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Aims The treatment of heart rhythm disorders has been significantly impacted by direct consequences of the current COVID-19 pandemic, as well as by restrictions aimed towards constraining viral spread. Methods and results Usually, catheter ablations of cardiac arrhythmias are guided by electro-anatomic mapping (EAM) systems. Technical staff with medical training, or medical staff with technical training, are needed to assist the operator. Travel restrictions due to the current COVID-19 pandemic have limited the in-person availability of technical support staff. To overcome these limitations, we explored the feasibility of a trans-atlantic remote technical support for EAM, with an internet-based communication platform, for complex electrophysiological ablation procedures. Conclusion Our first experience, based on nine ablation procedures of different arrhythmias, highlights the feasibility of this approach. Remote support for EAM might therefore facilitate continuous care for patients with arrhythmias during the COVID-19 pandemic, particularly in insular settings. Beyond COVID-19-related challenges, this approach will likely play a greater role in the cardiology field in years to come, due to its significant advantages., Graphical Abstract Graphical Abstract

Gay, bisexual, and other men who have sex with men (MSM) and transgender women are disproportionately affected by human papillomavirus (HPV). HPV vaccination is routinely recommended for U.S. adolescents at age 11-12years, with catch-up vaccination through age 26years. We assessed HPV vaccination coverage and associated factors among young MSM and transgender women. The Vaccine Impact in Men study enrolled MSM aged 18-26years from clinics in Seattle, Chicago, and Los Angeles, during February 2016-September 2018. Participants self-reported socio-demographic information and HPV vaccination status. Among 1416 participants, 673 (47.5%) reported ≥1 HPV vaccine dose. Among vaccinated participants, median age at first dose was 19years and median age at first sex was 17years; 493 (73.3%) reported that their age at first dose was older than their age at first sex. There were significant differences in HPV vaccination coverage by city (range 33%-62%), age, race/ethnicity, and gender identity. Coverage was highest in Seattle, where younger age was the only factor associated with vaccination. Differences in coverage by city may be due to variation in vaccination practices or enrollment at study sites. Increasing both routine and catch-up vaccination will improve coverage among MSM and transgender women.

Introduction The increasing proportion of outpatient allogeneic hematopoietic cell transplants (HCTs) coupled with increased access of once‐daily broad‐spectrum antibiotics and evidence that outpatient antibiotic treatment may be safer and less costly than inpatient treatment, suggest that allogeneic HCT recipients with Gram‐negative rod bacteremia (GNRBs) are increasingly being treated in ambulatory care settings. Methods Using data from the first GNRB event that occurred within the first 100 days posttransplantation among allogeneic HCT recipients transplanted at a single center between 2007 and 2016, we estimated the temporal trends in GNRB incidence and treatment management of GNRBs and identified if patient or infection characteristics impacted observed trends. Results A total of 11% (238/2165) of the observed allogeneic HCT recipients experienced ≥1 GNRB with available resistance data and contributed antibiotic treatment time. Patients, on average, received 55.1% of their antibiotic treatment in an outpatient setting and we observed a significant decline in the proportion of treatment time spent outpatient (crude: −3.3% [95% confidence interval: −5.0, −1.6%]). We observed similar declines in the proportion of treatment time spent outpatient among patients with similar GNRB and pretransplant complexity factors but not among patients with similar posttransplant complications (p value: .165). Conclusion These results suggest that, despite increased availability of outpatient suitable treatment options, allogeneic HCT recipients with GNRBs received less treatment in outpatient settings. However, among patients with similar posttransplant complications, the lack of significant decline suggests that treatment location decisions remained consistent for patients with similar posttransplant complications. These findings suggest the need for additional interventions targeting outpatient antibiotic treatment among allogeneic HCT recipients with GNRBs., Over a 10‐year period, Gram‐negative rod bacteremia (GNRB) incidence and the proportion of GNRBs treatment time spent outpatient declined significantly. However, among patients with similar posttransplant complications, no decline in outpatient treatment was observed. This suggests that the decline in outpatient antibiotic days may be linked to increased frequency of posttransplant complications.

Background: Potentiating current antidepressant treatment is much needed. Based on animal studies, caffeine may augment the effects of currently available antidepressants. Objective: Here, we tested whether habitual caffeine consumption moderates the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS). Methods: Forty patients with current depressive episodes were randomized to active iTBS ( n = 19) or sham treatment ( n = 21; shielded side of the coil and weak transcutaneous electrical stimulation) delivered two times per day for 10–15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the 2 days before the treatment starts. Results: Habitual caffeine consumption was associated with symptom improvement following active iTBS ( r = 0.51, 95% confidence interval (CI): 0.08–0.78, p = 0.025) but not following sham treatment ( r = −0.02, 95% CI: −0.45 to 0.42, p = 0.938). A multiple regression analysis corroborated the findings by showing a significant caffeine consumption × treatment group interaction (β = 0.62, p = 0.043), but no main effects of treatment group (β = 0.22, p = 0.140) or caffeine consumption (β = −0.01, p = 0.948). No group differences in pretreatment symptom scores or caffeine consumption were detected ( p values > 0.86). Conclusion: Habitual caffeine consumption moderated the antidepressant effect of dorsomedial iTBS, consistent with caffeine improving antidepressant pharmacological treatments in animals. Caffeine is an antagonist of adenosine receptors and may enhance antidepressant effects through downstream dopaminergic targets.

Background Cognitive interviewing is a well-established qualitative method used to develop and refine PRO measures. A range of digital technologies including phone, web conferencing, and electronic survey platforms can be leveraged to support the conduct of cognitive interviewing in both children and adults. These technologies offer a potential solution to enrolling underrepresented populations, including those with rare conditions, functional limitations and geographic or socioeconomic barriers. In the aftermath of the COVID-19 pandemic, the use of digital technologies for qualitative interviewing will remain essential. However, there is limited guidance about adapting cognitive interviewing procedures to allow for remote data capture, especially with children. Methods Synthesizing the literature and our research experiences during the COVID-19 pandemic, we examine considerations for implementing digitally supported cognitive interviews with children, adolescents, and adults. We offer recommendations to optimize data quality and empirical rigor and illustrate the application of these recommendations in an ongoing cognitive interviewing study to develop and refine a new pediatric PRO measure. Results Good research practices must address participant and researcher preparation for study-related procedures and should anticipate and pre-emptively manage technological barriers. Field notes should detail interview context, audio/video cues, and any impact of technological difficulties on data quality. The approaches we recommend have been tested in an ongoing cognitive interviewing study that is enrolling children/adolescents with cGVHD ages 5–17 and their caregivers [NCT 04044365]. The combined use of telephone and videoconferencing to conduct cognitive interviews remotely is feasible and acceptable and yields meaningful data to improve the content validity of our new PRO measure of cGVHD symptom bother. Conclusion Digitally supported cognitive interviewing procedures will be increasingly employed. Remote data collection can accelerate accrual, particularly in multi-site studies, and may allow for interviewer personnel and data management to be centralized within a coordinating center, thus conserving resources. Research is needed to further test and refine techniques for remote cognitive interviewing, particularly in traditionally underrepresented populations, including children and non-English speakers. Expansion of international standards to address digitally supported remote qualitative data capture appears warranted.

