Desfechos obstétricos adversos durante a COVID-19: uma série de casos retrospectiva / Adverse obstetric outcomes during COVID-19: a retrospective case series / Resultados obstétricos adversos durante el COVID-19: serie de casos retrospectiva

Objetivo: analisar as características e os desfechos obstétricos adversos em gestantes/puérperas infectadas pelo SARS-CoV-2 em serviço de referência. Método: série de casos retrospectiva entre gestantes com Covid-19 em um hospital universitário em Minas Gerais, Brasil, atendidas no serviço de 2020 a 2021, coletados em abril de 2022, empregando-se estatística descritiva para análise dos dados através do Statistical Package for the Social Science. Resultados: incluídas 26 gestantes, em sua maioria brancas, que tiveram como principais desfechos obstétricos adversos a internação em UTI (43,5%), parto prematuro (34,6%), dado reestratificado de semanas para dias para investigar o encurtamento da gestação, onde constatou-se média de 38,6 dias potenciais de gravidez perdidos dos 280 dias ideais, e ainda 15,4% evoluíram para óbito materno. Conclusão: o estudo proporcionou evidenciar a necessidade de vigilância e atenção às gestantes com foco nos principais desfechos adversos, podendo-se intervir em tempo oportuno para diminuir adversidades.

Objective: to analyze the characteristics and adverse obstetric outcomes in pregnant/puerperal women infected by SARS-CoV-2 at a reference service. Method: a retrospective case series conducted among pregnant women with Covid-19 in a university hospital from Minas Gerais, Brazil, treated at the service from 2020 to 2021. The cases were collected in April 2022 employing descriptive statistics for data analysis in the Statistical Package for the Social Science. Results: a total of 26 pregnant women were included, mostly white-skinned, whose main adverse obstetric outcomes were admission to the ICU (43.5%), premature birth (34.6%) and data restratified from weeks to days to investigate shortening of pregnancy, where a mean of 38.6 potential days of pregnancy were lost out of the ideal 280 days, and 15.4% resulted in maternal death. Conclusion: the study provided evidence of the need for surveillance and care for pregnant women with a focus on the main adverse outcomes, enabling timely intervention to reduce adversities.

Objetivo: analizar las características y resultados obstétricos adversos en gestantes/puérperas infectadas por SARS-CoV-2 en un servicio de referencia. Método: serie de casos retrospectiva entre gestantes con Covid-19 en un hospital universitario de Minas Gerais, Brasil, atendidas en el servicio de 2020 a 2021. Los datos se recolectaron en abril de 2022, se utilizó estadística descriptiva para analizar los datos mediante el Statistical Package for the Social Science. Resultados: se incluyeron 26 gestantes, la mayoría de raza blanca, cuyos principales resultados obstétricos adversos fueron ingreso a UCI (43,5%), parto prematuro (34,6%), dato reestratificado de semanas a días para investigar el acortamiento de la gestación, que arrojó como resultado un promedio de 38,6. Se comprobó que se perdieron en promedio 38,6 días potenciales de embarazo de los 280 días ideales, y muerte materna (15,4%). Conclusión: la evidencia que proporcionó el estudio indica que es necesario vigilar y atender a las gestantes enfocándose en los principales resultados adversos, lo que permite intervenir de forma oportuna para reducir adversidades.

Actitudes ante la muerte en profesionales de enfermería latinoamericanos: una revisión integrativa

Introducción: La muerte es parte de los tabúes sociales existentes y puede fomentar actitudes que distan de su abordaje explícito en relación con los cuidados. Objetivo: Analizar las actitudes ante la muerte en profesionales de enfermería de acuerdo con las publicaciones científicas en el contexto latinoamericano en el período 2018 a 2022. Metodología: Se realizó una revisión de literatura integrativa de las publicaciones científicas latinoamericanas respecto de las actitudes ante la muerte en el contexto de la enfermería, empleando los siguientes términos estandarizados: actitud, muerte, enfermería y cuidados de enfermería. Se incluyeron 8 artículos publicados en el período definido, en idioma español y portugués, en los que se abordó explícitamente la temática de la revisión. La información de los artículos fue analizada tomando como referencia los conceptos de la teoría de las transiciones. Resultados: Se encontraron diseños tanto cuantitativos (50 %) como cualitativos (50 %), elaborados en su totalidad en el ámbito hospitalario. Los principales resultados dan cuenta del predominio de la indiferencia ante la muerte en el contexto de los cuidados. En relación con la teoría de las transiciones, la mayoría de los artículos abordan las condiciones en que estas se dan, además de los conceptos de terapéutica de enfermería y patrones de respuesta. Conclusiones: La producción de investigaciones sobre la actitud ante la muerte en profesionales de enfermería es escasa en Latinoamérica. Las experiencias de pérdidas cercanas, la capacitación y el soporte institucional son la base para contribuir a una mejor actitud hacia la muerte

