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Detecting genetic variants enables risk factor identification, disease screening, and initiation of preventative therapeutics. However, current methods, relying on hybridization or sequencing, are unsuitable for point-of-care settings. In contrast, CRISPR-based-diagnostics offer high sensitivity and specificity for point-of-care applications. While these methods have predominantly been used for pathogen sensing, their utilization for genotyping is limited. Here, we report a multiplexed CRISPR-based genotyping assay using LwaCas13a, PsmCas13b, and LbaCas12a, enabling the simultaneous detection of six genotypes. We applied this assay to identify genetic variants in the APOL1 gene prevalent among African Americans, which are associated with an 8-30-fold increase in the risk of developing kidney disease. Machine learning facilitated robust analysis across a multicenter clinical cohort of more than 100 patients, accurately identifying their genotypes. In addition, we optimized the readout using a multi-analyte lateral-flow assay demonstrating the ability for simplified genotype determination of clinical samples. Our CRISPR-based genotyping assay enables cost-effective point-of-care genetic variant detection due to its simplicity, versatility, and fast readout.

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Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington's disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.

Asunto(s)

Encéfalo , Proteínas de Unión al ADN , Proteína Huntingtina , Enfermedad de Huntington , Células Madre Pluripotentes Inducidas , Mitocondrias , Proteínas Mitocondriales , Organoides , Factores de Transcripción , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Organoides/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Encéfalo/metabolismo , Encéfalo/patología , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Mitocondrias/metabolismo , Mutación , Dinámicas Mitocondriales/genética

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The Enterobacteriaceae are a scientifically and medically important clade of bacteria, containing the model organism Escherichia coli, as well as major human pathogens including Salmonella enterica and Klebsiella pneumoniae. Essential gene sets have been determined for several members of the Enterobacteriaceae, with the Keio E. coli single-gene deletion library often regarded as a gold standard. However, it remains unclear how gene essentiality varies between related strains and species. To investigate this, we have assembled a collection of 13 sequenced high-density transposon mutant libraries from five genera within the Enterobacteriaceae. We first assess several gene essentiality prediction approaches, investigate the effects of transposon density on essentiality prediction, and identify biases in transposon insertion sequencing data. Based on these investigations, we develop a new classifier for gene essentiality. Using this new classifier, we define a core essential genome in the Enterobacteriaceae of 201 universally essential genes. Despite the presence of a large cohort of variably essential genes, we find an absence of evidence for genus-specific essential genes. A clear example of this sporadic essentiality is given by the set of genes regulating the σE extracytoplasmic stress response, which appears to have independently acquired essentiality multiple times in the Enterobacteriaceae. Finally, we compare our essential gene sets to the natural experiment of gene loss in obligate insect endosymbionts that have emerged from within the Enterobacteriaceae. This isolates a remarkably small set of genes absolutely required for survival and identifies several instances of essential stress responses masked by redundancy in free-living bacteria.IMPORTANCEThe essential genome, that is the set of genes absolutely required to sustain life, is a core concept in genetics. Essential genes in bacteria serve as drug targets, put constraints on the engineering of biological chassis for technological or industrial purposes, and are key to constructing synthetic life. Despite decades of study, relatively little is known about how gene essentiality varies across related bacteria. In this study, we have collected gene essentiality data for 13 bacteria related to the model organism Escherichia coli, including several human pathogens, and investigated the conservation of essentiality. We find that approximately a third of the genes essential in any particular strain are non-essential in another related strain. Surprisingly, we do not find evidence for essential genes unique to specific genera; rather it appears a substantial fraction of the essential genome rapidly gains or loses essentiality during evolution. This suggests that essentiality is not an immutable characteristic but depends crucially on the genomic context. We illustrate this through a comparison of our essential genes in free-living bacteria to genes conserved in 34 insect endosymbionts with naturally reduced genomes, finding several cases where genes generally regarded as being important for specific stress responses appear to have become essential in endosymbionts due to a loss of functional redundancy in the genome.

