Elevated Glucose Research Articles

Cadmium exposure induces skeletal muscle insulin resistance through the reactive oxygen species-mediated PINK1/Parkin pathway

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNA-sequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Hashimoto's Thyroiditis in Diabetic Patients: A Prospective Study in Nasiriyah City

There is a connection between having Hashimoto's thyroiditis, an autoimmune disease marked by thyroid gland attacks, and an increased risk of type 2 diabetes mellitus, a metabolic disease marked by elevated blood glucose levels. The purpose of this research was to find out how common type 2 diabetes was in Nasiriyah City, Iraq, among individuals suffering from Hashimoto's thyroiditis. Methods: A study using a retrospective cohort was conducted involving thyroiditis caused by Hashimoto's in 100 patients diagnosed between January 2023 and January 2024 at Al Hussein Teaching Hospital. Patients' medical records were reviewed to extract data on demographics, clinical characteristics, and laboratory results, including HbA1c and fasting blood glucose levels. Confirmation of Based on ELISA data indicating positive anti-thyroid peroxidase antibody levels, Hashimoto's thyroiditis was diagnosed. Results: The prevalence of T2DM among the number of Hashimoto's thyroiditis patients was noticeably greater (45%) compared to the general population prevalence of 15%. the number of Hashimoto's thyroiditis patients was noticeably greater HbA1c and FBG levels compared to those without Hashimoto's thyroiditis. Specifically, an investigation of logistic regression revealed that Hashimoto’s thyroiditis was significantly associated with type 2 diabetes individually when OR = 4. 2, 95% CI 2. 1-8. 5). In conclusion, the result of the present investigation, it is clear that, Hashimoto’s thyroiditis has a positive relationship with T2DM in Nasiriyah city of Iraq. Hence, early identification and intervention of T2DM in patients with Hashimoto’s thyroiditis should be a routine practice to avoid complications associated with the two diseases.

The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.

Long-term hypoxia-induced physiological response in turbot Scophthalmus maximus L.

Hypoxia affects fish's survival, growth, and physiological metabolism processes. In this study, turbot plasma glucose and cortisol contents, hepatic glycolysis (hexokinase [HK], phosphofructokinase [PFK], pyruvate kinase [PK]) and lipolysis (fatty acid synthetase [FAS], lipoprotein lipase [LPL]) enzyme activities, anti-oxidant enzyme (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]) activities, malondialdehyde (MDA), lactate and glycogen contents, gill histological parameters (lamellar length [SLL], width [SLW], interlamellar distance [ID]), respiratory frequency (RF), the proportion of the secondary lamellae available for gas exchange (PAGE), and hifs (hif-1α, hif-2α, hif-3α) expression were determined during long-term hypoxia and reoxygenation. Results showed that long-term hypoxia (3.34 ± 0.17mg L-1) significantly elevated plasma cortisol and glucose contents; increased hepatic HK, PK, PFK, FAS, and LPL activity; decreased hepatic glycogen, lactate contents, and lipid drop numbers; and caused changes of hepatocyte (vacuolation, pyknotic, and lytic nucleus) after treatment for 4weeks. Hepatic SOD, CAT, GSH-Px activity, and MDA contents; lamellar perimeter, SLL, ID, RF, and PAGE; and hepatic hif-1α, hif-2α, and hif-3α manifested similar results. Meanwhile, hif-1α is significantly higher than hif-2α, and hif-3α. Interestingly, females and males demonstrated no sex dimorphism significantly different from the above parameters (except hepatic FAS, LPL activity, and lipid drop number) under hypoxia. The above parameters recovered to normal levels after reoxygenation treatment for 4weeks. Thus, long-term hypoxia promotes turbot hepatic glycogenolysis and lipolysis, induces oxidative damage and stimulates hepatic antioxidant capacity, and alters gill morphology to satisfy insufficient energy demand and alleviate potential damage, while hif-1α plays critical roles in the above physiological process.

Physiological assessment of the effects of experimental capture and transport in Pacific spiny dogfish

Sharks are collected from the wild as live specimens for display in aquariums and use in research. The methods by which live sharks are captured and transported can be associated with sub-lethal physiological outcomes or even mortality, which requires evaluation to determine optimal collection and transport methods for a given species. The present study evaluated the primary (i.e., endocrine) and secondary (i.e., biochemical) stress responses and mortality in Pacific spiny dogfish (Squalus suckleyi) following capture and subsequent transport between experimental rod-and-reel angling and longline fishing. Dogfish were resilient to transport following capture by either method, exhibiting no at-vessel mortality and 0.03% delayed mortality. Longline captured dogfish exhibited signs of primary (i.e., elevated corticosterone) and secondary (i.e., elevated plasma potassium, osmolality, glucose, and lactate; decreased blood pH) stress responses, whereas dogfish that experienced rod-and-reel capture and transport only exhibited a secondary stress response (i.e., elevated plasma potassium, osmolality, and lactate; decreased blood pH). Together, these data demonstrate that Pacific spiny dogfish are robust to capture and transport using experimental hook-and-line fishing techniques.

Hyperuricemia and associated factors among hypertensive patients attending an academic hospital of Ethiopia: A cross-sectional study

BackgroundHypertension is a major public health problem in developing countries. Globally, nearly 1.13 billion adults had hypertension in 2015 and this is estimated to increase to 1.56 billion by 2025. Hyperuricemia is an important predictor of the progression of hypertension and is common in hypertensive patients. Hypertensive patients with hyperuricemia are at higher risk of cardiovascular disease. ObjectiveTo assess the prevalence of hyperuricemia and its associated factors among hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital (UGCSH). MethodAn institutional-based cross-sectional study was conducted on 248 hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital from January 2020 to February 2021. A convenient sampling technique was employed to select study participants. Socio-demographic and clinical characteristics were collected using a structured questionnaire via face-to-face interviews and reviewing medical records respectively. The biochemical parameters were measured by using a Mindray BS-200E chemistry analyzer. Data was entered using EpiData version 4.6.0.0 and analyzed using STATA vs. 14.0. Bivariable and multivariable binary logistic regression were fitted to identify factors associated with hyperuricemia. The odds ratio and 95 % CI were calculated to assess the strength of the association and a P-value <0.05 in the multivariable was considered statistically significant. ResultsA total of 248 patients were enrolled; 140 (56.5 %) were female. The mean age of patients was 57.9 ± 10.5 years. The overall prevalence of hyperuricemia was 42.3 %; males had a prevalence of 36.1 % and females of 47.1 %. High waist circumference, high body mass index, dyslipidemia, low estimated Glomerular Filtration Rate, elevated fasting blood glucose, elevated total cholesterol, elevated triglycerides, elevated Low-Density Lipoprotein cholesterol, and Low High-Density Lipoprotein cholesterol were found to be significantly associated with hyperuricemia. ConclusionThis study demonstrated the predominant existence of hyperuricemia in hypertensive patients. Therefore, early diagnosis and monitoring of hyperuricemia are required before further complications occur.

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study.

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70-140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Risk factors for non-communicable diseases in Afghanistan: insights of the nationwide population-based survey in 2018

