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1.
Metabolism ; : 155931, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38852020

ABSTRACT

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

2.
Diabetes Obes Metab ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837542

ABSTRACT

AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

3.
Clin Chim Acta ; : 119819, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901629

ABSTRACT

Metabolic syndrome (MetS) represents a significant public health concern due to its association with an increased risk of cardiovascular disease, type 2 diabetes, and other serious health conditions. Despite extensive research, the underlying molecular mechanisms contributing to MetS pathogenesis remain elusive. This review aims to provide a comprehensive overview of the molecular mechanisms linking MetS and cluster of differentiation (CD) markers, which play critical roles in immune regulation and cellular signaling. Through an extensive literature review with a systematic approach, we examine the involvement of various CD markers in MetS development and progression, including their roles in adipose tissue inflammation, insulin resistance, dyslipidemia, and hypertension. Additionally, we discuss potential therapeutic strategies targeting CD markers for the management of MetS. By synthesizing current evidence, this review contributes to a deeper understanding of the complex interplay between immune dysregulation and metabolic dysfunction in MetS, paving the way for the development of novel therapeutic interventions.

4.
Int J Mol Sci ; 25(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732075

ABSTRACT

Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.


Subject(s)
Melanoma , Melatonin , Sericins , Wound Healing , Melatonin/therapeutic use , Melatonin/pharmacology , Humans , Wound Healing/drug effects , Melanoma/drug therapy , Melanoma/metabolism , Melanoma/pathology , Animals , Sericins/pharmacology , Sericins/therapeutic use , Antioxidants/therapeutic use , Antioxidants/pharmacology , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
5.
J Clin Anesth ; 95: 111438, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38484505

ABSTRACT

STUDY OBJECTIVE: Regional analgesia following visceral cancer surgery might provide an advantage but evidence for best treatment options related to risk-benefit is unclear. DESIGN: Systematic review of randomized controlled trials (RCT) with meta-analysis and GRADE assessment. SETTING: Postoperative pain treatment. PATIENTS: Adult patients undergoing visceral cancer surgery. INTERVENTIONS: Any kind of peripheral (PRA) or epidural analgesia (EA) with/without systemic analgesia (SA) was compared to SA with or without placebo treatment or any other regional anaesthetic techniques. MEASUREMENTS: Primary outcome measures were postoperative acute pain intensity at rest and during activity 24 h after surgery, the number of patients with block-related adverse events and postoperative paralytic ileus. MAIN RESULTS: 59 RCTs (4345 participants) were included. EA may reduce pain intensity at rest (mean difference (MD) -1.05; 95% confidence interval (CI): -1.35 to -0.75, low certainty evidence) and during activity 24 h after surgery (MD -1.83; 95% CI: -2.34 to -1.33, very low certainty evidence). PRA likely results in little difference in pain intensity at rest (MD -0.75; 95% CI: -1.20 to -0.31, moderate certainty evidence) and pain during activity (MD -0.93; 95% CI: -1.34 to -0.53, moderate certainty evidence) 24 h after surgery compared to SA. There may be no difference in block-related adverse events (very low certainty evidence) and development of paralytic ileus (very low certainty of evidence) between EA, respectively PRA and SA. CONCLUSIONS: Following visceral cancer surgery EA may reduce pain intensity. In contrast, PRA had only limited effects on pain intensity at rest and during activity. However, we are uncertain regarding the effect of both techniques on block-related adverse events and paralytic ileus. Further research is required focusing on regional analgesia techniques especially following laparoscopic visceral cancer surgery.


Subject(s)
Pain Management , Pain, Postoperative , Randomized Controlled Trials as Topic , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Pain Management/methods , Analgesia, Epidural/methods , Analgesia, Epidural/adverse effects , Nerve Block/methods , Nerve Block/adverse effects , Pain Measurement , Perioperative Care/methods , Anesthesia, Conduction/methods , Anesthesia, Conduction/adverse effects
6.
J Cereb Blood Flow Metab ; 44(4): 556-572, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37944245

