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Helena García-Castro, Nathan J. Kenny, Marta Iglesias, Patricia Álvarez-Campos, Vincent Mason, Anamaria Elek, Anna Schönauer, Victoria A. Sleight, Jakke Neiro, Aziz Aboobaker, et al.
Genome Biology, Volume 22, pp 1-34; doi:10.1186/s13059-021-02302-5

Abstract:
Single-cell sequencing technologies are revolutionizing biology, but they are limited by the need to dissociate live samples. Here, we present ACME (ACetic-MEthanol), a dissociation approach for single-cell transcriptomics that simultaneously fixes cells. ACME-dissociated cells have high RNA integrity, can be cryopreserved multiple times, and are sortable and permeable. As a proof of principle, we provide single-cell transcriptomic data of different species, using both droplet-based and combinatorial barcoding single-cell methods. ACME uses affordable reagents, can be done in most laboratories and even in the field, and thus will accelerate our knowledge of cell types across the tree of life.
Limin Liu, Maoying Zhu, Xiaoli Liu, Lumin Fei, Jianyun Shen,
Basic and Clinical Andrology, Volume 31, pp 1-10; doi:10.1186/s12610-021-00126-8

Abstract:
Background Occludin protein is the primary assembling protein of TJs and the structural basis for tight junction formation between Sertoli cells in the spermatogenic epithelium. The expression of miR-122-5p and occludin are negatively correlated. In order to investigate the regulation mechanism of miR-122-5p on occludin and TJ, the present study isolated primary Sertoli cells from C57BL/6 mice, identified a transcription factor of miR-122-5p in testicle, studied the modulating loci of miR-122-5p on occludin using a dual-luciferase reporter assay, analyzed the regulate of miR-122-5p on the expression of occludin with real-time RT-PCR and Western blot, and studied the effect of miR-122-5p on the tight junction using a Millicell Electrical Resistance System. Results The relative luciferase activity in the pcDNA-Sp1 + pGL3-miR-122-5p promoter group was significantly higher than that in the pcDNA-Sp1 + pGL3-basic group, which suggests that transcript factor Sp1 promotes the transcription of miR-122-5p. The relative luciferase activity in the occludin 3′-UTR (wt) + miR-122-5p mimic group was significantly lower than that in the other groups (p < 0.01), which indicates that miR-122-5p modulates the expression of occludin via the ACACTCCA sequence of the occludin-3’UTR. The levels of occludin mRNA and protein in the miR-122-5p mimic group were significantly lower than that in the other groups (p < 0.05), which indicates that miR-122-5p reduces the expression of occludin. The trans-epithelial resistance of the miR-122-5p mimic group was significantly lower than that of the blank control group after day 4 (p < 0.05), which indicates that miR-122-5p inhibited the assembly of the inter-Sertoli TJ permeability barrier in vitro. Conclusion These results displayed that miR-122-5p could regulate tight junctions via the Sp1-miR-122-5p-occludin-TJ axis.
Katherine M. Halloran, Emily C. Hoskins, Claire Stenhouse, Robyn M. Moses, Kathrin A. Dunlap, M. Carey Satterfield, Heewon Seo, Gregory A. Johnson, Guoyao Wu,
Journal of Animal Science and Biotechnology, Volume 12, pp 1-20; doi:10.1186/s40104-021-00567-1

Abstract:
Background Administration of progesterone (P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes (n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle (CO, n = 18) or 25 mg progesterone in CO (P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids, agmatine, polyamines, glucose, and fructose. Results Treatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1, SLC7A2, SLC2A1, AGMAT, and ODC1 in endometria, as well as SLC1A4, SLC2A5, SLC2A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes. Conclusions This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a ‘programming’ effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.
, Perrine Créquit, Isabelle Boutron
BMC Medicine, Volume 19, pp 1-15; doi:10.1186/s12916-021-01955-0

Abstract:
Background An accurate and comprehensive assessment of harms is a fundamental part of an accurate weighing of benefits and harms of an intervention when making treatment decisions; however, harms are known to be underreported in journal publications. Therefore, we sought to compare the completeness of reporting of harm data, discrepancies in harm data reported, and the delay to access results of oncological clinical trials between three sources: clinical study reports (CSRs), clinical trial registries and journal publications. Methods We used the EMA clinical data website to identify all trials submitted to the EMA between 2015 and 2018. We retrieved all CSRs and included all phase II, II/III or III randomised controlled trials (RCTs) assessing targeted therapy and immunotherapy for cancer. We then identified related records in clinical trial registries and journals. We extracted harms data for eight pre-specified variables and determined the completeness of reporting of harm data in each of the three sources. Results We identified 42 RCTs evaluating 13 different drugs. Results were available on the EMA website in CSRs for 37 (88%) RCTs, ClinicalTrials.gov for 36 (86%), the European Clinical Trials Register (EUCTR) for 20 (48%) and in journal publications for 32 (76%). Harms reporting was more complete in CSRs than other sources. We identified marked discrepancies in harms data between sources, e.g. the number of patients discontinuing due to adverse events differed in CSRs and clinical trial registers for 88% of trials with data in both sources. For CSRs and publications, the corresponding number was 90%. The median (interquartile range) delay between the primary trial completion date and access to results was 4.34 (3.09–7.22) years for CSRs, 2.94 (1.16–4.52) years for ClinicalTrials.gov, 5.39 (4.18–7.33) years for EUCTR and 2.15 (0.64–5.04) years for publications. Conclusions Harms of recently approved oncological drugs were reported more frequently and in more detail in CSRs than in trial registries and journal publications. Systematic reviews seeking to address harms of oncological treatments should ideally use CSRs as the primary source of data; however, due to problems with access, this is currently not feasible.
Bangmin Wang, Zheping Hong, Chen Zhao, Qing Bi, Junhui Yuan, , Yi Shen
Cancer Cell International, Volume 21, pp 1-9; doi:10.1186/s12935-021-01882-3

Abstract:
Background Osteosarcoma is an aggressive malignant tumor which has attracted worldwide attention. MEX3A may be associated with tumors while has not yet seen its coverage on osteosarcoma. Herein, this study was to investigate the correlation between MEX3A and the progression of osteosarcoma. Methods Firstly, we determined that expression of MEX3A was significantly higher in osteosarcoma tissues than that in marginal bone by immunohistochemical staining. Additionally, MEX3A expression was downregulated by the RNAi‐mediated knockdown. The functions of MEX3A knockdown on proliferation, apoptosis, cell cycle, migration was assessed by MTT assay, flow cytometry, wound-healing assay and Transwell assay, respectively. Knockdown of MEX3A resulted in suppressing cell proliferation, increasing cell apoptosis, inducing the G2 phase cell cycle arrest, and attenuating cellular migration. Furthermore, mouse xenograft model confirmed inhibitory effects of MEX3A knockdown on osteosarcoma formation. Results The preliminary exploration on the molecular mechanism of MEX3A in osteosarcoma cells showed that the induction of apoptosis needs the participation of a series of apoptosis- associated factors, such as upregulation of Caspase 3, Caspase 8 and HSP60, downregulation of HSP27 and XIAP. Conclusions In summary, these findings predicated that therapy directed at decreasing MEX3A expression is a potential osteosarcoma treatment.
, , Manuel J. Díaz, Juan Carlos García, Inmaculada Giráldez, Francisco López
Biotechnology for Biofuels, Volume 14, pp 1-14; doi:10.1186/s13068-021-01930-0

Abstract:
Background Burning fast-growing trees for energy production can be an effective alternative to coal combustion. Thus, lignocellulosic material, which can be used to obtain chemicals with a high added value, is highly abundant, easily renewed and usually inexpensive. In this work, hemicellulose extraction by acid hydrolysis of plant biomass from three different crops (Chamaecytisus proliferus, Leucaena diversifolia and Paulownia trihybrid) was modelled and the resulting solid residues were used for energy production. Results The influence of the nature of the lignocellulosic raw material and the operating conditions used to extract the hemicellulose fraction on the heat capacity and activation energy of the subsequent combustion process was examined. The heat power and the activation energy of the combustion process were found to depend markedly on the hemicellulose content of the raw material. Thus, a low content in hemicelluloses resulted in a lower increased energy yield after acid hydrolysis stage. The process was also influenced by the operating conditions of the acid hydrolysis treatment, which increased the gross calorific value (GCV) of the solid residue by 0.6–9.7% relative to the starting material. In addition, the activation energy of combustion of the acid hydrolysis residues from Chamaecytisus proliferus (Tagasaste) and Paulownia trihybrid (Paulownia) was considerably lower than that for the starting materials, the difference increasing with increasing degree of conversion as well as with increasing temperature and acid concentration in the acid hydrolysis. The activation energy of combustion of the solid residues from acid hydrolysis of tagasaste and paulownia decreased markedly with increasing degree of conversion, and also with increasing temperature and acid concentration in the acid hydrolysis treatment. No similar trend was observed in Leucaena diversifolia (Leucaena) owing to its low content in hemicelluloses. Conclusions Acid hydrolysis of tagasaste, leucaena and paulownia provided a valorizable liquor containing a large amount of hemicelluloses and a solid residue with an increased heat power amenable to efficient valorization by combustion. There are many potential applications of the hemicelluloses-rich and lignin-rich fraction, for example as multi-components of bio-based feedstocks for 3D printing, for energy and other value-added chemicals.
, Andreia Leite, Julian Perelman, Ausenda Machado, Ana Rita Torres, Hanna Tolonen, Baltazar Nunes
Archives of Public Health, Volume 79, pp 1-9; doi:10.1186/s13690-021-00562-y