Introdução: A morte faz parte dos tabus sociais existentes e pode fomentar atitudes que se distanciam de sua abordagem explícita em relação aos cuidados. Objetivo: analisar as atitudes diante da morte em profissionais de enfermagem de acordo com as publicações científicas no contexto latino-americano no período de 2018 a 2022. Metodologia: Foi realizada uma revisão de literatura integrativa de publicações científicas latino-americanas sobre atitudes diante da morte no contexto da enfermagem, utilizando os seguintes termos padronizados: atitude, morte, enfermagem e cuidados de enfermagem. Foram incluídos 8 artigos publicados no período definido, em espanhol e português, nos quais o tema da revisão foi abordado explicitamente. As informações dos artigos foram analisadas tendo como referência os conceitos da teoria das transições. Resultados: Foram identificados desenhos quantitativos (50 %) e qualitativos (50 %), elaborados totalmente no âmbito hospitalar. Os principais resultados mostram a predominância da indiferença diante da morte no contexto do cuidado. Em relação à teoria das transições, a maioria dos artigos aborda as condições em que as transições ocorrem, além dos conceitos de terapêutica de enfermagem e padrões de resposta. Conclusões: A produção de pesquisas sobre atitudes diante da morte em profissionais de enfermagem é escassa na América Latina. As experiências de perdas próximas, a capacitação e o apoio institucional são a base para contribuir para uma melhor atitude em relação à morte

Introduction: Death is part of the existing social taboos and can foster attitudes that are far from its explicit approach in relation to care. Objective: To analyze attitudes towards death in nursing professionals according to scientific publications in the Latin American context in the period 2018 to 2022. Methodology: An integrative literature review was conducted of Latin American scientific publications regarding attitudes towards death in the context of Nursing, using the following standardized terms: attitude, death, nursing and nursing care. Eight articles published in the defined period were included, in Spanish and Portuguese, in which the subject of the review was explicitly addressed. The information in the articles was analyzed using the concepts of the theory of transitions as a reference. Results: Both quantitative (50 %) and qualitative (50 %) designs were found, all of them elaborated in the hospital setting. The main results show the predominance of indifference to death in the context of care. In relation to the theory of transitions, most of the articles address the conditions under which these occur, in addition to the concepts of nursing therapeutics and response patterns. Conclusions: The production of research on the attitude towards death in nursing professionals is scarce in Latin America. Experiences of close losses, training and institutional support are the basis for contributing to a better attitude towards death

Causes and investigation of stillbirths in Brazil: A multicentre cross-sectional study in 10 referral maternity hospitals.

OBJECTIVE: Understanding the local characteristics and statistics related to stillbirths may be the first step in a series of strategies associated with a reduction in stillbirth ratio. The aim of this study was to estimate the fetal mortality ratio and evaluate the investigation processes related to the causes of death, comparing the investigation according to the specific cause of death. METHODS: A cross-sectional study was retrospectively conducted in 10 tertiary obstetric care centers. Medical records of women with stillbirth managed between January 1, 2009 and December 31, 2018 were analyzed and classified, according to sociodemographic characteristics, and gestational and childbirth data, culminating in stillbirth. The stillbirth ratio and its causes were presented in proportions for the study period and individually for each health facility. RESULTS: Cases of 3390 stillbirths were analyzed. The stillbirth ratio varied from 10.74/1000 live births (LBs) in 2009 to 9.31/1000 in 2018. "Intrauterine hypoxia and asphyxia" (ICD-10 P20) and "unspecific causes of death" (ICD-10 P95) represented 40.8% of the causes of death. Investigation for TORCHS and diabetes occurred in 90.8% and 61.4% of deaths, respectively. Placental and necroscopic tests were performed in 36.6% of the cases. CONCLUSION: The adoption of a rational and standardized investigation of stillbirth remains an unmet need; the use of additional tests and examinations are lacking, especially when unspecific causes are attributed.

