The association between adipokines dysregulation and the occurrence of atrial fibrillation and obese patients, is it relevant?

Atrial fibrillation (AF) is the most common arrhythmia, affecting approximately 33.5 millions of people worldwide. Unfortunately, the prevalence of this arrhythmia will increase within the following two decades, resulting in a higher mortality rate and a higher economic burden for public health services.

Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies.

Exome Sequence Data of Eight SLC Transporters Reveal That and Variants Alter Metformin Pharmacokinetics and Glycemic Control.

: Type 2 diabetes (T2D) is one of the leading causes of mortality and is a public health challenge worldwide. Metformin is the first-choice treatment for T2D; its pharmacokinetics (PK) is facilitated by members of the solute carrier (SLC) superfamily of transporters, it is not metabolized, and it is excreted by the kidney. Although interindividual variability in metformin pharmacokinetics is documented in the Mexican population, its pharmacogenomics is still underexplored.

Unveiling the state of the art: a systematic review and meta-analysis of paper-based microfluidic devices.

Introduction: This systematic review and meta-analysis present a comprehensive evaluation of paper-based microfluidic devices, focusing on their applications in immunoassays. These devices are emerging as innovative solutions to democratize access to diagnostic technologies, especially in resource-limited settings. Our review consolidates findings from diverse studies to outline advancements in paper-based microfluidic technology, including design intricacies and operational efficacy.

External validation of the natriuretic response prediction equation to discriminate diuretic response in heart failure.

Aims: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated.

High order sliding mode control for restoration of a population of predators in a Lotka-Volterra system.

Human-induced extinction and rapid ecological changes require the development of techniques that can help avoid extinction of endangered species. The most used strategy to avoid extinction is reintroduction of the endangered species, but only 31% of these attempts are successful and they require up to 15 years for their results to be evaluated. In this research, we propose a novel strategy that improves the chances of survival of endangered predators, like lynx, by controlling only the availability of prey.

Protein Science Meets Artificial Intelligence: A Systematic Review and a Biochemical Meta-Analysis of an Inter-Field.

Proteins are some of the most fascinating and challenging molecules in the universe, and they pose a big challenge for artificial intelligence. The implementation of machine learning/AI in protein science gives rise to a world of knowledge adventures in the workhorse of the cell and proteome homeostasis, which are essential for making life possible. This opens up epistemic horizons thanks to a coupling of human tacit-explicit knowledge with machine learning power, the benefits of which are already tangible, such as important advances in protein structure prediction.

Minimally-Invasive and Efficient Method to Accurately Fit the Bergman Minimal Model to Diabetes Type 2.

Introduction: Diabetes mellitus is a global burden that is expected to grow by 2030. This will increase the need for prevention, diagnosis and treatment of diabetes. Animal and individualized models will allow understanding and compensation for inter and intra-individual differences in treatment and management strategies for diabetic patients.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

What can we learn from β-cell failure biomarker application in diabetes in childhood? A systematic review.

Background: The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of β-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome.

Aim: To determine which biomarkers are currently used to identify β-cell failure among children and adolescents with high risk factors for diabetes mellitus.

Accurate diagnosis of sepsis using a neural network: Pilot study using routine clinical variables.

Background And Objectives: Sepsis is a severe infection that increases mortality risk and is one if the main causes of death in intensive care units. Accurate detection is key to successful interventions, but diagnosis of sepsis is complicated because the initial signs and symptoms are not specific. Biomarkers that have been proposed have low specificity and sensitivity, are expensive, and not available in every hospital.

The L125F MATE1 variant enriched in populations of Amerindian origin is associated with increased plasma levels of metformin and lactate.

Genetic factors that affect variability in metformin response have been poorly studied in the Latin American population, despite its being the initial drug therapy for type 2 diabetes, one of the most prevalent diseases in that region. Metformin pharmacokinetics is carried out by members of the membrane transporters superfamily (SLCs), being the multidrug and toxin extrusion protein 1 (MATE1), one of the most studied. Some genetic variants in MATE1 have been associated with reduced in vitro metformin transport.

