Transcranial direct current stimulation and cognitive changes in Parkinson's disease, a systematic review with meta-analysis and meta-regression.

Parkinson's disease is the second most common neurodegenerative disease, but therapeutic options such as neuromodulation continue to show variable effects, making clinical management of the disease difficult. This systematic review with meta-analysis and meta-regression aimed to analyze the isolated effect of cortical modulation with transcranial direct current stimulation (tDCS) compared to sham stimulation on cognitive changes in people with Parkinson's disease. The databases used were: Web of Science, Scopus, PsycINFO, PubMed, and Cochrane. The results showed that tDCS can influence the improvement of cognition in PD (Inverse Variance:0.24 [95% Confidence Interval: 0.09 to -0.40], p < 0.00). The meta-analysis showed that active tDCS can influence cognitive function by improving aspects related to memory (Inverse Variance:0.34 [95% Confidence Interval: 0.07 to 0.61], p < 0.01) and reducing reaction time in cognitive tasks (Inverse Variance:0.42 [95% Confidence Interval: 0.07 to 0.76], p < 0.02). Innovative meta-regression analyses showed that variables such as age (Q = 2.54, df = 1, p < 0.11), education level (Q = 2.62, df = 1, p < 0.10), disease duration (Q = 0.01, df = 1, p < 0.92), and Unified PD Rating Scale stage (Q = 0.01, df = 1, p < 0.92) did not influence the results. Thus, tDCS may be a therapeutic option for cognitive changes in people with PD, and we suggest further studies to identify protocols that can be replicated.

Histone H1x in mouse ventral hippocampus associates with, but does not cause behavioral adaptations to stress.

Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrated that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6 J mice were randomly assigned to groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing, respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced all stressed and single housed mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or single housed mice. In sum, although we confirm elevated vHipp protein levels of H1x associate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are associated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.

Social Motivation Differentiates Social Anxiety and Depression: A Daily Diary Study.

Because social anxiety and depression commonly co-occur, it can be challenging to disentangle the emotional and motivational features of these conditions in everyday life contexts. In this daily diary study, we sought to understand the interplay between daily social anxiety and depression symptoms and emotion and motivation, determining whether daily symptoms are independently linked with positive affect, negative affect, and social motivation (desire to approach or to withdraw from others). Community-dwelling adults (N = 269) with a wide range of social anxiety and depression symptoms completed daily assessments for 14 consecutive days (a total of 2,986 daily surveys). Within-person analyses found that increases in social anxiety and depression symptoms were uniquely associated with elevated negative affect; only increases in depression symptoms were associated with diminished positive affect. Increases in social anxiety symptoms were associated with an elevated desire to approach others but not a desire to withdraw from others. By contrast, increases in depression symptoms were associated with a diminished desire to approach others and an elevated desire to withdraw from others. Desire for social connection may distinguish social anxiety from depression. Examining patterns of daily social motivation may enhance clinicians' ability to differentiate the difficulties that arise from social anxiety from those that arise from depression.

Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study.

AIM: This longitudinal study aimed to evaluate the electromyographic activity of the masseter and temporal muscles in adult women who underwent buccal fat removal. MATERIALS AND METHODS: The sample consisted of 20 healthy adult women with no temporomandibular dysfunction and normal occlusion, who were assessed before, 30, and 60 days after the surgery. The electromyographic signal of the masseter and temporal muscles was captured through mandibular tasks including rest, protrusion, right and left laterality, and maximum voluntary contraction with and without parafilm. The results obtained were tabulated and the Shapiro-Wilk normality test was performed, which indicated a normal distribution. Statistical analysis was performed using the repeated measures test (p < 0.05). RESULTS: Significant differences were observed between time periods in maximum voluntary contraction for the left masseter muscle (p = 0.006) and in maximum voluntary contraction with parafilm for the right temporal (p = 0.03) and left temporal (p = 0.03) muscles. CONCLUSION: Bichectomy surgery did not modify the electromyographic activity of the masseter and temporal muscles during the rest task but may have influenced variations in the electromyographic signal during different mandibular tasks after 60 days of surgery, suggesting compensatory adaptations and functional recovery. CLINICAL SIGNIFICANCE: Understanding the impact of buccal fat removal surgery on the stomatognathic system function provides insights into postoperative functional recovery and potential compensatory adaptations, guiding clinical management and rehabilitation strategies for patients undergoing such procedures. How to cite this article: Cardoso AHDLS, Palinkas M, Bettiol NB, et al. Bichectomy Surgery and EMG Masticatory Muscles Function in Adult Women: A Longitudinal Study. J Contemp Dent Pract 2024;25(3):207-212.