Abstract:
Background Accurate data on hypertension is essential to inform decision-making. Hypertension prevalence may be underestimated by population-based surveys due to misclassification of health status by participants. Therefore, adjustment for misclassification bias is required when relying on self-reports. This study aims to quantify misclassification bias in self-reported hypertension prevalence and prevalence ratios in the Portuguese component of the European Health Interview Survey (INS2014), and illustrate application of multiple imputation (MIME) for bias correction using measured high blood pressure data from the first Portuguese health examination survey (INSEF). Methods We assumed that objectively measured hypertension status was missing for INS2014 participants (n = 13,937) and imputed it using INSEF (n = 4910) as auxiliary data. Self-reported, objectively measured and MIME-corrected hypertension prevalence and prevalence ratios (PR) by sex, age group and education were estimated. Bias in self-reported and MIME-corrected estimates were computed using objectively measured INSEF data as a gold-standard. Results Self-reported INS2014 data underestimated hypertension prevalence in all population subgroups, with misclassification bias ranging from 5.2 to 18.6 percentage points (pp). After MIME-correction, prevalence estimates increased and became closer to objectively measured ones, with bias reduction to 0 pp - 5.7 pp. Compared to objectively measured INSEF, self-reported INS2014 data considerably underestimated prevalence ratio by sex (PR = 0.8, 95CI = [0.7, 0.9] vs. PR = 1.2, 95CI = [1.1, 1.4]). MIME successfully corrected direction of association with sex in bivariate (PR = 1.1, 95CI = [1.0, 1.3]) and multivariate analyses (PR = 1.2, 95CI = [1.0, 1.3]). Misclassification bias in hypertension prevalence ratios by education and age group were less pronounced and did not require correction in multivariate analyses. Conclusions Our results highlight the importance of misclassification bias analysis in self-reported hypertension. Multiple imputation is a feasible approach to adjust for misclassification bias in prevalence estimates and exposure-outcomes associations in survey data.
Jane Williams, Gillian W. Shorter, Neil Howlett, Julia Zakrzewski-Fruer,
Sports Medicine - Open, Volume 7, pp 1-17; doi:10.1186/s40798-021-00311-z

Abstract:
Background In 2018, there were 616,014 registered deaths in the United Kingdom (UK). Grief is a natural consequence. Many mental health concerns, which can be identified as grief outcomes (e.g. anxiety and depression) in those who have experienced a bereavement, can be improved through physical activity. The objective of this review was to identify from the existing literature if physical activity can benefit grief outcomes in individuals who have been bereaved. Methods A systematic review of nine databases was performed. Included studies (qualitative and quantitative) explored physical activity to help individuals (of any age) who had experienced a human bereavement (excluding national loss). Results From 1299 studies screened, 25 met the inclusion criteria, detailing eight types of bereavement (parental (n = 5), spousal (n = 6), patient (n = 4), pre-natal (n = 3), later life (n = 1), caregiver (n = 1), multiple (n = 4) and non-defined (n = 1). Activities including yoga, running, walking and martial arts were noted as beneficial. Physical activity allowed a sense of freedom, to express emotions, provided a distraction and an escape from grief, whilst enhancing social support. Conclusion There is some evidence that physical activity may provide benefit for the physical health and psychological wellbeing of those who have been bereaved, including when the loss has happened at a young age. This review is timely, given the wide-scale national loss of life due to COVID-19 and extends knowledge in this area. More research is needed to explore the benefits of physical activity for those who have been bereaved. In particular, there is a need for well-designed interventions which are tailored to specific activities, populations and grief outcomes.
, Hiroki Yoke, Junya Inata
Journal of Medical Case Reports, Volume 15, pp 1-5; doi:10.1186/s13256-021-02769-7

Abstract:
Background Although drug-induced interstitial pneumonia is a well-known adverse side-effect of cancer chemotherapy, the disease is difficult to detect in the early phase. We report a case of oxaliplatin-induced interstitial pneumonia in which eosinophilia and high-grade fever with relative bradycardia were useful presenting signs for the early diagnosis. Case presentation A 76-year-old Japanese woman with postoperative recurrent rectal cancer (peritoneal dissemination and liver metastasis) was admitted to our hospital because of productive cough and consolidation on thoracic computed tomography (CT) images. Two months prior to the consultation, she had started chemotherapy (fluorouracil, oxaliplatin, and bevacizumab). After finishing three courses of chemotherapy, she developed fever and was noted to have relative bradycardia. After another two courses of chemotherapy, she developed productive cough, chest discomfort, and high-grade fever. At this time, thoracic CT revealed patchy areas of consolidation distributed predominantly in the periphery. Despite the administration of tazobacterium/piperacillin, the consolidation seen on CT scans gradually worsened. Fiberoptic bronchoscopy was performed, and bronchoalveolar lavage fluid analysis showed increased lymphocytes, eosinophils, and total cell count but a low CD4/ CD8 ratio. No specific pathogen was identified. With a diagnosis of interstitial pneumonia, prednisolone was started and chemotherapy was temporarily discontinued. Her productive cough gradually decreased, and the infiltrative shadows on the thoracic CT scans improved. Conclusion Although cases of oxaliplatin-related pneumonia with complicating relative bradycardia are not uncommon, drug-induced interstitial pneumonia should be taken into account in the differential diagnosis. In this case, an increased circulating eosinophil count and high-grade fever with relative bradycardia were the first signs of drug-induced interstitial pneumonia.
, Jamie O. Edgin, Stephanie L. Sherman, Audra Sterling, Andrea McDuffie, Elizabeth Berry-Kravis, Debra Hamilton, Leonard Abbeduto
Journal of Neurodevelopmental Disorders, Volume 13, pp 1-17; doi:10.1186/s11689-021-09361-6

Abstract:
Background The purpose of this study was to evaluate expressive language sampling (ELS) as a procedure for generating spoken language outcome measures for treatment research in Down syndrome (DS). We addressed (a) feasibility, (b) practice effects across two short-term administrations, (c) test-retest reliability across two short-term administrations, (d) convergent and discriminant construct validity, and (e) considered comparisons across the conversation and narration contexts. Method Participants were 107 individuals with DS between 6 and 23 years of age who presented with intellectual disability (IQ < 70). The utility of ELS procedures designed to collect samples of spoken language in conversation and narration were evaluated separately. Variables of talkativeness, vocabulary, syntax, utterance planning, and articulation quality, derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers), were considered. A 4-week interval was used to assess practice effects and test-retest reliability. Standardized direct assessments and informant report measures were collected to evaluate construct validity of the ELS variables. Results Low rates of noncompliance were observed; youth who were under 12 years of age, had phrase-level speech or less, and had a 4-year-old developmental level or less were at particular risk for experiencing difficulty completing the ELS procedures. Minimal practice effects and strong test-retest reliability across the 4-week test-retest interval was observed. The vocabulary, syntax, and speech intelligibility variables demonstrated strong convergent and discriminant validity. Although significant correlations were found between the variables derived from both the conversation and narration contexts, some differences were noted. Conclusion The ELS procedures considered were feasible and yielded variables with adequate psychometric properties for most individuals with DS between 6 and 23 years old. That said, studies of outcome measures appropriate for individuals with DS with more limited spoken language skills are needed. Context differences were observed in ELS variables suggest that comprehensive evaluation of expressive language is likely best obtained when utilizing both contexts.
Dong Ma, Zhe Pan, Quan Chang, Jin-Jin Zhang, , Na Hua, Guo-Hua Li
BMC Cancer, Volume 21, pp 1-10; doi:10.1186/s12885-021-08040-y

Abstract:
Background Epiplakin1 (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. However, the role of Eppk1 in cervical cancer (CC) remains unknown. Methods To express Eppk1 and KLF5 and their correlation, we used RNA-sequence, RT-qPCR, TCGA database and immunofluorescence staining in vitro and in different pathological cervical tissues. In CC cell lines, we tested adenovirus-mediated over expression or knockdown of KLF5 and siRNA-mediated knockdown of Eppk1 and a suiting assessment of cell proliferation and cell signaling by western blot and CCK8 tests. We studied the mechanism by which KLF5 regulates Eppk1 expression by reporter gene test and chromatin immunoprecipitation test. Results Eppk1 expression promoted in CC tissues and cell lines compared with increased KLF5 expression. The results of immunofluorescence staining further showed the increased co-expression of Eppk1 and KLF5 correlated substantially with tumorigenesis in cervical tissues. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanically, KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments reported that KLF5 promoted cell proliferation in Hela partly dependent on Eppk1 upregulation. Besides, KLF5-mediated activation of p38 signaling significantly decreased after Eppk1 knockdown compared with decline of proliferation, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation. Finally, Eppk1 expression is positively correlated with tumor size in clinicopathological features of CC. Conclusions Eppk1 may be an effective therapeutic target for affecting p38 signaling pathway and cell proliferation in cervical cancer.
M. Vailati-Riboni, D. N. Coleman, V. Lopreiato, A. Alharthi, R. E. Bucktrout, E. Abdel-Hamied, I. Martinez-Cortes, Y. Liang, E. Trevisi, I. Yoon, et al.
Journal of Animal Science and Biotechnology, Volume 12, pp 1-19; doi:10.1186/s40104-021-00560-8

Abstract:
Background We aimed to characterize the protective effects and the molecular mechanisms of action of a Saccharomyces cerevisiae fermentation product (NTK) in response to a mastitis challenge. Eighteen mid-lactation multiparous Holstein cows (n = 9/group) were fed the control diet (CON) or CON supplemented with 19 g/d NTK for 45 d (phase 1, P1) and then infected in the right rear quarter with 2500 CFU of Streptococcus uberis (phase 2, P2). After 36-h, mammary gland and liver biopsies were collected and antibiotic treatment started until the end of P2 (9 d post challenge). Cows were then followed until day 75 (phase 3, P3). Milk yield (MY) and dry matter intake (DMI) were recorded daily. Milk samples for somatic cell score were collected, and rectal and udder temperature, heart and respiration rate were recorded during the challenge period (P2) together with blood samples for metabolite and immune function analyses. Data were analyzed by phase using the PROC MIXED procedure in SAS. Biopsies were used for transcriptomic analysis via RNA-sequencing, followed by pathway analysis. Results DMI and MY were not affected by diet in P1, but an interaction with time was recorded in P2 indicating a better recovery from the challenge in NTK compared with CON. NTK reduced rectal temperature, somatic cell score, and temperature of the infected quarter during the challenge. Transcriptome data supported these findings, as NTK supplementation upregulated mammary genes related to immune cell antibacterial function (e.g., CATHL4, NOS2), epithelial tissue protection (e.g. IL17C), and anti-inflammatory activity (e.g., ATF3, BAG3, IER3, G-CSF, GRO1, ZFAND2A). Pathway analysis indicated upregulation of tumor necrosis factor α, heat shock protein response, and p21 related pathways in the response to mastitis in NTK cows. Other pathways for detoxification and cytoprotection functions along with the tight junction pathway were also upregulated in NTK-fed cows. Conclusions Overall, results highlighted molecular networks involved in the protective effect of NTK prophylactic supplementation on udder health during a subclinical mastitic event.
, Sonja McIlfatrick, Sheila Payne, Paul Slater, Dori-Anne Finlay, Tracey McConnell,
BMC Nursing, Volume 20, pp 1-8; doi:10.1186/s12912-021-00570-x

