Correlating COVID-19 severity with biomarker profiles and patient prognosis.

COVID-19's long-lasting and complex impacts have become a global concern, with diverse clinical outcomes. This study evaluated 226 participants to understand the clinical spectrum of COVID-19/Long COVID (LC), exploring how disease severity correlates with sociodemographic factors and biomarkers. Determinants related to COVID-19 severity included age (P < 0.001), lower education (P < 0.001), ethnicity (P = 0.003), overweight (P < 0.001), MTHFR gene rs1801133 (P = 0.035), cardiovascular diseases (P = 0.002), diabetes mellitus (DM) (P = 0.006), Factor VIII (FVIII) (P = 0.046), von Willebrand factor (VWF) (P = 0.002), and dimer D (DD) (P < 0.001). Six months later, in a portion of the monitored participants, a significant reduction in FVIII (P < 0.001), VWF (P = 0.002), and DD (P < 0.001) levels was observed, with only DD returning to normal values. Different systemic sequelae were identified, with higher incidences of joint pain and myalgia in participants with a clinical history of DM, chronic lung disease (CLD) and sustained high interleukin 6 values in the convalescent phase. CLD, COVID-19 severity and high DD levels increased the risk of developing dyspnea and palpitations. Women were more likely to develop lower limb phlebitis long-term, while sustained elevated FVIII in the convalescent phase was associated with an increased risk of swelling. Regular physical activity had a protective effect against swelling. This study highlights factors contributing to COVID-19 severity/LC, emphasizing endothelial cell activation as a potential mechanism.

Tributyltin Exposure Is Associated With Recognition Memory Impairments, Alterations in Estrogen Receptor α Protein Levels, and Oxidative Stress in the Brain of Female Mice.

Tributyltin (TBT) is a persistent organometallic pollutant widely used in several agricultural and industrial processes. TBT exposure is associated with various metabolic, reproductive, immune, and cardiovascular abnormalities. However, few studies have evaluated the effects of TBT on behavior. In the present study, we aimed to investigate whether TBT exposure results in oxidative, neuroendocrine, and behavioral alterations. TBT was administered to adult female mice (250, 500, or 750 ng/kg/day or veh for 14 days), and their recognition memory was assessed. We have also evaluated estrogen receptor (ER)α protein expression and oxidative stress (OS) in brain areas related to memory, as well as the correlation between them. A reduction in short- and long-term recognition memory (STM and LTM) performance, as well as in total exploration time was observed in TBT mice. Reduced ERα protein expression was observed in the prefrontal cortex (PFC) and hippocampus of TBT mice, while an increase in TBARS concentration was observed in the PFC of treated animals. Collectively, these data suggest that TBT exposure impairs recognition memory in female mice as a result of, at least in part, its toxicological effects on ERα expression and OS in specific brain areas related to memory.

URB597 ameliorates the deleterious effects induced by binge alcohol consumption in adolescent rats.

Heavy episodic drinking or binge drinking during adolescence may elicit serious neurotoxic consequences in cerebral areas (e.g., the prefrontal cortex, i.e., PFC) and the hippocampus, delay the maturation of the brain and increase the probability of drug abuse and dependence. The endocannabinoid system plays an important role in neuroprotection by reducing oxidative stress and neuroinflammation. In the present study, we aimed to investigate whether URB597, an inhibitor of the metabolic enzyme of the endocannabinoid anandamide (AEA), altered the effects of acute and chronic alcohol administration beginning during rat adolescence on recognition memory, neuroinflammation and brain-derived neurotrophic factor (BDNF) levels. The animals received intraperitoneal injections of URB597 (0.3 mg/Kg) or vehicle followed by the oral administration of ethanol (3 or 6 g/Kg) or distilled water for 3 consecutive days in one week (acute binging) or over 4 weeks (chronic binging). The groups were submitted to the novel object recognition task, and their PFCs and hippocampi were removed for analyses of the cytokine and BDNF levels. URB597 potentiated long-term memory after the 3 mg/Kg acute alcohol administration. The chronic binge alcohol administration increased the interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels in the PFC and hippocampus and the interleukin (IL)-10 and BDNF levels in the PFC, and these effects were prevented by URB597. Our results indicate that the neuromodulation facilitated by AEA can reduce the neuroimmune response induced by the chronic administration of alcohol beginning in adolescence in rats.

URB597 inhibits oxidative stress induced by alcohol binging in the prefrontal cortex of adolescent rats.

