Caracterización epidemiológica y hallazgos en homicidios por sofocación con bolsas de plástico en la ciudad de Medellín, Colombia 2008-2021 / Epidemiological characterization and findings in homicides due to suffocation with plastic bags in the city of Medellín, Colombia 2008-2021

Introducción el presente estudio describe las características de las víctimas de muertes por sofocación homicida con bolsas de plástico en el período comprendido entre 2008 y 2021, en necropsias practicadas en el Instituto Nacional de Medicina Legal y Ciencias Forenses de la ciudad de Medellín. Materiales y métodos se realizó un estudio descriptivo, retrospectivo, cuya información se obtuvo a partir de los informes de necropsia realizados por médicos forenses de la institución. Resultados de las 38.772 necropsias realizadas, 17.703 fueron homicidios de las cuales 96 (0,54%) fueron debidas a la utilización de bolsas de plástico para producir la muerte. De los 96 casos analizados el 92,7% (89) correspondieron a hombres y el 7,3% (7) a mujeres. La población masculina joven de los 15 a 27 años fue la más afectada; el 74,4% (71) ingresaron como cadáveres no identificados y en el 17,1% (14) fue considerado el diagnóstico de tortura dentro del análisis de la necropsia médico legal. Los hallazgos de sofocación en el examen externo fueron congestión facial 67,1% (55), petequias en las conjuntivas 63,4% (52), petequias en la cara 28,0% (23), lesiones en la mucosa oral interna 61,0% (50) y excoriaciones en las comisuras labiales 25,6% (21) por el uso de elementos extraños en la cavidad oral o la aplicación de maniobras asfícticas. El 58,5% (56) presentaban signos de trauma en otros sitios del cuerpo que no explicaban en sí la causa de la muerte. El 36,4% (35) presentaban bolsas de plástico cubriendo la cabeza y ajustadas al cuello con algún elemento, el 32,3% (31) cinta trasparente adherida a la bolsa plástica que cubría la cabeza y el 31,3% (30) presentaban una película plástica de nombre comercial Vinipel MR. El 76,8% (73) tenían las manos y los pies atados al momento del hallazgo del cuerpo en la escena. Conclusión ... (AU)

Introduction This study describes the characteristics of the victims of deaths by homicidal suffocation with plastic bags in the period between 2008 and 2021, in autopsies performed at the National Institute of Legal Medicine and Forensic Sciences of the city of Medellín. Materials and methods A descriptive, retrospective study was carried out, whose information was obtained from the autopsy reports made by forensic doctors of the institution. Results Of the 38,772 autopsies performed, 17,703 were homicides, of which 96 (0.54%) were due to the use of plastic bags to produce death. Of the 96 cases analyzed, 92.7% (89) corresponded to men and 7.3% (7) to women. The young male population between the ages of 15 and 27 was the most affected; 74.4% (71) entered as unidentified corpses and in 17.1% (14) the diagnosis of torture was considered within the analysis of the legal medical necropsy. The findings of suffocation in the external examination were facial congestion 67.1% (55), petechiae in the conjunctivae 63.4% (52), petechiae on the face 28.0% (23), lesions in the internal oral mucosa 61.0% (50), and abrasions in the labial commissures 25.6% (21) due to the use of foreign elements in the oral cavity or application of asphyctic maneuvers. 58.5% (56) presented signs of trauma in other parts of the body that did not explain the cause of death. 36.4% (35) had plastic bags covering the head and adjusted to the neck with some element, 32.3% (31) transparent tape attached to the plastic bag that covered the head and 31.3% (30) presented a plastic film with the trade name Vinipel MR. 76.8% (73) had their hands and feet tied when the body was found at the scene. Conclusion This is the first step to obtain information on the characterization of individuals and their macroscopic findings related to homicide deaths due to suffocation with plastic bags, to warn about the actions of organized criminal groups and their practices in the transnational ... (AU)

Moderate physical activity is associated with lower depression, anxiety and stress in health-care workers during the COVID-19 pandemic.

