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Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs

Recurrent Mandibular Ewing sarcoma in an 11-year-old boy: a rare pediatric case and review of the literature.

RATIONALE: Mandibular Ewing sarcoma is exceptionally rare in children and frequently mimics common odontogenic infections. This overlap leads to delayed diagnosis and potentially rapid tumor progression. Early recognition and appropriate multimodal management are critical for improving outcomes. PATIENT CONCERNS: An 11.5-year-old Iranian boy of Middle Eastern ethnicity presented with progressive left mandibular swelling and pain for 1 month, unresponsive to antibiotic therapy previously prescribed for presumed dental abscess. DIAGNOSIS: Imaging (CT, MRI) revealed an aggressive destructive ma

Adult-Onset Cerebral Adrenoleukodystrophy Without Adrenal Gland Involvement.

X-linked adrenoleukodystrophy (X-ALD) is a metabolic disorder characterized by endocrine and neurological degeneration. A rare and variegated entity in adults, diagnosis is often a significant challenge and can lead to extensive testing, including invasive procedures if clinical suspicion is not high. We present the case of a 46-year-old-male with neurological dysfunction that is uncommon in X-ALD with preserved adrenocortical function. Initially misdiagnosed with multiple sclerosis, the patient faced a significant neurological and cognitive decline in a short follow-up time frame, ultimately

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… Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Bezman L, Moser AB, Raymond GV, et al. Ann Neurol. 2001;1:512–517. 4. X-linked adrenoleukodystrophy: pathogenesis and treatment. Engelen M, Kemp S, Poll-The B. …

"Tough Things You're Going to Have to Go Through": Dyadic Interview Study Including the Perspectives and Needs of Patients and Their Caregivers Post-Hematopoietic Cell Transplant.

BACKGROUND: Patients undergoing hematopoietic cell transplant (HCT) and their caregivers are under a significant amount of stress throughout the HCT process with fear of disease recurrence, graft failure, and many other HCT-related complications. However, the needs and perspectives of patients undergoing HCT and their caregivers as dyadic units over the peri-HCT period are continuing to be studied and are an evolving field of research. OBJECTIVE: To better understand patient and caregiver perspectives throughout the HCT course, patients undergoing HCT and their caregivers were able to opt-in

Euthanasia as a safeguard for living: Anticipation and incurable cancer in a Colombian context.

This article builds on years of ethnographic conversations I sustained with my father, 89, who lives in Colombia. Soon after getting diagnosed with an incurable Multiple Myeloma-a cancer known for unleashing prolonged and painful agonies-he withdrew from oncology treatments and secured access to euthanasia (assisted-dying) on his own, bypassing medico-insurance guidelines created to regulate this medical practice and prevent abuses. Eight years after withdrawing treatments, my dad is still alive. His case shines a light on how securing access to euthanasia may have had unintended therapeutic e

Perceived stress, distress, burden, and caregiving preparedness in family caregivers of patients with hematologic malignancies during the first months of treatment.

BackgroundHematologic malignancies frequently require intensive treatment, leaving patients to rely on informal caregivers for emotional, logistical, and health care support. This high level of care and support can place an unintended burden on the caregiver. This study examined caregiver wellbeing during the initial treatment period.MethodsFamily caregivers identified by a patient with a hematologic malignancy were enrolled in this longitudinal, descriptive study. Participants answered questionnaires related to distress, stress, caregiver burden, and caregiver preparedness at baseline and six

Остеопонтин по хроническим воспламенительным болезням: механизмы, биомаркеры и терапевтические стратегии.

Хронические подстрекательские заболевания, такие, как ревматуидный артрит (RA), системный волчан Эрематосус (SLE), множественный склероз (MS), атеросклероз и воспалительный кишечник (IBD), вызывают серьезную озабоченность во всем мире. Эти расстройства характеризуются стойким воспалением, дисфункцией иммунной системы, повреждением тканей и фиброзом, что в конечном счете приводит к серьезной дисфункции органов и снижению качества жизни. Остеопонтин (OPS), многофункциональный внеклеточный белок, играет решающую роль в иммунном регулировании, воспалении и реконструкции тканей. Она поощряет набор

Протеиновая пальмитиоляция в гематологическое облучение: механистические связи с липидным метаболическим перепрограммированием и резистентностью к терапии.

Протеиновая пальмитиолация стала центральным постпереходным механизмом, регулирующим локализацию белков, стабильность и трансдукцию сигналов. В гематологических галактиках эта динамическая модификация находится на пересечении липидного метаболического перепрограммирования, взаимодействия между опухолью и иммуном и терапевтического сопротивления. Здесь мы рассматриваем вопрос о том, как дисрегулированные пальмитоилпереносазы и депальмитолазы изменяют метаболические ферменты, липидные переносчики, липидно-дрофтовые белки, онкогенные сигнальные компоненты и молекулы иммунного регулирования, созда

Natural-History Mapping of Lysosomal Storage Disorders (LSDs): Gaucher Disease as a Model for Precision Care.

Natural-history datasets have become pivotal for drug development and for shaping clinical-practice guidelines in rare diseases, yet many lysosomal storage disorders would benefit from deep phenotyping and modern analytic methods. Our objective was to integrate the past decade of genomic, cellular, treatment-outcome, and regulatory advances into a practical framework for capturing and interpreting natural-history data, using Gaucher disease (GD) as a paradigm. We reviewed more than 300 peer-reviewed articles (2005-2025), FDA guidance documents, and output from large real-world registries. Part

Качество жизни людей с множественным склерозом в Португалии.

