Metabolic Insight into Glioma Heterogeneity: Mapping Whole Exome Sequencing to In Vivo Imaging with Stereotactic Localization and Deep Learning.

Intratumoral heterogeneity (ITH) complicates the diagnosis and treatment of glioma, partly due to the diverse metabolic profiles driven by underlying genomic alterations. While multiparametric imaging enhances the characterization of ITH by capturing both spatial and functional variations, it falls short in directly assessing the metabolic activities that underpin these phenotypic differences. This gap stems from the challenge of integrating easily accessible, colocated pathology and detailed genomic data with metabolic insights. This study presents a multifaceted approach combining stereotactic biopsy with standard clinical open-craniotomy for sample collection, voxel-wise analysis of MR images, regression-based GAM, and whole-exome sequencing. This work aims to demonstrate the potential of machine learning algorithms to predict variations in cellular and molecular tumor characteristics. This retrospective study enrolled ten treatment-naïve patients with radiologically confirmed glioma. Each patient underwent a multiparametric MR scan (T1W, T1W-CE, T2W, T2W-FLAIR, DWI) prior to surgery. During standard craniotomy, at least 1 stereotactic biopsy was collected from each patient, with screenshots of the sample locations saved for spatial registration to pre-surgical MR data. Whole-exome sequencing was performed on flash-frozen tumor samples, prioritizing the signatures of five glioma-related genes: IDH1, TP53, EGFR, PIK3CA, and NF1. Regression was implemented with a GAM using a univariate shape function for each predictor. Standard receiver operating characteristic (ROC) analyses were used to evaluate detection, with AUC (area under curve) calculated for each gene target and MR contrast combination. Mean AUC for five gene targets and 31 MR contrast combinations was 0.75 ± 0.11; individual AUCs were as high as 0.96 for both IDH1 and TP53 with T2W-FLAIR and ADC, and 0.99 for EGFR with T2W and ADC. These results suggest the possibility of predicting exome-wide mutation events from noninvasive, in vivo imaging by combining stereotactic localization of glioma samples and a semi-parametric deep learning method. The genomic alterations identified, particularly in IDH1, TP53, EGFR, PIK3CA, and NF1, are known to play pivotal roles in metabolic pathways driving glioma heterogeneity. Our methodology, therefore, indirectly sheds light on the metabolic landscape of glioma through the lens of these critical genomic markers, suggesting a complex interplay between tumor genomics and metabolism. This approach holds potential for refining targeted therapy by better addressing the genomic heterogeneity of glioma tumors.

Citral relaxes umbilical vessels of normotensive and preeclamptic parturients.

INTRODUCTION: Citral is a low-toxicity monoterpene that has a vasodilator effect on various smooth muscles, and The present study aimed to evaluate its vasorelaxant effect on umbilical vessels of normotensive parturients (NTP) and with preeclampsia parturients (PEP). METHOD: Segments of human umbilical artery (HUA) and vein (HUV) of NTP or PEP were mounted in a bath to record the force of contraction, under tension of 3.0 gf and contracted with the contracting agents: K+ (60 mM), 5 -HT (10 µM) and Ba2+ (1-30 mM). Next, the effect of citral (1-3000 µM) on these contractions and on basal tone was evaluated. RESULTS: In HUA and HUV, citral (1-1000 µM), in NTP condition, inhibited contractions evoked by K+ (IC50 of 413.5 and 271.3, respectively) and by 5-HT (IC50 of 164.8 and 574.3). In the PEP condition, in HUA and HUV, citral also inhibited the contractions evoked by K+ (IC50 of 363.3 and 218.3, respectively) and 5-HT (IC50 of 432.1 and 520.4). At a concentration of 1000 µM, citral completely or almost completely (>90 %) inhibited all contractions. At a concentration of 100-1000 µM, citral, in general, was already able to reduce the contraction induced by 1-3 mM Ba2+ in both AUH and VUH, under NTP and PEP conditions. DISCUSSION: Citral has been shown to be an effective HUA and HUV vasodilator in NTP and PEP. As its toxicity is low, it suggests that this substance can be considered a potential therapeutic agent.

Extracellular Vesicles from Scedosporium apiospermum Mycelial Cells: Implication for Fungal-Host Interplays.