Abstract:
Background Most people spend their last year of life at home, with many wishing to die there, but patients may need access to care after hours. Out-of-hours palliative care is delivered by multi-disciplinary teams including Health Care Assistants (HCA). However, little is known about the role, contribution and impact Health Care Assistants have on out-of-hours palliative care services. The aim of this study is to examine the Health Care Assistant role, contribution and impact on service delivery and patient care in out-of-hours community palliative care provided by hospice organisations. Methods and analysis A mixed methods exploratory study consisting of four phases. Phase one involves a scoping review to systematically map and identify gaps in policy and literature on the HCA role in out-of-hours palliative care. In phase two, all United Kingdom hospices will be invited to participate in an online census to enable the development of a typology of out-of-hours services and the contribution of the Health Care Assistant. During phase three organisational case studies representing different service types will collect information from Health Care Assistants, patients, caregivers and service managers to gather qualitative and quantitative data about out-of-hours service provision and the Health Care Assistant role. Finally, phase four will synthesize and refine results through online focus groups. Ethics and dissemination Ethical approval has been obtained for phase two through Ulster University Research Governance Filter Committee, Nursing and Health Research. Findings will be disseminated through practitioner and/or research journals, conferences, and social media.
, Laila Fozouni, AbdulRazzaq Al-Saiedi, Kevin Coughlin, Patrick Vinck
BMC Public Health, Volume 21, pp 1-11; doi:10.1186/s12889-021-10734-8

Abstract:
Background Globally 70.8 million people have been forcibly displaced from their homes and are at disproportionally high risk for trauma. At the time of this study, there was an estimated 1.6 million internally displaced persons (IDP) in Iraq, more than two-thirds of whom reside in private, urban settings. This study aims to understand the impact of post-displacement accommodation on mental well-being of the Yazidi minority group displaced in Iraq. Methods Multi-stage stratified sampling was used to randomly select IDPs in camp and out of camp settlements in northern Iraq. Standardized questionnaires evaluated factors including exposure to violence and self-reported distress symptoms (measured by Impact of Event Scale-Revised). A multi-variate linear model assessed the relationship between settlement setting and distress symptoms. Results One thousand two hundred fifty-six displaced Yazidi participants were included in the study: 63% in camps and 37% out of camps. After controlling for exposure to violence, social cohesion, unemployment, and access to basic services, IDPs in camps were predicted to have a 19% higher mean distress symptom score compared to those out of camps. Conclusions This study provides a framework to investigate post-displacement accommodation as a potential intervention to improve well-being for displaced populations. With a shift towards new models of emergency and long-term housing, it is important to understand the potential and limitations of more decentralized models, and identify effective methods to maintain access to basic services while improving living conditions for both displaced populations and their host communities.
Almuth Angermund, Gary Inglese, , Laura Iserloh, Berit Libutzki
BMC Urology, Volume 21, pp 1-9; doi:10.1186/s12894-021-00814-7

Abstract:
Background Intermittent catheterization (IC) is a common medical technique to drain urine from the bladder when this is no longer possible by natural means. The objective of this study was to evaluate the standard of care and the burden of illness in German individuals who perform intermittent catheterization and obtain recommendations for improvement of care. Methods A descriptive study with a retrospective, longitudinal cohort design was conducted using the InGef research database from the German statutory health insurance claims data system. The study consisted of individuals with initial IC use in 2013–2015. Results Within 3 years 1100 individuals with initial IC were identified in the database (~ 19,000 in the German population). The most common IC indications were urologic diseases, spinal cord injury, Multiple Sclerosis and Spina Bifida. Urinary tract infections (UTI) were the most frequent complication occurring 1 year before index (61%) and in follow-up (year 1 60%; year 2 50%). Resource use in pre-index including hospitalizations (65%), length of stay (12.8 ± 20.0 days), physician visits (general practitioner: 15.2 ± 29.1), prescriptions of antibiotics (71%) and healthcare costs (€17,950) were high. Comorbidities, complications, and healthcare resource use were highest 1 year before index, decreasing from first to second year after index. Conclusions The data demonstrated that prior to initial catheterization, IC users experienced UTIs and high healthcare utilization. While this demonstrates a potential high burden of illness prior to initial IC, UTIs also decreased over time, suggesting that IC use may have a positive influence. The findings also showed that after the first year of initial catheterization the cost decreased. Further studies are needed to better understand the extent of the burden for IC users compared to non-IC users.
, Florian Glaser-Gallion, Thomas Steffen
Surgical Case Reports, Volume 7, pp 1-4; doi:10.1186/s40792-021-01173-z

Abstract:
Background The COVID-19 pandemic has rapidly spread worldwide. As it is a novel disease, we have less experience in its possible appearances. Predominantly affecting the respiratory tract, about 20–43% patients also present with extrapulmonary manifestations such as coagulation disorders with thrombotic angiopathy. Case presentation In our institution, a patient presented to the emergency department with acute abdominal pain which was caused by portal vein thrombosis. As a COVID-19 nasopharyngeal antigen swab few days earlier was negative, we performed several tests to find out its etiology. After all tests were inconclusive and the patient suffered flu-like symptoms 2 weeks before, we repeated COVID-19 molecular testing and received a positive test result. The patient was treated symptomatically and received therapeutic anticoagulation. Conclusion A COVID-19 infection can also be present without typical pulmonary symptoms. In patients with severe abdominal pain and new diagnosed portal vein thrombosis, it is important to think of a COVID-19 infection. Also, the reliability of antigen nasopharyngeal swab should be considered critically, especially if performed wrongly. We recommended to perform molecular tests when in doubt. After the diagnosis of portal vein thrombosis, immediate anticoagulation is recommended to reduce the risk of further complications like intestinal infarction.
Théo Pezel, Thierry Unterseeh, Marine Kinnel, Thomas Hovasse, Francesca Sanguineti, Solenn Toupin, Stéphane Champagne, Philippe Garot, Jérôme Garot
Journal of Cardiovascular Magnetic Resonance, Volume 23, pp 1-11; doi:10.1186/s12968-021-00737-0

Abstract:
Background To assess the incremental long-term prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients without known coronary artery disease (CAD). Methods Between 2010 and 2011, consecutive patients with cardiovascular risk factors without known CAD referred for stress CMR were followed for the occurrence of major adverse cardiac events (MACE), defined by cardiovascular mortality or recurrent non-fatal myocardial infarction (MI). Uni- and multivariable Cox regressions were performed to determine the prognostic value of ischemia and unrecognized MI defined by sub-endocardial or transmural late gadolinium enhancement (LGE). Results Among 2,295 patients without known CAD, 2058 (89.7%) (71.2 ± 12.5 years; 37.5% males) completed the follow-up (median [IQR]: 8.3 [7.3–8.7] years), and 203 had MACE (9.9%). Using Kaplan–Meier analysis, ischemia and unrecognized MI were associated with MACE (hazard ratio, HR: 4.64 95% CI: 3.69–6.17 and HR: 2.88; 95% CI: 2.08–3.99, respectively; both p < 0.001). In multivariable stepwise Cox regression, ischemia and unrecognized MI were independent predictors of MACE (HR = 3.71; 95% CI 2.73–5.05, p < 0.001 and HR = 1.73; 95% CI 1.22–2.45, p = 0.002; respectively) and cardiovascular mortality (HR: 3.13; 95% CI: 2.17–4.51, p < 0.001 and HR = 1.73; 95% CI 1.15–2.62, p = 0.009; respectively). The addition of ischemia and unrecognized MI led to an improved model discrimination for MACE (change in C statistic from 0.61 to 0.72; NRI = 0.431; IDI = 0.053). Conclusions Inducible ischemia and unrecognized MI identified by stress CMR have incremental long term prognostic value for the incidence of MACE in patients without known CAD over traditional risk factors and left ventricular ejection fraction.
Stine Karlsen Oversoe, Michelle Simone Clement, Britta Weber, , Stephen Jacques Hamilton-Dutoit, Boe Sandahl Sorensen, Jens Kelsen
BMC Cancer, Volume 21, pp 1-7; doi:10.1186/s12885-021-08103-0

Abstract:
Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
, Takashi Kamigaki, Takuji Gotoda, Toshimi Takahashi, Sachiko Okada, Hiroshi Ibe, Eri Oguma, Shigenori Goto
Journal of Medical Case Reports, Volume 15, pp 1-8; doi:10.1186/s13256-020-02634-z

Abstract:
Background Blocking the programmed death 1 pathway by immune checkpoint inhibitors induces dramatic antitumor activity in patients with malignant tumors. However, the clinical response to immune checkpoint inhibitors remains limited owing to the patients’ immunological status, such as the number of lymphocytes, programmed death ligand 1 expression, and tumor mutation burden. In this study, we successfully treated two patients with advanced esophageal cancer who responded to the combination of adoptive immune cell therapy and a low-dose immune checkpoint inhibitor, nivolumab. Case presentation Two Asian (Japanese) patients with advanced esophageal cancer who were resistant to conventional chemoradiation therapy were referred to our hospital for immune therapy. Case 1 was a 66-year-old woman who was diagnosed as having esophageal cancer. She received concurrent chemoradiation therapy and then underwent subtotal esophagectomy, after which she became cancer free. However, she relapsed, and cancer cells were found in the lung and lymph nodes 6 months later. She enrolled in a clinical trial at our institution (clinical trial number UMIN000028756). She received adoptive immune cell therapy twice at a 2-week interval followed by low-dose nivolumab with adoptive immune cell therapy four times at 2-week intervals. A follow-up computed tomography scan showed partial response, with mass reduction of the metastatic lung and mediastinal lesions. Case 2 was a 77-year-old man. He received concurrent chemoradiation therapy with fluoropyrimidine/platinum, and gastroscopy revealed complete remission of esophageal cancer. He was disease free for 5 months, but routine computed tomography revealed multiple metastases in his lungs and lymph nodes. He visited our clinic to receive adoptive immune cell therapy and immune checkpoint inhibitor combination therapy. Radiographic evidence showed continuous improvement of lesions. There was no evidence of severe adverse events during the combination therapy. Conclusion The combination of adoptive immune cell therapy and an immune checkpoint inhibitor might be a possible treatment strategy for advanced esophageal cancer. Trial registration UMIN000028756. Registered 14 September 2017
, Gennaro Catone, Antonella Gritti, Luisa Almerico, Anna Pezzella, Pia Santangelo, Carmela Bravaccio, Raffaella Iuliano, Vincenzo Paolo Senese
Italian Journal of Pediatrics, Volume 47, pp 1-8; doi:10.1186/s13052-021-01036-1

