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Abstract Seasonal snow in the extratropical Andes is a primary water source for major rivers supplying water for drinking, agriculture, and hydroelectric power in Central Chile. Here, we used estimates from the Moderate Resolution Imaging Spectroradiometer (MODIS) to analyze changes in snow cover extent over the period 2001–2022 in a total of 18 watersheds spanning approximately 1,100 km across the Chilean Andes (27–36°S). We found that the annual snow cover extent is receding in the watersheds analyzed at an average pace of approximately 19% per decade. These alarming trends have impacted meltwater runoff, resulting in historically low river streamflows during the dry season. We examined streamflow records dating back to the early 1980s for 10 major rivers within our study area. Further comparisons with large-scale climate modes suggest that the detected decreasing trends in snow cover extent are likely driven by the poleward migration of the westerly winds associated with a positive trend in the Southern Annular Mode (SAM).

Abstract This study aimed to determine the sequence type (ST) of Bartonella henselae infecting small Indian mongooses from Saint Kitts via multi-locus sequence typing (MLST). This investigation used stored EDTA blood (n = 22) samples from mongooses previously identified as positive for B. henselae. Chocolate agar plates were enriched with Bartonella alpha-Proteobacteria growth medium (BAPGM) to culture and isolate Bartonella from the blood samples. To perform MLST, DNA was extracted and purified from isolates followed by amplification by conventional PCR (300–500 bp) for eight genes (16S rDNA, batR, gltA, groEL, ftsZ, nlpD, ribC, and rpoB). Bartonella henselae STs were deposited in the PubMLST repository. Out of 22 B. henselae-positive blood samples, isolates were obtained from 12 mongooses (54.5%; 12/22). Each mongoose was infected with one ST. The studied mongoose population was infected with sequence types ST2, ST3, ST8, and a novel ST represented by ST38. Bartonella henselae ST2, ST3 and ST8 infecting mongooses are known to circulate in humans and cats, with ST2 and ST8 associated with Cat Scratch Disease (bartonellosis) in humans. The results presented herein denote the circulation of B. henselae STs with zoonotic potential in mongooses with risk of B. henselae transmission to humans.

Abstract This study aimed to evaluate the blood bacterial microbiota in healthy and febrile cats. High-quality sequencing reads from the 16S rRNA gene variable region V3-V4 were obtained from genomic blood DNA belonging to 145 healthy cats, and 140 febrile cats. Comparisons between the blood microbiota of healthy and febrile cats revealed dominant presence of Actinobacteria, followed by Firmicutes and Proteobacteria, and a lower relative abundance of Bacteroidetes. Upon lower taxonomic levels, the bacterial composition was significantly different between healthy and febrile cats. The families Faecalibacterium and Kineothrix (Firmicutes), and Phyllobacterium (Proteobacteria) experienced increased abundance in febrile samples. Whereas Thioprofundum (Proteobacteria) demonstrated a significant decrease in abundance in febrile. The bacterial composition and beta diversity within febrile cats was different according to the affected body system (Oral/GI, systemic, skin, and respiratory) at both family and genus levels. Sex and age were not significant factors affecting the blood microbiota of febrile cats nor healthy ones. Age was different between young adult and mature adult healthy cats. Alpha diversity was unaffected by any factors. Overall, the findings suggest that age, health status and nature of disease are significant factors affecting blood microbiota diversity and composition in cats, but sex is not.

Objectives To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months.Design An open-label, multicentre, non-randomised clinical trial.Setting Eight secondary and tertiary care hospitals (public and private) in Puerto Rico.Participants 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases.Interventions Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3–5 days after PCI. Adherence medication score was also measured.Primary and secondary outcomes The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models.Results The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p

Objectives: Describe the epidemiology of cuboid fracture, the mechanisms of injury and associated injuries, the progression to osteoarthritis, and propose a surgical management algorithm. Methods: A retrospective and descriptive study of patients with cuboid fractures operated on between 2009 and 2014. The variables analyzed were age, sex, mechanism of injury, classification, associated fractures, and osteoarthritis changes, among others. Results: Twenty-seven patients were included: 19 men and eight women. The mean age was 41.3 years (range 25 - 62). The mean followup was 3.3 years. The mechanisms of injury were motor vehicle accidents and falls from height. Among the patients, 44.4% had lateral column shortening, and 81.5% involved calcaneal cuboid articular surface. Cuboid locking plates were used in 15 patients, and single screw fixation was used in four patients. Three patients required a bone graft. Degenerative changes were observed in calcaneocuboid and cuboid-metatarsal joints. Conclusions: Cuboid fracture is an uncommon injury. In general, the injuries are caused by high-energy accidents. In our study, 40.7% of patients had an injury to the medial column. It is recommended the use of a cuboid locking plate for comminuted fractures, screw fixation for simple fractures, and a bridging plate or external fixation can be considered for most complex cases. Level of Evidence IV; Retrospective Case Series.

Introduction Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved.Methods and analysis A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance.Ethics and dissemination Ethical approval for the consensus process will be obtained from the Queen’s University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely.Registration The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Abstract Malaria is a severe public health problem in several developing tropical and subtropical countries. Anopheles aquasalis is the primary coastal malaria vector in Central and South America and the Caribbean Islands, and it has the peculiar feature of living in water with large changes in salinity. Recent research has recognised An. aquasalis as an important model for studying the interactions of murine and human Plasmodium parasites. This study presents the complete genome of An. aquasalis and offers insights into its evolution and physiology. The genome is similar in size and gene content to other Neotropical anophelines, with 162 Mb and 12,446 protein-coding genes. There are 1387 single-copy orthologs at the Diptera level (eg. An. gambiae, An. darlingi and Drosophila melanogaster). An. aquasalis diverged from An. darlingi, the primary malaria vector in inland South America, nearly 20 million years ago. Proteins related to ion transport and metabolism belong to the most abundant gene families with 660 genes. We identified gene families relevant to osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases, and carbonic anhydrases). Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in insecticide resistance and immunity-related genes for all known classical pathways. The data provided by this study offers candidate genes for further studies of parasite-vector interactions and for studies on how anophelines of brackish water deal with the high fluctuation in water salinity. We also established data and insights supporting An. aquasalis as an emerging Neotropical malaria vector model for genetic and molecular studies.

