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In 2020, Mexico reported the lowest tuberculosis (TB) incidence on record, and it is unclear to what extent COVID-19 has impacted TB surveillance, diagnosis, and treatment. It is important to understand COVID-19's impact in Baja California (BC), which has the highest TB burden in Mexico. With the increasing number of migrants and asylum seekers arriving in BC, limited resources and crowded living conditions increase the risk of TB transmission. The purpose of this study was to assess the impact of COVID-19 on TB diagnosis and treatment in BC. We were also interested in health disparities experienced by migrants in BC. We conducted a mixed methods analysis using quantitative surveillance data obtained from the Mexico National TB Program (NTP) and qualitative data collected through in-depth interviews and focus group discussions with TB program directors and personnel in BC's four provincial health jurisdictions. Compared to the year prior, surveillance data from March 2020 - February 2021 revealed that TB incidence in BC declined by 30.9% and favorable TB outcomes (TB cure or treatment completion) declined by 49.8%. Elucidating differences by migrant status was complicated by the lack of standardized collection of migrant status by the NTP. Qualitative analysis revealed that TB diagnostic and treatment supplies and services became limited and disproportionately accessible across jurisdictions since the pandemic began; however, favorable adaptations were also reported, such as increased telemedicine use and streamlined care referral processes. Participants shared that migrant status is susceptible to misclassification and that TB care is difficult due to the transitory nature of migrants. This study did not identify major differences in TB service delivery or access between migrants and non-migrants in BC; however, migrant status was frequently missing. COVID-19 has overwhelmed health systems worldwide, disrupting timely TB diagnostic and treatment services, and potentially caused underdiagnosis of TB in BC. TB programs in BC should quickly restore essential services that were disrupted by COVID-19 while identifying and preserving beneficial program adaptations, such as telemedicine and streamlined care referral processes. Improved methods for documenting migrant status of TB cases are also needed.

Between March 2020 and February 2021, the state of Baja California, Mexico, which borders the United States, registered 46,118 confirmed cases of COVID-19 with a mortality rate of 238.2 deaths per 100,000 residents. Given limited access to testing, the population prevalence of SARS-CoV-2 infection is unknown. The objective of this study is to estimate the seroprevalence and real time polymerase chain reaction (RT-PCR) prevalence of SARS-CoV-2 infection in the three most populous cities of Baja California prior to scale-up of a national COVID-19 vaccination campaign. Probabilistic three-stage clustered sampling was used to conduct a population-based household survey of residents five years and older in the three cities. RT-PCR testing was performed on nasopharyngeal swabs and SARS-CoV-2 seropositivity was determined by IgG antibody testing using fingerstick blood samples. An interviewer-administered questionnaire assessed participants' knowledge, attitudes, and preventive practices regarding COVID-19. In total, 1,126 individuals (unweighted sample) were surveyed across the three cities. Overall prevalence of SARS-CoV-2 infection by RT-PCR was 7.8% (95% CI 5.5-11.0) and IgG seroprevalence was 21.1% (95% CI 17.4-25.2). There was no association between border crossing in the past 6 months and SARS-CoV-2 prevalence (unadjusted OR 0.40, 95%CI 0.12-1.30). While face mask use and frequent hand washing were common among participants, quarantine or social isolation at home to prevent infection was not. Regarding vaccination willingness, 30.4% (95% CI 24.4-3 7.1) of participants said they were very unlikely to get vaccinated. Given the high prevalence of active SARS-CoV-2 infection in Baja California at the end of the first year of the pandemic, combined with its low seroprevalence and the considerable proportion of vaccine hesitancy, this important area along the Mexico-United States border faces major challenges in terms of health literacy and vaccine uptake, which need to be further explored, along with its implications for border restrictions in future epidemics.

Coccidioidomycosis, or Valley fever, is caused by two species of dimorphic fungi. Based on molecular phylogenetic evidence, the genus Coccidioides contains two reciprocally monophyletic species: C. immitis and C. posadasii. However, phenotypic variation between species has not been deeply investigated. We therefore explored differences in growth rate under various conditions. A collection of 39 C. posadasii and 46 C. immitis isolates, representing the full geographical range of the two species, was screened for mycelial growth rate at 37 °C and 28 °C on solid media. The radial growth rate was measured for 16 days on yeast extract agar. A linear mixed effect model was used to compare the growth rate of C. posadasii and C. immitis at 37 °C and 28 °C, respectively. C. posadasii grew significantly faster at 37 °C, when compared to C. immitis; whereas both species had similar growth rates at 28 °C. These results indicate thermotolerance differs between these two species. As the ecological niche has not been well-described for Coccidioides spp., and disease variability between species has not been shown, the evolutionary pressure underlying the adaptation is unclear. However, this research reveals the first significant phenotypic difference between the two species that directly applies to ecological research.

