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Introduction: Cardiovascular disease is the main cause of mortality in people with type 2 diabetes mellitus. Objective: Design a predictive model of macrovascular complications in patients with type 2 diabetes at the time of diagnosis. Methods: An observational, of cases and controls, retrospective study was carried out. The population studied were all patients diagnosed with type 2 diabetes mellitus in the "José Martí" health area of the province of Santiago de Cuba, during the period from September 2018 to December 2022. 40 cases with macrovascular complications and 80 controls were studied. randomly selected from the same population, without complications. To build the model, binary logistic regression was applied and those that were associated with macrovascular complications in a previous bivariate analysis were used as independent variables. Results: The variables that were included in the model, after the binary logistic regression analysis, were arterial stiffness, hyperlipidaemia, and arterial hypertension. Hosmer-Lemeshow test= 6.027; p= 0.644. The sensitivity of 77.50 % and specificity of 90.00 %; with a positive predictive value of 79.49 and negative predictive value of 88.89; and validity index equal to 85.83. The observed area under the Receiver Operating Characteristic curve is 0.933, with a significance associated with the calculated statistic of 0.000. Conclusions: The designed model is a good predictor of macrovascular complications in patients with type 2 diabetes at the time of diagnosis.

ABSTRACT Introduction and objectives: In patients with ST-segment elevation myocardial infarction (STEMI) treatment delay significantly affects outcomes. The effect of admission time in STEMI patients is unknown when percutaneous coronary intervention (PCI) is the preferred reperfusion strategy. This study aimed to determine the association between STEMI outcomes and the timing of admission in a PCI center in south-western Europe. Methods: This retrospective cohort study analyzed the local electronic data from 1222 consecutive STEMI patients treated with PCI. On-hours were defined as admission from Monday to Friday between 8:00 AM and 6:00 PM on non-national holidays. Results: A total of 439 patients (36%) were admitted on-hours and 783 patients (64%) were admitted off-hours. Baseline characteristics were well-balanced between the 2 groups, including the percentage of patients admitted in cardiogenic shock (on-hours 5% vs off-hours 4%; P = .62). The median time from first medical contact to reperfusion did not differ between the 2 groups (on-hours 120 minutes vs off-hours 123 minutes, P = .54) and no association was observed between admission time and in-hospital mortality (on-hours 5% vs off-hours 5%, P = .90) or 1-year mortality (on-hours 10% vs off-hours 10%, P = .97). Survival analysis showed no differences in on-hours PCI vs off-hours...

Abstract Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

Abstract Background Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. Methods Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. Results Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. Conclusions We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations. Graphical Abstract

Objectives Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma.Materials and methods This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 − Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6–11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition associated primarily with PKD1 and PKD2 genes. However, ADPKD patients in Latin America have had limited access to comprehensive care. The ProPKD score predicts the likelihood of kidney failure before the age of 60. This study aimed to describe the clinical and genetic characteristics of Chilean ADPKD patients and assess the ProPKD score. Methods We enrolled 40 ADPKD probands and 122 relatives from different centers. Genetic analysis of PKD1 and PKD2 genes was performed by combining direct and next-generation sequencing. Pathogenicity was determined using bioinformatic tools. ProPKD scores were calculated based on clinical and genetic data. Results ADPKD probands were diagnosed at a median age of 35 years. Pathogenic, likely pathogenic, or uncertain significance variants were identified in 38/40 pedigrees, with 89% involving PKD1 and 11% involving PKD2 variants. Among the identified variants, 62% were novel. Patients with PKD1 truncating variants had a more severe disease course, reaching kidney failure by a median age of 48.5 years. ProPKD scores were assessed in 72 individuals, stratifying them into high-, intermediate-, or low-risk categories and the median ages for kidney failure were 45, 49, and 52 years, respectively (log-rank p = 0.001). Conclusion This study provides valuable insights into the clinical and genetic profiles of ADPKD patients in Chile. ADPKD poses a significant public health concern, warranting improvements in diagnosis and treatment. The use of the ProPKD score to predict disease progression should be further explored to enhance patient care and management.

Introduction. Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. Objective. To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. Materials and methods. We performed a retrospective analysis of non-metastatic HER2-positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Results. Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR =0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti-HER2 therapy than in those with chemotherapy alone (48% versus 16%). Conclusion. In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.

Objectives: Human Polycystic Ovary/Ovarian Syndrome (PCOS), a frequent endocrine pathophysiology among women of fertile age, is associated with woman’s lifespan endocrine, metabolic and psychological implications. Long-term usage side effects of allopathic strategies and their low efficacy made complementary medicine treatments a relevant subject for these patients. The main aim of this work is to review the efficiency of the acupuncture treatment reported in the latest studies on literature regarding PCOS patients.Methods: A comprehensive literature search, in English language, about the use of acupuncture on the management of PCOS, was conducted in October 2020 using EBSCO, Cochrane, PubMed, Medline, Embase, databases for randomised and non-randomised controlled trials between 2015 and 2020 (09/2015-10/2020), following the PRISMA protocol.Results: This research led us to an analysis, according to PICOS, of six final papers selected among 178 in total. The articles addressed distinct aspects of the PCOS condition, diverse acupuncture techniques and different main and secondary outcomes in agreement to the respective main objective. According to this review, acupuncture seems to be useful for the treatment of this debilitating and chronic health condition which affects millions of women worldwide, many of them part of the workforce in their community.Conclusion: Despite of the display of these positive results addressing acupuncture treatments to manage PCOS major symptoms - whether they are reproductive, metabolic, or mental health features - more research is urgent. Randomized, double blinded controlled trials with improved quality design and following STRICTA and/or CONSORT recommendations are necessary to engage acupuncture as a standardized and scientific validated technique in PCOS condition.