A zinc finger transcription factor enables social behaviors while controlling transposable elements and immune response in prefrontal cortex.

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in rodent prefrontal cortex was previously demonstrated to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Following viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, inversion of ZFP189-mediated transcription in this brain area, achieved by viral delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. RNA sequencing of virally manipulated prefrontal cortex tissues reveals that ZFP189 transcription factors of opposing regulatory function (ZFP189WT versus ZFP189VPR) have opposite influence on the expression of genetic transposable elements as well as genes that participate in adaptive immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for complex social behaviors while regulating transposable element-rich regions of DNA and the expression of immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.

Magnetic resonance imaging findings in autoimmune hepatitis: how frequent and reproducible are they? / Achados de imagem por ressonância magnética na hepatite autoimune: quão frequentes e reprodutíveis são eles?

Abstract Objective: To determine the frequency and interobserver reproducibility of the magnetic resonance imaging (MRI) features considered diagnostic for autoimmune hepatitis. Materials and Methods: Two abdominal radiologists, blinded to pathology data, reviewed the MRI examinations of 20 patients with autoimmune hepatitis, looking for liver enhancement, lymphadenopathy, portal hypertension, and chronic liver disease. The pattern of liver fibrosis was categorized as reticular, confluent, or mixed. Interobserver agreement was assessed by calculating intraclass correlation coefficients and kappa statistics. Results: The most common abnormal finding on MRI was surface nodularity (in 85%), followed by liver fibrosis with a reticular pattern (in 80%)—categorized as mild (in 25.0%), moderate (in 43.8%), or severe (in 31.2%)—; heterogeneous liver enhancement (in 65%); splenomegaly (in 60%); caudate lobe enlargement (in 50%); and lymphadenopathy (in 40%). The interobserver agreement was almost perfect for surface nodularity (0.83), ascites (0.89), and liver volume (0.95), whereas it was just slight and fair for the degree of fibrosis and for heterogeneous liver enhancement (0.12 and 0.25, respectively). It was also slight and fair for expanded gallbladder fossa and enlarged preportal space (0.14 and 0.36, respectively), both of which are indicative of chronic liver disease. Conclusion: The interobserver agreement was satisfactory for surface nodularity (the most prevalent abnormal MRI finding), ascites, liver volume, and splenomegaly. Conversely, it was only slight or fair for common but less objective criteria.

Resumo Objetivo: Determinar a frequência e reprodutibilidade interobservador das características de imagem por ressonância magnética na hepatite autoimune. Materiais e Métodos: Dois radiologistas abdominais, cegos para dados patológicos, revisaram ressonâncias magnéticas de 20 pacientes com hepatite autoimune quanto ao realce hepático, linfadenopatia, hipertensão portal e doença hepática crônica. A fibrose foi classificada como reticular, confluente ou ambas. A concordância interobservador foi avaliada por coeficientes de correlação intraclasse e estatística kappa. Resultados: O achado anormal mais comum foi nodularidade superficial (85%), seguido de fibrose reticular hepática (80%) — leve (25%), moderada (43,8%), grave (31,2%) —, realce heterogêneo (65%), esplenomegalia (60%), aumento do lobo caudado (50%) e linfadenopatia (40%). A concordância interobservador foi quase perfeita para nodularidade superficial (0,83), ascite (0,89) e volume hepático (0,95); entretanto, foi apenas leve (0,12) e razoável (0,25) para grau de fibrose e realce heterogêneo, respectivamente. Também foi leve (0,14) ou regular (0,36) para achados de doença hepática crônica, como fossa da vesícula biliar expandida e espaço pré-portal alargado, respectivamente. Conclusão: A concordância geral foi satisfatória para nodularidade superficial (achado anormal mais prevalente), ascite, volume hepático e esplenomegalia. Critérios frequentes, porém menos objetivos, tiveram apenas concordância leve a razoável.

