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INTRODUCTION: Standardized patient (SP) encounters allow medical students to practice physical examination skills and clinical reasoning. SP cases are used for learning and assessment, but recorded encounters can also be valuable curriculum evaluation tools. We aimed to review SP encounters to improve abdominal examination skills and the broader physical examination curriculum. METHODS: We reviewed recorded SP encounters of third-year medical students on surgery clerkship rotation. Students examined a cisgender woman presenting with acute right lower abdominal pain. We observed abdominal examinations to determine which maneuvers were attempted and completed correctly. We then used these outcomes to develop targeted clerkship training for the subsequent student cohort. Our intervention targeted abdominal examination gaps by explaining how to integrate abdominal examination findings with a focused history for surgical patients. We evaluated the intervention's impact on abdominal examination skills with third-year medical students in comparison (2021-2022, n = 119) and intervention (2022-2023, n = 132) groups. RESULTS: In both the comparison and intervention groups, nearly all students attempted at least 1 general examination maneuver like auscultation, palpation, percussion, or rebound tenderness. Only 40% of students in the comparison group attempted an advanced maneuver like the Rovsing, Psoas, or Obturator sign. After the intervention, 75% of students in the intervention group attempted an advanced maneuver (χ2(1, 251) = 31.0, p < .001). Cohorts did not gain skills over time through the clerkship. Rebound tenderness was frequently assessed incorrectly by students in both groups, with many avoiding the right lower quadrant entirely. CONCLUSIONS: This project highlights how medical students struggle to utilize abdominal examination maneuvers and integrate findings. The results also showed that students did not consistently learn advanced examination skills either before or during clerkship rotation, which may be commonly assumed by clinical faculty. Finally, this work demonstrates how SP encounters can be used to evaluate and improve surgical education curriculum.
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Smart Nano-enabled Antiviral Therapeutic (SNAT) is a promising nanodrug that previously demonstrated efficacy in preclinical studies to alleviate SARS-CoV-2 pathology in hamsters. SNAT comprises taxoid (Tx)-decorated amino (NH2)-functionalized near-atomic size positively charged silver nanoparticles (Tx-[NH2-AgNPs]). Herein, we aimed to elucidate the molecular mechanism of the viral inhibition and safety of aerosolized SNAT treatment in SARS-CoV-2-infected golden Syrian hamsters. High-resolution transmission electron microscopy (HR-TEM) coupled with energy dispersive spectroscopy (EDS) and ELISAs showed SNAT binds directly to the SARS-CoV-2 virus by interacting with intact spike (S) protein, specifically to S2 subunit. SNAT (≥1 µg/mL) treatment significantly lowered SARS-CoV-2 infections of Calu-3 cells. Extraction-free whole transcriptome assay was used to detect changes in circulatory micronome in hamsters treated intranasally with SNAT (two doses of 10 µg/mL of 2 mL each administered 24 h apart). Uninfected hamsters treated with SNAT had altered circulatory concentrations of 18 microRNAs (8 miRNAs upregulated, 10 downregulated) on day 3 post-treatment compared to uninfected controls. SNAT-induced downregulation of miR-141-3p and miR-200b-3p may reduce viral replication and inflammation by targeting Ythdf2 and Slit2, respectively. Further, SNAT treatment significantly lowered IL-6 expression in infected hamster lungs compared to untreated infected hamsters. Taken together, we demonstrate that SNAT binds directly to SARS-CoV-2 via the S protein to prevent viral entry and propose a model by which SNAT alters the cellular miRNA-directed milieu to promote antiviral cellular processes and neutralize infection. Our results provide insights into the use of low-dose intranasally delivered SNAT in treating SARS-CoV-2 infections in a hamster model.
