Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

In newborns, hypoxia elicits defensive behaviors including awakening from sleep, body movements and crying. An inability to produce this defense response is a risk factor for sudden infant death syndrome and other respiratory control disorders. In this study, we examined the possibility that the defense response to hypoxia in newborns is partly determined by early exposure to hypoxia. We explored this possibility in 6-day-old mice, which resemble human preterm infants of approximately 25–30 weeks’ gestational age. Ultrasonic vocalizations (USVs) were recorded as a marker for the defense response to hypoxia. In a conditioning experiment, newborn mice were exposed to two artificial odors (conditioned stimuli, CS). For acquisition (two trials), pups were exposed to one odor (CS+) in a hypoxic gas mixture (10% O₂, which was the unconditioned stimulus, US) and to another odor (CS−) in air. Then, the pups were exposed to each odor while breathing air. Newborn mice produced significantly more USVs when exposed to the odor previously paired with hypoxia than to the control odor. Thus, associative learning may shape the defense response to hypoxia in newborns.     

Success rates of nuclear short tandem repeat typing from different skeletal elements

Aim

To evaluate trends in DNA typing success rates of different skeletal elements from mass graves originating from conflicts that occurred in the former Yugoslavia (Bosnia and Herzegovina and Kosovo) during the 1990s, and to establish correlation between skeletal sample age and success of high throughput short tandem repeat (STR) typing in the large data set of the International Commission on Missing Persons.

Method

DNA extraction and short tandem repeat (STR) typing have been attempted on over 25 000 skeletal samples. The skeletal samples originated from different geographical locations where the conflicts occurred and from different time periods from 1992 to 1999. DNA preservation in these samples was highly variable, but was often significantly degraded and of limited quantity. For the purpose of this study, processed samples were categorized according to skeletal sample type, sample age since death, and success rates tabulated.

Results

Well-defined general trends in success rates of DNA analyses were observed with respect to the type of bone tested and sample age. The highest success rates were observed with samples from dense cortical bone of weight-bearing leg bones (femur 86.9%), whereas long bones of the arms showed significantly lower success (humerus 46.2%, radius 24.5%, ulna 22.8%). Intact teeth also exhibited high success rates (teeth 82.7%). DNA isolation from other skeletal elements differed considerably in success, making bone sample selection an important factor influencing success.