The rapid spread of the new coronavirus disease (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Although specific vaccines are available and natural drugs are being researched, supportive care and specific treatments to alleviate symptoms and improve patient quality of life remain critical. Chinese medicine (CM) has been employed in China due to the similarities between the epidemiology, genomics, and pathogenesis of SARS-CoV-2 and SARS-CoV. Moreover, the integration of other traditional oriental medical systems into the broader framework of integrative medicine can offer a powerful approach to managing the disease. Additionally, it has been reported that integrated medicine has better effects and does not increase adverse drug reactions in the context of COVID-19. This article examines preventive measures, potential infection mechanisms, and immune responses in Western medicine (WM), as well as the pathophysiology based on principles of complementary medicine (CM). The convergence between WM and CM approaches, such as the importance of maintaining a strong immune system and promoting preventive care measures, is also addressed. Current treatment options, traditional therapies, and classical prescriptions based on empirical knowledge are also explored, with individual patient circumstances taken into account. An analysis of the potential benefits and challenges associated with the integration of complementary and Western medicine (WM) in the treatment of COVID-19 can provide valuable guidance, enrichment, and empowerment for future research endeavors.

Abstract Background and Aims The acute tropical infectious disease known as yellow fever (YF) is caused by an arbovirus and is characterized by fever, jaundice, hemorrhage, headache, muscle pain, nausea, vomiting, and fatigue. Angola experienced a yellow fever virus (YFV) outbreak that was documented in December 2015. However, little is known about the outcome of this outbreak. We aimed to demonstrate epidemic features and lessons learned during the YF epidemic in Angola. Methods A total of 4618 blood samples from suspected YF cases were sent to the Instituto Nacional de Investigação em Saúde (INIS), a national referral and public health laboratory, between December 5, 2015, and December 23, 2016. Sample analyses were conducted using enzyme‐linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT‐PCR) assays. Blood samples were sent from 16 out of the 18 provinces of Angola. Results We detected 884 (19.1%) cases that were positive for ELISA, which were confirmed by RT‐PCR assay. Considering the positive cases, the incidence among male patients was around three times higher (n = 223; 10.9%) than in female patients (n = 59; 2.6%) in the 20–29 age group, followed by the age group 10–19 with n = 211 (6.8%) in males versus n = 108 (3.3%) in females; and the age group 30–39 had n = 68 (4.8%) in males versus n = 28 (1.8%) in females. The other groups had an incidence below 3.0%. The case fatality ratio for YF was in young adults in the age group 20–29 with n = 39 cases, followed by the age group 10–19 with n = 16 cases, and finally the age group 0–9 with n = 13 cases. The other age groups had several deaths by YF below 10 cases. Conclusions This study demonstrates features of the YF epidemic that occurred in Angola. Also, it demonstrates that YF causes deaths in young people but is preventable by high vaccine coverage. Thus, public health laboratory surveillance must be strengthened to reduce the possibility of emerging and re‐emerging human infections.

Las asignaturas de Patología general y Anatomía patológica son impartidas durante el quinto y sexto semestre de la carrera de Medicina de la Universidad de Concepción. En estas se utiliza un estilo de enseñanza tipo aula invertida y se realiza una actividad práctica de “Diseño de Casos Clínico-Patológicos” (DCCP), iniciada en sala de patología quirúrgica, donde los estudiantes vivencian en forma real el trabajo del anatomopatólogo en grupos de 3 a 4 personas, realizando desde el dictado macroscópico hasta el diagnóstico microscópico, con una presentación final del caso a estudiantes y docentes. Se realizó un estudio observacional analítico transversal a una muestra de 87 estudiantes que cursaron ambas asignaturas. Se efectuó un análisis descriptivo cuantitativo y un método cualitativo de análisis de contenido, codificándose y clasificándose las respuestas de 2 instrumentos. La satisfacción general de la actividad DCCP fue de 82,4%, siendo percibida como innovadora y útil para el desarrollo de habilidades y aprendizajes teóricos de patología, que prepara a los alumnos de mejor manera para enfrentar los desafíos del mundo real como profesionales de la salud. No se debe olvidar la importancia de considerar las preferencias y necesidades de los estudiantes al diseñar estrategias de enseñanza. La evaluación cualitativa de la actividad DCCP y de las asignaturas entregó valiosa información para un mejoramiento continuo; reafirmando la importancia de incorporar éstas en las evaluaciones de prácticas docentes. Se concluye que la actividad práctica DCCP ayuda de mejor forma a los estudiantes de medicina a entender los aspectos macroscópicos y microscópicos de la Anatomía Patológica; superando incluso al aula invertida. La combinación de enfoques centrados en el alumno, trabajo en entornos reales, un apoyo docente adecuado y material de estudio de calidad puede conducir a una experiencia de aprendizaje más efectiva y satisfactoria para los estudiantes en estas disciplinas.

Visual representation of material culture plays a crucial role in prehistoric archaeology, from academic research to public outreach and communication. Scientific illustration is a valuable tool for visualising lithic artefacts and refittings, where technical attributes must be drawn to enhance our understanding of their significance. However, the representation of lithic refittings, which involve dynamic and sequential transformations of a volume, requires an alternative approach to traditional two-dimensional models such as photography or illustration. Advances in imaging technologies have improved our ability to capture and communicate the multifaceted nature of archaeological artefacts. In this context, we present the ReViBE protocol (Refitting Visualisation using Blender Engine), which integrates photogrammetry, 3D modelling and the animation software Blender© for the virtual representation of lithic refittings. This protocol allows the sequential study of core reduction phases and their associated flakes, as well as other aspects related to knapping decision making (core rotations, surface modifications, and direction and position of impact points). Thus, this method allows the visualisation of techno-cognitive aspects involved in core reduction through a step-by-step animation process. In addition, the 3D models and virtual reconstructions generated by ReViBE can be accessed through open repositories, in line with the principles of open science and FAIR (Findable, Accessible, Interoperable, and Reusable) data. This accessibility ensures that data on lithic technology and human behaviour are widely available, promoting transparency and knowledge sharing, and enabling remote lithic analysis. This in turn breaks down geographical barriers and encourages scientific collaboration.