Introduction Soluble forms of cytokine receptors can be involved in the endogenous regulation of cytokine activity. Soluble interleukin 7 receptor α (sCD127) naturally binds IL‐7, therefore there is interest in its potential application as an immunotherapeutic agent to regulate IL‐7. With the hypothesis that sCD127 enhances IL‐7 activity, thus promoting T‐cell proliferation in vivo, we sought to assess the effect of sCD127, IL‐7 or IL‐7 + sCD127 treatment on CD4+ and CD8+ T‐cells in the blood and spleen of mice. Methods Peripheral blood mononuclear cells and splenocytes were prepared, and analyzed for T‐cell number, phenotype and proliferation (Ki67+) by flow cytometry. Results IL‐7 treatment induced T‐cell proliferation, increased T‐cell number, and triggered T‐cell differentiation each of which was enhanced with the addition of sCD127. IL‐7 + sCD127 treatment significantly increased spleen weight over that seen with IL‐7 treatment alone. More pronounced proliferation and a greater increase in cell number was observed in CD8+ T‐cells relative to the effect on CD4+ T‐cells. Conclusions These findings suggest that the addition of sCD127 enhances IL‐7‐mediated T‐cell proliferation and suggests a potential therapeutic use for sCD127., IL‐7 alone can have a positive effect on T‐cell proliferation and T‐cell differentiation from a naive T‐cell. In this mouse study, we found that complexing IL‐7 with soluble CD127 could enhance these positive effects, suggesting a therapeutic use in vivo.

Avery A Rizio,1 Kristen L McCausland,1 Michelle K White,1 Tiffany P Quock2 1QualityMetric Incorporated, LLC, Johnston, RI, USA; 2Prothena Biosciences Inc, South San Francisco, CA, USACorrespondence: Avery A RizioQualityMetric Incorporated, LLC, 1301 Atwood Avenue, Suite 216E, Johnston, RI, 02919, USATel +1 401-903-4631Email arizio@qualitymetric.comBackground: Light chain (AL) amyloidosis is a rare and progressive disease that affects myriad organs and systems. Patients with cardiac involvement have the highest risk of death. This report compiles findings across three cohorts of patients with AL amyloidosis to understand patterns of employment and work impacts.Methods: Data came from three cohorts recruited through patient advocacy organizations in the US. Patients in Cohort 1 completed the SF-36v2® Health Survey (SF-36v2), the Work Productivity and Activity Impairments – Specific Health Problem (WPAI) questionnaire, and the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The relationship between work impacts (WPAI scores) and HRQoL (SF-36v2 scores) was investigated using multivariable logistic regression and summarized according to cardiac severity using New York Heart Association (NYHA) classes estimated from KCCQ-12 scores. Changes in employment, days of missed work, and long-term disability due to AL amyloidosis were summarized for patients diagnosed in the past 24 months and stratified by NYHA class (Cohort 2). Findings were contextualized using patient interviews (Cohort 3).Results: Work-related impacts, especially reduced productivity, were common among patients with AL amyloidosis. WPAI scores were significantly related to HRQoL (p< 0.05 for all models). Among patients with cardiac involvement, the greatest degree of work impacts was observed for those in NYHA class 3 or 4. Changes in employment, missed work, and long-term disability were common among newly diagnosed patients, especially among those in NYHA class 3 or 4. Patient interviews supported the survey findings; patients described absences, reduced productivity at work, and loss of employment due to the disease and its treatment.Conclusion: Patients with AL amyloidosis, particularly those with more advanced disease, experience impacts across a range of employment-related outcomes. These findings highlight the need for more effective treatments and interventions which may improve functioning and patient outcomes, while reducing indirect costs associated with the disease.Keywords: AL amyloidosis, patient-reported outcomes, employment, work outcomes

Background New technologies like next-generation sequencing have led to a proliferation of studies investigating the role of the gut microbiome in human health, particularly population-based studies that rely upon participant self-collection of samples. However, the impact of methodological differences in sample shipping, storage, and processing are not well-characterized for these types of studies, especially when transit times may exceed 24 h. The aim of this study was to experimentally assess microbiota stability in stool samples stored at 4 °C for durations of 6, 24, 48, 72, and 96 h with no additives to better understand effects of variable shipping times in population-based studies. These data were compared to a baseline sample that was immediately stored at − 80 °C after stool production. Results Compared to the baseline sample, we found that the alpha-diversity metrics Shannon’s and Inverse Simpson’s had excellent intra-class correlations (ICC) for all storage durations. Chao1 richness had good to excellent ICC. We found that the relative abundances of bacteria in the phyla Verrucomicrobia, Actinobacteria, and Proteobacteria had excellent ICC with baseline for all storage durations, while Firmicutes and Bacteroidetes ranged from moderate to good. We interpreted the ICCs as follows: poor: ICC 0.90. Using the Bray–Curtis dissimilarity index, we found that the greatest change in community composition occurred between 0 and 24 h of storage, while community composition remained relatively stable for subsequent storage durations. Samples showed strong clustering by individual, indicating that inter-individual variability was greater than the variability associated with storage time. Conclusions The results of this analysis suggest that several measures of alpha diversity, relative abundance, and overall community composition are robust to storage at 4 °C for up to 96 h. We found that the overall community richness was influenced by storage duration in addition to the relative abundances of sequences within the Firmicutes and Bacteroidetes phyla. Finally, we demonstrate that inter-individual variability in microbiota composition was greater than the variability due to changing storage durations.

Purpose To study the effectiveness of diabetic yoga protocol (DYP) against management of cardiovascular risk profile in a high-risk community for diabetes, from Chandigarh, India. Methods The study was a randomized controlled trial, conducted as a sub study of the Pan India trial Niyantrita Madhumeha Bharath (NMB). The cohort was identified through the Indian Diabetes Risk Scoring (IDRS) (≥ 60) and a total of 184 individuals were randomized into intervention (n = 91) and control groups (n = 93). The DYP group underwent the specific DYP training whereas the control group followed their daily regimen. The study outcomes included changes in glycemic and lipid profile. Analysis was done under intent-to-treat principle. Results The 3 months DYP practice showed diverse results showing glycemic and lipid profile of the high risk individuals. Three months of DYP intervention was found to significantly reduce the levels of post-prandial glucose levels (p = 0.035) and LDL-c levels (p = 0.014) and waist circumference (P = 0.001). Conclusion The findings indicate that the DYP intervention could improve the metabolic status of the high-diabetes-risk individuals with respect to their glucose tolerance and lipid levels, partially explained by the reduction in abdominal obesity. The study highlights the potential role of yoga intervention in real time improvement of cardiovascular profile in a high diabetes risk cohort. Trial registration: CTRI, CTRI/2018/03/012804. Registered 01 March 2018—Retrospectively registered, http://www.ctri.nic.in/CTRI/2018/03/012804.

