A transient brain endothelial translatome response to endotoxin is associated with mild cognitive changes post-shock in young mice.

Sepsis-associated encephalopathy (SAE) is a common manifestation in septic patients that is associated with increased risk of long-term cognitive impairment. SAE is driven, at least in part, by brain endothelial dysfunction in response to systemic cytokine signaling. However, the mechanisms driving SAE and its consequences remain largely unknown. Here, we performed translating ribosome affinity purification (TRAP) and RNA-sequencing (TRAP-seq) from the brain endothelium to determine the transcriptional changes after an acute endotoxemic (LPS) challenge. We found that LPS induces a strong acute transcriptional response in the brain endothelium that partially correlates with the whole brain transcriptional response and suggested an endothelial-specific hypoxia response. Consistent with a critical role for the IL-6 pathway, loss of the main regulator of this pathway, SOCS3, leads to a broadening of the population of genes responsive to LPS, suggesting that an overactivation of the IL-6/JAK/STAT3 pathway leads to an increased transcriptional response that could explain our prior findings of severe brain injury in these mice. To identify any potential sequelae of this acute response, we performed brain TRAP-seq following a battery of behavioral tests in mice after apparent recovery. We found that the transcriptional response returns to baseline within days post-challenge. Despite the transient nature of the response, we observed that mice that recovered from the endotoxemic shock showed mild, sex-dependent cognitive impairment, suggesting that the acute brain injury led to sustained, non-transcriptional effects. A better understanding of the transcriptional and non-transcriptional changes in response to shock is needed in order to prevent and/or revert the devastating consequences of septic shock.

DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth.

Transient early endosome (EE)-mitochondria interactions can mediate mitochondrial iron translocation, but the associated mechanisms are still elusive. We showed that Divalent Metal Transporter 1 (DMT1) sustains mitochondrial iron translocation via EE-mitochondria interactions in triple-negative MDA-MB-231, but not in luminal A T47D breast cancer cells. DMT1 silencing increases labile iron pool (LIP) levels and activates PINK1/Parkin-dependent mitophagy in MDA-MB-231 cells. Mitochondrial bioenergetics and the iron-associated protein profile were altered by DMT1 silencing and rescued by DMT1 re-expression. Transcriptomic profiles upon DMT1 silencing are strikingly different between 2D and 3D culture conditions, suggesting that the environment context is crucial for the DMT1 knockout phenotype observed in MDA-MB-231 cells. Lastly, in vivo lung metastasis assay revealed that DMT1 silencing promoted the outgrowth of lung metastatic nodules in both human and murine models of triple-negative breast cancer cells. These findings reveal a DMT1-dependent pathway connecting EE-mitochondria interactions to mitochondrial iron translocation and metastatic fitness of breast cancer cells.

Using Wearable Devices and Speech Data for Personalized Machine Learning in Early Detection of Mental Disorders: Protocol for a Participatory Research Study.

BACKGROUND: Early identification of mental disorder symptoms is crucial for timely treatment and reduction of recurring symptoms and disabilities. A tool to help individuals recognize warning signs is important. We posit that such a tool would have to rely on longitudinal analysis of patterns and trends in the individual's daily activities and mood, which can now be captured through data from wearable activity trackers, speech recordings from mobile devices, and the individual's own description of their mental state. In this paper, we describe such a tool developed by our team to detect early signs of depression, anxiety, and stress. OBJECTIVE: This study aims to examine three questions about the effectiveness of machine learning models constructed based on multimodal data from wearables, speech, and self-reports: (1) How does speech about issues of personal context differ from speech while reading a neutral text, what type of speech data are more helpful in detecting mental health indicators, and how is the quality of the machine learning models influenced by multilanguage data? (2) Does accuracy improve with longitudinal data collection and how, and what are the most important features? and (3) How do personalized machine learning models compare against population-level models? METHODS: We collect longitudinal data to aid machine learning in accurately identifying patterns of mental disorder symptoms. We developed an app that collects voice, physiological, and activity data. Physiological and activity data are provided by a variety of off-the-shelf fitness trackers, that record steps, active minutes, duration of sleeping stages (rapid eye movement, deep, and light sleep), calories consumed, distance walked, heart rate, and speed. We also collect voice recordings of users reading specific texts and answering open-ended questions chosen randomly from a set of questions without repetition. Finally, the app collects users' answers to the Depression, Anxiety, and Stress Scale. The collected data from wearable devices and voice recordings will be used to train machine learning models to predict the levels of anxiety, stress, and depression in participants. RESULTS: The study is ongoing, and data collection will be completed by November 2023. We expect to recruit at least 50 participants attending 2 major universities (in Canada and Mexico) fluent in English or Spanish. The study will include participants aged between 18 and 35 years, with no communication disorders, acute neurological diseases, or history of brain damage. Data collection complied with ethical and privacy requirements. CONCLUSIONS: The study aims to advance personalized machine learning for mental health; generate a data set to predict Depression, Anxiety, and Stress Scale results; and deploy a framework for early detection of depression, anxiety, and stress. Our long-term goal is to develop a noninvasive and objective method for collecting mental health data and promptly detecting mental disorder symptoms. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48210.

Resolvin D2-G-Protein Coupled Receptor 18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging.

Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

Shock drives a STAT3 and JunB-mediated coordinated transcriptional and DNA methylation response in the endothelium.

Endothelial dysfunction is a crucial factor in promoting organ failure during septic shock. However, the underlying mechanisms are unknown. Here, we show that kidney injury after lipopolysaccharide (LPS) insult leads to strong endothelial transcriptional and epigenetic responses. Furthermore, SOCS3 loss leads to an aggravation of the responses, demonstrating a causal role for the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. Experiments in cultured endothelial cells demonstrate that IL-6 mediates this response. Furthermore, bioinformatics analysis of in vivo and in vitro transcriptomics and epigenetics suggests a role for STAT, AP1 and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or the AP1 member JunB partially prevents the changes in gene expression, demonstrating a role for these transcription factors. In conclusion, endothelial cells respond with a coordinated response that depends on overactivated IL-6 signaling via STAT3, JunB and possibly other transcription factors. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.

SH2 domain-containing protein tyrosine phosphatase-2 is enriched in eyelid specimens of rosacea.

Background: Rosacea is a cutaneous disease that may secondarily affect the ocular surface. Due to the vision threatening, cosmetic, psychological, and work productivity impact, the identification of cellular targets that govern rosacea would enhance our understanding of the biology of the disease and delineate targets for therapeutic manipulation. Objective: To characterize the involvement of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in the pathogenesis of rosacea. Methods: Specimens from elective ectropion surgery (n = 20) were processed from patients with rosacea (n = 10) and control patients (n = 10). Immunohistochemistry (IHC) and quantitative western blotting (WB) were performed to identify and quantify the presence of SHP2 and 4G10 (a phosphotyrosine antibody) in rosacea compared to normal tissue. IHC samples were graded according to an intensity scale (0-4). Mann-Whitney statistical analyses were performed via a dedicated computerized software package. Results: On WB, SHP2 was expressed in higher concentrations in rosacea specimens (p < 0.05). On IHC, SHP2 was enriched in the epidermis in rosacea (p < 0.05), although 4G10 levels were not statistically significantly different between the two groups (p > 0.05). Conclusions: SHP2 is enriched in cutaneous specimens of rosacea, suggesting a critical role for this protein in the disease and indicating a modifiable therapeutic moiety.

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review.

OBJECTIVE: The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included. RESULTS: From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration. CONCLUSIONS: The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42022323757.

Impact of the 2021 La Palma volcanic eruption on air quality: Insights from a multidisciplinary approach.

The La Palma 2021 volcanic eruption was the first subaerial eruption in a 50-year period in the Canary Islands (Spain), emitting ~1.8 Tg of sulphur dioxide (SO2) into the troposphere over nearly 3 months (19 September-13 December 2021), exceeding the total anthropogenic SO2 emitted from the 27 European Union countries in 2019. We conducted a comprehensive evaluation of the impact of the 2021 volcanic eruption on air quality (SO2, PM10 and PM2.5 concentrations) utilising a multidisciplinary approach, combining ground and satellite-based measurements with height-resolved aerosol and meteorological information. High concentrations of SO2, PM10 and PM2.5 were observed in La Palma (hourly mean SO2 up to ~2600 µg m-3 and also sporadically at ~140 km distance on the island of Tenerife (> 7700 µg m-3) in the free troposphere. PM10 and PM2.5 daily mean concentrations in La Palma peaked at ~380 and 60 µg m-3. Volcanic aerosols and desert dust both impacted the lower troposphere in a similar height range (~ 0-6 km) during the eruption, providing a unique opportunity to study the combined effect of both natural phenomena. The impact of the 2021 volcanic eruption on SO2 and PM concentrations was strongly influenced by the magnitude of the volcanic emissions, the injection height, the vertical stratification of the atmosphere and its seasonal dynamics. Mean daily SO2 concentrations increased during the eruption, from 38 µg m-3 (Phase I) to 92 µg m-3 (Phase II), showing an opposite temporal trend to mean daily SO2 emissions, which decreased from 34 kt (Phase I) to 7 kt (Phase II). The results of this study are relevant for emergency preparedness in all international areas at risk of volcanic eruptions; a multidisciplinary approach is key to understand the processes by which volcanic eruptions affect air quality and to mitigate and minimise impacts on the population.

Realizing a 1D topological gauge theory in an optically dressed BEC.

Topological gauge theories describe the low-energy properties of certain strongly correlated quantum systems through effective weakly interacting models1,2. A prime example is the Chern-Simons theory of fractional quantum Hall states, where anyonic excitations emerge from the coupling between weakly interacting matter particles and a density-dependent gauge field3. Although in traditional solid-state platforms such gauge theories are only convenient theoretical constructions, engineered quantum systems enable their direct implementation and provide a fertile playground to investigate their phenomenology without the need for strong interactions4. Here, we report the quantum simulation of a topological gauge theory by realizing a one-dimensional reduction of the Chern-Simons theory (the chiral BF theory5-7) in a Bose-Einstein condensate. Using the local conservation laws of the theory, we eliminate the gauge degrees of freedom in favour of chiral matter interactions8-11, which we engineer by synthesizing optically dressed atomic states with momentum-dependent scattering properties. This allows us to reveal the key properties of the chiral BF theory: the formation of chiral solitons and the emergence of an electric field generated by the system itself. Our results expand the scope of quantum simulation to topological gauge theories and open a route to the implementation of analogous gauge theories in higher dimensions12.

SOCS3 limits TNF and endotoxin-induced endothelial dysfunction by blocking a required autocrine interleukin-6 signal in human endothelial cells.

Increased circulating levels of soluble interleukin (IL)-6 receptor α (sIL-6Rα) are commonly observed during inflammatory responses, allowing for IL-6 signaling in cells that express the ubiquitous receptor subunit gp130 but not IL-6Rα, such as endothelial cells. Activation of Toll-like receptor (TLR)-4 or the tumor necrosis factor (TNF) receptor leads to NF-κB-dependent increases in endothelial IL-6 expression. Thus, we hypothesize that danger signals may induce autocrine IL-6 signaling within the endothelium via sIL-6Rα-mediated trans-signaling. In support of this hypothesis, we recently demonstrated that conditional deletion in the endothelium of the IL-6 signaling inhibitor SOCS3 leads to rapid mortality in mice challenged with the TLR-4 agonist endotoxin through increases in vascular leakage, thrombosis, leukocyte adhesion, and a type I-like interferon response. Here, we sought to directly test a role for sIL-6Rα in LPS-treated human umbilical vein and dermal blood microvascular endothelial cells. We show that cotreatment with sIL-6Rα dramatically increases the loss of barrier function and the expression of COX2 and tissue factor mRNA levels induced by LPS. This cotreatment led to strong activation of STAT1 and STAT3 while not affecting LPS-induced activation of p38 and NF-κB signaling. Similar results were obtained when sIL-6Rα was added to a TNF challenge. JAK inhibition by pretreatment with ruxolitinib or by SOCS3 overexpression blunted LPS and sIL-6R synergistic effects, whereas SOCS3 knockdown further increased the response. Together, these findings demonstrate that IL-6 signaling downstream of NF-κB activation leads to a strong endothelial activation and may explain the acute endotheliopathy observed during critical illness.

Towards a Resilience to Stress Index Based on Physiological Response: A Machine Learning Approach.

This study proposes a new index to measure the resilience of an individual to stress, based on the changes of specific physiological variables. These variables include electromyography, which is the muscle response, blood volume pulse, breathing rate, peripheral temperature, and skin conductance. We measured the data with a biofeedback device from 71 individuals subjected to a 10-min psychophysiological stress test. The data exploration revealed that features' variability among test phases could be observed in a two-dimensional space with Principal Components Analysis (PCA). In this work, we demonstrate that the values of each feature within a phase are well organized in clusters. The new index we propose, Resilience to Stress Index (RSI), is based on this observation. To compute the index, we used non-supervised machine learning methods to calculate the inter-cluster distances, specifically using the following four methods: Euclidean Distance of PCA, Mahalanobis Distance, Cluster Validity Index Distance, and Euclidean Distance of Kernel PCA. While there was no statistically significant difference (p>0.01) among the methods, we recommend using Mahalanobis, since this method provides higher monotonic association with the Resilience in Mexicans (RESI-M) scale. Results are encouraging since we demonstrated that the computation of a reliable RSI is possible. To validate the new index, we undertook two tasks: a comparison of the RSI against the RESI-M, and a Spearman correlation between phases one and five to determine if the behavior is resilient or not. The computation of the RSI of an individual has a broader scope in mind, and it is to understand and to support mental health. The benefits of having a metric that measures resilience to stress are multiple; for instance, to the extent that individuals can track their resilience to stress, they can improve their everyday life.

Metabolic Features of Women With Polycystic Ovary Syndrome in Latin America: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that commonly affects women of childbearing age and has been associated with metabolic and reproductive abnormalities. Only a few studies have investigated metabolic traits in women with PCOS in Latin America. Therefore, we conducted a systematic review to provide an overview of the available evidence on the metabolic profile of Latin American women with PCOS. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and Embase databases for cross-sectional, case-control, or cohort studies focusing on populations of countries in South and Central America and Mexico, published until October 31, 2019. We selected studies that reported the diagnostic criteria for PCOS. In the absence of a control group, we included studies if they reported relevant metabolic data. Results: The initial search yielded 4878 records, of which 41 studies were included in the systematic review. Sample sizes ranged from 10 to 288 in PCOS groups and from 10 to 1500 in control groups. The prevalence of phenotypes A and B (classic PCOS) ranged from 65.8% to 87.5% as reported in studies from Argentina, Brazil, and Chile. Metabolic syndrome ranged from 33.3% to 44.0% for phenotype A, from 15.0% to 58.0% for phenotype B, from 11.9% to 36.0% for phenotype C, and from 14.2% to 66.0% for phenotype D. Women with PCOS had higher body mass index, waist circumference, blood pressure, glucose, and homeostasis model assessment index as well as a more adverse lipid profile than those without PCOS. Conclusions: Evidence from the present systematic review suggests that anthropometric and metabolic profiles are worse in women with PCOS who live in different Latin American countries than in women without PCOS living in the same region. Additional studies assessing metabolic comorbidities, such as diabetes, and distinct PCOS phenotypes in different Latin American countries are warranted and may produce invaluable information for primary and secondary prevention of PCOS in the region. This systematic review was registered with PROSPERO under number CRD42016038537. Systematic Review Registration: PROSPERO, identifier CRD42016038537.

Data Analysis and Forecasting of the COVID-19 Spread: A Comparison of Recurrent Neural Networks and Time Series Models.

To understand and approach the spread of the SARS-CoV-2 epidemic, machine learning offers fundamental tools. This study presents the use of machine learning techniques for projecting COVID-19 infections and deaths in Mexico. The research has three main objectives: first, to identify which function adjusts the best to the infected population growth in Mexico; second, to determine the feature importance of climate and mobility; third, to compare the results of a traditional time series statistical model with a modern approach in machine learning. The motivation for this work is to support health care providers in their preparation and planning. The methods compared are linear, polynomial, and generalized logistic regression models to describe the growth of COVID-19 incidents in Mexico. Additionally, machine learning and time series techniques are used to identify feature importance and perform forecasting for daily cases and fatalities. The study uses the publicly available data sets from the John Hopkins University of Medicine in conjunction with the mobility rates obtained from Google's Mobility Reports and climate variables acquired from the Weather Online API. The results suggest that the logistic growth model fits best the pandemic's behavior, that there is enough correlation of climate and mobility variables with the disease numbers, and that the Long short-term memory network can be exploited for predicting daily cases. Given this, we propose a model to predict daily cases and fatalities for SARS-CoV-2 using time series data, mobility, and weather variables.

Endothelial SOCS3 maintains homeostasis and promotes survival in endotoxemic mice.

SOCS3 is the main inhibitor of the JAK/STAT3 pathway. This pathway is activated by interleukin 6 (IL-6), a major mediator of the cytokine storm during shock. To determine its role in the vascular response to shock, we challenged mice lacking SOCS3 in the adult endothelium (SOCS3iEKO) with a nonlethal dose of lipopolysaccharide (LPS). SOCS3iEKO mice died 16-24 hours postinjection after severe kidney failure. Loss of SOCS3 led to an LPS-induced type I IFN-like program and high expression of prothrombotic and proadhesive genes. Consistently, we observed intraluminal leukocyte adhesion and neutrophil extracellular trap-osis (NETosis), as well as retinal venular leukoembolization. Notably, heterozygous mice displayed an intermediate phenotype, suggesting a gene dose effect. In vitro studies were performed to study the role of SOCS3 protein levels in the regulation of the inflammatory response. In human umbilical vein endothelial cells, pulse-chase experiments showed that SOCS3 protein had a half-life less than 20 minutes. Inhibition of SOCS3 ubiquitination and proteasomal degradation led to protein accumulation and a stronger inhibition of IL-6 signaling and barrier function loss. Together, our data demonstrate that the regulation of SOCS3 protein levels is critical to inhibit IL-6-mediated endotheliopathy during shock and provide a promising therapeutic avenue to prevent multiorgan dysfunction through stabilization of endothelial SOCS3.

Molecular Mechanisms of Vascular Damage During Lung Injury.

A variety of pulmonary and systemic insults promote an inflammatory response causing increased vascular permeability, leading to the development of acute lung injury (ALI), a condition necessitating hospitalization and intensive care, or the more severe acute respiratory distress syndrome (ARDS), a disease with a high mortality rate. Further, COVID-19 pandemic-associated ARDS is now a major cause of mortality worldwide. The pathogenesis of ALI is explained by injury to both the vascular endothelium and the alveolar epithelium. The disruption of the lung endothelial and epithelial barriers occurs in response to both systemic and local production of pro-inflammatory cytokines. Studies that evaluate the association of genetic polymorphisms with disease risk did not yield many potential therapeutic targets to treat and revert lung injury. This failure is probably due in part to the phenotypic complexity of ALI/ARDS, and genetic predisposition may be obscured by the multiple environmental and behavioral risk factors. In the last decade, new research has uncovered novel epigenetic mechanisms that control ALI/ARDS pathogenesis, including histone modifications and DNA methylation. Enzyme inhibitors such as DNMTi and HDACi may offer new alternative strategies to prevent or reverse the vascular damage that occurs during lung injury. This review will focus on the latest findings on the molecular mechanisms of vascular damage in ALI/ARDS, the genetic factors that might contribute to the susceptibility for developing this disease, and the epigenetic changes observed in humans, as well as in experimental models of ALI/ADRS.

Enhanced photocatalytic performance and reusability of N-doped carbon dots/zinc oxide hybrid nanostructures.

We report the fabrication of nitrogen-doped carbon dots-zinc oxide hybrid (NCDs-ZnO) nanostructures utilizing simple chemical procedures. The role of NCDs in ZnO nanostructured matrix has been analyzed through XRD, SEM, FTIR and PL characterization techniques. The introduction of NCDs was found to modify not only their aspect ratio, observed by a reduction in the preferredc-axis growth compared to thea- andb-axis, but also induced an additional emission around 441 nm, which is typical of NCDs. The hybrid nanostructures were utilized as catalyst for methylene blue dye degradation showing a 95% degradation after 2 h of UV irradiation in comparison to the ∼70% degradation obtained by utilizing pristine ZnO, while the dye half-life (t1/2) was reduced by ∼65% by utilizing NCDs-ZnO hybrid nanostructures when compared to the pristine ZnO. The reusability of the fabricated hybrid structures was tested up to eight times with no significant loss in their photocatalytic performance (>90%). The stability of the hybrid structures was verified through Z-potential measurements prior and after reutilization. Excellent reusability and simple processing presented by NCDs-ZnO hybrid nanostructures makes them promising for industrial level photocatalyst for the waste water treatment.

Metabolic profile of women with PCOS in Brazil: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease affecting women of reproductive age and associated with reproductive and metabolic dysfunction. Few studies are available regarding metabolic traits in Brazilian women with PCOS. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding metabolic traits and comorbidities in Brazilian women with polycystic ovary syndrome (PCOS). METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, and Embase for cross-sectional, case-control, or cohort studies focusing on populations of different regions from Brazil, published until July 31, 2019. Studies were selected if they reported PCOS diagnostic criteria. Studies without a control group were included if they presented relevant metabolic data. RESULTS: Of 4856 studies initially identified, 27 were included in the systematic review and 12 were included in the meta-analysis, for a total of 995 women with PCOS defined by Rotterdam criteria and 2275 controls from different regions of Brazil. Obesity, metabolic syndrome and IGT were prevalent, and standard mean differences for BMI (SMD 0.67, 95% CI, 0.29, 1.05), waist circumference (SMD 0.22, 95% CI 0.02, 0.41), systolic (SMD 0.66, 95% CI 0.30, 1.01) and diastolic blood pressure (SMD 0.55, 95% CI 0.24, 0.87), glucose (SMD 0.21, 95% CI 0.04, 0.38) and HOMA (SMD 0.78, 95% CI 0.52, 1.04) were significantly higher in Brazilian women with PCOS compared to controls. Lipid profile was more adverse in PCOS vs. non-PCOS women. Between-study heterogeneities were low/moderate for glucose and HOMA and moderate/high for the other variables. CONCLUSIONS: The data of this systematic review and meta-analysis indicate that Brazilian women with PCOS have a worse metabolic profile than women without PCOS with no important regional differences. The prevalence of metabolic changes is intermediate in Brazil vs. other countries.

Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality.

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape's association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes' transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.

Resolvin D1 Enhances Necroptotic Cell Clearance Through Promoting Macrophage Fatty Acid Oxidation and Oxidative Phosphorylation.

OBJECTIVE: Plaque necrosis is a key feature of defective resolution in atherosclerosis. Recent evidence suggests that necroptosis promotes plaque necrosis; therefore, we sought to determine how necroptotic cells (NCs) impact resolution programs in plaques. Approach and Results: To investigate the role(s) of necroptosis in advanced atherosclerosis, we used mice deficient of Mlkl, an effector of necroptosis. Mlkl-/- mice that were injected with a gain-of-function mutant PCSK9 (AAV8-gof-PCSK9) and fed a Western diet for 16 weeks, showed significantly less plaque necrosis, increased fibrous caps and improved efferocytosis compared with AAV8-gof-PCSK9 injected wt controls. Additionally, hypercholesterolemic Mlkl-/- mice had a significant increase in proresolving mediators including resolvin D1 (RvD1) and a decrease in prostanoids including thromboxane in plaques and in vitro. We found that exuberant thromboxane released by NCs impaired the clearance of both apoptotic cells and NCs through disruption of oxidative phosphorylation in macrophages. Moreover, we found that NCs did not readily synthesize RvD1 and that exogenous administration of RvD1 to macrophages rescued NC-induced defective efferocytosis. RvD1 also enhanced the uptake of NCs via the activation of p-AMPK (AMP-activated protein kinase), increased fatty acid oxidation, and enhanced oxidative phosphorylation in macrophages. CONCLUSIONS: These results suggest that NCs derange resolution by limiting key SPMs and impairing the efferocytic repertoire of macrophages. Moreover, these findings provide a molecular mechanism for RvD1 in directing proresolving metabolic programs in macrophages and further suggests RvD1 as a potential therapeutic strategy to limit NCs in tissues. Graphic Abstract: A graphic abstract is available for this article.

Resultados personales: una perspectiva longitudinal de la calidad de vida / Personal results: A Longitudinal Perspective of the Quality of Life

Ampros, Anfas, Aspanias, Atades, Gautena, Gorabide y Plena inclusión presentan una investigación cuyo objetivo es evaluar el impacto del plan individualizado en el que se incluyen los objetivos personales, la calidad de vida y la percepción de las personas. Se establecen puntos de referencia en un análisis longitudinal de los resultados. Con carácter previo a la elaboración del plan individual de cada persona, se han evaluado las necesidades de apoyo y la calidad de vida. En total, han participado 77 personas con discapacidad con diferentes necesidades de apoyo. Los objetivos de cada plan individual se han valorado al finalizar el primer año y al acabar el segundo, momento en el cual se volvieron a aplicar las escalas antes citadas. Se observan diferencias significativas en los resultados obtenidos en función de las necesidades de apoyo y la valoración que realizan los profesionales según los años de contacto con la persona con discapacidad. Se deben tener en cuenta las diferencias por la edad de los participantes, los problemas de comportamiento y la consecución de los objetivos individuales

Ampros, Anfas, Aspanias, Atades, Gautena, Gorabide, Plena Inclusión present an investigation with the aim to evaluate the impact of the individualized plan that includes personal objetives, the quality of life and the perception of the people. Reference points are established in a longitudinal analysis of the results. Prior to the development of each person's individual plan, support needs and quality of life were evaluated. In total, 77 people with disabilities participated with different support needs. The objectives of each individual plan were evaluated at the end of the first year and at the end of the second year, at which time the aforementioned scales were once again applied. Significant differences were observed in the results obtained according to the support needs and the assessment made by the professionals according to the years of contact with the person with the disability. The age differences of the participants, the behavioural problems and the achievement of the individual objectives must be taken into account