Histone H1x in mouse ventral hippocampus correlates with, but does not cause behavioral adaptations to stress.

Prior research has identified differential protein expression levels of linker histone H1x within the ventral hippocampus (vHipp) of stress-susceptible versus stress-resilient mice. These mice are behaviorally classified based on their divergent responses to chronic social stress. Here, we sought to determine whether elevated vHipp H1x protein levels directly contribute to these diverging behavioral adaptations to stress. First, we demonstrate that stress-susceptible mice uniquely express elevated vHipp H1x protein levels following chronic stress. Given that linker histones coordinate heterochromatin compaction, we hypothesize that elevated levels of H1x in the vHipp may impede pro-resilience transcriptional adaptations and prevent development of the resilient phenotype following social stress. To test this, 8-10-week-old male C57BL/6J mice were randomly assigned to stressed and unstressed groups undergoing 10 days of chronic social defeat stress (CSDS) or single housing respectively. Following CSDS, mice were classified as susceptible versus resilient based on their social interaction behaviors. We synthesized a viral overexpression (OE) vector for H1x and transduced experimental mice with either H1x or control GFP within vHipp. Following viral delivery, we conducted social, anxiety-like, and memory-reliant behavior tests on distinct cohorts of mice. We found no behavioral adaptations following H1x OE compared to GFP controls in susceptible, resilient, or unstressed mice. In sum, although we confirm vHipp protein levels of H1x correlate with susceptibility to social stress, we observe no significant behavioral consequence of H1x OE. Thus, we conclude elevated levels of H1x are correlated with, but are not singularly sufficient to drive development of behavioral adaptations to stress.

Reconstrução óssea de defeito crítico com a utilização de tela de titânio: relato de caso / Bone reconstruction of a critical defect using titanium mesh: case report / Reconstrucción ósea de un defecto crítico con malla de titanio: reporte de caso

Introdução: O uso de membranas de barreira de exclusão de epitélio para regeneração óssea guiada tem sido apresentado na literatura como abordagem de tratamento bem sucedida, essas barreiras irão impedir a incorporação de células de tecidos moles no enxerto ósseo ou no es paço criado pelo defeito e permitir que apenas as células osteogênicas estejam presentes. Relato de caso: Trata-se de um caso clinico de um paciente que evoluiu com perda óssea significativa por lesão Endo-periodontal levando a perda dentaria, para a reabilitação com implantes se fez necessário uma reconstrução de um defeito crítico com a utilização de tela de titânio para arcabouço ósseo de mistura de enxerto autógeno e biomaterial e recobrimento com membrana de colágeno, o enxerto autógeno foi removido de área doadora na mandíbula e utilizado de forma particulada. Conclusão: As telas de titânio apresentam viabilidade e previsibilidade no aumento ósseo vertical, horizontal e tridimensional em decorrência da sua ampla aplicabilidade, elasticidade, plasticidade adequadas e boas propriedades mecânicas. Avanços na diminuição de suas taxas de exposição e risco de complicações no período de cicatrização melhoram a cada dia a previsibilidade da técnica, bem como a associação com outros materiais como os hemoderivados... (AU)

Introduction: The use of epithelial exclusion barrier membranes for guided bone regeneration has been presented in the literature as a successful treatment approach, these barriers will prevent the incorporation of soft tissue cells into the bone graft or the space created by the defect and allow that only osteogenic cells are present. Case report: This is a clinical case of a patient who evolved with significant bone loss due to an endo-periodontal lesion leading to tooth loss, for rehabilitation with implants it was necessary to reconstruct a critical defect using mesh titanium for bone framework of mixture of autogenous graft and biomaterial and covering with collagen membrane, the autogenous graft was removed from the donor area in the mandible and used in a particulate form. Conclusion: Titanium meshes are viable and predictable in vertical, horizontal and three-dimensional bone augmentation due to their wide applicability, adequate elasticity and plasticity, good mechanical properties. Advances in reducing their exposure rates and risk of complications during the healing period improve the predictability of the technique every day, as well as the association with other materials such as blood products... (AU)