OBJECTIVE: Health-care workers are in high risk for COVID-19 and may experience associated mental health disturbances. Although physical activity (PA) has positive effects on mental disturbances, it has not been fully investigated in health-team during COVID-19 pandemic. Therefore, we analyzed depression, anxiety and stress in health-care workers, and their relationship with PA before and during a COVID-19 peak. METHODS: Retrospective cohort study. PA (IPAQ short-form) evaluated and associated with depression, anxiety and stress (DAAS-21) at the beginning of COVID-19 first wave in Mexico (April 2020) in 1146 workers of a tertiary-care hospital, and in a subsequent occasion at the first wave peak (July-August/2020) in 311 workers (from the first ones). Data collected from routine surveillance. RESULTS: Depression increased 9%, anxiety 15%, and stress 10% at the pandemic peak. Subjects with higher frequency of baseline moderate PA showed lower severity of depression, anxiety and stress at the peak (p < 0.05). At the pandemic peak, female sex (OR = 2.42, 95%CI 1.14-5.13), diabetes (OR = 21.9, 95%CI 2.09-221) and baseline depression (OR = 8.86, 95%CI 4.30-18.2) predicted depression; baseline anxiety (OR = 5.52, 95%CI 3.01-10.1), working in COVID-19 area (OR = 4.14, 95%CI 1.99-8.64), and baseline moderate PA (OR = 0.35, 95%CI 0.16-0.73) predicted anxiety; and baseline stress (OR = 8.64, 95%CI 4.11-18.2), and moderate PA (OR = 0.35, 95%CI 0.15-0.82) predicted stress. CONCLUSION: Depression, stress, and particularly anxiety, increased in health-care workers from the beginning to the COVID-19 pandemic peak, and were predicted by the presence of the corresponding baseline mental alterations, and in the case of anxiety and stress, by the lower frequency of moderate PA.

Co-occurring pathogenic variants in 6q27 associated with dementia spectrum disorders in a Peruvian family.

Evidence suggests that there may be racial differences in risk factors associated with the development of Alzheimer's disease and related dementia (ADRD). We used whole-genome sequencing analysis and identified a novel combination of three pathogenic variants in the heterozygous state (UNC93A: rs7739897 and WDR27: rs61740334; rs3800544) in a Peruvian family with a strong clinical history of ADRD. Notably, the combination of these variants was present in two generations of affected individuals but absent in healthy members of the family. In silico and in vitro studies have provided insights into the pathogenicity of these variants. These studies predict that the loss of function of the mutant UNC93A and WDR27 proteins induced dramatic changes in the global transcriptomic signature of brain cells, including neurons, astrocytes, and especially pericytes and vascular smooth muscle cells, indicating that the combination of these three variants may affect the neurovascular unit. In addition, known key molecular pathways associated with dementia spectrum disorders were enriched in brain cells with low levels of UNC93A and WDR27. Our findings have thus identified a genetic risk factor for familial dementia in a Peruvian family with an Amerindian ancestral background.

Study of the Rv1417 and Rv2617c Membrane Proteins and Their Interactions with Nicotine Derivatives as Potential Inhibitors of Erp Virulence-Associated Factor in Mycobacterium tuberculosis: An In Silico Approach.

The increasing emergence of Mycobacterium tuberculosis (Mtb) strains resistant to traditional anti-tuberculosis drugs has alarmed health services worldwide. The search for new therapeutic targets and effective drugs that counteract the virulence and multiplication of Mtb represents a challenge for the scientific community. Several studies have considered the erp gene a possible therapeutic target in the last two decades, since its disruption negatively impacts Mtb multiplication. This gene encodes the exported repetitive protein (Erp), which is located in the cell wall of Mtb. In vitro studies have shown that the Erp protein interacts with two putative membrane proteins, Rv1417 and Rv2617c, and the impairment of their interactions can decrease Mtb replication. In this study, we present five nicotine analogs that can inhibit the formation of heterodimers and trimers between these proteins. Through DFT calculations, molecular dynamics, docking, and other advanced in silico techniques, we have analyzed the molecular complexes, and show the effect these compounds have on protein interactions. The results show that four of these analogs can be possible candidates to counteract the pathogenicity of Mtb. This study aims to combine research on the Erp protein as a therapeutic target in the search for new drugs that serve to create new therapies against tuberculosis disease.

