Whole-Genome Sequencing Reveals a Novel Pathogenic GRIN2B Variant in a Patient with Neurodevelopmental Disorder and an inv(6)(p24p11.2)pat.

INTRODUCTION: Neurodevelopmental disorders (NDDs) are diverse and can be explained by either genomic aberrations or single nucleotide variants. Most likely due to methodological approaches and/or disadvantages, the concurrence of both genetic events in a single patient has hardly been reported and even more rarely the pathogenic variant has been regarded as the cause of the phenotype when a chromosomal alteration is initially identified. CASE PRESENTATION: Here, we describe a NDD patient with a 6p nonpathogenic paracentric inversion paternally transmitted and a de novo pathogenic variant in the GRIN2B gene. Molecular-cytogenetic studies characterized the familial 6p inversion and revealed a paternal 9q inversion not transmitted to the patient. Subsequent whole-genome sequencing in the patient-father dyad corroborated the previous findings, discarded inversions-related cryptic genomic rearrangements as causative of the patient's phenotype, and unveiled a novel heterozygous GRIN2B variant (p.(Ser570Pro)) only in the proband. In addition, Sanger sequencing ruled out such a variant in her mother and thereby confirmed its de novo origin. Due to predicted disturbances in the local secondary structure, this variant may alter the ion channel function of the M1 transmembrane domain. Other pathogenic variants in GRIN2B have been related to the autosomal dominant neurodevelopmental disorder MRD6 (intellectual developmental disorder, autosomal dominant 6, with or without seizures), which presents with a high variability ranging from mild intellectual disability (ID) without seizures to a more severe encephalopathy. In comparison, our patient's clinical manifestations include, among others, mild ID and brain anomalies previously documented in subjects with MRD6. CONCLUSION: Occasionally, gross chromosomal abnormalities can be coincidental findings rather than a prime cause of a clinical phenotype (even though they appear to be the causal agent). In brief, this case underscores the importance of comprehensive genomic analysis in unraveling the wide-ranging genetic causes of NDDs and may bring new insights into the MRD6 variability.

Targeted Glutamate Supply Boosts Insulin Concentrations, Ovarian Activity, and Ovulation Rate in Yearling Goats during the Anestrous Season.

The neuroendocrine regulation of the seasonal reproductive axis requires the integration of internal and external signals to ensure synchronized physiological and behavioral responses. Seasonal reproductive changes contribute to intermittent production, which poses challenges for optimizing goat product yields. Consequently, a significant objective in seasonal reproduction research is to attain continuous reproduction and enhance profitability in goat farming. Glutamate plays a crucial role as a modulator in several reproductive and metabolic processes. Hence, the aim of this study was to evaluate the potential impact of exogenous glutamate administration on serum insulin concentration and ovarian function during the out-of-season period in yearling goats. During the anestrous season, animals were randomly located in individual pens to form two experimental groups: (1) glutamate (n = 10, live weight (LW) = 29.1 ± 1.02 kg, body condition score (BCS) = 3.4 ± 0.2 units) and (2) control (n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2), with no differences (p < 0.05) regarding LW and BCS. Then, goats were estrus-synchronized, and blood sampling was carried out for insulin quantification. Ovaries were ultrasonographically scanned to assess ovulation rate (OR), number of antral follicles (AFs), and total ovarian activity (TOA = OR + AF). The research outcomes support our working hypothesis. Certainly, our study confirms that those yearling goats treated with exogenous glutamate displayed the largest (p < 0.05) insulin concentrations across time as well as an augmented (p < 0.05) out-of-season ovarian activity.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panamena de Hematología, Sociedad Peruana de Hematología, and SVH 2023 guidelines for diagnosis of venous thromboembolism and for its management in special populations in Latin America.

