Large-scale sequencing to identify disease causing variants in X-linked mental retardation

A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation
Tarpey et al. (2009)
Nature Genetics 41: 535–543     

A study of the effect of nasal modes of ventilation on the incidence of gastro-oesophageal reflux in preterm neonates

Background

Nasal modes of respiratory support cause variable amounts of gastric dilatation which may increase gastro-oesophageal reflux (GER) in preterms. To compare the incidence of GER in nasally ventilated, preterm babies with controls (babies not on ventilation). Type of study: A prospective, observational comparative study.

Method

Twenty-three preterm babies of gestational age 28–36 weeks and weight ranging between 1,000 g and < 2,500 g on either nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure venti-lation (nIPPV) were assessed for GER. They were compared with controls not on ventilation some of who were test babies when off ventilation (subgroup A) and some were unrelated babies not on ventilator but matched for gestational age and weight with test babies (subgroup B). All babies were subjected to continuous, oesophageal pH monitoring with dual sensor (upper and lower oesophageal) catheters. Reflux index (RI) was calculated as the percentage of study time the lower oesophageal pH was < 4. Primary outcome was the RI in the test and controls groups. Secondary outcome was the temporal relation of the reflux with symptoms if any. Numerical data were shown as mean with standard deviation and statistical comparisons were done using the χ²-test, Fischer test, and t-test wherever applicable.

Results

The RI was higher in ventilated babies as compared to the control group, particularly in the subgroup A, where test babies formed their own controls. Grade IV reflux (7 cases) was seen only in the ventilated babies. There was no difference in the incidence of GER in babies on nCPAP as compared with nIPPV. Grade IV reflux could not be reliably predicted by RI alone. No definite temporal relation between episodes of reflux and symptoms could be determined in this study.

Conclusion

There is an increase in GER in preterms on nasal modes of ventilation. A combination of upper (pharyngeal) and lower oesophageal sensors are preferred to a single lower oesophageal sensor when assessing GER by oesophageal pHmetry in neonates.     

Management of ��floating elbow�� in children

Background:

Supracondylar fractures associated with ipsilateral forearm fractures, aptly termed as “floating elbow” is a rare injury in children after a fall from height. The various authors have reported their results with conservative treatment of one or both injuries to aggressive emergency operative fixation of both components.

Materials and Methods:

During a period of three years, the author managed four cases of floating elbow in children. All cases were managed by closed reduction and pinning of both components of the injury.

Results:

All patients recovered full elbow range of motion at three months followup and were rated as excellent as per modified Flynn''s criteria. None of the patients developed cubitus varus deformity, complications related to the pins or delayed union.

Conclusions:

Early closed reduction and K wire fixation of both components of this injury gives better stability and prevents development of complications like compartment syndrome and elbow deformities.     

Deep veins of the calf: assessment with color Doppler flow imaging

The authors studied the ability of real-time ultrasound aided by color Doppler flow imaging to demonstrate the deep veins of the calf in ten healthy subjects and 49 patients (91 limbs) with suspected deep venous thrombosis. Posterior tibial and peroneal veins demonstrated flow accentuation in 98% (74 of 75) and 96% (72 of 75), respectively, of the limbs without thrombosis and in all 20 normal limbs. Sixteen legs were involved with deep venous thrombosis. Peroneal veins could not be seen in three legs with marked calf swelling due to proximal thrombosis. There were two cases of thrombosis limited to the calf, nine of popliteal thrombosis (seven with contiguous spread of thrombus), and five of thrombosis limited to above the knee (four with sparing of the deep veins of the calf). Visualization of anterior tibial veins, achieved in 65% of all legs, did not correlate with thrombosis. The authors conclude that color Doppler flow imaging can demonstrate patency of posterior tibial and peroneal veins in most patients without deep venous thrombosis and aid in detection of below-the-knee thrombosis.     

反转录病毒载体介导RNA干扰抑制EphA2在Hela细胞中的蛋白表达

目的：课题前期发现EphA2和配体EphrinAl在宫颈鳞癌细胞和肿瘤相关血管内皮细胞均呈高表达，为基因治疗宫颈癌提供了理想的靶向。以此为基础，利用反转录病毒载体介导的RNA干扰抑制EphA2在Hela宫颈癌细胞中的蛋白表达。方法：实验于2006—01／06在河南省肿瘤病理重点实验室完成。①实验材料：PA317细胞、Hela229细胞购自上海生化细胞所，小鼠NIH3T3细胞为本室保存。EphA2兔抗人多克隆抗体，Actin兔抗人多克隆抗体（美国SantaCruz公司）。②实验方法：从EphA2的mRNA全序列中筛选出1个19nt的靶序列，设计双链发夹结构。以siRNA互补双链寡核苷酸，构建反转录病毒表达载体pSIREN—EphA2，提取质粒，用BglⅡ和EcoRⅠ双酶切进行鉴定。选择经酶切鉴定的正确克隆测序。挑选pSIREN．EphA2抗性克隆细胞扩增，检测转染后Hela细胞中EphA2蛋白的表达水平。结果：@pSIREN-EphA2重组质粒的酶切鉴定：双酶切后形成328bp和6182bp两条电泳条带。②pSIREN-EphA2重组质粒测序：结果与已知序列完全一致。（DEphA2蛋白的表达：经Westernblot分析，重组pSIREN—EphA2转染的Hela细胞中EphA2蛋白表达水平明显降低。结论：通过反转录病毒载体介导的RNA干扰，能够抑制EphA2在Hela细胞中的蛋白表达，为以EphA2为靶点的宫颈癌基因治疗提供新的思路和手段。     

Suppression of mouse skin tumor promotion and induction of apoptosis in HL-60 cells by Alpinia oxyphylla Miquel (Zingiberaceae)

There have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Many components from dietary or medicinal plants have been identified that possess substantial chemopreventive properties. An example is curcumin (Curcuma longa Linn., Zingiberaceae), which has been shown to inhibit tumor promotion in experimental carcinogenesis. Alpinia oxyphylla Miquel, another plant of the ginger family used in oriental herbal medicine, contains diarylheptanoids whose structures are analogous to that of curcumin. In the present study, we have tested A.oxyphylla for its ability to suppress tumor promotion. Thus, topical application of the methanolic extract of dried fruits of A.oxyphylla significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor promotion as well as ear edema in female ICR mice. In another study, treatment of HL-60 cells with the methanolic extract of A.oxyphylla significantly reduced the viability of the cells and also inhibited DNA synthesis. Microscopic examination of the treated cells showed characteristic morphology of apoptosis. Furthermore, cells treated with the extract of A.oxyphylla exhibited internucleosomal DNA fragmentation in time- and concentration-dependent manners. TPA- stimulated generation of superoxide anion in differentiated HL-60 cells was also blunted by A.oxyphylla. Taken together, these findings suggest that A.oxyphylla possesses potential chemopreventive and antitumorigenic activities.