The search for an antiviral lead molecule to combat the neglected emerging Oropouche virus.

Oropouche virus (OROV) is a member of the Peribunyaviridae family and the causative agent of a dengue-like febrile illness transmitted by mosquitoes. Although mild symptoms generally occur, complications such as encephalitis and meningitis may develop. A lack of proper diagnosis, makes it a potential candidate for new epidemics and outbreaks like other known arboviruses such as Dengue, Yellow Fever and Zika virus. The study of natural molecules as potential antiviral compounds is a promising alternative for antiviral therapies. Wedelolactone (WDL) has been demonstrated to inhibit some viral proteins and virus replication, making it useful to target a wide range of viruses. In this study, we report the in silico effects of WDL on the OROV N-terminal polymerase and its potential inhibitory effects on several steps of viral infection in mammalian cells in vitro, which revealed that WDL indeed acts as a potential inhibitor molecule against OROV infection.

Quantum mechanics insights into melatonin and analogs binding to melatonin MT1 and MT2 receptors.

Melatonin receptors MT1 and MT2 are G protein-coupled receptors that mediate the effects of melatonin, a hormone involved in circadian rhythms and other physiological functions. Understanding the molecular interactions between these receptors and their ligands is crucial for developing novel therapeutic agents. In this study, we used molecular docking, molecular dynamics simulations, and quantum mechanics calculation to investigate the binding modes and affinities of three ligands: melatonin (MLT), ramelteon (RMT), and 2-phenylmelatonin (2-PMT) with both receptors. Based on the results, we identified key amino acids that contributed to the receptor-ligand interactions, such as Gln181/194, Phe179/192, and Asn162/175, which are conserved in both receptors. Additionally, we described new meaningful interactions with Gly108/Gly121, Val111/Val124, and Val191/Val204. Our results provide insights into receptor-ligand recognition's structural and energetic determinants and suggest potential strategies for designing more optimized molecules. This study enhances our understanding of receptor-ligand interactions and offers implications for future drug development.

Towards the correlates of stressful life events as precipitants of obsessive-compulsive disorder: a systematic review and metanalysis.

Obsessive-compulsive disorder (OCD) is a prevalent condition with multifactorial etiology involving genetic and environmental factors. The present study aims to summarize the correlates of stressful life events (SLEs) in OCD by reviewing studies comparing OCD associated or not with SLEs before its onset. To do so, a systematic review was performed by searching PubMed, Web of Science, Scopus, and PsycINFO databases for studies published between the database's inception and November 27, 2023. Studies including individuals whose OCD was precipitated or not by SLEs (SLEs OCD and NSLEs OCD, respectively) were assessed. Effect sizes or odds ratios were then calculated to identify the strength of association between SLEs and clinical characteristics, such as gender, age of onset, family history of OCD, severity of OCD symptoms, depressive symptoms, and mood comorbidities among patients with OCD. Out of the 4083 records initially identified, 5 studies met the inclusion criteria and 3 were comparable through a meta-analysis. Notably, the analyses were limited by the small number of studies available in the literature. The meta-analysis demonstrated SLEs OCD to be associated with female gender, later OCD onset, and increased comorbidity rates with mood disorders. Despite the cross-sectional nature of the reviewed studies, women may be more vulnerable to develop a later onset of OCD following SLEs, which may also lead to mood disorders. Caution is needed to avoid prematurely classifying this presentation as a distinct subtype of OCD.

Quantum biochemical analysis of the binding interactions between a potential inhibitory drug and the Ebola viral glycoprotein.

Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability. We identified ASP522, GLU100, TYR517, THR519, LEU186, LEU515 as the most attractive residues in the EBOV glycoprotein structure that form the binding pocket. We divided toremifene into three regions and evaluated that region i was more important than region iii and region ii for the formation of the TOR-GP1/GP2 complex, which might control the molecular remodeling process of TOR. The mutations that caused more destabilization were ARG134, LEU515, TYR517 and ARG559, while those that caused stabilization were GLU523 and ASP522. TYR517 is a critical residue for the binding of TOR, and is highly conserved among EBOV species. Our results may help to elucidate the mechanism of drug action on the GP protein of the Ebola virus and subsequently develop new pharmacological approaches against EVD.Communicated by Ramaswamy H. Sarma.

Acridones as promising drug candidates against Oropouche virus.