ABSTRACT

Hypoglycemia increases the risk related to stroke and neurodegenerative diseases, however, the underlying mechanisms are unclear. For the first time, we studied the effect of a single episode (acute) of severe (ASH) and mild (AMH) hypoglycemia on mouse brain microvascular proteome. After four-hour fasting, insulin was administered (i.p) to lower mean blood glucose in mice and induce ∼30 minutes of ASH (∼30 mg/dL) or AMH (∼75 mg/dL), whereas a similar volume of saline was given to control mice (∼130 mg/dL). Blood glucose was allowed to recover over 60 minutes either spontaneously or by 20% dextrose administration (i.p). Twenty-four hours later, the brain microvessels (BMVs) were isolated, and tandem mass tag (TMT)-based quantitative proteomics was performed using liquid chromatography-mass spectrometry (LC/MS). When compared to control, ASH significantly downregulated 13 proteins (p ≤ 0.05) whereas 23 proteins showed a strong trend toward decrease (p ≤ 0.10). When compared to AMH, ASH significantly induced the expression of 35 proteins with 13 proteins showing an increasing trend. AMH downregulated only 3 proteins. ASH-induced downregulated proteins are involved in actin cytoskeleton maintenance needed for cell shape and migration which are critical for blood-brain barrier maintenance and angiogenesis. In contrast, ASH-induced upregulated proteins are RNA-binding proteins involved in RNA splicing, transport, and stability. Thus, ASH alters BMV proteomics to impair cytoskeletal integrity and RNA processing which are critical for cerebrovascular function.


Subject(s)
Hypoglycemia , Proteome , Mice , Animals , Proteome/metabolism , Blood Glucose , Tandem Mass Spectrometry/methods , Brain/metabolism
7.
Gen Dent ; 72(1): 34-42, 2024.
Article in English | MEDLINE | ID: mdl-38117639

ABSTRACT

About 6.2 million adults in the United States suffer from heart failure (HF). For patients with advanced HF refractory to medical therapy, an orthotopic heart transplant or a ventricular assist device (VAD) is the only long-term survival option. The most commonly used form of these devices is the left VAD (LVAD), implanted to support the left ventricle. As many as 2754 LVADs were implanted annually between 2006 and 2015, allowing recipients to maintain a relatively normal lifestyle, including both elective and emergency dental care in the ambulatory setting. As more LVADs are implanted, oral healthcare providers (OHCPs) are more likely to encounter these patients in an outpatient clinical setting. This study aims to educate OHCPs on the specific needs of these patients and to begin development of clinical guidelines for their dental management. A literature review using electronic resources was conducted to identify all literature relevant to the clinical topic. Appropriate literature was selected based on established inclusion and exclusion criteria, and 3 articles published between 2015 and 2020 were identified. None offered clinical practice guidelines for the care of patients with implanted LVADs. However, it is known that patients supported by an LVAD are at higher risk of thrombotic complications, which can lead to pump system failure and embolic stroke. To reduce the risk of complications, these patients are treated with anticoagulation therapy. Interruption of these drugs prior to dental treatment is not recommended. Due to the side effects of anticoagulation therapy and acquired coagulopathy, patients with an LVAD are also at increased risk of bleeding events. Thus, perioperative hemorrhagic risk during routine oral surgical procedures must be considered. While most dental care can be done in an outpatient setting, OHCPs should be aware of the special needs of these patients and provide appropriate care through close coordination with the LVAD/transplant team.


Subject(s)
Heart Failure , Heart-Assist Devices , Adult , Humans , Heart-Assist Devices/adverse effects , Heart Failure/therapy , Heart Failure/etiology , Heart Ventricles , Anticoagulants , Dental Care
8.
Neurooncol Adv ; 5(1): vdad108, 2023.
Article in English | MEDLINE | ID: mdl-37781088

ABSTRACT

Background: Hypersomnolence is a common and disruptive side effect of cranial radiotherapy and is associated with fatigue and disturbances in mood and cognition in primary brain tumor (PBT) patients. The biological underpinnings of this effect are not understood. Our laboratory has previously found that the presence of a single nucleotide polymorphism (rs934945, G-E mutation) in the PERIOD2 (PER2) clock gene was associated with a decreased likelihood of fatigue in PBT patients. Here, we aim to understand the effects of PER2 polymorphism on radiation susceptibility within a murine model of cranial-irradiation-induced hypersomnolence (C-RIH). Methods: Male and female transgenic mice were generated using CRISPR-Cas9, replacing the endogenous mouse PER2:CRY1 binding domain with its human isoform with (hE1244 KI) or without the SNP rs934945 (hG1244 KI). Activity and sleep were monitored continuously 10 days before and after cranial irradiation (whole brain, 15Gy, single fraction). Behavioral assessments measuring anxiety, depression, and working memory were used to assess mood and cognitive changes 2 months postradiation. Results: During their active phase, hE1244 knock-ins (KIs) had less radiation-induced suppression of activity relative to hG1244 KIs and female hE1244 KIs saw a reduction of hypersomnolence over 10 days. hE1244 KIs displayed less anxiety behavior and were more ambulatory within all behavioral tests. Conclusions: The PER2 rs934945 polymorphism had long-lasting behavioral effects associated with radiation toxicity, particularly in sleep in females and the activity of all animals. Our findings shed light on biological mechanisms underlying C-RIH.

