (National Institutes of Health, 2017). Exercise is an effective intervention that can elicit functional changes in adults with PD. Women with PD should follow an exercise prescription that somewhat deviates from the current exercise guidelines, which are not categorized according to sex. 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Sci. 289, 74–80. doi: 10.1016/j.jns.2009.08.031 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: aerobic, female, flexibility, functional abilities, neurodegenerative, resistance Citation: Rigby BR and Davis RW (2018) Should Exercise Be Prescribed Differently Between Women and Men? An Emphasis on Women Diagnosed With Parkinson's Disease. Front. Physiol. 9:1040. doi: 10.3389/fphys.2018.01040 Received: 30 March 2018; Accepted: 12 July 2018; Published: 02 August 2018. Edited by: Reviewed by: Copyright © 2018 Rigby and Davis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Brandon R. Rigby, [email protected]
, Yannis Jaquet, Djilani J. Kebaili, Laura Symul,
Published: 4 July 2018
Frontiers in Nutrition, Volume 5; https://doi.org/10.3389/fnut.2018.00057

Abstract:
Metabolic disorders, such as diabetes or obesity, have become a major public health concern, with increasingly large parts of the global population affected (1, 2). Nutritional epidemiologists hope to better understand the underlying causes, the potential treatments and prevention strategies by analyzing population and individual patterns through studies that generally rely on surveying dietary habits. Traditional food-intake survey methods are based on questionnaires filled by participants at a given frequency. The frequency of diet records is an important factor contributing to the accuracy of the study (3). Multiple-day diet records might provide good accuracy when not based on memory, but require strong motivation and time commitment by the participants. Approaches like multiple/single 24-h recalls—involving a specialized interviewer performing surveys in person or on the phone with the participants—require less engagement, but pose issues with missing data as they rely on short-term memory. Finally, so-called Food Frequency Questionnaires, where participants are asked to indicate the frequency of intake of certain foods over long periods of time (typically 1 year), demand minimal participants' commitment, therefore allowing for large cohort studies on long-term dietary habits. However, the likelihood of missing or incorrect data increases as they count on participants' long-term memory. Overall, self-reported dietary data present biases which limit their applications, especially when they heavily rely on participants' memory (4). Such limitations, which should be properly addressed in further epidemiological studies, may be overcome with more advanced recording methodologies such as dietary biomarkers and digital technologies (5). Recent technological advances, and in particular the emergence and almost complete market penetration of smartphones, have offered interesting surveying alternatives. In particular, mobile phones have been successfully deployed in several food-related studies (6), for example using food photography (7–12). Other research has also explored the possibility of recording dietary habits by asking participants to scan the barcodes of their consumed food (13, 14). Although further investigations are required to assess self-reporting biases, these advances in nutritional research have triggered the release of mobile apps oriented mainly toward diabetes and weight-loss self-management (15–19), showing the willingness and interest of users to monitor their food intake if it provides potential health benefits. The further expansion of self-monitoring for research and medical purposes relies on comprehensive and continuously updated food databases. A few databases of barcoded products already exist, for example Open Food Facts (20) or the USDA Food Composition Databases (21). While they each have their strength, not all of them are openly accessible or, and they often have a limited product coverage, and are often not regularly updated. For Switzerland, we did not find any database whose product coverage was sufficiently high, where the data was completely open, and easily accessible through an Application Programming Interface (API). The last point was particularly important to us, as APIs are necessary for third parties to dynamically use the data in their products and services. Our approach was therefore to build an openly accessible database of barcoded food products with sufficiently high coverage, accessible through a stable API. Rather than focusing on a wide geographic range, we focused on a small country (Switzerland) in order to obtain the necessary coverage. The focus on the Swiss market further benefits from the need to support multiple languages from the beginning, thus making the system readily expandable to other countries, which we are now planning to do. Here, we present this system, which we call FoodRepo (https://www.foodrepo.org), an openly accessible database of barcoded food products, and we describe the data-acquisition framework, its quality control and maintenance. Here, the word repository is meant to be understood as a data repository, where the community can deposit an increasing number of datapoints on food products. The growing community around FoodRepo and the validation of new products make our database robust, scalable and self-sustainable in the long run. Currently, the FoodRepo database mostly holds products sold in Switzerland, from the main grocery stores in the country. Its international expansion is under development. Any item in the database is accessible through the FoodRepo website (for an example of products contained in the FoodRepo database, please see Figure 1A) or via our API, described in section Usage Notes. The CC-BY-4 license under which our database is released will allow its exploitation by different type of users, from academic researchers to commercial partners. For instance, a Swiss consumers association is using FoodRepo data in their NutriScan mobile app (22) to make the food package information more accessible, and to provide their users with an overall nutritional score. Figure 1. (A) Screenshot from the webpage of a product on the FoodRepo website. (B) Schematic representation of the pipeline behind our API. When a user or an application (left column) sends a call to the API, the request is handled by the server that hosts the API (middle column). This sends then a query to the server which hosts the FoodRepo database (right column), where the query is handled by the Elastic Search engine. The data is returned to the API server which performs final formatting before giving it back to the user or the application. (C) Distribution of API response times, color-coded according to different sections of the back-end pipeline, as shown in (B). In green (main plot and inset) the response-times of the Elastic Search server to the application server; in blue the full time needed for a user to have the data after a call to our API. Beyond this specific example, the FoodRepo database opens the way for promising research opportunities in the field of digital epidemiology and personalized nutrition. Notably, we foresee that, through dietary live-tracking, this database can support studies which combine other recent technological developments and new findings in our understanding of the human metabolism. For example, phone-connected devices for continuous monitoring of blood glucose levels have recently been made available to diabetic patients (23, 24), as well as numerous direct-to-consumer devices to estimate glucose levels have appeared on the market. A plethora of other wireless sensors are now also available to record various physiological parameters such as heart rate or blood pressure, marking a new era of “high-throughput human phenotyping” (25). Studies that would simultaneously track participants' parameters, food intake, glycemic response and physical activity might provide detailed insights on the variability of individual metabolic responses. Interestingly, one of the factors which has recently been found to account for a large part of this variability is microbiota (26–30). Large-scale testing of these hypotheses through self-tracking could contribute to the assessment of the complex metabolic response of the human body to different energy sources. This requires detailed records of food intake that includes nutritional information as well as eating times (31) and food portion sizes (32–34), all challenges that FoodRepo may help to overcome. However, we highlight an important limitation of all food databases. Generally, the curators of such repositories cannot ensure the validity of the data reported by the producers on the nutrition facts labels. It is indeed well known in the literature that there might be large discrepancies between the reported nutrients and the actual food content, due to different factors, such as food pre-processing or the different industry standards (35–40). Therefore, all studies using databases such as the one presented here would do well to assess the validity of such data and ideally quantify the reporting errors, especially when using the reported data on nutritional values. Analyses of the database evolution will give interesting indication on the dietary trends and on the overall modification of the nutritive quality of packaged food. Although the database itself does not inform on the buying frequency, the continuous introduction of specific products in the market and thus in the database can potentially indicate how retailers react to customer demands and changing dietary habits. The database building and maintenance process relies on the following steps: (i) collection of product pictures from local retailers, (ii) data extraction from the pictures, (iii) validation of the extracted data, and (iv) permanent storage in the database (Figure 2). For the initial build of the database, we designed a specific pipeline (bootstrap workflow, Figure 2A, which allowed us to validate the first 20,000 food products in a few months. Given the dynamic nature of our data and the cost of the bootstrap workflow, we designed a second pipeline (currently under development) which relies on the growing FoodRepo community. This workflow (community-based, Figure 2B) allows us to keep up with the new and seasonal products introduced to the market by the retail shops, as well as to ensure the scalability and self-sustainability of FoodRepo in the long run. Figure 2. Schematic overview of FoodRepo data collection and validation processes. The two workflows are illustrated here. The bootstrap workflow (A) was based on the joint work of the FoodRepo team and crowd-sourced workers collecting and validating the data. This allowed the storage of the first 14,000 or so products in the database. The community-based workflow (B) allows for long-term sustainability of the database thanks to customers uploading new products through FoodRepo mobile app and the continuous support of the FoodRepo team. The bootstrap workflow (Figure 2A) consists of 3 main steps. The first step entailed a massive manual data collection from three large groceries stores in Switzerland upon approval from the shops (specifically Migros, Coop, and Lidl). We hired students to take pictures of all barcoded food items in retail shops located in the Lausanne area. To facilitate the data collection, we specifically designed a simple phone app with which students could scan the products' barcode and take pictures of the front and back of the package, the product's name, ingredients list, and nutrition facts. These pictures were then automatically uploaded to the database. At the end of this step, students had collected on average 4.4 pictures per item. The second step focused on the extraction of information contained in the pictures. Due to the presence of multi-language ingredients and the often wrinkled surfaces of item packaging, Optical Character Recognition (OCR) systems could not achieve a reliable accuracy. We therefore opted for a crowd-sourced solution and in particular we decided to recruit workers on Amazon Mechanical Turk (41) (AMT). AMT is a platform connecting requesters to workers, the latter being financially compensated to achieve tasks requiring human intelligence (HITs—Human Intelligence Tasks). Here, we designed a graphical user interface (GUI) allowing workers to transcribe the text they could read from product