Utility of Fasting C-Peptide for the Diagnostic Differentiation of Patients with Type 1, Type 2 Diabetes, MODY, and LADA.

Background: The prevalence of obesity has increased in patients with type 1 diabetes (T1D) and latent autoimmune diabetes of the adult (LADA), limiting the use of clinical features such as the body mass index for its differentiation with type 2 diabetes (T2D). Additionally, some patients with maturity-onset diabetes of the young (MODY) or LADA are misdiagnosed as having T2D. The evaluation of autoantibodies and genetic testing are not fully available.

Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells.

Pluripotent stem (PS) cells enable the scalable production of tissue-specific derivatives with therapeutic potential for various clinical applications, including muscular dystrophies. Given the similarity to human counterparts, the non-human primate (NHP) is an ideal preclinical model to evaluate several questions, including delivery, biodistribution, and immune response. While the generation of human-induced PS (iPS)-cell-derived myogenic progenitors is well established, there have been no data for NHP counterparts, probably due to the lack of an efficient system to differentiate NHP iPS cells towards the skeletal muscle lineage.

In Vitro Maturation of Human Pluripotent Stem Cell-Derived Myotubes.

Pluripotent stem cells have a multitude of potential applications in the areas of disease modeling, drug screening, and cell-based therapies for genetic diseases, including muscular dystrophies. The advent of induced pluripotent stem cell technology allows for the facile derivation of disease-specific pluripotent stem cells for any given patient. Targeted in vitro differentiation of pluripotent stem cells into the muscle lineage is a key step to enable all these applications.

Downregulation of SLC16A11 is Present in Offspring of Mothers with Gestational Diabetes.

Background: Studies have identified that diseases in pregnancy affect fetal growth and development of the newborn. In Mexican population, the gene SLC16A11 has been identified as a factor that increases the risk of developing type 2 diabetes mellitus. To date, information is scarce about its expression in gestational diabetes mellitus (GDM); epigenetic modifications due to maternal hyperglycemic state could be identified early in fetal development.

Micronutrients of the one-carbon metabolism cycle are altered in mothers and neonates by gestational diabetes and are associated with weight, height and head circumference at birth.

While several studies have previously described the levels of one-carbon metabolism-related micronutrients in women with gestational diabetes mellitus (GDM) and their neonates, the results in these literature reports have been contradictory. We hypothesized that the concentrations of micronutrients involved in the one-carbon cycle are altered in pregnant women and their neonates by GDM, and that these changes could further modify the neonatal anthropometry. Micronutrient levels were measured in 123 pregnant women with normal glucose levels (M-ND) and their neonates (N-ND), as well as in 54 pregnant women with gestational diabetes (M-GDM) and their neonates (M-GDM).

Endothelial dysfunction in children with chronic kidney disease.

Background And Objective: Cardiovascular disease (CVD) is the main cause of death in children with chronic kidney disease (CKD). Inflammation and endothelial dysfunction (ED) are found in the majority of these patients and are factors associated to CVD. Flow mediated dilatation (FMD) is a surrogate marker validated for evaluating ED.

Toxoplasma gondii excreted/secreted proteases disrupt intercellular junction proteins in epithelial cell monolayers to facilitate tachyzoites paracellular migration.

Toxoplasma gondii shows high dissemination and migration properties across biological barriers infecting immunologically privileged organs. Toxoplasma uses different routes for dissemination; however, the mechanisms are not fully understood. Herein, we studied the effects of proteases present in excretion/secretion products (ESPs) of Toxoplasma on MDCK cell monolayers.

The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction.

β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery-Dreifuss muscular dystrophy (EDMD).

Loss of Dystroglycan Drives Cellular Senescence via Defective Mitosis-Mediated Genomic Instability.

Nuclear β-dystroglycan (β-DG) is involved in the maintenance of nuclear architecture and function. Nonetheless, its relevance in defined nuclear processes remains to be determined. In this study we generated a C2C12 cell-based DG-null model using CRISPR-Cas9 technology to provide insights into the role of β-DG on nuclear processes.

Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes.

Targeted differentiation of pluripotent stem (PS) cells into myotubes enables in vitro disease modeling of skeletal muscle diseases. Although various protocols achieve myogenic differentiation in vitro, resulting myotubes typically display an embryonic identity. This is a major hurdle for accurately recapitulating disease phenotypes in vitro, as disease commonly manifests at later stages of development.

Age-Related Gene Expression Signature in Rats Demonstrate Early, Late, and Linear Transcriptional Changes from Multiple Tissues.

To understand the changes in gene expression that occur as a result of age, which might create a permissive or causal environment for age-related diseases, we produce a multi-time point age-related gene expression signature (AGES) from liver, kidney, skeletal muscle, and hippocampus of rats, comparing 6-, 9-, 12-, 18-, 21-, 24-, and 27-month-old animals. We focus on genes that changed in one direction throughout the lifespan of the animal, either early in life (early logistic changes), at mid-age (mid-logistic), late in life (late-logistic), or linearly, throughout the lifespan of the animal. The pathways perturbed because of chronological age demonstrate organ-specific and more-global effects of aging and point to mechanisms that could potentially be counter-regulated pharmacologically to treat age-associated diseases.

