Search Results (6,090)

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Background: Cognitive decline is a growing public health concern in Latin America, driven by rapid aging, widespread micronutrient inadequacies, and socioeconomic disparities. Despite the recognized importance of nutrition, many older adults struggle to meet daily dietary micronutrients requirements, increasing the risk of mild cognitive impairment (MCI). This study aimed to establish expert consensus on the role of Multivitamin and Mineral supplements (MVMs) in promoting cognitive healthy aging among older adults in Latin America. Methods: A panel of nine experts in geriatrics, neurology, and nutrition applied a modified Delphi methodology to generate consensus statements. The panel reviewed the literature, engaged in expert discussions, and used structured voting to develop consensus statements. Results: Consensus was reached on 14 statements. Experts agreed that cognitive aging in Latin America is influenced by neurobiological, lifestyle, and socioeconomic factors, including widespread micronutrient inadequacies (vitamins B-complex, C, D, E, and minerals such as zinc, magnesium, chromium, copper, iron and selenium), which were identified as critical for global cognitive function and brain structures, yet commonly inadequate in the elderly. While a balanced diet remains essential, MVMs can be recommended as a complementary strategy to bridge nutritional gaps. Supporting evidence, including the COSMOS-Mind trials, demonstrate that MVM use improves memory and global cognition, and reduces cognitive aging by up to 2 years in older adults. Conclusions: MVMs offer a promising, accessible adjunct for cognitive healthy aging in Latin America’s elderly population, particularly where dietary challenges persist. Region-specific guidelines, public health initiatives, and targeted research are warranted to optimize outcomes and reduce health inequities. Full article

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Biofilms, structured communities of microorganisms encased in an extracellular matrix, are a major cause of persistent infections, particularly when formed on medical devices. This study investigated the kinetics of biofilm formation by Escherichia coli and Pseudomonas aeruginosa, two clinically significant pathogens, on two medical-grade polymers: polyether ether ketone (PEEK) and polyamide 12 (PA12). Using a modified crystal violet staining method and spectrophotometric quantification, we evaluated biofilm development over time on polymer granules and catheter segments composed of these materials. Results revealed that PEEK surfaces supported significantly more biofilm formation than PA12, with peak accumulation observed at 24 h for both pathogens. Conversely, PA12 demonstrated reduced bacterial adhesion and lower biofilm biomass, suggesting surface characteristics less conducive to microbial colonization. Additionally, the study validated a reproducible protocol for assessing biofilm formation, providing a foundation for evaluating anti-biofilm strategies. While the assays were performed under static in vitro conditions, the findings highlight the importance of material selection and early prevention strategies in the design of infection-resistant medical devices. This work contributes to the understanding of how surface properties affect microbial adhesion and underscores the critical need for innovative surface modifications or coatings to mitigate biofilm-related healthcare risks. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

Background/Objectives: Myelodysplastic syndrome (MDS) is a heterogeneous clonal hematopoietic disorder characterized by ineffective hematopoiesis and leukemic transformation risk. Current therapies show limited efficacy, with ~50% of patients failing hypomethylating agents. This review aims to synthesize recent discoveries through an integrated network model and examine translation into precision therapeutic approaches. Methods: We reviewed breakthrough discoveries from the past three years, analyzing single-cell multi-omics technologies, epitranscriptomics, stem cell architecture analysis, and precision medicine approaches. We examined cell-type-specific splicing aberrations, distinct stem cell architectures, epitranscriptomic modifications, and microenvironmental alterations in MDS pathogenesis. Results: Four interconnected mechanisms drive MDS: genetic alterations (splicing factor mutations), aberrant stem cell architecture (CMP-pattern vs. GMP-pattern), epitranscriptomic dysregulation involving pseudouridine-modified tRNA-derived fragments, and microenvironmental changes. Splicing aberrations show cell-type specificity, with SF3B1 mutations preferentially affecting erythroid lineages. Stem cell architectures predict therapeutic responses, with CMP-pattern MDS achieving superior venetoclax response rates (>70%) versus GMP-pattern MDS (<30%). Epitranscriptomic alterations provide independent prognostic information, while microenvironmental changes mediate treatment resistance. Conclusions: These advances represent a paradigm shift toward personalized MDS medicine, moving from single-biomarker to comprehensive molecular profiling guiding multi-target strategies. While challenges remain in standardizing molecular profiling and developing clinical decision algorithms, this systems-level understanding provides a foundation for precision oncology implementation and overcoming current therapeutic limitations. Full article

This study aims to develop an optimal underwriting strategy for affordable (H1 and M1) and premium (L1 and M2) electric vehicles (EVs), balancing financial risk and sustainability commitments. The research is motivated by regulatory pressures, risk management needs, and sustainability goals, necessitating an adaptation of traditional underwriting models. The study employs a modified Delphi method with industry experts to identify key risk factors, including accident risk, repair costs, battery safety, driver behavior, and PCAF carbon impact. A sensitivity analysis was conducted to examine premium adjustments under different risk scenarios, categorizing EVs into four risk segments: Low-Risk, Low-Carbon (L1); Medium-Risk, Low-Carbon (M1); Medium-Risk, High-Carbon (M2); and High-Risk, High-Carbon (H1). Findings indicate that premium EVs (L1 and M2) exhibit lower volatility in underwriting costs, benefiting from advanced safety features, lower accident rates, and reduced carbon attribution penalties. Conversely, budget EVs (H1 and M1) experience higher premium fluctuations due to greater accident risks, costly repairs, and higher carbon costs under PCAF implementation. The worst-case scenario showed a 14.5% premium increase, while the best-case scenario led to a 10.5% premium reduction. The study recommends prioritizing premium EVs for insurance coverage due to their lower underwriting risks and carbon efficiency. For budget EVs, insurers should implement selective underwriting based on safety features, driver risk profiling, and energy efficiency. Additionally, incentive-based pricing such as telematics discounts, green repair incentives, and low-carbon charging rewards can mitigate financial risks and align with net-zero insurance commitments. This research provides a structured framework for insurers to optimize EV underwriting while ensuring long-term profitability and regulatory compliance. Full article

Glaucoma is recognized as a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) is considered the only modifiable risk factor, current medical treatments are challenged by issues such as inadequate IOP control and ocular side effects. Rho kinase (ROCK) inhibitors have been developed as a novel pharmacologic class targeting the trabecular meshwork to enhance conventional aqueous humor outflow. In this review, the pharmacokinetics and IOP-lowering efficacy of key ROCK inhibitors are summarized. Beyond IOP reduction, ROCK inhibitors exhibit neuroprotective, anti-inflammatory, antifibrotic, and ocular perfusion-enhancing effects. Finally, we analyzed the limitations and future prospects of ROCK inhibitors in the management of glaucoma. Full article

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by inattention, hyperactivity, and impulsivity, frequently observed in juvenile offenders. This systematic review explores the interplay between ADHD and juvenile delinquency, focusing on behavioural, psychological, and social dimensions. Following the PRISMA guidelines, a systematic literature review was conducted using EBSCO Discovery Service, Science Direct, PubMed, and snowballing techniques. Studies meeting specific inclusion criteria, including juvenile offenders diagnosed with ADHD and comparisons to non-offender or non-ADHD control groups, were analysed. The methodological quality of studies was assessed using the Joanna Briggs Institute appraisal tools. A total of 21 studies were included, highlighting significant associations between ADHD and juvenile delinquency. ADHD symptoms, especially impulsivity and emotional dysregulation, were linked to an earlier onset of offending and higher rates of property crimes. Comorbidities such as conduct disorder, substance use disorder, and depression exacerbated these behaviours. Sociodemographic factors like low education levels and adverse family environments were also critical modifiers. Early intervention and tailored treatment approaches were emphasised to address these challenges. The findings underscore the need for early diagnosis, individualised treatment, and integrative rehabilitation programmes within the juvenile justice system to mitigate long-term risks and promote social inclusion. Full article

Progress in establishing environmental risk factors and, consequently, prophylactic measures for glial tumors, particularly for glioblastomas, is of utmost importance, considering the dismal prognosis and limited treatment options. This report surveyed updates on established and recently identified factors that can predispose a patient to glioma formation while highlighting possible mechanistic links and further research directions. In addition to established factors that increase the risk of glioma, i.e., brain irradiation and several genetic syndromes, another group consists of likely factors contributing to such risks, such as the use of tobacco and those yielding ambiguous results (e.g., UV exposure). Oxidative stress is a common denominator for several types of exposure, and a mechanistic background for other factors remains elusive. Nevertheless, the analysis of clinical and basic research strongly suggests that, apart from the effect of environmental stressors on DNA alterations and mutation burden, the impact of modifying the tumor microenvironment should be considered. Identifying the involvement of environmental hazards in gliomagenesis and glial tumor progression would lower overall risk by modifying clinical practice, patient management, and lifestyle choices. Further verifying the environmental hazards in glioma formation and progression would have far-reaching implications for neurologists, neurosurgeons, and patients. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Background/Objectives: Neurodegenerative proteinopathies, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB), are increasingly prevalent worldwide mainly due to population aging. These conditions are marked by complex etiologies, overlapping pathologies, and progressive clinical decline, with significant consequences for patients, caregivers, and healthcare systems. This review aims to synthesize evidence on the healthcare complexities of major neurodegenerative proteinopathies to highlight current knowledge gaps, and to inform future care models, policies, and research directions. Methods: We conducted a comprehensive literature search in PubMed/MEDLINE using combinations of MeSH terms and keywords related to neurodegenerative diseases, proteinopathies, diagnosis, sex, management, treatment, caregiver burden, and healthcare delivery. Studies were included if they addressed the clinical, pathophysiological, economic, or care-related complexities of aging-related neurodegenerative proteinopathies. Results: Key themes identified include the following: (1) multifactorial and unclear etiologies with frequent co-pathologies; (2) long prodromal phases with emerging biomarkers; (3) lack of effective disease-modifying therapies; (4) progressive nature requiring ongoing and individualized care; (5) high caregiver burden; (6) escalating healthcare and societal costs; and (7) the critical role of multidisciplinary and multi-domain care models involving specialists, primary care, and allied health professionals. Conclusions: The complexity and cost of neurodegenerative proteinopathies highlight the urgent need for prevention-focused strategies, innovative care models, early interventions, and integrated policies that support patients and caregivers. Prevention through the early identification of risk factors and prodromal signs is critical. Investing in research to develop effective disease-modifying therapies and improve early detection will be essential to reducing the long-term burden of these disorders. Full article

Floods are natural hazards that have the greatest socioeconomic impact worldwide, given that 23% of the global population live in urban areas at risk of flooding. In this field of research, the analysis of flood risk has traditionally been studied based mainly on approaches specific to civil engineering such as hydraulics and hydrology. However, these patterns of approaching the problem in research seem to be changing in recent years. During the last few years, a growing trend has been observed towards the use of methodology-based approaches oriented towards urban planning and land use management. In this context, this study analyzes the evolution of these research patterns in the field by developing a bibliometric meta-analysis of 2694 scientific publications on this topic published in recent decades. Evaluating keyword co-occurrence using VOSviewer software version 1.6.20, we analyzed how phenomena such as climate change have modified the way of addressing the study of this problem, giving growing weight to the use of integrated approaches improving territorial planning or implementing adaptive strategies, as opposed to the more traditional vision of previous decades, which only focused on the construction of hydraulic infrastructures for flood control. Full article

Sleep is crucial to overall health and plays a significant role in skin function. While the circadian rhythm has been extensively researched for its impact on the body’s optimal functioning, the skin also possesses an independent circadian system that serves many important functions. Sleep disruptions or deprivation can significantly affect skin conditions, by compromising the skin barrier and impairing processes such as collagen production, cellular repair, and wound healing. Given the commonality of sleep disturbances, it is crucial to understand the connection between sleep, circadian regulation, and skin health. This is particularly important in understudied populations, such as those with occupational sleep disruption and individuals with hormone-related conditions like PCOS and menopause. Bidirectional relationships have been established between sleep and several inflammatory skin conditions, including atopic dermatitis, psoriasis, rosacea, and hidradenitis suppurativa. While acne is influenced by sleep, the reverse relationship, how acne affects sleep quality, has not been well established. Chronic sleep disruption can increase cortisol levels and oxidative stress, both of which contribute to skin aging and the progression of autoimmune skin conditions, including systemic lupus erythematosus. As sleep is a modifiable risk factor, it is crucial to consider therapeutic options and interventions to prevent or alleviate skin conditions. This review discusses various therapeutic approaches, including melatonin, L-Theanine, Magnesium-L-threonate, Inositol, Cinnamomi cortex, nervous system regulation, and proper sleep hygiene. These therapeutic options have been studied for their impact on sleep, and importantly, several have been evaluated for their utility as adjuncts for treating skin conditions. Overall, the relationship between sleep and skin health is clear, and incorporating sleep-focused therapeutic interventions offers potential to improve both sleep quality and skin health in individuals with a variety of skin conditions. Full article