pictures. Specifically, the GUI presented text boxes where AMT workers provided the product name, nutritional values (in a table format) and ingredients, in every language present on the label (German and/or French for almost all items; Italian and/or English in addition for some products). Three different HITs were set up: one for nutrients, one for product name and one for ingredients. For the last two, we set up qualification rounds for AMT workers as their transcription involved some language skills. AMT workers could choose to either enter from scratch the information they saw on the pictures, or to approve/modify the suggestions given by an OCR (42) system. At the end of the second step, all annotated products were uploaded into the database, flagged as ready for validation. The third step was thus dedicated to data validation, which was based on extensive manual checking by the FoodRepo team, and was additionally informed by manual reports from visitors to the FoodRepo website and with error-detection analyses of nutritional values. Such online reports are encouraged by the presence of a “report an issue” button on each product web-page, which prompts a visitor to file an issue when spotting a potential error. Details about the error-detection analyses are given in the Technical Validation section. Before the final validation of the data, the FoodRepo team as well as students manually checked all products thoroughly. The community-based workflow (Figure 2B) is similar to the bootstrap workflow, but instead of counting on AMT workers, it relies on the growing FoodRepo community. As new products become available in retail shops, FoodRepo users can submit them by uploading the corresponding package pictures, using the FoodRepo smartphone app. Currently, the information extraction is still performed by the FoodRepo team, but additional features are being implemented in the app, which will allow users to directly type the product details contained on the package. Before user-provided information is permanently stored in the FoodRepo database, consistent entries will need to be submitted by at least three different FoodRepo users. If such consensus will not be reached after seven independent submissions (i.e., there are still less than three consistent entries), the item will be manually analyzed by the FoodRepo team for definitive validation and inclusion into the database. This procedure will ensure minimal intervention from our team, while still guaranteeing the reliability of the data. The FoodRepo team is currently fostering the development of an active community through which the continuity of FoodRepo is assured, and which will likely accelerate the birth of independent exploitations of the database, from both public and private partners. All FoodRepo data are stored in a PostgreSQL (43) database, physically hosted on a server in Ireland. For a quick overview of the dataset, a database dump can be downloaded from the dedicated folder in our API repository (44). However, these dumps are not generated regularly, and we strongly encourage the use of the API which delivers up-to-date information. For each product, which comes with a unique numerical identifier, the database contains pictures of the item as found in the shop (usually between three to seven .jpg files), together with the main information presented on the package, i.e., the product name, nutritional values, ingredients list, barcode, and country of origin. The database holds as well the dates of the creation and last modification of the related item in the database (see Table 1). The programmatic access to the database is allowed by an API, described in the section Usage Notes. Table 1. Sample product from the FoodRepo database with its values for the most relevant fields. As described in the Methods section, during the bootstrap stage (Figure 2A) the final validation was performed manually by the FoodRepo team, while in the community workflow (Figure 2B), the accuracy of the data is ensured by the consensus test (the FoodRepo team intervenes only if fewer than three matches are achieved after the uploads of the same product by seven different users). We highlight here that FoodRepo strictly reflects the information printed on products packages, even when suspicious values are present on the labels. All validation processes have thus been set-up to detect transcription errors. Within this rationale, computational analyses were implemented for the detection of outliers, in particular regarding the nutritional values. These tests reflect basic constraints, such as the mass upper-limit: where p, f, c are respectively the product's protein, fat and carbohydrates concentrations expressed in grams per 100 g of product. From Equation (1), one can also derive other linear inequalities for a single nutrient or couples of nutrients, namely p + f ≤ 100, p + c ≤ 100, and c + f ≤ 100. These simple tests allowed us to detect transcription errors in earlier versions of the database, as illustrated by the outliers in Figure 3A which shows the distribution of products in the fat-carbohydrates space with the joint mass boundary. Figure 3. Examples of tests implemented with linear boundaries on nutritional values. Dots outside the boundaries have been inspected and corrected whenever data were different from the products packages. Products in the fat/carbohydrates concentrations space (A), saturated fat/fat concentrations space (B) and energy density/fat concentration space (C). Similarly, other typos could be spotted by checking that the concentration of a subclass of nutrient is smaller than the one of the parent-class. This is the case for instance of sugars vs. carbohydrates, or saturated-fat vs. fat, shown in Figure 3B. Another simple relation that helps check products' nutrition facts can be derived from the standard approximation of energy density based on nutrients composition (45): where the product's energy content E is expressed in kCal/100 g. Combining expressions 1 and 2 provides upper and lower boundaries for the energy content (for example Figure 3C). In this case however, not all dots that fall outside the boundaries were due to typos in transcription. Indeed, the approximation in Equation (2) does not take into account the different contribution to energy of complex carbohydrates such as polyols, which account for less than 4 kCal/g. This is why products such as candies and chewing gums would fall below the energy boundaries. In order to facilitate the access to the database, we built an openly accessible API. Any terminal user, including third party apps or services, can send API requests to retrieve specific data. The API pipeline is illustrated in Figure 1B. User's requests are handled on an application server, where an Elastic Search (ES) application handles the queries on another cloud computing service, based in Ireland. The ES response is then returned to the user after JSON formatting and compression (on demand). We checked that handling the request between the two servers does not critically compromise the total user-response time. We run series of single-page API calls, every 6 h, over a week, in order to measure the full response-time and the application server response-time. We observed that the latter was consistently fast across all experiments (in the range of 20–50 ms) and that the bottleneck was rather the transmission between the terminal user and the application server (the average full response time was about 250 ms—see Figure 1C). For a quick introduction to the API endpoints, users are welcome to try them out on the API Playground page (46). Furthermore, on the project's GitHub repository, one can also find usage cases (47) in Python, Ruby, Curl and JavaScript, as well as examples of complex queries which include fuzzy searches (48). When fetching a large amount of data, we suggest using the option of compressed data1 and the possibility to include/exclude specific fields of each product [see for details the API documentation (46)]. In this way, one could reduce the response payload size by up to a factor of 10. We remind readers that all contents (other than computer software) made available by FoodRepo on its websites, apps or services are licensed under the Creative Commons Attribution 4.0 International License. We however would like to highlight the fact that product images may contain copyrighted data such as brand logos. GL performed the descriptive and validation analysis of the dataset. YJ built the FoodRepo database, website, API and AMT HITs. DK maintained the API, coordinated the manual data validation and built the framework for the FoodRepo community. GL, LS, and MS wrote the manuscript. MS initiated and supervised the project. This project was supported by a grant from the Jebsen foundation (49). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We are grateful to Migros, Coop, and Lidl for access to their retail shops. • API: Application Programming Interface—an set of tools and methods that allow to types of software to communicate. The FoodRepo API allows other applications to get and use the data. • CC-BY-4: Creative-Commons public license, with the “Attribution” term. It implies that anyone is free to share and transform the content of FoodRepo, even for commercial purposes, with the obligation to properly give credit to FoodRepo, and to display any modification without claiming direct endorsement from FoodRepo. For a detailed description, see the license text at https://creativecommons.org/licenses/by/4.0/ • OCR: Optical Character Recognition—tools that allow for automatic conversion of text contained in images to machine-readable formats. • AMT: Amazon Mechanical Turk—web platform providing a marketplace, where workers perform tasks set up by requesters, usually in exchange of money. • HIT: Human Intelligence Task—task related performed by workers in crowd-sourcing platform, such as AMT. • PostgreSQL: A popular and freely available relational database. • JSON: a JavaScript-based file format commonly used for browser-server data exchange. • Elastic Search: a very popular open-source search-engine. 1. ^This can be done by simply setting in the request header: Accept-Encoding: gzip 1. WHO. Diabetes. Available online at: http://www.who.int/mediacentre/factsheets/fs312/en/. 2. WHO. Obesity and Overweight. Available online at: http://www.who.int/mediacentre/factsheets/fs311/en/. 3. 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(2006) 384:1341–55. doi: 10.1007/s00216-005-0294-0 PubMed Abstract | CrossRef Full Text | Google Scholar 40. Deharveng G, Charrondiere U, Slimani N, Southgate D, Riboli E. Comparison of nutrients in the food composition tables available in the nine European countries participating in EPIC. Eur J Clin Nutr. (1999) 53:60. doi: 10.1038/sj.ejcn.1600677 PubMed Abstract | CrossRef Full Text | Google Scholar 41. Amazon Mechanical Turk. Available online at: https://www.mturk.com/. 42. Text, Recognition API Overview,. Google Developers. Available online at: https://developers.google.com/vision/text-overview. 43. PostgreSQL. The World's Most Advanced Open Source Database. Available online at: https://www.postgresql.org/. 44. FoodRepo Database Dumps. Available online at: https://github.com/salathegroup/foodrepo_api/tree/master/data. 45. COUNCIL DIRECTIVE of 24 September 1990 on Nutrition Labelling for Foodstuffs. Available online at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:1990L0496:20081211:EN:PDF. 46. OpenFood API Documentation. Available online at: https://www.foodrepo.org/api-docs/swaggers/v3. 47. OpenFood API GitHub Repository. Available online at: https://github.com/salathegroup/foodrepo_api/tree/master/v3/code. 48. Elasticsearch Queries Example. Available online at: https://github.com/salathegroup/foodrepo_api/blob/master/v3/code/meta/es_sample_queries_product.md. 49. Kristian Gerhard Jebsen Foundation. Available online at: http://www.kgjf.org/. Keywords: open data, digital health, nutrition, API, digital epidemiology Citation: Lazzari G, Jaquet Y, Kebaili DJ, Symul L and Salathé M (2018) FoodRepo: An Open Food Repository of Barcoded Food Products. Front. Nutr. 5:57. doi: 10.3389/fnut.2018.00057 Received: 05 March 2018; Accepted: 12 June 2018; Published: 04 July 2018. Edited by: Reviewed by: Copyright © 2018 Lazzari, Jaquet, Kebaili, Symul and Salathé. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Marcel Salathé, [email protected]
Journal of Christian Nursing, Volume 35, pp 11-11; https://doi.org/10.1097/cnj.0000000000000471

