Search Results (438)

Background and objectives: Life expectancies have increased globally, including in Romania, leading to an aging population and thus increasing the burden of chronic diseases. Over 80% of individuals over 65 have more than three chronic conditions, with many exceeding ten and often requiring multiple medications and supplements. This widespread polypharmacy raises concerns about drug interactions, side effects, and inappropriate prescribing. This review examines the impact of polypharmacy in older adult patients, focusing on the physiological changes affecting drug metabolism and the potential risks associated with excessive medication use. Special attention is given to proton pump inhibitors (PPIs), a commonly prescribed drug class with significant benefits but also risks when misused. The aging process alters drug absorption and metabolism, necessitating careful prescription evaluation. Methods: We conducted literature research on polypharmacy and PPIs usage in the older adult population and the risk associated with this practice, synthesizing 217 articles within this narrative review. Results: The overuse of medications, including PPIs, may lead to adverse effects and increased health risks. Clinical tools such as the Beers criteria, the STOPP/START Criteria, and the FORTA list offer structured guidance for optimizing pharmacological treatments while minimizing harm. Despite PPIs’ well-documented safety and efficacy, inappropriate long-term use has raised concerns in the medical community. Efforts are being made internationally to regulate their consumption and reduce the associated risks. Conclusions: Physicians across all specialties must assess the risk–benefit balance when prescribing medications to older adult patients. A personalized treatment approach, supported by evidence-based prescribing tools, is essential to ensure safe and effective pharmacotherapy. Addressing inappropriate PPI use is a priority to prevent potential health complications. Full article

Background: Renal trauma accounts for approximately 3–5% of all trauma cases, predominantly affecting young males. The most common etiology is blunt trauma, particularly due to road traffic accidents, and it frequently occurs as part of polytrauma involving multiple organ systems. Management strategies are primarily dictated by hemodynamic stability, overall clinical condition, comorbidities, and injury severity graded according to the AAST classification. This study aimed to evaluate the effectiveness of non-operative management (NOM) in high-grade renal trauma (AAST grades III–V), beyond its established role in low-grade injuries (grades I–II). Secondary endpoints included the identification of independent prognostic factors for NOM failure and in-hospital mortality. Methods: We conducted a retrospective observational study including patients diagnosed with blunt renal trauma who presented to the Emergency Department of Policlinico Umberto I in Rome between 1 January 2013 and 30 April 2024. Collected data comprised demographics, trauma mechanism, vital signs, hemodynamic status (shock index), laboratory tests, blood gas analysis, hematuria, number of transfused RBC units in the first 24 h, AAST renal injury grade, ISS, associated injuries, treatment approach, hospital length of stay, and mortality. Statistical analyses, including multivariable logistic regression, were performed using SPSS v28.0. Results: A total of 244 patients were included. Low-grade injuries (AAST I–II) accounted for 43% (n = 105), while high-grade injuries (AAST III–V) represented 57% (n = 139). All patients with low-grade injuries were managed non-operatively. Among high-grade injuries, 124 patients (89%) were treated with NOM, including observation, angiography ± angioembolization, stenting, or nephrostomy. Only 15 patients (11%) required nephrectomy, primarily due to persistent hemodynamic instability. The overall mortality rate was 13.5% (33 patients) and was more closely associated with the overall injury burden than with renal injury severity. Multivariable analysis identified shock index and active bleeding on CT as independent predictors of NOM failure, whereas ISS and age were significant predictors of in-hospital mortality. Notably, AAST grade did not independently predict either outcome. Conclusions: In line with the current international literature, our study confirms that NOM is the treatment of choice not only for low-grade renal injuries but also for carefully selected hemodynamically stable patients with high-grade trauma. Our findings highlight the critical role of physiological parameters and overall ISS in guiding management decisions and underscore the need for individualized assessment to minimize unnecessary nephrectomies and optimize patient outcomes. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Right ventricular apex (RVA) pacing has historically been the default approach for cardiac pacing; however, it is associated with the development of progressive left ventricular dysfunction and heart failure (HF), particularly in patients with high pacing burdens. While advances in device programming and modern algorithms have sought to mitigate these effects, preserving physiological activation has proven to be more critical than reducing ventricular pacing. Conduction system pacing (CSP) techniques—namely, His-bundle pacing (HBP) and particularly left bundle branch area pacing (LBBAP)—have emerged as superior alternatives, enabling improved left ventricular function and reduced rates of pacing-induced cardiomyopathy (PICM). Nevertheless, despite the clinical advantages of these procedures over RVA, they face limitations including variable implantation success rates, increased pacing thresholds and lead revision rates, technical challenges, and occasional procedure prolongation. Thus, while CSP approaches represent the future of physiological pacing, RVA pacing continues to provide a necessary and reliable option in the current clinical practice. Full article

Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) from inception until 30 June 2024. Results: Breast cancer-related lymphedema (BCRL) is indeed an important healthcare burden both due to the significant patient-related outcomes and the overall social impact of this condition. Even though lymphedema is not life-threatening, the literature underlined harmful consequences in terms of pain, infections, distress, and functional impairment with a subsequent and relevant decrease in quality of life. Currently, since there is no cure, the therapeutic approach to BCRL aims to slow disease progression and prevent related complications. A comprehensive overview of postmastectomy lymphedema is offered. First, the pathophysiology and risk factors associated with BCRL were detailed; then, diagnosis modalities were depicted highlighting the importance of early detection. According to non-negligible changes in patients’ everyday lives, novel criteria for patients’ functioning assessment are reported. Regarding the treatment modalities, a wide array of conservative and surgical methods both physiologic and ablative were analyzed with their own outcomes and downsides. Conclusions: Combined strategies and multidisciplinary protocols for BCRL, including specialized management by reconstructive surgeons and physiatrists, along with healthy lifestyle programs and personalized nutritional counseling, should be compulsory to address patients’ demands and optimize the treatment of this harmful and non-curable condition. The Lymphedema-specific ICF Core Sets should be included more often in the overall outcome evaluation with the aim of obtaining a comprehensive appraisal of the treatment strategies that take into account the patient’s subjective score. Full article

High-density lipoprotein (HDL) and small dense low-density lipoprotein (sdLDL) represent two critical yet contrasting components in lipid metabolism and cardiovascular risk modulation. While HDL has traditionally been viewed as cardioprotective due to its role in reverse cholesterol transport and anti-inflammatory effects, emerging evidence emphasizes that HDL functionality—rather than concentration alone—is pivotal in atheroprotection. Conversely, sdLDL particles are increasingly recognized as highly atherogenic due to their enhanced arterial penetration, oxidative susceptibility, and prolonged plasma residence time. This review critically examined the physiological roles, pathological implications, and therapeutic interventions targeting HDL function and sdLDL burden. Lifestyle modifications, pharmacologic agents including statins, fibrates, PCSK9 inhibitors, and novel therapies such as icosapent ethyl were discussed in the context of their effects on HDL quality and sdLDL reduction. Additionally, current clinical guidelines were analyzed, highlighting a paradigm shift away from targeting HDL-C levels toward apoB-driven risk reduction. Although HDL-targeted therapies remain under investigation, the consensus supports focusing on lowering apoB-containing lipoproteins while leveraging lifestyle strategies to improve HDL functionality. In the setting of heart failure, particularly with preserved ejection fraction (HFpEF), alterations in HDL composition and elevated sdLDL levels have been linked to endothelial dysfunction and systemic inflammation, further underscoring their relevance beyond atherosclerosis. A comprehensive understanding of HDL and sdLDL dynamics is essential for optimizing cardiovascular prevention strategies. Full article

This study explores how Black student leaders (BSLs) at public historically white institutions (HWIs) in Florida and Georgia navigate racial battle fatigue (RBF) in the context of anti-DEI legislation. Amid rising political hostility toward diversity, equity, and inclusion (DEI) efforts, this research examines the lived experiences of 11 BSLs as they respond to racialized campus climates that are increasingly ambiguous and unsupportive. Using a critical qualitative approach, data were collected through two in-depth interviews per participant and analyzed using inductive and deductive coding. Four major findings emerged: (1) BSLs experience heightened psychological, physiological, and emotional forms if stress linked to their identity and leadership roles; (2) anti-DEI policies contribute to institutional erasure and confusion; (3) students express emotional withdrawal, hypervigilance, and disillusionment with performative leadership; (4) students employ culturally grounded coping strategies centered on self-care, spirituality, and community. This study underscores that BSLs are both empowered and burdened by their leadership, especially under politically restrictive conditions. The findings call for student affairs educators to prioritize engagement and belonging and offer identity-affirming support. Further, scholars with academic freedom are urged to continue documenting racialized student experiences. These insights are critical to protecting Black student leadership and equity-centered educational transformation. Full article

Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual’s physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accelerated aging and increased cancer risk, including LN. Immunosenescence, the age-related decline in immune function characterized by thymic involution, altered lymphocyte populations, and chronic inflammation (inflammaging), appears to be a key mechanistic link between aging and LN development, potentially providing a more accurate predictor of cancer risk than mutation accumulation alone. Accelerated biological aging, measured by various clocks, correlates with LN risk and progression (e.g., in chronic lymphocytic leukemia), and may influence treatment tolerance and outcomes, particularly in older adults who are often burdened by frailty and comorbidities like sarcopenia. Integrating biological age assessments into clinical practice holds promise for refining diagnosis, prognosis, and personalizing treatment strategies (including guiding intensity and considering anti-aging interventions), and improving outcomes for patients with LN. This review synthesizes the current understanding of the intricate relationship between LN, immunosenescence, biological age, and aging clocks, highlighting clinical implications and key future research directions aimed at translating these insights into better patient care. Full article

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms. Full article

Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and evolution, as an integrative framework. Mechanistically, Hg disrupts neuroendocrine pathways, gene expression, immune function, and hormone regulation, leading to behavioural changes such as reduced foraging, altered parental care, and impaired predator avoidance. Early-life exposure affects neural development, learning, and social behaviour into adulthood. Functionally, these changes reduce fitness by compromising reproduction and survival. Phylogenetic comparisons show interspecific variability, with piscivorous and insectivorous birds exhibiting high Hg burdens and sensitivity, linked to ecological roles and exposure. Behavioural responses often precede physiological or demographic effects, highlighting their value as early indicators. Both field and laboratory studies show that even low Hg concentrations can alter behaviour, though outcomes vary by species, life stage, and exposure route. Integrating behavioural endpoints into ecotoxicological risk assessments is essential to improve conservation strategies and understanding of sublethal pollutant effects on wildlife. Full article

Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut–brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF’s capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and β-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience. Full article

Objectives: This review aims to systematically evaluate the clinical outcomes of left ventricle-only fusion pacing (LV-only fCRTp) and identify evidence-based selection criteria that may optimize patient response and long-term therapeutic benefit. Background: Cardiac resynchronization therapy (CRT) is traditionally associated with biventricular pacing (BiVp). However, approximately 20–40% of patients seem to remain non-responders to this therapy. LV-only fCRTp offers a more physiological alternative by combining left ventricular epicardial pacing with the intrinsic ventricular activation wavefront. Beyond optimization strategies, the observed variability in response highlights the need for better patient selection in order to fully unlock its therapeutic potential. Methods: A systematic literature search was conducted in PubMed and Cochrane Library for original articles published up to April 2025, following PRISMA 2020 guidelines. The search focused on LV-only fCRTp performed either through standard RA/LV/RV biventricular devices or RA/LV dual-chamber systems. Results: Twenty-seven studies met the inclusion criteria. Among these, 17 studies obtained LV-only fCRTp using biventricular devices, and 10 were considered true LV-only fCRTp using RA/LV dual-chamber devices. Standard and specific selection criteria were used to qualify patients for LV-only fCRTp. Preserved atrioventricular conduction, ischemic cardiomyopathy, arrhythmic risk stratification, and the management of supraventricular arrhythmias were common overlapping parameters among studies with high variability, highlighting their potential role in response. RA/LV devices yielded consistent clinical benefits and low complication rates, particularly in nonischemic patients with stable AV conduction and low arrhythmic risk, while having a lower financial burden. Conclusions: Beyond guideline recommendations for CRT, this review identifies supplementary selection criteria that could further influence the effectiveness and stability of fusion pacing. Full article