This study investigated the implementation status, attitudes, and practices regarding maternal pertussis vaccination in delivery facilities in Kanagawa, Japan. We conducted a questionnaire survey of pertussis vaccination during pregnancy at 125 delivery service facilities, excluding midwifery clinics, in Kanagawa Prefecture from June 18 to July 20, 2020. The questionnaire comprised multiple-choice items, with single or multiple answers depending on the question. Of the 125 facilities surveyed, valid responses were obtained from 72 facilities (58%). There were 41 primary clinics with birthing facilities (57%), 16 general hospitals (not designated perinatal centers) (22%), 10 regional perinatal centers (14%), and five tertiary perinatal centers (7%). None of the facilities administered pertussis vaccination during pregnancy. Forty facilities (56%) reported knowledge of the severity of neonatal and infant pertussis infections. Twenty-three facilities (32%) reported knowledge of the prevention of pertussis infection by vaccination during pregnancy. All facilities reported willingness to consider vaccination if included in the Japanese guidelines. In Japan, the pertussis vaccination during pregnancy is not highly practiced by obstetricians; thus, it is not as popular as in other countries. Further studies are needed to promote strategies to prevent pertussis infection in the neonatal and infant periods.

Eighty-seven years ago, Köhler reported that the majority of students picked the same answer in a quiz: Which novel word form (‘maluma’ or ‘takete’) went best with which abstract line drawing (one curved, one angular). Others have consistently shown the effect in a variety of contexts, with only one reported failure by Rogers and Ross. In the spirit of transparency, we report our own failure in the same journal. In our study, speakers of Syuba, from the Himalaya in Nepal, do not show a preference when matching word forms ‘kiki’ and ‘bubu’ to spiky versus curvy shapes. We conducted a meta-analysis of previous studies to investigate the relationship between pseudoword legality and task effects. Our combined analyses suggest a common source for both of the failures: ‘wordiness’ – We believe these tests fail when the test words do not behave according to the sound structure of the target language. Published version

Brucellosis is a zoonotic disease with more than half a million people diagnosed worldwide. In China, 99% of cases were historically reported in the northern part of the country, and few were diagnosed in Guangdong province. Recently, Guangzhou has become as an emerging focus for brucellosis, with personal awareness of brucellosis and inexperience of clinicians hindering timely clinical diagnosis. To improve clinical management of this disease, we retrospectively analyzed 60 brucellosis cases from 2010 to 2020 in Guangdong Provincial People’s Hospital. There were no manifestation differences between southern and northern patients. However, 68.3% of patients lacked awareness of risk factors for Brucella infection. Therefore, to prevent its spread and avoid delays in diagnosis, implemented infected-animal control programs and enhanced education on brucellosis are necessary.

Sierra Leone relies heavily on histidine-rich protein 2–based diagnostics for malaria because of the high transmission of Plasmodium falciparum. During the 2015 recombinant vesicular stomatitis virus (VSV)−Zaire Ebola virus envelope glycoprotein (GP) vaccine trial, 77 participants with asymptomatic Plasmodium infection were enrolled, with all but four having P. falciparum malaria. Of the 73 participants with P. falciparum malaria, one infection (1 of 73, 1.4%; 95% CI, 0.03–7.4) showed P. falciparum with a pfhrp3 single deletion, and two P. falciparum infections (2 of 73, 2.7%; 95% CI, 0.03–9.6) showed pfhrp2/pfhrp3 dual deletions. This study shows evidence of pfhrp2- and pfhrp3-deleted parasites in Freetown, Sierra Leone. Additional studies for more precise estimates of prevalence are warranted.

BackgroundHealthcare workers (HCWs) are frontline responders to emergency infectious disease outbreaks such as COVID-19. To avoid the rapid spread of disease, adherence to protective measures is paramount. We investigated rates of correct use of personal protective equipment (PPE), hand hygiene and physical distancing in UK HCWs who had been to their workplace at the start of the COVID-19 pandemic and factors associated with adherence.MethodsWe used an online cross-sectional survey of 1035 UK healthcare professionals (data collected 12–16 June 2020). We excluded those who had not been to their workplace in the previous 6 weeks, leaving us with a sample size of 831. Respondents were asked about their use of PPE, hand hygiene and physical distancing in the workplace. Frequency of uptake was reported descriptively; adjusted logistic regressions were used to separately investigate factors associated with adherence to use of PPE, maintaining good hand hygiene and physical distancing from colleagues.ResultsAdherence to personal protective measures was suboptimal (PPE use: 80.0%, 95% CI 77.3 to 82.8; hand hygiene: 67.8%, 95% CI 64.6 to 71.0; coming into close contact with colleagues: 74.7%, 95% CI 71.7 to 77.7). Adherence to PPE use was associated with having received training about health and safety in the workplace for COVID-19, greater perceived social pressure to adopt the behaviour and availability of PPE. Non-adherence was associated with fatalism about COVID-19 and greater perceived difficulty of adopting protective measures. Workplace design using markings to facilitate distancing was associated with adherence to physical distancing.ConclusionsUptake of personal protective behaviours among UK HCWs at the start of the pandemic was variable. Factors associated with adherence provide insight into ways to support HCWs to adopt personal protective behaviours, such as ensuring that adequate PPE is available and designing workplaces to facilitate physical distancing.

There is experimental and clinical data to indicate the contribution of immune-escape mechanisms in relapsed/refractory pediatric leukemia. Studies have shown the accumulation of mutations that translate to peptides containing tumor-specific epitopes (neoantigens). The effectiveness of neoantigen-based vaccines has been shown in several clinical trials in adults. Though the initial results are encouraging, this knowledge must be developed to account for the uniqueness of pediatric cancer biology. We have completed the initial proof-of-concept analysis on a high-risk pediatric leukemia specimen and identified usable neoantigen sequences. We describe this approach, including the bioinformatics method and experimental model to verify their function that can be further broadened for personalized neoantigen prediction and testing for the generation of anticancer vaccines against high-risk pediatric leukemias.

The emergence of COVID-19 highlights globalisation realties, where diseases may emerge from anywhere and rapidly spread globally. Lessons emphasise the necessity for strengthening regional and global collaboration and coordination to allow rapid risk identification, resource mobilisation and joint actions. We report the experience of the Regional Action through Data (RAD) partnership in fostering regional cooperation and collaboration to use data for battling infectious diseases and the effects of COVID-19. The Partnership comprised;BoadReach company, The West African Health Organization (WAHO) and the Intergovernmental Authority on Development (IGAD); Duke University Global Health Centre and the Jembi Health Systems, South Africa. Main objective: To address the problem of limited used of data to drive performance in healthcare service delivery in sub-Saharan Africa; by changing how and why data is collected, analysed, and then used to achieve results. Specific objectives: 1. Regional level: To equip and empower IGAD and WAHO with evidence-based analytics to drive data use for evidence-based policy and program action in public health (regional level). 2. Patient -provider level: To deploy and implement a digital health solution for child-hood vaccination services focused on mobile cross-border populations along the Uganda-Kenya border. Engagement approaches used included; meetings, workshops, technical working groups, establishing monitoring system and annual implementation revision. Targeted training and capacity building were conducted. All activities were built on existing systems and structures to strengthen ownership and sustainability. Regional level achievements: 1. Regional health data sharing and protection policy, 2. Strengthened regional health information platform. Patient provider level: Deployment of a cloud based digital health solution to enhance childhood access to vaccination services for cross border populations of Kenya and Uganda, 3. Both regions developed resource mobilisation plans for sustainability. RAD established the foundation for building trust and strengthening regional collaboration and coordination in health in Sub-Saharan Africa.