BackgroundNoncommunicable diseases (NCDs) account for a substantial number of deaths in Afghanistan. Understanding the prevalence and correlates of major NCD risk factors could provide a benchmark for future public health policies and programs to prevent and control NCDs. Therefore, this study aimed to examine the prevalence and correlates of NCD risk factors among adults aged 18–69 years in Afghanistan.MethodsWe used data from the Afghanistan STEPS Survey 2018. The study population were 3650 (1896 males and 1754 females) adults aged 18–69 years sampled from all 34 provinces through a multistage cluster sampling process. Information on behavioural and biological risk factors was collected. We used STATA (version 18.0) for data analysis.ResultsOf the total participants, 42.8% were overweight or obese, 8.6% were current smokers, 26.9% had insufficient physical activities, 82.6% had low consumption of fruits and vegetables, and only 0.5% had ever consumed alcohol. Approximately 15% of participants had a high salt intake, while 25% and 8% had elevated blood pressure and blood glucose levels, respectively. Similarly, around 18% had elevated total cholesterol. The study revealed a lower prevalence of current smoking among females [AOR = 0.17, 95%CI (0.09–0.30)] compared with males, but a higher prevalence in those who had higher education levels [1.95 (1.13–3.36)] compared with those with no formal education. Insufficient physical activity was higher in participants aged 45–69 years [1.96 (1.39–2.76)], females [4.21 (1.98–8.84)], and urban residents [2.38 (1.46–3.88)] but lower in those with higher education levels [0.60 (0.37–0.95)]. Participants in the 25th to 75th wealth percentiles had higher odds of low fruit and vegetable consumption [2.11 (1.39–3.21)], while those in the > 75th wealth percentile had lower odds of high salt intake [0.63 (0.41–0.98)]. Being overweight/obese was more prevalent in participants aged 45–69 years [1.47 (1.03–2.11)], females [1.42 (0.99–2.01)], currently married [3.56 (2.42–5.21)] or ever married [5.28 (2.76–10.11)], and urban residents [1.39 (1.04–1.86)]. Similarly, high waist circumference was more prevalent in participants aged 45–69 years [1.86 (1.21–2.86)], females [5.91 (4.36–8.00)], those being currently married [4.82 (3.12–7.46)], and those being in 25th to 75th wealth percentile [1.76 (1.27–2.43)]. A high prevalence of elevated blood pressure was observed in participants aged 45–69 years [3.60 (2.44–5.31)] and currently married [2.31 (1.24–4.31)] or ever married [6.13 (2.71–13.8)] participants. Elevated blood glucose was more prevalent in older adults ([1.92 (1.09–3.39)] for 45–69 and [3.45 (2.44–5.31)] for 30–44 years), urban residents [2.01 (1.33–3.03)], and ever-married participants [4.89 (1.48–16.2)]. A higher prevalence of elevated cholesterol was observed in females [2.68 (1.49–4.82)] and those currently married [2.57 (1.17–5.63)] or ever married [4.24 (1.31–13.73)].ConclusionThis study used up-to-date available data from a nationally representative sample and identified the prevalence of NCDs and associated risk factors in Afghanistan. Our findings have the potential to inform and influence health policies by identifying people at high risk of developing NCDs and can assist policymakers, health managers, and clinicians to design and implement targeted health interventions.

Dietary fiber of jicama (Pachyrhizus erosus L., Fabaceae) tuber ameliorates kidney structure and function in mice fed with high-sucrose drink

Frequent consumption of high-sugar drinks (HSD) including sugar-sweetened beverages has been associated with the development of kidney disease. Otherwise, proper intake of dietary fiber extracted from the tuber of jicama (Pachyrhizus erosus L., Fabaceae) is shown to exert counteractive effects against HSD-induced metabolic syndrome including diabetes. However, it remains unelucidated whether the incorporation of jicama fiber in the diet could exert a beneficial effect on kidney function. This study aimed to elucidate the protective effect of jicama fiber in the diet against kidney disease caused by HSD. A total of thirty adult male albino mice were randomly assigned into three groups, the control group (fed with distilled water drink and standard diet), the high-sucrose drink group (HSD; fed with 30% sucrose solution drink and standard diet), and the high-sucrose drink + JF group (HSD + JF; fed with 30% sucrose drink and a standard diet supplemented with 25% of jicama fiber). The treatments were performed for ten weeks followed by the measurements of fasting blood glucose, plasma creatinine and kidney indices including urine protein, urine specific gravity, and refractive index and the examination of histopathological alterations in the kidney. The results demonstrated that the incorporation of JF in the diet at the dose of 25% could effectively counteract the elevation of fasting blood glucose and indicators of kidney damage including plasma creatinine, urine protein, urine specific gravity, and urine refractive index caused by HSD. However, JF failed to prevent HSD-induced mass reduction of the kidney but could ameliorate histopathological alterations in the kidney. Furthermore, JF effectively prevented tubular atrophy and fibrosis in the kidney in HSD-treated mice. Therefore, supplementation of the diet with JF at the dose of 25% could be effective in protecting the kidney against HSD. Thus, proper consumption of dietary fiber of jicama tuber has the potential to reduce HSD-induced kidney disease.

