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Higher blood pressure levels are associated with vascular dysfunction as early as childhood. Here, we aim to compare two blood pressure devices for use in childhood populations within a school setting to screen for elevated blood pressure in children.Systolic and diastolic blood pressure, mean arteriolar pressure (MAP) as well as heart rate (HR) were measured with the validated Oscillomate 9002 and Mindray VS-900 in 82 randomly selected children between 10 and 12 years taking part in the EXAMIN YOUTH study in 2020. Measurements were performed after 5 min at rest in a sitting position in the school environment.Both devices showed strong correlations for systolic (r = 0.62, t[80] = 7, p 0.001) and diastolic blood pressure (r = 0.73, t[80] = 9.52, p 0.001), MAP (r = 0.75, t[80] = 10.22, p 0.001) and HR (r = 0.89, t[79] = 17.77, p 0.001). There was no evidence for a statistically significant difference of both devices for systolic (110 ± 9 mmHg vs. 111 ± 9 mmHg, p = 0.574), diastolic blood pressure (67 ± 9 mmHg vs. 66 ± 9 mmHg, p = 0.301) as well as MAP (81 ± 8 mmHg vs. 80 ± 8 mmHg, p = 0.400) and HR (83 ± 12 BPM vs. 83 ± 11 BPM, p = 0.994).Both devices, the older Oscillomate 9002 and the current Mindray VS-900 showed good agreement for the measurement of blood pressure in school children. It therefore appears to be feasible to measure childhood blood pressure with either device or replace one device with another in prospective long-term studies or screening programmes as long as both are validated for use in children.

Gα proteins as part of heterotrimeric G proteins are molecular switches essential for G protein-coupled receptor- mediated intracellular signaling. The role of the Gα subunits has been examined for decades with various guanine nucleotides to elucidate the activation mechanism and Gα protein-dependent signal transduction. Several approaches describe fluorescent ligands mimicking the GTP function, yet lack the efficient estimation of the proteins' GTP binding activity and the fraction of active protein. Herein, we report the development of a reliable fluorescence anisotropy-based method to determine the affinity of ligands at the GTP-binding site and to quantify the fraction of active Gαi1 protein. An advanced bacterial expression protocol was applied to produce active human Gαi1 protein, whose GTP binding capability was determined with novel fluorescently labeled guanine nucleotides acting as high-affinity Gαi1 binders compared to the commonly used BODIPY FL GTPγS. This study thus contributes a new method for future investigations of the characterization of Gαi and other Gα protein subunits, exploring their corresponding signal transduction systems and potential for biomedical applications.

Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension.; Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks.; Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group.; Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future.

IntroductionHypertension is a global healthcare burden that affects the structure and function of the macrocirculation and microcirculation and induces disease-specific end-organ damage. Vascular biomarkers are essential to timely diagnose this end-organ damage to improve cardiovascular (CV) risk stratification and medical decision making. Exercise therapy is an effective means to improve vascular health and reduce overall CV risk. However, it is still not clear whether high-intensity interval training (HIIT) is recommendable for patients with hypertension to reduce blood pressure, increase cardiorespiratory fitness and ameliorate vascular health.Methods and analysisThe ‘Hypertension and retinal microvascular dysfunction’ trial will investigate macrovascular and microvascular impairments in hypertensive patients compared with healthy controls to investigate hypertension-induced end-organ damage by using gold-standard methods as well as newly developed unique retinal microvascular biomarkers. In addition, this trial will investigate the reversibility of retinal end-organ damage by assessing the effects of an 8-week supervised and walking based HIIT on blood pressure, cardiorespiratory fitness as well as macrovascular and microvascular health, compared with a control group following standard physical activity recommendations. Primary outcome will be the arteriolar-to-venular diameter ratio. Secondary outcomes will be arteriolar and venular diameters as well as the flicker-light-induced dilation. Further outcomes will be other retinal microvascular biomarkers, flow-mediated dilation of the brachial artery as well as blood pressure, cardiorespiratory fitness, microalbuminuria, hypertensive retinopathy and classical CV risk markers. Analysis of variance and analysis of covariance will be used to investigate group differences between healthy controls and hypertensive patients and training effects in hypertensive patients, respectively.Ethics and disseminationThe Ethics Committee of Northwestern and Central Switzerland approved this study (EKNZ-2021-00086). All participants will give informed consent.Trial registration numberNCT04763005.