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Although the advent of organoids has opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here, we established organoids from the thymus, the lymphoid organ responsible for T-cell development. We identified conditions enabling mouse thymic epithelial progenitor cell proliferation and development into organoids with diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. In contrast to these two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T-cell development upon reaggregation with T-cell progenitors. The reaggregates showed in vivo-like epithelial diversity and the ability to attract T-cell progenitors. Thymic epithelial organoids are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T-cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries.

Asunto(s)

Diferenciación Celular , Células Epiteliales , Organoides , Linfocitos T , Timo , Animales , Organoides/citología , Timo/citología , Linfocitos T/citología , Linfocitos T/metabolismo , Linfocitos T/inmunología , Células Epiteliales/citología , Células Epiteliales/metabolismo , Ratones , Proliferación Celular , Ratones Endogámicos C57BL , Células Madre/citología , Células Madre/metabolismo

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Introduction: Breast reduction mammoplasty (BRM) is a common procedure performed by plastic surgeons treating patients with hypermastia. It is customary to give preoperative prophylactic intravenous antibiotics for BRM, followed by several days of postoperative prophylactic oral antibiotics, despite the lack of evidence of their effectiveness in preventing surgical site infections (SSIs). The purpose of this study is to determine if the addition of prophylactic postoperative antibiotics is more effective in preventing SSIs in comparison to a single dose of preoperative prophylactic antibiotics in BRM. Methods: A retrospective analysis of 124 elective BRM cases by a single senior plastic surgeon was completed. Two study groups were formed based on the location of surgery and each group was assigned a different antibiotic regimen. The first antibiotic regimen consisted of a single preoperative intravenous dose of antibiotics (group 1), while the second regimen consisted of a preoperative intravenous dose followed by a 5-day course of oral antibiotics (group 2). Results: Overall SSI rate was 5.6%. Infection rate in group 1 was 8.1% in comparison to 3.2% for group 2 (P value .44). Overall, the incidence of complications was 29.0%; 38.7% in group 1 and 19.4% in group 2 (P value .03). Complications consisted of 35 cases of delayed wound healing, 7 SSIs and 2 hematomas requiring evacuation. Conclusion: Study results demonstrated that the use of postoperative prophylactic antibiotics for BRM had no significant effect on the rate of SSIs.

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Introduction: La mammoplastie de réduction mammaire (MRM) est une procédure couramment pratiquée par les chirurgiens plastiques traitant des patientes ayant une hypertrophie mammaire. Il est habituel d'administrer une prophylaxie intraveineuse préopératoire pour la MRM puis plusieurs jours d'antibiothérapie prophylactique postopératoire par voie orale en dépit de l'absence de données probantes de leur efficacité à prévenir les infections du site chirurgical. L'objectif de cette étude était de déterminer si l'ajout d'antibiotiques postopératoires à visée prophylactique est plus efficace pour la prévention des infections de la cicatrice opératoire que la seule administration préopératoire d'une dose unique d'antibiotiques à visée prophylactique dans la MRM. Méthodes: Une analyse rétrospective a été réalisée par un seul chirurgien plastique expérimenté de 124 cas de MRM planifiés. Deux groupes d'étude ont été constitués en fonction du lieu de la chirurgie parmi deux centres chirurgicaux et chaque groupe ayant reçu l'un des deux protocoles d'antibiothérapie suivants : le premier schéma thérapeutique était constitué d'une seule dose préopératoire administrée par voie intraveineuse (groupe 1) et le deuxième consistait en l'administration de la dose préopératoire par voie intraveineuse suivie de 5 jours d'antibiotiques par voie orale (groupe 2). Résultats: Le taux global d'infections de la cicatrice opératoire était de 5,6%. Le taux d'infections dans le groupe 1 a été de 8,1%, comparativement à 3,2% dans le groupe 2 (P = 0,44). L'incidence globale des complications a été de 29,0%; 38,7% dans le groupe 1 et 19,4% dans le groupe 2 (P = 0,03). Les complications ont été 35 cas de retard de cicatrisation, 7 cas d'infection du site chirurgical et 2 hématomes nécessitant leur évacuation. Conclusion: Les résultats de l'étude ont montré que l'utilisation postopératoire d'antibiotiques à visée prophylactique pour la mammoplastie de réduction mammaire n'avait pas d'effet significatif sur le taux d'infections du site chirurgical.