Introducción: El uso de membranas de barrera de exclusión epitelial para la regeneración ósea guiada se ha presentado en la literatura como un enfoque de tratamiento exitoso, estas barreras evitarán la incorporación de células de tejido blando al injerto óseo o el espacio creado por el defecto y permitirán que solo presencia de células osteogénicas. Reporte de caso: Este es un caso clínico de un paciente que evolucionó con una pérdida ósea importante debido a una lesión endo-periodontal que lo llevó a la pérdida de un diente, para rehabilitación con implantes fue necesario reconstruir un defecto crítico utilizando malla de titanio para armazón óseo de mezcla de injerto autógeno y biomaterial y cubriendo con membrana de colágeno, el injerto autógeno se extrajo del área donante en la mandíbula y se usó en forma de partículas. Conclusión: Las mallas de titanio son viables y predecibles en el aumento óseo vertical, horizontal y tridimensional debido a su amplia aplicabilidad, adecuada elasticidad y plasticidad, buenas propiedades mecánicas. Los avances en la reducción de sus tasas de exposición y riesgo de complicaciones durante el periodo de cicatrización mejoran día a día la predictibilidad de la técnica, así como la asociación con otros materiales como los hemoderivados... (AU)

Suppression of HIV in the first 12 months of antiretroviral therapy: a comparative analysis of dolutegravir- and efavirenz-based regimens.

OBJECTIVE: To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. METHODS: We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. RESULTS: Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. CONCLUSION: Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered.

A zinc finger transcription factor tunes social behaviors by controlling transposable elements and immune response in prefrontal cortex.

The neurobiological origins of social behaviors are incompletely understood. Here we utilized synthetic biology approaches to reprogram the function of ZFP189, a transcription factor whose expression and function in the rodent prefrontal cortex was previously determined to be protective against stress-induced social deficits. We created novel synthetic ZFP189 transcription factors including ZFP189VPR, which activates the transcription of target genes and therefore exerts opposite functional control from the endogenous, transcriptionally repressive ZFP189WT. Upon viral delivery of these synthetic ZFP189 transcription factors to mouse prefrontal cortex, we observe that ZFP189-mediated transcriptional control promotes mature dendritic spine morphology on transduced pyramidal neurons. Interestingly, dysregulation of ZFP189-mediated transcription in this brain area, achieved by delivery of synthetic ZFP189VPR, precipitates social behavioral deficits in terms of social interaction, motivation, and the cognition necessary for the maintenance of social hierarchy, without other observable behavioral deficits. By performing RNA sequencing in virally manipulated prefrontal cortex tissues, we discover that ZFP189 transcription factors of opposing regulatory function have opposite influence on the expression of genetic transposable elements as well as genes that participate in immune functions. Collectively, this work reveals that ZFP189 function in the prefrontal cortex coordinates structural and transcriptional neuroadaptations necessary for social behaviors by binding transposable element-rich regions of DNA to regulate immune-related genes. Given the evidence for a co-evolution of social behavior and the brain immune response, we posit that ZFP189 may have evolved to augment brain transposon-associated immune function as a way of enhancing an animal's capacity for functioning in social groups.

Reformulating provider profiling by grouping providers treating similar patients prior to evaluating performance.

Standard approaches to comparing health providers' performance rely on hierarchical logistic regression models that adjust for patient characteristics at admission. Estimates from these models may be misleading when providers treat different patient populations and the models are misspecified. To address this limitation, we propose a novel profiling approach that identifies groups of providers treating similar populations of patients and then evaluates providers' performance within each group. The groups of providers are identified using a Bayesian multilevel finite mixture of general location models. To compare the performance of our proposed profiling approach to standard methods, we use patient-level data from 119 skilled nursing facilities in Massachusetts. We use simulated and observed outcome data to explore the performance of these profiling methods in different settings. In simulations, our proposed method classifies providers to groups with similar patients' admission characteristics. In addition, in the presence of limited overlap in patient characteristics across providers and misspecifications of the outcome model, the provider-level estimates obtained using our approach identified providers that under- and overperformed compared to the standard regression-based approaches more accurately.

