David Spiegel

Bio: David Spiegel is an academic researcher from Stanford University. The author has contributed to research in topics: Medicine & Breast cancer. The author has an hindex of 106, co-authored 733 publications receiving 46276 citations. Previous affiliations of David Spiegel include Tel Aviv University & University of Adelaide.

Illuminating HIV gp120-ligand recognition through computationally-driven optimization of antibody-recruiting molecules

Abstract: Here we report on the structure-based optimization of antibody-recruiting molecules targeting HIV gp120 (ARM-H). These studies have leveraged a combination of medicinal chemistry, biochemical and cellular assay analysis, and computation. Our findings have afforded an optimized analog of ARM-H, which is ∼1000 fold more potent in gp120-binding and MT-2 antiviral assays than our previously reported derivative. Furthermore, computational analysis, taken together with experimental data, provides evidence that azaindole- and indole-based attachment inhibitors bind gp120 at an accessory hydrophobic pocket beneath the CD4-binding site and can also adopt multiple distinct binding modes in interacting with gp120. These results are likely to prove enabling in the development of novel HIV attachment inhibitors, and more broadly, they suggest novel applications for ARMs as probes of conformationally flexible systems.

Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM- HI's, function through orthogonal pathways, by inhibiting the gpl20-CD4 interaction, and by recruiting anti-DNP antibodies to gpl20-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gpl20 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gpl20-expressing cells. Compounds and methods are described herein.

The Dissociative Subtype of PTSD Interview (DSP-I): Development and Psychometric Properties

Abstract: The inclusion of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reflects the importance of assessing PTSD-DS. We developed the Dissociative Subtype of PTSD Interview (DSP-I). This clinician-administered instrument assesses the presence and severity of PTSD-DS (i.e., symptoms of depersonalization or derealization) and contains a supplementary checklist that enables assessment and differentiation of other trauma-related dissociative symptoms (i.e., blanking out, emotional numbing, alterations in sensory perception, amnesia, and identity confusion). The psychometric properties were tested in 131 treatment-seeking individuals with PTSD and histories of multiple trauma, 17.6 % of whom met criteria for PTSD-DS in accordance with the DSP-I. The checklist was tested in 275 treatment-seeking individuals. Results showed the DSP-I to have high internal consistency, good convergent validity with PTSD-DS items of the CAPS-5, and good divergent validity with scales of somatization, anxiety and depression. The depersonalization and derealization scales were highly associated. Moreover, the DSP-I accounted for an additional variance in PTSD severity scores of 8% over and above the CAPS-5 and number of traumatic experiences. The dissociative experiences of the checklist were more strongly associated with scales of overall distress, somatization, depression, and anxiety than scales of depersonalization and derealization. In conclusion, the DSP-I appears to be a clinically relevant and psychometrically sound instrument that is valuable for use in clinical and research settings.

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

Abstract: 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。

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

Abstract: 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.

Standards of Medical Care in Diabetes

Abstract: 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.