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PurposeTo develop models for progression of nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and determine if incorporating updated information improves model performance.DesignRetrospective cohort study.ParticipantsElectronic health record (EHR) data from a tertiary academic center, University of California San Francisco (UCSF), and a safety-net hospital, Zuckerberg San Francisco General (ZSFG) Hospital were used to identify patients with a diagnosis of NPDR, age ≥ 18 years, a diagnosis of type 1 or 2 diabetes mellitus, ≥ 6 months of ophthalmology follow-up, and no prior diagnosis of PDR before the index date (date of first NPDR diagnosis in the EHR).MethodsFour survival models were developed: Cox proportional hazards, Cox with backward selection, Cox with LASSO regression and Random Survival Forest. For each model, three variable sets were compared to determine the impact of including updated clinical information: Static0 (data up to the index date), Static6m (data updated 6 months after the index date), and Dynamic (data in Static0 plus data change during the 6-month period). The UCSF data were split into 80% training and 20% testing (internal validation). The ZSFG data were used for external validation. Model performance was evaluated by the Harrell's concordance index (C-Index).Main outcome measuresTime to PDR.ResultsThe UCSF cohort included 1130 patients and 92 (8.1%) patients progressed to PDR. The ZSFG cohort included 687 patients and 30 (4.4%) patients progressed to PDR. All models performed similarly (C-indices ∼ 0.70) in internal validation. The random survival forest with Static6m set performed best in external validation (C-index 0.76). Insurance and age were selected or ranked as highly important by all models. Other key predictors were NPDR severity, diabetic neuropathy, number of strokes, mean Hemoglobin A1c, and number of hospital admissions.ConclusionsOur models for progression of NPDR to PDR achieved acceptable predictive performance and validated well in an external setting. Updating the baseline variables with new clinical information did not consistently improve the predictive performance.Financial disclosuresProprietary or commercial disclosure may be found after the references.

【Objective】Deformable Mirror(DM) is a key device in adaptive optics system for wavefront correction, and its performance directly determines the wavefront correction capability of the system. By studying DM and their control algorithm, the wavefront correction capability of adaptive optics system can be continuously improved. On one hand, the accuracy and response speed of DM can be enhanced to better correct various complex wavefront distortions. On the other hand, the control algorithm can be improved to increase the efficiency and accuracy of the correction. These studies will directly affect the imaging quality and performance of adaptive optics system. Therefore, investigating the DM and their control algorithm is of great significance for improving the wavefront correction capability, expanding application fields, and enhancing imaging quality and performance of adaptive optics system.【Methods】The article aims to summarize the research progress on DM and their control algorithm both domestically and internationally, as well as analyze the correction accuracy of different control algorithm for wavefront distortion, establishing the groundwork for the advancement of adaptive optics. Firstly, several typical DMs are used as examples to model the DM and provide detailed introductions to the structures and working principles of separate actuator DM, splicer DM, thin film DM, dual piezoelectric DM, Micro Electromechanical System (MEMS) DM and voice coil DM. Then, several control algorithms such as the Prandtl-Ishlinskii (PI) hysteresis model-based control algorithm, decoupled control algorithm, and sparse sampling control algorithm are analyzed.【Results】Summarized the work done by Xi'an Technological University in this field, and finally pointed out the future technological breakthroughs and improvement directions in this field.【Conclusion】The research progress on DM and their control algorithm lays the foundation for the development of adaptive optics, enabling its application in more fields and further improving the performance of adaptive optics system. This will help improve imaging quality and drive the development of adaptive optics technology.

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle—a well-balanced diet and physical activity. There is also a group of compounds—including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others—that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy and safety of tofacitinib in treatment-refractory inflammatory myositis in a real-world clinical setting. Methods All patients with refractory inflammatory myositis treated with tofacitinib from a single urban centre in Vancouver, British Columbia, Canada, were included from June 2016 to December 2022. The medical records of these patients were retrospectively reviewed. Results A total of 41 patients were included, 23 with classic DM, 12 with amyopathic DM (ADM) and six with PM phenotype. The patients failed an average of four to five non-steroidal immunosuppressants before initiation of tofacitinib. In the classic DM and ADM group, tofacitinib offered clinically and statistically significant cutaneous improvement. In all myositis patients including the PM phenotype, no meaningful muscle strength response to tofacitinib was observed. 53.7% of the patients discontinued tofacitinib due to lack of benefit or death. Of the 19 patients who remained on tofacitinib at the conclusion of this study, tofacitinib demonstrated clinically and statistically significant improvement in cutaneous disease activity. Conclusion Tofacitinib appears to be highly effective in targeting cutaneous manifestations in classic DM and ADM; however, minimal benefit in muscle strength in the DM or PM phenotype were observed. [ABSTRACT FROM AUTHOR]

Objectives Clinical observations in patients with dermatomyositis (DM) and autoantibodies against the melanoma differentiation–associated protein 5 (MDA5) suggest that the autoantibodies contribute to the pathogenesis of MDA5(+) DM. To gain insight into the role of the anti-MDA5 autoantibodies, we aimed to identify their binding sites on the different domains of the MDA5 protein. Methods We developed an in-house ELISA to assess the reactivity against the MDA5 domains (conformational epitopes) in plasma (n  = 8) and serum (n  = 24) samples from MDA5(+) patients with varying clinical manifestations and disease outcomes. The reactivities were also assessed using western blot (linearized epitopes). An ELISA-based depletion assay was developed to assess cross-reactivity among the different MDA5 domains. Results All eight plasma samples consistently showed reactivity towards conformational and linearized epitopes on the helicase domains of the MDA5 protein. The ELISA-based depletion assay suggests that anti-MDA5 autoantibodies specifically target each of the three helicase domains. Twenty-two of the 24 serum samples showed reactivity in the in-house ELISA and all 22 displayed reactivity towards the helicase domains of the MDA5 protein. Conclusions Our data revealed that the main immunogenic targets of anti-MDA5 autoantibodies from MDA5(+) patients are the helicase domains. Considering that the helicase domains are responsible for the enzymatic activity and subsequent triggering of an inflammatory response, our findings suggest that binding of anti-MDA5 autoantibodies could alter the canonical activity of the MDA5 protein and potentially affect the downstream induction of a pro-inflammatory cascade. [ABSTRACT FROM AUTHOR]