Heavy episodic drinking (binging), which is highly prevalent among teenagers, results in oxidative damage. Because the prefrontal cortex (PFC) is not completely mature in adolescents, this brain region may be more vulnerable to the effects of alcohol during adolescence. As endocannabinoids may protect the immature PFC from the harmful effects of high doses of alcohol, this study investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on oxidative stress induced by acute or chronic binge alcohol intake in adolescent rats. At 40min after intraperitoneal pre-treatment with URB597 (0.3mg/kg) or vehicle (Veh), ethanol (EtOH; 3 or 6g/kg, intragastrically) or distilled water (DW) was administered in 3 consecutive sessions (acute binging) or 3 consecutive sessions over 4 weeks (chronic binging). Oxidative stress in PFC slices in situ was measured by dihydroethidium fluorescence staining. At the higher EtOH dose (6g/kg), pre-treatment with URB597 significantly reduced (p<0.01) the production of superoxide anions in the PFC after acute (42.8% decrease) and chronic binge EtOH consumption (44.9% decrease) compared with pre-treatment with Veh. As URB597 decreases anandamide metabolism, this evidence shows an antioxidant effect of endocannabinoids to suppress acute and chronic binge alcohol intake-induced oxidative stress in the PFC of adolescent rats.

Neuroinflammation as a possible link between cannabinoids and addiction.

OBJECTIVE: Substance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction. METHODS: We conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions. RESULTS: In all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation. CONCLUSION: The literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

Perfil epidemiológico dos pacientes HIV-positivo cadastrados no município de Teresópolis, RJ / Epidemiological profile of HIV positive patients registered in the district of Teresópolis, state of Rio de Janeiro

A partir da década de 1980 teve início a epidemia pelo vírus da imunodeficiência humana (HIV), a síndrome da imunodeficiência humana(aids). Por não haver opção terapêutica, naquela época, os pacientes diagnosticados evoluíram rapidamente a óbito. Desde 1996, com a inserção da terapia antirretroviral, a infecção pelo HIV tornou-se uma doença crônica, o que dificulta a adesão ao tratamento proposto, em vários casos. Objetivo: avaliar operfil dos pacientes acompanhados no ambulatório de DST/aids da Divisão de Vigilância Epidemiológica de Teresópolis-RJ e relacioná-lo com o índicede comparecimento às consultas, as dosagens de CD4 e carga viral e os óbitos. Métodos: este é um estudo transversal retrospectivo de caráter qualiquantitativo.Analisamos prontuários de pacientes com diagnóstico de aids disponíveis na Divisão de Vigilância Epidemiológica de Teresópolis cadastrados no período de 2000 a 2010. Resultados: pacientes que realizavam acompanhamento médico a cada 3 meses apresentaram carga viral menor e níveis de CD4 maiores em relação aos que não acompanhavam regularmente (p < 0,01). Pacientes que foram a óbito tiveram menor comparecimento regular às consultas,como também menor tempo de evolução da doença (p < 0,01 nas duas análises). Conclusão: foram poucas as diferenças entre os dados confrontados por nós e aqueles encontrados na literatura, sendo a principal divergência relacionada à predominância de casos de HIV/aids no sexo feminino e maior númeroda carga viral nesse grupo.

The human immunodeficiency virus (HIV) epidemic began in the 1980's. As there were no therapeutic options at that time, diagnosed patients evolved rapidly to death. With the implementation of anti-retroviral therapy in 1996, HIV infection became a chronic disease, which in many cases can make adherence difficult to the proposed treatment. Objective: evaluate the profile of patients monitored at the STD/Aids clinic of the Epidemiological Surveillance Division of Teresópolis-RJ, and relate it to the attendance at consultations rate, CD4 measurements, viral load, and death. Methods: this is aretrospective, qualitative and quantitative cross-sectional study. We analysed available medical records of patients diagnosed with aids at the Division ofEpidemiological Surveillance of Teresópolis, registered from 2000 to 2010. Results: patients with medical follow-up every 3 months had lower viral loadand higher CD4 levels compared to those who were not regularly monitored (p < 0.01). Patients who died had less regular attendance at consultations, aswell as a decreased time in the disease progression (p < 0.01). Conclusion: there were a few differences between our data and those found in the literature,and the main disagreement is related to the prevalence of HIV/aids cases among female patients and a higher viral load in this group.