The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus Scedosporium apiospermum. Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density. The mean diameter of the EVs, evaluated by the light scattering technique, was 179.7 nm. Overall, the structural stability of S. apiospermum EVs was preserved during incubation under various storage conditions. The lipid, carbohydrate and protein contents were quantified, and the EVs' protein profile was evidenced by SDS-PAGE, revealing proteins with molecular masses ranging from 20 to 118 kDa. Through immunoblotting, ELISA and immunocytochemistry assays, antigenic molecules were evidenced in EVs using a polyclonal serum (called anti-secreted molecules) from a rabbit inoculated with conditioned cell-free supernatant obtained from S. apiospermum mycelial cells. By Western blotting, several antigenic proteins were identified. The ELISA assay confirmed that the anti-secreted molecules exhibited a positive reaction up to a serum dilution of 1:3200. Despite transporting immunogenic molecules, S. apiospermum EVs slightly induced an in vitro cytotoxicity effect after 48 h of contact with either macrophages or lung epithelial cells. Interestingly, the pretreatment of both mammalian cells with purified EVs significantly increased the association index with S. apiospermum conidia. Furthermore, EVs were highly toxic to Galleria mellonella, leading to larval death in a typically dose- and time-dependent manner. Collectively, the results represent the first report of detecting EVs in the S. apiospermum filamentous form, highlighting a possible implication in fungal pathogenesis.

Perillyl Alcohol Promotes Relaxation in Human Umbilical Artery.

BACKGROUND: Perillyl alcohol (POH) is a monoterpenoid found in plant essential oils and has been shown to relax murine vessels, but its effect on human vessels remains poorly studied. OBJECTIVE: The study aimed to characterize the effect of POH on human umbilical arteries (HUA). METHODS: Rings of HUA were obtained from uncomplicated patients and suspended in an organ bath for isometric recording. The vasorelaxant effect of POH in HUA was evaluated on basal tone and electromechanical or pharmacomechanical contractions, and possible mechanisms of action were also investigated. RESULTS: POH (1-1000 µM) altered the basal tone of HUA and completely relaxed HUA rings precontracted with KCl (60 mM) or 5-HT (10 µM), obtaining greater potency in the pharmacomechanical pathway (EC50 110.1 µM), suggesting a complex interference in the mobilization of extra- and intracellular Ca2+. POH (1000 µM) inhibited contractions induced by BaCl2 (0.1-30 mM) in a similar way to nifedipine (10 µM), indicating a possible blockade of L-type VOCC. In the presence of potassium channel blockers, tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (10 µM), an increase in the EC50 value of the POH was observed, suggesting a modulation of the activity of BKCa, KV, and KATP channels. CONCLUSION: The data from this study suggest that POH modulates Ca2+ and K+ ion channels to induce a relaxant response in HUA.

Structural analysis of the Trypanosoma brucei EIF4E6/EIF4G5 complex reveals details of the interaction between unusual eIF4F subunits.

Recognition of the mRNA 5' end is a critical step needed for translation initiation. This step is performed by the cap binding protein eIF4E, which joins the larger eIF4G subunit to form the eIF4F complex. Trypanosomatids have a minimum of five different eIF4F-like complexes formed through specific but not well-defined interactions between four different eIF4E and five eIF4G homologues. The EIF4E6/EIF4G5 complex has been linked with the stage-specific translation of mRNAs encoding the major Trypanosoma brucei virulence factors. Here, to better define the molecular basis for the TbEIF4E6/TbEIF4G5 interaction, we describe the identification of the peptide interacting with TbEIF4E6 in the region comprising residues 79-166 of TbEIF4G5. The TbEIF4E6-TbEIF4G5_79-116 complex reconstituted with recombinant proteins is highly stable even in the absence of cap-4. The crystal structure of the complex was subsequently solved, revealing extensive interacting surfaces. Comparative analyses highlight the conservation of the overall structural arrangement of different eIF4E/eIF4G complexes. However, highly different interacting surfaces are formed with distinct binding contacts occurring both in the canonical and noncanonical elements within eIF4G and the respective eIF4E counterpart. These specific pairs of complementary interacting surfaces are likely responsible for the selective association needed for the formation of distinct eIF4F complexes in trypanosomatids.

Exploring uterine inflammation in postpartum primiparous precocious and conventional and multiparous Bos indicus beef cows.

