The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

退行性腰椎侧凸与骨质疏松症的关系探讨

目的探讨退行性腰椎侧凸（degenerativelumbarscoliosis,DIS）与骨质疏松症（osteoporosis,OP）两者之间的关系。方法选取2006年6月-2010年6月来我院就诊的DIS患者58例及对照组（非腰椎侧凸的腰痛患者）58例,对DIS组Cobb’s角进行测量,并采用双能x线吸收法检测两组患者腰椎（k～L4）、股骨颈、股骨粗隆和Ward’s三角区骨密度T值,分析患者年龄、Cobb’s角与骨密度T值的相关性。结果DIS组平均骨密度T值为-2．7±1．8,合并OP45例,发病率为77．59％;对照组平均骨密度T值为-1．3±1．0,合并OP8例,发病率为13．79％,两组比较有显著性差异（P〈0．05）。相关分析显示,DIS患者T值与年龄呈正相关（r=-0．318,P〈0．01）,与侧凸Cobb’s角无关。结论OP是DLS发病的危险因素,同时年龄越大OP程度越重,但与DLS进展程度无关。临床DLS治疗时要考虑到OP的影响。     

Antigen presentation in SARS-CoV-2 infection: the role of class I HLA and ERAP polymorphisms

Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent responsible for the recent COVID-19 pandemic. Several correlations have already been established between the expression of a specific HLA allele/haplotype and susceptibility/progression of SARS-CoV-2 infection and new ones are continuously emerging. Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the huge amount of existing variants, the data gathered in such a brief span of time are to some extent confusing and contradictory. The aim of this mini-review is to provide a snap-shot of the main findings so far collected on the HLA-SARS-CoV-2 interaction, so as to partially untangle this intricate yarn. As key factors in the generation of antigenic peptides to be presented by HLA molecules, ERAP1 and ERAP2 role in SARS-CoV-2 infection will be revised as well.     

CDDO-Im is a stimulator of megakaryocytic differentiation

Although the triterpene CDDO and its potent derivatives, CDDO-Im and CDDO-Me, are now in phase I/II studies in the treatment of some pathological conditions, their effects on normal hematopoiesis are not known. In the present study we provide evidence that CDDO-Im exerts in vitro a potent inhibitory effect on erythroid cell proliferation and survival and a stimulatory action on megakaryocytic differentiation.The effect of CDDO-Im on erythroid and megakaryocytic differentiation was evaluated both on normal hemopoietic progenitor cells (HPCs) induced to selective erythroid (E) or megakaryocytic (Mk) differentiation and on erythroleukemic cell lines HEL and TF1.The inhibitory effect of CDDO-Im on erythroid cell survival and proliferation is mainly related to a reduced GATA-1 expression. This conclusion is supported by the observation that GATA-1 overexpressing TF1 cells are partially protected from the inhibitory effect of CDDO-Im on cell proliferation and survival. The stimulatory effect of CDDO-Im on normal megakaryopoiesis is seemingly related to upmodulation of GATA2 expression and induction of mitogen-activated protein kinases ERK1/2.     

Effectiveness of a Lifestyle Intervention Program Among Persons at High Risk for Cardiovascular Disease and Diabetes in a Rural Community

Purpose: To evaluate the feasibility of translating the Diabetes Prevention Program (DPP) lifestyle intervention into practice in a rural community. Methods: In 2008, the Montana Diabetes Control Program worked collaboratively with Holy Rosary Healthcare to implement an adapted group-based DPP lifestyle intervention. Adults at high risk for diabetes and cardiovascular disease were recruited and enrolled (N = 101). Participants set targets to reduce fat intake and increase physical activity (≥150 mins/week) in order to achieve a 7% weight loss goal. Findings: Eighty-three percent (n = 84) of participants completed the 16-session core program and 65 (64%) participated in 1 or more after-core sessions. Of those completing the core program, the mean participation was 14.4 ± 1.6 and 3.9 ± 1.6 sessions during the core and after core, respectively. Sixty-five percent of participants met the 150-min-per-week physical activity goal during the core program. Sixty-two percent achieved the 7% weight loss goal and 78% achieved at least a 5% weight loss during the core program. The average weight loss per participant was 7.5 kg (range, 0 to 19.7 kg), which was 7.5% of initial body weight. At the last recorded weight in the after core, 52% of participants had met the 7% weight loss goal and 66% had achieved at least a 5% weight loss. Conclusion: Our findings suggest that it is feasible to implement a group-based DPP in a rural community and achieve weight loss and physical goals that are comparable to those achieved in the DPP.     

A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells

OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.     

研究诊断准确性的论著的质量:STARD公布后无改变——STARD公布前后的比较研究

目的确定对诊断准确性进行研究的论著的规范(STARD)公布前、后该类论著的质量改善情况,并比较执行STARD和未执行STARD的杂志的该类论著质量有无差     

非亲缘异基因外周血干细胞移植重建白血病幼儿造血功能：1例报告

目的:分析非亲缘异基因外周血干细胞移植治疗幼儿急性非淋巴性白血病的可行性。方法:患儿,男,3岁,于2005-07-18为行造血干细胞移植入本院血液科骨髓移植病房,入院诊断为急性非淋巴细胞性白血病-M5b。经抗肿瘤药物治疗病情获得完全缓解。患儿首先接受清髓性预处理,然后接受同性别非亲缘异基因外周血造血干细胞移植。①移植预处理包括马利兰、阿糖胞苷和环磷酰胺。移植前依次用药为马利兰3.2mg/(kg·d)×4d,口服,于移植前6,7,8,9d给药;阿糖胞苷3.2g/(m2·d)×2d,于移植前4,5d给药;环磷酰胺54mg/(kg·d),于移植前2,3d给药。②急性移植物抗宿主病的预防用药包括环孢菌素A和氨甲蝶呤、抗胸腺细胞球蛋白及吗替麦考酚酯。供者接受粒细胞集落刺激因子动员4d后采集外周血造血干细胞,供、受者间HLA全相合,患者血型A,供者血型B,主次要均不合。结果:①患儿移植后早期获得造血重建,中性粒细胞>0.5×109L-1和血小板>50×109L-1的天数分别是12d和11d。②移植后1个月经DNA短串联重复序列多态性分析证明为供者型完全植入,移植后3个月查骨髓象正常。③移植后3,6个月定期行淋巴细胞亚群检查表明除CD19 ,CD4 细胞未恢复外,自然杀伤细胞在移植后3个月恢复正常,T淋巴细胞CD3 与CD8 、体液免疫球蛋白在移植后6个月中均获得重建。④整个移植过程顺利,未出现明显感染和重度急性移植物抗宿主病。移植后96d时出现Ⅰ度皮肤移植物抗宿主病,经加用激素治疗,皮疹消失。移植术后已随访观察12个月,患儿正常生活。结论:如果患儿有HLA完全相合的供者,非亲缘异基因外周血干细胞移植治疗儿童高危白血病是一种有效和安全的方法,对国内独生子女家庭拓宽供者来源有重要的实用价值。