Abstract The conservation of forest landscapes is crucial for global climate strategies, and the forest in Tierra del Fuego, located in Patagonia, represents the southernmost example on Earth. These ecosystems are critical for Chile’s roadmap toward carbon neutrality. Unfortunately, these ecosystems have been impacted by logging and beaver activities. Currently, the precise contribution of each driver to forest cover and carbon stock loss remains insufficiently quantified, impeding effective policymaking and the implementation of strategies to safeguard and enhance carbon stocks in these ecosystems. In this study, we conducted an assessment of forest carbon stock loss resulting from both logging and beaver activities in Chilean Tierra del Fuego from 1986 to 2019. While beavers have received significant attention for their substantial contribution to forest cover loss (56.1% forest cover, ≈ 1.4 MtC), our findings suggest that logging has nearly equally contributed to carbon stock depletion (43.8% forest cover, ≈ 1.2 MtC). Consequently, the prevailing focus on beavers has obscured the ongoing logging-induced carbon stock loss. The implications of our study highlight the urgency for comprehensive consideration of both drivers in Chile’s climate strategy to fulfill the country’s mitigation commitments.

Introduction Management controversy and clinical equipoise exist in treatments of long bone fractures and traumatic hip dislocation in paediatric patients due to the lack of high-quality clinical evidence. This protocol describes the effort of a large prospective global multicentre cohort study (registry) aiming at providing quality data to assist evidence-based treatment decision-making.Methods and analysis Eligible paediatric patients (N=750–1000) with open physes suffering from proximal humerus fractures, distal humerus fractures, proximal radius fractures, forearm shaft fractures, traumatic hip dislocations, femoral neck fractures or tibial shaft fractures will be recruited over a period of 24–36 months. Hospitalisation and treatment details (including materials and implants) will be captured in a cloud-based, searchable database. Outcome measures include radiographic assessments, clinical outcomes (such as range of motion, limb length discrepancies and implant removal), patient-reported outcomes (Patient Reported Outcomes Of Fracture, Patient-Reported Outcomes Measurement Information System (PROMIS) and EuroQol-5D (EQ-5D-Y)) and adverse events.Aside from descriptive statistics on patient demographics, baseline characteristics, types of fractures and adverse event rates, research questions will be formulated based on data availability and quality. A statistical analysis plan will be prepared before the statistical analysis.Ethics and dissemination Ethics approval will be obtained before patients are enrolled at each participating site. Patient enrolment will follow an informed consent process approved by the responsible ethics committee. Peer-reviewed publication is planned to disseminate the study results.Trial registration number NCT04207892.

Introducción: El dolor lumbar es una condición frecuente en los estudiantes de medicina identificándose diversos factores de riesgo, el objetivo del estudio fue evaluar la asociación entre la presencia de dolor lumbar crónico (DL) y la conducta sedentaria en estudiantes de medicina de una universidad privada. Materiales y métodos: estudio transversal analítico, prospectivo observacional, participaron 167 encuestados (101 hombres y 66 mujeres). Las mediciones principales fueron la conducta sedentaria y actividad física fueron medidas a través del Cuestionario Mundial sobre Actividad Física (GPAQ); el dolor lumbar crónico se midió con una temporalidad de 12 meses mediante el cuestionario nórdico de Kuorinka de trastornos musculoesqueléticos. Resultados: La frecuencia de dolor lumbar fue 67,7% y una media de conducta sedentaria de 9.5 horas (D.T: 3,04), el 70.6%, mantiene un nivel de actividad física saludable, se encontró mayor conducta sedentaria asociada a mayor presencia de DL, al análisis multivariado se encontró que para cada hora sentado se aumenta significativamente la probabilidad de padecer DL (OR 1,17: p= 0.013). Los estudiantes que permanecen de 10 a más horas sentados/recostados presentan un aumento de riesgo de padecer dolor lumbar (ORa = 4,13: p= 0.001) frente a los que permanecen menos de 10 horas sentados/recostados. Conclusión: Se observa que por cada hora en posición sedente/recostado aumenta en 15% la razón de chance de sufrir dolor lumbar crónico en los estudiantes, así como acumular de 10 a más horas al día en posición sedente recostado aumenta significativamente el padecer de dolor lumbar en los últimos 12 meses.

ObjectiveTo collect evidence on the possibility that patients with depression experience self-stigmatization based on label information for medications.MethodsWe developed a discrete-choice experiment (DCE) survey instrument that asked respondents to make choices between hypothetical treatments for major depressive disorder (MDD). We also included treatment type (antidepressants versus antipsychotics) and approved indications for the medication. The choice questions mimicked the information presented in product inserts and required systematic tradeoffs between treatment efficacy, treatment type, and indication. We calculated how many patients were willing to forgo efficacy to avoid treatments with information associated with self-stigmatization, and how much efficacy they were willing to forgo. We also evaluated the impact of contextualizing the treatment information to reduce self-stigmatization by randomizing respondents who received additional context.ResultsA total of 501 patients with MDD were recruited to complete the DCE survey. Respondents had well-defined preferences for treatment outcomes. Over 60% (63.4%) of respondents were found to be significantly affected by treatment indication. These respondents were willing to forgo about 2.5 percentage points in the chance of treatment efficacy to avoid treatments indicated for schizophrenia. We also find that some level of contextualization of the treatment details could help reduce the negative impact of treatment type and indications.ConclusionsProduct-label treatment indication can potentially lead to patient self-stigmatization as shown by patients' avoidance of treatments that are also used to treat schizophrenia. While the effect appears to be relatively small, results suggests that the issue is likely pervasive.

Rodents are recognized as the main reservoirs of Leptospira spp. Rats, in particular, serve as hosts for the widely predominant Leptospira interrogans serovar Icterohaemorrhagiae, found worldwide. Several studies have shown the importance of other reservoirs, such as mice or hedgehogs, which harbor other leptospires' serovars. Nevertheless, our knowledge of circulating Leptospira spp. in reservoirs other than rats remains limited. In this context, we proposed an eco-health approach to assess the health hazard associated with leptospires in urban green spaces, where contacts between human/small mammals and domestic animals are likely. We studied the prevalence, the diversity of circulating strains, and epidemiology of pathogenic Leptospira species in small terrestrial mammal communities (rodents and shrews), between 2020-2022, in two parks in Lyon metropolis, France. Our study showed a significant carriage of Leptospira spp. in small terrestrial mammals in these parks and unveiled a global prevalence rate of 11.4%. Significant variations of prevalence were observed among the small mammal species (from 0 to 26.1%), with Rattus norvegicus exhibiting the highest infection levels (26.1%). We also observed strong spatio-temporal variations in Leptospira spp. circulation in its reservoirs. Prevalence seems to be higher in the peri-urban park and in autumn in 2021 and 2022. This is potentially due to differences in landscape, abiotic conditions and small mammal communities' composition. Our study suggests an important public health relevance of rats and in a lesser extent of other rodents (Apodemus spp., Clethrionomys glareolus and Mus musculus) as reservoirs of L. interrogans, with rodent species carrying specific serogroups/serovars. We also emphasize the potential hazard associated between the shrew Crocidura russula and L. kirschneri. Altogether, these results improve our knowledge about the prevalence of leptospirosis in an urban environment, which is an essential prerequisite for the implementation of prevention of associated risks.