Conclusion

The success of DNA typing is related to the type of skeletal sample. By carefully evaluating skeletal material available for forensic DNA testing with regard to sample age and type of skeletal element available, it is possible to increase the success and efficiency of forensic DNA testing.The aftermath of the 1992-1995 conflict in the area of former Yugoslavia was marked with estimated 40 000 missing individuals. To address the issue of missing persons, the International Commission on Missing Persons (ICMP) was created in 1996 following the G-7 Summit in Lyon, France. ICMP’s mandate was expanded to also cover the DNA typing of missing persons resulting from 1999 conflict in Kosovo region.ICMP employs a “population based, DNA-led” identification system for the identification of missing persons in the region of former Yugoslavia. On a regional scale, DNA profiles from reference samples of living relatives of missing persons are continuously compared in a batch mode to the DNA profiles obtained from mortal remains of victims. To date, more than 84 000 blood samples representing over 28 000 missing individuals have been collected, analyzed, and entered into the database. Since 2001, short tandem repeat (STR) profiles from more than 21 000 skeletal samples, representing more than 15 000 different individuals, have also been entered into the ICMP database (1). DNA matching reports of greater than 99.95% probability of identity have been issued for over 11 600 individuals.ICMP DNA laboratories currently operate at a target rate of 105 bone or tooth extractions per day, using a silica-based extraction method (1-3). Bone and teeth samples tested are between 8 and 15 years post mortem. The quality of DNA preservation in these bones is highly variable and often substantially limited or/and degraded. This reflects the fact that the remains were buried or disposed in many different environmental contexts, with differential exposure to potentially harsh extrinsic factors such as temperature, UV radiation, humidity, and exposure to animals, insects, and microbes. Different disposal conditions are marked by burial in different soil types, complete or partial immersion of remains in water, contact with fire, or use of plastic sheeting. Microbial degradation is variably evidenced in these samples by both bone morphology and co-extraction of sometimes large amounts of microbial DNA (our unpublished observation). As always in this type of work, co-extraction of DNA inhibitors is a serious issue, and is also variable among samples.Bone and teeth samples clearly protect DNA through their physical and/or chemical robustness to environmental degradation and/or biological attack. An elementary manifestation of this is that bone and teeth are often the only surviving material that can be tested. However, the mechanisms by which DNA is preserved in bone are not very well characterized (4). Bone tissue is primarily composed of protein and mineral. The two most abundant proteins in bone tissue are collagen and osteocalcin. Approximately 70% of the mineral portion of the bone is composed of hydroxyapatite, which includes calcium phosphate, calcium carbonate, calcium fluoride, calcium hydroxide, and citrate. Structural arrangement of bone tissue is such that the mineral portion provides structural support to the protein portion in the bone and, by doing so, physically excludes exogenous/extracellular agents/enzymes that are potentially harmful to the protein portion of the bone (4). DNA has a very strong affinity for hydroxyapatite. DNA degradation is linked to the loss of crystallinity in the hydroxyapatite, but it may also be related to the loss of collagen (5).Overall, it seems reasonable to suppose that the characteristics of the bone that are correlated with its general long term survival, ie its resistance to morphological degradation at the macroscopic and microscopic level, would be those that contribute to the protection of DNA from degradation. Bone density, ie the extent of mineralization, is one of the most important intrinsic factors in survival of bone material. There is a significant difference in bone density between men and women, with the latter showing lower density values. The difference in bone density is also specific for different areas of the skeletal element morphology, with the highest density values noted for the mid-shaft region (6). Teeth are the hardest tissue in the human body because of the dental enamel (7).To know which bones best preserve DNA is of fundamental importance to DNA identification casework in mass fatality incidents and mass graves from armed conflict or genocide. The question equally applies to “ancient DNA” analyses in archaeological or human molecular evolutionary investigations. Despite the logical expectation that denser, more intact bones may be preferable, there is very little empirical data published on this issue (8). We also note that a successful recovery of DNA is linked not only to the degree of protection within the bone, but also the total amount of starting DNA. One reason for the lack of precise information on the best samples for DNA testing from degraded bone is the difficulty in performing controlled experiments, with regard to the effect of relevant environmental variables, inter-individual variation (related to for example sex or age), the long periods of time involved, and the need for large sample size.The aim of our study was to analyze DNA typing success rates from very large sample sizes of various skeletal elements from victims of conflict in the former Yugoslavia. Given the large number of variables affecting DNA preservation, a large sample size helps to average out the influences of a wide range of environmental contexts and permit general conclusions. Further, we divided our data into three time periods, with respect to time since death. This allows the analysis of the relative rate of degradation in different skeletal elements over time. These empirical data can serve as a useful guide to sampling strategies from degraded skeletal remains.     

Excessive body weight is associated with additional loss of quality of life in children with asthma

BACKGROUND: Asthma and excessive body weight frequently coexist, whereas the exact relationship between the 2 diseases is unknown. OBJECTIVE: To study whether asthma combined with excessive body weight has a greater effect on quality of life in children than the separate effects of asthma or excessive body weight alone. METHODS: In a cross-sectional design, 1758 school children (age 7-10 years) participated: 4 study groups were composed of children with asthma and with/without excessive body weight, and healthy controls with/without excessive body weight. Diagnosis of asthma was defined by either a doctor's diagnosis or by core questions of the International Study of Asthma and Allergies in Childhood questionnaire in combination with either reversible airway obstruction or bronchial hyperresponsiveness. Excessive body weight was defined by using international cutoff points for body mass index. Quality of life was evaluated by the Pediatric Asthma Quality of Life Questionnaire. RESULTS: For all domains of quality of life, children with both asthma and excessive body weight had lower scores than children with either asthma alone or excessive body weight alone. Compared with healthy controls, the score was 25% lower in children with asthma and excessive body weight, 14% lower in children with asthma and normal weight, and only 1% lower in overweight controls. CONCLUSION: Excessive body weight is associated with an additional decrease in quality of life in children with asthma. CLINICAL IMPLICATIONS: Clinicians should be aware of the interaction between asthma and excessive body weight and the effect on quality of life and should give extra attention to children with both conditions.     

