Intensive Medical Nutrition Therapy Alone or with Added Metformin to Prevent Gestational Diabetes Mellitus among High-Risk Mexican Women: A Randomized Clinical Trial

The aim of this study was to examine the efficacy of intensive medical nutrition therapy (MNT) plus metformin in preventing gestational diabetes mellitus (GDM) among high-risk Mexican women. An open-label randomized clinical trial was conducted. Inclusion criteria were pregnant women with three or more GDM risk factors: Latino ethnic group, maternal age >35 years, body mass index >25 kg/m², insulin resistance, and a history of previous GDM, prediabetes, a macrosomic neonate, polycystic ovarian syndrome, or a first-degree relative with type 2 diabetes. Women before 15 weeks of gestation were assigned to group 1 (n = 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (n = 45): intensive MNT without metformin. Intensive MNT included individual dietary counseling, with ≤50% of total energy from high carbohydrates. The primary outcome was the GDM incidence according to the International Association of Diabetes Pregnancy Study Groups criteria. There were no significant differences in baseline characteristics and adverse perinatal outcomes between the groups. The GDM incidence was n = 11 (24.4%) in the MNT plus metformin group versus n = 7 (15.5%) in the MNT without metformin group: p = 0.42 (RR: 1.57 [95% CI: 0.67–3.68]). There is no benefit in adding metformin to intensive MNT to prevent GDM among high-risk Mexican women. Clinical trials registration: {"type":"clinical-trial","attrs":{"text":"NCT01675310","term_id":"NCT01675310"}}NCT01675310.     

Sod1 integrates oxygen availability to redox regulate NADPH production and the thiol redoxome

Cu/Zn superoxide dismutase (Sod1) is a highly conserved and abundant antioxidant enzyme that detoxifies superoxide (O₂^•−) by catalyzing its conversion to dioxygen (O₂) and hydrogen peroxide (H₂O₂). Using Saccharomyces cerevisiae and mammalian cells, we discovered that a major aspect of the antioxidant function of Sod1 is to integrate O₂ availability to promote NADPH production. The mechanism involves Sod1-derived H₂O₂ oxidatively inactivating the glycolytic enzyme, GAPDH, which in turn reroutes carbohydrate flux to the oxidative phase of the pentose phosphate pathway (oxPPP) to generate NADPH. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1. Thus, Sod1 senses O₂ via O₂^•− to balance glycolytic and oxPPP flux, through control of GAPDH activity, for adaptation to life in air. Importantly, this mechanism for Sod1 antioxidant activity requires the bulk of cellular Sod1, unlike for its role in protection against O₂^•− toxicity, which only requires <1% of total Sod1. Using mass spectrometry, we identified proteome-wide targets of Sod1-dependent redox signaling, including numerous metabolic enzymes. Altogether, Sod1-derived H₂O₂ is important for antioxidant defense and a master regulator of metabolism and the thiol redoxome.

