Search Results (1,269)

Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article

Background/Objectives: Neonatal Intensive Care Units (NICUs) constitute a highly complex clinical environment characterized by patient fragility and frequent ethically sensitive decisions. To date, systematic studies investigating how Italian NICUs address these challenges and what forms of ethics support are effectively available are lacking. The aim of this study is therefore to assess how ethical issues are managed in Italian NICUs, with particular attention to the availability, use, and perceived usefulness of clinical ethics support in everyday practice. Methods: A 25-item questionnaire was developed by adapting an existing tool for investigating clinical ethics activities to the neonatal context. Following expert review by the GIBCE (Gruppo Interdisciplinare di Bioetica Clinica e Consulenza Etica in ambito sanitario), the final instrument covered four areas (general data, experience with ethical dilemmas, tools and procedures, opinions and training needs). A manual web search identified all Italian NICUs and their clinical directors, who were asked to disseminate the survey among staff. Participation was voluntary and anonymous. Data collection was conducted via Google Forms and analyzed through qualitative thematic analysis. Results: A total of 217 questionnaires were collected. The most frequent ethical dilemmas concern quality of life with anticipated multiple or severe disabilities (72.4%) and decisions to withdraw or withhold life-sustaining treatments (64.5%). Major challenges include fear of medico-legal repercussions (57.6%) and communication divergences between physicians and nurses (49,8%). More than half of respondents (52.1%) reported no formal training in clinical ethics, and 68.7% had never developed a Shared Care Plan (Shared Document for healthcare ethics planning) as defined by the Italian Law 219/2017. Conclusions: Findings highlight marked fragmentation in ethical practices across Italian NICUs. On this basis, establishing structured and accessible CEC services could help promote consistency, reinforce shared ethical standards, and support transparent and equitable decision-making in critical neonatal care. Full article

Total hip arthroplasty (THA) is a widely performed procedure that significantly enhances patients’ quality of life. However, nerve injury remains a concerning complication, with an incidence ranging from 0.6% to 3.7%, depending on patient and surgical variables. This narrative review provides a comprehensive overview of nerve injuries associated with THA, focusing on etiology, risk factors, clinical manifestations, prevention, and treatment strategies. The most affected nerves include the sciatic, femoral, lateral femoral cutaneous (LFCN), superior gluteal, and obturator nerves. Anatomical factors such as developmental hip dysplasia (DDH), limb length discrepancy, and aberrant nerve courses, along with patient-specific conditions like female sex, obesity, and pre-existing spinal disorders, increase the risk of nerve damage. Surgical complexity, revision procedures, and surgeon experience also influence injury likelihood. Clinical manifestations range from sensory disturbances to motor deficits including foot drop, Trendelenburg gait, or impaired knee extension, depending on the nerve involved. Diagnosis is primarily clinical, supported by electrophysiological studies and imaging when needed. Prevention hinges on careful preoperative planning, appropriate surgical approach selection, meticulous intraoperative technique, and attention to limb positioning. Treatment is typically conservative, involving pain control, physical therapy, and neurostimulation. In refractory or severe cases, interventions such as nerve decompression, repair, or tendon transfer may be considered. Pharmacological agents including vitamin B12, tacrolimus, and melatonin show potential in promoting nerve regeneration. Although most nerve injuries resolve spontaneously or with conservative measures, some cases may result in long-term deficits. Understanding the mechanisms, risk factors, and management strategies is essential to mitigating complications and optimizing functional outcomes in patients undergoing THA. Full article

This paper explores recent advancements in end-of-life (EOL) care in Canada, focusing on palliative care (PC) in oncology, advance care planning (ACP), and medical assistance in dying (MAiD). Despite improvements in cancer treatment, cancer remains a leading cause of death in Canada, with patients facing significant physical, psychosocial, and emotional challenges throughout the illness trajectory. Over the past few decades, PC has evolved to address serious illness from diagnosis onward, enhancing symptom management, quality of life, and patient satisfaction, while reducing hospital admissions and unnecessary treatments. However, barriers such as misconceptions about PC, late PC referrals, and limited access to PC, particularly in rural and remote areas, still exist. This perspective paper draws on the authors’ collective clinical and research experience in oncology and PC, complemented by a focused review of key literature. Ongoing education for oncology nurses on EOL care, including on PC, ACP, and MAiD, as well as continued efforts to expand access to PC for all Canadians, are imperative in order to improve the EOL experience for people affected by cancer nationwide. Full article

