抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Mindfulness is an attribute of consciousness long believed to promote well-being. This research provides a theoretical and empirical examination of the role of mindfulness in psychological well-being. The development and psychometric properties of the dispositional Mindful Attention Awareness Scale (MAAS) are described. Correlational, quasi-experimental, and laboratory studies then show that the MAAS measures a unique quality of consciousness that is related to a variety of well-being constructs, that differentiates mindfulness practitioners from others, and that is associated with enhanced selfawareness. An experience-sampling study shows that both dispositional and state mindfulness predict self-regulated behavior and positive emotional states. Finally, a clinical intervention study with cancer patients demonstrates that increases in mindfulness over time relate to declines in mood disturbance and stress. Many philosophical, spiritual, and psychological traditions emphasize the importance of the quality of consciousness for the maintenance and enhancement of well-being (Wilber, 2000). Despite this, it is easy to overlook the importance of consciousness in human well-being because almost everyone exercises its primary capacities, that is, attention and awareness. Indeed, the relation between qualities of consciousness and well-being has received little empirical attention. One attribute of consciousness that has been much-discussed in relation to well-being is mindfulness. The concept of mindfulness has roots in Buddhist and other contemplative traditions where conscious attention and awareness are actively cultivated. It is most commonly defined as the state of being attentive to and aware of what is taking place in the present. For example, Nyanaponika Thera (1972) called mindfulness “the clear and single-minded awareness of what actually happens to us and in us at the successive moments of perception” (p. 5). Hanh (1976) similarly defined mindfulness as “keeping one’s consciousness alive to the present reality” (p. 11). Recent research has shown that the enhancement of mindfulness through training facilitates a variety of well-being outcomes (e.g., Kabat-Zinn, 1990). To date, however, there has been little work examining this attribute as a naturally occurring characteristic. Recognizing that most everyone has the capacity to attend and to be aware, we nonetheless assume (a) that individuals differ in their propensity or willingness to be aware and to sustain attention to what is occurring in the present and (b) that this mindful capacity varies within persons, because it can be sharpened or dulled by a variety of factors. The intent of the present research is to reliably identify these inter- and intrapersonal variations in mindfulness, establish their relations to other relevant psychological constructs, and demonstrate their importance to a variety of forms of psychological well-being.

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The Benefits of Being Present: Mindfulness and Its Role in Psychological Well-Being

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma

Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy. Most TPD technologies use the ubiquitin-proteasome system, and are therefore limited to targeting intracellular proteins. To address this limitation, we developed a class of modular, bifunctional synthetic molecules called MoDE-As (molecular degraders of extracellular proteins through the asialoglycoprotein receptor (ASGPR)), which mediate the degradation of extracellular proteins. MoDE-A molecules mediate the formation of a ternary complex between a target protein and ASGPR on hepatocytes. The target protein is then endocytosed and degraded by lysosomal proteases. We demonstrated the modularity of the MoDE-A technology by synthesizing molecules that induce depletion of both antibody and proinflammatory cytokine proteins. These data show experimental evidence that nonproteinogenic, synthetic molecules can enable TPD of extracellular proteins in vitro and in vivo. We believe that TPD mediated by the MoDE-A technology will have widespread applications for disease treatment.

Bifunctional small molecules that mediate the degradation of extracellular proteins.

The hypothesis that the alleviation of chronic pain with hypnosis is mediated by endorphins was tested. Six patients with chronic pain secondary to peripheral nerve irritation were taught to control the pain utilizing selfhypnosis. Each subject was tested at 5-min intervals during four 1-h sessions for the amount of reduction of pain sensation and suffering associated with hypnosis while being given, in a random double-blind crossover fashion, an IV injection of either 10 mg naloxone or a saline placebo through an indwelling catheter. The patients demonstrated significant alleviation of the pain with hypnosis, but this effect was not significantly diminished in the naloxone condition. These findings contradict the hypothesis that endorphins are involved in hypnotic analgesia

Naloxone fails to reverse hypnotic alleviation of chronic pain

The very existence of hysterical psychosis as a diagnostic entity has been questioned as part of the general difficulty in defining both hysteria and psychosis. However, several recent investigations have documented a syndrome that usually involves brief and intense periods of psychotic behavior, generally with graphic decompensation, severe environmental stress, and rapid recompensation, in individuals with other hysterical features. The authors assert that such a syndrome does exist as a clinical entity and that the differential diagnosis can be facilitated by using a standardized measure of hypnotic trance capacity. They hypothesize that patients with hysterical psychosis are highly hypnotizable, while those who are schizophrenic and psychotic have low hypnotizability. The authors review the literature and present two case examples.

Hysterical psychosis and hypnotizability

Recognizing Traumatic Dissociation

External fixation (EF) of tibia fractures has been associated with nonunions and malunions at our large pediatric trauma center. This study was designed to determine the successes and shortcomings of EF, especially with respect to maintenance of alignment and time to union. We believe that this will contribute to the limited amount of literature examining the complications associated with this treatment modality in the pediatric population. Thirty-one consecutive high-energy tibia fractures treated with EF over 4.5 years were analyzed. There were 22 boys and 9 girls (4-17 years old; mean, 11.9 years). Mean length of follow-up was 15 months. Of the 31 fractures analyzed, 19 were open fractures (12 closed, 3 grade I, 9 grade II, and 7 grade III). Of 30 fractures, 3 required skin graft, whereas 7 required fasciotomy. Mean duration of EF was 3.2 months. Mean time to union was 4.8 months. For complication rates, 4 of 30 had delayed union, 2 of 30 had nonunion, 8 of 30 had minor malunion, 3 of 30 had major malunion, 3 of 30 had leg length discrepancy, 8 of 30 had pin track infection, 3 of 30 had wound infection, 2 of 30 had osteomyelitis, and 4 of 30 required surgery for nonunion. Time to union differed between those aged 11 years or younger and those aged 12 years or older (means of 3.2 and 6.0 months, respectively; P = 0.001). Union time also differed between those with closed or grade I open fractures and those with grade II or III open fractures (3.9 and 5.7 months, respectively; P = 0.035). Leg length discrepancy rate differed between children aged 11 years or younger and those aged 12 years or older (3/13 and 0/18, respectively; P = 0.05). Although EF has been touted as the standard treatment of high-energy pediatric tibia fractures, our close analysis revealed a high rate of problems such as long union times (especially ages >or=12), malunion, leg length discrepancy (especially ages <or=11), and pin track infection.

David Spiegel

Papers

Bifunctional small molecules that mediate the degradation of extracellular proteins.

Naloxone fails to reverse hypnotic alleviation of chronic pain

Hysterical psychosis and hypnotizability

Recognizing Traumatic Dissociation

External fixation of high-energy tibia fractures.