Peroral Endoscopic Myotomy Can Improve Esophageal Motility in Patients with Achalasia from a Large Sample Self-Control Research (66 Patients)

Background

Peroral endoscopic myotomy (POEM) as a new approach to achalasia attracts broad attention. The primary objective of this study was to evaluate the results with esophageal motility after POEM through the first large sample clinical research.

Patients and Methods

We have a self-control research with all patients (205 in total) who underwent POEM from 2010 to 2014 at our Digestive Endoscopic Center, 66 patients of which underwent high resolution manometry (HRM) before and after POEM in our motility laboratory. Follow-ups last for 5.6 months on average. Outcome variables analyzed included upper esophageal sphincter pressure (UESP), upper esophageal sphincter residual pressure (UESRP), lower esophageal sphincter pressure (LESP), lower esophageal sphincter residual pressure (LESRP) and esophageal body peristalsis. We have a statistical analysis to illustrate how POEM impacts on the change of esophageal motility.

Results

The symptoms related to dysphagia were relieved in 95% of patients in recent term after POEM. While HRM showed a statistically significant reduction of URSRP, LESP and LESRP (P<0.01), however, peristalsis was not consistently affected. There were 11 patients who had undergone other prior endoscopic treatment (endoscopic dilation or botulinum toxin injection) and 55 patients had not. The statistical difference (P>0.05) did not occur for these two groups on LESP and LESRP reduction.

Conclusions

POEM clearly relieved the symptoms related to dysphagia by lowering the pressure of upper esophageal sphincter (UES) and lower esophageal sphincter (LES),and other endoscopic treatment before POEM did not affect the improvement of LES pressure. These results are concluded from our short-term follow-up study, while the long-term efficacy remains to be further illustrated.

Trial Registration

Chinese Clinical Trial Register ChiCTR-TRC-12002204)     

Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis

Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1–10% in the general population, notifications of symptomatic pertussis only comprise 0.01–0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D₃ (VD₃) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection.     

The Association of Cardioprotective Medications with Pneumonia-Related Outcomes

Introduction

Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.

Materials and Methods

We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.

Results

Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.

Discussion

While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.     

癔球症患者食管测压结果、心理特征分析及小剂量阿米替林的干预效果研究

摘要 目的：分析患者的食管测压结果、心理特征及小剂量阿米替林的干预效果。方法：选取2017年5月~2019年5月期间上海市静安区市北医院收治的癔球症患者137例（癔球症组）,另选取同期到上海市静安区市北医院体检的健康志愿者50例（非癔球症组）,比较两组食管测压结果、癔球症症状评分量表（GETS）评分、汉密尔顿抑郁量表-17（HAMD-17）评分、汉密尔顿焦虑量表-14（HAMA-14）评分。按随机数字表法将癔球症患者分为对照组（n=68）和研究组（n=69）,对照组给予常规治疗,研究组则在对照组的基础上联合小剂量阿米替林干预。比较对照组、研究组的临床疗效、不良反应。结果：癔球症组、非癔球症组患者食管上括约肌（UES）长度、UES残余压、食管下括约肌（LES）静息压、收缩前沿速度（CFV）、远端潜伏时间（DL）组间比较差异无统计学意义（P>0.05）;癔球症组患者UES静息压高于非癔球症组（P<0.05）。癔球症组患者GETS、HAMA-14、HAMD-17评分高于非癔球症组（P<0.05）。研究组治疗后的临床总有效率为84.06%（58/69）,高于对照组的66.18%（45/68）（P<0.05）。两组不良反应发生率比较差异无统计学意义（P>0.05）。结论：相对于非癔球症患者,癔球症患者具有较高的UES静息压,癔球症症状及较为严重的不良情绪,采用小剂量阿米替林对癔球症进行干预可提高治疗有效率,用药安全性较好。     