Resumen: Introducción: La simulación clínica es una estrategia eficaz para mejorar la seguridad del paciente. La simulación in situ puede tener beneficios al utilizar las instalaciones de cuidados intensivos, el equipo, los suministros clínicos habituales y ser realizado durante la jornada laboral.El objetivo de este estudio fue evaluar la percepción de los participantes de un programa de simulación in situ de alta fidelidad en el Centro de Paciente Crítico Adulto. Métodos: Posterior a los debriefing de las simulaciones in situ realizadas en la Unidad de Paciente Crítico Adulto de Clínica Las Condes, se aplicó una encuesta anónima semiestructurada a modo de evaluar la percepción del personal de salud que participó de la simulación. Resultados: A lo largo de 25 sesiones de simulación realizadas se obtuvieron 144 encuestas. La mayoría de las variables evaluadas tuvieron una puntuación superior a 9, lo que significa excelente o muy relevante, excepto la pregunta “¿Se siente más seguro de sus habilidades en un escenario de caso real similar después de esta actividad?”, que presentó una puntuación de 8,65 ± 1,5. Al analizar las variables según el rol del profesional, solo hubo diferencias entre los enfermeros y técnicos de enfermería. No hubo diferencias entre los equipos de cuidados intensivos y de cuidados intermedios en ninguna de las variables. Conclusiones: Las percepciones de los participantes, relacionadas a la simulación in situ como un proceso formativo fue interpretado como efectivo generando un alto grado de satisfacción. Abstract: Introduction: Clinical simulation is an effective strategy to improve patient safety. In Situ simulation may accrue benefits by utilizing the intensive care facility, routine clinical supplies and equipment, as well as being performed during the workday.The objective of this study was to evaluate participants’ perception of a high-fidelity in situ simulation program in an adult critical patient center. Methods: A semi-structured anonymous survey was applied after the debriefing of the in situ simulation that evaluated the reaction of the health personnel of the adult critical patient unit of Clinica Las Condes. Results: A total of 144 surveys were obtained during 25 simulation sessions. Most of the variables evaluated had a score above 9, interpreted as excellent or very relevant, except for the question “After this activity, do you feel more confident of your skills in a similar real case scenario?”, which presented a score of 8.65 ± 1.5. When analyzing the variables according to the role of the professional, there were only differences between nurses and nursing technicians. There were no differences between intensive care and intermediate care teams in any of the variables. Conclusions: The participants’ perceptions with regards to in situ simulation as a training process were interpreted as effective, generating a high degree of satisfaction.

Abstract The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases.

Abstract Prostate cancer is one of the few malignancies that includes vaccination as a treatment modality. Elements of an effective cancer vaccine should include the ability to elicit a Type I T-cell response and target multiple antigenic proteins expressed early in the disease. Using existing gene datasets encompassing normal prostate tissue and tumors with Gleason Score ≤ 6 and ≥ 8, 10 genes were identified that were upregulated and conserved in prostate cancer regardless of the aggressiveness of disease. These genes encoded proteins also expressed in prostatic intraepithelial neoplasia. Putative Class II epitopes derived from these proteins were predicted by a combination of algorithms and, using human peripheral blood, epitopes which selectively elicited IFN-γ or IL-10 dominant antigen specific cytokine secretion were determined. Th1 selective epitopes were identified for eight antigens. Epitopes from three antigens elicited Th1 dominant immunity in mice; PSMA, HPN, and AMACR. Each single antigen vaccine demonstrated significant anti-tumor activity inhibiting growth of implanted Myc-Cap cells after immunization as compared to control. Immunization with the combination of antigens, however, was superior to each alone in controlling tumor growth. When vaccination occurred simultaneously to tumor implant, multiantigen immunized mice had significantly smaller tumors than controls (p = 0.002) and a significantly improved overall survival (p = 0.0006). This multiantigen vaccine shows anti-tumor activity in a murine model of prostate cancer.

Background: The European Working Group on Sarcopenia in the Elderly defined sarcopenia as a geriatric syndrome with a diagnostic criteria of low skeletal muscle mass (LMM). Various sarcopenia consensuses recommend as cut-offs for LMM, the use of below 2 SDs from the mean skeletal muscle mass index (SMI) of a young reference group. Given the contrast between reported cut-offs, the objective of this study was to establish cut-offs for LMM from older adults in Manizales and compare them with those published in the literature. Methods: This was a prospective, cross-sectional analytical study in 237 healthy elderly patients from the city of Manizales, Colombia. Anthropometric measurements of weight, height and body mass index were estimated. The SMI was estimated with the Xitron Technologies bioimpedance meter using the Janssen formula. For the comparison of SMI cut-offs, studies that evaluated this parameter with bioelectrical impedance analysis (BIA) were taken into account, in addition to being obtained from the −2 SD from the sex-specific mean of a young reference group. Results: The cut-off points for SMI were 8.0 kg/m2 for men and 6.1 kg/m2 for women. There was a statistically significant difference when evaluating LMM from the cut-offs of the present study and those reported in Spain, Turkey, and Finland. The cut-off points of SMI derived from this sample of Colombian men and women may be adequate for the diagnosis in the Colombian geriatric population. However, we did not find significant differences when comparing the cut-offs for SMI from a population of older adults and young adults from the same city. Conclusions: The cut-off points of SMI by BIA derived from a sample of Colombian men and women may be adequate for the diagnosis of LMM in the Colombian geriatric population or populations with similar characteristics to those of the sample evaluated here.