Implementation of international guidelines in Latin American settings requires additional considerations (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The purpose of this guideline is to provide evidence-based recommendations about the diagnosis of venous thromboembolism (VTE) and its management in children and during pregnancy. We used the GRADE ADOLOPMENT method to adapt recommendations from 3 American Society of Hematology (ASH) VTE guidelines (diagnosis of VTE, VTE in pregnancy, and VTE in the pediatric population). ASH and 12 local hematology societies formed a guideline panel comprising medical professionals from 10 countries in Latin America. Panelists prioritized 10 questions about the diagnosis of VTE and 18 questions about its management in special populations that were relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context. In comparison with the original guideline, there were significant changes in 2 of 10 diagnostic recommendations (changes in the diagnostic algorithms) and in 9 of 18 management recommendations (4 changed direction and 5 changed strength). This guideline ADOLOPMENT project highlighted the importance of contextualizing recommendations in other settings based on differences in values, resources, feasibility, and health equity impact.

O-Linked Glycans of Candida albicans Interact with Specific GPCRs in the Coronary Endothelium and Inhibit the Cardiac Response to Agonists.

Candida albicans is an opportunistic fungal pathogen that may cause invasive infections in immunocompromised patients, disseminating through the bloodstream to other organs. In the heart, the initial step prior to invasion is the adhesion of the fungus to endothelial cells. Being the fungal cell wall's outermost structure and the first to come in contact with host cells, it greatly modulates the interplay that later will derive in the colonization of the host tissue. In this work, we studied the functional contribution of N-linked and O-linked mannans of the cell wall of C. albicans to the interaction with the coronary endothelium. An isolated rat heart model was used to assess cardiac parameters related to vascular and inotropic effects in response to phenylephrine (Phe), acetylcholine (aCh) and angiotensin II (Ang II) when treatments consisting of: (1) live and heat-killed (HK) C. albicans wild-type yeasts; (2) live C. albicans pmr1Δ yeasts (displaying shorter N-linked and O-linked mannans); (3) live C. albicans without N-linked and O-linked mannans; and (4) isolated N-linked and O-linked mannans were administered to the heart. Our results showed that C. albicans WT alters heart coronary perfusion pressure (vascular effect) and left ventricular pressure (inotropic effect) parameters in response to Phe and Ang II but not aCh, and these effects can be reversed by mannose. Similar results were observed when isolated cell walls, live C. albicans without N-linked mannans or isolated O-linked mannans were perfused into the heart. In contrast, C. albicans HK, C. albicans pmr1Δ, C. albicans without O-linked mannans or isolated N-linked mannans were not able to alter the CPP and LVP in response to the same agonists. Taken together, our data suggest that C. albicans interaction occurs with specific receptors on coronary endothelium and that O-linked mannan contributes to a greater extent to this interaction. Further studies are necessary to elucidate why specific receptors preferentially interact with this fungal cell wall structure.

Goats as Valuable Animal Model to Test the Targeted Glutamate Supplementation upon Antral Follicle Number, Ovulation Rate, and LH-Pulsatility.

The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) Glutamate supplemented (GLUT; n = 10, Live Weight (LW) = 29.6 ± 1.02 kg, Body Condition (BCS) = 3.4 ± 0.2 units; i.v. supplemented with 7 mg GLUT kg−1 LW) or (2) Non-supplemented (CONT; n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2 units; i.v. saline). The oats were estrus-synchronized; blood sampling (6 h × 15 min) was carried out for LH quantification. Response variables included pulsatility (PULSE), time to first pulse (TTFP), amplitude (AMPL), nadir (NAD), and area under the curve (AUC) of LH. Ovaries were ultra-sonographically scanned to assess ovulation rate (OR), number of antral follicles (AF), and total ovarian activity (TOA = OR + AF). LH-PULSE was quantified with the Munro algorithm; significant treatment x time interactions were evaluated across time. The variables LW and BCS did not differ (p > 0.05) between the experimental groups. Nevertheless, OR (1.77 vs. 0.87 ± 0.20 units), TOA (4.11 vs. 1.87 ± 0.47 units) and LH-PULSE (5.0 vs. 2.2 pulses 6 h-1) favored (p < 0.05) to the GLUT group. Our results reveal that targeted glutamate supplementation, the main central nervous system neurotransmitter, arose as an interesting strategy to enhance the hypothalamic−hypophyseal−ovarian response considering the anestrous-yearling goat as an animal model, with thought-provoking while promising translational applications.

