Teresa Corona

Background/Objectives: Multiple Sclerosis (MS) is a chronic immune-mediated disorder characterized by neuroinflammation and neurodegeneration. Increasing evidence implies the kynurenine pathway (KP) in the MS pathophysiology; however, data from Mexican populations are lacking. This exploratory study aimed to characterize central and circulating KP metabolites in Mexican patients with MS and to investigate potential genetic variants in KP-related genes. Methods: Serum concentrations of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK), as well as cerebrospinal fluid (CSF) levels of KYNA, quinolinic acid (QUIN), interleukin-4 (IL-4), and interleukin-6 (IL-6), were determined in treatment-naïve relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and treated PMS patients. Serum levels were compared with those of healthy controls, and CSF findings contrasted with those of non-MS neurological patients and individuals with neurocysticercosis (NCC). Public whole-exome datasets were analyzed for variants in KP-related genes, and target exome sequencing was performed in three Mexican patients with MS. Results: Serum concentrations of KYNA and 3-HK were decreased in MS patients compared with healthy controls. CSF KYNA and QUIN levels did not differ significantly among MS subtypes or the non-MS neurological group, but they were lower than those observed in NCC. IL-4 and IL-6 were detectable in MS CSF samples, supporting the presence of intrathecal inflammation. Genetic and bioinformatic analyses identified variants in genes encoding KP enzymes in both public MS datasets and in Mexican patients with MS. Conclusions: These findings indicate an altered KP metabolism in Mexican MS patients, particularly during the relapse phase, and suggest a possible contribution of genetic variability. Further large-scale studies are needed to confirm these observations and to determine the functional implications of KP-related genetic variants in MS.

Objective. To analyzes the gender gap among residents enrolled in the medical specialization program of the Graduate Division at the Universidad Nacional Autónoma de México (UNAM), Facultad de Medicina. Materials and methods. We conducted a descriptive observational study of students registered in all 78 medical specialties offered by UNAM over a period of 7 years (2015-2022) at approximately 161 hospitals in Mexico. Results. A total of 79 175 students were studied, we observed a predominance of women 51.69%, compared to 48.30% men. In medical specialties, we found a predominance of women of 57.33%, in contrast to surgical specialties with 44.76% women. The specialties with the most women enrolled were dermatology, neonatology, pediatrics, gynecology, and psychiatry. In men, the specialties with the most enrollment were general surgery, cardiology, neurosurgery, plastic surgery among others. Conclusion. Women predominance is observed in some medical specialties, especially those that require caregiving tasks. However, a gap remains between men and women, particularly in surgical specialties and in higher decision-making positions. We suggest extending support networks to include men as well as women.

Introduction: The objective of this study was to describe and analyze residents’ perceptions of characteristics on the expansive/restrictive continuum of their clinical learning environment. Methods: We conducted a quantitative, descriptive and cross-sectional study. A self-administered questionnaire was designed, programmed and applied to residents at the Faculty of Medicine of the National Autonomous University of Mexico. The instrument was structured in eight sections, and for this article, Section 3, which referred to clinical environments and violence was considered. The questionnaire had an 85% response rate, with 12,612 residents from 113 medical units and 78 specialties participating. The reliability and internal consistency measured with alpha omega obtained a value of ω 0.835 (CI; 0.828–0.843). Results: Unpleasant, competitive, tense and conflictive contexts were related to restrictive environments. Sexual orientation influenced the perception of intolerance in the clinical setting with respect to discriminatory comments, such that for gender minorities, the environment was experienced as exclusionary. First-year residents perceived environments as more aggressive, a perception that tended to decrease in later years of residency. Discussion: Abuses in power relations, rigid hierarchical positions and offensive clinical interactions may foster restrictive environments. In such settings, the reproduction of socio-culturally learned violence is feasible; however, asymmetrical relationships may be deconstructed and transformed.

Purpose Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. Methods We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). Results In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. Conclusions The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Alternative chemotherapy regimens, including cisplatin, carmustine, or other agents, have been shown to be effective; however, the use of carboplatin plus vincristine (C/V) has not been studied before. In this study, we aimed to determine the survival rates in patients treated with C/V, by comparing our findings with treatments based on temozolomide (TMZ), and to explore a possible relationship with the methylation status of the methylguanine methyltransferase (MGMT) promoter in patients with glioblastoma (GB). A retrospective cohort study was conducted involving 45 surgically treated patients diagnosed with GB. Fresh tissue samples were examined by the DNA bisulfite conversion method to determine methylation status. After surgery, different chemotherapy regimens were employed as adjuvants. Follow-up of participants was performed as outpatients at three-month intervals to determine overall survival (OS), by comparing the use of TMZ versus C/V. MGMT promoter methylation status could only be determined in 35 samples; 20 patients received adjuvant chemotherapy, of which 14 were treated with C/V and six with TMZ-based schemes. The median OS (mOS) was eight months (range: 1-24 months). OS was 57.25% at six months, 48.7% at 12 months, and 28.5% at 24 months. In the TMZ group, an OS of 83% was observed at 24 months. In the C/V group, OS was 71.4% at six months, 57.1% at 12 months, and 35.7% at 24 months. Patients who did not receive adjuvant chemotherapy treatment had the lowest survival rates with an OS of 39.9% at six months, 26.6% at 12 months, and 19.9% ​​at 24 months. Based on our findings, C/V offers an accessible and effective alternative treatment when the TMZ-based scheme is not accessible, providing higher rates of OS compared to patients without chemotherapy management. The methylation status of the MGMT promoter is a significant prognostic factor, resulting in higher survival rates among patients when it is methylated.