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Frontiers in Nutrition 2019An individual's dietary and supplement strategies can influence markedly their physical performance. Personalized nutrition in athletic populations aims to optimize... (Review)
Review
An individual's dietary and supplement strategies can influence markedly their physical performance. Personalized nutrition in athletic populations aims to optimize health, body composition, and exercise performance by targeting dietary recommendations to an individual's genetic profile. Sport dietitians and nutritionists have long been adept at placing additional scrutiny on the one-size-fits-all general population dietary guidelines to accommodate various sporting populations. However, generic "one-size-fits-all" recommendations still remain. Genetic differences are known to impact absorption, metabolism, uptake, utilization and excretion of nutrients and food bioactives, which ultimately affects a number of metabolic pathways. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients and other food components. Although there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to an ergogenic aid, there is a growing foundation of research linking gene-diet interactions on biomarkers of nutritional status, which impact exercise and sport performance. This foundation forms the basis from which the field of sport nutrigenomics continues to develop. We review the science of genetic modifiers of various dietary factors that impact an athlete's nutritional status, body composition and, ultimately athletic performance.
PubMed: 30838211
DOI: 10.3389/fnut.2019.00008 -
The Yale Journal of Biology and Medicine Dec 2022Worldwide, remains a leading nosocomial pathogen that is difficult to treat and constitutes a challenging menace to healthcare systems. shows increased and alarming... (Review)
Review
Worldwide, remains a leading nosocomial pathogen that is difficult to treat and constitutes a challenging menace to healthcare systems. shows increased and alarming resistance to carbapenems, long acknowledged as last-resort antibiotics for treatment of resistant infections. Varied and recalcitrant pathways of resistance to carbapenems can simultaneously occur in , including the production of carbapenemases, broadest spectrum types of β-lactamases that hydrolyze virtually almost all β-lactams, including carbapenems. The organism can produce chromosomal, plasmid-encoded, and integron- or transposon-mediated carbapenemases from different molecular classes. These include Ambler class A (KPC and some types of GES enzymes), class B (different metallo-β-lactamases such as IMP, VIM, and NDM), and class D (oxacillinases with carbapenem-hydrolyzing capacity like OXA-198) enzymes. Additionally, derepression of chromosomal AmpC cephalosporinases in contributes to carbapenem resistance in the presence of other concomitant mechanisms such as impermeability or efflux overexpression. Epidemiologic and molecular evidence of carbapenemases in has been long accumulating, and reports of their existence in different geographical areas of the world currently exist. Such reports are continuously being updated and reveal emerging varieties of carbapenemases and/or new genetic environments. This review summarizes carbapenemases of importance in , highlights their genetic profile, and presents current knowledge about their global epidemiology.
Topics: Humans; Pseudomonas aeruginosa; Genetic Profile; beta-Lactamases; Anti-Bacterial Agents; Carbapenems; Microbial Sensitivity Tests
PubMed: 36568831
DOI: No ID Found -
JAMA Jul 2023Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal... (Comparative Study)
Comparative Study
IMPORTANCE
Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results.
OBJECTIVE
To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test.
DESIGN, SETTING, AND PARTICIPANTS
The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021.
EXPOSURE
Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform.
MAIN OUTCOMES AND MEASURES
Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care).
RESULTS
A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis.
CONCLUSIONS AND RELEVANCE
The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.
Topics: Clinical Decision-Making; Genetic Profile; Genomics; Prospective Studies; Whole Genome Sequencing; Genetic Testing; Genetic Diseases, Inborn; Humans; Infant, Newborn; Neonatal Screening; Infant; Sequence Analysis, DNA; Mutation
PubMed: 37432431
DOI: 10.1001/jama.2023.9350 -
Cell May 2019Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in...
Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 WGS human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. Additionally, six agents produced double-substitution signatures and eight produced indel signatures. Investigating mutation asymmetries across genome topography revealed fully functional mismatch and transcription-coupled repair pathways. DNA damage induced by environmental mutagens can be resolved by disparate repair and/or replicative pathways, resulting in an assortment of signature outcomes even for a single agent. This compendium of experimentally induced mutational signatures permits further exploration of roles of environmental agents in cancer etiology and underscores how human stem cell DNA is directly vulnerable to environmental agents. VIDEO ABSTRACT.
Topics: Carcinogens, Environmental; DNA Damage; DNA Mutational Analysis; DNA Repair; DNA Replication; Genetic Profile; Genome, Human; Humans; INDEL Mutation; Mutagenesis; Mutation; Neoplasms; Pluripotent Stem Cells; Whole Genome Sequencing
PubMed: 30982602
DOI: 10.1016/j.cell.2019.03.001 -
Cancers Apr 2022Recent advances in our understanding of cancer, driven mainly by the emergence of new technologies have highlighted that heterogeneity shapes not only the genetic...
Recent advances in our understanding of cancer, driven mainly by the emergence of new technologies have highlighted that heterogeneity shapes not only the genetic profile of tumors but also their epigenetic and gene expression profile [...].
PubMed: 35454790
DOI: 10.3390/cancers14081885 -
Cancers Feb 2021The steady improvement of high-throughput technologies greatly facilitates the implementation of personalized precision medicine. Characterization of tumor heterogeneity... (Review)
Review
The steady improvement of high-throughput technologies greatly facilitates the implementation of personalized precision medicine. Characterization of tumor heterogeneity through image-derived features-radiomics and genetic profile modifications-genomics, is a rapidly evolving field known as radiogenomics. Various radiogenomics studies have been dedicated to colorectal cancer so far, highlighting the potential of these approaches to enhance clinical decision-making. In this review, a general outline of colorectal radiogenomics literature is provided, discussing the current limitations and suggested further developments.
PubMed: 33652647
DOI: 10.3390/cancers13050973 -
ImmunoTargets and Therapy 2018Melanoma represents the most aggressive and the deadliest form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic... (Review)
Review
Melanoma represents the most aggressive and the deadliest form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. The therapeutic strategy can include single agents or combined therapies, depending on the patient's health, stage, and location of the tumor. The efficiency of these treatments can be decreased due to the development of diverse resistance mechanisms. New therapeutic targets have emerged from studies of the genetic profile of melanocytes and from the identification of molecular factors involved in the pathogenesis of the malignant transformation. In this review, we aim to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis.
PubMed: 29922629
DOI: 10.2147/ITT.S134842 -
World Journal of Oncology Oct 2021The study of genetic polymorphisms has significantly advanced the field of personalized medicine. Polymorphism of genes influence the efficacy of drugs used for treating... (Review)
Review
The study of genetic polymorphisms has significantly advanced the field of personalized medicine. Polymorphism of genes influence the efficacy of drugs used for treating medical conditions such as depression, cardiac diseases, thromboembolic disorders, oncological diseases, etc. The study of genetic polymorphism is beneficial for drug safety as well as for assessing therapeutic outcomes. Understanding and detecting genetic polymorphisms early on in patients can be useful in selecting the correct chemotherapeutic agent and appropriate dosage for a patient. Knowing the genetic profile of a patient and the interindividual response to various drugs significantly influences the proper selection of medication - a key step towards personalized medicine. Polymorphisms also make patients susceptible to certain cancers and identification of these polymorphisms early can be useful for a personalized treatment plan. The Genome-Wide Association Studies (GWAS) project where millions of genetic variants in the genomes of many individuals are studied to identify connections between what is present on the gene and the phenotype of the patient has enhanced the prospect of personalized medicine. GWAS has been used to identify hundreds of diseases associated to genetic polymorphisms. Individual pharmacokinetic profiles of patients to drugs enable the development of early surveillance protocols to prophylactically prevent patients from having adverse reactions. Furthermore, patient-derived cellular organoids are another advancement that allows researchers to screen for polymorphisms of the patient for adverse reactions from chemotherapy and will allow for the development of new medications that are specific to the profile of the patient's tumor. These advances have led to significant progress towards personalized medicine. The functional consequences of genetic polymorphism on cancer drugs and treatment are studied here.
PubMed: 34804277
DOI: 10.14740/wjon1405 -
OncoTargets and Therapy 2020Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We... (Review)
Review
Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and distinct subtype of non-small-cell lung carcinoma associated with Epstein-Barr virus (EBV) infection. We systematically reviewed the recent research that expands our knowledge about PLELC, with main focus on its genetic profile, tumor-infiltrating environment, PD-L1 expression, circulating EBV-DNA, clinical utility of 18F-FDG PET/CT, and treatment strategy. A low frequency of typical driver mutations and widespread existence of copy number variations was detected in PLELC. Persistent EBV infection may trigger intense infiltration of lymphocytes, representing enhanced tumor immunity and possibly resulting in a better prognosis. Circulating EBV-DNA in the plasma of patients with PLELC may predict disease progression and response to therapy. PLELC is 18F-FDG avid, and 18F-FDG PET may help refine palliation strategies and subsequently improve the prognosis. Most of the reported patients present at early and resectable stage, and surgical resection with curative intent is the preferred approach. There is currently no consensus on the regimen of chemotherapy for patients with advanced stages. EGFR-targeted therapies seem to have no therapeutic effect, and the clinical impact of PD-1/PD-L1 therapy is uncertain but worthy of further research.
PubMed: 32494151
DOI: 10.2147/OTT.S241337 -
Healthcare (Basel, Switzerland) May 2022Thrombophilia, also called hypercoagulability or prothrombotic condition, usually reflects a certain imbalance that occurs either in the coagulation cascade or in the... (Review)
Review
Thrombophilia, also called hypercoagulability or prothrombotic condition, usually reflects a certain imbalance that occurs either in the coagulation cascade or in the anticoagulation/fibrinolytic system. A similar imbalance may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thrombotic complications are associated with multiorgan failure and increased mortality. In this context, activation of coagulation and thrombocytopenia appeared as prognostic markers in COVID-19. Our work provides a structured and updated analysis of inherited thrombophilia and its involvement in COVID-19, emphasizing the importance of diagnosing and initiating thromboprophylaxis. Since the state of hypercoagulation is directly correlated with COVID-19, we consider that studies on the genetic profiles of proteins involved in thrombophilia in patients who have had COVID-19 and thrombotic events are of great importance, both in treating and in preventing deaths due to COVID-19.
PubMed: 35742044
DOI: 10.3390/healthcare10060993