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The fungus Blumeria graminis f. sp. tritici causes wheat powdery mildew disease. Here, we study its spread and evolution by analyzing a global sample of 172 mildew genomes. Our analyses show that B.g. tritici emerged in the Fertile Crescent during wheat domestication. After it spread throughout Eurasia, colonization brought it to America, where it hybridized with unknown grass mildew species. Recent trade brought USA strains to Japan, and European strains to China. In both places, they hybridized with local ancestral strains. Thus, although mildew spreads by wind regionally, our results indicate that humans drove its global spread throughout history and that mildew rapidly evolved through hybridization.

Funder: China Scholarship Council, Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here we examine the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) in type 1 diabetes using high-resolution single-cell multiomics and flow cytometry on longitudinally-collected peripheral blood samples. Our results confirm that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+ regulatory T cells and CD56bright NK cells, and show that the treatment reduces the frequency of IL-21-producing CD4+ T cells and of two innate-like mucosal-associated invariant T and Vγ9Vδ2 CD8+ T cell subsets. The cellular changes induced by iLD-IL-2 associate with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. These findings warrant investigations into the potential longer-term clinical benefits of iLD-IL-2 in immunotherapy., This work was supported by the Sir Jules Thorn Trust (13/JTA (OCT2013/DR/1044)), the JDRF (1-SRA-2019-657-A-N), and the NIHR Cambridge Biomedical Research Centre. The Diabetes and Inflammation Laboratory was supported by a strategic award from the Wellcome (107212/A/15/Z) and the JDRF (4-SRA-2017-473-A-A). JYZ was supported by the China Scholarship Council-University of Oxford Scholarship. The research was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with additional support from the NIHR Oxford BRC. The University of Cambridge has received salary support for ME through the National Health Service in the East of England through the Clinical Academic Reserve. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Purpose Osteopenia is common in postmenopausal women and effective interventions increasing or stabilizing bone mineral density (BMD) to prevent fractures are urgently needed. Methods Sixty-five postmenopausal women diagnosed with osteopenia (T-score between -1.0 and -2.5) were randomly assigned to either a vibration training group (VT), a resistance training group (RT), or a control group (CG). BMD T-score values (primary endpoint) were assessed at baseline (T0) and after 12 months (T12), secondary endpoints (muscle strength, postural control, and health-related quality of life) at baseline (T0), after 6 months (T6), after 12 months (T12), and as follow-up after 15 months (T15). Results After the intervention period, neither the VT nor the RT showed any significant changes in BMD T-score values compared to the CG. Isokinetic strength improved significantly within all training groups, with the exception of the flexors of VT at an angular velocity of 240°/s. Health-related quality of life as well as postural control improved significantly for the RT only. Conclusions We conclude that participants of all three groups were able to maintain their BMD. The improvements in quality of life and postural control after resistance training are nevertheless meaningful for postmenopausal osteopenic women and support the importance of regular loadings of the musculoskeletal system. This study was retrospectively registered in January 2022 at the DRKS (S00027816) as clinical trial.

C-peptide declines in type 1 diabetes, although many long-duration patients retain low, but detectable levels. Histological analyses confirm that β-cells can remain following type 1 diabetes onset. We explored the trends observed in C-peptide decline in the UK Genetic Resource Investigating Diabetes (UK GRID) cohort (N = 4,079), with β-cell loss in pancreas donors from the network for Pancreatic Organ donors with Diabetes (nPOD) biobank and the Exeter Archival Diabetes Biobank (EADB) (combined N = 235), stratified by recently reported age at diagnosis endotypes (

Our objective was to investigate three levels of resilience (low, medium, and high), identify associated characteristics, and measure the impact of increasing resilience on quality of life (QOL), healthcare utilization and expenditures, and preventive services compliance. The study sample was identified from adults age ≥65 who completed surveys during May-June 2019 (N=3,573). Other protective factors, including purpose-in-life, optimism, locus of control, and social connections, were dichotomized as high/low and counted with equal weighting (0 to 4). Among survey respondents, the prevalence of low, medium, and high resilience levels was 27%, 29%, and 44%, respectively. The strongest predictors of medium and high resilience included increasing number of other protective factors, lower stress, and no depression. Individuals with medium and high resilience had significantly higher QOL and lower healthcare utilization and expenditures. Resilience strategies integrated into healthy aging programming could be associated with improvements in QOL and/or healthcare utilization and expenditure outcomes.

Background Wolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, presents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age. In clinical trials, enzyme replacement therapy (ERT) with sebelipase alfa led to improved survival, growth and biological parameters in WD patients followed up to 5 years. Long-term follow-up and health-related quality of life (HRQoL) evaluation are lacking. Results We performed a nationwide, retrospective study of sebelipase alfa in WD patients. Five patients with abolished LAL activity and bi-allelic LIPA mutations were included with a median follow-up of 7 years (1–10). ERT was initiated at a median age of 1 month (0–4). Infusion tolerance was excellent on the long-term with only one patient requiring systematic pre-medication. Cholestyramine, fat-soluble vitamin supplements and a specific diet (high in medium-chain triglycerides and low in long-chain fatty acids) were prescribed. Liver function tests, plasma lipid profiles, fat-soluble vitamin levels and growth parameters improved. Three patients transiently exhibited a neuromyopathic phenotype (footdrop gait, waddling walk or muscle fatigue) but electromyography and muscle strength testing were normal. At last follow-up, all patients were alive with normal growth parameters and a satisfactory HRQoL, no patient had special education needs, and one patient required parenteral nutrition since an acute gastroenteritis. Conclusions Early ERT initiation allowed 100% survival with positive outcomes. Very long-term follow-up and hematopoietic stem cell transplantation while on ERT should be evaluated to strengthen the benefits of sebelipase alfa.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe cardiorespiratory collapse. Although prior large database reviews of ECMO use in the peripartum population exist, they do not stratify by ECMO indication nor do they include obstetric conditions such as preeclampsia. Our objective was to characterize the incidence, indication-associated mortality, and factors associated with mortality in pregnant patients who underwent ECMO. METHODS: We examined the United States National Inpatient Sample database to identify hospitalizations for pregnancy from January 1, 2010 to December 31, 2016. We identified pregnant patients who underwent ECMO using International Classification of Diseases ninth and tenth revisions codes. The primary outcome was in-hospital all-cause mortality across pregnant patients who underwent ECMO for any indication. We evaluated the indication for ECMO, incidence, prevalence of risk factors, comorbidities and conditions, and their association with in-hospital mortality. RESULTS: Fifty-nine of 5'346,517 pregnant patients underwent ECMO during our study period (incidence, 1.1; 95% confidence interval [CI], 0.84-1.4 per 100,000 hospitalizations). Indications for ECMO support included respiratory failure (79.7%), cardiogenic shock (64.4%), or circulatory arrest (25.4%). Most patients (57.6%) had more than 1 indication. The overall in-hospital mortality rate was 30.5%. Mortality was 29.8% in patients with respiratory failure, 39.5% with cardiogenic shock, 46.7% with cardiac arrest, and 42.4% in those with combined diagnoses. Cardiogenic shock was associated with a significantly higher mortality rate and adjusted odds ratio 5.0 (95% CI, 1.25-27.0). Most patients (62.7%) had one or more comorbidities. CONCLUSIONS: The frequency of ECMO use across the pregnant population was low over this time period, with a mortality rate of 1 in 3 patients. Mortality was greatest in patients with cardiogenic shock. Further work is needed to understand how best to improve ECMO outcomes in pregnant patients.

