Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Maximizing intelligence obtained from higher-order DNA mixtures from volume crime samples

ABSTRACT

This work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated.     

Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

TLR9在不同胎龄新生儿脐血中的表达变化

目的 通过观察早产儿不同胎龄Toll样受体9（TLR9）的表达，探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份，按胎龄分为4组，28~31周组，31~34周组，34~37周组，≥37周组，采用流式细胞术和实时荧光定量PCR方法，分别检测其TLR9的蛋白和mRNA表达情况，了解其与胎龄之间的关系，并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组，31~34周组，34~37周组，≥37周组分别为（15.93±6.23）%，（11.63±6.70）%，（13.66±6.88）%，（20.51±12.06）%；其在胎龄28~31周较高，至31~34周逐渐下降至最低，两组差异有统计学意义（P<0.05）；34~37周后TLR9阳性细胞率表达逐渐升高，至≥37周达最高，两胎龄组比较，差异具有统计学意义（P<0.05）。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关（r=0.273，P=0.006）。TLR9 mRNA表达在28~31周组，31~34周组，34~37周组，≥37周组分别为（4.95±3.44）%，（8.89±8.49）%，（13.91±10.92）%，（7.19±7.11）%；其在28~36周逐渐升高，与胎龄呈正相关（r=0.355，P< 0.001）。≥37周TLR9 mRNA表达量下降，该值虽高于28~31周，但差异无统计学意义（P>0.05）。相关性分析表明，同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关（r=-0.227，P=0.011）。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异，TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加，TLR9 mRNA在28~36周间随着胎龄的增加而增加。     

The primary health care physician and the cancer patient: tips and strategies for managing sexual health

There is a large and growing population of long-term cancer survivors. Primary care physicians (PCPs) are playing an increasingly greater role in the care of these patients across the continuum of cancer survivorship. In this role, PCPs are faced with the responsibility of managing a range of medical and psychosocial late effects of cancer treatment. In particular, the sexual side effects of treatment which are common and have significant impact on quality of life for the cancer survivor, often go unaddressed. This is an area of clinical care and research that has received increasing attention, highlighted by the presentation of this special issue on Cancer and Sexual Health. The aims of this review are 3-fold. First, we seek to overview common presentations of sexual dysfunction related to major cancer diagnoses in order to give the PCP a sense of the medical issues that the survivor may present with. Barriers to communication about sexual health issues between patient/PCPs in order are also described in order to emphasize the importance of PCPs initiating this important conversation. Next, we provide strategies and resources to help guide the PCP in the management of sexual dysfunction in cancer survivors. Finally, we discuss case examples of survivorship sexual health issues and highlight the role that a PCP can play in each of these case examples.     

Changes in Quality of Health Care Delivery after Vertical Integration

ObjectivesTo fill an empirical gap in the literature by examining changes in quality of care measures occurring when multispecialty clinic systems were acquired by hospital-owned, vertically integrated health care delivery systems in the Twin Cities area.ConclusionsMoving a clinic system into a vertically integrated delivery system resulted in limited increases in quality of care indicators. Caution is warranted when the acquisition causes disruption in referral patterns.     

中国精神分裂症患者不同家庭干预措施效果比较的meta分析

目的对中国精神分裂症患者采取家庭干预的研究文献进行综合回顾和系统评价, 比较不同条件下家庭干预效果的差异。方法在中国知网、维普、万方、中国生物医学文献数据库四大中文数据库及OVID Medline、Science Direct、Web of Science、EBSCO四大英文数据库中, 检索各数据库建库至2015年1月为止使用社会功能缺陷筛选量表(SDSS)、简明精神病(科)量表(BPRS)、阳性与阴性症状量表(PANSS)研究中国精神分裂症患者家庭干预效果的文献, 以标准化加权均数差( SMD)作为效应量, 采用meta分析比较不同干预时间、不同干预类型、对不同病程和不同严重程度的精神分裂症患者的家庭干预效果差异。 结果共纳入57篇符合标准的文献。SDSS、PANSS分析结果显示:① 干预时间越长干预效果越好( P < 0.0001、 P=0.0025);② 单独家庭干预比多个家庭合并单独家庭干预的效果更明显( P < 0.0001、 P=0.0131);③ 干预对于病情较重患者效果较好( P < 0.0001、 P=0.0280)。SDSS量表还显示家庭干预对于病程短的患者效果更好( P < 0.0001)。 结论家庭干预更适合病程较短的精神分裂症患者, 干预应实施较长时间; 单独家庭干预更有利于患者阴性症状的改善和社会功能的康复, 且对于病情较轻患者的阴性症状改善效果更好。     

Innovation in Indigenous Health and Medical Education: The Leaders in Indigenous Medical Education (LIME) Network as a Community of Practice

Problem: The Leaders in Indigenous Medical Education (LIME) Network aims to improve the quality and effectiveness of Indigenous health in medical education as well as best practice in the recruitment, retention, and graduation of Indigenous medical students. Intervention: In this article we explore the utility of Etienne Wenger's “communities of practice” (CoP) concept in providing a theoretical framework to better understand the LIME Network as a form of social infrastructure to further knowledge and innovation in this important area of health care education reform. Context: The Network operates across all medical schools in Australia and New Zealand. Outcome: Utilizing a model of evaluation of communities of practice developed by Fung-Kee-Fung et al., we seek to analyze the outcomes of the LIME Network as a CoP and assess its approach and contribution to improving the implementation of Indigenous health in the medical curriculum and the graduation of Indigenous medical students. Lessons Learned: By reflecting on the Network through a community of practice lens, this article highlights the synthesis between the LIME Network and Wenger's theory and provides a framework with which to measure Network outputs. It also posits an opportunity to better capture the impact of Network activities into the future to ensure that it remains a relevant and sustainable entity.     

Anatomically contoured large femoral heads can reduce iliopsoas impingement: A cadaver verification study

While use of large heads in total hip arthroplasty (THA) continues to grow, concerns have been raised regarding anterior hip pain resulting from impingement of the prosthetic head against soft-tissues like the iliopsoas. To address these concerns, a new anatomically contoured head (ACH) was developed. In this study cadaver tests were utilized to show that iliopsoas impingement/tenting caused by conventional heads is significantly relieved with the more rounded and reduced distal profile of the ACH. Thus, the ACH implant may be able to decrease the risk of soft-tissue impingement with conventional heads, particularly in the smaller hip.