Situación del suicidio en Antioquia-Colombia durante los años 2016 y 2017: Resultados de los datos de vigilancia epidemiológica

Introducción: la vigilancia epidemiológica del suicidio en una región permite identificar los patrones, la distribución y las características con que ocurre y sentar las bases de intervenciones para prevenirlo. Objetivo: describir la situación del suicidio en Antioquia para el periodo 2016-2017. Métodos: estudio descriptivo basado en datos del Sistema de Vigilancia Epidemiológica de Lesiones de Causa Externa del Instituto Nacional de Medicina Legal y Ciencias forenses. Se calcularon las tasas de suicidio y los años de vida potencialmente perdidos (AVPP) y se describieron las circunstancias del evento. Resultados: hubo 425 suicidios en 2016 y 419 en el 2017, con una tasa de suicidio de 6,50 y 6,34 por 100.000 habitantes/año respectivamente, y 16.446,8 AVPP para 2016 y 16.019,94 para 2017. La mayor parte de los suicidios se presentó en el sexo masculino, en los grupos de edad jóvenes, residentes en área urbana y estado civil soltero. Con respecto a las características del suicidio, el mecanismo más frecuentemente utilizado fue la asfixia mecánica seguido por el envenenamiento, en cerca del 40% de los casos se estableció un evento vital desencadenante como los conflictos de pareja, y se presentaron con mayor frecuencia los días domingo y lunes y en la noche y madrugada. Conclusión: las tasas de suicidio en Antioquia se han incrementado en 2016 y 2017 con respecto a años anteriores. Es más frecuente en hombres y en edades económicamente productivas, lo que explica los altos AVPP. La descripción de las características del suicidio podría facilitar la discusión de intervenciones preventivas.

Summary Background: Identifying the patterns, distribution, and characteristics of suicide in a region is possible with epidemiological surveillance which may lay the foundations for suicide prevention. Objective: To describe the situation of suicide in Antioquia during the period 2016-2017. Methods: Descriptive study based on data from the Epidemiological Surveillance System for External Cause Injuries of the National Institute of Legal Medicine and Forensic Sciences. Suicides rates and Years of Life Lost (YLL) were calculated and the circumstances of the event were described. Results: There were 425 suicides in 2016 and 419 in 2017, with a suicides rate of 6.50 and 6.34 per 100,000 inhabitants/year respectively, and 16,446.8 YLL for 2016 and 16,019.94 YLL for 2017. Most of the suicides occurred in males, in young age groups, urban residents and single marital status. Regarding the characteristics of suicide, the most frequently used mechanism was mechanical asphyxia followed by poisoning, in about 40% of cases a triggering life event was established, such as partner conflicts, and were more frequent on Sunday and Monday and at night and early morning. Conclusion: The incidence of suicide in Antioquia increased in 2016 and 2017 compared to previous years. It was more frequent in economically productive ages, which explains the high YLL. The description of the characteristics of suicide may facilitate the discussion of preventive interventions.

Novel In Silico Insights into Rv1417 and Rv2617c as Potential Protein Targets: The Importance of the Medium on the Structural Interactions with Exported Repetitive Protein (Erp) of Mycobacterium tuberculosis.

