Influence of maternal periuterine and periovarian fat on reproductive performance and fetal growth in rats.

We aimed to evaluate how high-fat diet consumption can interfere with rat reproductive performance and fetal development. High-fat diet (HFD) was initiated in 30-day-old rats, distributed into two groups (n=7 animals/group): Rats receiving a standard diet and rats receiving HFD. At adulthood, the rats were mated, and on day 21 of pregnancy, the females were anesthetized, decapitated, and submitted to laparotomy to obtain visceral and periovarian adipose tissue. The uterine horns were exposed for analysis of maternal reproductive performance. The fetuses and placentas were weighed and analyzed. Pearson's correlation test was used, and p<0.05 was considered significant. There was a significant positive correlation (HFD consumption x increased periovarian fat) and a negative correlation with the implantation, live fetus numbers and lower litter weight. Furthermore, the increased relative weight of periuterine fat was related to the lower number of live fetuses and litter weight. Regarding the fetal weight classification, there was a negative correlation between the relative weight of periovarian fat and the percentage of fetuses appropriate for gestational age and large for gestational age. Therefore, our findings show that HFD maternal intake negatively influenced on reproductive performance and fetal growth.

RASopathy Cohort of Patients Enrolled in a Brazilian Reference Center for Rare Diseases: A Novel Familial LZTR1 Variant and Recurrent Mutations.

Purpose: Noonan syndrome and related disorders are genetic conditions affecting 1:1000-2000 individuals. Variants causing hyperactivation of the RAS/MAPK pathway lead to phenotypic overlap between syndromes, in addition to an increased risk of pediatric tumors. DNA sequencing methods have been optimized to provide a molecular diagnosis for clinical and genetic heterogeneity conditions. This work aimed to investigate the genetic basis in RASopathy patients through Next Generation Sequencing in a Reference Center for Rare Diseases (IFF/Fiocruz) and implement the precision medicine at a public health institute in Brazil. Patients and Methods: This study comprises 26 cases with clinical suspicion of RASopathies. Sanger sequencing was used to screen variants in exons usually affected in the PTPN11 and HRAS genes for cases with clinical features of Noonan and Costello syndrome, respectively. Posteriorly, negative and new cases with clinical suspicion of RASopathy were analyzed by clinical or whole-exome sequencing. Results: Molecular analysis revealed recurrent variants and a novel LZTR1 missense variant: 24 unrelated individuals with pathogenic variants [PTPN11(11), NF1(2), SOS1(2), SHOC2(2), HRAS(1), BRAF(1), LZTR (1), RAF1(1), KRAS(1), RIT1(1), a patient with co-occurrence of PTPN11 and NF1 mutations (1)]; familial cases carrying a known pathogenic variant in PTPN11 (mother-two children), and a previously undescribed paternally inherited variant in LZTR1. The comparative modeling analysis of the novel LZTR1 variant p.Pro225Leu showed local and global changes in the secondary and tertiary structures, showing a decrease of about 1% in the ß-sheet content. Furthermore, evolutionary conservation indicated that Pro225 is in a highly conserved region, as observed for known dominant pathogenic variants in this protein. Conclusion: Bringing precision medicine through NGS towards congenital syndromes promotes a better understanding of complex clinical and/or undiagnosed cases. The National Policy for Rare Diseases in Brazil emphasizes the importance of incorporating and optimizing diagnostic methodologies in the Unified Brazilian Health System (SUS). Therefore, this work is an important step for the NGS inclusion in diagnostic genetic routine in the public health system.

O Papel bidirecional da nicotina na tarefa Go/No-go: um ensaio clínico piloto / The bidirectional role of nicotine in a Go/No-go task: a pilot clinical trial / El papel bidireccional de la nicotina en la tarea Go/no-go: un ensayo clínico piloto

