Neurol Sci. 2022 Jun 10. doi: 10.1007/s10072-022-06195-5. Online ahead of print.

ABSTRACT

Chronic migraine (CM) is a great challenge for physicians dealing with headaches. Despite the introduction of the monoclonal antibodies (mAbs) acting against the calcitonin gene-related peptide (CGRP) that has revolutionized the treatment of CM, some patients still experience an incomplete relief. So, the association of two preventive treatments may be a reliable option for these patients. So, onabotulinumtoxinA (BT-A) and anti-CGRP mAbs may be used together, and some pre-clinical and clinical evidence of an additive action of the 2 drugs is emerging. In particular, since BT-A acts mainly on C-fibers and anti-CGRP mAbs on Aδ ones, their association may prevent the wearing-off phenomenon of BT-A, thus giving an additional benefit in those patients experiencing an incomplete response to BT-A alone. Despite this, the clinical studies available in the literature have a small sample size, often a retrospective design, and are heterogeneous in terms of the outcomes chosen. Considering this, the evidence of a favorable effect of the association between BT-A and anti-CGRP mAbs is still scarce. Furthermore, this association is explicitly forbidden by many National regulatory agencies, due to the high costs of both treatments. Anyway, their association could help in reducing the burden associated with the most severe cases of CM, thus relieving the direct and indirect costs of this condition. More well-designed studies with big samples are needed to unveil the real therapeutic gain of this association. Moreover, pharmacoeconomics studies should be performed, to assess the economic suitability of this association.

PMID:35680766 | DOI:10.1007/s10072-022-06195-5

Pharmacol Res. 2022 Jun 6:106290. doi: 10.1016/j.phrs.2022.106290. Online ahead of print.

ABSTRACT

Glioblastoma multiforme (GBM) is an aggressive brain tumor, often occurring with seizures managed with antiepileptic drugs, such as levetiracetam (LEV). This study is aimed at associating progression-free survival (PFS) and overall survival (OS) of GBM patients with LEV plasma concentration, MGMT promoter methylation, and sex In this retrospective, non-interventional, and explorative clinical study, GBM patients underwent surgery and/or radiotherapy and received LEV during adjuvant temozolomide (TMZ) treatment. A high-performance liquid chromatography with UV-detection was used for therapeutic drug monitoring of LEV plasma concentrations. Follow-up average drug concentration was related to patients' clinical characteristics and outcomes. Forty patients (42.5% female; mean age=54.73±11.70 years) were included, and GBM MGMT methylation status was assessed. All were treated with adjuvant TMZ, and LEV for seizure control. Patients harboring methylated MGMT promoter showed a longer median PFS (460 vs. 275 days, log-rank p<0.001). The beneficial effect of MGMT promoter methylation was more evident for females (p<0.001) and in patients with LEV concentration ≤20.6µg/mL (562 days vs. 274.5 days, p=0.032). Female patients also showed longer OS (1220 vs. 574 days, p=0.03). Also, higher LEV concentration (>20.6µg/mL) synergized with MGMT promoter methylation by extending the OS (1014 vs. 406 days of patients with no methylation and low LEV average concentration, p=0.021). Beneficial effect of higher LEV plasma levels was more evident in males (p=0.024). Plasma concentrations of LEV may support better outcomes for chemoradiotherapy when other positive prognostic factors are lacking and may promote overall survival by synergizing with MGMT promoter methylation and male sex.

PMID:35680010 | DOI:10.1016/j.phrs.2022.106290

Curr Issues Mol Biol. 2022 Apr 22;44(5):1838-1850. doi: 10.3390/cimb44050126.

ABSTRACT

Our research group, through the analysis of miRNomes in platelet concentrates (PCs) stored in blood banks, identified and validated the miR-127 and miR-320a miRNAs as biomarkers of platelet storage lesions (PSLs) in PCs. In order to validate the miRNAs 127 and 320a methodologically, as PSL biomarkers in a large number of PC bags, we also evaluated important immunological markers involved in the platelet activation/aggregation process-the CD62P receptor (P-selectin), the surface glycoproteins (GP) IIb/IIIa, and the purinergic P2Y12 receptor-via flow cytometry. The miRNAs miR-127 and miR-320a were quantified by real-time quantitative PCR (RT-qPCR). To carry out this study, 500 collection tubes were used at the upper edge of the PC bags containing platelets. Each tube was divided into seven equal parts (totaling 3500 samples) for platelet analysis from 7 different storage days, where the 1st day represents the high-quality control, and the 7th day corresponds to the low-quality control of the platelets. After analyzing all parameters during storage days, it was concluded that the relative quantification of miR-320a below 0.50 and the CD62P receptor below 27.92% are reliable indicators of the absence of storage lesions in blood banks. We believe that the values found in the expression of the CD62P receptor legitimize the use of the miR-320a and miR-127 miRNAs to build a kit capable of accurately measuring whether the stored platelets are suitable for transfusion.

PMID:35678655 | DOI:10.3390/cimb44050126

Biomed Pharmacother. 2022 Jul;151:113189. doi: 10.1016/j.biopha.2022.113189. Epub 2022 May 28.

ABSTRACT

Tuberculosis (TB) and human immunodeficiency virus (HIV) represent a significant burden of disease on a global scale. Despite improvements in the global epidemic status, largely facilitated by increased access to pharmacotherapeutic interventions, slow progress in the development of new clinical interventions coupled with growing antimicrobial resistance to existing therapies represents a global health crisis. There is an urgent need to expand the armamentarium of TB and HIV therapeutic strategies. Host mediated immune responses represent an untapped reservoir of novel approaches for TB and HIV. Antimicrobial peptides (AMPs) are an essential aspect of the immune system. Cathelicidins and defensins AMPs have been studied for their potential applications in TB and HIV therapeutic interventions. Genetic polymorphism across different population groups may affect endogenous expression or activity of AMPs, potentially influencing therapeutic outcomes. However, certain genetic polymorphisms in autophagy pathways may alter the downstream effects of nano-delivery of cathelicidin. On the other hand, certain genetic polymorphisms in beta-defensins may provide a protective role in reducing HIV-1 mother-to-child-transmission. Pharmaceutical development of cathelicidins and defensins is disadvantaged with complex challenges. Nanoparticle formulations improve pharmacokinetics and biocompatibility while facilitating targeted drug delivery, potentially minimising the risk of immunogenicity or non-specific haemolytic activity. This review aims to explore the potential viability of using cathelicidins and defensins as novel pharmacotherapy in the management of TB and HIV, highlight potential pharmacogenomic implications in host mediated immunity and AMP therapeutic applications, as well as propose novel drug delivery strategies represented by nanomedicine for AMPs.

PMID:35676789 | DOI:10.1016/j.biopha.2022.113189

BMC Genomics. 2022 Jun 8;23(1):430. doi: 10.1186/s12864-022-08665-8.

ABSTRACT

BACKGROUND: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive.

OBJECTIVE: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients.

METHODS: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor.

RESULTS: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance.

CONCLUSION: These findings can offer a fresh perspective on GRE-induced brain network changes.

PMID:35676651 | DOI:10.1186/s12864-022-08665-8

PLoS One. 2022 Jun 8;17(6):e0268534. doi: 10.1371/journal.pone.0268534. eCollection 2022.

ABSTRACT

BACKGROUND: The clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT infrastructures. We report results of CDS implementation in the large-scale European research project Ubiquitous Pharmacogenomics (U-PGx), in which PGx CDS was rolled out and evaluated across more than 15 clinical sites in the Netherlands, Spain, Slovenia, Italy, Greece, United Kingdom and Austria, covering a wide variety of healthcare settings.

METHODS: We evaluated the CDS implementation process through qualitative and quantitative process indicators. Quantitative indicators included statistics on generated PGx reports, median time from sampled upload until report delivery and statistics on report retrievals via the mobile-based CDS tool. Adoption of different CDS tools, uptake and usability were further investigated through a user survey among healthcare providers. Results of a risk assessment conducted prior to the implementation process were retrospectively analyzed and compared to actual encountered difficulties and their impact.

RESULTS: As of March 2021, personalized PGx reports were produced from 6884 genotyped samples with a median delivery time of twenty minutes. Out of 131 invited healthcare providers, 65 completed the questionnaire (response rate: 49.6%). Overall satisfaction rates with the different CDS tools varied between 63.6% and 85.2% per tool. Delays in implementation were caused by challenges including institutional factors and complexities in the development of required tools and reference data resources, such as genotype-phenotype mappings.

CONCLUSIONS: We demonstrated the feasibility of implementing a standardized PGx decision support solution in a multinational, multi-language and multi-center setting. Remaining challenges for future wide-scale roll-out include the harmonization of existing PGx information in guidelines and drug labels, the need for strategies to lower the barrier of PGx CDS adoption for healthcare institutions and providers, and easier compliance with regulatory and legal frameworks.

PMID:35675343 | DOI:10.1371/journal.pone.0268534

Bioinformatics. 2022 Jun 8:btac383. doi: 10.1093/bioinformatics/btac383. Online ahead of print.

ABSTRACT

MOTIVATION: The increasing number of publicly available databases containing drugs' chemical structures, their response in cell lines, and molecular profiles of the cell lines has garnered attention to the problem of drug response prediction. However, many existing methods do not fully leverage the information that is shared among cell lines and drugs with similar structure. As such, drug similarities in terms of cell line responses and chemical structures could prove to be useful in forming drug representations to improve drug response prediction accuracy.

RESULTS: We present two deep learning approaches, BiG-DRP and BiG-DRP+, for drug response prediction. Our models take advantage of the drugs' chemical structure and the underlying relationships of drugs and cell lines through a bipartite graph and a heterogenous graph convolutional network that incorporate sensitive and resistant cell line information in forming drug representations. Evaluation of our methods and other state-of-the-art models in different scenarios shows that incorporating this bipartite graph significantly improves the prediction performance. Additionally, genes that contribute significantly to the performance of our models also point to important biological processes and signaling pathways. Analysis of predicted drug response of patients' tumors using our model revealed important associations between mutations and drug sensitivity, illustrating the utility of our model in pharmacogenomics studies.

AVAILABILITY AND IMPLEMENTATION: An implementation of the algorithms in Python is provided in https://github.com/ddhostallero/BiG-DRP.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35674359 | DOI:10.1093/bioinformatics/btac383

Pharmacogenomics. 2022 Jun 8. doi: 10.2217/pgs-2022-0037. Online ahead of print.

ABSTRACT

Antidepressant medications are frequently used as the first line of treatment for depression. However, their effectiveness is highly variable and influenced by genetic factors. Recently, pharmacogenetic studies, including candidate-gene, genome-wide association studies or polygenic risk scores, have attempted to uncover the genetic architecture of antidepressant response. Genetic variants in at least 27 genes are linked to antidepressant treatment response in both coding and non-coding genomic regions, but evidence is largely inconclusive due to the high polygenicity of the trait and limited cohort sizes in published studies. Future studies should increase the number and diversity of participants to yield sufficient statistical power to characterize the genetic underpinnings and biological mechanisms of treatment response, improve results generalizability and reduce racial health-related inequities.

PMID:35673953 | DOI:10.2217/pgs-2022-0037

Rom J Morphol Embryol. 2021 Oct-Dec;62(4):897-906. doi: 10.47162/RJME.62.4.02.

ABSTRACT

Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23∕T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1∕Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.

PMID:35673809 | DOI:10.47162/RJME.62.4.02

J Diabetes Metab Disord. 2022 Jan 11;21(1):133-139. doi: 10.1007/s40200-021-00947-4. eCollection 2022 Jun.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common chronic condition characterized by high blood glucose levels which is caused by genetic and environmental factors. Currently, pharmacogenomics (PGx) is anticipated to enable the development of personalized treatment in a wide range of health issues. Sulfonylureas (SFUs) are among the oral anti-diabetic drugs that are very popular due to their low cost. Genetic variants in transcription factor 7 like 2 (TCF7L2) and potassium voltage-gated channel subfamily Q member 1 (KCNQ1) have been reported for altered therapeutic response to sulfonylurea. The aim of the present study is to evaluate any association between common genetic variant of the TCF7L2 and KCNQ1 (rs7903146 and rs2237892, respectively) and the response to sulfonylurea in a group of Iranian patients for the first time.

METHODS: Genotyping was carried out in 30 T2DM patients who received sulfonylurea treatment for more than two months in addition to previous medication using the Sanger sequencing method.

RESULTS: In 30 T2DM patients who received SFUs treatment, 60%, 33.3% and 6.7% had CC, CT and TT genotypes, respectively. After treatment, adjusted fasting blood sugar (FBS) mean reduction level in CT and TT carriers was lower than CC carriers. Adjusted hemoglobin A1c (HbA1c) mean reduction level was also lower in CT and TT compared with CC carriers, but, none of these differences were statistically significant. Genotype frequencies of TT, CT and CC genotypes of rs2237892 variant of KCNQ1 gene were 0 (0%), 3 (10%) and 27 (90%) respectively. Patients with CT and CC genotypes of rs2237892 variant had also similar changes in FBS (P=0.200) and HbA1c (P=0.436) after treatment with SFUs.

CONCLUSIONS: Genotypes of TCF7L2 and KCNQ1 common variant did not show any impact on the treatment response among T2DM patients receiving SFUs.

PMID:35673510 | PMC:PMC9167329 | DOI:10.1007/s40200-021-00947-4

J Diabetes Metab Disord. 2021 Aug 24;21(1):853-861. doi: 10.1007/s40200-021-00880-6. eCollection 2022 Jun.

ABSTRACT

Genomic medicine has created a great deal of hope since the completion of the Human Genome Project (HGP). Genomic medicine promises disease prevention and early diagnosis in the context of precision medicine. Precision medicine as a scientific discipline has introduced as an evolution in medicine. The rapid growth of high-development technologies permits the assessment of biological systems. Study of the integrated profiles of omics, such as genome, transcriptome, proteome and other omics information lead to significant advances in personalized and precision medicine. In the context of precision medicine, pharmacogenomics can play an important role in order to discriminate responders and non-responders to medications and avoiding toxicity and achieving the optimum dose. So precision medicine in accordance with genomic medicine will transform medicine from conventional evidence-based medicine in the diagnosis and treatment towards precision based-medicine. In this review, we have summarized the related issues for genomic medicine and precision medicine.

PMID:35673457 | PMC:PMC9167337 | DOI:10.1007/s40200-021-00880-6

J Diabetes Metab Disord. 2021 Nov 24;21(1):881-888. doi: 10.1007/s40200-021-00913-0. eCollection 2022 Jun.

ABSTRACT

It has been well established that understanding the underlying heterogeneity of numerous complex disease process needs new strategies that present in precision medicine for prediction, prevention and personalized treatment strategies. This approach must be tailored for each individual's unique omics that lead to personalized management of disease. The correlation between different omics data should be considered in precision medicine approach. The interaction provides a hypothesis which is called domino effect in the present minireview. Here we review the various potentials of omics data including genomics, transcriptomics, proteomics, metabolomics, pharmacogenomics. We comprehensively summarize the impact of omics data and its major role in precision medicine and provide a description about the domino effect on the pathophysiology of diseases. Each constituent of the omics data typically provides different information in associated with disease. Current research, although inadequate, clearly indicate that the information of omics data can be applicable in the concept of precision medicine. Integration of different omics data type in domino effect hypothesis can explain the causative changes of disease as it is discussed in the system biology too. While most existing studies investigate the omics data separately, data integration is needed on the horizon of precision medicine by using machine learning.

PMID:35673436 | PMC:PMC9167178 | DOI:10.1007/s40200-021-00913-0

J Diabetes Metab Disord. 2021 Dec 1;21(1):863-879. doi: 10.1007/s40200-021-00908-x. eCollection 2022 Jun.

ABSTRACT

PURPOSE: Genetic factors have a role in response to a target medication (personalized medicine). This study aimed to review available evidence about the relationship between gene variants and therapeutic response to sulfonylureas in type 2 diabetes, systematically.

METHODS: An extensive search was done in Scopus, PubMed, and Web of Science with specific search strategy in the field from the beginning until the 1st of Jan. 2021. After sending records to endnote software and removing duplicate records remained documents were screened by title and abstract. Full texts of remained documents were assessed after removing un-related records. Required data was extracted from remained documents and records were categorized according to gene/SNP studied.

RESULTS: Finally, 26 studies with 9170 T2DM patients with a mean age of 59.47 ± 6.67 (49.7-75.2 years) remained. The most contribution was from China, Slovakia and Greece, respectively and the most genes studied were CYP2C9, KCNJ11, and both KCNQ1 and ABCC8 with 10, 7, and 4 articles, respectively. Also, rs1799853 and rs1057910 (each with seven studies), rs5219 with six studies and CYP2C9*1(with four articles), respectively were the most common variants investigated. Studies about each gene obtained different positive or negative results and were not consistent.

CONCLUSION: Considering heterogeneity between SFUs pharmacogenomic studies regarding the method, sample size, population, gene/variant studied, and outcome and findings, these studies are not conclusive and need further studies.

PMID:35673432 | PMC:PMC9167353 | DOI:10.1007/s40200-021-00908-x

Biotechnol Lett. 2022 Jun 7. doi: 10.1007/s10529-022-03266-7. Online ahead of print.

ABSTRACT

PURPOSE: Hepatocellular carcinoma (HCC) is the uncontrolled growth of hepatocytes which results in nearly 5 million deaths worldwide. Specific strategies have been developed to treat HCC, including surgery, chemotherapy and radiotherapy. But, the effective disease dealing requires synergistic collaboration with other approaches, which often results in moderate to severe side effects during and after the treatment period. Therefore, the focus is now shifting to explore and retrieve those plant-based products that could be utilized to treat HCC with maximum efficacy without causing any side effects. Strigolactones (SL) are compounds of plant origin derived from Striga lutea responsible for controlling the branching pattern of stem and have reported anti-cancerous activity by promoting apoptosis at micromolar concentrations. However, little work has been done concerning determining the pharmacogenomic effect of strigolactones on HCC.

METHODS: Current work focuses on comparing therapeutic efficiencies of SL analogs against core targets of HCC using network pharmacology approach, pharmacokinetics analysis, gene ontogeny, functional enrichment analysis, molecular docking and Molecular Dynamics simulation.

RESULTS: Drug-target prediction and functional enrichment analysis showed that HDAC1 and HDAC2 are the core proteins involved in hepatocellular carcinoma that strigolactone analogs can target. Consequently, results from molecular docking and MD simulation analyses report that among all the SL analogs strigol, epistrigol and nijmegen1 can turn out to be most effective in downregulating the expression of HDAC1, HDAC2 and CYP19A.

CONCLUSION: Strigol, epistrigol and nijmegen1 could be used as potential inhibitors against HCC and can be further validated through in vitro/in vivo studies.

PMID:35672528 | DOI:10.1007/s10529-022-03266-7

Semin Arthritis Rheum. 2022 May 28;55:152036. doi: 10.1016/j.semarthrit.2022.152036. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine genetic influence on the risk of elevations in liver function tests (AST and ALT) among patients using low-dose methotrexate (LD-MTX).

METHODS: We examined data from the LD-MTX arm of a randomized double-blind placebo-controlled trial conducted among subjects without rheumatic disease. Genome wide association studies (GWAS) were performed in subjects of European ancestry to test the association between single nucleotide polymorphisms (SNPs) and the log transformed maximum values of AST, ALT, and dichotomized outcome with AST or ALT > 2 times upper limit of normal (ULN). The association between variants in MTX metabolism candidate genes and the outcomes was also tested. Furthermore, associations between a drug induced liver injury (DILI) weighted genetic risk score (wGRS) and the outcomes were tested, combining 10 SNPs and 11 classical HLA alleles associated with DILI.

RESULTS: In genome-wide genetic analyses among 1,429 subjects of European ancestry who were randomized to receive LD-MTX, two SNPs reached genome wide significance for association with log transformed maximum ALT. We observed associations between established candidate genes in MTX pharmacogenetics and log transformed maximum AST and ALT, as well as in dichotomized outcome with AST or ALT > 2 x ULN. There was no association between DILI wGRS or candidate variants and AST, ALT, or DILI response.

CONCLUSIONS: Modest evidence was observed that common variants affected AST and ALT levels in subjects of European ancestry on LD-MTX, but this genetic effect is not useful as a clinical predictor of MTX toxicity.

PMID:35671649 | DOI:10.1016/j.semarthrit.2022.152036

Eur J Cancer Prev. 2022 May 27. doi: 10.1097/CEJ.0000000000000757. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore compliance with the smoke-free policy in hospitals in Catalonia, Spain, by exploring inpatients' perceptions.

METHODS: We conducted a cross-sectional study of a random sample of 1047 inpatients from 13 public hospitals. We collected data about: (a) type of information about the smoke-free policy provided by the hospital, (b) patients' knowledge about the policy, (c) general appreciation of the compliance with the policy, and (d) specific appreciation of such compliance by noticing any sign of tobacco consumption. We described the data by several patients' and hospitals' characteristics and assessed their association with the perceived noncompliance using prevalence ratios (PR) and their 95% confidence intervals (CIs).

RESULTS: Few patients were informed about the smoke-free policy (4.8% orally, 6.1% in writing, and 55.6% through sign postings). About 64% were aware of the regulation and 73.5% believed that it was properly obeyed. While 0.7% had never or rarely observed smoking indoors, 36.2% had seen someone smoking outdoors sometimes or many times. Signs of tobacco consumption were observed indoors and outdoors. Factors associated with the perception of noncompliance were: being less than 45 years old versus being more than 64 years old (adjusted PR, 2.33; 95% CI, 1.09-4.98) and currently smoking versus have never smoked (adjusted PR, 1.84; 95% CI, 1.02-3.34).

CONCLUSION: Compliance with the smoke-free policy in hospitals according to the patients' view is notable, although several infringements were reported, mainly outdoors. The smoke-free policy in hospitals should be reinforced by prompting continuous awareness campaigns and the exemplary role of hospital workers.

PMID:35671260 | DOI:10.1097/CEJ.0000000000000757

Pharmacogenomics. 2022 Jun 7. doi: 10.2217/pgs-2022-0056. Online ahead of print.

ABSTRACT

Implementation of personalized medicine in the clinic is a lengthy and multifaceted approach that is also dependent on the raising of the general public's awareness of genomics. The Festival of Genetics and Personalized Medicine aims to familiarize the general public with the principles and applications of genetics and personalized medicine using numerous approaches - namely, a theatrical performance; a roundtable discussion of emerging topics in the field, such as pharmacogenomics, clinical genetics, bioinformatics, bioethics and health economics; the 'Genome: Unlocking Life's Code' exhibition, with its do-it-yourself format; and a live demonstration of 2MoBiL, a portable molecular biology laboratory. This festival attracted more than 900 participants and helped disseminate to a broader audience the principles of genetics and personalized medicine.

PMID:35670264 | DOI:10.2217/pgs-2022-0056

Pharmacogenomics. 2022 Jun 7. doi: 10.2217/pgs-2022-0025. Online ahead of print.

ABSTRACT

Cystic fibrosis is a genetic, multiorgan system disease that involves the use of many medications to control symptoms associated with the underlying condition. Many of these medications have Clinical Pharmacogenetics Implementation Consortium evidence-based guidelines for pharmacogenomics that are available to guide dosing. The aim of this article is to review relevant literature and evaluate the utility of preemptive pharmacogenomics testing for persons with cystic fibrosis and propose a pharmacogenomics panel that could be considered standard of care for persons with cystic fibrosis.

PMID:35670256 | DOI:10.2217/pgs-2022-0025

Clin Transl Sci. 2022 Jun 6. doi: 10.1111/cts.13347. Online ahead of print.

ABSTRACT

Sertraline is a commonly used SSRI antidepressant drug, metabolised by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n=840). Compared to the reference group (CYP2C19*1/*1, n=160), sertraline exposure was increased by 128% in CYP2C19 PMs (n=29, p<0.001) but decreased by about 20% in CYP2C19 UMs (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG or CYP2C19*17/CYP2C:TG (n=135, p<0.003, p=0.022, p<0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, also carrying CYP2C19*17 and CYP2C:TG alleles (n=10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being PM in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype, had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6 and *9 alleles. Knowing CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions.

PMID:35668575 | DOI:10.1111/cts.13347

Nat Commun. 2022 Jun 6;13(1):3124. doi: 10.1038/s41467-022-30875-7.

ABSTRACT

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P < 1 × 10-3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

PMID:35668104 | DOI:10.1038/s41467-022-30875-7