Interrater Variability among Anaesthesiologists Using American Society of Anesthesiologists Physical Status Classification System.

BACKGROUND: The American Society of Anaesthesiologists Physical Status classification is deployed by the anaesthesiologists worldwide to classify operative surgical patients. Many studies have found moderate degree of interrater variability among anaesthesiologists. The general objective of the study was to find out interrater variability among Nepalese anesthesiologists using this classification system in Nepal. The specific objectives of the study were to find out the correctness of assignment and inter-rater variability among anaesthesiologists based on their experience. METHODS: Ten clinical cases were distributed among 130 registered anaesthesiologist practitioners of Nepal after validation with the experts. Respondents were asked to assign each of ten cases to a specific physical status class. Anaesthesiologists were classified to two classes based on clinical experience as having more or less than five years of experience. RESULTS: We found substantial agreement among < 5 year's (0.66) and > 5 year's experience group (0.753) and among all raters (0.736). The mean score of the group with less than 5 years of experience was more. There was no significant difference between the mean score (p = 0.595). Overall mean score for the both groups was 5.66 with SD 1.66. There was no significant difference between the groups. CONCLUSIONS: The study shows that there is very less variation among registered practising anaesthesiologists of Nepal using American Society of Anesthesiologists Physical Status classification system.

Implementation of the classification of medical devices of Ukraine in international approaches.

OBJECTIVE: Aim: To study the level of compliance of the National Classifier of Ukraine ≪Classifier of Medical Devices of Ukraine NC 024: 2023≫ with international approaches to the classification and use of medical devices. PATIENTS AND METHODS: Materials and Methods: National Classifier of Ukraine ≪Classifier of Medical Devices of Ukraine NC 024: 2023≫ and the international nomenclature of medical devices Global Medical Device Nomenclature. Methods: bibliosemantic, of content analysis and of structural-and-logical analysis. CONCLUSION: Conclusions: In the course of the study, full compliance of the national classifier of medical devices of Ukraine NC 024: 2023 with the GMDN system was established.

Structure-guided mutagenesis of Henipavirus receptor-binding proteins reveals molecular determinants of receptor usage and antibody-binding epitopes.

Nipah virus (NiV) is a highly lethal, zoonotic Henipavirus (HNV) that causes respiratory and neurological signs and symptoms in humans. Similar to other paramyxoviruses, HNVs mediate entry into host cells through the concerted actions of two surface glycoproteins: a receptor-binding protein (RBP) that mediates attachment and a fusion glycoprotein (F) that triggers fusion in an RBP-dependent manner. NiV uses ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3) as entry receptors. Ghana virus (GhV), a novel HNV identified in a Ghanaian bat, uses EFNB2 but not EFNB3. In this study, we employ a structure-informed approach to identify receptor-interfacing residues and systematically introduce GhV-RBP residues into a NiV-RBP backbone to uncover the molecular determinants of EFNB3 usage. We reveal two regions that severely impair EFNB3 binding by NiV-RBP and EFNB3-mediated entry by NiV pseudotyped viral particles. Further analyses uncovered two-point mutations (NiVN557SGhV and NiVY581TGhV) pivotal for this phenotype. Moreover, we identify NiV interaction with Y120 of EFNB3 as important for the usage of this receptor. Beyond these EFNB3-related findings, we reveal two domains that restrict GhV binding of EFNB2, confirm the HNV-head as an immunodominant target for polyclonal and monoclonal antibodies, and describe putative epitopes for GhV- and NiV-specific monoclonal antibodies. Cumulatively, the work presented here generates useful reagents and tools that shed insight to residues important for NiV usage of EFNB3, reveal regions critical for GhV binding of EFNB2, and describe putative HNV antibody-binding epitopes. IMPORTANCE: Hendra virus and Nipah virus (NiV) are lethal, zoonotic Henipaviruses (HNVs) that cause respiratory and neurological clinical features in humans. Since their initial outbreaks in the 1990s, several novel HNVs have been discovered worldwide, including Ghana virus. Additionally, there is serological evidence of zoonotic transmission, lending way to concerns about future outbreaks. HNV infection of cells is mediated by the receptor-binding protein (RBP) and the Fusion protein (F). The work presented here identifies NiV RBP amino acids important for the usage of ephrin-B3 (EFNB3), a receptor highly expressed in neurons and predicted to be important for neurological clinical features caused by NiV. This study also characterizes epitopes recognized by antibodies against divergent HNV RBPs. Together, this sheds insight to amino acids critical for HNV receptor usage and antibody binding, which is valuable for future studies investigating determinants of viral pathogenesis and developing antibody therapies.

Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.

Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.

Structurally divergent and recurrently mutated regions of primate genomes.

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Heat and desiccation tolerances predict bee abundance under climate change.