Abstract:
Background Several studies have shown that during COVID-19 pandemic outbreak, emotional symptoms increased in the general population. Less is known about youths. Methods We surveyed a sample of Italian adolescents during the strictest quarantine period and assessed the effects of socio-demographic and psychological factors on current emotional symptoms. A convenient sample of 326 adolescents (age range 14–19 years) participated in a web-based survey. We collected data on several socio-demographic and psychological variables (summarized into three indexes: environmental context, changes in lifestyle, and worries about infection) and psychopathological symptoms (previous psychopathological status, current anxiety and depressive symptoms). Results Descriptive analysis showed that adolescents have experienced quarantine under very different conditions; they reported 47.5 and 14.1% of anxiety and depressive symptoms, respectively. Regression analyses indicated that previous psychopathological status and worries about infection are linked to anxiety and that female gender, previous psychopathological status (moderated by change in lifestyle), worse environmental context are linked to depression. Conclusion This study indicates that, facing the COVID-19 pandemic and its related safety measures, adolescents show relevant emotional symptoms and therefore should be monitored, assessed and supported.
Matic Mihevc, Metka Koren Krajnc, Maja Bombek Ihan,
Annals of Clinical Microbiology and Antimicrobials, Volume 20, pp 1-7; doi:10.1186/s12941-021-00426-x

Abstract:
Background Non-Helicobacter pylori species (NHPS) are newly emerging bacteria that naturally inhabit birds and mammals apart from humans and rarely cause diseases in humans. In recent years, a rise in the number of cases associated with NHPS infections in humans has been observed. Among them, infections with Helicobacter (H.) canis are sporadic and challenging to recognise clinically. To date, ten cases of H. canis infections in mainly immunocompromised humans have been reported in the literature. Transmission pathway is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake. No clear guidelines for successful antibiotic regimen are known. Important additional risk factor for infection might be biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions. Herein we present the first case of H. canis bacteraemia in a RA patient treated with novel JAKi tofacitinib. Case presentation A 65-year-old female patient with RA and rituximab-induced hypogammaglobulinemia treated with tofacitinib, methotrexate, and methylprednisolone came to a planned visit in our outpatient rheumatology clinic. She presented with a history of back pain that significantly worsened 2 days before visit. She had numbness and tingling sensation in both legs and muscle weakness. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. She was in close contact with her pet dogs. Laboratory examination showed increased markers of inflammation. She was found to have H. canis bacteraemia with underlying multilevel degenerative lumbar spinal stenosis. Identification of H. canis was performed by MALDI-TOF MS and 16 S rRNA gene sequence analysis of isolate from subcultured positive aerobic blood culture bottles. Antimicrobial susceptibility testing showed low minimum inhibitory concentrations to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin. She was treated with combined antibiotic regimen (ceftriaxone, doxycycline) for 14 days, which resulted in total remission of the infection. Conclusions Clinicians should recognise H. canis infection risk in patients with recent pet exposure and predisposing factors such as immunodeficiency disorders or diseases that demand immunosuppressive drug therapy. A minimum of two weeks of antibiotic therapy is suggested.
Yu-Chen S. H. Yang, Po-Jui Ko, Yi-Shin Pan, , Jacqueline Whang-Peng, Paul J. Davis, Kuan Wang
Journal of Biomedical Science, Volume 28, pp 1-13; doi:10.1186/s12929-021-00719-5

Abstract:
Thyroid hormone analogues—particularly, l-thyroxine (T4) has been shown to be relevant to the functions of a variety of cancers. Integrin αvβ3 is a plasma membrane structural protein linked to signal transduction pathways that are critical to cancer cell proliferation and metastasis. Thyroid hormones, T4 and to a less extend T3 bind cell surface integrin αvβ3, to stimulate the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway to stimulate cancer cell growth. Thyroid hormone analogues also engage in crosstalk with the epidermal growth factor receptor (EGFR)-Ras pathway. EGFR signal generation and, downstream, transduction of Ras/Raf pathway signals contribute importantly to tumor cell progression. Mutated Ras oncogenes contribute to chemoresistance in colorectal carcinoma (CRC); chemoresistance may depend in part on the activity of ERK1/2 pathway. In this review, we evaluate the contribution of thyroxine interacting with integrin αvβ3 and crosstalking with EGFR/Ras signaling pathway non-genomically in CRC proliferation. Tetraiodothyroacetic acid (tetrac), the deaminated analogue of T4, and its nano-derivative, NDAT, have anticancer functions, with effectiveness against CRC and other tumors. In Ras-mutant CRC cells, tetrac derivatives may overcome chemoresistance to other drugs via actions initiated at integrin αvβ3 and involving, downstream, the EGFR-Ras signaling pathways.
Elahe Allahyari, Parichehr Hanachi, Seyed Jamal Mirmoosavi, Gordon A.Ferns, ,
BMC Nutrition, Volume 7, pp 1-9; doi:10.1186/s40795-021-00413-7

Abstract:
Background There are increasing data highlighting the effectiveness of vitamin D supplementation in the treatment of vitamin D deficiency. But individuals vary in their responsiveness to vitamin D supplementation. In this study, the association between several cardiometabolic risk factors and the magnitude of response to vitamin D supplementation (change in vitamin D level) was investigated using a novel artificial neural networks (ANNs) approach. Methods Six hundred eight participants aged between 12 to 19 years old were recruited to this prospective interventional study. Nine vitamin D capsules containing 50,000 IU vitamin D/weekly were given to all participants over the 9 week period. The change in serum 25(OH) D level was calculated as the difference between post-supplementation and basal levels. Suitable ANNs model were selected between different algorithms in the hidden and output layers and different numbers of neurons in the hidden layer. The major determinants for predicting the response to vitamin D supplementation were identified. Results The sigmoid in both the hidden and output layers with 4 hidden neurons had acceptable sensitivity, specificity and accuracy, assessed as the area under the ROC curve, was determined in our study. Baseline serum vitamin D (30.4%), waist to hip ratio (10.5%), BMI (10.5%), systolic blood pressure (8%), heart rate (6.4%), and waist circumference (6.1%) were the most important factors in predicting the response to serum vitamin D levels. Conclusion We provide the first attempt to relate anthropometric specific recommendations to attain serum vitamin D targets. With the exception of cardiometabolic risk factors, the relative importance of other factors and the mechanisms by which these factors may affect the response requires further analysis in future studies (Trial registration: IRCT201509047117N7; 2015-11-25; Retrospectively registered).
Zhaonan Li, Chaoyan Wang, Guangyan Si, Xueliang Zhou, Yahua Li, Jing Li, ,
BMC Cancer, Volume 21, pp 1-9; doi:10.1186/s12885-021-08099-7

Abstract:
Background Given their widespread availability and relatively low cost, percutaneous thermal ablation is commonly performed under the guidance of computed tomography (CT) or ultrasound (US). However, such imaging modalities may be restricted due to insufficient image contrast and limited tumor visibility, which results in imperfect intraoperative treatment or an increased risk of damage to critical anatomical structures. Currently, magnetic resonance (MR) guidance has been proven to be a possible solution to overcome the above shortcomings, as it provides more reliable visualization of the target tumor and allows for multiplanar capabilities, making it the modality of choice. Unfortunately, MR-guided ablation is limited to specialized centers, and the cost is relatively high. Is ablation therapy under MR guidance better than that under CT guidance? This study retrospectively compared the efficacy of CT-guided and MR-guided microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC ≤ 5.0 cm). Methods In this retrospective study, 47 patients and 54 patients received MWA under the guidance of CT and MR, respectively. The inclusion criteria were a single HCC ≤ 5.0 cm or a maximum of three. The local tumor progression (LTP), overall survival (OS), prognostic factors for local progression, and safety of this technique were assessed. Results All procedures were technically successful. The complication rates of the two groups were remarkably different with respect to incidences of liver abscess and pleural effusion (P < 0.05). The mean LTP was 44.264 months in the CT-guided group versus 47.745 months in the MR-guided group of HCC (P = 0.629, log-rank test). The mean OS was 56.772 months in the patients who underwent the CT-guided procedure versus 58.123 months in those who underwent the MR-guided procedure (P = 0.630, log-rank test). Multivariate Cox regression analysis further illustrated that tumor diameter (< 3 cm) and the number of lesions (single) were important factors affecting LTP and OS. Conclusions Both CT-guided and MR-guided MWA are comparable therapies for the treatment of HCC (< 5 cm), and there was no difference in survival between the two groups. However, MR-guided MWA could reduce the incidence of complications.
Wafaa S. Ramadan, , Mahmood Y. Hachim, Annette Lischka, Timo Gemoll,
Clinical Epigenetics, Volume 13, pp 1-18; doi:10.1186/s13148-021-01060-2

Abstract:
Background The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical significance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy. Expression of CBP, GCN5, estrogen receptor α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in BC was analyzed in cell lines by western blot and in patients’ tissues by immunohistochemistry. The gene amplification data were also analyzed for CBP and GCN5 using the publicly available data from BC patients. Results Elevated expression of CBP and GCN5 was detected in BC tissues from patients and cell lines more than normal ones. In particular, CBP was more expressed in luminal A and B subtypes. Using chemical and biological inhibitors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreover, analysis of the CREBBP (for CBP) and KAT2A (for GCN5) genes in a larger number of patients in publicly available databases showed amplification of both genes in BC patients. Amplification of CREBBP gene was observed in luminal A, luminal B and triple-negative but not in HER2 overexpressing subtypes. Furthermore, patients with high CREBBP or KAT2A gene expression had better 5-year disease-free survival than the low gene expression group (p = 0.0018 and p < 0.00001, respectively). Conclusions We conclude that the persistent amplification and overexpression of CBP in ERα- and PR-positive BC highlights the significance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.
Thang Nguyen-Tien, Duy Cuong Do, Xuan Luat Le, Thi Hai Dinh, Mats Lindeborg, Hung Nguyen-Viet, Åke Lundkvist, Delia Grace,
BMC Public Health, Volume 21, pp 1-13; doi:10.1186/s12889-021-10687-y