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Globally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to treatment failure with current antibiotics. Enterobacteria, particularly Escherichia coli, cause infections of surgical wound, bloodstream, and urinary tract, including pneumonia and sepsis. Herein, we tested in vitro antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH2-AgNP) against the AR bacteria. Two AR E. coli strains (i.e., ampicillin- and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5α, were tested for susceptibility to NH2-AgNP using Kirby-Bauer disk diffusion and standard growth assays. Dynamic light scattering (DLS) was used to determine cell debris and relative conductance was used as a measure of cell leakage, and results were confirmed with transmission electron microscopy (TEM). Multiple oxidative stress assays were used for in vitro safety evaluation of NH2-AgNP in human lung epithelial cells. Results showed that ampicillin and kanamycin did not inhibit growth in either AR bacterial strain with doses up to 160 µg/mL tested. NH2-AgNP exhibited broad-spectrum bactericidal activity, inhibiting the growth of all three bacterial strains at doses ≥1 µg/mL. DLS and TEM revealed cell debris formation and cell leakage upon NH2-AgNP treatment, suggesting two possible MoAs: electrostatic interactions followed by cell wall damage. Safety evaluation revealed NH2-AgNP as noncytotoxic and antioxidative to human lung epithelial cells. Taken together, these results suggest that NH2-AgNP may serve as an effective and safer bactericidal therapy against AR bacterial infections compared to common antibiotics.
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Infecciones Bacterianas , Nanopartículas del Metal , Humanos , Antibacterianos/toxicidad , Escherichia coli , Plata/toxicidad , Nanopartículas del Metal/toxicidad , Bacterias , Ampicilina/farmacología , Kanamicina/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Post-intensive care syndrome describes the physical, cognitive and emotional symptoms which persist following critical illness. At present there is limited understanding of the pathological mechanisms contributing to the development of post-intensive care syndrome. The aim of this systematic review was to synthesise current evidence exploring the association between inflammation and features of post-intensive care syndrome in survivors of critical illness. Relevant databases were systematically searched for studies of human participants exposed to critical illness. We sought studies that reported results for biomarkers with an identified role in the pathophysiology of inflammation obtained at any time-point in the patient journey and an outcome measure of any feature of post-intensive care syndrome at any point following hospital discharge. We included 32 studies, with 23 in the primary analysis and nine in a brain injury subgroup analysis. In the primary analysis, 47 different biomarkers were sampled and 44 different outcome measures were employed. Of the biomarkers which were sampled in five or more studies, interleukin-8, C-reactive protein and interleukin-10 most frequently showed associations with post-intensive care syndrome outcomes in 71%, 62% and 60% of studies, respectively. There was variability in terms of which biomarkers were sampled, time-points of sampling and outcome measures reported. Overall, there was mixed evidence of a potential association between an inflammatory process and long-term patient outcomes following critical illness. Further high-quality research is required to develop a longitudinal inflammatory profile of survivors of critical illness over the recovery period and evaluate the association with outcomes.
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Biomarcadores , Cuidados Críticos , Enfermedad Crítica , Inflamación , Humanos , Inflamación/sangre , Biomarcadores/sangreRESUMEN
Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.
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COVID-19 , SARS-CoV-2 , Humanos , Cinética , Aerosoles y Gotitas RespiratoriasRESUMEN
Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.
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Analgesia Epidural , Analgesia Obstétrica , Dolor de Parto , Trabajo de Parto , Embarazo , Humanos , Femenino , Niño , Analgesia Epidural/efectos adversos , Analgesia Obstétrica/efectos adversos , Analgésicos , Dolor de Parto/tratamiento farmacológico , Escocia , Factores SocioeconómicosRESUMEN
BACKGROUND: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is an innate defence protein that acts as an anti-microbial agent and regulates airway surface liquid volume through inhibition of the epithelial sodium channel (ENaC). SPLUNC1 levels were found to be reduced in airway secretions of adults with cystic fibrosis (CF). The potential of SPLUNC1 as a biomarker in children with CF is unknown. METHODS: We quantified SPLUNC1, interleukin-8 (IL-8) and neutrophil elastase (NE) in sputum of CF children treated with either intravenous antibiotics or oral antibiotics for a pulmonary exacerbation (PEx)s, and in participants of a prospective cohort of CF children with preserved lung function on spirometry, followed over a period of two years. RESULTS: Sputum SPLUNC1 levels were significantly lower before compared to after intravenous and oral antibiotic therapy for PEx. In the longitudinal cohort, SPLUNC1 levels were found to be decreased at PEx visits compared to both previous and subsequent stable visits. Higher SPLUNC1 levels at stable visits were associated with longer PEx-free time (hazard ratio 0.85, p = 0.04). SPLUNC1 at PEx visits did not correlate with IL-8 or NE levels in sputum or forced expiratory volume in one second (FEV1) but did correlate with the lung clearance index (LCI) (r=-0.53, p < 0.001). CONCLUSION: SPLUNC1 demonstrates promising clinometric properties as a biomarker of PEx in children with CF.