Long-lasting effects of control measures on trends in incidence in neonatal late-onset sepsis due to multiresistant bacteria in a Brazilian neonatal unit.

BACKGROUND: In response to a 1995 outbreak of sepsis caused by multidrug-resistant (MR) Gram-negative bacteria (GNB), a Brazilian level III neonatal unit established a series of control and prevention measures. This study evaluated the long-term effects of these measures on late-onset neonatal sepsis (LONS) caused by MR bacteria from 2000 to 2020 and examined their impact on in-hospital mortality. METHODS: Newborns with LONS and positive cultures for Staphylococcus aureus, GNB, and Enterococcus sp were selected, adhering to Center for Desease Control and Prevention and local criteria. Joinpoint regression analysis was used to assess annual trends. RESULTS: Over the 21-year period, the overall LONS rate was 4.6%, showing a significant decline from 2000 to 2016 (P < .0001, slope -0.36). However, from 2016 to 2020, there was a non-significant increase in sepsis rates (slope +0.92, P = .08). MR sepsis were in 15.8% of sepsis cases and displayed a non-significant upward trend (slope +0.50, P = .08) with no major shifts. In-hospital mortality rates for MR and non-MR LONS showed no significant differences (P = .413). DISCUSSION: The study indicates a low prevalence of MR sepsis due to effective antimicrobial use and educational interventions. CONCLUSIONS: MR sepsis prevalence remained low and stable, not increasing in-hospital mortality.

Effects of artemisinin and cisplatin on the malignant progression of oral leukoplakia. In vitro and in vivo study.

OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

Accuracy of estimating postmortem interval using the relationship between total body score and accumulated degree-days: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the relationship between Total Body Score (TBS) and Accumulated Degree-Days (ADD) for estimating postmortem interval (PMI) using the decomposition quantification system by Megyesi et al. (Megyesi MS, Nawrocki SP, Haskell NH (2005) Using Accumulated Degree-Days to Estimate the Postmortem Interval from Decomposed Human Remains. J Forensic Sci 50:1-9. https://doi.org/10.1520/jfs2004017 ). DESIGN: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The methodological quality and risk of bias were assessed using the QUADAS-2 scoring system. Statical tests, including I2 for heterogeneity assessment and subgroup analysis comparing human and pig proxies across different decomposition stages, were performed for meta-analysis. RESULTS: The search identified 25 studies that underwent qualitative evaluation, all of which were included for quantitative analysis. The findings indicate that the TBS formula tends to overestimate ADD with a moderate mean difference of 0.5758 overall. Specifically, in pigs, ADD is overestimated significantly (1.1128), while there is a slight underestimation in humans (-0.0038). Across decomposition stages, fresh body (0.0066) and early decomposition (0.0338) show an insignificant overestimation, whereas advanced decomposition reveals a slight underestimation (-0.3378) and skeletonization indicates a substantial overestimation (1.6583). CONCLUSIONS: The relationship between TBS and ADD demonstrates high accuracy in humans during early decomposition stages, without differences in statistical significance. However, its accuracy diminishes as decomposition progresses, potentially leading to an overestimation of PMI.

Global Leadership Initiative on Malnutrition criteria using calf and upper arm circumference as phenotypic criteria for assessing muscle mass demonstrate satisfactory validity for diagnosing malnutrition in hospitalized patients: A prospective cohort study.

BACKGROUND: Hospitalized individuals present high rates of malnutrition and loss of muscle mass (MM). Imaging techniques for assessing MM are expensive and scarcely available in hospital practice. The Global Leadership Initiative on Malnutrition (GLIM) proposed a framework for malnutrition diagnosis that includes simple measurements to assess MM, such as calf circumference (CC) and mid-upper arm circumference (MUAC). This study aimed to analyze the validity of the GLIM criteria with CC and MUAC for malnutrition diagnosis, using Subjective Global Assessment (SGA) as the reference standard, in inpatients. METHODS: A prospective cohort study was conducted on 453 inpatient adults in a university hospital. The presence of malnutrition was assessed within 48 h of hospital admission using SGA and GLIM criteria using CC and MUAC as phenotypic criteria for malnutrition diagnosis. Accuracy, agreement tests, and logistic regression analysis adjusted for confounders were performed to test the validity of the GLIM criteria for malnutrition diagnosis. RESULTS: The patients were aged 59 (46-68) years, 51.4% were male, and 67.8% had elective surgery. Compared with SGA, the GLIM criteria using the two MM assessment measures showed good accuracy (area under the curve > 0.80) and substantial agreement (κ > 0.60) for diagnosing malnutrition. The highest sensitivity was obtained with GLIMCC (89%), whereas GLIMMUAC showed high specificity (>90%). Also, malnutrition identified by GLIMCC and GLIMMUAC was significantly associated with prolonged hospitalization and in-hospital death. CONCLUSION: In the absence of imaging techniques to assess MM, the use of CC and MUAC measurements from the GLIM criteria demonstrated satisfactory validity for diagnosing malnutrition in hospitalized patients.