Objective Autoantibodies against MDA5 (melanoma differentiation-associated protein 5) serve as a biomarker for DM (dermatomyositis) and indicate a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus infection and activating signalling pathways against it. However, little is known about the antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody–antigen epitope. Methods Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study. Results We demonstrated that DM patient autoantibodies recognize MDA5 epitopes in a native conformation–dependent manner. Furthermore, we identified the central helicase domain （3Hel） formed by Hel1, Hel2i, Hel2, and pincer as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay. Conclusion Our study uncovered the nature of the antigen epitopes on MDA5 and can provide guidance for diagnosis and a targeted therapeutic approach development. [ABSTRACT FROM AUTHOR]

Purpose: A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. Materials and Methods: We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. Results: IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. Conclusion: Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET− groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12–0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14–0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0–2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting. [ABSTRACT FROM AUTHOR]

The concept of interval-valued picture fuzzy sets (IVPFSs) is the most generalized form of fuzzy sets (FSs) and is proven a useful tool to manipulate complications that arise due to incomplete information more effectively. One of the most powerful feature of IVPFSs is that it allocates the membership, non membership and neutral membership values as intervals to any element of the given data. Due to this, IVPFSs play a key role to deal uncertain data with multiple attributes. In this study, we introduce the notion of interval-valued picture fuzzy hypergraphs (IVPFHGs) which is the combination of both IVPFSs and hypergraphs and provide its application in decision making. We describe several types of IVPFHGs such as partial, simple, support, support simple, elementary IVPFHGs etc. We also initiate the concepts of dual of IVPFHGs. Moreover, ([ ι , κ ] , [ λ , ϵ ] , [ ρ , ν ]) -level cuts of IVPFHGs are also addressed. We present a comparative analysis of our newly established terms with those existing in the literature and elaborate the superiority of IVPFHGs over the other existing fuzzy hypergraphs structures. Finally, we provide an application of IVPFHGs with algorithm and flowchart towards decision making. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Umbilical cord‐derived mesenchymal stem cells (UCMSCs) could alleviate diabetes‐induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs‐derived exosomal circHIPK3 (exo‐circHIPK3) in diabetes mellitus (DM). Methods HFF‐1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs‐derived exo‐circHIPK3 or miR‐20b‐5p mimics or Unc‐51‐like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR‐20b‐5p and circHIPK3, and between miR‐20b‐5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. Results Up‐regulation of circHIPK3 was found in UCMSCs‐derived exosomes. Exo‐circHIPK3 decreased the miR‐20b‐5p level while increasing the contents of ULK1 and autophagy‐related gene 13 (Atg13) in HG‐induced fibroblasts. In addition, exo‐circHIPK3 activated HG‐induced fibroblast autophagy and proliferation. Overexpressed miR‐20b‐5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo‐circHIPK3 enhanced autophagy and cell viability in HG‐induced fibroblasts through the miR‐20b‐5p/ULK1/Atg13 axis. Conclusion UCMSCs‐derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR‐20b‐5p/ULK1/Atg13 axis.

Objectives To utilize whole-body CT imaging and calcium scoring techniques as tools for calcinosis assessment in a prospective cohort of patients with adult and juvenile dermatomyositis (DM and JDM, respectively). Methods Thirty-one patients (14 DM and 17 JDM) who fulfilled Bohan and Peter Classification criteria as probable or definite DM, the EULAR-ACR criteria for definite DM, and with calcinosis identified by physical examination or prior imaging studies were included. Non-contrast whole-body CT scans were obtained using low-dose radiation procedures. Scans were read qualitatively and quantitated. We calculated the sensitivity and specificity of calcinosis detection of physician physical exam against CT. We quantified calcinosis burden using the Agatston scoring technique. Results We identified five distinct calcinosis patterns: Clustered, Disjoint, Interfascial, Confluent and Fluid-filled. Novel locations of calcinosis were observed, including the cardiac tissue, pelvic and shoulder bursa, and the spermatic cord. Quantitative measures using Agatston scoring for calcinosis were used in regional distributions across the body. Physician physical exams had a sensitivity of 59% and a specificity of 90% compared with CT detection. A higher calcium score correlated with higher Physician Global Damage, Calcinosis Severity scores, and disease duration. Conclusion Whole-body CT scans and the Agatston scoring metric define distinct calcinosis patterns and provide novel insights relating to calcinosis in DM and JDM patients. Physicians' physical examinations underrepresented the presence of calcium. Calcium scoring of CT scans correlated with clinical measures, which suggests that this method may be used to assess calcinosis and follow its progression. [ABSTRACT FROM AUTHOR]

Objectives Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). Methods Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut‐off value of galectin-9. Results Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85–32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42–7.89) ng/ml, P  < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (r s=0.3065, P  = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85–38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23–27.91) ng/ml, P  = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97–28.02) ng/ml, P  = 0.0258], and tumour patients without DM [7.46 (4.90–8.51) ng/ml, P  < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04–41.43) ng/ml vs 13.88 (5.15–20.37) ng/ml, P  = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803–0.977) showed the highest predictive value for the presence of cancer in DM. Conclusion Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome. [ABSTRACT FROM AUTHOR]