Abstract:
Background Dengue is a mosquito-borne flavivirus present in many metropolitan cities of tropical countries. Methods During and after the dengue season (September 2018 to January 2019), we conducted a case-control study in order to determine the risk factors for dengue fever in Hanoi city, Vietnam. 98 dengue patients and 99 patients with other acute infections, such as Hepatitis B virus infection, were recruited at Department of Infectious Disease of Bach Mai national hospital in Hanoi. Patients were interviewed using a structured questionnaire covering demographic, housing, environmental factors and knowledge, attitude, and practice on dengue prevention and control. Univariate analysis and multivariable logistic regression were used to determine the risk factors of dengue status. Results The mean score of knowledge items and practice items was only 7.9 out of total 19 points and 3.9 out of total 17 points, respectively. While the mean score of attitude items was 4.8 out of total 6 points. Multivariable logistic regression indicated that older patients had lesser risk of getting dengue infection as compared to younger adults aged 16–30, and patients living in peri-urban districts were less likely to suffer of dengue fever than patients living in central urban districts (OR = 0.31; 95% CI 0.13–0.75). This study could not find any association with occupation, water storage habit, knowledge, attitude, or practice on dengue prevention. Conclusions All patients had a relatively low level of knowledge and practice on dengue prevention and control. However, the attitude of the participants was good. We found that age group and living district were the risk factors correlated with the dengue status. Communication programs on raising dengue awareness should be repeated all year round and target particular groups of adolescents, younger adults, landlords and migrants from other provinces to improve their knowledge and encourage them to implement preventive measures against dengue fever.
, Ingela Lundgren, Gunnel Hensing, Anna Dencker, Monica Eriksson, Ing-Marie Carlsson
BMC Health Services Research, Volume 21, pp 1-13; doi:10.1186/s12913-021-06311-9

Abstract:
Background The theory of salutogenesis focuses on resources for health and health-promoting processes. In the context of midwives’ work, this is not well described despite the importance for occupational health and the intention to remain in the profession. In order to promote a healthy workplace, it is necessary to consider the facilitating conditions that contribute to a sustainable working life. Therefore, the aim of this study was to explore health-promoting facilitative conditions in the work situation on labour wards according to midwives. Methods A constant comparative analysis was applied to face-to-face interviews with midwives that constituted the empirical material in this classical grounded theory study. Results The substantive theory of Professional courage to create a pathway within midwives’ fields of work emerged as an explanation of the health-promoting facilitative conditions in midwives’ work situation. The theory consists of a four-stage process with prerequisite contextual conditions: visualising midwifery, organisational resources and a reflective and learning environment, that were needed to fulfil the midwives’ main concern a Feasibility of working as a midwife. This meant being able to work according to best-known midwifery theory and practice in each situation. Positive consequences of a fulfilled main concern were a professional identity and grounded knowledge that enabled the development of the resistant resource professional courage. The courage made it feasible for midwives to move freely on their pathway within the different fields of work extending between normal and medicalised birth and being autonomous and regulated. Conclusions A professional courage was required to create a pathway within midwives’ fields of work, to move freely depending on what actions were needed in a particular work situation. Professional courage could be seen as a resistance resource, enabling midwives to become resilient when dealing with the unpredictable work situation. However, there are vital organisational preconditions that needed to be fulfilled for workplaces to become facilitative, organisational resources, visualising midwifery and a reflective environment. The theory can be used to foster health-promoting and sustainable work situations for midwives, which is possible if the organisational preconditions are met. This could be a key factor in retaining midwives in the profession.
BMC Health Services Research, Volume 21, pp 1-7; doi:10.1186/s12913-021-06331-5

Abstract:
Background To foster access to care and reduce the burden of health expenditures on people living with HIV (PLHIV), several sub-Saharan African countries, including Cameroon, have adopted a policy of removing HIV-related fees, especially for antiretroviral treatment (ART). We investigate the impact of Cameroon’s free antiretroviral treatment (ART) policy, enacted in May 2007, on catastrophic health expenditure (CHE) risk according to socioeconomic status, in PLHIV enrolled in the country’s treatment access program. Methods Based on primary data from two cross-sectional surveys of PLHIV outpatients in 2006–2007 and 2014 (i.e., before and after the policy’s implementation, respectively), we used inverse propensity score weighting to reduce covariate imbalances between participants in both surveys, combined with probit regressions of CHE incidence. The analysis included participants treated with ART in one of the 11 HIV services common to both surveys (n = 1275). Results The free ART policy was associated with a significantly lower risk of CHE only in the poorest PLHIV while no significant effect was found in lower-middle or upper socioeconomic status PLHIV. Unexpectedly, the risk of CHE was higher in those with middle socioeconomic status after the policy’s implementation. Conclusions Our findings suggest that Cameroon’s free ART policy is pro-poor. As it only benefitted PLHIV with the lowest socioeconomic status, increased comprehensive HIV care coverage is needed to substantially reduce the risk of CHE and the associated risk of impoverishment for all PLHIV.
, Eleanor F. G. Neal, Peter Nguyen, Jennifer G. McIntosh, Jon D. Emery
BMC Cancer, Volume 21, pp 1-14; doi:10.1186/s12885-021-08100-3

Abstract:
Background Successful breast cancer screening relies on timely follow-up of abnormal mammograms. Delayed or failure to follow-up abnormal mammograms undermines the potential benefits of screening and is associated with poorer outcomes. However, a comprehensive review of inadequate follow-up of abnormal mammograms in primary care has not previously been reported in the literature. This review could identify modifiable factors that influence follow-up, which if addressed, may lead to improved follow-up and patient outcomes. Methods A systematic literature review to determine the extent of inadequate follow-up of abnormal screening mammograms in primary care and identify factors impacting on follow-up was conducted. Relevant studies published between 1 January, 1990 and 29 October, 2020 were identified by searching MEDLINE®, Embase, CINAHL® and Cochrane Library, including reference and citation checking. Joanna Briggs Institute Critical Appraisal Checklists were used to assess the risk of bias of included studies according to study design. Results Eighteen publications reporting on 17 studies met inclusion criteria; 16 quantitative and two qualitative studies. All studies were conducted in the United States, except one study from the Netherlands. Failure to follow-up abnormal screening mammograms within 3 and at 6 months ranged from 7.2–33% and 27.3–71.6%, respectively. Women of ethnic minority and lower education attainment were more likely to have inadequate follow-up. Factors influencing follow-up included physician-patient miscommunication, information overload created by automated alerts, the absence of adequate retrieval systems to access patient’s results and a lack of coordination of patient records. Logistical barriers to follow-up included inconvenient clinic hours and inconsistent primary care providers. Patient navigation and case management with increased patient education and counselling by physicians was demonstrated to improve follow-up. Conclusions Follow-up of abnormal mammograms in primary care is suboptimal. However, interventions addressing amendable factors that negatively impact on follow-up have the potential to improve follow-up, especially for populations of women at risk of inadequate follow-up.
Qianwen Dai, Baolin Xu, Huanwen Wu, Yan You, ,
Orphanet Journal of Rare Diseases, Volume 16, pp 1-8; doi:10.1186/s13023-021-01802-8

Abstract:
Background The prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS. Methods Patients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities. Results Fifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2–30.8) and 75.0% (68.0–82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5–13.1, 1.3–7.3, and 0.1–0.7; and p = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1–1.0 and 0.1–1.0, p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse. Conclusion For patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.
BMC Nursing, Volume 20, pp 1-10; doi:10.1186/s12912-021-00572-9

Abstract:
Aim To gain in-depth knowledge of mothers’ and fathers’ experiences of the whole trajectory of an early in-home care programme supported by video consultations with a neonatal nurse. Design A qualitative interview study. Methods Data were collected through dyadic semi-structured interviews with mothers and fathers participating in virtual early in-home care programmes and were subjected to inductive content analysis. Findings The mothers and fathers were anxious about mastering the care of their premature infants at the start of the early in-home care phase but gradually developed confidence by the completion of the early in-home care programme. Being at home during the early in-home care programme gave the mothers and fathers an opportunity to test their decision making concerning the care of the infant while having the ability to obtain support from nurses when needed. Conclusion Our findings indicate that the trajectory of early in-home care programmes combined with video consultations contributes to parents’ increased confidence as mothers and fathers. Trial registration Clinical trial registration: REG-113-2014 and SJ-431.
G. Prashanth, , , , Iranna Kotturshetti
BMC Endocrine Disorders, Volume 21, pp 1-65; doi:10.1186/s12902-021-00709-6

Abstract:
Background Type 1 diabetes (T1D) is a serious threat to childhood life and has fairly complicated pathogenesis. Profound attempts have been made to enlighten the pathogenesis, but the molecular mechanisms of T1D are still not well known. Methods To identify the candidate genes in the progression of T1D, expression profiling by high throughput sequencing dataset GSE123658 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and gene ontology (GO) and pathway enrichment analyses were performed. The protein-protein interaction network (PPI), modules, target gene - miRNA regulatory network and target gene - TF regulatory network analysis were constructed and analyzed using HIPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, validation of hub genes was conducted by using ROC (Receiver operating characteristic) curve and RT-PCR analysis. A molecular docking study was performed. Results A total of 284 DEGs were identified, consisting of 142 up regulated genes and 142 down regulated genes. The gene ontology (GO) and pathways of the DEGs include cell-cell signaling, vesicle fusion, plasma membrane, signaling receptor activity, lipid binding, signaling by GPCR and innate immune system. Four hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell-cell signaling, cytokine signaling in immune system, signaling by GPCR and innate immune system. ROC curve and RT-PCR analysis showed that EGFR, GRIN2B, GJA1, CAP2, MIF, POLR2A, PRKACA, GABARAP, TLN1 and PXN might be involved in the advancement of T1D. Molecular docking studies showed high docking score. Conclusions DEGs and hub genes identified in the present investigation help us understand the molecular mechanisms underlying the advancement of T1D, and provide candidate targets for diagnosis and treatment of T1D.
, Vanessa Piechotta, Termeh Feinberg, Emilie Ludeman, Brian Hutton, Salmaan Kanji, Dugald Seely, Chantelle Garritty
BMC Complementary Medicine and Therapies, Volume 21, pp 1-15; doi:10.1186/s12906-021-03283-5