Development of an Animal Model of Military-Relevant Traumatic Stress.

INTRODUCTION: Acute Stress Reactions (ASRs) affect a subgroup of individuals who experience traumatic stress. In the context of military operations, such reactions are often termed Combat and Operational Stress Reactions (COSRs). COSRs not only encompass all symptoms of ASRs but also include additional symptoms related to military combat and may develop at a rate higher than the general public experiences ASRs. Despite an obvious need, there are currently no approved pharmacologic treatments or guidelines for ASR and/or COSR. Preclinical rodent stress models and behavioral assessments are used to evaluate pharmacotherapies and elucidate underlying mechanisms. Here, we combined established traumatic stress models to develop a model of traumatic stress relevant to military trauma exposure and measured behavioral outcomes that reflect outcomes observed in ASRs and COSRs. MATERIALS AND METHODS: Adult male rats underwent exposure to either a combination of two or three traumatic stress exposures (e.g., predator exposure, underwater trauma (UWT), and/or inescapable shock) or control procedures. Behavioral performance on the open field, elevated plus maze, and acoustic startle response (SR) was then assessed 24- and 48-hours following stress/control procedures. RESULTS: In Experiment 1, rats were exposed to a two-stressor model, where predator exposure was coupled with UWT. Minor behavioral deficits were observed in SR for stress-exposed rats as compared to controls. In Experiment 2, inescapable shock was added to predator exposure and UWT. Behavioral performance deficits were observed across all behavioral tests. In Experiment 3, procedures from Experiment 2 were repeated with the only major modification being a shortened predator exposure duration, which resulted in performance deficits in SR only. CONCLUSIONS: We found that the three-stressor model of Experiment 2 resulted in the greatest overall behavioral disturbance (both in the number of variables and magnitude of stress effects). Interestingly, behavioral deficits elicited from the shorter predator exposure were distinct from those observed with longer predator exposure times. Together, these results generally suggest that combined preclinical stressors with military-relevant elements result in behavioral performance deficits reflective of post-trauma phenotypes in Soldiers. The present findings support the use of both physical and psychological stressors to model operationally relevant traumatic stress exposure.

CREB Binding at the Zfp189 Promoter Within Medium Spiny Neuron Subtypes Differentially Regulates Behavioral and Physiological Adaptations Over the Course of Cocaine Use.

BACKGROUND: Over the course of chronic drug use, brain transcriptional neuroadaptation is thought to contribute to a change in drug use behavior over time. The function of the transcription factor CREB (cAMP response element binding protein) within the nucleus accumbens (NAc) has been well documented in opposing the rewarding properties of many classes of drugs, yet the gene targets through which CREB causally manifests these lasting neuroadaptations remain unknown. Here, we identify zinc finger protein 189 (Zfp189) as a CREB target gene that is transcriptionally responsive to acute and chronic cocaine use within the NAc of mice. METHODS: To investigate the role of the CREB-Zfp189 interaction in cocaine use, we virally delivered modified clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9 constructs capable of selectively localizing CREB to the Zfp189 gene promoter in the NAc of mice. RESULTS: We observed that CREB binding to the Zfp189 promoter increased Zfp189 expression and diminished the reinforcing responses to cocaine. Furthermore, we showed that NAc Zfp189 expression increased within D1 medium spiny neurons in response to acute cocaine but increased in both D1- and D2-expressing medium spiny neurons in response to chronic cocaine. CREB-mediated induction of Zfp189 potentiated electrophysiological activity of D1- and D2-expressing medium spiny neurons, recapitulating the known effect of CREB on these neurons. Finally, targeting CREB to the Zfp189 promoter within NAc Drd2-expressing neurons, but not Drd1-expressing neurons, was sufficient to diminish cocaine-conditioned behaviors. CONCLUSIONS: Together, these findings point to the CREB-Zfp189 interaction within the NAc Drd2+ neurons as a molecular signature of chronic cocaine use that is causal in counteracting the reinforcing effects of cocaine.

Suppression of HIV in the first 12 months of antiretroviral therapy: a comparative analysis of dolutegravir- and efavirenz-based regimens

ABSTRACT Objective To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. Results Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. Conclusion Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered.