Objective To investigate pathogenic mechanisms underlying JDM, we defined the effect of type I IFN, IFN-α and IFN-β, on pediatric skeletal muscle function and expression of myositis-related proteins using an in vitro engineered human skeletal muscle model (myobundle). Methods Primary myoblasts were isolated from three healthy pediatric donors and used to create myobundles that mimic functioning skeletal muscle in structural architecture and physiologic function. Myobundles were exposed to 0, 5, 10 or 20 ng/ml IFN-α or IFN-β for 7 days and then functionally tested under electrical stimulation and analyzed immunohistochemically for structural and myositis-related proteins. Additionally, IFN-β-exposed myobundles were treated with Janus kinase inhibitors (JAKis) tofacitinib and baricitinib. These myobundles were also analyzed for contractile force and immunohistochemistry. Results IFN-β, but not IFN-α, was associated with decreased contractile tetanus force and slowed twitch kinetics. These effects were reversed by tofacitinib and baricitinib. Type I IFN paradoxically reduced myobundle fatigue, which did not reverse after JAKi. Additionally, type I IFN correlated with MHC I upregulation, which normalized after JAKi treatment, but expression of myositis-specific autoantigens Mi-2, melanocyte differentiation-associated protein 5 and the endoplasmic reticulum stress marker GRP78 were variable and donor specific after type I IFN exposure. Conclusion IFN-α and IFN-β have distinct effects on pediatric skeletal muscle and these effects can partially be reversed by JAKi treatment. This is the first study illustrating effective use of a three-dimensional human skeletal muscle model to investigate JDM pathogenesis and test novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycaemia. Diabetes is considered a lifestyle disease and diet plays an important role in the development of DM and its associated complications. It is claimed that there is an inverse relationship between Mg intake and incidence of diabetes mellitus (DM)2. Mg deficiency is common in diabetic patients. Magnesium deficiency may lead to decreased synthesis of glutathione thereby enhancing the process of lipid peroxidation. The free radical mediated lipid peroxidation (oxidative stress) has also been implicated in the pathogenesis of diabetes mellitus. Methodology- The study was conducted on 70 patients of type 2 diabetes mellitus admitted to GIMS, Kalaburagi between January 2020 and December 2021. Also 70 non diabetic patients admitted during the same period were included in the study under the control group. Patients were considered to be diabetic based on WHO criteria for diagnosis of diabetes mellitus. All the necessary investigations were done. Estimation of serum magnesium was done and the results were interpreted. Results- The mean serum magnesium was 1.65 mg/dl and 1.99 mg/dl in diabetics and control respectively. The mean serum magnesium level in patients on OHA was 1.99 mg/dl on insulin was 1.59 mg/dl and in patients on both OHA and insulin was 1.26 mg/dl. The serum magnesium in patients who had diabetes under control was 1.75 mg/dl and that in whom it was uncontrolled was 1.23 mg/dl. Conclusion- Hypomagnesemia is a factor in type 2 diabetes mellitus patients leading to various complications. Hence, it is worthwhile estimating magnesium levels in type 2 diabetes mellitus patients and probably correlates their relationship with various complications. [ABSTRACT FROM AUTHOR]

Introduction- Diabetes mellitus (DM) is a very common disorder with distressing effects on metabolism causing various complications including bone disorders. The aim of the study was to assess the occurrence of osteoporosis in diabetics along with other factors, to closely observe the relation of diabetes with risk of fractures & osteoporosis. Material and method- DM patients visiting outpatient clinic of GMC (Government medical college), Srinagar, J&K (Jammu & Kashmir) were recruited in the study along with healthy volunteers as control. Lumbar spine (LS) and femoral neck (FN) T-score was assessed by DXA (dual x-ray absorptiometry) scan and then WHO interpretation of T-score was done to evaluate risk of osteoporosis. Data was analyzed and “P≤ 0.05 was considered as statistically significant.” Result- Mean difference in age (between diabetics and control group) and association of gender with diabetes was found non-significant. The BMI (body mass index), FBS (fasting blood sugar) and HbA1c (glycosylated hemoglobin) levels were significantly higher in diabetics than non-diabetics. Mean LS T-score was significantly lower and FN T-score was non-significantly lower in diabetics than non-diabetics. LS and FN T-score of diabetic males was significantly more than diabetic females. Risk of osteoporosis was found significantly more in diabetic females than diabetic males. Conclusion- The Study recommends screening of DM population for bone health regardless of age and sex. Further for prevention and better management of osteoporosis in DM patients, clinicians must counsel them regarding adequate nutrient intake for good glycaemic control and bone health. [ABSTRACT FROM AUTHOR]