Investigation of Anti-Diabetic Properties of Ceylon Cinnamon Bark Extracts by In-Vitro α-Amylase and α-Glucosidase Inhibition, Molecular Modeling, and Postprandial Blood Glucose Regulation for Potential Nutraceuticals

Background: Diabetes Mellitus (DM) can appear due to the absence of insulin (DM1- type 1) or poor response of cells to insulin (DM2-type 2). Even though DM1 cannot be controlled using general treatments, DM2 can be easily controlled or prevented using pharmaceuticals, nutraceuticals, or dietary practices. Ceylon cinnamon (Cinnamomum zeylanicum) is one such natural remedy that has been consumed against elevated blood glucose levels in the past. Cinnamon and different types of cinnamon extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes that are responsible for carbohydrate metabolism and are effective in blood glucose regulation. However, the combined effect of aqueous and ethanol extracts of cinnamon bark on blood glucose regulation is still lacking. In this study, Water Extract of Cinnamon (CWE), Ethanol Extracts of Cinnamon (hot ethanol extract of cinnamon-CHEE, cold ethanol extract of cinnamon-CEE, and 50% ethanol extract of cinnamon- CEE-50) were studied for their sugar-controlling properties. Objectives: This study was performed to identify the efficacy of different cinnamon extracts on the inhibition of α-amylase and α-glucosidase enzymes, followed by animal studies to confirm the use of the extracts in nutraceutical formulations. Methods: Water and ethanol-based extraction method was used to prepare cinnamon extracts. These extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes. Molecular docking studies were used to identify the binding of the active molecules to the substrate binding sites of α-amylase and α-glucosidase. In-vivo time dependence postprandial blood glucose regulation studies have been performed with healthy Wistar male rats. Results: Yields of the CHEE, CEE, and CWE were 14±2%, 12±2%, and 8±1% respectively. According to the LCMS data, the major component in the CEE was cinnamaldehyde. Both CWE and CEE were subjected to the Total Polyphenol assay (TPC) and Total Flavonoids (TFC) assays. The TPC of CWE and CEE were 117±1 mg (Gal)/g and 170±10 mg (Gal)/g, while the TFC of CWE and CEE were 359±1 mg (Qc)/g and 254±4 mg (Qc)/g, respectively. In the α-amylase inhibition assay, Acarbose; a known α-amylase inhibitor, and CEE showed IC50 values of 65.4 ppm and 2.6 ppm, while CWE failed to show inhibition against α-amylase. In the α-glucosidase inhibition assay, Acarbose; a known α-amylase inhibitor, CEE, and CWE showed IC50 values of 312 ppm, 4.5 ppm, and 1.3 ppm, respectively. In-vivo time dependence postprandial blood glucose regulation studies that have been performed with healthy Wistar male rats showed a lowering of blood glucose concentrations by 22%, 11%, and 10% of glucose at 30 min, 60 min, and 90 min compared to the control group. Conclusion: The CEE contains polyphenols and flavonoids and is effective in inhibiting both α- amylase and α-glucosidase. The CWE also contains polyphenols and a comparatively higher level of flavonoids and is effective in inhibiting α-glucosidase while not affecting α-amylase inhibition. Overall, the IC50 data, TPC data, and TFC data proposed that the inhibition of carbohydrate hydrolyzing enzymes by polyphenols may depend on the polarity of particular polyphenols. Based on the rat trials, it can be concluded that the 1:1 combination of CWE and CEE may be useful in formulating postprandial blood glucose level-regulating nutraceuticals.

Metabolic syndrome and cardiovascular disease among adult cancer patients: results from NHANES 2007–2018

BackgroundMetabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD), and CVD is a major challenge for cancer patients. This study aimed to investigate the prevalence and association of MetS and CVD among adult cancer patients.MethodsThis cross-sectional study included cancer patients aged > 18 years from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The prevalence of MetS and CVD was calculated using weighted analysis. Multivariable logistic regression was used to assess the association between MetS and CVD.ResultsThe study included 2658 adult cancer patients, of whom 1260 exhibited MetS and 636 had CVD. The weighted prevalence of MetS and CVD in cancer patients was 45.44%, and 19.23%, respectively. Multivariable logistic regression showed a 79% increased risk in higher CVD prevalence in cancer patients with MetS, with the OR (95% CI) of 1.79 (1.31, 2.44). Notably, obesity, elevated blood pressure (BP), high glucose, and low high density lipoprotein cholesterol (HDL-C) in the MetS components were significantly associated with higher CVD prevalence after adjusting for covariates. Moreover, the risk of CVD prevalence in cancer patients increased with more MetS components. Notably, MetS was more strongly linked to CVD in patients aged < 65 and women.ConclusionsAmong adult cancer patients, over two-fifths (45.44%) were estimated to have MetS, while about one-fifth (19.23%) were considered to have CVD. Notably, obesity, elevated BP, high glucose, low HDL-C, and higher number of MetS components were found to be significantly associated with higher CVD prevalence among cancer adults. Cancer patients under 65 and women with MetS may be at increased risk of CVD.

Computer-Aided Diagnosis of Diabetic Retinopathy Lesions Based on Knowledge Distillation in Fundus Images

At present, the early diagnosis of diabetic retinopathy (DR), a possible complication of diabetes due to elevated glucose concentrations in the blood, is usually performed by specialists using a manual inspection of high-resolution fundus images based on lesion screening, leading to problems such as high work-intensity and accessibility only in specialized health centers. To support the diagnosis of DR, we propose a deep learning-based (DL) DR lesion classification method through a knowledge distillation (KD) strategy. First, we use the pre-trained DL architecture, Inception-v3, as a teacher model to distill the dataset. Then, a student model, also using the Inception-v3 model, is trained on the distilled dataset to match the performance of the teacher model. In addition, a new combination of Kullback–Leibler (KL) divergence and categorical cross-entropy (CCE) loss is used to measure the difference between the teacher and student models. This combined metric encourages the student model to mimic the predictions of the teacher model. Finally, the trained student model is evaluated on a validation dataset to assess its performance and compare it with both the teacher model and another competitive DL model. Experiments are conducted on the two datasets, corresponding to an imbalanced and a balanced dataset. Two baseline models (Inception-v3 and YOLOv8) are evaluated for reference, obtaining a maximum training accuracy of 66.75% and 90.90%, respectively, and a maximum validation accuracy of 35.94% and 81.52%, both for the imbalanced dataset. On the other hand, the proposed DR classification model achieves an average training accuracy of 99.01% and an average validation accuracy of 97.30%, overcoming the baseline models and other state-of-the-art works. Experimental results show that the proposed model achieves competitive results in DR lesion detection and classification tasks, assisting in the early diagnosis of diabetic retinopathy.

Neonatal overfeeding promotes anxiety, impairs episodic-like memory, and disrupts transcriptional regulation of hippocampal steroidogenic enzymes

The objective of our study was to investigate the impact of neonatal overfeeding on cognitive functions and neurosteroidogenesis in male rats. Offspring were assigned to either small litters (SL; 4 pups/mother), resulting in increased milk intake and body weight gain, or normal litters (NL; 10 pups/mother). On postnatal day (PND) 21, half of the male rats were euthanized, while the remaining were kept under standard conditions (4 rats/cage) until PND70. At this stage, subjects underwent assessments for locomotor activity, anxiety levels via the elevated plus maze, and episodic-like memory (ELM) tests. By PND90, the rats were euthanized for brain dissection. Utilizing micropunch techniques, dentate gyrus (DG), CA1, and CA3 regions were extracted for analysis of mRNA expression and methylation patterns. At PND21, SL rats exhibited increased body and adipose tissue weights, alongside elevated cholesterol, glucose, and triglyceride levels compared to NL counterparts. By PND90, although metabolic disparities were no longer evident, SL rats demonstrated heightened anxiety-like behavior and diminished performance in ELM tests. Early life changes included a decreased expression of aromatase (P450arom) and 3α-HSD in CA1, with increased levels in CA3 and DG among SL rats. Additionally, PND90 rats from SL exhibited increased P450arom and decreased 5α-reductase 1 (5αR-1) expression in DG. Notably, some of these variations were correlated with changes in methylation patterns of their promoter regions. Our findings reveal that neonatal overfeeding exerts a long-term adverse effect on cognitive abilities and neurosteroidogenic pathways, underscoring the lasting impact of nutritional experiences during critical early postnatal development periods.

