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Oxidative Stress in Heat Stress Nephropathy: Crosstalk.2 days agoHeat stress (HS) is a growing public health concern as rising global temperatures and occupational hazards expose a significant portion of the world's population to extreme heat. The kidneys are particularly vulnerable to heat-induced injuries, with oxidative stress (OS) playing a central role in their pathogenesis. The process involves heat-induced mitochondrial dysfunction and stimulation of inflammatory pathways. This leads to the production of excessive reactive oxygen species (ROS) that eventually overwhelm the kidney's natural antioxidant defenses. The resultant OS directly damages lipids, proteins, and DNA in renal tubular cells, a condition that is worsened by systemic inflammation and renal hypoxia. Although cells initially activate protective mechanisms involving heat shock proteins (HSPs) to preserve mitochondrial integrity, prolonged heat exposure undermines these defenses, increasing stress and triggering apoptotic pathways. This article focuses on the impact of HS on kidney health and the role of OS in the pathogenesis of heat-induced kidney injuries. Key markers of heat-induced OS, such as lipid peroxidation products (e.g., malondialdehyde [MDA], F2-isoprostanes, 4-hydroxynonenal [4-HNE], and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) and their effects on hematological indices and inflammatory response are highlighted. Ultimately, clarifying these specific mechanisms is essential to guide the development of early diagnostic tools and targeted treatments. This will help to reduce kidney damage, especially in vulnerable populations. We suggest that strategies such as adequate hydration, educating vulnerable groups on signs of heat strain, wearing light clothing, and heat acclimatization can mitigate the adverse effects of the rising global temperatures on kidney health.Non-Communicable DiseasesCare/Management
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Genomic Alterations and Their Clinical Implications in Pancreatic Ductal Adenocarcinoma in a Large-Scale Chinese Cohort.2 days agoGenomic sequencing has made precision oncology of pancreatic ductal adenocarcinoma (PDAC) feasible and is recommended by numerous clinical guidelines. The clinical significance of genomic alterations in PDAC remains to be revealed. This study was designed to bridge this gap by elucidating the clinical relevance of genomic profiling in a diverse PDAC population. From January 1, 2021 to April 30, 2023, we prospectively collected tumor tissues and peripheral blood from 1135 patients diagnosed with PDAC at Fudan University Shanghai Cancer Center (FUSCC). Germline and somatic mutations were identified using a 676-gene panel. PDAC with KRAS/ARID1A co-mutation was featured with early metastasis and poor prognosis. Patients with BRCA1/2 and PALB2 mutations showed a trend towards improved survival with platinum-containing regimens, although statistical significance was not reached. In contrast, we observed a statistical preference for platinum-containing adjuvant chemotherapy in KRAS wild-type PDAC patients. For the mutational landscape, the current cohort had a lower mutation rate of KRAS, while mutations related to the WNT, Hippo, and PI3K signaling pathways were more prevalent, compared with Caucasian PDAC. Somatic RAD50 p.L719fs, ATR p.I774fs, and germline RAD51D p.K91fs were homologous recombination repair (HRR) gene mutations enriched in this Chinese cohort relative to reported Caucasian series. These results highlighted that genomic sequencing could guide the management of PDAC, including prognosis prediction and chemotherapy regimen selection. Trial Registration: Chinese Clinical Trial Registry registration number: ChiCTR2500097983.Non-Communicable DiseasesCancerCare/Management
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Efficacy of second generation capacitive-resistive non-invasive radiofrequency in improving perfusion index and attenuating lower limb painful diabetic peripheral neuropathy.2 days agoDiabetic peripheral neuropathy is a prevalent consequence of diabetes mellitus that impairs quality of life. This study aimed to investigate the impact of second generation capacitive-resistive non-invasive radiofrequency (transfer of energy capacitive and resistive, TECAR) therapy as a non-invasive modality to increase peripheral perfusion assessed using pulse oximetry by measuring the perfusion index (PI), and to improve pain in patients with painful diabetic peripheral neuropathy (PDPN).