Nowadays, tuberculosis is the second leading cause of death from a monopathogenic transmitted disease, only ahead of COVID-19. The role of exported repetitive protein (Erp) in the virulence of Mycobacterium tuberculosis has been extensively demonstrated. In vitro and in vivo assays have identified that Erp interacts with Rv1417 and Rv2617c proteins, forming putative transient molecular complexes prior to localization to the cell envelope. Although new insights into the interactions and functions of Erp have emerged over the years, knowledge about its structure and protein-protein interactions at the atomistic level has not been sufficiently explored. In this work, we have combined several in silico methodologies to gain new insights into the structural relationship between these proteins. Two system conditions were evaluated by MD simulations: Rv1417 and Rv2617c embedded in a lipid membrane and another with a semi-polar solvent to mimic the electrostatic conditions on the membrane surface. The Erp protein was simulated as an unanchored structure. Stabilized structures were docked, and complexes were evaluated to recognize the main residues involved in protein-protein interactions. Our results show the influence of the medium on the structural conformation of proteins. Globular conformations were favored under high polarity conditions and showed a higher energetic affinity in complex formation. Meanwhile, disordered conformations were favored under semi-polar conditions and an increase in the number of contacts between residues was observed. In addition, the electrostatic potential analysis showed remarkable changes in protein interactions due to the polarity of the medium, demonstrating the relevance of Erp protein in heterodimer formation. On the other hand, contact analysis showed that several C-terminal residues of Erp were involved in the protein interactions, which seems to contradict experimental observations; however, these complexes could be transient forms. The findings presented in this work are intended to open new perspectives in the studies of Erp protein molecular interactions and to improve the knowledge about its function and role in the virulence of Mycobacterium tuberculosis.

Kinetics of the Glass Transition of Silica-Filled Styrene-Butadiene Rubber: The Effect of Resins.

Resins are important for enhancing both the processability and performance of rubber. Their efficient utilization requires knowledge about their influence on the dynamic glass transition and their miscibility behavior in the specific rubber compound. The resins investigated, poly-(α-methylstyrene) (AMS) and indene-coumarone (IC), differ in molecular rigidity but have a similar aromaticity degree and glass transition temperature. Transmission electron microscopy (TEM) investigations show an accumulation of IC around the silanized silica in styrene-butadiene rubber (SBR) at high contents, while AMS does not show this effect. This higher affinity between IC and the silica surface leads to an increased compactness of the filler network, as determined by dynamic mechanical analysis (DMA). The influence of the resin content on the glass transition of the rubber compounds is evaluated in the sense of the Gordon-Taylor equation and suggests a rigid amorphous fraction for the accumulated IC. Broadband dielectric spectroscopy (BDS) and fast differential scanning calorimetry (FDSC) are applied for the characterization of the dielectric and thermal relaxations as well as for the corresponding vitrification kinetics. The cooling rate dependence of the vitrification process is combined with the thermal and dielectric relaxation time by one single Vogel-Fulcher-Tammann-Hesse equation, showing an increased fragility of the rubber containing AMS.

Malignant Central Airway Obstruction: What's New?

Malignant central airway obstruction (MCAO) is a debilitating and life-limiting complication that occurs in an unfortunately large number of individuals with advanced intrathoracic cancer. Although the management of MCAO is multimodal and interdisciplinary, the task of providing patients with prompt palliation falls increasingly on the shoulders of interventional pulmonologists. While a variety of tools and techniques are available for the management of malignant obstructive lesions, advancements and evolution in this therapeutic venue have been somewhat sluggish and limited when compared with other branches of interventional pulmonary medicine (e.g., the early diagnosis of peripheral lung nodules). Indeed, one pragmatic, albeit somewhat uncharitable, reading of this article's title might suggest a wry smile and shug of the shoulders as to imply that relatively little has changed in recent years. That said, the spectrum of interventions for MCAO continues to expand, even if at a less impressive clip. Herein, we present on MCAO and its endoscopic and nonendoscopic management-that which is old, that which is new, and that which is still on the horizon.

Influence of the Polarity of the Plasticizer on the Mechanical Stability of the Filler Network by Simultaneous Mechanical and Dielectric Analysis.

