Isolating Synaptic Vesicles from Neurospheres for Proteomics.

This chapter presents an optimized method for isolating synaptic vesicles (SVs) from neurospheres derived from human induced pluripotent stem cells (hiPSCs). The protocol begins with neurosphere cultivation to achieve mature neurons, which is essential for the functional studies of neuronal activity. Following this, neurosphere-derived synaptosomes are isolated, and SVs are enriched through differential centrifugation.

Optimized pipeline for personalized neurobiological insights from single patient-derived Neurospheres.

This pipeline presents a refined approach for deriving personalized neurobiological insights from iPSC-derived neurospheres. By employing Tandem Mass Tag (TMT) labeling, we optimized sample pooling and multiplexing for robust comparative analysis across experimental conditions, maximizing data yield per sample. Through single-patient-derived neurospheres-composed of neural progenitor cells, early neurons, and radial glia-this study explores proteomic profiling to mirror the cellular complexity of neurodevelopment more accurately than traditional 2D cultures.

The burden, clinical features and outcomes of SARS-CoV-2, Influenza and co-infections during concurrently out-of-season outbreaks in Brazil.

Objectives: Little is known about the burden and the clinical presentation and prognosis of individuals with Influenza and SARS-CoV-2 during concurrent outbreaks. We aimed to describe the burden, clinical characteristics and outcomes of hospitalized adults during the Influenza A/H3N2 and Omicron outbreaks in Brazil.

Study Design: Cross-sectional analysis of national surveillance data.

Cognitive, behavioral, neuroimaging and inflammatory biomarkers after hospitalization for covid-19 in Brazil.

Post-COVID-19 Condition (PCC) refers to a multisystemic syndrome that persists for months after SARS-CoV-2 infection. Cognitive deficits, fatigue, depression, and anxiety are common manifestations of the condition, but the underlying mechanisms driving these long-lasting neuropsychiatric features are still unclear. We conducted a prospective multi-method investigation of post-hospitalization COVID-19 patients in Rio de Janeiro, Brazil.

Effect of various perioperative semaglutide interruption intervals on residual gastric content assessed by esophagogastroduodenoscopy: A retrospective single center observational study.

Background: Recent evidence suggests that perioperative semaglutide use is associated with increased residual gastric content (RGC) and risk of bronchoaspiration under anesthesia. We compared the occurrence of increased RGC in semaglutide users and non-users undergoing esophagogastroduodenoscopy to define the time interval at which RGC becomes comparable between groups.

Methods: This was a single-center retrospective electronic chart review at a tertiary hospital.

Persistent Activation of the P2X7 Receptor Underlies Chronic Inflammation and Carcinogenic Changes in the Intestine.

Aberrant signaling through damage-associated molecular patterns (DAMPs) has been linked to several health disorders, attracting considerable research interest over the last decade. Adenosine triphosphate (ATP), a key extracellular DAMP, activates the purinergic receptor P2X7, which acts as a danger sensor in immune cells and is implicated in distinct biological functions, including cell death, production of pro-inflammatory cytokines, and defense against microorganisms. In addition to driving inflammation mediated by immune and non-immune cells, the persistent release of endogenous DAMPs, including ATP, has been shown to result in epigenetic modifications.

Diacerein reduces inflammasome activation and SARS-CoV-2 virus replication: a proof-of-concept translational study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.

Persistent carbapenem resistance in mechanically ventilated ICU patients: A before-and-after analysis of the COVID-19 surge.

Background: The evolution of antimicrobial resistance among critically ill patients before, during, and after the COVID-19 surge remains unclear.

Methods: We retrospectively analyzed critically ill mechanically ventilated adult patients admitted to 8 Brazilian hospitals from Jan 1, 2018 to Apr 30, 2023. We stratified the patients into 3 periods: pre-surge (Jan 01, 2018-Mar 01, 2020), surge (Mar 01, 2020-Oct 01, 2021), and post-surge (after October 01, 2021).

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA.

Genome Editing Therapy for the Blood: Success and Prospects.

