AUTO-TUNE: SELECTING THE DISTANCE THRESHOLD FOR INFERRING HIV TRANSMISSION CLUSTERS.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained hetero-sexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

People with type 1 diabetes exhibit lower exercise capacity compared to a control population with similar physical activity levels.

AIMS: We aimed to assess physical activity (PA) levels, adherence to PA guidelines, and fitness capacity in individuals with type 1 diabetes (T1D) and control population. METHODS: This cross-sectional study included 232 T1D and 248 controls. PA levels (IPAQ-SF questionnaire), adherence to guidelines (>150 min/week of moderate-to-vigorous PA), fitness capacity (VO2max, maximal incremental test on a cycle ergometer and 1RM test) were assessed, along with other clinical variables. RESULTS: Total PA levels (T1D 2202 ± 1839 vs. controls 2357 ± 2189 METs/min/week), adherence (T1D 53.1 % vs controls 53.2 %), and sedentariness (T1D 27.3 % vs. controls 25.1 %) were similar between groups. However, participants with T1D exhibited significantly lower levels of VO2max (29.1 ± 10.5 vs. 32.5 ± 11.5 mlO2/kg/min, p < 0.001), work capacity (2.73 ± 1.03 vs. 3 ± 10 W/kg of body weight, p = 0.004) and strength capacity (2.29 ± 0.53 vs. 2.41 ± 0.79 kg/kg body weight in 1RM, p = 0.01) than controls, after adjusting for sex and age. CONCLUSIONS: Individuals with T1D exhibit lower fitness capacity compared to a control population, regardless of age and sex, even when presenting similar levels of total physical activity and adherence to guidelines.

Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes / Impacto del subtipo KRASG12D y mutaciones patogénicas concurrentes en los resultados del cáncer de pulmón de células no pequeñas avanzado

Purpose: Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10–40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited. Methods: A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023. Results: KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRASG12D (n = 16, 32%) and KRASG12C (n = 16, 32%) represented the most prevalent subtypes. KRASG12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRASG12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23–17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16–0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08–0.70; p = 0.009). Conclusions: To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.(AU)

IMPLEMENTING SYSTEMATIC PATIENT-REPORTED MEASURES FOR CHRONIC CONDITIONS THROUGH THE NAVETA VALUE-BASED TELEMEDICINE INITIATIVE: RESULTS OF AN OBSERVATIONAL, RETROSPECTIVE AND MULTICENTER STUDY.

BACKGROUND: Patient-reported outcome and experience measures can play a critical role in providing patient-centered and value-based healthcare to a growing population of chronically ill patients. Value-based telemedicine platforms such as the Naveta initiative may facilitate the effective integration of these tools into healthcare systems. OBJECTIVE: This study aims to evaluate the response rate to electronic patient-reported outcome measures (ePROMs) and electronic patient-reported experience measures (ePREMs) among patients participating in the Naveta telemedicine initiative, its correlations with sociodemographic and clinical characteristics, and the evolution of the rates over time. METHODS: Between January 1, 2021, and June 30, 2023, a total of 53,364 ePREMs and ePROMs for 20 chronic conditions were administered through the Naveta-Phemium platform. Descriptive statistics were used to summarize continuous and categorical variables. Differences in response rates within each sociodemographic variable were analyzed using logistic regression models, with significance assessed via the chi-square and post-hoc Tukey tests. Two-way ANOVA was used to examine the interaction between time interval and disease type on response rate evolution. RESULTS: A total of 3,372 patients with severe chronic diseases from 64 public hospitals in Spain participated in the Naveta health questionnaire project. The overall response rate to ePROMs and ePREMs during the first 2.5 years of the Naveta initiative was 46.12%, with a baseline rate of 53.33%. Several sociodemographic factors correlated with lower response rates, including male gender, older age, lower education level, frequent alcohol use, being a student, and not being physically active. There were also significant variations in response rates among different types of chronic conditions, with the highest rates for respiratory (71.45%), oncologic (62.70%), digestive (62.40%), and rheumatic diseases (57.82%), and the lowest for HIV+ patients (32.93%). During the first 6 months of follow-up, response rates decreased in all disease types, except for the oncology group, which increased up to 100%. Subsequently, the overall response rate approached baseline levels. CONCLUSIONS: Recognizing the influence of sociodemographic factors on response rates is critical to identifying barriers to participation in telemonitoring programs and ensuring inclusiveness in patient-centered healthcare practices. The observed decline in response rates at follow-up may be due to survey fatigue, highlighting the need for strategies to mitigate this effect. In addition, the variation in response rates across chronic conditions emphasizes the importance of tailoring telemonitoring approaches to specific patient populations.