Magnetic resonance imaging findings in autoimmune hepatitis: how frequent and reproducible are they?

Objective: To determine the frequency and interobserver reproducibility of the magnetic resonance imaging (MRI) features considered diagnostic for autoimmune hepatitis. Materials and Methods: Two abdominal radiologists, blinded to pathology data, reviewed the MRI examinations of 20 patients with autoimmune hepatitis, looking for liver enhancement, lymphadenopathy, portal hypertension, and chronic liver disease. The pattern of liver fibrosis was categorized as reticular, confluent, or mixed. Interobserver agreement was assessed by calculating intraclass correlation coefficients and kappa statistics. Results: The most common abnormal finding on MRI was surface nodularity (in 85%), followed by liver fibrosis with a reticular pattern (in 80%)-categorized as mild (in 25.0%), moderate (in 43.8%), or severe (in 31.2%)-; heterogeneous liver enhancement (in 65%); splenomegaly (in 60%); caudate lobe enlargement (in 50%); and lymphadenopathy (in 40%). The interobserver agreement was almost perfect for surface nodularity (0.83), ascites (0.89), and liver volume (0.95), whereas it was just slight and fair for the degree of fibrosis and for heterogeneous liver enhancement (0.12 and 0.25, respectively). It was also slight and fair for expanded gallbladder fossa and enlarged preportal space (0.14 and 0.36, respectively), both of which are indicative of chronic liver disease. Conclusion: The interobserver agreement was satisfactory for surface nodularity (the most prevalent abnormal MRI finding), ascites, liver volume, and splenomegaly. Conversely, it was only slight or fair for common but less objective criteria.

Objetivo: Determinar a frequência e reprodutibilidade interobservador das características de imagem por ressonância magnética na hepatite autoimune. Materiais e Métodos: Dois radiologistas abdominais, cegos para dados patológicos, revisaram ressonâncias magnéticas de 20 pacientes com hepatite autoimune quanto ao realce hepático, linfadenopatia, hipertensão portal e doença hepática crônica. A fibrose foi classificada como reticular, confluente ou ambas. A concordância interobservador foi avaliada por coeficientes de correlação intraclasse e estatística kappa. Resultados: O achado anormal mais comum foi nodularidade superficial (85%), seguido de fibrose reticular hepática (80%) ­ leve (25%), moderada (43,8%), grave (31,2%) ­, realce heterogêneo (65%), esplenomegalia (60%), aumento do lobo caudado (50%) e linfadenopatia (40%). A concordância interobservador foi quase perfeita para nodularidade superficial (0,83), ascite (0,89) e volume hepático (0,95); entretanto, foi apenas leve (0,12) e razoável (0,25) para grau de fibrose e realce heterogêneo, respectivamente. Também foi leve (0,14) ou regular (0,36) para achados de doença hepática crônica, como fossa da vesícula biliar expandida e espaço pré-portal alargado, respectivamente. Conclusão: A concordância geral foi satisfatória para nodularidade superficial (achado anormal mais prevalente), ascite, volume hepático e esplenomegalia. Critérios frequentes, porém menos objetivos, tiveram apenas concordância leve a razoável.

Facial processing in bipolar disorder is mediated by clinical and biological aspects

Objective: The process of detecting faces can be considered one of the initial steps in face recognition, which is essential for human interaction. We sought to investigate whether a face perception task reliably detects subtle perceptual disturbances between patients with bipolar disorder (BD) and healthy controls. Methods: In this multisite study, we examined differences between BD patients and matched healthy controls. Participants were instructed to detect the orientation (either left or right) of a face when it was presented as a face/non-face pair on a computer screen using Bayesian entropy estimation. Data analyses compared performance between the groups. Results: Overall, BD patients exhibited more perceptual disturbances compared with controls. BD patients who took olanzapine had better performance and faster reaction times (RTs) than patients who took lithium or were medication-naive. BD patients who took lithium had better performance and faster RTs than medication-naive patients. The medication-naive BD group exhibited greater disturbances than all other groups. Conclusion: These findings highlight the reliability of the face perception task used herein and may be important for public health initiatives and follow-up studies that seek to understand the diverse effects of other variables that can affect sensory processing in this population.

