The genetic structure of native Americans in North America based on the Globalfiler® STRs

Current forensic STR databases, such as CODIS, lack population genetic data on Native American populations. Information from a geographically diverse array of tribes is necessary to provide improved statistical estimates of the strength of associations with DNA evidence. The Globalfiler® STR markers were used to characterize the genetic structure of ten tribal populations from seven geographic regions in North America, including those not presently represented in forensic databases. Samples from the Arctic region, Baja California, California/Great Basin, the Southeast, Mexico, the Midwest, and the Southwest were analyzed for allele frequencies, observed and expected heterozygosities, and F-statistics. The tribal samples exhibited an F_ST or θ value above the conservative 0.03 estimate recommended by the National Research Council (NRC) for calculating random match probabilities among Native Americans. The greater differentiation among tribal populations computed here (θ = 0.04) warrants the inclusion of additional regional Native American samples into STR databases.     

腺病毒介导的靶向P85和Akt1短发夹RNA对人胃腺癌细胞生长抑制作用的研究

目的 构建靶向P85和蛋白激酶B1(PKB1/Akt1)的短发夹RNA(shRNA)腺病毒载体,研究其对人胃腺癌细胞SGC-7901生长的抑制效果.方法 构建腺病毒载体rAd5-P+A,体外转染SGC-7901细胞后,以实时定量PCR和Western blot分别检测P85和Akt1的mRNA和蛋白质的表达.以噻唑蓝比色分析法(MTT法)和流式细胞法评价转染后胃癌细胞的增殖活性.构建裸鼠皮下荷瘤模型进一步观察rAd5-P+A对SGC-7901细胞生长的抑制效果,并应用原位末端标记技术(TUNEL法)检测肿瘤细胞的凋亡情况.结果 成功构建的rAd5-P+A重组腺病毒载体转染SGC-7901细胞后可显著抑制p85和Akt1的mRNA表达,而P85和Aktl蛋白表达量在转染48 h、72 h后分别下调57.5%、63.7%和67.8%、75.6%,与空白对照组和通用腺病毒对照(rAd5-HK)组相比,差异具有统计学意义(P=0.005,P=0.003).与空白对照组和rAd5-HK组相比,SGC-7901细胞的增殖活性在rAd5-P+A转染后第2天明显下降(P<0.001),且rAd5-P+A转染组进入S期的细胞数减少了5.9%～7.1%,而进入G0/G1期的细胞增加了12.1%～13.7%.裸鼠皮下荷瘤模型治疗实验也显示,rAd5-P+A可抑制胃癌细胞的生长,诱导细胞的凋亡.结论 腺病毒介导的靶向P85和Akt1的shRNA可抑制人胃腺癌细胞的生长,这可能为胃腺癌靶向性联合基因治疗提供新的策略.     

Patient acceptable symptom state and minimal clinically important difference for patient-reported outcomes in systemic sclerosis: A secondary analysis of a randomized controlled trial comparing personalized physical therapy to usual care

Background

To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc).

α1,3GT siRNA打靶杂合子猪肝细胞阴性表达半乳糖转移酶

目的 研究联合应用基因敲除及RNA干扰(siRNA)技术对猪α1，3半乳糖转移酶(α1，3GT)基因修饰后，阳性猪杂合子( ／-)肝细胞的GT基因是否获得有效沉默并影响人天然抗体介导的细胞毒性作用。方法用pPNTloxPneo和PMXSV／U6载体构建猪GT基因敲除并siRNA载体，转染中国实验用小型猪的肝细胞，筛选获取杂合子克隆( ／-)。Northern blot检测GT mRNA表达，四甲基偶氮唑盐方法评估天然抗体细胞毒性。结果 野生型和pPNTloxPGT转染的杂合子猪肝细胞的inRNA表达阳性，而pPNTloxPGTsiRNA载体转染的杂合猪肝细胞阴性表达α1，3GT mRNA;pPNTloxPGT转染细胞( ／-)和野生型( ／ )猪肝细胞对人天然抗体介导的细胞毒性实验敏感，而pPNTloxPGTsiRNA转染细胞( ／-)则对毒性试验敏感性明显下降，只检测到17％细胞毒性。结论 对猪GT联合应用基因敲除及SiRNA能够在阳性猪杂合子肝细胞内有效沉默GT基因，降低猪肝细胞对人天然抗体细胞毒的敏感性。     

透明短帽辅助初级操作者单人结肠镜检查的作用

目的：探讨透明短帽辅助初级操作者单人结肠镜检查的作用。方法门诊接受结肠镜检查1200例患者,按照入组顺序分为奇数组及偶数组,奇数组采用常规结肠镜检查法,偶数组采用透明短帽辅助结肠镜检查法。比较初级操作者采用两种方法检查的成功率、平均到达回盲部时间、进入回肠末端成功率及时间、息肉检出率、平均疼痛评分及并发症情况。结果透明短帽辅助结肠镜检查法操作成功率、平均到达回盲部时间、进入回肠末端成功率及时间、平均疼痛评分、息肉检出率均优于常规结肠镜检查法,比较均有统计学意义,结果分别为（94% v 89%,P=0.00）、（8分 v 12分,P=0.00）、（87% v 81%,P=0.00）、（24s v 31s,P=0.02）、（4.2 v 4.9,P=0.01）、（27%v 21%,P=0.01）,两组均未出现严重并发症。结论对初级操作者来说,透明短帽辅助结肠镜操作法更加简单、有效,对患者造成痛苦更小。     