Impact of KRASG12D subtype and concurrent pathogenic mutations on advanced non-small cell lung cancer outcomes.

PURPOSE: Mutations in the Kirsten rat sarcoma viral (KRAS) oncogene constitute a significant driver of lung adenocarcinoma, present in 10-40% of patients, which exhibit heterogeneous clinical outcomes, mainly driven by concurrent genetic alterations. However, characterization of KRAS mutational subtypes and their impact on clinical outcomes in Latin America is limited. METHODS: A cohort study was conducted at the National Cancer Institute (INCan) of Mexico. Individuals with advance-staged of adenocarcinoma and KRAS mutations, detected by next-generation sequencing, having undergone at least one line of therapy were included for analysis. Clinical and pathological characteristics were retrieved from institutional database from June 2014 to March 2023. RESULTS: KRAS was identified in fifty-four (15.6%) of 346 patients, among which 50 cases were included for analysis. KRASG12D (n = 16, 32%) and KRASG12C (n = 16, 32%) represented the most prevalent subtypes. KRASG12D mutations were associated with female (p = 0.018), never smokers (p = 0.108), and concurrences with EGFR (25.0% vs. 17.6%, p = 0.124) and CDKN2A (18.8% vs. 14.7%, p = 0.157). KRASG12D patients showed a better ORR (66.6% vs. 30.0%; OR 4.66, 95% CI 1.23-17.60, p = 0.023) and on multivariate analysis was significantly associated with better PFS (HR 0.36, 95% CI 0.16-0.80; p = 0.012) and OS (HR 0.24, 95% CI 0.08-0.70; p = 0.009). CONCLUSIONS: To our knowledge, this study represents the first effort to comprehensively characterize the molecular heterogeneity of KRAS-mutant NSCLC in Latin American patients. Our data reinforce the current view that KRAS-mutated NSCLC is not a single oncogene-driven disease and emphasizes the prognostic impact of diverse molecular profiles in this genomically defined subset of NSCLC. Further validation is warranted in larger multicenter Latin American cohorts to confirm our findings.

The gray zone between legitimate and predatory open access scientific publishing.

Certain open access publishers based on the article processing charges model have found it highly profitable to operate within a gray zone that encompasses both legitimate and predatory publishing practices. In this context, maximum profits can be obtained by adequate combinations of journal acceptance rates and elevated article processing charges. Considering that the gray zone can be particularly challenging to identify and that it poses risks for authors aiming to establish academic carreers, we believe it is important to provide a comprehensive description of it.

Assessing HIV knowledge in Mexican people living with HIV: development and validation of CC-VIH questionnaire.

The level of knowledge that people living with human immunodeficiency virus (HIV) have about their disease can impact their adherence to treatment. The aim of this study was to develop a tool to assess the knowledge about HIV among people receiving treatment at a specialized clinic in Mexico City. To establish content validity, expert judges were invited to conceptualize the tool and propose items for the defined dimensions. A total of 490 individuals living with HIV completed the 91-item questionnaire, with 82.2% being male and a mean age of 36.1 years. We conducted an exploratory factor analysis, resulting in a reduced questionnaire of 45 questions. A three-factor solution explained 36.2% of the variance in HIV knowledge. The total scale had a reliability coefficient of 0.937, and each subscale had reliabilities of 0.828, 0.856 and 0.859. Lower educational level (F(336) = 8.488, p < 0.001) and female gender (t(399) = 2.003, p = 0.046) were associated with lower scores on the HIV knowledge questionnaire. This tool appears suitable for measuring HIV knowledge in people living with HIV, although future studies are required to confirm its structure and reduce its extension.