Climate change could pose an urgent threat to pollinators, with critical ecological and economic consequences. However, for most insect pollinator species, we lack the long-term data and mechanistic evidence that are necessary to identify climate-driven declines and predict future trends. Here we document 16 years of abundance patterns for a hyper-diverse bee assemblage1 in a warming and drying region2, link bee declines with experimentally determined heat and desiccation tolerances, and use climate sensitivity models to project bee communities into the future. Aridity strongly predicted bee abundance for 71% of 665 bee populations (species × ecosystem combinations). Bee taxa that best tolerated heat and desiccation increased the most over time. Models forecasted declines for 46% of species and predicted more homogeneous communities dominated by drought-tolerant taxa, even while total bee abundance may remain unchanged. Such community reordering could reduce pollination services, because diverse bee assemblages typically maximize pollination for plant communities3. Larger-bodied bees also dominated under intermediate to high aridity, identifying body size as a valuable trait for understanding how climate-driven shifts in bee communities influence pollination4. We provide evidence that climate change directly threatens bee diversity, indicating that bee conservation efforts should account for the stress of aridity on bee physiology.

A host-microbiota interactome reveals extensive transkingdom connectivity.

The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown1-3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the 'exoproteome'). Commensal microorganisms may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct exoproteome-microbiota interactions remain largely unexplored. Here we developed and validated a novel technology, BASEHIT, that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, we interrogated more than 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host-microorganism interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic; for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodelling and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and effects on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host-microbiota interactions that may underlie causal effects of indigenous microorganisms on human health and disease.

Diagnosis and Management of Myotonic Dystrophy Type 1.

This JAMA Insights discusses the signs and symptoms, diagnosis, and treatment of myotonic dystrophy type 1.

Analgesia con bloqueo TAP y bomba elastomérica en la reparación de hernias ventrales (primarias e incisionales) abdominales por laparoscopia en régimen de cirugía mayor ambulatoria / Analgesia with TAP block and elastomeric pump in the repair of ventral (primary and incisional) abdominal hernias by laparoscopy in major outpatient surgery

Antecedentes: El dolor moderado severo es una limitación para la incorporación de procedimientos en cirugía mayor ambulatoria (CMA), siendo uno de los principales motivos de reingreso o consulta a urgencias en las primeras horas del postoperatorio. Representa un indicador de calidad para las unidades de CMA. Algún estudio ya mide la eficacia de las bombas elastoméricas en el domicilio en CMA, pero no para la reparación de eventración de línea media por laparoscopia. Objetivo: Se diseñó un estudio para medir el dolor postoperatorio en la reparación de hernias ventrales, primarias o incisionales, de línea media por vía laparoscópica (malla fijada con tackers y cola de cianocrialato) con un diámetro transverso inferior a los 8 centímetros, en pacientes ASA I-II. Se valoró la viabilidad de la utilización de las bombas elastoméricas, con infusión continua de antinfl amatorio, opiáceos débiles y antieméticos en el domicilio del paciente. Pacientes y métodos: Estudio prospectivo observacional en pacientes ASA I-II, intervenidos de reparación de hernia ventral por laparoscopia, bajo una estrategia de control de dolor multimodal. Se realizó anestesia general endovenosa, con propofol y remifentanilo, junto a perfusión de lidocaína, y bloqueo TAP ecoguiado con levobupivacaína y mepivacaína con punción bilateral. Se inició la analgesia endovenosa intraoperatoriamente y para domicilio se pautó bomba elastomérica con dexketoprofeno, tramadol y ondansetrón, que se inció en la zona de recuperación postanestésica, junto a paracetamol fi jo y metamizol de rescate. La enfermería integrante de la unidad de hospitalización a domicilio se encargó del control postoperatorio en el domicilio del paciente. Se midió a las 24 h y 48 h el dolor postoperatorio a través de las escalas EVA y Andersen, además de las complicaciones que hubieran surgido (disfunción del dispositivo, náuseas/vómitos, complicaciones quirúrgicas)...(AU)

Background: Severe moderate pain is a limitation for the incorporation of procedures in major ambulatory surgery (MOS), being one of the main reasons for readmission or consultation to the emergency department in the first postoperative hours. It represents a quality indicator for AMC units. Some studies have already measured the efficacy of elastomeric pumps in the home in the AMC, but not for laparoscopic repair of midline eventration. Objective: A study was designed to measure postoperative pain in the repair of ventral, primary or incisional, midline hernias by laparoscopy (mesh fixed withtackers and cyanocryalate glue) with a transverse diameter of less than 8 centimeters, in ASA I-II patients. The feasibility of using elastomeric pumps withcontinuous infusion of anti-inflammatory drugs, weak opioids and antiemetics at the patient’s home was assessed. Patients and methods: Prospective observational study in ASA I-II patients who underwent laparoscopic ventral hernia repair under a multimodal pain control strategy. Intravenous general anesthesia was performed with propofol and remifentanil, together with lidocaine perfusion, and ultrasound-guided TAP block with levobupivacaine and mepivacaine with bilateral puncture. Intravenous analgesia was started intraoperatively and an elastomeric pump with dexketoprofen, tramadoland ondansetron was prescribed for home use, which was started in the postanesthetic recovery area, together with fixed paracetamol and rescue metamizole. The nursing staff of the home hospitalization unit was in charge of postoperative monitoring at the patient’s home. Postoperative pain was measured at 24 h and 48 h using the VAS and Andersen scales, as well as any complications that might have arisen (device dysfunction, nausea/vomiting, surgical complications). Patient satisfaction was measured by means of a survey at 30 days, during the postoperative follow-up with the surgeon.(AU)