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Biomarcadores , Fibrosis Quística , Glicoproteínas , Interleucina-8 , Fosfoproteínas , Esputo , Humanos , Fibrosis Quística/fisiopatología , Fibrosis Quística/tratamiento farmacológico , Biomarcadores/análisis , Biomarcadores/metabolismo , Masculino , Femenino , Niño , Esputo/metabolismo , Glicoproteínas/metabolismo , Glicoproteínas/análisis , Fosfoproteínas/metabolismo , Fosfoproteínas/análisis , Interleucina-8/metabolismo , Interleucina-8/análisis , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Estudios Prospectivos , Elastasa de Leucocito/metabolismo , Elastasa de Leucocito/análisis , Adolescente , Progresión de la Enfermedad , Pruebas de Función Respiratoria/métodosRESUMEN
The planned withdrawal of life-sustaining treatment is a common practice in the intensive care unit for patients where ongoing organ support is recognised to be futile. Predicting the time to asystole following withdrawal of life-sustaining treatment is crucial for setting expectations, resource utilisation and identifying patients suitable for organ donation after circulatory death. This systematic review evaluates the literature for variables associated with, and predictive models for, time to asystole in patients managed on intensive care units. We conducted a comprehensive structured search of the MEDLINE and Embase databases. Studies evaluating patients managed on adult intensive care units undergoing withdrawal of life-sustaining treatment with recorded time to asystole were included. Data extraction and PROBAST quality assessment were performed and a narrative summary of the literature was provided. Twenty-three studies (7387 patients) met the inclusion criteria. Variables associated with imminent asystole (<60 min) included: deteriorating oxygenation; absence of corneal reflexes; absence of a cough reflex; blood pressure; use of vasopressors; and use of comfort medications. We identified a total of 20 unique predictive models using a wide range of variables and techniques. Many of these models also underwent secondary validation in further studies or were adapted to develop new models. This review identifies variables associated with time to asystole following withdrawal of life-sustaining treatment and summarises existing predictive models. Although several predictive models have been developed, their generalisability and performance varied. Further research and validation are needed to improve the accuracy and widespread adoption of predictive models for patients managed in intensive care units who may be eligible to donate organs following their diagnosis of death by circulatory criteria.
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Paro Cardíaco , Privación de Tratamiento , Humanos , Paro Cardíaco/terapia , Unidades de Cuidados Intensivos , Cuidados para Prolongación de la Vida , Factores de TiempoRESUMEN
Arguably the most ecologically and economically valuable pollinators worldwide, honey bees play a significant role in food production and enrich biodiversity through pollination. Varroa destructor is an invasive ectoparasitic mite that attacks and feeds on European honey bee, Apis mellifera. Because literature on the effectiveness and sustainability of various treatment modalities available for Varroa mite control in honey bee colonies are scattered, this scoping review was conducted to serve as a guiding document with a focus on: (1) identifying the detrimental impact Varroa mites have on the European honey bee; (2) determining current methods for Varroa mite control and their limitations; (3) examining current market landscape and key players in the pesticide market; and (4) identifying opportunities for more sustainable Varroa mite control methods. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, 397 articles published between 1998 and 2022 were screened; of which 65 articles were retained using inclusion/exclusion criteria, which were systematically analyzed in-depth, information extracted, and included in this scoping review. The results suggest that Varroa mites are one of the predominant causes of global honey bee decline as they lack natural resistance to Varroa mites, thereby negatively affecting honey bee reproduction and immunity, killing broods, and transmitting pathogenic viruses to colonies. Further, our findings suggest that: apiarists have many options for Varroa control, but no method has proven to be effective, safe and nonpersistent in the environment; adoption of nano-pesticides and development of sustainable alternatives to traditional pesticides are key drivers for growing pesticide market; and nano-pesticides may have potential to serve as an effective, safe and non-ecopersistent pesticide for Varroa mite and associated virus control. In conclusion, this review highlights an unmet need for effective and sustainable control strategies and tools for Varroa mite and virus control.
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Plaguicidas , Varroidae , Abejas , Animales , Inmunidad Innata , Interacciones Huésped-ParásitosRESUMEN
PURPOSE: Observations requiring evaluation and critical thinking can be powerful learning experiences. Video-recorded standardized patient encounters are underused resources for evaluation and research. The authors engaged premedical students in medical education research reviewing standardized patient encounters. This study aims to explore participant perceptions of the research experience and how they gained clinical skills. METHOD: This mixed-method study was completed between 2019 and 2022. Premedical participants coded medical students' clinical skills in video-recorded standardized patient encounters. Each participant also completed their own new patient history in a standardized patient encounter at both the beginning and end of their research project. Participants then completed an end-of-program debrief to discuss their experiences coding the clinical skills encounters. The authors coded communication skills implemented in the pre/postencounters and completed a thematic analysis of the debrief transcripts. RESULTS: All 21 participants demonstrated significant clinical skills gain after their research project, which included spending more time with the patient (pre-M=5 minutes, post-M=19 minutes, t=13.2, P<.001) and asking more questions (pre-M=13, post-M=40, t=9.3, P<.001). Prior clinical experience did not influence pre- or postoutcomes, but the number of videos coded was associated with asking more questions in the postencounter. Participants described learning actively and reflected that their clinical skills research project gave them greater insight into patient-care aspects of medical school and how medical students learn. CONCLUSIONS: These data demonstrate that observational studies in which premedical students evaluate standardized patient encounters gave the students context to medical education while enabling them to develop and transfer their own clinical skills. Studies observing standardized patient encounters provide rich insight into clinical skills development, and this work generates both research outcomes and actionable program evaluation data for medical educators. Purposefully engaging premedical students in such experiential learning opportunities benefits the students and helps cultivate early medical education pathways for these learners.
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Educación Médica , Estudiantes de Medicina , Humanos , Competencia Clínica , Estudiantes Premédicos , AprendizajeRESUMEN
Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.
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Parkinson's disease (PD), multisystem atrophy (MSA), and progressive supranuclear palsy (PSP) present similarly with bradykinesia, tremor, rigidity, and cognitive impairments. Neuroimaging studies have found differential changes in the nigrostriatal pathway in these disorders, however whether the volume and shape of specific regions within this pathway can distinguish between atypical Parkinsonian disorders remains to be determined. This paper investigates striatal and thalamic volume and morphology as distinguishing biomarkers, and their relationship to neuropsychiatric symptoms. Automatic segmentation to calculate volume and shape analysis of the caudate nucleus, putamen, and thalamus were performed in 18 PD patients, 12 MSA, 15 PSP, and 20 healthy controls, then correlated with clinical measures. PSP bilateral thalami and right putamen were significantly smaller than controls, but not MSA or PD. The left caudate and putamen significantly correlated with the Neuropsychiatric Inventory total score. Bilateral thalamus, caudate, and left putamen had significantly different morphology between groups, driven by differences between PSP and healthy controls. This study demonstrated that PSP patient striatal and thalamic volume and shape are significantly different when compared with controls. Parkinsonian disorders could not be differentiated on volumetry or morphology, however there are trends for volumetric and morphological changes associated with PD, MSA, and PSP.