Objective Among specific autoantibodies in DM, the anti–small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE–positive DM. Methods Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE–negative DM and a review of the literature. Results Of the patients in the study (n  = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE–negative DM (n  = 85) showed less and milder muscle weakness (P  = 0.02 and P  = 0.006, respectively), lower creatinine kinase levels (P  < 0.0001) and less dyspnoea (P  = 0.003). Conclusion Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT04637672. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord‐derived mesenchymal stem cells (UCMSCs) could alleviate diabetes‐induced injury. Hence, this investigation aimed to explore the role and mechanism of UCMSCs‐derived exosomal circHIPK3 (exo‐circHIPK3) in diabetes mellitus (DM). Methods: HFF‐1 cells were cultured in high glucose (HG) medium or normal medium, and treated with UCMSCs‐derived exo‐circHIPK3 or miR‐20b‐5p mimics or Unc‐51‐like autophagy activating kinase 1 (ULK1) overexpression vector. The surface markers of UCMSCs were analyzed using a flow cytometer. The differentiation potential of UCMSCs was evaluated using oil red O staining, alizarin red staining and alkaline phosphatase (ALP) staining. Cell proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The miRNA expressions were analyzed by reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR). Protein levels were quantified by western blot. An immunofluorescence staining was used for observing LC3 expression. The interaction between miR‐20b‐5p and circHIPK3, and between miR‐20b‐5b and ULK1 were identified by a RNA immunoprecipitation (RIP) assay and a luciferase reporter assay. Results: Up‐regulation of circHIPK3 was found in UCMSCs‐derived exosomes. Exo‐circHIPK3 decreased the miR‐20b‐5p level while increasing the contents of ULK1 and autophagy‐related gene 13 (Atg13) in HG‐induced fibroblasts. In addition, exo‐circHIPK3 activated HG‐induced fibroblast autophagy and proliferation. Overexpressed miR‐20b‐5p promoted fibroblast injury by inhibiting cell autophagy via the ULK1/Atg13 axis in HG conditions of high glucose. Moreover, exo‐circHIPK3 enhanced autophagy and cell viability in HG‐induced fibroblasts through the miR‐20b‐5p/ULK1/Atg13 axis. Conclusion: UCMSCs‐derived exosomal circHIPK3 promoted cell autophagy and proliferation and accelerated the fibroblast injury repair by the miR‐20b‐5p/ULK1/Atg13 axis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies—of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of −1.2%; 95% CI −2.0, −0.4) and pro-BNP (SMD −335.9 pmol/L; 95% CI −438.9, −232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD −1.1 mg/dL; 95% CI −1.8, −0.3) and increased weight loss (SMD −2.2 kg; 95% CI −2.9, −1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a widespread illness that affects around 347 million individuals globally. DM not only has many clinical implications but also has a detrimental impact on the quality of sleep in patients. Insufficient sleep quality hinders the proper regulation of blood sugar levels, which is considered a fundamental aspect of managing diabetes. It also has other harmful repercussions that significantly affect one's overall quality of life. Increasing data suggests that sleep disturbances and sleep deprivation have an impact on glucose metabolism and insulin resistance. Simultaneously, changes in glucose metabolism can potentially affect the quality of sleep. The association between T2DM and sleep-disturbed breathing has been thoroughly investigated. Individuals diagnosed with T2DM exhibit a remarkably elevated incidence of obstructive sleep apnea, which subsequently leads to suboptimal management of blood sugar levels. Conversely, the correlation between T1DM and sleep has not been well-studied. [ABSTRACT FROM AUTHOR]

Verapamil is a well-known drug used for treating angina and hypertension. Emerging data from current clinical trials suggest that this calcium channel blocker has a potential benefit for pancreatic β-cells through the elevation and sustenance of C-peptide levels in patients with diabetes mellitus (DM). This is intriguing, given the fact that the current therapeutic options for DM are still limited to using insulin and incretins which, in fact, fail to address the underlying pathology of β-cell destruction and loss. Moreover, verapamil is widely available as an FDA-approved, cost-effective drug, supported also by its substantial efficacy and safety. However, the molecular mechanisms underlying the β-cell protective potentials of verapamil are yet to be fully elucidated. Although, verapamil reduces the expression of thioredoxin-interacting protein (TXNIP), a molecule which is involved in β-cell apoptosis and glucotoxicity-induced β-cell death, other signaling pathways are also modulated by verapamil. In this review, we revisit the historical avenues that lead to verapamil as a potential therapeutic agent for DM. Importantly, this review provides an update on the current known mechanisms of action of verapamil and also allude to the plausible mechanisms that could be implicated in its β-cell protective effects, based on our own research findings. [ABSTRACT FROM AUTHOR]

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Abstract Background Sleep disordered breathing (SDB) is a widespread disorder with a wide range of harmful outcomes including obstructive sleep apnea (OSA), central sleep apnea (CSA), or sleep-related hypoventilation. Purpose The aim of the present study was to screen for the occurrence of sleep apnea syndrome in patients with type 2 diabetes mellitus (DM) and to evaluate the relation between the presence of sleep apnea and the level of glycemic control. Methods This was a prospective clinical study that enrolled 59 patients who were previously diagnosed as type 2 DM. Sleep study level IV was done using overnight recording of oxygen saturation and pulse. Results Among the studied patients, 42 were females and 17 were males, Their mean age was 59.76 ± 11.13 years. Obstructive sleep apnea was diagnosed in 46 patients (78%). Thirty three (86.8%) patients among those with uncontrolled glycemic level were diagnosed as OSA, whereas 13(61.9%) patients with controlled glycemic level were diagnosed as OSA showing statistically significant difference, p = 0.047. There was no correlation between either HbA1c, age, Mallampati score, or BMI and ODI but there was a correlation between STOP-BANG questionnaire and ODI (P = 0.036). The variables that were significantly related to presence of OSA, were comorbidities, ESS, Mallampati score, STOP-BANG, and sleep symptoms (nocturia and snoring) P value (0.029), (0.031), (0.022), (0.005), (0.049), and (0.012), respectively. Conclusion Patients with type 2 diabetes showed a significant high prevalence of OSA. With significant higher prevalence among patients with uncontrolled DM versus controlled DM.

AbstractAcute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional "risk enhancing" factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.

