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Ageing Research Reviews Sep 2021Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and... (Review)
Review
Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting.
Topics: Aged; Dietary Supplements; Energy Intake; Frailty; Humans; Malnutrition; Nutritional Status; Protein-Energy Malnutrition; Sarcopenia
PubMed: 34237434
DOI: 10.1016/j.arr.2021.101401 -
Trends in Cell Biology Oct 2019Poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with deficiency for homologous recombination (HR), a pathway essential for DNA double-strand break... (Review)
Review
Poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with deficiency for homologous recombination (HR), a pathway essential for DNA double-strand break repair. PARP inhibitors (PARPi) therefore hold great promise for the treatment of tumors with disruptive mutations in BRCA1/2 or other HR factors. Unfortunately, PARPi resistance has proved to be a major problem in the clinic. Knowledge about PARPi resistance is expanding quickly, revealing four main mechanisms that alter drug availability, affect (de)PARylation enzymes, restore HR, or restore replication fork stability. We discuss how studies on resistance mechanisms have yielded important insights into the regulation of DNA double-strand break (DSB) repair and replication fork protection, and how these studies could pave the way for novel treatment options to target resistance mechanisms or acquired vulnerabilities.
Topics: Animals; BRCA1 Protein; Breast Neoplasms; DNA Breaks, Double-Stranded; DNA Repair; DNA, Neoplasm; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Homologous Recombination; Humans; Mice; Mutation; Ovarian Neoplasms; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Tumor Cells, Cultured
PubMed: 31421928
DOI: 10.1016/j.tcb.2019.07.008 -
Microbial Pathogenesis Jan 2021Kwashiorkor and marasmus are two clinical syndromes observed in severe acute malnutrition. In this review, we highlighted the differences between these two syndromes by... (Meta-Analysis)
Meta-Analysis Review
Kwashiorkor and marasmus are two clinical syndromes observed in severe acute malnutrition. In this review, we highlighted the differences between these two syndromes by reviewing the data comparing kwashiorkor and marasmus in literature, combined with recent microbiological findings and meta-analysis. Depletion of antioxidants, vitamins and minerals were more severe in kwashiorkor than marasmus. This was consistent with the severe and uncontrolled oxidative stress associated with the depletion of gut anaerobes and the relative proliferation of aerotolerant gut pathogens. This relative proliferation and invasion of gut microbes belonging to the aerotolerant Proteobacteria phylum and pathogens suggested a specific microbial process critical in the pathogenesis of kwashiorkor. Liver mitochondrial and peroxisomal dysfunction could be secondary to toxic microbial compounds produced in the gut such as ethanol, lipopolysaccharides and endotoxins produced by Proteobacteria, particularly Klebsiella pneumoniae, and aflatoxin produced by Aspergillus species. The gut-liver axis alteration is characterized by oedema and a fatty and enlarged liver and was associated with a dramatic depletion of methionine and glutathione, an excessive level of free circulating iron and frequent lethal bacteraemia by enteric pathogens. This was consistent with the fact that antibiotics improved survival only in children with kwashiorkor but not marasmus. The specific pathogenic characteristics of kwashiorkor identified in this review open new avenues to develop more targeted and effective treatments for both marasmus and/or kwashiorkor. Urgent correction of plasma glutathione depletion, alongside supply of specific essential amino acids, particularly methionine and cysteine, early detection of pathogens and an antibiotic more efficient than amoxicillin in supressing gut Proteobacteria including K. pneumoniae, and probiotics to restore the human gut anaerobic mature microbiota could save many more children with kwashiorkor.
Topics: Amoxicillin; Child; Gastrointestinal Microbiome; Humans; Infant; Kwashiorkor; Protein-Energy Malnutrition; Severe Acute Malnutrition
PubMed: 33359074
DOI: 10.1016/j.micpath.2020.104702 -
Drugs Nov 2020Risdiplam (Evrysdi™) is an orally administered, survival motor neuron 2 (SMN2)-directed RNA splicing modifier being developed by Roche, PTC Therapeutics Inc and the... (Review)
Review
Risdiplam (Evrysdi™) is an orally administered, survival motor neuron 2 (SMN2)-directed RNA splicing modifier being developed by Roche, PTC Therapeutics Inc and the SMA Foundation for the treatment of the spinal muscular atrophy. The small molecule is designed to treat spinal muscular atrophy caused by mutations in chromosome 5q leading to SMN protein deficiency. The drug boosts the ability of an alternative gene SMN2 to produce full-length and functional SMN protein. In August 2020, Evrysdi™ (risdiplam) received its first approval in the USA for the treatment of spinal muscular atrophy in patients 2 months of age and older. Risdiplam is in pre-registration for this indication in numerous countries worldwide, including the European Union, Brazil, Chile, China, Indonesia, Russia, South Korea and Taiwan. This article summarizes the milestones in the development of risdiplam leading to this first approval for spinal muscular atrophy.
Topics: Administration, Oral; Adolescent; Alternative Splicing; Azo Compounds; Child; Child, Preschool; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Approval; Humans; Infant; Multicenter Studies as Topic; Muscular Atrophy, Spinal; Mutation; Pyrimidines; Survival of Motor Neuron 2 Protein; United States; United States Food and Drug Administration; Young Adult
PubMed: 33044711
DOI: 10.1007/s40265-020-01410-z -
Advances in Kidney Disease and Health Nov 2023The use of peritoneal dialysis (PD) has been associated with improved quality of life, cost-effectiveness, and better outcomes for patients with kidney failure. However,... (Review)
Review
The use of peritoneal dialysis (PD) has been associated with improved quality of life, cost-effectiveness, and better outcomes for patients with kidney failure. However, many patients utilizing PD for replacement therapy face numerous nutritional hurdles. As the use of PD continues to increase worldwide, malnutrition has become an increasingly recognized concern for patients undergoing PD. The nephrology community needs to recognize and treat malnutrition to promote optimal nutritional states for our patients. In this review, we discuss several factors that contribute to malnutrition and protein-energy wasting and explore the benefits and limitations of nutritional parameters used to assess protein-calorie malnutrition. We also emphasize updated guidelines on daily caloric, protein, and micronutrient recommendations, as well as their effects on electrolyte homeostasis.
Topics: Humans; Quality of Life; Nutritional Status; Peritoneal Dialysis; Malnutrition; Protein-Energy Malnutrition
PubMed: 38453271
DOI: 10.1053/j.akdh.2023.12.008 -
Clinical Endocrinology Dec 2023Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21-hydroxylase, 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase type 2, 17α-hydroxylase/17,20-lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme deficiencies are considered within the definition of CAH, the term 'CAH' is often used to refer to '21-hydroxylase deficiency (21OHD)' since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH.
PubMed: 38126084
DOI: 10.1111/cen.15009 -
Nutrients May 2021Life extension in modern society has introduced new concepts regarding such disorders as frailty and sarcopenia, which has been recognized in various studies. At the... (Review)
Review
Life extension in modern society has introduced new concepts regarding such disorders as frailty and sarcopenia, which has been recognized in various studies. At the same time, cutting-edge technology methods, e.g., renal replacement therapy for conditions such as hemodialysis (HD), have made it possible to protect patients from advanced lethal chronic kidney disease (CKD). Loss of muscle and fat mass, termed protein energy wasting (PEW), has been recognized as prognostic factor and, along with the increasing rate of HD introduction in elderly individuals in Japan, appropriate countermeasures are necessary. Although their origins differ, frailty, sarcopenia, and PEW share common components, among which skeletal muscle plays a central role in their etiologies. The nearest concept may be sarcopenia, for which diagnosis techniques have recently been reported. The focus of this review is on maintenance of skeletal muscle against aging and CKD/HD, based on muscle physiology and pathology. Clinically relevant and topical factors related to muscle wasting including sarcopenia, such as vitamin D, myostatin, insulin (related to diabetes), insulin-like growth factor I, mitochondria, and physical inactivity, are discussed. Findings presented thus far indicate that in addition to modulation of the aforementioned factors, exercise combined with nutritional supplementation may be a useful approach to overcome muscle wasting and sarcopenia in elderly patients undergoing HD treatments.
Topics: Aged; Aged, 80 and over; Dietary Supplements; Elder Nutritional Physiological Phenomena; Exercise; Female; Humans; Japan; Male; Muscle, Skeletal; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic; Sarcopenia
PubMed: 34063269
DOI: 10.3390/nu13051538 -
Frontiers in Immunology 2021Obstructive sleep apnea (OSA) associated neurocognitive impairment is mainly caused by chronic intermittent hypoxia (CIH)-triggered neuroinflammation and oxidative...
NLRP3 Deficiency Protects Against Intermittent Hypoxia-Induced Neuroinflammation and Mitochondrial ROS by Promoting the PINK1-Parkin Pathway of Mitophagy in a Murine Model of Sleep Apnea.
Obstructive sleep apnea (OSA) associated neurocognitive impairment is mainly caused by chronic intermittent hypoxia (CIH)-triggered neuroinflammation and oxidative stress. Previous study has demonstrated that mitochondrial reactive oxygen species (mtROS) was pivotal for hypoxia-related tissue injury. As a cytosolic multiprotein complex that participates in various inflammatory and neurodegenerative diseases, NLRP3 inflammasome could be activated by mtROS and thereby affected by the mitochondria-selective autophagy. However, the role of NLRP3 and possible mitophagy mechanism in CIH-elicited neuroinflammation remain to be elucidated. Compared with wild-type mice, NLRP3 deficiency protected them from CIH-induced neuronal damage, as indicated by the restoration of fear-conditioning test results and amelioration of neuron apoptosis. In addition, NLRP3 knockout mice displayed the mitigated microglia activation that elicited by CIH, concomitantly with elimination of damaged mitochondria and reduction of oxidative stress levels (malondialdehyde and superoxide dismutase). Elevated LC3 and beclin1 expressions were remarkably observed in CIH group. experiments, intermittent hypoxia (IH) significantly facilitated mitophagy induction and NLRP3 inflammasome activation in microglial (BV2) cells. Moreover, IH enhanced the accumulation of damaged mitochondria, increased mitochondrial depolarization and augmented mtROS release. Consistently, NLRP3 deletion elicited a protective phenotype against IH through enhancement of Parkin-mediated mitophagy. Furthermore, Parkin deletion or pretreated with 3MA (autophagy inhibitor) exacerbated these detrimental actions of IH, which was accompanied with NLRP3 inflammasome activation. These results revealed NLRP3 deficiency acted as a protective promotor through enhancing Parkin-depended mitophagy in CIH-induced neuroinflammation. Thus, NLRP3 gene knockout or pharmacological blockage could be as a potential therapeutic strategy for OSA-associated neurocognitive impairment.
Topics: Animals; Brain; Cell Line; Disease Models, Animal; Hypoxia; Inflammasomes; Inflammation; Male; Mice, Inbred C57BL; Mice, Knockout; Microglia; Mitochondria; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroimmunomodulation; Oxidative Stress; Protein Kinases; Reactive Oxygen Species; Signal Transduction; Sleep Apnea Syndromes; Ubiquitin-Protein Ligases; Mice
PubMed: 33717152
DOI: 10.3389/fimmu.2021.628168