Four styrene butadiene rubber (SBR) compounds were prepared to investigate the influence of the plasticizer polarity on the mechanical stability of the filler network using simultaneous mechanical and dielectric analysis. One compound was prepared without plasticizer and serves as a reference. The other three compounds were expanded with different plasticizers that have different polarities. Compared with an SBR sample without plasticizer, the conductivity of mechanically unloaded oil-extended SBR samples decreases by an order of magnitude. The polarity of the plasticizer shows hardly any influence because the plasticizers only affect the distribution of the filler clusters. Under static load, the dielectric properties seem to be oil-dependent. However, this behavior also results from the new distribution of the filler clusters caused by the mechanical damage and supported by the polarity grade of the plasticizer used. The Cole-Cole equation affirms these observations. The Cole-Cole relaxation time τ and thus, the position of maximal dielectric loss increases as the polarity of the plasticizer used is also increased. This, in turn, decreases the broadness parameter α implying a broader response function.

In Silico Analysis of the Antagonist Effect of Enoxaparin on the ApoE4-Amyloid-Beta (Aß) Complex at Different pH Conditions.

Apolipoprotein E4 (ApoE4) is thought to increase the risk of developing Alzheimer's disease. Several studies have shown that ApoE4-Amyloid ß (Aß) interactions can increment amyloid depositions in the brain and that this can be augmented at low pH values. On the other hand, experimental studies in transgenic mouse models have shown that treatment with enoxaparin significantly reduces cortical Aß levels, as well as decreases the number of activated astrocytes around Aß plaques. However, the interactions between enoxaparin and the ApoE4-Aß proteins have been poorly explored. In this work, we combine molecular dynamics simulations, molecular docking, and binding free energy calculations to elucidate the molecular properties of the ApoE4-Aß interactions and the competitive binding affinity of the enoxaparin on the ApoE4 binding sites. In addition, we investigated the effect of the environmental pH levels on those interactions. Our results showed that under different pH conditions, the closed form of the ApoE4 protein, in which the C-terminal domain folds into the protein, remains stabilized by a network of hydrogen bonds. This closed conformation allowed the generation of six different ApoE4-Aß interaction sites, which were energetically favorable. Systems at pH5 and 6 showed the highest energetic affinity. The enoxaparin molecule was found to have a strong energetic affinity for ApoE4-interacting sites and thus can neutralize or disrupt ApoE4-Aß complex formation.

Alzheimer's Disease: A Silent Pandemic - A Systematic Review on the Situation and Patent Landscape of the Diagnosis.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment, tau protein deposits, and amyloid beta plaques. AD impacted 44 million people in 2016, and it is estimated to affect 100 million people by 2050. AD is disregarded as a pandemic compared with other diseases. To date, there is no effective treatment or diagnosis. OBJECTIVE: We aimed to discuss the current tools used to diagnose COVID-19, point out their potential to be adapted for AD diagnosis, and review the landscape of existing patents in the AD field and future perspectives for AD diagnosis. METHODS: We carried out a scientific screening following a research strategy in PubMed; Web of Science; the Derwent Innovation Index; the KCI-Korean Journal Database; Sci- ELO; the Russian Science Citation index; and the CDerwent, EDerwent, and MDerwent index databases. RESULTS: A total of 326 from 6,446 articles about AD and 376 from 4,595 articles about COVID-19 were analyzed. Of these, AD patents were focused on biomarkers and neuroimaging with no accurate, validated diagnostic methods, and only 7% of kit development patents were found. In comparison, COVID-19 patents were 60% about kit development for diagnosis; they are highly accurate and are now commercialized. CONCLUSION: AD is still neglected and not recognized as a pandemic that affects the people and economies of all nations. There is a gap in the development of AD diagnostic tools that could be filled if the interest and effort that has been invested in tackling the COVID-19 emergency could also be applied for innovation.

Protocol to assess the effects of dysfunctional human vascular smooth muscle cells on other brain cells using in vitro models of Alzheimer's disease.

Here, we present a protocol to culture primary human vascular smooth muscle cells (VSMCs) under Alzheimer's disease (AD)-like conditions, including steps for morphological characterization with microscopy. We then describe functional assays, including wound healing, transwell, coculture, and supernatant assays, to evaluate the effect of dysfunctional VSMCs on the induction of the AD-associated microglial phenotype. Our approach can be applied to assess the effects of dysfunctional VSMCs on other cerebral cell lines including pericytes, astrocytes, and neurons under AD-like conditions in vitro. For complete details on the use and execution of this protocol, please refer to Aguilar-Pineda et al. (2021).