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early β-cell damage in obesity and diabetes.

Background And Aims: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when β-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early β-cell damage.

Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus.

The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with β- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place.

Exome sequencing of 20,791Â cases of type 2 diabetes and 24,440Â controls.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.

Rapid automatic identification of parameters of the Bergman Minimal Model in Sprague-Dawley rats with experimental diabetes for adaptive insulin delivery.

Glucose-Insulin regulation models can be used to individualize insulin therapy. However, the experimental techniques currently used to identify the appropriate parameter sets of an individual are expensive, time consuming, and very unpleasant for the patient. Since there is a wide range of intrapersonal parameter variability, the identified parameters in a laboratory setting (at rest) are not optimal for dynamic conditions of daily activities.

Gene variants in AKT1, GCKR and SOCS3 are differentially associated with metabolic traits in Mexican Amerindians and Mestizos.

Amerindian ancestry appears to be a risk factor for metabolic diseases (MetD), making Mexicans an ideal population to better understand the genetic architecture of metabolic health. In this study, we determine the association of genetic variants previously reported with metabolic entities, in two Mexican populations, including the largest sample of Amerindians reported to date. We investigated the association of eigth single-nucleotide polymorphisms (SNPs) in AKT1, GCKR, and SOCS3 genes with different metabolic traits in 1923 Mexican Amerindians (MAs) belonging to 57 ethnic groups, and 855 Mestizos (MEZs).

Diabetes Drug Discovery: hIAPP Polymorphic Amyloid Structures as Novel Therapeutic Targets.

Human islet amyloid peptide (hIAPP) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs.

Significant and safe reduction of propofol sedation dose for geriatric population undergoing pacemaker implantation: randomized clinical trial.

Objective: A previous multidisciplinary pilot study based on computer simulations for the geriatric population showed that a dose of 0.5 mg/kg/h of propofol could sedate patients older than 65 for pacemaker implantation. The present study validates that the pacemaker implantation can be done in the elderly using 0.

Novel insight into streptozotocin-induced diabetic rats from the protein misfolding perspective.

Protein folding is a process of self-assembly defined by the sequence of the amino acids of the protein involved. Additionally, proteins tend to unfold, misfold and aggregate due to both intrinsic and extrinsic causes. Human islet amyloid polypeptide (hIAPP) aggregation is an early step in diabetes mellitus.

A Loss-of-Function Splice Acceptor Variant in Is Protective for Type 2 Diabetes.

Type 2 diabetes (T2D) affects more than 415 million people worldwide, and its costs to the health care system continue to rise. To identify common or rare genetic variation with potential therapeutic implications for T2D, we analyzed and replicated genome-wide protein coding variation in a total of 8,227 individuals with T2D and 12,966 individuals without T2D of Latino descent. We identified a novel genetic variant in the gene associated with ∼20% reduced risk for T2D.

Clinical testing of propofol geriatic dose for sedation designed via in silico trial.

The geriatric population shows significant physiological changes due to aging and the multiple co-morbidities that they often present. Conventionally the propofol sedation dose for patients older than 65 years is 80% of the adult dose. We performed an in silico trial for elderly population and the results showed that the necessary simulated dose of propofol was lower than the conventional dose; therefore, a clinical trial was implemented to test three different propofol doses, two of them lower than the conventional dose, during a pacemaker implantation.

Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components.

Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress.

Prevalence of Prehypertension in Mexico and Its Association With Hypomagnesemia.

Background: Prehypertension (preHTN) increases the risk of developing hypertension. The objectives of this study were to estimate the prevalence of preHTN in the Mexican adult population and evaluate the association between hypomagnesemia and preHTN.

Methods: This study was a 2-phase, population-based study.