云南不明原因聚集性猝死中心肌炎病例的病理特点分析

目的观察分析云南不明原因聚集性猝死病例心肌炎的病理改变特点,探讨心肌炎在这类猝死中的作用。方法心肌炎的病理诊断参照Dallas和世界心脏联合会的标准。分析云南省1991—2006年进行猝死监测期间收集的尸检病例29例,其中14例为心肌炎病例。心肌炎患者年龄8～68岁,平均30岁。男9例、女5例。回顾流行病学资料,核查心脏标本,观察心脏等器官的组织切片,其中3例做了心脏传导系统检查。结果心肌炎共14例,占尸检病例的48％。其中淋巴细胞性心肌炎11例,中性粒细胞性心肌炎3例。心肌炎均表现为局灶性,未见弥漫性心肌炎。仅20％（8％～42％）的心肌组织切片可检出炎性病灶,病灶多分布在左心室侧壁,少数在室间隔和右心室部心肌。病灶区心肌细胞形态损伤多数较轻微,个别病例出现片状心肌溶解或凝固性坏死。多数病变为急性炎,也可见机化和急性损伤共存。4例还伴有心包炎,1例伴亚急性心内膜炎,3例行传导系统检查者中1例炎症波及房室结。心脏外观多无异常,仅2例左室或全心扩大。5例伴有呼吸道和肺部感染。结论心肌炎是云南不明原因聚集性猝死的主要病变之一,病理表现以局灶性为主,病变形态提示病毒和细菌性感染均有可能,但是,尚不能确定心肌炎症与中毒的关系。心肌炎的病因及其与猝死聚集性的关系值得进一步研究。     

Comparing limb proprioception and oculomotor signals during hand-guided saccades

We previously showed that saccades tend to overshoot briefly flashed targets that were manually displaced in the dark (Ren et al. 2006). However it was not clear if the overshoot originated from a sensory error in measuring hand displacement or from a premotor error in saccade programming, because gaze and hand position started at the same central position. Here, we tested between these hypotheses by dissociating the initial eye and hand position. Five hand/target positions (center, far, near, right, left) on a frontally-placed horizontal surface were used in four paradigms: Center or Peripheral Eye-hand Association (CA or PA, both gaze and right hand started from the center or a same peripheral location) and Hand or Eye Dissociation (HD or ED, hand or gaze started from one of three non-target peripheral locations). Subjects never received any visual feedback about the final target location and the subjects’ hand displacement. In the CA paradigm, subjects showed the same overshoot that we showed previously. However, changing both initial eye and hand positions relative to the final target (PA) affected the pattern, significantly altering the directions of overshoots. Changing only the initial position of hand (HD) did not have this effect, whereas changing only initial eye position (ED) had the same effect as the PA condition (CA ≈ HD, PA ≈ ED). Furthermore, multiple regression analysis showed that the direction of the ideal saccade contributed significantly to the endpoint direction error, not the direction of the hand path. These results suggest that these errors do not primarily arise from misestimates of the hand trajectory, but rather from a process of comparing the initial eye position and the limb proprioceptive signal during saccade programming.     

Stock-outs! Improvisations and processes of infrastructuring in Uganda’s HIV/Aids and malaria programmes

ABSTRACT

This paper examines the stock-outs of medicines and diagnostic devices in Uganda. Our aim is to trace and compare interruptions in the supply of antiretrovirals and Rapid Diagnostic Tests in order to provide an ethnographic account of the complex role that improvisations play within global health infrastructures. We will argue that the fragmented and mobile infrastructures of these key global health technologies require and necessitate improvisations by the different actors involved as well as on almost all levels of the Ugandan health-care system. The extent and abundance of improvisations in itself works to acquire infrastructural capacities, a process that we will call the infrastructuring of care and treatment. We will also show how this process of infrastructuring of care and treatment – here rendered visible through improvisations – produces new dilemmas and uncertainties. Our approach to infrastructure challenges technocratic overtones prevalent in current debates around the much-needed strengthening of health systems. Our study of stock-outs aims to show how the infrastructure of under-resourced health systems is maintained by a complex nexus of socio-material practices and improvisations.     

从药品质量标准的视角探讨药品的监督与管理

目的：从药品质量标准的视角探讨如何进一步加强药品的监督与管理,促进医药产业发展、保障公众用药安全。方法：通过对监督抽检发现的药品质量标准存在的问题进行分析研究,提出相应的解决措施和意见建议。结果与结论：部分药品质量标准在标准制定、审批发布、标准管理、标准执行以及质量标准的可及性等方面存在不足,影响了质量标准的执行和药品生产及安全监管,应从建立药品审评审批与药品质量标准管理的联动机制、完善监督抽检机制、加强对药品质量标准执行的监管等方面加以解决。