Oropouche virus (OROV) is an emerging vector-borne arbovirus found in South America that causes Oropouche fever, a febrile infection similar to dengue fever. It has a high epidemic potential, causing illness in over 500,000 cases diagnosed since the virus was first discovered in 1955. Currently, the prevention of human viral infection depends on vaccination, but availability for many viruses is limited, and they are classified as neglected viruses. At present, there are no vaccines or antiviral treatments available. An alternative approach to limiting the spread of the virus is to selectively disrupt viral replication mechanisms. Here, we demonstrate the inhibitory effect of acridones, which efficiently inhibited viral replication by 99.9 % in vitro. To evaluate possible mechanisms of action, we conducted tests with dsRNA, an intermediate in virus replication, as well as MD simulations, docking, and binding free energy analysis. The results showed a strong interaction between FAC21 and the OROV endonuclease, which possibly limits the interaction of viral RNA with other proteins. Therefore, our results suggest a dual mechanism of antiviral action, possibly caused by ds-RNA intercalation. In summary, our findings demonstrate that a new generation of antiviral drugs could be developed based on the selective optimization of molecules.

Novel computational and drug design strategies for the inhibition of human T-cell leukemia virus 1-associated lymphoma by Astilbin derivatives.

Human T-cell leukemia virus 1 (HTLV-1) associated lymphoma is a devastating malignancy triggered by HTLV-1 infections. We employeda comprehensive drug design and computational strategy in this work to explore the inhibitory activitiesof Astilbin derivatives against HTLV-1-associated lymphoma. We evaluated the stability, binding affinities, and various computational analysis of Astilbin derivatives against target proteins, such as HTLV-1 main protease and HTLV-1 capsid protein. The root mean square deviation (RMSD), root mean square fluctuation, radius of gyration, hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM) were applied to characterize these protein-ligand interactions further. Ligand-03 and ligand-04 exhibited notable binding affinity to HTLV-1 capsid protein, while ligand-05 displayed high binding affinity to HTLV-1 protease. MD simulation analysis revealed that ligand-03, bound to HTLV-1 capsid protein, demonstrated enhanced stability with lower RMSD values and fewer conformational changes, suggesting a promising binding orientation. Ligand-04, despite stable binding, exhibited increased structural deviations, making it less suitable. Ligand-05 demonstrated stable binding to HTLV-1 protease throughout the simulation period at 100 nanoseconds. Hydrogen bond analysis indicated that ligand-05 formed persistent hydrogen bonds with significantresidues, contributing to its stability. PCA highlighted ligand-03's more remarkable conformational changes, while DCCM showed ligand-05's distinct dynamics, indicating its different behavior in the complex. Furthermore, binding free energy calculations supported the favorable interactions of ligand-03 and ligand-04 with HTLV-1 capsid protein, while ligand-05 showed weaker interactions with HTLV-1 protease. Molecular electrostatic potential and frontier molecular orbital analyses provided insights into these compounds' charge distribution and stability. In conclusion, this research found Astilbin derivatives as potential inhibitors of HTLV-1-associated lymphoma. Future attempts at drug development will benefit from the steady interaction landscape provided by Ligand-03, Ligand-04 and Ligand-05, which showed the most attractive binding profile with the target protein. These results open up new opportunities for innovative drug development, and more experimental testing should be done between Astilbin derivatives and HTLV-1-associated lymphoma.Communicated by Ramaswamy H. Sarma.

Antiviral Activity and Molecular Dynamics Simulation of Hops Compounds against Oropouche Virus (Peribunyaviridae).

The Oropouche virus (OROV) is a member of the family Peribunyaviridae (order Bunyavirales) and the cause of a dengue-like febrile illness transmitted mainly by biting midges and mosquitoes. In this study, we aimed to explore acylphloroglucinols and xanthohumol from hops (Humulus lupulus L.) as a promising alternative for antiviral therapies. The evaluation of the inhibitory potential of hops compounds on the viral cycle of OROV was performed through two complementary approaches. The first approach applies cell-based assay post-inoculation experiments to explore the inhibitory potential on the latest steps of the viral cycle, such as genome translation, replication, virion assembly, and virion release from the cells. The second part covers in silico methods evaluating the ability of those compounds to inhibit the activity of the endonuclease domain, which is essential for transcription, binding, and cleaving RNA. In conclusion, the beta acids showed strongest inhibitory potential in post-treatment assay (EC50 = 26.7 µg/mL). Xanthohumol had the highest affinity for OROV endonuclease followed by colupulone and cohumulone. This result contrasts with that observed for docking and MM/PBSA analysis, where cohumulone was found to have a higher affinity. Finally, among the three tested ligands, Lys92 and Arg33 exhibited the highest affinity with the protein.

