OBJECTIVES:Launched in 2012, the Choosing Wisely initiative promotes evidence-based recommendations to reduce unnecessary tests and treatments. This study reviewed laboratory-related recommendations from five countries (USA, UK, Germany, Switzerland, and Austria) to assess their scientific validity. METHODS:Choosing Wisely websites were searched for laboratory-related recommendations. After removing duplicates, 49 randomly selected unique recommendations remained for this study. They were categorized by specialty and assessed for evidence quality using the Oxford 2009 system based on the sources cited by the original authors. Guidelines were rated by the study types supporting the recommendation, while narrative reviews and expert opinions received a lower level of evidence due to their weaker methodology, even if higher-quality studies were cited. The highest possible level of evidence was assigned from the sources provided. RESULTS:Of 49 Choosing Wisely recommendations 58 % were based on high evidence (levels I-II), 14 % on moderate evidence (level III), 18 % on low evidence (level IV-V) and 10 % could not be classified. Hematology, transfusion/coagulation medicine, and oncology had the most level I evidence (75 %), while infectiology, pediatrics, and reproductive medicine relied more on level V sources (each 29 %). Cross-country comparison showed notable differences in the recommendations for laboratory medicine, reflecting national priorities in healthcare. CONCLUSIONS:Some of Choosing Wisely's laboratory-related recommendations are based on a high level of evidence, while others lack strong empirical support. Regular updates with high-quality research, international collaboration, and greater transparency are needed to improve the evidence base and patient care.

Both short and long sleep duration have been associated with poor glycemic control and an increased risk of developing type 2 diabetes mellitus. Although sleep duration may differentially modify the effects of genetic risk factors for type 2 diabetes, this has not been systematically investigated. In the present study, we conducted genome-wide gene by sleep duration meta-analyses, separately assessing interactions of short and long sleep, for fasting glucose, fasting insulin, and hemoglobin A1c in up to 489,309 individuals without diabetes from seven different population groups. In total, 16 loci were identified to interact with sleep duration - six with short sleep and ten with long sleep. Of these, four loci were identified through cross-population meta-analysis. Mapped genes exhibit pathway connections to pericyte apoptosis, NMDA receptor activity, the GLUT1 receptor, neurological health, and sleep architecture. Eleven loci (VRK2, PCDH7, TFAP2A, CAP2, PAPPA, ZCCHC2, MYH9, SGIP1, JAKMIP3, RRAS2, MAPT) have not been reported in previous glycemic trait genome-wide association studies. Interaction loci identify divergent biological mechanisms for short and long sleep duration influencing glycemic control, suggesting specific pathways of intervention for precision medicine approaches to diabetes prevention and management.

Genetic predisposition is a risk factor for office hypertension. We sought to determine whether genetic predisposition identifies individuals with ambulatory daytime hypertension. 1444 participants from the GAPP study (ages 25-41) were analyzed. We evaluated two measures of predisposition to hypertension: family history and polygenic risk scores (PRS). We evaluated correlation of predisposition with blood pressure traits and compared incremental value of each predisposition measure to a validated ambulatory BP prediction model. 12% of participants had office hypertension, while 37% had out-of-office hypertension. The correlation between PRS and family history of hypertension was low (R2 = 4.96x10-3), but both were strongly associated with ambulatory blood pressure (2.2 mmHg per 1 SD increase [95% CI: 1.6, 2.7] & 2.4 mmHg increase with positive family history [95% CI: 1.3, 3.4], respectively). PRS provides incremental improvement predicting ambulatory systolic blood pressure beyond a validated blood pressure prediction score (ΔAIC = -33), whereas family history does not (ΔAIC = 1). The difference between a baseline prediction algorithm for identifying ambulatory systolic hypertension (positive likelihood ratio of 6.87 [95% CI: 5.56, 8.49]; negative likelihood ratio of 0.45 [95% CI: 0.39, 0.51]) and the same model with PRS integrated (positive likelihood ratio of 7.69 [95% CI: 6.18, 9.57]; negative likelihood ratio of 0.43 [95% CI: 0.37, 0.49]) was modest. In a white European sample from Liechtenstein, PRS provides incremental information in identification of individuals with ambulatory hypertension, unlike family history. However, these gains are modest and warrant further development to improve predictive utility at the point-of-care.

Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID (LC), remains a significant burden for public health, with limited long-term data. This study aimed to assess the prevalence and evolution of PASC symptoms after ancestral SARS-CoV-2 (aSCV2) infection in a longitudinal healthcare worker (HCW) cohort. A multicentre cohort study involving HCWs from 14 institutions was conducted in Switzerland. Infection status was based on self-reported positive swabs, with additional serology used to confirm uninfected controls. Baseline was defined as the first survey conducted in 2022 (median 18.5 months post-infection), with follow-up surveys every 6 months through November 2024. To identify PASC-specific symptoms, 24 chronic symptoms were compared between 456 aSCV2-infected and 571 uninfected participants using chi-square tests at baseline. In aSCV2-infected individuals reporting PASC-specific symptoms, symptom trajectories and subjective LC were analyzed across follow-up surveys. Functional limitations were assessed using the Post-COVID Functional Status (PCFS) scale. Thirteen of 24 symptoms were more common in aSCV2-infected individuals, with fatigue (22.8

Background: Test descriptions from major diagnostic manufacturers do not include ferritin reference intervals (RIs) for individuals aged 60 and older. The absence of older adults-specific RIs contrasts with the widespread use of serum ferritin testing in older adults. We aimed to establish and verify RIs using two common analytical methods. Methods: For this study, 1467 older adults were prospectively enrolled and monitored for morbidity and mortality, and exclusion criteria were applied. Ferritin was measured using chemiluminescent microparticle immunoassay (CMIA) and transferred to an electrochemiluminescence immunoassay (ECLIA) using method comparison. RIs were evaluated using a direct method with a prospective observational study based on healthy individuals according to the Clinical and Laboratory Standards Institute (CLSI) 28-A3c guideline and compared with RIs obtained using an indirect approach based on data obtained in clinical routine outpatients, where normal and abnormal values are supposed to be statistically differentiated to determine RIs. When applied within a countrywide population-based setting in Liechtenstein, the impact of novel RIs on the frequency of abnormal values was analyzed. Results: A total of 386 men and 532 women were included in the direct RI determination. Women (W) had significantly lower ferritin levels than men (M), while age over the age of 60 years had no significant association with ferritin in men and women. RIs were 23-241 ng/mL (W) and 19-396 ng/mL (M) for CMIA and 27-293 ng/mL (W) and 23-480 ng/mL (M) for ECLIA. These RIs are higher than those mentioned in the test descriptions in both tests. In comparison, the indirect method for both assays showed comparably lower reference limits, whereas upper reference limits were only approximately similar. The prevalence of high abnormal ferritin levels was considerably lower with this study's RIs compared with manufacturer RIs. Conclusions: Employing older adults-specific RIs in clinical routine seems to be advisable. This reduces the frequency of abnormal high values in comparison with the widely applied practice of extrapolating RIs obtained from younger age groups to older adults and therefore leads to fewer follow-up investigations.

Rare coding genetic variants may exert large effects on risk of common disease, yet their contribution to disease architecture and their utility in gene prioritization remain limited by inadequate sample sizes. Here, we performed a massive-scale rare variant association study (RVAS), analyzing over 1.1 million sequenced participants among which 130,000 had atrial fibrillation (AF). Through a multi-mask burden testing approach, we identified 15 genes significantly associated with AF through rare large-effect variation. Integrative analyses revealed strong convergence between genes implicated by rare and common variation, and highlighted instances where RVAS data may aid in GWAS prioritization. Nevertheless, several RVAS genes were not among GWAS loci ( FAM189A2 , ACTC1 , FNIP1 , FBN1 ), or were not nominated through contemporary GWAS prioritization ( KDM5B , ZFP36L2 ). Finally, we observed that ultra-rare protein-disrupting variants - concentrated in a small number of large-effect size genes - explained at least 2% of AF susceptibility across European and African ancestry groups. These findings refine the genetic architecture of AF, while highlighting the value and cost of RVAS for genomic discovery in common disease.

Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 were derived from non-European populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4 and MAGI2) and neuronal signaling (CCK, UGDH, and SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets linked to pathways involved in mood disorders as well as known anti-hypertensive drugs. Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.

Background Foehn winds—warm, dry downslope winds common in alpine regions—may impact human health, especially in weather-sensitive individuals, though evidence is lacking. Wearable devices now enable continuous health monitoring, offering new insights into physiological reactions to such weather conditions. This study investigates the association between Foehn winds and physiological parameters. Methods In a repeated-measures design, healthy adults in Liechtenstein wore medical sensory bracelets for 11 months, recording nightly heart rate (HR), heart rate variability (HRV), wrist skin temperature (WST), respiratory rate (RR), perfusion index (PI) and sleep duration. Foehn exposure was determined using local weather data. Linear mixed-effects models assessed associations, adjusting for confounders. Results A total of 714 participants (59.7% women; mean age 44.0 years) were included. Foehn was associated with changes in HR (+ 0.25 bpm; 95% CI: 0.17, 0.33), PI (+ 0.78%; 95% CI: 0.22, 1.33), and HRV (–0.29%; 95% CI: − 0.55, − 0.04), while RR, WST, and sleep duration remained unchanged. 40.8% disclosed being Foehn-sensitive via questionnaire. They showed a 9.92% lower PI irrespective of Foehn. Effects of Foehn differed by Foehn sensitivity: HR (+ 0.32 bpm vs. +0.15 bpm) and HRV (–0.53% vs. +0.04%) responses were more pronounced in non-sensitive individuals. Conclusions Our findings show that Foehn winds are linked to changes in physiological parameters, suggesting a weather-induced stress response. These effects were independent of sex. Interestingly, Foehn-sensitive individuals showed a lower baseline perfusion index (irrespective of Foehn), indicating a potential physiological predisposition. However, contrary to expectations, stronger physiological responses occurred in non-sensitive individuals.

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B in stem-cell-derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction. Our results highlight the contribution of rare coding and structural variants to AF, including genetic links between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia.

BACKGROUND AND AIMS:Dried blood spots (DBS) have been proposed as a cost-effective surveillance method for population-wide screening of SARS-CoV-2 immunity but sensitivity of DBS based on self-collected DBS samples is unknown. To evaluate the success of vaccination strategies, it is necessary to differentiate vaccination from natural infection. Therefore, a test for antibodies against the viral nucleocapsid protein (anti-N) is desirable. MATERIALS AND METHODS:In our prospectively followed cohort of healthcare workers (HCW) in eastern Switzerland, we assessed SARS-CoV-2-anti-N-seroprevalence using DBS on a biweekly basis from March to September 2020. Phlebotomy samples were collected in March and September and tested for anti-N-seropositivity, as well as SARS-CoV-2 spike antibodies for quantitative validation. Venous antibody testing was compared with DBS results for anti-N using the Roche Elecsys electro-chemiluminescence immunoassay. RESULTS:792 HCW (median age 38.3 years) were included, 35 (4.4 %) were SARS-CoV-2-anti-N-seropositive. Of 43 matching DBS, 25 tested positive for anti-N, accounting for a sensitivity of 58.1 % (95 %CI 43.3-71.6 %). We found a significant correlation of anti-N from DBS with results from phlebotomy samples (r = 0.77;p < 0.0001), with higher levels being associated with a higher true-positive rate. Anti-N in DBS correlated significantly with quantitatively validated anti-S obtained from serum (r = 0.67;p < 0.0001). CONCLUSION:Although home DBS collection was feasible in a larger cohort and we found a high correlation between anti-N detection in DBS and phlebotomy samples, the sensitivity of self-collected DBS samples was significantly impaired for the Roche Elecsys anti-N assay. Therefore, we cannot recommend this method for DBS when testing from venous blood is possible.