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We've expanded the Resources column where you found books, website reviews, and Going Deeper into more Bible study and discussion questions. We've given more space to delve deeper into select articles from this issue of JCN and dig into God's Word. The new Chat Room can be found on page 65. Chat Room is a great resource for your NCF meetings, whether for students, nurses, or faculty! Look at the end of each feature article in the Web Resources box to find additional content related to the article. Next issue, we will add books to the Web Resources list found with our feature articles. In September 2017, Nurses Christian Fellowship USA started Member Video Chats—a gathering of NCF USA members, for fellowship, discussion, and prayer via Zoom technology. The first chat focused on “Jesus, remember me,” the words of the dying criminal at the Crucifixion (Mark 15; Luke 23). In October, former NCF director Jane Hall led a discussion based on the JCN article Effective Listening: Five Lessons from the Best (Vol. 34, No. 3, pp. 159-163). In November we discussed professional and biblical responses to moral distress. NCF Member Video Chats are announced in the members-only eNewsletter Charting the Way and in special member emails. The chats and technology are free, and a Journal Club feature with 1 hour of free CE credit (ANCC approved) will be offered four times a year beginning in 2018! If you are an NCF USA member, watch for Video Chat information and join us! Not a member? Join NCF at http://ncf-jcn.org/membership. We are looking for quality, continuing education feature articles from a Christian worldview on these topics: Substance Abuse—Christian response to the opioid crisis, pain management of noncancer chronic pain (appropriate opioid use) Global Health Issues—Zika, spread of communicable diseases; Lyme Disease; nurses' roles/support; taking nursing students abroad Update on HIV/AIDS Inter-professional Collaboration Bio-Terrorism/Disaster Preparedness Infection Control Update Changing the Culture of Mistakes in the Workplace CE articles must be well documented, with current references; 4,900-5,600 words in length, including references, tables, and figures; case studies enhance content. Include additional content, slides, or videos beyond 5,600 words as supplemental digital content. Submit your article at http://www.edmgr.com/NCF-JCN/default.aspx JCN, a publication of Nurses Christian Fellowship USA, reaches around the globe. NCF USA is a member country of Nurses Christian Fellowship International (NCFI), which has over 40 member countries in six regions around the world! Read JCN's newest column—NCFI: Your Global Connection on page 10 to meet the NCFI president and learn more about NCFI. These and other events of interest can be found at www.journalofchristiannursing.com under Save the Dates and at Nurses Christian Fellowship's Events page http://ncf-jcn.org/resources/events Indiana Wesleyan University will hold its biannual Innovations in Faith-Based Nursing Conference, June 18-21, 2018, on the campus of IWU in Marion, Indiana. Find information at https://www.indwes.edu/events/nursing-innovations/ The Nurses Christian Fellowship International Caribbean and North America Quadrennial Regional Conference, Infusing Hope in Nursing: A Christian Perspective will be held on July 19-22, 2018, at Azusa Pacific University, California, USA. Information posted at http://ncfi.
Journal of Communications and Networks, Volume 19, pp 1-5; https://doi.org/10.1109/jcn.2017.000110