SARSCoV-2 antibody prevalence and titers in persons living with HIV cared for at a large tertiary reference center in Mexico City.

OBJECTIVE: To assess SARS-CoV-2 antibody prevalence and titers in people living with HIV (PLWHIV) on antiretroviral treatment (ART) enrolled at a tertiary reference hospital in Mexico. METHODS: Two plasma aliquots per person, used for HIV viral load follow-up between 01/2020 and 09/2021, were used to assess total anti-N and neutralizing SARS-CoV-2 antibodies. Sociodemographic, clinical, and SARS-CoV-2 exposure risk information were collected. The risk associated with SARS-CoV-2 exposure and associations with antibody titers were analyzed with logistic, Cox, and linear multivariable models. RESULTS: 803 PLWHIV participated; 233 had detectable SARS-CoV-2 antibodies (prevalent cases), and 132 seroconverted (incident cases). Overall, the adjusted prevalence was 46.45%, with an incidence rate of 3.78 cases/100 person-months. Factors associated with prevalent cases included lower age, location (western zone of Mexico City and the neighboring Mexico State), use of public transport, attendance at meetings without social distancing, and higher CD4 + T cell counts (p < 0.05; multivariable logistic model). BNT162b2 vaccination reduced incident cases (Cox adjusted HR = 0.4; p = 0.013). Notably, previously infected and vaccinated individuals showed maximization of neutralizing activity (p < 0.001). No associations between SARS-CoV-2 neutralization and HIV-related variables (CD4 + T cell counts, viral load, number of years in viral suppression, ART regimen) were found in multivariable analysis. CONCLUSIONS: SARS-CoV-2 infection was associated with community risk rather than HIV-associated variables in PLWH on ART and clinical follow-up. Antibody neutralization activity in vaccinated participants was maximized with previous SARS-CoV-2 infection.

Molecular epidemiology of HIV-1 among adult female sex workers at the Guatemala-Mexico border.

ABSTRACTSex workers have been demonstrated to have increased vulnerabilities to HIV and a high population prevalence of the disease. Despite their increased risk, sex workers have been underrepresented in molecular epidemiology studies assessing HIV in Mesoamerica. This study aims to describe the sociodemographic characteristics and phylogenetic profile of HIV-1 within a cohort of HIV-positive female sex workers (FSW) situated at the Guatemala-Mexico border. HIV viral sequences were collected from a cohort of FSW ≥18 years of age from San Marcos, Guatemala (n = 6) and compared to viral sequences collected as part of the Mesoamerican Drug Resistance Monitoring Programme to assess HIV viral diversity in Mexico and Guatemala (n = 3956). All of the FSW sampled were determined to have genetically unrelated HIV infections, suggesting multiple introductions of the virus and/or the potential existence of populations not captured by current surveillance efforts. Many reported numerous vulnerabilities that may have heightened their risk of acquiring and transmitting HIV through sex work activities. Our phylogenetic analysis indicated that national surveillance programmes may not fully capture the viral diversity among FSW and their clients within this region. Additional research is needed to fully capture HIV diversity and transmission in Mesoamerica, especially in the Guatemala-Mexico border region.

Honduras HIV cohort: HLA class I and CCR5-Δ32 profiles and their associations with HIV disease outcome.

IMPORTANCE: We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

Anxiety and Depression in Family Members of Critically Ill Covid-19 Inpatients: Brief Psychological Interventions via Telephone, an Exploratory Study.

