Potential use of sludge from El Ferrol Bay (Chimbote, Peru) for the production of lipids in the culture of Scenedesmus acutus (Meyen, 1829).

Despite the extensive development of microalgae biotechnology, it still requires new methodologies to lower production costs, especially in the field of biofuel production. Therefore, innovative methods that facilitate operations and enable cost-effective production are important in driving this industry. In this study, we propose a new low-cost and easy-to-use procedure, addressed to the generation of a culture medium for Scenedesmus acutus. The medium was obtained by thermal reduction of a sludge sample from El Ferrol Bay (Chimbote, Peru), whereby we obtained an aqueous medium. Our results indicated that the aqueous medium incorporates all necessary nutrients for microalgae production; allowing a maximum biomass of 0.75 ± 0.07 g/L with 60% of the medium; while high lipids production (59.42 ± 6.16%) was achieved with 20%. Besides, we quantified, in the experimental medium and at the end of the cultures, the levels of inorganic nutrients such as ammonium, nitrites, nitrates, and phosphates; in addition to COD and TOC, which were significantly reduced ( p < 0.05) after 7 days of culture, mainly in the treatment with 20%. These results suggest tremendous potential for sludge reuse, which also entails a cost reduction in microalgae biomass production, with additional positive impacts on large-scale application over highly polluted environments.

Fungicide ingestion reduces net energy gain and microbiome diversity of the solitary mason bee.

Fungicides are frequently used during tree fruit bloom and can threaten insect pollinators. However, little is known about how non-honey bee pollinators such as the solitary bee, Osmia cornifrons, respond to contact and systemic fungicides commonly used in apple production during bloom. This knowledge gap limits regulatory decisions that determine safe concentrations and timing for fungicide spraying. We evaluated the effects of two contact fungicides (captan and mancozeb) and four translaminar/plant systemic fungicides (cyprodinil, myclobutanil, penthiopyrad, and trifloxystrobin) on larval weight gain, survival, sex ratio, and bacterial diversity. This assessment was carried out using chronic oral ingestion bioassays where pollen provisions were treated with three doses based on the currently recommended field use dose (1X), half dose (0.5X), and low dose (0.1X). Mancozeb and penthiopyrad significantly reduced larval weight and survival at all doses. We then sequenced the 16S gene to characterize the larvae bacteriome of mancozeb, the fungicide that caused the highest mortality. We found that larvae fed on mancozeb-treated pollen carried significantly lower bacterial diversity and abundance. Our laboratory results suggest that some of these fungicides can be particularly harmful to the health of O. cornifrons when sprayed during bloom. This information is relevant for future management decisions about the sustainable use of fruit tree crop protection products and informing regulatory processes that aim to protect pollinators.

Thrombotic risk assessed by PAI-1 in patients with COVID-19: The influence of hyperglycemia and diabetes mellitus.

OBJECTIVE: To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM. METHODS: A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA. RESULTS: The mean age was 59.4±16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8-315.9) vs 158.1 (113.4-201.4) ng/mL; p=0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r=0.284, p=0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19. CONCLUSION: Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Strategies to prevent, diagnose and treat kidney disease related to systemic arterial hypertension: a narrative review from the Mexican Group of Experts on Arterial Hypertension.

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.

Lung Ultrasound Elastography by SWE2D and "Fibrosis-like" Computed Tomography Signs after COVID-19 Pneumonia: A Follow-Up Study.

The aim of this study was to assess the shear wave velocity by LUS elastography (SWE2D) for the evaluation of superficial lung stiffness after COVID-19 pneumonia, according to "fibrosis-like" signs found by Computed Tomography (CT), considering the respiratory function. Seventy-nine adults participated in the study 42 to 353 days from symptom onset. Paired evaluations (SWE2D and CT) were performed along with the assessment of arterial blood gases and spirometry, three times with 100 days in between. During the follow-up and within each evaluation, the SWE2D velocity changed over time (MANOVA, p < 0.05) according to the extent of "fibrosis-like" CT signs by lung lobe (ANOVA, p < 0.05). The variability of the SWE2D velocity was consistently related to the first-second forced expiratory volume and the forced vital capacity (MANCOVA, p < 0.05), which changed over time with no change in blood gases. Covariance was also observed with age and patients' body mass index, the time from symptom onset until hospital admission, and the history of diabetes in those who required intensive care during the acute phase (MANCOVA, p < 0.05). After COVID-19 pneumonia, SWE2D velocity can be related to the extent and regression of "fibrotic-like" involvement of the lung lobes, and it could be a complementary tool in the follow-up after COVID-19 pneumonia.

[Severe post-COVID-19 dialysis dependence and inpatient acute kidney injury]. / Dependencia a diálisis posterior a COVID-19 grave y lesión renal aguda intrahospitalaria.

Background: COVID-19 challenged our health system, within the broad clinical spectrum acute kidney injury was presented as a catastrophic event, acute kidney injury and the risk of dependency after dialysis constitute a clinical problem with high repercussions in the funcionality. Objective: To identify risk factors for dialysis dependence after acute kidney injury from COVID-19. Material and methods: A retrospective observational cohort study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, of the Mexican Institute of Social Security, from March 2020 to March 2021. 317 patients were included, we performed descriptive statistics, we compared differences between the stages of acute kidney injury, finding a difference in obesity with a frequency of 2.2% in stage 1, 20.82% stage 2 and 14.51% stage 3, with p value = 0.018. Results: We found dialysis dependence one year after hospital-acquired acute kidney injury induced by COVID-19 in 58 patients (18.9%), we analyzed by KDIGO stage, in those patients who had AKI KDIGO 1 (2.83%) it depended on dialysis at one year, in the KDIGO stage 2 (3.78%), in the KDIGO stage 3 (11.67%). Conclusions: Our study allowed us to identify that the risk factors associated with dialysis dependence are: male gender, type 2 diabetes mellitus, obesity, cardiovascular disease.

Introducción: la COVID-19, retó a nuestro sistema de salud, dentro del amplio espectro clínico la lesión renal aguda se presentó como un evento catastrófico, la lesión renal aguda y el riesgo de dependencia posterior a diálisis constituye un problema clínico con alta repercusión en la funcionalidad. Objetivo: identificar los factores de riesgo para la dependencia a diálisis posterior a lesión renal aguda por COVID-19. Material y métodos: se realizó un estudio de cohorte observacional retrospectivo en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social, del periodo de marzo del 2020 a marzo del 2021. Se incluyeron 317 pacientes, realizamos estadística descriptiva, comparamos diferencias entre los estadios de lesión renal aguda encontrando diferencia en obesidad con frecuencia de 2.2% en estadio 1, de 20.82% estadio 2 y de 14.51% estadio 3, con valor p = 0.018. Resultados: encontramos la dependencia a diálisis a un año posterior a lesión renal aguda intrahospitalaria inducida por COVID-19 en 58 pacientes (18.9%), analizamos por estadio de KDIGO, en aquellos pacientes que cursaron con LRA KDIGO 1 (2.83%) dependió de diálisis a un año, en el estadio KDIGO 2 (3.78%), en el estadio KDIGO 3 (11.67%). Conclusiones: nuestro estudio permitió identificar que los factores de riesgo que se asocian con dependencia a diálisis son: sexo masculino, diabetes mellitus tipo 2, obesidad, enfermedad cardiovascular.

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Ciberbullying en adolescentes que consultan en un hospital pediátrico de referencia: frecuencia y formas de victimización

Introducción: la utilización de internet conlleva riesgos, como la aparición de las diferentes formas de acoso o ciberbullying. Objetivos: Determinar la frecuencia de diferentes formas de victimización por ciberbullying en adolescentes. Materiales y Métodos: Estudio observacional, descriptivo, prospectivo. Adolescentes de 12 a 18 años edad, que concurrieron al Hospital pediátrico, fueron invitados a participar de una encuesta vía formulario de Google, enviada por WhatsApp, utilizando un cuestionario validado en español en el periodo dé marzo a octubre del 2020. Variables: datos demográficos, exposición a mensajes amenazantes, imágenes humillantes, bromas, rumores, difusión online de información personal o imágenes de índole sexual y segregación del grupo. Los resultados fueron analizados en SPSS. El comité de ética aprobó el estudio con consentimiento informado de los participantes y sus padres. Resultados: Fueron incluidos 406 encuestados, con edad media 15,4±1.99. El 60,1% de sexo femenino, 88,4% de residencia urbana. El 22,5% sufrieron al menos un episodio de ciberbullying. El 19,7% y 26,6% recibieron mensajes amenazantes mensajes y redes sociales respectivamente. El 14,5% fueron humillados con imágenes en internet y el 30,3% con exposición de datos personales. El 10,3% fueron despojados de sus contraseñas. El 7,9 que han sido grabados en situaciones humillantes y el 1% ha sido grabado en situaciones de violencia física. 49,3% de los encuestados han sido apartados del grupo. Conclusión: El 22,5% de los adolescentes fueron objeto de algún tipo de acoso en línea. Los más frecuentes fueron la exposición de información personal y segregación del grupo.

Introduction: the use of the Internet carries risks, such as the appearance of different forms of harassment or cyberbullying. Objectives: To determine the frequency of different forms of cyberbullying victimization in adolescents. Materials and Methods: This was an observational, descriptive and prospective study. Adolescents from 12 to 18 years of age, who consulted at Pediatric Referral Hospital, were invited to participate in a survey via Google form, sent by WhatsApp, using a validated questionnaire in Spanish from March to October 2020. Variables: demographic data, exposure to threatening messages, humiliating images, jokes, rumors, online dissemination of personal information or images of a sexual nature, and exclusion from their peer group. The results were analyzed in SPSS. The ethics committee approved the study with the informed consent of the participants and their parents. Results: 406 respondents were included, with a mean age of 15.4 ± 1.99. 60.1% female, 88.4% urban residence. 22.5% suffered at least one episode of cyberbullying. 19.7% and 26.6% received threatening messages, vía instant messaging and social networks, respectively. 14.5% were humiliated with images on the internet and 30.3% with exposure of personal data. 10.3% were stripped of their passwords. 7.9% have been recorded in humiliating situations and 1% have been recorded in situations of physical violence. 49.3% of those surveyed have been excluded from their peer group. Conclusion : 22.5% of adolescents were subjected to some type of online bullying. The most frequent were the exposure of personal information and exclusion from their peer group.

CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting cyclin-dependent kinases 4 and 6 (CDK4/6), MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST models. EXPERIMENTAL DESIGN: Patient-matched MPNSTs and precursor lesions were examined by FISH, RNA sequencing, IHC, and Connectivity-Map analyses. Antitumor activity of CDK4/6 and MEK inhibitors was measured in MPNST cell lines, patient-derived xenografts (PDX), and de novo mouse MPNSTs, with the latter used to determine anti-PD-L1 response. RESULTS: Patient tumor analyses identified CDK4/6 and MEK as actionable targets for MPNST therapy. Low-dose combinations of CDK4/6 and MEK inhibitors synergistically reactivated the retinoblastoma (RB1) tumor suppressor, induced cell death, and decreased clonogenic survival of MPNST cells. In immune-deficient mice, dual CDK4/6-MEK inhibition slowed tumor growth in 4 of 5 MPNST PDXs. In immunocompetent mice, combination therapy of de novo MPNSTs caused tumor regression, delayed resistant tumor outgrowth, and improved survival relative to monotherapies. Drug-sensitive tumors that regressed contained plasma cells and increased cytotoxic T cells, whereas drug-resistant tumors adopted an immunosuppressive microenvironment with elevated MHC II-low macrophages and increased tumor cell PD-L1 expression. Excitingly, CDK4/6-MEK inhibition sensitized MPNSTs to anti-PD-L1 immune checkpoint blockade (ICB) with some mice showing complete tumor regression. CONCLUSIONS: CDK4/6-MEK inhibition induces a novel plasma cell-associated immune response and extended antitumor activity in MPNSTs, which dramatically enhances anti-PD-L1 therapy. These preclinical findings provide strong rationale for clinical translation of CDK4/6-MEK-ICB targeted therapies in MPNST as they may yield sustained antitumor responses and improved patient outcomes.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Physicians' Distress Related to Moral Issues and Mental Health In-Between Two Late Waves of COVID-19 Contagions.

In addition to the sanitary constrains implemented due to the pandemic, frontline physicians have faced increased workloads with insufficient resources, and the responsibility to make extraordinary clinical decisions. In 108 physicians who were at the forefront of care of patients with COVID-19 during the first two years of the pandemic, mental health, moral distress, and moral injury were assessed twice, in between two late waves of COVID-19 contagions, according to their adverse psychological reactions, in-hospital experience, sick leave due to COVID-19, quality of sleep, moral sensitivity, clinical empathy, resilience, and sense of coherence. Three months after the wave of contagions, the adverse emotional reactions and moral distress decreased, while moral injury persisted. Moral distress was related to clinical empathy, with influence from burnout and sick leave due to COVID-19, and moral injury was related to the sense of coherence, while recovery from moral distress was related to resilience. The results suggest that measures to prevent physician infection, as well as strengthening resilience and a sense of coherence, may be helpful to prevent persistent mental damage after exposure to a sanitary crisis.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort. DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay. RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all). CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update.

Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms.

Potential of ATR-FTIR-Chemometrics in Covid-19: Disease Recognition.

The COVID-19 pandemic has caused major disturbances to human health and economy on a global scale. Although vaccination campaigns and important advances in treatments have been developed, an early diagnosis is still crucial. While PCR is the golden standard for diagnosing SARS-CoV-2 infection, rapid and low-cost techniques such as ATR-FTIR followed by multivariate analyses, where dimensions are reduced for obtaining valuable information from highly complex data sets, have been investigated. Most dimensionality reduction techniques attempt to discriminate and create new combinations of attributes prior to the classification stage; thus, the user needs to optimize a wealth of parameters before reaching reliable and valid outcomes. In this work, we developed a method for evaluating SARS-CoV-2 infection and COVID-19 disease severity on infrared spectra of sera, based on a rather simple feature selection technique (correlation-based feature subset selection). Dengue infection was also evaluated for assessing whether selectivity toward a different virus was possible with the same algorithm, although independent models were built for both viruses. High sensitivity (94.55%) and high specificity (98.44%) were obtained for assessing SARS-CoV-2 infection with our model; for severe COVID-19 disease classification, sensitivity is 70.97% and specificity is 94.95%; for mild disease classification, sensitivity is 33.33% and specificity is 94.64%; and for dengue infection assessment, sensitivity is 84.27% and specificity is 94.64%.

Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Vegetative forms of Clostridium chauvoei trigger apoptotic and inflammatory responses on macrophages.

BACKGROUND: Clostridium chauvoei is a gram-positive, spore-forming, strictly anaerobic bacterium that causes blackleg, a disease that affects cattle by inducing fulminant myonecrosis, thereby leading to high and constant losses of cattle. Macrophages (Mɸs) are depleted in tissues infected with the vegetative form of C. chauvoei, but the mechanism remains partially known. Consequently, Mɸs may be a critical target in the pathogenicity of C. chauvoei. AIM: The objective of this work was to study the mechanism of death of mouse-primary Mɸs infected in vitro for 24 h with the vegetative form of C. chauvoei. METHODS: Mouse peritoneal Mɸs were infected in vitro with different multiplicities of infection (MOIs) of C. chauvoei (i.e., 5:1, 20:1, and 100:1). After 24 h post-infection, cell viability (MTT reduction assay), apoptosis (apoptotic bodies, DNA ladder, and Annexin V assays), and inflammatory cell response (iNOS and TNF-α expression) were assessed. RESULTS: All the MOIs investigated decreased cell viability. An MOI of 20:1 caused the highest production of apoptotic bodies and an electrophoretic DNA-ladder pattern typical of an apoptosis cell death process. These results were corroborated using the Annexin V-flow cytometry assay. Concurrently with apoptotic cell death, Mφs expressed iNOS and TNF-α. CONCLUSION: Inflammation-mediated apoptosis of Mφs can be a potential mechanism of evasion of the immune response used by C. chauvoei in tissues for depleting phagocytic cells at the site of infection.

Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. We therefore aimed to assess whether alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease. METHODS: We used the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using the urinary fractional excretion of lactulose-to-mannitol ratio (LMR). Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. The cohort was divided into a discovery cohort (n = 2472) and a validation cohort (n = 655). A regression model was used to assess microbial associations with the LMR. A random forest classifier algorithm was performed to assess microbial community contribution to barrier function. RESULTS: Individuals with impaired barrier function (LMR >0.025) had reduced alpha-diversity (Chao1 index, P = 4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, R2 = 0.001, P = 1.0e-3) compared with individuals with an LMR ≤0.025. When taxa were assessed individually, we identified 8 genera and 52 microbial pathways associated with an LMR >0.025 (q < 0.05). Four genera (decreased prevalence of Adlercreutzia, Clostridia UCG 014, and Clostridium sensu stricto 1 and increased abundance of Colidextribacter) and 8 pathways (including decreased biosynthesis of glutamate, tryptophan, and threonine) were replicated in the validation cohort. The random forest approach revealed that the bacterial community is associated with gut barrier function (area under the curve, 0.63; P = 1.4e-6). CONCLUSIONS: The gut microbiome community and pathways are associated with changes in gut barrier function. These findings may identify potential microbial targets to modulate gut barrier.

Mediterranean-Like Dietary Pattern Associations With Gut Microbiome Composition and Subclinical Gastrointestinal Inflammation.

BACKGROUND & AIMS: Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD. METHODS: As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters. RESULTS: DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota. CONCLUSIONS: Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.