Hematopoietic stem cells (HSCs) provide the body with a continuous supply of healthy, functional blood cells. In patients with hematopoietic malignancies, immunodeficiencies, lysosomal storage disorders, and hemoglobinopathies, therapeutic genome editing offers hope for corrective intervention, with even modest editing efficiencies likely to provide clinical benefit. Engineered white blood cells, such as T cells, can be applied therapeutically to address monogenic disorders of the immune system, HIV infection, or cancer.

Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis.

Introduction And Objectives: Microbial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis.

Materials And Methods: We prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates.

Hedgehog components are overexpressed in a series of liver cancer cases.

Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and the third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six of the cases involved hepatic explants, and three involved hepatic segmentectomy for tumor resection.

The autophagy proteome in the brain.

As one of the most important cellular housekeepers, autophagy directly affects cellular health, homeostasis, and function. Even though the mechanisms behind autophagy are well described, how molecular alterations and dysfunctions can lead to pathology in disease contexts still demands deeper investigation. Proteomics is a widely employed tool used to investigate molecular alterations associated with pathological states and has proven useful in identifying alterations in protein expression levels and post-translational modifications in autophagy.

Potential of extracellular vesicles in the pathogenesis, diagnosis and therapy for parasitic diseases.

Parasitic diseases have a significant impact on human and animal health, representing a major hazard to the public and causing economic and health damage worldwide. Extracellular vesicles (EVs) have long been recognized as diagnostic and therapeutic tools but are now also known to be implicated in the natural history of parasitic diseases and host immune response modulation. Studies have shown that EVs play a role in parasitic disease development by interacting with parasites and communicating with other types of cells.

Comparing causal random forest and linear regression to estimate the independent association of organisational factors with ICU efficiency.

Purpose: Parametric regression models have been the main statistical method for identifying average treatment effects. Causal machine learning models showed promising results in estimating heterogeneous treatment effects in causal inference. Here we aimed to compare the application of causal random forest (CRF) and linear regression modelling (LRM) to estimate the effects of organisational factors on ICU efficiency.

OmicScope unravels systems-level insights from quantitative proteomics data.

Shotgun proteomics analysis presents multifaceted challenges, demanding diverse tool integration for insights. Addressing this complexity, OmicScope emerges as an innovative solution for quantitative proteomics data analysis. Engineered to handle various data formats, it performs data pre-processing - including joining replicates, normalization, data imputation - and conducts differential proteomics analysis for both static and longitudinal experimental designs.

Impact of disabilities in activities of daily living on opioid use for chronic pain in older adults: an exploratory secondary analysis from ELSI-Brazil.

Objectives: Problematic use of opioids by older adults is associated with adverse effects and has become a public health crisis worldwide. Ageing-related disabilities in activities of daily living (ADL) could promote unnecessary use of opioids in this population. This study evaluates the association between ADL disability and opioid consumption in Brazilian older adults.

Associations of Adult ADHD symptoms with binge eating spectrum conditions, psychiatric and somatic comorbidity, and healthcare utilization in a metropolitan Brazilian city.

Objectives: To investigate the associations among symptoms of attention deficit hyperactivity disorder (ADHD) with binge eating spectrum conditions - BESC - [binge eating disorder (BED), bulimia nervosa (BN), and recurrent binge eating (RBE)], and psychiatric and somatic comorbidity and healthcare utilization in a representative sample of a Brazilian city.

Methods: A household survey with 2,297 adults and residents in Rio de Janeiro was conducted. The Adult Self-Rating Scale Screener was used to assess ADHD symptoms.

Cognitive inflexibility moderates the relationship between relief-driven drinking motives and alcohol use.

Introduction: Drinking motives and neurocognition play significant roles in predicting alcohol use. There is limited research examining how relief-driven drinking motives interact with neurocognition in alcohol use, which would help to elucidate the neurocognitive-motivational profiles most susceptible to harmful drinking. This study investigated the interactions between neurocognition (response inhibition and cognitive flexibility) and relief-driven drinking, in predicting problem drinking.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored.

Biomarkers in pulmonary infections: a clinical approach.

Severe acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections.