Pharmacogenomics

Understanding the effects of Moringa Oleifera in chronic unpredictable stressed zebrafish using metabolomics analysis

Sun, 2021-06-06 06:00

J Ethnopharmacol. 2021 Jun 3:114290. doi: 10.1016/j.jep.2021.114290. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa leaves have been used for thousands of years to maintain skin health and mental fitness. People also use it to relieves pain and stress.

AIM OF THE STUDY: To determine the effects of Moringa oleifera leaves ethanol-aqueous (ratio 7:3) extract (MOLE) on the chronically stressed zebrafish.

METHOD: The changes in the stress-related behaviour and the metabolic pathways in response to MOLE treatment in zebrafish were studied. A chronic unpredictable stress model was adopted in which zebrafish were induced with different stressors for 14 days. Stress-related behaviour was assessed using a depth-preference test and a light and dark test. Three doses of MOLE (500, 1000, and 2000 mg/L) were administered to the zebrafish. Upon sacrifice, the brains were harvested and processed for LC-MS QTOF based, global metabolomics analysis.

RESULTS: We observed significant changes in the behavioural parameters, where the swimming time at the light phase and upper phase of the tank were increased in the chronically stressed zebrafish treated with MOLE compared to those zebrafish which were not treated. Further, distinctive metabolite profiles were observed in zebrafish with different treatments. Several pathways that shed light on effects of MOLE were identified. MOLE is believed to relieve stress by regulating pathways that are involved in the metabolism of purine, glutathione, arginine and proline, D-glutamine, and D-glutamate.

CONCLUSION: MOLE is potentially an effective stress reliever. However, its effects in human needs to be confirmed with a systematic randomised control trial.

PMID:34090909 | DOI:10.1016/j.jep.2021.114290

Categories: Literature Watch

In Reply

Sun, 2021-06-06 06:00

J Am Acad Child Adolesc Psychiatry. 2021 Jun;60(6):664-666. doi: 10.1016/j.jaac.2021.04.007. Epub 2021 May 5.

ABSTRACT

Thank you for the opportunity to respond to the letter, "Thoughtful Clinical Use of Pharmacogenetics in Child and Adolescent Psychopharmacology." We appreciate the thoughtful consideration by Ramsey et al.1 of the American Academy of Child and Adolescent Psychiatry (AACAP) policy statement on the Clinical Use of Pharmacogenetic Tests in Prescribing Psychotropic Medications for Children and Adolescents.2 In this reply, we will highlight many of the important points that the authors have included and will also express our concerns regarding some of the authors' conclusions in light of the current level of evidence.

PMID:34090655 | DOI:10.1016/j.jaac.2021.04.007

Categories: Literature Watch

Genome-based therapeutic interventions for β-type hemoglobinopathies

Sun, 2021-06-06 06:00

Hum Genomics. 2021 Jun 5;15(1):32. doi: 10.1186/s40246-021-00329-0.

ABSTRACT

For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms of effectiveness and safety. So far, the most prevalent and promising treatment options for patients with β-types hemoglobinopathies, among others, predominantly include drug treatment and gene therapy. Despite the significant improvements of such interventions to the patient's quality of life, a variable response has been demonstrated among different groups of patients and populations. This is essentially due to the complexity of the disease and other genetic factors. In recent years, a more in-depth understanding of the molecular basis of the β-type hemoglobinopathies has led to significant upgrades to the current technologies, as well as the addition of new ones attempting to elucidate these barriers. Therefore, the purpose of this article is to shed light on pharmacogenomics, gene addition, and genome editing technologies, and consequently, their potential use as direct and indirect genome-based interventions, in different strategies, referring to drug and gene therapy. Furthermore, all the latest progress, updates, and scientific achievements for patients with β-type hemoglobinopathies will be described in detail.

PMID:34090531 | DOI:10.1186/s40246-021-00329-0

Categories: Literature Watch

The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study

Sat, 2021-06-05 06:00

Eur Neuropsychopharmacol. 2021 Jun 2;49:122-132. doi: 10.1016/j.euroneuro.2021.04.024. Online ahead of print.

ABSTRACT

This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges' g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.

PMID:34090255 | DOI:10.1016/j.euroneuro.2021.04.024

Categories: Literature Watch

What Influences Coital Frequency Among Chinese Men?: A Cross-Sectional Study

Sat, 2021-06-05 06:00

Sex Med. 2021 Jun 1;9(3):100363. doi: 10.1016/j.esxm.2021.100363. Online ahead of print.

ABSTRACT

INTRODUCTION: There are many Western reports on factors influencing coital frequency among men. However, no articles could be found about the factors influencing sexual activity among Chinese men.

AIM: The aim of this study was to identify the factors that influence the coital frequency of Chinese men.

MAIN OUTCOME MEASURES: The main outcome measures included self-reported monthly coital frequency, age, occupation, education level, andrology-related scales and dietary habits.

METHODS: Data for 1,407 men aged 18-79 years were collected in the Health Management Center of the Third Xiangya Hospital of Central South University from January 2019 to May 2019. The respondents completed the questionnaires independently or with the help of an interviewer (who read or explained the questionnaires to them) to analyse the factors that influence coital frequency.

RESULTS: In the previous 6 months, the sample had a mean monthly coital frequency (±SD) of 4.34 ± 3.18. Univariate logistic regression results indicated that the number of children (P = 0.004), IIEF-5 scores (P <0.001), EHSs (P <0.001) and frequency of milk consumption (P = 0.001) were associated with more frequent sexual activity. These statistical associations did not change after further adjustment for age, occupation, and reproductive history. We observed that the frequency of sexual activity showed an increasing trend with a greater number of children, higher IIEF-5 scores, higher EHSs and greater frequency of milk consumption (test for trend, P<0.05). Both univariate and multivariate analysis results indicated that the frequency of sexual activity decreased with increasing age (test for trend, P<0.001).

CONCLUSION: The coital frequency of Chinese men is associated with erectile function, anthropometric parameters, age, occupation, and dietary habits. Xiang Y, Peng J, Yang J, et al. What Influences Coital Frequency Among Chinese Men?: A Cross-Sectional Study. Sex Med 2021;9:100363.

PMID:34090240 | DOI:10.1016/j.esxm.2021.100363

Categories: Literature Watch

A quantitative analysis of total and free 11-oxygenated androgens and its application to human serum and plasma specimens using liquid-chromatography tandem mass spectrometry

Sat, 2021-06-05 06:00

J Chromatogr A. 2021 May 8;1650:462228. doi: 10.1016/j.chroma.2021.462228. Online ahead of print.

ABSTRACT

Bioactive 11-oxygenated C19 adrenal-derived steroids (11-oxy C19) are potentially relevant in diverse endocrine and metabolic contexts. We report the development and validation of a liquid chromatography electrospray ionization tandem mass spectrometric method (LC-ESI-MS/MS) for the simultaneous quantification of seven 11-oxy C19 using 200 µL of plasma or serum. Sample preparation involved chemical derivatization using hydroxylamine after liquid-liquid extraction to improve specificity and sensitivity. The method allowed the quantitation of total 11-oxy C19 (free + sulfate and glucuronide conjugates) following enzymatic hydrolysis. This included the abundant precursor 11-hydroxyandrostenedione (11OHA4) and the most potent androgenic derivatives 11-keto-testosterone (11KT) and 11-keto-dihydrotestosterone (11KDHT), their abundant metabolites 11-hydroxyandrosterone (11OHAST) and 11-keto-androsterone (11KAST) potentially feeding back into the pool of potent androgens, in addition to 11-keto-androstenedione (11KA4) and 11-hydroxytestosterone (11OHT). Stable isotopes were used as internal standards, and calibrators and quality controls were prepared in the same matrix as the study samples. Performance was validated against the Food and Drug Administration Criteria. The method was sensitive with lower limit of quantification (LLOQ) values of 10 and 20 pg/mL for free and total 11-oxy C19, respectively. The applicability was demonstrated in men and women adult donors that showed sex-differences. All steroids were quantified well above LLOQ, except 11KDHT that remained undetectable suggesting interfering endogenous molecules present in non-derivatized samples in which a peak was observed. By providing accurate and reliable quantitative data, this method will permit to evaluate how profiling of 11-oxy C19 will be most informative as diagnostic, prognostic and/or theranostic tools.

PMID:34090133 | DOI:10.1016/j.chroma.2021.462228

Categories: Literature Watch

TaqMan real time PCR for the Detection of the Gilbert's Syndrome Markers UGT1A1*28; UGT1A1*36 and UGT1A1*37

Sat, 2021-06-05 06:00

Mol Biol Rep. 2021 Jun 4. doi: 10.1007/s11033-021-06454-2. Online ahead of print.

ABSTRACT

Gilbert's syndrome is characterized by mild unconjugated hyperbilirubinemia. The key of this disease is a diminished activity of UDP-glucuronosyltransferase 1A1 (UGT1A1). TA insertion into the TATA box promoter region of the UGT1A1 gene on chromosome 2 is the genetic basis of Gilbert's syndrome (UGT1A1*28). An extra TA insert leads to eight (TA)8 repeats (UGT1A1*37) resulting in a further reduction of glucuronidation activity. A variant lacking one TA repeat (TA)5 (UGT1A1*36) has been identified. (TA)8 repeats (UGT1A1*37) and (TA)5 (UGT1A1*36) have been detected in Africans (frequency up to 0.07 and 0.08 respectively). We present a real time PCR method for genotyping the UGT1A1 (TA)n polymorphism (UGT1A1*28, UGT1A1*36, UGT1A1*37) using Taqman PCR on 7500 and cfx96 Real-Time PCR System. We present a real time PCR method for genotyping the UGT1A1 (TA)n polymorphism (UGT1A1*28, UGT1A1*36, UGT1A1*37) using Taqman PCR. About clinical validation, all 53 samples collected from patients referred for suspected Gilbert's syndrome were analyzed. We found 21 on the 53 patients (39.6%) were homozygotes (UGT1A1-TATA (TA)6) and referred as wild-type, 13 on the 53 patients (24.5%) were homozygotes (UGT1A1-TATA (TA)7) and referred as mutated, 1 on the 53 patients (1.9%) were homozygotes (UGT1A1-TATA (TA)8) and referred as mutated, 1 on the 53 patients (1.9%) were heterozygotes (UGT1A1-TATA (TA)7/8) and referred as mutated, 1 on the 53 patients (1.9%) were heterozygotes (UGT1A1-TATA (TA)5/6) and referred as mutated, and 16 on the 53 patients (30.2%) were heterozygotes (UGT1A1-TATA (TA)6/7). None were homozygotes UGT1A1-TATA (TA)5, homozygotes UGT1A1-TATA (TA)8, or heterozygotes with (TA)5 or (TA)8 alleles. The newly described technique represents a valid alternative method to sequencing, mainly due to its rapidity, easiness, and minor costs.

PMID:34089128 | DOI:10.1007/s11033-021-06454-2

Categories: Literature Watch

Evaluation of the need for pharmacogenomics testing among physicians in the West Bank of Palestine

Fri, 2021-06-04 06:00

Drug Metab Pers Ther. 2021 Jun 4. doi: 10.1515/dmdi-2021-0121. Online ahead of print.

ABSTRACT

OBJECTIVES: Pharmacogenomics (PGx) testing optimizes pharmacotherapy and reduces interindividual variation in drug responses. However, it is still not implemented in clinical practice in the West Bank of Palestine (WBP). The aim of this study was to determine the need for PGx education and testing among physicians from different specialties in WBP.

METHODS: This study used a cross-sectional survey that was administered to 381 physicians from different cities in WBP. The questionnaire consisted of 27 closed-ended questions that evaluate the exposure and attitude toward PGx education, the role of PGx testing in clinical practice, and the capabilities of physicians in PGx testing.

RESULTS: It was found that exposure to PGx education is low, with most of the respondents (81.1%) answering that PGx was not an integral part of their medical education. The majority (>90%) of the participants agreed that PGx should be included in the medical school curriculum. It was also found that 58.5% of the participants agreed that PGx testing is relevant to their current clinical practice. In addition, most of the participant physicians (>60%) think that they are currently not capable of prescribing and making decisions for pharmacotherapy based on PGx testing.

CONCLUSIONS: It is concluded that there is a high need for PGx education and implementation in clinical practice in WBP. We recommend adding PGx courses to the curricula of medical schools and going forward with the implementation of PGx testing in clinical practice in WBP.

PMID:34087962 | DOI:10.1515/dmdi-2021-0121

Categories: Literature Watch

Insights into the role of complement regulatory proteins in HPV mediated cervical carcinogenesis

Fri, 2021-06-04 06:00

Semin Cancer Biol. 2021 Jun 1:S1044-579X(21)00161-9. doi: 10.1016/j.semcancer.2021.05.031. Online ahead of print.

ABSTRACT

The persistent infection of high-risk Human papilloma virus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications. This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics.

PMID:34087416 | DOI:10.1016/j.semcancer.2021.05.031

Categories: Literature Watch

Pharmacogenomic considerations for repurposing of dexamethasone as a potential drug against SARS-CoV-2 infection

Fri, 2021-06-04 06:00

Per Med. 2021 Jun 4. doi: 10.2217/pme-2020-0183. Online ahead of print.

ABSTRACT

Immunomodulatory and analgesic effects of dexamethasone are clinically well established, and this synthetic corticosteroid acts as an agonist of glucocorticoid receptors. Early results of the RECOVERY Trial from the United Kingdom and others suggest certain benefits of dexamethasone against COVID-19 chronic patients. The efforts have been acknowledged by World Health Organization with an interim guideline to use in patients with a severe and critical illness. The inherent genetic variations in genes such as CYP3A5, NR3C1, NR3C2, etc., involved in the pharmacokinetic and pharmacodynamic processes may influence dexamethasone's effects as an anti-inflammatory drug. Besides, the drug may influence transcriptome or metabolic changes in the individuals. In the present review, we summarize the reported genetic variations that impact dexamethasone response and discuss dexamethasone-induced changes in transcriptome and metabolome that may influence potential treatment outcome against COVID-19.

PMID:34086487 | DOI:10.2217/pme-2020-0183

Categories: Literature Watch

Ethics and equity in rare disease research and healthcare

Fri, 2021-06-04 06:00

Per Med. 2021 Jun 4. doi: 10.2217/pme-2020-0144. Online ahead of print.

ABSTRACT

Rapid advances in next-generation sequencing technology, particularly whole exome sequencing and whole genome sequencing, have greatly affected our understanding of genetic variation underlying rare genetic diseases. Herein, we describe ethical principles of guiding consent and sharing of genomics research data. We also discuss ethical dilemmas in rare diseases research and patient recruitment policies and address bioethical and societal aspects influencing the ethical framework for genetic testing. Moreover, we focus on addressing ethical issues surrounding research in low- and middle-income countries. Overall, this perspective aims to address key aspects and issues for building proper ethical frameworks, when conducting research involving genomics data with a particular emphasis on rare diseases and genetics testing.

PMID:34085867 | DOI:10.2217/pme-2020-0144

Categories: Literature Watch

Correlations between Urinary Monoethylhexyl Phthalate Concentration in Healthy Individuals, Individuals with Colorectal Adenomas, and Individuals with Colorectal Cancer

Fri, 2021-06-04 06:00

J Agric Food Chem. 2021 Jun 3. doi: 10.1021/acs.jafc.1c00953. Online ahead of print.

ABSTRACT

Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. A recent study suggested a link between exposure to endocrine-disrupting chemicals (EDCs) and increased susceptibility to pathology. Exposure to di-(2-ethylhexyl) phthalate (DEHP), an EDC and plasticizer widely used in consumer products, has been reported to be significantly positively correlated with increased risks of various cancers. We explored this connection of DEHP exposure with the development of CRC through the detection of urinary monoethylhexyl phthalate (MEHP), a potent metabolite of DEHP. Participants comprised 221 individuals recruited between October 2016 and November 2019 from a single institution. Overall, urinary MEHP concentrations were significantly higher in patients with CRC than in the patients with adenoma or healthy participants (both P < 0.001). Higher exposure to DEHP may contribute to the occurrence of CRC. Urinary MEHP detection may serve as a beneficial noninvasive indicator of increased CRC risk.

PMID:34082531 | DOI:10.1021/acs.jafc.1c00953

Categories: Literature Watch

What do we need to obtain high quality circulating tumor DNA (ctDNA) for routine diagnostic test in oncology? - Considerations on pre-analytical aspects by the IFCC workgroup cfDNA

Thu, 2021-06-03 06:00

Clin Chim Acta. 2021 May 31:S0009-8981(21)00189-3. doi: 10.1016/j.cca.2021.05.033. Online ahead of print.

ABSTRACT

The analysis of circulating cell free DNA is an important tool for the analysis of tumor resistance, tumor heterogeneity, detection of minimal residual disease and detection of allograft rejection in kidney or heart transplant patients. The proper use of this technique is important, and starts with considering pre-analytic aspects. The current paper addresses some important technical considerations to ensure the proper and harmonized use of cfDNA techniques.

PMID:34081934 | DOI:10.1016/j.cca.2021.05.033

Categories: Literature Watch

Current challenges and opportunities for pharmacogenomics: perspective of the Industry Pharmacogenomics Working Group (I-PWG)

Thu, 2021-06-03 06:00

Hum Genet. 2021 Jun 3. doi: 10.1007/s00439-021-02282-3. Online ahead of print.

ABSTRACT

Pharmaceutical companies have increasingly utilized genomic data for the selection of drug targets and the development of precision medicine approaches. Most major pharmaceutical companies routinely collect DNA from clinical trial participants and conduct pharmacogenomic (PGx) studies. However, the implementation of PGx studies during clinical development presents a number of challenges. These challenges include adapting to a constantly changing global regulatory environment, challenges in study design and clinical implementation, and the increasing concerns over patient privacy. Advances in the field of genomics are also providing new opportunities for pharmaceutical companies, including the availability of large genomic databases linked to patient health information, the growing use of polygenic risk scores, and the direct sequencing of clinical trial participants. The Industry Pharmacogenomics Working Group (I-PWG) is an association of pharmaceutical companies actively working in the field of pharmacogenomics. This I-PWG perspective will provide an overview of the steps pharmaceutical companies are taking to address each of these challenges, and the approaches being taken to capitalize on emerging scientific opportunities.

PMID:34081195 | DOI:10.1007/s00439-021-02282-3

Categories: Literature Watch

Pharmacogenomic-based Personalized Medicine: Multi-Stakeholder Perspectives on Implementational Drivers and Barriers in the Canadian Healthcare System

Thu, 2021-06-03 06:00

Clin Transl Sci. 2021 Jun 3. doi: 10.1111/cts.13083. Online ahead of print.

ABSTRACT

Pharmacogenomics (PGx) based personalized medicine (PM) is increasingly utilized to guide treatment decisions for many drug-disease combinations. Notably, London Health Sciences Centre (LHSC) has pioneered a PGx program that has become a staple for London-based specialists. While implementational studies have been conducted in other jurisdictions, the Canadian healthcare system is understudied. Herein, the multi-stakeholder perspectives on implementational drivers and barriers are elucidated. Using a mixed-method qualitative model, key stakeholders and patients from LHSC's PGx-based PM clinic were interviewed and surveyed respectively. Interview transcripts were thematically analyzed in a stepwise process of customer profiling, value mapping and business model canvasing. Value for LHSC located specialist users of PGx was driven by the quick turnaround time, independence of the PGx clinic, and the quality of information. Engagement of external specialists was only limited by access and awareness, while other healthcare non-users were limited by education and applicability. The major determinant of successful adoption at novel sites were institutional champions. Patients valued and approved of the service, expressed a general willingness to pay, but often traveled far to receive genotyping. This paper discusses the critical pillars of education, awareness, advocacy, and efficiency required to address implementation barriers to healthcare service innovation in Canada. Further adoption of PGx practices into Canadian hospitals is an important factor for advancing system-level changes in care delivery, patient experiences and outcomes. The findings in this paper can help inform efforts to advance clinical PGx practices, but also the potential adoption and implementation of other innovative healthcare service solutions.

PMID:34080317 | DOI:10.1111/cts.13083

Categories: Literature Watch

CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM)

Thu, 2021-06-03 06:00

Endosc Int Open. 2021 Jun;9(6):E843-E847. doi: 10.1055/a-1401-9853. Epub 2021 May 27.

ABSTRACT

Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013-2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8-11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.

PMID:34079865 | PMC:PMC8159581 | DOI:10.1055/a-1401-9853

Categories: Literature Watch

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Thu, 2021-06-03 06:00

Nat Commun. 2021 Jun 2;12(1):3289. doi: 10.1038/s41467-021-23492-3.

ABSTRACT

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

PMID:34078897 | DOI:10.1038/s41467-021-23492-3

Categories: Literature Watch

Correction to: Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma

Thu, 2021-06-03 06:00

J Exp Clin Cancer Res. 2021 Jun 2;40(1):181. doi: 10.1186/s13046-021-01992-w.

NO ABSTRACT

PMID:34078416 | DOI:10.1186/s13046-021-01992-w

Categories: Literature Watch

Genetic variants of <em>PEAR1</em> and ischemic clinical outcomes in coronary artery disease patients: a systematic review and meta-analysis

Wed, 2021-06-02 06:00

Pharmacogenomics. 2021 Jun 2. doi: 10.2217/pgs-2021-0022. Online ahead of print.

ABSTRACT

Aim: The aim of this study was to assess the association between PEAR1 polymorphisms and ischemic clinical outcomes. Materials & methods: We searched the electronic database for articles on the relationship of PEAR1 SNPs and ischemic events in patients with coronary artery disease (CAD) up to October 2020. Results: A total of 9914 patients with CAD from six studies focusing on 12 SNPs of PEAR1 were included in this study. The A allele of rs12041331 were associated with ischemic events (odds ratio: 1.40; 95% CI: 1.04-1.88; p = 0.03). The AA homozygotes of rs2768759 was related to a higher risk of ischemic events than carriers of the C allele (odds ratio: 2.08; 95% CI: 1.09-3.97; p = 0.03). Conclusion: PEAR1 rs12041331 and rs2768759 are significantly associated with ischemic events in patients with CAD.

PMID:34075782 | DOI:10.2217/pgs-2021-0022

Categories: Literature Watch

Determining the potential clinical value of panel-based pharmacogenetic testing in patients with chronic pain or gastroesophageal reflux disease

Wed, 2021-06-02 06:00

Pharmacogenomics J. 2021 Jun 1. doi: 10.1038/s41397-021-00244-6. Online ahead of print.

ABSTRACT

We aimed to determine the potential value of panel-based pharmacogenetic (PGx) testing in patients with chronic pain or gastroesophageal reflux disease (GERD) who underwent single-gene PGx testing to guide opioid or proton pump inhibitor (PPI) therapy, respectively. Of 448 patients included (chronic pain, n = 337; GERD, n = 111), mean age was 57 years, 68% were female, and 73% were white. Excluding opiates for the pain cohort and PPIs for the GERD cohort, 76.6% of patients with pain and 71.2% with GERD were prescribed at least one additional medication with a high level of PGx evidence, most commonly ondansetron or selective serotonin reuptake inhibitors. The most common genes that could inform PGx drug prescribing were CYP2C19, CYP2D6, CYP2C9, and SLCO1B1. Our findings suggest that patients with chronic pain or GERD are commonly prescribed drugs with a high level of evidence for a PGx-guided approach, supporting panel-based testing in these populations.

PMID:34075203 | DOI:10.1038/s41397-021-00244-6

Categories: Literature Watch

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