Frontal aslant tract: Anatomy and tractography description in the Mexican population.

Background: The aim of the study was to describe the origin, course, and termination of frontal aslant tract (FAT) in the Mexican population of neurosurgical referral centers. Methods: From January 2018 to May 2019, we analyzed 50 magnetic resonance imaging (MRI) studies in diffusion tensor imaging sequences of patients of the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez." Five brains were fixed by the Klingler method and dissected in the neurosurgery laboratory of the Hospital Civil de Guadalajara to identify the origin, trajectory, and ending of the FAT. Results: FAT was identified in 100% of the MRI and brain dissections. The origin of the FAT was observed in 63% from the supplementary premotor area, 24% from the supplementary motor area, and 13% in both areas. Its ending was observed in the pars opercularis in 81%, pars triangularis in 9%, and in both pars opercularis and ventral premotor area in 10% in the magnetic resonance images, with a left side predominance. In the hemispheres dissections, the origin of FAT was identified in 60% from the supplementary premotor area, 20% from the supplementary motor area, and 20% in both areas. Its ending was observed in the pars opercularis in 80% and the pars triangularis in 20%. It was not identified as an individual fascicle connected with the contralateral FAT. Conclusion: In the Mexican population, FAT has a left predominance; it is originated more frequently in the supplementary premotor area, passes dorsal to the superior longitudinal fascicle II and the superior periinsular sulcus, and ends more commonly in the pars opercularis.

A Novel Automatic Quantification Protocol for Biomarkers of Tauopathies in the Hippocampus and Entorhinal Cortex of Post-Mortem Samples Using an Extended Semi-Siamese U-Net.

Efforts have been made to diagnose and predict the course of different neurodegenerative diseases through various imaging techniques. Particularly tauopathies, where the tau polypeptide is a key participant in molecular pathogenesis, have significantly increased their morbidity and mortality in the human population over the years. However, the standard approach to exploring the phenomenon of neurodegeneration in tauopathies has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of the tau protein, which forms neurofibrillary tangles that replace neuronal populations in the hippocampal and cortical regions. The main objective of this work is to implement a novel quantification protocol for different biomarkers based on pathological post-translational modifications undergone by tau in the brains of patients with tauopathies. The quantification protocol consists of an adaptation of the U-Net neural network architecture. We used the resulting segmentation masks for the quantification of combined fluorescent signals of the different molecular changes tau underwent in neurofibrillary tangles. The quantification considers the neurofibrillary tangles as an individual study structure separated from the rest of the quadrant present in the images. This allows us to detect unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understanding the pathogenesis of dementias with another computational analysis approach in subsequent studies.

Taquicardia sinusal post-COVID-19: patogenia, identificación y estratificación temprana / Post-COVID-19 sinus tachycardia: pathogenesis, identification and early stratification

Resumen La COVID-19 ha sido responsable de una alta morbimortalidad, la cual se caracteriza principalmente por síntomas respiratorios. Su ingreso a la célula está favorecido por la enzima convertidora de angiotensina tipo 2, presente en diversas células del organismo con efectos sistémicos. Los principales síntomas en el sistema cardiovascular son arritmias, insuficiencia cardiaca, choque cardiogénico, síndrome coronario agudo, bradicardia y taquicardia sinusal. Esta enfermedad tiene un pronóstico dependiente de factores genéticos y demográficos, con una evolución a la recuperación, la muerte o secuelas; a esto último diversos autores lo han descrito como «síndrome post-COVID-19¼. El compromiso cardiovascular se ve reflejado por la alta incidencia de taquicardia, detectada en el seguimiento de pacientes recuperados de la COVID-19 que refieren palpitaciones, y al explorar los signos vitales se comprueba el aumento en la frecuencia cardiaca. Sin embargo, su patogenia es desconocida, motivo por el que se realizó una revisión sistemática con el propósito de proponer hipótesis sobre los mecanismos fisiopatológicos para explicarla, algoritmos para la detección temprana y un tratamiento estratificado, para así contribuir en futuras investigaciones sobre esta asociación de taquicardia como daño cardiovascular posterior a la COVID-19, debido a la escasa evidencia científica sobre el tema.