Healthcare personnel (HCP) have an occupation-related risk of an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can transmit COVID-19 to patients. The related occupational disease is the BK 3101.The frequency of suspected claims of occupation-related SARS-CoV‑2 infections and confirmed claims of COVID-19 occupational diseases, reporting obligations under the German Infection Protection Act (IfSG) and mandatory notification requirements of physicians.Selective literature search with special respect to data of accident insurance institutions regarding occupation-related SARS-CoV‑2 infections among HCP.The SARS-CoV‑2 pandemic also represents a challenge for occupational healthcare and the public health service. In recent months an increased number of suspected cases of an occupational disease (BK 3101) associated with COVID-19 were registered at the accident insurance institutions as well as notifications of accidents at work. The public health service handles registrations under the IfSG and coordinates the tracking of contact persons.Occupation-related SARS-CoV‑2 infections are a real reason for concern. The registration data of the accident insurance institutions confirm high case numbers. Preventive measures, such as wearing personal protective equipment (PPE) and COVID-19 vaccinations significantly reduce the risk of infection among HCP as well as the risk of nosocomial transmission to patients.HINTERGRUND: Medizinisches Personal hat ein arbeitsbedingtes Risiko für eine Infektion mit dem „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV‑2) und kann COVID‑19 auf Patienten übertragen. Bei der zugehörigen Berufskrankheit handelt es sich um die BK 3101.Häufigkeit von Verdachtsmeldungen berufsbedingter SARS-CoV-2-Infektionen und anerkannter COVID-19-Berufskrankheiten, Meldepflichten nach Infektionsschutzgesetz (IfSG) und Anzeigepflichten des Arztes.Selektive Literaturrecherche unter besonderer Berücksichtigung von Daten der Unfallversicherungsträger zu arbeitsbedingten SARS-CoV-2-Infektionen des medizinischen Personals.Die SARS-CoV-2-Pandemie stellt sich auch als Herausforderung der Arbeitsmedizin und des Öffentlichen Gesundheitsdienstes (ÖGD) dar. In den letzten Monaten wurden bei den Unfallversicherungsträgern im Zusammenhang mit COVID-19 vermehrt Verdachtsfälle einer Berufskrankheit (BK 3101) sowie eine steigende Zahl von Arbeitsunfallmeldungen registriert. Der ÖGD bearbeitet die Meldungen gemäß dem IfSG und koordiniert die Kontaktpersonennachverfolgung.Arbeitsbedingte SARS-CoV-2-Infektionen geben Anlass zur Sorge. Die Meldedaten der Unfallversicherungsträger belegen hohe Fallzahlen. Präventive Maßnahmen, z. B. das Tragen der persönlichen Schutzausrüstung (PSA) und COVID-19-Impfungen, reduzieren sowohl das Infektionsrisiko der Beschäftigten signifikant als auch das Risiko einer nosokomialen Übertragung auf die Patienten.

Objective The nucleus reticularis of the thalamus (nRT) is most studied in epilepsy for its role in the genesis of absence seizures; much less is known regarding its role in other seizure types, including those originating in limbic structures and the temporal lobe. As it is a major source of inhibitory input to higher order thalamic nuclei, stimulation of the nRT may be an effective strategy to disrupt seizure activity that requires thalamic engagement. Methods We recorded single unit activity from the nRT prior to and after infusion of bicuculline into the area tempestas. We monitored single unit activity time-locked with interictal spikes. We optogenetically activated the nRT in both the area tempestas and amygdala kindling models. We tested a role for projections from the nRT to higher order midline thalamic nuclei through the use of retrogradely trafficked viral vector. Results Mean firing rate in the nRT was decreased after infusion of bicuculline into the area tempestas as compared to the preinfusion baseline. nRT unit firing in response to interictal spikes was heterogeneous, with an approximately equal proportion of neurons displaying (1) no change in firing, (2) increased firing, and (3) decreasing firing. Optogenetic activation of the nRT significantly suppressed seizure activity in both the area tempestas and amygdala kindling models. Optogenetic activation of contralaterally targeting projections but not ipsilaterally targeting projections from the nRT to the midline thalamus significantly suppressed seizures in the kindling model. Significance Although the nRT is typically thought of in the context of absence seizures, our data show that it may be a viable target for other seizure types. In two models that recapitulate the seizure types seen in temporal lobe epilepsy, nRT activation suppressed both electrographic and behavioral seizures. These data suggest that the nRT should be considered more broadly in the context of epilepsy.

Depletion of the enzyme cofactor, tetrahydrobiopterin (BH4), in T-cells was shown to prevent their proliferation upon receptor stimulation in models of allergic inflammation in mice, suggesting that BH4 drives autoimmunity. Hence, the clinically available BH4 drug (sapropterin) might increase the risk of autoimmune diseases. The present study assessed the implications for multiple sclerosis (MS) as an exemplary CNS autoimmune disease. Plasma levels of biopterin were persistently low in MS patients and tended to be lower with high Expanded Disability Status Scale (EDSS). Instead, the bypass product, neopterin, was increased. The deregulation suggested that BH4 replenishment might further drive the immune response or beneficially restore the BH4 balances. To answer this question, mice were treated with sapropterin in immunization-evoked autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Sapropterin-treated mice had higher EAE disease scores associated with higher numbers of T-cells infiltrating the spinal cord, but normal T-cell subpopulations in spleen and blood. Mechanistically, sapropterin treatment was associated with increased plasma levels of long-chain ceramides and low levels of the poly-unsaturated fatty acid, linolenic acid (FA18:3). These lipid changes are known to contribute to disruptions of the blood–brain barrier in EAE mice. Indeed, RNA data analyses revealed upregulations of genes involved in ceramide synthesis in brain endothelial cells of EAE mice (LASS6/CERS6, LASS3/CERS3, UGCG, ELOVL6, and ELOVL4). The results support the view that BH4 fortifies autoimmune CNS disease, mechanistically involving lipid deregulations that are known to contribute to the EAE pathology. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01043-4.

Purpose Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) replicates predominantly in the upper respiratory tract and is primarily transmitted by droplets and aerosols. Taking the medical history for typical COVID-19 symptoms and PCR-based SARS-CoV-2 testing have become established as screening procedures. The aim of this work was to describe the clinical appearance of SARS-CoV-2-PCR positive patients and to determine the SARS-CoV-2 contact risk for health care workers (HCW). Methods The retrospective study included n = 2283 SARS-CoV-2 PCR tests from n = 1725 patients with otorhinolaryngological (ORL) diseases performed from March to November 2020 prior to inpatient treatment. In addition, demographic data and medical history were assessed. Results n = 13 PCR tests (0.6%) were positive for SARS-CoV-2 RNA. The positive rate showed a significant increase during the observation period (p n = 4) or had symptoms that were interpreted as symptoms typical of the ORL disease or secondary diagnoses (n = 9). Conclusion The identification of SARS-CoV-2-positive patients is a considerable challenge in clinical practice. Our findings illustrate that taking a medical history alone is of limited value and cannot replace molecular SARS-CoV-2 testing, especially for patients with ORL diseases. Our data also demonstrate that there is a high probability of contact with SARS-CoV-2-positive patients in everyday clinical practice, so that the use of personal protective equipment, even in apparently “routine cases”, is highly recommended.

