Search Results (1,841)

For a few decades, Type 2 Diabetes (T2D) has been recognized as a worldwide public health issue. T2D relies on systemic insulin resistance leading to Beta cell dysfunction. Nowadays, lifestyle modifications, such as improving eating habits and increasing physical activity, represent the first recommendations for managing T2D. Physical exercise, as a structured physical activity, is now considered as a non-pharmacological treatment with a wide range of beneficial effects, especially for people living with T2D. The review intends to summarize the current knowledge of physical exercise benefits in a context of T2D: from “unwanted” adipose tissue reduction to Beta cell health improvement. Moreover, we try to suggest an underlying mechanism explaining physical exercise beneficial effects in the context of T2D focusing on exerkines, molecules secreted in response to physical exercise. With this review, we highlight the beneficial impact of post-exercise secretions on Beta cell health and encourage research to continue in this direction. Identifying new exerkines with beneficial effects in the context of T2D could represent a promising approach for managing metabolic diseases. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

Drawing on in-depth interviews and thematic analysis, this study explores the therapeutic benefits of outdoor experiences through the lived experiences of 24 outdoor practitioners, including educators, environmentalists, therapists, and program leaders. Three core themes emerged: (a) nature as an emotional regulator and reflective space; (b) therapeutic benefits of human–nature relationships; and (c) decolonial, bioregional, and cultural healing. Although practitioners facilitated physical challenges and skill-building for their participants, they primarily described outdoor experiences as relational, somatic, and culturally rooted practices that foster emotional regulation, grief processing, identity integration, and social inclusion. Healing emerged through solitude, silence, ancestral connections, sacred landscapes, inclusive dynamics, and the restoration of cultural knowledge. This study’s results challenge Western-centric outdoor education models by foregrounding Indigenous and postcolonial perspectives embedded in Indian ecological traditions. The results contribute to global discussions on decolonizing outdoor fields and offer implications for culturally responsive, emotionally safe, and ecologically grounded practices. Full article

Diabetes represents one of the major challenges in preserving health in the 21st century. It has been estimated that in 2050, 853 million subjects will live with diabetes. It was also reported that 3.4 million adults died from diabetes and related comorbidities. Chronic hyperglycemia, if not properly managed, leads to skeletal fragility with fracture risk that augments with age. In type 1 diabetes (T1D), the augmented fracture risk can be partially explained by lower areal bone mineral density (aBMD). Interestingly, in type 2 diabetes (T2D), the risk of fractures increases with normal or elevated aBMD. In this review, the recent updates on diabetes and bone health (2023–2025) are reported, thus describing bone quality and the role of mediators involved in diabetes pathogenesis. Consequently, the role of Vitamin D, Incretins, Glucagon-like peptide-2 (GLP-2), neurotensin, asprosin, irisin, and Thioredoxin-interacting protein (TXNIP) will be described considering the interplay between diabetes and bone health. The importance of monitoring diabetic patients’ bone health is underlined, together with the therapeutic approaches to avoid fractures. Full article

The escalating global threat of antimicrobial resistance (AMR) underscores the urgent need for innovative therapeutics. Bacteriophages (phages), natural bacterial predators, offer promising solutions, especially when harnessed through advances in artificial intelligence (AI). This review explores how AI-driven innovations are transforming phage biology, with an emphasis on three pivotal areas: (1) AI-enhanced structural prediction (e.g., AlphaFold); (2) deep learning functional annotation; (3) bioengineering strategies, including CRISPR-Cas. We further discuss applications extending to medical therapy, biosensing, agricultural biocontrol, and environmental remediation. Despite progress, critical challenges persist—including high false-positive rates, difficulties in modeling disordered protein regions, and biosafety concerns remain. Overcoming these requires experimental validation, robust computational frameworks, and global regulatory oversight. AI integration in phage research is accelerating the development of next-generation therapeutics to combat AMR and advance engineered living therapeutics. Full article

Background and Objectives: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide and, beyond its oncogenic potential, may impair reproductive health in both sexes. This review examines HPV’s effects on male and female fertility, obstetric outcomes, vertical transmission, and fertility-sparing management in oncology. Materials and Methods: A systematic search of PubMed, Embase, and Scopus was conducted using terms related to HPV and reproduction. Additional search terms included those related to therapeutic vaccines, antivirals, and genotype prevalence. English-language human studies reporting clinical reproductive outcomes were included. Thirty-seven studies met the inclusion criteria. Two reviewers independently screened and assessed study quality using a simplified GRADE framework. Results: In men, seminal HPV infection correlates with reduced progressive motility (SMD ≈ −0.85), abnormal morphology, and increased DNA fragmentation. In women, high-risk HPV doubles the odds of infertility (OR ≈ 2.3) and is associated with endometrial involvement. High first-trimester viral load predicts vertical transmission (aOR 6.4), which is also increased by vaginal delivery (RR 1.8) and is linked to PROM (OR 1.8) and preterm birth (OR 1.8). Modeling suggests that nine-valent vaccination plus 5-year HPV-based screening could reduce CIN2+ by up to 80% and excisional treatments by >75%. Fertility-sparing surgery in early cervical cancer yields a <4% recurrence and up to 68% live birth rates. Conclusions: This review uniquely synthesizes reproductive and oncologic impacts of HPV and emphasizes risk stratification, multidisciplinary prevention, and fertility preservation. Integration of HPV DNA quantification, personalized care, and vaccine-based strategies offers a path toward optimized outcomes in both sexes. Full article

