Robo family of proteins exhibit differential expression in mouse spinal cord and Robo-Slit interaction is required for midline crossing in vertebrate spinal cord.

The ventral midline of the central nervous system is an important intermediate target where growing commissural axons either cross and project contralaterally or remain on the same side of the body. New studies on mice and humans show that this decision by commissural axons is largely dependent on Slits, extracellular matrix proteins that are widely expressed in the midline of the nervous system, and their receptors, Robos (Long et al. [2004] Neuron 42:213-223; Sabatier et al. [2004] Cell 117:157-169; Jen et al. [2004] Science 304:1509-1513). Here, we show that the Robo family proteins Robo1 and Rig-1 exhibit differential expression patterns on commissural axons as they approach, cross, and leave the midline of the developing mouse spinal cord and demonstrate that Robo1 and Robo2 bind Slit1 and Slit2, but Rig-1 does not. In addition, we show that cultured chick commissural axons are repelled by a source of Slit protein, and the soluble Robo-Fc proteins are capable of neutralizing this repulsion. Finally, we exploit the large size and accessibility of the early chick embryo to analyze the function of Slit/Robo signaling in midline commissural axon guidance, and we demonstrate that the in vivo perturbation of Robo-Slit interaction at the floor plate causes consistent guidance defects of commissural axons during midline crossing. These findings demonstrate the evolutionarily conserved role for Robo-Slit interaction in the control of midline crossing axons in vertebrates.     

Outpatient management of severe gonococcal ophthalmia without genital infection

We report a case of severe gonococcal ophthalmia and peri-orbital cellulitis in an HIV-positive man without genital infection who was treated successfully in the outpatient department. We also highlight the importance of early diagnosis, treatment and liaison with ophthalmology in order to prevent visual complications.     

Gender norms and economic empowerment intervention to reduce intimate partner violence against women in rural Côte d’Ivoire: a randomized controlled pilot study

Background

Gender-based violence against women, including intimate partner violence (IPV), is a pervasive health and human rights concern. However, relatively little intervention research has been conducted on how to reduce IPV in settings impacted by conflict. The current study reports on the evaluation of the incremental impact of adding “gender dialogue groups” to an economic empowerment group savings program on levels of IPV. This study took place in north and northwestern rural Côte d’Ivoire.

Methods

Between 2010 and 2012, we conducted a two-armed, non-blinded randomized-controlled trial (RCT) comparing group savings only (control) to “gender dialogue groups” added to group savings (treatment). The gender dialogue group consisted of eight sessions that targeted women and their male partner. Eligible Ivorian women (18+ years, no prior experience with group savings) were invited to participate. 934 out of 981 (95.2%) partnered women completed baseline and endline data collection. The primary trial outcome measure was an overall measure of past-year physical and/or sexual IPV. Past year physical IPV, sexual IPV, and economic abuse were also separately assessed, as were attitudes towards justification of wife beating and a woman’s ability to refuse sex with her husband.

Results

Intent to treat analyses revealed that compared to groups savings alone, the addition of gender dialogue groups resulted in a slightly lower odds of reporting past year physical and/or sexual IPV (OR: 0.92; 95% CI: 0.58, 1.47; not statistically significant). Reductions in reporting of physical IPV and sexual IPV were also observed (not statistically significant). Women in the treatment group were significantly less likely to report economic abuse than control group counterparts (OR?=?0.39; 95% CI: 0.25, 0.60, p?<?.0001). Acceptance of wife beating was significantly reduced among the treatment group (β?=?-0.97; 95% CI: -1.67, -0.28, p?=?0.006), while attitudes towards refusal of sex did not significantly change Per protocol analysis suggests that compared to control women, treatment women attending more than 75% of intervention sessions with their male partner were less likely to report physical IPV (a OR: 0.45; 95% CI: 0.21, 0.94; p?=?.04) and report fewer justifications for wife beating (adjusted β?=?-1.14; 95% CI: -2.01, -0.28, p?=?0.01) ; and both low and high adherent women reported significantly decreased economic abuse (a OR: 0.31; 95% CI: 0.18, 0.52, p?<?0.0001; a OR: 0.47; 95% CI: 0.27, 0.81, p?=?01, respectively). No significant reductions were observed for physical and/or sexual IPV, or sexual IPV alone.

Conclusions

Results from this pilot RCT suggest the importance of addressing household gender inequities alongside economic programming, because this type of combined intervention has potential to reduce levels of IPV. Additional large-scale intervention research is needed to replicate these findings.

Trial registration

Registration Number: NCT01629472.