Estudos mostram que o tabagismo é responsável por afetar algumas funções cognitivas. No entanto, a nicotina é apenas um dos componentes existentes no cigarro e existem evidências de que pode servir como agente neuroprotetivo e causar melhoras em algumas funções cognitivas. O objetivo desta pesquisa foi investigar como a nicotina interage com algumas funções cognitivas. Um ensaio clínico piloto com administração de gomas de nicotina contendo 2-mg ou 4-mg, ou gomas placebo contendo a mesma textura, sabor e aparência, foi realizado. Quarenta e dois participantes participaram da pesquisa e os resultados indicaram que a relação entre nicotina e o desempenho na tarefa Go/No-Go podem ser bidirecionais. Os resultados indicaram que participantes do grupo que utilizaram 4-mg de nicotina apresentaram menor desempenho, enquanto os participantes que fizeram uso de 2-mg de nicotina tiveram melhor desempenho do que os demais. Esta pesquisa tem aplicações biopsicossociais e podem ajudar na compreensão da relação entre tabagismo e nicotina, além de contribuir para estratégias que possam ajudar no abandono do cigarro ou na melhora de condições que afetem a cognição (AU).

Past findings in the literature indicated that smoking could affect given cognitive functions. However, nicotine is only one of the components in cigarettes and there is evidence that it may act as a neuroprotective agent and improve some cognitive functions. The purpose of this research was to investigate how nicotine interacts with certain cognitive functions. We conducted a pilot clinical trial using nicotine gum containing 2-mg or 4-mg, or placebo gum with the same texture, flavor, and appearance. Forty-two healthy nonsmokers were enrolled in this research. Our findings indicated that the relationship between nicotine and performance on the Go/No-Go task might be opposite. The results showed that participants in the 4-mg group performed worse, while participants who used 2-mg of nicotine performed better than the others. This research supports biopsychosocial applications and can help interpret the relationship between smoking and nicotine, and contribute to strategies that may support smoking cessation, or improve conditions that affect cognition (AU).

Estudios demuestran que el tabaquismo es responsable de afectar a algunas funciones cognitivas. Sin embargo, la nicotina es solo uno de los componentes de los cigarrillos, y existen evidencias de que la nicotina puede actuar como un agente neuroprotector y mejorar algunas funciones cognitivas. El objetivo de este estudio fue investigar cómo la nicotina interactúa con algunas funciones cognitivas. Se realizó un ensayo clínico piloto con la administración de chicles de nicotina de 2 mg o 4 mg, o chicles de placebo con la misma textura, sabor y apariencia. Cuarenta y dos participantes participaron en la investigación y los resultados indicaron que la relación entre la nicotina y el rendimiento en la tarea Go/No-go puede ser bidireccional. Los resultados indicaron que los participantes del grupo de 4 mg obtuvieron un menor rendimiento en las variables del Go/No-Go, mientras que los participantes que utilizaron 2 mg de nicotina obtuvieron un mejor rendimiento que los demás. Esta investigación respalda las aplicaciones biopsicosociales y puede ayudar a interpretar la relación entre el tabaquismo y la nicotina, además de contribuir a las estrategias que pueden ayudar a dejar de fumar o mejorar las condiciones que afectan la cognición (AU).

Effects of Nicotine Gum Administration on Vision (ENIGMA-Vis): Study Protocol of a Double-Blind, Randomized, and Controlled Clinical Trial.

Studies reported that tobacco addiction was related to visual impairments, but one unresolved issue is whether the impairments are related to the many compounds existing in the cigarettes or to the effects of nicotine. On the other hand, nicotine gum can be used as replacement therapy or as a neuroprotective agent for some diseases. The main purpose of this controlled trial is to investigate the effects of nicotine gum on vision. The ENIGMA-Vis trial aims to compare two dosages of nicotine gum (2 and 4 mg) and a placebo gum in a randomized, double-blind, placebo-controlled trial of 100 participants to be allocated into a single group assignment of repeated measures (two studies; N = 50 for each one). Eligibility criteria are healthy non-smokers not diagnosed with substance abuse and without an acute or chronic medical condition. Intervention will last three sessions for each participant with a window frame of 1 week per session. Study outcomes are (1) short-term effects of nicotine gum on contrast sensitivity; (2) short-term effects of nicotine gum on chromatic contrast discrimination; and (3) whether demographics, body mass index, or serum cotinine predicts response of visual processing. This study addresses an important gap in the effects of nicotine on vision. One of the main takeaways of this study is to understand the effects of nicotine on contrast sensitivity and chromatic contrast discrimination. This information will provide a further understanding of how nicotine interacts with early visual processes and help determine how the different components present during smoking can affect vision. Clinical Trial Registration Number: RBR-46tjy3.