Association between O-GlcNAc levels and platelet function in obese insulin-resistant subjects.

Obesity is an epidemic associated with platelet and vascular disorders. Platelet O-GlcNAcylation has been poorly studied in obese subjects. We aimed to evaluate O-linked N-acetyl-glucosamine (O-GlcNAc) levels and platelet activity in obese insulin-resistant (ObIR) subjects. Six healthy and six insulin-resistant obese subjects with a body mass index of 22.6 kg/m2 (SD ± 2.2) and 35.6 kg/m2 (SD ± 3.8), respectively, were included. Flow cytometry was used to measure markers of platelet activity, expression of P-selectin (CD62P antibody), glycoprotein IIb/IIIa (integrins αIIbß3 binding to PAC-1 antibody), and thrombin stimulation. O-GlcNAc was determined in the platelets of all test subjects by cytofluometry, intracellular calcium, percentage of platelet aggregation, and immunofluorescence microscopy and Western blot were used to assess O-GlcNAc and OGT (O-GlcNAc transferase) in platelets. Platelets from ObIR subjects had on average 221.4 nM intracellular calcium, 81.89% PAC-1, 22.85% CD62P, 57.48% OGT, and 66.62% O-GlcNAc, while platelets from healthy subjects had on average 719.2 nM intracellular calcium, 4.99% PAC-1, 3.17% CD62P, 18.38% OGT, and 23.41% O-GlcNAc. ObIR subjects showed lower platelet aggregation than healthy subjects, 13.83% and 54%, respectively. The results show that ObIR subjects have increased O-GlcNAc, and increased intraplatelet calcium associated with platelet hyperactivity and compared to healthy subjects, suggesting that changes in platelet protein O-GlcNAcylation and platelet activity might serve as a possible prognostic tool for insulin resistance, prediabetes and its progression to type 2 diabetes mellitus.

O-GlcNAcylation: Crosstalk between Hemostasis, Inflammation, and Cancer.

O-linked ß-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients' healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network.

Attention to health care in the context of instability. In health care for women international.

In Mexico, the first attack dates back to 1988, but it was not identified until 2022. This violence remained invisible and minimized, but since then 42 acid attacks against women have been recorded, of which 5 victims died as a result of the attack and its medical complications. We think that families should be educated to eliminate misogyny in families and ensure that women are valued equally as men. We also think that education from childhood, questioning one's own beliefs, challenging stereotypes and gender roles, deconstructing prejudices, reporting, and acting with empathy and compassion are fundamental in a society with gender equity.

Re. Re.: "Immunothrombotic dysregulation in Chagas disease and COVID19: a comparative study of anticoagulation".

Re. Re.: "Immunothrombotic dysregulation in Chagas disease (CD) and COVID-19: a comparative study of anticoagulation": In the commentary on our paper, Hasslocher-Moreno made the point that indeterminate and digestive forms are not related to thromboembolic events, only thrombogenic alterations occur in CD with cardiopathy, however there is indirect evidence related to thombotic alterations, such as cerebral thrombosis. Our assertion is based on previous data discussed in this letter.

Associations of Dynapenic Obesity and Sarcopenic Obesity with the Risk of Complications in COVID-19.

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.

Analysis of SARS-CoV-2 mutations in Mexico, Belize, and isolated regions of Guatemala and its implication in the diagnosis.

The genomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide are publicly available and are derived from studies due to the increase in the number of cases. The importance of study of mutations is related to the possible virulence and diagnosis of SARS-CoV-2. To identify circulating mutations present in SARS-CoV-2 genomic sequences in Mexico, Belize, and Guatemala to find out if the same strain spread to the south, and analyze the specificity of the primers used for diagnosis in these samples. Twenty three complete SARS-CoV-2 genomic sequences, available in the GISAID database from May 8 to September 11, 2020 were analyzed and aligned versus the genomic sequence reported in Wuhan, China (NC_045512.2), using Clustal Omega. Open reading frames were translated using the ExPASy Translate Tool and UCSF Chimera (v.1.12) for amino acid substitutions analysis. Finally, the sequences were aligned versus primers used in the diagnosis of COVID-19. One hundred and eighty seven distinct variants were identified, of which 102 are missense, 66 synonymous and 19 noncoding. P4715L and P5828L substitutions in replicase polyprotein were found, as well as D614G in spike protein and L84S in ORF8 in Mexico, Belize, and Guatemala. The primers design by CDC of United States showed a positive E value. The genomic sequences of SARS-CoV-2 in Mexico, Belize, and Guatemala present similar mutations related to a virulent strain of greater infectivity, which could mean a greater capacity for inclusion in the host genome and be related to an increased spread of the virus in these countries, furthermore, its diagnosis would be affected.