Violence against women or gender-based violence (GBV) is a significant public health issue facing women and girls in different settings. It is reported to have worsened globally during the COVID-19 pandemic. Despite the impact of the COVID-19 pandemic on increased violence against women in general, which has been reported in many settings globally, there is a paucity of evidence of its impact on violence against highly vulnerable women living with HIV or tuberculosis (TB). Using a qualitative design, this study aimed to explore the views and experiences of women living with HIV (n = 19) or TB (n = 23) in Timor Leste regarding the GBV they faced during the COVID-19 pandemic. They were recruited using the snowballing sampling technique. Data were collected using one-on-one, in-depth interviews and focus group discussions. The five steps of qualitative data analysis suggested in Ritchie and Spencer's analysis framework were employed to guide the analysis of the findings. Findings indicated that women in this study experienced intensified physical, verbal, sexual and psychological violence by their partners, spouses, in-laws, and parents or other family members during the COVID-19 pandemic. Several prominent risk factors that worsened violence against women during the pandemic were (i) HIV or TB-positive status, (ii) traditional gender roles or responsibilities and expectations, (iii) economic and financial difficulties reflected in the loss of jobs and incomes due to the pandemic, and (iv) individual factors such as jealousy and increased alcohol drinking developed during the lockdowns. The women's experience of GBV during the pandemic also led to various negative psychological impacts. The findings underscore the urgent need for multifaceted interventions to address GBV, which should encompass challenging traditional gender norms, addressing economic inequalities, and targeting individual-level risk factors. The findings also indicate the need for the development of robust monitoring and evaluation systems to assess the effectiveness of policies and interventions addressing GBV where the results can inform future improvement. The findings also indicate the need to include GBV in the protocol or guidelines for HIV and TB management. Future large-scale quantitative studies to capture the magnitude and specific drivers of GBV against women living with HIV and TB during the pandemic are recommended.

Introduction Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.Methods and analysis The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5–4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12–18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.Ethics and dissemination The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.Trial registration number EudraCT 2021-004868-95; NCT05809414.

Background Loss of biological connectivity increases the vulnerability of ecological dynamics, thereby affecting processes such as pollination. Therefore, it is important to understand the roles of the actors that participate in these interaction networks. Nonetheless, there is a significant oversight regarding the main actors in the pollination networks within the highly biodiverse forests of Colombia. Hence, the present study aims to evaluate the interaction patterns of a network of potential pollinators that inhabit an Andean Forest in Totoró, Cauca, Colombia. Methods The interactions between plants and potential pollinators were recorded through direct observation in 10 transects during six field trips conducted over the course of one year. Subsequently, an interaction matrix was developed, and network metrics such as connectance, specialization, nestedness, and asymmetry of interaction strength were evaluated by applying null models. An interpolation/extrapolation curve was calculated in order to assess the representativeness of the sample. Finally, the key species of the network were identified by considering degree (k), centrality, and betweenness centrality. Results A total of 53 plant species and 52 potential pollinator species (including insects and birds) were recorded, with a sample coverage of 88.5%. Connectance (C = 0.19) and specialization (H2’ = 0.19) were low, indicating a generalist network. Freziera canescens, Gaiadendron punctatum, Persea mutisii, Bombus rubicundus, Heliangelus exortis, Chironomus sp., and Metallura tyrianthina were identified as the key species that contribute to a more cohesive network structure. Discussion The present study characterized the structure of the plant-pollinator network in a highly diverse Andean forest in Colombia. It is evident that insects are the largest group of pollinators; however, it is interesting to note that birds form a different module that specializes in pollinating a specific group of plants. On the other hand, the diversity and generality of the species found suggest that the network may be robust against chains of extinction. Nevertheless, the presence of certain introduced species, such as Apis mellifera, and the rapid changes in vegetation cover may affect the dynamics of this mutualistic network. So, it is imperative to apply restoration and conservation strategies to these ecosystems in order to enhance plant-animal interactions and prevent the loss of taxonomical and functional diversity.

Abstract Rehabilitation can promote brain plasticity and improve motor control after central nervous system injuries. Our working model is that motor control is encoded using dynamic primitives: submovements, oscillations, and mechanical impedances. We hypothesize that therapies focusing on these primitives can achieve greater motor recovery. At the observational level, these primitives lead to discrete and rhythmic movements. Here, we propose two novel biomarkers to evaluate rhythmic and discrete movements in gait based on the feet forward position: the smoothness of their relative position, using the mean-squared jerk ratio (MSJR), to assess rhythmicity; and the angle between principal components of consecutive trajectories (dPCA), to detect discrete movements amidst rhythmic motion. We applied these methods to kinematic data collected with healthy individuals during experiments employing the MIT-Skywalker: level-ground walking at five speeds, with and without imposed ankle stiffness; walking at constant speed on ascending, descending, and laterally tilted slopes; and performing sidesteps. We found a decrease in MSJR as speed increases, related to increased rhythmicity, even with imposed stiffness. Rhythmicity seems unaffected by the terrain perturbations imposed. Finally, dPCA successfully detects sidesteps, discrete events amidst rhythmic movement. These biomarkers appear to accurately assess rhythmic and discrete movements during walking and can potentially improve clinical evaluation and rehabilitation of neurological patients.

Abstract Schinus terebinthifolia Raddi is a species with several potential uses; selecting the proper substrate and fertilizer rate can be vital for seedling production in a nursery environment. This study aims to evaluate two substrates, namely: (i) sewage sludge (SS) from Ilha WWTP; (ii) a commercial substrate (CS) made of organic materials (mainly sphagnum peat). Increasing rates of controlled-release fertilizer – CRF (0, 3, 6, and 12 kg m−3) were applied. The experiment was completely randomized with a factorial 2 × 4 scheme (substrates × rates). The seedlings’ growth, biomass, and quality were evaluated. The treatments were compared by Tukey test and regression analysis, where linear, quadratic, and cubic models were considered. Principal components analysis (PCA) and cluster analysis were performed. The CRF rates showed non-significant effects for most of the investigated variables in the SS substrate. In the CS, a 7.8 kg m−3 rate of CRF showed the best growth performance. The multivariate analysis of the morphological parameters proved suitable as a complementary approach to evaluate the seedlings’ quality. Seedlings reached recommended values for height, diameter, and quality in the 100% SS substrate without chemical fertilizers; thus, Schinus terebinthifolia production in the SS from Ilha is recommended. Besides the growth advantage, the SS can promote nursery cost savings with commercial substrates and chemical fertilizers.