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), remains a leading cause of death from infectious diseases globally. The treatment of active TB relies on first- and second-line drugs, however, the emergence of drug resistance poses a significant challenge to global TB control efforts. Recent advances in whole-genome sequencing combined with machine learning have shown promise in predicting drug resistance. This study aimed to evaluate the performance of four machine learning models in classifying resistance to ethambutol, isoniazid, and rifampicin in M. tuberculosis isolates. Methods: Four machine learning models—Extreme Gradient Boosting Classifier (XGBC), Logistic Gradient Boosting Classifier (LGBC), Gradient Boosting Classifier (GBC), and an Artificial Neural Network (ANN)—were trained using a Variant Call Format (VCF) dataset preprocessed by the CRyPTIC consortium. Three datasets were used: the original dataset, a principal component analysis (PCA)-reduced dataset, and a dataset prioritizing significant mutations identified by the XGBC model. The models were trained and tested across these datasets, and their performance was compared using sensitivity, specificity, Precision, F1-scores and Accuracy. Results: All models were applied to the PCA-reduced dataset, while the XGBC model was also evaluated using the mutation-prioritized dataset. The XGBC model trained on the original dataset outperformed the others, achieving sensitivity values of 0.97, 0.90, and 0.94; specificity values of 0.97, 0.99, and 0.96; and F1-scores of 0.93, 0.94, and 0.92 for ethambutol, isoniazid, and rifampicin, respectively. These results demonstrate the superior accuracy of the XGBC model in classifying drug resistance. Conclusions: The study highlights the effectiveness of using a binary representation of mutations to train the XGBC model for predicting resistance and susceptibility to key TB drugs. The XGBC model trained on the original dataset demonstrated the highest performance among the evaluated models, suggesting its potential for clinical application in combating drug-resistant tuberculosis. Further research is needed to validate and expand these findings for broader implementation in TB diagnostics. [ABSTRACT FROM AUTHOR]

Background: Exercise is an essential pillar for human health, as it contributes to physical, mental, and emotional well-being. Well-recognized international organizations, such as the World Health Organization, advocate for integrating exercise into healthy lifestyles, recognizing its importance in disease prevention and improving quality of life. However, despite the consensus on its value, there is no universal agreement on specific prescriptions for vulnerable groups, highlighting the need for personalized approaches that consider the unique characteristics and needs of everyone. Emerging studies have demonstrated that exercise training performed at the intensity that elicits maximal fat oxidation improves insulin sensitivity, cardiorespiratory fitness, and body composition in patients with obesity, making it a highly effective strategy for long-term weight management and metabolic health in this specific population. Methods: The present study protocol settles the basis for a 16-week randomized clinical trial based on exercise prescription at the maximal fat oxidation rate combined with resistance training in young individuals with overweight and obesity. Expected Results: This study will elucidate how FatMax, with or without resistance exercises, can enhance metabolic flexibility, increase fat oxidation, and improve body composition, evaluating changes in biochemical parameters (cholesterol, glucose, triglycerides, and inflammatory markers), metabolic biomarkers (determination of fat and carbohydrate utilization rates during rest and exercise), and epigenetic indicators (focusing on microRNAs associated with adipogenesis, inflammation, and fat metabolism). ClinicalTrials.gov identification number: NCT06553482 (FatMax Training on Metabolic and Epigenetic Parameters). [ABSTRACT FROM AUTHOR]

Approximately 80% of breast cancer (BC) cases are estrogen receptor positive (ER+) and sensitive to hormone treatment; Tamoxifen is a prodrug, and its main plasmatic active metabolites are 4-hydroxytamoxifen (4-OH Tam) and endoxifen. Despite the effectiveness of tamoxifen therapy, resistance can be developed. An increment in eukaryotic initiation factor-4A complex (eIF4A) activity can result in tamoxifen-resistant tumor cells. For this work, we developed a cell variant resistant to 4-OH Tam and endoxifen, denominated MCF-7Var E; then, the aim of this research was to reverse the acquired resistance of this variant to tamoxifen metabolites by incorporating the natural compound auraptene. Combination treatments of tamoxifen derivatives and auraptene successfully sensitized the chemoresistant MCF-7Var E. Our data suggest a dual regulation of eIF4A and ER by auraptene. Joint treatments of 4-OH Tam and endoxifen with auraptene identified a novel focus for chemoresistance disruption. Synergy was observed using the auraptene molecule and tamoxifen-derived metabolites, which induced a sensitization in MCF-7Var E cells and ERα parental cells that was not observed in triple-negative breast cancer cells (TNBC). Our results suggest a synergistic effect between auraptene and tamoxifen metabolites in a resistant ER+ breast cancer model, which could represent the first step to achieving a pharmacologic strategy. [ABSTRACT FROM AUTHOR]

Mangrove forests in the Gulf of California, Mexico represent the northernmost populations along the Pacific coast and thus they are likely to be source populations for colonization at higher latitudes as climate becomes more favorable. Today, these populations are relatively small and fragmented and prior research has indicated that they are poor in genetic diversity. Here we set out to investigate whether the low diversity in this region was a result of recent colonization, or fragmentation and genetic drift of once more extensive mangroves due to climatic changes in the recent past. By sampling the two major mangrove species, Rhizophora mangle and Avicennia germinans, along the Pacific and Atlantic coasts of Mexico, we set out to test whether concordant genetic signals could elucidate recent evolution of the ecosystem. Genetic diversity of both mangrove species showed a decreasing trend toward northern latitudes along the Pacific coast. The lowest levels of genetic diversity were found at the range limits around the Gulf of California and the outer Baja California peninsula. Lack of a strong spatial genetic structure in this area and recent northern gene flow in A. germinans suggest recent colonization by this species. On the other hand, lack of a signal of recent northern dispersal in R. mangle, despite the higher dispersal capability of this species, indicates a longer presence of populations, at least in the southern Gulf of California. We suggest that the longer history, together with higher genetic diversity of R. mangle at the range limits, likely provides a gene pool better able to colonize northwards under climate change than A. germinans.