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This index covers all papers that appeared in JCN during 2017. The Author Index contains the primary entry for each item, listed under the first author’s name, and cross-references from all coauthors. The Title Index contains paper titles for each Division in the alphabetical order from No. 1 to No. 6. Please refer to the primary entry in the Author Index for the exact title, coauthors, and comments / corrections.
Journal of Communications and Networks, Volume 19, pp 542-542; https://doi.org/10.1109/jcn.2017.000088

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Journal of Communications and Networks (JCN) membership application.
Journal of Communications and Networks, Volume 18; https://doi.org/10.1109/jcn.2016.000097

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Provides a listing of the editorial board, current staff, committee members and society officers.
Frontiers in Cardiovascular Medicine, Volume 3; https://doi.org/10.3389/fcvm.2016.00011

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Cascade screening is one of the more forceful demonstrations that molecular biology and genetics are not just a tool for researchers, but represent an important and by now essential component of good medical care. – Peter J. Schwartz (1) There is much attention and excitement in the current health care environment on the potential of precision medicine based on a patient’s genomic data. Today, what arguably remains as one of the most valuable and informative genetic tests is that of predictive testing for a known familial pathogenic variant. Predictive genetic testing determines whether the pathogenic variant previously identified in an affected family member(s) is present or not in relatives at risk. Previous research has documented that affected individuals undergoing genetic testing cite obtaining genetic information for others as being the most important, if not the only, motivation for undergoing genetic testing (2). Predictive, cascade testing is able to separate at-risk relatives who require vigilant serial screening from those who do not. For those with the predisposition, clinical screening allows for early identification of the family’s phenotype, which when present, may require lifelong medical therapy, implantation of devices, and/or other types of medical management. Relatives who test negative for the familial variant can typically be released from lifelong screening. In addition, it is also then known that their children are not at increased risk for the family’s disease. This approach can save the health care system, and the family itself, thousands of dollars. Cascade screening is imperative with “high-stakes” cardiovascular conditions, such as familial hypercholesterolemia (FH), long QT syndrome (LQTS), and other inherited arrhythmias, as well as other heritable cardiovascular phenotypes, including cardiomyopathies and aneurysms, where there is an increased risk for sudden cardiac death and severe morbidities such as heart failure. The value of cascade screening for highly penetrant cardiovascular (and cancer) phenotypes has been acknowledged by public health officials. The United States Centers for Disease Control Office of Public Health Genomics classifies cascade screening of at-risk relatives for certain conditions, FH being one, as a Tier 1 genomic application, meaning it meets the criteria for analytic and clinical validity and utility and therefore has evidence supporting its implementation into practice (3). Cascade screening may include targeted genetic testing as well as clinical screening (e.g., lipid panel) of at-risk relatives. This opinion provides a brief summary of research in this area and poses questions to facilitate future discussion regarding the potential for direct contact of at-risk relatives. As a practicing genetic counselor in clinical genetic medicine for 14 years who has provided genetic counseling and testing to thousands of families with heritable cardiovascular and cancer conditions, it is my opinion that more could be done to provide assistance to probands for at-risk relative notification and that genetic counselors are in the ideal position to facilitate cascade testing and lead forward-thinking research in this area (4). Cascade screening is a mechanism for identifying people at risk for a genetic condition by a process of systematic family tracing. It should begin with first-degree relatives (parents, siblings, and children) and then extend to second- and third-degree relatives in a stepwise, cascade fashion, moving through the pedigree in sequential steps as additional family members are diagnosed until all at-risk relatives have been screened (5). Cascade screening for FH is a cost-effective method for identifying new cases of FH (6–8). Cascade screening in families with inherited arrhythmia syndromes has been shown to lead to immediate prophylactic treatment, including drug treatment or implantation of pacemakers or cardioverter defibrillators (9). However, cascade screening is not effective unless at-risk relatives are first notified of their risk, the health implications of the inherited condition in their family, the availability of testing, with subsequent uptake. However, uptake of genetic counseling and predictive genetic testing has been shown to be inadequate (10). While there is support from payers, public health, and health care providers (HCPs) regarding the importance of cascade testing, how best to inform relatives of their risk and systematically implement cascade testing has yet to be determined. Psychological, educational, geographical, and other barriers exist to family communication of genetic risk information. Ethical factors and family dynamics, including maintenance of confidentiality and privacy, potential for psychological harm and genetic discrimination (i.e., life insurance), balancing the right “not to know” with “duty to warn,” among others, must be considered (11). The currently recommended approach for FH, made by the International FH Foundation, includes the following: (1) the proband’s HCP should construct a pedigree that facilitates identification of at-risk relatives who should be offered testing; (2) the HCP should discuss risk notification with the proband; and (3) the proband should be provided with written information that includes general information about the family’s condition, the benefit, and availability of preventive therapies, emphasizes health consequences without testing, and be encouraged to share this with relatives (12). This approach should be taken with other highly penetrant autosomal dominant conditions. In one study specific to inherited arrhythmias and cardiomyopathies, probands were asked to distribute “family letters” containing information on risks, genetic and other screening tests, and preventive options to relatives at risk. In this study, 57% of informed relatives underwent screening (80% in arrhythmia families; 45% in cardiomyopathy families), and this was statistically significant when compared to the group where no family letter was provided (35%). While such “family letters” increased the number of relatives who presented for evaluation, over 50% in cardiomyopathy families and 43% overall of at-risk relatives had no documentation that they underwent cascade evaluation (13). It has been suggested that it is not outrageous to expect that clinicians, once they have diagnosed a patient with a genetic arrhythmia, “track down” all at-risk family members and determine their genetic status (1). However, realistically, implementation of this approach is problematic since many health care systems do not support this type of family-centric care model. Specifically, a recent review presents health policy-related limitations faced in the United States to effective implementation of cascade screening and includes (1) a low rate of reimbursement for comprehensive genetic counseling services; (2) an individual, versus family-centric, approach to prevention and insurance coverage; (3) insufficient genetic risk assessment and knowledge by a majority of HCPs without genetics credentials; and (4) a shortage of genetics specialists (in rural areas especially) (14). In order to begin addressing and overcoming these challenges, research should be conducted demonstrating effectiveness of novel methods and tools that have the capacity to efficiently notify relatives of risk. These tools should provide education, offer support, and provide attainable next steps with calls to action so that probands can be assisted, and their relatives can understand their own risk and be supported to act on it. Different methods of informing relatives of risk exist including (1) proband, or family-mediated, contact; (2) proband, or