As active learning is being encouraged in pharmacy education, valid active learning pedagogies should be investigated. Peer instruction pedagogy has yet to be explored in the pharmacy education setting. Peer instruction assesses student understanding of a topic through multiple choice questions called ConcepTests. When the class scores below a threshold, students are given time to discuss the ConcepTest. They are then given an opportunity to repeat the same ConcepTest.Peer instruction pedagogy was implemented in the 2017 fall semester of PHAR 6112: Introduction to Self-Care. Changes in student responses were recorded via Turning Technologies software to identify if peer instruction increased the number of students who answered ConcepTests correctly. Changes in responses were analyzed via a paired t-test and McNemar test. Students were also surveyed on their perceptions of the pedagogy.A total of 51 questions proceeded through the entirety of the peer instruction algorithm. Peer instruction was associated with an increase in correct response (P .001). Students' total number of correct responses to ConcepTest questions increased by an average of 16.1 (31.5%) following peer instruction (P.001). Over 86% of students would recommend that other instructors use ConcepTests.Peer instruction resulted in an increase in correct responses to session ConcepTests. This pedagogy has potential as an active learning method to deliver pharmacy material.

This clinical study evaluated the reliability of the 1,1,1,2-tetrafluoroethane (Endo Ice) cold test to determine the pulpal diagnosis of teeth with full-coverage restorations (FCR). The effect of several variables on its reliability was also investigated.Data collected from 825 patients treated in the Advanced Education Program in Endodontics at the University of Iowa, USA were analysed. The experimental group included 425 teeth with FCR, whilst the control group consisted of 400 teeth with natural crowns (NC). The pulp sensibility test results, tooth type, tooth number, type of crown, age, gender, presence or absence of caries and recent use of analgesics were recorded. Bivariate analyses were performed to assess the variables associated with the accuracy of dental pulp sensibility tests for either teeth with crowns or teeth without crowns using chi-square tests, Fisher's exact tests, Cochran-Mantel-Haenszel tests, and the Wilcoxon rank-sum tests. A P-value of less than 0.05 was used as a criterion for statistical significance, and a P-value in 0.05 P 0.10 was used as a criterion for marginal relevance.The sensibility test results for FCR teeth had an accuracy of 0.866; sensitivity of 0.835; specificity of 0.879; a positive predictive value of 0.746; and a negative predictive value of 0.926. The data indicated a significant difference in the accuracy of pulp sensibility test results between the experimental and control groups (P 0.001). Although the cold test in FCR teeth still had high accuracy, teeth with NC were significantly more likely to have true-positive and true-negative results (91.5% NC vs. 86.6% FCR, P = 0.024). No significant differences between FCR and NC were found concerning gender, tooth type, type of crown, the presence of abutment and recent use of analgesic (P 0.05).Pulp sensibility cold testing with 1,1,1,2-tetrafluoroethane (TFE) on teeth with FCR was less accurate than on teeth without full-coverage crowns. However, the use of TFE cold testing is still a relevant and reliable diagnostic tool, particularly for teeth with a pulpal diagnosis of symptomatic irreversible pulpitis. Clinicians should routinely carry out cold pulp sensibility testing on teeth when making a pulpal diagnosis.

Objective. This study aimed to provide further validity evidence for the KCES by analyzing data collected from multiple administrations of the KCES along with cognitive interviews of students in pharmacy and nursing programs to identify revisions of the Kiersma-Chen Empathy Scale: The KCES– Revised (KCES-R). Methods. De-identified data from previous KCES administrations were used for scale evaluation. Response process validity evidence was enhanced through cognitive interviews with 20 pre-pharmacy/pharmacy students at Cedarville University. After survey revisions, the cognitive interview process was repeated with 10 University of Wyoming nursing students. Results. Based on psychometric data and cognitive interviews, the KCES was revised as follows: (1) key components of cognitive and affective empathy were retained, (2) scaling was changed to reflect necessity and empathy ability, (3) negatively-worded items were removed, and (4) instrument was changed to two parallel subscales. Conclusion. This study used data from thousands of geographically and professionally diverse samples. Based on potential problems identified in quantitative analyses, cognitive interviews with nursing and pharmacy students were conducted, and modifications to the KCES were made. Further psychometric validation is needed regarding the KCES-R.

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.

The primary objectives were to investigate the association of physical activity levels with 1) loneliness and social isolation; 2) protective factors: resilience, purpose-in-life, and perception of aging; and 3) the impact of these factors on healthcare expenditure patterns across physical activity levels. The study sample was identified from adults age ≥65 who completed a health survey in 2018 or 2019 (N=6,652). Among survey respondents, the prevalence of low, moderate, and high physical activity levels was 29%, 31%, and 41%, respectively. Moderate and high physical activity were associated with 15%-30% lower likelihoods of loneliness and social isolation; and with 27% to 150% higher protective factors. In addition, physical activity was associated with the mitigation of increased healthcare expenditures associated with loneliness, social isolation, and low levels of protective factors. Thus, physical activity could serve as an intervention to reduce loneliness and social isolation, augment protective factors, and mitigate excess healthcare expenditures.

The adoptive transfer of regulatory T-cells (Tregs) is a promising therapeutic approach in transplantation and autoimmunity. However, because large cell numbers are needed to achieve a therapeutic effect, in vitro expansion is required. By comparing their function, phenotype and transcriptomic profile against ex vivo Tregs, we demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A) driven acquisition of CD73 expression. In conjunction with CD39, CD73 expression enables expanded Tregs to convert ATP to immunosuppressive adenosine. We conclude that for maximum therapeutic benefit, Treg expansion protocols should be optimised for CD39/CD73 co-expression., Jarvis et al demonstrate that expanded human Tregs switch their metabolism to aerobic glycolysis and show enhanced suppressive function through hypoxia-inducible factor 1-alpha (HIF1A)-driven acquisition of CD73 expression, which along with CD39, enables expanded Tregs to convert ATP to immunosuppressive adenosine. Given this, the data suggests that Treg expansion protocols should be optimised for CD39/CD73 co-expression to enhance therapeutic potential.

The majority of patients undergoing bariatric surgery have hepatic steatosis. Liver biopsy is not technically difficult to perform at the time of metabolic and bariatric surgery (MBS), but there may be concerns for bleeding complications. The safety of liver biopsy (LBx) at the time of MBS has been studied in single institutional studies but has not been studied on a national level. The MBSAQIP database for 2015–2018 was examined. The codes for Roux-en-Y gastric bypass (RYGB) of 43644 and sleeve gastrectomy (SG) 43775 were used along with 47000 (percutaneous liver biopsy), 47001 (percutaneous liver biopsy at time of other procedure), and 47379 (unlisted laparoscopic procedure, liver). Outcomes such as operative time, complications, and length of stay were examined. Propensity-matched analysis was performed to evaluate for adjusted associations. There were 546,532 patients that met our inclusion criteria. Of those, 21,367 (3.9%) underwent LBx. Only 5.5% (8012) of patients undergoing RYGB had a LBx and 3.3% (13,355) of SG patients. Patients who underwent a LBx had a longer operative time before (103 min vs 84 min, p < 0.001) and after propensity matching [regression coefficient (RC): 10.7 (8.87, 12.5)]. There was no increase in length of stay. There was an increased risk in mortality in the unadjusted analysis (prevalence ratio = 1.61, p = 0.02), but when propensity-matched analysis was done, there was no statistically significant difference between the two groups. Concerning bleeding or transfusion, there was no difference in bleeding or rates of transfusion (p= 0.22, p = 0.21). Liver biopsy at the time of MBS is safe. It adds operative time, but there is no increase in length of stay, bleeding complications, morbidity, or death.

For neonates, group B Streptococcus is life threatening. Current prevention strategies remain insufficient, especially for cases of late-onset sepsis, where intrapartum antibiotic prophylaxis has demonstrated no benefit. One promising approach is the vaccination of pregnant women, which offers protective immunity via transplacental transmission of neutralizing antibodies. Our nationwide, prospective surveillance study aimed to characterize the prevalence of pilus antigen, capsular polysaccharide serotypes, and antibiotic resistance from invasive GBS infections in neonates and compare these results with those from children and adults in Germany. Our study includes 173 neonatal isolates of a total of 450 reported cases during the study period (incidence: 0.34/1000 live births), in addition to 2 pediatric and 803 adult isolates. The comparison between neonatal and adult isolates reveals age-dependent differences in capsular serotype and pilus type distribution and differences in antibiotic resistance patterns.

