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Two-photon ophthalmoscopy has potential for in vivo assessment of function of normal and diseased retina. However, light safety of the sub-100 fs laser typically used is a major concern and safety standards are not well established. To test the feasibility of safe in vivo two-photon excitation fluorescence (TPEF) imaging of photoreceptors in humans, we examined the effects of ultrashort pulsed light and the required light levels with a variety of clinical and high resolution imaging methods in macaques. The only measure that revealed a significant effect due to exposure to pulsed light within existing safety standards was infrared autofluorescence (IRAF) intensity. No other structural or functional alterations were detected by other imaging techniques for any of the exposures. Photoreceptors and retinal pigment epithelium appeared normal in adaptive optics images. No effect of repeated exposures on TPEF time course was detected, suggesting that visual cycle function was maintained. If IRAF reduction is hazardous, it is the only hurdle to applying two-photon retinal imaging in humans. To date, no harmful effects of IRAF reduction have been detected.

Objectives: To develop and assess the validity of measures of patients' attachment-related perceptions of experiences with healthcare providers (HCPs)., Setting: Online survey., Participants: 181 people provided consent and 119 completed the survey (66%). Most participants were women (80%)., Primary and Secondary Outcome Measures: Questions were developed to assess possible attachment functions served by an HCP and patients' attachment-related attitudes towards an HCP. Scales were constructed based on exploratory factor analysis. Measures of adult attachment, therapeutic alliance, perceived HCP characteristics and health utilisation were used to validate scales., Results: Possible safe haven and secure base functions served by HCPs were strongly endorsed. A model with good fit (root mean square error of approximation=0.056) yielded 3 factors: 'HCP experienced as supportive and safe' (SUPPORT, α=0.94), 'HCP experienced as aversive' (AVERSE, α=0.86) and 'more and closer contact wanted with HCP' (WANT, α=0.85). SUPPORT was correlated with positive HCP characteristics and not with attachment insecurity. AVERSE was inversely correlated with positive HCP attributes and correlated with attachment insecurity. WANT was unrelated to positive HCP attributes, but correlated with attachment insecurity. Frequency of HCP contact was related to WANT (Kruskal-Wallis=21.9, p<0.001) and SUPPORT (Kruskal-Wallis=13.2, p=0.02), but not to AVERSE (Kruskal-Wallis=1.7, p=0.89)., Conclusions: Patients attribute attachment functions of secure base and safe haven to HCPs. SUPPORT is related to positive appraisal of HCP characteristics; AVERSE is associated with discomfort in the HCP relationship that is related with perceived HCP characteristics and patients' insecure attachment; WANT is associated with unmet needs for connection with an HCP related to insecure attachment, but not to perceived HCP characteristics. These scales may be useful in studying the application of attachment theory to the HCP-patient relationship., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: Although extrinsic fluorophores can be introduced to label specific cell types in the retina, endogenous fluorophores, such as NAD(P)H, FAD, collagen, and others, are present in all retinal layers. These molecules are a potential source of optical contrast and can enable noninvasive visualization of all cellular layers. We used a two-photon fluorescence adaptive optics scanning light ophthalmoscope (TPF-AOSLO) to explore the native autofluorescence of various cell classes spanning several layers in the unlabeled retina of a living primate eye., Methods: Three macaques were imaged on separate occasions using a custom TPF-AOSLO. Two-photon fluorescence was evoked by pulsed light at 730 and 920 nm excitation wavelengths, while fluorescence emission was collected in the visible range from several retinal layers and different locations. Backscattered light was recorded simultaneously in confocal modality and images were postprocessed to remove eye motion., Results: All retinal layers yielded two-photon signals and the heterogeneous distribution of fluorophores provided optical contrast. Several structural features were observed, such as autofluorescence from vessel walls, Müller cell processes in the nerve fibers, mosaics of cells in the ganglion cell and other nuclear layers of the inner retina, as well as photoreceptor and RPE layers in the outer retina., Conclusions: This in vivo survey of two-photon autofluorescence throughout the primate retina demonstrates a wider variety of structural detail in the living eye than is available through conventional imaging methods, and broadens the use of two-photon imaging of normal and diseased eyes.

Purpose: The retinoid cycle maintains vision by regenerating bleached visual pigment through metabolic events, the kinetics of which have been difficult to characterize in vivo. Two-photon fluorescence excitation has been used previously to track autofluorescence directly from retinoids and pyridines in the visual cycle in mouse and frog retinas, but the mechanisms of the retinoid cycle are not well understood in primates., Methods: We developed a two-photon fluorescence adaptive optics scanning light ophthalmoscope dedicated to in vivo imaging in anesthetized macaques. Using pulsed light at 730 nm, two-photon fluorescence was captured from rods and cones during light and dark adaptation through the eye's pupil., Results: The fluorescence from rods and cones increased with light exposure but at different rates. During dark adaptation, autofluorescence declined, with cone autofluorescence decreasing approximately 4 times faster than from rods. Rates of autofluorescence decrease in rods and cones were approximately 4 times faster than their respective rates of photopigment regeneration. Also, subsets of sparsely distributed cones were less fluorescent than their neighbors immediately following bleach at 565 nm and they were comparable with the S cone mosaic in density and distribution., Conclusions: Although other molecules could be contributing, we posit that these fluorescence changes are mediated by products of the retinoid cycle. In vivo two-photon ophthalmoscopy provides a way to monitor noninvasively stages of the retinoid cycle that were previously inaccessible in the living primate eye. This can be used to assess objectively photoreceptor function in normal and diseased retinas.

