Search Results (1,558)

Background/Objectives: This single-cohort follow-up study describes the median overall survival (OS) in patients with unresectable head and neck squamous cell carcinoma (HNSCC) due to invasion of vital structures, which is under-represented in the current literature. Secondarily, subgroups were evaluated according to the type of presentation, in order to identify clinical characteristics and contribute to developing an appropriate treatment plan and managing patient’s expectations. Methods: This single-cohort observational study analysed the OS of 39 patients from the Otolaryngology Department with advanced-stage head and neck cancer with invasion of vital anatomical structures considered ineligible for surgical treatment. Secondarily, subgroups were evaluated according to type of presentation and various clinical characteristics. Results: A total of 39 patients radiologically classified as having unresectable HNSCC (i.e., unsuitable for surgical resection), with a mean age of 66.87 years, were included during a 24-month follow-up. By the end of the study, 56.4% of the patients had died. The median OS was 16.09 months. Statistically significant differences were observed when comparing human papilloma virus (HPV)-positive and -negative status and when comparing initial and recurrent tumours. Conclusions: The invasion of anatomical structures such as the skull base, internal carotid artery, and prevertebral space was associated with a marked decrease in survival, with an OS time of 16 months. This study provides valuable evidence in patients with unresectable HNSCC, highlighting tumour recurrence and HPV-negative status as important indicators of poor prognosis. Full article

Background: The progression of Alzheimer’s Disease (AD) deeply affects not only the diagnosed person but also their close relatives, who are often called to take on the role of informal caregivers. This transition is frequently unplanned and emotionally complex, yet poorly understood in its deeper processual dimensions. This study aims to explore and theorize the transition experienced by a family member becoming the primary informal caregiver for a person with advanced AD. Methods: A qualitative study based on the Constructivist Grounded Theory according to Charmaz’s approach (2006) was conducted. In-depth interviews were carried out with 10 participants who had become informal caregivers for a loved one with advanced AD. Data were analyzed using initial coding, focused coding, the constant comparative method, and theoretical coding. Results: Ten caregivers (mean age 39 years, range 35–54; nine females) of patients with advanced AD participated in the study. The analysis revealed a complex, emotionally intense caregiving experience marked by sacrifice, feelings of powerlessness, identity loss, and the necessity of sharing caregiving responsibilities. A core category emerged: A Silent and Certain Willingness to Care, representing the caregivers’ deep, often unconscious commitment to prioritize the care of their loved ones above their own needs. Four interconnected phases characterized the caregiving process: (1) The Changing Daily Life—involving significant sacrifices in personal and social life; (2) Feeling Powerless—confronting the inevitable decline without means to alter the course; (3) Losing Oneself—experiencing physical and psychological exhaustion and a sense of identity loss; and (4) Sharing with Others—seeking external support to sustain caregiving. These findings highlight the evolving nature of becoming a caregiver and the enduring dedication that sustains this role despite the challenges. Conclusions: The progression of AD deeply transforms the lives of caregivers, who become co-sufferers and active participants in the disease’s management. The results underscore the urgency of designing integrative care strategies—including psychological, social, and potentially technological support—that can enhance both patient outcomes and caregiver resilience. Grounded in real-world experiences, this study contributes to the broader neurodegeneration discourse by emphasizing caregiving as a critical factor in long-term disease management and therapeutic success. Full article

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

Adolescence is marked by identity formation and moral development, often accompanied by increased transgressive behaviors. While existing research highlights the interplay between moral constructs and transgression in adolescence, the role of kindness remains underexamined. This study conceptualizes kindness as a multidimensional moral construct and investigates the relationship between different stages of kindness (i.e., egocentric, social/normative, extrinsically motivated, authentic) and transgressive behaviors among adolescents, also considering the moderating role of self-importance of moral identity. The participants were 215 Italian adolescents (aged 15–19) who completed a self-report questionnaire. The results showed that egocentric and authentic kindness were positively and negatively associated with transgression, respectively. Moreover, moral identity significantly enhanced the protective role of authentic kindness. These findings suggest that the relationship between kindness and transgression varies based on the stage of kindness and the importance adolescents attribute to their moral identity. They contribute to extending the understanding of kindness during adolescence, offering implications for reducing transgressive behaviors through targeted and innovative interventions. Full article

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. 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