In Silico Analysis of Metabolites from Peruvian Native Plants as Potential Therapeutics against Alzheimer's Disease.

BACKGROUND: Despite research on the molecular bases of Alzheimer's disease (AD), effective therapies against its progression are still needed. Recent studies have shown direct links between AD progression and neurovascular dysfunction, highlighting it as a potential target for new therapeutics development. In this work, we screened and evaluated the inhibitory effect of natural compounds from native Peruvian plants against tau protein, amyloid beta, and angiotensin II type 1 receptor (AT1R) pathologic AD markers. METHODS: We applied in silico analysis, such as virtual screening, molecular docking, molecular dynamics simulation (MD), and MM/GBSA estimation, to identify metabolites from Peruvian plants with inhibitory properties, and compared them to nicotinamide, telmisartan, and grapeseed extract drugs in clinical trials. RESULTS: Our results demonstrated the increased bioactivity of three plants' metabolites against tau protein, amyloid beta, and AT1R. The MD simulations indicated the stability of the AT1R:floribundic acid, amyloid beta:rutin, and tau:brassicasterol systems. A polypharmaceutical potential was observed for rutin due to its high affinity to AT1R, amyloid beta, and tau. The metabolite floribundic acid showed bioactivity against the AT1R and tau, and the metabolite brassicasterol showed bioactivity against the amyloid beta and tau. CONCLUSIONS: This study has identified molecules from native Peruvian plants that have the potential to bind three pathologic markers of AD.

CO2 Adsorption on PtCu Sub-Nanoclusters Deposited on Pyridinic N-Doped Graphene: A DFT Investigation.

To reduce the CO2 concentration in the atmosphere, its conversion to different value-added chemicals plays a very important role. Nevertheless, the stable nature of this molecule limits its conversion. Therefore, the design of highly efficient and selective catalysts for the conversion of CO2 to value-added chemicals is required. Hence, in this work, the CO2 adsorption on Pt4-xCux (x = 0-4) sub-nanoclusters deposited on pyridinic N-doped graphene (PNG) was studied using the density functional theory. First, the stability of Pt4-xCux (x = 0-4) sub-nanoclusters supported on PNG was analyzed. Subsequently, the CO2 adsorption on Pt4-xCux (x = 0-4) sub-nanoclusters deposited on PNG was computed. According to the binding energies of the Pt4-xCux (x = 0-4) sub-nanoclusters on PNG, it was observed that PNG is a good material to stabilize the Pt4-xCux (x = 0-4) sub-nanoclusters. In addition, charge transfer occurred from Pt4-xCux (x = 0-4) sub-nanoclusters to the PNG. When the CO2 molecule was adsorbed on the Pt4-xCux (x = 0-4) sub-nanoclusters supported on the PNG, the CO2 underwent a bond length elongation and variations in what bending angle is concerned. In addition, the charge transfer from Pt4-xCux (x = 0-4) sub-nanoclusters supported on PNG to the CO2 molecule was observed, which suggests the activation of the CO2 molecule. These results proved that Pt4-xCux (x = 0-4) sub-nanoclusters supported on PNG are adequate candidates for CO2 adsorption and activation.

Caracterización clínico-epidemiológica del tromboembolismo pulmonar en autopsias del Instituto de Medicina Legal de Medellín 2010-2020 / Clinical-epidemiological characterization of pulmonary embolism in autopsies of the Medellín Institute of Legal Medicine 2010-2020