Importance: Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy., Observations: Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P < .001) with a dark cone appearance. No foveal cones were detected in the older brother. In the younger brother, foveal cones were enlarged with low density (peak cone density, 48.3 × 103 cones/mm2). The ratio of cone to rod spacing was increased in both patients, with greater divergence from normal approaching the foveal center, indicating that cone loss predominates centrally and rod loss increases peripherally. Both parents had normal photoreceptor mosaics. Genetic testing revealed 3 disease-causing mutations., Conclusions and Relevance: This study provides in vivo images of rods and cones in STGD1. Although the primary clinical features of STGD1 are retinal pigment epithelial lesions, adaptive optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1.

Anthocyanin and mechanical properties were evaluated on Shiraz grapes, picked from both sides of North-South and East-West vineyard row orientations at two harvest dates. Wines were made from each combination. The evaluation and evolution of crushed skin mechanical properties during maceration-fermentation, as also affected by grape ripeness, are shown for the first time. No significant differences in anthocyanin content were found in the grapes between the two vineyard row orientations. However, a significant decrease in anthocyanins and berry skin break force (also referred as skin hardness or strength) was found between the two harvest dates. During maceration, a reduction in the crushed berry skin break force of more than 15% occurred. The intact berries and macerated skins showed similarity in skin break energy values. The anthocyanin profile of the grapes and of the wines prominently displayed malvidin forms, changed mainly by the ripeness level of the grapes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Advances in retinal imaging have led to the discovery of long-lasting retinal changes caused by light exposures below published safety limits, including disruption of the RPE. To investigate the functional consequences of RPE disruption, we combined adaptive optics ophthalmoscopy with retinal densitometry., Methods: A modified adaptive optics scanning light ophthalmoscope (AOSLO) measured the apparent density and regeneration rate of rhodopsin in two macaques before and after four different 568-nm retinal radiant exposures (RREs; 400-3200 J/cm(2)). Optical coherence tomography (OCT) was used to measure the optical path length through the photoreceptor outer segments before and after RPE disruption., Results: All tested RREs caused visible RPE disruption. Apparent rhodopsin density was significantly reduced following 1600 (P = 0.01) and 3200 J/cm(2) (P = 0.007) exposures. No significant change in apparent density was observed in response to 800 J/cm(2). Surprisingly, exposure to 400 J/cm(2) showed a significant increase in apparent density (P = 0.047). Rhodopsin recovery rate was not significantly affected by these RREs. Optical coherence tomography measurements showed a significant decrease in the optical path length through the photoreceptor outer segments for RREs above 800 J/cm(2) (P < 0.001)., Conclusions: At higher RREs, optical path length through the outer segments was reduced. However, the rate of photopigment regeneration was unchanged. While some ambiguity remains as to the correlation between measured reflectivity and absolute rhodopsin density; at the lowest RREs, RPE disruption appears not to be accompanied by a loss of apparent rhodopsin density, which would have been indicative of functional loss., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact., Methods: An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared., Results: We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003)., Conclusions: These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Background: Teaching healthcare providers (HCPs) effective communication skills can be challenging, but is crucial for managing complex patient encounters., Aim: To provide medical trainees strategies for recognizing and understanding problematic interactions., Methods: The Twelve Tips are based on a study of communication skills teaching with family medicine trainees (n = 26) who received controlled exposure to common clinical difficulties simulated by standardized patients (SPs). The following tips were derived from a thematic analysis of a subset of the transcribed coaching sessions., Results: These tips demonstrate that doctor-patient communication difficulties can arise from any of three sources: the patient's issues, the HCP's misunderstanding or inaccurate responsiveness to an issue, and/or the interaction between the HCP and the patient. These tips are heuristically grouped into two themes: (1) guiding principles to hold in mind and (2) behaviors that can be used to apply these principles., Conclusion: We believe that these strategies will help trainees to remain attentive to the patient, the interaction, and their own reactions, to improve the overall clinical encounter.

Two-photon excitation microscopy can image retinal molecular processes in vivo. Intrinsically fluorescent retinyl esters in subcellular structures called retinosomes are an integral part of the visual chromophore regeneration pathway. Fluorescent condensation products of all-trans-retinal accumulate in the eye with age and are also associated with age-related macular degeneration (AMD). Here, we report repetitive, dynamic imaging of these compounds in live mice through the pupil of the eye. By leveraging advanced adaptive optics, we developed a data acquisition algorithm that permitted the identification of retinosomes and condensation products in the retinal pigment epithelium by their characteristic localization, spectral properties and absence in genetically modified or drug-treated mice. This imaging approach has the potential to detect early molecular changes in retinoid metabolism that trigger light- and AMD-induced retinal defects and to assess the effectiveness of treatments for these conditions.