This study aimed to compare the postpartum uterine dynamics of primiparous precocious (PP), primiparous conventional (PC) and multiparous conventional (MC) Bos indicus beef cows. For this purpose, PP (n = 8), PC (n = 18) and MC (n = 12) cows were enrolled in this study. These cows were evaluated at 20 and 10 days prepartum and weekly from parturition to 42 days postpartum (DPP). During this period, body weight (BW), subcutaneous fat thickness (SFT) and serum concentrations of glucose, ß-hydroxybutyrate, albumin and haptoglobin were measured. Proportion of polymorphonuclear (PMN) cells, and abundance of mRNA transcripts of genes involved in uterine inflammation and uterine health were evaluated. The PP cows had lower (p < .05) BW and SFT than that for PC and MC cows during the study period. The serum concentration of albumin after 35 DPP was lower (p < .05) in PP cows. The PP cows had the highest proportion of PMN on 28 and 35 DPP compared to PC and MC cows. The relative mRNA abundance of IL-1ß and IL-8 increased after 21 DPP in PP cows compared to the other groups. The PC had the highest, MC had an intermediate, and PP cows had the lowest relative abundance of IL10 mRNA. Overall, these findings indicated that uterine inflammation was more pronounced in PP cows. Moreover, based on the proportion of PMN and abundance of transcripts associated with inflammation in the uterus, PP cows may require a longer period to recover their uterine health after calving.

Critically ill patients with COVID-19-associated acute kidney injury treated with kidney replacement therapy: Comparison between the first and second pandemic waves in São Paulo, Brazil.

INTRODUCTION: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil. METHODS: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves. RESULTS: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves. CONCLUSIONS: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.

Microbial Biosurfactant: Candida bombicola as a Potential Remediator of Environments Contaminated by Heavy Metals.

Industrial interest in surfactants of microbial origin has intensified recently due to the characteristics of these compounds, such as biodegradability and reduced toxicity, and their efficiency in removing heavy metals and hydrophobic organic compounds from soils and waters. The aim of this study was to produce a biosurfactant using Candida bombicola URM 3712 in a low-cost medium containing 5.0% molasses, 3.0% corn steep liquor and 2.5% residual frying oil for 144 h at 200 rmp. Measurements of engine oil tension and emulsification were made under extreme conditions of temperature (0 °C, 5 °C, 70 °C, 100 °C and 120 °C), pH (2-12) and NaCl concentrations (2-12), demonstrating the stability of the biosurfactant. The isolated biosurfactant was characterized as an anionic molecule with the ability to reduce the surface tension of water from 72 to 29 mN/m, with a critical micellar concentration of 0.5%. The biosurfactant had no toxic effect on vegetable seeds or on Eisenia fetida as a bioindicator. Applications in the removal of heavy metals from contaminated soils under dynamic conditions demonstrated the potential of the crude and isolated biosurfactant in the removal of Fe, Zn and Pb with percentages between 70 and 88%, with the highest removal of Pb being 48%. The highest percentage of removal was obtained using the cell-free metabolic liquid, which was able to remove 48, 71 and 88% of lead, zinc and iron from the soil, respectively. Tests in packed columns also confirmed the biosurfactant's ability to remove Fe, Zn and Pb between 40 and 65%. The removal kinetics demonstrated an increasing percentage, reaching removal of 50, 70 and 85% for Pb, Zn and Fe, respectively, reaching a greater removal efficiency at the end of 24 h. The biosurfactant was also able to significantly reduce the electrical conductivity of solutions containing heavy metals. The biosurfactant produced by Candida bombicola has potential as an adjuvant in industrial processes for remediating soils and effluents polluted by inorganic contaminants.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: cognitive-behavioral therapy

Objectives: To summarize evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The literature on CBT interventions for adult OCD, including BT and exposure and response prevention, was systematically reviewed to develop updated clinical guidelines for clinicians, providing comprehensive details about the necessary procedures for the CBT protocol. We searched the literature from 2013-2020 in five databases (PubMed, Cochrane, Embase, PsycINFO, and Lilacs) regarding study design, primary outcome measures, publication type, and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association. Results: We examined 44 new studies used to update the 2013 American Psychiatric Association guidelines. High-quality evidence supports CBT with exposure and response prevention techniques as a first-line treatment for OCD. Protocols for Internet-delivered CBT have also proven efficacious for adults with OCD. Conclusion: High-quality scientific evidence supports the use of CBT with exposure and response prevention to treat adults with OCD.

Brazilian research consortium on obsessive-compulsive spectrum disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: Cognitive-Behavior Therapy treatment.

OBJECTIVE: To summarize the evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). METHODS: A systematic review of the literature on CBT interventions for the treatment of adult OCD, comprising behavior therapy and exposure and response prevention (ERP) was done. The objective of this study is to present updated clinical guidelines to clinicians, providing comprehensive details regarding the necessary procedures to be incorporated into the CBT protocol. We searched the literature published from 2013-2020 in five databases (PubMed, Cochrane, Embase, Psycinfo and Lilacs), considering: study design, primary outcome measures, type of publication and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). RESULTS: We examined 44 new studies used to update the APA guidelines from 2013. High-quality evidence supports CBT including ERP techniques as the first-line CBT treatment for OCD. In addition, protocols for internet-delivered CBT have also demonstrated their efficacy for the treatment of adults with OCD. CONCLUSION: CBT based on ERP is a widely used treatment according to high-quality scientific evidence to treat adults with OCD.