Superoxide dismutases (SODs) serve on the frontline of defense against reactive oxygen species (ROS). SODs, which detoxify O₂^•− by catalyzing its disproportionation into O₂ and hydrogen peroxide (H₂O₂), are unique among antioxidant enzymes in that they also produce a ROS byproduct. While much is known about the necessity of scavenging O₂^•−, it is less clear what the physiological consequences of SOD-derived H₂O₂ are. Paradoxically, increased expression of Cu/Zn SOD (Sod1), which accounts for the majority of SOD activity in cells (1), is associated with reduced cellular H₂O₂ levels (2), suggesting there may be additional unknown mechanisms underlying Sod1 antioxidant activity.The cytotoxicity of O₂^•− stems from its ability to oxidize and inactivate [4Fe-4S] cluster-containing enzymes, which results in defects in metabolic pathways that utilize [4Fe-4S] proteins and Fe toxicity due to its release from damaged Fe/S clusters (3–6). The released Fe can catalyze deleterious redox reactions and, in particular, production of hydroxyl radicals (^•OH) via Haber-Weiss and Fenton reactions, which indiscriminately oxidizes lipids, proteins, and nucleic acids (4, 7). The importance of Sod1 in oxidative stress protection is underscored by reduced proliferation, decreased lifespan, and numerous metabolic defects, including cancer, when SOD1 is deleted in various cell lines and organisms (7–11). It was previously proposed that Sod1 limits steady-state H₂O₂ levels because of its ability to prevent the O₂^•−-mediated oxidation of Fe/S clusters, which results in the concomitant formation of H₂O₂ (2, 12, 13). However, since vanishingly small amounts of Sod1 (<1% of total cellular Sod1) is sufficient to protect cells against O₂^•− toxicity, including oxidative inactivation of Fe/S enzymes (14–16), any changes in Sod1 expression would not be expected to alter H₂O₂ arising from O₂^•− oxidation of Fe/S clusters. How then can Sod1, an enzyme that catalyzes H₂O₂ formation, act to reduce cellular [H₂O₂]?Two previously reported but unexplained metabolic defects in sod1Δ strains of Saccharomyces cerevisiae point to a potential role for Sod1 in regulating the production of NADPH, a key cellular reductant required for reductive biosynthesis and the reduction and regeneration of H₂O₂ scavenging thiol peroxidases (17) and catalases (18, 19). Yeast strains lacking SOD1 exhibit increased glucose consumption (20) and defects in the oxidative phase of the pentose phosphate pathway (oxPPP) (21), the primary source of NADPH. Inhibition of key rate-limiting enzymes in glycolysis—including phosphofructose kinase (22), GAPDH (23, 24), and pyruvate kinase (25, 26)—reduces glucose uptake (27–29) and increases the concentration of glucose-6-phosphate (G6P), a glycolytic intermediate that is also the substrate for the first enzyme in the oxPPP, G6P dehydrogenase (G6PDH), which in turn increases oxPPP flux and NADPH production (30–35). Taking these data together, we surmised that Sod1 negatively regulates a rate-determining enzyme in glycolysis, thereby accounting for the observed metabolic defects in glucose utilization and the oxPPP in sod1Δ cells (20, 21).GAPDH, which catalyzes a rate-determining step in glycolysis (36, 37), is very abundant (38), and contains a H₂O₂-reactive catalytic Cys (k ∼ 10² to 10³ M⁻¹s⁻¹), represents a critical redox regulated node that can toggle flux between glycolysis and the oxPPP (32). As such, we hypothesized that a novel aspect of the antioxidant activity of Sod1 is to oxidatively inactivate GAPDH using Sod1-catalyzed H₂O₂, which would in turn stimulate NADPH production via the oxPPP and enhance cellular peroxide scavenging by thiol peroxidases. This mechanism for Sod1-mediated antioxidant activity would explain a number of prior observations, including the findings that elevated Sod1 expression decreases peroxide levels and loss of SOD1 increases glucose consumption and attenuates oxPPP activity. In addition, more generally, since Sod1-derived H₂O₂ has previously been implicated in the redox regulation of other enzymes, including protein tyrosine phosphatases (39) and casein kinases (15, 16, 40), we also sought to identify proteome-wide redox targets of Sod1.In the present report we provide evidence highlighting an antioxidant function for Sod1-derived H₂O₂ in integrating O₂ availability to control NADPH production to support aerobic growth and metabolism. The mechanism involves the conversion of O₂ to O₂^•− by mitochondrial respiration and an NADPH oxidase, followed by the Sod1-catalyzed conversion of O₂^•− to H₂O₂, which in turn oxidatively inactivates GAPDH. The inhibition of GAPDH serves to reroute metabolism from glycolysis to the oxPPP in order to maintain sufficient NADPH for metabolism in air. The aerobic oxidation of GAPDH is dependent on and rate-limited by Sod1, suggesting that it provides a privileged pool of peroxides to inactivate GAPDH under physiological conditions. Finally, we revealed a larger network of cysteine-containing proteins that are oxidized in a Sod1-dependent manner using mass spectrometry-based redox proteomics approaches. Altogether, these results highlight a mechanism for O₂ sensing and adaptation, reveal an important but previously unknown antioxidant role of Sod1 that goes beyond O₂^•− scavenging to include the stimulation of aerobic NADPH production, and places Sod1 as a master regulator of proteome-wide thiol oxidation and multiple facets of metabolism.     

Adenoid cystic carcinoma: A case of rare breast cancer

Adenoid cystic carcinoma is a rare form of breast cancer accounting for 0.1%-1.0% of all mammary malignancies. It is characterized by an indolent clinical course and favorable prognosis, contrary to other breast cancers. Diagnostic mammogram and breast ultrasound play a pivotal role in the early detection and diagnosis of breast adenoid cystic carcinoma. Treatment may consist of lumpectomy and radiation therapy vs mastectomy alone. Even though rare, late disease recurrence and metastasis has been reported in the literature thus long-term surveillance is of utmost importance for these patients. We will review the literature and discuss the case of a 52-year-old female who presented with a palpable lump of the right breast, which was pathologically proven to be adenoid cystic carcinoma of the breast.     