Abstract:
Background Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of ‘cytokine storm’. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. Methods We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. Results We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. Conclusions Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.
Mohammad Saeid Salami, Gholamreza Bahrami, Elham Arkan, Zhila Izadi, Shahram Miraghaee,
BMC Complementary Medicine and Therapies, Volume 21, pp 1-12; doi:10.1186/s12906-021-03284-4

Abstract:
Background Interactive dressings are innovatively designed to interact with the wound surface and alter the wound environment to promote wound healing. In the current study, we integrated the physicochemical properties of Poly (caprolactone)/ Poly (vinyl alcohol)/Collagen (PCL/PVA/Col) nanofibers with the biological activities ofMomordica charantiapulp extract to develop an efficient wound dressing. The electrospinning method was applied to fabricate the nanofibers, and the prepared wound dressings were thoroughly characterized. Results SEM imaging showed that the nanofibers were uniform, straight, without any beds with a diameter in the range of 260 to 480 nm. Increasing the concentration of the extract increased the diameter of the nanofibers and also the wettability characteristics while reduced the ultimate tensile strength from 4.37 ± 0.90 MPa for PCL/PVA/Col to 1.62 ± 0.50 MPa for PCL/PVA/Col/Ex 10% (p < 0.05). The in vivo studies showed that the application of the wound dressings significantly enhanced the healing process and the highest wound closure, 94.01 ± 8.12%, was obtained by PCL/PVA/Col/Ex 10% nanofibers (p < 0.05). Conclusion The incorporation of the extract had no significant effects on nanofibers’ porosity, water vapor permeability, and swelling characteristics. The in vitro evaluations showed that the fabricated nanofibers were hemocompatible, cytocompatible, and prevent bacterial penetration through the dressing. These findings implied that the PCL/PVA/Col/Ex nanofibers can be applied as the wound dressing materials.
, I. Laso-García, J. Lorca-Álvaro, M. Mata-Alcaraz, G. Duque-Ruiz, M. Hevia-Palacios, F. Arias-Funez, F. J. Burgos-Revilla
BMC Urology, Volume 21, pp 1-7; doi:10.1186/s12894-021-00800-z

Abstract:
Background Xanthogranulomatous pyelonephritis (XGP) is an inflammatory condition of the kidney and its treatment most often involves a combination of antibiotics and nephrectomy. This study aimed to define the clinical features and management of XGP, focusing on microbiological aspects and antibiotic therapy. Methods We performed a retrospective study of 27 cases of XGP diagnosed between January 2001 and January 2020 to analyse their clinical and management characteristics. In addition, a literature review was conducted of XGP case series covering the period from 2000–2020. We searched PubMed for case series through April 2020 without language restrictions. Studies reporting case series of XGP (more than ten cases) were included if they were relevant to this study. Results Twenty-seven patients were diagnosed with XGP, and 26 of them were histologically proven to have XGP. A total of 81.5% of the patients were female and the mean age was 59.6 years (SD 19.2). The most frequent symptoms were flank pain (70.4%) and fever (59.3%), while 77.8% of patients had renal stones. Proteus mirabilis was detected in the urine culture in 18.5% of patients, followed by detection of Escherichia coli in 14.8% of patients. The computed tomography (CT) findings included perirenal (29.6%) or pararenal (29.6%) involvement in the majority of patients. Twenty-six patients underwent nephrectomy. Piperacillin/tazobactam and ceftriaxone were the most commonly prescribed antibiotics for treatment. The reported piperacillin/tazobactam and ceftriaxone resistance rates were 14.3% and 16.6%, respectively. Twenty-six case series were included in the literature review, reporting 693 cases in total. Conclusion We found well-established characteristics of XGP patients among series in terms of previous history, clinical, laboratory and imaging findings, and operative and postoperative outcomes. It is important to know the clinical presentation and potential severity of XGP, as well as the most frequently involved microorganisms and their antibiotic resistance profiles, to select the most appropriate antibiotic therapy.
Chenwen Xiao, Jiaoyu Wang, Zhenfeng Liao, Yee Huang, Quanan Ji, Yan Liu, Fei Su, Lijun Xu, Qiang Wei, Yao Pan, et al.
BMC Genomics, Volume 22, pp 1-16; doi:10.1186/s12864-021-07520-6

Abstract:
Background Trichophyton mentagrophyte (TM), a zoonotic pathogen, has been endangering public health due to emerging drug resistance. Although increased attention is paid to this issue, there is very limited research available on drug resistance in TM. In this study, we studied the gene and proteomic changes, morphological changes, cellular fat localization, fat content changes, and biofilm of TM treated with different substances. Results The TM growth curve showed a positive correlation with the concentration of Fenarimol (FE), genistein (GE), clotrimazole (KM), and Miconazole nitrate salt (MK). The morphology of TM cells changed in different degrees after treatment with different substances as observed by TEM and SEM. The results showed that under KM and berberine hydrochloride (BB) treatment, a total of 3305 differentially expressed genes were detected, with the highest number in the KM-treated group (578 up-regulated and 615 down-regulated). A total of 847 proteins and 1850 peptides were identified in TM proteomics. Nile red staining showed that the fat content of TM was significantly higher in the BB-, ethidium bromide- (EB), FE-, KM-, Adriamycin hydrochloride- (YA), and MK-treated group compared to the control group. Results of the biofilm thickness showed that it gradually increased under treatment with specific concentrations of KM or BB, which may be related to the up-regulation of ERG25 and CYP related gene proteins. Conclusions It is suggested that in order to effectively deal with dermatomycosis caused by TM, it is necessary to inhibit the expression of ERG25 and CYP related genes and fat metabolism, which can result in the inhibition of the production of biofilm by the fungus and solve the problem of fungal drug resistance in clinical settings.
Mingming Cao, , Qiang Deng, Huizhe Wang, Ruihuan Yang
BMC Genomics, Volume 22, pp 1-11; doi:10.1186/s12864-021-07548-8

Abstract:
Background Cucumber (Cucumis sativus L.) is cultivated worldwide, and it is essential to produce enough high-quality seeds to meet demand. Pre-harvest sprouting (PHS) in cucumber is a critical problem and causes serious damage to seed production and quality. Nevertheless, the genetic basis and molecular mechanisms underlying cucumber PHS remain unclear. QTL-seq is an efficient approach for rapid quantitative trait loci (QTL) identification that simultaneously takes advantage of bulked-segregant analysis (BSA) and whole-genome resequencing. In the present research, QTL-seq analysis was performed to identify QTLs associated with PHS in cucumber using an F2 segregating population. Results Two QTLs that spanned 7.3 Mb on Chromosome 4 and 0.15 Mb on Chromosome 5 were identified by QTL-seq and named qPHS4.1 and qPHS5.1, respectively. Subsequently, SNP and InDel markers selected from the candidate regions were used to refine the intervals using the extended F2 populations grown in the 2016 and 2017 seasons. Finally, qPHS4.1 was narrowed to 0.53 Mb on chromosome 4 flanked by the markers SNP-16 and SNP-24 and was found to explain 19–22% of the phenotypic variation in cucumber PHS. These results reveal that qPHS4.1 is a major-effect QTL associated with PHS in cucumber. Based on gene annotations and qRT-PCR expression analyses, Csa4G622760 and Csa4G622800 were proposed as the candidate genes. Conclusions These results provide novel insights into the genetic mechanism controlling PHS in cucumber and highlight the potential for marker-assisted selection of PHS resistance breeding.
Byung-Soo Park, Sung Hwan Cho, , Hyun Sung Kim, Yong-Hoon Cho, Dae Gon Ryu, , , , , et al.
BMC Gastroenterology, Volume 21, pp 1-10; doi:10.1186/s12876-021-01729-1

Abstract:
Background Clinically diagnosing high-grade (III–V) rectal prolapse might be difficult, and the prolapse can often be overlooked. Even though defecography is the significant diagnostic tool for rectal prolapse, it is noticed that rectoanal inhibitory reflex (RAIR) can be associated with rectal prolapse. This study investigated whether RAIR can be used as a diagnostic factor for rectal prolapse. Methods In this retrospective study, we evaluated 107 patients who underwent both anorectal manometry and defecography between July 2012 and December 2019. Rectal prolapse was classified in accordance with the Oxford Rectal Prolapse Grading System. Patients in the high-grade (III–V) rectal prolapse (high-grade group, n = 30), and patients with no rectal prolapse or low-grade (I, II) rectal prolapse (low-grade group, n = 77) were analyzed. Clinical variables, including symptoms such as fecal incontinence, feeling of prolapse, and history were collected. Symptoms were assessed using yes/no surveys answered by the patients. The manometric results were also evaluated. Results Frequencies of fecal incontinence (p = 0.002) and feeling of prolapse (p < 0.001) were significantly higher in the high-grade group. The maximum resting (77.5 vs. 96 mmHg, p = 0.011) and squeezing (128.7 vs. 165 mmHg, p = 0.010) anal pressures were significantly lower in the high-grade group. The frequency of absent or impaired RAIR was significantly higher in the high-grade group (19 cases, 63% vs. 20 cases, 26%, p < 0.001). In a multivariate analysis, the feeling of prolapse (odds ratio [OR], 23.88; 95% confidence interval [CI], 4.43–128.78; p < 0.001) and absent or impaired RAIR (OR, 5.36; 95% CI, 1.91–15.04, p = 0.001) were independent factors of high-grade (III–V) rectal prolapse. In addition, the percentage of the absent or impaired RAIR significantly increased with grading increase of rectal prolapse (p < 0.001). The sensitivity of absent or impaired RAIR as a predictor of high-grade prolapse was 63.3% and specificity 74.0%. Conclusions Absent or impaired RAIR was a meaningful diagnostic factor of high-grade (III–V) rectal prolapse. Furthermore, the absent or impaired reflex had a positive linear trend according to the increase of rectal prolapse grading.
, Franziska Bertram, Fabian Heinrich, Victoria van Rüth, Benjamin Ondruschka, Benedikt Kretzler, Christine Schüler, Klaus Püschel, Hans-Helmut König
BMC Health Services Research, Volume 21, pp 1-7; doi:10.1186/s12913-021-06314-6