Central pulse wave velocity (cPWV) is a biomarker for cardiovascular (CV) risk and a predictor for CV events in adulthood. Alterations of arterial stiffness have also been associated with CV risk in childhood. The study aimed to systematically review and meta-analyze the association of blood pressure (BP), body mass index (BMI), and cardiorespiratory fitness (CRF) with cPWV in children. Literature search was through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials. Twenty-two articles were included in the systematic review and eight articles in the meta-analysis. Higher systolic and diastolic BP were associated with higher cPWV (pooled estimated effect size (ES) 0.02 (95% CI: 0.012−0.027; P

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Swiss National Foundation Background Prevention of cardiovascular (CV) disease should start early in life. The study aimed to investigate the association of changes in physical activity, sedentary behavior and cardiorespiratory fitness (CRF) with development of body mass index (BMI), blood pressure (BP) and retinal microvascular health in children over four years. Methods In 2014, 391 children aged 6-8 years were screened, and thereof 262 children were reexamined after four years following standardized protocols. Retinal arteriolar (CRAE) and venular diameters were measured by a retinal vessel analyzer. CRF was objectively assessed by a 20m shuttle run, physical activity and sedentary behavior by use of a questionnaire. Results Children who achieved higher CRF levels reduced their BMI (β [95% CI] -0.35 [-0.46 to -0.25] kg/m2 per stage, P ≤ 0.001) and thereby developed wider CRAE (β [95% CI] 0.25 [0.24 to 0.48] µm per stage, P = 0.03) at follow-up. Moreover, children with elevated or high systolic BP at baseline, but lower levels of sedentary behavior during the observation period, had wider CRAE at follow-up (β [95% CI] -0.37 [-0.66 to -0.08] µm per 10 min/d, P = 0.013). Conclusion An increase of CRF over four years was associated with a reduced BMI and consequently wider retinal arterioles at follow-up. In children with elevated or high systolic BP, a reduction of sedentary behavior by merely 10 min per day significantly improved retinal microvascular health as a primary prevention strategy to promote childhood health and combat development of manifest CV disease later in life.

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection. Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27. Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads

Research question Are selected cell adhesion molecules useful as urinary biomarkers for diagnosing endometriosis? Design Prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent laparoscopic surgery for benign gynaecological pathologies. A total of 149 patients not receiving hormonal treatment for at least 3 months prior to recruitment were included and preoperative urine protein levels of soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), E-selectin and P-selectin were measured using a magnetic bead-based multiplex assay, normalized to creatinine levels of each sample. Levels were correlated with endometriosis status, menstrual cycle phase, body mass index, cigarette smoking and severity and entity of the lesions. Results Urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin did not differ between women with (n = 84) and without (n = 65) endometriosis and among subgroups. Accordingly, receiver operating characteristic analysis to examine the value of using sVCAM-1, sICAM-1, E-selectin and P-selectin levels and sVCAM/sICAM ratio to diagnose endometriosis were not significant. Whether the serum sVCAM-1 levels correlated with the urine levels of the protein in the same women was also investigated, which revealed no significant correlations for sVCAM or sICAM. Conclusion Although a previous study had suggested that serum sVCAM is a promising biomarker for diagnosing endometriosis, no significant differences were found in urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin between women with and without endometriosis. Other markers should be studied in an effort to establish a truly non-invasive urinary test for diagnosing endometriosis.

Objective: The aim of this study was to examine neurocognitive course over time among people with well treated HIV. Design: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up. Setting: Seven SHCS centres. Participants: Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets. Intervention: Standardized neuropsychological assessment at baseline and 2-year follow-up. Main outcome measure: Neurocognitive performance using Frascati criteria and mean z-scores. Results: Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/μl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement. Conclusion: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.