Has Omicron Changed the Evolution of the Pandemic?

BackgroundVariants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy.ObjectiveThe aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak.MethodsWe analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections.ResultsThe observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread.ConclusionsThe transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.     

Main factors influencing long-term outcomes of liver transplantation in 2022

Liver transplant(LT) outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbidities,including complications of metabolic syndrome and de novo neoplasms,seem to play a key role in determining long-term outcomes in LT recipients.This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term managemen...     

Dietary Sodium and Potassium Intake: Data from the Mexican National Health and Nutrition Survey 2016

Population studies have demonstrated an association between sodium and potassium intake and blood pressure levels and lipids. The aim of this study was to describe the dietary intake and contribution of sodium and potassium to the Mexican diet, and to describe its association with nutrition status and clinical characteristics. We analyzed a national survey with 4219 participants. Dietary information was obtained with a 24-h recall. Foods and beverages were classified according to level of processing. The mean intake (mg/d) of Na was 1512 in preschool children, 2844 in school-age children, 3743 in adolescents, and 3132 in adults. The mean intake (mg/d) of K was 1616 in preschool children, 2256 in school-age children, 2967 in adolescents, and 3401 in adults. Processed and ultra-processed foods (UPF) contribute 49% of Na intake in preschool children, 50% in school-age children, 47% in adolescents, and 39% in adults. Adults with high Na intake had lower serum concentrations of cholesterol, HDL-c, and LDL-c. A significant proportion of the Mexican population has a high intake of Na (64–82%) and low K (58–73%). Strategies to reduce Na and increase K intake need to reduce the possibility of having high BP and serum lipid disturbances.     

Factors associated with gastro-duodenal ulcer in compensated type 2 diabetic patients: a Romanian single-center study

IntroductionHelicobacter pylori infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in countries with a high prevalence of infection. The aim of the study was to investigate the influence of H. pylori infection, medication, associated medical conditions or social habits on endoscopic ulcer occurrence in the compensated type 2 diabetic population.Material and methodsTwo hundred and sixty type 2 diabetic patients investigated on endoscopy (57 patients with peptic ulcer and 203 controls) with a complete set of biopsies, demographic and medical data were enrolled.ResultsOn univariate regression analysis, H. pylori infection (42.1% vs. 35.5%, p = 0.359) or a history of peptic ulcer (61.4% vs. 61.6%, p = 0.981) was not a predictor for ulcer on endoscopy in the diabetic population, and heartburn was more frequent in diabetics without ulcer (21.2% vs. 8.8%, p = 0.033). Anemia was the best predictor for ulcer on endoscopy in both diabetics with (p < 0.001, OR = 4.77, 95% CI: 2.02–11.28) and without (p = 0.027, OR = 2.76, 95% CI: 1.10–6.91) chronic proton pump inhibitor (PPI) therapy. In diabetic patients on PPI more than 1 month anticoagulants – acenocoumarol or low-weight molecular heparin (p = 0.038, OR = 2.37, 95% CI: 1.04–5.40), low-dose aspirin 75–125 mg/day (p = 0.029, OR = 2.61, 95% CI: 1.08–6.28) and alcohol consumption (p = 0.015, OR = 2.70, 95% CI: 1.19–6.13) were predictors for ulcer on endoscopy.ConclusionsIn diabetic patients, anemia is the most important predictor for ulcer on endoscopy, but not H. pylori or digestive symptoms, while low-dose aspirin or anticoagulant therapy and alcohol consumption are the most important predictors for ulcer in diabetics on chronic proton pump inhibitor therapy.     

Ethnicity,self-care,and use of medical care among the elderly with joint symptoms

Elderly individuals with self-reported joint symp-toms representing three ethnic groups (i.e., blacks [n = 105], Hispanics[n = 100], and whites of Eastern European origin [n = 112] answered questions about their use of self-care and medical care for these symptoms. Ethnic groups differed in both self-care practices and their use of medical care for joint symptoms. Multiple regression analyses demonstrated that arthritis-specific and general health status were better predictors than ethnicity of the tendency to rely on self-care and medical care. There was no evidence that self-care served as a substitute for medical care.