Health-care workers are an important vaccination target group, they are more frequently exposed to infectious diseases and can contribute to nosocomial infections. We established a country-wide online monitoring system to estimate influenza vaccine uptake and its determinants among German hospital staff (OKaPII). The online questionnaire included items on vaccination behavior and reasons for and against influenza vaccination. After a pilot phase in 2016, a country-wide roll-out was performed in 2017. Questions on measles (2018) and hepatitis B (2019) vaccination status were added in subsequent years. In 2017, 2018 and 2019 in total 52, 125 and 171 hospitals with 5 808, 17 891 and 27 163 employees participated, respectively. Influenza vaccination coverage in season 2016/17 and 2017/18 was similar (39.5% and 39.3%) while it increased by 12% in 2018/19 (52.3%). Uptake was higher for physicians than for nurses. Self-protection was the most common reason for influenza vaccination. While physicians mainly identified constraints as reasons for being unvaccinated, nurses mainly referred to a lack of vaccine confidence. Of the hospital staff, 87.0% were vaccinated against measles, 6.3% claimed to be protected due to natural infection; 97.7% were vaccinated against hepatitis B. OKaPII shows that influenza vaccination coverage among German hospital staff is low. Occupational group-specific differences should be considered: physicians might benefit from easier access; information campaigns might increase nurses’ vaccine confidence. OKaPII serves as a platform to monitor the uptake of influenza and other vaccines; it also contributes to a better understanding of vaccination behavior and planning of targeted interventions.

Objective The primary purpose of this study was to explore the efficacy of robotic pets in alleviating loneliness for older adults. Method Self-reported lonely individuals with AARP Medicare Supplement plans insured by UnitedHealthcare who participated in a program with a robotic pet (n = 20) were recruited to participate in semi-structured interviews. Participants were asked to provide feedback about their experiences interacting with a robotic pet, their perceptions about the potential impact on loneliness, and recommendations for improving the program. Interviews were audio-recorded and transcribed verbatim. Participants’ responses were analyzed using qualitative content analysis. Constant comparison and consensus-gaining processes were used to develop categories that later formed representative themes. Results Seven themes emerged from analysis: Openness to Adoption of Robotic Pet, Reactions to Pet and its Attributes, Integration of Pet in Daily Life, Strategic Utilization and Forging New Connections, Deriving Comfort and Camaraderie, Advice for Future Users, and Recommendations for Enhancing Ownership Experience. Participants living alone, with fewer social connections and less active lifestyles, derived the most benefit from interacting with their pets. Common responses to pets included cuddling, petting, grooming, and sleeping with them. Some shared or loaned their pets, while others refused to loan their pets to interested peers. Most reported showing their pets to others, which helped some facilitate communication and social connections. Conclusion Robotic pets may be an effective solution for alleviating loneliness in older adults, especially among those who live alone, have fewer social connections, and live less active lifestyles.

Background Parkinson's disease (PD) causes chronic pain in two-thirds of patients, in part originating from sensory neuropathies. The aim of the present study was to describe the phenotype of PD-associated sensory neuropathy and to evaluate its associations with lipid allostasis, the latter motivated by recent genetic studies associating mutations of glucocerebrosidase with PD onset and severity. Glucocerebrosidase catalyzes the metabolism of glucosylceramides. Methods We used quantitative sensory tests, pain ratings, and questionnaires and analyzed plasma levels of multiple bioactive lipid species using targeted lipidomic analyses. The study comprised 2 sets of patients and healthy controls: the first 128 Israeli PD patients and 224 young German healthy controls for exploration, the second 50/50 German PD patients and matched healthy controls for deeper analyses. Results The data showed a 70% prevalence of PD pain and sensory neuropathies with a predominant phenotype of thermal sensory loss plus mechanical hypersensitivity. Multivariate analyses of lipids revealed major differences between PD patients and healthy controls, mainly originating from glucosylceramides and endocannabinoids. Glucosylceramides were increased, whereas anandamide and lysophosphatidic acid 20:4 were reduced, stronger in patients with ongoing pain and with a linear relationship with pain intensity and sensory losses, particularly for glucosylceramide 18:1 and glucosylceramide 24:1. Conclusions Our data suggest that PD-associated sensory neuropathies and PD pain are in part caused by accumulations of glucosylceramides, raising the intriguing possibility of reducing PD pain and sensory loss by glucocerebrosidase substituting or refolding approaches. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Zusammenfassung Hintergrund Männer in Deutschland sterben früher als Frauen und nehmen weniger häufig Krebsvorsorgeuntersuchungen wahr. Fragestellung Ziel war die prospektive Evaluation einer „Movember-Gesundheitsinitiative“ am Universitätsklinikum Frankfurt (UKF) im November 2019. Methoden Im Rahmen der „Movember-Gesundheitsinitiative“ wurde allen männlichen Mitarbeitern des UKF ab dem 45. Lebensjahr und bei erstgradiger familiärer Vorbelastung eines Prostatakarzinoms ab dem 40. Lebensjahr im November 2019 gemäß S3-Leitlinien der Deutschen Gesellschaft für Urologie (DGU) eine Prostatakarzinom-Vorsorgeuntersuchung angeboten. Ergebnisse Insgesamt nahmen 14,4 % der Mitarbeiter teil. Eine familiäre Vorbelastung gaben insgesamt 14,0 % Teilnehmer an. Das mediane Alter betrug 54 Jahre. Der mediane PSA(prostataspezifisches Antigen)-Wert lag bei 0,9 ng/ml, der mediane PSA-Quotient bei 30 %. Bei 5 % (n = 6) zeigte sich ein suspekter Tastbefund in der DRU (digital-rektale Untersuchung). Nach Altersstratifizierung (≤ 50 vs. > 50 Lebensjahre) zeigten sich signifikante Unterschiede im medianen PSA-Wert (0,7 ng/ml vs. 1,0 ng/ml, p p Schlussfolgerungung Im Rahmen der UKF-Movember-Gesundheitsinitiative 2019 konnten durch ein Vorsorgeangebot 121 Männer für eine Prostatakrebs-Vorsorge inklusive PSA-Testung gewonnen werden. Auffällige/kontrollbedürftige Befunde zeigten sich bei 32,2 %. Bei einem Mitarbeiter wurde ein therapiebedürftiges Prostatakarzinom entdeckt und therapiert.

Variants of vitamin D metabolism-genes may predispose to type 2 diabetes (T2D). This study investigated the impact of these variants on disease susceptibility, Vitamin D, parathyroid hormone, C-peptide and HbA1c levels before and after cholecalciferol supplementation in patients with T2D.Twelve polymorphisms within CYP2R1, CYP27B1, DBP, VDR and CYP24A1 were genotyped in 553 T2D patients and 916 controls. In addition 65 patients receiving either cholecalciferol or placebo were analyzed during 6 months intervention and 6 months follow-up.T2D risk alleles are VDR rs7975232 “G” (pc=0.031), rs1544410 “G” (pc=0.027) and CYP2R1 rs10741657 “A” (pc=0.016). Patients with genotypes CYP27B1 rs10877012 “CC” (pc=4x10-5), DBP rs7041 “GG” (pc=0.003), rs4588 “CC” (pc = 3x10-4), CYP24A1 rs2585426 “CG” (pc=0.006) and rs2248137 “CG” (pc=0.001) showed lower 25(OH)D3 and DBP rs4588 “CC” lower 1,25(OH)2D3 levels (pc=0.005). Whereas DBP rs4588 “CC” (pc=0.009), CYP27B1 rs10877012 “AC” (pc=0.059), VDR rs7975323 “AG” (pc=0.033) and rs1544410 “GG” (pc=0.013) are associated with higher 25(OH)D3 levels at 6 months’ follow-up. Significant PTH suppression was detected for CYP2R1 “AG“ (pc=0.002), DBP rs4588 “CC” (pcGenetic variants of the vitamin D system predispose to type 2 diabetes and regulate – partially - vitamin D metabolism, concentrations and the vitamin D status. Vitamin D insufficiency is a T2D risk factor. The response to cholecalciferol supplementation can be measured as 25(OH)D3 increment and PTH suppression. This process is regulated by genes of the vitamin D system conferring modest T2D risk.

TRA-1–60 (TRA) is a cell-surface antigen implicated in drug resistance, relapse, and recurrence. Its expression has been reported in breast, prostate, pancreatic, ovarian tumors, and follicular lymphoma, which paved the development of the therapeutic antibody, Bstrongomab (Bsg), and its drug conjugates. Because patient selection is critical to achieve clinical benefit, a noninvasive imaging agent to select TRA+ lesions in patients is needed. Herein, we report the development of the immunopositron emission tomography (immunoPET) radiotracer (89)Zr-radiolabeled Bsg and its potential to delineate TRA+ tumors. Bsg was conjugated to the bifunctional chelator desferrioxamine (DFO) and radiolabeled with [(89)Zr]Zr-oxalate. [(89)Zr]Zr-DFO-Bsg was characterized in vitro and evaluated in vivo for uptake and specificity in high and low TRA-expressing BxPC-3 pancreatic and PC-3 prostate cancer models, respectively. Uptake was compared against[(89)Zr]Zr-DFO-IgG, a nonspecific control radiotracer. Immunohistochemical (IHC) staining of patient cancer tissues using Bsg was performed to explore its clinical significance. A specific activity of 0.18 ± 0.01 GBq/mg (4.8 ± 0.3 mCi/mg) was obtained for [(89)Zr]Zr-DFO-Bsg. BxPC-3 xenografts exhibited three-fold higher radiotracer uptake compared to [(89)Zr]Zr-DFO-IgG. Competitive saturation studies using BxPC-3 xenografts further confirmed tracer specificity. The TRA-specific probe had lower accumulation in PC-3 xenografts. Ex vivo autoradiographs correlated with TRA expression from the histopathology of the resected tumor xenografts. Additionally, patient cancer tissues demonstrated positive staining with Bsg with metastatic lesions exhibiting the highest staining. This study demonstrates the potential of [(89)Zr]Zr-DFO-Bsg as an imaging agent for noninvasive detection of TRA+ tumors.

Airborne transmission of the COVID-19 virus increased the need for health policies to reduce transmission in congregate settings associated with minimal risk before the pandemic. While a large literature estimates tradeoffs between policies designed to reduce negative health outcomes, no empirical research addresses consumer willingness to pay (WTP) for health policies designed to reduce airborne virus transmission. Using survey data from 1381 fans of professional sports, we estimate consumers' WTP for reduced likelihood of coronavirus transmission through mask and social distancing policies using a stated preference approach. The results indicate increased attendance likelihood if the venue requires masks and limits attendance, with significant heterogeneity in WTP across risk scenarios and sports. We characterize consumers as casual fans who prefer a mask requirement but are indifferent to capacity constraints, strong fans who are anti-maskers and prefer capacity constraints, and a second group of casual fans with positive WTP under both mask and limited capacity requirements. For example, casual fans' WTP for masking, $38 per National Basketball Association (NBA) game attended, is more than double their WTP for capacity constraints only. Strong fans' WTP for attending capacity constrained NBA games was $490, more than 400% higher than the pre-pandemic average WTP of $105. © 2022 John Wiley & Sons Ltd.

Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here we examine the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) in type 1 diabetes using high-resolution single-cell multiomics and flow cytometry on longitudinally-collected peripheral blood samples. Our results confirm that iLD-IL-2 selectively expands thymic-derived FOXP3

Staple line leaks are a serious problem in bariatric surgery and a major cause of serious morbidity and mortality. Adverse events caused by medical devices are reported to the Food and Drug Administration which maintains the Manufacturer and User Facility Device Experience (MAUDE) database. We examined adverse stapler events reported to the MAUDE database, specifically with regards to bariatric surgery.The MAUDE database was queried for adverse events caused by staplers between January 1, 2018 - December 31, 2020; events reported by Intuitive, Ethicon, and Medtronic/Covidien; and limited our search to "gastric bypass", "sleeve gastrectomy", "stapler malfunction" combined with each company.There were 883 adverse events reported for Medtronic, 353 for Ethicon, and 35 for Intuitive. Approximately 3.5 million staple reloads sold in the study period. The reported misfire rate for Medtronic was 0.04% and for Ethicon was 0.02%. Data for Intuitive was unavailable. The most common reported event for Medtronic was failure to fire (n = 349), followed by misfire (n = 186). For Ethicon, the most common event was failure to fire (n = 146), followed by mechanical problems (n = 27). The most common event with the Intuitive stapler was leak (n = 10) and bleeding from staple line (n = 8).Stapler malfunction is a very rare event in metabolic and bariatric surgery. All of the major stapler producers have transitioned to powered staplers with excellent safety profiles. Open and honest reporting about stapler malfunction is essential to determine the true safety of these ubiquitous devices.

The immune cytokine interleukin-12 (IL-12) is involved in cancer initiation and progression, autoimmunity, as well as graft versus host disease. The ability to monitor IL-12 via imaging may provide insight into various immune processes, including levels of antitumor immunity, inflammation, and infection due to its functions in immune signaling. Here, we report the development and preclinical evaluation of an antibody-based IL-12-specific positron emission tomography (PET) tracer. To mimic localized infection and stimulate IL-12 production, BALB/c mice were administered lipopolysaccharide (LPS) intramuscularly. [89Zr]Zr-DFO-αIL12 tracer was given one hour post LPS administration and PET images were taken after 5, 24, 48, and 72 hours. We observed significantly higher uptake in LPS-treated mice as compared to controls. Biodistribution of the tracer was evaluated in a separate cohort of mice, where tracer uptake was elevated in muscle, spleen, lymph nodes, and intestines after LPS administration. To evaluate the utility of [89Zr]Zr-DFO-αIL12 as an indicator of antigen presenting cell activation after cancer immunotherapy, we compared PET imaging with and without intratumoral delivery of oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (Adv/GM-CSF), which we have shown promotes anti-tumor immunity. BALB/c mice were inoculated orthotopically with the mouse mammary carcinoma line TUBO. Once TUBO tumors reached a volume of ~50 mm3, mice were treated with either three intratumoral injections of 108 PFU Adv/GM-CSF or vehicle control, given every other day. Upon the last dose, [89Zr]Zr-DFO-αIL12 was injected intravenously and 72 hours later all mice were imaged via PET. Tumor-specific uptake of [89Zr]Zr-DFO-αIL12 was higher in Adv/GM-CSF treated mice versus controls. Tissues were harvested after imaging, and elevated levels of macrophages and CD8+ Tc cells were detected in Adv/GM-CSF treated tumors by immunohistochemistry. We validated that IL-12 expression was induced after Adv/GM-CSF by qRT-PCR. Importantly, expression of genes activated by IL-12 (IFNγ, TNFα, and IL-18) were unaffected after IL-12 imaging relative to mice receiving an IgG control tracer, suggesting the tracer antibody does not significantly disrupt signaling. Our results indicate that targeting soluble cytokines such as IL-12 by PET imaging with antibody tracers may serve as a noninvasive method to evaluate the function of the immune milieu in situ.

There is a large unmet need for improved treatment for temporal lobe epilepsy (TLE); circuit-specific manipulation that disrupts the initiation and propagation of seizures is promising in this regard. The midline thalamus, including the mediodorsal nucleus (MD) is a critical distributor of seizure activity, but its afferent and efferent pathways that mediate seizure activity are unknown. Here, we used chemogenetics to silence input and output projections of the MD to discrete regions of the frontal cortex in the kindling model of TLE in rats. Chemogenetic inhibition of the projection from the amygdala to the MD abolished seizures, an effect that was replicated using optogenetic inhibition. Chemogenetic inhibition of projections from the MD to the prelimbic cortex likewise abolished seizures. By contrast, inhibition of projections from the MD to other frontal regions produced partial (orbitofrontal cortex, infralimbic cortex) or no (cingulate, insular cortex) attenuation of behavioral or electrographic seizure activity. These results highlight the particular importance of projections from MD to prelimbic cortex in the propagation of amygdala-kindled seizures.

A recent publication in Parasitology Research by (Old et al. Parasitol Res 120:1077-1090, 2021) raises the topical and often controversial issue of the treatment of wildlife by personnel with little or no formal scientific training (e.g. wildlife carers). In a valuable contribution to the subject, Old and colleagues document a wide range of topical (pour-on) application doses and frequencies of moxidectin (Cydectin®) administered in situ to bare-nosed wombats (Vombatus ursinus) by members of the wildlife carer/treater community in southeast Australia to treat sarcoptic mange disease. This treatment occurred under minor use permits issued by the Australian Pesticides and Veterinary Management Authority (APVMA). These permits do not require veterinary supervision, although carers are registered and are expected to comply with the guidelines of this permit.The prevalence and severity of sarcoptic mange in wildlife is influenced by a variety of factors including mite biology, environmental conditions, population density, animal behaviour and immune susceptibility (Browne et al. Bioscience, 2021). In bare-nosed wombats, combinations of these elements play a substantial role in making the treatment of an already difficult disease more complex. (Moroni et al. Parasit Vectors 13:471, 2020) comment that any pharmacological treatment of free-ranging wildlife must consider these factors when assessing their feasibility and implications, especially in the context of emerging drug resistance and potential long-term ecological impacts. As individuals with significant interest in sarcoptic mange and representing a range of professional research and veterinary expertise, we see value in providing expert commentary on this issue.

Influenza is a communicable respiratory illness that can cause serious public health hazards. Due to its huge threat to the community, accurate forecasting of Influenza-like-illness (ILI) can diminish the impact of an influenza season by enabling early public health interventions. Machine learning models are increasingly being applied in infectious disease modelling, but are limited in their performance, particularly when using a longer forecasting window. This paper proposes a novel time series forecasting method, Randomized Ensembles of Auto-regression chains (Reach). Reach implements an ensemble of random chains for multistep time series forecasting. This new approach is evaluated on ILI case counts in Auckland, New Zealand from the years 2015-2018 and compared to other standard methods. The results demonstrate that the proposed method performed better than baseline methods when applied to this ILI time series forecasting problem.

Standardised surveillance of COVID-19 infections among healthcare personnel during the current pandemic was and is not available. In particular, the proportion of occupational infections among healthcare personnel and which workers among them are most at risk remains unclear.The aim of this study was to analyse the reported COVID-19 cases among healthcare personnel in Frankfurt/Main during the first six months of the pandemic, to determine the number of occupational infections and thus to allow a better interpretation of the data published by the Robert Koch Institute.Data from the Frankfurt/Main Health Protection Authority was analysed for the period from 1 March to 31 August 2020, and healthcare personnel were recruited for a cross-sectional survey. Three subgroups were defined and analysed according to whether the infectious contact occurred at work, in private or in an unknown setting.Healthcare personnel accounted for 11.8% (319/2700) of all reported COVID-19 cases in Frankfurt/Main during the period studied. In the survey, 47.2% of respondents reported that their infection was acquired in the workplace. There was an association of contact with COVID-19 patients as well as employment in the internal medicine ward and a reported work-related infection. Also apparent was an association between suspected occupational infections and consequently filed reports for alleged occupational disease.Health protection authorities are in a position to collect relevant data on work-related transmissions in healthcare occupations and workplaces and should generate standardised data on infected healthcare personnel. This data is necessary to take targeted infection control and prevention measures that protect healthcare personnel and their patients.HINTERGRUND: Eine standardisierte Erhebung von COVID-19-Infektionen bei Gesundheitspersonal während der laufenden Pandemie war und ist nicht gegeben. Vor allem der Anteil von arbeitsbedingten Infektionen beim Gesundheitspersonal und die Frage, welche Arbeitnehmer/-innen darunter am meisten gefährdet sind, bleiben unklar. ZIEL: Ziel dieser Studie war es, die gemeldeten COVID-19-Fälle beim Gesundheitspersonal in Frankfurt/Main in den ersten 6 Monaten der Pandemie zu analysieren, die Zahl der arbeitsbedingten Infektionen zu ermitteln und somit eine bessere Interpretation der durch das Robert Koch-Institut veröffentlichten Daten zu ermöglichen.Die Daten des Gesundheitsamts Frankfurt/Main wurden für den Zeitraum vom 01.03. bis zum 31.08.2020 betrachtet und medizinisches Personal für eine Querschnittserhebung im Rahmen einer Umfrage rekrutiert. Drei Subgruppen wurden nach Ort des Infektionskontakts, am Arbeitsplatz, im Privaten und unbekannt, unterteilt und analysiert.Medizinisches Personal machte 11,8 % (319/2700) aller gemeldeten COVID-19-Fälle in Frankfurt/Main im untersuchten Zeitraum aus. In der Umfrage gaben 47,2 % der Befragten an, dass ihre Infektion am Arbeitsplatz erworben wurde. Es zeigte sich eine Assoziation von Kontakt zu COVID-19-Patient/-innen sowie der Beschäftigung auf einer internistischen Station und einer arbeitsbedingten Infektion. Ersichtlich wurde außerdem ein Zusammenhang zwischen mutmaßlichen Infektionen am Arbeitsplatz und folglich gestellten Verdachtsanzeigen auf Berufskrankheit.Gesundheitsämter sind in der Lage, relevante Daten von arbeitsbedingten Transmissionen in Berufen und Arbeitsplätzen im Gesundheitswesen zu erheben, und sollten standardisierte Daten zu infiziertem Gesundheitspersonal generieren. Diese Daten sind notwendig, um gezielte Maßnahmen der Infektionsprävention zu ergreifen, die Gesundheitspersonal und ihre Patient/-innen schützen.

Objective: Work-related vaccinations are recommended for employees in nursing and health care professions due to their elevated risk of infection because of job-related exposure. These vaccinations prevent work-related infections, protect patients and help to maintain the medical infrastructure. Thorough training and imparting of knowledge about vaccinations and work-related infections are essential pillars of the vaccination decision and thus for achieving a protective immune status. The present study examines the knowledge, attitudes and behavior of nursing- and health care students in Hesse regarding work-related infections and vaccinations. Methods: In spring 2018, seven nursing schools in Hesse took part in an anonymous survey study. A total of 690 surveys from students of various health care professions were included in the study. The content of the survey was based on the recommendations of the Standing Committee on Vaccination (STIKO), a literature review and sample questions from the World Health Organization (WHO) regarding ���vaccine hesitancy���. Vaccination cards were also evaluated based on the STIKO recommendations concerning standard vaccinations and occupational vaccinations for health care workers. Results: The risk of acquiring a work-related infection was estimated to be quite high over all years of training. Gaps in knowledge were particularly evident in the area of vaccinations. Only three quarter of those surveyed believed that the effectiveness of vaccinations has been proven, and nearly 30% believed that the doses of the drugs used in vaccines were dangerous. Over 80% of the students had never had an influenza vaccination documented in their vaccination card. Conclusions: The knowledge about vaccinations imparted in the course of the education should be expanded. A special course on the subject of vaccinations and the immune system with practical elements could contribute to a better understanding of how vaccinations work and misunderstandings could be eliminated in early stages of the training through the dialog between the students and the teacher in the classroom and the occupational physician as part of preventive occupational health check-ups., Zielsetzung: Besch��ftige in der Krankenpflege und medizinischen Ausbildungsberufen sind berufsbedingt einer erh��hten Infektionsgef��hrdung ausgesetzt, daher bestehen f��r sie Empfehlungen f��r beruflich indizierte Impfungen. Diese dienen neben der Vermeidung arbeitsbedingter Infektionen auch dem Patientenschutz, sowie der Aufrechterhaltung der medizinischen Infrastruktur. Eine profunde Ausbildung und Wissensvermittlung ��ber Impfungen und arbeitsbedingte Infektionen sind wichtige Grundlagen der Impfentscheidung und somit zur Erlangung eines sch��tzenden Immunstatus. Die vorliegende Studie untersucht das Wissen, die Einstellung und das Verhalten von Auszubildenden in medizinischen Ausbildungsberufen in Hessen zu arbeitsbedingten Infektionen und Impfungen. Methodik: Im Fr��hjahr 2018 nahmen sieben Pflegeschulen in Hessen an einer anonymen Fragebogenstudie teil. Insgesamt wurden 690 Frageb��gen von Sch��lerinnen und Sch��lern verschiedener medizinischer Ausbildungsberufe in die Studie aufgenommen. Der Inhalt der Fragen orientierte sich an den Empfehlungen der St��ndigen Impfkommission (STIKO), einer Literaturrecherche, sowie an den Beispielfragen der Weltgesundheitsorganisation (WHO) bez��glich ���vaccine hesitancy���. Ebenso erfolgte die Auswertung von Impfp��ssen anhand der STIKO-Empfehlungen hinsichtlich Standardimpfungen, sowie den beruflich bedingten Impfungen f��r Besch��ftigte im Gesundheitswesen. Ergebnisse: Das Risiko an einer arbeitsbedingten Infektion zu erkranken wurde ��ber alle Ausbildungsjahre hinweg als ziemlich gro�� eingesch��tzt. Wissensl��cken zeigten sich vor allem im Bereich der Impfungen. Nur knapp drei Viertel der Befragten hielt die Wirksamkeit von Impfung f��r belegt und fast 30% waren der Meinung, dass die Dosierungen der in Impfstoffen erhaltenen Arzneistoffe gef��hrlich sind. ��ber 80% der Sch��lerinnen und Sch��ler hatten noch niemals eine Influenza-Impfung erhalten. Schlussfolgerung: Das im Rahmen der Ausbildung vermittelte Wissen ��ber Impfungen sollte ausgebaut werden. Eine spezielle Unterrichtseinheit zum Thema Impfungen und Immunsystem mit praktischen Anteilen k��nnte zum besseren Verst��ndnis ��ber die Wirkungsweise von Impfungen beitragen und Missverst��ndnisse k��nnten im Dialog der Sch��lerinnen und Sch��ler mit der Lehrkraft im Unterricht und dem Betriebsarzt im Rahmen der arbeitsmedizinischen Vorsorgen bereits in fr��hen Stadien der Ausbildung beseitigt werden.

Thousands of genetic variants are associated with human disease risk, but linkage disequilibrium (LD) hinders fine-mapping the causal variants. Both lack of power, and joint tagging of two or more distinct causal variants by a single non-causal SNP, lead to inaccuracies in fine-mapping, with stochastic search more robust than stepwise. We develop a computationally efficient multinomial fine-mapping (MFM) approach that borrows information between diseases in a Bayesian framework. We show that MFM has greater accuracy than single disease analysis when shared causal variants exist, and negligible loss of precision otherwise. MFM analysis of six immune-mediated diseases reveals causal variants undetected in individual disease analysis, including in IL2RA where we confirm functional effects of multiple causal variants using allele-specific expression in sorted CD4+ T cells from genotype-selected individuals. MFM has the potential to increase fine-mapping resolution in related diseases enabling the identification of associated cellular and molecular phenotypes., Statistical fine-mapping to pinpoint likely causal variants in a genomic region is complicated by linkage disequilibrium (LD). Here, Asimit et al. compare stepwise and stochastic approaches to fine-mapping and propose a Bayesian multinomial stochastic search method which they apply to six immune-mediated diseases.

Background The gastric bypass is a commonly performed bariatric procedure. The stomach is divided into a small pouch as well as leaving a larger remnant that is bypassed by the gastrojejunal anastomosis. This makes access to the biliary system difficult as an endoscope cannot transverse the esophagus, roux limb, and biliopancreatic limb. Therefore, a transgastric approach (endoscopic retrograde cholangiopancreatography [t-ERCP]) through the abdominal wall and remnant stomach is necessary. This involves the surgical team providing access to the remnant stomach for the gastroenterologist to perform the t-ERCP. We have performed a number of these for biliary pathology that ranges from cancer to retained gallstones. We evaluated these patients with at least a 3-year follow-up to determine long term outcomes. Methods We conducted a chart review of patients who underwent a t-ERCP with at least a 3-year follow-up. We collected de-identified data including demographics, operative details, complications, and postoperative courses. Results There were 12 patients who underwent t-ERCP. Eleven patients had at least a 3-year follow-up with a mean follow-up of 68.1 months (excluding one death from pancreatic cancer). The most common pathology was benign biliary stricture (n = 6), followed by retained gallstones (n = 4), with one pancreatic cancer, and one normal examination. Two patients still had epigastric pain at long term follow-up after 3 years. Conclusion T-ERCP is safe and efficacious with good long-term results.

This paper explores how the salutogenic theory can enable us to re-envision health promotion work with marginalized communities, towards an approach that acknowledges and honours their resilience. We use the three core concepts in Antonovsky’s salutogenic model of health – sense of coherence, generalized resistance resources and specific resistance resources – to explore the theory’s relevance to health equity, thus presenting new opportunities for how we might radically re-evaluate current health promotion approaches. We conclude that a more equitable health promotion requires increased participation of marginalized communities in shaping their futures and suggest a new model for historically grounded salutogenic health promotion.

SummaryRacism is a public health crisis. Black communities (including Africans, the African diaspora and people of African descent) experience worse health outcomes as demonstrated by almost any measure of health and wellbeing—e.g. life expectancy; disease prevalence; maternal mortality rates. While health promotion has its foundation in promoting equity and social justice, it is clear that however well-intended, we are not affecting meaningful change for Black communities quickly enough. Through this article, we outline the intersection of social determinants of health and anti-Black racism. We describe how in the first 8 months of 2020 Black communities around the globe have been disproportionately affected by COVID-19, while also having to respond to new instances of police brutality. We assert that the time has come for health promotion to stop neutralizing the specific needs of Black communities into unspoken ‘good intentions’. Instead, we offer some concrete ways for the field to become outspoken, intentional and honest in acknowledging what it will take to radically shift how we promote health and wellbeing for Black people.

Background Laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (SG) are the two most common bariatric operations. With the implementation of enhanced recovery protocols, the use of drains should decrease. Methods The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database was queried for the years 2015–2017. Our inclusion criteria included all patients undergoing a primary LRYGB, SG, and revisions. We examined demographics, operative characteristics, the use of drains, and postoperative complications. Continuous variables were summarized using means and standard deviations (SD). Categorical variables were summarized using frequencies and proportions. Student’s T test (Wilcoxon sum rank test in the case of skewed data) and chi-squared analysis were used to assess the baseline differences in drain utilization. Results From 2015 to 2017, there were 388,239 bariatric cases performed without drains and 100,221 performed with drains. Twenty-nine percent of LRYGB patients had a drain placed but only 16.7% of SG patients. The percentage of LRYGB that had a drain dropped from 33.1 to 24.6% during the study period and that of SG dropped from 20.3 to 13.6%. Patients that had drains placed were more likely to have a provocative test at the time of surgery (prevalence ratio (PR) 2.24) and to have a postoperative swallow study (PR 1.93). Conclusions Drains are still commonly used in bariatric patients. Over the study period, there was a decrease in the use of drains in both bypass and sleeve patients. Patients with a drain were more likely to have had a provocative test and a swallow study and have a higher rate of complications and mortality. Electronic supplementary material The online version of this article (10.1007/s11695-019-04215-6) contains supplementary material, which is available to authorized users.

Background The sleeve gastrectomy (SG) is the most common bariatric surgery in the United States today. There is a trend toward performing SG as an outpatient procedure, either in an ambulatory setting or as an outpatient at a larger hospital. The term “outpatient” is used to designate essentially any patient without an inpatient order. Texas maintains the Texas Inpatient Public Use Data File (IPUDF) database and the Texas Outpatient Public Use Data File (OPUDF) database for inpatient and outpatient settings, respectively. Objectives To determine where SGs are performed by evaluating the Texas IPUDF and OPUDF for 2016. Setting University hospital, United States. Methods The Texas IPUDF and OPUDF were searched with the Current Procedural Terminology code of 43775 and the International Classification of Diseases, 10th revision, procedure code of 0DB64Z3. Patient demographic characteristics were also examined. We looked at the top 5 diagnoses in each database. Results Of the 16,855 SGs performed in Texas in 2016, outpatient SGs accounted for 31.0% (5227 cases), and inpatient SGs accounted for 69% of the total with 11,628 cases reported. For patients reported in the OPUDF, mean length of stay (LOS) was 2.1 (standard deviation 3.2) days with a median of 1.0 (interquartile range = 1, 2) days; for patients in the IPUDF, mean LOS was 1.6 (standard deviation 1.5) days, and the median was 1.0 (interquartile range = 1, 1) days. Conclusion A third of SGs in Texas were performed under outpatient status. Further study is needed to determine the safety of this practice.

Group B streptococcus (GBS) is a leading cause of morbidity and mortality in newborns worldwide. From 2000 to 2008, national guidelines in Germany recommended intrapartum antibiotic prophylaxis for pregnant women displaying risk factors (eg, perinatal anogenital GBS colonization, rupture of the membranes ≥18 hours before birth) for the vertical transmission of GBS to their children. In 2008, these guidelines were revised to advocate universal, culture-based screening for GBS colonization among all pregnant women between 35 and 37 weeks of gestation. For the period 2009-2010, our prospective active surveillance study assessed the incidence of invasive GBS infections in infants 0-90 days of age in Germany. We did this by means of a capture-recapture analysis of 2 separate, independent systems (pediatric reporting versus laboratory reporting). We compared our results with those from a previous study by employing an equivalent design (2001-2003). We detected a 32% reduction in GBS incidence, from 0.47 per 1000 live births (n = 679) in 2001-2003 to 0.34 per 1000 live births (n = 450) in 2009-2010. This decline primarily is tied to a reduced number of GBS cases in children under 1 week of age. In 2009-2010, the ratio of early-onset disease to late-onset disease reversed from 1.52 (206:136), as determined in 2001-2003, to 0.75 (92:122). This study is the first to assess changes in the incidence of invasive GBS in Germany after the implementation of the guidelines for intrapartum prophylaxis for pregnant women colonized with GBS.

After treatment of an inpatient with measles, an outbreak occurred within the unprotected healthcare workers (HCW) of a regional hospital in Hesse, Germany in February and March 2017. Overall, 10 HCW contracted measles. Remarkably, none of the affected HCW had direct contact to the index patient. One nosocomial transmission to a patient occurred. The economic impact of the outbreak is estimated to approximately 700,000€. Medical institutions play a major role in the management of measles outbreaks, since the risk of exposure as well as nosocomial transmission to vulnerable patients and HCW is very high. To avoid outbreaks it is essential to have an easily accessible documentation of the immune-status of all HCW. The role of occupational medicine in identifying and closing vaccination gaps is of particular importance.

Objective. Student pharmacists must cultivate self-awareness to ensure that they can assess their skill development and abilities, including affective domain skills such as empathy. External feedback can augment development, but validated assessments are needed for accuracy. Thus, the objectives of this study were to establish validity evidence for the revised version of the Kiersma-Chen Empathy Scale (KCES-R), compare student self-perceptions and simulated patient perceptions of student empathy using a parallel patient scale (KCES-PV), and evaluate student reflections on the encounter. Methods. Student pharmacists completed an assessment of their self-perceptions of empathy (KCES-R) before and after the patient encounter. Simulated patients completed the KCES-PV regarding the student pharmacists’ empathy immediately after the encounter. Student pharmacists also watched their encounter videos and completed a self-reflection on their use of empathy. Responses were analyzed using statistical tests, whereas students’ reflections were examined using thematic analysis. Results. Results showed that the KCES-R contains two factors with high internal consistency and can detect changes in empathy. Student pharmacists’ self-perceptions of their empathy abilities appeared higher than when their empathy abilities were evaluated by simulated patients. Student pharmacists had a strong belief in the importance of expressing empathy during patient encounters and indicated a need for further development. Conclusion. This study provides validity evidence for the use of the KCES-R and presents a parallel scale that may be used by simulated patients. Validated parallel scales along with reflective practice could be a potential avenue to grow self-awareness and empathy by allowing students to receive feedback and then reflect on their perceived versus actual demonstration of the skill.

While the issue of opioid misuse is very complex, pharmacists have a unique opportunity to participate in interprofessional, team-based care. Motivational interviewing (MI) has been shown to be effective in chronic disease management and could improve patient engagement and chronic pain outcomes.To determine the impact of an MI-based provider training on changes in chronic pain management prescribing and on provider and patient perceptions.Providers participated in a pharmacist-led, 4-session educational intervention covering the CDC opioid prescribing guidelines, pain management, clinical pearls, and MI. Providers were then asked to implement the training in patient appointments for chronic pain management and refer appropriate patients for follow-up on goals. In the follow-up, student pharmacists called patients twice monthly for three months using MI. To address the primary outcome, the number of opioid prescriptions, morphine daily equivalents, and naloxone prescriptions were recorded and compared from the electronic medical record for the year preceding and following the intervention. Patients and providers completed surveys to assess the impact of these interventions.Providers (n = 11) reported increased confidence in MI from baseline to 12 months following the intervention but no change in satisfaction. Patients (n = 19) were able to set and accomplish 20 goals throughout the phone call intervention. Meanwhile, the number of opioid prescriptions significantly decreased from 569 to 368 prescriptions per year before and after the intervention, respectively. Morphine daily equivalents per prescription decreased from 26.8 to 26.4 for the year before versus the year following the intervention.MI interventions for providers and patients may positively impact goal setting and opioid prescribing. However, MI alone may not successfully address provider satisfaction and patient physical functioning. Pain management is an area that may benefit from a multi-faceted, interprofessional approach.