Background for shared decision-making, it is important to discuss of the patients’ priorities in order to align treatment decisions with these priorities. Objective to assess the most important health outcome for older patients on the verge of making a treatment decision, using the Outcome Prioritization Tool (OPT). Secondary objectives were the feasibility of the OPT and patient variables associated with prioritising different health outcomes. Design retrospective cohort study. Setting and subjects at the University Medical Hospital Groningen, the Netherlands, 350 patients were included who visited the geriatric outpatient clinic during the work-up regarding a complex treatment decision (such as cancer treatment or heart valve replacement). Methods during geriatric assessment, patients prioritised between four health outcomes, using the OPT. Results median age was 78.5 years, 172 (49.1%) were referred regarding a treatment decision for a malignant disease. Cognitive impairment was present in 23.6%. Most patients (55.2%) prioritised maintaining independence as their most important goal, followed by extending life in 21.1%. Only cognitive impairment was significantly associated with prioritising extending life as the most important health outcome. For 107 patients (30.6%), the OPT was not feasible; these patients more often had malnutrition and assisted living. Conclusions the main health outcome of older patients on the verge of making a treatment decision was maintaining independence, followed by extending life. Patients with cognitive impairment more often prioritised extending life. The OPT was feasible as a decision aid for most patients. For optimal shared decision-making, it is crucial to take patient preferences into account.

To respond to potential public health impacts of social media influencing vaccine confidence, Facebook proposed that prior to proceeding to any link about Human Papillomavirus (HPV) vaccination, a pop-up will prompt the user to visit a reputable website on vaccine information. This study explored the acceptability of a pop-up Facebook message for HPV vaccine information. A national sample of U.S. adults (n = 579) was surveyed online. Most participants rated the pop-up messages as acceptable, useful, and factual. Regression results indicated that being male, seeing HPV content on social media in the past month, believing that information on social media is credible, holding positive HPV vaccination attitudes, and having shared HPV content on their own social media were associated with greater likelihood of clicking on a pop-up. While the pop-up approach may be acceptable, there are many factors that may be associated with being less likely to click on the pop-up.

Introduction Recent studies have shown that myosin light chain 9 (MYL9) plays a vital role in immune infiltration, tumor invasion, and metastasis; however, the prognostic and immunological role of MYL9 has not been reported. The purpose of this study was to explore the potential prognostic and immunological roles of MYL9 in human cancers by public datasets mainly including the cancer genome atlas (TCGA) and Gene expression omnibus. Methods The expression pattern and prognostic value of MYL9 were analyzed across multiple public datasets in different cancer. The correlations between MYL9 expression and immune infiltration among multiple cancers were analyzed by using the TIMER2.0. The MYL9‐related gene enrichment analysis was implemented by mainly using KEGG and GO datasets. Results MYL9 was lowly expressed in most cancers, such as breast cancer, lung adenocarcinoma and squamous cell carcinoma, and stomach adenocarcinoma; but it was highly expressed in several cancers, such as cholangiocarcinoma, head and neck squamous cell carcinoma, and liver hepatocellular carcinoma. Furthermore, MYL9 expression was distinctively associated with prognosis in adrenocortical carcinoma, colon adenocarcinoma, brain glioma, lung cancer, ovarian cancer, gastric cancer, breast cancer, blood cancer, and prostate cancer patients. The expressions of MYL9 were significantly associated with the infiltration of cancer‐associated fibroblasts, B cell, CD8+T cell, CD4+T cell, macrophage, neutrophil, dendritic cell in different tumors as well as immune markers. In addition, we found that the functional mechanisms of MYL9 involved muscle contraction and focal adhesion. Conclusion MYL9 can serve as a prognostic signature in pan‐cancer and is associated with immune infiltration. This pan‐cancer study is the first to show a relatively comprehensive understanding of the prognostic and immunological roles of MYL9 across different cancers., Our first pan‐cancer analyses of MYL9 indicated statistical correlations of MYL9 expression with clinical prognosis, immune cell infiltration across multiple tumors, which aids in understanding the role of MYL9 in tumorigenesis from the perspective of clinical tumor samples. Our results indicated that MYL9 can serve as a prognostic signature in pan‐cancer and is associated with immune infiltration.

Clinical data sets have very special properties and suffer from many caveats in machine learning. They typically show a high-class imbalance, have a small number of samples and a large number of parameters, and have missing values. While feature selection approaches and imputation techniques address the former problems, the class imbalance is typically addressed using augmentation techniques. However, these techniques have been developed for big data analytics, and their suitability for clinical data sets is unclear.This study analyzed different augmentation techniques for use in clinical data sets and subsequent employment of machine learning-based classification. It turns out that Gaussian Noise Up-Sampling (GNUS) is not always but generally, is as good as SMOTE and ADASYN and even outperform those on some datasets. However, it has also been shown that augmentation does not improve classification at all in some cases.

Hans De Loof,1 Ellen De Win,1 Nathalie Moens,1 Veronique Verhoeven,2 Paul Van Royen,2 Elke O Kreps,3 Hilde Philips2 1Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium; 2Research Group, Primary and Interdisciplinary Care (ELIZA), Department Family Medicine and Population Health (FAMPOP) University of Antwerp, Antwerp, Belgium; 3Department of Ophthalmology, Ghent University Hospital, Ghent, BelgiumCorrespondence: Hans De LoofLaboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, BelgiumTel +32 3 265 91 39Email hans.deloof@uantwerpen.beAbstract: Prescribing patterns by primary care physicians concerning ophthalmic problems were studied using the iCAREdata, a database containing information from the out-of-hours care setting in the Flanders region of Belgium. A very high percentage of prescribed ophthalmic medication was topical antibiotics (89.4%) with tobramycin as the most prevalent substance and in clear conflict with the prevailing guidelines. In addition, a very substantial fraction of prescribed medication contained corticosteroids (30.4%). This is a potentially unsafe option within the technical infrastructure of this setting, which limits the diagnostic possibilities concerning viral infections or preexisting glaucoma risk. We conclude that more efforts are required to limit unnecessary and inappropriate prescribing behavior to further promote patient safety.Keywords: antibiotics, conjunctivitis, drug utilization research, referral process

Amy F Ho,1,&ast; Yuan Zhou,2,&ast; Jessica J Kirby,1 Md Mamunur Rahman,2 Kathryn Tessitore,1 Yousef Abdel-Raziq,1 James P d’Etienne,1 Chet D Schrader,1 Hao Wang1 1Department of Emergency Medicine, Integrative Emergency Services, John Peter Smith Health Network, Fort Worth, TX, 76104, USA; 2Department of Industrial, Manufacturing, and Systems Engineering, The University of Texas at Arlington, Arlington, TX, 76019, USA&ast;These authors contributed equally to this workCorrespondence: Yuan ZhouDepartment of Industrial, Manufacturing, and Systems Engineering, The University of Texas at Arlington, 701 S. Nedderman Dr., Arlington, TX, 76019, USAEmail yuan.zhou@uta.eduHao WangIntegrative Emergency Services, John Peter Smith Health Network, 1500 S. Main St., Fort Worth, TX, 76104, USATel +1 817-702-8696Fax +1 817-702-1143Email hwang@ies.healthcareObjective: Patient perceptions of physician trust and respect are important factors for patient satisfaction evaluations. However, perceptions are subjective by nature and can be affected by patient and physician demographic characteristics. We aim to determine the causal effect on patient–physician demographic concordance and patient perceptions of physician trust and respect in an emergency care setting.Methods: We performed a causal effect analysis in an observational study setting. A near-real-time patient satisfaction survey was sent via telephone to patients within 72 h of discharge from an emergency department (ED). Patient-trust-physician (PTP) and physician-show-respect (PSR) scores were measured. Patient and physician demographics (age, gender, race, and ethnicity) were matched. Causal effect was analyzed to determine the direct effect of patient–physician demographic concordance on PTP/PSR scores.Results: We enrolled 1815 patients. The treatment effect of patient–physician age concordance on PTP scores was − 0.119 (p = 0.036). Other treatment effect of patient–physician demographic concordance on patient perception of physician trust and respect ranged from − 0.02 to − 0.2 (p > 0.05).Conclusion: Patient–physician age concordance may cause a negative effect on patient perception of physician trust. Otherwise, patient–physician demographic concordance has no effect on patient perceptions of physician trust and respect.Keywords: patient, physician, demographics, trust, respect