Background/Objectives: Preoperative sarcopenia in liver transplantation (LT) recipients is an important prognostic factor of LT outcomes. Systemic inflammatory status (SIS) has been proposed as a unifying mechanism for skeletal muscle loss; thus, considering SIS and sarcopenia together may enhance prognosis assessment in patients undergoing LT. Herein, we aimed to describe the relationship between the SIS and skeletal muscle index (SMI) with short-term and long-term mortality post-living donor LT (LDLT). Methods: In total, 3387 consecutive adult LDLT recipients were retrospectively evaluated. The neutrophil-to-lymphocyte ratio (NLR, using a cut-off of 3) was utilized as an SIS. SMI was calculated using computed tomography scans, measured at the third lumbar vertebra; sex-specific cut-offs were determined from contemporary donors. Univariate and multivariable Cox proportional hazard analyses were performed. Results: Decreasing SMI was associated with increasing NLR. Increasing NLR and decreasing SMI both showed dose-dependent relationships with a risk of 90-day mortality. Within sarcopenic patients, NLR > 3 (vs. NLR ≤ 3) was associated with higher 90-day (9.3% vs. 3.5%, p = 0.049) and overall mortality (28.4% vs. 19.1%, p = 0.045). Sarcopenia and NLR > 3 (vs. neither) were independent predictors of 90-day mortality (hazard ratio [HR] 2.48 [1.40–4.40], p = 0.002) and overall mortality (HR, 1.81 [1.37–2.38], p < 0.001) after multivariable adjustment. When stratified by age, sex, and MELD score, the association between sarcopenia and overall mortality persisted in all subgroups, with the highest risk observed in women (HR 3.43, 95% CI 1.83–6.43). Conclusions: Sarcopenia, with the systemic inflammatory response, nearly doubled the risk of 90-day and overall mortality post-LT, proposing that these readily available biomarkers are a practical index for predicting survival post-LT. Considering that these are potentially modifiable factors, our result may provide a new therapeutic target to improve survival post-LT. Full article

Benzene, a well-established human carcinogen and major industrial pollutant, poses significant health risks through occupational exposure due to its no-threshold effect, leading to multi-system damage involving the hematopoietic, nervous, and immune systems. This makes the investigation of its toxic mechanisms crucial for precise prevention and control of its health impacts. Programmed cell death (PCD), an orderly and regulated form of cellular demise controlled by specific intracellular genes in response to various stimuli, has emerged as a key pathway where dysfunction may underlie benzene-induced toxicity. This review systematically integrates evidence linking benzene toxicity to PCD dysregulation, revealing that benzene and its metabolites induce abnormal subtypes of PCD (apoptosis, autophagy, ferroptosis) in hematopoietic cells. This occurs through mechanisms including activation of Caspase pathways, regulation of long non-coding RNAs, and epigenetic modifications, with recent research highlighting the IRP1-DHODH-ALOX12 ferroptosis axis and oxidative stress–epigenetic interactions as pivotal. Additionally, this review describes a comprehensive monitoring system for early toxic effects comprising benzene exposure biomarkers (urinary t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA)), PCD-related molecules (Caspase-3, let-7e-5p, ACSL1), oxidative stress indicators (8-OHdG), and genetic damage markers (micronuclei, p14ARF methylation), with correlative analyses between PCD mechanisms and benzene toxicity elaborated to underscore their integrative roles in risk assessment. Furthermore, the review details analytical techniques for these biomarkers, including direct benzene detection methods—direct headspace gas chromatography with flame ionization detection (DHGC-FID), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and portable headspace sampling (Portable HS)—alongside molecular imprinting and fluorescence probe technologies, as well as methodologies for toxic effect markers such as live-cell imaging, electrochemical techniques, methylation-specific PCR (MSP), and Western blotting, providing technical frameworks for mechanistic studies and translational applications. By synthesizing current evidence and mechanistic insights, this work offers novel perspectives on benzene toxicity through the PCD lens, identifies potential therapeutic targets associated with PCD dysregulation, and ultimately establishes a theoretical foundation for developing interventional strategies against benzene-induced toxicity while emphasizing the translational value of mechanistic research in occupational and environmental health. Full article

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Background/Objectives: This study examines the effectiveness of equine-assisted intervention (EAI) in improving adaptive behaviour and motor skills in children with autism spectrum disorder (ASD). Methods: To that effect, a self-controlled experimental analytical study has been designed, which is longitudinal and prospective in nature, with pre- and post-intervention measures, using the Vineland Adaptive Behavior Scale II (VABS-II) as the assessment instrument. The sample consists of 19 children who participated in weekly therapeutic sessions involving horses for eight months; these sessions included horseback riding, groundwork, hygiene, and preparation of the horse. Results: The results show significant improvements both in the overall score of the VABS-II test ($\overline{\mathrm{x}}$pre: 65.84 ± 10.38–$\overline{\mathrm{x}}$post: 72.47 ± 16.21, p = 0.003) and in the areas of communication ($\overline{\mathrm{x}}$pre: 64.84 ± 15.50 ~ $\overline{\mathrm{x}}$post: 72.26 ± 21.93, p = 0.010), social skills ($\overline{\mathrm{x}}$pre: 61.26 ± 8.99 ~ $\overline{\mathrm{x}}$post: 66.53 ± 13.79, p = 0.008) and daily living skills (DLS) ($\overline{\mathrm{x}}$pre: 66.21 ± 11.15 ~ $\overline{\mathrm{x}}$post: 69.95 ± 12.32, p = 0.0004), as well as a non-significant slight improvement in motor skills ($\overline{\mathrm{x}}$pre: 72.50 ± 8.83 ~ $\overline{\mathrm{x}}$post: 75.17 ± 7.88, p = 0.363). In addition, these gains were greater in those children attending standard classroom settings and receiving early stimulation. Conclusions: This study suggests equine-assisted intervention (EAI) may contribute to improvements in adaptive behaviour, including communication, social skills, and daily living skills, in children with autism spectrum disorder (ASD). Benefits were notably enhanced in children receiving early stimulation within standard classroom settings. Full article

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

Pain is a fundamental yet complex biological and psychosocial phenomenon. While acute pain serves as a defense mechanism, alerting the body to potential tissue damage, chronic pain loses this protective function and becomes a persistent, independent condition. Chronic pain in the elderly is particularly significant due to age-related changes in pain perception, a higher prevalence of comorbidities, and an increased susceptibility to pharmacological side effects. Diagnosing pain in older adults presents unique challenges owing to cognitive decline, multimorbidity, and impaired communication. This narrative review aims to summarize the current knowledge on chronic pain in the elderly, with a particular emphasis on diagnostic difficulties, therapeutic strategies, and the essential role of nurses in multidisciplinary management. Both objective scales and subjective assessment tools are essential for an accurate evaluation. Effective management requires a multidisciplinary approach that integrates individualized pharmacological and non-pharmacological therapies. Analgesic use must be tailored to account for altered pharmacokinetics and risks such as sedation or falls. Non-drug interventions, including physiotherapy and psychological techniques, are especially valuable in geriatric care. Nurses play a pivotal role in the recognition, assessment, and ongoing management of pain in this population. Developing age-appropriate, personalized strategies is essential for improving the quality of life in older adults living with chronic pain. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve as essential diagnostic and prognostic markers. Their detection supports disease classification, guides clinical decision-making, and offers insight into disease activity and therapeutic response. Traditional markers such as anti-nuclear antibodies (ANA), anti-dsDNA, and anti-Sm antibodies remain diagnostic cornerstones, but growing attention is given to anti-C1q, anti-nucleosome antibodies (ANuA), anti-ribosomal P, antiphospholipid, and anti-cytokine antibodies due to their associations with specific disease phenotypes and activity. These markers may reflect disease activity, specific organ involvement, or predict flares. The mechanisms underlying their persistence include B cell tolerance failure and long-lived plasma cell activity. The aim of this review is to summarize current knowledge on the major autoantibodies in SLE, appraise available detection methods, highlight their clinical utility and limitations and present evidence on the association between antibodies and disease phenotypes. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Hypoxic–ischaemic encephalopathy (HIE), a leading cause of perinatal mortality and neurological impairment, affects 1–8/1000 live births in developed countries. Therapeutic hypothermia (TH), the standard treatment for moderate to severe HIE, reduces brain injury by lowering metabolic demand and inhibiting apoptosis. This case study presents a full-term female newborn delivered via caesarean section due to intrauterine asphyxia, with meconium aspiration syndrome and severe HIE (Apgar 0/0/0/2). Notwithstanding the presence of multiorgan failure and grade II intraventricular haemorrhage, TH was initiated within six hours. The patient received circulatory and respiratory support, sedation, and nitric oxide. Early rehabilitation was initiated immediately. Neurofunctional assessment using the TIMP test revealed initial delays (16–25th percentile) at 11 weeks of age; however, the subsequent two evaluations, conducted approximately every two weeks, indicated that the patient was within normal developmental ranges. A similar outcome was observed in the AIMS assessment conducted at seven months of age, which also yielded normal results. Despite MRI findings post-TH showing hypoxic and haemorrhagic lesions, the patient achieved normal development. This case demonstrates the effectiveness of combining TH with early physiotherapy in mitigating severe consequences of HIE, such as cerebral palsy and epilepsy. Long-term follow-up remains crucial for detecting later deficits, particularly during school age. The outcome of this case underscores the significance of timely intervention and multidisciplinary care. While TH and rehabilitation have been shown to improve prognosis, ongoing monitoring is crucial to ensure optimal neurological development trajectories. Full article