-
Molecular Psychiatry Oct 2021Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular... (Review)
Review
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; tau Proteins
PubMed: 34456336
DOI: 10.1038/s41380-021-01249-0 -
European Urology Nov 2022International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate... (Review)
Review
CONTEXT
International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate opportunities to reduce its incidence through prevention and surveillance.
OBJECTIVE
To retrieve and summarize global incidence and mortality rates of KC and risk factors associated with its development, and to describe known familial syndromes and genetic alterations that represent biologic risk factors.
EVIDENCE ACQUISITION
A systematic review was conducted via Medline (PubMed) and Scopus to include meta-analyses, reviews, and original studies regarding renal cell carcinoma, epidemiology, and risk factors.
EVIDENCE SYNTHESIS
Our narrative review provides a detailed analysis of KC incidence and mortality, with significant variations across time, geography, and sex. In particular, while KC incidence has continued to increase, mortality models have leveled off. Among the many risk factors, hypertension, obesity, and smoking are the most well established. The emergence of new genetic data coupled with observational data allows for integrated management and surveillance strategies for KC care.
CONCLUSIONS
KC incidence and mortality rates vary significantly by geography, sex, and age. Associations of the development of KC with modifiable and fixed risk factors such as obesity, hypertension, smoking, and chronic kidney disease (CKD)/end-stage kidney disease (ESKD) are well described. Recent advances in the genetic characterization of these cancers have led to a better understanding of the germline and somatic mutations that predispose patients to KC development, with potential for identification of therapeutic targets that may improve outcomes for these at-risk patients.
PATIENT SUMMARY
We reviewed evidence on the occurrence of kidney cancer (KC) around the world. Currently, the main avoidable causes are smoking, obesity, and high blood pressure. Although other risk factors also contribute, prevention and treatment of these three factors provide the best opportunities to reduce the risk of developing KC at present.
Topics: Biological Products; Carcinoma, Renal Cell; Humans; Hypertension; Kidney Neoplasms; Obesity
PubMed: 36100483
DOI: 10.1016/j.eururo.2022.08.019 -
British Journal of Sports Medicine Jun 2022Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association.
DESIGN
A systematic review and meta-analysis. Pooled effect sizes, dose-response analysis and funnel plots were used to synthesise the results.
DATA SOURCES
CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021).
ELIGIBILITY CRITERIA
Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer's disease or vascular dementia were included (n=58).
RESULTS
PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer's disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (≥20 years) for all-cause dementia and Alzheimer's disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose-response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer's disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer's disease.
CONCLUSION
PA was associated with lower incidence of all-cause dementia and Alzheimer's disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.
Topics: Alzheimer Disease; Dementia, Vascular; Disease Progression; Exercise; Humans; Prospective Studies; Protective Factors
PubMed: 35301183
DOI: 10.1136/bjsports-2021-104981 -
The Lancet. Infectious Diseases Aug 2022According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and... (Review)
Review
According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and mortality and a rising pressure on health-care systems. However, the development of new antibiotics is an expensive and time-consuming process, urging scientists to seek alternative antimicrobial strategies. Over the past few decades, the concept of therapeutic administration of bacteriophages (also known as phages) has gained popularity worldwide. Although conceptually promising, the widespread implementation of phage therapy in routine clinical practice is restricted by the scarcity of safety and efficacy data obtained according to the strict standards of the applicable clinical trial regulations. In this systematic review, we list clinical data published between Jan 1, 2000 and Aug 14, 2021 on the safety and efficacy of phage therapy for difficult-to-treat bacterial infections, and provide an overview of trials and case studies on the use of phage therapy in several medical disciplines.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Humans; Phage Therapy
PubMed: 35248167
DOI: 10.1016/S1473-3099(21)00612-5 -
Acta Neuropathologica Communications Mar 2023In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified... (Review)
Review
In the contexts of aging, injury, or neuroinflammation, activated microglia signaling with TNF-α, IL-1α, and C1q induces a neurotoxic astrocytic phenotype, classified as A1, A1-like, or neuroinflammatory reactive astrocytes. In contrast to typical astrocytes, which promote neuronal survival, support synapses, and maintain blood-brain barrier integrity, these reactive astrocytes downregulate supportive functions and begin to secrete neurotoxic factors, complement components like C3, and chemokines like CXCL10, which may facilitate recruitment of immune cells across the BBB into the CNS. The proportion of pro-inflammatory reactive astrocytes increases with age through associated microglia activation, and these pro-inflammatory reactive astrocytes are particularly abundant in neurodegenerative disorders. As the identification of astrocyte phenotypes progress, their molecular and cellular effects are characterized in a growing array of neuropathologies.
Topics: Humans; Astrocytes; Microglia; Central Nervous System; Blood-Brain Barrier; Chemokines; Neurotoxicity Syndromes
PubMed: 36915214
DOI: 10.1186/s40478-023-01526-9 -
Sleep Medicine Reviews Feb 2022Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic... (Review)
Review
Current theories of the glymphatic system (GS) hypothesize that it relies on cerebrospinal fluid (CSF) circulation to disseminate growth factors and remove metabolic waste from the brain with increased CSF production and circulation during sleep; thereby, linking sleep disturbance with elements of CSF circulation and GS exchange. However, our growing knowledge of the relations between sleep, CSF, and the GS are plagued by variability in sleep and CSF measures across a wide array of pathologies. Hence, this review aims to summarize the dynamic relationships between sleep, CSF-, and GS-related features in samples of typically developing individuals and those with autoimmune/inflammatory, neurodegenerative, neurodevelopmental, sleep-related, neurotraumatic, neuropsychiatric, and skull atypicalities. One hundred and ninety articles (total n = 19,129 participants) were identified and reviewed for pathology, CSF circulation and related metrics, GS function, and sleep. Numerous associations were documented between sleep problems and CSF metabolite concentrations (e.g., amyloid-beta, orexin, tau proteins) and increased CSF volumes or pressure. However, these relations were not universal, with marked differences across pathologies. It is clear that elements of CSF circulation/composition and GS exchange represent pathways influenced by sleep; however, carefully designed studies and advances in GS measurement are needed to delineate the nuanced relationships.
Topics: Amyloid beta-Peptides; Brain; Glymphatic System; Humans; Sleep; Sleep Wake Disorders
PubMed: 34902819
DOI: 10.1016/j.smrv.2021.101572 -
Nutrients Dec 2021Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using... (Meta-Analysis)
Meta-Analysis
Whether the gut microbiome in obesity is characterized by lower diversity and altered composition at the phylum or genus level may be more accurately investigated using high-throughput sequencing technologies. We conducted a systematic review in PubMed and Embase including 32 cross-sectional studies assessing the gut microbiome composition by high-throughput sequencing in obese and non-obese adults. A significantly lower alpha diversity (Shannon index) in obese versus non-obese adults was observed in nine out of 22 studies, and meta-analysis of seven studies revealed a non-significant mean difference (-0.06, 95% CI -0.24, 0.12, = 81%). At the phylum level, significantly more Firmicutes and fewer Bacteroidetes in obese versus non-obese adults were observed in six out of seventeen, and in four out of eighteen studies, respectively. Meta-analyses of six studies revealed significantly higher Firmicutes (5.50, 95% 0.27, 10.73, = 81%) and non-significantly lower Bacteroidetes (-4.79, 95% CI -10.77, 1.20, = 86%). At the genus level, lower relative proportions of and and higher , , , , , , , , , , , , and were found in obese versus non-obese adults. Although a proportion of studies found lower diversity and differences in gut microbiome composition in obese versus non-obese adults, the observed heterogeneity across studies precludes clear answers.
Topics: Bacteria; Feces; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Obesity
PubMed: 35010887
DOI: 10.3390/nu14010012 -
Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
BMC Psychology Apr 2023Adolescents have extensive use of screens and, they have common complains related to mental health. Here a systematic review was done to understand the association...
BACKGROUND
Adolescents have extensive use of screens and, they have common complains related to mental health. Here a systematic review was done to understand the association between screen time and adolescent's mental health.
METHOD
This review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. An update search was performed in January 2023 with the following keywords: "screen time," "adolescent," and "mental health" on PubMed, PsycINFO and Scopus databases.
RESULTS
50 articles were included, most have found associations between screen exposure and mental health in adolescents. The most used device by adolescents was the smartphone and the use on weekdays was associated with diminished mental well-being. Social media use was negatively associated with mental well-being and, in girls, associated at higher risk for depression.
CONCLUSION
Excessive screen time in adolescents seems associated with mental health problems. Given the profusion and disparity of the results, additional studies are needed to clarify elements such as the screen content or the interaction of adolescents with different screen devices.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022302817.
Topics: Female; Humans; Adolescent; Screen Time; Mental Health; Smartphone; Depression; Psychological Well-Being
PubMed: 37081557
DOI: 10.1186/s40359-023-01166-7 -
Frontiers in Neurology 2020Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the... (Review)
Review
Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies.
PubMed: 33473247
DOI: 10.3389/fneur.2020.00778