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CASE: We present a 63-year-old patient diagnosed with Waldenstrom macroglobulinemia (WM) through histopathology of bone tissue after total knee arthroplasty for routine osteoarthritis. The patient, surgical team, and the pathologist were unaware of this diagnosis before the surgery. CONCLUSION: The cost-effectiveness of routine histopathologic examination of bone cuts and synovial samples after total joint arthroplasty continues to be a source of debate. Our case highlights an example of the utility of histopathology because it led to the early detection of WM, resulting in prompt treatment to improve quality of life.

Asunto(s)

Artroplastia de Reemplazo de Rodilla , Osteoartritis , Macroglobulinemia de Waldenström , Humanos , Persona de Mediana Edad , Macroglobulinemia de Waldenström/diagnóstico , Calidad de Vida , Huesos

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BACKGROUND AND AIMS: Pain is a cardinal symptom in inflammatory bowel disease [IBD]. An important structure in the transduction of pain signalling is the myenteric plexus [MP]. Nevertheless, IBD-associated infiltration of the MP by immune cells lacks in-depth characterisation. Herein, we decipher intra- and periganglionic immune cell infiltrations in Crohn´s disease [CD] and ulcerative colitis [UC] and provide a comparison with murine models of colitis. METHODS: Full wall specimens of surgical colon resections served to examine immune cell populations by either conventional immuno-histochemistry or immunofluorescence followed by either bright field or confocal microscopy. Results were compared with equivalent examinations in various murine models of intestinal inflammation. RESULTS: Whereas the MP morphology was not significantly altered in IBD, we identified intraganglionic IBD-specific B cell- and monocyte-dominant cell infiltrations in CD. In contrast, UC-MPs were infiltrated by CD8+ T cells and revealed a higher extent of ganglionic cell apoptosis. With regard to the murine models of intestinal inflammation, the chronic dextran sulphate sodium [DSS]-induced colitis model reflected CD [and to a lesser extent UC] best, as it also showed increased monocytic infiltration as well as a modest B cell and CD8+ T cell infiltration. CONCLUSIONS: In CD, MPs were infiltrated by B cells and monocytes. In UC, mostly CD8+ cytotoxic T cells were found. The chronic DSS-induced colitis in the mouse model reflected best the MP-immune cell infiltrations representative for IBD.

Asunto(s)

Colitis Ulcerosa , Colitis , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Colitis Ulcerosa/metabolismo , Enfermedad de Crohn/metabolismo , Plexo Mientérico/metabolismo , Colitis/inducido químicamente , Neurotransmisores/efectos adversos , Dolor , Inflamación

RESUMEN

OBJECTIVE: To assess diagnostic value and clinical utility of multidetector computed tomographic positive contrast arthrography (CTA) for meniscal lesions in dogs. STUDY DESIGN: Prospective case series. STUDY POPULATION: Client-owned dogs (n = 55) with cranial cruciate ligament injuries. METHODS: Sedated dogs underwent CTA using a 16-slice scanner, and subsequently received mini-medial arthrotomy for meniscal assessment. Scans were anonymized, randomized, and reviewed twice for meniscal lesions by three independent observers with varying experience. Results were compared with surgical findings. Reproducibility and repeatability were assessed with kappa statistics, intraobserver changes in diagnosis by McNemar's test, and interobserver differences using Cochran's Q test. Test performance was calculated using sensitivity, specificity, proportion correctly identified, and positive and negative predictive values and likelihood ratios. RESULTS: Analysis was based on 52 scans from 44 dogs. Sensitivity for identifying meniscal lesions was 0.62-1.00 and specificity was 0.70-0.96. Intraobserver agreement was 0.50-0.78, and interobserver agreement was 0.47-0.83. There was a significant change between readings one and two for the least experienced observers (p < .05). The sum of sensitivity and specificity exceeded 1.5 for both readings and all observers. CONCLUSION: Diagnostic performance was suitable for identifying meniscal lesions. An effect of experience and learning was seen in this study.