Resumen Introducción: A pesar de disponer de métodos diagnósticos y terapéuticos eficaces, el tromboembolismo pulmonar (TEP) es una afección que a lo largo de décadas ha causado una elevada morbilidad y mortalidad. Objetivo: Describir las características clínico-epidemiológicas y anatomo-patológicas de los diagnósticos de TEP en cadáveres que ingresaron por muerte súbita al Instituto Nacional de Medicina Legal y Ciencias Forenses de Medellín 2010-2020. Métodos: Estudio descriptivo de una cohorte retrospectiva, formada por los casos que ingresaron al Instituto de Medicina Legal por muerte súbita con causa de muerte por establecer, diagnosticados con TEP. Los análisis se realizaron con frecuencias y medidas de resumen en SPSS 27.0. Resultados: Entre 46097 necropsias médico legales realizadas en el período estudiado, 164 casos (0,36 %) corresponden a TEP. La edad media fue 57,0±19,3 años y 51,2% mujeres. El 57,9% fue muerte natural, en 37,2% se presentó trauma y 36,0% otro evento circulatorio. En la mayoría de los casos, el deceso ocurrió en la vivienda (47,0%) y la vía pública (25,6%). En la trombosis, 45,1% fue de la arteria pulmonar (trombo cabalgado); 34,8% de arterias pulmonares intraparenquimatosas y 52,4% de los fallecidos presentaron trombosis venosa profunda de miembros inferiores. Conclusión: El TEP es una importante causa de muerte en pacientes intra y extrahospitalarios, a pesar de los métodos diagnósticos, farmacológicos y no farmacológicos existentes para su prevención. La realización de un mayor número de autopsias clínicas permitirá revelar el verdadero impacto en nuestro medio de esta complicación y mejorar la calidad en el cuidado de los pacientes.

Abstract Introduction: Pulmonary embolism (PE) is a medical complication that has caused high morbidity and mortality for a long time despite having highly effective diagnostic and therapeutic methods for treating it. Objective: To describe the clinical-epidemiological and anatomopathological characteristics of the diagnosis of PE in corpses that were ingressed in the National Institute of Legal Medicine and Forensic Sciences of Medellín due to sudden death between the period 2010-2020. Methods: This is a descriptive cohort study carried out through the analysis of sudden death cases with cause of death to be established that were admitted at the Institute. Additionally, a diagnosis of PE was conducted on them and the analyzes were performed with frequencies and summary measures of SPSS 27.0. Results: From 46.097 legal-medical autopsies of the period studied, 164 cases (0.36%) corresponded to PE. The mean age was 57.0 ± 19.3 years and 51.2% were women. A percentage of 57.9% were natural deaths, 37.2% had trauma, and 36.0% presented another circulatory event. The highest proportion of deaths occurred in living places (47.0%) and public roads (25.6%). In terms of thrombosis, 45.1% occurred in the pulmonary artery, 34.8% in intraparenchymal pulmonary arteries, and 52.4% of the deceased had deep vein thrombosis of the lower limbs. Conclusion: PE is a recurrent cause of death in intra-hospital and out-of-hospital patients despite the existing diagnostic, pharmacological and non-pharmacological methods for its prevention. Carrying out a greater number of clinical autopsies will reveal the true impact of this complication in our environment and improve the quality of patient care.

Bringing high spatial resolution to the far-infrared: A giant leap for astrophysics.

The far-infrared (FIR) regime is one of the wavelength ranges where no astronomical data with sub-arcsecond spatial resolution exist. None of the medium-term satellite projects like SPICA, Millimetron, or the Origins Space Telescope will resolve this malady. For many research areas, however, information at high spatial and spectral resolution in the FIR, taken from atomic fine-structure lines, from highly excited carbon monoxide (CO), light hydrides, and especially from water lines would open the door for transformative science. A main theme will be to trace the role of water in proto-planetary discs, to observationally advance our understanding of the planet formation process and, intimately related to that, the pathways to habitable planets and the emergence of life. Furthermore, key observations will zoom into the physics and chemistry of the star-formation process in our own Galaxy, as well as in external galaxies. The FIR provides unique tools to investigate in particular the energetics of heating, cooling, and shocks. The velocity-resolved data in these tracers will reveal the detailed dynamics engrained in these processes in a spatially resolved fashion, and will deliver the perfect synergy with ground-based molecular line data for the colder dense gas.

Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

Vascular smooth muscle cell dysfunction contribute to neuroinflammation and Tau hyperphosphorylation in Alzheimer disease.

Despite the emerging evidence implying early vascular contributions to neurodegenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimer disease (AD) is still not well understood. Herein, we show that VSMCs in brains of patients with AD and animal models of the disease are deficient in multiple VSMC contractile markers which correlated with Tau accumulation in brain arterioles. Ex vivo and in vitro experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205, and S262. We also observed that VSMC dysfunction occurred in an age-dependent manner and that expression of Sm22α protein was inversely correlated with CD68 and Tau expression in brain arterioles of the 3xTg-AD and 5xFAD mice. Together, these findings further support the contribution of dysfunctional VSMCs in AD pathogenesis and nominate VSMCs as a potential therapeutic target in AD.

Structural and Energetic Affinity of Annocatacin B with ND1 Subunit of the Human Mitochondrial Respiratory Complex I as a Potential Inhibitor: An In Silico Comparison Study with the Known Inhibitor Rotenone.

ND1 subunit possesses the majority of the inhibitor binding domain of the human mitochondrial respiratory complex I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experiments, that some metabolites from Annona muricata called acetogenins have important biological activities, such as anticancer, antiparasitic, and insecticide. Previous studies propose an inhibitory activity of bovine mitochondrial respiratory complex I by bis-tetrahydrofurans acetogenins such as annocatacin B, however, there are few studies on its inhibitory effect on human mitochondrial respiratory complex I. In this work, we evaluate the in silico molecular and energetic affinity of the annocatacin B molecule with the human ND1 subunit in order to elucidate its potential capacity to be a good inhibitor of this subunit. For this purpose, quantum mechanical optimizations, molecular dynamics simulations and the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) analysis were performed. As a control to compare our outcomes, the molecule rotenone, which is a known mitochondrial respiratory complex I inhibitor, was chosen. Our results show that annocatacin B has a greater affinity for the ND1 structure, its size and folding were probably the main characteristics that contributed to stabilize the molecular complex. Furthermore, the MM/PBSA calculations showed a 35% stronger binding free energy compared to the rotenone complex. Detailed analysis of the binding free energy shows that the aliphatic chains of annocatacin B play a key role in molecular coupling by distributing favorable interactions throughout the major part of the ND1 structure. These results are consistent with experimental studies that mention that acetogenins may be good inhibitors of the mitochondrial respiratory complex I.

Diagnosis of Alzheimer's Disease in Developed and Developing Countries: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy.

BACKGROUND: The present systematic review and meta-analysis of diagnostic test accuracy summarizes the last three decades in advances on diagnosis of Alzheimer's disease (AD) in developed and developing countries. OBJECTIVE: To determine the accuracy of biomarkers in diagnostic tools in AD, for example, cerebrospinal fluid, positron emission tomography (PET), and magnetic resonance imaging (MRI), etc. METHODS: The authors searched PubMed for published studies from 1990 to April 2020 on AD diagnostic biomarkers. 84 published studies were pooled and analyzed in this meta-analysis and diagnostic accuracy was compared by summary receiver operating characteristic statistics. RESULTS: Overall, 84 studies met the criteria and were included in a meta-analysis. For EEG, the sensitivity ranged from 67 to 98%, with a median of 80%, 95% CI [75, 91], tau-PET diagnosis sensitivity ranged from 76 to 97%, with a median of 94%, 95% CI [76, 97]; and MRI sensitivity ranged from 41 to 99%, with a median of 84%, 95% CI [81, 87]. Our results showed that tau-PET diagnosis had higher performance as compared to other diagnostic methods in this meta-analysis. CONCLUSION: Our findings showed an important discrepancy in diagnostic data for AD between developed and developing countries, which can impact global prevalence estimation and management of AD. Also, our analysis found a better performance for the tau-PET diagnostic over other methods to diagnose AD patients, but the expense of tau-PET scan seems to be the limiting factor in the diagnosis of AD in developing countries such as those found in Asia, Africa, and Latin America.