9.
Prim Care Diabetes ; 17(6): 661-664, 2023 12.
Article in English | MEDLINE | ID: mdl-37827908

ABSTRACT

In the U.S., ethnic minorities with pre-diabetes, undiagnosed type 2 diabetes (T2D), and newly diagnosed T2D had a higher prevalence of microvascular complications than non-Hispanic Whites and exhibited distinct risk factors, whereas Whites had a higher rate of cardiovascular disease.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Prediabetic State , Humans , United States/epidemiology , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Risk Factors , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Prevalence , White
10.
J Clin Invest ; 133(24)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37856216

ABSTRACT

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes and reduced O2 consumption. Furthermore, the application of the GPR84 agonist 6-n-octylaminouracil (6-OAU) counteracted these effects, effectively reinstating the brown adipocyte activity. These compelling in vivo and in vitro findings converge to highlight mitochondrial dysfunction as the primary cause of BAT anomalies in GPR84-KO mice. The activation of GPR84 induced an increase in intracellular Ca2+ levels, which intricately influenced mitochondrial respiration. By modulating mitochondrial Ca2+ levels and respiration, GPR84 acts as a potent molecule involved in BAT activity. These findings suggest that GPR84 is a potential therapeutic target for invigorating BAT and ameliorating metabolic disorders.


Subject(s)
Adipocytes, Brown , Calcium , Receptors, G-Protein-Coupled , Animals , Mice , Adipocytes, Brown/metabolism , Adipose Tissue, Brown/metabolism , Calcium/metabolism , Fatty Acids/metabolism , Mice, Inbred C57BL , Signal Transduction , Thermogenesis/genetics , Receptors, G-Protein-Coupled/metabolism , Mitochondria/metabolism , Mitochondria/physiology
11.
Mol Metab ; 78: 101812, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37777009

ABSTRACT

OBJECTIVE: Sialic acid is a terminal monosaccharide of glycans in glycoproteins and glycolipids, and its derivation from glucose is regulated by the rate-limiting enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Although the glycans on key endogenous hepatic proteins governing glucose metabolism are sialylated, how sialic acid synthesis and sialylation in the liver influence glucose homeostasis is unknown. Studies were designed to fill this knowledge gap. METHODS: To decrease the production of sialic acid and sialylation in hepatocytes, a hepatocyte-specific GNE knockdown mouse model was generated, and systemic glucose metabolism, hepatic insulin signaling and glucagon signaling were evaluated in vivo or in primary hepatocytes. Peripheral insulin sensitivity was also assessed. Furthermore, the mechanisms by which sialylation in the liver influences hepatic insulin signaling and glucagon signaling and peripheral insulin sensitivity were identified. RESULTS: Liver GNE deletion in mice caused an impairment of insulin suppression of hepatic glucose production. This was due to a decrease in the sialylation of hepatic insulin receptors (IR) and a decline in IR abundance due to exaggerated degradation through the Eph receptor B4. Hepatic GNE deficiency also caused a blunting of hepatic glucagon receptor (GCGR) function which was related to a decline in its sialylation and affinity for glucagon. An accompanying upregulation of hepatic FGF21 production caused an enhancement of skeletal muscle glucose disposal that led to an overall increase in glucose tolerance and insulin sensitivity. CONCLUSION: These collective observations reveal that hepatic sialic acid synthesis and sialylation modulate glucose homeostasis in both the liver and skeletal muscle. By interrogating how hepatic sialic acid synthesis influences glucose control mechanisms in the liver, a new metabolic cycle has been identified in which a key constituent of glycans generated from glucose modulates the systemic control of its precursor.