A prospective interventional study was performed in the outpatient clinic of a tertiary care hospital. Twenty-three patients of both sexes, aged 40-70 years, with type 2 diabetes mellitus (T2DM) and PDPN in the lower limbs, with Visual Analogue Scale (VAS) ≥3 in the feet, were included in the study. All patients received 12 sessions of TECAR therapy over four weeks under PI monitoring of the big toe on the targeted side. The change in PI at the end of the first session was defined as a primary outcome. Pain scoring and analgesic effect at the end of all sessions were set as secondary outcomes.
PI increased significantly after each session compared to the session before VAS showed significant improvement from the third session onward, lasting for one month after the 12th session. Tactile sensation showed significant improvement from the fourth session through the end of the sessions. By the end of the sessions, 18 patients (78.3%) achieved complete remission, with a significant Difference compared to baseline (P value <0.001). The Total Remission Rate was 82.08±11.33%.
TECAR therapy is proposed as an effective, safe, and non-invasive approach for improving symptoms of peripheral neuropathy associated with T2DM.DiabetesDiabetes type 2AccessCare/ManagementAdvocacy -
Dietary perceptions and challenges in the management of type 2 diabetes in rural communities of the Eastern Cape, South Africa: a qualitative study.2 days agoDiabetes mellitus (DM) is an increasing public health concern globally, particularly in low- and middle-income countries (LMICs). Socioeconomic challenges complicate disease management. Dietary management is central to diabetes care; however, adherence to recommended dietary practices remains difficult in many rural and resource-constrained settings. This study explored perceptions of healthy eating and barriers influencing dietary practices among individuals living with diabetes in rural communities of the Mnquma sub-region in the Eastern Cape (EC), South Africa (SA). A qualitative descriptive study was conducted among adults diagnosed with type 2 diabetes attending four primary healthcare clinics. Purposive sampling was used to recruit 35 participants. Data were collected through semi-structured interviews conducted in IsiXhosa or English, audio-recorded, transcribed verbatim, translated into English, and analysed using thematic analysis. Four major themes and fifteen sub-themes emerged: knowledge and perceptions of diabetes and healthy eating; emotional and psychological factors affecting eating habits; structural, economic, and environmental barriers to healthy eating; and the role of healthcare providers and support systems. Understanding of diabetes and healthy eating, with dietary practices often shaped by personal experiences rather than formal health education. Emotional responses to diagnosis, including fear and distress, influenced self-management behaviours. Financial insecurity, food insecurity, household food practices, agricultural instability, competing health conditions, and inconsistent dietary information emerged as major barriers to healthy eating. Although healthcare professionals were viewed as trusted sources of information, participants reported limited dietary counselling and fragmented health messages, while family support varied across households. These findings highlight that healthy eating among individuals living with diabetes in rural Mnquma is shaped by complex interactions between knowledge, emotional experiences, socioeconomic conditions, and health system support. While consistent with the Theory of Planned Behaviour (TPB), the results also highlight the importance of broader socioecological influences in shaping behaviour in resource-constrained settings. These findings underscore the need for context-sensitive diabetes interventions that extend beyond individual-level education to strengthen family and community support, improve dietary counselling within primary healthcare, and address broader socioecological and structural determinants, including food insecurity, poverty, and constrained food environments in rural settings.DiabetesAccess
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Health Disparities Among Hispanic Patients With Type 2 Diabetes in the United States: An Educational Workshop.2 days agoType 2 diabetes (T2D) is a major health concern for Hispanic populations in the United States. Hispanic patients experience a higher prevalence of T2D and more severe outcomes than non-Hispanic White populations, driven largely by systemic and structural factors such as limited access to care, insurance coverage gaps, language barriers, and social determinants of health. Access to culturally responsive and humility-based health care approaches remains limited, hindering patient-centered care.