Asunto(s)

Lesiones del Ligamento Cruzado Anterior , Enfermedades de los Perros , Humanos , Perros , Animales , Artrografía/veterinaria , Artrografía/métodos , Rodilla de Cuadrúpedos/cirugía , Ligamento Cruzado Anterior/cirugía , Reproducibilidad de los Resultados , Meniscos Tibiales/cirugía , Medios de Contraste , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/veterinaria , Sensibilidad y Especificidad , Artroscopía/veterinaria , Enfermedades de los Perros/diagnóstico por imagen

RESUMEN

Vaccines are among the most powerful tools to combat the COVID-19 pandemic. They are highly effective against infection and substantially reduce the risk of severe disease, hospitalization, ICU admission, and death. However, their potential for attenuating long-term changes in personal health and health-related wellbeing after a SARS-CoV-2 infection remains a subject of debate. Such effects can be effectively monitored at the individual level by analyzing physiological data collected by consumer-grade wearable sensors. Here, we investigate changes in resting heart rate, daily physical activity, and sleep duration around a SARS-CoV-2 infection stratified by vaccination status. Data were collected over a period of 2 years in the context of the German Corona Data Donation Project with around 190,000 monthly active participants. Compared to their unvaccinated counterparts, we find that vaccinated individuals, on average, experience smaller changes in their vital data that also return to normal levels more quickly. Likewise, extreme changes in vitals during the acute phase of the disease occur less frequently in vaccinated individuals. Our results solidify evidence that vaccines can mitigate long-term detrimental effects of SARS-CoV-2 infections both in terms of duration and magnitude. Furthermore, they demonstrate the value of large-scale, high-resolution wearable sensor data in public health research.

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Various positioning techniques have been described for the osteosynthesis of olecranon fractures, each with their own pros and cons. The supine position is time-efficient and better suited in a polytrauma setting but frequently requires an assistant to maintain optimal limb positioning. Also, adequate fluoroscopic imaging is not possible without moving the operative extremity outside the sterile field. We describe a simple and reproducible method addressing these limitations while providing excellent surgical access and intraoperative imaging.

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Classic ecological research into the determinants of biodiversity patterns emphasised the important role of three-dimensional (3D) vegetation heterogeneity. Yet, measuring vegetation structure across large areas has historically been difficult. A growing focus on large-scale research questions has caused local vegetation heterogeneity to be overlooked compared with more readily accessible habitat metrics from, for example, land cover maps. Using newly available 3D vegetation data, we investigated the relative importance of habitat and vegetation heterogeneity for explaining patterns of bird species richness and composition across Denmark (42,394 km2 ). We used standardised, repeated point counts of birds conducted by volunteers across Denmark alongside metrics of habitat availability from land-cover maps and vegetation structure from rasterised LiDAR data (10 m resolution). We used random forest models to relate species richness to environmental features and considered trait-specific responses by grouping species by nesting behaviour, habitat preference and primary lifestyle. Finally, we evaluated the role of habitat and vegetation heterogeneity metrics in explaining local bird assemblage composition. Overall, vegetation structure was equally as important as habitat availability for explaining bird richness patterns. However, we did not find a consistent positive relationship between species richness and habitat or vegetation heterogeneity; instead, functional groups displayed individual responses to habitat features. Meanwhile, habitat availability had the strongest correlation with the patterns of bird assemblage composition. Our results show how LiDAR and land cover data complement one another to provide insights into different facets of biodiversity patterns and demonstrate the potential of combining remote sensing and structured citizen science programmes for biodiversity research. With the growing coverage of LiDAR surveys, we are witnessing a revolution of highly detailed 3D data that will allow us to integrate vegetation heterogeneity into studies at large spatial extents and advance our understanding of species' physical niches.

Asunto(s)

Biodiversidad , Ecosistema , Animales , Aves/fisiología , Telemetría , Dinamarca

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BACKGROUND: The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear. METHODS: We conducted a systematic review until 1 November 2022 searching for randomized controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir [±standard of care (SoC)] versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach. RESULTS: Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality [risk ratio (RR) 0.27, 95% CI 0.07-1.02, high-certainty evidence] and probably does not reduce the risk for 'hospitalization or death' (RR 0.81, 95% CI 0.55-1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02-1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92-1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50-28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence). CONCLUSIONS: In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on 'hospitalization or death' and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.

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COVID-19 , Humanos , SARS-CoV-2

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PURPOSE: Postoperative wound complications are common in patients undergoing resection of lower extremity soft tissue tumors. Postoperative drainage therapy ensures adequate wound healing but may delay or complicate it. The aim of this study is to evaluate the incidence of postoperative wound complications and delayed or prolonged drainage treatment and to propose a standardized definition and severity grading of complex postoperative courses. METHODS: A monocentric retrospective analysis of 80 patients who had undergone primary resection of lower extremity soft tissue tumors was performed. A new classification was developed, which takes into account postoperative drainage characteristics and wound complications. Based on this classification, risk factors and the prognostic value of daily drainage volumes were evaluated. RESULTS: According to this new definition, regular postoperative course grade 0 (no wound complication and timely drainage removal) occurred in 26 patients (32.5%), grade A (minor wound complications or delayed drainage removal) in 12 (15.0%), grade B (major wound complication or prolonged drainage therapy) in 31 (38.8%), and grade C (reoperation) in 11 (13.7%) patients. Tumor-specific characteristics, such as tumor size (p = 0.0004), proximal tumor location (p = 0.0484), and tumor depth (p = 0.0138) were identified as risk factors for complex postoperative courses (grades B and C). Drainage volume on postoperative day 4 was a suitable predictor for complex courses (cutoff of 70 ml/d). CONCLUSION: The proposed definition incorporates wound complications and drainage management while also being clinically relevant and easy to apply. It may serve as a standardized endpoint for assessing the postoperative course after resection of lower extremity soft tissue tumors.

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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Estudios Retrospectivos , Radioterapia Adyuvante/efectos adversos , Sarcoma/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Extremidad Inferior/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de los Tejidos Blandos/patología , Drenaje/efectos adversos

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The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear. In this study, we investigate the role of MALT1 proteolytic activity in the context of mucosal inflammation. We demonstrate a significant enrichment of MALT1 gene and protein expression in colonic epithelial cells of UC patients, as well as in the context of experimental colitis. Mechanistically we demonstrate that MALT1 protease function inhibits ferroptosis, a form of iron-dependent cell death, upstream of NF-κB signaling, which can promote inflammation and tissue damage in IBD. We further show that MALT1 activity contributes to STAT3 signaling, which is essential for the regeneration of the intestinal epithelium after injury. In summary, our data strongly suggests that the protease function of MALT1 plays a critical role in the regulation of immune and inflammatory responses, as well as mucosal healing. Understanding the mechanisms by which MALT1 protease function regulates these processes may offer novel therapeutic targets for the treatment of IBD and other inflammatory diseases.

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Enfermedades Inflamatorias del Intestino , Transducción de Señal , Humanos , Inflamación , Enfermedades Inflamatorias del Intestino/genética , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/genética , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas/metabolismo , FN-kappa B/metabolismo , Proteolisis , Células Epiteliales

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OBJECTIVES: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose). METHODS: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID100 ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits. Patients with reported COVID-19 during follow-up were excluded. Predictors of serological immune response were analyzed using multivariate regression models. RESULTS: Of 84 people living with HIV who received an mRNA-based booster vaccination, 76 were eligible for analysis. Participants were on effective antiretroviral therapy (ART) and had a median of 670 CD4+ cells/µL (interquartile range [IQR] 540-850). Following booster vaccination, median anti-spike RBD IgG increased by 705.2 binding antibody units per millilitre (BAU/mL) and median VNA titres increased by 1000 ID100 at the follow-up assessment (median 13 weeks later). Multivariate regression revealed that time since second vaccination was a predictor of stronger serological responses (p < 0.0001). No association was found for other factors, including CD4+ status, choice of mRNA vaccine, or concomitant influenza vaccination. In total, 45 patients (59%) had a reactive baseline IGRA, of whom two lost reactivity during follow-up. Of 31 patients (41%) with non-reactive baseline IGRA, 17 (55%) converted to reactive and seven (23%) remained unchanged following booster vaccination. CONCLUSIONS: People living with HIV with ≥500 CD4+ cells/µL showed favourable immune responses to mRNA-based COVID-19 booster vaccination. A longer time (up to 29 weeks) since second vaccination was associated with higher serological responses, whereas choice of mRNA vaccine or concomitant influenza vaccination had no impact.