Introduction: Because of the the complex physiopathology of spasticity, it is distinguished as one of the most significant positive clinical signs of upper motor neuron syndrome, constituting a clinical feature that has great impact in the neurorehabilitation setting. Thus, the current study aimed to determine the prevalence, onset, evolution, and prediction of spasticity after a stroke. Materials and Methods: A correlational, longitudinal design was used. A total of 136 patients were evaluated at the following times: 10 days (T1), 3 months (T2), and 12 months (T3) poststroke. The initial evaluation included sociodemographic and clinical data (T1). Muscle tone was measured (T1, T2, and T3) using the Modified Ashworth Scale. Results: The prevalence of poststroke spasticity in the elbow was 37.5% at T1 and 57.4% at T2 and T3. Among patients with motor damage, the onset of spasticity occurred at T1 in 44.7%, between T1 and T2 in 23.7%, and between T2 and T3 in 0.9%. Significant predictors of the alteration in muscular tone for at least two of the evaluation times were ethnic self-classification, type, area, extent of stroke, and number of sessions. Conclusions: Spasticity onset occurs during the first 10 days after a stroke. More clinical than sociodemographic variables predicted spasticity.

Abstract Optical vortex beams are under considerable scrutiny due to their demonstrated potential for applications ranging from quantum optics to optical communications and from material processing to particle trapping. However, upon interaction with inhomogeneous material systems, their deterministic properties are altered. The way these structured beams are affected by different levels of disturbances is critical for their uses. Here, for the first time, we quantify the degradation of perfect optical vortex beams after their interaction with localized random media. We developed an analytical model that (1) describes how the spatial correlation and the phase variance of disturbance affect the phase distribution across the vortex beams and (2) establishes the regimes of randomness for which the beams maintain the memory of their initial vorticity. Systematic numerical simulations and controlled experiments demonstrate the extent of this memory effect for beams with different vorticity indices.

Abstract The objective of this systematic review and meta-analyses is to estimate the prevalence of long-COVID in children and adolescents and to present the full spectrum of symptoms present after acute COVID-19. We have used PubMed and Embase to identify observational studies published before February 10th, 2022 that included a minimum of 30 patients with ages ranging from 0 to 18 years that met the National Institute for Healthcare Excellence (NICE) definition of long-COVID, which consists of both ongoing (4 to 12 weeks) and post-COVID-19 (≥ 12 weeks) symptoms. Random-effects meta-analyses were performed using the MetaXL software to estimate the pooled prevalence with a 95% confidence interval (CI). Heterogeneity was assessed using I2 statistics. The Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) reporting guideline was followed (registration PROSPERO CRD42021275408). The literature search yielded 8373 publications, of which 21 studies met the inclusion criteria, and a total of 80,071 children and adolescents were included. The prevalence of long-COVID was 25.24%, and the most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), and sleep disorders (8.42%). Children infected by SARS-CoV-2 had a higher risk of persistent dyspnea, anosmia/ageusia, and/or fever compared to controls. Limitations of the studies analyzed include lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and a high level of heterogeneity.

Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. There are no curative, long-lasting treatments for CIPN available to humans. We investigated the ability of chronic CBG to alleviate mechanical hypersensitivity due to CIPN in mice by measuring responses to 7 and 14 days of daily CBG. We found that CBG treatment (i.p.) for 7 and 14 consecutive days significantly reduced mechanical hypersensitivity in male and female mice with CIPN and reduced pain sensitivity up to 60–70% of baseline levels (p < 0.001 for all), 24 h after the last injection. Additionally, we found that daily treatment with CBG did not evoke tolerance and did not incur significant weight change or adverse events. The efficacy of CBG was independent of the estrous cycle phase. Therefore, chronic CBG administration can provide at least 24 h of antinociceptive effect in mice. These findings support the study of CBG as a long-lasting neuropathic pain therapy, which acts without tolerance in both males and females.

The absence of IFN-γ receptor (IFN-γR) or STAT1 signaling in donor cells has been shown to result in reduced induction of acute graft-versus-host disease (GVHD). In this study, we unexpectedly observed increased activation and expansion of donor lymphocytes in both lymphohematopoietic organs and GVHD target tissues of IFN-γR/STAT1–deficient recipient mice, leading to rapid mortality following the induction of GVHD. LPS-matured, BM-derived Ifngr1–/– Stat1–/– DCs (BMDCs) were more potent allogeneic stimulators and expressed increased levels of MHC II and costimulatory molecules. Similar effects were observed in human antigen-presenting cells (APCs) with knockdown of Stat1 by CRISPR/Cas9 and treatment with a JAK1/2 inhibitor. Furthermore, we demonstrated that the absence of IFN-γR/STAT1 signaling in hematopoietic APCs impaired the presentation of exogenous antigens, while promoting the presentation of endogenous antigens. Thus, the indirect presentation of host antigens to donor lymphocytes was defective in IFN-γR/STAT1–deficient, donor-derived APCs in fully donor chimeric mice. The differential effects of IFN-γR/STAT1 signaling on endogenous and exogenous antigen presentation could provide further insight into the roles of the IFN-γ/STAT1 signaling pathway in the pathogenesis of GVHD, organ rejection, and autoimmune diseases.

The Theory of Evolution (TE) is the backbone of biology and is the best way to explain the diversity of species that exist on the planet. However, despite all the supporting evidence, TE remains poorly understood and accepted. In this study, the levels of acceptance and understanding of TE were measured, respectively, using the Inventory of Student Evolution Acceptance (I-SEA) and Knowledge of Evolution Exam (KEE) questionnaires, in high school students in Monterrey, Mexico (N = 370). The results show that the acceptance of TE ranges from moderate (90.3 out of 120) to high (3.7 out of 5), depending on the scale with which it is measured, while the level of comprehension is low (4.5 out of 10). Statistical analysis of the data collected reveals that there is a positive relationship between acceptance and understanding of TE (r = 0.34). In addition, the proportions of I-SEA and KEE were evaluated based on several factors, such as religion and educational level of the parents, among others. It was found that the level of education of the parents positively affects the understanding of the basic concepts of TE, while religion is the main factor of negative influence on both acceptance and understanding. Finally, the low comprehension shown in this study suggests a revision and readjustment of the contents that are taught in the upper secondary education curriculum.