Die Anwendungen der Künstlichen Intelligenz sind immer noch neu, wenig sichtbar, werden in der Öffentlichkeit kont-rovers diskutiert und sind für die Mitarbeitenden sowohl mit negativen und als auch mit positiven Szenarien verbunden. Das Forschungsprojekt, das diesem Beitrag zugrunde liegt, möchte die Auswirkungen von KI-Anwendungen auf das Anforderungsprofil und das Learning-on-the-Job von Mitarbeitenden feststellen, und auch klären, welche Auswirkungen dies auf die Arbeitsproduktivität und auf die arbeitende Person selbst hat. Dazu wurden narrative Interviews mit sieben Interviewpartner:innen aus sechs Branchen aus der Schweiz, mehrheitlich der Zentralschweiz, geführt. Die Gesprächspro-tokolle der Interviews wurden in mehreren Stufen inhaltlich analysiert. Die Ergebnisse zeigen Auswirkungen auf die menschlichen Fähigkeiten, die Mensch-Maschine-Interaktion und die Unterstützung des Menschen bei der täglichen Ar-beit. Es zeigen sich Vorteile, wie z.B. produktivere Prozesse, Herausforderungen, wie z.B. der geringere Kundenkontakt, aber auch kritische Aspekte in Bezug auf die Aus- und Weiterbildung.

Objective: Central hemodynamics are related to cardiovascular (CV) outcomes in adults, but associations with childhood CV risk remain unclear. The study aimed to investigate the association of obesity, physical activity, and fitness with parameters of central pulse wave reflection in young prepubertal children.Methods: In this cross-sectional study, 1,324 primary school children (aged 7.2 ± 0.4 years) were screened for parameters of pulse wave reflection such as augmentation index (AIx), central pulse pressure (CPP), body mass index (BMI), and cardiorespiratory fitness (CRF) by standardized procedures for children.Results: The mean AIx and AIx@75 were 22.2 ± 7.7 and 29.2 ± 9.2%, respectively. With each unit increase in BMI, AIx [−0.226 (−0.328; −0.125)%] and AIx@75 [−0.444(−0.660; −0.229)%] decreased, whereas peak forward pulse wave increased (p < 0.001). Increasing BMI was associated with higher CPP, but did not remain significant after adjustment for CRF and heart rate. One unit increase in CRF was associated with lower AIx@75 [−0.509(−0.844; −0.173)%, p = 0.003] and lower reflection magnitude [RM: −0.559 (−0.890; −0.227), p = 0.001], independent of body weight and height. Girls had significantly higher AIx, AIx@75, peak backward pulse wave, and RM compared with boys.Conclusion: Childhood obesity was associated with higher CPP but lower augmentation of the reflected pulse wave in children. Assessment of central blood pressures appears to be a valuable asset to childhood CV risk screening. The validity of augmentation indices during childhood development and the association with early vascular aging in children need to be verified in long-term follow-up studies. Physical activity and fitness have the potential to improve vascular hemodynamics in susceptible children and, thus, counteract vascular aging.Trial registry: ClinicalTrials.gov: Exercise and Arterial Modulation in Youth. Identifier: NCT02853747; URL: https://clinicaltrials.gov/ct2/show/NCT02853747.

The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children (initial age 6–8 years) were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54–4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64–4.77) m/s) (p = 0.049). Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.

We have explored the impact of elevated growth and annealing temperatures on the local interfacial structure of thin Fe(12 nm)/Pt(10 nm) spintronic bilayers, epitaxially grown on MgO (100), and their correlation to magnetization reversal and dynamics. Electron-beam evaporation growth and subsequent annealing at 450 °C causes significant roughening of the MgO/Fe interface with irregular steps and multilevel (100) MgO surface terraces. Consequently, threading dislocations emerging at the step edges propagated in the Fe layer and terminated at the Fe/Pt interface, which appears pitted with pits 1.5–3 nm deep on the Fe side. Most of the pits are filled with the overlying Pt, whereby others by ferrimagnetic Fe3O4, forming nanoparticles that occupy nearly 9% of the Fe/Pt interfacial area. Fe3O4 nanoparticles occur at the termination sites of threading dislocations at the Fe/Pt interface, and their population density is equivalent to the density of threading dislocations in the Fe layer. The morphology of the Fe/Fe3O4/Pt system has a strong impact on the magnetization reversal, enhancing the coercive field and inducing an exchange bias below 200 K. Furthermore, low-temperature spin pumping and inverse spin Hall effect voltage measurements reveal that below their blocking temperature the nanoparticles can influence the spin current transmission and the spin rectification effects.

STUDY QUESTION Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis? SUMMARY ANSWER Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells. WHAT IS KNOWN ALREADY We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. TACE was identified as the protease responsible for phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 release in murine endothelial cells. Additionally, it has recently been shown that TACE is upregulated in the endometrial luminal epithelium of the mid-secretory phase in infertile women. STUDY DESIGN, SIZE, DURATION This study was conducted at the Tertiary Endometriosis Referral Center of the Medical University of Vienna. Samples from a total number of 97 women were collected between July 2013 and September 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS After complete surgical exploration of the abdominopelvic cavity, 49 women with histologically proven endometriosis and 48 endometriosis-free control women were enrolled. Each participating woman contributed only one sample of eutopic endometrium and normal peritoneum, and some of the women with endometriosis contributed samples of diverse types of endometriotic lesions (in total 52 ectopic samples). Among the 49 women with endometriosis, 36 matched samples of endometriotic lesions and corresponding eutopic endometrium were collected. In order to detect sVCAM-1 and TACE protein by ELISA, peritoneal fluid (PF) samples were collected from 44 cases and 32 controls during surgery. Expression of TACE mRNA was analyzed by qRT-PCR in 111 endometrium tissue samples (28 eutopic control samples, 33 eutopic samples from women with endometriosis, 50 ectopic samples from lesions) and 37 healthy peritoneum samples. Immunohistochemistry was performed in 123 tissue samples (39 eutopic control samples, 42 eutopic samples from women with endometriosis, 42 ectopic samples from lesions) and the relation between tissue TACE protein levels and sVCAM-1 secretion was examined. PMA-induced sVCAM-1 release, and TACE- and VCAM-1-transcripts or proteins were measured in an immortalized endometriotic epithelial cell line (11Z) pre-incubated either with TACE inhibitors or following TACE siRNA knockdown. MAIN RESULTS AND THE ROLE OF CHANCE Here, we demonstrate that TACE protein is overexpressed in epithelium of tissue samples of both eutopic endometrium and ectopic lesions of women with endometriosis compared to disease-free controls (P < 0.001 both) and that the overexpression of the protein in the lesions is due to activation of TACE gene transcription (P < 0.001). Moreover, epithelial TACE protein was significantly higher in ectopic samples than in corresponding eutopic tissue of women with the disease (P < 0.001). High endometrial tissue TACE protein expression correlated with higher serum sVCAM-1 levels (P < 0.05) but not with sICAM-1 levels. Inhibition of TACE either by TACE inhibitors or by TACE siRNA knockdown resulted in decreased PMA-induced shedding of sVCAM-1 in vitro (P < 0.005 or P < 0.01, respectively), but the TACE inhibitors did not affect transcription of TACE or VCAM-1. Additionally, we observed an upregulation of TACE in proliferative endometrial epithelium of infertile (P < 0.005), compared to fertile women. TACE was increased in infertile women with endometriosis (P = 0.051) but not in infertile women without endometriosis. LIMITATIONS, REASONS FOR CAUTION Albeit well characterized, our control population included women with other gynecologic diseases, which may have impacted the levels of sVCAM-1 and tissue TACE expression levels, e.g. benign ovarian cysts or uterine fibroids. Thus, the results of our analysis have to be interpreted carefully and in the context of the current experimental settings. WIDER IMPLICATIONS OF THE FINDINGS The dysregulation of TACE substrate shedding represents a promising yet relatively unexplored area of endometriosis progression and could serve as a basis for the development of new treatments of the disease. STUDY FUNDING AND COMPETING INTEREST(S) This work was supported by the Ingrid Flick Foundation. The authors have no competing interests to declare.

Background/Aims: Socioeconomic barriers and lifestyle conditions affect development of cardiovascular disease in adults, but little is known about the association of parental lifestyle and education with childhood health. We aimed to investigate the association of socioeconomic status (SES), migration background, parental physical activity (PA) and smoking status with micro-and macrovascular health in children.Methods: In 2016/2017, 833 school children (aged 7.2 ± 0.4 years) in Basel (Switzerland) were screened for retinal arteriolar-to-venular ratio (AVR), pulse wave velocity (PWV), SES, migration background and parental PA as well as smoking status.Results: High parental PA levels were associated with a favorable higher AVR (p = 0.020) and lower PWV (p = 0.035), but not independent of parental smoking status. Children with parents who smoked had a higher PWV [4.39 (4.35–4.42) m/s] compared to children with non-smoking parents [4.32 (4.29–4.34) m/s, p = 0.001]. Children of parents with a low household income had a higher PWV [4.36 (4.32–4.41) m/s] compared to children of parents with a high household income [4.30 (4.26–4.34) m/s, p = 0.033]. Low parental educational level was associated with a lower AVR [0.86 (0.85–0.88)] compared to children with highly educated parents [AVR:0.88 (0.87–0.88), p = 0.007; PWV: 4.33 (4.30–4.35) m/s, p = 0.041]. Children with a European background showed a higher AVR [0.88 (0.87–0.88)] compared to non-European children [AVR: (0.86 (0.85–0.87), p = 0.034].Conclusion: Parental PA is associated with better macro- and microvascular childhood health. However, the positive association is lost when parental smoking is considered in the analysis. Socioeconomic factors seem to associate with subclinical vascular alterations in children. Primary prevention programs should focus on including parental lifestyle interventions and educational programs to reduce the burden of lifestyle-associated barriers in order to improve cardiovascular health during lifespan.Clinical Trial Registration:ClinicalTrials.gov Exercise and Arterial Modulation in Youth, https://clinicaltrials.gov/ct2/show/NCT02853747, NCT02853747.

OBJECTIVES The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at high risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

BackgroundAtherosclerotic remodeling starts early in life and can accelerate in the presence of cardiovascular risk (CV) factors. Regular physical activity (PA) can mitigate development of large and small artery disease during lifespan. We aimed to investigate the association of changes in body mass index (BMI), blood pressure (BP), PA behavior and retinal microvascular diameters with large artery pulse wave velocity (PWV) in prepubertal children over 4 years.MethodsThe school-based prospective cohort study included 262 children initially aged 6–8 years, assessing the above CV risk factors and retinal vessels by standardized procedures at baseline (2014) and follow-up (2018). PWV was assessed by an oscillometric device at follow-up.ResultsChildren with increased systolic BP over 4 years showed higher PWV at follow-up (β [95% CI] 0.006 [0.002 to 0.011] mmHg per unit, P = 0.002). In contrast, increased vigorous PA corresponded to a lower PWV at follow-up (β [95% CI] −0.009 [−0.018 to P = 0.047). Progression of retinal arteriolar narrowing and venular widening were linked to a higher PWV after 4 years (β [95% CI] −0.014 [−0.023 to −0.004] 0.01 changes per unit, P = 0.003).ConclusionIncrease in systolic BP and progression of microvascular dysfunction were associated with higher PWV after 4 years. Children with increasing levels of vigorous PA were found to have lower PWV at follow-up. Habitual vigorous PA has the potential to decelerate the process of early vascular aging in children and may thus help counteract CV disease development later in life.Clinical Trial RegistrationClinicalTrials.gov, Identifier: NCT03085498.

BACKGROUND Serological immunoassays that can identify protective immunity against SARS-CoV-2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS-CoV-2 proteins and assessed the neutralizing activity of antibodies in patient sera. METHODS Consecutive patients admitted with confirmed SARS-CoV-2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in-house enzyme-linked immunosorbent assay utilizing recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was developed and compared to three commercially available enzyme-linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full-length spike protein. Neutralization assays with live SARS-CoV-2 were performed. RESULTS One-thousand four-hundred and seventy-seven individuals were included comprising 112 SARS-CoV-2 positives (defined as a positive real-time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS-CoV-2 positive individuals, 96.3% showed full neutralization of live SARS-CoV-2 at serum dilutions ≥1:16, while none of the 6 SARS-CoV-2 negative sera revealed neutralizing activity. CONCLUSIONS ELISAs targeting RBD and S1 protein of SARS-CoV-2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS-CoV-2.

We present a novel process that allows the transfer of monocrystalline yttrium-iron-garnet microstructures onto virtually any kind of substrate. The process is based on a recently developed method that allows the fabrication of freestanding monocrystalline YIG bridges on gadolinium-gallium-garnet. Here the bridges' spans are detached from the substrate by a dry etching process and immersed in a watery solution. Using drop casting the immersed YIG platelets can be transferred onto the substrate of choice, where the structures finally can be reattached and thus be integrated into complex devices or experimental geometries. Using time resolved scanning Kerr microscopy and inductively measured ferromagnetic resonance we can demonstrate that the structures retain their excellent magnetic quality. At room temperature we find a ferromagnetic resonance linewidth of $\mu_0\Delta H_{HWHM}\approx 195\,\mu T$ and we were even able to inductively measure magnon spectra on a single micron-sized yttrium-iron-garnet platelet at a temperature of 5 K. The process is flexible in terms of substrate material and shape of the structure. In the future this approach will allow for new types of spin dynamics experiments up to now unthinkable., Comment: 4 pages, 6 figures

Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989-2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples 10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n=18) remained seropositive in all samples following seroconversion, whereas for 7 cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women versus men who have sex with men (adjusted OR=4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR=6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 versus

Background and aims Physical activity (PA) and fitness are important modulators of vascular ageing and may therefore help expand individual health span. We aimed to systematically review the association of PA and fitness, as well as the effects of exercise interventions on the new microvascular biomarkers retinal arteriolar (CRAE) and venular (CRVE) diameters and the retinal flicker light-induced dilatation (FID) in children and adults. Methods PubMed, Ovid, The Cochrane, EMBASE and Web of Science were searched. 805 studies were found, and 25 full-text articles analysed. Twenty-one articles were included in this systematic review. Results Higher PA levels were associated with narrower CRVE in children and adults. Physical inactivity was associated with wider CRVE in both age groups. Combined aerobic and motor skill training in school settings lead to wider CRAE in children. Aerobic exercise interventions in adults with or without CV risk factors induced wider CRAE and narrower CRVE. Studies on the effect of exercise on FID are scarce. In a twelve-week randomized controlled trial, high-intensity interval training significantly improved FID in older patients with CV risk factors. Conclusions Higher PA and fitness levels were associated with improved retinal microvascular health in children and adults. Short-term exercise interventions in healthy children and adults, as well as CV risk patients, improved retinal microvascular structure and function. Exercise has the potential to counteract microvascular remodelling and development of small vessel disease during lifespan. Retinal vessel analysis can differentiate the beneficial effects of exercise on target microvascular organ damage.

OBJECTIVES Toxic serum cefepime trough concentrations are not well defined in the current literature. We aimed to define a more precise plasma trough concentration threshold for this antibiotic's neurological toxicity and to identify patients at risk for developing neurotoxic side effects. METHODS Retrospective study including all patients who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Patients with cefepime concentrations other than trough were excluded. The primary outcome was to assess the incidence of neurotoxicity and its relationship with cefepime plasma trough concentrations. Secondary outcomes were the relationship of renal function, cefepime daily dose, age, cerebral and general comorbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalisation in patients with and without neurotoxicity, and the possible impact of neuroprotective co-medications on the outcomes. RESULTS Cefepime concentrations were determined in 584 patients. Among 319 patients with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 patients). Higher cefepime plasma trough concentrations were significantly associated with risk of (no neurotoxicity 6.3 mg/L [IQR 4.1, 8.6] vs with neurotoxicity 21.6 mg/L [IQR 17.0, 28.6], p