Introduction: It aimed to explore the diversity of gut microbiota (GM) and the effect of different microbiota on insulin resistance in diabetes mellitus (DM) patients through bioinformatics analysis. Material and Method: Microarray data were obtained from GEO database. GM samples from DM patients and healthy controls were collected, and 16S rRNA gene sequencing was carried out adopting high-throughput sequencing technology. The differential expression genes were screened using the Qlucore Omics Explorer 3.0 software. Subsequently, online tools such as STRING and DAVID were utilized for bioinformatics analysis of the differential expression genes. The differences in bacterial diversity between DM patients and healthy controls were evaluated by analyzing the diversity indicators of the microbiota, such as Shannon and Chao1 indexes. Differential abundance and functional prediction analysis were adopted to explore the different microbiota and its possible metabolic pathways between DM patients and controls. And differences in insulin resistance in specific bacterial taxa were analyzed. Result: GM diversity between DM patients and controls had significant differences. GM diversity was lower in DM patients compared with controls, as indicated by a decrease in Shannon and Chao1 indexes. The differential abundance analysis showed that there were multiple different bacterial communities between DM patients and controls, including some bacterial communities at the genus-level. Functional prediction analysis also revealed potential metabolic pathways related to GM and insulin resistance in DM patients. HEXB, ZC3H12A, CCR, CXCR3, GBR10, CDK9, TXN, IGFBP3, PDHA1, and NDUFB3 genes may be potential targets for treatment. Conclusion: There are differences in GM diversity between DM patients and healthy controls, and the different microbiota may be related to the occurrence and development of insulin resistance.

The relationship between the blood glucose levels of diabetes mellitus patients and intake of carbohydrates, fiber, and vitamin D Background: Diabetes Mellitus (DM) is a non-communicable disease with a combination of symptoms that appear in a person due to an increase in blood glucose levels (hyperglycemia) above average values. Good intake by following the guidelines for persons with diabetes, a nutritious diet that contains carbs, fiber, and vitamin D can help keep blood glucose levels within acceptable ranges. Objective: This study aims to the relationship between the blood glucose levels of patients at RSI Siti Hajar Sidoarjo and their intake of carbohydrates, fiber, and vitamin D. Methods: The method in this study was a quantitative study with a cross-sectional approach, the population in this study were DM patients who were hospitalized at RSI Siti Hajar Sidoarjo. The number of samples was estimated using the cross-sectional sample size calculation and the purposive sampling technique with 60 respondents. The patient's intake was measured using a 3x24 hour food recall questionnaire. Data were analyzed using the Chi-Square test. Results: The result showed that there was a relationship between carbohydrate intake and blood glucose levels (p=0.000) and fiber intake and blood glucose levels (p=0.003), but there was no significant relationship between vitamin D intake and blood glucose levels (p=1.00). Conclusion: Carbohydrate and fiber intake significantly correlated with the patient's blood glucose levels but not vitamin D intake.

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle—a well-balanced diet and physical activity. There is also a group of compounds—including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others—that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM.

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET− groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12–0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14–0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0–2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

There is cumulative evidence that pancreatic exocrine insufficiency (PEI) is under-recognised and can occur in patients with 'at-risk' conditions. Thus, we aimed to assess the current practice and yield of requesting faecal elastase FEL-1), an indicator of PEI, in patients with 'at-risk' conditions. We prospectively recruited patients attending secondary care clinics with diabetes mellitus (DM), people living with HIV (PLHIV) and inpatients admitted to hospital with high alcohol intake (HAI). All patients underwent testing with FEL-1. Those patients with PEI (FEL-1 <200 μg/g) were contacted and offered a follow-up review in gastroenterology clinic. In total, 188 patients were recruited (HAI, n=78; DM, n=64; and PLHIV, n=46). Previous FEL-1 testing had not been performed in any of the patients. The return rate of samples was 67.9% for patients with HAI, 76.6% for those with DM and 56.5% for those with PLHIV. The presence of PEI was shown in 20.4% of patients with DM, 15.4% of patients with PLHIV and 22.6% in those with HAI. Diarrhoea and bloating were the most reported symptoms in followed-up patients with low FEL-1 (31.8% and 22.7% of patients, respectively). Follow-up computed tomography (CT) scans in those patients with PEI identified chronic pancreatitis changes in 13.6% and pancreatic atrophy in 31.8% of patients. These results suggest that there is a lack of testing for PEI in 'at-risk' groups. Our findings also suggest that using FEL-1 to test for PEI in patients with DM, PLHIV and HAI has a significant impact, although further studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Objective The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening. Methods Data from adult dermatomyositis/polymyositis patients in the rituximab (n  = 147), etanercept (n  = 14), and abatacept (n  = 19) trials, and consensus patient profiles (n  = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC. Results Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories. Conclusion The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: Sleep disordered breathing (SDB) is a widespread disorder with a wide range of harmful outcomes including obstructive sleep apnea (OSA), central sleep apnea (CSA), or sleep-related hypoventilation. Purpose: The aim of the present study was to screen for the occurrence of sleep apnea syndrome in patients with type 2 diabetes mellitus (DM) and to evaluate the relation between the presence of sleep apnea and the level of glycemic control. Methods: This was a prospective clinical study that enrolled 59 patients who were previously diagnosed as type 2 DM. Sleep study level IV was done using overnight recording of oxygen saturation and pulse. Results: Among the studied patients, 42 were females and 17 were males, Their mean age was 59.76 ± 11.13 years. Obstructive sleep apnea was diagnosed in 46 patients (78%). Thirty three (86.8%) patients among those with uncontrolled glycemic level were diagnosed as OSA, whereas 13(61.9%) patients with controlled glycemic level were diagnosed as OSA showing statistically significant difference, p = 0.047. There was no correlation between either HbA1c, age, Mallampati score, or BMI and ODI but there was a correlation between STOP-BANG questionnaire and ODI (P = 0.036). The variables that were significantly related to presence of OSA, were comorbidities, ESS, Mallampati score, STOP-BANG, and sleep symptoms (nocturia and snoring) P value (0.029), (0.031), (0.022), (0.005), (0.049), and (0.012), respectively. Conclusion: Patients with type 2 diabetes showed a significant high prevalence of OSA. With significant higher prevalence among patients with uncontrolled DM versus controlled DM. [ABSTRACT FROM AUTHOR]