Megan McCrohan,1,&ast; Linnea Nierenberg,1,&ast; Patrick Karabon,2 Tracy Wunderlich-Barillas,2 Alexandra Halalau1,3 1Oakland University William Beaumont School of Medicine, Rochester, MI, USA; 2Office of Research, Oakland University William Beaumont School of Medicine, Rochester, MI, USA; 3Internal Medicine Department, Beaumont Health, Royal Oak, MI, USA&ast;These authors contributed equally to this workCorrespondence: Linnea Nierenberg Email nierenberglinnea@gmail.comImportance: The COVID-19 pandemic continues to impact the health-care system in the United States and has brought further light on health disparities within it. However, only a few studies have examined hospitalization risk with regard to social determinants of health.Objective: We aimed to identify how health disparities affect hospitalization rates among patients with COVID-19.Design: This observational study included all individuals diagnosed with COVID-19 from February 25, 2020 to December 31, 2020. Uni- and multivariate analyses were utilized to evaluate associations between demographic data and inpatient versus outpatient status for patients with COVID-19.Setting: Multicenter (8 hospitals), largest size health system in Southeast Michigan, a region highly impacted by the pandemic.Participants: All outpatients and inpatients with a positive RT-PCR for SARS-CoV-2 on nasopharyngeal swab were included. Exclusion criteria included missing demographic data or status as a non-permanent Michigan resident.Exposure: Patients who met inclusion and exclusion criteria were divided in 2 groups: outpatients and inpatients.Main Outcome and Measures: We described the comparative demographics and known disparities associated with hospitalization status.Results: Of 30,292 individuals who tested positive for SARS-CoV-2, 34.01% were admitted to the hospital. White or Caucasian race was most prevalent (57.49%), and 23.35% were African-American. The most common ethnicity was non-Hispanic or Latino (70.48%). English was the primary language for the majority of patients (91.60%). Private insurance holders made up 71.11% of the sample. Within the hospitalized patients, lower socioeconomic status, African-American race and Hispanic and Latino ethnicity, non-English speaking status, and Medicare and Medicaid were more likely to be admitted to the hospital.Conclusions and Relevance: Several health disparities were associated with greater rates of hospitalization due to COVID-19. Addressing these inequalities from an individual to system level may improve health-care outcomes for those with health disparities and COVID-19.Keywords: COVID-19, hospitalization, social determinants of health, disparities

Objective Blau syndrome (BS), a rare, autosomal-dominant autoinflammatory syndrome, is characterized by a clinical triad of granulomatous recurrent uveitis, dermatitis, and symmetric arthritis and associated with mutations of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Aim of this study was to assess the efficacy of tofacitinib in Chinese paediatric patients with BS. Methods Tofacitinib was regularly administered to three BS patients (Patient 1, Patient 2, and Patient 3) at different dosages: 1.7 mg/day (0.11 mg/kg), 2.5 mg/day (0.12 mg/kg), and 2.5 mg/day (0.33 mg/kg). The clinical manifestations of the patients, magnetic resonance imaging results, serological diagnoses, therapeutic measures and outcomes of treatments are described in this report. Results The clinical characteristics and serological diagnoses of all BS patients were greatly improved after the administration of tofacitinib treatment. All patients reached clinical remission of polyarthritis and improvements in the erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and inflammatory cytokines. Conclusion Tofacitinib, a Janus kinase (JAK) inhibitor, is a promising agent for BS patients who have unsatisfactory responses to corticosteroids, traditional disease-modifying antirheumatic drugs, and biological agents.

Background Despite a national decrease in emergency department visits in the United States during the first 10 months of the pandemic, preliminary Consumer Product Safety Commission data indicate increased firework-related injuries. We hypothesized an increase in firework-related injuries during 2020 compared to years prior related to a corresponding increase in consumer firework sales. Methods The National Electronic Injury Surveillance System (NEISS) was queried from 2018 to 2020 for cases with product codes 1313 (firework injury) and narratives containing “fireworks”. Population-based national estimates were calculated using US Census data, then compared across the three years of study inclusion. Patient demographic and available injury information was also tracked and compared across the three years. Firework sales data obtained from the American Pyrotechnics Association were determined for the same time period to examine trends in consumption. Results There were 935 firework-related injuries reported to the NEISS from 2018 to 2020, 47% of which occurred during 2020. National estimates for monthly injuries per million were 1.6 times greater in 2020 compared to 2019 (p p = 0.38). The same results were found when the month of July was excluded. Firework consumption in 2020 was 1.5 times greater than 2019 or 2018, with a 55% increase in consumer fireworks and 22% decrease in professional fireworks sales. Conclusions Firework-related injures saw a substantial increase in 2020 compared to the two years prior, corroborated by a proportional increase in consumer firework sales. Increased incidence of firework-related injuries was detected even with the exclusion of the month of July, suggesting that the COVID-19 pandemic may have impacted firework epidemiology more broadly than US Independence Day celebrations.

Maoti Wei,1,&ast; Li Dong,2,&ast; Fenghua Wang,1 Kai Cui,3 Delong Ma,2 Ning Yang,4 Yuming Li4 1Center of Clinical Epidemiology, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China; 2Department of Pediatrics, Center Hospital of Beikuo Town, Rizhao City, Shandong Province, People’s Republic of China; 3Department of Disease Prevention and Control, Hospital of Gaoxing Town, Rizhao City, Shandong Province, People’s Republic of China; 4Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang; Yuming Li Email yangningzxdl@sina.com; cardiolab@live.comObjective: To understand the prevalence and control of type 2 diabetes mellitus (T2DM) in a rural area, a cross-sectional study was carried out.Methods: Blood glucose was determined in residents over 60 years during the National Basic Public Health Service project carrying on in a rural town of Shandong province. Combined with detail information of diabetic history, the prevalence rate of this disease was calculated with a cutoff of more than 7.0 mmol/L of fasting plasma glucose (FPG). Furthermore, according to FPG levels, the control rate of diabetes was evaluated. Basic information and clinical laboratory tests were analyzed with proper methods for univariate analysis. Multivariable logistic analysis was used to explore multiple variables associated with the control effect of T2DM.Results: The prevalence rate of T2DM was 13.5% (95% CI 12.4%∼ 14.7%) without age difference in residents over 60-year old (X2= 1.078, P = 0.898). And the rate was higher in the female (16.1%, 95% CI 14.4%∼ 17.8%) than that in the male (11.3%, 95% CI 9.7%∼ 12.9%). The control rate of diabetes was 44.5% (95% CI 39.4– 49.6%, cutoff < 6.1 mmol/L for FPG) and 59.6% (95% CI 54.5– 64.6%, cutoff < 7.0 mmol/L for FPG), respectively. Most T2DM residents had balance foods, and a high proportion of drugs or insulin were used; however, the proportion of keeping exercise and modifying behaviors was low. Nearly 80% of the diabetic individuals used at least one drug or insulin. However, the more drugs or insulin used, the higher the FPG level was.Conclusion: A relative high level of T2DM prevailed in the rural area under fast economy-transforming. T2DM was controlled poor and measures should be further optimized to achieve ideal effect, especially for the use of anti-diabetic drugs.Keywords: rural area, type 2 diabetes mellitus, the control of diabetes

BackgroundFragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells.ResultsWe show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in theFmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development.ConclusionsWe reveal the abnormal regulation of these mRNAs in theFmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.