吞咽困难对食管早期肿瘤及癌前病变患者食管动力、心理状态和临床相关症状的影响

摘要 目的：探讨吞咽困难对食管早期肿瘤及癌前病变患者食管动力、心理状态和临床相关症状的影响。方法：纳入2020年3月-2021年9月在南京医科大学第一附属医院消化内科住院确诊为食管早期肿瘤及癌前病变拟行内镜治疗的60例患者，根据有无合并吞咽困难将患者分为吞咽困难组和无吞咽困难组，分别比较两组患者在临床特征、高分辨率食管测压（HRM）参数以及焦虑自评量表（SAS）、抑郁自评量表（SDS）、胃食管反流病自评量表（GERDQ）评分的差异，分析HRM异常参数与原发病灶参数的相关性。结果：吞咽困难组患者的食管下括约肌（LES）中心点位置低于无吞咽困难组患者，LES静息压、LES残余压、无效吞咽百分比显著高于无吞咽困难组患者（P<0.05），HRM异常参数与原发病灶参数之间未见明显相关性（P>0.05），吞咽困难组患者的SAS、SDS评分高于无吞咽困难组（P<0.05），而两组患者GERDQ评分比较差异无统计学意义（P>0.05）。结论：食管早期肿瘤及癌前病变患者出现的吞咽困难症状与合并的异常食管动力有关，同时在一定程度上影响了患者的心理状态，对患者的临床相关症状无明显影响。     

Human Placental-Specific Epipolymorphism and its Association with Adverse Pregnancy Outcomes

Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic “on-or-off” pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%–25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such “epipolymorphism” in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility.     

Association of Sickness Absence with Poor Sleep and Depressive Symptoms in Shift Workers

A cross-sectional study was conducted to evaluate the contribution of daily sleep habits and depressive symptoms to sickness absences of shift workers. A self-administered questionnaire that solicited answers about sleep, symptoms of depression, sickness absence, diseases/injuries, and lifestyle factors was submitted to a sample of 522 rotating shift workers between the ages of 18–59 (mean 27) yrs of an electric equipment manufacturing company. The seven features of sleep queried were daily hours of sleep, time to fall asleep, awakening during sleep, early morning awakening, sleep well at night, sufficiency of sleep, and excessive daytime sleepiness at work. The responses were assessed over the subject's previous 1-yr period. Each sleep feature, except daily sleeping hours, was dichotomized by the following responses: (1) taking more than 30 min to fall asleep (difficulty initiating sleep; DIS), (2) awakening during sleep almost every day (difficulty maintaining sleep; DMS), (3) early morning awakening almost every day (EMA), (4) sleeping very poorly or not so well at night, (5) definite or somewhat insufficient nightly sleep, and (6) excessive daytime sleepiness at work almost every day (EDS). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Sickness absence was calculated by asking subjects “How many days in total have you been absent from work due to sickness, including paid vacation, in the last 1-yr period?” The responses were divided into three groups that included no (0 days) sickness absences (reference group, n = 235 subjects), 1 to 4 days (short-term, n = 199 subjects), and 5 days or more (long-term, n = 88 subjects). Compared to the prevalence of sleep features of the reference group, workers with short-term absence showed a significantly higher prevalence of EMA with an odds ratio (OR) of 5.3, 95% confidence interval (CI) 1.3–22.0. Long-term absence was significantly associated with DMS (OR = 2.1, 95%CI 1.0–4.6), EMA (OR = 5.6, 95%CI 1.0–28.7), sleeping poorly at night (OR = 2.6, 95%CI 1.4–5.0), and high depressive symptoms (OR = 2.0, 95%CI 1.0–3.7) according to the CES-D score of ≥16, after adjusting for multiple confounding variables. These data point to an association between both the parameters of poor sleep and symptoms of deep depression when self-reported sickness absence is frequent. The association is particularly strong with long-term absence in male shift workers.     

舌骨肌切开悬吊术结合腭咽成形术治疗重度OSAHS

目的：应用联合应用舌骨肌切开悬吊术和腭咽成形术治疗重度阻塞性睡眠呼吸暂停低通气综合征。方法：用多导睡眠监测确定52例重度阻塞性睡眠呼吸暂停低通气综合征,不同方法确定均为以舌根平面阻塞为主的上气道多平面狭窄。采用舌骨肌切开悬吊术联合腭咽成形术进行治疗。结果：所有接受手术的患者术后鼾声均有不同程度的减轻,手术总有效率94．2％。无1例出现不良并发症。结论：舌骨肌切开悬吊术安全、易行,结合腭咽成形术治疗重度阻塞性睡眠呼吸暂停低通气综合征效果良好。     

Analysis of Genome-Wide Association Studies with Multiple Outcomes Using Penalization

Genome-wide association studies have been extensively conducted, searching for markers for biologically meaningful outcomes and phenotypes. Penalization methods have been adopted in the analysis of the joint effects of a large number of SNPs (single nucleotide polymorphisms) and marker identification. This study is partly motivated by the analysis of heterogeneous stock mice dataset, in which multiple correlated phenotypes and a large number of SNPs are available. Existing penalization methods designed to analyze a single response variable cannot accommodate the correlation among multiple response variables. With multiple response variables sharing the same set of markers, joint modeling is first employed to accommodate the correlation. The group Lasso approach is adopted to select markers associated with all the outcome variables. An efficient computational algorithm is developed. Simulation study and analysis of the heterogeneous stock mice dataset show that the proposed method can outperform existing penalization methods.     

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m²/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.     

Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms

Background

The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus-Pituitary-Adrenal axis response having been implicated in its pathophysiology.

Methods

The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided.

Results

Women with postpartum EPDS score ≥ 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7–9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5–14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively).

Conclusions

Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression.     

Association of Ideal Cardiovascular Metrics and Serum High-Sensitivity C-Reactive Protein in Hypertensive Population

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of cardiovascular disease. However, ideal cardiovascular health indicates lower risk of cardiovascular disease. This study aimed to investigate the effect of ideal cardiovascular health behaviors and health factors on hs-CRP levels among a hypertensive population. From 2006 to 2007, a cross-sectional study was conducted to survey 41,476 hypertensive subjects among the employees of Kailuan Corporation. Data from unified questionnaires and blood biochemical examinations were collected. The effects of ideal cardiovascular health behaviors and health factors on hs-CRP levels were evaluated through multivariate logistic regression analysis. A negative correlation was observed between hs-CRP levels and the number of ideal cardiovascular health metrics. The mean hs-CRP levels of subjects with zero to one, two, three, and four to six ideal cardiovascular health metrics were 1.11, 0.96, 0.90, and 0.80 mg/L, respectively (P<0.01). Multivariate logistic regression analysis revealed that after adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, the risks for subjects with two, three, and four to six ideal health metrics with serum hs-CRP >3 mg/L were lower than those with zero to one ideal health metrics, with corresponding odd ratios of 0.86 (95%CI: 0.79–0.93, P<0.01), 0.76 (95%CI: 0.69–0.83, P<0.01), and 0.68 (95%CI: 0.64–0.75, P<0.01), respectively. This finding suggests that ideal cardiovascular health behaviors and health factors were related to decreased hs-CRP levels in a hypertensive population.

Clinical Trial Registration

Unique identifier: ChiCTR-TNC-11001489.     

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.     

Association of Major Depressive Episode with Negative Outcomes of Tuberculosis Treatment

Background

Pulmonary tuberculosis (TB) persists an important contributor to the burden of diseases in developing countries. TB control success is based on the patient’s compliance to the treatment. Depressive disorders have been negatively associated with compliance of therapeutic schemes for chronic diseases. This study aimed to estimate the significance and magnitude of major depressive episode as a hazard factor for negative outcomes (NO), including abandon or death in patients receiving TB treatment.