High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 dams

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Frequency of a Positive Cerebrospinal Fluid Study in Patients Presenting With Febrile Seizures

Background: Febrile seizures are a common neurological condition in pediatric practice, affecting 2-5% of children globally. These seizures occur in the context of fever without evidence of central nervous system infection or metabolic disturbance. While often benign, febrile seizures are associated with significant morbidity and can cause considerable distress for both patients and caregivers. The role of cerebrospinal fluid (CSF) abnormalities in the pathogenesis of febrile seizures is not well understood, but identifying these factors may help predict the risk of seizure occurrence. Objective: To determine the frequency of positive cerebrospinal fluid abnormalities in pediatric patients with febrile seizures and to assess the impact of these abnormalities on the risk of febrile seizures. Methods: This prospective cohort study was conducted from January 2022 to December 2023 at the Department of Paediatrics, Combined Military Hospital, Rawalpindi. A total of 117 pediatric patients aged 1 to 12 years with a history of febrile seizures presenting with a febrile illness were included. Patients with prior febrile seizures, metabolic/electrolyte disorders, or signs of meningeal infection were excluded. Comprehensive data collection included demographic information, clinical history, and CSF analysis for cell count, total protein, glucose, lactate, and electrolyte levels. Patients were monitored for febrile seizure occurrence during hospitalization. Data were analyzed using SPSS version 25, with continuous variables expressed as medians and interquartile ranges (IQR) and categorical variables as frequencies and percentages. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between CSF abnormalities and febrile seizures. Results: The median age of the patients was 3.0 years (IQR: 2.0), with 57.3% (n=67) being male. Febrile seizures occurred in 22.2% (n=26) of patients during hospitalization. Elevated CSF total protein (&gt;60 mg/dL) was observed in 28.2% of patients, CSF glucose (&gt;42 mg/dL) in 12.0%, CSF lactate (&gt;2.0 mmol/L) in 13.7%, and CSF calcium (&gt;1.25 mmol/L) in 10.3%. These abnormalities were significantly associated with an increased risk of febrile seizures: CSF total protein (OR: 3.55, 95% CI: 1.42–8.86, p=0.005), CSF glucose (OR: 13.59, 95% CI: 3.79–48.71, p&lt;0.001), CSF lactate (OR: 4.61, 95% CI: 1.53–13.92, p=0.004), and CSF calcium (OR: 15.52, 95% CI: 3.81–63.36, p&lt;0.001). Conclusion: This study identified significant associations between elevated CSF total protein, glucose, lactate, and calcium levels and an increased risk of febrile seizures in pediatric patients. CSF analysis could be a valuable tool in identifying children at higher risk for febrile seizures, potentially guiding preventive strategies and clinical management.

Causal link between metabolic related factors and osteoarthritis: a Mendelian randomization investigation.

Metabolic syndrome (MetS) is significantly associated with osteoarthritis (OA), especially in MetS patients with blood glucose abnormalities, such as elevated fasting blood glucose (FG), which may increase OA risk. Dietary modifications, especially the intake of polyunsaturated fatty acids (PUFAs), are regarded as a potential means of preventing MetS and its complications. However, regarding the effects of FG, Omega-3s, and Omega-6s on OA, the research conclusions are conflicting, which is attributed to the complexity of the pathogenesis of OA. Therefore, it is imperative to thoroughly evaluate multiple factors to fully understand their role in OA, which needs further exploration and clarification. Two-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were employed to examine the causal effect of metabolic related factors on hip OA (HOA) or knee OA (KOA). The exposure and outcome datasets were obtained from Open GWAS IEU. All cases were independent European ancestry data. Three MR methods were performed to estimate the causal effect: inverse-variance weighting (IVW), weighted median method (WMM), and MR-Egger regression. Additionally, the intercept analysis in MR-Egger regression is used to estimate pleiotropy, and the IVW method and MR-Egger regression are used to test the heterogeneity. The UVMR analysis revealed a causal relationship between FG and HOA. By MVMR analysis, the study discovered a significant link between FG (OR = 0.79, 95%CI: 0.64∼0.99, p = 0.036) and KOA after accounting for body mass index (BMI), age, and sex hormone-binding globulin (SHBG). However, no causal effects of FG on HOA were seen. Omega-3s and Omega-6s did not have a causal influence on HOA or KOA. No significant evidence of pleiotropy was identified. The MR investigation showed a protective effect of FG on KOA development but no causal relationship between FG and HOA. No causal effect of Omega-3s and Omega-6s on HOA and KOA was observed. Shared genetic overlaps might also exist between BMI and age, SHBG and PUFAs for OA development. This finding offers a novel insight into the treatment and prevention of KOA from glucose metabolism perspective. The FG cutoff value should be explored in the future, and consideration should be given to demonstrating the study in populations other than Europeans.

Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease and Cardiometabolic Risk Factor in US Adolescents.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is widespread worldwide, and a strong link between MASLD and cardiometabolic risk factors (CMRFs) was emphasized. This study characterized the prevalence of MASLD in adolescent population and overlapping CMRFs conditions in MASLD. This is a cross-sectional study of US adolescents aged 12--19 years in the 2017-2020 cycles of the National Health and Nutrition Examination Survey. The relationship between CMRFs and liver steatosis, evaluated by the median controlled attenuation parameter (CAP), was assessed. The prevalence of MASLD in adolescents was 23.77%. Isolated overweight/obesity (35%) was the top CMRF. Non-Hispanic Black patients had the highest proportion of overweight/obesity plus elevated glucose (24%), while non-Hispanic Asian had the highest burden of dyslipidemia (2%, 14%, and 19%). Except hypertension, overweight/obesity (β=48.7; 95% CI, 43.4-54.0), hypertriglyceridemia (β=15.5; 95% CI, 7.2-28.3), low HDL-C (β=10.0; 95% CI, 3.1-16.9), elevated glucose (β=6.9; 95% CI, 0.6-13.2) were all significantly associated with increased CAP values. Increased CAP was linked to the synergistic interactions between overweight/obesity and dyslipidemia or elevated glucose (overweight/obesity and elevated glucose: RERI=8.21, AP=0.45, SI=1.91; overweight/obesity and hypertriglyceridemia: RERI=19.00, AP=0.69, SI=3.53; overweight/obesity and low HDL-C: RERI=10.83, AP=0.58, SI=2.61). Adolescents with combination of overweight/obesity, dyslipidemia (β=15.1; 95% CI, 0.1-30.2) and combination of overweight/obesity, dyslipidemia and elevated glucose (β=48.0; 95% CI, 23.3-72.6) had a significantly higher CAP values. The prevalence of MASLD was alarmingly high in adolescents, and overweight/obesity was the most important CMRF. Overweight/obesity and dyslipidemia or elevated glucose had positive additive interaction effects on liver steatosis.

RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade

BackgroundObesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated.MethodsIn this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo.ResultsIn hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling.ConclusionsOur study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.Graphical

Association of Elevated Perioperative Blood Glucose With Complications and Postoperative Outcomes Following Traumatic Spine Surgery.

Perioperative blood glucose control has been demonstrated to influence outcomes following spine surgery, though this association has not been fully elucidated in patients with traumatic spine injuries. This study sought to determine the association between perioperative blood glucose levels and complications or outcomes in patients undergoing spine surgery due to injury. A retrospective review was conducted to identify patients who underwent spine surgery due to traumatic injuries between 1 March 2020 and 29 September 2022 at a single academic institution. Descriptive factors, complications, and outcomes were compared between those with a postoperative blood glucose level of <200 mg/dL and those with a preoperative glucose of <200 mg/dL. Patients with a post- and preoperative blood glucose of ≥200 mg/dL had significantly higher odds of respiratory complications (OR = 2.1, 2.1, P = 0.02, 0.03), skin/wound complications (OR = 2.2, 2.8, P = 0.04, 0.03), and increased hospital length of stay (OR = 9.6, 12.1, P = 0.02, 0.03) compared with those with blood glucose of <200 mg/dL. Those with postoperative glucose ≥200 mg/dL also had significantly higher odds of inpatient mortality (OR = 4.5, P = 0.04) when controlling for confounding factors. Neither pre- nor postoperative blood glucose of ≥200 mg/dL was associated with an improvement in American Spinal Injury Association Impairment Scale score at the final follow-up when controlling for multiple confounding factors (P = 0.44, 0.06). Elevated blood glucose both pre- and postoperatively was associated with an increased rate of postoperative complications and negative postoperative outcomes. However, there was no association between elevated blood glucose levels and neurological recovery following traumatic spinal injury.