Emerging Treatment Targets for Migraine and Other Headaches

Migraine is a complex disorder that is characterized by an assortment of neurological and systemic effects. While headache is the most prominent feature of migraine, a host of symptoms affecting many physiological functions are also observed before, during, and after an attack. Furthermore, migraineurs are heterogeneous and have a wide range of responses to migraine therapies. The recent approval of calcitonin gene-related-peptide based therapies has opened up the treatment of migraine and generated a renewed interest in migraine research and discovery. Ongoing advances in migraine research have identified a number of other promising therapeutic targets for this disorder. In this review, we highlight emergent treatments within the following biological systems: pituitary adenylate cyclase activating peptdie, 2 non-mu opioid receptors that have low abuse liability – the delta and kappa opioid receptors, orexin, and nitric oxide-based therapies. Multiple mechanisms have been identified in the induction and maintenance of migraine symptoms; and this divergent set of targets have highly distinct biological effects. Increasing the mechanistic diversity of the migraine tool box will lead to more treatment options and better patient care.     

放射核素血池显象诊断肝血管瘤

目的观察放射核素血池显象肝血管瘤的图象特点和诊断价值．方法肝占位性病变患者７５例，其中肝海绵状血管瘤６２例．采用９９ｍＴｃＯ４体内标记自体红细胞、肝动脉灌注动态显象和肝血池静态放射性核素显象的方法，计算机感兴趣区技术描记血流灌注曲线，静态显象显示肝占位性病变处的血流分布．结果肝海绵状血管瘤的核素血池显象表现为：①肝胶体显象局部放射性稀疏缺损，②血池显象放射性过度填充．６２例临床诊断肝血管瘤者，５３例有上述典型表现，１３例原发性肝癌和肝转移癌无一例过度填充．血池显象检出肝血管瘤的灵敏度为８５％，特异性１００％．核素显象对于肝血管瘤的检出率与病变的大小和位置有关．结论放射性核素肝血池显象对于肝血管瘤具有良好的诊断价值     

Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age

More frequent skewing of X-chromosome inactivation patterns (XCIPs) occurs in the white blood cells of elderly females; this study was performed to determine whether this occurs in myeloid or lymphoid lineages. XCIPs were analysed in purified neutrophils and T cells from 80 females  > 75 years and the results were compared with 23 cord blood and 94 younger adult blood samples. The degree of XCIP skewing in cord blood and younger adult blood cells was similar, with 3–4% having  > 90% expression of one allele. Skewing was markedly increased in the neutrophils of elderly females, with 33% having  > 90% expression of one allele ( P < 0.0001). Extreme skewing was present in only 9% of the elderly T-cell samples and no evidence of T-cell clonality was found by PCR analysis of the TCRγ gene. The high level of acquired skewing of the XCIPs in myeloid cells of the elderly suggests that with time there is a change in stem cell usage with stochastic loss of some of the original stem cells. This has major implications for the use of XCIP analysis in the diagnosis of myeloid malignancies in the elderly and for gene therapy into haemopoietic stem cells.     

Risks of new-onset allergic sensitization and airway inflammation after early age swimming in chlorinated pools

Rationale

Irritant chlorination products in swimming pools can cause respiratory problems in swimmers but their possible implication in allergies development is still unclear.

Objectives

To assess prospectively whether early-life attendance at chlorinated pools increases the risks of IgE sensitization and of airways inflammation later during childhood.

Methods

We conducted a two-year prospective study among 196 kindergarten children (mean age of 5.7 years, 54% of boys). We measured exhaled nitric oxide (eNO) and aeroallergen-specific IgE in nasal mucosa. Parents completed a questionnaire about the child's health, chlorinated pool attendance and potential confounders.

Main Results

Ever swimming at indoor or outdoor chlorinated pools before the age of three years was associated with higher odds for new-onset IgE sensitization to house dust mite (adjusted odds ratio [aOR] 2.93, 95% confidence interval [CI] 1.14–7.55) and for new-onset increased eNO (>15 ppb; aOR, 4.54, 95% CI 1.48–13.9). For both outcomes, aORs increased dose-dependently with time spent in chlorinated pools with values reaching, respectively, 3.60 (95% CI 1.21–10.7) and 5.92 (95% CI 1.72–20.5) when the cumulative pool attendance exceeded 60 h These risks appeared independently of each other, of parental history of allergies and of pre-existing diseases, including eczema, which at baseline was more prevalent in early swimmers (aOR, 2.91; 95% CI 1.23–6.89). Such associations were not seen with IgE sensitization to pollen or cat allergens.

Conclusion

Attendance at chlorinated swimming pools in early life is associated with higher risks of new-onset airways inflammation and IgE sensitization to house dust mite, independently of other risk factors.     