PD-L1 expression in non-small cell lung carcinoma in Latin America: a systematic review and meta-analysis.

Background: Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is a crucial factor in predicting responses to immunotherapy. This systematic review and meta-analysis focuses on the prevalence of PD-L1 expression and clinicopathological features among Hispanic/Latino (H/L) populations. Methods: Embase, LILACS, Medline, and Virtual Health Library were searched for studies that evaluated the prevalence of PD-L1 in H/L patients. The protocol was submitted to PROSPERO with ID CRD42023488547. We employed the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses to assess the methodological quality and applicability of the included studies. Meta-analyses were done to determine the prevalence using a random effects model. Results: The meta-analysis, encompassing 21 articles with 16,486, revealed that 80.2% of patients had PD-L1 expression data available (n=13,222). The prevalence calculated of PD-L1 expression in Latino NSCLC patients was 55% [95% confidence interval (CI): 0.54-0.55], with 31% (95% CI: 0.27-0.36) showing a tumoral proportion score (TPS) of 1-49%, and 23% (95% CI: 0.16-0.30) registering a TPS ≥50%. Higher expression was observed in male gender, smoking, adenocarcinoma subtypes, poor tumor differentiation, and advanced stages. PD-L1 expression was most frequent in EGFR wild-type status (82.5%) with a odds ratio (OR) 1.54 (95% CI: 1.24-1.92) and PD-L1 expression was associated with ALK positive (OR =1.54; 95% CI: 1.24-1.92). Conclusions: This meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC in the H/L population. The findings underscore the significant prevalence of PD-L1 expression and emphasize the relevance of immunotherapy in this population. Understanding the clinicopathological features associated with PD-L1 expression can contribute to tailored treatment strategies for NSCLC in Latin America.

Mistakes are not an option: aggression from peers and other correlates of anxiety and depression in pediatricians in training.

Introduction: Pediatricians in training are a population at risk for anxiety and depression: they face long working hours, they are confronted with the suffering and death of a vulnerable population and may have personal characteristics that put them in danger. Nonetheless, few studies have looked at their prevalence and associated factors. We aimed to compare demographic, professional activities, adversities and perfectionism personality features between a group of pediatricians in training with depression and/or anxiety and a group of pediatricians in training without depression nor anxiety and, to identify the variables that increase the probabilities of depression and/or anxiety in pediatricians in training. Methods: Pediatric residents who voluntarily answered an online survey distributed via personal and institutional social media channels from October 2019 to April 2021, as part of a cross-sectional study with medical specialists and residents from Mexico were included. Demographic information, professional activities and adversities, perfectionism personality features (Multidimensional Perfectionism Scale), depression and anxiety (ICD-11 PHC) were evaluated. For comparison purposes Chi-square tests (χ2) and independent sample t-tests were used. A logistic regression analysis was used to identify those variables that increase the probabilities of depression and/or anxiety. Results: 934 pediatric residents answered the survey. 11.6% reported having depression and 20% anxiety. Being single, a history of anxious or depressive episodes, being the resident in charge of a patient who died, aggressions from colleagues and a high concern for errors were associated with current depression and/or anxiety. Discussion: Screening for depressive and anxious symptoms should be routinely performed from entry to the residency to favor early intervention. A shift from promoting perfectionism to a more compassionate training could serve a population facing so many adversities.

Vulnerable Lives, Irrelevant Deaths? Dying Alone and Receiving Flawed Care in an Institution for the Aged in Lima, Peru.

This ethnographic exploration of death in the Peruvian context draws on fieldwork among abandoned-both by their families and the state-older adults in a shelter for the homeless in Lima, Peru. I examine the conditions and local forces that shape the ways people at this institution socially and physically die. My argument is that people in this long-term care facility who have lived entire lives on the margins, usually, end up having irrelevant deaths to their families, other residents of the institution, and the Peruvian state. At this shelter, dying in an irrelevant way means dying without companionship from family members and receiving poor and flawed care from the institution that shelters them.