Abstract COVID-19 has been responsible for a high morbi-mortality which is characterized by respiratory symptoms; its entrance to the cell is favored by angiotensin-converting enzyme 2, which is found in a variety of cells with systemic effects. The main symptoms in the cardiovascular system are: arrhythmia, heart failure, cardiogenic shock, acute coronary syndrome, bradycardia and sinus tachycardia. This disease has a prognosis that depends on genetic and demographic factors, with a progress whether to recovery, death or aftermath, then latter being described as "post-COVID-19 syndrome". Cardiovascular compromise is reflected by the high incidence in tachycardia detected in tracing of the recovered patients of COVID-19 that refer palpitations and that during exploration of vital signs can be ascertained by an increase in heart frequency. Nevertheless its pathogenic features are still unknown, for this reason a systematic review was made with the purpose of proposing hypotheses about the physiopathological mechanisms to explain it, algorithms for early detection and a stratified treatment, so it would contribute to future investigations about the association of tachycardia as cardiovascular damage after COVID-19, due to the lack of scientific evidence in this topic.

Consensus in acute myeloid leukemia in Mexico.

Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

La leucemia mieloide aguda (LMA) comprende un grupo heterogéneo de neoplasias de células hematopoyéticas de linaje mieloide que surgen de la expansión clonal de sus precursores en la médula ósea, interfiriendo con la diferenciación celular, lo que conlleva a un síndrome de falla medular. La LMA es una consecuencia de cambios genéticos y epigenéticos (mutaciones puntuales, rearreglos de genes, deleciones, amplificaciones y arreglos en cambios epigenéticos que influyen en la expression del gen) en las células hematopoyéticas precursoras, la cual crea una clona de células anormales que son capaces de proliferar, pero no se pueden diferenciar en células hematopoyéticas maduras ni sufrir una muerte celular programada. El diagnostic requiere más del 20% de blastos mieloides en médula ósea y ciertas anormalidades citogénicas. El tratamiento dependerá de la edad, comorbilidades, riesgo citogenético entre las más frecuentes.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, Sociedad Peruana de Hematología, and SVH 2022 guidelines for prevention of venous thromboembolism in surgical and medical patients and long-distance travelers in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementation of international guidelines in Latin American settings requires additional considerations. OBJECTIVE: To provide evidence-based guidelines about VTE prevention for Latin American patients, clinicians, and decision makers. METHODS: We used the GRADE ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Prevention of VTE in Surgical Patients and Prophylaxis for Medical Patients). ASH and 12 local hematology societies formed a guideline panel composed of medical professionals from 10 countries in Latin America. Panelists prioritized 20 questions relevant to the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context, that is, values and preferences, resources, accessibility, feasibility, and impact on health equity. RESULTS: The panel agreed on 21 recommendations. In comparison with the original guideline, 6 recommendations changed direction and 4 recommendations changed strength. CONCLUSIONS: This guideline ADOLOPMENT project highlighted the importance of contextualization of recommendations in other settings, based on differences in values, resources, feasibility, and health equity impact.

Remitting neuropsychiatric symptoms in COVID-19 patients: Viral cause or drug effect?

Numerous reports of neuropsychiatric symptoms highlighted the pathologic potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship the onset and/or exacerbation of mental disease. However, coronavirus disease 2019 (COVID-19) treatments, themselves, must be considered as potential catalysts for new-onset neuropsychiatric symptoms in COVID-19 patients. To date, immediate and long-term neuropsychiatric complications following SARS-CoV-2 infection are currently unknown. Here we report on five patients with SARS-CoV-2 infection with possible associated neuropsychiatric involvement, following them clinically until resolution of their symptoms. We will also discuss the contributory roles of chloroquine and dexamethasone in these neuropsychiatric presentations.