Purpose: This study aimed to assess the level of anxiety and depression in relatives of critically ill COVID-19 patients admitted to the intensive care unit (ICU), and to perform an exploratory pilot study on the implementation of telephone psychological interventions to reduce the initial levels of anxiety and depression in this population. Patients and Methods: Family members of COVID-19 inpatients at ICU answered GAD-7, PHQ-9 and questions on socio-demographic data. A brief psychological intervention was applied via telephone based on the needs of the participants (with adequate adaptation, with symptoms of anxiety, depression, or both). After intervention, participants completed the Patient Global Impression of Change Scale. Results: A total of 1307 relatives were included (66.5% female), 34% and 29% had anxiety and depressive symptoms, respectively. These symptoms were associated with female gender, unemployment, and being the parent or partner of the patient. After intervention, 57.9% reported felt better, 31.3% a little better and 6.6% much better; and with emotional regulation techniques and psychoeducation, higher percentages of feeling better or much better were reported. Conclusion: Brief interventions to reduce the psychological impact of inpatient family members could be effective but will need to be explored further in future studies.

Transcriptional signature of early cisplatin drug-tolerant persister cells in lung adenocarcinoma.

Resistance to cisplatin is the main cause of treatment failure in lung adenocarcinoma. Drug-tolerant-persister (DTP) cells are responsible for intrinsic resistance, since they survive the initial cycles of treatment, representing a reservoir for the emergence of clones that display acquired resistance. Although the molecular mechanisms of DTP cells have been described, few studies have investigated the earliest molecular alterations of DTP cells in intrinsic resistance to cisplatin. In this work, we report a gene expression signature associated with the emergence of cisplatin-DTP cells in lung adenocarcinoma cell lines. After a single exposure to cisplatin, we sequenced the transcriptome of cisplatin-DTPs to identify differentially expressed genes. Bioinformatic analysis revealed that early cisplatin-DTP cells deregulate metabolic and proliferative pathways to survive the drug insult. Interaction network analysis identified three highly connected submodules in which SOCS1 had a significant participation in controlling the proliferation of cisplatin-DTP cells. Expression of the candidate genes and their corresponding protein was validated in lung adenocarcinoma cell lines. Importantly, the expression level of SOCS1 was different between CDDP-susceptible and CDDP-resistant lung adenocarcinoma cell lines. Moreover, knockdown of SOCS1 in the CDDP-resistant cell line partially promoted its susceptibility to CDDP. Finally, the clinical relevance of the candidate genes was analyzed in silico, according to the overall survival of cisplatin-treated patients from The Cancer Genome Atlas. Survival analysis showed that downregulation or upregulation of the selected genes was associated with overall survival. The results obtained indicate that these genes could be employed as predictive biomarkers or potential targets to improve the effectiveness of CDDP treatment in lung cancer patients.

Impact of Tyrosine Kinase Inhibitors on the Immune Response to SARS-CoV-2 Vaccination in Patients with Non-Small Cell Lung Cancer.

Immune dysregulation and cancer treatment may affect SARS-CoV-2 vaccination protection. Antibody production by B-cells play a vital role in the control and clearance of the SARS-CoV-2 virus. This study prospectively explores B-cell seroconversion following SARS-CoV-2 immunization in healthy individuals and non-small cell lung cancer (NSCLC) patients undergoing oncological treatment. 92 NSCLC patients and 27 healthy individuals' blood samples were collected after receiving any COVID-19 vaccine. Serum and mononuclear cells were isolated, and a serum surrogate virus neutralization test kit evaluated SARS-CoV-2 antibodies. B-cell subpopulations on mononuclear cells were characterized by flow cytometry. Patients were compared based on vaccination specifications and target mutation oncological treatment. A higher percentage of healthy individuals developed more SARS-CoV-2 neutralizing antibodies than NSCLC patients (63% vs. 54.3%; p = 0.03). NSCLC patients receiving chemotherapy (CTX) or tyrosine kinase inhibitors (TKIs) developed antibodies in 45.2% and 53.7%, of cases, respectively, showing an impaired antibody generation. CTX patients exhibited trends towards lower median antibody production than TKIs (1.0, IQR 83 vs. 38.23, IQR 89.22; p = 0.069). Patients receiving immunotherapy did not generate antibodies. A sub-analysis revealed that those with ALK mutations exhibited non-significant trends towards higher antibody titers (63.02, IQR 76.58 vs. 21.78, IQR 93.5; p = 0.1742) and B-cells quantification (10.80, IQR 7.52 vs. 7.22, IQR 3.32; p = 0.1382) against the SARS-CoV-2 spike protein than EGFR patients; nonetheless, these differences were not statistically significant. This study shows that antibodies against SARS-CoV-2 may be impaired in patients with NSCLC secondary to EGFR-targeted TKIs compared to ALK-directed treatment.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection.

