Severe Malaria Not Responsive to Artemisinin Derivatives in Man Returning from Angola to Vietnam

Resistance to artemisinin derivatives, the most potent antimalarial drugs currently used, has emerged in Southeast Asia and threatens to spread to Africa. We report a case of malaria in a man who returned to Vietnam after 3 years in Angola that did not respond to intravenous artesunate and clindamycin or an oral artemisinin-based combination.     

Salmonella Subtypes with Increased MICs for Azithromycin in Travelers Returned to the Netherlands

Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999–2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.     

CK2 activates kinesin via induction of a conformational change

Kinesin is the canonical plus-end microtubule motor and has been the focus of intense study since its discovery in 1985. We previously demonstrated a time-dependent inactivation of kinesin in vitro that was fully reversible by the addition of purified casein kinase 2 (CK2) and showed that this inactivation/reactivation pathway was relevant in cells. Here we show that kinesin inactivation results from a conformational change that causes the neck linker to be positioned closer to the motor domain. Furthermore, we show that treatment of kinesin with CK2 prevents and reverses this repositioning. Finally, we demonstrate that CK2 treatment facilitates ADP dissociation from the motor, resulting in a nucleotide-free state that promotes microtubule binding. Thus, we propose that kinesin inactivation results from neck-linker repositioning and that CK2-mediated reactivation results from CK2’s dual ability to reverse this repositioning and to promote ADP release.Intracellular microtubule-based transport is crucial for the creation and maintenance of cellular order, and altered transport is implicated in both neurodegeneration and cancer. Frequently, in vivo cargos are moved by multiple microtubule-based molecular motors (1–6), and changing the number of active motors on the cargo can change cargo force production (4) and also potentially the mean travel distance for predominantly unidirectionally moving cargos (7). However, until recently, it has been unclear how activity of cargo-bound motors might be regulated.Transport is frequently regulated by signaling cascades [see, e.g., cAMP control of pigment granule transport (8) or APP transport (9)]. Thus, multiple signaling pathways might contribute to control of transport under different conditions, and signaling altered in disease might affect transport, which could then contribute to disease progression. Nonetheless, mechanistic understanding of such effects is limited. For these reasons, we would like to understand transport roles of specific disease-relevant kinases. One such kinase is casein kinase 2 (CK2), which is involved in development (10), is up-regulated in various cancers (11), and is decreased in neurodegeneration (12). We found that, over time, kinesin loses its ability to bind microtubules (becomes “inactive”) and that this loss of activity could be reversed by CK2 (13).Mechanistically, how kinesin became inactive—and what CK2 did to reactivate it—was unknown. Here we discover that kinesin’s inactivation results from a conformational change involving repositioning of the neck linker (NL) and that reactivation reverses this conformational change. Intriguingly, the conformational change that results in reactivation causes release of ADP, converting kinesin from a weak microtubule-interacting state (K⋅ADP) to a strong one (K), so that in some ways CK2 acts like a small G-protein nucleotide-exchange factor.     

Comparison between urinary diaries completed with and without intensive patient instructions

The evaluation of the incontinent patient relies on accurate assessment of urinary symptoms. Although the 7 day urinary diary is a reproducible method of data collection, the optimal means of implementing this diary is unknown. The urinary diary is usually employed after the initial clinical pathophysiologic evaluation has been performed and the patient has received intensive instructions on the correct method of diary completion. This study aims to determine if a urinary diary provided to the patient prior to the initial clinical evaluation along with minimal instructions will provide symptom data comparable with that obtained by conventional methods. Two hundred seventy-eight women were recruited to participate in one of three clinical trials for urinary incontinence treatment. All subjects completed a diary prior to the initial clinical evaluation, the Minimal Instruction Diary, and a second diary after clinical evaluation, the Intensive Instruction Diary. The Minimal and the Intensive Instruction Diaries were compared for number of episodes of diurnal and nocturnal voluntary micturition and incontinence. Pearsons' correlation coefficients ranged from 0.67 to 0.78 for each of the urinary symptoms. Intra-subject comparison indicated a decline in reports of nocturnal voluntary micturitions from the Minimal to the Intensive Instruction Diary. No demographic or urodynamic parameters could account for the difference. The 7 day urinary diary is a reliable tool to assess urinary symptoms, which can be utilized prior to the initial clinical evaluation. Its ease of use and practicality make this diary promising for use in a wider patient population. © 1996 Wiley-Liss, Inc.     

血脂监测日记在高脂血症患者自我管理中的应用与效果

目的 探讨血脂监测日记在高脂血症患者自我管理中的应用与效果.方法 将血脂异常的83例患者随机分为两组,对照组43例,观察组40例,两组患者均接受调脂治疗,出院后接受常规的电话随访及院外健康教育;观察组在此基础上使用血脂监测日记记录每日的生活方式及阶段血脂变化.1年后比较两组患者的血脂各项指标达标率.结果 观察组患者的总...     

癌痛患者口袋日记本的设计与临床应用

目的：为癌痛患者制作一种携带方便的癌痛管理日记本,提高肿瘤患者对癌痛知识的掌握,促进患者主动参与癌痛规范化治疗。方法选取四川省肿瘤医院6个癌痛示范病房的299例中重度癌痛患者,将病房分别编号,随机分为研究组156例和对照组143例。对照组采用常规癌痛健康教育指导,研究组在此基础上给每个患者分发一本癌痛患者口袋日记本,动态记录疼痛控制情况及不良反应。采用自制肿瘤患者癌痛知识自评问卷和肿瘤患者癌痛控制满意度问卷于患者出院前进行测试和评价。结果研究组患者癌痛评估与药物使用得分与对照组比较差异无统计学意义(P>0.05),研究组不良反应预防得分(15.84±1.70)分,不良反应观察(15.84±1.70)分,癌痛误区鉴别(18.52±1.16)分,均高于对照组,差异有统计学意义(t 值分别为5.25,2.38,13.53;P <0.05)。研究组非常满意98例,满意55例,不满意3例,满意度高于对照组,差异有统计学意义(Z=8.87,P<0.05)。结论癌痛患者口袋日记本制作简单、携带方便、实用性强,有利于提高肿瘤患者对癌痛知识的掌握水平,促进患者参与癌痛规范化治疗,提高癌痛控制自我管理能力和满意度。