ВВЕДЕНИЕ: Множественный склероз существенно влияет на качество жизни тех, кто страдает от этого конкретного состояния. ЦЕЛЬ: Оценка качества жизни людей с множественным склерозом и анализ взаимосвязи между болезнью и связанными с ней последствиями и различными социально-демографическими, клиническими и функциональными переменными. МАТЕРИАЛЫ И МЕТОДЫ: Наблюдение, перекрестное, описательное и количественное исследование, проведенное с использованием непробивной удобной выборки, состоящей из 70 пациентов, страдающих множественным склерозом, зарегистрированных Ассоциацией по множественному склероз

Patients' and family members' dyadic experience of post-operative delirium in the intensive care unit: A qualitative study.

BACKGROUND: Post-operative delirium is a complication with long-lasting consequences for both patients and their families. This is particularly true for those transferred to the intensive care unit after surgery, where the incidence of post-operative delirium is high, and patient outcomes are often poor. Despite the acknowledged role of family engagement in delirium management, previous research has mainly focused on patients, with limited exploration of the shared experiences between patients and family members. AIM: This study aims to explore the experiences of patients and family members d

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… Considering the increased insecurity of patients in this context, some patients and their families believed that POD would subside or would not occur in cases of extended family presence, and might lead to an improvement in the patients' poor treatment adherence due to POD. …

Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies.

The intersection of psychiatry and medicine presents unique diagnostic and ethical challenges, particularly for conditions involving significant brain-body interactions, such as psychosomatic, somatopsychic, and complex systemic disorders. This article explores the historical and contemporary issues in diagnosing such conditions, emphasizing the fragmentation of medical and psychiatric knowledge, biases in clinical guidelines, and the mismanagement of complex illnesses. Diagnostic errors often arise from insufficient integration between general medicine and psychiatry, compounded by the relian

Barriers, facilitators, perceptions and preferences influencing physical activity participation, and the similarities and differences between cancer types and treatment stages - A systematic rapid review.

The aim of this systematic rapid review was to explore barriers, facilitators, perceptions and preferences of physical activity for people diagnosed with cancer, by cancer type and treatment stage. The search strategy, implemented through four databases, included terms relating to cancer, physical activity, barriers, facilitators, perceptions and preferences, and relevant study designs. Studies reporting the outcomes of interests for adults diagnosed with cancer and living in Western countries were included and grouped according to the Social-Ecological Model and the Health Belief Model, and p

LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.

Lysosomal-associated protein transmembrane (LAPTM) family members-LAPTM4A, LAPTM4B, and LAPTM5-regulate lysosomal integrity, autophagy-lysosome flux, lipid homeostasis, and immune signaling, pathways increasingly implicated in neurological disease. This review synthesizes structure-function evidence for LAPTM proteins and examines how their dysregulation contributes to Alzheimer's and Parkinson's disease, ischemia-reperfusion injury, and gliomas. Based on a targeted narrative analysis of primary and translational studies, we highlight that LAPTM proteins influence lysosomal acidification and m

Caregiver burden and quality of life in palliative care: cross-sectional study.

BACKGROUND: Literature on caregiver burden is limited in India and Kerala. We examined the prevalence and factors associated with caregiver burden and its impact on their quality of life. METHODS: We conducted a cross-sectional study among 115 informal caregivers (mean age 70 years, 80% female) of palliative care patients in Kerala. Caregivers were interviewed using the Zarit Burden Interview-22 and the WHOQOL-BREF questionnaires. Factors associated with caregiver burden were analysed using binary logistic regression. RESULTS: The prevalence of moderate to severe burden was 32.1% (95% CI 23.

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021.

The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition ("first-in-indication"), (2) first drug using a novel molecular mechanism ("first-in-class"), and (3) "next-in-class", i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indicati

Online education for rare genetic diseases: a systematic review.

IntroductionRare genetic diseases are, collectively, not in fact rare. However, educational opportunities focused on rare genetic disease can be limited. The Internet has increased the availability of education related to rare genetic disease and is accessible to a diverse range of people who seek out such information, including healthcare professionals, researchers, students, patients, and the public.PurposeTo assess the potential educational outreach of the Internet, this systematic literature review will appraise the landscape of what education for rare genetic disease is available online,

Nuances in the treatment of malignant tumors of the clival and petroclival region.

Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnost

Площадь метилирования ДНК клеток цереброспинальной жидкости в множестве склероза: исследование эпигеномной ассоциации.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, в которой метилация ДНК может увязывать генетические и экологические факторы риска. Methods: Мы профилировали содержание метилации ДНК по всему геному в клетках цереброспиновой жидкости (CSF) у людей с MS (pwMS) и совпадающими контрольными устройствами. Дифференцированные метилированные позиции (DMP) и регионы (DMR) были интегрированы с транскриптомными данными, аннотациями клеточного хроматина Т и анализом путей. Выражение гамма-протокадерина (ПХДГ) было оценено в первичных подмножествах C

Assessment of Psychiatric Disorders in Consultation-Liaison Setting.

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