Purpose: Noninvasive two-photon imaging of a living mammalian eye can reveal details of molecular processes in the retina and RPE. Retinyl esters and all-trans-retinal condensation products are two types of retinoid fluorophores present in these tissues. We measured the content of these two types of retinoids in monkey and human eyes to validate the potential of two-photon imaging for monitoring retinoid changes in human eyes., Methods: Two-photon microscopy (TPM) was used to visualize excised retina from monkey eyes. Retinoid composition and content in human and monkey eyes were quantified by HPLC and mass spectrometry (MS)., Results: Clear images of inner and outer segments of rods and cones were obtained in primate eyes at different eccentricities. Fluorescence spectra from outer segments revealed a maximum emission at 480 nm indicative of retinols and their esters. In cynomolgus monkey and human retinal extracts, retinyl esters existed predominantly in the 11-cis configuration along with notable levels of 11-cis-retinol, a characteristic of cone-enriched retinas. Average amounts of di-retinoid-pyridinium-ethanolamine (A2E) in primate and human eyes were 160 and 225 pmol/eye, respectively., Conclusions: These data show that human retina contains sufficient amounts of retinoids for two-photon excitation imaging. Greater amounts of 11-cis-retinyl esters relative to rodent retinas contribute to the fluorescence signal from both monkey and human eyes. These observations indicate that TPM imaging found effective in mice could detect early age- and disease-related changes in human retina., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: Many retinal imaging instruments use infrared wavelengths to reduce the risk of light damage. However, we have discovered that exposure to infrared illumination causes a long-lasting reduction in infrared autofluorescence (IRAF). We have characterized the dependence of this effect on radiant exposure and investigated its origin., Methods: A scanning laser ophthalmoscope was used to obtain IRAF images from two macaques before and after exposure to 790-nm light (15-450 J/cm(2)). Exposures were performed with either raster-scanning or uniform illumination. Infrared autofluorescence images also were obtained in two humans exposed to 790-nm light in a separate study. Humans were assessed with direct ophthalmoscopy, Goldmann visual fields, multifocal ERG, and photopic microperimetry to determine whether these measures revealed any effects in the exposed locations., Results: A significant decrease in IRAF after exposure to infrared light was seen in both monkeys and humans. In monkeys, the magnitude of this reduction increased with retinal radiant exposure. Partial recovery was seen at 1 month, with full recovery within 21 months. Consistent with a photochemical origin, IRAF decreases caused by either raster-scanning or uniform illumination were not significantly different. We were unable to detect any effect of the light exposure with any measure other than IRAF imaging. We cannot exclude the possibility that changes could be detected with more sensitive tests or longer follow-up., Conclusions: This long-lasting effect of infrared illumination in both humans and monkeys occurs at exposure levels four to five times below current safety limits. The photochemical basis for this phenomenon remains unknown., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions., (Copyright © 2014. Published by Elsevier Ltd.)

Though in vivo two-photon imaging has been demonstrated in non-human primates, improvements in the signal-to-noise ratio (SNR) would greatly improve its scientific utility. In this study, extrinsic fluorophores, expressed in otherwise transparent retinal ganglion cells, were imaged in the living mouse eye using a two-photon fluorescence adaptive optics scanning laser ophthalmoscope. We recorded two orders of magnitude greater signal levels from extrinsically labeled cells relative to previous work done in two-photon autofluorescence imaging of primates. Features as small as single dendrites in various layers of the retina could be resolved and predictions are made about the feasibility of measuring functional response from cells. In the future, two-photon imaging in the intact eye may allow us to monitor the function of retinal cell classes with infrared light that minimally excites the visual response.

Objective: Effective communication between physicians and their patients is important in optimizing patient care. This project tested a brief, intensive, interactive medical education intervention using coaching and standardized psychiatric patients to teach physician-patient communication to family medicine trainees., Methods: Twenty-six family medicine trainees (9 PGY1, 11 PGY2, 6 fellows) from five university-affiliated hospitals conducted four once-weekly, 30-minute videotaped interviews with "difficult" standardized patients. After each interview, trainees received 1 hour of individual coaching that incorporated self-assessment and skills-teaching from experienced psychiatrists. Two follow-up interviews with standardized patients occurred 1 week and an average of 6 months post-intervention. Trainee self-reported physician-patient communication efficacy was measured as a control 1 month before the intervention; during the month of the intervention; and an average of 6 months after the intervention. Coach-rated physician-patient communication competence was measured each week of the intervention., Results: Improvements in physician-patient communication were demonstrated. Self-efficacy for physician-patient communication improved significantly during the intervention, in contrast to no improvement during the control period (i.e., training-as-usual). This improvement was sustained during the follow-up period., Conclusions: This innovative educational intervention was shown to be highly effective in improving trainee communication competence and self-efficacy. Future applications of this brief model of physician training have potential to improve communication competence and, in turn, can improve patient care.

Models of adult attachment have proven to be useful for understanding illness behavior, stress responses, susceptibility to disease processes, and psychotherapeutic approaches to difficult patients. Two methods of assessing patterns of attachment, using self-report instruments and using techniques such as the Adult Attachment Interview (AAI), are only weakly related and each has drawbacks for clinical use. We have previously assessed commonalities and differences in the descriptions of attachment patterns that emerge from these schools and synthesized them in empirically based attachment prototypes. In this companion article, we describe a prototype-based model of attachment. This model defines dimensions of attachment anxiety and attachment avoidance as composites of particular aspects of internal working models of self and other, behavior in current close relationships, patterns of expression of affect, and narrative coherence. The model emphasizes the clinical importance of the severity of attachment insecurity, defined as a dimension which incorporates problems in the previously listed domains of attachment as well as deficits in mentalizing, self-agency, and resolution of trauma. The model locates the central tendencies of prototypic ("textbook") descriptions of four patterns of attachment (secure, dismissing, preoccupied, and fearful/disorganized) while avoiding definitions of the boundaries between categories of attachment. We compare the prototype-based model to the two most prominent current models of attachment, the 4-category, 2-dimension model derived from self-report methods of assessment and categories of "attachment states of mind" derived from the Adult Attachment Interview. Finally, we discuss limitations of the prototype-based model and areas requiring further research.

Purpose: To understand molecular mechanisms underlying photobleaching of the RPE fluorophores responsible for fundus autofluorescence., Methods: ARPE-19 cells were allowed to accumulate the bisretinoid, A2E, and were irradiated at 430 nm. For some experiments, the cells were pretreated with vitamin E or sulforaphane and N-acetylcysteine; samples included A2E-free cells. The cells were analyzed by fluorescence microscopy and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. A2E free cells were also irradiated and analyzed. Cell death was quantified by double labeling with a membrane impermeable dye and 4',6'-diamino-2-phenylindole (DAPI)., Results: A2E that had accumulated in ARPE-19 cells exhibited irradiation-associated autofluorescence bleaching despite the absence of appreciable cell death. Chromatographic analysis with absorbance, fluorescence, and mass spectrometry detection revealed that irradiation of A2E was associated with A2E photoisomerization, photooxidation, and photodegradation. Pretreatment with vitamin E favored fluorescence recovery; this finding was consistent with a process involving photooxidation. A2E that was not cell-associated underwent irradiation-induced bleaching, but fluorescence recovery was not observed., Conclusions: Using cell-associated A2E as a model of RPE bisretinoid behavior, photobleaching and autofluorescence recovery was observed; these changes were similar to RPE autofluorescence reduction in vivo. The potential for autofluorescence recovery is dependent on light dose and antioxidant status. Fluorescence bleaching of bisretinoid involves photooxidative and photodegradative processes.

Background: The relationship of psychological stress to relapse in ulcerative colitis (UC) is inconsistent. This may be due to a failure to identify patient characteristics, such as social support, which moderate the transduction of stress from the central nervous system to the immune system. In this study we tested the hypothesis that social support enhances parasympathetic modulation of heart rate in UC., Methods: An indirect measure of autonomic function (heart rate variability; HRV) was measured in 108 patients with UC in remission during a standard protocol involving periods of stress, paced breathing, and relaxation. Social support was measured with the Social Support Questionnaire., Results: After controlling for age, which is strongly related to HRV, both satisfaction with social support (F = 5.7, significance = 0.002) and its interaction with age (F = 7.8, significance <0.001) were associated with high-frequency HRV, which measures parasympathetic modulation of heart rate. Social support was associated with higher levels of high-frequency HRV at almost all points in the stress protocol. Neither age nor social support was associated with differences in the LF/HF ratio, which measures sympathetic modulation of heart rate., Conclusions: Social support is related to parasympathetic activity in UC. Given previous evidence of an antiinflammatory role for the parasympathetic nervous system, this suggests that autonomic function could serve as a mediating link between social support and reduced inflammatory activity., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

