Detection and diversity of gastrointestinal viruses in wastewater from Caracas, Venezuela, 2021-2022.

Gastrointestinal viruses (GIV) are an important cause of childhood morbidity and mortality, particularly in developing countries. Their epidemiological impact in Venezuela during the COVID-19 pandemic remains unclear. GIV can also be detected in domestic sewage. Ninety-one wastewater samples from urban areas of Caracas collected over 12 months and concentrated by polyethylene-glycol-precipitation, were analyzed by multiplex reverse-transcription-PCR for rotavirus/calicivirus/astrovirus and enterovirus/klassevirus/cosavirus, and monoplex-PCR for adenovirus and Aichi virus. The overall frequency of virus detection was 46.2%, fluctuating over months, and peaking in the rainy season. Adenoviruses circulated throughout the year, especially type F41, and predominated (52.7%) over caliciviruses (29.1%) that peaked in the rainy months, rotaviruses (9.1%), cosaviruses (5.5%), astroviruses and enteroviruses (1.8%). Aichi-virus and klassevirus were absent. Rotavirus G9/G12, and P[4]/P[8]/P[14] predominated. The occurrence of GIV in wastewater reflects transmission within the population of Caracas and the persistence of a potential public health risk that needs to be adequately monitored.

Risk assessment of food contact materials.

Bisphenol A (BPA) is authorised for use as a chemical compound for the production of plastic food contact materials (FCMs) under Regulation (EU) No 10/2011. But according to requirements of the Regulation (EU) No 2018/213, BPA has been banned in the manufacture of polycarbonate drinking cups or feeding bottles intended for infants and young children. Food has been identified as the main source of human exposure to BPA, followed by dermal absorption, air and dust inhalation, revealing ubiquitous and continuous contact with BPA. Considering that BPA is able to enter the food chain through the migration from food packaging into foodstuffs, assessment of dietary exposure is necessary for accurate estimations and identification of potential exposure from food sources. In 2015, EFSA set a temporary tolerable daily intake (TDI) for BPA of 4 µg/kg body weight (bw) per day and concluded that no health concern from BPA exposure for any age group was to be expected. In 2023, EFSA has re-evaluated BPA safety and the new TDI was reduced by a factor of 20,000 resulting in a TDI of 0.2 ng/kg bw per day. In this case, the CEP Panel concluded that there is a health concern from dietary exposure to BPA. Amongst others, the BfR identified several points of criticism which, in the opinion of the BfR, call into question the risk assessment carried out by EFSA. The BfR derived a TDI of 200 ng/kg bw per day and suggests taking this into account for risk assessment. In the proposed EU-FORA programme, the fellow had the opportunity to gain experience in the exposure assessment and then integrate the data together with the BfR hazard assessment to perform a comprehensive risk assessment. As second objective of the work programme, the fellow was in charge of performing a toxicokinetic analysis in an attempt to correlate external exposure with urinary BPA levels.

Effects of internet-based, psychosocial, and early medical interventions on professional burnout in health care workers: Systematic literature review and meta-analysis.

Background: The prevalence of professional burnout increased among healthcare workers during the coronavirus 2019 (COVID-19) pandemic, with negative effects on their mental health. Consequently, research interest in methods to decrease the prevalence of burnout and reduce the effects of burnout on healthcare workers has increased. Objective: This study was designed to evaluate the effects of Internet-based, psychosocial, and early medical interventions on professional burnout among healthcare workers. Methodology: This systematic review and meta-analysis involved 8004 articles identified from four databases: Cochrane, Web of Science, PubMed/Medline, and clinical trials. Results: Four articles were included in the systematic review, of which two could be meta-analyzed. The pooled effect of the group of interventions compared to control conditions was not statistically significant. Discussion: Evaluating therapeutic effectiveness requires more clinical trials that allow its evaluation. Although we did not find improvements in the three intervention categories, the methodological heterogeneity in each intervention and the need for a standardized intervention guide for managing and decreasing professional burnout, subject to the evaluation of its impact, are highlighted.

Molecular characterization of human adenovirus causing infantile acute gastroenteritis in Venezuela before and after rotavirus vaccine implementation.

