Genetic medicine

BACKGROUND: CYP2C8 is responsible for the metabolism of 5% of clinically prescribed drugs, including antimalarials, anti-cancer and anti-inflammatory drugs. Genetic variability is an important factor that influences CYP2C8 activity and modulates the pharmacokinetics, efficacy and safety of its substrates. RESULTS: We profiled the genetic landscape of CYP2C8 variability using data from 96 original studies and data repositories that included a total of 33,185 unrelated participants across 44 countries and 43 ethnic groups...

BACKGROUND: TAS-102 (Lonsurf® ) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity. METHODS: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m2 , twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12)...

BACKGROUND: Dravet syndrome is an infantile-onset developmental and epileptic encephalopathy (DEE) characterized by drug resistance, intractable seizures, and developmental comorbidities. This article focuses on manifestations in two Indonesian children with Javanese ethnicity who experienced Dravet syndrome with an SCN1A gene mutation, presenting genetic analysis findings using next-generation sequencing. CASE PRESENTATION: We present a case series involving two Indonesian children with Javanese ethnicity whom had their first febrile seizure at the age of 3 months, triggered after immunization...

Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans...

BACKGROUND: Staphylococcus aureus is a notorious multidrug resistant pathogen prevalent in healthcare facilities worldwide. Unveiling the mechanisms underlying biofilm formation, quorum sensing and antibiotic resistance can help in developing more effective therapy for S. aureus infection. There is a scarcity of literature addressing the genetic profiles and correlations of biofilm-associated genes, quorum sensing, and antibiotic resistance among S. aureus isolates from Malaysia. METHODS: Biofilm and slime production of 68 methicillin-susceptible S...

Medicinal plants are rich sources for treating various diseases due their bioactive secondary metabolites. Fenugreek (Trigonella foenum-graecum) is one of the medicinal plants traditionally used in human nutrition and medicine which contains an active substance, called diosgenin, with anticancer properties. Biosynthesis of this important anticancer compound in fenugreek can be enhanced using eliciting agents which involves in manipulation of metabolite and biochemical pathways stimulating defense responses...

BACKGROUND: Bleomycin, a potent antitumor agent, is limited in clinical use due to the potential for fatal pulmonary toxicity. The accelerated DNA damage and senescence in alveolar epithelial cells (AECs) is considered a key factor in the development of lung pathology. Understanding the mechanisms for bleomycin-induced lung injury is crucial for mitigating its adverse effects. METHODS: Human lung epithelial (A549) cells were exposed to bleomycin and subsequently assessed for cellular senescence, DNA damage, and double-strand break (DSB) repair...

This study aimed to explore polymorphisms in the promoter region of the caprine BMPR1B (Bone morphogenetic protein receptor 1 beta) gene and its association with body measurement and litter size traits in Damani does. A total of 53 blood samples were collected to analyze the association between the BMPR1B gene polymorphism and 11 phenotypic traits in Damani female goats. The results revealed that three novel SNPs were identified in the promoter region of the caprine BMPR1B gene, including g.67 A > C (SNP1), g...

It is pivotal to avoid cross-sample contamination in forensic genetic laboratories and optimal cleaning protocols for the removal of DNA are essential. A survey was performed, and ten forensic genetic laboratories shared their cleaning protocols in pre-PCR and post-PCR laboratories. The cleaning frequencies on different surface areas were somewhat similar, whereas none of the laboratories used the same cleaning reagents. Therefore, the efficiencies of the cleaning protocol utilised were tested and compared...

In the late twentieth century, increasing numbers of women in wealthy nations waited until they were aged in their 30s to give birth and become parents. This article examines responses to the changing demographics of maternity among social researchers, doctors, pregnant women and mothers in Aotearoa New Zealand. The article analyses raw research data from historical social survey projects The Right Time (interviews completed in 1982-1983) and Motherhood After 30 (1987) by the grassroots organisation the Society for Research on Women in New Zealand...

CONTEXT.—: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia. OBJECTIVE.—: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.—: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing...

RESEARCH QUESTION: What is the clinical outcome of the first attempt at conception between two embryo selection methods, blastocyst morphology and preimplantation genetic testing for aneuploidies (PGT-A), chosen at the initial physician IVF consultation? DESIGN: In this prospective analysis, a clinical decision regarding embryo selection, blastocyst morphology (group A) or PGT-A (group B) was made during initial physician IVF consultation. Female infertility patients were matched based on maternal age (mean 32...

Empirical studies in multiple disciplines have frequently observed an immigrant mortality advantage. Yet, questions remain regarding the possible mechanisms underlying this phenomenon. We obtained data from 61 studies of relative immigrant mortality from single origin-destination country pairings, providing information on immigrants from 77 origin countries. We systematically review the arguments made in these studies about origin-country factors that might influence immigrant mortality and then use meta-analyses to examine the veracity of these arguments...

The etiology of hidradenitis suppurativa (HS)-a chronic, relapsing, inflammatory disorder-is multifactorial, encompassing lifestyle, microbiota, hormonal status, and genetic and environmental factors. These factors propagate the production of deep-seated inflammatory nodules seen in HS through aberrant immune response activation and inflammation. The high prevalence of depression in individuals with HS and its association with systemic inflammation increases the likelihood that depression also may be a contributing etiology to HS...

Frontal fibrosing alopecia (FFA) is an increasingly common diagnosis, especially in middle-aged women, and has garnered growing attention in the scientific literature. This variant of lichen planopilaris (LPP) is recognized as a progressive scarring alopecia affecting the frontal and temporal regions of the scalp as well as the eyebrows and occasionally other sites. Although its precise etiology remains elusive, various factors such as genetics, medications, hormonal influences, and environmental exposures-including specific chemicals present in sunscreens-have been implicated in its pathogenesis but without evidence of causality...

Introduction. During the development of the SARS-CoV-2 pandemic in Antioquia, we experienced epidemiological peaks related to the α, ɣ, β, ƛ, and δ variants. δ had the highest incidence and prevalence. This lineage is of concern due to its clinical manifestations and epidemiological characteristics. A total of 253 δ sublineages have been reported in the PANGOLIN database. The sublineage identification through genomic analysis has made it possible to trace their evolution and propagation...

INTRODUCTION: Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population...

OBJECTIVE: This study comprehensively evaluated the causal relationship between different types of statins use and knee/hip osteoarthritis (OA) using a two-sample and multivariate Mendelian randomization (MR) method. METHODS: MR analysis was conducted using publicly available summary statistics data from genome-wide association studies (GWAS) to assess the causal associations between total statins use (including specific types) and knee/hip OA. The primary analysis utilized the inverse variance-weighted (IVW) method, with sensitivity analysis conducted to assess robustness...

Hereditary, or vertically-transmitted, symbioses affect a large number of animal species and some plants. The precise mechanisms underlying transmission of functions of these associations are often difficult to describe, due to the difficulty in separating the symbiotic partners. This is especially the case for plant-bacteria hereditary symbioses, which lack experimentally tractable model systems. Here, we demonstrate the potential of the leaf symbiosis between the wild yam Dioscorea sansibarensis and the bacterium Orrella dioscoreae (O...

Genome-wide association studies have revealed >270 loci associated with schizophrenia risk, yet these genetic factors do not seem to be sufficient to fully explain the molecular determinants behind this psychiatric condition. Epigenetic marks such as post-translational histone modifications remain largely plastic during development and adulthood, allowing a dynamic impact of environmental factors, including antipsychotic medications, on access to genes and regulatory elements. However, few studies so far have profiled cell-specific genome-wide histone modifications in postmortem brain samples from schizophrenia subjects, or the effect of antipsychotic treatment on such epigenetic marks...