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis / Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Objectives: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. Methods: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). Results: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. Conclusions: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.(AU)

Objetivos: La actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. Métodos: Se realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). Resultados: Se incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad.Conclusiones: La medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular.(AU)

Intersección de síntomas en el trastorno del espectro autista y trastornos psicóticos: a propósito de un caso / Intersection of symptoms in autism spectrum disorder and psychotic disorders: A case report

El rastorno de espectro autista es un trastorno del neurodesarrollo con una prevalencia que llega al 1% de la población. Es frecuente que los síntomas principales de este trastorno, tales como el deterioro de las interacciones sociales, los intereses restringidos o atípicos y las deficiencias cognitivas y de la comunicación verbal, puedan confundirse con la sintomatología de la esfera psicótica propia de la esquizofrenia. Una adecuada evaluación es necesaria, dado que ambas entidades pueden coexistir con una prevalencia variable del 12 al 50%. Presentamos el caso clínico de una mujer que a los 20 años inicia seguimiento en la unidad de salud mental por sintomatología compatible con un trastorno obsesivo-compulsivo junto a una clínica caracterizada por apatía, anhedonia, abandono del autocuidado y progresivo deterioro funcional. Tras varias sesiones de evaluación, llegamos al diagnóstico de un trastorno del espectro autista. Realizamos una revisión bibliográfica en la que concluimos que la intersección de síntomas entre el autismo y la esquizofrenia es común y se aportan recomendaciones clínicas para diferenciar ambas entidades clínicas. (AU)

Autism spectrum disorder is a neurodevelopmental disorder with a current global prevalence of approximately 1%. It is common that the main symptoms of this disorder, such as deterioration in social interactions, restricted or atypical interests, and cognitive and verbal communication deficiencies, can be confused with symptoms of the psychotic sphere typical of schizophrenia. An adequate evaluation is necessary due that both entities can coexist with a variable prevalence of 12 to 50%. Moreover, both disorders can coexist with a variable prevalence of 12 to 50%. We present the clinical case of a woman who, at the age of 20, began follow-up in the mental health unit due to symptoms compatible with an obsessive-compulsive disorder along with a clinic characterized by apathy, anhedonia, abandonment of self-care and progressive functional deterioration. After several evaluation sessions, we diagnosed an autism spectrum disorder. We carry out a bibliographic review with which we conclude that the intersection of symptoms between autism and schizophrenia is common and clinical recommendations are provided to differentiate both clinical entities. (AU)

Evolution-inspired engineering of nonribosomal peptide synthetases.

Many clinically used drugs are derived from or inspired by bacterial natural products that often are produced through nonribosomal peptide synthetases (NRPSs), megasynthetases that activate and join individual amino acids in an assembly line fashion. In this work, we describe a detailed phylogenetic analysis of several bacterial NRPSs that led to the identification of yet undescribed recombination sites within the thiolation (T) domain that can be used for NRPS engineering. We then developed an evolution-inspired "eXchange Unit between T domains" (XUT) approach, which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments.

Gars truly are 'living fossils,' massive DNA data set shows.

The fish's genomes change so slowly that species separated since the dinosaurs can produce fertile hybrids today.

Identification of microbial pathogens in Neolithic Scandinavian humans.

With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.

What Is Priapism?

This JAMA Patient Page describes the diagnosis, prevention, and treatment of priapism.

The evolution of menopause in toothed whales.

Understanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan1,2. Although progress has been made in understanding the adaptive value of menopause in humans3,4, the generality of these findings remains unclear. Toothed whales are the only mammal taxon in which menopause has evolved several times5, providing a unique opportunity to test the theories of how and why menopause evolves in a comparative context. Here, we assemble and analyse a comparative database to test competing evolutionary hypotheses. We find that menopause evolved in toothed whales by females extending their lifespan without increasing their reproductive lifespan, as predicted by the 'live-long' hypotheses. We further show that menopause results in females increasing their opportunity for intergenerational help by increasing their lifespan overlap with their grandoffspring and offspring without increasing their reproductive overlap with their daughters. Our results provide an informative comparison for the evolution of human life history and demonstrate that the same pathway that led to menopause in humans can also explain the evolution of menopause in toothed whales.

Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans.

Humans, like all mammals, depend on the gut microbiome for digestion of cellulose, the main component of plant fiber. However, evidence for cellulose fermentation in the human gut is scarce. We have identified ruminococcal species in the gut microbiota of human populations that assemble functional multienzymatic cellulosome structures capable of degrading plant cell wall polysaccharides. One of these species, which is strongly associated with humans, likely originated in the ruminant gut and was subsequently transferred to the human gut, potentially during domestication where it underwent diversification and diet-related adaptation through the acquisition of genes from other gut microbes. Collectively, these species are abundant and widespread among ancient humans, hunter-gatherers, and rural populations but are rare in populations from industrialized societies thus indicating potential disappearance in response to the westernized lifestyle.