Human adenoviruses (HAdV) of species F are commonly involved in pediatric acute gastroenteritis (AGE). The real impact on Venezuelan health is unknown. To investigate the prevalence and molecular diversity of HAdV in Venezuela, 630 fecal samples collected from children with AGE in 3 cities, from 2001 to 2013, were tested by PCR. Species F and types F40/41 were identified by REA. HAdV was detected in 123 cases (19.5%), most from outpatient females under 24 months old. A progressive and substantial increase in the detection rate was observed over time, significantly higher in rotavirus vaccinated than unvaccinated children (28.4% vs. 9.5%, P = 0.00019). Phylogenetic analysis of 28 randomly selected genomes showed high similarity among HAdV-F40/41 and those worldwide. HAdV-F of type 41 prevailed (79.8%) and clustered into 2 intratypic major clades. The significant involvement of HAdV-F41 in AGE suggests the importance of actively monitoring viral agents other than rotavirus, especially after vaccine introduction.

Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain.

Ex vivo-loaded white blood cells (WBC) can transfer cargo to pathological foci in the central nervous system (CNS). Here we tested affinity ligand driven in vivo loading of WBC in order to bypass the need for ex vivo WBC manipulation. We used a mouse model of acute brain inflammation caused by local injection of tumor necrosis factor alpha (TNF-α). We intravenously injected nanoparticles targeted to intercellular adhesion molecule 1 (anti-ICAM/NP). We found that (A) at 2 h, >20% of anti-ICAM/NP were localized to the lungs; (B) of the anti-ICAM/NP in the lungs >90% were associated with leukocytes; (C) at 6 and 22 h, anti-ICAM/NP pulmonary uptake decreased; (D) anti-ICAM/NP uptake in brain increased up to 5-fold in this time interval, concomitantly with migration of WBCs into the injured brain. Intravital microscopy confirmed transport of anti-ICAM/NP beyond the blood-brain barrier and flow cytometry demonstrated complete association of NP with WBC in the brain (98%). Dexamethasone-loaded anti-ICAM/liposomes abrogated brain edema in this model and promoted anti-inflammatory M2 polarization of macrophages in the brain. In vivo targeted loading of WBC in the intravascular pool may provide advantages of coopting WBC predisposed to natural rapid mobilization from the lungs to the brain, connected directly via conduit vessels.

Espectroscopía visible y del infrarrojo cercano para el análisis de nutrientes en tejido vegetal de caña de azúcar para producción de panela

La espectroscopía de reflectancia en el infrarrojo cercano (NIRS) es una tecnología rápida, multiparamétrica, amigable con el ambiente, de bajo costo y gran exactitud, para el análisis de diversos componentes en alimentos, en suelo y en agricultura. El objetivo del presente estudio fue construir modelos de calibración NIRS, para la predicción de nutrientes en tejido vegetal de caña de azúcar, para producción de panela, cultivada en la región de la Hoya del río Suárez. Un total de 416 muestras de tejido fueron escaneadas en el segmento espectral Vis-NIR. El análisis quimiométrico, se realizó con el software WinISI V4.10, aplicando la regresión de mínimos cuadrados parciales modificados, junto a una validación cruzada. Se evaluaron cuatro modelos con diferentes tratamientos matemáticos y el rendimiento de las calibraciones, se hizo por medio de la validación externa, analizando las medidas de bondad de ajuste, como el coeficiente de determinación de la predicción, el error estándar de la predicción ajustado por el sesgo y la desviación predictiva residual. Los resultados muestran que el modelo de calibración para N presentó el mayor poder predictivo. Para macronutrientes, las calibraciones, con mayor poder predictivo, fueron P y K y para micronutrientes, el modelo para B, mientras que para Cu presentó el más bajo poder predictivo. Se encontraron modelos adecuados para la predicción de los contenidos de N, Ca y P; para los demás nutrientes, se recomienda ampliar el conjunto de calibración.

Near Infrared Reflectance Spectroscopy (NIRS) is a fast, multiparametric, environmentally friendly, low-cost, and highly accurate technology for the analysis of components in food, soil, and agriculture. The purpose of this study was to generate NIRS calibration models for the prediction of nutrients in plant tissue of sugarcane to panela production cultivated in the Hoya del Río Suárez region. A total of 416 tissue samples were scanned in Vis-NIR spectral segment. Chemometric analysis was performed with the WinISI V4.10 software applying modified partial least squares regression with cross-validation. Four models with different mathematical treatments were evaluated, and the performance of calibrations was made through external validation analyzing the goodness-of-fit measures as prediction determination coefficient, standard error of the bias-adjusted prediction, and residual predictive deviation. The results showed that the calibration model for N had the highest predictive power. For macronutrients, the calibrations with the best predictive power were for P and K, and micronutrients for B, while Cu presented the lowest predictive power. Adequate models were found for the prediction of N, Ca, and P. In the case of the other nutrients, it is recommended to expand the calibration set.

Delayed mechanical ventilation with prolonged high-flow nasal cannula exposure time as a risk factor for mortality in acute respiratory distress syndrome due to SARS-CoV-2.

In a high proportion of patients, infection by COVID-19 progresses to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation (IMV) and admission to an intensive care unit (ICU). Other devices, such as a high-flow nasal cannula (HFNC), have been alternatives to IMV in settings with limited resources. This study evaluates whether HFNC exposure time prior to IMV is associated with mortality. This observational, analytical study was conducted on a historical cohort of adults with ARDS due to SARS-CoV-2 who were exposed to HFNC and subsequently underwent IMV. Univariate and multivariate logistic regression was used to analyze the impact of HFNC exposure time on mortality, controlling for multiple potential confounders. Of 325 patients with ARDS, 41 received treatment with HFNC for more than 48 h before IMV initiation. These patients had a higher mortality rate (43.9% vs. 27.1%, p: 0.027) than those using HFNC < 48 h. Univariate analysis evidenced an association between mortality and HFNC ≥ 48 h (OR 2.16. 95% CI 1.087-4.287. p: 0.028). Such an association persisted in the multivariable analysis (OR 2.21. 95% CI 1.013-4.808. p: 0.046) after controlling for age, sex, comorbidities, basal severity of infection, and complications. This study also identified a significant increase in mortality after 36 h in HFNC (46.3%, p: 0.003). In patients with ARDS due to COVID-19, HFNC exposure ≥ 48 h prior to IMV is a factor associated with mortality after controlling multiple confounders. Physiological mechanisms for such an association are need to be defined.

Association of genetic polymorphisms in detoxifying systems and urinary metal(loid) levels with excess body weight among Spanish children: A proof-of-concept study.

Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6-12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children.

Effect of exposure to endocrine disrupting chemicals in obesity and neurodevelopment: The genetic and microbiota link.

Current evidence highlights the importance of the genetic component in obesity and neurodevelopmental disorders (attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID)), given that these diseases have reported an elevated heritability. Additionally, environmental stressors, such as endocrine disrupting chemicals (EDCs) have been classified as obesogens, neuroendocrine disruptors, and microbiota disrupting chemicals (MDCs). For this reason, the importance of this work lies in examining two possible biological mechanistic pathways linking obesity and neurodevelopmental/behavioural disorders: EDCs - gene and EDCs - microbiota interactions. First, we summarise the shared mechanisms of action of EDCs and the common genetic profile in the bidirectional link between obesity and neurodevelopment. In relation to interaction models, evidence from the reviewed studies reveals significant interactions between pesticides/heavy metals and gene polymorphisms of detoxifying and neurotransmission systems and metal homeostasis on cognitive development, ASD and ADHD symptomatology. Nonetheless, available literature about obesity is quite limited. Importantly, EDCs have been found to induce gut microbiota changes through gut-brain-microbiota axis conferring susceptibility to obesity and neurodevelopmental disorders. In view of the lack of studies assessing the impact of EDCs - gene interactions and EDCs - mediated dysbiosis jointly in obesity and neurodevelopment, we support considering genetics, EDCs exposure, and microbiota as interactive factors rather than individual contributors to the risk for developing obesity and neurodevelopmental disabilities at the same time.

Curtobacterium, A Foliar Pathogen Isolated from Maize in Central Argentina.

Plant pathogens, such as fungi, bacteria, and viruses, can cause serious damage to crops and significantly reduce yield and quality. Bacterial diseases of agronomic crops, however, have been little studied. The present study aims to isolate and identify bacteria recovered from symptomatic maize (Zea mays) leaves collected from field samples in the province of Cordoba, Argentina. Bacterial strains were identified using whole-cell matrix-assisted laser-desorption-ionization-time-off light mass spectrometry and 16S rDNA sequencing. Members of the genera Exiguobacterium and Curtobacterium were dominant in the studied vegetal material. Two strains (RC18-1/2 and RC18-3/1) were selected for further studies. The pathogenicity test showed that plants inoculated with Curtobacterium sp. RC18-1/2 exhibited the same symptoms as those previously detected in the field. To our knowledge, this study provides the first evidence about the isolation of a Curtobacterium pathogenic strain in maize. Effective crop disease management will require the use of integrated strategies, such as resistant cultivars and/or biocontrol agents.