Abstract Fungicides are extensively used in agriculture to control fungal pathogens which are responsible for significant economic impact on plant yield and quality. The conventional antifungal screening techniques, such as water agar and 96-well plates, are based on laborious protocols and bulk analysis, restricting the analysis at the single spore level and are time consuming. In this study, we present a droplet-based microfluidic platform that enables antifungal analysis of single spores of filamentous fungus Alternaria alternata. A droplet-based viability assay was developed, allowing the germination and hyphal growth of single A. alternata spores within droplets. The viability was demonstrated over a period of 24 h and the antifungal screening was achieved using Kunshi/Tezuma as antifungal agent. The efficacy results of the droplet-based antifungal analysis were compared and validated with the results obtained from conventional protocols. The percentage inhibitions assessed by the droplet-based platform were equivalent with those obtained by the other two methods, and the Pearson correlation analysis showed high correlation between the three assays. Taken together, this droplet-based microfluidic platform provides a wide range of potential applications for the analysis of fungicide resistance development as well as combinatorial screening of other antimicrobial agents and even antagonistic fungi.

Magnetic nanoparticles (MNPs) have been used in several medical applications, including targeted hyperthermia, resonance tomography, diagnostic sensors, and localized drug delivery. Further applications of magnetic field manipulation through MNPs in tissue engineering have been described. The current study aims to develop tissue-engineered polymeric scaffolds with incorporated MNPs for applications that require stimulation of the tissues such as nerves, muscles, or heart. Electrospun scaffolds were obtained using 14%w/v polycaprolactone (PCL) in 2,2,2-Trifluoroethanol (TFE) at concentrations of 5% & 7.5%w/v of dispersed MNPs (iron oxide, Fe3O4, or cobalt iron oxide, CoFe2O4). Scaffolds were analyzed using scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy, uniaxial tensile testing, and cell seeding for biocompatibility. Human bone marrow mesenchymal stem cells (bmMSCs) were seeded on the scaffolds. Biocompatibility was assessed by metabolic activity with Resazurin reduction assay on day 1, 3, 7, 10. Cell-cell and cell-scaffold interactions were analyzed by SEM. Electrospun scaffolds containing MNPs showed a decrease in fiber diameter as compared to scaffolds of pure PCL. The maximum force increases with the inclusion of MNPs, with higher values revealed for iron oxide. The metabolic activity decreased with MNPs, especially for cobalt iron oxide at a higher concentration. On the other hand, the cells developed good cell-scaffold and cell-cell interactions, making the proposed scaffolds good prospects for potential use in tissue stimulation.

NK cell deficiencies (NKD) are a type of primary immune deficiency in which the major immunologic abnormality affects NK cell number, maturity, or function. Since NK cells contribute to immune defense against virally infected cells, patients with NKD experience higher susceptibility to chronic, recurrent, and fatal viral infections. An individual with recurrent viral infections and mild hypogammaglobulinemia was identified to have an X-linked damaging variant in the transcription factor gene ELF4. The variant does not decrease expression but disrupts ELF4 protein interactions and DNA binding, reducing transcriptional activation of target genes and selectively impairing ELF4 function. Corroborating previous murine models of ELF4 deficiency (Elf4–/–) and using a knockdown human NK cell line, we determined that ELF4 is necessary for normal NK cell development, terminal maturation, and function. Through characterization of the NK cells of the proband, expression of the proband’s variant in Elf4–/– mouse hematopoietic precursor cells, and a human in vitro NK cell maturation model, we established this ELF4 variant as a potentially novel cause of NKD.

Abstract COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17–87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

Solid organ transplantation is the preferred treatment for end-stage organ failure. Although transplant recipients take life-long immunosuppressive drugs, a substantial percentage of them still reject their allografts. Strikingly, barrier organs colonized with microbiota have significantly shorter half-lives than non-barrier transplanted organs, even in immunosuppressed hosts. We previously demonstrated that skin allografts monocolonized with the common human commensal Staphylococcus epidermidis (S.epi) are rejected faster than germ-free (GF) allografts in mice because the presence of S.epi augments the effector alloimmune response locally in the graft. Here, we tested whether host immune responses against graft-resident commensal microbes, including S.epi, can damage colonized grafts independently from the alloresponse. Naive hosts mounted an anticommensal T cell response to colonized, but not GF, syngeneic skin grafts. Whereas naive antigraft commensal T cells modestly damaged colonized syngeneic skin grafts, hosts with prior anticommensal T cell memory mounted a post-transplant immune response against graft-resident commensals that significantly damaged colonized, syngeneic skin grafts. Importantly, allograft recipients harboring this host-versus-commensal immune response resisted immunosuppression. The dual effects of host-versus-commensal and host-versus-allograft responses may partially explain why colonized organs have poorer outcomes than sterile organs in the clinic.

Abstract Mexico took swift action and has strictly followed mitigation measures to prevent the spread of coronavirus disease, COVID-19. In this study we compared influenza activity indicators in our country after the implementation of public health measures for COVID-19. We compared indicators of influenza activity in 2020 before and after public health measures were taken to reduce COVID-19 with the corresponding indicators from three preceding years and the immediate one, and the potential decrease in seasonal influenza cases/deaths. Nationwide surveillance data revealed a drastic decline in influenza diagnosis in outpatient clinics and public hospitals, influenza positivity rates of clinical specimens, and confirmed severe cases during the following 10 weeks of 2020 as lockdown activities and control measures were established compared with the same period of 2019. Our results suggest that the measures taken for COVID-19 were effective in reducing the spread of other viral respiratory diseases as influenza in our country.

OBJECTIVES/GOALS: Non-alcoholic fatty liver disease increases with aging and may be associated with MCI. Thus, adults >65 years with NAFLD have a greater risk of MCI. Our objective is to associate NAFLD with MCI and, therefore, optimize the management of MCI through prevention strategies and early interventions. METHODS/STUDY POPULATION: We will recruit 100 patients >65 of all sexes from the GI and Geriatrics clinics of the University of Puerto Rico (UPR). NAFLD prevalence in aging adults will be estimated via ICD-10 codes and definition will be liver fat accumulation or steatosis (AASLD) without secondary causes. We will exclude patients RESULTS/ANTICIPATED RESULTS: We expect to find a higher NAFLD prevalence in aging adults >65 years old compared to younger ones. Furthermore, we aim to elucidate an association of NAFLD with MCI in aging adults. Besides, as the literature has shown, we anticipate that the main cognitive domains affected by NAFLD will be the visuospatial and executive functions. As the population ages, this study will help identify future targets for early interventions in people diagnosed with NAFLD that could have a greater risk for cognitive impairment. DISCUSSION/SIGNIFICANCE: To our knowledge, no study has determined the association of NAFLD with MCI in Hispanics >65 in PR. Raising awareness of NAFLD as a possible treatable or preventable risk factor for MCI by screening NAFLD patients for MCI may improve not only their global health but their quality of life as well.