Abstract:
Background To identify the determinants of health care use among homeless individuals. Methods Data were taken from the Hamburg survey of homeless individuals (n = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates. Results Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60–10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12–0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96–0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89–0.98]), having health insurance (OR: 8.11 [2.11–30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94–0.99]). Conclusions Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.
, Borsika Rabin, Erin Almklov, Niloofar Afari, Elizabeth Floto, Eusebio Rodriguez, Laurie Lindamer
Implementation Science Communications, Volume 2, pp 1-11; doi:10.1186/s43058-021-00132-x

Abstract:
Background The Veterans Health Administration (VHA) developed a comprehensive mobile screening technology (eScreening) that provides customized and automated self-report health screening via mobile tablet for veterans seen in VHA settings. There is agreement about the value of health technology, but limited knowledge of how best to broadly implement and scale up health technologies. Quality improvement (QI) methods may offer solutions to overcome barriers related to broad scale implementation of technology in health systems. We aimed to develop a process guide for eScreening implementation in VHA clinics to automate self-report screening of mental health symptoms and psychosocial challenges. Methods This was a two-phase, mixed methods implementation project building on an adapted quality improvement method. In phase one, we adapted and conducted an RPIW to develop a generalizable process guide for eScreening implementation (eScreening Playbook). In phase two, we integrated the eScreening Playbook and RPIW with additional strategies of training and facilitation to create a multicomponent implementation strategy (MCIS) for eScreening. We then piloted the MCIS in two VHA sites. Quantitative eScreening pre-implementation survey data and qualitative implementation process “mini interviews” were collected from individuals at each of the two sites who participated in the implementation process. Survey data were characterized using descriptive statistics, and interview data were independently coded using a rapid qualitative analytic approach. Results Pilot data showed overall satisfaction and usefulness of our MCIS approach and identified some challenges, solutions, and potential adaptations across sites. Both sites used the components of the MCIS, but site 2 elected not to include the RPIW. Survey data revealed positive responses related to eScreening from staff at both sites. Interview data exposed implementation challenges related to the technology, support, and education at both sites. Workflow and staffing resource challenges were only reported by site 2. Conclusions Our use of RPIW and other QI methods to both develop a playbook and an implementation strategy for eScreening has created a testable implementation process to employ automated, patient-facing assessment. The efficient collection and communication of patient information have the potential to greatly improve access to and quality of healthcare.
, Mohammad Abdulwahab
BMC Medical Education, Volume 21, pp 1-9; doi:10.1186/s12909-021-02614-x

Abstract:
Background To evaluate the self-confidence of undergraduate dental students in relation to oral and maxillofacial surgery (OMFS) to assess the teaching curriculum at Kuwait University using a validated questionnaire originally developed by the Association of British Academic Oral Maxillofacial Surgeons (ABAOMS). Methods A cross-sectional survey of sixth year (n = 20) and seventh year (n = 19) dentistry students was conducted by Kuwait University Faculty of Dentistry between the 1st and 15th of May 2020. The ABAOMS questionnaire is composed of 17 questions assessing various areas of the undergraduate OMFS curriculum. The response options to the questionnaire utilised a Likert scale. Independent sample t-tests were performed to assess the difference in responses between the 2 year groups. Spearman’s rho correlations were calculated to measure the strength of association between confidence in all aspects of surgical and forceps exodontia. Results A total of 39 questionnaires were completed by the students. The majority of students expressed feelings of confidence that they have enough knowledge to undertake independent practice (61%). General aspects of the questionnaire were answered favourably except for surgical extraction of teeth, in which both classes reported a lower level of self-confidence. Conclusions The ABAOMS survey revealed the students’ self-confidence in undertaking independent practice and preforming basic oral surgery procedures. Students felt comfortable with exodontia using forceps and elevators, root removal, managing acute pericoronitis, managing haemorrhage from a socket, assessing impacted teeth, and recognising the clinical features of potentially malignant and malignant lesions of the oral cavity. They reported a lower level of confidence in performing surgical procedures.
, Christopher R. Sudfeld, Álvaro J. M. Leite, Márcia M. T. Machado, Sabrina G. M. O. Rocha, Jocileide S. Campos, Anamaria C. e Silva, Luciano L. Correia
BMC Pediatrics, Volume 21, pp 1-9; doi:10.1186/s12887-021-02623-1

Abstract:
Background The first 1000 days of life are a critical period when the foundations of child development and growth are established. Few studies in Latin America have examined the relationship of birth outcomes and neonatal care factors with development outcomes in young children. We aimed to assess the association between pregnancy and neonatal factors with children’s developmental scores in a cross-sectional, population-based study of children in Ceará, Brazil. Methods Population-based, cross-sectional study of children aged 0–66 months (0–5.5 years) living in Ceará, Brazil. We examined the relationship of pregnancy (iron and folic acid supplementation, smoking and alcohol consumption) and neonatal (low birth weight (LBW) gestational age, neonatal care interventions, and breastfeeding in the first hour) factors with child development. Children’s development was assessed with the Ages and Stages Questionnaire (ASQ-BR). We used multivariate generalized linear models that accounted for clustering sampling to evaluate the relationship of pregnancy and neonatal factors with development domain scores. Findings A total of 3566 children were enrolled. Among pregnancy factors, children whose mothers did not receive folic acid supplementation during pregnancy had lower fine motor and problem-solving scores (p-values< 0.05). As for neonatal factors, LBW was associated with 0.14 standard deviations (SD) lower (CI 95% -0.26, − 0.02) communication, 0.24 SD lower (95% CI: − 0.44, − 0.04) fine motor and 0.31 SD lower (CI 95% -0.45, − 0.16) problem-solving domain scores as compared to non-LBW children (p values < 0.05). In terms of care, newborns that required resuscitation, antibiotics for infection, or extended in-patient stay after birth had lower development scores in selected domains. Further, not initiating breastfeeding within the first hour after birth was associated with lower gross motor and person-social development scores (p-values < 0.05). Conclusion Pregnancy and neonatal care factors were associated with later child development outcomes. Infants at increased risk of suboptimal development, like LBW or newborns requiring extended in-patient care, may represent groups to target for supplemental intervention. Further, early integrated interventions to prevent adverse pregnancy and newborn outcomes may improve child development outcomes.
Ling-Yu Qi, Yu Wang, Li-Qiong Wang, Yan-Fen She, Guang-Xia Shi, Ying Li, Li-Li Chi, Bang-Qi Wu, Jian-Feng Tu, Fang-Ting Yu, et al.
Trials, Volume 22, pp 1-9; doi:10.1186/s13063-021-05211-x

Abstract:
Background Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases. Although acupuncture has become a common alternative therapy for IBS, there is insufficient evidence for its effectiveness. This study was designed to assess the efficacy and feasibility of acupuncture in the treatment of IBS. Methods/design This is a multicenter randomized controlled clinical trial. According to the ratio of 1:1:1, 90 patients with irritable bowel syndrome will be randomly divided into specific acupoints (SA) group, non-specific acupoints (NSA) group, and non-acupoints (NA) group. All patients will be treated with acupuncture 12 times within 4 weeks and followed up for 8 weeks. The primary outcome is the response rate, the percentage of patients whose average value of worst abdominal pain is 30% better and the days of loose stool is 50% less than the baseline, at week 4 after randomization. The secondary outcomes include the response rates at other time points, IBS Symptom Severity Scale (IBS-SSS), Patient Health Questionnaire-9 depression scale (PHQ-9), IBS-Quality of Life scale (IBS-QOL), IBS Adequate Relief (IBS-AR), Abdominal Pain Score, Abdominal Bloating Score, Bristol Stool Score (BBS), blinding assessment, and credibility evaluation. Adverse events will be monitored and recorded during the trial. Trial registration Chictr.org.cn ChiCTR2000030670. Registered on 9 March 2020.
Tekle Olbamo, , Tizazu Gebre, Fekadu Massebo
Parasites & Vectors, Volume 14, pp 1-9; doi:10.1186/s13071-021-04694-6

Abstract:
Background Plant-based mosquito control methods may use as a supplementary malaria vector control strategy. This study aimed to evaluate the effect of smoking ethno-medicinal plants on indoor density and feeding activity of malaria vectors at early hours of the night and its residual effect after midnight in southern Ethiopia. Methods Both field and tent trials were conducted to evaluate the impact of smoking Juniperus procera leaves, Eucalyptus globulus seeds and Olea europaea leaves in Kolla Shara Village from July 2016 to February 2017. For the field trial, five grass-thatched traditional huts (three for ethno-medicinal plants and two as control [only charcoal smoking and non-charcoal smoking]) were used. Indoor host-seeking mosquitoes were collected by CDC light traps. A Latin square design was employed to minimize the bias due to the variation in house location and different sampling nights. For the tent experiment, 25 3–5-day-old starved wild female Anopheles mosquitoes reared from the larvae were released into the tents where a calf was tethered at the mid-point of each tent. Results A total of 614 Anopheles mosquitoes belonging to 5 species were collected from 5 huts, of which 93.4% was An. arabiensis; O. europaea, E. globulus and J. procera reduced the indoor density of An. arabiensis, with the mean percentage drop of 80%, 73% and 70%, respectively. In the tent trial, smoking of these plants had significant knockdown effects and inhibited feeding on the calves (F = 383.5, DF = 3, P < 0.01). The mean knockdown effect due to O. europaea was relatively high (17.7 ± 0.54; 95% CI 16.8–18.6), while it was only 0.9 ± 0.1 (95% CI 0.29–1.52) in the control tents. All the test plants used in the tent trial caused significantly inhibited feeding activity of An. arabiensis on the host (F = 383.5, DF = 3, P < 0.01). About 94.5%, 89.5% and 86% of mosquitoes were unfed because of the smoking effect of O. europaea, E. globulus and J. procera, respectively, whereas only 19.5% were unfed in the control tent. Conclusions Smoking ethno-medicinal plant materials reduced indoor density of malaria vectors and inhibited feeding on calves inside the tents. Thus, plant-based mosquito control methods may play a vital role in reducing mosquito bites in the early hours of the night and thereby reduce residual malaria transmission.
, Wietske Kuijer, Anke Persoon, Loek Nieuwenhuis,
Health Research Policy and Systems, Volume 19, pp 1-9; doi:10.1186/s12961-021-00715-z