Background Therapeutic drug monitoring for voriconazole is recommended for its optimum pharmacotherapy. Although the feedback of the measurement result of serum voriconazole concentration by outsourcing needs a certain time (days within a 1 week), there was no medical equipment for the measurement available in clinical practice. Recently, a medical equipment based on high performance liquid chromatography, named LM1010, has been developed and authorized for clinical use. In this study, to validate the clinical performance of LM1010, we compared the measured serum voriconazole concentrations by LM1010 with those by outsourcing measurement using liquid chromatography-tandem mass spectrometry. Methods We conducted the observational study approved by the institutional review board of Kumamoto University Hospital (No. 1786). Residual serum samples harvested for therapeutic drug monitoring were separated. Measured concentrations by LM1010 by the standard filter method (needs serum volume of > 400 μL) or the dilute method (needs serum volume of 150 μL) were compared with those by outsourcing, respectively. Acceptable measurement error range of 0.72–1.33 was considered. There were 69 serum samples, where the 35 or 34 samples were employed for evaluation of the standard filter method or the dilute method, respectively. Results The measured concentration using the standard filter method/outsourcing was 2.22/2.10 μg/mL as the median, 1.57–3.40/1.53–3.62 as the interquartile range, Conclusion Measurement of serum voriconazole concentration by LM1010 can be acceptable in clinical TDM practice.

Several natural disasters and the appearance of the coronavirus disease 2019 (COVID-19) pandemic created stressful situations to many health-care workers in the Philippines. New health-related challenges surfaced, and health-care workers felt lost since many of the challenges were either directly or indirectly caused by the fast-spreading coronavirus infections and its variants. Further, the way people die also changed, causing confusion and influencing the Filipino grief and bereavement processes. In response to the need of the health-care workers, a nongovernmental organization (NGO) through its education portal created and offered free webinars, aimed to help health-care workers understand and make sense of what was happening, thus empowering them with knowledge on how to manage the challenges and provide better care to the patients and the community as well. This article relates the process of planning and implementing online webinars during the era of social distancing and COVID-19 pandemic.

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

This brief report aimed to describe a narrative review about the application of machine learning (ML) methods and Blockchain technology (BCT) in the healthcare field, and to illustrate the integration of these two technologies in cancer survivorship care. A total of six eligible papers were included in the narrative review. ML and BCT are two data-driven technologies, and there is rapidly growing interest in integrating them for clinical data management and analysis in healthcare. The findings of this report indicate that both technologies can integrate feasibly and effectively. In conclusion, this brief report provided the state-of-art evidence about the integration of the most promising technologies of ML and BCT in health field, and gave an example of how to apply these two most disruptive technologies in cancer survivorship care.

Introduction: Postpartum blues in 20% of cases develops into postnatal depression if it lasts longer than 14 days, so the condition requires attention. To help Slovenian midwives in screening for postpartum blues, we aimed to translate the Kennerly–Garth Blues Questionnaire (BQ). Methods: The blues questionnaire was translated using a double-blind translation method. The Cathedra for Midwifery at the Faculty Health Sciences Ljubljana reviewed the ethics and research design of the study. The online survey was conducted among Slovenian postpartum women who had to be between the 3rd and 15th day postpartum (inclusion criteria). A snowball sampling was used. The online questionnaire was active from January to March 2020. Women voluntarily participated in the survey and were assured of anonymity. Results: A total of 101 women participated in the study. More than half (58%) scored ≥7 points in the questionnaire, which is the cut-off score, indicating postpartum blues. More single women obtained a high score (66.6%) than those who were married (63.6%) or in an extramarital relationship (50.9%). High questionnaire scores were more common among women who had had their second child. Cronbach alpha for the Slovenian version of the Blues questionnaire was 0.995. Conclusions: The survey instrument can be used easily and quickly and is a good way to open discussion with women about emotional and mental health in the postnatal period. The Slovenian version of the Blues questionnaire showed a satisfactory level of internal consistency, but a larger study should be conducted to evaluate the cut-off score and the content validity

More than a year after the start of the COVID-19 pandemic, long-term neurological manifestations of COVID-19 are increasingly being reported. The long-term sequelae of COVID-19-related leukoencephalopathy, however, remain unclear. Here, we present long-term neuroimaging follow-up in two cases of COVID-19-related leukoencephalopathy. The two cases demonstrate the utility of brain MRI for evaluating neurologic symptoms in critically ill patients with COVID-19, for diagnosis of underlying neural injury and prognostication of future recovery. The presence of leukoencephalopathy may result in chronic neurologic manifestations and may represent a poor prognosticator of neurologic recovery. The presence of leukoencephalomalacia on follow-up neuroimaging is potentially an indicator of irreversible white matter damage, which may be associated with more severe chronic deficits.

Introduction Middle East Respiratory Syndrome (MERS) caused by MERS‐coronavirus (CoV) is a lower respiratory tract disease characterized by a high mortality rate. MERS‐CoV spread from Saudi Arabia to other countries, including South Korea. Dysfunction of the human leukocyte antigen (HLA) system has many effects due to genetic complexity and its role in the adaptive immune response. We investigated the association of HLA class I and II alleles with MERS‐CoV in 32 patients with MERS. Methods HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, and ‐DPB1 were genotyped by polymerase chain reaction sequence‐based typing. Results HLA‐DQB1*03:02 are significantly associated with moderate/mild cases of MERS‐CoV. Other alleles are no statistical significance. Conclusions Treatment strategies based on current research on the HLA gene and MERS‐CoV will provide potential therapeutic targets.