Methodology/Principal Findings

A longitudinal study was conducted to evaluate the association of major depressive episode (MDE), as measured by a 5-item version of the Center for Epidemiological Studies Depression Scale (CES-D) with NO to TB treatment. Patients with confirmed TB were enrolled before the start of TB treatment. Baseline measurements included socio-demographic variables as well as the CES-D, which was also applied every month until the end of the treatment. Death and treatment default were assessed monthly. Survivor function (SF) for NO according to MDE status (CES-D≥6) at baseline (MDEb) was estimated. Cox’s Regression was performed for bivariate analyses as well as for the multivariate model. A total of 325 patients accepted to participate in the study, of which 34 where excluded for diagnosis of MDR-TB. NO was observed in 24 patients (8.2%); 109 (37%) presented MDEb. Statistically significant difference was found on the SF of patients with and without MDEb (0.85 vs. 0.96, p-value = 0.002). The hazard ratio for NO, controlled for age, sex, marital status and instruction level was 3.54 (95%CI 1.43–8.75; p-value = 0.006).

Conclusion

The presence of MDE at baseline is associated to NO of TB treatment. Targeting detection and treatment of MDE may improve TB treatment outcomes.     

Cognitive Functioning in Patients with Bipolar Disorder: Association with Depressive Symptoms and Alcohol Use

Background

Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored.

Methodology/Principal Findings

The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R² 7%), speed of information processing (adjusted beta 0.36; R² 20%), attentional switching (adjusted beta 0.24; R² 16%) and the mean score (adjusted beta 0.23; R² 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction.

Conclusions/Significance

Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.     

Association of mTOR Polymorphisms with Cancer Risk and Clinical Outcomes: A Meta-Analysis

Genetic polymorphisms in mTOR gene may be associated with cancer risk and clinical outcomes of cancer patients by affecting mTOR gene expression or its activation. However, inconsistent results have been reported. The aim of this study is to systematically evaluate the association between mTOR polymorphisms (rs2295080, rs2536 and rs11121704) and cancer risk as well as clinical outcome by a meta-analysis. We identified 10 eligible studies and extracted data by two investigators. Based on dominant and recessive models, odds ratio (ORs) and 95% confidence intervals (CIs) were calculated by using Stata, version 11 to evaluate the association strength. Our meta-analysis results showed that the wild genotype TT of rs2295080 polymorphism was associated with increased cancer risk under dominant model (OR = 1.24, 95%CI: 1.12–1.36, p<0.0005) in Chinese but not with clinical outcome parameters, while the TT genotype of rs11121704 was associated with poor clinical outcome parameters (OR = 1.53, 95%CI: 1.01–2.32, p = 0.044), such as death, metastasis and resistance to chemotherapy. However, rs2536 may not influence cancer susceptibility. In conclusion, this meta-analysis indicated the common polymorphisms in mTOR gene might be genetic risk factors for the carcinogenesis and clinical outcomes of cancer patients. However, further investigation on large population and different ethnicities are warranted.     

Association of the Common Genetic Polymorphisms and Haplotypes of the Chymase Gene with Left Ventricular Mass in Male Patients with Symptomatic Aortic Stenosis

We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-β activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84×10⁻⁵), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload.     

Association of Polymorphisms in HLA Antigen Presentation-Related Genes with the Outcomes of HCV Infection

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).     

Association of a Distinct Begomovirus and a Betasatellite with Leaf Curl Symptoms in Pedilanthus tithymaloides

Pedilanthus tithymaloides (Redbird flower) is an ornamental shrub that occasionally exhibits leaf curl and enation symptoms in Pakistan. Symptoms were shown to be associated with a monopartite begomovirus and a betasatellite. The complete nucleotide sequence of the begomovirus was found to be 2764 nucleotides in length and have the highest nucleotide sequence identity to a begomovirus previously isolated from tomato (90.3% nucleotide sequence identity), followed by Radish leaf curl virus (86.3%). The complete betasatellite sequence was determined to be 1358 nucleotides in length and has the highest sequence identity (97%) with Tobacco leaf curl betasatellite . The analysis shows the begomovirus associated with leaf curl disease of Pedilanthus to be a distinct and previously unreported begomovirus for which the name Pedilanthus leaf curl virus (PedLCV) is proposed. This virus is one of an increasing number of monopartite begomoviruses shown to be associated with a betasatellite.