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COVID-19 , Infecciones por VIH , Gripe Humana , Humanos , Estudios Retrospectivos , COVID-19/prevención & control , Vacunación , ARN Mensajero , Inmunidad , Inmunoglobulina G , Anticuerpos Antivirales

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CASE: Phosphodiesterase type-5 enzyme (PDE5) inhibitors are well tolerated and used to treat erectile dysfunction. We report a case of prosthetic knee effusions associated with PDE5 inhibitor use in a 65-year-old man after total knee arthroplasty (TKA). PDE5 inhibitor treatment was stopped, and the patient had no further episodes of painful effusions. CONCLUSION: This report describes a previously unknown adverse effect of PDE5 inhibitor use in a prosthetic joint after TKA. We hope to encourage physicians managing patients after joint replacement to be aware of the association between PDE5 inhibitor use and recurrent joint effusions to improve postoperative outcomes.

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Artroplastia de Reemplazo de Rodilla , Disfunción Eréctil , Masculino , Humanos , Anciano , Inhibidores de Fosfodiesterasa 5/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Disfunción Eréctil/inducido químicamente , Disfunción Eréctil/tratamiento farmacológico , Hidrolasas Diéster Fosfóricas/uso terapéutico

RESUMEN

The human gut microbiome is an important reservoir of antimicrobial resistance genes (ARGs), collectively termed the 'resistome'. To date, few studies have examined the dynamics of the human gut resistome in healthy individuals. Previously, the authors observed high rates of ARG acquisition and significant abundance shifts during international travel. In order to provide insight into commonly occurring dynamics, this study investigated longitudinal fluctuations in prevalent ARGs (cfxA, tetM and ermB) in the resistomes of non-travelling healthy volunteers. In addition, this study assessed the prevalence of acquirable ARGs (blaCTX-M, qnrB, qnrS, vanA and vanB) over time. Faecal samples from 23 participants were collected at baseline and after 2 and 4 weeks. DNA was isolated, and ARG quantification was performed by quantitative polymerase chain reaction adjusting for the total amount of bacterial 16S rDNA. vanA and qnrS were not detected in any of the samples, while the prevalence rates of vanB of non-enterococcal origin and qnrB were 73.9% and 5.7%, respectively. The ß-lactamase encoding blaCTX-M was detected in 17.4% of healthy participants. The results were compared with previous data from 122 travellers. ARG acquisitions observed in travellers were rare in non-travelling individuals during 4 weeks of follow-up, supporting the hypothesis of ARG acquisition during international travel. However, median -1.04- to 1.04-fold abundance changes were observed for 100% of cfxA, tetM and ermB, which did not differ from those found in travellers. Thus, common abundance shifts in prevalent ARGs of the gut resistome were found to occur independent of travel behaviour.

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Antibacterianos , Farmacorresistencia Bacteriana , Microbioma Gastrointestinal , Humanos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Heces/microbiología , Microbioma Gastrointestinal/genética , Genes Bacterianos/genética

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This cohort study examines traditional surveillance and self-reported COVID-19 test result data collected from independent smartphone app­based studies in the US and Germany.

