T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.

T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.

Impairment of health-related quality of life among people with type 2 diabetes and advanced liver fibrosis.

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (ß: - 0.247; 95% CI - 0.419, - 0.077) and AF (ß: - 0.222; 95% CI - 0.383, - 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM.

An in-depth review of the dermal toxicity of T-2 toxin: Clinical symptoms, injury mechanisms, and treatment approach.

T-2 toxin, a notable mycotoxin derived from the Fusarium genus, possesses significant heat and ultraviolet radiation resilience, making its elimination from food or feed sources a challenging task. T-2 toxin can be rapidly absorbed from inhalation dust particles, ingest food and skin contact. T-2 toxin has skin toxicity, which can cause varying degrees of structural and functional damage to the skin tissue depending on the type of animal, age, and dose of toxin. Skin contact is not a prerequisite for T-2 toxin to exert skin toxicity, T-2 toxin can also cause skin damage when ingested through the digestive tract. The core dermal toxic molecular mechanism of T-2 toxin is oxidative damage and inflammatory reaction. Some physical methods and chemical methods were used to remove T-2 toxin from the surface of the skin, to have a certain mitigating effect on dermal toxicity caused by T-2 toxin. Grasping T-2 toxin's skin toxicity mechanism is vital for creating effective prevention and treatments. This paper summarizes the comprehensive date from in vitro and in vivo studies, highlighting the molecular mechanism of skin damage by T-2 toxin and current treatment strategies, to provide reference for further research on the skin toxicity of T-2 toxin.

Impact of COVID-19 on Type 2 Diabetes Mellitus Diagnosis and Management in the US.

The COVID-19 pandemic has negatively affected individuals with chronic conditions, such as type 2 diabetes mellitus (T2DM). The full extent of the impact however remains unknown, mainly due to the limited research availability. This study examines the pandemic's impact on T2DM diagnosis and management in the United States. The methods include a literature review and an online survey of American healthcare professionals regarding their experiences of T2DM during the pandemic. Findings indicated significant reductions in healthcare utilisation among T2DM patients and a decline in the quality of care for this population. These reductions may have been attributed to fewer HbA1C tests being performed and emergency department visits, with a high proportion of individuals experiencing uncontrolled diabetes and receiving treatment intensification, especially among racial/ethnic minority groups, rural populations, and those with comorbidities. Effective strategies are needed to support T2DM regular follow-up and self-management, tailored to patient needs and culturally appropriated. Technologies like telemedicine can help address these needs, potentially reducing healthcare costs and improving clinical outcomes and quality of life for people with T2DM.

A Temporospatial Analysis of Activity Patterns for Fall Risk Assessment in Older Adults with Comorbid Type 2 Diabetes.

This study explores how daily activities, including duration and location within the home, affect fall risk in older adults with type 2 diabetes. Body-worn cameras on 26 participants provided data on activity (e.g. exercise), time and location (kitchen, living room). Demographics and health factors were considered to understand their influence. By visualising activity patterns, this study aimed to identify behaviours linked to falls to inform personalised fall prevention strategies and digital technologies for independent living.

Characterizing Protein Concentration in Cerebrospinal Fluid with T2 Component Analysis.

PURPOSE: T2 values are hypothesized to be reduced where protein accumulates in the cerebrospinal fluid (CSF). We aimed to verify the accuracy of Carr-Purcell-Meiboom-Gil (CPMG) pulses and non-negative least squares (NNLS) analysis in visualizing protein concentrations by mapping the T2 values. METHODS: We first dissolved 1.2g of bovine serum albumin powder in 4 mL of artificial CSF to purify an albumin solution with a concentration of 4.5 mM. Artificial CSF was added thereto, and eight types of albumin solutions, with concentrations of 0.002-4.5 mM, were purified. We acquired this albumin solution with CPMG pulses and NNLS, decomposed the T2 values per pixel, and derived 25 T2 component values of 60-2000 ms. We assessed the change of T2 values by the difference in albumin concentration of a single voxel. Finally, we used the method to assess T2 values from two patients, one with a subdural hematoma and one with a suprasellar cystic tumor. T2 component values were plotted graphically, presented individually, and created in color maps. RESULTS: T2 component values for albumin concentrations ranging from 0.056 to 4.55 mM showed different T2 peaks, whereas, for concentrations 0.002 to 0.019 mM, the peaks were similar heights and overlapped. Peak width was similar for all concentrations. The color maps successfully reflected the changes in T2 values across both RGB color patterns. T2 components for albumin samples with 2.5 mM and 6.1 mM concentrations within a single voxel were represented separately and reflected the ratio of the two samples in nine different regions of interest within one slice. In the clinical cases, the T2 component map imaged differences in albumin concentrations, similar to those observed in the albumin samples. CONCLUSION: The present method with CPMG sequences and NNLS provide adequate images to differentiate accumulating protein concentrations in the CSF, even at the level of a single pixel.

Initiation of Insulin Degludec in Chinese Hospitalized Patients with Type 2 Diabetes - A Single Center's Experience.

Introduction: The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM. Methods: We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles. Results: The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings. Conclusion: The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation.

Performance of MR learned pulse sequences for 3D bi-exponential, stretched-exponential, and mono-exponential T2 and T1ρ mapping of knee cartilage.

PURPOSE: To compare the performance of a learned magnetization-prepared gradient echo (L-MPGRE) sequence against a commonly used sequence for 3D T2 and T1ρ mapping of the knee joint, the magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS), on bi-exponential (BE), stretched-exponential (SE), and mono-exponential (ME) relaxation models. METHODS: We used a combined differentiable and non-differentiable optimization to learn pulse sequence structure and its parameters for 3D T2 and T1ρ mapping of the knee joint using ME, SE, and BE models. The learned pulse sequence framework was used to improve quantitative accuracy and SNR and to reduce filtering effects. We compare the measured multi-compartment values between the two sequences (n = 8), and their repeatability (n = 4) in healthy volunteers (n = 12 total). RESULTS: The voxel-wise median absolute percentage difference (MAPD) between the T2 and T1ρ maps obtained with each sequence was 18.6% and 19.9%, respectively. The T2 and T1ρ repeatability tests showed a MAPD of 18.5% and 19.1% for MAPSS, and 16.8% and 15.5% for L-MPGRE. Bland-Altman region of interest (ROI)-wise analysis shows that bias is small, close to -1.5%, and the coefficient of variation is around 5.5% when comparing ROIs from both sequences. CONCLUSION: The L-MPGRE sequences can be used as a replacement for MAPSS for T2 and T1ρ mapping in the knee cartilage with advantages, achieving similar accuracy and 15% better repeatability in only half of its scan time.

CMR native T1 and T2 Mapping in Olympic athletes: the influence of sport discipline and sex.

BACKGROUND: Cardiac Magnetic Resonance (CMR) has a growing role in evaluating athletes' hearts. Mapping techniques provide added value for tissue characterisation, but data on athletes and sports disciplines are lacking. AIM: To describe native mapping values in a cohort of Olympic Athletes and evaluate the influence of sports discipline and sex. METHODS: A group of 300 Olympic athletes (13% skill, 20% power, 25% mixed, 42% endurance, 58% male) with unremarkable cardiovascular screening and a control group of 42 sedentary subjects (52% male) underwent CMR without contrast administration. Athletes were divided based on sex and sports categories according to the ESC classification. RESULTS: Among athletes of different sports categories and controls, endurance presented the lowest value of T1 mapping (p<0.001). No differences in T2 mapping were observed (p=0.472). Female athletes had higher values of T1 native myocardial mapping compared to males (p=0.001), while there were no differences in T2 mapping (p=0.817). Male athletes with higher left ventricular mass indexed (LV-Massi) had lower values of T1 mapping (p=0.006) and slightly higher values of T2 mapping, even if not significant (p=0.150). Female athletes with higher LV-Massi did not show significant differences in T1 and T2 mapping (p=0.053 and p=0.438). CONCLUSIONS: T1 native myocardial mapping showed significant differences related to sports disciplines and gender. Athletes with the largest LV remodelling, mostly endurance and mixed, showed the lowest values of T1 mapping. Male athletes showed lower values of T1 mapping than females. No significant differences were observed in T2 mapping related to sports disciplines and gender.

Unraveling Quercetin's Potential: A Comprehensive Review of Its Properties and Mechanisms of Action, in Diabetes and Obesity Complications.

The prevalence of diabetes is escalating alarmingly, placing a significant economic burden on the global healthcare system. The use of chemical substances extracted from plants has been demonstrated to be an effective method for the treatment and control of insulin resistance and Type 2 diabetes mellitus (T2DM). New research indicates that natural phytochemicals present in fruits and vegetables are expected to become drugs for the treatment of diabetes and the prevention of related complications. Quercetin, a widely distributed flavonoid, is well-known for its antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. This article provides a comprehensive account of the mechanism of action of quercetin on diabetes and obesity complications in vivo and in vitro. It elucidates the impact of quercetin on various cells. These include hepatocytes, renal cells, skeletal muscle cells, and adipocytes. Furthermore, this article discusses the mechanism of quercetin on organ damage in diabetic mice induced by STZ, alloxan, diet, and spontaneous Type 2 diabetic mice caused by genetic defects. Additionally, it addresses the pharmacokinetics of quercetin and its potential for synergistic effects with existing diabetic drugs.

Use of Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitor is Associated with reduced Emergency Room Visits and Hospitalization in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Diabetes Mellitus.

BACKGROUND: The Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are a class of anti-diabetic medications that confer cardio-renal-metabolic (CRM) benefits. Emerging evidence also suggests that these agents provide better benefits for chronic pulmonary conditions, especially chronic obstructive pulmonary disease (COPD). RESEARCH QUESTION: We aimed to assess the association between SGLT2i use and outcomes in patients with COPD and concomitant Type 2 Diabetes Mellitus (T2DM). STUDY DESIGN AND METHODS: We conducted a retrospective cohort study on adults with T2DM and COPD in a primary care clinic from 01/01/2019 to 01/01//2023. Patients were categorized into two groups based on SGLT2i use. We collected demographic information and outcomes such as emergency room (ER) visits, hospitalizations secondary to COPD exacerbation over the period of four years and time to hospitalization and ER visits. Chi-square analysis was used for categorical variables, whereas an unpaired t-test was used for continuous variables. Cox regression was performed to identify significant prognostic factors of hospitalization and ER visits. The first univariate analysis was performed and those variables that were statistically significant (p<0.1) were then subjected to a multivariate analysis. A Kaplan-Meir analysis was used to visualize the probability of non-hospitalization and the probability of not visiting the ER. Statistical significance was set at p-value < 0.05. RESULTS: Of the 220 patients screened, 94 met the inclusion criteria, of which 20 patients (21.3%) had SGLT2i use at admission, and 74 (78.7%) did not. Baseline demographic information were well-matched between the two groups. SGLT2i use was associated with a significant reduction in ER visits (70% vs. 97.3%, p-0.001) and the number of hospitalizations (55% vs 87.8%, p-0.001). Further multivariate analysis showed lower hazards of hospitalization (adjusted HR-0.156; CI:0.073 to 0.331) and ER visits ( HR)-0.232; CI:0.118 to 0.453) in patients on SGLT2i. INTERPRETATION: In patients with T2DM with COPD, SGLT2i use was associated with reduced ER visits and hospitalizations related to COPD. This protective effect of SGLT2i could be explained by reduced systemic proinflammatory markers and increased anti-inflammatory markers via inhibition of Node like receptor protein 3(NLRP3) inflammasome activation in multiple tissues, including the lungs.

T2-FLAIR imaging-based radiomic features for predicting early postoperative recurrence of grade II gliomas.

Aim: To develop and validate a T2-weighted-fluid attenuated inversion recovery (T2-FLAIR) images-based radiomics model for predicting early postoperative recurrence (within 1 year) in patients with low-grade gliomas (LGGs).Methods: A retrospective analysis was performed by collecting clinical, pathological and magnetic resonance imaging (MRI) data from patients with LGG between 2017 and 2022. Regions of interest were delineated and radiomic features were extracted from T2-FLAIR images using 3D-Slicer software. To minimize redundant features, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was used. Patients were categorized into two groups based on recurrence status: the recurrence group (RG) and the non-recurrence group (NRG). Radiomic features were used to develop models using three machine learning approaches: logistic regression (LR), random forest (RF) and support vector machine (SVM). The performance of the radiomic features was validated using fivefold cross-validation.Results: After rigorous screening, 105 patients met the inclusion criteria, and five radiomic features were identified. After 5-folds cross-validation, the average areas under the curves for LR, RF and SVM were 0.813, 0.741 and 0.772, respectively.Conclusion: T2-FLAIR-based radiomic features effectively predicted early recurrence in postoperative LGGs.

[Box: see text].

Telomerase reverse transcriptase protects against diabetic kidney disease by promoting AMPK/PGC-1a-regulated mitochondrial energy homeostasis.

Disordered glucose and lipid metabolism, coupled with disturbed mitochondrial bioenergetics, are pivotal in the initiation and development of diabetic kidney disease (DKD). While the essential role of telomerase reverse transcriptase (TERT) in regulating mitochondrial function in the cardiovascular system has been recognized, its specific function in maintaining mitochondrial homeostasis in DKD remains unclear. This study aimed to explore how TERT regulates mitochondrial function and the underlying mechanisms. In vitro, human renal proximal tubular HK-2 cells exposed to high glucose/high fat (HG/HF) presented significant downregulation of TERT and AMPK dephosphorylation. This led to decreased ATP production, altered NAD+/NADH ratios, reduced mitochondrial complex activities, increased mitochondrial dysfunction, lipid accumulation, and reactive oxygen species (ROS) production. Knockdown of TERT (si-TERT) further exacerbated mitochondrial dysfunction, decreased mitochondrial membrane potential, and lowered levels of cellular oxidative phosphorylation and glycolysis, as determined via a Seahorse X24 flux analyzer. Conversely, mitochondrial dysfunction was significantly alleviated after pcDNA-TERT plasmid transfection and adeno-associated virus (AAV) 9-TERT gene therapy in vivo. Notably, treatment with an AMPK inhibitor, activator, and si-PGC-1a (peroxisome proliferator-activated receptor γ coactivator-1α), resulted in mitochondrial dysfunction and decreased expression of genes related to energy metabolism and mitochondrial biogenesis. Our findings reveal that TERT protects mitochondrial function and homeostasis by partially activating the AMPK/PGC-1a signaling pathway. These results establish a crucial foundation for understanding TERT's critical role inmitochondrial regulation and its protective effect on DKD.

Investigating Interleukin-6 Levels in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN), a severe complication affecting 40% of diabetic individuals, is a leading cause of chronic kidney disease (CKD). It involves a progressive increase in urinary albumin and a decline in the glomerular filtration rate. Early detection and intervention are crucial to preventing CKD progression. The current marker, albuminuria, measured as the urine albumin-to-creatinine ratio (UACR), has limitations, highlighting the need for alternative biomarkers. Researchers have linked the proinflammatory cytokine interleukin-6 (IL-6) to the progression of DN, observing elevated levels in DN patients compared to those without DN. IL-6 also regulates glucose metabolism, promoting insulin effectiveness and secretion. Inflammation and glucose control are two things that IL-6 does. This makes it a promising biomarker and therapeutic target for DN and type 2 diabetes mellitus (T2DM). This study focuses on IL-6 levels in T2DM patients with and without DN. METHODS AND MATERIALS: From September 2022 to June 2024, the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, conducted an observational cross-sectional comparative study on 80 T2DM patients, with 40 in group A (cases = T2DM patients with DN) and 40 in group B (controls = T2DM patients without DN). The study included patients with T2DM between the ages of 40 and 80. The study excludes conditions such as diabetic ketoacidosis, patients with end-stage renal disease, and conditions that increase IL-6, such as COVID-19. The study excluded autoimmune conditions with elevated IL-6, such as rheumatoid arthritis, systemic lupus erythematous, ankylosing spondylitis, psoriasis, and Crohn's disease. We obtained ethical approval and written consent from participants. RESULTS: In the current study, 61 patients (76.2%) were 60 years old or younger, while 19 patients (23.8%) were older than 60 years. Among the participants, 38 were females (47.5%) and 42 were males (52.5%). The case group, which consisted of 40 T2DM patients with DN, had a mean glycated hemoglobin (HbA1c) of 7.1700 ± 0.71044. In contrast, the control group, comprising 40 T2DM patients without DN, had a mean HbA1c of 6.8650 ± 0.57179. This difference was statistically significant, with a p value of 0.038. Additionally, the mean UACR in the case group was 134.34 ± 95.56, significantly higher than the control group's mean UACR of 22.32 ± 9.90. This difference was highly significant, with a p value of 0.001. Furthermore, the case group exhibited elevated mean IL-6 levels of 15.48 ± 4.27 compared to the control group's 7.02 ± 2.46, which is also highly significant, reflected by a p value of 0.001. CONCLUSION: As the concentration of IL-6 rises in diabetic patients with nephropathy, this study suggests that IL-6 may have an effect on the development of DN. This cytokine is necessary for both the initiation and progression of the condition. Using IL-6 as a supportive diagnostic test could help rule out other potential causes of DN in T2DM. Moreover, this marker does not require invasive procedures, and early measurement may help reduce mortality and morbidity.

Preoperative Simulation of Intraoperative Findings in Surgical Clipping of Posterior Communicating Artery Aneurysms Using T2-Weighted 3D Images.

BACKGROUND: Tentorium resection and detachment from the oculomotor nerve are sometimes required for surgical clipping of unruptured posterior communicating artery (PCoA) aneurysms. Using T2-weighted 3D images, we aimed to identify the preoperative radiological features required to determine the necessity of these additional procedures. METHODS: We reviewed 30 patients with unruptured PCoA aneurysms who underwent surgical clipping and preoperative simulation using T2-weighted 3D images for measurement of the distance between the tentorium and aneurysm. Aneurysms were classified into superior type (superior to the tentorium) and inferior type (inferior to the tentorium). RESULTS: Seven patients (23%) underwent tentorium resection; all had the inferior type (superior vs. inferior, 0% vs. 33%, p = 0.071). In the 21 patients with the inferior type, the distance from the tentorium to the aneurysmal neck was 2.2 ± 1.1 mm and 0.0 ± 0.5 mm without and with tentorium resection (p < 0.01), respectively. An optimal cutoff value of ≤ +0.84 mm was identified for tentorium resection (area under the curve (AUC) = 0.96). Furthermore, 17 patients (57%) showed tight aneurysm attachment to the oculomotor nerve; all had the inferior type (0% vs. 81%, p < 0.01). The distance from the aneurysm tip to the tentorium was 1.1 ± 1.2 mm and -1.7 ± 1.4 mm without and with attachment (p < 0.01). The optimal cutoff value was ≤ +0.45 mm (AUC = 0.92). CONCLUSIONS: Measurement of the distance between the tentorium and aneurysmal neck or tip with T2-weighted 3D images is effective for preoperative simulation for surgical clipping of PCoA aneurysms.

Cardiac remodeling and inflammation detected by magnetic resonance imaging in COVID-19 survivors.

Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19. Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity. Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced. Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high.

Unraveling the potential effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on the Protein structure and function of the human SLC30A8 gene on type 2 diabetes and colorectal cancer: An In silico approach.

Background and aims: The single nucleotide polymorphisms (SNPs) in SLC30A8 gene have been recognized as contributing to type 2 diabetes (T2D) susceptibility and colorectal cancer. This study aims to predict the structural stability, and functional impacts on variations in non-synonymous SNPs (nsSNPs) in the human SLC30A8 gene using various computational techniques. Materials and methods: Several in silico tools, including SIFT, Predict-SNP, SNPs&GO, MAPP, SNAP2, PhD-SNP, PANTHER, PolyPhen-1,PolyPhen-2, I-Mutant 2.0, and MUpro, have been used in our study. Results: After data analysis, out of 336 missenses, the eight nsSNPs, namely R138Q, I141N, W136G, I349N, L303R, E140A, W306C, and L308Q, were discovered by ConSurf to be in highly conserved regions, which could affect the stability of their proteins. Project HOPE determines any significant molecular effects on the structure and function of eight mutated proteins and the three-dimensional (3D) structures of these proteins. The two pharmacologically significant compounds, Luzonoid B and Roseoside demonstrate strong binding affinity to the mutant proteins, and they are more efficient in inhibiting them than the typical SLC30A8 protein using Autodock Vina and Chimera. Increased binding affinity to mutant SLC30A8 proteins has been determined not to influence drug resistance. Ultimately, the Kaplan-Meier plotter study revealed that alterations in SLC30A8 gene expression notably affect the survival rates of patients with various cancer types. Conclusion: Finally, the study found eight highly deleterious missense nsSNPs in the SLC30A8 gene that can be helpful for further proteomic and genomic studies for T2D and colorectal cancer diagnosis. These findings also pave the way for personalized treatments using biomarkers and more effective healthcare strategies.

The effects of dipeptidyl peptidase-4 inhibitors on cardiac structure and function using cardiac magnetic resonance: a meta-analysis of clinical studies.

Objective: The aim of the study was to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP4i) on cardiac structure and function by cardiac magnetic resonance (CMR). Research Methods & Procedures: Database including PubMed, Cochrane library, Embase and SinoMed for clinical studies of DPP4i on cardiac structure and function by CMR were searched. Two authors extracted the data and evaluated study quality independently. Mean difference (MD) or standardized MD and 95% confidence intervals (CI) were used for continuous variables. Review Manager 5.3 was used to performed the analysis. Results: Ten references (nine studies) were included in this meta-analysis. Most of the studies were assessed as well quality by the assessment of methodological quality. For clinical control studies, the merged MD values of △LVEF by fixed-effect model and the pooled effect size in favor of DPP4i was 1.55 (95% CI 0.35 to 2.74, P=0.01). Compared with positive control drugs, DPP4i can significantly improve the LVEF (MD=4.69, 95%CI=2.70 to 6.69), but no such change compared to placebo (MD=-0.20, 95%CI=-1.69 to 1.29). For single-arm studies and partial clinical control studies that reported LVEF values before and after DPP4i treatment, random-effect model was used to combine effect size due to a large heterogeneity (Chi2 = 11.26, P=0.02, I2 = 64%), and the pooled effect size in favor of DPP4i was 2.31 (95% CI 0.01 to 4.62, P=0.05). DPP4i significantly increased the Peak filling rate (PFR) without heterogeneity when the effect sizes of two single-arm studies were combined (MD=31.98, 95% CI 13.69 to 50.27, P=0.0006; heterogeneity test: Chi2 = 0.56, P=0.46, I2 = 0%). Conclusions: In summary, a possible benefit of DPP4i in cardiac function (as measured by CMR) was found, both including ventricular systolic function and diastolic function.

Schizophrenia and type 2 diabetes risk: a systematic review and meta-analysis.

Objectives: The metabolic syndrome in patients with schizophrenia has consistently been a challenge for clinicians. Previous studies indicate that individuals with schizophrenia are highly prone to developing type 2 diabetes mellitus (T2DM). In recent years, a continuous stream of new observational studies has been reported, emphasizing the pressing need for clinicians to gain a more precise understanding of the association between schizophrenia and T2DM. The objective of this meta-analysis is to integrate new observational studies and further explore the potential link between schizophrenia and the risk of T2DM. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, and Web of Science using medical subject headings (MeSH) and relevant keywords. The risk of bias in cohort studies and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies were evaluated using the Agency for Healthcare Research and Quality scale (AHRQ), scoring was based on the content of the original studies. A fixed-effects model was employed if P > 0.1 and I2 ≤ 50%, indicating low heterogeneity. Conversely, a random-effects model was utilized if I2 > 50%, indicating substantial heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Statistical analyses were carried out using Stata statistical software version 14.0. Results: This meta-analysis comprised 32 observational studies, involving a total of 2,007,168 patients with schizophrenia and 35,883,980 without schizophrenia, published from 2004 to 2023. The pooled analysis revealed a significant association between a history of schizophrenia and an increased risk of T2DM (Odds Ratio [OR] = 2.15; 95% Confidence Interval [CI]: 1.83-2.52; I2 = 98.9%, P < 0.001). Stratified by gender, females with schizophrenia (OR = 2.12; 95% CI: 1.70-2.64; I2 = 90.7%, P < 0.001) had a significantly higher risk of T2DM than males (OR = 1.68; 95% CI: 1.39-2.04; I2 = 91.3%, P < 0.001). Regarding WHO regions, EURO (OR = 2.73; 95% CI: 2.23-3.35; I2 = 97.5%, P < 0.001) exhibited a significantly higher risk of T2DM compared to WPRO (OR = 1.72; 95% CI: 1.32-2.23; I2 = 95.2%, P < 0.001) and AMRO (OR = 1.82; 95% CI: 1.40-2.37; I2 = 99.1%, P < 0.001). In terms of follow-up years, the >20 years subgroup (OR = 3.17; 95% CI: 1.24-8.11; I2 = 99.4%, P < 0.001) showed a significantly higher risk of T2DM than the 10-20 years group (OR = 2.26; 95% CI: 1.76-2.90; I2 = 98.6%, P < 0.001) and <10 years group (OR = 1.68; 95% CI: 1.30-2.19; I2 = 95.4%, P < 0.001). Conclusions: This meta-analysis indicates a strong association between schizophrenia and an elevated risk of developing diabetes, suggesting that schizophrenia may function as an independent risk factor for T2DM. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023465826.

Fetal body organ T2* relaxometry at low field strength (FOREST).

Fetal Magnetic Resonance Imaging (MRI) at low field strengths is an exciting new field in both clinical and research settings. Clinical low field (0.55T) scanners are beneficial for fetal imaging due to their reduced susceptibility-induced artifacts, increased T2* values, and wider bore (widening access for the increasingly obese pregnant population). However, the lack of standard automated image processing tools such as segmentation and reconstruction hampers wider clinical use. In this study, we present the Fetal body Organ T2* RElaxometry at low field STrength (FOREST) pipeline that analyzes ten major fetal body organs. Dynamic multi-echo multi-gradient sequences were acquired and automatically reoriented to a standard plane, reconstructed into a high-resolution volume using deformable slice-to-volume reconstruction, and then automatically segmented into ten major fetal organs. We extensively validated FOREST using an inter-rater quality analysis. We then present fetal T2* body organ growth curves made from 100 control subjects from a wide gestational age range (17-40 gestational weeks) in order to investigate the relationship of T2* with gestational age. The T2* values for all organs except the stomach and spleen were found to have a relationship with gestational age (p<0.05). FOREST is robust to fetal motion, and can be used for both normal and fetuses with pathologies. Low field fetal MRI can be used to perform advanced MRI analysis, and is a viable option for clinical scanning.