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1.
Pyrosequencing: Current forensic methodology and future applications-a review.
Ghemrawi, M, Tejero, NF, Duncan, G, McCord, B
Electrophoresis. 2023;(1-2):298-312
Abstract
The recent development of small, single-amplicon-based benchtop systems for pyrosequencing has opened up a host of novel procedures for applications in forensic science. Pyrosequencing is a sequencing by synthesis technique, based on chemiluminescent inorganic pyrophosphate detection. This review explains the pyrosequencing workflow and illustrates the step-by-step chemistry, followed by a description of the assay design and factors to keep in mind for an exemplary assay. Existing and potential forensic applications are highlighted using this technology. Current applications include identifying species, identifying bodily fluids, and determining smoking status. We also review progress in potential applications for the future, including research on distinguishing monozygotic twins, detecting alcohol and drug abuse, and other phenotypic characteristics such as diet and body mass index. Overall, the versatility of the pyrosequencing technologies renders it a useful tool in forensic genomics.
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Pharmacological advances in the treatment of nonalcoholic fatty liver diseases : focused on global results of randomized controlled trials.
An, J, Sohn, JH
Clinical and molecular hepatology. 2023;(Suppl):S268-S275
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease globally, and its prevalence is rapidly increasing. Nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD, is characterized by hepatocellular injury, inflammation, and fibrosis. Patients with NASH or severe fibrosis should be treated according to international NAFLD guidelines. Currently, regulatory agencies have not approved any pharmaceutical treatment for NAFLD. Vitamin E and pioglitazone are efficacious for NASH resolution; however, their benefits must be weighed against the reported risks. In a phase 2 trial, a glucagon-like peptide-1 agonist commonly used for diabetes and obesity was found to improve liver histology in patients with NASH. Furthermore, therapeutic agents targeting NASH pathogenesis, including bile acid signaling, insulin resistance, and lipid metabolism, are in various phases of clinical development. In this article, we review the benefits and drawbacks of current pharmacotherapy and the efficacy of upcoming treatments for NASH.
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3.
Inflammasome activation in traumatic brain injury and Alzheimer's disease.
Johnson, NH, de Rivero Vaccari, JP, Bramlett, HM, Keane, RW, Dietrich, WD
Translational research : the journal of laboratory and clinical medicine. 2023;:1-12
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Abstract
Traumatic brain injury (TBI) and Alzheimer's disease (AD) represent 2 of the largest sources of death and disability in the United States. Recent studies have identified TBI as a potential risk factor for AD development, and numerous reports have shown that TBI is linked with AD associated protein expression during the acute phase of injury, suggesting an interplay between the 2 pathologies. The inflammasome is a multi-protein complex that plays a role in both TBI and AD pathologies, and is characterized by inflammatory cytokine release and pyroptotic cell death. Products of inflammasome signaling pathways activate microglia and astrocytes, which attempt to resolve pathological inflammation caused by inflammatory cytokine release and phagocytosis of cellular debris. Although the initial phase of the inflammatory response in the nervous system is beneficial, recent evidence has emerged that the heightened inflammatory response after trauma is self-perpetuating and results in additional damage in the central nervous system. Inflammasome-induced cytokines and inflammasome signaling proteins released from activated microglia interact with AD associated proteins and exacerbate AD pathological progression and cellular damage. Additionally, multiple genetic mutations associated with AD development alter microglia inflammatory activity, increasing and perpetuating inflammatory cell damage. In this review, we discuss the pathologies of TBI and AD and how they are impacted by and potentially interact through inflammasome activity and signaling proteins. We discuss current clinical trials that target the inflammasome to reduce heightened inflammation associated with these disorders.
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Recommended Reference Values for Risk Assessment of Oral Exposure to Copper.
Taylor, AA, Tsuji, JS, McArdle, ME, Adams, WJ, Goodfellow, WL
Risk analysis : an official publication of the Society for Risk Analysis. 2023;(2):211-218
Abstract
The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) database, the authoritative source of U.S. risk assessment toxicity factors, currently lacks an oral reference dose (RfD) for copper. In the absence of such a value, various health-based reference values for copper are available for use in risk assessment. We summarize the scientific bases and differences in assumptions among key reference values for ingested copper to guide selection of appropriate values for risk assessment. A comprehensive review of the scientific literature best supports the oral RfD of 0.04 mg/kg body weight/day derived by EPA from their Drinking Water Action Level. This value is based on acute gastrointestinal effects but is further supported by broader analysis of copper deficiency and toxicity.