Using the 6-step Kern model, we designed, implemented, and evaluated a 60-minute interactive workshop to educate first- and second-year preclinical medical students about T2D in Hispanic patients. The workshop included a presentation, case-based discussions, a large-group debriefing, and pre- and postsession evaluations. Statistical analysis assessed changes in participant knowledge and confidence.
Following an initial virtual pilot session, the revised curriculum was delivered in person. Medical students completed pre- and postsession evaluations. The Mann-Whitney U test demonstrated significant increases in confidence across all learning objectives (P < .01). Knowledge scores also improved from pre- to postsession evaluations. Overall, 91% of participants rated the workshop as good or excellent. Feedback highlighted the value of content and structure, with suggestions to expand case discussions and introduce more varied activities.
The workshop effectively demonstrated an increase in medical student awareness of preventing and managing T2D among Hispanic patients. It emphasized cultural humility and provided a framework for exploring complex social, cultural, and structural factors. This workshop can be adapted for prehealth students, residents, or practicing physicians working with Hispanic patients.DiabetesDiabetes type 2AccessAdvocacy -
Exploration of the causal relationship between inflammatory cytokines and type 2 diabetes via mendelian randomization and polygenic score.2 days agoTo investigate the potential causal relationship between inflammatory cytokines and type 2 diabetes (T2D) using two-sample Mendelian randomization (MR) and to explore the transferability of inflammatory genetic susceptibility in a Mongolian population through polygenic score (PGS) analysis.
A two-sample MR analysis was conducted using genome-wide association study (GWAS) summary statistics. Inflammatory cytokine data were obtained from protein quantitative trait locus GWAS datasets (GCST90274758-GCST90274848), and T2D summary statistics were derived from the IEU Open GWAS database (ebi-a-GCST006867). The inverse variance weighted method was used as the primary MR approach, complemented by sensitivity analyses. In an independent Mongolian cohort (N = 351), a PGS was constructed from directly genotyped cytokine-associated SNPs. We assessed PGS-T2D associations using logistic regression adjusted for age, sex, and principal components (PCs), with sensitivity analyses to determine the optimal PC number.
In the European population, genetically predicted higher FGF-21 levels were associated with an increased risk of T2D (OR = 1.141, 95% CI: 1.032-1.261, P = 0.010), and IL-5 also showed a positive association with T2D risk (OR = 1.114, 95% CI: 1.004-1.237, P = 0.042). In contrast, ARTN, CD5, CSF-1, CXCL10, CXCL9, FGF-19, and SLAMF1 were associated with lower T2D risk. In the Mongolian population, the PGS for inflammation-related cytokine levels demonstrated a significant association with T2D status across models adjusting for 0 to 6 principal components (all P< 0.05). In the full model (adjusted for age, sex, and the first 4 PCs), each 1-SD increase in the PGS corresponded to a 25.4% increase in the odds of T2D (OR = 1.254, 95% CI: 1.005-1.575, P = 0.048; AUC = 0.625). These findings are suggestive and exploratory, necessitating further validation in independent cohorts.
This study identified nine inflammatory cytokines with potential causal associations with T2D in European populations. Notably, in a Mongolian cohort, a PGS for genetically predicted cytokine levels showed a modest yet independent association with T2D risk after controlling for population stratification. These cross-population findings warrant replication in larger-scale studies.DiabetesDiabetes type 2AccessAdvocacy -
Profile of Acute Kidney Injury Patients Admitted to a Tertiary Care Centre in Urban South India: A Prospective Observational Study.2 days agoAcute kidney injury (AKI) is a common clinical syndrome associated with significant morbidity, mortality, and healthcare burden. Data regarding the prevalence, causes, and outcomes of AKI in tertiary care settings in South India remain limited. This study aimed to evaluate the prevalence, aetiology, clinical profile, and in-hospital outcomes of AKI among adults admitted to a tertiary care centre.