Subject(s)
Insulin Resistance , N-Acetylneuraminic Acid , Mice , Animals , N-Acetylneuraminic Acid/metabolism , Glucagon , Muscle, Skeletal/metabolism , Liver/metabolism , Glucose , Insulin , Homeostasis , Polysaccharides
12.
Syst Rev ; 12(1): 185, 2023 09 30.
Article in English | MEDLINE | ID: mdl-37777803

ABSTRACT

BACKGROUND: In the USA, access to quality healthcare varies greatly across racial and ethnic groups, resulting in significant health disparities. A new term, "racial health equity" (RHE), is increasingly reported in the medical literature, but there is currently no consensus definition of the term. Additionally, related terms such as "health disparities," "health inequities," and "equality" have been inconsistently used when defining RHE. METHODS: The primary purpose of this scoping review is to investigate the current use and underlying concepts used to define racial health equity. The study will address two key questions: (1) "What terminology and definitions have been used to characterize RHE?" and (2) "What knowledge gaps and challenges are present in the current state of RHE research and theory?" The review will collect and analyze data from three sources: (1) websites from key national and international health organizations, (2) theoretical and narrative published articles, and (3) evidence synthesis studies addressing interventions targeting racial health equity and minority stakeholder engagement. DISCUSSION: Defining "racial health equity" and related terminology is the first step to advancing racial health equity within the USA. This review aims to offer an improved understanding of RHE constructs and definitions, bringing greater unity to national racial health equity research efforts across disciplines. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered with the Open Science Framework at https://osf.io/7pvzq .


Subject(s)
Health Equity , Humans , Ethnicity , Health Status Disparities , Minority Groups , Racial Groups , Review Literature as Topic , Systematic Reviews as Topic
13.
Nutr J ; 22(1): 38, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37528391

ABSTRACT

BACKGROUND: Currently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals. METHODS: Patients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status. RESULTS: A total of 803 patients were recruited. 84.4% were female, 67.2% African American, 26.1% received Medicaid, and 65.5% made less than $40,000. No differences in F/V intake were seen between the ILI and UC groups at months 6, 12, or 24. The ILI group reduced percent fat at months 6, 12, and 24 compared to UC. Change in F/V intake was negatively correlated with weight change at month 6 whereas change in fat intake was positively associated with weight change at months 6, 12, and 24 for the ILI group. CONCLUSIONS: The pragmatic weight loss intervention in primary care did not increase F/V intake but did reduce fat intake in an underserved population with obesity. F/V intake was negatively associated with weight loss at month 6 whereas percent fat was positively correlated with weight loss throughout the intervention. Future efforts better targeting both increasing F/V intake and reducing fat intake may promote greater weight loss in similar populations. TRIAL REGISTRATION: NCT Registration: NCT02561221.


Subject(s)
Eating , Vulnerable Populations , Humans , Female , Male , Obesity/therapy , Weight Loss , Primary Health Care
14.
Diabetes Res Clin Pract ; 203: 110856, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37499878

ABSTRACT

Using two large prospective epidemiological studies in the U.S., we examined biomarkers that reflect sex-specific pathophysiological pathways to cardiovascular complications among people with pre-diabetes. Women with pre-diabetes exhibited higher levels of adipokines, while men had lower eGFR. Sex differences in lipoproteins and vascular inflammatory markers during pre-diabetes indicate sex-specific lipoprotein and inflammatory mechanisms to cardiovascular complications.


Subject(s)
Cardiovascular Diseases , Heart Diseases , Prediabetic State , Humans , Male , Female , Prediabetic State/complications , Prospective Studies , Sex Characteristics , Sex Factors , Biomarkers , Lipoproteins , Heart Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Risk Factors
15.
J Clin Endocrinol Metab ; 108(11): e1193-e1198, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37259605