MAPPING MENTAL HEALTH INTERVENTIONS DURING THE COVID-19 PANDEMIC. A COMPARISON REVIEW OF CHINA AND WESTERN EUROPE.

OBJECTIVE: The aim: To map and compare mental health interventions during the Covid-19 pandemic in China and Western-Europe. The focus was specifically on the availability, duration, target group, content, setting, and outcomes of the interventions. PATIENTS AND METHODS: Materials and methods: A scoping review was conducted by utilising several scientific databases. A total of 479 articles were found after removing the duplicate records. After screening, 36 articles were included in the study. Relevant intervention characteristics were systematically mapped, and compared within and among countries. CONCLUSION: Conclusions: All interventions had shared aims to improve the psychological resilience and to reduce psychological distress. In particular, anxiety- and depression-related symptoms were commonly addressed. On average, interventions in China were larger scaled, had longer durations, and often used combinations of strategies such as therapies and exercises both in-person and remotely. Interventions in Western-Europe tend to be locally implemented on a smaller scale, and often used a single strategy. Most Chinese interventions targeted adolescents, while all interventions in Western-Europe were meant for adults. Most interventions were assessed using quantitative methods using various mental health scales, showing statistically significant effects in improving mental health.

Variation in trauma-related behavioral effects using a preclinical rat model of three predator exposure stress.

The underlying mechanisms of trauma-related disorders are challenging to discover and the disorders are difficult to treat, in part due to the complex and varied expressions of response to traumatic stress. These challenges will be easier to overcome as more is understood about the variability in response to trauma. Incorporating assessment of variability into animal models of traumatic stress may allow better translation to clinical research and treatment development. In this study, we characterized variability in behavioral responses following traumatic stress exposure using a predator exposure (PE) animal model. Elevated plus maze (EPM) and acoustic startle response (SR) were used to study avoidance and arousal symptoms in male Sprague-Dawley rats. Behavioral data were compared between control (n = 31) and predator-exposed (n = 30) rats. PE behavior was clustered using k-means principal components analysis. Four clusters and three distinct subgroups were identified and were characterized as avoidant (Cluster 4, 30%), moderately avoidant (Clusters 2 and 3, 49%), and unaffected (Cluster 1, 17%). These results demonstrate that rodent responses to PE are varied, similar to human presentations following traumatic stress, suggesting it may be possible to develop treatment strategies for varied symptom presentations using a preclinical animal model.

Tolerance and Cross-Tolerance among Psychedelic and Nonpsychedelic 5-HT2A Receptor Agonists in Mice.

Classical psychedelics represent a subgroup of serotonergic psychoactive substances characterized by their distinct subjective effects on the human psyche. Another unique attribute of this drug class is that such effects become less apparent after repeated exposure within a short time span. The classification of psychedelics as a subgroup within the serotonergic drug family and the tolerance to their effects are replicated by the murine head twitch response (HTR) behavioral paradigm. Here, we aimed to assess tolerance and cross-tolerance to HTR elicited by psychedelic and nonpsychedelic serotonin 2A receptor (5-HT2AR) agonists in mice. We show that repeated (4 days) administration of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induced a progressive decrease in HTR behavior. Tolerance to DOI-induced HTR was also observed 24 h after a single administration of this psychedelic. Pretreatment with the 5-HT2AR antagonist M100907 reduced not only the acute manifestation of DOI-induced HTR, but also the development of tolerance to HTR. Additionally, cross-tolerance became apparent between the psychedelics DOI and lysergic acid diethylamide (LSD), whereas repeated administration of the nonpsychedelic 5-HT2AR agonist lisuride did not affect the ability of these two psychedelics to induce HTR. At the molecular level, DOI administration led to down-regulation of 5-HT2AR density in mouse frontal cortex membrane preparations. However, development of tolerance to the effect of DOI on HTR remained unchanged in ß-arrestin-2 knockout mice. Together, these data suggest that tolerance to HTR induced by psychedelics involves activation of the 5-HT2AR, is not observable upon repeated administration of nonpsychedelic 5-HT2AR agonists, and occurs via a signaling mechanism independent of ß-arrestin-2.