Assessing Adherence to Vaccination, Social Distancing and Other Preventive Behaviors by Patients With Mental Disorders in the Context Of Covid-19 Pandemic: A Scoping Review Protocol.

The COVID-19 pandemic has emerged as a worldwide public health crisis, leading to significant disruptions in societal behaviors and norms. Within the affected population, individuals with mental health disorders are considered a vulnerable group, experiencing higher infection rates and poorer outcomes. These adverse outcomes can be attributed to various factors, including inadequate adherence to vaccination and other preventive measures. To address this issue, this study aims to present the research protocol for a scoping review that will comprehensively examine the literature on the adherence of individuals with mental disorders to preventive behaviors during the COVID-19 pandemic. The scoping review will adhere to the methodological guidelines outlined by the Joanna Briggs Institute and will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A comprehensive search for published literature containing original data will be conducted in the Embase, MEDLINE, PsycINFO, and Web of Science databases. The search strategy will be developed based on the Population, Concept, and Context inclusion criteria. Two authors will independently screen titles, abstracts, and full texts for inclusion and extract relevant data. The findings of the review will be presented using descriptive statistics, including tables, charts, and flow diagrams, to elucidate the key concepts of interest.

Habit-, reward- and fear-related motivations in alcohol use disorder: A one-year prospective study.

OBJECTIVE: Cross-sectional studies show that habitual use of alcohol is associated with severity of alcohol dependence reflected across a range of domains and lower number of detoxifications in multiple settings. In this study, we investigated whether alcohol use disorder (AUD) patients with greater habitual use of alcohol at baseline showed worse outcomes after one year of follow-up. METHODS: A sample of inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorder (AUD) was assessed at baseline (n = 50) and after one year (n = 30). The Habit, Reward, and Fear Scale (HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) drives for alcohol use, the Alcohol Dependence Scale (ADS) was used to assess clinical outcomes, and the Depression, Anxiety and Stress Scale (DASS-21) was used to quantify and control for associated affective symptoms. RESULTS: There was a significant reduction in the three HRFS scores at the follow-up. Regression analyses demonstrated that greater habit- and fear-related drives at baseline predicted greater decreases in the ADS scores at the endpoint. However, after controlling for age, sex and affective symptoms, only reward and fear were associated with reductions in ADS scores at the end of one year. Prescriptions of naltrexone and antidepressants/benzodiazepines did not predict decreases in reward and fear-related motivations. CONCLUSION: Although we were unable to confirm that habitual subscores at baseline predict worse long-term outcomes among inpatients with AUD, we found that a greater fear and reward motives for the use of alcohol predicted a greater magnitude of improvement in the AUD symptoms after one year. We hope that these findings will help develop new approaches toward AUD treatment and inform models of addiction research.

Considerations for the treatment of obsessive-compulsive disorder in patients who have comorbid major depression.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that affects a significant number of individuals worldwide. Major depressive disorder (MDD) is among the most common comorbidities reported in people with OCD. The emergence of MDD in individuals with OCD can be attributed to the increased severity of OCD symptoms and their profound impact on daily functioning. Depressive symptoms can also modify the course of OCD. AREAS COVERED: In this review, the authors explore potential shared neurobiological mechanisms that may underlie both OCD and MDD, such as disturbed sleep patterns, immunological dysregulations, and neuroendocrine changes. Furthermore, they address the challenges clinicians face when managing comorbid OCD and MDD. The authors also discuss a range of treatment options for OCD associated with MDD, including augmentation strategies for serotonin reuptake inhibitors (e.g. aripiprazole), psychotherapy (especially CBT/EPR), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and deep brain stimulation (DBS). EXPERT OPINION: Although there is no 'rule of thumb' or universally acceptable strategy in the treatment of OCD comorbid with MDD, many clinicians, including the authors, tend to adopt a unique transdiagnostic approach to the treatment of OCD and related disorders, focusing on strategies known to be effective across diagnoses. Nevertheless, the existing 'cisdiagnostic approaches' still retain importance, i.e. specific therapeutic strategies tailored for more severe forms of individual disorders.

A "transatlantic" follow-up study of the impact of the COVID-19 pandemic on patients with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive symptom fluctuations may be contingent on the number of stressful pandemic-related events and the resilience characterizing different cultures. We investigated the influence of the pandemic on symptom changes in a sample of obsessive-compulsive disorder (OCD) patients from Brazil and Italy, two countries that were highly affected by the outbreak. METHODS: Ninety-one OCD outpatients were evaluated at baseline and about one year later. Thirty of them were assessed in Brazil and 61 in Italy. Socio-demographic variables, symptoms' severity and the number of stressful pandemic-related events were collected. Comparisons between countries' samples were performed, and a linear regression examined whether the country of origin, demographic features and the number of stressful events were able to predict the symptoms' severity at the follow-up. RESULTS: Brazilian patients experienced more stressful pandemic-related events than Italian patients (p = 0.018). However, along with higher age (p < 0.01) and increased severity of symptoms at baseline (p < 0.01), lower number of events predicted increased symptoms' severity after one year (p < 0.01). Country of origin was not a significant predictor of severity. LIMITATIONS: Small number of subjects; lack of information regarding duration of illness; and potential sample differences between countries. CONCLUSIONS: During the pandemic, the occurrence of more stressful pandemic-related events was associated with decreased severity of patients' OCD symptoms. Nevertheless, older patients and those with more severe symptoms seemed prone to exhibit increased OCD severity at follow-up.

Concealing, Tolerating, and Adjusting to Emotions in Obsessive-Compulsive and Anxiety Disorders: A Cross-Sectional Study.

BACKGROUND: Although research has shown that mood and anxiety disorders manifest disturbed emotion regulation, it is unclear whether anxiety disorders differ between each other in terms of their emotion regulation strategies. In the present study, we investigated whether patients with anxiety disorders present different affective styles. METHODS: We assessed affective styles of 32 obsessive-compulsive disorder (OCD) patients, 29 social anxiety disorder (SAD) patients, 29 panic disorder (PD) patients, and 20 healthy controls through the Affective Style Questionnaire (ASQ). A multivariate analysis of covariance (MANCOVA) was performed to compare the affective styles across groups (OCD, SAD, PD and control), while controlling for depression, anxiety symptoms and age. RESULTS: The MANCOVA revealed a significant, small-medium, main effect of diagnostic group on affective styles. The planned contrasts revealed that OCD and SAD patients reported significantly lower scores for "tolerance" (ASQ-T) compared to healthy controls group. There were no differences between PD group and healthy controls. CONCLUSIONS: Our findings provide evidence that OCD and SAD have difficulty tolerating strong emotions existing in the present moment in an open and non-defensive way.

Antiviral Activity of Quercetin Hydrate against Zika Virus.

Zika virus (ZIKV) has re-emerged in recent decades, leading to outbreaks of Zika fever in Africa, Asia, and Central and South America. Despite its drastic re-emergence and clinical impact, no vaccines or antiviral compounds are available to prevent or control ZIKV infection. This study evaluated the potential antiviral activity of quercetin hydrate against ZIKV infection and demonstrated that this substance inhibits virus particle production in A549 and Vero cells under different treatment conditions. In vitro antiviral activity was long-lasting (still observed 72 h post-infection), suggesting that quercetin hydrate affects multiple rounds of ZIKV replication. Molecular docking indicates that quercetin hydrate can efficiently interact with the specific allosteric binding site cavity of the NS2B-NS3 proteases and NS1-dimer. These results identify quercetin as a potential compound to combat ZIKV infection in vitro.

Caffeic Acid Has Antiviral Activity against Ilhéus Virus In Vitro.

Ilhéus virus (ILHV) is a neglected mosquito-borne flavivirus. ILHV infection may lead to Ilhéus fever, an emerging febrile disease like dengue fever with the potential to evolve into a severe neurological disease characterized by meningoencephalitis; no specific treatments are available for this disease. This study assessed the antiviral properties of caffeic acid, an abundant component of plant-based food products that is also compatible with the socioeconomic limitations associated with this neglected infectious disease. The in vitro activity of caffeic acid on ILHV replication was investigated in Vero and A549 cell lines using plaque assays, quantitative RT-PCR, and immunofluorescence assays. We observed that 500 µM caffeic acid was virucidal against ILHV. Molecular docking indicated that caffeic acid might interact with an allosteric binding site on the envelope protein.

Virtual screening of small natural compounds against NS1 protein of DENV, YFV and ZIKV.

Diseases caused by viruses of the genus Flavivirus are among the main diseases that affect the world and they are a serious public health problem. Three of them stand out: Dengue, Yellow fever and Zika viruses. The non-structural protein 1 (NS1), encoded by this viral genus, in its dimeric form, plays important roles in the pathogenesis and RNA replication of these viruses. Therefore, the identification of chemicals with the potential to inhibit the formation of the NS1 protein dimer of DENV, YFV and ZIKV would enable them to act as a multi-target drug. For this, we selected conformations of the NS1 protein monomer with similar ß-roll domain structure among the three virus species from conformations obtained from molecular dynamics simulations performed in GROMACS in 5 replicates of 150 ns for each species. After selecting the protein structures, a virtual screening of compounds from the natural products catalog of the ZINC database was performed using AutoDock Vina. The 100 best compounds were classified according efficiency criteria. Two compounds were observed in common to the species, with energy scores ranging from -9.2 kcal/mol to -10.1 kcal/mol. The results obtained here demonstrate the high similarity of NS1 proteins in the Flavivirus genus and high affinity for the same compounds; thus justifying the potential of these small molecules act in multitarget therapy.Communicated by Ramaswamy H. Sarma.

Sífilis congênita e recusa terapêutica da gestante: análise jurídica e bioética / Congenital syphilis and treatment refusal by pregnant women: a bioethical and legal analysis / Sífilis congénita y rechazo terapéutico por las mujeres embarazadas: análisis legal y bioético

Resumo A infecção congênita pela sífilis é uma doença que, apesar dos esforços públicos, ainda se mantém na rotina do sistema de saúde. Embora haja métodos de prevenção efetivos e muito disseminados, tratamento com alto custo-benefício e disponível no Sistema Único de Saúde, além de assistência pré-natal com alta cobertura, as taxas epidemiológicas da enfermidade continuam relevantes e preocupantes. Umas das barreiras à erradicação desse cenário é a recusa terapêutica da genitora. Com isso, indagações importantes são levantadas, como a responsabilidade médica em relação à recusa, a responsabilidade da gestante para com o nascituro e as implicações jurídicas que perpassam essa problemática. O propósito deste artigo é responder a essas questões e suas repercussões bioéticas e jurídicas.

Abstract Despite public policies, congenital syphilis infection remains a reality in the health system routine. Moreover, its epidemiological rates continue to be relevant and worrisome despite widespread and effective preventive methods, highly cost-effective treatments available in the Unified Health System, and high-coverage pre-natal care. A major obstacle to eradicating this scenario is treatment refusal by the progenitor. Important questions regarding medical responsibility in relation to refusal, the pregnant woman's responsibility towards the unborn child, and the legal implications involved arise from this context. This article seeks to answer these questions and their legal and bioethical repercussions.

Resumen La sífilis congénita es una enfermedad que aún sigue en la rutina del sistema de salud a pesar de los esfuerzos públicos. Aunque existen métodos de prevención efectivos y generalizados, los tratamientos con alto costo-beneficio y disponibles en el Sistema Único de Salud, además de la atención prenatal con alta cobertura, las tasas epidemiológicas de la enfermedad siguen siendo relevantes y preocupantes. Una de las barreras para su erradicación es el rechazo terapéutico de la madre. Por lo tanto, se plantean cuestiones importantes, como la responsabilidad médica con relación al rechazo, la responsabilidad de la mujer embarazada por el feto y las implicaciones legales que impregnan este problema. El propósito de este artículo es responder a estos interrogantes y sus repercusiones bioéticas y legales.

Online group therapies for anxiety, obsessive-compulsive, and trauma-related disorders: a systematic review.

Background: This systematic review examined the existing literature to determine the evidence supporting the efficacy of online group treatments for anxiety-, obsessive-compulsive- and trauma-related disorders (AOTDs). Methods: A systematic review using the PUBMED, PsycInfo, Web of Science, and ClinicalTrials databases with no language, date, or study design filters was performed. The inclusion criteria comprised studies that examined individuals who had received a formal diagnosis of AOTDs, were aged 18 years or older, and had baseline and endpoint assessments of symptom severity using formal tools. Results: Five studies on social anxiety disorder (SAD), four on post-traumatic stress disorder (PTSD) and one on tic disorders (TDs) were found. The studies were open-label (n = 2) and randomized controlled trials (RCTs) (n = 8), with five of the RCTs being non-inferiority trials. Most studies were conducted in the US and investigated psychological CBT based interventions via internet-based therapies (IBT: n = 4), video teleconferencing (VTC: n = 5) or a combination of both (n = 1). In SAD, IBT studies associated with a clinician assisted web-based forum (here termed "forum-enhanced" studies) were superior to waiting lists and not inferior to similar versions that were also "forum enhanced" but self-guided, "telephone enhanced" by a contact with a non-specialist, and "email enhanced" by a contact with a clinician individually. Studies involving VTC have shown comparable effectiveness to in-person interventions across some online group CBT based treatments for PTSD. Two open trials also demonstrated symptoms reductions of social anxiety and tics through VTC. Conclusion: There is evidence supporting the effectiveness of online group treatments for SAD and PTSD. Further studies from different research groups may be needed to replicate the use of these and other forms of online treatments in individuals with SAD, PTSD, and other clinical populations, such as OCD, panic disorder, agoraphobia and specific phobias. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023408491.

A longitudinal evaluation of free will related cognitions in obsessive-compulsive disorder.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) often feel compelled to perform (compulsive) behaviors, thus raising questions regarding their free will beliefs and experiences. In the present study, we investigated if free will related cognitions (free will beliefs or experiences) differed between OCD patients and healthy subjects and whether these cognitions predicted symptom changes after a one-year follow up. METHODS: Sixty OCD outpatients were assessed for their beliefs in and experiences of free will at baseline and after one year of treatment. A subsample of 18 OCD patients had their beliefs compared to 18 age and gender matched healthy controls. A regression analysis was performed to investigate whether free will cognitions at baseline were able to predict long-term OCD severity scores. RESULTS: Patients with OCD and healthy controls do not seem to differ in terms of their beliefs in free will (U = 156.0; p = 0.864). Nonetheless, we found significant negative correlation between (i) duration of illness and strength of belief in determinism (ρ = -0.317; p = 0.016), (ii) age and perception of having alternative possibilities (ρ = -0.275; p = 0.038), and (iii) symptoms' severity and perception of having alternative possibilities (ρ = -0.415; p = 0.001). On the other hand, the experience of being an owner of ones' actions was positive correlated with the severity of symptoms (ρ = 0.538; p < 0.001) and were able to predict the severity of OCD symptoms at the follow up assessment. CONCLUSIONS: Older individuals or those with a greater severity of symptoms seem to have a perception of decreased free will. In addition, patients with a longer duration of illness tend to have a lower strength of belief in determinism. Finally, the experience of being the owner of the compulsions, along with the baseline severity of symptoms, can be a predictor of a worse outcome in the OCD sample.

Retrospective Investigation in Horses with Encephalitis Reveals Unnoticed Circulation of West Nile Virus in Brazil.

During these past years, several studies have provided serological evidence regarding the circulation of West Nile virus (WNV) in Brazil. Despite some reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the country. Recently, genomic monitoring activities in horses revealed the circulation of WNV in several Brazilian regions. These findings on the paucity of genomic data reinforce the need for prompt investigation of WNV infection in horses, which may precede human cases of encephalitis in Brazil. Thus, in this study, we retrospectively screened 54 suspicious WNV samples collected between 2017 and 2020 from the spinal cord and brain of horses with encephalitis and generated three new WNV genomes from the Ceará and Bahia states, located in the northeastern region of Brazil. The Bayesian reconstruction revealed that at least two independent introduction events occurred in Brazil. The first introduction event appears to be likely related to the North American outbreak, and was estimated to have occurred in March 2013.The second introduction event appears to have occurred in September 2017 and appears to be likely related to the South American outbreak. Together, our results reinforce the importance of increasing the priority of WNV genomic monitoring in equines with encephalitis in order to track the dispersion of this emerging pathogen through the country.

Dynamics and Determinants of SARS-CoV-2 RT-PCR Testing on Symptomatic Individuals Attending Healthcare Centers during 2020 in Bahia, Brazil.

RT-PCR testing data provides opportunities to explore regional and individual determinants of test positivity and surveillance infrastructure. Using Generalized Additive Models, we explored 222,515 tests of a random sample of individuals with COVID-19 compatible symptoms in the Brazilian state of Bahia during 2020. We found that age and male gender were the most significant determinants of test positivity. There was evidence of an unequal impact among socio-demographic strata, with higher positivity among those living in areas with low education levels during the first epidemic wave, followed by those living in areas with higher education levels in the second wave. Our estimated probability of testing positive after symptom onset corroborates previous reports that the probability decreases with time, more than halving by about two weeks and converging to zero by three weeks. Test positivity rates generally followed state-level reported cases, and while a single laboratory performed ~90% of tests covering ~99% of the state's area, test turn-around time generally remained below four days. This testing effort is a testimony to the Bahian surveillance capacity during public health emergencies, as previously witnessed during the recent Zika and Yellow Fever outbreaks.