The effect of atrovastatin on the ovarian arterial blood flow and serum androgen level in PCOS patient

Various researches have been conducted over the recent years on the therapeutic effects of statins on the metabolic and hyper-androgenic state of the patients suffering from PCOS. The present research seeks to evaluate the treatment with atorvastatin and its effect on the lipid profile level, serum androgen status and morphology and blood flow of polycystic ovaries. A double blind clinical trial was designed for this research where the women with PCOS resorting to the gynecology clinic of Firouzgar Hospital were randomly divided into two groups: case and Control. Early at the beginning of the research, variables such as body mass, lipid profile, blood androgen level, fasting blood Sugar, size of the ovary, and resistance of the stromal artery of ovary were studied. For a period of 6 weeks, one group was given with a daily dose of 40 mg atorvastatin, while the other group just received placebo. All the variables were studied once again after 6 weeks and the results were analyzed using SPSS v.16. The case group included 20 patients suffering from PCOS who received atorvastatin, while there were 20 patients with PCOS in the witness group who just received placebo. The average ages in the atorvastatin and placebo groups were 27.7 ± 3.41 and 30.9 ± 4.8 years old respectively. A significant difference was observed between the two groups in terms of changes in the average cholesterol and LDL levels before and after the intervention. This reduction was more significant in the atorvastatin group. After prescription of atorvastatin, the level of Androstenedione had decreased significantly in treatment group. A statistically significant reduction was observed in the size of left and right ovaries in the group receiving atorvastatin. No significant changes were observed in the size of the ovaries in the group receiving placebo. The average arterial resistance level of left and right ovaries before and after intervention in atorvastatin group exhibited a significant reduction. Having discarded the confounding effect of RI, this difference with the witness group was statistically significant. Keeping in mind the effects of atorvastatin such as improving the lipid profile status and reduction of androstenedione among those with PCOS, it can be used as an auxiliary treatment to control symptoms and long-term side effects among patients. Considering the shrinkage of ovary size and enhancement of blood flow to PCOS ovary, future researches can focus on effectiveness of statins in improving the ovulation status of performance of PCO ovaries

Two-scale modelling of fracture of magnesium phosphate cement under bending using X-ray computed tomography characterisation

This paper presents an efficient experimental-numerical analysis of fracture mechanics in magnesium phosphate cement (MPC) based on the structural and mechanical properties of its constituents including potassium magnesium phosphate hexahydrate (MKP), magnesium oxide (MgO) and pores. At micro-scale, the fracture energy and material strength of solid phases were obtained relying on the combination of nanoindentation experiments and simulation. The X-ray computed tomography (XCT) image-based 3D meso-structure model of MPC beam was generated and incorporated with the finite element cohesive zone model to analyse the fracture process of MPC beam under three-point bending. The unknown fracture parameters of cohesive elements at the interface between MKP and MgO were determined via the model calibration process conditional to the experimental data in terms of relationship between macro-load and crack mouth opening displacement. The cohesive strengths obtained for MKP, MgO and MKP-MgO were found to be 5.8, 106 and 24 MPa, respectively. In the same order, the fracture energies were0.02, 0.08 and 0.04 N/mm, respectively

The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders:A Systematic Review and Meta-Analysis

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010–2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p &lt; 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.</p

Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders:The Functional Role of CYP2D6 and CYP2C19

Schizophrenia spectrum disorders (SSD) are complex mental disorders, and while treatment with antipsychotics is important, many patients do not respond or develop serious side effects. Genetic variation has been shown to play a considerable role in determining an individual’s response to antipsychotic medication. However, previous pharmacogenetic (PGx) studies have been limited by small sample sizes, lack of consensus regarding relevant genetic variants, and cross-sectional designs. The current study aimed to investigate the association between PGx variants and long-term clinical outcomes in 691 patients of European ancestry with SSD. Using evidence from the literature on candidate genes involved in antipsychotic pharmacodynamics, we created a polygenic risk score (PRS) to investigate its association with clinical outcomes. We also created PRS using core variants of psychotropic drug metabolism enzymes CYP2D6 and CYP2C19. Furthermore, the CYP2D6 and CYP2C19 functional activity scores were calculated to determine the relationship between metabolism and clinical outcomes. We found no association for PGx PRSs and clinical outcomes; however, an association was found with CYP2D6 activity scores by the traditional method. Higher CYP2D6 metabolism was associated with high positive and high cognitive impairment groups relative to low symptom severity groups. These findings highlight the need to test PGx efficacy with different symptom domains. More evidence is needed before pharmacogenetic variation can contribute to personalized treatment plans.</p

Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders:The Functional Role of CYP2D6 and CYP2C19

Schizophrenia spectrum disorders (SSD) are complex mental disorders, and while treatment with antipsychotics is important, many patients do not respond or develop serious side effects. Genetic variation has been shown to play a considerable role in determining an individual’s response to antipsychotic medication. However, previous pharmacogenetic (PGx) studies have been limited by small sample sizes, lack of consensus regarding relevant genetic variants, and cross-sectional designs. The current study aimed to investigate the association between PGx variants and long-term clinical outcomes in 691 patients of European ancestry with SSD. Using evidence from the literature on candidate genes involved in antipsychotic pharmacodynamics, we created a polygenic risk score (PRS) to investigate its association with clinical outcomes. We also created PRS using core variants of psychotropic drug metabolism enzymes CYP2D6 and CYP2C19. Furthermore, the CYP2D6 and CYP2C19 functional activity scores were calculated to determine the relationship between metabolism and clinical outcomes. We found no association for PGx PRSs and clinical outcomes; however, an association was found with CYP2D6 activity scores by the traditional method. Higher CYP2D6 metabolism was associated with high positive and high cognitive impairment groups relative to low symptom severity groups. These findings highlight the need to test PGx efficacy with different symptom domains. More evidence is needed before pharmacogenetic variation can contribute to personalized treatment plans.</p

Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders:The Functional Role of CYP2D6 and CYP2C19

Schizophrenia spectrum disorders (SSD) are complex mental disorders, and while treatment with antipsychotics is important, many patients do not respond or develop serious side effects. Genetic variation has been shown to play a considerable role in determining an individual’s response to antipsychotic medication. However, previous pharmacogenetic (PGx) studies have been limited by small sample sizes, lack of consensus regarding relevant genetic variants, and cross-sectional designs. The current study aimed to investigate the association between PGx variants and long-term clinical outcomes in 691 patients of European ancestry with SSD. Using evidence from the literature on candidate genes involved in antipsychotic pharmacodynamics, we created a polygenic risk score (PRS) to investigate its association with clinical outcomes. We also created PRS using core variants of psychotropic drug metabolism enzymes CYP2D6 and CYP2C19. Furthermore, the CYP2D6 and CYP2C19 functional activity scores were calculated to determine the relationship between metabolism and clinical outcomes. We found no association for PGx PRSs and clinical outcomes; however, an association was found with CYP2D6 activity scores by the traditional method. Higher CYP2D6 metabolism was associated with high positive and high cognitive impairment groups relative to low symptom severity groups. These findings highlight the need to test PGx efficacy with different symptom domains. More evidence is needed before pharmacogenetic variation can contribute to personalized treatment plans.</p

Acrocyanosis and digital necrosis are associated with poor prognosis in COVID-19

Acrocyanosis and digital necrosis, which caused by microangiopathic and immunothrombosis phenomenon, may accompanied by microvascular involvement of other organs. Therefore, this finding can play a prognostic role in covid-19 outcome. © 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Lt

A genome-wide association study of radiotherapy induced toxicity in head and neck cancer patients identifies a susceptibility locus associated with mucositis

PURPOSE: A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT.MATERIALS AND METHODS: The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site.RESULTS: We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48-2.41; ppooled = 4.34 × 10-16).CONCLUSION: This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.</p