Prediction of metabolic subphenotypes of type 2 diabetes via continuous glucose monitoring and machine learning.

The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them).

Alkaloids are associated with increased microbial diversity and metabolic function in poison frogs.

Shifts in host-associated microbiomes can impact both host and microbes. It is of interest to understand how perturbations, like the introduction of exogenous chemicals, impact microbiomes. In poison frogs (family Dendrobatidae), the skin microbiome is exposed to alkaloids that the frogs sequester for defense.

IVC filter use in patients with a history of venous thromboembolism undergoing bariatric surgery: a MBSAQIP study.

Background: Research on the use of prophylactic inferior vena cave filter (IVCF) placement prior to metabolic and bariatric surgery (MBS) in high risk patients has yielded conflicting results. We evaluated thrombotic events and mortality in patients with a history of venous thromboembolism (VTE) who underwent IVCF placement in anticipation of MBS.

Methods: We queried the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for all patients undergoing primary sleeve gastrectomy or Roux-en-Y gastric bypass from 2015 to 2019 with a history of VTE.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies.

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN) to help induce "dopamine homeostasis" in patients with PANDAS, especially those with known DNA-induced hypodopaminergia.

Lifestyle Profiling Using Wearables and Prediction of Glucose Metabolism in Individuals with Normoglycemia or Prediabetes.

This study examined the relationship between lifestyles (diet, sleep, and physical activity) and glucose responses at a personal level. 36 healthy adults in the Bay Area were monitored for their lifestyles and glucose levels using wearables and continuous glucose monitoring (NCT03919877). Gold-standard metabolic tests were conducted to phenotype metabolic characteristics.

Sec18 side-loading is essential for universal SNARE recycling across cellular contexts.

SNARE proteins drive membrane fusion as their core domains zipper into a parallel four-helix bundle. After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/ α-SNAP to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains.

Predicting Type 2 Diabetes Metabolic Phenotypes Using Continuous Glucose Monitoring and a Machine Learning Framework.

Type 2 diabetes (T2D) and prediabetes are classically defined by the level of fasting glucose or surrogates such as hemoglobin HbA1c. This classification does not take into account the heterogeneity in the pathophysiology of glucose dysregulation, the identification of which could inform targeted approaches to diabetes treatment and prevention and/or predict clinical outcomes. We performed gold-standard metabolic tests in a cohort of individuals with early glucose dysregulation and quantified four distinct metabolic subphenotypes known to contribute to glucose dysregulation and T2D: muscle insulin resistance, β-cell dysfunction, impaired incretin action, and hepatic insulin resistance.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor () gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the gene listed in PUBMED.

Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography.

Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).

Multimodal approach utilising a weight management programme prior to bariatric surgery in patients with BMI ≥50 kg/m: A propensity score matching retrospective cohort study.

We evaluated preoperative weight loss and days from initial consult to surgery in patients with BMI ≥50 kg/m who were and were not enrolled in medical weight management (MWM) prior to laparoscopic sleeve gastrectomy. We retrospectively identified patients with BMI ≥50 kg/m who had primary sleeve gastrectomy between 2014 and 2019 at two bariatric surgery centres in our healthcare system. Patients presenting after 2017 that received preoperative MWM (n = 28) were compared to a historical cohort of non-MWM patients (n = 118) presenting prior to programme initiation in 2017 on preoperative percent total body weight loss (%TBWL) and days from initial consult to surgery.

Five-year outcomes of revisional bariatric surgery: gastric band to sleeve gastrectomy or to Roux-en-Y gastric bypass.

Background: Revisional bariatric surgery after an index adjustable gastric band (AGB) may be indicated to remedy weight relapse or band-related complications. We examined outcomes five years following revision from AGB to laparoscopic sleeve gastrectomy (AGB-LSG) or to Roux-en-Y gastric bypass (AGB-RYGB).

Methods: We conducted a retrospective review to identify patients (men and women, age 18-80) who underwent one revisional bariatric procedure with AGB as the index procedure at two medical centers in our healthcare system between January 2012 and February 2017.