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation.

Chagas and COVID-19 are diseases caused by Trypanosoma cruzi and SARS-CoV-2, respectively. These diseases present very different etiological agents despite showing similarities such as susceptibility/risk factors, pathogen-associated molecular patterns (PAMPs), recognition of glycosaminoglycans, inflammation, vascular leakage hypercoagulability, microthrombosis, and endotheliopathy; all of which suggest, in part, treatments with similar principles. Here, both diseases are compared, focusing mainly on the characteristics related to dysregulated immunothrombosis. Given the in-depth investigation of molecules and mechanisms related to microthrombosis in COVID-19, it is necessary to reconsider a prompt treatment of Chagas disease with oral anticoagulants.

The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics.

Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.

Obesity subtypes, related biomarkers & heterogeneity.

Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity.

Aggregation and Molecular Properties of ß-Glucosidase Isoform II in Chayote (Sechium edule).

The presence of isoforms of ß-glucosidase has been reported in some grasses such as sorghum, rice and maize. This work aims to extract and characterize isoform II in ß-glucosidase from S. edule. A crude extract was prepared without buffer solution and adjusted to pH 4.6. Contaminating proteins were precipitated at 4 °C for 24 h. The supernatant was purified by chromatography on carboxymethyl cellulose (CMC) column, molecular exclusion on Sephacryl S-200HR, and exchange anionic on QFF column. Electrophoretic analyzes revealed a purified enzyme with aggregating molecular complex on SDS-PAGE, Native-PAGE, and AU-PAGE. Twelve peptides fragments were identified by nano liquid chromatography-tandem mass spectrometry (nano LC-ESI-MS/MS), which presented as 61% identical to Cucurbita moschata ß-glucosidase and 55.74% identical to ß-glucosidase from Cucumis sativus, another Cucurbitaceous member. The relative masses which contained 39% hydrophobic amino acids ranged from 982.49 to 2,781.26. The enzyme showed a specificity to ß-d-glucose with a Km of 4.59 mM, a Vmax value of 104.3 µM∙min-1 and a kcat of 10,087 µM∙min-1 using p-nitrophenyl-ß-D-glucopyranoside. The presence of molecular aggregates can be attributed to non-polar amino acids. This property is not mediated by a ß-glucosidase aggregating factor (BGAF) as in grasses (maize and sorghum). The role of these aggregates is discussed.

[Efficacy of the strategy to improve the quality indicators of Diabetes Mellitus 2 Care Process in Advanced Diabetes Centre Macarena]. / Eficacia de una estrategia para mejorar los indicadores de calidad del Proceso Asistencial Integrado Diabetes Mellitus 2 en el Centro Avanzado de Diabetes Macarena.

INTRODUCTION: The assessment of the Diabetes Mellitus 2 Care Process (PAI-DM2) through the assessment tool for the chronic illness' care models (IEMAC-Diabetes) allows the design of health interventions for the improvement of medical care. OBJECTIVE: Analysing the quality of healthcare provided to DM2 patients. DESIGN: Quasiexperimental study before and after intervention with a not randomised control group. LOCATION: Health care district of primary care Sevilla. PARTICIPANTS: 12 groups of ascribed patients, 5 Primary Care Healthcenter, chosen in a discretionary way. INTERVENTION: Physicians and nurses from the 12 intervention groups took part in a training program, including an external rotation in the Diabetes Daycare Hospital. MAIN MEASUREMENTS: Number of included patients, glycated hemoglobin, feet exploration (FE), and ocular fundus (OF). RESULTS: 1,475 DM-2 patients were analysed. The proportion of included patients per group was 8.5%, 45.5% were women. At the beginning of the study, the rate of patients with HbA1c<7% were 38.9% in 2013 against 47.7% in 2014 and 40.2% in 2016; 33% of the patients had an OF in 2013 against 41.77% in 2014; 51.6% of patients had an EF against 54.7% in 2014. After the intervention, statistically significant differences were reached in HbA1c (p=0.01) and retinography requested (p=0.01). CONCLUSIONS: IEMAC-Diabetes allows spotting improvement areas in the PAI-DM2. The absence of statistically significant differences may be the result of contamination in the sample and/or Hawthorne effect.

Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

Reduced platelet aggregation in women after intercourse: a possible role for the cyclooxygenase pathway.

