Phenotypic Characterization of Patients with Polycystic Ovary Syndrome in a Population from the Ecuadorian Andes: A Cross-Sectional Study.

Background: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in women of reproductive age. Diagnosis is based on the evidence-based international guideline 2018 and the Rotterdam Consensus to classify PCOS phenotypes. This study aims to characterize the biodemographic, clinical, metabolic, and reproductive variables and their relationship with PCOS phenotypes in a population from the Ecuadorian Andes. Methodology: A cross-sectional study was conducted with a non-random consecutive sample of 92 women who attended the outpatient gynecology and endocrinology clinic at the Hospital of the Technical University of Loja (UTPL)-Santa Inés, Loja, Ecuador, between January 2022 and July 2023. Descriptive statistics, mean calculations, standard deviation, parametric and nonparametric tests, odds ratios (OR), confidence intervals (CI), and p-values were employed. Results: The average age was 22 ± 3.4 years, with a predominantly mestizo, urban, single, highly educated, and medium-high socioeconomic level population. It was identified that phenotypes A + B are at a higher risk of developing oligomenorrhea and hypertriglyceridemia compared to phenotypes C + D, with statistically significant differences (p < 0.05). Furthermore, in terms of reproductive variables, phenotypes A + B exhibit a significantly higher frequency of elevated anti-Müllerian hormone (AMH) compared to phenotypes C + D, also with statistical significance (p < 0.05). Conclusions: The classical phenotypes A and B of PCOS are the most common in Ecuadorian Andean women and carry a higher risk of insulin resistance, anovulation, metabolic disorders, and elevated triglyceride levels compared to phenotypes C and D. Ethnic diversity and sociocultural habits influence the prevalence and clinical manifestations of these phenotypes.

NHD2-15, a novel antagonist of Growth Factor Receptor-Bound Protein-2 (GRB2), inhibits leukemic proliferation.

The majority of chronic myeloid leukemia (CML) cases are caused by a chromosomal translocation linking the breakpoint cluster region (BCR) gene to the Abelson murine leukemia viral oncogene-1 (ABL1), creating the mutant fusion protein BCR-ABL1. Downstream of BCR-ABL1 is growth factor receptor-bound protein-2 (GRB2), an intracellular adapter protein that binds to BCR-ABL1 via its src-homology-2 (SH2) domain. This binding constitutively activates growth pathways, downregulates apoptosis, and leads to an over proliferation of immature and dysfunctional myeloid cells. Utilizing novel synthetic methods, we developed four furo-quinoxaline compounds as GRB2 SH2 domain antagonists with the goal of disrupting this leukemogenic signaling. One of the four antagonists, NHD2-15, showed a significant reduction in proliferation of K562 cells, a human BCR-ABL1+ leukemic cell line. To elucidate the mode of action of these compounds, various biophysical, in vitro, and in vivo assays were performed. Surface plasmon resonance (SPR) assays indicated that NHD2-15 antagonized GRB2, binding with a KD value of 119 ± 2 µM. Cellulose nitrate (CN) assays indicated that the compound selectively bound the SH2 domain of GRB2. Western blot assays suggested the antagonist downregulated proteins involved in leukemic transformation. Finally, NHD2-15 was nontoxic to primary cells and adult zebrafish, indicating that it may be an effective clinical treatment for CML.

Variabilidade da frequência cardíaca durante a utilização de espirômetros de incentivo / Heart rate variability while using incentive spirometers

Fundamentos: Devido à influência da respiração sobre o sistema autonômico, alguns estudos têm avaliado a variabilidade da frequência cardíaca (VFC) durante a realização de técnicas utilizadas pela fisioterapia respiratória. Objetivos: Avaliar e comparar os efeitos da execução da espirometria de incentivo (EI) a fluxo e a volume na VFC de indivíduos saudáveis. Métodos: Estudo prospectivo cruzado, com 33 voluntários (25,88±4,65 anos). Os indivíduos realizaram EI a fluxo e a volume de forma randomizada. A VFC foi registrada em um único dia durante cinco momentos: repouso inicial, primeiro EI, repouso, segundo EI e repouso final, com duração de 5 minutos cada um. Foram analisadas as variáveis pNN50 e rMSSD. A comparação entre os efeitos da EI a fluxo e a volume na VFC foi realizada pelo ANOVA two way, seguida da análise post hoc pelo teste de Tukey, quando necessário. As diferenças foram consideradas significativas quando p<0,05.Resultados: O pNN50 aumentou significativamente durante ambos EI quando comparado aos seus respectivos tempo de repouso inicial (fluxo: 8,11±7,31%vs. 13,12±7,15 % p<0,001; volume: 7,12±5,39 % vs. 13,44±6,79 %, p<0,001). O mesmo ocorreu com o índice rMSSD (fluxo: 36,56±19,34 ms vs. 50,91±20,48 ms, p<0,001; volume: 34,93±13,48 ms vs. 50,75±18,93 ms, p<0,001). Entretanto, não houve diferenças significativas entre os tipos de EI. Conclusão: A realização da EI ocasiona aumento da modulação vagal de indivíduos saudáveis, que ocorre de forma similar nos dispositivos a fluxo e a volume.

Background: Due to the influence of breathing on the autonomic system, some studies have evaluated heart rate variability (HRV) while using respiratory physiotherapy techniques. Objectives: To assess and compare the effects of flow-oriented (FIS) and volume-oriented (VIS) incentive spirometry on HRV in healthy subjects. Methods: A crossover prospective study with 33 volunteers (25.88 ± 4.65 years old). The subjects underwent FIS and VIS randomly. Their HRV was recorded during a day at five moments: initial rest, first incentive spirometry, at rest, second incentive spirometry and final rest, with each phase lasting five minutes. The pNN50 and rMSSD variables were analyzed, comparing the effects of FIS and VIS on HRV through two-way variance analysis, followed by post-hoc analysis using the Tukey test, when necessary. Differences were considered significant when p<0.05.Results: During both incentive spirometry sessions, the pNN50 increased significantly compared to the respective initial rest time (FIS: 8.11±7.31% vs. 13.12±7.15%, p<0.001; VIS: 7.12±5.39% vs. 13.44±6.79%, p<0.001;) The same occurred with the rMSSD rating (FIS: 36.56±19.34ms vs. 50.91±20.48ms, p<0.001; VIS: 34.93±13.48ms vs. 50.75±18.93ms, p<0.001). However, there were no significant differences between the types of incentive spirometry. Conclusion: Incentive spirometry causes increased vagal modulation in healthy individuals, occurring similarly in the flow and volume devices.