Background Medical care re-engagement is critical to suppressing viral load and preventing HIV transmission, morbidity and mortality, yet few rigorous intervention studies address this outcome. We assessed the effectiveness of a Ryan White Part A-funded HIV Care Coordination Program relative to ‘usual care,’ for short-term care re-engagement and viral suppression among people without recent HIV medical care. Methods The Care Coordination Program was launched in 2009 at 28 hospitals, health centers, and community-based organizations in New York City. Designed for people with HIV (PWH) experiencing or at risk for poor HIV outcomes, the Care Coordination Program provides long-term, comprehensive medical case management utilizing interdisciplinary teams, structured health education and patient navigation. The intervention was implemented as a safety-net services program, without a designated comparison group. To evaluate it retrospectively, we created an observational, matched cohort of clients and controls. Using the HIV surveillance registry, we identified individuals meeting program eligibility criteria from December 1, 2009 to March 31, 2013 and excluded those dying prior to 12 months of follow-up. We then matched clients to controls on baseline status (lacking evidence of viral suppression, consistently suppressed, inconsistently suppressed, or newly diagnosed in the past 12 months), start of follow-up and propensity score. For this analysis, we limited to those out of care at baseline (defined as having no viral load test in the 12 months pre-enrollment) and still residing within jurisdiction (defined as having a viral load or CD4 test reported to local surveillance and dated within the 12-month follow-up period). Using a GEE model with binary error distribution and logit link, we compared odds of care re-engagement (defined as having ≥ 2 laboratory events ≥ 90 days apart) and viral suppression (defined as having HIV RNA ≤ 200 copies/mL on the most recent viral load test) at 12-month follow-up. Results Among 326 individuals out of care at baseline, 87.2% of clients and 48.2% of controls achieved care re-engagement (Odds Ratio: 4.53; 95%CI 2.66, 7.71); 58.3% of clients and 49.3% of controls achieved viral suppression (Odds Ratio: 2.05; 95%CI 1.30, 3.23). Conclusions HIV Care Coordination shows evidence of effectiveness for care and treatment re-engagement.

Co-infections have a key role in virus transmission in wild reservoir hosts. We investigated the simultaneous presence of astroviruses, coronaviruses, and paramyxoviruses in bats from Madagascar, Mayotte, Mozambique, and Reunion Island. A total of 871 samples from 28 bat species representing 8 families were tested by polymerase chain reactions (PCRs) targeting the RNA-dependent RNA-polymerase genes. Overall, 2.4% of bats tested positive for the presence of at least two viruses, only on Madagascar and in Mozambique. Significant variation in the proportion of co-infections was detected among bat species, and some combinations of co-infection were more common than others. Our findings support that co-infections of the three targeted viruses occur in bats in the western Indian Ocean region, although further studies are needed to assess their epidemiological consequences. Supplementary Information The online version contains supplementary material available at 10.1186/s12985-021-01673-2.

Background Some studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt. Methods Single‐center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8–24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8‐week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re‐evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL). Results During OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all. Conclusion In this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

BackgroundAs a neurodegenerative disorder with high case-fatality, there is a need to identify primary, modifiable risk factors for amyotrophic lateral sclerosis (ALS). Their detection has, however, proved elusive and this may be ascribed to the scarcity of well-characterised, sufficiently-powered cohort studies necessary to explore the aetiology of this rare condition.MethodsUK Biobank is an on-going, closed, prospective cohort study in which 502,524 participants (273,420 women) have been linked to national hospital and mortality registries. Baseline data collection took place between 2006 and 2010 when a range of psychosocial, physiological, and demographic data were captured.ResultsApproximately 11 years of event surveillance gave rise to 301 hospitalisations and 279 deaths ascribed to ALS. After left censoring to account for reverse causality and adjustment for confounding factors, being older (hazard ratio per 10 year increase; 95% confidence interval: 1.92; 1.58, 2.33) and male (1.37; 1.00, 1.87) were associated with elevated rates of hospitalisation for ALS. Similar effects were apparent when death due to the disorder was the outcome of interest. Of the remaining 23 potential risk indices, however, there was only a suggestion that taller people experienced an increased risk of hospitalisation (per SD increase: 1.31; 1.09, 1.59).ConclusionsIn the present study, a comprehensive array of potential risk indices were essentially unrelated to later ALS.

Background Common mental disorders (CMD) are among the largest contributors to global maternal morbidity and mortality. Although research on perinatal mental health in India has grown in recent years, important evidence gaps remain, especially regarding CMD. Our study aims to improve understanding of CMD among perinatal and non-perinatal women of reproductive age across two settings in India: Bangalore (Karnataka) and Tanda (Himachal Pradesh). Methods The study is embedded within the Maternal and Perinatal Health Research Collaboration India (MaatHRI). This mixed-methods observational study comprises three consecutive phases: (i) focus group discussions and individual interviews to explore women’s knowledge and seek feedback on CMD screening tools; (ii) validation of CMD screening tools; and (iii) prospective cohort study to identify CMD incidence, prevalence and risk factors among perinatal and non-perinatal women. Results of the three phases will be analyzed using inductive thematic analysis, psychometric analysis and multivariable regression analysis, respectively. Conclusion Improving understanding, detection and management of CMD among women is key to improving women’s health and promoting gender equality. This study will provide evidence of CMD screening tools for perinatal and non-perinatal women in two diverse Indian settings, produce data on CMD prevalence, incidence and risk factors and enhance understanding of the specific contribution of the perinatal state to CMD.

INTRODUCTION: Addressing smokers who smoke in a voluntary smoke-free area is vital to its successful implementation. Many people perceive barriers in addressing smokers due to fear of negative responses. Insights in actual responses are currently lacking. METHODS: This is an observational field study at the voluntary smoke-free zone surrounding the Erasmus MC and two schools in Rotterdam, the Netherlands. In the first month after implementing the zone, Erasmus MC representatives performed rounds to address smokers who were smoking inside the zone. Four people observed addressors for two weeks then they also addressed the smokers. Smokers were classified as employees, patients, students, or other. We noted whether smokers were addressed directly or indirectly, and their verbal and behavioral responses to being addressed. Differences between the responses of the groups were assessed using chi-squared tests. RESULTS: In all, 331 smokers were observed of whom 73% were addressed directly. Most verbal reactions were positive (46%) or neutral (18%). Employees were more likely to respond guiltily, whereas patients more often responded angrily than the others. After being addressed, the majority of smokers either extinguished their cigarette (41%) or left to continue smoking outside the smoke-free zone (34%). CONCLUSIONS: Most smokers showed a positive or neutral response when being addressed about smoking inside the smoke-free zone and the majority adapted their behavior to comply with the policy. These findings may help decrease barriers for those in doubt about addressing smokers that fail to comply with a smoke-free policy. ispartof: TOBACCO PREVENTION & CESSATION vol:7 ispartof: location:Greece status: published

The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+ cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemagglutinin that also correlated with disease severity. In summary, our data suggest that the consequences of disease severity account for the changes in PD T cells, rather than age, age of onset, duration or the disease progression rate.

We here described a ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone (YL201) with moderate-level resistance to azithromycin in Shenzhen, South China in 2020. The NG-STAR type of YL201 is ST2238, containing a mosaic penA-60.001 allele, which is a typical characteristic of FC428 clone. YL201 harbours four copies of the 23S rRNA C2611T mutation, conferring moderate-level resistance to azithromycin. The MLST type is ST1600, identical with two N. gonorrhoeae FC428 clones identified in Hangzhou. Genome-wide phylogeny analysis demonstrates that YL201 is clustered with other FC428 clones from Hangzhou (South-east China) and Chengdu (South-west China). Isolates within this cluster have relatively higher MIC for ceftriaxone and display closely related MLST STs (ST1600 and ST7363) but are different from the ST of typical FC428 clone (ST1903). As ST1600 and ST7363 are common STs in Shenzhen, the further spread of FC428 clones may increase the severity of gonococcal resistance. In summary, identifying a multidrug-resistant (MDR) N. gonorrhoeae isolate in Shenzhen showed FC428 clones have undergone further transmission in China and presented more extensive and concerning antimicrobial resistance (AMR) characteristics during the spread.

