Effects of a Multicomponent Preventive Intervention in Women at Risk of Sarcopenia: A Pilot Study.

Sarcopenia is defined by the presence of decreased skeletal muscle mass, strength, and functionality in older people. Multicomponent interventions represent an alternative to non-pharmacological treatment for preventing disease progression. This study aimed to evaluate the effects of a multicomponent intervention approach in women at risk of sarcopenia. METHODS: A quasi-experimental pilot study of 12 weeks was conducted, with 24 sessions of dancing and resistance exercises and 12 sessions of nutritional education. The outcomes were changes in muscle mass, grip strength, gait speed, and body composition. The project was registered on Clinical Trials: NCT06038500 (14 September 2023). RESULTS: Twelve women aged 55-75 years participated in this study; after the intervention, changes were found in the following variables: grip strength, from 18.70 (17.98-19.23) at baseline to 21.57 (20.67-23.16) kg (p = 0.002); gait speed, from 0.95 (0.81-1.18) at baseline to 1.34 (1.20-1.47) m/s (p = 0.003); and hip circumference, from 99.75 (94.75-110.37) at baseline to 97.65 (93.92-109.50) cm (p = 0.023). Other measurements that appeared without changes were appendicular skeletal muscle mass, from 21.17 (18.58-22.33) at baseline to 20.77 (18.31-22.39) kg (p = 0.875), and the appendicular skeletal muscle mass index, from 8.64 (8.08-9.35) at baseline to 8.81 (7.91-9.38) kg/m2 (p = 0.875) after the intervention. CONCLUSIONS: The three-month multicomponent intervention in women at risk of sarcopenia improved their grip strength and gait speed.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.

The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E2 (PGE2), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE2 and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE2 whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair.

La mala autopercepción de salud oral se asocia con la presencia de fragilidad en personas mayores que viven en la comunidad.

OBJETIVO: Determinar la asociación entre mala autopercepción de salud oral y fragilidad en personas mayores. Material y métodos. Estudio transversal en personas mayores de la Ciudad de México. La autopercepción de salud oral se midió con el Geriatric/General Oral Health Assessment Index (GOHAI) y la fragilidad con el fenotipo de Fried y colaboradores. RESULTADOS: 1 173 personas mayores, media de edad de 66.0 (5.7) años, mujeres 46.1% (n=541). La media (IC95%) de GOHAI-Sp fue de 49.2 (48.9-49.6). El 9.2% (n=108) presentaron fragilidad, 59.9% (n=703) prefrágil y 30.9% (n=362) no frágiles. La fuerza de asociación (RM) para mala autopercepción de salud oral y frágil fue RM 2.4 (IC95% 1.5,3.7) y RM ajustada RM 1.7 (IC95% 1.1,2.8), referencia no frágil. No existe asociación significativa para la mala autopercepción de salud oral y prefrágil. Conclusión. La mala autopercepción de salud oral se asocia con la presencia de fragilidad en personas mayores.

Factores que afectan el estado nutricional en personas mayores mexicanas: Enasem, 2018.

OBJETIVO: Analizar los factores que afectan el estado nutricional en personas mayores mexicanas del Estudio Nacional de Salud y Envejecimiento en México 2018 (Enasem 2018). Material y métodos. Análisis transversal secundario de determinantes sociales, factores relativos a la salud y eventos estresantes de la vida con dos problemas nutricionales relevantes en personas mayores: 1) desnutrición y 2) exceso de peso considerando sobrepeso y obesidad, mediante regresión logística múltiple. RESULTADOS: 4 587 participantes. La prevalencia de desnutrición fue 16.1% y está relacionada con edad ≥80 años, sin pareja, sin escolaridad, sobrestimación de índice de masa corporal (IMC), dificultad motriz, dependencia funcional instrumental, hospitalización en año previo y caídas en los últimos dos años, autorreporte de fuerza prensil débil, reporte de desastre que afectó vivienda o accidente que afectó la salud. La prevalencia de exceso de peso fue 43.6%, relacionada con ser mujer, tener 60 a 79 años, percibirse sin sobrepeso u obesidad y subestimarlo contra IMC, tener ≥3 enfermedades, síntomas somáticos e inactividad física. CONCLUSIONES: Los factores que afectan el estado nutricional hacia desnutrición o exceso de peso en las personas mayores requieren considerarse como áreas de intervención importante en el envejecimiento.