Infertility affects thousands of couples internationally, leaving a profound effect on their families and communities. According to the World Health Organization (WHO), approximately one out of six individuals of reproductive age worldwide experiences infertility in their life span. Approximately 35% of infertile couples are affected by male factor infertility, in which semen analysis is the gold standard diagnostic procedure. Oxidative stress (OS) is considered to play a pivotal role in the pathogenesis of male infertility. A thorough literature search was conducted in PubMed/MEDLINE, Scopus and Google Scholar databases, using MeSH terms and free-text keywords, to retrieve eligible articles published in the last decade, focusing on the potential beneficial role of oral antioxidants in male infertility. Antioxidant supplementation appears to improve the majority of sperm parameters. Therefore, antioxidant therapy is emerging as a promising aid in addressing male infertility. The purpose of this comprehensive literature review is to evaluate the significance of antioxidant supplementation in improving sperm parameters. Most of the included randomized controlled trials demonstrated the positive effects of oral antioxidants in various parameters, such as sperm concentration, total sperm count, motility and progressive motility. Consequently, pregnancy outcomes were evaluated, and increased pregnancy rates were reported in the majority of the included studies. Full article

Background/Objectives: Iron deficiency (ID) is the most common nutritional disorder in childhood worldwide. It has profound consequences for growth, neurodevelopment, behaviour, and overall health. Despite the long-standing efficacy of oral ferrous salts, their poor gastrointestinal tolerability and adherence challenges have spurred the development of alternative formulations and innovative dosing strategies. Methods: We conducted a narrative review of national and international guidelines, pediatric randomized controlled trials, observational and cohort studies, cost-effectiveness analyses, diagnostic method papers, and reviews, with emphasis on diagnostic innovations, therapeutic outcomes, tolerability, and formulation-specific efficacy. Results: Ferrous salts remain the gold standard for efficacy, low cost, and guideline endorsement, but up to 40% of children experience GI intolerance. Therefore, a lower dosage of ferrous salts has been proposed for IDA as still being an efficacious and better-tolerated schedule. Also, alternate-day dosing improves absorption and tolerability and is supported by a recent pediatric RCT. Newer formulations—ferric polymaltose, ferrous bisglycinate, co-processed bisglycinate with alginate (Feralgine™), and vesicular encapsulated forms such as sucrosomial and liposomal ferric pyrophosphate—showed improved tolerability and palatability, supporting adherence with hematologic outcomes comparable to ferrous salts, particularly in children with intolerance, malabsorption, or inflammatory comorbidities. Intravenous iron is effective and safe with modern preparations and is reserved for severe anemia, malabsorption, or oral therapy failure. Conclusions: Oral ferrous salts should remain the first-line therapy in pediatric ID/IDA. Future pediatric trials should prioritize head-to-head comparisons of formulations, hepcidin-guided dosing, and patient-centred outcomes, including neurocognitive trajectories and quality of life. Full article

The built environment (BE) plays a central role in shaping everyday mobility patterns and determining how physical activity (PA) is integrated into daily life. Foundational BE frameworks such as the 5Ds (density, diversity, design, distance to transit, and destination accessibility) have shaped policy and planning worldwide. However, these frameworks remain predominantly spatial and overlook temporal dynamics. This review addresses this omission by introducing Duration as the sixth dimension (6th D) of the BE framework, reframing accessibility in terms of the lived temporal experience of movement rather than static spatial distance. Travel conditions vary across the day. Routes that are safe and efficient at one time often become congested, stressful, and prohibitive at another. Such variability undermines PA and active transport (AT) and diminishes the health benefits of supportive BE. Methodologically, the review synthesises evidence from 1991 to 2025 across public health, transport planning, BE, and environmental psychology. Pertinent literature (102 shortlisted articles) published in English was retrieved from Scopus, Web of Science (WoS), and PubMed, which collectively provide comprehensive coverage of multidisciplinary research spanning transport planning, public health, and behavioural sciences. The PRISMA 2020 approach and VOSviewer (version 1.6.20), were used, together with a structured, Excel-based integrative synthesis, to analyse publication trends, conceptual evolution, and integrative patterns in the retrieved literature. The synthesis shows that accessibility, mobility stress, and travel behaviour are strongly time-dependent. This time dependence is systematic rather than incidental across contexts. Globally, commute durations beyond 45 min are associated with lower life satisfaction and poorer health outcomes. Embedding Duration within BE frameworks establishes a time-responsive and equity-sensitive paradigm for healthier and more resilient urban systems. Full article

Objective: To provide a narrative overview of the scientific knowledge on Last Aid Courses and experiences from different countries. Background: The levels of death literacy, grief literacy, and knowledge about palliative care are low in many countries around the world. For many people, dying, death, and grief are still a taboo. Public Palliative Care Education (PPCE), the public knowledge approach, and the Last Aid Course (LAC) aim to increase death literacy, grief literacy, and public knowledge about palliative care. Methods: A literature search in the databases PubMed/Medline, CINAHL, and PsycInfo was undertaken. Other additional sources were found by hand searching, books, reference lists, and the internet. A narrative overview of the existing literature on LAC and Public Palliative Care Education (PPCE) is provided. Experiences with PPCE and LAC from different countries are presented. Based on the findings, a future agenda for research on PPCE and LAC is presented. Results and Discussion: PPCE and LAC have been introduced in 23 countries. A total of 17 articles and reviews on Last Aid were included. Research on the effects of LAC in different countries and cultural issues connected to LAC are ongoing. Conclusions: Since 2015, LACs have been introduced in 23 different countries. The LAC, the LAC-KT, and PPCE may enhance the public debate on dying, death, grief, and palliative care and may empower people to contribute to end-of-life care in the community. Future research on PPCE, the LAC, and the LAC-KT should focus on retention over time and the long-term effects of the courses. Full article

Incivility and civility have been studied for more than a century across disciplines and in many areas ranging from workplaces to communication, the digital world, and everyday life. They are often used to the detriment of marginalized groups. Their negative use is seen to set the groundwork for other negative treatments, such as bullying and harassment, impacting the social climate in a negative way. Ostracism is seen to be linked to incivility. Disabled people disproportionally face negative treatments, such as bullying and harassment, and experience a negative social climate, as highlighted by the UN Convention on the Rights of People with Disabilities, suggesting that they also disproportionately experience incivility and ostracism. Climate surveys aim to expose toxic social climate in workplaces, schools, and communities caused by incivility, ostracism, bullying, and harassment. As such, how incivility, civility, ostracism, and the design of climate surveys are discussed in the literature is of importance to disabled people. We could find no review that analyzed the use of climate surveys beyond individual surveys and the concepts of incivility and ostracism in relation to disabled people. The objective of our study was to contribute to filling this gap by analyzing the academic literature present in SCOPUS, EBSCO HOST (70 databases), and Web of Science, performing keyword frequency and content analysis of abstracts and full texts. Our findings provide empirical evidence for a systemic neglect of disabled people in the topics covered: from 21,215 abstracts mentioning “civilit*” or “incivilit*”, only 14 were relevant, and of the 8358 abstracts mentioning ostracism, only 26 were relevant. Of the 3643 abstracts mentioning “climate surveys,” 12 sources covered disabled people by focusing on a given survey, but not one study performed an evaluation of the utility of climate surveys for disabled people in general. Racism is seen as a structural problem facilitating civility/incivility. Ableism, the negative judgments of a given set of abilities someone has, and disablism, the systemic discrimination based on such judgments, are structural problems experienced by disabled people, facilitating civility/incivility. However, ableism generated only 2 hits, and disablism/disableism had no hits. Most of our sources focused on workplace incivility, and authors were mostly from the USA. We found no linkage to social and policy discourses that aim to make the social environment better, such as equity, diversity, and inclusion, well-being, and science and technology governance. This is the first paper of its kind to look in depth at how the academic literature engages with the concepts of civility, incivility, and ostracism and with the instrument of social climate surveys in relation to disabled people. Our findings can be used by many different disciplines and fields to strengthen the theoretical and practical discussions on the topics in relation to disabled people and beyond. Full article

The study conducted a review of Listeria prevalence, virulence, and adaptations associated with leafy vegetables from small-scale farms and their journey to markets. PubMed, Taylor and Francis, Oxford, and Google Scholar databases were utilised to search for English-language journal articles published between January 1992 and 2025. Studies utilised multi-locus sequence typing (MLST), polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), multiplex PCR, pulsed-field gel electrophoresis (PFGE), and whole genome sequencing WGS, confocal scanning laser microscopy technique for the detection of Listeria species, followed by transcriptomic, phenotypic analyses, strand-specific RNA-sequencing, and membrane lipid profiling. ST₅, ST₁₂₁, and ST₃₂₁ are considered predominant and virulent and have been identified in two ready-to-eat commodities, while ST₁, ST₂, and ST₂₀₄ are considered hypervirulent strains in food processing environments. Immunocompromised groups can experience severe life-threatening infections, even death. Significant economic losses due to shutdowns for sanitary procedures can occur, impacting food security. Full article

Background: Major airway injuries, regardless of whether their aetiology is traumatic or iatrogenic, are rare but potentially fatal. In selected cases, surgery plays a key role; however, it has to be performed by highly experienced professionals in emergency settings. Methods: We reviewed all surgical procedures involving the trachea which were performed at our institution in the last 5 years (365 procedures). We report here our experiences with major airway injuries, both traumatic and iatrogenic (19 procedures). All patients, including individuals from within our hospital and from other peripheral centres, were treated in an emergency setting within 12 h of correct diagnosis. Results: The location and extent of tracheal lesions can be different in every patient. After a proper evaluation with CT scan and bronchoscopy, we approached all our cases of tracheal injuries with a cervicotomy, using, in some selected cases, an endoscopic camera to better visualise lesions that involved the carina. However, in extremely severe cases, such as one we report here, where multiple repair attempts fail and tissue viability is compromised, demolitive surgery by means of posterolateral thoracotomy may represent the only remaining therapeutic option. Conclusions: Surgery on tracheal injuries is complex, highly specialised, and time-dependent. In selected cases, it has to be performed quickly by highly qualified professionals after proper evaluation in an emergency setting. Every airway injury differs in its location, extent, aetiology, and clinical presentation, and there is no unanimous consensus on standardising treatment. Only high-volume centres with highly experienced professionals can guarantee correct management of this rare but life-threatening event. Full article

Background/Objectives: Type 1 diabetes (T1D) is a common childhood condition with rising global incidence. Because early-onset T1D coincides with key periods of brain maturation, affected children may face neurocognitive risks. This review summarizes current evidence on the neurocognitive impact of pediatric T1D and related clinical implications. Methods: A structured search of PubMed, Scopus, and Web of Science (inception–October 2025) used combinations of terms related to T1D, cognitive outcomes, and brain imaging. Studies involving participants under 18 years that reported cognitive or neuroimaging findings were included. Results: Diabetic ketoacidosis (DKA) at diagnosis is consistently linked with acute and longer-term neurological injury, including reduced brain volume and potential persistent deficits in memory and executive functioning. Severe or recurrent hypoglycemia disproportionately affects the hippocampus, contributing to lasting learning and memory impairments. Chronic hyperglycemia is a major driver of progressive neurocognitive decline; higher HbA1c is associated with smaller brain volumes and poorer executive function, attention, and processing speed. Early-onset disease and longer duration further increase vulnerability. These neurocognitive effects translate into modest reductions in academic performance and quality of life, especially with poor glycemic control. Emerging evidence suggests that continuous glucose monitoring, insulin pumps, and hybrid closed-loop systems improve metabolic stability and may support healthier brain development. Conclusions: T1D children experience subtle but meaningful neurocognitive risks shaped by glycemic extremes and early disease onset. Routine neuropsychological monitoring, strengthened academic support, and wider use of advanced diabetes technologies may help preserve cognitive development. Larger, longitudinal neuroimaging studies are needed to guide targeted neuroprotective strategies. Full article

