Esketamine Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder: A Retrospective Chart Review.

OBJECTIVE: Converging evidence supports the role of the glutamate, an excitatory amino acid neurotransmitter, in the pathophysiology of obsessive-compulsive disorder (OCD). Ketamine and esketamine, both noncompetitive N -methyl- d -aspartate antagonists, have emerged as a promising medication for this psychiatric disorder, given its possible efficacy with faster onset and good tolerability. The purpose of this retrospective chart review is to evaluate whether unbiased clinical documentation supports formal clinical trials of esketamine for an OCD indication. METHODS: A retrospective chart review of patients with treatment-resistant OCD receiving a single dose of esketamine (0.5mg/kg) added to standard therapy was conducted. The Yale-Brown Obsessive-Compulsive Scale and the Montgomery-Åsberg Depression Rating Scale were used to evaluate OCD and depressive symptoms respectively at baseline, 24 hours, and 7 days after esketamine administration. Descriptive statistics were used to analyze the data. RESULTS: Eight subjects were identified in this retrospective chart review: esketamine was administered subcutaneously in 7 and intravenously in 1. One week after infusion, 25% of the sample met criteria for treatment response and 50% for partial response. Major depressive disorder was a comorbid diagnosis in 75% of the sample and 2 of these subjects showed a positive antidepressant response. CONCLUSIONS: Our findings provide preliminary evidence that esketamine may reduce obsessive-compulsive symptoms in a subset of treatment-resistant OCD patients.

Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study.

BACKGROUND: Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. METHODS: This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. RESULTS: Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. LIMITATIONS: This was a pilot study with a small sample and underpowered. CONCLUSIONS: Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.

Pathogenic Escherichia coli, Salmonella spp. and Campylobacter spp. in Two Natural Conservation Centers of Wildlife in Portugal: Genotypic and Phenotypic Characterization.

Human-wildlife coexistence may increase the potential risk of direct transmission of emergent or re-emergent zoonotic pathogens to humans. Intending to assess the occurrence of three important foodborne pathogens in wild animals of two wildlife conservation centers in Portugal, we investigated 132 fecal samples for the presence of Escherichia coli (Shiga toxin-producing E. coli (STEC) and non-STEC), Salmonella spp. and Campylobacter spp. A genotypic search for genes having virulence and antimicrobial resistance (AMR) was performed by means of PCR and Whole-Genome Sequencing (WGS) and phenotypic (serotyping and AMR profiles) characterization. Overall, 62 samples tested positive for at least one of these species: 27.3% for STEC, 11.4% for non-STEC, 3.0% for Salmonella spp. and 6.8% for Campylobacter spp. AMR was detected in four E. coli isolates and the only Campylobacter coli isolated in this study. WGS analysis revealed that 57.7% (30/52) of pathogenic E. coli integrated genetic clusters of highly closely related isolates (often involving different animal species), supporting the circulation and transmission of different pathogenic E. coli strains in the studied areas. These results support the idea that the health of humans, animals and ecosystems are interconnected, reinforcing the importance of a One Health approach to better monitor and control public health threats.

Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.

Long-lasting forms of synaptic plasticity that underlie learning and memory require new transcription and translation for their persistence. The remarkable polarity and compartmentalization of neurons raises questions about the spatial and temporal regulation of gene expression within neurons. Alternative cleavage and polyadenylation (APA) generates mRNA isoforms with different 3' untranslated regions (3'UTRs) and/or coding sequences. Changes in the 3'UTR composition of mRNAs can alter gene expression by regulating transcript localization, stability and/or translation, while changes in the coding sequences lead to mRNAs encoding distinct proteins. Using specialized 3' end deep sequencing methods, we undertook a comprehensive analysis of APA following induction of long-term potentiation (LTP) of mouse hippocampal CA3-CA1 synapses. We identified extensive LTP-induced APA changes, including a general trend of 3'UTR shortening and activation of intronic APA isoforms. Comparison with transcriptome profiling indicated that most APA regulatory events were uncoupled from changes in transcript abundance. We further show that specific APA regulatory events can impact expression of two molecules with known functions during LTP, including 3'UTR APA of Notch1 and intronic APA of Creb1. Together, our results reveal that activity-dependent APA provides an important layer of gene regulation during learning and memory.