Prevalence, and Risk Indicators of Coronal and Root Caries in Mexican Older Adults in Nursing Homes.

Background: Several factors are associated with coronal and root caries in older persons. The purpose of this study was to determine the experience, prevalence, and risk indicators (socioeconomic, sociodemographic, and dental variables) of coronal and root caries in older persons residing in nursing homes in Mexico. Methods: A cross-sectional study was carried out in 227 dentate participants with natural teeth. Convenience sample, where all dentate residents were invited to participate. The dependent variables were coronal caries and root caries, which were determined through an oral clinical examination. The independent variables were sociodemographic factors, location, type of center, surfaces free of dental biofilm and calculus, surfaces with recession, retainers in contact with surfaces with recession, xerostomia, smoking, and the previous use of dental services. The binary logistic regression model was used in the analysis. Results: The mean age of the participants in this study was 77.7±8.8 years, and 69.2% were women. Moreover, 71.8% live in long-term care facilities, and 48.0% live in Mexico City. The prevalence of coronal and root caries was found to be 67.8% and 50.7%, respectively. Being male and living in Mexico City were risk indicators for coronal caries, and with a 1% increase in surfaces with no biofilm, the risk decreased by 2%. Being widowed, having government or no social security, denture retainers, and coronal caries were risk indicators for root caries, while the utilization of dental services indicated lower risk. Conclusion: Several variables that differ in nature were found to be risk indicators for coronal and root caries. Coronal caries increases the risk of root caries. Prevention should be aimed at identifying persons at higher risk, and dental care should be improved for persons living in long-term care institutions.

Lipoxin-mediated signaling: ALX/FPR2 interaction and beyond.

In the aftermath of tissue injury or infection, an efficient resolution mechanism is crucial to allow tissue healing and preserve appropriate organ functioning. Pro-resolving bioactive lipids prevent uncontrolled inflammation and its consequences. Among these mediators, lipoxins were the first described and their pro-resolving actions have been mainly described in immune cells. They exert their actions mostly through formyl-peptide receptor 2 (ALX/FPR2 receptor), a G-protein-coupled receptor whose biological function is tremendously complex, primarily due to its capacity to mediate variable cellular responses. Moreover, lipoxins can also interact with alternative receptors like the cytoplasmic aryl hydrocarbon receptor, the cysteinyl-leukotrienes receptors or GPR32, triggering different intracellular signaling pathways. The available information about this complex response mediated by lipoxins is addressed in this review, going over the different mechanisms used by these molecules to stop the inflammatory reaction and avoid the development of dysregulated and chronic pathologies.

Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity.

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer.

Defining the metabolic signatures associated with human macrophage polarisation.

Macrophages are essential components of the innate immune system that play both homeostatic roles in healthy organs, and host defence functions against pathogens after tissue injury. To accomplish their physiological role, macrophages display different profiles of gene expression, immune function, and metabolic phenotypes that allow these cells to participate in different steps of the inflammatory reaction, from the initiation to the resolution phase. In addition, significant differences exist in the phenotype of macrophages depending on the tissue in which they are present and on the mammalian species. From a metabolic point of view, macrophages are essentially glycolytic cells; however, their metabolic fluxes are dependent on the functional polarisation of these cells. This metabolic and cellular plasticity offers the possibility to interfere with the activity of macrophages to avoid harmful effects due to persistent activation or the release of molecules that delay tissue recovery after injury.

Insomnia Impairs Both the Pro-BDNF and the BDNF Levels Similarly to Older Adults with Cognitive Decline: An Exploratory Study.

Sleep disorders, including insomnia, are common during aging, and these conditions have been associated with cognitive decline in older adults. Moreover, during the aging process, neurotransmitters, neurohormones, and neurotrophins decrease significantly, leading to the impairment of cognitive functions. In this sense, BDNF, the most abundant neurotrophic factor in the human brain, has been suggested as a potential target for the prevention and improvement of cognitive decline during aging; however, the current evidence demonstrates that the exogenous administration of BDNF does not improve cognitive function. Hence, in the present study, we quantified pro-BDNF (inactive) and BDNF (active) concentrations in serum samples derived from older individuals with insomnia and/or cognitive decline. We used linear regression to analyze whether clinical or sociodemographic variables impacted the levels of BNDF concentration. We observed that insomnia, rather than cognitive decline, is significantly associated with BDNF concentration, and these effects are independent of other variables. To our knowledge, this is the first study that points to the impact of insomnia on improving the levels of BDNF during aging and suggests that opportune treatment of insomnia may be more beneficial to prevent cognitive decline during aging.

Beneficial effect of TLR4 blockade by a specific aptamer antagonist after acute myocardial infarction.

Experimental evidence indicates that the control of the inflammatory response after myocardial infarction is a key strategy to reduce cardiac injury. Cellular damage after blood flow restoration in the heart promotes sterile inflammation through the release of molecules that activate pattern recognition receptors, among which TLR4 is the most prominent. Transient regulation of TLR4 activity has been considered one of the potential therapeutic interventions with greater projection towards the clinic. In this regard, the characterization of an aptamer (4FT) that acts as a selective antagonist for human TLR4 has been investigated in isolated macrophages from different species and in a rat model of cardiac ischemia/reperfusion (I/R). The binding kinetics and biological responses of murine and human macrophages treated with 4FT show great affinity and significant inhibition of TLR4 signaling including the NF-κB pathway and the LPS-dependent increase in the plasma membrane currents (Kv currents). In the rat model of I/R, administration of 4FT following reoxygenation shows amelioration of cardiac injury function and markers, a process that is significantly enhanced when the second dose of 4FT is administered 24 h after reperfusion of the heart. Parameters such as cardiac injury biomarkers, infiltration of circulating inflammatory cells, and the expression of genes associated with the inflammatory onset are significantly reduced. In addition, the expression of anti-inflammatory genes, such as IL-10, and pro-resolution molecules, such as resolvin D1 are enhanced after 4FT administration. These results indicate that targeting TLR4 with 4FT offers new therapeutic opportunities to prevent cardiac dysfunction after infarction.

Association of loneliness and social isolation with all-cause mortality among older Mexican adults in the Mexican health and aging study: a retrospective observational study.

BACKGROUND: Plenty of evidence shows how social isolation and loneliness are associated with increased risk for numerous diseases and mortality. But findings about their interactive or combined effects on health outcomes and mortality remains inconclusive. OBJECTIVE: Analyze the longitudinal association of loneliness, social isolation and their interactions, with the all-cause mortality among older adults in Mexico. METHODS: A retrospective observational study was conducted. Mexican adults older than 50 years were included. Data from the Mexican Health and Aging Study (MHAS) in the 2015 and 2018 waves were used. The subjects were classified according to their level of loneliness and the presence of social isolation. Multivariate logistic regression analyzes were performed to determine the degree of association between loneliness and social isolation with all-cause mortality at a 3-year follow-up. RESULTS: From the total sample of 11,713 adults aged 50 years or over, 707 (6%) did not survive, 42% presented loneliness, and 53% were classified as socially isolated. After multivariate adjustment only social isolation (OR = 1.30, 95%CI:1.03-1.64) was associated with all-cause mortality, loneliness (Mild: OR = 0.83, 95%CI:0.59-1.16; Severe: OR = 1.03, 95%CI:0.71-1.64), and the interaction between loneliness and social isolation were not associated with all-cause mortality. CONCLUSION: Social isolation, but not loneliness or their interaction, was associated with all-cause mortality in Mexican adults older than 50 years. This finding may help direct possible future interventions that help improve mental health in older adults from a highly collectivistic country.