     

Effects and mechanisms of PCB ecotoxicity in food chains: Algae  fish  seal  polar bear 1

Wildlife populations are adversely affected in polluted environments. Nevertheless, a cause‐and‐effect relationship between excessive exposure to chlorinated hydrocarbons and induction of pathologic disorders in animals, is difficult to demonstrate without verification from experiments following the rationale of Koch's postulates. Deleterious effects of chlorinated chemicals such as DDT on songbird reproduction, as demonstrated by the clutch size of eggs in a nest, however, is an example, where exposure and causation are apparent. With amelioration of DDT pollution, clutch size increases, and the cause‐and‐effect relationship is established. Similar examples of exposure to DDT and PCBs inducing reproductive disorders and endocrine disruption among marine mammals have been documented in industrialized nations of northern Europe and in the upper latitudes of the Northern Hemisphere. Population declines in ringed, grey and harbor seals are apparently due to a rapid decrease in their rates of reproduction¹. These latter observations are best interpreted in light of experiments conducted by Reijnders². Reijnders exposed harbor seals to relatively high dietary levels of PCBs and induced PCB‐blood‐lipids among seals to an average of 25 mg/kg compared to 10 mg/kg among controls. The treated seals had a significantly reduced reproductive rate. A relationship between increased PCB‐blood‐levels in vivo and the decrease in reproductive rates in this experiment is highly instructive for interpreting the decline of fertility in seal populations in polluted Baltic Sea waters. These linked observations are dependent upon demonstration of pathologic mechanisms associated with occlusion and stenosis of the uterine lumen among affected females in seal populations.

PCB congeners apparently disrupt endocrine‐system‐functions leading to, or associated with, increases in endometriosis, fetal abortion, glomerulonephropathies and osteoporosis. This observation is further highlighted by Reijnders experiment, which closely replicated the range of PCB concentrations found in seal populations living in a variety of PCB polluted waters.

Various PCB congeners differentially accumulate in brain, liver and adipose tissues in young and old seals. Further research of PCB toxic effects on organ systems of these animals and other species is thus indicated.

This report, then, examines the process of PCB bioaccumulation within the marine food chain from fish to seals, whales, other marine mammals and to polar bears. Environmental toxic pollutants affect animals within the food chain in different ways but ultimately they affect humans as well.     

循证医学理念与方法在全科医学教学中的应用及意义

在全科教学中引入循证医学,可以有效提高全科医生临床决策能力,促进全科医学服务模式转变,丰富全科医学内涵。将循证医学理念应用到全科医学教育的途径包括强化全科循证医学师资力量、创新全科循证医学教学方式、将循证医学技能评价与考核引入全科医生考核体系。全科医学教学中引入循证医学教育尚面临诸多问题,需持续改进全科医生循证医学教学手段,科学开展全科医生循证医学教学评估。     

免疫检查点抑制剂联合抗血管生成药物治疗晚期非鳞状细胞非小细胞肺癌的研究进展

评价重组人血管内皮抑制素联合阿法替尼及替吉奥二线治疗晚期肺鳞癌患者的有效性和安全性。

共25例驱动基因阴性晚期肺鳞癌患者被纳入这项单臂前瞻性研究,按期二线给予入组患者重组人血管内皮抑制素联合阿法替尼及替吉奥治疗,观察分析患者无进展生存期(progression-free-survival,PFS)、总生存期(overall survival,OS)、疾病控制率(disease control rate,DCR)、客观缓解率(objective response rate,ORR)和不良反应(adverse reaction,AR)。

25例入组患者接受了≥2个周期的二线治疗方案,随访时间截至2023年3月31日,其中4例患者病情部分缓解,17例患者病情稳定,4例患者病情进展。经研究者确认的ORR为16%(95%CI,4.5%~36.1%),DCR为84%(95%CI,63.9%~95.5%),中位PFS为5.3个月(95%CI,3.5~6.9个月),中位OS尚未达到。全组患者治疗耐受良好,治疗相关的Ⅲ级或Ⅳ级AR最常见的是白细胞下降(20%)和皮疹(12%),没有与治疗相关的死亡报告。

重组人血管内皮抑制素联合阿法替尼及替吉奥二线治疗晚期肺鳞癌可延长患者PFS且相对安全,值得进一步探究及推广。

     

复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎的临床研究

目的　观察复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎患者的临床疗效和安全性。方法　采用开放、多中心临床研究设计。患者每次口服 1粒复方盐酸伪麻黄碱缓释胶囊、每日 2次、间隔 12h ,连服 7d ,然后观察患者症状和体征的改善情况。结果　本研究最终有 370例患者可供疗效分析 ,371例患者可供安全性分析。与服药前相比 ,患者服药第 1～ 7天各临床症状 (包括鼻塞、流涕、鼻痒、打喷嚏、流泪、眼痒、耳 /腭痒 )及体征 (包括鼻甲、鼻黏膜情况和眼部充血 )评分的改善均有统计学意义 (P <0 0 0 1)。复方盐酸伪麻黄碱缓释胶囊治疗季节性变应性鼻炎症状和体征的显效率分别为 70 %和 6 8% ,总有效率分别为 89%和 80 %。在用药过程中共有 5 4例患者报告了 6 1例次不良反应 ,主要为轻、中度困倦和口干。未出现严重不良反应。结论　复方盐酸伪麻黄碱缓释胶囊可持续有效控制季节性变应性鼻炎患者的症状和体征 ,疗效较高 ,耐受性较好