Development of a parent-proxy quality-of-life chronic cough-specific questionnaire: clinical impact vs psychometric evaluations

BACKGROUND: Chronic cough affects at least 7% of children, and the impact of this on families is significant. Although adult cough-specific quality-of-life (QOL) instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QOL for parents of children with chronic cough exists. This article compares two methods of item reduction (clinical impact and psychometric) and reports on the statistical properties of both QOL instruments. METHOD: One hundred seventy children (97 boys and 73 girls; median age, 4 years; interquartile range, 3 to 7.25 years) and one of their parents participated. A preliminary 50-item parent cough-specific QOL (PC-QOL) questionnaire was developed from conversations with parents of children with chronic cough (ie, cough for > 3 weeks). Parents also completed generic QOL questionnaires (eg, Pediatric Quality of Life Inventory, version 4.0 [PedsQL4.0] and the 12-item Short Form Health Survey, version 2 [SF-12v2]). RESULTS: The clinical impact and psychometric method of item reduction resulted in 27-item and 26-item PC-QOL questionnaires, respectively, with approximately 50% of items overlapping. Internal consistency among the final items from both methods was excellent. Some evidence for concurrent and criterion validity of both methods was established as significant correlations were found between subscales of the PC-QOL questionnaire and the scales of the SF-12v2 and PedsQL4.0 scores. The PC-QOL questionnaire derived from both methods was sensitive to change following an intervention. CONCLUSION: Chronic cough significantly impacts on the QOL of both parents and children. Although the PC-QOL questionnaires derived from a clinical impact method and from a psychometric method contained different items, both versions were shown to be internally consistent and valid. Further testing is required to compare both final versions to objective and subjective cough measures.     

Short-Pouch and Low-Anastomosis Duhamel Procedure Results in Better Fecal Control and Normal Defecation Pattern

PURPOSE The purpose of this study was to analyze the long-term outcome of the short-pouch and low-anastomosis Duhamel procedure and to evaluate the quality of life after pull-through. We also tried to answer the questions: Does the modified Duhamel procedure produce fecal continence? Is the quality of life correlated to normal bowel function (1–3 per day) without the use of laxatives?MATERIALS AND METHODS Between January 1993 and January 2002, 53 patients, 44 (83 percent) males and 9 (17 percent) females, who underwent a Duhamel procedure were assessed retrospectively. Of the 53 children, 36 (67.9 percent) underwent a primary Duhamel procedure at our institute (Group A). Seventeen (32.1 percent) patients had a primary Duhamel pull-through and subsequently a stoma before a redo modified Duhamel procedure (Group B). The technical modification was creation of a short rectal pouch of 35 mm, achieving a low colorectal anastomosis 0.5 cm from or on the dentate line. All 53 patients were assessed prospectively by a disease-specific questionnaire. The total score provided a single index of the quality of life associated with fecal continence.RESULTS For Group A (n = 36), the mean period of follow-up was 71.4 ± 29 months. Constipation was seen in four (11.1 percent) patients. In two (5.6 percent) patients there was a mild degree of soiling. Sensation and urge to defecate was intact in 34 (94.4 percent) children who could wait to go to the toilet until it was socially convenient. For Group B (n = 17), the mean period of follow-up was 73.9 ± 31.2 months. Constipation occurred in 17 (100 percent), encopresis in 14 (82.4 percent), and enterocolitis in 15 (88.2 percent) after the primary Duhamel procedure. In comparison, there was complete absence of constipation (100 percent), encopresis (100 percent), and complete resolution of enterocolitis (100 percent) after the redo modified Duhamel (P = 0.001). Continence to solid stools after primary Duhamel was seen in 5 (29.4 percent) vs. 17 (100 percent) after redo modified Duhamel. After the redo modified Duhamel all 17 (100 percent) patients have retained the sensation and urge to defecate and 15 (88.2 percent) can wait to get to the toilet until it is socially convenient. In all 53 patients, the quality of life was good in 86.8 percent (46/53) and correlated directly with fecal continence (r = 0.977). There was no correlation between age of patient and fecal continence (r = 0.597) and rate of fecal incontinence did not decrease with age. Direct correlation was seen with the presence of constipation and the incidence of late onset enterocolitis (r = 0.942).CONCLUSIONS Short-pouch, low-anastomosis Duhamel pull-through procedure results in fecal continence and complete emptying. The above procedure has a positive impact on the quality of life in these children.     

Functional Gastrointestinal Disorders and Associated Health Impairment in Individuals with Celiac Disease

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