Objectives To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS). Methods Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods. Results 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P  < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P  < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P  < 0.001). Conclusion PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected. [ABSTRACT FROM AUTHOR]

It has been suggested that primordial planets could have formed in the early universe and the missing baryons in the universe could be explained by primordial free-floating planets of solid hydrogen. Many such planets were recently discovered around the old and metal-poor stars, and such planets could have formed in early epochs. Another possibility for missing baryons in the universe could be that these baryons are admixed with DM particles inside the primordial planets. Here, we discuss the possibility of the admixture of baryons in the DM primordial planets discussed earlier. We consider gravitationally bound DM objects with the DM particles constituting them varying in mass from 20 to100 GeV. Different fractions of DM particles mixed with baryonic matter in forming the primordial planets are discussed. For the different mass range of DM particles forming DM planets, we have estimated the radius and density of these planets with different fractions of DM and baryonic particles. It is found that for heavier-mass DM particles with the admixture of certain fractions of baryonic particles, the mass of the planet increases and can reach or even substantially exceed Jupiter mass. The energy released during the process of merger of such primordial planets is discussed. The energy required for the tidal breakup of such an object in the vicinity of a black hole is also discussed. [ABSTRACT FROM AUTHOR]

Objectives: To explore the impact of diabetes itself and glycemic control status on tuberculosis (TB). Methods: A total of 3393 patients with TB and diabetes mellitus (DM) who were hospitalized in the Public Health Clinical Center of Chengdu from January 1, 2019, to December 31, 2021, were retrospectively included and divided into three groups according to baseline glycemic control status: two groups according to glycemic status at discharge, two groups according to cavity occurrence, three groups according to sputum results, and three groups according to lesion location. The influencing factors and the differences in cavity occurrence, sputum positivity and lesion location among different glycemic control groups or between different glycemic status groups were analyzed. Results: In this TB with DM cohort, most of the subjects were male, with a male to female ratio of 4.54:1, most of them were 45-59 years old, with an average age of 57.44 ± 13.22 years old. Among them, 16.8% (569/3393) had cavities, 52.2% (1770/3393) were sputum positive, 30.4% (1030/3393) had simple intrapulmonary lesions, 68.1% (2311/3393) had both intra and extrapulmonary lesions, only 15.8% (537/3393) had good glycemic control,16.0% (542/3393) and 68.2% (2314/3393) had fair and poor glycemic control, respectively. Compared with the non-cavity group, the sputum-negative group and the extrapulmonary lesion group, the cavity group, sputum-positive group, intrapulmonary lesion group and the intra and extrapulmonary lesion group all had higher fasting plasma glucose (FPG) and glycosylated hemoglobin A 1c (HbA1c) and lower good glycemic control rates at admission (all P<0.001). Another aspect, compared with the good glycemic control group, the poor glycemic control group had a higher cavity occurrence rate, sputum positive rate, and greater proportion of intrapulmonary lesions. Moreover, FPG and HbA1c levels and poor glycemic control were significantly positively correlated with cavity occurrence, sputum positivity, and intrapulmonary lesions and were the main risk factors for TB disease progression. On the other hand, cavity occurrence, sputum positivity, and intrapulmonary lesions were also main risk factors for hyperglycemia and poor glycemic control. Conclusion: Diabetes itself and glycemic control status could impact TB disease. Good glycemic control throughout the whole process is necessary for patients with TB and DM to reduce cavity occurrence and promote sputum negative conversion and lesion absorption. [ABSTRACT FROM AUTHOR]

Wavefront distortion caused by atmospheric turbulence can be described as different types of aberrations, such as piston, tilt, defocusing, astigmatism, coma and so on. The operation of dual deformable mirrors can have mutual coupling effects, which affect the correction effect of wavefront distortion. This study combines a fast-steering mirror (FSM) and a deformable mirror (DM) to form a dual-deformable-mirrors wavefront correction system, and proposes a decoupling algorithm that can correct any specified aberration. In this decoupling algorithm, both the FSM and the DM are controlled using the mode method, and the specific corrected aberrations are obtained based on a limited matrix. The compensation ability of the DM is directly characterized by the mode coefficients of the aberrations, which can achieve independent correction of any order of aberrations and effectively reduce the coupling effect of the dual-deformable-mirrors wavefront correction system. An adaptive optical dual-deformable-mirrors wavefront correction system experiment was built to verify the decoupling algorithm. When the DM corrects the 3rd-, 10th-, and 25th-order aberrations, and the FSM only corrects the 1st- and 2nd-order aberrations, the coupling coefficients are approximately 1.17 × 1 0 − 3 , 1.814 × 1 0 − 2 and 7.81 × 1 0 − 3 , respectively, and their magnitude reaches 10−2 and below 10−2, respectively. The experimental results show that the decoupling algorithm can effectively suppress the coupling effect between the FSM and the DM. [ABSTRACT FROM AUTHOR]

