scholarly journals The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A Narrative Synthesis of Evidence

Drug Research ◽  
2018 ◽  
Vol 69 (04) ◽  
pp. 185-193 ◽  
Author(s):  
Xingang Li ◽  
Shusen Sun ◽  
Xiaowei Xu ◽  
Zhigang Zhao ◽  
Wei Li

Abstract Background and study aim Genetic polymorphisms may play a role in muscular injury associated with simvastatin, but results were inconclusive. This study aimed to summarize evidence from the literature investigating the effects of genetic polymorphism on simvastatin-induced myopathy. Methods Studies regarding the association between genetic polymorphisms and simvastatin-induced myopathy were retrieved through electronic databases from February 1, 1990 to March 15, 2018. Two authors independently extracted data, including PMID, author, publication year, country, race, age, population characteristics, drugs, definition of case and control, gene, allele, SNP position, Hardy-Weinberg equilibrium, number of genotypes (case and control), minor allele frequency of cases and controls, association, study type and the Newcastle-Ottawa scale. Due to high heterogeneity in study design and outcome measurements among the included articles, a narrative synthesis of the evidence was conducted. Results A total of 10 association studies were identified in this study, including SLCO1B1, ABCB1, GATM, HTR3B, HTR7, RYR2 and HLA-DRB1. The evidence linking myopathy to rs4149056 in SLCO1B1 is of high quality, and this association has been reproduced in randomized trials and clinical practice-based cohorts. As for other candidate genetic markers, the evidences are limited or controversial, and additional well-designed studies with larger sample sizes, are required to further elucidate this association. Conclusion SLCO1B1 genotype is a useful biomarker for predicting an increased risk of simvastatin-induced myopathy.

2018 ◽  
Vol 27 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Gintare Dargiene ◽  
Greta Streleckiene ◽  
Jurgita Skieceviciene ◽  
Marcis Leja ◽  
Alexander Link ◽  
...  

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum.Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed.Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG.


2019 ◽  
Vol 2 (1) ◽  
pp. 280-298
Author(s):  
Lara van Meeteren ◽  
Bart Wissink

AbstractResponding to Open Philosophy’s call ‘Does public art have to be bad art?’, in this paper we argue that this discussion should pay attention to the consequences of structural transformations that guide the production and presentation of public art in today’s increasingly private city. While entrepreneurial governance and corporate branding strategies generate new opportunities, they might also result in increased risk averseness and control over the content of public art, thus putting its critical potential at risk. That observation ushers in urgent questions about control, complicity and criticality. We aim to reflect on those questions through two public art projects in Hong Kong: Antony Gormley’s Event Horizon (2015) and Our 60-second friendship begins now (2016) by Sampson Wong Yu-hin and Jason Lam Chi-fai. After drawing conclusions on the justification of public funding for co-productions, the legitimacy for artists to sometimes not ‘follow the rules’, and the problematic nature of a narrow definition of professionalism as a means to discredit artists, our analysis underlines the urgent need to develop a framework that can guide discussions on the consequences of control and complicity for the critical potential of public art.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kanyarat Khaeso ◽  
Sariya Udayachalerm ◽  
Patcharee Komvilaisak ◽  
Su-on Chainansamit ◽  
Kunanya Suwannaying ◽  
...  

Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted.Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author’s name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed.Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11–18.35) and 16.35 (95% CI 10.20–26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65–24.27) and early neutropenia (OR 15.85; 95% CI 8.80–28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia.Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary.


VASA ◽  
2016 ◽  
Vol 45 (4) ◽  
pp. 275-282 ◽  
Author(s):  
Christina Jeanneret ◽  
Konstantin Beier ◽  
Alexander von Weymarn ◽  
Jürg Traber

Abstract. Knowledge of the anatomy of the pelvic, gonadal and renal veins is important to understand pelvic congestion syndrome (PCS) and left renal vein compression syndrome (LRCS), which is also known as the nutcracker syndrome. LRCS is related to PCS and to the presence of vulvar, vaginal and pudendal varicose veins. The diagnosis of the two syndromes is difficult, and usually achieved with CT- or phlebography. The gold standard is the intravenous pressure measurement using conventional phlebography. The definition of PCS is described as pelvic pain, aggravated in the standing position and lasting for more than 6 months. Pain in the left flank and microhaematuria is seen in patients with LRCS. Women with multiple pregnancies are at increased risk of developing varicose vein recurrences with pelvic drainage and ovarian vein reflux after crossectomy and stripping of the great saphenous vein. The therapeutic options are: conservative treatment (medroxyprogesteron) or interventional (coiling of the ovarian vein) or operative treatment (clipping of the ovarian vein). Controlled prospective trials are needed to find the best treatment.


2020 ◽  
Author(s):  
Isra Revenia

This article is made to know the destinantion and the administrasi functions of the school in order to assist the leader of an organazation in making decisions and doing the right thing, recording of such statements in addition to the information needs also pertains to the function of accountabilitty and control functions. Administrative administration is the activity of recording for everything that happens in the organization to be used as information for leaders. While the definition of administration is all processing activities that start from collecting (receiving), recording, processing, duplicating, minimizing and storing all the information of correspondence needed by the organization. Administration is as an activity to determine everything that happens in the organization, to be used as material for information by the leadership, which includes all activities ranging from manufacturing, managing, structuring to all the preparation of information needed by the organization.


1994 ◽  
Vol 30 (1) ◽  
pp. 167-175
Author(s):  
Alan H. Vicory ◽  
Peter A. Tennant

With the attainment of secondary treatment by virtually all municipal discharges in the United States, control of water pollution from combined sewer overflows (CSOs) has assumed a high priority. Accordingly, a national strategy was issued in 1989 which, in 1993, was expanded into a national policy on CSO control. The national policy establishes as an objective the attainment of receiving water quality standards, rather than a design storm/treatment technology based approach. A significant percentage of the CSOs in the U.S. are located along the Ohio River. The states along the Ohio have decided to coordinate their CSO control efforts through the Ohio River Valley Water Sanitation Commission (ORSANCO). With the Commission assigned the responsibility of developing a monitoring approach which would allow the definition of CSO impacts on the Ohio, research by the Commission found that very little information existed on the monitoring and assessment of large rivers for the determination of CSO impacts. It was therefore necessary to develop a strategy for coordinated efforts by the states, the CSO dischargers, and ORSANCO to identify and apply appropriate monitoring approaches. A workshop was held in June 1993 to receive input from a variety of experts. Taking into account this input, a strategy has been developed which sets forth certain approaches and concepts to be considered in assessing CSO impacts. In addition, the strategy calls for frequent sharing of findings in order that the data collection efforts by the several agencies can be mutually supportive and lead to technically sound answers regarding CSO impacts and control needs.


2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.


1996 ◽  
Vol 118 (3) ◽  
pp. 482-488 ◽  
Author(s):  
Sergio Bittanti ◽  
Fabrizio Lorito ◽  
Silvia Strada

In this paper, Linear Quadratic (LQ) optimal control concepts are applied for the active control of vibrations in helicopters. The study is based on an identified dynamic model of the rotor. The vibration effect is captured by suitably augmenting the state vector of the rotor model. Then, Kalman filtering concepts can be used to obtain a real-time estimate of the vibration, which is then fed back to form a suitable compensation signal. This design rationale is derived here starting from a rigorous problem position in an optimal control context. Among other things, this calls for a suitable definition of the performance index, of nonstandard type. The application of these ideas to a test helicopter, by means of computer simulations, shows good performances both in terms of disturbance rejection effectiveness and control effort limitation. The performance of the obtained controller is compared with the one achievable by the so called Higher Harmonic Control (HHC) approach, well known within the helicopter community.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucas D. Ward ◽  
Ho-Chou Tu ◽  
Chelsea B. Quenneville ◽  
Shira Tsour ◽  
Alexander O. Flynn-Carroll ◽  
...  

AbstractUnderstanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum activities have proven useful for investigating liver biology. Here we report 100 loci associating with both enzymes, using GWAS across 411,048 subjects in the UK Biobank. The rare missense variant SLC30A10 Thr95Ile (rs188273166) associates with the largest elevation of both enzymes, and this association replicates in the DiscovEHR study. SLC30A10 excretes manganese from the liver to the bile duct, and rare homozygous loss of function causes the syndrome hypermanganesemia with dystonia-1 (HMNDYT1) which involves cirrhosis. Consistent with hematological symptoms of hypermanganesemia, SLC30A10 Thr95Ile carriers have increased hematocrit and risk of iron deficiency anemia. Carriers also have increased risk of extrahepatic bile duct cancer. These results suggest that genetic variation in SLC30A10 adversely affects more individuals than patients with diagnosed HMNDYT1.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Juliette Servante ◽  
Gill Swallow ◽  
Jim G. Thornton ◽  
Bethan Myers ◽  
Sandhya Munireddy ◽  
...  

Abstract Background As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Methods Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Results One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. Conclusions Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.


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