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COVID-19 , Humanos , COVID-19/epidemiología , Autoinforme , Prevalencia , SARS-CoV-2 , Alemania/epidemiología

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BACKGROUND: The effectiveness of virtual reality exposure (VRE) in the treatment of anxiety disorders is well established. Several psychological mechanisms of VRE have been identified, whereby both emotional processing and the sense of presence play a key role. However, there are only few studies that contribute to our knowledge of examples of implementation in the case of VRE for claustrophobia based on patients' experiences and the perspective of therapists. OBJECTIVE: This study asks for key elements of a VRE app that are necessary for effective exposure for people with claustrophobic symptoms. METHODS: A mixed methods design was applied in which patients (n=15) and therapeutic experts (n=15) tested a VRE intervention of an elevator ride at 5 intensity levels. Intensity was varied by elevator size, duration of the elevator ride, and presence of virtual humans. Quantitative measures examined self-reported presence with the Igroup Presence Questionnaire (IPQ) ranging from 0 to 6 and 15 Likert-scaled evaluation items that had been developed for the purpose of this study, ranging from 1 to 5. In both measures, higher scores indicate higher levels of presence or agreement. Think-aloud protocols of the patients and semistructured interviews posttreatment of all participants were conducted to gain in-depth perspectives on emotional processes. RESULTS: The intervention induced a feeling of presence in patients and experts, posttreatment scores showed a high IPQ presence score (mean 3.84, SD 0.88), with its subscores IPQ spatial presence (mean 4.53, SD 1.06), IPQ involvement (mean 3.83, SD 1.22), and IPQ experienced realism (mean 2.75, SD 1.02). Patients preferred a setting in the presence of a therapist (mean 4.13, SD 0.83) more than the experts did (mean 3.33, SD 1.54). Think-aloud protocols of the patients revealed that presence and anxiety both were achieved. Qualitative interviews of patients and experts uncovered 8 topics: feelings and emotions, personal story, telepresence, potential therapeutic effects, barriers, conditions and requirements, future prospects, and realization. The intensity levels were felt to appropriately increase in challenge, with ambivalent results regarding the final level. Virtual humans contributed to feelings of fear. CONCLUSIONS: Key elements of a VRE app for claustrophobic symptoms should include variation of intensity by adding challenging cues in order to evoke presence and anxiety. Virtual humans are a suitable possibility to make the intervention realistic and to provide a sense of closeness; however, some of the fears might then be related to symptoms of social phobia or agoraphobia. Patients may need the physical presence of a therapist, though not all of them share this view. A higher degree of sophistication in the intensity levels is needed to deliver targeted help for specific symptoms of anxiety.

RESUMEN

Climate warming is inducing widespread vegetation changes in Arctic tundra ecosystems, with the potential to alter carbon and nutrient dynamics between vegetation and soils. Yet, we lack a detailed understanding of how variation in vegetation and topography influences fine-scale temperatures ("microclimate") that mediate these dynamics, and at what resolution vegetation needs to be sampled to capture these effects. We monitored microclimate at 90 plots across a tundra landscape in western Greenland. Our stratified random study design covered gradients of topography and vegetation, while nested plots (0.8-100 m2 ) enabled comparison across different sampling resolutions. We used Bayesian mixed-effect models to quantify the direct influence of plot-level topography, moisture and vegetation on soil, near-surface and canopy-level temperatures (-6, 2, and 15 cm). During the growing season, colder soils were predicted by shrub cover (-0.24°C per 10% increase), bryophyte cover (-0.35°C per 10% increase), and vegetation height (-0.17°C per 1 cm increase). The same three factors also predicted the magnitude of differences between soil and above-ground temperatures, indicating warmer soils at low cover/height, but colder soils under closed/taller canopies. These findings were consistent across plot sizes, suggesting that spatial predictions of microclimate may be possible at the operational scales of satellite products. During winter, snow cover (+0.75°C per 10 snow-covered days) was the key predictor of soil microclimate. Topography and moisture explained little variation in the measured temperatures. Our results not only underline the close connection of vegetation and snow with microclimate in the Arctic tundra but also point to the need for more studies disentangling their complex interplay across tundra environments and seasons. Future shifts in vegetation cover and height will likely mediate the impact of atmospheric warming on the tundra soil environment, with potential implications for below-ground organisms and ecosystem functioning.

Asunto(s)

Ecosistema , Nieve , Estaciones del Año , Teorema de Bayes , Tundra , Suelo , Regiones Árticas , Cambio Climático