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Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Trastornos Parkinsonianos , Parálisis Supranuclear Progresiva , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Atrofia de Múltiples Sistemas/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Tálamo/metabolismoRESUMEN
For the past 50 years, superconducting detectors have offered exceptional sensitivity and speed for detecting faint electromagnetic signals in a wide range of applications. These detectors operate at very low temperatures and generate a minimum of excess noise, making them ideal for testing the non-local nature of reality1,2, investigating dark matter3,4, mapping the early universe5-7 and performing quantum computation8-10 and communication11-14. Despite their appealing properties, however, there are at present no large-scale superconducting cameras-even the largest demonstrations have never exceeded 20,000 pixels15. This is especially true for superconducting nanowire single-photon detectors (SNSPDs)16-18. These detectors have been demonstrated with system detection efficiencies of 98.0% (ref. 19), sub-3-ps timing jitter20, sensitivity from the ultraviolet21 to the mid-infrared22 and microhertz dark-count rates3, but have never achieved an array size larger than a kilopixel23,24. Here we report on the development of a 400,000-pixel SNSPD camera, a factor of 400 improvement over the state of the art. The array spanned an area of 4 × 2.5 mm with 5 × 5-µm resolution, reached unity quantum efficiency at wavelengths of 370 nm and 635 nm, counted at a rate of 1.1 × 105 counts per second (cps) and had a dark-count rate of 1.0 × 10-4 cps per detector (corresponding to 0.13 cps over the whole array). The imaging area contains no ancillary circuitry and the architecture is scalable well beyond the present demonstration, paving the way for large-format superconducting cameras with near-unity detection efficiencies across a wide range of the electromagnetic spectrum.
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Evidence suggests that patients with long COVID can experience neuropsychiatric, neurologic, and cognitive symptoms. However, these clinical data are mostly associational studies complicated by confounding variables, thus the mechanisms responsible for persistent symptoms are unknown. Here we establish an animal model of long-lasting effects on the brain by eliciting mild disease in K18-hACE2 mice. Male and female K18-hACE2 mice were infected with 4 × 103 TCID50 of SARS-CoV-2 and, following recovery from acute infection, were tested in the open field, zero maze, and Y maze, starting 30 days post infection. Following recovery from SARS-CoV-2 infection, K18-hACE2 mice showed the characteristic lung fibrosis associated with SARS-CoV-2 infection, which correlates with increased expression of the pro-inflammatory kinin B1 receptor (B1R). These mice also had elevated expression of B1R and inflammatory markers in the brain and exhibited behavioral alterations such as elevated anxiety and attenuated exploratory behavior. Our data demonstrate that K18-hACE2 mice exhibit persistent effects of SARS-CoV-2 infection on brain tissue, revealing the potential for using this model of high sensitivity to SARS-CoV-2 to investigate mechanisms contributing to long COVID symptoms in at-risk populations. These results further suggest that elevated B1R expression may drive the long-lasting inflammatory response associated with SARS-CoV-2 infection.
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COVID-19 , Femenino , Masculino , Animales , Humanos , Ratones , COVID-19/complicaciones , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Enfermedades Neuroinflamatorias , CininasRESUMEN
Sustaining the organisms, ecosystems and processes that underpin human wellbeing is necessary to achieve sustainable development. Here we define critical natural assets as the natural and semi-natural ecosystems that provide 90% of the total current magnitude of 14 types of nature's contributions to people (NCP), and we map the global locations of these critical natural assets at 2 km resolution. Critical natural assets for maintaining local-scale NCP (12 of the 14 NCP) account for 30% of total global land area and 24% of national territorial waters, while 44% of land area is required to also maintain two global-scale NCP (carbon storage and moisture recycling). These areas overlap substantially with cultural diversity (areas containing 96% of global languages) and biodiversity (covering area requirements for 73% of birds and 66% of mammals). At least 87% of the world's population live in the areas benefitting from critical natural assets for local-scale NCP, while only 16% live on the lands containing these assets. Many of the NCP mapped here are left out of international agreements focused on conserving species or mitigating climate change, yet this analysis shows that explicitly prioritizing critical natural assets and the NCP they provide could simultaneously advance development, climate and conservation goals.