The photoreceptor/RPE complex must maintain a delicate balance between maximizing the absorption of photons for vision and retinal image quality while simultaneously minimizing the risk of photodamage when exposed to bright light. We review the recent discovery of two new effects of light exposure on the photoreceptor/RPE complex in the context of current thinking about the causes of retinal phototoxicity. These effects are autofluorescence photobleaching in which exposure to bright light reduces lipofuscin autofluorescence and, at higher light levels, RPE disruption in which the pattern of autofluorescence is permanently altered following light exposure. Both effects occur following exposure to visible light at irradiances that were previously thought to be safe. Photopigment, retinoids involved in the visual cycle, and bisretinoids in lipofuscin have been implicated as possible photosensitizers for photochemical damage. The mechanism of RPE disruption may follow either of these paths. On the other hand, autofluorescence photobleaching is likely an indicator of photooxidation of lipofuscin. The permanent changes inherent in RPE disruption might require modification of the light safety standards. AF photobleaching recovers after several hours although the mechanisms by which this occurs are not yet clear. Understanding the mechanisms of phototoxicity is all the more important given the potential for increased susceptibility in the presence of ocular diseases that affect either the visual cycle and/or lipofuscin accumulation. In addition, knowledge of photochemical mechanisms can improve our understanding of some disease processes that may be influenced by light exposure, such as some forms of Leber's congenital amaurosis, and aid in the development of new therapies. Such treatment prior to intentional light exposures, as in ophthalmic examinations or surgeries, could provide an effective preventative strategy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Deliberate foreign body ingestion (DFBI) is often impulsively driven, repetitive and refractory to intervention and frequently necessitates multiple medical interventions. As such, the frustrations among health care providers are great, and the financial toll on health care is significant. Nevertheless, the literature on DFBI is sparse, and suggestions for treatment planning and management are limited. The authors sought to investigate and uncover efficacious treatments and strategies for preventing reoccurrence in DFBI. We build on earlier work by offering both broad and diagnosis-specific management strategies., Method: A literature review was performed addressing the presentation, management and prevention of reoccurrences of DFBI. Four cases of DFBI are presented illustrating those psychiatric diagnoses (psychosis, malingering, obsessive-compulsive disorder and borderline personality disorder) most frequently encountered in hospital practice. Both broad and specific treatment approaches are presented., Results: Patients engaging in DFBI are best managed through a multidisciplinary approach, following acute medical management. Successful strategies for the prevention of reoccurrences of DFBI are inconclusive., Conclusion: Understanding the function of this behavior is critical in developing treatment for patients who engage in these dangerous, potentially life-threatening, self-injurious behaviors. An amalgam of medical, pharmacological and cognitive-behavioral interventions is recommended, as is additional research., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Atherosclerosis is a condition that is increasingly contributing to worldwide mortality through complications such as stroke and myocardial infarction. IL-1β plays multiple direct, local roles in the formation and stability of the atheroma by eliciting the production of additional cytokines and proteolytic enzymes from macrophages, endothelial cells (EC) and smooth muscle cells (SMC). We therefore tested whether an anti-IL-1β antibody, XOMA 052, might inhibit the secretion of pro-atherogenic cytokines from macrophages in vitro and affect a positive outcome in the Apolipoprotein E-deficient mouse (ApoE(-/-)) model of atherosclerosis in vivo., Methods and Results: In an in vitro co-culture model, XOMA 052 inhibited macrophage-induced secretion of key atherogenic cytokines from EC and SMC, including IL-6, IL-8, MCP-1 and TNFα. The release of degradative enzymes, such as the matrix metalloproteinases MMP-3 and MMP-9, was also decreased by XOMA 052. In addition, XOMA 052 inhibited the secretion of IL-7 from EC and IL-4 from SMC, cytokines not previously reported to be driven by IL-1β in this context. In vivo, XMA052 MG1K, a chimeric murine version of XOMA 052, inhibited the formation of atherosclerotic lesions in the ApoE(-/-) model at all three doses tested. This effect was comparable to that reported for complete genetic ablation of IL-1β or IL-1R1 on an ApoE(-/-) background and was associated with decreases in plasma non-HDL/HDL cholesterol ratio and plaque lipid content and macrophage infiltration., Conclusions: These results demonstrate for the first time that an antibody targeting IL-1β can inhibit the progression of atherosclerosis in vivo, highlighting the importance of this key cytokine in cardiovascular disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans., Methods: In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters., Results: AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters--human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)--AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis., Conclusions: The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea.

Adaptive optics imaging of cone photoreceptors has provided unique insight into the structure and function of the human visual system and has become an important tool for both basic scientists and clinicians. Recent advances in adaptive optics retinal imaging instrumentation and methodology have allowed us to expand beyond cone imaging. Multi-wavelength and fluorescence imaging methods with adaptive optics have allowed multiple retinal cell types to be imaged simultaneously. These new methods have recently revealed rod photoreceptors, retinal pigment epithelium (RPE) cells, and the smallest retinal blood vessels. Fluorescence imaging coupled with adaptive optics has been used to examine ganglion cells in living primates. Two-photon imaging combined with adaptive optics can evaluate photoreceptor function non-invasively in the living primate retina.

Objective: Adult attachment insecurity is associated with many health outcomes and may be associated with sleep disturbance. The purpose of this study was to test the hypothesis that sleep disturbance mediates the relationship between attachment insecurity and three measures of health (perceived general health, physical symptoms and sick days) in a group that is at high risk of sleep disturbance: hospital based health-care workers., Methods: One hundred thirty-one nondepressed female hospital workers completed self-report measures of adult attachment, sleep disturbance, depressive symptoms (excluding sleep-related items) and health outcomes. The hypothesis of mediation was tested with sequential regression analyses., Results: Both attachment anxiety and attachment avoidance were significantly associated with impairment in global sleep quality (ρ=.20 and .19, respectively, P<.05) and physical symptoms (ρ=.21 and .19, P<.05). Attachment anxiety was also associated with depressive symptoms (ρ=.33, P<.001) and sick days (ρ=.21, P<.05). For both physical symptoms and sick days, mediation analyses were consistent with global sleep quality acting as a partial mediator of the relationship between attachment anxiety and physical health. Non-sleep-related depressive symptoms were a stronger mediator., Conclusions: This study corroborates evidence that attachment insecurity is associated with sleep disturbance and extends this association to the occurrence of physical symptoms and time off work due to sickness among workers in a high-stress occupation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In vivo two-photon imaging through the pupil of the primate eye has the potential to become a useful tool for functional imaging of the retina. Two-photon excited fluorescence images of the macaque cone mosaic were obtained using a fluorescence adaptive optics scanning laser ophthalmoscope, overcoming the challenges of a low numerical aperture, imperfect optics of the eye, high required light levels, and eye motion. Although the specific fluorophores are as yet unknown, strong in vivo intrinsic fluorescence allowed images of the cone mosaic. Imaging intact ex vivo retina revealed that the strongest two-photon excited fluorescence signal comes from the cone inner segments. The fluorescence response increased following light stimulation, which could provide a functional measure of the effects of light on photoreceptors.

