HIV-1 integrates into resting CD4+ T cells even at low inoculums as demonstrated with an improved assay for HIV-1 integration

Human Immunodeficiency Virus Type 1 (HIV-1) establishes a latent reservoir early in infection that is resistant to the host immune response and treatment with highly active antiretroviral therapy (HAART). The best understood of these reservoirs forms in resting CD4(+) T cells. While it remains unclear how reservoirs form, a popular model holds that the virus can only integrate in activated CD4(+) T cells. Contrary to this model, our previous results suggest that HIV-1 can integrate directly into the genomes of resting CD4(+) T cells. However, a limitation of our previous studies was that they were conducted at high viral inoculum and these conditions may lead to cellular activation or saturation of restriction factors. In the present study, we tested if our previous findings were an artifact of high inoculum. To do this, we enhanced the sensitivity of our integration assay by incorporating a repetitive sampling technique that allowed us to capture rare integration events that occur near an Alu repeat. The new technique represents a significant advance as it enabled us to measure integration accurately down to 1 provirus/well in 15,000 genomes--a 40-fold enhancement over our prior assay. Using this assay, we demonstrate that HIV can integrate into resting CD4(+) T cells in vitro even at low viral inoculum. These findings suggest there is no threshold number of virions required for HIV to integrate into resting CD4(+) T cells.     

Numerical modeling and simulations of type B aortic dissection treated by stent-grafts with different oversizing ratios

Retrograde type A dissection after thoracic endovascular aortic repair has been a major drawback of endovascular treatment. This study investigated the biomechanical mechanism of stent-graft-induced new lesions after implantation and analyzed the relationship between radial force and spring-back force of the stent-graft when it was implanted virtually under different oversizing ratios. Based on the computed tomography angiography images, a three-dimensional geometric model of a patient-specific aortic dissection was established. The stent was designed in CAD software and the stent-graft implantation procedure under different oversizing ratios was simulated in the finite element analysis software. Implantation simulations were performed six times for each stent-graft model under 0%, 3%, 6%, 9%, 12%, and 15% oversizing ratios and the peak stress of the aorta was compared among groups. It was observed that the peak stress of the aorta was located where the proximal bare stent interacted with aortic wall and its value was increased by 62.2% from 0% to 15% oversizing ratio. The conclusions are reached that the long-term higher stress in the aortic wall may lead to the emergence of new lesions in these areas, and the radial force plays a key role in the formation of a new entry in the real aorta model.     

Important factors improving outcome of young adults with acute lymphoblastic leukemia (ALL)

Four categories of important factors improving outcome of young adults and older adolescents with acute lymphoblastic leukemia (ALL) are biologic type, clinical trials, pediatric vs. adult treatment regimen, and psychosocial challenges. Overall, the outcome of ALL in the age group has improved and beginning to catch up with that in children, as exemplified by CALGB 10403, a pediatric treatment regimen. Each is dependent for optimum development, however, on progress in the others. Without adequate psychosocial support and improvement, progress in clinical trials, translational research, and pediatric regimen application is impaired. Without clinical trials, advances in translational research, optimal pediatric regimen application and adequate psychosocial research are restricted. Overall, we have improved the outcome and outlook of ALL in AYAs, as exemplified by CALGB 10403, but we and our current and future patients still have a long way to go.     

宽QRS波心动过速的诊治进展

宽QRS波是临床常见的心律失常,常分为室性心动过速和室上性心动过速,由于两者治疗原则及方法不相同,所以鉴别宽QRS波心动过速非常重要,现介绍Brugada法、Vereckei法、aVR法、Ⅱ导联R波峰值标准法以及各种方法的特异性及敏感性。对于不同类型的宽QRS波心动过速有着不同的治疗方法,如药物、电复律及射频消融术。     

前导式双垫对生长发育高峰期后骨性Ⅱ类下颌后缩的疗效

目的 探讨前导式双垫对生长发育高峰期后骨性Ⅱ类下颌后缩患者的治疗效果。方法 回顾性选择2018年9月至2021年7月在上海市闵行区牙病防治所采用前导式双垫完成Ⅰ期矫治的生长发育高峰期后骨性Ⅱ类下颌后缩患者23例。在Ⅰ期矫治前后拍摄X线头颅侧位片,测量治疗前后颌面部软、硬组织及上气道指标。结果 Ⅰ期治疗后,硬组织测量指标中下颌平面角（MP-FH）、Y轴角（SGn-FH）、面角（NP-FH）、SNB、下中切牙-下颌平面角（L1-MP）、下面高（ANS-Me）增大（P<0.05）,ANB、上下中切牙角（U1-L1）、S-Co减小（P<0.01）;软组织测量指标中下唇突度（LLP）、下唇长（LLL）、颏部长度（LL-Pos）增大（P<0.01）,面型角（FCA）、上唇突度（ULP）、颏唇沟深度（Si-LLPos）减小（P<0.05）;上气道测量指标中SPP-SPPW、U-MPW、TB-TPPW增大（P<0.01）。结论 对于生长发育高峰期后骨性Ⅱ类下颌后缩患者,前导式双垫可通过前导下颌骨协调上下颌骨矢状向和垂直向关系,并有效扩张腭咽与舌咽矢状向宽度。     

Encoding of nested levels of acoustic regularity in hierarchically organized areas of the human auditory cortex

Our auditory system is able to encode acoustic regularity of growing levels of complexity to model and predict incoming events. Recent evidence suggests that early indices of deviance detection in the time range of the middle‐latency responses (MLR) precede the mismatch negativity (MMN), a well‐established error response associated with deviance detection. While studies suggest that only the MMN, but not early deviance‐related MLR, underlie complex regularity levels, it is not clear whether these two mechanisms interplay during scene analysis by encoding nested levels of acoustic regularity, and whether neuronal sources underlying local and global deviations are hierarchically organized. We registered magnetoencephalographic evoked fields to rapidly presented four‐tone local sequences containing a frequency change. Temporally integrated local events, in turn, defined global regularities, which were infrequently violated by a tone repetition. A global magnetic mismatch negativity (MMNm) was obtained at 140–220 ms when breaking the global regularity, but no deviance‐related effects were shown in early latencies. Conversely, Nbm (45–55 ms) and Pbm (60–75 ms) deflections of the MLR, and an earlier MMNm response at 120–160 ms, responded to local violations. Distinct neuronal generators in the auditory cortex underlay the processing of local and global regularity violations, suggesting that nested levels of complexity of auditory object representations are represented in separated cortical areas. Our results suggest that the different processing stages and anatomical areas involved in the encoding of auditory representations, and the subsequent detection of its violations, are hierarchically organized in the human auditory cortex. Hum Brain Mapp 35:5701–5716, 2014. © 2014 Wiley Periodicals, Inc.