Gene Correction of LGMD2A Patient-Specific iPSCs for the Development of Targeted Autologous Cell Therapy.

Limb girdle muscular dystrophy type 2A (LGMD2A), caused by mutations in the Calpain 3 (CAPN3) gene, is an incurable autosomal recessive disorder that results in muscle wasting and loss of ambulation. To test the feasibility of an autologous induced pluripotent stem cell (iPSC)-based therapy for LGMD2A, here we applied CRISPR-Cas9-mediated genome editing to iPSCs from three LGMD2A patients to enable correction of mutations in the CAPN3 gene. Using a gene knockin approach, we genome edited iPSCs carrying three different CAPN3 mutations, and we demonstrated the rescue of CAPN3 protein in myotube derivatives in vitro.

Transplantation studies reveal internuclear transfer of toxic RNA in engrafted muscles of myotonic dystrophy 1 mice.

Background: Stem cell transplantation represents a potential therapeutic option for muscular dystrophies (MD). However, to date, most reports have utilized mouse models for recessive types of MD. Here we performed studies to determine whether myotonic dystrophy 1 (DM1), an autosomal dominant type of MD, could benefit from cell transplantation.

Adipocytokines and High Blood Pressure in Mexican Children.

Given that adipocytokines may play an important role in the pathophysiology of high blood pressure (HBP) and because related reports in children are scarce and controversial, we evaluated the relationship of leptin, resistin, tumor necrosis factor-α, interleukin-6, adiponectin, and interferon-γ with HBP. . A total of 129 (53.

Time-dependent Pax3-mediated chromatin remodeling and cooperation with Six4 and Tead2 specify the skeletal myogenic lineage in developing mesoderm.

The transcriptional mechanisms driving lineage specification during development are still largely unknown, as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors-mesogenin 1 (Msgn1), T-box 6 (Tbx6), forkhead box C1 (Foxc1), paired box 3 (Pax3), Paraxis, mesenchyme homeobox 1 (Meox1), sine oculis-related homeobox 1 (Six1), and myogenic factor 5 (Myf5)-in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage.

[Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social].

Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide.

Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS).

Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10 Revision.

Publisher Correction: Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Recapitulating muscle disease phenotypes with myotonic dystrophy 1 induced pluripotent stem cells: a tool for disease modeling and drug discovery.

Myotonic dystrophy 1 (DM1) is a multisystem disorder primarily affecting the central nervous system, heart and skeletal muscle. It is caused by an expansion of the CTG trinucleotide repeats in the 3' untranslated region of the gene. Although patient myoblasts have been used for studying the disease , the invasiveness as well as the low accessibility to muscle biopsies motivate the development of alternative reliable myogenic models.

Agreement between the 'point of care' tests for microalbuminuria and HbA1c performed in mexican family medicine units and the results of standard laboratory tests.

The albumin-creatinine ratio is considered an indicator of microalbuminuria, precursor to chronic kidney disease, while HbA1c is used to measure glycemic control. Given the prevalence of diabetes-related nephropathy, spot testing of albumin has long been recommended as a preventative measure, for the timely detection of microalbuminuria. However, many countries do not have this testing available in primary care, and sometimes not even in second- and third-level care.

Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus.

β-Dystroglycan (β-DG) is a transmembrane protein with critical roles in cell adhesion, cytoskeleton remodeling and nuclear architecture. This functional diversity is attributed to the ability of β-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin α/β mediated nuclear import pathway has already been described for β-DG, the intracellular trafficking route by which β-DG reaches the nucleus is unknown.

Stepwise strategies to successfully recruit diabetes patients in a large research study in Mexican population.

Aims: Describe stepwise strategies (electronic chart review, patient preselection, call-center, personnel dedicated to recruitment) for the successful recruitment of >5000 type 2 diabetes patients in four months.

Methods: Twenty-five family medicine clinics from Mexico City and the State of Mexico participated: 13 usual care, 6 specialized diabetes care and 6 chronic disease care. Appointments were scheduled from 11/3/2015 to 3/31/2016.

Association of V249I and T280M variants of fractalkine receptor CX3CR1 with carotid intima-media thickness in a mexican population with type 2 diabetes.

Objective: To evaluate the association of the V249I and T280M variants of CX3CR1 fractalkine gene with carotid intima-media thickness in Mexican subjects with and without type 2 diabetes.

Methods: We analyzed the V249I and T280M variants of the CX3CR1 receptor by TaqMan assays in 111 subjects with type 2 diabetes and 109 healthy controls. Hemoglobin A1c, glucose, and lipid profile were determined.

[Level of expression of gene CTSL and its correlation with natural killer T-Cells in mexican pediatric patients with recent-onset type 1 diabetes].

Objective: To compare the level of expression of the gene CTSL and its correlation with NKT cells in patients with recent-onset type 1 diabetes (T1D), their siblings, and healthy controls.

Methods: Analytical cross-sectional design. Patients with T1D < 3 months evolution, their siblings, and healthy controls were included.

HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes.

Background: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific β-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes.

Objective: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with β-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls.