Engineered mesoporous silica reduces long-term blood glucose, HbA1c, and improves metabolic parameters in prediabetics.

Aim: To investigate the effect of oral consumption of engineered mesoporous silica particles, SiPore15®, on long-term blood glucose levels and other metabolic parameters in individuals with prediabetes and newly diagnosed Type 2 diabetes. Method: An open-label, single-arm, multicenter trial was conducted in which SiPore15 was consumed three times daily for 12 weeks. Hemoglobin A1c (HbA1c, primary end point) and an array of metabolic parameters were measured at baseline and throughout the trial. Result: SiPore15 treatment significantly reduced HbA1c by a clinically meaningful degree and improved several disease-associated parameters with minimal side effects. Conclusion: The results from this study demonstrate the potential use of SiPore15 as a treatment for prediabetes that may also delay or prevent the onset of Type 2 diabetes.

Lay abstract Prediabetes is a health condition in which blood sugar levels are higher than normal but below diabetes diagnosis level. Without intervention, prediabetic adults and children are most likely to progress to Type 2 diabetes. To try and prevent this progression, the authors of this article are proposing an innovative solution with an engineered material called SiPore15^®. SiPore15 is classified as a medical device, and is made up entirely of porous silica particles. It has been proven to be safe to take orally. The effects of SiPore15 were investigated in people with prediabetes and newly diagnosed Type 2 diabetes. SiPore15 was taken three times a day for 12 weeks. It significantly reduced long-term blood glucose levels and improved other factors related to the disease with minimal side effects. The results from this study show that SiPore15 has the potential to be used as a treatment for prediabetes. This may help to delay or prevent the onset of Type 2 diabetes. Clinical Trial Registration: NCT03823027 (ClinicalTrials.gov).

Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans.

Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic  α-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.

Case Series: Rapid Induction Onto Long Acting Buprenorphine Injection for High Potency Synthetic Opioid Users.

BACKGROUND AND OBJECTIVES: Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States. METHODS: In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms. RESULTS: Two participants received the BXR injection on the second day of the induction and three participants on the third day. DISCUSSION AND CONCLUSION: All five participants were retained at least 1-month postinduction. SCIENTIFIC SIGNIFICANCE: It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).

Inhibition of 2C Coxsackie B Virus Protein to Decrease Pathogenicity of Diabetes Mellitus Type 1.

BACKGROUND: Insulin-dependent Diabetes Mellitus Type 1 (T1D) also referred to as autoimmune diabetes. T1D is a chronic disease which is characterized by way of insulin deficiency. The deficiency is due to the loss of pancreatic ß cells and leads to hyperglycemia. There are many factors which play a significant role in T1D disease pathogenicity including genetic predisposition, the immune system, and environmental factors. The environmental factors may include Coxsackie B4 virus, a small RNA virus. OBJECTIVE: The objective of current in silico study is to identify active lead compounds against Coxsackie B4 virus, a small RNA virus which has been reported in diabetic patients after PCR. There is a need to predict inhibitors against TID caused by Coxsackie B4 viral protein that may be used as a drug against TID in the future. METHODS: For this purpose, different bioinformatics databases and tools were used. The protein structure generation and validation, retrieval of ligands and their properties analysis were performed by different databases, web servers, and software tools. Moreover, the docking tools were used to identify the target site of the protein and interaction of different inhibitors with the target protein molecule. RESULTS: Based on the analysis, two lead compounds ZINC00034488 and ZINC00034585 were selected as potential drugs. These compounds are non-toxic and have best interaction energy and fulfill Lipinski rule, Veber rule, Ghose Rule, Weighted QED, Unweighted QED and BBB likeness parameters. CONCLUSION: Our work will help researchers to get an idea about the understanding of chemicals against Coxsackie B4 Viruses and helpful to design a drug and test these chemicals to overcome Diabetes Mellitus Type 1 caused by Coxsackie B4 virus.

Subthreshold depression and its association with cardiovascular risk.

BACKGROUND: Cardiovascular disease (CVD) is a widespread condition that is associated with significant morbidity, mortality, and cost. It is considered one of the leading causes of death in the world. Individuals with CVD and major depressive disorder have greater morbidity and mortality. Subthreshold depression (SubD) is a form of affective disorder that shares similar characteristics with major depressive disorder. METHODS: This systemic review of the literature was derived from Medline and PubMed searches. Our search yielded more than 30 articles. We narrowed them down to 11 studies based on the quality of the research done. Our main emphasis was on the assessment of the prevalence of and risk association between SubD and CVD. RESULTS: We should consider SubD as a variant of depressive disorder. Health care providers need to be taught to identify such patients in order to treat them appropriately, using both pharmacologic and nonpharmacologic interventions. CONCLUSIONS: SubD can significantly impact quality of life and is a decrement on the health of patients with CVD.

Treatment for Substance Use Disorder With Co-Occurring Mental Illness.

Substance use disorder is a highly prevalent condition, leading to significant morbidity, mortality, and burden on the health care system. Substance use disorders are overrepresented among individuals with a mental illness. The term "dual diagnosis" was introduced by the World Health Organization in the mid-1990s and refers to the co-occurrence of a substance use disorder with mental illness-a more recently used term is "co-occurring disorders." In the past decade, substantial progress has been made toward expanding psychotherapeutic and pharmacotherapeutic treatments for treating co-occurring disorders. Yet management remains a challenge among clinicians and has been a source of confusion and considerable controversy. This review describes the epidemiology and treatment of co-occurring disorders, with a focus on major depressive disorder, anxiety disorders, and attention-deficit hyperactivity disorder. Substance use may make diagnosis of the underlying psychiatric condition difficult, and a period of abstinence may be necessary. Findings from efficacy studies of medications used to treat co-occurring disorders are reviewed, as are results of preliminary studies of newer treatments, such as topiramate, ketamine, noninvasive brain stimulation, and deep brain stimulation. Treatment recommendations that combine medications and psychosocial interventions are summarized.