Many therapeutic antibodies act as antagonists to competitively block cellular signaling pathways. We describe here an approach for the therapeutic use of monoclonal antibodies based on context-dependent attenuation to reduce pathologically high activity while allowing homeostatic signaling in biologically important pathways. Such attenuation is achieved by modulating the kinetics of a ligand binding to its various receptors and regulatory proteins rather than by complete blockade of signaling pathways. The anti-interleukin-1beta (IL-1beta) antibody XOMA 052 is a potent inhibitor of IL-1beta activity that reduces the affinity of IL-1beta for its signaling receptor and co-receptor but not for its decoy and soluble inhibitory receptors. This mechanism shifts the effective dose response of the cytokine so that the potency of IL-1beta bound by XOMA 052 is 20-100-fold lower than that of IL-1beta in the absence of antibody in a variety of in vitro cell-based assays. We propose that by decreasing potency of IL-1beta while allowing binding to its clearance and inhibitory receptors, XOMA 052 treatment will attenuate IL-1beta activity in concert with endogenous regulatory mechanisms. Furthermore, the ability to bind the decoy receptor may reduce the potential for accumulation of antibody.target complexes. Regulatory antibodies like XOMA 052, which selectively modulate signaling pathways, may represent a new mechanistic class of therapeutic antibodies.

Background: Working in a hospital during an extraordinary infectious disease outbreak can cause significant stress and contribute to healthcare workers choosing to reduce patient contact. Psychological training of healthcare workers prior to an influenza pandemic may reduce stress-related absenteeism, however, established training methods that change behavior and attitudes are too resource-intensive for widespread use. This study tests the feasibility and effectiveness of a less expensive alternative - an interactive, computer-assisted training course designed to build resilience to the stresses of working during a pandemic., Methods: A "dose-finding" study compared pre-post changes in three different durations of training. We measured variables that are likely to mediate stress-responses in a pandemic before and after training: confidence in support and training, pandemic-related self-efficacy, coping style and interpersonal problems., Results: 158 hospital workers took the course and were randomly assigned to the short (7 sessions, median cumulative duration 111 minutes), medium (12 sessions, 158 minutes) or long (17 sessions, 223 minutes) version. Using an intention-to-treat analysis, the course was associated with significant improvements in confidence in support and training, pandemic self-efficacy and interpersonal problems. Participants who under-utilized coping via problem-solving or seeking support or over-utilized escape-avoidance experienced improved coping. Comparison of doses showed improved interpersonal problems in the medium and long course but not in the short course. There was a trend towards higher drop-out rates with longer duration of training., Conclusions: Computer-assisted resilience training in healthcare workers appears to be of significant benefit and merits further study under pandemic conditions. Comparing three "doses" of the course suggested that the medium course was optimal.

Purpose: A prior study showed that long exposure to 568-nm light at levels below the maximum permissible exposure safety limit produces retinal damage preceded by a transient reduction in the autofluorescence of retinal pigment epithelial (RPE) cells in vivo. The present study shows how the effects of exposure power and duration combine to produce this autofluorescence reduction and find the minimum exposure causing a detectable autofluorescence reduction., Methods: Macaque retinas were imaged using a fluorescence adaptive optics scanning laser ophthalmoscope to resolve individual RPE cells in vivo. The retina was exposed to 568-nm light over a square subtending 0.5 degrees with energies ranging from 1 to 788 J/cm(2), where power and duration were independently varied., Results: In vivo exposures of 5 J/cm(2) and higher caused an immediate decrease in autofluorescence followed by either full autofluorescence recovery (exposures or= 247 J/cm(2)). No significant autofluorescence reduction was observed for exposures of 2 J/cm(2) and lower. Reciprocity of exposure power and duration held for the exposures tested, implying that the total energy delivered to the retina, rather than its distribution in time, determines the amount of autofluorescence reduction., Conclusions: That reciprocity held is consistent with a photochemical origin, which may or may not cause retinal degeneration. The implementation of safe methods for delivering light to the retina requires a better understanding of the mechanism causing autofluorescence reduction. Finally, RPE imaging was demonstrated using light levels that do not cause a detectable reduction in autofluorescence.

Purpose: The ability to resolve single retinal cells in rodents in vivo has applications in rodent models of the visual system and retinal disease. The authors have characterized the performance of a fluorescence adaptive optics scanning laser ophthalmoscope (fAOSLO) that provides cellular and subcellular imaging of rat retina in vivo., Methods: Enhanced green fluorescent protein (eGFP) was expressed in retinal ganglion cells of normal Sprague-Dawley rats via intravitreal injections of adeno-associated viral vectors. Simultaneous reflectance and fluorescence retinal images were acquired using the fAOSLO. fAOSLO resolution was characterized by comparing in vivo images with subsequent imaging of retinal sections from the same eyes using confocal microscopy., Results: Retinal capillaries and eGFP-labeled ganglion cell bodies, dendrites, and axons were clearly resolved in vivo with adaptive optics. Adaptive optics correction reduced the total root mean square wavefront error, on average, from 0.30 microm to 0.05 microm (measured at 904 nm, 1.7-mm pupil). The full width at half maximum (FWHM) of the average in vivo line-spread function (LSF) was approximately 1.84 microm, approximately 82% greater than the FWHM of the diffraction-limited LSF., Conclusions: With perfect aberration compensation, the in vivo resolution in the rat eye could be approximately 2x greater than that in the human eye because of its large numerical aperture (approximately 0.43). Although the fAOSLO corrects a substantial fraction of the rat eye's aberrations, direct measurements of retinal image quality reveal some blur beyond that expected from diffraction. Nonetheless, subcellular features can be resolved, offering promise for using adaptive optics to investigate the rodent eye in vivo with high resolution.