A literature review about polymer composites reveals that natural fibers have been widely used as a reinforcement phase in recent years. In this framework, the lignocellulosic fibers have received marked attention because of their environmental, thermomechanical, and economic advantages for many industrial sectors. This research aims to identify the impact behavior of ramie reinforced epoxy composites with medium- and high-volume fractions of fibers in intact (nonaged) and aged conditions as well as to analyze if the influence of interface quality on the impact fracture energy can be described by a novel mathematical model. To reach these objectives, the study is designed with three groups (40%, 50%, and 60% of fiber theoretical volume fractions) of intact specimens and three groups of aged samples by condensation and ultraviolet radiation (C-UV) simulation containing the same fiber percentages. Consecutively, impact strength and fracture surface analyses are done to expand the comprehension of the damage mechanisms suffered by the biocomposites and to support the development of the mathematical relation. Certainly, this novel model can contribute to more sustainable and greener industries in the near future. Full article

Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. While extensively characterized in breast MRI, the role of BPE in contrast-enhanced mammography (CEM) remains uncertain due to inconsistent findings regarding its correlation with breast density and cancer risk. Unlike breast density—standardized through the ACR BI-RADS lexicon—BPE lacks a uniform classification system in CEM, leading to variability in clinical interpretation and research outcomes. To address this gap, we introduce the BPE-CEM Standard Scale (BCSS), a structured four-tiered classification system specifically tailored to the two-dimensional characteristics of CEM, aiming to improve consistency and diagnostic alignment in BPE evaluation. Materials and Methods: In this retrospective single-center study, 213 patients who underwent mammography (MG), ultrasound (US), and contrast-enhanced mammography (CEM) between May 2022 and June 2023 at the “A. Perrino” Hospital in Brindisi were included. Breast density was classified according to ACR BI-RADS (categories A–D). BPE was categorized into four levels: Minimal (< 10% enhancement), Light (10–25%), Moderate (25–50%), and Marked (> 50%). Three radiologists independently assessed BPE in a subset of 50 randomly selected cases to evaluate inter-observer agreement using Cohen’s kappa. Correlations between BPE, breast density, and age were examined through regression analysis. Results: BPE was Minimal in 57% of patients, Light in 31%, Moderate in 10%, and Marked in 2%. A significant positive association was found between higher breast density (BI-RADS C–D) and increased BPE (p < 0.05), whereas lower-density breasts (A–B) were predominantly associated with minimal or light BPE. Regression analysis confirmed a modest but statistically significant association between breast density and BPE (R² = 0.144), while age showed no significant effect. Inter-observer agreement for BPE categorization using the BCSS was excellent (κ = 0.85; 95% CI: 0.78–0.92), supporting its reproducibility. Conclusions: Our findings indicate that breast density is a key determinant of BPE in CEM. The proposed BCSS offers a reproducible, four-level framework for standardized BPE assessment tailored to the imaging characteristics of CEM. By reducing variability in interpretation, the BCSS has the potential to improve diagnostic consistency and facilitate integration of BPE into personalized breast cancer risk models. Further prospective multicenter studies are needed to validate this classification and assess its clinical impact. Full article

Grapholita molesta is a globally significant fruit pest. Females achieve maximal reproductive output through efficient sperm utilization following a single copulation. Post-mating maturation of eupyrene sperm is a critical step in reproductive success. Here, we report that a male accessory gland-derived serine protease (named GmAGSP1) is essential for this process. GmAGSP1 was only distantly related to other identified sperm-activating SPs, and its transcript was highly expressed in the AG at 48 h after emergence. RNAi-mediated knockdown of GmAGSP1 in males did not affect courtship rate, copulation duration, or mating frequency, whereas male fertility decreased significantly. Mating with GmAGSP1-knockdown males markedly impaired eupyrene sperm maturation in the spermatophores, with phenotypes including failure of eupyrene sperm bundles to dissociate normally and marked reduction in viability of the dissociated eupyrene sperm. Finally, untargeted metabolomic analysis preliminarily demonstrated marked alterations in multiple metabolic pathways within the spermatophore following mating with GmAGSP1-knockdown males. This study advances our understanding of the regulatory mechanism of “sperm activation in the spermatophore’s metabolic microenvironment mediated by male AG-derived SP” while providing critical insights for the development of novel genetic control strategies targeting G. molesta. Full article

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35–75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values. Full article

Background: Western dietary patterns worldwide are increasingly dominated by energy-dense, nutrient-deficient industrial foods, often identified as ultra-processed foods (UPFs). Such products may have detrimental health implications, particularly if nutritionally inadequate. This study aimed to examine the intake of unhealthy UPFs among children and adolescents from five Mediterranean countries (Italy, Spain, Portugal, Egypt, and Lebanon) involved in the DELICIOUS project and to assess the association with dietary quality indicators. Methods: A survey was conducted with a sample of 2011 parents of children and adolescents aged 6 to 17 years to evaluate their dietary habits. Diet quality was assessed using the Youth Healthy Eating Index (Y-HEI), the KIDMED index to determine adherence to the Mediterranean diet, and compliance with national dietary guidelines. Results: Increased UPF consumption was not inherently associated with healthy or unhealthy specific food groups, although children and adolescents who consumed UPF daily were less likely to exhibit high overall diet quality and adherence to the Mediterranean diet. In all five countries, greater UPF intake was associated with poorer compliance with dietary recommendations concerning fats, sweets, meat, and legumes. Conclusions: Increased UPF consumption among Mediterranean children and adolescents is associated with an unhealthy dietary pattern, possibly marked by a high intake of fats, sweets, and meat, and a low consumption of legumes. Full article

Red sandstones of the Cambrian age are globally distributed and represent an important sedimentation phase during this critical time interval. Their sedimentology and geochemistry can provide key information about the sedimentation style, paleoclimatic conditions, and weathering trends during the Cambrian. In the Salt Range of Pakistan, the Khewra Sandstone constitutes the Lower Cambrian strata and consists of red–maroon sandstones with minor siltstone and shale in the basal part. Cross-bedding, graded bedding, ripple marks, parallel laminations, load casts, ball and pillows, desiccation cracks, and bioturbation are the common sedimentary features of the formation. The sandstones are fine to medium to coarse-grained with subangular to subrounded morphology and display an overall coarsening upward trend. Petrographic analysis indicates that the sandstones are sub-arkose and sub-lithic arenites, and dolomite and calcite are common cementing materials. X-ray Diffraction (XRD) analysis indicates that the main minerals in the formation are quartz, feldspars, kaolinite, illite, mica, hematite, dolomite, and calcite. Geochemical analysis indicates that SiO₂ is the major component at a range of 53.3 to 88% (averaging 70.4%), Al₂O₃ ranges from 3.1 to 19.2% (averaging 9.2%), CaO ranges from 0.4 to 25.3% (averaging 7.4%), K₂O ranges from 1.2 to 7.4% (averaging 4.8%), MgO ranges from 0.2 to 7.4% (averaging 3.5%), and Na₂O ranges from 0.1 to 0.9% (averaging 0.4%), respectively. The results of the combined proxies indicate that the sedimentation occurred in fluvial–deltaic settings under overall arid to semi-arid paleoclimatic conditions with poor to moderate chemical weathering. The Khewra Sandstone represents the red Cambrian sandstones on the NW Indian Plate margin of Gondwana and can be correlated with contemporaneous red sandstones in the USA, Europe, Africa, Iran, and Turkey (Türkiye). Full article

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article

Primary and secondary immunodeficiencies comprise a wide array of illnesses marked by immune system abnormalities, resulting in heightened vulnerability to infections, autoimmunity, and cancers. Notwithstanding progress in diagnostic instruments and an enhanced comprehension of the underlying pathophysiology, delayed diagnosis and underreporting persist as considerable obstacles. The implementation of artificial intelligence into clinical practice has surfaced as a viable method to enhance early detection, risk assessment, and management of immunodeficiencies. Recent advancements illustrate how artificial intelligence-driven models, such as predictive algorithms, electronic phenotyping, and automated flow cytometry analysis, might enable early diagnosis, minimize diagnostic delays, and enhance personalized treatment methods. Furthermore, artificial intelligence-driven immunopeptidomics and phenotypic categorization are enhancing vaccine development and biomarker identification. Successful implementation necessitates overcoming problems associated with data standardization, model validation, and ethical issues. Future advancements will necessitate a multidisciplinary partnership among physicians, data scientists, and governments to effectively use the revolutionary capabilities of artificial intelligence, therefore ushering in an age of precision medicine in immunodeficiencies. Full article