Awake prone positioning and oxygen therapy in patients with COVID-19: the APRONOX study.

BACKGROUND: The awake prone positioning strategy for patients with acute respiratory distress syndrome is a safe, simple and cost-effective technique used to improve hypoxaemia. We aimed to evaluate intubation and mortality risk in patients with coronavirus disease 2019 (COVID-19) who underwent awake prone positioning during hospitalisation. METHODS: In this retrospective, multicentre observational study conducted between 1 May 2020 and 12 June 2020 in 27 hospitals in Mexico and Ecuador, nonintubated patients with COVID-19 managed with awake prone or awake supine positioning were included to evaluate intubation and mortality risk through logistic regression models; multivariable and centre adjustment, propensity score analyses, and E-values were calculated to limit confounding. RESULTS: 827 nonintubated patients with COVID-19 in the awake prone (n=505) and awake supine (n=322) groups were included for analysis. Fewer patients in the awake prone group required endotracheal intubation (23.6% versus 40.4%) or died (19.8% versus 37.3%). Awake prone positioning was a protective factor for intubation even after multivariable adjustment (OR 0.35, 95% CI 0.24-0.52; p<0.0001, E=2.12), which prevailed after propensity score analysis (OR 0.41, 95% CI 0.27-0.62; p<0.0001, E=1.86) and mortality (adjusted OR 0.38, 95% CI 0.26-0.55; p<0.0001, E=2.03). The main variables associated with intubation among awake prone patients were increasing age, lower baseline peripheral arterial oxygen saturation/inspiratory oxygen fraction ratio (P aO2 /F IO2 ) and management with a nonrebreather mask. CONCLUSIONS: Awake prone positioning in hospitalised nonintubated patients with COVID-19 is associated with a lower risk of intubation and mortality.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

resumen está disponible en el texto completo

Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

Spontaneous splenic rupture, an unusual presentation of tuberculosis.

INTRODUCTION: Spontaneous splenic rupture from tuberculosis (TB) is a very unusual presentation within the wide range of presentations of this infectious disease. CLINICAL CASE: A 40-year-old male with a diagnosis of human immunodeficiency virus, begins with fever and pain in the left hypochondrium. A computed tomography scan was performed, showing probable splenic abscesses; suddenly, it begins with hemodynamic deterioration, exacerbation of pain, a surgical exploration was performed, showing spontaneous splenic rupture. Microscopic study of the spleen shows the presence of Mycobacterium tuberculosis. CONCLUSIONS: This is yet another presentation of TB, which can become a surgical emergency.

INTRODUCCIÓN: La ruptura esplénica espontánea por tuberculosis es una presentación muy inusual dentro de la amplia gama de presentaciones de esta enfermedad infectocontagiosa. CASO CLÍNICO: Masculino de 40 años con diagnóstico de VIH, inicia con fiebre y dolor en hipocondrio izquierdo. Se realiza TAC evidenciando probables abscesos esplénicos; súbitamente comienza con deterioro hemodinámico, agudización del dolor, se realiza exploración quirúrgica evidenciando ruptura esplénica espontánea. Al estudio microscópico del bazo se observa presencia de Mycobacterium Tuberculosis. CONCLUSIONES: Esta es una presentación más de la TB, la cual puede convertirse en una urgencia quirúrgica.

Methodology for adaptation of the ASH Guidelines for Management of Venous Thromboembolism for the Latin American context.