Association of polymorphisms rs2303729, rs10880, and rs1131620 of LTBP4 with sarcopenia in elderly patients with type 2 diabetes mellitus.

BACKGROUND: Latent TGFß binding protein 4 (LTBP4) modifies skeletal muscle function, and polymorphisms in this gene have been associated with a longer ambulation time in patients with Duchenne muscular dystrophy. However, no studies associate these polymorphisms with an acquired muscle condition. AIM: The study aims to determine whether three functional variants within the LTBP4 were associated with sarcopenia in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: We performed an analysis with 144 elderly individuals with T2DM, including 101 without sarcopenia and 43 with sarcopenia. Polymorphism frequency was determined by real-time PCR allelic discrimination TaqMan assay. RESULTS: Under different genetic models, the univariant analysis did not show a significant association of any polymorphism with sarcopenia. But the multivariate model analysis showed that variant rs1131620 (OR 7.852, 95% CI 1.854-33.257, p = 0.005) was significantly associated with sarcopenia under a dominant model. Under the same analysis, the variants rs2303729 and rs10880 had a more discrete association (OR 3.537 95% CI 1.078-11.607, p = 0.037; OR 5.008, 95% CI 1.120-22.399, p = 0.035, respectively). CONCLUSIONS: Our study highlights the importance of studying LTBP4 polymorphisms associated with sarcopenia. These findings suggest that the rs1131620 polymorphism of the LTBP4 may be part of the observed sarcopenia process in patients with T2DM.

[Answer to "Comment on article "Sleep disorders in older people. How do older people in Mexico City sleep?""]. / Respuesta a "Comentario al artículo: "Trastornos del sueño en personas mayores. ¿Cómo duermen las personas mayores de la Ciudad de México?"".

The response of the authors of the article "Sleep disorders in older people. How do older people in Mexico City sleep?" is presented, in which they carry out pertinent clarifications.

Se presenta la respuesta de los autores del artículo "Trastornos del sueño en personas mayores. ¿Cómo duermen las personas mayores de la Ciudad de México?" en la que llevan a cabo aclaraciones pertinentes.

Patterns of Muscle-Related Risk Factors for Sarcopenia in Older Mexican Women.

Early detriment in the muscle mass quantity, quality, and functionality, determined by calf circumference (CC), phase angle (PA), gait time (GT), and grip strength (GSt), may be considered a risk factor for sarcopenia. Patterns derived from these parameters could timely identify an early stage of this disease. Thus, the present work aims to identify those patterns of muscle-related parameters and their association with sarcopenia in a cohort of older Mexican women with neural network analysis. Methods: Information from the functional decline patterns at the end of life, related factors, and associated costs study was used. A self-organizing map was used to analyze the information. A SOM is an unsupervised machine learning technique that projects input variables on a low-dimensional hexagonal grid that can be effectively utilized to visualize and explore properties of the data allowing to cluster individuals with similar age, GT, GSt, CC, and PA. An unadjusted logistic regression model assessed the probability of having sarcopenia given a particular cluster. Results: 250 women were evaluated. Mean age was 68.54 ± 5.99, sarcopenia was present in 31 (12.4%). Clusters 1 and 2 had similar GT, GSt, and CC values. Moreover, in cluster 1, women were older with higher PA values (p < 0.001). From cluster 3 upward, there is a trend of worse scores for every variable. Moreover, 100% of the participants in cluster 6 have sarcopenia (p < 0.001). Women in clusters 4 and 5 were 19.29 and 90 respectively, times more likely to develop sarcopenia than those from cluster 2 (p < 0.01). Conclusions: The joint use of age, GSt, GT, CC, and PA is strongly associated with the probability women have of presenting sarcopenia.

Functional Crosstalk between PCSK9 Internalization and Pro-Inflammatory Activation in Human Macrophages: Role of Reactive Oxygen Species Release.

Atherosclerosis is a cardiovascular disease caused mainly by dyslipidemia and is characterized by the formation of an atheroma plaque and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that induces the degradation of the LDL receptor (LDLR), which contributes to increased levels of LDL cholesterol and the progress of atherosclerosis. Given that macrophages are relevant components of the lipidic and inflammatory environment of atherosclerosis, we studied the effects of PCSK9 treatment on human macrophages. Our data show that human macrophages do not express PCSK9 but rapidly incorporate the circulating protein through the LDLR and also activate the pro-inflammatory TLR4 pathway. Both LDLR and TLR4 are internalized after incubation of macrophages with exogenous PCSK9. PCSK9 uptake increases the production of reactive oxygen species and reduces the expression of genes involved in lipid metabolism and cholesterol efflux, while enhancing the production of pro-inflammatory cytokines through a TLR4-dependent mechanism. Under these conditions, the viability of macrophages is compromised, leading to increased cell death. These results provide novel insights into the role of PCSK9 in the crosstalk of lipids and cholesterol metabolism through the LDLR and on the pro-inflammatory activation of macrophages through TLR4 signaling. These pathways are relevant in the outcome of atherosclerosis and highlight the relevance of PCSK9 as a therapeutic target for the treatment of cardiovascular diseases.

Specialized Proresolving Mediators Protect Against Experimental Autoimmune Myocarditis by Modulating Ca2+ Handling and NRF2 Activation.

Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum-adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.

Serum Levels of Glial Fibrillary Acidic Protein Association with Cognitive Impairment and Type 2 Diabetes.

BACKGROUND: Peripheral biomarkers associated with neurocognitive disorders (NCD) have been evaluated in an attempt to improve diagnosis and early detection and potentially even prevent them. Along with increasing age, type 2 diabetes (T2D) increases the risk of central nervous system disorders and cognitive impairment due to the loss of synaptic function. Central damage triggers an astroglial response, increasing the expression of glial fibrillary acidic protein (GFAP), which can be found peripherally when the blood-brain barrier is compromised. AIM OF THE STUDY: To evaluate the value of GFAP as a peripheral biomarker of central dysfunction. METHODS: Serum levels of GFAP were compared between cases of NCD (n = 69) and age-matched controls (n = 69), analyzing the influence of diabetes as contributing factor. RESULTS: We found higher levels of serum GFAP in subjects with NCD compared with the control group (p <0.0001). The receiver operating characteristic (ROC) curve using the GFAP levels showed 65.22% sensitivity and 71.01% specificity (AUC = 0.7608), indicating good performance in the classification of controls and NCD patients. Logistic regression indicated a positive predictive power of 67.50% considering T2D status; adding GFAP levels, the predictive power rises to 71.93%. GFAP levels and T2D could be considered good predictors of NCD risk. CONCLUSIONS: Our findings open the possibility that peripheral GFAP could be used as an objective measurement related, under certain conditions, to central damage; thereby serving as a follow-up marker to refer diabetic patients for appropriate neurological evaluation, which could offer a low cost, minimally invasive strategy to improve the assessment of cognitive affectation and subsequent treatment.

[Interinstitutional Command Mexico: organizational decision-making in the face of COVID-19]. / Comando interinstitucional México: toma de decisiones organizacionales ante COVID-19.