Background: Magnesium (Mg²⁺) plays a fundamental role in various physiological processes, including neuromuscular function, glucose metabolism, cardiovascular regulation, and bone health. Despite its significance, the influence of sex on magnesium metabolism, requirements, and health outcomes remains unexplored. The aim of this review is to analyze sex-based differences in magnesium homeostasis, with a particular focus on hormonal regulation, body composition, and disease susceptibility. Methods: This narrative review, based on a non-systematic MEDLINE search conducted in January 2025, prioritized clinical trials from the past 15 years on human subjects and explored gender-specific aspects of magnesium intake, status, metabolism, and supplementation. Results: Hormonal fluctuations, particularly variations in estrogen levels, affect magnesium absorption, distribution, and retention, thereby influencing magnesium balance across different life stages such as puberty, pregnancy, and menopause. Additionally, dietary intake and lifestyle factors often differ between men and women, further impacting magnesium status. Emerging evidence suggests that suboptimal magnesium levels may differentially contribute to conditions such as osteoporosis, cardiovascular disease, and metabolic disorders in each sex. Conclusions: In conclusion, acknowledging sex-specific differences in magnesium metabolism is essential for developing personalized dietary guidelines and therapeutic strategies. Tailored nutritional approaches could significantly improve magnesium status, enhance overall health, and reduce the burden of chronic diseases linked to magnesium imbalance. Full article

Changes in hepatic lipoprotein metabolism are responsible for the majority of metabolic dysfunction-associated disorders, including familial hypercholesterolemia (FH), metabolic syndrome (MetS), metabolic dysfunction-associated fatty liver disease (MAFLD), and age-related diseases such as atherosclerosis, a major health burden in modern society. This review aims to advance the understanding of state-of-the-art mechanistic concepts in lipoprotein metabolism, with a particular focus on lipoprotein uptake and secretion and their dysregulation in disease, and to provide a comprehensive overview of experimental models used to study these processes. Human lipoprotein research faces several challenges. First, significant differences in lipoprotein metabolism between humans and other species hinder the reliability of non-human model systems. Additionally, ethical constraints often limit studies on human lipoprotein metabolism using tracers. Lastly, while 2D hepatocyte cell culture systems are widely used, they are commonly of cancerous origins, limiting their physiological relevance and necessitating the use of more physiologically representative models. In this review, we will elaborate on key findings in lipoprotein metabolism, as well as limitations and challenges of currently available study tools, highlighting mechanistic insights throughout discussion of these models. These include human tracer studies, animal studies, 2D tissue culture-based systems derived from cancerous tissue as well as from induced pluripotent stem cells (iPSCs)/embryonic stem cells (ESCs). Finally, we will discuss precision-cut liver slices, liver-on-a-chip models, and, particularly, improved 3D models: (i) spheroids generated from either hepatoma cancer cell lines or primary human hepatocytes and (ii) organoids generated from liver tissues or iPSCs/ESCs. In the last section, we will explore future perspectives on liver-in-a-dish models in studying mechanisms of liver diseases, treatment options, and their applicability in precision medicine approaches. By comparing traditional and advanced models, this review will highlight the future directions of lipoprotein metabolism research, with a focus on the growing potential of 3D liver organoid models. Full article

Extracellular vesicles (EVs) can be distributed in various bodily fluids, such as serum and urine, and play an essential role in immune regulation, substance transport, and other aspects. Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), which places a tremendous burden on public health prevention and control within society. Researchers are committed to developing various diagnoses and treatment plans to eliminate TB effectively. The results of some studies conducted to date demonstrate that the serum EVs of TB patients, which carry components related to Mtb, can be used as relevant markers for TB detection and improve diagnostic efficiency. However, no relevant reports exist on the particular physiological functions such EVs perform, thus warranting further exploration. In this study, we collected serum EVs from both healthy individuals and TB patients. After identifying the morphology, concentration, and expression of classic markers (CD63, CD81, and CD9) of EVs, we explored their physiological functions at the cellular level and their physiological functions and effects on BCG colonization in the lungs at the mouse level. It was found that EVs were abundant in TB patients and healthy individuals, and the number of CD63 and CD9 markers co-expressed on the surface of serum EVs in healthy individuals was greater than that in TB patients. Serum EVs in patients with TB can stimulate cells to secrete more immune cytokines, such as TNF-α and IL-6, compared with those in healthy individuals; induce an increase in the M1/M2 ratio of macrophages in the peripheral blood mononuclear cells of mice; and inhibit the colonization of Mycobacterium bovis bacillus Calmette Guérin (BCG) in the lungs of mice. In addition, they can inhibit the occurrence of inflammatory responses in the lung tissue of mice. The above results suggest that serum EVs in TB patients may exert their physiological function by regulating immune responses. This finding also indicates that exploring serum EVs in TB patients with regard to their physiological functions shows excellent potential. Full article