Neurometabolic diseases encompass a diverse group of rare and often progressive genetic disorders affecting the nervous system due to abnormalities in metabolic pathways. These conditions, including mitochondrial disorders, lysosomal storage diseases, and others, can manifest in adults with a range of neurological symptoms, which will be reviewed here. Given their complexity and chronic nature, comprehensive management is crucial for improving patients’ quality of life. In this Invited Perspective, we review the neurological signs and symptoms of the most commonly encountered inherited metabolic disorders in adult neurology. Furthermore, drawing on our clinical experience, we demonstrate that an integrated local care approach is fundamental for these patients, as it enables continuous monitoring, early intervention, and coordinated multidisciplinary support. Full article

Irritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by recurrent abdominal pain associated with a change in the frequency and/or form of stools. Approximately one in three patients with quiescent inflammatory bowel disease (IBD), defined as the absence of endoscopic evidence of active inflammation, experience IBS-type symptoms. These symptoms are associated with reduced quality of life and increased psychological burden, and can complicate clinical assessment by mimicking conditions such as small intestinal bacterial overgrowth, bile acid malabsorption, or post-inflammatory complications. This up-to-date narrative review examines the mechanisms, diagnostic challenges, and management of IBS-type symptoms in quiescent IBD. Evidence suggests that these symptoms arise from a complex “matrimony” of functional and organic processes, including low-grade residual inflammation, altered intestinal permeability, microbiota dysbiosis, visceral hypersensitivity, and psychosocial impairment. Diagnosing IBS-type symptoms in IBD requires a “positive”, symptom-focused approach while carefully excluding active inflammation. Management should adopt a biopsychosocial approach, integrating dietary strategies (e.g., low-FODMAP diet), brain–gut behavioral therapy, biofeedback therapy, and/or pharmacological treatments such as antispasmodics, antidiarrheals, laxatives, and neuromodulators to address both physiological and psychological factors. Future research should integrate sensitive biomarkers and longitudinal follow-up to enhance diagnostic precision and guide personalized therapy. Understanding and addressing the overlap between IBS and IBD is essential to reduce the multidimensional burden on physical health, psychological well-being, and daily functioning. Full article

MEDNIK syndrome (Mental Retardation, Enteropathy, Deafness, Neuropathy, Ichthyosis and Keratodermia) is a severe hyper-rare condition resulting from the biallelic variants in the AP1S1 gene, implicated in intracellular trafficking and copper homeostasis. Only 18 affected individuals (seven AP1S1 pathogenic variants overall) have been reported to date, with a high early lethality due to life-threatening congenital enteropathy. Seven patients have been empirically treated with zinc. Due to the paucity of literature data, little is known about the clinical course of individuals affected by MEDNIK syndrome, and the possible early association with epilepsy needs to be investigated. We present the first case of Italian origin affected by MEDNIK syndrome carrying a new homozygous AP1S1 stop variant, presenting with congenital severe enteropathy and feeding-related seizures, thus representing an early, singular manifestation of the disease. We describe her clinical course and the zinc acetate therapeutic experience. We also reviewed the literature focusing on clinical manifestations (especially neurological), brain neuroimaging and the symptom evolution of patients with AP1S1-related MEDNIK syndrome and discuss possible future therapeutic attempts. Full article