Vasodilation promoted by (E,E)-farnesol involving ion channels in human umbilical arteries.

Background: (E,E)-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown. Purpose: Thus, this study aims to characterize the vasodilatory effect of (E,E)-farnesol in human umbilical arteries (HUA). Study design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments. Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath. Results: (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC50 225.3 µmol/L) than the pharmacomechanical coupling induced by 5-HT 10 µmol/L (EC50 363.5 µmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl2 or BaCl2 were attenuated by (E,E)-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of (E,E)-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 µmol/L) suggesting a possible influence of different potassium channels (BKCa, KV and KATP). Conclusion: These results suggest that (E,E)-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders.

Genomic profiling informs diagnoses and treatment in vascular anomalies.

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

Safety climate in the surgical center during the Covid-19 pandemic: mixed-method study.

CONTEXT: The gradual impact of the Covid-19 pandemic had important effects on routines in surgical environments. In order to cope with the impact and re-establish anaesthesiology and surgery procedures, it was imperative to pursue in-depth studies with a view to ensuring safe surgical care, reducing hazards, as well as protecting the health, safety and wellbeing of the health personnel involved. The purpose of this study was to evaluate quantitative and qualitative approaches to domains of safety climate among multi-professional staffs of surgical centres during the Covid-19 pandemic and to identify intersections. METHODS: This mixed-method project employed a concomitant triangulation strategy on a quantitative approach in an exploratory, descriptive, cross-sectional study, as well as a qualitative approach by way of a descriptive study. Data were collected using the validated, self-applicable Safety Attitudes Questionnaire/Operating Room (SAQ/OR) questionnaire and a semi-structured interview script. The 144 participants were the surgical, anaesthesiology, nursing and support teams working in the surgical centre during the Covid-19 pandemic. RESULTS: The study found an overall safety climate score of 61.94, the highest-scoring domain being 'Communication in the surgical environment' (77.91) and the lowest, 'Perception of professional performance' (23.60). On integrating the results, a difference was found between the domains 'Communication in the surgical environment' and 'Working conditions'. However, there was intersection by the 'Perception of professional performance' domain, which permeated important categories of the qualitative analysis. CONCLUSIONS: For care practice, it is hoped to encourage improved patient safety, educational interventions to strengthen the patient safety climate and promote in-job wellbeing on the job for health personnel working in surgical centres. It is suggested that further studies explore the subject in greater depth among several surgical centres with mixed methods, so as to permit future comparisons and to monitor the evolving maturity of safety climate.

Análise comparativa de classificação do risco nutricional entre a mini avaliação nutricional reduzida e a nutritional risk screening 2002 em pacientes hospitalizados com insuficiência cardíaca / Comparative analysis of nutritional risk classification between the mini nutritional assessment-short form and the nutritional risk screening 2002 in hospitalized patients with heart failure

INTRODUÇÃO: A triagem nutricional é responsável pela prévia seleção e encaminhamento do paciente em Risco Nutricional (RN) para avaliações mais sensíveis. A Nutritional Risk Screening-2002 (NRS-2002) foi confiável em detectar a presença ou o risco de desenvolver desnutrição em um estudo recente. A Mini Nutritional Assessment-Short Form (MNA-SF) é voltada para idosos, mas atualmente é amplamente utilizada entre demais adultos, e demonstrou se correlacionar fortemente com a MNA completa. OBJETIVOS: verificar se a aplicação da MNA-SF reclassificará os pacientes internados com resultados semelhantes à NRS-2002 e analisar as concordâncias e discordâncias entre as triagens, considerando a classificação do risco nutricional, ingestão alimentar e perda de peso. METODOLOGIA: estudo transversal realizado com pacientes recém-internados com insuficiência cardíaca, onde a NRS2002 e a MNA-SF foram aplicadas no mesmo momento, nas primeiras 72 horas. As avaliações contínuas dos escores NRS 2002 e MNA-SF foram apresentadas com a sua relação linear, e descrita por coeficientes de correlação de Pearson. A concordância entre os métodos foi apresentada com intervalos de confiança de 95% e coeficiente de Kappa. RESULTADOS: foram incluídos 148 pacientes, com média de idade de 63,1 ± 14,0 anos, onde 28 eram desnutridos, 62 eutróficos e 38 estavam em sobrepeso ou obesidade segundo IMC. A NRS-2002 classificou 4 pacientes a mais em RN que a MNA-SF (136 vs. 132), porém, apresentaram concordância fraca (kappa=0,21). Ingestão alimentar e perda de peso apresentaram discordância significativa. A correlação de Pearson foi de -0,44. CONCLUSÃO: A NRS-2002 classificou 4 pacientes a mais em RN, onde o IMC e a insuficiência cardíaca foram cruciais para classificar os pacientes dessa maneira. Apesar da semelhança, nossa pesquisa apresentou concordância fraca em relação ao RN, condizendo com a literatura. Ingestão alimentar e perda de peso discordaram siginitivamente entre as triagens.

Matrix metalloproteinases -2 and -9 expression in dogs with visceral leishmaniasis: A systematic review.

The matrix metalloproteinases (MMPs) are engaged in the degradation and remodeling of the extracellular matrix and vessels, allowing the progression of pathological processes. Recent studies pointed that MMP -2 and -9 are promising visceral leishmaniasis biomarkers. Thus, the present studystudy aimed to review published scientific literature related to MMP-2 and -9 activity on canine visceral leishmaniasis (CVL). The review followed the PRISMA method, searching for articles in ScienceDirect, PubMed, Scopus, Lilacs, Medline and Google Scholar from inception until 20 March 2022 by employing the following terms: "dog", "matrix metalloproteinases" and "Visceral Leishmaniasis" or "Kala Azar". The selected articles were read in full and only those consistent with the eligibility criteria were included in the review. Of 238 articles from the initial search, only five were deemed eligible, which were conducted between 2010 and 2018. All studies were performed in Brazil. It was observed that there was a higher expression of proMMP-2 in cerebrospinal (CS) fluid and serum and active MMP-2 in different skin areas, mainly in high parasite load areas. As for MMP-9, the pro and active forms were both expressed in CS fluid, serum and different skin areas. The MMP-2 can be considered a biomarker of bad prognostic as it plays an inflammatory role with a greater release in the initial phase of the disease, where MMP-9 is perceived in the chronic phase of CVL. Future research on the subject with greater methodological rigor and bigger sample sizes are mandatory to clarify the role of MMPs on disease progression.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment

Objectives: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). Results: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. Conclusion: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.

Physical exercise practice was positively associated with better dietary practices of aged people during COVID-19 social distance: A cross-sectional study.

BACKGROUND & AIMS: COVID-19 is a respiratory syndrome caused by SARS-CoV-2. In the absence of effective treatment and vaccines, social distance (SD) is essential to reduce the spread of the virus. However, SD generates several behavioral changes, especially in psychological (i.e., emotions and depressive symptoms) and lifestyle-related parameters (i.e., diet, physical activity, and sleep), and the aged people could be more susceptible to COVID-19 SD-related effects (i.e., loneliness, stress, fear, concerns about life, etc.). As such, we aimed to explore the relationship between lifestyle- (physical exercise practice and sleep quality) and psychological-related factors with the dietary practices derived from the Brazilian National Food Guide of older adult during the COVID-19 SD. METHODS: A web-based survey was conducted in São Paulo, Brazil. Data were collected between August and December 2020 (a period of social isolation due to the COVID-19 pandemic). The questions were extracted from validated questionnaires to verify dietary practices (score of adhesion to the food guide for the Brazilian population), sleep quality (by Pittsburgh questionnaire), emotional food-related dimensions (by Three-factor Eating Questionnaire), and depression symptoms (by Beck's questionnaire). RESULTS: Results were from 229 aged people (mean age 66.5 ± 6.02 years old; mean BMI 27.5 ± 4.32 kg/m2; mean sleep duration 8.23 ± 1.41 h; Pittsburg sleep quality score 6.55 ± 4.83; dietary practice score 42.5 ± 6.47). In the adjusted-linear regression model, we verified that physical exercise practice at home (ß = 2.179; 95% CI: 0.599 to 3.758; p = 0.007) during COVID-19 SD was positively associated with better dietary practices in aged people. In contrast, emotional eating was negatively associated with dietary practices (ß = -0.051; 95% CI: -0.092 to - 0.009; p = 0.015). CONCLUSION: We conclude that in aged people, physical exercise practice at home during COVID-19 SD was positively associated with better dietary practices, while emotional eating was negatively associated.

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.

Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment.

OBJECTIVES: To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD). METHODS: The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA). RESULTS: We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD. CONCLUSION: SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.