Magnesium is an essential mineral required for energy metabolism, glucose regulation, cardiovascular function, bone integrity, and neural activity. Despite the vital physiological roles of magnesium, , dietary magnesium deficiency remains a widespread and underrecognized global public health concern. The recommended dietary allowance (RDA) for adults in the United States is approximately 420 mg/day for men and 320 mg/day for women, yet large proportions of the population fail to meet these levels with national nutrition surveys consistently documenting inadequate intake. For instance, 64.4% of Chinese adults consume less than the estimated average requirement (EAR) of 270 mg/day for both males and females. Globally, an estimated 2.4 billion people, or roughly 31% of the global population, fail to meet the recommended magnesium intake levels. This deficiency reflects multiple converging factors, including modern dietary patterns low in whole grains and vegetables, soil nutrient depletion from intensive agriculture, food processing losses, aged populations, chronic diseases, and socioeconomic disparities. The health implications are substantial, as magnesium deficiency is associated with elevated risks of cardiovascular disease, metabolic disorders, bone loss, and neuropsychiatric conditions. This review synthesizes current evidence on the biological importance of magnesium, global intake patterns, and determinants of deficiency, and discusses strategic interventions (such as dietary diversification, food fortification, biofortification, supplementation, and public health policies) to enhance magnesium nutrition and reduce the burden of noncommunicable diseases worldwide.

Hypertension is the most common chronic non-communicable disease and one of the most significant risk factors for cardiovascular and cerebrovascular diseases. Sphingosine (SPH) is a central bioactive lipid metabolite positioned at the crucial intersection of ceramide and sphingosine-1-phosphate (S1P) synthesis is increasingly implicated in cardiometabolic health. However, its precise role in the pathophysiology of hypertension and its interplay with inflammatory pathways remain largely unknown. This study aimed to research the therapeutic effects of SPH in hypertension and to explore its underlying mechanisms, focus on a key driver of sterile inflammation that the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway.

An Angiotensin II (Ang II)-induced hypertensive mouse model and an in vitro model using human umbilical vein endothelial cells (HUVECs) were established. The effects of SPH administration on Ang II-induced hypertension, end-organ damage, and the activation status of the NLRP3 inflammasome were systematically evaluated.

In vivo, Ang II infusion triggered significant hypertension, cardiac hypertrophy, and aortic fibrosis, which was accompanied by activation of the NLRP3 inflammasome in cardiovascular tissues. Therapeutic administration of SPH, in a manner comparable to the specific NLRP3 antagonist MCC950, markedly lowered blood pressure and attenuated these pathological changes. In vitro, SPH treatment effectively suppressed Ang II-induced NLRP3 inflammasome activation.and released of pro-inflammatory cytokines in HUVECs. Furthermore, SPH exhibited direct protective effects on the endothelium by promoting HUVEC proliferation and against Ang II-induced injury. Mechanistically, SPH suppressed the expression and activation of key inflammasome components, including NLRP3, cleaved Caspase-1, and mature IL-1β and IL-18.

This study reveals a novel protective role for Sphingosine in hypertension, acting via the suppression of the NLRP3 inflammasome pathway to decrease inflammation and oxidative stress. These findings explore a new mechanistic link between sphingolipid metabolism and blood pressure regulation and highlight SPH as a potential therapeutic agent for targeting the critical series of metabolic dysregulation and inflammation in hypertensive cardiovascular disease.

PRECIDENTD (PRevention of CardIovascular and DiabEtic KidNey Disease in Type 2 Diabetes) is a PCORnet® Study evaluating 2 classes of medications, SGLT2 inhibitors and GLP-1 receptor agonists, among people with type 2 diabetes. Participants obtain their assigned medication through their health insurance and complete semi-annual study assessments.

We engaged multiple partners to develop a centralized text message-based program to facilitate adherence and retention in PRECIDENTD and evaluated its performance from April 2024 to April 2025.

The PRECIDENTD study team applied best practices in digital health tool design and built the program with technology company MEMOTEXT. Patient partners identified program goals, co-wrote message content, and completed internal testing. We then deployed the program to PRECIDENTD participants and analyzed responses.

We assessed response rate to interactive text messages, proportion of messages flagging participants needing additional support, and the adherence problems identified.

The text messaging program includes interactive messages querying if participants are taking the study medication, as well as one-way study timeline messages. During the first year, 450 PRECIDENTD participants across 20 sites received texts. Interactive message response rate was 80%, and 25% of responses identified problems (ie, trouble getting fills/refills and experiencing a health concern or side effect), prompting an outreach call.

We co-designed a digital tool that engaged participants and helped identify study participants needing assistance obtaining and adhering to study medications. Collaborative development of similar centralized tools may augment the capacity of national studies to answer important comparative effectiveness research questions.

Type 2 diabetes is a global health issue, with unique challenges in Qassim, Saudi Arabia. Patients face barriers such as lifestyle, diet, healthcare access, and psychological impacts. Understanding these challenges is crucial for improving diabetes care and support.

The aim of this study was to explore the challenges and barriers faced by patients in managing Type 2 diabetes at a University Hospital in Qassim, Saudi Arabia, to provide insights for improving diabetes care and support.

A qualitative descriptive phenomenological design used semi-structured interviews and purposive sampling. Face-to-face interviews (Sept 2024-Jan 2025) were audio recorded and transcribed verbatim. Data were analyzed using Collaizi's thematic analysis.

This study provides a comprehensive understanding of the key challenges and facilitators influencing the management of Type 2 diabetes. Thematic analysis identified five core themes: Challenges in Adapting Lifestyle and Behavior, Dietary Struggles and Social Pressures, Barriers to Effective Healthcare and Medication Use, Psychological and Emotional Burden of Diabetes, and Gaps in Patient Education and Support for Self-Management. Participants faced challenges of balancing self-care with work and social duties, dietary struggles tied to culture, healthcare barriers, emotional distress, and the vital role of education in disease management.

A patient-centered approach is key to managing Type 2 diabetes in Qassim, Saudi Arabia. Addressing lifestyle, healthcare, and psychological challenges can improve self-management and outcomes. Providers should offer tailored education, enhance care access, and support emotional and social needs. Policies should promote culturally sensitive, community-based interventions to improve adherence and quality of life.

Major lower extremity amputations are frequently performed for end-stage peripheral arterial disease and progressive diabetic foot complications. Wound complications after amputation affect up to one-third of limbs. The patient cohort undergoing amputation are typically high risk for poor wound healing, often with unmodifiable risk factors in an urgent clinical setting. Incisional negative pressure wound therapy (NPWT) has been shown to reduce wound complications in other high-risk populations. This randomized controlled trial investigates whether prophylactic NPWT reduces wound complications in patients after major amputation compared with standard dry dressings.

This protocol describes a prospective, multicentre, randomized controlled trial with an internal pilot recruiting patients undergoing major lower extremity amputation for any indication. Limbs will be randomized to receive either a single-use NPWT device on their closed surgical incision or a dry dressing. The primary clinical outcome is the rate of wound complications. Secondary outcomes include reoperation rates, length of hospital stay, cost-effectiveness of NPWT, and patient-reported quality of life. Follow-up will continue to 6 months after surgery. The initial pilot phase has a recruitment target of 96 limbs, whereas an estimated 728 patients will be required to power a definitive trial adequately.

This trial aims to supplement the existing poor-quality data on this important aspect of care and equip healthcare professionals to make cost-effective decisions regarding postoperative wound management.

This study assessed the long-term clinical benefits and cost savings associated with achieving composite treatment targets (CTT) of stringent glycemic control, weight reduction and no hypoglycemia in predominantly Chinese patients with Type 2 Diabetes (T2D) inadequately controlled with metformin and/or sulfonylurea.

The study was conducted using an implementation of the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS OM2) in Microsoft Excel, with additional modules for treatment switching, weight change, and hypoglycemia. Thirty-year healthcare costs were projected to capture macro- and microvascular complications, hypoglycemia and diabetic treatment. Baseline and efficacy inputs were extracted from the SURPASS-AP-Combo trial (NCT04093752), a predominantly Chinese cohort. Cost inputs were derived from literature review. Patients were categorized as "Achieved" or "Failed" based on whether they met the CTT (i.e. HbA1c ≤6.5%, ≥10% weight reduction, and no hypoglycemia event [blood glucose < 3.0 mmol/L or severe hypoglycemia]) at the end of SURPASS-AP-Combo trial, regardless of treatment received. For the Achieved group, sustained CTT was assumed for 3, 5, or 10 years before natural disease progression per UKPDS OM2 progression trajectories. The Failed group followed UKPDS OM2 progression trajectories throughout. Treatment intensification to basal-bolus insulin was triggered when HbA1c levels reached predefined CTT-based thresholds. Scenario analyses applied less stringent CTT.

Sustained achievement of CTT for 3, 5 and 10 years yielded 0.31, 0.40 and 0.56 quality-adjusted life years (QALYs) and cost savings of ¥22,336, ¥32,692, ¥53,234 per patient, respectively. These savings were attributable to reduced complications, hypoglycemia and delayed treatment intensification. Slightly smaller savings were observed applying less stringent CTT.

In this modeling study, a sustained achievement of CTT led to improved clinical benefits and significant direct medical cost savings. The longer the achievement period and the more stringent CTT, the greater the clinical benefits and cost savings.

One of the surgical treatment options for advanced ankle joint destruction with various etiologies is the total joint replacement. Its significant upside is the preservation of range of motion of the ankle joint and less stress on forefoot joints compared to ankle arthrodesis. Since 2022, we have been using the Zimmer Trabecular Metal Total Ankle inserted via a lateral transfibular approach. This study aims to evaluate the initial outcomes and experience with this implant.

Between 2022 and 2024, 65 total ankle replacements were performed in 63 patients using the lateral transfibular approach. Long oblique osteotomy is newly performed in the frontal plane, replacing the original type of osteotomy in the sagittal plane. After releasing and removing the distal fragment of the fibula distally and dorsally, the lower limb and ankle are placed in an alignment frame, which is fixed with Steinmann pins to the calcaneus, anterior border of the tibia, and the talus bone. The centre of rotation of the ankle is identified using the side bars anchored in the frame. Using the burs, guided by Cutting Guides that are locked to the frame, the talus and distal tibia are removed. After testing, rail holes are drilled in the resected surfaces for the original implants. After releasing the tourniquet, the original components are inserted and osteosynthesis of the fibula is performed. During the study, the previously performed fibula osteosynthesis with LCP was replaced by lag screws. Postoperatively, the ankle is supported with a brace for the period of 5 weeks, after which the patient is permitted to fully weight-bear.

A total of 63 patients (32 women and 31 men) were followed, in whom 65 total ankle replacements were performed. The mean age of the patient was 56 years (age range 30 to 80 years). The mean follow-up period was 14.6 ± 9.3 months (3 to 38 months). The most frequent indication was post-traumatic ankle arthritis, namely in 46 cases (70.8%). Furthermore, there were 5 patients (7.7%) with post-traumatic ankle ankylosis, 9 patients (13.8%) with primary osteoarthritis, and in 5 patients (7.7%) the indication was the damage caused by rheumatoid arthritis. Deep bacterial infection of the prosthesis requiring revision was reported in 3 cases (4.6%). Superficial infection of the surgical wound was seen in 4 other cases (6.2%), which did not require hospitalization. Plate osteosynthesis of the fibula was removed in 7 cases (13.8%), 5 times due to infection and 2 times due to soft tissue irritation. One case of asymptomatic non-union of fibula was observed.

The benefit of total ankle replacement is the preservation of motion of the operated joint, whereas the complication rate is twice as high as in arthrodesis. Contraindications for ankle replacement include significant varus and valgus deformities of the ankle, ankle instability, necrosis of the talus, severe diabetes mellitus, and severe limb ischemia. The advantage of the transfibular approach is the ability to partly correct deformities of the ankle joint and the position of varus or valgus. It provides a better view of the dorsal structures of the ankle and allows accurate identification of the centre of rotation. Another advantage is the low thickness of the components, requiring minimal bone resection. The main disadvantage is the longer operative time and longer learning curve. Other disadvantages include the complications associated with osteosynthesis and fibula healing, such as non-union or soft tissue irritation by plate. The incidence of superficial and deep infection is also slightly higher compared to the anterior approach.

The Zimmer Trabecular Metal Total Ankle system is one of the treatment options for ankle joint destruction provided it is correctly indicated. However, the surgical procedure is a challenge and requires an experienced surgeon. When the indication is correct, the system brings very good short-term outcomes. Nonetheless, longer follow-up period is necessary since the incidence of complications will certainly increase over time.

Diabetic peripheral neuropathy (DPN), a prevalent microvascular complication of diabetes mellitus, poses a substantial clinical burden and has a detrimental impact on quality of life. This triple-blind, randomized, placebo-controlled trial investigated the effects of an 8-week supplementation with selenium-enriched yeast on DPN symptoms, neuropathy severity, pro-oxidant-antioxidant balance (PAB), and sexual satisfaction in individuals aged 40-70 years with DPN.

Fifty participants were randomized in a 1:1 ratio to receive either a daily 200 μg dose of Saccharomyces cerevisiae yeast-derived selenium (in a 500 mg capsule) or a placebo. Outcomes were assessed using validated tools: The Michigan Neuropathy Screening Instrument (MNSI) for symptoms, the Toronto Clinical Scoring System (TCSS) for severity, the Larson Sexual Satisfaction Questionnaire (LSSQ), and serum PAB levels via a specialized assay. Analyses followed a modified intention-to-treat approach, with ANCOVA and logistic regression used to adjust for confounders.

Post-intervention, both groups exhibited significant reductions in neuropathy symptoms (selenium: p < 0.001; placebo: p = 0.001), though intergroup differences were non-significant [adjusted mean difference (aMD): -0.92; 95% CI: -1.9 to 0.10]. Neuropathy severity decreased significantly in the selenium group (p = 0.002) but not in the placebo group. While PAB levels declined markedly with selenium (p = 0.001), the between-group difference was non-significant (aMD: -32.1; 95% CI: -66.02 to 1.87). Sexual satisfaction scores improved significantly in the selenium group versus the placebo group (aMD: 8.51; 95% CI: 0.74 to 16.28).

These findings suggest that selenium-enriched yeast supplementation may enhance biochemical markers (PAB) and quality-of-life parameters (sexual satisfaction) in DPN. However, its limited efficacy in improving neuropathy-specific outcomes underscores the need for larger trials to clarify its therapeutic potential.

This trial was registered at the Iranian Registry of Clinical Trials (IRCT20131009014957N10, https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20131009014957N10).

Exosomes are extracellular vesicles that carry a variety of biomolecules, including nucleic acids, proteins, and lipids, and they play a vital role in intercellular communication. These endogenous carriers offer several advantages over conventional nanocarriers, such as liposomes. These advantages include high biocompatibility, low immunogenicity, and the ability to cross biological barriers such as the blood-brain barrier, making them a promising platform for targeted drug delivery. In this review, we systematically summarize the biological characteristics of exosomes, methods for their isolation and purification, strategies for drug loading (including endogenous and exogenous approaches), and surface engineering techniques (such as genetic engineering and chemical modification) to enhance targeting and therapeutic efficacy, based on a comprehensive PubMed literature search. We particularly focus on the modification of engineered exosomes as drug delivery systems in various clinical contexts, covering multiple diseases including cancer, diabetes, neurological diseases, cardiovascular diseases, and tissue repair. Administration routes include oral, subcutaneous, intranasal, and intravenous delivery. While exosomes have shown promise in preclinical studies, challenges remain in terms of large-scale production, standardized isolation, drug loading efficiency, and safety evaluation. Herein, we aim to provide a theoretical foundation and suggest future directions for developing exosomes as a next-generation drug delivery platform.

To determine whether initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA) within 3 months of type 2 diabetes (T2DM) diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index (BMI).

This retrospective cohort study used electronic health records from the TriNetX U.S. research network. Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis. Following 1:1 propensity score matching, both the GLP-1 RA user and non-user groups included 183,264 patients. The study outcome was defined as a diagnosis of malignant neoplasms. Hazard ratios (HRs) for overall and site-specific cancer risk were estimated using Cox proportional hazards models. Kaplan-Meier analysis and stratified analysis by BMI were performed.

Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk (HR 0.93; 95% CI: 0.90-0.96). Reduced risks were noted for cancers of the digestive (HR 0.81), respiratory (HR 0.66), and female genital (HR 0.87) systems. In stratified analysis, benefits were more pronounced in patients with BMI ≥ 30, particularly for pancreatic and colorectal cancers.

Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk, particularly among individuals with obesity. These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.