BACKGROUND: From 2017 to 2020, the American Society of Hematology (ASH) collaborated with 12 hematology societies in Latin America to adapt the ASH guidelines on venous thromboembolism (VTE). OBJECTIVE: To describe the methods used to adapt the ASH guidelines on venous thromboembolism. METHODS: Each society nominated 1 individual to serve on the guideline panel. The work of the panel was facilitated by the 2 methodologists. The methods team selected 4 of the original VTE guidelines for a first round. To select the most relevant questions, a 2-step prioritization process was conducted through an on-line survey and then through in-person discussion. During an in-person meeting in Rio de Janeiro, Brazil, from 23 April through 26 April 2018, the panel developed recommendations using the ADOLOPMENT approach. Evidence about health effects from the original guidelines was reused, but important data about resource use, accessibility, feasibility, and impact in health equity were added. RESULTS: In the guideline accompanying this paper, Latin American panelists selected 17 questions from an original pool of 49. Of the 17 questions addressed, substantial changes were introduced for 5 recommendations, and remarks were added or modified for 12 recommendations. CONCLUSIONS: By using the evidence from an international guideline, a significant amount of work and time were saved; by adding regional evidence, the final recommendations were tailored to the Latin American context. This experience offers an alternative to develop guidelines relevant to local contexts through a global collaboration.

ASH, ABHH, ACHO, Grupo CAHT, Grupo  CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, SPH, and SVH 2021 guidelines for management of venous thromboembolism in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelinn Aes in Latimerican settings requires additional considerations. OBJECTIVE: The purpose of our study was to provide evidence-based guidelines about managing VTE for Latin American patients, clinicians, and decision makers. METHODS: We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)-ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Treatment of VTE and Anticoagulation Therapy). ASH and local hematology societies formed a guideline panel comprised of medical professionals from 10 countries in Latin America. Panelists prioritized 18 questions relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). RESULTS: The panel agreed on 17 recommendations. Compared with the original guideline, 4 recommendations changed direction and 1 changed strength. CONCLUSIONS: This guideline adolopment project highlighted the importance of contextualization of recommendations suggested by the changes to the original recommendations. The panel also identified 2 implementation priorities for the region: expanding the availability of home treatment and increasing the availability of direct oral anticoagulants (DOACs). The guideline panel made a conditional recommendation in favor of home treatment for individuals with deep venous thrombosis and a conditional recommendation for either home or hospital treatment for individuals with pulmonary embolism. In addition, a conditional recommendation was made in favor of DOACs over vitamin K antagonists for several populations.

Human visceral leishmaniasis prevalence by different diagnostic methods in Latin America: a systematic review and meta-analysis.

Visceral leishmaniasis is a neglected zoonotic disease that affects animals and humans in different tropical and subtropical regions and even beyond, with variable prevalence among infected hosts. To date, there have been no systematic reviews on human visceral leishmaniasis prevalence in Latin America. We therefore performed a systematic literature review with meta-analysis, using six databases to assess prevalence of visceral leishmaniasis in human patients in Latin American countries. Observational studies were included but analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). In all, 10,435 articles were retrieved for the time frame (1950-2019). After initial screening, 120 articles were selected for full-text assessment, 97 being finally included for qualitative and quantitative analyses. Overall, VL pooled prevalence was estimated at 38.8% (95% CI 33.8-43.8%), derived from 97 studies, including 44,986 individuals. Many aspects of the transmission dynamics of Leishmania and the exact burden of this parasitosis on public health remain largely unknown. Although the elimination of zoonotic VL in the Americas appears an unrealistic goal, additional efforts need to be put in place to achieve better diagnosis, treatment, and prevention of VL.

Synthesis of Polysubstituted Isoindolinones via Radical Cyclization of 1,3-Dicarbonyl Ugi-4CR Adducts Using Tetrabutylammonium Persulfate and TEMPO.

The development of an efficient method for the synthesis of polysubstituted isoindolinones from 1,3-dicarbonyl Ugi-4CR adducts, employing an aromatic radical cyclization process promoted by tetrabutylammonium persulfate and 2,2,6,6-tetramethyl-1-piperidine 1-oxyl (TEMPO), is described. The protocol allowed the construction of a library of isoindolinones bearing a congested carbon in good to excellent yields under mild conditions and in short reaction times.