Active Tuberculosis Is Associated with Depletion of HIV-Specific CD4 and CD8 T Cells in People with HIV.

Infection with (Mtb) in people with HIV (PWH) is associated with depletion of Mtb-specific CD4 T cell responses, increased risk of progression to active tuberculosis (TB) disease, and increased immune activation. Although higher HIV viral loads have been reported in Mtb/HIV co-infection, the extent to which Mtb infection and TB disease impact the frequency and phenotype of HIV-specific T cell responses has not been well described. We enrolled a cohort of PWH in Kenya across a spectrum of Mtb infection states, including those with no evidence of Mtb infection, latent Mtb infection (LTBI), and active pulmonary TB disease, and evaluated the frequency, immune activation, and cytotoxicity phenotype of HIV-specific CD4 and CD8 T cell responses in peripheral blood by flow cytometry.

A toxic environment selects for specialist microbiome in poison frogs.

Shifts in microbiome community composition can have large effects on host health. It is therefore important to understand how perturbations, like those caused by the introduction of exogenous chemicals, modulate microbiome community composition. In poison frogs within the family Dendrobatidae, the skin microbiome is exposed to the alkaloids that the frogs sequester from their diet and use for defense.

Are We Getting High Cause the Thrill is Gone?

In the USA alone, opioid use disorder (OUD) affects approximately 27 million people. While the number of prescriptions may be declining due to increased CDC guidance and prescriber education, fatalities due to fentanyl-laced street heroin are still rising. Our laboratory has extended the overall concept of both substance and non-substance addictive behaviors, calling it "Reward Deficiency Syndrome (RDS).

Neurogenetics and Epigenetics of Loneliness.

Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets.

Essential Role of XBP1 in Maintaining Photoreceptor Synaptic Integrity in Early Diabetic Retinopathy.

Purpose: Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults characterized by retinal dysfunction and neurovascular degeneration. We previously reported that deletion of X-box binding protein 1 (XBP1) leads to accelerated retinal neurodegeneration in diabetes; however, the mechanisms remain elusive. The goal of this study is to determine the role of XBP1 in the regulation of photoreceptor synaptic integrity in early DR.

Digital health application integrating wearable data and behavioral patterns improves metabolic health.

The effectiveness of lifestyle interventions in reducing caloric intake and increasing physical activity for preventing Type 2 Diabetes (T2D) has been previously demonstrated. The use of modern technologies can potentially further improve the success of these interventions, promote metabolic health, and prevent T2D at scale. To test this concept, we built a remote program that uses continuous glucose monitoring (CGM) and wearables to make lifestyle recommendations that improve health.

Achieving COVID-19 vaccination equity in South Eastern Metropolitan Victoria, Australia: a population-based study.

Background: We describe COVID-19 first and second vaccine uptake across Local Government Areas (LGAs) in Victoria using southeast metropolitan Melbourne catchment as a case study. We explore key policy and implementation strategies that contributed to equitable uptake.

Methods: Population level data within the South East Public Health Unit (SEPHU) was used to compare trends in COVID-19 vaccination first and second dose uptake for each of the 11 LGAs in year 2021.

The impact of farming on prehistoric culinary practices throughout Northern Europe.

To investigate changes in culinary practices associated with the arrival of farming, we analysed the organic residues of over 1,000 pottery vessels from hunter-gatherer-fisher and early agricultural sites across Northern Europe from the Lower Rhine Basin to the Northeastern Baltic. Here, pottery was widely used by hunter-gatherer-fishers prior to the introduction of domesticated animals and plants. Overall, there was surprising continuity in the way that hunter-gatherer-fishers and farmers used pottery.

Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.

Pancreatic β-cell dysfunction and death are central to the pathogenesis of type 2 diabetes (T2D). We identified a novel role for the inflammatory extracellular matrix polymer hyaluronan (HA) in this pathophysiology. Low concentrations of HA were present in healthy pancreatic islets.

Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry.

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.