Cigarette smoking influences blood pressure (BP) levels. Studying and accounting for potential gene-smoking interactions can help discover novel loci and provide insights into biological pathways for smoking-associated BP regulation. We conducted a genome-wide association meta-analysis involving 1,188,241 individuals from 66 studies in five ancestry groups, analyzing systolic BP, diastolic BP, and pulse pressure while considering interactions between genetic variants and three smoking exposures: smoking status, cigarettes per day, and pack years. These analyses identified twelve novel loci for BP at genome-wide significance ( P < 5 × 10 - 9 ), and highlighted biological processes including tight junction integrity, mitochondrial health, vascular relaxation, and endothelial function. In smoking status-stratified analyses, smoking modifies the genetic effect of six variants on BP. To prioritize likely causal, we developed and applied SuSiEgxe, a fine-mapping method based on a two-degree-of-freedom joint test using gene-environment interaction summary statistics. Fine-mapped loci uncovered immune-related pathway for smoking-associated BP regulation.

Maintaining the integrity of blood samples during transport is essential for accurate laboratory diagnostics. Hemolytic, lipemic, and icteric (HIL) indices are critical preanalytical markers that detect hemolysis, lipemia, and icterus, which can interfere with diagnostic results. With the growing interest in drones as a method of medical transport, particularly for remote or underserved areas, it is crucial to evaluate their impact on the stability of HIL indices. This study investigates whether blood samples transported by drones maintain their integrity, focusing on four common sample types: serum, EDTA whole blood, lithium-heparin plasma, and citrate plasma. A total of 25 samples for each of the four blood types were collected and transported by a custom-built medical drone. The drone covered a 25 km route in 30 minutes at a cruising speed of 100 km/h and an altitude of 100 meters. Samples were placed in secure containers designed to minimize vibration and temperature fluctuations. Environmental conditions were monitored using data loggers and accelerometers. Hemolytic, lipemic, and icteric indices were measured spectrophotometrically before and after transport using standard absorbance techniques. Paired t-tests were performed to assess statistical significance, with a threshold of p < 0.05. The study found no significant changes in the HIL indices for any sample type after drone transport. Serum samples exhibited minimal variations, with the hemolytic index showing a mean change of -0.15 (p = 0.19) and the lipemic index a decrease of -0.20 (p = 0.38). EDTA whole blood demonstrated similarly stable results, with the hemolytic index showing a delta of -0.15 (p = 0.42) and the lipemic index increasing by +0.25 (p = 0.23). Lithium-heparin plasma displayed absolute stability in the hemolytic index (0.00, p = 1.00) and minor, non-significant changes in the icteric and lipemic indices (+0.05, p = 0.79). Citrate plasma results reflected comparable stability, with all p-values exceeding 0.19. Across all sample types, the variations in mean values were statistically and clinically insignificant, confirming the stability of preanalytical quality during drone transport. This study demonstrates that blood samples transported via drone maintain stable hemolytic, lipemic, and icteric indices, supporting the reliability of this method in medical logistics. Drones offer significant advantages, including bypassing traffic, reducing delays, and enabling transport in remote or underserved areas. Additionally, they present a sustainable alternative to traditional transportation methods. By ensuring the integrity of transported blood samples, this research supports the integration of drones into healthcare systems as an innovative, efficient, and environmentally friendly solution. Further exploration of drone scalability and its effects on additional diagnostic parameters is warranted to expand its application in modern laboratory medicine.

Background:Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample. Results:Our study included 564,680 adults aged 18 years or older from 67 cohorts and 4 population backgrounds (African (5%), Asian (7%), European (85%), and Hispanic (3%)). We discovered seven novel gene-DEPR interaction loci for BP traits. These loci mapped to genes implicated in neurogenesis (TGFA, CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6, DBI). We also identified evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 loci were derived from African, Asian, or Hispanic populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4, MAGI2) and neuronal signaling (CCK, UGDH, SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets, including genes implicated in pathways linked to mood disorders as well as gene products targeted by known antihypertensive drugs. Conclusions:Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.