We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay. Platelets and prostanoids were evaluated in women, periodically, before and after intercourse. The platelets were tested with adenosine diphosphate (ADP) and arachidonic acid (AA). To block the interaction between the uterus and SF, some couples used condoms. We found that the 6-keto prostaglandin F1α in urine at 2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre-intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in platelet aggregation was observed in women whose partners did not use condoms. Averages for platelet aggregation were 20.16% with ADP, and more significantly, 37.79% with AA after 2 hours. In contrast, couples using condoms showed no changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were taking aspirin or indomethacin also showed no changes. SF from men taking aspirin or indomethacin led to no reduction in platelet aggregometry in their partners. These results indicate that in cases of exposure to SF, the transient change in women's platelet activity could be related to the cyclooxygenase pathway.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: the FRESCO Study.

OBJECTIVE: To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD: Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS: The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS: The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Relevance of a Customized Version of ChatGPT Explaining Laboratory Test Results in Patient Education.

ChatGPT is an artificial intelligence (AI) chatbot application. In this study, we explore the creation and use of a customized version of ChatGPT designed specifically for patient education, called "Lab Explainer." Lab Explainer aims to simplify and clarify the results of complex laboratory tests for patients, using the sophisticated capabilities of AI in natural language processing; it analyses various laboratory test data and provides clear explanations and contextual information. The approach involved adapting OpenAI's ChatGPT model specifically to analyze laboratory test data. The results suggest that Lab Explainer has the potential to improve understanding by providing an interpretation of laboratory tests to the patient. In conclusion, the Lab Explainer can assist patient education by providing intelligible interpretations of laboratory tests.

A Late Pleistocene hominin footprint site on the North African coast of Morocco.

Footprints represent a relevant vestige providing direct information on the biology, locomotion, and behaviour of the individuals who left them. However, the spatiotemporal distribution of hominin footprints is heterogeneous, particularly in North Africa, where no footprint sites were known before the Holocene. This region is important in the evolution of hominins. It notably includes the earliest currently known Homo sapiens (Jebel Irhoud) and the oldest and richest African Middle Stone Age hominin sites. In this fragmented ichnological record, we report the discovery of 85 human footprints on a Late Pleistocene now indurated beach surface of about 2800 m2 at Larache (Northwest coast of Morocco). The wide range of sizes of the footprints suggests that several individuals from different age groups made the tracks while moving landward and seaward across a semi-dissipative bar-trough sandy beach foreshore. A geological investigation and an optically stimulated luminescence dating of a rock sample extracted from the tracksite places this hominin footprint surface at 90.3 ± 7.6 ka (MIS 5, Late Pleistocene). The Larache footprints are, therefore, the oldest attributed to Homo sapiens in Northern Africa and the Southern Mediterranean.

Non-Coding RNAs and Innate Immune Responses in Cancer.

Non-coding RNAs (ncRNAs) and the innate immune system are closely related, acting as defense mechanisms and regulating gene expression and innate immunity. Both are modulators in the initiation, development and progression of cancer. We aimed to review the major types of ncRNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and long non-coding RNAs (lncRNAs), with a focus on cancer, innate immunity, and inflammation. We found that ncRNAs are closely related to innate immunity, epigenetics, chronic inflammation, and cancer and share properties such as inducibility, specificity, memory, and transfer. These similarities and interrelationships suggest that ncRNAs and modulators of trained immunity, together with the control of chronic inflammation, can be combined to develop novel therapeutic approaches for personalized cancer treatment. In conclusion, the close relationship between ncRNAs, the innate immune system, and inflammation highlights their importance in cancer pathways and their potential as targets for novel therapeutic strategies.

Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.

Burnout Syndrome and Related Factors in Mexican Police Workforces.

Burnout (BO) is a response to prolonged exposure to work-related stressors characterized by emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). The police working environment includes continued critical life-threatening situations, violence, and injuries, among other related factors putting them at high risk of distress. The objective of this study was to evaluate the association between Burnout Syndrome and sociodemographic, occupational, and health factors in Mexican police officers. We applied the Maslach Burnout Inventory Human Services Survey (MBI-HSS) to 351 active members of the Mexican police workforce. In addition, a specific questionnaire identified the presence of chronic degenerative diseases, hypertension, diabetes, digestive diseases, self-perception of food quality, and hours of sleep. Furthermore, 23.36% of police workforces presented high levels of burnout; 44.16% of police were highly emotionally exhausted, 49.29% had lost empathy with people, and 41.03% presented low personal achievement. Moreover, the worst levels of the syndrome were present in people with a poor self-perceived health status, poor perception of diet quality, without regular mealtimes, bad sleep habits, and elevated Body Mass Index. Data suggest that in Mexican police officers, BO is dimensionally different from all other groups previously studied (DP > EE > PA).