Background: Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed., Methods: We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue., Results: Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections., Conclusion: This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma.

In the simplest model of eye growth, the ocular optics uniformly scale upwards, as do monochromatic higher-order aberrations (HOA) and linear blur on the retina. However, measured HOA remain constant or decrease with growth in some species. A new model, which holds HOA and the associated linear blur on the retina constant, was used to predict changes in HOA and resulting image quality on the retina during growth, in each of chick, monkey, and human. Models used rates of growth in each of the three species. Angular optical quality on the retina due to HOA, and its metrics improved, in contrast to the constancy predicted by uniform scaling. The model with constant linear HOA blur predicts well the improvement in human optical quality between infant and adult. Overall, in chick and monkey, angular blur improves at a rate faster than that predicted by the constant linear blur model, implying that linear retinal blur due to HOA decreases with age. On the other hand, in chick, angular blur due to third-order aberrations decreased at a rate predicted by the constant linear blur model. Growth changes in retinal blur due to HOA are species dependent but can be better understood by comparison with the new model predictions.

The degree of polarization (DOP) of the light reflected from the optic nerve head has been assessed by means of a polarimetric scanning laser ophthalmoscope as a function of the age of the participants. Four fundus images corresponding to independent polarization states in the recording pathway were used to compute the spatially-resolved DOP. This was not uniform across the optic nerve head and depended on both the location and the participant's age. Along a peripapillary annulus the DOP followed a double-peak pattern. Moreover, the values along this annulus decreased significantly with increasing age. This depolarization appears to originate in part in the retinal nerve fiber layer. Detailed age-dependent knowledge of the ocular depolarization properties may help to improve clinical diagnosis of the retinal nerve fiber layer.

Objective: Patterns of adult attachment affect physical health and yet are unfamiliar to many clinicians. The purpose of this review was to derive descriptions of prototypic patterns of adult attachment that are relevant to health care., Methods: Observations from attachment research using diverse methods to measure adult attachment were reviewed. A synthetic approach was used to integrate these observations into coherent descriptions of prototypic patterns of attachment., Results: Four patterns of adult attachment (secure, preoccupied, dismissing and fearful) are distinguished by prototypic patterns in intimate relationships, affect regulation, use of social support, trait descriptors, mentalization and narrative coherence. These patterns are linked to health care relationships and health outcomes., Conclusion: Prototypic descriptions of patterns of adult attachment may guide clinicians in appreciating individual differences in interpersonal style that affect the health of patients.

Objective: Family practitioners are significant providers of mental health care and routinely report difficulty acquiring timely support in this area. The Collaborative Mental Health Care Network assembled groups of family practitioners and provided them with mental health practitioner mentors. This article addresses communication in the Network, its effect on family practitioners, and the role e-mail plays., Methods: This descriptive study utilizes two sources of data: a quality assurance survey administered to family practitioners in the Network and a sampling of e-mail correspondence between family practitioners and mental health and addiction mentors, examined qualitatively., Results: Family practitioners in the Network requested consultation on pharmacotherapy (53%), psychotherapy (34%), treatment review (27%), and diagnosis (24%). Satisfaction with the Network was high, with 88% of family practitioners reporting an improvement in ability to provide mental health care. E-mail analysis suggests that mentors convey information directly and indirectly and that a knowledge hierarchy, but not a power hierarchy, develops. The trusted relationship between the mentee and mentor is an important context for effective education., Conclusion: This model of mentoring is highly satisfactory to family practitioners and correlates with increased confidence in caring for patients with mental health issues. E-mail is a promising strategy for effective feedback and support between family practitioners and specialists.

Purpose: Autofluorescence fundus imaging using an adaptive optics scanning laser ophthalmoscope (AOSLO) allows for imaging of individual retinal pigment epithelial (RPE) cells in vivo. In this study, the potential of retinal damage was investigated by using radiant exposure levels that are 2 to 150 times those used for routine imaging., Methods: Macaque retinas were imaged in vivo with a fluorescence AOSLO. The retina was exposed to 568- or 830-nm light for 15 minutes at various intensities over a square (1/2) degrees per side. Pre- and immediate postexposure images of the photoreceptors and RPE cells were taken over a 2 degrees field. Long-term AOSLO imaging was performed intermittently from 5 to 165 days after exposure. Exposures delivered over a uniform field were also investigated., Results: Exposures to 568-nm light caused an immediate decrease in autofluorescence of RPE cells. Follow-up imaging revealed either full recovery of autofluorescence or long-term damage in the RPE cells at the exposure. The outcomes of AOSLO exposures and uniform field exposures of equal average power were not significantly different. No effects from 830-nm exposures were observed., Conclusions: The study revealed a novel change in RPE autofluorescence induced by 568-nm light exposure. Retinal damage occurred as a direct result of total average power, independent of the light-delivery, Method: Because the exposures were near or below permissible levels in laser safety standards, these results suggest that caution should be used with exposure of the retina to visible light and that the safety standards should be re-evaluated for these exposure conditions.