Diabetes: This term includes a number of disorders that are characterized by problems with the hormone insulin, which the pancreas naturally produces to help the body absorb the sugar in the blood, as issues in the production of this hormone raise the level of sugar in the blood and may lead to many other diseases and problems. That may lead to death. We use technology in the field of artificial intelligence to help medical specialists to classify diseases of humans by taking some measurements such as blood pressure, diabetes, heart rate, and other readings according to the diagnosis of the disease within periods of time and working on analyzing these readings to visualize the patient's health state. And may analysis to determine the patient's ability to respond to the system. In this paper, we used a Wireless sensor network technology to transmit patient data to the training server, then used artificial intelligence (AI) in the training and classification phase to find out if a patient has diabetes or not. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is quite heterogeneous in its patho-physiological mechanism associated with atherosclerosis. Little is known about measures for prevention of the disease apart from latest technologies and medications. Method: 100 patients of different age groups were studied with MRA, to rule out occlusion or lesion; tropical distribution of infarction, clinical manifestations, recurrence after treatment was also noted. Results: Clinical manifestations included 33% alcoholic, 21% homocystine, 80% HTN, 54% DM, 30% Hyperlipidemia, 35% smoking, 48% HTN + DM, 17% HTN + DM +Hyper-lipidemia, 7% HTN + DM + Hyper-lipidemia, + smoking + Alcohol. Highest occlusion was observed 51 (39.9%) in MCA followed by 20 (14.4%) ICA, 23 (16.6%) BA, 18 (13.04%) VA and least was 2 (1.4%) in VA+BA. Highest tropical distribution of infarction was 28% cortical followed by 24% sub cortical and cortical, 23% cortical, 11% cerebellum, 8% Brainstem and recurrence was observed in 19% patients. Conclusion: The present pragmatic study will help for efficient management and risk control for Neuro-physician and neurosurgeon because risk factor control remains the best strategy for preventing recurrence because recurrence of the stroke worsen the physical and mental conditions of the patients. [ABSTRACT FROM AUTHOR]

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Latar Belakang; Diabetes mellitus merupakan dapat menyebabkan berbagai komplikasi metabolik akut seperti ketoasiosis dan sindrom hiperglikemia yang mengakibatkan sindrome hipeglikemia hiperosmoler nonketotik (HHNK). Salah satu metode yang digunakan dalam pendidikan kesehatan dan promosi kesehatan adalah Health Belief Model (HBM). Tujuan: Menganalis efektifitas implementasi health believe model terhadap perilaku pencegahan penyakit diabetes mellitus di wilayah kerja PKM Perumnas. Desain Penelitian menggunakan metode kualitatif untuk mengetahui peresepsi subjek terhadap implementasi HBM dalam upaya pencegahan komplikasi penyakit diabetes mellitus tehadap 7 orang subjek. Penelitian ini dilaksanakan di wilayah PKM Perumnas Kec. Curup Tengah Kabupaten Rejang Lebong pada bulan Oktober sampai dengan November 2021. Pengolahan dan analisis data dilakukan dengan melakukan ongoing content analisis. Etik penelitian diperoleh dari komisi etik penelitian Poltekkes Kemenkes Bengkulu no KEPK.M/189/10/2021 tanggal 11 Oktober 2021. Hasil penelitian; didapatkan bahwa walaupun DM adalah penyakit yang berbahaya tapi tidak boleh takut dan dapat dikontrol dengan rutin berobat dan konsultasi untuk selalu menjaga kesehatan. Hambatan yang dirasakan oleh responden dalam melakukan pengobatan rutin adalah tidak adanya anggota keluarga yang mengantarkan untuk mengambil obat ke puskesmas serta adanya rasa malu karena selalu berkunjung ke puskesmas untuk mengambil obat dan panjangnya alur administrasi yang harus diselesaikan seperti mengambil surat rujukan ke Rumah Sakit. Saran: diaharapkan kepada masyarakat utuk tetap melakukan pengobatan secara rutin dan selalu melakukan deteksi dini dalam pencegahan komplikasi penyakit DM.

Introduction: End stage renal disease (ESRD) is a late stage of chronic kidney disease (CKD) requiring chronic dialysis or renal transplant to survive. End stage renal disease is a growing problem worldwide. In Bhutan too, there are anecdotal evidence showing increasing number of ESRD patients every year, which has become a cause of serious concern for the country. Methods: This retrospective descriptive study was conducted at the National Referral Hospital of Bhutan, from 2019 to 2020 to find out the aetiology of ESRD in the country. The demographic information and aetiology of ESRD were collected from the past record of the patients. A total of 202 eligible ESRD patients were enrolled in this study. Results: The study showed that the mean age of patients was 47.3 ±13.20 years. The majority of the patients 139 (68.8%) were in the age group 24-60 years. Of the total patients, 107 (53.0%) were females. The common aetiologies of ESRD were hypertension (HTN), chronic glomerulonephritis (CGN) and Diabetes Mellitus (DM) constituting 20.8%, 12.9%, and 8.9% of the total patients respectively. In 50.0% of the patients, the aetiology of ESRD were unexplained. Conclusions: The most common aetiologies of ESRD were HTN (20.8%), CGN (12.9%) and DM (8.9%); in 50.0% of the patients, the aetiologies remained unexplained. The majority of ESRD patients (68.8%) in this study were from middle age group, with female predominance (53.0%).

Abstract Aim This study aimed to identify the predictors of mortality and ICU requirements in hospitalized COVID‐19 Patients with Diabetes. Design Cross‐sectional study. Methods It was a retrospective study of patients hospitalized with COVID‐19 infection from October 2020–February 2021 in four hospitals in Sylhet, Bangladesh. Logistic regression analysis was applied to explore the predictors of ICU requirement and in‐hospital mortality. Results In the whole cohort (n = 500), 11% of patients died and 24% of patients required intensive care unit (ICU) support. Non‐survivors had significantly higher prevalence of lymphopenia, thrombocytopenia and leukocytosis. Significant predictors of in‐hospital mortality were older age, neutrophil count, platelet count and admission peripheral capillary oxygen saturation (SpO2). Older age, ischemic heart disease, WBC count, D‐dimer and admission SpO2 were identified as significant predictors for ICU requirement. Patient or Public Contribution No.

Introduction. The 2018 Riskesdas data shows that the prevalence of diabetes mellitus is increasing each year. Strobilanthes crispus leaves are known for lowering blood glucose levels. This study aimed to determine the difference in the effectiveness of S. crispus leaves ethanolic extract on fasting blood glucose (FBG) and post-oral glucose tolerance test (OGTT). Methods. True experimental study using post-test only control group design and Rattus norvegicus as experimental animals. Rattus norvegicus were selected by random sampling which were then divided into 4 groups (K, P1, P2, P3), each group consisted of 5 animals. The animals were subsequently induced with diabetes mellitus via a single injection of 160 mg/kgBW/IP alloxan. Group K was given 0.5% NaCMC solution at a dose of 1 ml/200 g BW/day/oral/day. Group P1, P2, and P3 received extract at a dose of 100, 400, 600 mg/kg BW/oral/day for 21 days using oral gavage. Statistical analysis was performed using ANOVA, Tukey, Brown-Forsythe, and Kruskal-Wallis tests. Results. Mean FBG level in group K, P1, P2, P3 were 338.40 mg/dL, 270.80 mg/dL, 200.00 mg/dL, and 138.60 mg/dL, respectively. Mean value of 60 minutes OGTT blood glucose level in group K, P1, P2, P3 were 355.60 mg/dL, 289.00 mg/dL, 188.00 mg/dL, and 164.40 mg/dL, respectively. Meanwhile, mean value of 120 minutes OGTT blood glucose level in group K, P1, P2, P3 were 346.60 mg/dL, 236.20 mg/dL, 175.40 mg/dL, and 117.20 mg/dL, respectively. The hypothesis test results showed a significant difference in 120 minutes OGTT blood glucose level (p= 0.031). Conclusion. The use of ethanol extract from S. crispus leaves is more beneficial in reducing blood glucose levels in 120 minutes OGTT compared to FBG level and 60 minutes OGTT level, with the highest reduction observed in the group given a dose of 600 mg/kgBW/oral/day compared to control.

Background and Aim:Two-dimensional (2D) speckle tracking echocardiography (STE) has shown promising results being a recent technology to assess “myocardial performance” in cardiac patients. Three-dimensional echocardiography 3DE has been shown to be accurate in the assessment of left ventricular (LV) systolic function. The multigated acquisition (MUGA) scan provides a more accurate quantification of the ventricular ejection fraction To Assess the role of 2D-STE and 3DE in the assessment of LV systolic function in type II patients with diabetes with negative myocardial perfusion imaging in correlation with the MUGA scan.Materials and Methods:The study included 30 patients with type 2 diabetes mellitus (T2DM) [Group 1, 25 (83%) female and 5 (16%) males with mean age 48.40 ± 7.44], their stress myocardial perfusion imaging was negative for coronary ischemia. The control group included 15 apparently healthy age and sex-matched subjects, [Group 2, 11 (73%) females and 4 (26%) males with mean age 50.20 ± 7.74], LV systolic function was evaluated using conventional, TDI, 2D-STE (LV-GLS), 3-DE and MUGA scan.Results:The group with diabetes showed statistically highly significant reduction in LV-GLS (-18.07 ± 2.73 in group 1 vs -21.24 ± 1.29 in group 2, P < 0.001), and in 3D LVEF (52.30 ± 5.28 in Group 1 vs 58.93 ± 4.69 in Group 2, P < 0.001). We found an agreement between three modalities (speckle tracking, 3DE and MUGA scan) by 33% in 10 patients [3 patients (10%) had impaired LV functions and 7 patients (23%) had preserved LV functions]. There was an agreement between speckle tracking and 3D echo by 76.6% in 23 patients [16 patients (53.3%) had impaired LV functions and 7 patients (23.3%) had preserved LV functions].Conclusion:T2DM is associated with subclinical LV systolic dysfunction that can be assessed by different noninvasive modalities (speckle tracking, 3DE and the MUGA scan). 2D speckle tracking and 3DE might have an edge compared with MUGA scan in the detection of subclinical LV systolic dysfunction.

Objectives The B-cell depleting biologic, rituximab, is used to treat refractory autoimmune myositis. However, the beneficial effects of rituximab appear to outweigh the known contribution of B cells in myositis. We aimed to elucidate how myositis patients respond differently to rituximab and possible alternative mechanisms of action. Methods Here we have: (i) comprehensively investigated concurrent mRNA and microRNA expression in muscle biopsies taken at baseline and 16 weeks post treatment in 10 patients who were part of the rituximab in myositis (RIM) trial; and (ii) investigated the beneficial effect of rituximab on myositis muscle cells. Results Our analyses identified an increased number of changes in gene expression in biopsies from patients who had a clinical response to rituximab (n  =   5) compared with non-responders (n  =   5). The two groups had completely different changes in microRNA and mRNA expression following rituximab therapy, with the exception of one mRNA, BHMT2. Networks of mRNA and microRNA with opposite direction of expression changes highlighted ESR1 as upregulated in responders. We confirmed ESR1 upregulation upon rituximab treatment of immortalized myotubes and primary human dermatomyositis muscle cells in vitro , demonstrating a direct effect of rituximab on muscle cells. Notably, despite showing a response to rituximab, human dermatomyositis primary muscle cells did not express the rituximab target, CD20. However, these cells expressed a possible alternative target of rituximab, sphingomyelinase-like phosphodiesterase 3 b (SMPDL3B). Conclusion In addition to B-cell depletion, rituximab may be beneficial in myositis due to increased ESR1 signalling mediated by rituximab binding to SMPDL3B on skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis. Methods This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n  = 23) and non-response (n  = 15) groups, and between those in the relapse (n  = 5) and non-relapse (n  = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis. Results The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis. Conclusion The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity. [ABSTRACT FROM AUTHOR]