family-mediated, contact with assistance (provision of materials, such as a family letter or other written information aids, by the HCP to the proband); and (3) direct contact of at-risk relatives by the clinical service itself. Research suggests that clinical providers may take an active approach and directly contact relatives to notify them of their risk without compromising privacy or autonomy, with significantly higher numbers of relatives whose genetic status is clarified for greater efficiency, and with high levels of acceptability (15–18). A thematic analysis of FH proband interviews found that probands believed they had insufficient authority or control to persuade family members to attend screening and that they welcomed greater assistance from the clinic for contact with relatives (19). Also in support of direct contact is increased accuracy, as errors may occur in proband-mediated transmission of genetic testing result information through families (20). However, a prior study found that FH patients who expressed a preference regarding cascading method favored indirect contact because they considered it less threatening to family members (21). A genetic counseling intervention study that offered direct contact to the index patient as a last option for assistance in informing at-risk relatives reported no uptake; only eight index patients were offered this service, however, and none of the patients in this study had cardiovascular phenotypes (22). A recent literature review concluded that most studies support direct contact of relatives via letter mailed from the provider and that provider-initiated communication more often resulted in relatives being tested compared to other methods of communication (16). Regarding additional Tier 1 conditions, a prospective study of families with BRCA mutations associated with Hereditary Breast Ovarian Cancer syndrome compared proband-mediated contact to a direct contact intervention protocol that included a letter and subsequent phone call to at-risk relatives (17). This study concluded that the direct contact protocol nearly doubled the number of relatives tested and was also found to be psychologically safe. A direct contact study in families with Lynch syndrome, or hereditary non-polyposis colorectal cancer, demonstrated high approval in those who consented to participate, with a third of newly diagnosed mutation carriers having cancer identified in their first post-test colonoscopy. This type of data demonstrates acceptability of direct contact risk notification programs, as well as efficacy, feasibility, and also ethical responsibility. From the perspective of those potentially at risk, a study conducted in Australia assessing community members’ viewpoints showed that over 90% of respondents indicated their desire to be informed about a familial risk of FH and to be offered screening, with evidence of strong community support for direct contact by an FH clinic (23). The “right to know” must also be considered. Research evaluating genetic counseling interventions focused on strengthening family communication, the number of relatives informed of risk, and the impact on uptake of genetics services is ongoing and will help inform future efforts (22, 24). A randomized controlled trial studying whether a specifically designed genetic counseling intervention that included telephone support up to three times post new genetic diagnosis showed no overall significant difference for the level of family communication between the intervention and control groups (25). In this study, the level of family communication was the highest for conditions with appropriate treatments or active surveillance, such as LQTS and hypertrophic cardiomyopathy. While promising, the level still only reached ~30%. These data again beg the question regarding the potential role for direct contact, especially in “high stakes” conditions. Most, if not all, of the research conducted to date specific to direct contact has been done outside the United States. Therefore, there is a real need for research to determine whether direct contact methods would be acceptable to probands, at-risk relatives, and HCPs within the United States. How many probands might indeed welcome and appreciate this assistance and support and opt in to programs that work with and/or for them to assist in disclosure of risk information to relatives? This opinion piece does not propose that we break probands’ confidentiality and throw privacy to the wind. Instead, it hopes to promote additional conversation and brainstorming that may lead to the development and testing of innovative models of care for probands with highly penetrant, yet manageable conditions. The ultimate goal is that we will have greater impact in our work with these families where there are clear risk-reducing interventions. Probands and family members should be engaged in shaping these models and the research testing them, starting now! The next question becomes, what is feasible now in the landscape of our current health care system? Can we systematize the collection of informed consent from probands to directly share their protected health information with relatives for which they provide the clinic contact information? Can we offer probands active assistance in family communication of genetic risk information? In the pediatric setting, is there a role for standardized direct contact of HCPs caring for the at-risk children in our pedigrees with FH, other Tier One conditions, and beyond? This may be a service welcomed by the affected parent proband, who may appreciate greater assistance in coordination of care for their at-risk children and other pediatric members of their family. Advances in web-based technologies and novel models for the delivery of genetic counseling may be able to bring cascade testing more effectively and efficiently to larger numbers of at-risk relatives. For example, home-based online genetic counseling sessions for cardiovascular genetic cascade screening can be effective (26), allowing at-risk individuals to access their genetic risk information at the time of their choosing and without having to travel to a hospital or clinic, a barrier mentioned previously. In addition, interactive e-learning and decisional support e-tools available via informative websites and mobile applications have been used in pre-test genetic counseling with high knowledge and satisfaction, leading toward the “e-informed” patient (27). Mobile health applications have been shown to result in more “activated” patients – defined as individuals who believe their roles are important, that they have the confidence and knowledge needed to take action, and that they can engage in health-promoting behaviors (28), such as predictive genetic testing. Probands with higher activation may lead toward more at-risk relatives notified of their risk. In turn, e-learning information, such as an informational video about the family’s inherited cardiovascular disease, could then be delivered to relatives, who may then become activated themselves to pursue cascade testing. The power of preventive genetic and genomic information is real – that is not the question. How to ensure this information gets into the hands of all that need it, including children, however, needs more active attention. In conclusion, a powerful quote from Newson and Humphries (11): “Our biology does not stop: the risk of developing coronary heart disease as a consequence of FH will still be present, even if relatives live in ignorance.” The author confirms being the sole contributor of this work and approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 1. Schwartz PJ. Cascades or waterfalls, the cataracts of genetic screening are being opened on clinical cardiology. J Am Coll Cardiol (2010) 55(23):2577–9. doi: 10.1016/j.jacc.2009.12.064 CrossRef Full Text | Google Scholar 2. Hallowell N, Foster C, Eeles R, Ardern-Jones A, Murday V, Watson M. 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Patient Educ Couns (2015) 99(4):578–82. doi:10.1016/j.pec.2015.11.006 CrossRef Full Text | Google Scholar Keywords: direct contact, cardiovascular genetics, familial hypercholesterolemia, genetic counselor, genetic counseling, cascade screening, cascade testing, genetic testing Citation: Sturm AC (2016) Cardiovascular Cascade Genetic Testing: Exploring the Role of Direct Contact and Technology. Front. Cardiovasc. Med. 3:11. doi: 10.3389/fcvm.2016.00011 Received: 22 February 2016; Accepted: 05 April 2016; Published: 19 April 2016 Edited by: Reviewed by: Copyright: © 2016 Sturm. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Amy C. Sturm, [email protected]
Journal of Communications and Networks, Volume 18, pp 1-1; https://doi.org/10.1109/jcn.2016.000016

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Journal of Communications and Networks, Volume 17, pp 1-1; https://doi.org/10.1109/jcn.2015.000093

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JCN invites submission of high-quality papers in the areas of Communication Theory and Systems, Wireless Communications, and Networks and Services. JCN is an all-electronic processing journal that stresses fast turnaround together with expert peer reviewing. Typically, a manuscript, if accepted after one round of review, will be ready for publication in about 6 months after submission, with 2~3 months additionally required for each additional round of review. SUBMISSION A prospective author should submit the manuscript for publication consideration in electronic file (LaTex) via JCN website (http://jcn.or.kr) to an appropriate Division Editor (for regular papers) or to any Guest Editor of an appropriate Special Issue. (Special Issues may include regular papers to avoid unnecessary publication delays.)
Journal of Communications and Networks, Volume 16, pp 1-1; https://doi.org/10.1109/jcn.2014.000116

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JCN invites submission of high-quality papers in the areas of Communication Theory and Systems, Wireless Communications, and Networks and Services. JCN is an all-electronic processing journal that stresses fast turnaround together with expert peer reviewing. Typically, a manuscript, if accepted after one round of review, will be ready for publication in about 6 months after submission, with 2~3 months additionally required for each additional round of review. SUBMISSION A prospective author should submit the manuscript for publication consideration in electronic file (LaTex or MS Word) via JCN website (http://jcn.or.kr) to an appropriate Division Editor (for regular papers) or to any Guest Editor of an appropriate Special Issue. (Special Issues may include regular papers to avoid unnecessary publication delays.) JCN is available in both paper and electronic formats, with the latter available in the JCN Digital Library in the JCN Web site, http://jcn.or.kr. For further details on paper submission and subscription, please visit the JCN Web site.
Frontiers in Systems Neuroscience, Volume 8; https://doi.org/10.3389/fnsys.2014.00187