Effects of genetic polymorphisms in body mass index according to dietary exposure to bisphenols and parabens.

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16-24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (ß) = 1.20, 95% CI: 1.04-1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (ß) = 1.27, 95% CI: 1.03-1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (ß) = 1.33, 95% CI: 1.08-1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure.

Role of endocrine disrupting chemicals in children's neurodevelopment.

Environmental stressors, like endocrine disrupting chemicals (EDC), are considered important contributors to the increased rates of neurodevelopmental dysfunctions. Considering the cumulative research on adverse neurodevelopmental effects associated with prenatal exposure to EDC, the purpose of this study was to review the available limited literature about the effects of postnatal exposure to EDC on child neurodevelopment and behaviour. Despite widespread children's exposure to EDC, there are a limited number of epidemiological studies on the association of this exposure with neurodevelopmental disorders, in particular in the postnatal period. The available research suggests that postnatal EDC exposure is related to adverse neurobehavioral outcomes in children; however the underlying mechanisms of action remain unclear. Timing of exposure is a key factor determining potential neurodevelopmental consequences, hence studying the impact of multiple EDC co-exposure in different vulnerable life periods could guide the identification of sensitive subpopulations. Most of the reviewed studies did not take into account sex differences in the EDC effects on children neurodevelopment. We believe that the inclusion of sex in the study design should be considered as the role of EDC on children neurodevelopment are likely sex-specific and should be taken into consideration when determining susceptibility and potential mechanisms of action.

Lesión autoinducida por el paciente en la pandemia por COVID-19, una situación de recursos limitados. Revisión de tema / Patient self-induced lung injury in the COVID-19 pandemic, a resource-limited situation. Review

La ventilación mecánica invasiva (VMI) es una estrategia importante de manejo en el paciente con síndrome de dificultad respiratoria aguda (SDRA). En la pandemia por COVID-19 los innumerables casos de SDRA han llevado al uso de otros dispositivos de oxigenación no invasivos, que han expuesto al paciente a mayor esfuerzo respiratorio, evidenciándose lo que se conoce como "lesión pulmonar autoinducida por el paciente" (P-SILI, por sus siglas en inglés). El objetivo de esta revisión es exponer la evidencia científica disponible relacionada con este fenómeno en el contexto de la pandemia por COVID-19. Se realizó una revisión narrativa de la literatura del tema mencionado; la búsqueda se realizó hasta septiembre de 2020 en las bases de datos Medline, Embase, Central y Google Académico y se seleccionaron los artículos más representativos. La VMI es fundamental en el tratamiento del SDRA, pero en manos inexpertas puede generar lesión pulmonar por diferentes mecanismos. Por otro lado, el uso de otros dispositivos de ventilación no invasiva como la cánula nasal de alto flujo, podrían favorecer la P-SILI, una condición que al parecer, perpetúa la inflamación y lesión pulmonar inicial al paciente en respiración espontánea. La información disponible aún es insuficiente.

In the COVID-19 pandemic, invasive mechanical ventilation is an important management strategy in handling patients with acute respiratory distress syndrome (ARDS). The multitudinous ARDS cases have resulted in use of other non-invasive oxygenation devices, which expose the patient to a greater breathing effort, developing patient self-induced lung injury (PSILI). The goal of the present review is to present the available scientific evidence associated with this phenomenon in the context of the COVID-19 pandemic. A narrative literature review on the topic was performed with a search in MEDLINE, EMBASE, CENTRAL and Google Scholar databases until September 2020. Based on the abstracts the most representative articles were selected. Invasive mechanical ventilation (IVM) is essential in ARDS, however, in unexperienced hands it can lead to lung injury by different mechanisms. In other side, ARDS patients have been managed with other non-invasive ventilation devices, such as high-flow nasal cannula, which favor PSILI; a condition that apparently perpetuates initial lung lesion and inflammation by different mechanisms, when patients are submitted to spontaneous breathing. The information is still insufficient.