Análise de coliformes termotolerantes e Salmonella sp. em hortaliças minimamente processadas comercializadas em Belo Horizonte - MG / Analysis of fecal coliform and Salmonella sp. in vegetables minimally processed commercialized in Belo Horizonte - Minas Gerais

A qualidade de alimentos minimamente processados (MP) é de grande importância para a saúde do consumidor, sendo o controle microbiológico e a sanitização correta desses alimentos uma prioridade. O presente estudo teve como objetivo verificar a qualidade microbiológica de 12 tipos de hortaliças minimamente processadas, comercializadas em 5 redes de supermercados do estado de Minas Gerais, na cidade de Belo Horizonte. As amostras foram analisadas no Laboratório de Microbiologia de Alimentos do Centro Universitário Una com base na determinação da presença de coliformes termotolerantes e Salmonella sp., por meio da técnica do Compendium of Methods for the Microbiological Examination of Food. Os resultados revelaram a presença de Salmonella sp., nas hortaliças dos supermercados A (alface lisa e alface crespa), C (salada italiana) e E (Agrião, almeirão e espinafre). Nenhuma das amostras de hortaliças apresentou contaminação por coliformes termotolerantes. Dessa forma, mostra-se primordial implementar medidas para melhorar a qualidade higiênico sanitária dos produtos minimamente processados para garantir incremento da segurança ao consumidor.

Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes.

Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate the function of cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that Rbfox1 bound predominantly to introns in nascent RNA, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and Rbfox1 and miRNA binding sites overlapped significantly. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease.

Avaliação da condição gengivalde escolares / Evaluation of the gingival condition of school children

Verificar a condição periodontal e fatores associados de crianças e adolescentes matriculados em escola pública e privada de Caruaru-PE. Material e Métodos: A amostra foi composta por 121 escolares, de ambos os sexos, na faixa etária de sete a catorze anos. Para a coleta de dados foram utilizados o índice gengival (IG) e o índice de placa (IP). Também foi aplicado um questionário aos pais e responsáveis para avaliação da renda familiar e da escolaridade materna. Foram aplicados o teste do qui-quadrado e/ou Exato de Fischer; t-Student e Anova (α<0,05). Resultados: A maioria dos escolares tinha entre sete e dez anos de idade (57,9%), era do sexo feminino (55,4%), de escola pública (61,2%), com renda familiar abaixo de um salário-mínimo (51,2%) cujas mães tinham menos de 12 anos de estudo (62,8%). A prevalência de gengivite e índice de placa não aceitável foi de 18,2% e 79,3%, respectivamente. Verificou-se associação significativa entre o índice gengival e mães sem instrução(p=0,025) . Com exceção da variável sexo, houve associação significativa entre o índice de placa e as demais variáveis (p<0,05). Conclusão: A maioria dos pesquisados não apresentou alterações gengivais e dentre os que apresentaram gengivite, a inflamação leve foi predominante. Faz-se necessário uma melhor atenção à saúde bucal no serviço público, bem como o aumento da informação aos pais, em especial aqueles em situação de deprivação social...

To verify the periodontal condition and associated factors of children and adolescents enrolled in public and private schools in Caruaru-PE. Materials and Methods: The sample consisted of 121 students of both sexes, aged from seven to fourteen years old. Data was collected according to the gingival index (GI) and the plaque index (PI). Parents were asked to answer a questionnaire in order to assess family income and maternal education. We applied the Chi-Square and / or Fisher’s Exact, Student t test and ANOVA (α<0,05). Results: Of the 121 respondents, the majority (57.9%) was between seven and ten years old, were females (55.4%), from public school (61.2%), with family income lower than one minimum salary (51.2%), whose mothers had less than 12 years of education (62.8%). The prevalence of gingivitis and plaque index was not acceptable by 18.2% and 79.3%, respectively. There was a significant association between the gingival index and illiterate mothers(p=0,025). With the exception of gender, there was a significant association between the plaque index and the other variables (p <0.05). Conclusion: It’s necessary to pay more attention to oral health in the public service, as well as to increase the amount of information given to parents, specially to those in situations of social deprivation...

Mulher 40 graus à sombra: reflexões sobre a vida a partir dos 40 anos / Reflexions about life after forty years old

Reflexões sobre a crise dos quarenta anos