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The motivations behind the development of many neuromorphic processors have been dominated by either the creation of better artificial intelligence, or novel non-von Neumann computing paradigms. A result of this impetus has been a number of low-power processors capable of simulating many different biological features of the nervous system. Power efficiency is crucial for deployed neuromorphic systems, but it also opens this technology up to other energy restricted applications. In this opinion, we suggest two such applications pertaining to therapeutic stimulation of the nervous system where closing the control loop could be assisted by advances in neuromorphic architectures: (1) deep brain stimulation (DBS) in the treatment of Parkinson's disease and (2) epidural spinal cord stimulation (ESS) for restoring voluntary motor functions. Though there are still questions that must be addressed before this would be feasible, but we are suggesting that the technological barriers—in both the algorithms and hardware—can be overcome with directed funding and research. Neuromorphic processor research is centered around the creation of brain-like intelligence through power-efficient circuits that borrow elements directly from biology (Mead, 1989). The applications for these projects range from brain-scale simulations (Gao et al., 2012; Benjamin et al., 2014) and in silica experimentation (Schemmel et al., 2010; Furber et al., 2012), to brain-like computing and learning (Merolla et al., 2011; Srinivasa and Cruz-Albrecht, 2012; Cruz-Albrecht et al., 2013; Rahimi Azghadi et al., 2014; Schmuker et al., 2014). These projects promise unrivaled access to large-scale models of the brain as well as insight into the unique non-von Neumann computation that biological systems appear to achieve. Regardless of the motivation, the tangible result of these efforts has been an accumulation of low-power circuits capable of emulating various elements of the nervous system. Although these are essential for embodying robotic systems and augmenting current super-computing paradigms, they also have the potential to assist in nervous system stimulation control. This application is outside the scope of the currently funded neuromorphic hardware projects, but with new insights and technological advances, it is one that will be particularly beneficial. In our current capacity to monitor neural circuits, most system variables are unobservable. One strategy for estimating these unknown system variables and parameters is by employing an Unscented Kalman Filter (UKF) to combine the observable and unobservable states. The UKF employs a set of known dynamical equations and observation functions with the measurable data to update an approximation of the state and its uncertainty. At each update, sigma points—system states that are consistent with the current state uncertainty—are selected and used to integrate the system. These are combined with estimated mean state values and the approximate uncertainty. A gain matrix then updates the new most likely state of the system. The schematic for this organization is illustrated in Figure 1A. Applying this kind of feedback control to biological systems was initially demonstrated by Voss et al. (2004) but has since been demonstrated on a number of control and estimation problems (Abarbanel et al., 2008; Li et al., 2009; Ullah and Schiff, 2009, 2010; Schiff, 2010; ODoherty et al., 2011; Aprasoff and Donchin, 2012; Schiff, 2012; Liu et al., 2014). Figure 1. Example therapeutic applications of model based control. (A) The system dynamics are described by a model, F, and the observations are described by a function, A. In most systems those observations are going to be noisy, so a covariance matrix, R, will account for that. After one step of F, using the resulting sigma points will provide X˜i = F(Xi). A new set of observations can then be found, i = A(Xi). The means over these two matrices are the a priori state and measurement estimates. The a posteriori state estimate, x^, is now dependent on the state estimate, x˜, the measurement estimate, ỹ, the actual measurement, y, and the Kalman gain matrix, G. (B) Diagram of deep brain stimulation in the treatment of Parkinson's disease. Adapted from Thibeault and Srinivasa (2013). (C) Example epidural spinal cord stimulation for restoring voluntary motor functions. By using a model of the area under stimulation, both the activity and state of that area can be approximated—something that is not directly measurable. The model, constructed from the current understanding of the anatomy, can then be used to find an optimal set of stimulation parameters. In addition, the model output can be used as the feedback into a control system that can not only dynamically tune the stimulation parameters but also adapt to the physiological circuit remodeling—providing the highest possible therapeutic benefit. Embedding these models in low-power neuromorphic hardware would facilitate a transition into implantable devices. A discussion of control inherently implies observability of the system. However, observability alone is useful to current nervous system stimulation strategies. Observing the unknown—or unreachable—states of the physical system, would provide a way to automatically tune the stimulation parameters—assisting clinicians in finding the optimal set points in open-loop control. Finally, in addition to the UKF there are other model-based control schemes that could be employed here. The application of DBS to patients with pharmacoresistant Parkinson's disease can be traced back to the early 1980's (Montgomery Jr, 2012). In DBS, dual electrodes are implanted bilaterally into the nuclei of the basal ganglia (see Figure 1B)—the current target is the subthalamic nucleus. Constant electrical pulses are then injected into the electrodes. After implantation, clinicians will experiment with frequency, amplitude, and duration of those electrical pulses to find a configuration with the highest benefit. Finding that point however, is an inexact science and periodic adjustments to compensate for neural plasticity are required. Although there is a proven clinical benefit to DBS, there is no clear explanation for its mechanism of action. Although the open-loop configuration of DBS has proven capable, closed-loop control of DBS has been shown to be a more effective treatment in both theoretical (Santaniello et al., 2011), and physiological experiments (Rosin et al., 2011). For example, in Rosin et al. (2011) a simple feedback loop was created where the activation of the DBS pulse was triggered by spiking in a reference structure—either the internal segment of the globus pallidus or primary motor cortex. The control paradigm demonstrated a larger reduction in pallidal oscillations and akinesia compared to open-loop DBS. The resulting system—although brilliantly designed—is an incredibly simple solution and one that exemplifies the therapeutic advances that can be made with adaptive feedback control systems. The class of model-based control of DBS suggested here has already been demonstrated in simulation space by Schiff (2010) using the simple neuron implementation of Rubin and Terman (2004). Although the mathematical model used in that study was computationally cheaper than the alternative, it is still difficult to simulate in a low-power microprocessor. Aspects of the original Rubin and Terman (2004) results were implemented using a more hardware friendly model in Thibeault and Srinivasa (2013), however, the required level of abstraction in a control paradigm is still unclear. Despite unanswered questions, these studies are encouraging and demonstrate the feasibility of the strategy. The recent discoveries in the use of epidural spinal cord stimulation—diagrammed in Figure 1C—on patients with motor complete paraplegia has revealed a therapeutic pathway toward restoring voluntary motor function (Harkema et al., 2011). However, the mechanisms behind this benefit as well as the supporting technology is still immature. The current state-of-the-art involves randomly tuning the stimulation parameters manually until a physiological improvement is observed—these parameters include both the duration and amplitude of the stimulus as well as anode/cathode pairings. There have been efforts to apply Bayesian optimization approaches to automating the parameter search but these did not directly account for the relevant biological structures (Desautels, 2014). Additionally, it has been suggested that the therapeutic restoration of motor control is mechanistically dependent on the remodeling of the remaining spinal circuits (van den Brand et al., 2012). Having a control strategy as well as a model that are adaptive to the plastic changes within the spinal circuits would require less manual parameter adjustments over the life of the implant. As a clinical treatment, ESS is still underdeveloped. However, it is one that could benefit from a model-based control strategy—either as an observer system for parametric optimization or as a complete closed-loop solution. Although the fidelity of the spinal cord model and the source of sensory feedback have not been fully explored, in many ways this appears to be a more tractable problem compared to DBS—it may also prove to be an ideal alternative as well (Fuentes et al., 2009). The accessibility of the spinal cord as well as the simplicity of the microcircuit may make closing the loop on ESS more feasible. However, if more finely tuned control of the individual muscles is required, the complexity of the problem could quickly out pace that of DBS. Despite the technological and theoretical advances outlined here, there are still obstacles to overcome. Where and what to measure when closing the loop for both DBS and ESS is not entirely clear. The stability of the hardware measuring those signals is also a concern. Furthermore, as mentioned above, the appropriate level of biological fidelity required in the model has not been fully resolved. The proposed use of neuromorphic hardware implies that the model for the control system actually requires high-fidelity. In DBS treatment of Parkinson's disease this appears to be the case. However, for spinal-cord stimulation, it may not be required. Regardless, closed-loop strategies are clearly more effective and the theoretical and technological barriers are low enough that a concerted effort should be made to advance this concept toward clinical treatments. Finally, model-based control strategies will not only improve the therapeutic benefit but the power consumption as well. Rather than blindly applying stimulation, pulses can be applied only as needed. Utilizing neuromorphic hardware will add to that power savings by both reducing the computational burden and providing the necessary biological detail for model-based control. 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(2004). Nonlinear dynamical system identification from uncertain and indirect measurements. Int. J. Bifurcation Chaos 14, 1905–1933. doi: 10.1142/S0218127404010345 CrossRef Full Text | Google Scholar Keywords: model-based control, neuromorphic hardware, deep brain stimulation, brain augmentation, spinal-cord stimulation Citation: Thibeault CM (2014) A role for neuromorphic processors in therapeutic nervous system stimulation. Front. Syst. Neurosci. 8:187. doi: 10.3389/fnsys.2014.00187 Received: 12 August 2014; Accepted: 16 September 2014; Published online: 07 October 2014. Edited by: Reviewed by: Copyright © 2014 HRL Laboratories LLC. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: [email protected]
Journal of Communications and Networks, Volume 16, pp 1-1; https://doi.org/10.1109/jcn.2014.000081