Abstract:
Background A group of clinician-scientists and managers working within a Dutch academic network, experienced difficulties in clearly defining the knowledge broker role of the clinician-scientists. They found no role clarity in literature, nor did they find tools or methods suitable for clinician-scientists. Clarifying role expectations and providing accountability for funding these knowledge broker positions was difficult. The aim of this research was to design a theory-informed tool that allowed clinician-scientists to make their knowledge broker role visible. Methods A participatory design research was conducted in three phases, over a 21-month period, with a design group consisting of an external independent researcher, clinician-scientists and their managers from within the academic network. Phase 1 constituted a literature review, a context analysis and a needs analysis. Phase 2 constituted the design and development of a suitable tool and phase 3 was an evaluation of the tool’s perceived usefulness. Throughout the research process, the researcher logged the theoretic basis for all design decisions. Results The clinician-scientist’s knowledge broker role is a knowledge-intensive role and work-tasks associated with this role are not automatically visible (phase 1). A tool (the SP-tool) was developed in Microsoft Excel. This allowed clinician-scientists to log their knowledge broker activities as distinct from their clinical work and research related activities (phase 2). The SP-tool contributed to the clinician-scientists’ ability to make their knowledge broker role visible to themselves and their stakeholders (phase 3). The theoretic contribution of the design research is a conceptual model of professionalisation of the clinician-scientist’s knowledge broker role. This model presents the relationship between work visibility and the clarification of functions of the knowledge broker role. In the professionalisation of knowledge-intensive work, visibility contributes to the definition of clinician-scientists broker functions, which is an element necessary for the professionalisation of an occupation. Conclusions The SP-tool that was developed in this research, contributes to creating work visibility of the clinician-scientists’ knowledge broker role. Further research using the SP-tool could establish a clearer description of the knowledge broker role at the day-to-day professional level and improved ability to support this role within organisations.
BMC Psychiatry, Volume 21, pp 1-6; doi:10.1186/s12888-021-03175-5

Abstract:
Background Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by unpleasant and distressing sensations in the lower limbs that are more pronounced in the evening, commence or worsen at rest, and show partial or complete relief following movement. It can occur as a primary disorder, secondary to medical conditions or treatment with medications including but not limited to antidepressants or antipsychotics. Case presentation A 32-year old man with major depressive disorder showed partial response to Escitalopram 10 mg daily. Agomelatine 25 mg at night was added to Escitalopram to treat his residual depressive symptoms, namely insomnia and tiredness. Within two days he developed restlessness and unpleasant sensations in his legs which were worse at night. Symptom severity increased over the following days, prompting an urgent consultation a week later. The patient’s presentation met the criteria for RLS. Agomelatine was discontinued leaving the patient on Escitalopram alone. The patient’s symptoms improved within 24 h of stopping Agomelatine, with complete resolution four days later. There was no recurrence of RLS during follow-up. The patient scored 6 on Naranjo’s adverse drug reaction probability scale, indicating a probable adverse drug reaction caused by Agomelatine. Conclusions To the best of our knowledge, this is the first case report of suspected Agomelatine-induced RLS. Clinicians need to be aware of RLS to enable prompt diagnosis and management. We suggest adding Agomelatine to the list of agents that can potentially induce RLS.
, Chelsea Doktorchik, Natalie Wiebe, Hude Quan, Catherine Eastwood
BMC Health Services Research, Volume 21, pp 1-9; doi:10.1186/s12913-021-06302-w

Abstract:
Background The International Classification of Diseases (ICD) is the reference standard for reporting diseases and health conditions globally. Variations in ICD use and data collection across countries can hinder meaningful comparisons of morbidity data. Thus, we aimed to characterize ICD and hospital morbidity data collection features worldwide. Methods An online questionnaire was created to poll the World Health Organization (WHO) member countries that were using ICD. The survey included questions focused on ICD meta-features and hospital data collection systems, and was distributed via SurveyMonkey using purposive and snowball sampling. Accordingly, senior representatives from organizations specialized in the topic, such as WHO Collaborating Centers, and other experts in ICD coding were invited to fill out the survey and forward the questionnaire to their peers. Answers were collated by country, analyzed, and presented in a narrative form with descriptive analysis. Results Responses from 47 participants were collected, representing 26 different countries using ICD. Results indicated worldwide disparities in the ICD meta-features regarding the maximum allowable coding fields for diagnosis, the definition of main condition, and the mandatory type of data fields in the hospital morbidity database. Accordingly, the most frequently reported answers were “reason for admission” as main condition definition (n = 14), having 31 or more diagnostic fields available (n = 12), and “Diagnoses” (n = 26) and “Patient demographics” (n = 25) for mandatory data fields. Discrepancies in data collection systems occurred between but also within countries, thereby revealing a lack of standardization both at the international and national level. Additionally, some countries reported specific data collection features, including the use or misuse of ICD coding, the national standards for coding or lack thereof, and the electronic abstracting systems utilized in hospitals. Conclusions Harmonizing ICD coding standards/guidelines should be a common goal to enhance international comparisons of health data. The current international status of ICD data collection highlights the need for the promotion of ICD and the adoption of the newest version, ICD-11. Furthermore, it will encourage further research on how to improve and standardize ICD coding.
Guohua Liang, Wenjie Ma, Yanfang Zhao, Eryu Liu, Xiaoyu Shan, Weiwei Ma, Dabei Tang, Liru Li, Xingjian Niu, Wenhui Zhao, et al.
BMC Cancer, Volume 21, pp 1-10; doi:10.1186/s12885-021-08028-8

Abstract:
Background Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients’ quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. Methods We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. Results A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138–0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. Conclusions Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.
Yi-Sin Wong, Chi-Shun Wu,
BMC Neurology, Volume 21, pp 1-9; doi:10.1186/s12883-021-02177-w

Abstract:
Background The risk factors for seizures in patients with intracerebral hemorrhage (ICH) stroke and the effect of seizure prevention by anticonvulsant are not well understood. Limited studies have investigated the risk of seizure after discontinuing antiepileptic drugs in patients with ICH. This study aimed to investigate the role of valproic acid (VA) for seizure prevention and to access the risk of seizure after anticonvulsant withdrawal in patients with spontaneous ICH. Methods Between 2013 and 2015, 177 patients with ICH were enrolled in this 3-year retrospective study. Seizures were classified as early seizure (first seizure within 1 week of ICH), delayed seizure (first seizure after 1 week), and late seizure (any seizure after 1 week). Binary logistic regression was used to evaluate the relationship between baseline clinical factors and late seizures between study periods. VA was prescribed or discontinued based on the decision of the physician in charge. Results Seizures occurred in 24 patients, including early seizure in 6.78% (12/177) of the patients, delayed seizure in 7.27% (12/165) of the patients without early seizure, and late seizure in 9.60% (17/177) of the patients. Most seizures occurred within the first year. Binary logistic regression analysis showed ICH with cortex involvement as the independent risk factor for seizures. VA did not decrease the risk of seizures. Patients with ICH with cortical involvement using anticonvulsants for longer than 3 months did not have a decreased risk of seizures (odds ratio 1.86, 95% CI: 0.43–8.05). Conclusions Spontaneous ICH with cortex involvement is the risk factor for seizure. Most seizures occurred within 1 year after stroke onset over a 3-year follow up. Discontinuation of antiepileptic drug within 3 months in patients does not increase the risk of seizure.
Isaac A. Hinne, Simon K. Attah, Benedicta A. Mensah, Akua O. Forson,
Parasites & Vectors, Volume 14, pp 1-14; doi:10.1186/s13071-021-04701-w

Abstract:
Background Understanding the ecology of larval malaria and lymphatic filariasis mosquitoes in a changing environment is important in developing effective control tools or programmes. This study characterized the breeding habitats of Anopheles mosquitoes in rural communities in different ecological zones in Ghana during the dry and rainy seasons. Methods The spatio-temporal distribution, species composition, and abundance of larval Anopheles mosquitoes in breeding habitats were studied in five locations in three ecological zones of Ghana. These were Anyakpor (coastal savannah area), Duase (forest area), and Libga, Pagaza, and Kpalsogu (Sahel savannah area). Larvae were collected using standard dippers and were raised in the insectary for identification. Results Out of a total of 7984 mosquito larvae collected, 2152 (27.26%) were anophelines and were more abundant in the rainy season (70.82%) than in the dry season (29.18%). The anophelines comprised 2128 (98.88%) An. gambiae s.l., 16 (0.74%) An. rufipes, and 8 (0.37%) An. pharoensis. In the coastal savannah and forest zones, dug-out wells were the most productive habitat during the dry (1.59 larvae/dip and 1.47 larvae/dip) and rainy seasons (11.28 larvae/dip and 2.05 larvae/dip). Swamps and furrows were the most productive habitats in the Sahel savannah zone during the dry (0.25 larvae/dip) and rainy (2.14 larvae/dip) seasons, respectively. Anopheles coluzzii was the most abundant sibling species in all the ecological zones. Anopheles melas and An. arabiensis were encountered only in the coastal savannah and the Sahel savannah areas, respectively. Larval habitat types influenced the presence of larvae as well as larval density (p < 0.001). The land-use type affected the presence of Anopheles larvae (p = 0.001), while vegetation cover influenced larval density (p < 0.05). Conclusion The most productive habitats were dug-out wells in the coastal savannah and forest zones, and furrows from irrigated canals in the Sahel savannah zone. Anopheles coluzzii was the predominant vector species in all the ecological zones. The abundance of Anopheles breeding habitats and larvae were influenced by anthropogenic activities. Encouraging people whose activities create the larval habitats to become involved in larval source management such as habitat manipulation to stop mosquito breeding will be important for malaria and lymphatic filariasis control.
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