Background: The third wave of COVID-19 in Mexico produced a high demand for hospital care, which is why it was created a multidisciplinary group to optimize decision-making: the Interinstitutional Command for the Health Sector (COISS, according to its initials in Spanish). So far, there is no scientific evidence of the COISS processes or their effect on the behavior of epidemiological indicators and the hospital care needs of the population in the context of COVID-19 in the entities involved. Objectives: To analyze the trend on epidemic risk indicators throughout the COISS group's management in the third wave of COVID-19 in Mexico. Material and methods: Mixed study: 1) non-systematic review of information from technical documents issued by COISS, 2) secondary analysis of open-access institutional databases through the description of healthcare needs of cases notified with COVID-19 symptoms, and an ecological analysis by each Mexican state on the behavior of hospital occupancy, RT-PCR positivity, and COVID-19 mortality in two-time points. Results: The COISS activity in identifying states with epidemic risk generated actions aimed at a reduction in hospital occupancy of beds, positivity by RT-PCR, and mortality from COVID-19. Conclusions: The decisions of the COISS group reduced the indicators of epidemic risk. Continuing the work of the COISS group is an urgent need. Conclusions: The decisions of the COISS group reduced the indicators of epidemic risk. Continuing the work of the COISS group is an urgent need.

Introducción: la tercera ola por COVID-19 en México provocó una alta demanda de atención hospitalaria, por lo cual se conformó un grupo multidisciplinario para optimizar la toma de decisiones sanitarias: Comando Interinstitucional del Sector Salud (COISS). Hasta el momento, no hay evidencia científica de los procesos del COISS ni de su efecto sobre el comportamiento de indicadores epidemiológicos y las necesidades de atención hospitalaria de la población bajo el contexto de COVID-19 en entidades federativas involucradas. Objetivos: analizar la tendencia de indicadores de riesgo epidémico durante la gestión del grupo COISS en la tercera ola por COVID-19 en México. Material y métodos: estudio mixto: 1) revisión no sistemática de documentos técnicos del COISS, 2) análisis secundario de bases de datos de libre acceso, mediante la descripción de necesidades de atención hospitalaria de los casos notificados con síntomas de la COVID-19 y un análisis ecológico por entidades federativas sobre el comportamiento de la ocupación hospitalaria, positividad y mortalidad por COVID-19 en dos cortes temporales. Resultados: la actividad del COISS en la identificación de entidades federativas de riesgo epidémico generó acciones encaminadas a una reducción en la ocupación hospitalaria de camas generales, positividad por RT-PCR y mortalidad por COVID-19. Conclusiones: las decisiones del grupo COISS disminuyeron los indicadores de riesgo epidémico. Continuar el trabajo del grupo COISS es una necesidad apremiante.

Genotyping NUDT15*3 rs1166855232 reveals higher frequency of potential adverse effects of thiopurines in Natives and Mestizos from Mexico.

BACKGROUND: Thiopurines are effectively prescribed for immune and oncology diseases but their toxicity leads to severe myelosuppression. Therefore, TPMT genetic variants have been used to adjust dosing for poor and intermediate metabolizers, significantly preventing adverse drug reactions. In 2018, the Clinical Pharmacogenetics Implementation Consortium included NUDT15 rs116855232 to also guide thiopurines dosing. This variant is not present in Caucasians but have been identified in 10% of Asian and Latin American populations. Despite research efforts to portrait the world's genetic variation, few studies include the investigation of NUDT15 in large samples. METHODS: Fifteen NUDT15 and TPMT variants were retrieved for 1270 Mestizos and 20 Natives genotyped from previous studies using the GSA-Illumina microarray. After bioinformatic quality controls, genotypes were available for 12 variants, TPMT rs2842949, rs2842950, rs2842934, rs1800460, rs12201199, rs12663332, rs2518463, rs4449636, rs12529220, rs3931660, rs200591577, and NUD15 rs116855232. Allele frequencies and haplotypes were assessed using PLINK, R, and Haploview. Dosing inferences were described according to the Clinical Pharmacogenomics Implementation Consortium. RESULTS: We report relevant populations differences in actionable TPMT*3B and NUDT15 rs116855232 as the allele frequency of the former is higher in Mestizos compared to Caucasians, and for the latter we report twofold and 1.35-fold higher allele frequencies in Natives and Mestizos compared to Mexicans from Los Angeles. CONCLUSIONS: TPMT*3B and NUDT15 rs116855232 actionable markers showed population differences that ought to be considered as dosing inferences highlight the relevance of routine genotyping of these variants for the prescription of thiopurines in Mexican populations.