Cystatin C was identified as a marker of glomerular filtration rate (GFR) in 1979, and the parallel analysis of cystatin C and creatinine led to the identification of shrunken pore syndrome (SPS) - a new kidney disorder - in 2015. Since then, it has been shown that cystatin C in many aspects is superior to creatinine as a marker of GFR and cardiovascular risk. SPS, an entity within the selective glomerular hypofiltration syndromes (SGHS), has been demonstrated to be associated with a strong increase in morbidity and mortality in several populations. Despite the seriousness of SPS and SGHS, and the availability of potential treatments, many patients with these conditions remain undiagnosed, due to the limitations of the international Kidney Disease Improving Global Outcomes Organization (KDIGO) guidelines. Given the significant clinical advantages of cystatin C in diagnosing and treating kidney disorders, there is a need to expand the KDIGO guidelines to include cystatin C measurements alongside creatinine at least in the initial patient evaluation but also in follow-up evaluations. This would improve the early detection and management of patients with kidney diseases, ultimately enhancing patient outcomes. The present discourse summarizes the development of this understanding from the original observations in 1979 and 2015 to the latest findings.

The increasing adoption of drones in medical logistics raises concerns about the potential cumulative effects of repeated transport on the quality of blood samples and the variability in laboratory results. This study investigates the stability of 35 analytes, including potassium, thrombocytes, international normalized ratio (INR), Quick value, and activated partial thromboplastin time (aPTT), over ten consecutive drone transport cycles, focusing on four blood types: serum, EDTA plasma, lithium-heparin plasma, and citrate plasma. Blood samples of four different materials (serum, citrate, EDTA, Li-Hep) were subjected to ten drone transport cycles over a standard route, with each cycle lasting approximately 30 minutes. A total of 35 analytes were measured pre- and post-transport using standard laboratory methods. Key transport parameters such as vibration and temperature fluctuations were monitored. Pre- and post-transport analyte concentrations were assessed using spectrophotometric and hematological techniques. Statistical analyses, including Passing-Bablok regression and Bland-Altman plots, were employed to evaluate variability, and paired t-tests determined significant changes in mean values. The majority of analytes exhibited stability across all blood types, with minimal variation in pre- and post-transport results. Potassium levels demonstrated a statistically significant increase in variability (Passing-Bablok slope: 1.07, r = 0.98) after repeated transport cycles, accompanied by a mean bias of +2.5%. Thrombocyte counts showed a similar trend, with Bland-Altman analysis revealing a proportional bias of +3.2% after the tenth cycle. The Quick value exhibited a significant increase from a mean pre-transport value of 91.05% to 107.12%, with a Passing-Bablok slope of 1.177 and a mean bias of +15.0%. In contrast, INR values decreased slightly from 0.94 to 0.90, with a Passing-Bablok slope of 1.000 and a mean bias of -0.04%. Additionally, the aPTT increased by 4.46 seconds on average, rising from 20.32 seconds pre-transport to 24.78 seconds post-transport, with a Passing-Bablok slope of 1.220 and a mean bias of +18.0%. Other analytes, such as bilirubin and alkaline phosphatase, remained within clinically acceptable limits across all cycles, confirming the robustness of drone transport for most laboratory parameters. Repeated drone transport does not compromise the integrity of the majority of blood analytes, supporting its viability for medical logistics. However, increased variability in potassium levels, thrombocyte counts, Quick values, and aPTT times, as well as the slight decrease in INR, highlight the need for cautious interpretation in clinical scenarios involving multiple transport cycles. This study underscores the importance of validating drone-based logistics for specific analytes to ensure reliable laboratory diagnostics.

Maintaining blood sample integrity is essential for accurate laboratory diagnostics. The hemolytic, lipemic, and icteric (HIL) indices are critical markers of sample quality, detecting common preanalytical interferences such as hemolysis, lipemia, and icterus. Drone technology offers a novel transport method for medical logistics, particularly in remote or underserved regions. This study assessed the stability of HIL indices in blood samples transported by drone. Twenty-five samples each of serum, EDTA whole blood, lithium-heparin plasma, and citrate plasma were collected from healthy volunteers using standard venipuncture techniques. Serum samples were collected in gel separator tubes. Samples were transported unprocessed using a rotor-type hybrid drone (Jedsy Glider) over a 25-kilometer route. Temperature and vibration were monitored during flight using data loggers and accelerometers. HIL indices were measured preflight and postflight using a Roche Cobas 6000 system. Paired t-tests assessed significant changes (P < 0.05). No statistically significant differences were observed in the HIL indices preflight and postflight for all blood sample types. For serum samples, the hemolytic index decreased slightly from 9.60 to 9.45 (P = 0.19), with negligible changes in lipemic and icteric indices. Similar stability was observed for EDTA whole blood, lithium-heparin plasma, and citrate plasma. Drone transport is a viable alternative for blood sample logistics, preserving HIL index stability across various sample types. These findings underscore the potential of drones to enhance healthcare logistics in remote or underserved environments. This study was conducted as a quality assurance project for the Institute of Clinical Chemistry at Dr. Risch, Buchs, Switzerland. The Ethics Committee Ostschweiz reviewed the study under BASEC-ID Req-2024-01510 and determined that it does not fall within the scope of the Swiss Human Research Act and therefore does not require formal ethics committee approval. This determination was based on the project's designation as a quality assurance initiative rather than a human research study. As per the committee's guidance, data protection and confidentiality were strictly maintained throughout the study, ensuring compliance with all relevant legal and institutional requirements.

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci. Furthermore, we assayed chromatin accessibility using assay for transposase-accessible chromatin with sequencing and histone H3 lysine 4 trimethylation in stem cell-derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility for our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known risk loci will facilitate a greater understanding of the pathways underlying AF.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes’ functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

BACKGROUND:Rapid and early detection of SARS-CoV-2 infections, especially during the pre- or asymptomatic phase, could aid in reducing virus spread. Physiological parameters measured by wearable devices can be efficiently analysed to provide early detection of infections. The COVID-19 Remote Early Detection (COVID-RED) trial investigated the use of a wearable device (Ava bracelet) for improved early detection of SARS-CoV-2 infections in real-time. TRIAL DESIGN:Prospective, single-blinded, two-period, two-sequence, randomised controlled crossover trial. METHODS:Subjects wore a medical device and synced it with a mobile application in which they also reported symptoms. Subjects in the experimental condition received real-time infection indications based on an algorithm using both wearable device and self-reported symptom data, while subjects in the control arm received indications based on daily symptom-reporting only. Subjects were asked to get tested for SARS-CoV-2 when receiving an app-generated alert, and additionally underwent periodic SARS-CoV-2 serology testing. The overall and early detection performance of both algorithms was evaluated and compared using metrics such as sensitivity and specificity. RESULTS:A total of 17,825 subjects were randomised within the study. Subjects in the experimental condition received an alert significantly earlier than those in the control condition (median of 0 versus 7 days before a positive SARS-CoV-2 test). The experimental algorithm achieved high sensitivity (93.8-99.2%) but low specificity (0.8-4.2%) when detecting infections during a specified period, while the control algorithm achieved more moderate sensitivity (43.3-46.4%) and specificity (66.4-65.0%). When detecting infection on a given day, the experimental algorithm also achieved higher sensitivity compared to the control algorithm (45-52% versus 28-33%), but much lower specificity (38-50% versus 93-97%). CONCLUSIONS:Our findings highlight the potential role of wearable devices in early detection of SARS-CoV-2. The experimental algorithm overestimated infections, but future iterations could finetune the algorithm to improve specificity and enable it to differentiate between respiratory illnesses. TRIAL REGISTRATION:Netherlands Trial Register number NL9320.

Molecular methods to detect antimicrobial resistance in Neisseria gonorrhoeae (Ng) are increasingly needed worldwide to improve diagnostic tests and enable individualized patient treatments. The Allplex™ NG DR Assay (NG DR assay) was assessed for its ability to detect Ng and its antimicrobial resistance. The assay predicts ciprofloxacin resistance and susceptibility by targeting the molecular antimicrobial resistance (AMR) determinant gyrA S91F. The AMR determinants 23 S rRNA A2059G and C2611T were investigated to predict azithromycin wild-type and nonwild-type genotypes. After antimicrobial susceptibility testing, 153 Ng isolates were evaluated with the NG DR assay. Furthermore, 394 clinal specimens, including 76 with corresponding antimicrobial susceptibility results, were analyzed simultaneously by the NG DR assay and the in-house SYBR-Green assay. The NG DR assay predicted ciprofloxacin resistance and susceptibility with a sensitivity and specificity of 98.2