Introduction: Our understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children. Methods: We enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata. Results: Children had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively). Conclusion: The gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Checklist for studies of HIV drug resistance prevalence or incidence: rationale and recommended use.

HIV drug resistance (HIVDR) is a major challenge to the effectiveness of antiretroviral therapy. Global efforts in addressing HIVDR require clear, transparent, and replicable reporting in HIVDR studies. We describe the rationale and recommended use of a checklist that should be included in reports of HIVDR incidence and prevalence. After preliminary consultations with experts on HIVDR and establishing the need for guidance on HIVDR reporting, we used a sequential, explanatory, mixed methods approach to create the checklist; together with the accompanying articles, the checklist was reviewed by the authors and validated externally. The checklist for studies on HIVDR prevalence or incidence (CEDRIC-HIV) includes 15 recommended items that would enhance transparency and facilitate interpretation, comparability, and replicability of HIVDR studies. CEDRIC-HIV will help authors of HIVDR studies prepare research reports and assist reviewers and editors in assessments of completeness of reporting. The checklist will also facilitate statistical pooling and interpretation of HIVDR data.

Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. METHODS: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. RESULTS: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. CONCLUSIONS: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

Mental health and adherence to antiretroviral therapy among Mexican people living with HIV during the COVID-19 pandemic.

BACKGROUND: The mental health and medical follow-up of people living with HIV (PLWH) have been disrupted by the COVID-19 pandemic. The objectives of this study were to assess anxiety, depression and substance use in Mexican PLWH during the pandemic; to explore the association of these symptoms with adherence to antiretroviral therapy (ART), and to compare patients with and without vulnerability factors (low socioeconomic level, previous psychological and/or psychiatric treatment). METHODS: We studied 1259 participants in a cross-sectional study, PLWH receiving care at the HIV clinic in Mexico City were contacted by telephone and invited to participate in the study. We included PLWH were receiving ART; answered a structured interview on sociodemographic data and adherence to ART; and completed the psychological instruments to assess depressive and anxiety symptoms and substance use risk. Data collection was performed from June 2020 to October 2021. RESULTS: 84.7% were men, 8% had inadequate ART adherence, 11% had moderate-severe symptoms of depression, and 13% had moderate-severe symptoms of anxiety. Adherence was related to psychological symptoms (p < 0.001). Vulnerable patients were more likely to be women, with low educational level and unemployed (p < 0.001). CONCLUSIONS: It is important to address mental health of PLWH during the COVID-19 pandemic, with special attention to the most vulnerable individuals. Future studies are needed to understand the relationship between mental health and ART adherence.

Higher versus lower nut consumption and changes in cognitive performance over two years in a population at risk of cognitive decline: a cohort study.

BACKGROUND: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function. OBJECTIVE: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk. METHODS: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as <1, ≥1 to <3, ≥3 to <7, and ≥7 servings/wk (1 serving=30 g). Multivariable-adjusted linear regression models were fitted to assess associations between baseline nut consumption and 2-y cognitive changes. RESULTS: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend <0.001). Compared with participants consuming <1 serving/wk of nuts, those categorized as consuming ≥3 to <7 and ≥7 servings/wk showed more favorable changes in general cognitive performance (ß z-score [95% CI] = 0.06 [0.00,0.12] and 0.13 [0.06,0.20], respectively). No significant changes were observed in the multivariable-adjusted models for other cognitive domains assessed. CONCLUSION: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted.