Differential analysis of the bacterial community in colostrum samples from women with gestational diabetes mellitus and obesity.

Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.

Minimally Invasive Hemodynamic Assessment during Obstetric Hysterectomy for Invasive Placentation with Epidural Anesthesia.

BACKGROUND: The present study aimed to describe the evolution of hemodynamic parameters over time of patients with invasive placentation during their third trimester who were delivered via cesarean section and subsequently underwent obstetric hysterectomy under epidural anesthesia. METHODS: A prospective, descriptive, longitudinal, 11-month cohort study of 43 patients aged between 18 and 37 years who presented with invasive placentation. Minimal invasive monitoring was placed before the administration of epidural anesthesia for hemodynamic parameter tracking during the cesarean section. After delivery, the patients underwent an obstetric hysterectomy. Blood loss, hemodynamic parameters, and coagulation were managed via goal-directed therapy. Parameters were compared via repeated measures ANOVA and effect size estimation (Cohen's d). RESULTS: The mean age of the patients was 29.2 ± 3.4 years and was moderately overweight. They had minor cardiac index variance (P=NS, no significance), vascular systemic resistance index (NS), heart rate (P=NS), and median arterial pressure (P=NS). Differences were observed in the stroke volume index (P=0.015) due to moderately higher values (d = 0.3, P=0.016) in the middle of the surgery. Patients had lower cardiac index (d = -0.36, NS) and cardiac workload requirements (d = -0.29, P=0.034) toward the completion of surgery. CONCLUSION: Patients who are in their third trimester and who subsequently underwent obstetric hysterectomy under epidural anesthesia had modest surgical hemodynamic variance and reduced cardiac workload requirements toward the end of the surgery.

Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring.

BACKGROUND: To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism. RESULTS: In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R2 = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks. CONCLUSION: Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.

Clinical and cytogenetic characterization of a patient with tetrasomy 18p / Caracterización clínica y citogenética de un paciente con tetrasomía 18p

The 18p tetrasomy is a structural chromosomal abnormality with the presence of an extra isochromosome 18p, caused by a nondisjunction failure during maternal meiosis II. This additional i(18p) occurs in 1 of 180,000 live-born children worldwide, affecting males and females equally. It is characterized by craniofacial dysmorphisms; ears, nose and throat (ENT) abnormalities; musculoskeletal alterations; and global development delay. We aim to present the clinical and cytogenetic findings of a 3-year-10-month-old Latin American male with i(18p), to support the gene dosage effects, comparing his features with the ones reported in literature. This patient was product of the second pregnancy of a 39-year-old woman and the first son of a 49-year-old man. His main clinical features were microcephaly, facial dysmorphism, generalized hypotonia, and developmental delay. A blood sample of the patient was required to perform a GTG-banded karyotype and a fluorescence in situ hybridization (FISH) for chromosome 18 short arm. In addition, an SNP microarray analysis was carried out to detect genomic imbalances. Cytogenetic analysis revealed the presence of a metacentric supernumerary marker chromosome. The FISH study confirmed the origin of the marker chromosome by showing two signals for the 18p subtelomere and an intermediate signal for the 18 centromere. The microarray analysis showed a copy number gain of 18,385 Mb within the 18p.Tetrasomy tends to be a result of de novo events. The presence of the patient's isochromosome could be explained by advanced maternal age as it is known that this factor has high influence in isochromosome formation. Despite that there were no genes associated with the i(18p)'s clinical manifestations, these features are negatively correlated with dosage effects of the entire short arm. Physical and language therapy was recommended to the patient; the family received medical orientation, and awareness in family planning was raised.

La tetrasomía 18p es una anormalidad cromosómica estructural con la presencia de un isocromosoma extra 18p, causado por una no disyunción durante la meiosis materna II. Este adicional i(18p) ocurre en 1 de 180.000 niños nacidos vivos en todo el mundo, y afecta a hombres y mujeres por igual. Se caracteriza por dismorfias craneofaciales; anomalías en oídos, nariz y garganta (ENT); alteraciones musculoesqueléticas y del desarrollo global. Nuestro objetivo es presentar los hallazgos clínicos y citogenéticos de un varón latinoamericano de 3 años y 10 meses de edad con i(18p), para explicar los efectos de dosificación génica, comparando sus características con las reportadas en la literatura. Este paciente es producto del segundo embarazo de una mujer de 39 años y el primer hijo de un hombre de 49 años. Sus principales características clínicas fueron microcefalia, dismorfia facial, hipotonía generalizada y retraso global en el desarrollo. Se requirió una muestra de sangre del paciente para realizar un cariotipo con bandas GTG y una hibridación fluorescente in situ (FISH) para el análisis del brazo corto del cromosoma 18. Además, se llevó a cabo un análisis de microarreglos para detectar desequilibrios genómicos. El análisis citogenético reveló la presencia de un cromosoma supernumerario metacéntrico. Mientras que el estudio FISH confirma el origen del cromosoma marcador al mostrar dos señales para subtelómeros 18p y una señal intermedia para el centrómero 18. El análisis de microarreglos mostró una ganancia en el número de copias de 18,385 Mb dentro de la región 18p.La tetrasomía tiende a ser el resultado de eventos de novo. El isocromosoma del paciente podría explicarse por la edad materna avanzada, ya que se sabe que tiene una gran influencia en su formación. A pesar de que no hay genes asociados con las manifestaciones clínicas de i(18p), estas características están negativamente correlacionadas con los efectos de dosificación de todo el brazo corto. Se le recomendó terapia física y de lenguaje al paciente, la familia recibió orientación médica y se concientiza sobre la planificación familiar.

Growth hormone insensitivity: Mexican case report.

Herein, we present a 14-year-old patient with short stature (134 cm) referred from Paediatrics to our department for complementary evaluation since growth hormone (GH) treatment failed to show any improvement. He was born premature and small for gestational age. Genital examination classified the patient as Tanner I-II with small penis and testicular size for his age. Biochemical analyses revealed normal GH levels with low serum insulin-like growth factor-1 (IGF-1). Molecular diagnosis confirmed several mutations in IGF1R and IGFALS, and so he was diagnosed with Laron Syndrome or GH insensibility and treated with IGF-1 substitutive therapy. LEARNING POINTS: Evaluation of the GH/IGF-1 axis when short stature does not respond to conservative treatment must be included in the ordinary practice.Laron Syndrome real incidence should be calculated once undiagnosed cases arise, as treatment, due to lack of market, is unaffordable.Even when adulthood is reached, and no longitudinal growth can be achieved, still IGF-1 treatment in Laron Syndrome patients should be pursued as metabolic and protective derangements could arise.

IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture.

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1+/-, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.

Altered liver expression of genes involved in lipid and glucose metabolism in mice with partial IGF-1 deficiency: an experimental approach to metabolic syndrome.

BACKGROUND: Insulin growth factor 1 (IGF-1) has multiple effects on metabolism. Much evidence suggests that the deficiency of this hormone increases insulin resistance, impairs lipid metabolism, augments oxidative damage and deregulates the neuro-hormonal axis. An inverse relationship between IGF-1 levels and the prevalence of Metabolic Syndrome (MetS) with its cardiovascular complications has been identified. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. In order to elucidate such mechanisms, the aim of this work was to study, in mice with partial IGF-1 deficiency, liver expression of genes involved in glucose and lipid metabolism as well as serum levels of glucose, triglycerides and cholesterol, as well as liver malondialdehyde (MDA) levels, as a marker for oxidative damage. METHODS: Three experimental groups were studied in parallel: Controls (CO), wild type mice (igf-1 (+/+)); untreated heterozygous mice (Hz, igf-1 (+/-)) and Hz (igf-1 (+/-)) mice treated with low doses of IGF-1 for 10 days (Hz + IGF-1). RESULTS: A reduction of IGF-1 serum levels in the Hz group was found, which was normalized by IGF-1 therapy. Serum levels of glucose, triglycerides and cholesterol were significantly increased in the untreated Hz group as compared to both controls and Hz + IGF-1 groups. The expression of genes involved in gluconeogenesis, glycogenolysis, lipid synthesis and transport, and catabolism were altered in untreated Hz animals and the expression of most of them was normalized by IGF-1 therapy; MDA was also significantly increased in the Hz untreated group. CONCLUSIONS: The mere partial IGF-1 deficiency is responsible for the reduction in the expression of genes involved in glucose and lipid metabolism, resulting in dyslipidemia and hyperglycemia. Such genetic alterations may seriously contribute to the establishment of MetS.