Metabolic pathways, alterations in miRNAs expression and effects of genetic polymorphisms of bisphenol a analogues: A systematic review.

Bisphenol A (BPA) is one of the most common endocrine disruptors found in the environment and its harmful health effects in humans and wildlife have been extensively reported One of the main aims of this review was to examine the metabolic pathways of BPA and BPA substitutes and the endocrine disrupting properties of their metabolites. According to the available literature, phase I and phase II metabolic reactions play an important role in the detoxification process of bisphenols (BPs), but their metabolism can also lead to the formation of highly reactive metabolites. The second part of this work addresses the associations between exposure to BPA and its analogues with the alterations in miRNAs expression and the effects of single nucleotide polymorphisms (SNPs). Available scientific evidence shows that BPs can dysregulate the expression of several miRNAs, and in turn, these miRNAs could be considered as epigenetic biomarkers to prevent the development of a variety of BP-mediated diseases. Interestingly, genetic polymorphisms are able to modify the relationship of BPA exposure with the risk of adverse health effects, suggesting that interindividual genetic differences modulate the susceptibility to the effects of environmental contaminants.

La educación en el estudiante de medicina. La transición de la universidad al hospital / Education in medical students. The transition from the university to the hospital

Resumen La acreditación en alta calidad otorgada a las instituciones universitarias para sus facultades de medicina no representa la calidad en educación durante el periodo de prácticas en las instituciones hospitalarias. Debido a la importancia de esta fase en el proceso académico del estudiante de medicina, es necesario considerar un cambio en el proceso educativo. Hay que explorar nuevos modelos pedagógicos fundamentados en el aprendizaje basado en problemas y con el uso de nuevas tecnologías para lograr una óptima formación médica.

Abstract The high-quality accreditation granted to universities for their medical schools does not represent the quality of education during practical rotations in the hospitals. Due to the importance of this phase in the medical students' academic process, a change in the educational process must be considered. New pedagogical models founded on problem-based learning and using new technologies to achieve optimal medical training must be explored.

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness.

Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

Enfermedad por coronavirus (COVID-19) en embarazo, parto y lactancia / Coronavirus disease 2019 (COVID-19) in pregnancy, childbirth, and lactation

Resumen La pandemia de COVID-19 ha generado múltiples interrogantes respecto a su comportamiento en la población gestante y en los resultados peri- natales. Los datos disponibles sobre la infección por SARS-CoV-2 en el embarazo son limitados. Se realizó una búsqueda de artículos publicados en las bases de datos PubMed, Scopus y Embase utilizando los términos asociados a COVID-19 y embarazo, hasta el 4 de abril de 2020. En la revisión de 43 artículos se tuvieron en cuenta 25, que corresponden a reportes y series de casos, revisiones y guías de manejo. No se encontró evidencia concluyente respecto a transmisión vertical o a mal resultado perinatal en enfermedad leve o moderada. Los síntomas clínicos de COVID-19 en el embarazo no varían de los de la población general. Existe controversia en cuanto a lactancia materna. En conclusión, existe escasa evidencia de calidad sobre el efecto de COVID-19 en el embarazo. Dada la ausencia de evidencia concluyente se plantea la realización de un registro nacional de COVID-19 y embarazo para Colombia y la región.

Abstract The COVID-19 pandemic has raised a number of questions regarding its behavior in the pregnant population and perinatal outcomes. Currently, data available on the COVID-19 infection during pregnancy is limited. A search was conducted of all the articles published in the PubMed, Scopus, and Embase databases, using terms associated with COVID-19 and pregnancy from January 2017 to 04 April 2020, and including all the types of articles published on COVID-19 and pregnancy. The review of 43 articles, of which 23 were considered, demonstrated that all refer to case reports, case series and reviews and management guides. No conclusive evidence was found with respect to vertical transmission or poor perinatal outcome in mild-moderate disease. The clinical symptoms of COVID-19 during pregnancy do not vary from those in the general population. Controversy exists with regards to breastfeeding. In conclusion, quality evidence is scarce on the effect of COVID-19 during pregnancy. Given the lack of conclusive evidence, a national registry is proposed on COVID-19 and pregnancy for Colombia.