ABSTRACT

CONTEXT: Intermediate-term glycemic control metrics may represent a viable alternative to continuous glucose monitoring (CGM) in patients without access to CGM. OBJECTIVE: This work aimed to compare the relationship between CGM parameters and glycated albumin (GA), glycated hemoglobin A1c (HbA1c), and fructosamine for 24 weeks. METHODS: We conducted exploratory comparative analyses of CGM subgroup data from a previously published 24-week prospective study of assay performance in 8 US clinics. Participants included 34 individuals with type 1 (n = 18) and type 2 diabetes (n = 16) undergoing changes to improve glycemic control (n = 22; group 1) or with stable diabetes therapy (n = 12; group 2). Main outcome measures included Pearson correlations between CGM and glycemic indices and receiver operating characteristic (ROC) analysis of glycemic index values predictive of time in range (TIR) greater than 70%. RESULTS: At weeks 4 and 8, GA correlations with TIR were higher than HbA1c correlations in group 1. In group 2, GA correlations with TIR were statistically significant, whereas HbA1c correlations were not. In both groups over the first 12 weeks, GA correlations with TIR were higher than fructosamine-TIR correlations. In the ROC analysis, GA predicted a TIR greater than 70% during weeks 2 to 24 (area under the curve >0.80); HbA1c was predictive during weeks 12 to 24. Cutoff values for TIR greater than 70% were 17.5% (sensitivity and specificity, 0.88) for GA and 7.3% (0.86) for HbA1c. CONCLUSION: GA is the most accurate predictor of TIR over 8 weeks compared with other glycemic indices, which may assist in clinical evaluation of changes in treatment where CGM is not possible and it is too early to use HbA1c (NCT02489773).


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Glycated Hemoglobin , Diabetes Mellitus, Type 2/drug therapy , Fructosamine , Blood Glucose/analysis , Blood Glucose Self-Monitoring , Prospective Studies , Glycated Serum Albumin , Glycation End Products, Advanced , Serum Albumin
16.
Front Immunol ; 14: 1128582, 2023.
Article in English | MEDLINE | ID: mdl-37228592

ABSTRACT

Introduction: Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic 'non-viral' vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery. Methods: We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell. Results and Discussion: Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides.


Subject(s)
Gold , Metal Nanoparticles , RNA, Messenger , Transfection , Endocytosis
17.
Int J Mol Sci ; 24(9)2023 May 05.
Article in English | MEDLINE | ID: mdl-37175989

ABSTRACT

Paired box 4 (Pax4) is a key transcription factor involved in the embryonic development of the pancreatic islets of Langerhans. Consisting of a conserved paired box domain and a homeodomain, this transcription factor plays an essential role in early endocrine progenitor cells, where it is necessary for cell-fate commitment towards the insulin-secreting ß cell lineage. Knockout of Pax4 in animal models leads to the absence of ß cells, which is accompanied by a significant increase in glucagon-producing α cells, and typically results in lethality within days after birth. Mutations in Pax4 that cause an impaired Pax4 function are associated with diabetes pathogenesis in humans. In adulthood, Pax4 expression is limited to a distinct subset of ß cells that possess the ability to proliferate in response to heightened metabolic needs. Upregulation of Pax4 expression is known to promote ß cell survival and proliferation. Additionally, ectopic expression of Pax4 in pancreatic islet α cells or δ cells has been found to generate functional ß-like cells that can improve blood glucose regulation in experimental diabetes models. Therefore, Pax4 represents a promising therapeutic target for the protection and regeneration of ß cells in the treatment of diabetes. The purpose of this review is to provide a thorough and up-to-date overview of the role of Pax4 in pancreatic ß cells and its potential as a therapeutic target for diabetes.


Subject(s)
Diabetes Mellitus , Islets of Langerhans , Animals , Humans , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Paired Box Transcription Factors/genetics , Paired Box Transcription Factors/metabolism , Islets of Langerhans/metabolism , Cell Differentiation , Gene Expression Regulation , Diabetes Mellitus/genetics
18.
J Am Acad Child Adolesc Psychiatry ; 62(6): 696-698, 2023 06.
Article in English | MEDLINE | ID: mdl-37244653

ABSTRACT

Pediatric anxiety disorders (AD) are prevalent disorders with an impact on all aspects of a child's life and functioning.1 Although evidence supports commonly used treatments, there are notable concerns with the research to date.2 Heterogeneity in outcome selection, measurement, analysis, and reporting is a contributing factor to the hinderance of the translation of research into clinical practice.3 Recognition for outcome standardization in pediatric mental health disorders is evolving and there are several initiatives of importance, including the International Consortium for Health Outcomes Measurement (ICHOM), which has developed standardized outcome sets for use in the routine clinical mental health treatment of children and adolescents.4 Similarly, the International Alliance of Mental Health Research Funders5 advocate for use of 1 specific outcome measurement instrument (OMI) in the youth mental health research that they fund. Development of a Core Outcome Set (COS), a minimal set of outcomes that should be measured and reported in clinical trials, has been a solution in other areas of medicine to address heterogeneity in outcome selection and measurement across trials.6 The Core Outcomes and Measures in Pediatric Anxiety Clinical Trials (COMPACT) Initiative will develop a harmonized, evidence- and consensus-based COS that is meaningful to youth and families for use in future trials in pediatric AD.