This is a case of a 22-year-old, HIV-negative, male patient with asymptomatic syphilitic osteomyelitis of the skull in the context of secondary syphilis. The diagnosis was made based on serology as well as CT and MRI scans. CT volumetric data was post-processed with cinematic rendering, which is a novel algorithm that allows for a photorealistic visualization of the lesions. Imaging and follow-up scans after treatment confirmed the diagnosis without the need to perform invasive procedures such as a biopsy., Neuroscience; Infectious disease; Medical microbiology; Nervous system; Medical imaging; Radiology; Syphilis; Osteomyelitis; Skull; Infectious; Sexually transmitted diseases; Postprocessing; Cinematic rendering; CT; MRI

OBJECTIVES In Switzerland, universal health insurance does not cover any routine testing for sexually transmitted infections (STIs), not even in individuals at high risk, and extra-genital swabbing is not standard of care. We compared STI prevalence in a multicentre prospective observational cohort of multi-partner women with/without sex work and evaluated associated risk factors. MATERIALS AND METHODS Between January 2016 and June 2017, we offered free STI testing to women with multiple sexual partners (three or more in the previous 12 months), with follow-up examinations every 6 months. We used multiplex polymerase chain-reaction testing (for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium) for pooled swabs (pharynx, urethra/vagina, anus), and antibody tests for human immunodeficiency virus (HIV) and Treponema pallidum at every visit, and for hepatitis B and C at baseline. RESULTS We screened 490 female sex workers (FSWs), including 17 trans women, and 92 other multi-partner women. More than half reported a steady partner. Previously undiagnosed HIV was found in 0.2% vs 0.0%, respectively, and T. pallidum antibodies in 5.9% vs 0.0%. STIs requiring antibiotic treatment comprised: active syphilis 1.2% vs 0.0%; N. gonorrhoeae 4.9% vs 0.0%; C. trachomatis 6.3% vs 5.4%, T. vaginalis 10.4% vs 0.0%; M. genitalium 6.7% vs 6.5%. One in four FSWs vs one in nine other women had one or more of these STIs at baseline. 15.8% vs 3.8% had a history of hepatitis B, 45.5% vs 22.8% had no immunity (HBs-AB

Background: Significant hope and expectation has been placed on serological immunoassays to test for previous COVID-19 infection, to determine immunity against

Background: Serological immunoassays that are able to identify protective immunity against SARS-CoV-2 are urgently required to adapt quarantine measures, assess

While coupling of spin waves and mechanical excitations could be used for quantum information processing, creating chip-integrable magnon resonators which at the same time are mechanical oscillators at suitable frequencies has seemed futile---until now. The authors develop a process that allows them to fabricate three-dimensional, freestanding yttrium iron garnet (YIG) magnon resonators of various shapes. These devices exhibit surprisingly low Gilbert damping, rivaling that of high-quality YIG thin films. At the same time, their dimensions and material properties promise mechanical resonances in the upper MHz or even GHz regime.

By means of Swiss tweet–reply pairs recorded using the Twitter Application Programming Interface (API), we analyze the question of how geographical proximity plays a role in digital communication. Additionally, we investigate how the patterns of Twitter-based communication relate to the functional qualities of space. The results show a strong bias of tweet–reply relationships toward short distances even if we control for age, urbanization or language. While roughly only half of a percent of all messages would occur within the same municipality in a random setting, this was the case for about one-third of all observed Twitter communications. Moreover, the median for tweet–reply distances within Switzerland should have been about ten times larger than observed, if proximity had played no special role. Finally, the degree of urbanization influences the intensity of Twitter-based communication, even if we control for size. The more urbanized a municipality, the higher the probability that a tweet–reply communication will occur.

Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of Ne-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M–1 s–1, which resulted in comprehensive structure–activity relationships. Structure–activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the...