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Journal of Communications and Networks, Volume 15, pp 1-1; https://doi.org/10.1109/jcn.2013.000056

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The Journal of Communications and Networks (JCN) invites submission of high-quality papers in the areas of Communication Theory and Systems, Wireless Communications, and Networks and Services. JCN is an all-electronic processing journal that stresses fast turnaround together with expert peer reviewing. Typically, a manuscript, if accepted after one round of review, will be ready for publication in about 6 months after submission, with 2~3 months additionally required for each additional round of review. SUBMISSION A prospective author should submit the manuscript for publication consideration in electronic file (LaTex or MS Word) via JCN website (http://jcn.or.kr) to an appropriate Division Editor (for regular papers) or to any Guest Editor of an appropriate Special Issue. (Special Issues may include regular papers to avoid unnecessary publication delays.) JCN is available in both paper and electronic formats, with the latter available in the JCN Digital Library in the JCN Web site, http://jcn.or.kr. For further details on paper submission and subscription, please visit the JCN Web site.
Journal of Communications and Networks, Volume 15, pp 1-1; https://doi.org/10.1109/jcn.2013.000058

Abstract:
This form is provided for original papers submitted to Journal of Communications and Networks (JCN) and must be received by the JCN office before the paper is accepted for publication in JCN. Please read this form carefully before signing.
Journal of Communications and Networks, Volume 15, pp 1-1; https://doi.org/10.1109/jcn.2013.000059

Abstract:
Provides tyhe latest subscription application/renewal form for the JOURNAL OF COMMUNICATIONS AND NETWORKS (JCN), a Publication of the Korean Institute of Communications and Information Sciences (KICS)
Journal of Biomolecular Structure and Dynamics, Volume 31, pp 788-808; https://doi.org/10.1080/07391102.2012.712458

Abstract:
Inosine monophosphate dehydrogenase (IMPDH) is involved in de novo biosynthesis pathway of guanosine nucleotide. Type II isoform of this enzyme is selectively upregulated in lymphocytes and chronic myelogenous leukemia (CML) cells, and is an excellent target for antileukemic agent. The molecular dynamics simulation results (15 ns) of three unliganded 1B3O, 1JCN, and 1JR1 structures have clearly revealed that IN, IC (N- and C-terminal of catalytic domains) and C1, C2 (cystathionine-beta-synthase-1 and 2) domains of IMPDH enzyme have been stabilized by six conserved water (center) mediated salt bridge interactions. These conserved water molecules could be involved in interdomain or intradomain recognition, intradomain coupling, and charge transfer processes. The binding propensity of cystathionine-beta-synthase domain to catalytic domain (through conserved water-mediated salt bridges) has provided a new insight to the biochemistry of IMPDH. Stereospecific interaction of IN with C2 domain through conserved water molecule (K109–WII1–D215/D216) is observed to be unique in the simulated structure of hIMPDH-II. The geometrical/structural consequences and topological feature around the WII1 water center may be utilized for isoform specific inhibitor design for CML cancer. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:1
Journal of Communications and Networks, Volume 15; https://doi.org/10.1109/jcn.2013.000020

Abstract:
Aim and scope: The Journal of Communications and Networks is published four times per year, and is committed to publishing high-quality papers that advance the state-of-the-art and practical applications of communications and information networks. Theoretical research contributions presenting new techniques, concepts, or analyses, applied contributions reporting on experiences and experiments, and tutorial expositions of permanent reference value are welcome. The subjects covered by this journal include all topics in communication theory and systems, wireless communications, and networks and services.
Journal of Communications and Networks, Volume 15; https://doi.org/10.1109/jcn.2013.000002

Abstract:
Provides a listing of current committee members and society officers.
Journal of Communications and Networks, Volume 15, pp 1-1; https://doi.org/10.1109/jcn.2013.000018

Abstract:
Advertisement: Journal of Communications and Networks (JCN) - a publication of the Korean Institute of Communications and Information Sciences (KICS). JCN subscription application / renewal form.
Journal of Communications and Networks, Volume 12; https://doi.org/10.1109/jcn.2010.6388316

Abstract:
Provides instructions and guidelines to prospective authors who wish to submit manuscripts.
Journal of Communications and Networks, Volume 12; https://doi.org/10.1109/jcn.2010.6388503

Abstract:
Provides instructions and guidelines to prospective authors who wish to submit manuscripts.
Journal of Communications and Networks, Volume 12; https://doi.org/10.1109/jcn.2010.6388461

Abstract:
Provides instructions and guidelines to prospective authors who wish to submit manuscripts.
Journal of Communications and Networks, Volume 12; https://doi.org/10.1109/jcn.2010.6391380

Abstract:
Provides instructions and guidelines to prospective authors who wish to submit manuscripts.
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