2010-2012年大连市游泳池水水质卫生状况监测结果分析

目的了解大连市泳池水的水质卫生状况及变化趋势,为进一步提高泳池水的卫生质量,预防感染性疾病暴发。方法按照GB／T18204—2000《公共场所卫生标准检验方法》对大连市泳池水中的尿素、细菌总数、大肠菌群进行检验;按照GB／T5750-2006（（生活饮用水标准检验方法》进行游离性余氯的检验。结果近3a合计检测403份水样,合格的287份,合格率为71．22％;各年的合格率分别为63．95％、69．94％、84．95％,不同年份间合格率的差异有统计学意义（X^2=12．473,P〈0．01）。近3a总项目的样品份数为1612份,合格份数1464份,合格率为90．80％;不同项目游离性余氯尿素、细菌总数、大肠菌群合格率的差异有统计学意义（X^2=170．44,P〈0．01）。结论大连市游泳池水水质卫生状况逐年趋好,但还是不容忽视,今后应加强卫生监督监测管理工作,加强对管理者的卫生管理意识,进一步提高泳池水的卫生质量,保障游泳者的身体健康。     

2007-2012年四川双流县游泳池水水质检测结果分析

目的了解双流县游泳池水质的卫生状况,为游泳场所的卫生监督管理提供可靠的参考数据。方法 2007-2012年在双流县对公众开放游泳场所的游泳池水采样,按GB/T 5750-2006《生活饮用水卫生标准》、GB/T18204-2000《公共场所卫生标准检验方法》进行检验,依据GB 9667-1996《游泳场所卫生标准》进行评价。结果 2007-2012年共检验游泳池水580份,合格为347份,总合格率为58.10%。pH合格率最高（99.31%）,游离余氯合格率最低（77.93%）。专营游泳池水质合格率最高（75.38%）,居民小区游泳池合格率最低（52.15%）,差异有统计学意义（χ^2=16.57,P〈0.05）。结论双流县游泳池水总合格率不高,不同类型的游泳池水合格率有差异,卫生监管和宣传工作还需进一步加强。     

萍乡市一起咽结膜热暴发疫情调查报告

目的分析萍乡市一起咽结膜热暴发的流行特征和病因,为今后此类传染病防控提供参考。方法制定病例定义进行病例搜索,对所有病例进行个案调查,对游泳馆进行现场卫生学调查,对患者咽拭子标本和游泳池水进行实验室检测。结果本起疫情累计病例84例,发病高峰在8月1～5日;年龄以5～13岁最多,占总病例数的77.38%。患者发病前均有游泳史,临床表现主要为发热伴咽痛、扁桃体红肿、眼结膜充血等。8份现症病人咽拭子标本经Real-time PCR方法检测,确定为腺病毒感染。结论本起咽结膜热暴发疫情的病原体为腺病毒,暴发可能是通过被污染的游泳池水造成传播。     

2009--2013年双流县游泳池水质调查

目的为了解双流县人工游泳池水质卫生状况,提供卫生安全的游泳池水,保证游泳人群的健康。方法按照GB/T17220-1998《公共场所卫生监测技术规范》要求,采集双流县2009～2013年人工游泳池水进行检测,并对结果进行分析。结果 2009～2013年游泳池水质总体合格率为75.76%,且呈逐年上升趋势;合格率较低的指标为尿素、游离余氯等;5年合计检测297份水样,合格225份,合格率为75.76%,2009～2013年检测合格率分别为70.00%、52.78%、79.45%、86.36%,77.78%（P〈0.05）。检测合格率对外开放的公共泳池为73.08%,酒店泳池为76.00%,住宅小区泳池为74.89%,学校泳池为78.26%（P〉0.05）。游离性余氯、尿素、pH值、浑浊度、大肠菌群、细菌总数的合格率分别为93.27%、89.23%、100.00%、100.00%、94.61%、90.91%。结论双流县游泳池水质合格率较低,应加强游泳池水质卫生管理,大力开展相关知识的宣传,提高人群自我保护意识。     

Increasing access to renal transplantation in India through our single‐center kidney paired donation program: a model for the developing world to prevent commercial transplantation

Because access to transplantation with HLA‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end‐stage renal disease (ESRD) patient in India. We present a government and institutional ethical review board approved study of 56 ESRD patients [25 two‐way and 2 three‐way pairs] who consented to participate in KPD transplantation at our center in 2013, performed to avoid blood group incompatibility (n = 52) or positive cross‐match (n = 4). All patients had anatomic, functional, and immunologically comparable donors. The waiting time in KPD was short as compared to deceased donor transplantation. Laparoscopic donor nephrectomy was performed in 54 donors. Donor relationships were spousal (n = 40), parental (n = 13), others (n = 3), with median HLA match of 1. Graft survival was 97.5%. Three patients died with functioning graft. 16% had biopsy‐proven acute rejection. Mean serum creatinine was 1.2 mg/dl at 0.73 ± 0.32 months follow‐up. KPD is a viable, legal, and rapidly growing modality for facilitating LDRT for patients who are incompatible with their healthy, willing living donor. To our knowledge, this is the largest single‐center report from India.