Background The ability to track individual immune cells within the central nervous system has revolutionized our understanding of the roles that microglia and monocytes play in synaptic maintenance, plasticity, and neurodegenerative diseases. However, distinguishing between similar subpopulations of mobile immune cells over time during episodes of neuronal death and tissue remodeling has proven to be challenging. Methods We recombineered a photoconvertible fluorescent protein (Dendra2; D2) downstream of the Cx3cr1 promoter commonly used to drive expression of fluorescent markers in microglia and monocytes. Like the popular Cx3cr1–GFP line (Cx3cr1+/GFP), naïve microglia in Cx3cr1–Dendra2 mice (Cx3cr1+/D2) fluoresce green and can be noninvasively imaged in vivo throughout the CNS. In addition, individual D2-expressing cells can be photoconverted, resulting in red fluorescence, and tracked unambiguously within a field of green non-photoconverted cells for several days in vivo. Results Dendra2-expressing retinal microglia were noninvasively photoconverted in both ex vivo and in vivo conditions. Local in vivo D2 photoconversion was sufficiently robust to quantify cell subpopulations by flow cytometry, and the protein was stable enough to survive tissue processing for immunohistochemistry. Simultaneous in vivo fluorescence imaging of Dendra2 and light scattering measurements (Optical Coherence Tomography, OCT) were used to assess responses of individual microglial cells to localized neuronal damage and to identify the infiltration of monocytes from the vasculature in response to large scale neurodegeneration. Conclusions The ability to noninvasively and unambiguously track D2-expressing microglia and monocytes in vivo through space and time makes the Cx3cr1–Dendra2 mouse model a powerful new tool for disentangling the roles of distinct immune cell subpopulations in neuroinflammation. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02285-x., Key points New mouse for tracking microglia and all mononuclear phagocytes both ex and in vivo within the CNS over time.Dendra2 protein is stable enough to survive tissue processing for immunohistochemistry and flow cytometry quantification.Simultaneous fluorescence imaging of Dendra2 and light scattering measurements can be used to assess the immune response to retinal damage.Chronic in vivo imaging reveals mixed populations of microglia and monocytes during retinal degeneration. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-021-02285-x.

Concomitant prevention of SARS-CoV-2 and extensively drug-resistant bacteria transmission is a difficult challenge in intensive care units dedicated to COVID-19 patients. We report a nosocomial cluster of four patients carrying NDM-1 plasmid-encoded carbapenemase-producing Enterobacter cloacae. Two main factors may have contributed to cross-transmission: misuse of gloves and absence of change of personal protective equipment, in the context of COVID-19-associated shortage. This work highlights the importance of maintaining infection control measures to prevent CPE cross-transmission despite the difficult context and that this type of outbreak can potentially involve several species of Enterobacterales. Supplementary Information The online version contains supplementary material available at 10.1186/s13756-021-01022-6.

Background It has been demonstrated that children who had been breastfed remain better protected against various infections, and notably respiratory tract infections, well beyond infancy. Since the role of breastfeeding to explain why children are less affected by COVID-19 has not been studied until now, the aim of this study was to determine whether any history of breastfeeding reduces the incidence rate of COVID-19 in children. Methods This was a secondary analysis of an observational study on clinical and epidemiological characteristics of pediatric COVID-19 in Majorca. A total of 691 children were recruited during the 5 months of August–December 2020. Eligible participants were children under 14 who were tested for SARS-CoV-2 in pediatric emergency services. The independent explanatory variable was any breastfeeding. Bivariate analyses were conducted through the Chi-square test, the Fisher’s Exact test or the Student’s T test. All children had the same demographic, epidemiological and clinical data collected through a study team member interview and via the participants medical records. Results Within the sample of children who visited emergency services with symptoms of potential COVID-19, we found higher prevalence of positive SARS-CoV-2 RT-PCR test results among those who were exclusively formula fed compared with those who were ever breastfed (OR 2.48; 95% CI 1.45, 3.51; P = 0.036). Conclusions The present study suggests that ever breastfeeding reduces the risk of COVID-19 among children, as documented for other infections.

The emergence of the Asian invasive malaria vector, Anopheles stephensi, has been identified in Khartoum, the capital city of Sudan. This is the first report that confirms the geographical expansion of this urban mosquito into Central Sudan. We urgently recommend the launch of a national entomological survey to determine the distribution of this invasive disease vector and to generate essential information about its bionomics and susceptibility to available malaria control measures. Graphical Abstract

Background Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD). Methods Dogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC Results Of the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563). Conclusions This study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD. Graphical abstract

Background Through an arsenal of microbial enzymes, the gut microbiota considerably contributes to human metabolic processes, affecting nutrients, drugs, and environmental poisons. Azoreductases are a predominant group of microbiota-derived enzymes involved in xenobiotic metabolism and drug activation, but little is known about how compositional changes in the gut microbiota correlate with its azo-reducing activity. Results To this end, we used high-throughput 16S rRNA amplicon sequencing, with Illumina MiSeq, to determine the microbial community composition of stool samples from 16 adults with different azo-reducing activity. High azo-reducing activity positively correlated with the relative abundance of phylum Firmicutes (especially genera Streptococcus and Coprococcus) but negatively with phylum Bacteroidetes (especially genus Bacteroides). Typical variations in the Firmicutes-to-Bacteroidetes and Prevotella-to-Bacteroides ratios were observed among samples. Multivariate analysis of the relative abundance of key microbial taxa and other diversity parameters confirmed the Firmicutes proportion as a major variable differentiating high and non-azo-reducers, while Bacteroidetes relative abundance was correlated with azo-reduction, sex, and BMI. Conclusions This pilot study showed that stool samples with higher azo-reducing activity were enriched in Firmicutes but with relatively fewer Bacteroidetes. More samples and studies from different geographical areas are needed to bolster this conclusion. Better characterization of different azoreductase-producing gut microbes will increase our knowledge about the fate and differential human responses to azodye-containing drugs or orally consumed chemicals, thus contributing to efforts towards implementing microbiome testing in precision medicine and toxicology.

Introduction Some but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We hypothesized that different factors are involved in the severity of ACD and AD. Recently we reported that hsa‐miR‐628‐3p could affect the balance of innate immunity by suppressing pathogen‐associated molecular patterns such as toll‐like receptor 3 (TLR3), RIG‐I, and MDA‐5. We also reported that TLR3 positively regulates ocular surface‐ and skin inflammation such as contact dermatitis and AD. Here we compared the plasma level of miR‐628‐3p in AD patients with severe AKC with giant papillae and/or shield ulcers, with the level in healthy controls and AD patient without AKC or with very mild AKC. Methods We used the plasma from 32 AD patients with severe AKC, from 40 healthy controls, and from 23 AD patient without AKC or with very mild AKC without giant papillae nor shield ulcers. Quantitative microRNA PCR assays were used to measure their plasma level of miR‐628‐3p. Results We found that plasma miR‐628‐3p was upregulated in AD with severe AKC, but not in severe AD without severe AKC, nor in our healthy controls. Conclusion Our new findings suggest that the plasma miR‐628‐3p level may represent a marker to predict the presence of severe AKC in AD patients.