Objetivos. Estimar la carga de enfermedad por COVID-19 en el departamento de Nariño, Colombia, a partir del indicador años de vida saludables ajustados por discapacidad (AVISA) entre marzo del 2020 a agosto del 2021. Materiales y métodos. Con la información del sistema de vigilancia nacional SIVIGILA se hizo la descripción y caracterización de los casos de COVID-19 reportados entre marzo/2020 a agosto/2021, según grupos de edad, sexo, etnia, municipios de residencia y subregiones de Nariño. Se estimaron tasas crudas y de mortalidad acumulada por COVID-19 para las variables previamente descritas. Se calcularon años perdidos por muerte prematura (APMP) y años vividos por discapacidad (AVD). Se estimaron los AVISA totales mediante la suma de APMP + AVD. Estos se calcularon por sexo, etnia, grupo de edad y subregiones de Nariño. Se estimaron los riesgos relativos a partir de las razones de tasas (RT) e intervalos de confianza del 95% para las variables del estudio. Resultados. Las tasas de morbilidad, mortalidad y AVISA más altas ocurrieron entre febrero y septiembre del 2021, en hombres, en mayores de 70 años, del grupo étnico minoritario afrodescendiente y en las subregiones Centro, Obando y Juanambú. La carga de enfermedad por COVID-19 en Nariño en el periodo de estudio es atribuida a los APMP, los cuales explican más del 97% de la misma. Conclusiones. Este es uno de los primeros estudios de carga de enfermedad a nivel regional, realizados en Colombia, que emplea una metodología estandarizada para COVID-19. Esta medición generaría estimaciones que permitirían focalizar recursos de forma intersectorial, mitigar el daño a poblaciones y áreas geográficas determinadas, especialmente las más vulnerables.

Summary: Background: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. Methods: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. Findings: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. Interpretation: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. Funding: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund “A way to make Europe” (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund “A way to make Europe”) (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Introducción. La anemia de células falciformes (ACF) es una enfermedad genética que provoca una malformación en el glóbulo rojo, volviéndolo más frágil y desencadenando su lisis. Por su forma anómala predispone a eventos oclusivos en vasos de menor tamaño, incluyendo aquellos en el sistema nervioso central. La literatura documenta presencia de infartos cerebrales silentes y no silentes asociados a ACF, con sus respectivas alteraciones cognitivas. En los últimos años se ha reportado que existe compromiso cognitivo y mayor presencia de trastornos del neurodesarrollo, como el trastorno por déficit de atención e hiperactividad (TDAH) en aquellos niños con ACF que aún no han tenido eventos cerebrales isquémicos. Método. Se llevó a cabo un estudio experimental y prospectivo de caso único, que consistió en un programa de rehabilitación por medio de la plataforma de entrenamiento cognitivo para la atención y concentración de CogniFit. Durante 45 sesiones, se realizaron mediciones de respuestas en atención y control inhibitorio, utilizando la Batería de Evaluación Cognitiva para la Atención (CAB-AT). Resultados. Se observó que la intervención tuvo un impacto significativo en el componente de atención, el cual se mantuvo por encima de la línea de base, incluso después de suspender la intervención. Sin embargo, no se encontró un impacto importante en el control inhibitorio. Conclusión. Aunque la intervención mejoró la atención, no lo hizo con el control inhibitorio. Se recomienda complementar la rehabilitación con manejo farmacológico y diseñar nuevos estudios con poblaciones heterogéneas.

Background Defining Andean anurans through their altitudinal limits has been a common practice in species lists, studies of responses to climate change among others, especially in the northern Andes. At least three proposals to differentiate Andean anurans from lowland anurans through elevation and at least one to differentiate Andean anurans from high mountain anurans have been formulated. However, the most frequently used altitudinal limits are not based on theoretical or numerical support, but on observations or practical definitions. Additionally, these proposals have been applied equally to different portions of the Andes, ignoring the fact that even between slopes of the same mountain, environmental conditions (and therefore the distribution of species) may differ. The objective of this work was to evaluate the concordance between the altitudinal distribution of anurans in the Colombian Andes and four different altitudinal delimitation proposals. Methods We constructed our study area in a manner that allowed us to include species from the Andean region (as traditionally defined) and adjacent lowlands, because if the boundaries criteria were applied they would separate the species of the latter by themselves. We divided the study area into eight entities according to the watershed and the course of the most important rivers. We conducted a bibliographic search for all anurans in the cordilleras and inter-Andean valleys of Colombia and complemented the search with information on anurans for the region available in the GBIF. After curing the species distribution points, we generated elevation bands of 200 m amplitude for both the study area and for each Andean entity. Subsequently, we performed a cluster analysis to evaluate the grouping of the elevation bands according to their species composition. Results In none of the cases (neither for the entire study area nor for any of the entities) we found a correspondence of any of the traditionally used boundaries and the altitudinal distribution of Anurans in the Andean region of Colombia. Instead, on average, the altitudinal delimitation proposals arbitrarily spanned the altitudinal distribution of about one third of the species distributed in the study area. Conclusions We suggest that, although, based on our results, some Andean entities can be divided according to the altitudinal composition of the species that occur in them, we did not find any results that support the idea of a generalizable altitudinal limit for the Colombian Andes. Thus, to avoid biases in studies that may later be used by decision makers, the selection of anuran species in studies in the Colombian Andes should be based on biogeographic, phylogenetic or natural history criteria and not on altitudinal limits as they have been used.

Olive leaves are consumed as an extract or as a whole herbal powder with several potential therapeutic benefits attributed to polyphenols, tocopherol’s isomers, and flavonoids, among others. This study assessed the potential variance in the functional features presented by olive leaves from three different Portuguese cultivars—Cobrançosa, Madural, and Verdeal—randomly mix-cultivated in the geographical area of Vale de Salgueiros. Inorganic analysis determined their mineral profiles while an organic analysis measured their total phenolic and flavonoid content, and scanned their phenolic and tocopherol and fatty acid composition. The extracts’ biological activity was tested by determining their antimicrobial and antioxidant power as well as their ability to inhibit acetylcholinesterase, butyrylcholinesterase, MAO-A/B, and angiotensin-I-converting enzyme. The inorganic profiles showed them to be an inexpensive source able to address different mineral deficiencies. All cultivars appear to have potential for use as possible antioxidants and future alternative antibiotics against some multidrug-resistant microorganisms, with caution regarding the arsenic content in the Verdeal cultivar. Madural’s extract displayed properties to be considered a natural multitarget treatment for Alzheimer’s and Parkinson’s diseases, depression, and cardiometabolic and dual activity for blood pressure modulation. This work indicates that randomly cultivating different cultivars significantly modifies the leaves’ composition while keeping their multifaceted therapeutic value.

Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis.

Highlights - About one third of the patients who undergo a thrombectomy for acute stroke experience headache directly related to the procedure. - Having a previous history of primary headache is associated with the presence of headache after thrombectomy. - Headache related to thrombectomy usually coincides with the distribution of the affected artery, although it is bilateral in 45% of the cases, mostly oppressive, of an average duration between 1 and 2 days and of a moderate intensity.

La hipoacusia súbita es una entidad de aparición aguda secundaria a múltiples etiologías, como las enfermedades reumáticas autoinmunes sistémicas (ERAS). La afectación suele ser unilateral, asociada a taponamiento de oídos y tinnitus. El diagnóstico se basa en la historia clínica, el examen físico y la audiometría. Según la etiología, el tratamiento de primera línea son los corticoides sistémicos y otros agentes terapéuticos. El pronóstico depende del grado de pérdida auditiva, el momento de inicio de la terapia y factores inherentes al paciente. A continuación, se presentan tres casos clínicos de pacientes que debutaron con hipoacusia súbita como manifestación inicial de ERAS.

Introducción. Una vez declarada la pandemia por COVID-19, los servicios de rehabilitación empezaron a prepararse para la atención, mediante diferentes abordajes, de los pacientes que se recuperaran de esta enfermedad. Objetivo. Correlacionar los resultados obtenidos en el Cuestionario Respiratorio de Saint George (CRSG), la Escala de Severidad de la Fatiga (FSS) y la Escala de Actividades de la Vida Diaria London Chest (LCADL) aplicados en pacientes recuperados de COVID-19 para medir su calidad de vida y la fatiga. Métodos. Estudio descriptivo retrospectivo realizado en 60 pacientes recuperados de COVID-19, moderado o grave, que ingresaron al programa de rehabilitación pulmonar de un hospital de tercer nivel de Bogotá, Colombia, entre el primero de octubre de 2020 y el 30 de junio de 2021. Se analizaron variables demográficas y para caracterizar la calidad de vida y la fatiga de los participantes se utilizó el cuestionario CRSG, la escala FSS y la escala LCADL, cuyos resultados se compararon mediante correlación de Spearman. Para el análisis estadístico se utilizó el programa de SPSS versión 28. Resultados. La fatiga está correlacionada con la calidad de vida, y al ser identificada se puede intervenir mediante los ejercicios terapéuticos de los programas de rehabilitación pulmonar, lo cual optimiza los resultados esperados. Conclusiones. Existe una adecuada correlación entre las escalas CRSG y LCADL; esto es importante porque aplicar escalas de calidad de vida en pacientes con SARS-CoV-2 permite conocer las áreas que pueden ser intervenidas mediante programas de rehabilitación pulmonar para lograr una intervención adecuada

Introducción. La atrofia muscular espinal es una enfermedad neurodegenerativa huérfana de origen genético que afecta las neuronas motoras del asta anterior de la médula espinal, y produce atrofia y debilidad muscular. En Colombia, son pocos los estudios publicados sobre la enfermedad y no hay ninguno con análisis funcional. Objetivo. Caracterizar clínica y funcionalmente una serie de casos de atrofia muscular espinal del centro-occidente colombiano. Materiales y métodos. Se hizo un estudio descriptivo transversal, entre el 2007 y el 2020, de pacientes con diagnóstico clínico y molecular de atrofia muscular espinal que consultaron en el centro de atención. La evaluación funcional se realizó con las escalas Hammersmith y Chop Intend. En la sistematización de los datos, se empleó el programa Epi-Info, versión 7.0. Resultados. Se analizaron 14 pacientes: 8 mujeres y 6 hombres. La atrofia muscular espinal más prevalente fue la de tipo II, la cual se presentó en 10 casos. Se encontró variabilidad fenotípica en términos de funcionalidad en algunos pacientes con atrofia muscular espinal de tipo II, cinco de los cuales lograron alcanzar la marcha. La estimación de la supervivencia fue de 28,6 años. Conclusiones. Los hallazgos en el grupo de pacientes analizados evidenciaron que los puntajes de la escala de Hammersmith revisada y expandida, concordaron con la gravedad de la enfermedad.

Introducción. El estigma se ha asociado negativamente al control metabólico y la calidad de vida de pacientes con diabetes de tipo 2. El cuestionario Diabetes Stigma Assesment Scale 2 (DSAS 2) fue diseñado para medir específicamente el estigma asociado en personas con este tipo de diabetes. Sin embargo, las propiedades psicométricas de su versión en español aún no han sido analizadas. Objetivo. Analizar la validez y confiabilidad de la versión en español del DSAS 2 en población colombiana. Materiales y métodos. Se solicitó a 501 pacientes con diabetes de tipo 2 en Barranquilla contestar la versión en español del DSAS 2, un cuestionario con indicadores sociodemográficos y clínicos, así como instrumentos de medición de la depresión, la autoeficacia y el estrés. Se hizo un análisis factorial (exploratorio y confirmatorio) para determinar la estructura interna del DSAS 2 en español y se usó el coeficiente alfa (α) para evaluar su confiabilidad. Además, se analizó la relación entre los puntajes del DSAS 2 y las otras variables estudiadas. Resultados. La estructura de tres factores (trato diferente-juicio, culpa y vergüenza) se ajustó adecuadamente a los datos (raíz del error cuadrático medio (RMSEA)=0,081, índice de ajuste comparativo (CIF)=0,959, índice de Tucker-Lewis (TLI)=0,95) y su confiabilidad fue buena (α=0,76). Se observaron correlaciones significativas del puntaje del DSAS 2 en español con la autoeficacia (rs=-0,37; p

Abstract Expression quantitative trait loci (eQTLs) are associations between genetic variants, such as Single Nucleotide Polymorphisms (SNPs), and gene expression. eQTLs are an important tool to understand the genetic variance of gene expression of complex phenotypes. eQTLs analyses are common in biomedical models but are scarce in woody crop species such as fruit trees or grapes. In this study, a comprehensive bioinformatic analysis was conducted leveraging with expression data from two different growth stages, around ripening onset, of 10 genotypes of grape (Vitis vinifera L.). A total of 2170 cis-eQTL were identified in 212 gene modulated at ripening onset. The 48% of these DEGs have a known function. Among the annotated protein-coding genes, terpene synthase, auxin-regulatory factors, GRFS, ANK_REP_REGION domain-containing protein, Kinesin motor domain-containing protein and flavonol synthase were noted. This new inventory of cis-eQTLs influencing gene expression during fruit ripening will be an important resource to examine variation for this trait and will help to elucidate the complex genetic architecture underlying this process in grape.