Development and Holocrine Secretion of Resin Ducts in Kielmeyera appariciana (Calophyllaceae).

The modes of formation and release of secretion are complex processes that occur in secretory ducts and their description has great divergence in some species. The use of modern techniques to detect hydrolytic enzymes, cytoskeleton arrangement and indicators of programmed cell death may help clarify the processes involved during the ontogeny of that gland. The goal of our study was to analyze subcellular changes during schizogenous formation and secretion production and release into the lumen in resin ducts of Kielmeyera appariciana. Our results demonstrate the participation of pectinase through the loosening of the central cells of the rosette, which subsequently split from each other through polarized growth mediated by a rearrangement of the microtubules. The resin is mainly synthesized in plastids and endoplasmic reticulum and is observed inside vesicles and small vacuoles. The secretion release is holocrine and occurs through programmed cell death related to the release of reactive oxygen species, causing cytoplasm darkening, chromatin condensation, vacuole rupture and plastid and mitochondria degeneration. Cellulase activity was identified prior to the rupture of the cell wall, causing the release of secretion into the lumen of the duct. The participation of the cytoskeleton was observed for the first time during schizogeny of ducts as well as programmed cell death as part of the process of the release of holocrine secretion. This type of secretion release may be a key innovation in Kielmeyera since it has not been observed in ducts of any other plant thus far.

Clinical, epidemiological characteristics and mortality of pregnant and postpartum women associated with COVID-19 in Brazil: cohort study.

Objective: To analyze the death of Brazilian pregnant and postpartum women due to COVID-19 or unspecific cause. Methods: This is retrospective, descriptive-exploratory, population-based study carried out with the Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe) database, with pregnant and postpartum women of reproductive age who died from confirmed COVID-19 between 2020 and 2021. The chosen variables were: age, gestational period, type and number of comorbidities, skin color, using the statistical software R Foundation for Statistical Computing Platform, version 4.0.3 and Statistical Package for Social Science, version 29.0 for analysis. Results: A total of 19,333 cases of pregnant and postpartum women aged between 10 and 55 years diagnosed with SARS were identified, whether due to confirmed COVID-19 or unspecific causes. Of these, 1,279 died, these cases were classified into two groups according to the cause of death: deaths from COVID-19 (n= 1,026) and deaths from SARS of unspecific cause (n= 253). Conclusion: The risk of death increased among black and brown women, in the postpartum period and with the presence of comorbidities, mainly diabetes, cardiovascular diseases and obesity. The data presented here draw attention to the number of deaths from SARS, especially among sociodemographic profiles, precarious access to health, such as the black population. In addition, limitations in adequate access to health care are reinforced by even lower rates of ICU admissions among women who died from SARS of an unspecified cause.

Modified mesenchymal stromal cells by in vitro transcribed mRNA: a therapeutic strategy for hepatocellular carcinoma.

BACKGROUND: Mesenchymal stromal cells (MSCs) tropism for tumours allows their use as carriers of antitumoural factors and in vitro transcribed mRNA (IVT mRNA) is a promising tool for effective transient expression without insertional mutagenesis risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with antitumor properties by stimulating the specific immune response. The aim of this work was to generate modified MSCs by IVT mRNA transfection to overexpress GM-CSF and determine their therapeutic effect alone or in combination with doxorubicin (Dox) in a murine model of hepatocellular carcinoma (HCC). METHODS: DsRed or GM-CSF IVT mRNAs were generated from a cDNA template designed with specific primers followed by reverse transcription. Lipofectamine was used to transfect MSCs with DsRed (MSC/DsRed) or GM-CSF IVT mRNA (MSC/GM-CSF). Gene expression and cell surface markers were determined by flow cytometry. GM-CSF secretion was determined by ELISA. For in vitro experiments, the J774 macrophage line and bone marrow monocytes from mice were used to test GM-CSF function. An HCC model was developed by subcutaneous inoculation (s.c.) of Hepa129 cells into C3H/HeN mice. After s.c. injection of MSC/GM-CSF, Dox, or their combination, tumour size and mouse survival were evaluated. Tumour samples were collected for mRNA analysis and flow cytometry. RESULTS: DsRed expression by MSCs was observed from 2 h to 15 days after IVT mRNA transfection. Tumour growth remained unaltered after the administration of DsRed-expressing MSCs in a murine model of HCC and MSCs expressing GM-CSF maintained their phenotypic characteristic and migration capability. GM-CSF secreted by modified MSCs induced the differentiation of murine monocytes to dendritic cells and promoted a proinflammatory phenotype in the J774 macrophage cell line. In vivo, MSC/GM-CSF in combination with Dox strongly reduced HCC tumour growth in C3H/HeN mice and extended mouse survival in comparison with individual treatments. In addition, the tumours in the MSC/GM-CSF + Dox treated group exhibited elevated expression of proinflammatory genes and increased infiltration of CD8 + T cells and macrophages. CONCLUSIONS: Our results showed that IVT mRNA transfection is a suitable strategy for obtaining modified MSCs for therapeutic purposes. MSC/GM-CSF in combination with low doses of Dox led to a synergistic effect by increasing the proinflammatory tumour microenvironment, enhancing the antitumoural response in HCC.