This prospective observational study was conducted over 18 months among adult patients admitted to the general medicine wards of a tertiary care hospital in South India. Patients fulfilling the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria for AKI were enrolled. Demographic, clinical, laboratory, and outcome data were collected using a structured proforma. AKI was classified as pre-renal, intrinsic renal, or post-renal based on clinical and laboratory findings. Statistical analysis was performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA), with p<0.05 considered statistically significant.
Among 2,427 hospital admissions, 65 patients met KDIGO criteria for AKI, yielding a prevalence of 2.67%. Most patients were male (44, 67.7%), and the most affected age group was 51-65 years (24, 36.9%). Type 2 diabetes mellitus (29, 44.6%) and hypertension (26, 40.0%) were the most common comorbidities. Sepsis was the leading aetiology (32, 49.2%), followed by cardiac failure (12, 18.5%) and chronic liver disease (5, 7.7%). Pre-renal AKI accounted for 34 (52.3%) cases, intrinsic renal AKI for 28 (43.1%), and post-renal AKI for three (4.6%). Complete renal recovery occurred in 28 (43.1%) patients, partial recovery in 22 (33.8%), and in-hospital mortality in 15 (23.1%). Oliguria (p=0.01), hypotension (p<0.001), elevated leukocyte count (p<0.01), blood urea nitrogen (p<0.01), peak serum creatinine (p<0.01), urine sodium (p=0.01), and fractional excretion of sodium (p<0.01) were significantly associated with adverse outcomes.
AKI remains an important cause of morbidity and mortality among hospitalised adults. Sepsis was the predominant aetiology, while hypotension, oliguria, and severe biochemical abnormalities were associated with poor outcomes. Early recognition and prompt management of high-risk patients may improve renal recovery and reduce mortality.DiabetesDiabetes type 2AccessCare/Management -
Epidemiological Pattern and Precipitating Factors of Diabetic Ketoacidosis: A Retrospective Study at King Fahad Specialist Hospital, Buraidah, Saudi Arabia.2 days agoDiabetic ketoacidosis (DKA) is an acute and severe complication of diabetes that results in increased morbidity and utilization of healthcare resources. Understanding the local patterns and triggers of DKA is important for improving prevention and patient care. This study aimed to assess the epidemiological features and precipitating factors of DKA and evaluate their association with disease severity and time to DKA resolution.
A retrospective review of 193 patients with DKA admitted to King Fahad Specialist Hospital, Buraydah, Saudi Arabia, from 2023 to 2025 was conducted. Demographic, clinical, biochemical, and etiological variables were analyzed. Associations between DKA severity and resolution time were assessed using the chi-square test, t-test, ANOVA, and multivariate logistic regression.
Most patients were young, with 90 patients (46.6%) aged <18 years. Moderate DKA was the most frequent presentation, affecting 114 patients (59.1%), followed by mild DKA in 51 patients (26.4%) and severe DKA in 28 patients (14.5%). The mean HbA1c level was 11.9%. Missing insulin doses were the main trigger for DKA in 122 patients (63.2%), followed by respiratory tract infections in 21 patients (10.9%) and newly diagnosed diabetes and not on any medications in 16 patients (8.3%). Severe DKA was associated with lower pH, lower bicarbonate, higher anion gap, higher glucose, more pronounced electrolyte abnormalities, and longer resolution times. The etiology of DKA was not significantly associated with severity (p = 0.644) or duration of resolution (p = 0.052); however, infection-related etiologies showed a trend toward longer recovery times.
Although missing insulin doses were the leading trigger for DKA, precipitating etiology did not significantly influence DKA severity or recovery duration. There was no statistically significant relationship between age, chronic diseases, and DKA severity based on the adjusted regression model. DKA severity was the primary determinant of prolonged resolution time. Strengthening adherence, early diagnosis, and risk‑stratified management is essential to reduce the burden of DKA.DiabetesChronic respiratory diseaseDiabetes type 1AccessCare/Management -
Discriminating prevalent type 2 diabetes among community-dwelling older adults with metabolic dysfunction-associated steatotic liver disease: a comparative analysis of 12 insulin resistance surrogates.2 days agoMetabolic dysfunction-associated steatotic liver disease frequently coexists with type 2 diabetes mellitus (T2DM). Because the gold standard for assessing insulin resistance (IR) is difficult to implement in primary care settings, this cross-sectional study aimed to compare the associations and discriminatory ability of 12 surrogate IR indexes for prevalent T2DM among community-dwelling older adults with metabolic dysfunction-associated fatty liver disease.
This study was based on a health examination cohort from a community in northwestern China and included 2641 eligible participants, of whom 605 were older adults with metabolic dysfunction-associated steatotic liver disease. Multivariable logistic regression, receiver operating characteristic (ROC) curve analysis, restricted cubic spline (RCS) analysis, subgroup analysis, and exploratory internal model-discrimination analyses were performed to evaluate the associations and discriminatory ability of 12 surrogate IR indexes for prevalent T2DM.
After multivariable adjustment, TyG, TyG-ABSI, TyG-WWI, and TyG-WC were significantly associated with prevalent T2DM in participants with metabolic dysfunction-associated steatotic liver disease (all P < 0.05). TyG showed the highest discriminatory ability (AUC = 0.726, 95% CI: 0.686-0.766), with an optimal cut-off value of 9.225. After Bonferroni correction, it performed significantly better than the other indicators. Sensitivity analyses addressing the mathematical coupling between TyG and T2DM diagnostic criteria confirmed the robustness of these findings. Even after excluding T2DM cases defined solely by fasting plasma glucose, TyG remained the best-performing index (AUC = 0.707). RCS analyses showed significant overall associations but did not support statistically significant nonlinearity for TyG, TyG-ABSI, TyG-WWI, or TyG-WC (all P-nonlinear > 0.05). No significant interactions were observed in subgroup analyses.
TyG, TyG-ABSI, TyG-WWI, and TyG-WC were associated with prevalent T2DM and showed moderate discriminatory ability. Sensitivity analyses addressing the shared FPG component confirmed the robustness of these associations. These findings support TyG as a simple, integrated metabolic marker for alerting to prevalent T2DM in this population.DiabetesDiabetes type 2AccessAdvocacy -
Association between CTLA-4 gene polymorphisms and Type 1 diabetes in Kurdish patients.2 days agoType 1 diabetes (T1D) is an increasingly complex disease influenced by both genetic and environmental triggers, leading to overactivity of the immune system. This preliminary study was conducted to investigate the association of two common cytotoxic T lymphocyte antigen-4 (CTLA-4) variants with T1D susceptibility in the Kurdish population of Iraq. Additionally, we evaluated the correlation between these polymorphisms and anti-GAD antibody positivity, as well as their possible influence on CTLA-4 gene expression. In this study, 52 patients (28 males and 24 females) with T1D and 21 healthy control subjects were genotyped for two (CTLA-4) SNPs, A>G (rs231775) and -318 C>T (rs5742909), using direct DNA sequencing. Furthermore, serum anti-GAD antibody levels were measured by ELISA technique, and the expression of CTLA-4 levels was assessed with quantitative real-time PCR. We discovered that the A>G (rs231775) variant was significantly associated with T1DM. The G allele frequency was significantly higher in type 1 diabetes patients (36.5%, P = 0.0188). The -318 C/T polymorphism showed no significant differences between groups. The GG genotype of the +49A/G polymorphism exhibited a greater prevalence in anti-GAD positive patients relative to negative individuals (77.78% vs. 22.22%), indicating an elevated risk trend (OR = 2.77, 95% CI: 0.51-14.91); however, this finding did not achieve statistical significance (P = 0.28). The (CTLA-4) mRNA gene expression was observed to be non-significantly elevated in T1D relative to the control group (p = 0.1239). Our data indicate that the G allele of the CTLA-4 + 49 A>G variant is associated with increased T1D susceptibility in the Kurdish population, while the genotypic association showed a nominal trend.DiabetesDiabetes type 1AccessAdvocacy