Aim: Glioblastoma (GB) is an aggressive tumor type and the detection of circulating endothelial cells (CECs) in peripheral blood has been related to angiogenesis. Materials & methods: A prospective single-center pilot study of CEC detection at diagnosis in 22 patients with GB was performed, using the US FDA-approved CellSearch system. Results: A CEC cutoff value was estimated using a receiver operating curve (ROC) and patients were classified into two groups: 40 CEC/4 ml blood. Median overall survival was 25.33 months for group 1 and 8.23 months for group 2 cases (p = 0.02). There was no correlation between CEC and PWI (perfusion-weighted imaging) RM. Conclusion: CEC detection has a prognostic value in GB cases at diagnosis.

Mutation of the TET2 DNA-hydroxymethylase has been associated with a number of immune pathologies. The disparity in phenotype and clinical presentation among these pathologies leads to questions regarding the role of TET2 mutation in promoting disease evolution in different immune cell types. Here we show that, in primary mast cells, Tet2 expression is induced in response to chronic and acute activation signals. In TET2-deficient mast cells, chronic activation via the oncogenic KITD816V allele associated with mastocytosis, selects for a specific epigenetic signature characterized by hypermethylated DNA regions (HMR) at immune response genes. H3K27ac and transcription factor binding is consistent with priming or more open chromatin at both HMR and non-HMR in proximity to immune genes in these cells, and this signature coincides with increased pathological inflammation signals. HMR are also associated with a subset of immune genes that are direct targets of TET2 and repressed in TET2-deficient cells. Repression of these genes results in immune tolerance to acute stimulation that can be rescued with vitamin C treatment or reiterated with a Tet inhibitor. Overall, our data support a model where TET2 plays a direct role in preventing immune tolerance in chronically activated mast cells, supporting TET2 as a viable target to reprogram the innate immune response for innovative therapies.

No one likes to be wrong. Previous research has shown that participants may underweight information incompatible with previous choices, a phenomenon called confirmation bias. In this paper, we argue that a similar bias exists in the way information is actively sought. We investigate how choice influences information gathering using a perceptual choice task and find that participants sample more information from a previously chosen alternative. Furthermore, the higher the confidence in the initial choice, the more biased information sampling becomes. As a consequence, when faced with the possibility of revising an earlier decision, participants are more likely to stick with their original choice, even when incorrect. Critically, we show that agency controls this phenomenon. The effect disappears in a fixed sampling condition where presentation of evidence is controlled by the experimenter, suggesting that the way in which confirmatory evidence is acquired critically impacts the decision process. These results suggest active information acquisition plays a critical role in the propagation of strongly held beliefs over time.

ABSTRACT Objective The aim of this study was to translate and cross-culturally adapt the Insulin Delivery System Rating Questionnaire (IDSRQ) for Brazilian users. Validation and reliability analysis of measures were also performed. Materials and methods Methodological study comprising the following stages: forward translation, synthesis, back-translation, assessment by Expert Committee, pre-test and validation. International guidelines for translation and cross-cultural adaptation of measurement tools were followed. Validation data provided information about reliability (internal consistency, test-retest) and construct validity of the IDSRQ. Results Content validation by Experts’ assessment was successful, with a mean Content Validity Index of 0.87 (±0.2). The IDSRQ validation study involved 113 T1DM patients, 46% male, mean age 32.61 (±12.59) years and mean age at diagnosis of diabetes of 17.51 (±12.41). The scale presented good internal consistency (Cronbach’s alpha =0.786). The reliability analysis of the instrument was conducted by calculating the Intra-class Correlation Coefficient 0.885 (0.834-0.921), which indicated adequate concordance in all measures. Conclusion The translated and cross-culturally adapted Brazilian Portuguese version of the IDSRQ may be used to assess health-related quality of life (HRQOL) and treatment preferences for insulin delivery systems in T1DM Brazilian patients.

Abstract Despite the recent development of safe and highly effective direct-acting antivirals, hepatitis C virus (HCV) infection remains a significant health problem. In 2016, the World Health Organization set out to reduce the rate of new HCV infections by 90% by 2030. Still, global control of the virus does not seem to be achievable in the absence of an effective vaccine. Current approaches to the development of a vaccine against HCV include the production of recombinant proteins, synthetic peptides, DNA vaccines, virus-like particles, and viral vectors expressing various antigens. In this review, we focus on the development of vaccines targeting the humoral immune response against HCV based on the cumulative evidence supporting the important role of neutralizing antibodies in protection against HCV infection. The main targets of HCV-specific neutralizing antibodies are the glycoproteins E1 and E2. Recent advances in the knowledge of HCV glycoprotein structure and their epitopes, as well as the possibility of getting detailed information on the human antibody repertoire generated by the infection, will allow rational structure-based antigen design to target specific germline antibodies. Although obtaining a vaccine capable of inducing sterilizing immunity will be a difficult task, a vaccine that prevents chronic hepatitis C infections, a more realistic goal in the short term, would have a considerable health impact.

The Human Immunodeficiency Virus (HIV) Viral Infectivity Factor (Vif) is a 192-amino acid accessory protein essential to viral replication which counteracts host APOBEC3 proteins. APOBEC3 proteins interfere with the replication of HIV, hepatitis C virus, hepatitis B virus and retrotransposons. Vif is a recent candidate target for therapeutic and preventative interventions in HIV/AIDS yet little is known about its clinical relevance. We describe the results of applying different machine learning algorithms (Apriori, Multifactor Dimensionality Reductor, C4.5, Artificial Neural Networks and ID3) to the search of associations between HIV-1 Vif protein attributes and clinical endpoints. Final iterations showed that the presence of mutations in BC Boxes, APOBEC motifs and Cullin5 binding motifs were together associated with higher initial CD4 T cells while mutations of specific APOBEC motifs coupled with the conservation of other APOBEC motifs were associated with lower historic CD4 T cells. Conservation of specific APOBEC motifs and BC boxes were linked to lower initial viral loads while different combinations of mutations in the Nuclear Localisation Inhibition Signal and BC Boxes were associated with higher historic viral loads. Further scrutiny of these combinations through traditional statistical methods revealed striking differences in both CD4 T cells and viral loads in patients stratified into those having the previous combinations. While artificial intelligence algorithms do not phase out traditional statistical methods, our Artificial Intelligence (AI)-based approach highlights their use at reducing the dimensionality of large and complex datasets and at proposing novel, unimaginable, associations of biological patterns with functional relevance or clinical roles.