Heat stress in plants: sensing, signalling and ferroptosis.

In the current context of global warming, high temperature events are becoming more frequent and intense in many places around the world. In this context, understanding how plants sense and respond to heat is essential to develop new tools to prevent plant damage and address global food security, as high temperature events are threatening agricultural sustainability. This review summarizes and integrates our current understanding underlying the cellular, physiological, biochemical and molecular regulatory pathways triggered in plants under moderately high and extremely high temperature conditions. Given that extremely high temperatures can also trigger ferroptosis, the study of this cell death mechanism constitutes a strategic approach to understand how plants might overcome otherwise lethal temperature events.

Clinical Characteristics of Hospitalized Patients With COVID-19 and Their Association With the Progression to Critical Illness and Death: A Single-Center Retrospective Study From Northwestern Mexico.

OBJECTIVE: The objective of this study was to associate the epidemiological and clinical characteristics of patients hospitalized for COVID-19 with the progression to critical illness and death in northwestern Mexico. METHODS: From March to October 2020, we collected the demographic and clinical characteristics of 464 hospitalized patients from northwestern Mexico. RESULTS: Sixty-four percent (295/464) of the patients became critically ill. Age, occupation, steroid and antibiotic use at previous hospitalization, and underlying diseases (hypertension, obesity, and chronic kidney disease) were associated with critical illness or death (p: < 0.05). No symptoms were associated with critical illness. However, the parameters such as the heart rate, respiratory rate, oxygen saturation, and diastolic pressure and the laboratory parameters such as the glucose, creatinine, white line cells, hemoglobin, D-dimer, and C-reactive protein, among others, were associated with critical illness (p: < 0.05). Finally, advanced age, previous hospital treatment, and the presence of one or more underlying diseases were associated with critical illness and death (p: < 0.02). CONCLUSIONS: Several epidemiological (e.g., age and occupation) and clinical factors (e.g., previous treatment, underlying diseases, and vital signs and laboratory parameters) were associated with critical illness and death in patients hospitalized with COVID-19. These data provide us with possible markers to avoid critical illness or death from COVID-19 in our region.

Effects of chronic oral exposure to insecticide teflubenzuron on the midgut of the honey bee Apis mellifera workers: histopathological insights into pesticide toxicity.

The honey bee Apis mellifera plays a significant role as a pollinator of native and cultivated plants, by increasing the productivity of several cultures, preserving the flora, and producing forest seeds. However, bee populations are declining worldwide, including A. mellifera, due to Colony Collapse Disorder, mainly resulting from the constant use of pesticides in the crops. Teflubenzuron is a physiological insecticide that belongs to the benzoylurea group, which inhibits chitin synthesis, the main component of the insect integument classified as safe for non-target insects, including bees. However, its effect on non-target organs of insects remains unknown. The midgut is the main organ of the digestive tract, which works in digestion and absorption and may be exposed to pesticides that contaminate food resources. The present work aimed to verify if the insecticide teflubenzuron is toxic and has histopathological effects on the midgut of A. mellifera adult workers. Workers exposed orally and chronically to the field-realistic concentration of teflubenzuron present 81.54% mortality. The epithelium of the midgut of these bees presents high vacuolization, spherocrystals, cell fragments released to the organ lumen, apocrine secretion, nuclear pyknosis, loss of cell-cell contact, and damage to regenerative cell nests and to the peritrophic matrix. These results indicate that the chitin synthesis-inhibiting insecticide teflubenzuron is toxic to A. mellifera after chronic oral exposure, at realistic field concentration, although it is classified as non-toxic to adult and non-target insects.

