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.

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.

Symptom Persistence Following COVID-19 Infection among an Indigenous Community Residing in the Isthmus of Tehuantepec, Oaxaca, Mexico.

Introduction/Objectives: Several studies have documented the development and persistence of symptoms related to COVID-19 and its secondary complications up to 12 months after the infection. We aimed to identify the medical complications following COVID-19 infection in the Indigenous Zapotec population of the Isthmus of Tehuantepec region in Oaxaca, Mexico. Methods: This is a cross-sectional analytical study that included 90 Indigenous Zapotec participants (30 males and 60 females) from the Tehuantepec region, Oaxaca, Mexico, who had an infectious process due to SARS-CoV-2. Sociodemographic and clinical data were identified through questionnaires. Results: Among the 201 participants, 90 individuals (66.7% women, 33.3% men) had contracted COVID-19. Out of these, 61 individuals reported persistent symptoms post-infection, with a mean symptom duration of 13.87 months. The results show significant variations in symptom duration based on age, marital status, educational attainment, vaccination status, and blood group. The most commonly reported symptoms included a dry cough, fever, myalgia, fatigue, headache, and depressive symptoms. Conclusions: This study highlights the post-COVID-19 symptoms and their prevalence within a specific sample of the Indigenous Zapotec population in Oaxaca, along with the sociodemographic and clinical factors influencing the duration of these symptoms. It underscores the necessity of personalized recovery strategies and highlights the critical role of vaccination in mitigating the long-term impacts of SARS-CoV-2.

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.

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.

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.

Experimental Study of White Light Interferometry in Mach-Zehnder Interferometers Based on Standard Single Mode Fiber.

In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.

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.

LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Veillonella and Bacteroides are associated with gestational diabetes mellitus exposure and gut microbiota immaturity.

BACKGROUND: Dysbiosis during childhood impacts the configuration and maturation of the microbiota. The immaturity of the infant microbiota is linked with the development of inflammatory, allergic, and dysmetabolic diseases. AIMS: To identify taxonomic changes associated with age and GDM and classify the maturity of the intestinal microbiota of children of mothers with GDM and children without GDM (n-GDM). METHODS: Next-generation sequencing was used to analyze the V3-V4 region of 16S rRNA gene. QIIME2 and Picrust2 were used to determine the difference in the relative abundance of bacterial genera between the study groups and to predict the functional profile of the intestinal microbiota. RESULTS: According to age, the older GDM groups showed a lower alpha diversity and different abundance of Enterobacteriaceae, Veillonella, Clostridiales, and Bacteroides. Regarding the functional profile, PWY-7377 and K05895 associated with Vitamin B12 metabolism were reduced in GDM groups. Compared to n-GDM group, GDM offspring had microbiota immaturity as age-discriminatory taxa in random forest failed to classify GDM offspring according to developmental age (OOB error 81%). Conclusion. Offspring from mothers with GDM have a distinctive taxonomic profile related to taxa associated with gut microbiota immaturity.

The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus.

Glycosylation is a post-translational modification that affects the stability, structure, antigenicity and charge of proteins. In the immune system, glycosylation is involved in the regulation of ligand-receptor interactions, such as in B-cell and T-cell activating receptors. Alterations in glycosylation have been described in several autoimmune diseases, such as systemic lupus erythematosus (SLE), in which alterations have been found mainly in the glycosylation of B lymphocytes, T lymphocytes and immunoglobulins. In immunoglobulin G of lupus patients, a decrease in galactosylation, sialylation, and nucleotide fucose, as well as an increase in the N-acetylglucosamine bisector, are observed. These changes in glycoisolation affect the interactions of immunoglobulins with Fc receptors and are associated with pericarditis, proteinuria, nephritis, and the presence of antinuclear antibodies. In T cells, alterations have been described in the glycosylation of receptors involved in activation, such as the T cell receptor; these changes affect the affinity with their ligands and modulate the binding to endogenous lectins such as galectins. In T cells from lupus patients, a decrease in galectin 1 binding is observed, which could favor activation and reduce apoptosis. Furthermore, these alterations in glycosylation correlate with disease activity and clinical manifestations, and thus have potential use as biomarkers. In this review, we summarize findings on glycosylation alterations in SLE and how they relate to immune system defects and their clinical manifestations.

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.

Modulatory role of prolactin in type 1 diabetes.

OBJECTIVES: Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus. CONTENT: Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus. SUMMARY: Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control. OUTLOOK: Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.

Effect of a light-darkness cycle on the body weight gain of preterm infants admitted to the neonatal intensive care unit.

The Continuous bright light conditions to which premature infants are subjected while hospitalized in Neonatal Intensive Care Units (NICU) can have deleterious effects in terms of growth and development. This study evaluates the benefits of a light/darkness cycle (LDC) in weight and early hospital discharge from the NICU. Subjects were recruited from three participating institutions in Mexico. Eligible patients (n = 294) were premature infants who were hospitalized in the low-risk and high-risk neonatal units classified as stable. The subjects randomized to the experimental group (n = 150) were allocated to LDC conditions are as follows: light from 07:00 to 19:00 and darkness (25 lx) from 19:00 to 07:00. The control group (n = 144) was kept under normal room light conditions (CBL) 24 h a day. Main outcome was weight gain and the effect of reducing the intensity of nocturnal light in development of premature infants. Infants to the LDC gained weight earlier, compared with those randomized to CBL, and had a significant reduction in length of hospital stay. These results highlight those premature infants subjected to a LDC exhibit improvements in physiological development, favoring earlier weight gain and consequently a decrease in hospital stays. ClinicalTrials.gov; 02/09/2020 ID: NCT05230706.

Accuracy of machine learning algorithms for the assessment of upper-limb motor impairments in patients with post-stroke hemiparesis: A systematic review and meta-analysis.

BACKGROUND: The assessment of motor function is vital in post-stroke rehabilitation protocols, and it is imperative to obtain an objective and quantitative measurement of motor function. There are some innovative machine learning algorithms that can be applied in order to automate the assessment of upper extremity motor function. OBJECTIVES: To perform a systematic review and meta-analysis of the efficacy of machine learning algorithms for assessing upper limb motor function in post-stroke patients and compare these algorithms to clinical assessment. MATERIAL AND METHODS: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed using 6 electronic databases. The meta-analysis was performed with the data from the correlation coefficients using a random model. RESULTS: The initial search yielded 1626 records, but only 8 studies fully met the eligibility criteria. The studies reported strong and very strong correlations between the algorithms tested and clinical assessment. The meta-analysis revealed a lack of homogeneity (I2 = 85.29%, Q = 48.15), which is attributable to the heterogeneity of the included studies. CONCLUSION: Automated systems using machine learning algorithms could support therapists in assessing upper extremity motor function in post-stroke patients. However, to draw more robust conclusions, methodological designs that minimize the risk of bias and increase the quality of the methodology of future studies are required.

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.

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).

Increased O-GlcNAcylation promotes IGF-1 receptor/PhosphatidyI Inositol-3 kinase/Akt pathway in cervical cancer cells.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.