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Comorbidities with Familial Hypercholesterolemia (FH): A Systematic Review.
Vaseghi, G, Javanmard, SH, Heshmat-Ghahdarijani, K, Sarrafzadegan, N, Amerizadeh, A
Current problems in cardiology. 2023;(5):101109
Abstract
Familial hypercholesterolemia (FH) is linked to high levels of low-density lipoprotein cholesterol (LDL-C), atherosclerotic, and aortic stenosis to a lesser extent. We looked at the incidence of prevalent comorbid disorders other than cardiovascular disease (CVD), such as diabetes, chronic kidney disease (CKD), hypertension, and cancer in heterozygous FH (HeFH) patients. PubMed, Web of Science, and Google Scholar were searched systematically for studies reporting comorbidities in FH patients. Finally, 23 studies were included after excluding duplicates, papers with unrelated titles, reviews, abstracts, and papers with not sufficient data. Results showed that among the comorbidities that have been studied; FH patients had a greater prevalence of CKD. In terms of diabetes, the data are inconsistent, with some research indicating a higher prevalence of diabetes in FH patients and mostly indicating the opposite. Polymorphism study showed that hypertension has been linked to FH; however, the prevalence of the hypertensive subjects varies among FH groups. In comparison to the general population, cancer was found to have a lower or similar prevalence in FH patients. More research is needed in this area due to the variability of the results of the relationship between diabetes and FH and the small number of studies on cancer. In conclusion only CKD can be considered as an important and prevalent comorbidity in FH population after CVDs.
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Effects of chronic consumption of specific fruit (berries, cherries and citrus) on cognitive health: a systematic review and meta-analysis of randomised controlled trials.
Wang, Y, Haskell-Ramsay, C, Gallegos, JL, Lodge, JK
European journal of clinical nutrition. 2023;(1):7-22
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Abstract
OBJECTIVES The cognitive-protective effects related to the consumption of a variety of fruits are supported by several intervention studies. This systematic review and meta-analysis compared the magnitude of effects following chronic (≥1 week) consumption of frozen, freeze-dried powder including extracts and juices of fruits, covering berries, cherries and citrus, on cognition and mood in adults. METHODS PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until February, 2021. Inclusion criteria were randomised controlled trials assessing memory, executive function, psychomotor speed, mood and mini mental state examination in adult participants ≥18 years of age. Cognition was tested by global or domain specific tasks. RESULTS Out of 13,861 articles identified, 16 papers were included; 11 studies provided suitable data for meta-analysis. Fourteen studies reported improvement or trend for improvement in cognition, five studies assessed mood and one study supplementing grape juice found trend for mood improvement. From the meta-analysis, cherry juice supplementation was suggested to improve psychomotor speed by -0.37 of standardised mean difference (95% CI [-0.74, 0.01]) in reaction time (P = 0.05). CONCLUSIONS The meta-analysis did not sufficiently support a role for fruits or fruit forms to improve cognition and mood.
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Functionalized reactive polymers for the removal of chemical warfare agents: A review.
Snider, VG, Hill, CL
Journal of hazardous materials. 2023;:130015
Abstract
Protection from and removal of chemical warfare agents (CWAs) from the environment remains a global goal. Activated charcoal, metal oxides, metal organic frameworks (MOFs), polyoxometalates (POMs) and reactive polymers have all been investigated for CWA removal. Composite polymeric materials are rapidly gaining traction as versatile building blocks for personal protective equipment (PPE) and catalytic devices. Polymers are inexpensive to produce and easily engineered into a wide range of materials including films, electro-spun fibers, mixed-matrix membranes/reactors, and other forms. When containing reactive side-chains, hydrolysis catalysts, and/or oxidative catalysts polymeric devices are primed for CWA decontamination. In this review, recent advances in reactive polymeric materials for CWA removal are summarized. To aid in comparing the effectiveness of the different solid catalysts, particular attention is paid to the stoichiometric ratio of reactive species to toxic substrate (CWA or CWA simulant).
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A perfect fit: Bacteriophage receptor-binding proteins for diagnostic and therapeutic applications.
Klumpp, J, Dunne, M, Loessner, MJ
Current opinion in microbiology. 2023;:102240
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Abstract
Bacteriophages are the most abundant biological entity on earth, acting as the predators and evolutionary drivers of bacteria. Owing to their inherent ability to specifically infect and kill bacteria, phages and their encoded endolysins and receptor-binding proteins (RBPs) have enormous potential for development into precision antimicrobials for treatment of bacterial infections and microbial disbalances; or as biocontrol agents to tackle bacterial contaminations during various biotechnological processes. The extraordinary binding specificity of phages and RBPs can be exploited in various areas of bacterial diagnostics and monitoring, from food production to health care. We review and describe the distinctive features of phage RBPs, explain why they are attractive candidates for use as therapeutics and in diagnostics, discuss recent applications using RBPs, and finally provide our perspective on how synthetic technology and artificial intelligence-driven approaches will revolutionize how we use these tools in the future.
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Nutritional screening in a cancer prehabilitation programme: A cohort study.
Burden, ST, Bibby, N, Donald, K, Owen, K, Rowlinson-Groves, K, French, C, Gillespie, L, Murphy, J, Hurst, SJ, Mentha, R, et al
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2023;(2):384-394
Abstract
BACKGROUND Cancer patients are often malnourished pre-operatively. The present study aimed to establish whether current screening was appropriate for use in prehabilitation and investigate any association between nutritional risk, functionality and quality of life (QoL). METHODS This cohort study used routinely collected data from September 2020 to August 2021 from patients in a Prehab4cancer programme. Included patients were aged ≥ 18 years, had colorectal, lung or oesophago-gastric cancer and were scheduled for surgery. Nutritional assessment included Patient-Generated Subjective Global Assessment (PG-SGA) Short-Form and QoL with a sit-to-stand test. Association between nutritional risk and outcomes was analysed using adjusted logistic regression. RESULTS From 928 patients referred to Prehab4Cancer service over 12 months, data on nutritional risk were collected from 526 patients. Pre-operatively, 233 out of 526 (44%) patients were at nutritional risk (score ≥ 2). During prehabilitation, 31% of patients improved their PG-SGA and 74% of patients maintained or improved their weight. Odds ratios (OR) with confidence intervals (CI) showed that patients with better QoL using EuroQol-5 Dimensions (OR = 0.05, 95% CI = 0.01, 0.45, p = 0.01), EuroQol Visual Analogue Scale (OR = 0.96, 95% CI = 0.93, 1.00, p = 0.04) or sit-to-stand (OR = 0.96, 95% 0.93, 1.00, p = 0.04) were less likely to be nutritional at risk. CONCLUSIONS Almost half of patients in Prehab4Cancer programme assessed using PG-SGA were at risk of malnutrition. However, almost half of the sample did not have their risk assessed. Patients at risk of malnutrition were more likely to have a poorer QoL and sit-to-stand test than those who were not at risk.
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Single-Molecule Imaging of Membrane Proteins on Vascular Endothelial Cells.
Park, J, Jin, S, Jang, J, Seo, D
Journal of lipid and atherosclerosis. 2023;(1):58-72
Abstract
Transporting substances such as gases, nutrients, waste, and cells is the primary function of blood vessels. Vascular cells use membrane proteins to perform crucial endothelial functions, including molecular transport, immune cell infiltration, and angiogenesis. A thorough understanding of these membrane receptors from a clinical perspective is warranted to gain insights into the pathogenesis of vascular diseases and to develop effective methods for drug delivery through the vascular endothelium. This review summarizes state-of-the-art single-molecule imaging techniques, such as super-resolution microscopy, single-molecule tracking, and protein-protein interaction analysis, for observing and studying membrane proteins. Furthermore, recent single-molecule studies of membrane proteins such as cadherins, integrins, caveolins, transferrin receptors, vesicle-associated protein-1, and vascular endothelial growth factor receptor are discussed.