Doxorubicin-induced Immunogenic Cell Death Impairs Tumor Progression and Distant Metastasis in a 4T1 Breast Cancer Tumor Model.

INTRODUCTION: Cancer is an individual disease and its formation and development are specific to each host. Conventional treatments are ineffective in complex cases, such as metastasis, and have severe adverse side effects. New strategies are needed to address the problem, and the use of immunogenic cell death (ICD) as a trigger or booster of the immune system through the exposure of damage-associated molecular patterns, along with tumor antigens, by cancerous cells is presented as an immunization approach in this work. METHODS: For this purpose, 4T1 cells were exposed to doxorubicin (DOX) for 24 hours and then, these cells undergoing ICD were subcutaneously administered to mice. The ICD induction by DOX on 4T1 was assessed by flow cytometry and image analysis. This immunization process was performed three times and after the last administration, the immunized mice were challenged with a subcutaneous xenograft of live cancer cells. RESULTS: The results demonstrate that the mice immunized with cells undergoing ICD after exposure to DOX presented no primary tumor or indications of distant metastatic lesion development. CONCLUSION: In summary, our findings indicate that the immunization process utilizing ICD is indeed efficacious in managing this aggressive form of pre-clinical breast cancer.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Impact of Genomic Mutation on Melanoma Immune Microenvironment and IFN-1 Pathway-Driven Therapeutic Responses.

The BRAFV600E mutation, found in approximately 50% of melanoma cases, plays a crucial role in the activation of the MAPK/ERK signaling pathway, which promotes tumor cell proliferation. This study aimed to evaluate its impact on the melanoma immune microenvironment and therapeutic responses, particularly focusing on immunogenic cell death (ICD), a pivotal cytotoxic process triggering anti-tumor immune responses. Through comprehensive in silico analysis of the Cancer Genome Atlas data, we explored the association between the BRAFV600E mutation, immune subtype dynamics, and tumor mutation burden (TMB). Our findings revealed that the mutation correlated with a lower TMB, indicating a reduced generation of immunogenic neoantigens. Investigation into immune subtypes reveals an exacerbation of immunosuppression mechanisms in BRAFV600E-mutated tumors. To assess the response to ICD inducers, including doxorubicin and Me-ALA-based photodynamic therapy (PDT), compared to the non-ICD inducer cisplatin, we used distinct melanoma cell lines with wild-type BRAF (SK-MEL-2) and BRAFV600E mutation (SK-MEL-28, A375). We demonstrated a differential response to PDT between the WT and BRAFV600E cell lines. Further transcriptomic analysis revealed upregulation of IFNAR1, IFNAR2, and CXCL10 genes associated with the BRAFV600E mutation, suggesting their involvement in ICD. Using a gene reporter assay, we showed that PDT robustly activated the IFN-1 pathway through cGAS-STING signaling. Collectively, our results underscore the complex interplay between the BRAFV600E mutation and immune responses, suggesting a putative correlation between tumors carrying the mutation and their responsiveness to therapies inducing the IFN-1 pathway, such as the ICD inducer PDT, possibly mediated by the elevated expression of IFNAR1/2 receptors.

The Potential of Photodynamic Therapy Using Solid Lipid Nanoparticles with Aluminum Phthalocyanine Chloride as a Nanocarrier for Modulating Immunogenic Cell Death in Murine Melanoma In Vitro.

Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells (DCs) and consequently modulate the immune response in the tumor microenvironment. However, PDT still has limitations, such as the activity of photosensitizers in aqueous media and poor bioavailability. Therefore, a new photosensitizer system, SLN-AlPc, has been developed to improve the therapeutic efficacy of PDT. In vitro experiments showed that the light-excited nanocarrier increased ROS production in murine melanoma B16-F10 cells and modulated the profile of DCs. PDT induced cell death accompanied by the exposure of DAMPs and the formation of autophagosomes. In addition, the DCs exposed to PDT-treated B16-F10 cells exhibited morphological changes, increased expression of MHCII, CD86, CD80, and production of IL-12 and IFN-γ, suggesting immune activation towards an antitumor profile. These results indicate that the SLNs-AlPc protocol has the potential to improve PDT efficacy by inducing ICD and activating DCs.