Clinical testing typically relies on invasive blood draws and biopsies. Alternative methods of sample collection are continually being developed to improve patient experience; swabbing the skin is one of the least invasive sampling methods possible. To show that skin swabs in combination with untargeted mass spectrometry (metabolomics) can be used for non-invasive monitoring of an oral drug, we report the kinetics and metabolism of diphenhydramine in healthy volunteers (n = 10) over the course of 24 hours in blood and three regions of the skin. Diphenhydramine and its metabolites were observed on the skin after peak plasma levels, varying by compound and skin location, and is an illustrative example of how systemically administered molecules can be detected on the skin surface. The observation of diphenhydramine directly from the skin supports the hypothesis that both parent drug and metabolites can be qualitatively measured from a simple non-invasive swab of the skin surface. The mechanism of the drug and metabolites pathway to the skin’s surface remains unknown.

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy that accounts for 15–20% of all cases of leukemia. CML is caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR::ABL1. The amount of BCR::ABL1 transcript RNA is a marker of disease progression and the effectiveness of tyrosine kinase inhibitor (TKI) treatment. This study determined the analytical and clinical performance of a droplet digital PCR based assay (QXDx BCR-ABL %IS Kit; Bio-Rad) for BCR::ABL1 quantification. The test has a limit of detection of MR4.7 (0.002%) and a linear range of MR0.3–4.7 (50–0.002%IS). Reproducibility of results across multiple sites, days, instruments, and users was evaluated using panels made from BCR::ABL1 positive patient samples. Clinical performance of the assay was evaluated on patient samples and compared to an existing FDA-cleared test. The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7–4.2. The assay demonstrated excellent clinical correlation with the comparator test using a Deming regression with a Pearson R of 0.99, slope of 1.037 and intercept of 0.1084. This data establishes that the QXDx™ BCR-ABL %IS Kit is an accurate, precise, and sensitive system for the diagnosis and monitoring of CML.

BackgroundMachine learning applications in the health care domain can have a great impact on people’s lives. At the same time, medical data is usually big, requiring a significant number of computational resources. Although this might not be a problem for the wide adoption of machine learning tools in high-income countries, the availability of computational resources can be limited in low-income countries and on mobile devices. This can limit many people from benefiting from the advancement in machine learning applications in the field of health care. ObjectiveIn this study, we explore three methods to increase the computational efficiency and reduce model sizes of either recurrent neural networks (RNNs) or feedforward deep neural networks (DNNs) without compromising their accuracy. MethodsWe used inpatient mortality prediction as our case analysis upon review of an intensive care unit dataset. We reduced the size of RNN and DNN by applying pruning of “unused” neurons. Additionally, we modified the RNN structure by adding a hidden layer to the RNN cell but reducing the total number of recurrent layers to accomplish a reduction of the total parameters used in the network. Finally, we implemented quantization on DNN by forcing the weights to be 8 bits instead of 32 bits. ResultsWe found that all methods increased implementation efficiency, including training speed, memory size, and inference speed, without reducing the accuracy of mortality prediction. ConclusionsOur findings suggest that neural network condensation allows for the implementation of sophisticated neural network algorithms on devices with lower computational resources.

Abstract Bing‐Neel syndrome (BNS) remains a rare complication of Waldenstrom Macroglobulinemia. Given the paucity of this disease, treatment guidelines are based on small clinical trials with limited participants. Here, we present a case of primary CNS diffuse large B‐cell lymphoma masqueraded as BNS that developed while on ibrutinib therapy.

Most eukaryotic cells retain a mitochondrial fatty acid synthesis (FASII) pathway whose acyl carrier protein (mACP) and 4-phosphopantetheine (Ppant) prosthetic group provide a soluble scaffold for acyl chain synthesis and biochemically couple FASII activity to mitochondrial electron transport chain (ETC) assembly and Fe-S cluster biogenesis. In contrast, the mitochondrion of Plasmodium falciparum malaria parasites lacks FASII enzymes yet curiously retains a divergent mACP lacking a Ppant group. We report that ligand-dependent knockdown of mACP is lethal to parasites, indicating an essential FASII-independent function. Decyl-ubiquinone rescues parasites temporarily from death, suggesting a dominant dysfunction of the mitochondrial ETC. Biochemical studies reveal that Plasmodium mACP binds and stabilizes the Isd11-Nfs1 complex required for Fe-S cluster biosynthesis, despite lacking the Ppant group required for this association in other eukaryotes, and knockdown of parasite mACP causes loss of Nfs1 and the Rieske Fe-S protein in ETC complex III. This work reveals that Plasmodium parasites have evolved to decouple mitochondrial Fe-S cluster biogenesis from FASII activity, and this adaptation is a shared metabolic feature of other apicomplexan pathogens, including Toxoplasma and Babesia. This discovery unveils an evolutionary driving force to retain interaction of mitochondrial Fe-S cluster biogenesis with ACP independent of its eponymous function in FASII.

Avascular necrosis of the talus is a rare condition that can lead to important functional sequelae. There are few therapeutic alternatives for more advanced stages of this disease, the majority of which sacrifice the ankle joint. We report the case of a 50-year-old patient with nontraumatic avascular necrosis that compromised a large part of the talar surface. After non-structural autograft failed, it was reconstructed using fresh structural talar allograft. At one year of follow-up, the patient reported a considerable decrease in pain. To our knowledge, this is the first reported case in which fresh structural allograft was used in the treatment of nontraumatic avascular necrosis of the talus. Level of Evidence V; Therapeutic Studies; Expert Opinion.