Subject(s)
Anxiety Disorders , Research Design , Adolescent , Humans , Child , Delphi Technique , Endpoint Determination , Anxiety Disorders/therapy , Outcome Assessment, Health Care , Treatment Outcome
19.
J Cross Cult Gerontol ; 38(2): 115-135, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37209245

ABSTRACT

The percentage of older adult immigrants in Canada and the United States is increasing with older adult immigrants from Africa forming a small proportion of the population, but one of the fastest growing groups in the area. Depending on the circumstances leading to the move, migration can be very stressful, especially for older adults. The purpose of this scoping review is to summarize the evidence on the social connectedness of older African immigrants in Canada and the United States. The researchers searched databases including Cochrane Library, BMJ Online, CINAHL, Medline (Ovid), PsycInfo (Ovid), PsycArticles (Ovid), Web of Science, SpringerLINK, CBCA Canadian Business and Current Affairs Database, Academic Search Complete, Sage Journals Online, ABI/Inform, Emerald Fulltext, Expanded Academic ASAP, General OneFile, Joanna Briggs Institute EBP Database, Journals@Ovid, JSTOR, Oxford Journals Online, Taylor & Francis Journals, Wiley Online Library, ProQuest Dissertations and Thesis Global, and Google Scholar from 2000-2020. Four manuscripts met the search inclusion criteria of published peer-reviewed and unpublished research studies in the English language on aging, older adult, social connectedness, African immigrants, Canada, and the United States. The authors found limited studies on African older adult immigrants' social connectedness in Canada and the United States with dearth of research on the older adults' access to health care, use of smart technology and social media to promote their health and social connectedness which are gaps in the literature that should be researched in the future.


Subject(s)
Emigrants and Immigrants , Humans , United States , Aged , Canada , North America , Africa , Aging
20.
Am J Prev Med ; 65(5): 854-862, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37192710

ABSTRACT

INTRODUCTION: Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men. METHODS: Data were pooled from 18,745 cardiovascular disease-free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. The risk of coronary heart disease, ischemic stroke, and atherosclerotic cardiovascular disease (coronary heart disease or stroke) associated with prediabetes or undiagnosed T2D was estimated using Cox models adjusting for sociodemographic factors, concomitant risk factors, medication use, and menopausal status. Data were collected in 2022, and the analysis was performed in 2023. RESULTS: During a median follow-up of 18.6 years, the associations between prediabetes and risk of atherosclerotic cardiovascular disease were only significant in women (hazard ratio=1.18, 95% CI=1.01, 1.34, p=0.03) but not in men (hazard ratio=1.08, 95% CI=1.00, 1.28, p=0.06) (p-interaction=0.18). The associations between undiagnosed T2D and cardiovascular disease outcomes were significant in both sexes, but the effect was more pronounced in women (coronary heart disease: hazard ratio=1.83, 95% CI=1.4, 2.41, p<0.0001 in women vs hazard ratio=1.6, 95% CI=1.38, 2.07, p=0.007 in men; stroke: hazard ratio=1.99, 95% CI=1.39, 2.72, p<0.0001 vs hazard ratio=1.81, 95% CI=1.36, 2.6, p<0.0001; atherosclerotic cardiovascular disease: hazard ratio=1.86, 95% CI=1.5, 2.28, p<0.0001 vs hazard ratio=1.65, 95% CI=1.4, 1.98, p<0.0001) (all p-interactions≤0.2). Both White and Black patients exhibit similar sex differences. CONCLUSIONS: Prediabetes or undiagnosed T2D was associated with a greater excess risk of cardiovascular disease in women than in men. The sex differential in cardiovascular disease risk among those without the T2D diagnosis suggests the need for sex-specific guidelines in T2D screening and treatment.

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