Resumen: A 50 años de experiencia, el trasplante cardíaco continúa siendo el tratamiento de elección en pacientes con insuficiencia cardíaca terminal. La creciente necesidad de trasplantes de corazón está incrementando las listas de espera. Lamentablemente, debido a la escasez de donantes, la demanda por órganos es mucho mayor que el número de trasplantes. En el presente manuscrito se revisa el estado actual del trasplante cardíaco, haciendo énfasis en la experiencia en el Reino Unido. Se comentan los criterios para la selección de receptores y la de donantes de órganos, examinando la donación en muerte encefálica (donation after brain death, DBD por sus siglas en inglés) y la donación por paro circulatorio (donation after circulatory death, DCD por sus siglas en inglés) y en como esta última ha contribuido a aumentar la oferta de órganos para trasplante. Se discuten las terapias alternativas al trasplante cardíaco en pacientes que exhiben deterioro mientras se encuentran en la lista de espera y que cumplen con las indicaciones actuales para el implante de un dispositivo de asistenca circulatoria (left ventricular assist device, LVAD por sus siglas en inglés). Los avances de supervivencia en el corto y mediano plazo se discuten, asi como tambien el manejo perioperatorio y el de mediano y largo plazo. Abstract: After just over 50 years of experience, heart transplantation continues tobethetreatmentofchoiceinpatients with end stage heart failure. The need for heart transplants is increasing the waiting lists. Regrettably, due to donor shortage and lack of suitable donors, the demand for donor organs is much higher than the rate at which patients are transplanted. In the following paper we review the current status of heart transplantation with some emphasis regarding the status of transplantation in the United Kingdom. We review selection criteria for recipients and organ donation looking into donation after brain death (DBD) and donation after circulatory death (DCD) and how the latter has contributed to the increase of available donor hearts. Alternatives to heart transplantation are discussed for patients who deteriorate while on the waiting list and that have an indication for implantation of a left ventricular assist device (LVAD). Improvements in short and medium term survival are discussed as well as perioperative, intermediate and long term management.

Abstract Objective Environmental enrichment is used to treat social, communication, and behavioral deficits and is known to modify the expression of synaptic receptors. We compared the effects of environmental enrichment in the expression of glutamate and endocannabinoid receptors, which are widely expressed in the cerebellar cortex. These two receptors interact to regulate neuronal function and their dysregulation is associated with behavioral changes. We used BTBR + Itpr3tf/J mice, a strain that models behavioral disorders, and C57BL/6 mice for comparison. We studied the effects of genetic background, sex, environmental conditions, and layer of the cerebellar cortex on the expression of each receptor. Results The influence of genetic background and environmental enrichment had the same pattern on glutamate and endocannabinoid receptors in males. In contrast, in females, the effect of environmental enrichment and genetic background were different than the ones obtained for males and were also different between the glutamate and endocannabinoid receptors. Furthermore, an analysis of both receptors from tissue obtained from the same animals show that their expression is correlated in males, but not in females. Our results suggest that environmental enrichment has a receptor dependent and sexual dimorphic effect on the molecular expression of different receptors in the cerebellar cortex.

Abstract Massive molecular testing for COVID-19 has been pointed out as fundamental to moderate the spread of the pandemic. Pooling methods can enhance testing efficiency, but they are viable only at low incidences of the disease. We propose Smart Pooling, a machine learning method that uses clinical and sociodemographic data from patients to increase the efficiency of informed Dorfman testing for COVID-19 by arranging samples into all-negative pools. To do this, we ran an automated method to train numerous machine learning models on a retrospective dataset from more than 8000 patients tested for SARS-CoV-2 from April to July 2020 in Bogotá, Colombia. We estimated the efficiency gains of using the predictor to support Dorfman testing by simulating the outcome of tests. We also computed the attainable efficiency gains of non-adaptive pooling schemes mathematically. Moreover, we measured the false-negative error rates in detecting the ORF1ab and N genes of the virus in RT-qPCR dilutions. Finally, we presented the efficiency gains of using our proposed pooling scheme on proof-of-concept pooled tests. We believe Smart Pooling will be efficient for optimizing massive testing of SARS-CoV-2.

Abstract The health effects of e-cigarettes remain relatively unknown, including their impact on sleep quality. We previously showed in a pilot study that females who smoke both conventional tobacco and vape e-cigarettes (dual users) had decreased sleep quality (measurement of how well an individual is sleeping) and increased sleep latency (amount of time to fall asleep), suggesting an influence by gender. Cough is also known to adversely impact sleep quality and may be caused by inhalant use. As a result, we undertook this study to assess the impact of e-cigarette, conventional tobacco, and dual use on sleep quality, sleep latency, cough, and drug use. Participants (n = 1198) were recruited through online surveys posted to social media sites with a monetary incentive. Participants were grouped by inhalant use, with 8% e-cigarette users, 12% conventional tobacco users, 30% dual users, and 51% non-smokers/non-vapers. Dual use of e-cigarettes and conventional tobacco was associated with increased sleep latency relative to non-smokers/non-vapers by multivariable linear regression (mean difference of 4.08; 95% CI: 1.12 to 7.05, raw p = 0.007, adjusted p = 0.042); however, dual usage was not significantly associated with sleep quality relative to non-smokers/non-vapers (mean difference 0.22, 95%CI: (−0.36, 0.80), raw p = 0.452, adjust p = 0.542). Dual use was also associated with a higher reporting of cough (p = 0.038), as well as increased marijuana (p