The human brain excels at constructing and using abstractions, such as rules, or concepts. Here, in two fMRI experiments, we demonstrate a mechanism of abstraction built upon the valuation of sensory features. Human volunteers learned novel association rules based on simple visual features. Reinforcement-learning algorithms revealed that, with learning, high-value abstract representations increasingly guided participant behaviour, resulting in better choices and higher subjective confidence. We also found that the brain area computing value signals – the ventromedial prefrontal cortex – prioritised and selected latent task elements during abstraction, both locally and through its connection to the visual cortex. Such a coding scheme predicts a causal role for valuation. Hence, in a second experiment, we used multivoxel neural reinforcement to test for the causality of feature valuation in the sensory cortex, as a mechanism of abstraction. Tagging the neural representation of a task feature with rewards evoked abstraction-based decisions. Together, these findings provide a novel interpretation of value as a goal-dependent, key factor in forging abstract representations.

Abstract The snowpack is an important source of water for many Andean communities. Because of its importance, elemental and mineralogical composition analysis of the Andean snow is a worthwhile effort. In this study, we conducted a chemical composition analysis (major and trace elements, mineralogy, and chemical enrichment) of surface snow sampled at 21 sites across a transect of about 2,500 km in the Chilean Andes (18–41°S). Our results enabled us to identify five depositional environments: (i) sites 1–3 (in the Atacama Desert, 18–26°S) with relatively high concentrations of metals, high abundance of quartz and low presence of arsenates, (ii) sites 4–8 (in northern Chile, 29–32°S) with relatively high abundance of quartz and low presence of metals and arsenates, (iii) sites 9–12 (in central Chile, 33–35°S) with anthropogenic enrichment of metals, relatively high values of quartz and low abundance of arsenates, (iv) sites 13–14 (also in central Chile, 35–37°S) with relatively high values of quartz and low presence of metals and arsenates, and v) sites 15–21 (in southern Chile, 37–41°S) with relatively high abundance of arsenates and low presence of metals and quartz. We found significant anthropogenic enrichment at sites close to Santiago (a major city of 6 million inhabitants) and in the Atacama Desert (that hosts several major copper mines).

Background: Few studies have examined the use of ergogenic supplements (ESs) by young athletes residing in a sports specialized school. Methods: In this cross-sectional study, 120 students from a sports specialized school (ages 12–19) completed a questionnaire to assess the prevalence of use of ES according to sex, sport, type of supplement, reasons for use, knowledge of supplements, and sources of information. Results: Most athletes were males (55%) and participated in track and field (32%). Mean age was 14.7 ± 1.6 years. Approximately 98% of athletes indicated using one or more supplements. Sport beverages (95.0%), proteins/amino acids (57%), and vitamins (54%) were the most commonly used. Athletes practicing racquet sports were more likely to consume proteins/amino acids every day than those in any other type of sport (P < 0.05). The adjusted odds of using vitamins were 14% (95% confidence interval [CI]: 0.22–3.30) and 71% (95% CI: 0.09–0.96) lower among athletes practicing explosive sports and high intensity, respectively, as compared to those practicing endurance-intensive sports. On the other hand, the odds of using proteins/amino acids was higher for those practicing explosive (adjusted odds ratio [AOR]: 3.48, 95% CI: 1.02–11.86) and high-intensity (AOR: 2.88, 95% CI: 1.00–8.26) sports. Approximately 62% of athletes used supplements to improve performance. Only 8% of athletes were willing to use a prohibited substance to achieve participation in the Olympics. Conclusion: There was a very high prevalence of use of ES in a sports specialized school. Education regarding supplement use is warranted for athletes, coaches, and family.

The COVID-19 pandemic will likely take years to control globally, and constant epidemic surveillance will be required to limit the spread of SARS-CoV-2, especially considering the emergence of new variants that could hamper the effect of vaccination efforts. We developed a simple and robust – Phone Screen Testing (PoST) – method to detect SARS-CoV-2-positive individuals by RT-PCR testing of smartphone screen swab samples. We show that 81.3–100% of individuals with high-viral-load SARS-CoV-2 nasopharyngeal-positive samples also test positive for PoST, suggesting this method is effective in identifying COVID-19 contagious individuals. Furthermore, we successfully identified polymorphisms associated with SARS-CoV-2 Alpha, Beta, and Gamma variants, in SARS-CoV-2-positive PoST samples. Overall, we report that PoST is a new non-invasive, cost-effective, and easy-to-implement smartphone-based smart alternative for SARS-CoV-2 testing, which could help to contain COVID-19 outbreaks and identification of variants of concern in the years to come.

Introduction: The objective of physical training in military training is to develop physical and psychological preparation in adverse environmental conditions. Objective: Determine the changes in body composition and somatotype product of basic physical training in military training for four weeks in conscript soldiers. Methods: 28 men were evaluated (age: 18.9 ± 0.9 years; height: 1.75 ± 0.1 m; weight: 67 ± 8.7 kg; BMI: 22.5 ± 2.4 and ∑6 folds 70.88 ± 26.57) who entered the period of military training in the Chilean Air Force, Quintero headquarters. Informed consent was given before the study; the indications established in the Declaration of Helsinki were followed.The participants were incorporated into a physical training plan for 4 weeks. The program was carried out in the facilities of a military center. Results: After physical training there was a significant decrease in adipose mass (p

Supplemental feeding of wildlife is a common practice often undertaken for recreational or management purposes, but it may have unintended consequences for animal health. Understanding cryptic effects of diet supplementation on the gut microbiomes of wild mammals is important to inform conservation and management strategies. Multiple laboratory studies have demonstrated the importance of the gut microbiome for extracting and synthesizing nutrients, modulating host immunity, and many other vital host functions, but these relationships can be disrupted by dietary perturbation. The well-described interplay between diet, the microbiome, and host health in laboratory and human systems highlights the need to understand the consequences of supplemental feeding on the microbiomes of free-ranging animal populations. This study describes changes to the gut microbiomes of wild elk under different supplemental feeding regimes. We demonstrated significant cross-sectional variation between elk at different feeding locations and identified several relatively low-abundance bacterial genera that differed between fed versus unfed groups. In addition, we followed four of these populations through mid-season changes in supplemental feeding regimes and demonstrated a significant shift in microbiome composition in a single population that changed from natural forage to supplementation with alfalfa pellets. Some of the taxonomic shifts in this population mirrored changes associated with ruminal acidosis in domestic livestock. We discerned no significant changes in the population that shifted from natural forage to hay supplementation, or in the populations that changed from one type of hay to another. Our results suggest that supplementation with alfalfa pellets alters the native gut microbiome of elk, with potential implications for population health.