Centrally Acting Angiotensin-Converting Enzyme Inhibitor Suppresses Type I Interferon Responses and Decreases Inflammation in the Periphery and the CNS in Lupus-Prone Mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ damage. Neuropsychiatric lupus (NPSLE) is one of the most common manifestations of human SLE, often causing depression. Interferon-α (IFNα) is a central mediator in disease pathogenesis. Administration of IFNα to patients with chronic viral infections or cancers causes depressive symptoms. Angiotensin-converting enzyme (ACE) is part of the kallikrein-kinin/renin-angiotensin (KKS/RAS) system that regulates many physiological processes, including inflammation, and brain functions. It is known that ACE degrades bradykinin (BK) into inactive peptides. We have previously shown in an in vitro model of mouse bone-marrow-derived dendritic cells (BMDC) and human peripheral blood mononuclear cells that captopril (a centrally acting ACE inhibitor-ACEi) suppressed Type I IFN responsive gene (IRG) expression. In this report, we used the MRL/lpr lupus-prone mouse model, an established model to study NPSLE, to determine the in vivo effects of captopril on Type I IFN and associated immune responses in the periphery and brain and effects on behavior. Administering captopril to MRL/lpr mice decreased expression of IRGs in brain, spleen and kidney, decreased circulating and tissue IFNα levels, decreased microglial activation (IBA-1 expression) and reduced depressive-like behavior. Serotonin levels that are decreased in depression were increased by captopril treatment. Captopril also reduced autoantibody levels in plasma and immune complex deposition in kidney and brain. Thus, ACEi's may have potential for therapeutic use for systemic and NPSLE.

Tobacco smoke and morphine alter peripheral and CNS inflammation following HIV infection in a humanized mouse model.

Tobacco smoking is common in HIV-infected patients, and is prevalent among intravenous opiate abusers. Conversely, intravenous opiate abusers are more likely HIV-infected, and opiate abuse is associated with more severe neuroinflammation. Given the coincident use of tobacco smoking among HIV-infected intravenous drug users (IVDUs), we set out to study the effects of smoke exposure, chronic morphine administration, and HIV infection using the NSG humanized mouse model. Our results show that smoke, morphine, and the combination promotes the decline in CD4+ T cells in HIV-infected mice. Further, chronic morphine administration increases the numbers of circulating CD8+ T cells which express the inhibitory receptor PD-1, as well as the cytolytic proteins perforin and granzyme B in the infected mice. We also found that the combination of smoke and morphine inhibited the expression of IL-1α, IL-4 and IL-17A. Finally, the combination of smoke and morphine exposure induces microglial activation following infection, as well as in the absence of HIV infection. To our knowledge, this is the first report to assess the combined effects of smoke and chronic morphine exposure on the inflammation associated with HIV infection, and demonstrate that these two insults exert significant neuroinflammatory activity.

Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.

Drug targeting to inflammatory brain pathologies such as stroke and traumatic brain injury remains an elusive goal. Using a mouse model of acute brain inflammation induced by local tumor necrosis factor alpha (TNFα), we found that uptake of intravenously injected antibody to vascular cell adhesion molecule 1 (anti-VCAM) in the inflamed brain is >10-fold greater than antibodies to transferrin receptor-1 and intercellular adhesion molecule 1 (TfR-1 and ICAM-1). Furthermore, uptake of anti-VCAM/liposomes exceeded that of anti-TfR and anti-ICAM counterparts by ∼27- and ∼8-fold, respectively, achieving brain/blood ratio >300-fold higher than that of immunoglobulin G/liposomes. Single-photon emission computed tomography imaging affirmed specific anti-VCAM/liposome targeting to inflamed brain in mice. Intravital microscopy via cranial window and flow cytometry showed that in the inflamed brain anti-VCAM/liposomes bind to endothelium, not to leukocytes. Anti-VCAM/LNP selectively accumulated in the inflamed brain, providing de novo expression of proteins encoded by cargo messenger RNA (mRNA). Anti-VCAM/LNP-mRNA mediated expression of thrombomodulin (a natural endothelial inhibitor of thrombosis, inflammation, and vascular leakage) and alleviated TNFα-induced brain edema. Thus VCAM-directed nanocarriers provide a platform for cerebrovascular targeting to inflamed brain, with the goal of normalizing the integrity of the blood-brain barrier, thus benefiting numerous brain pathologies.