Abstract Genetic diversity and relatedness of accessions for coconut growing in Colombia was unknown until this study. Here we develop single nucleotide polymorphisms (SNPs) along the coconut genome based on Genotyping by Sequencing (GBS) with the goal of analyze the genetic diversity, population structure, and linkage disequilibrium (LD) of a diverse coconut panel consisting of 112 coconut accessions from the Atlantic and Pacific coasts of Colombia. A comprehensive catalog of approximately 40,000 SNPs with a minor allele frequency (MAF) of > 0.05 is presented. A total of 40,614 SNPs were found but only 19,414 anchored to chromosomes. Of these, 10,338 and 4606 were exclusive to the Atlantic and Pacific gene pools, respectively, and 3432 SNPs could differentiate both gene pools. A filtered subset of unlinked and anchored SNPs (1271) showed a population structure at K = 4, separating accessions from the Pacific and Atlantic coasts that can also be distinguished by palm height, as found in previous studies. The Pacific groups had a slow LD decay, low Fixation Index (Fst) and low nucleotide diversity (π), while the Atlantic group had slightly higher genetic diversity and faster LD decay. Genome-wide diversity analyses are of importance to promote germplasm conservation and breeding programs aimed at developing new cultivars better adapted to the region.

Data show that antibody-related immunity against SARS-CoV-2 may not be long-lasting. We report two cases regarded as cured from COVID-19, which presented again with symptoms and a positive SARS-CoV-2 RT-PCR test. Case one, a 60-year-old male, had a biphasic presentation of symptoms compatible with COVID-19 infection, associated with a positive RT-PCR test. Case two, a 25-year-old female, had a first positive RT-PCR test during hospital screening, and months later a symptomatic presentation of COVID-19, associated with a positive RT-PCR test. All cases were immunocompetent. Anti-IgG-SARS-CoV-2 blood samples were negative in both. Elevation of analytical inflammatory markers suggested new infection in both cases. COVID-19 reinfection may be a differential diagnosis and primary care physicians should acknowledge it. Previously cured patients should be encouraged to comply with health public preventive measures.

BackgroundPhysician burnout has a negative impact on both physicians and patients. Limited information is available on professional burnout of neurologists. The aim of this study was to assess the presence of burnout among neurologists caring for patients with cognitive disorders and to identify associated factors.MethodsAn online, cross-sectional study was conducted in collaboration with the Spanish Society of Neurology. Neurologists involved in the care of patients with cognitive disorders answered a survey composed of demographic characteristics, professional background, clinical practice setting, and behavioral factors. Burnout was assessed using a single-item measure from the Physician Work Life Study. A multivariate logistic regression analysis was conducted to determine the association between neurologists' characteristics and burnout.ResultsA total of 188 neurologists answered the survey. The mean age (standard deviation-SD) was 40.6 (11.3) years and 52.7% were male. The majority of participants were general neurologists (60.6%) who attending a median of 20 patients with cognitive disorders (interquartile range 10.0-30.0) weekly. Thirty-nine participants (20.7%) reported burnout. Participants with burnout had greater experiences of regret associated with past clinical decisions than their counterparts (mean Regret Intensity Scale scores of 2.3 and 1.9, respectively; p = 0.003). Burnout was associated with non-academic practice (OR = 3.02 [95% CI 1.18, 7.73], p = 0.021) and care-related regret (OR = 2.53 [95% CI 1.13, 5.64], p = 0.023) in the multivariate analysis after adjustment for confounders.ConclusionsProfessional burnout was a common phenomenon among neurologists managing cognitive disorders. Identifying physician burnout and its associated factors may be critical for implementing preventive intervention strategies.

The relationship between Earlier Stone Age (ESA) hominins and the southern African coastal environment has been poorly investigated, despite the high concentration of open-air sites in marine and fluvial terraces of the coastal plain from c. 1Ma onward during the Mid-Pleistocene Transition. Southern Africa provides some of the earliest evidence of coastal subsistence strategies since the end of the Middle Pleistocene, during the Middle Stone Age (MSA). These coastal MSA sites showcase the role of coastal environments in the emergence and development of modern human behaviors. Given the high prevalence of coastal ESA sites throughout the region, we seek to question the relationship between hominins and coastal landscapes much earlier in time. In this regard, the +100 m raised beaches of the Benguela Province, Angola, are key areas as they are well-preserved and contain a dense record of prehistoric occupation from the beginning of the Middle Pleistocene, including sites like Dungo, Mormolo, Sombreiro, Macaca and Punta das Vacas. Accordingly, this paper provides a critical review of the coastal ESA record of southern Africa and a detailed presentation of the Dungo IV site, through a qualitative technological analysis coupled with a quantitative inter-site comparison with contemporary southern African coastal plain sites. Through our detailed technological analyses, we highlight the influence of coastal lithological resources on the technical behaviors of hominin groups, and we propose the existence of a "regional adaptive strategy" in a coastal landscape more than 600 000 years ago. Finally, we argue for the integration of coastal landscapes into hominins' territories, suggesting that adaptation to coastal environments is actually a slower process which begins with "territorialization" well before the emergence and development of Homo sapiens.

Abstract Achieving justice could be considered a complex social decision-making scenario. Despite the relevance of social decisions for legal contexts, these processes have still not been explored for individuals who work as criminal judges dispensing justice. To bridge the gap, we used a complex social decision-making task (Ultimatum game) and tracked a heart rate variability measurement: the square root of the mean squared differences of successive NN intervals (RMSSD) at their baseline (as an implicit measurement that tracks emotion regulation behavior) for criminal judges (n = 24) and a control group (n = 27). Our results revealed that, compared to controls, judges were slower and rejected a bigger proportion of unfair offers. Moreover, the rate of rejections and the reaction times were predicted by higher RMSSD scores for the judges. This study provides evidence about the impact of legal background and expertise in complex social decision-making. Our results contribute to understanding how expertise can shape criminal judges’ social behaviors and pave the way for promising new research into the cognitive and physiological factors associated with social decision-making.

To the Editor, Transcatheter aortic valve implantation (TAVI) is a therapeutic alternative that has proven safe and effective across different clinical settings. Over the last few years, more and more cases of «emergency TAVI» have been reported.1-2 Currently, this term is often used for those implantation procedures performed during admission due to decompensated heart failure although this concept includes very different situations. The therapeutic option to treat cardiogenic shock should be «emergency TAVI», that is, implantation performed within the first 72 hours after admission.3 This is the case of a patient with severe aortic stenosis who was transferred to our center with signs of cardiogenic shock. This is the case of a 67-year-old man. The patient was a former smoker and a regular drinker. Initially, he had been admitted to a different center with early signs of heart failure. Arterial pressure at admission was 120/90 mmHg with global congestion and need for low-flow oxygen therapy. Diuretic treatment was started, and the echocardiogram revealed the presence of severe aortic stenosis with left systolic dysfunction. The patient had signs of liver (alanine aminotransferase, aspartate aminotransferase, and bilirubin levels of 1244 u/L, 1808 u/L, and 2 mg/dL, respectively, and normalized international ratio of 2), and...

Chronic inflammatory airway diseases, including asthma, chronic rhinosinusitis, eosinophilic COPD and allergic rhinitis are a global health concern. Despite the coexistence of these diseases and their common pathophysiology, they are often managed independently, resulting in poor asthma control, continued symptoms and poor quality of life. Understanding disease pathophysiology is important for best treatment practice, reduced disease burden and improved patient outcomes. The pathophysiology of type 2 inflammation is driven by both the innate immune system triggered by pollutants, viral or fungal infections involving type 2 innate lymphoid cells (ILC2) and the adaptive immune system, triggered by contact with an allergen involving type 2 T-helper (Th2) cells. Both ILC2 and Th2 cells produce the type-2 cytokines (interleukin (IL)-4, IL-5 and IL-13), each with several roles in the inflammation cascade. IL-4 and IL-13 cause B-cell class switching and IgE production, release of pro-inflammatory mediators, barrier disruption and tissue remodelling. In addition, IL-13 causes goblet-cell hyperplasia and mucus production. All three interleukins are involved in trafficking eosinophils to tissues, producing clinical symptoms characteristic of chronic inflammatory airway diseases. Asthma is a heterogenous disease; therefore, identification of biomarkers and early targeted treatment is critical for patients inadequately managed by inhaled corticosteroids and long-acting β-agonists alone. The Global Initiative for Asthma guidelines recommend add-on biological (anti IgE, IL-5/5R, IL-4R) treatments for those not responding to standard of care. Targeted therapies, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab, were developed on current understanding of the pathophysiology of type 2 inflammation. These therapies offer hope for improved management of type 2 inflammatory airway diseases.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the “Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs”. To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just “pandemic vaccines”. Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

CASE RESOLUTION We decided to end the procedure because the patient became asymptomatic and the ST-segment elevation resolved. After the procedure, the blood test performed revealed a new increase of troponin I levels (4.4 ng/mL). The patient started therapy with dihydropyridine calcium channel blockers due to the observed vasospasm. While in observation, the patient remained asymptomatic. Five days later, she was discharged on dual antiplatelet therapy. One month later, the patient was readmitted to undergo an elective coronary angiography to reassess the lesion. The coronary angiography only revealed the presence of irregularities without further lesions (videos 1 and 2 of the supplementary data). Therefore, the most probable diagnosis was a spontaneous coronary artery dissection (SCAD). The management of SCAD is still a matter of great discussion especially regarding left main coronary artery lesions and situations of hemodynamic instability as it is well-known that SCADs can heal spontaneously after 1 month.1-3 In this case, we decided not to proceed with the percutaneous coronary intervention because the patient became asymptomatic and the electrocardiographic alterations resolved after the administration of intracoronary nitrates and because we were not sure about the etiology of the severe vasospasm (SCAD vs atherosclerotic lesion). The reassessment coronary angiography performed...

Los tumores del estroma gastrointestinal (GIST) son las neoplasias mesenquimales más frecuentes del tracto digestivo. Los criterios de estadificación del riesgo, como angioinvasion, tamaño, infiltración y el índice mitótico, permiten realizar un adecuado diagnóstico y tratamiento. Se presenta un paciente masculino de 67 años de edad, quien consultó por he-matemesis y melenas. Endoscópicamente se observó una masa en el estómago de 20x10x6 cm de diámetro de la cual se tomó biopsia para estudio. Al examen histopatológico se diagnósticó un GIST con invasión microscópica de la lámina propia y angioinvasión, estos dos componentes histopatológicos son escasamente tomados en cuenta para clasificar GIST; sin embargo, son muy importantes en este contexto, pues cambian el pronóstico de la enfermedad y con requerimiento de terapia adyuvante con imatinib. El desenlace del paciente fue favorable, debido a la conducta terapéutica establecida. El comportamiento biológico del GIST varía dependiendo de las características clínicas e histopatológicas. Este caso resalta los criterios de alto riesgo del GIST y la necesidad de modificar el tratamiento cuando están presentes.

La diabetes es una epidemia a nivel mundial. Los factores psicosociales han sido reconocidos como un elemento importante en el manejo y control de la enfermedad. El estigma asociado a la diabetes ha emergido recientemente como un nuevo factor psicosocial que afecta negativamente la salud de los pacientes con diabetes. Sin embargo, la evidencia reciente en torno a este fenómeno aún no ha sido sintetizada. Esta revisión narrativa de literatura aborda: (i) elementos conceptuales y epidemiológicos que contribuyen a la comprensión del fenómeno y su magnitud; (ii) los factores psicosociales, conductuales y fisiológicos involucrados en la relación entre el estigma asociado a la diabetes y los resultados en salud en pacientes con la enfermedad; (iii) desafíos y posibles áreas de investigación.

The prevalence of allergic diseases has been on the rise during the past decades. Epidemiological studies have shown that extensive exposure to bio-aerosols causes adverse health effects such as respiratory disorders, allergic reactions and infections. Aeroallergens are allergic airborne particles that disperse from environmental sources over great distances by air currents and ultimately are inhaled by, ingested by, or come into contact with individuals who have had no previous contact with the allergenic agent. The most important bioaerosols in Iran are pollen grains, molds, house dust mites, and animal dander causing lots of allergic reactions in the country every year. Geographical variation is an important role in the prevalence of allergic diseases, most likely due to different environmental factors. Therefore, identifying geographical and seasonal distribution of allergens not only enables us to warn patients to avoid them but also contributes significantly in the diagnosis, prevention and management of the progress of allergic disorders and provides the possibility of performing immunotherapy. The results of this survey about the most common aeroallergens in different geographic areas of Iran may provide proper prevention activities and therefore reduce treatment costs for allergic patients.