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Ecosistema , Planetas , Humanos , Animales , Conservación de los Recursos Naturales , Biodiversidad , Aves , MamíferosRESUMEN
Wide variability exists with host response to SARS-CoV-2 infection among individuals. Circulatory micro RNAs (miRNAs) are being recognized as promising biomarkers for complex traits, including viral pathogenesis. We hypothesized that circulatory miRNAs at 48 h post hospitalization may predict the length of stay (LOS) and prognosis of COVID-19 patients. Plasma miRNA levels were compared between three groups: (i) healthy volunteers (C); (ii) COVID-19 patients treated with remdesivir (an antiviral) plus dexamethasone (a glucocorticoid) (with or without baricitinib, a Janus kinase inhibitor) on the day of hospitalization (I); and COVID-19 patients at 48 h post treatment (T). Results showed that circulatory miR-6741-5p expression levels were significantly different between groups C and I (p < 0.0000001); I and T (p < 0.0000001); and C and T (p = 0.001). Our ANOVA model estimated that all patients with less than 12.42 Log2 CPM had a short LOS, or a good prognosis, whereas all patients with over 12.42 Log2 CPM had a long LOS, or a poor prognosis. In sum, we show that circulatory miR-6741-5p may serve as a prognostic biomarker effectively predicting mortality risk and LOS of hospitalized COVID-19 patients.
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COVID-19 , MicroARNs , Humanos , Tiempo de Internación , Pronóstico , COVID-19/diagnóstico , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , MicroARNs/metabolismo , BiomarcadoresRESUMEN
Introduction: Transgender and gender-diverse (TGD) patients experience health disparities and bias in health care settings. To improve care for TGD patients, medical trainees can practice gender-affirming care skills such as inclusive communication and discussing hormone therapy through patient simulation. Systematically evaluating these simulation outcomes also helps educators improve training on gender-affirming care. Methods: A standardized patient case with a patient establishing primary care was developed for rising third-year medical students. The case featured multiple patient iterations to portray individuals with the same health history but a different gender identity and/or sex assigned at birth. Each student was randomly assigned to one patient encounter. Gender-affirming care skills were assessed through standardized patient checklists, postencounter notes, and preventive care recommendations. Results: Over 2 years, 286 students participated in the simulation. Transgender men and women, cisgender men and women, and genderqueer patients were portrayed. Performance gaps such as misgendering patients and incorrect cancer screening recommendations based on perceived gender identity (rather than sex assigned at birth) were documented. Ninety-eight percent of students agreed that the encounter helped them practice clinical skills needed to see actual patients, and students described the case as challenging but important. Discussion: This case served dual roles for medical training: (1) Students working with TGD patients practiced skills for gender-affirming care, and (2) portraying TGD patients along with cisgender patients allowed educators to identify biased recommendations that necessitated additional training. The outcomes further highlighted the importance of students routinely practicing gender-inclusive communication with all patients during simulation.
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Personas Transgénero , Competencia Clínica , Femenino , Identidad de Género , Humanos , Recién Nacido , Masculino , Simulación de Paciente , EstudiantesRESUMEN
Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta-analysis investigated whether further reducing the concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra-low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta-analysis with random-effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra-low compared with low (weighted mean difference -14.96 mg, 95% credible interval [-28.38 to -1.00]) and low compared with high groups (weighted mean difference -14.99 [-28.79 to -2.04]), though there was no difference in the number of rescue top-ups administered between the groups. Compared with high concentration, ultra-low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 [1.18 to 1.86]), reduced motor block (Bromage score >0; OR 0.32 [0.18 to 0.54]) and reduced duration of second stage of labour (weighted mean difference -13.02 min [-21.54 to -4.77]). Compared with low, ultra-low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference -1.92 min [-14.35 to 10.20]); spontaneous vaginal delivery (OR 1.07 [0.75 to 1.56]; assisted vaginal delivery (OR 1.35 [0.75 to 2.26]); caesarean section (OR 0.76 [0.49 to 1.22]); pain (scale 1-100, weighted mean difference -5.44 [-16.75 to 5.93]); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 [0.15 to 0.79]) was reported for ultra-low compared with low concentration, this was not sustained at 5 min (OR 0.12 [0.00 to 2.10]). Ultra-low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.