Childhood adversity alters the relational world of the child and inhibits the development of secure attachment bonds. The purpose of this article is to survey recent evidence that attachment insecurity has the potential to impair physical health throughout the lifespan. It is proposed that attachment insecurity contributes to disease risk through a range of mechanisms which include (1) disturbances in arousal and recovery within physiological systems that respond to stress; (2) physiological links between the mediators of social relationships, stress, and immunity; (3) links between relationship style and various health behaviors; and (4) disease risk factors that serve as external regulators of dysphoric affect, such as nicotine and alcohol. The evidence for these mechanisms, particularly the evidence that has accumulated since the model was first proposed in 2000, is presented and discussed.

Background: The alpha-EEG anomaly during sleep, originally associated with chronic pain, is noted in several psychiatric and medical conditions and is also present in some normal subjects. The exact significance of the alpha-EEG anomaly is uncertain, but it has been suggested to be a nonspecific response to a variety of noxious stimuli. We propose that attachment insecurity, which is often associated with a state of hypervigilance during wakefulness, may be associated with the alpha-EEG anomaly during sleep., Methods: Thirty one consecutive patients referred to a Sleep Disorders Clinic for clinical assessment of sleep complaints underwent standard polysomnographic recording. The degree of alpha activity in polysomnographs was scored visually according to standard criteria. Attachment insecurity was measured with the Experience in Close Relationships - Revised questionnaire., Results: Attachment anxiety was significantly associated with the proportion of sleep in which alpha waves were present (df = 1, F = 5.01, p = 0.03). The relationship between the alpha-EEG anomaly and attachment anxiety was not explained by the distribution of sleep and mood diagnoses, medications, anxiety symptoms or depression symptoms., Conclusion: Interpersonal style in close relationships may be related to sleep physiology. Further research to determine the nature of the relationship between attachment, sleep and other factors that are related to each of these, such as a history of personal adversity, is warranted.

Objective: Little has been written about teaching consultation-liaison inpatient psychotherapy to residents or other trainees., Method: Resident interviews at completion of consultation-liaison training identified learning needs. In response, the authors created a seminar series and modified it reiteratively eight times., Results: In this approach, the primary task of consultation-liaison psychotherapy assessment is to determine the success of a patient's adaptation to hospitalization, and to identify obstacles to adaptation. Selected determinants of adaptation are reviewed and organized as individual factors and intrahospital and extrahospital environmental factors. This provides a viable means of organizing and integrating disparate bodies of knowledge for the student., Conclusions: The teaching model awaits empirical validation as a tool that enhances teaching and patient care outcomes.

Aurora A is a serine/threonine protein kinase essential for normal mitotic progression. Aberrant increased expression of Aurora A, which occurs frequently in human cancers, results in abnormal mitoses leading to chromosome instability and possibly tumorigenesis. Consequently, Aurora A has received considerable attention as a potential target for anticancer therapeutic intervention. Aurora A coordinates several essential mitotic activities through phosphorylation of a variety of proteins, including TACC3, which modulates microtubule stabilization of the mitotic spindle. Recent studies identified a conserved serine in Xenopus (Ser(626)) and Drosophila (Ser(863)) TACC3 orthologues that is phosphorylated by Aurora A. We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner. Furthermore, oral administration of MLN8054 to nude mice bearing HCT-116 human tumor xenografts caused a dose-dependent mislocalization of TACC3 away from spindle poles that correlated with tumor growth inhibition. As TACC3 localization to mitotic spindles depends on Aurora A-mediated phosphorylation, quantifying TACC3 mislocalization represents a novel pharmacodynamic approach for measuring Aurora A activity in cancer patients treated with inhibitors of Aurora A kinase.

We quantify the effects on scanning laser ophthalmoscope image quality of controlled amounts of scattered light, confocal pinhole diameter, and age. Optical volumes through the optic nerve head were recorded for a range of pinhole sizes in 12 subjects (19-64 years). The usefulness of various overall metrics in quantifying the changes in fundus image quality is assessed. For registered and averaged images, we calculated signal-to-noise ratio, entropy, and acutance. Entropy was best able to distinguish differing image quality. The optimum confocal pinhole diameter was found to be 50 microm (on the retina), providing improved axial resolution and image quality under all conditions.

We present a polarimetric technique to improve fundus images that notably simplifies and extends a previous procedure [Opt. Lett.27, 830 (2002)]. A generator of varying polarization states was incorporated into the illumination path of a confocal scanning laser ophthalmoscope. A series of four images, corresponding to independent incoming polarization states, were recorded. From these images, the spatially resolved elements of the top row of the Mueller matrix were computed. From these elements, images with the highest and lowest quality (according to different image quality metrics) were constructed, some of which provided improved visualization of fundus structures of clinical importance (vessels and optic nerve head). The metric values were better for these constructed images than for the initially recorded images and better than averaged images. Entropy is the metric that is most sensitive to differences in the image quality. Improved visualization of features could aid in the detection, localization, and tracking of ocular disease and may be applicable in other biomedical imaging.

Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.

Introduction: Studies of psychological factors in ulcerative colitis (UC) have produced inconsistent findings. This study sought to determine whether perinuclear antineutrophil cytoplasmic antibody (pANCA) demarcates subtypes which differ with respect to psychobiological interactions., Methods: In 148 outpatients with UC, the strength of the relationship between current UC disease activity and psychological distress was assessed. pANCA was determined by ELISA and immunofluorescence, disease activity was determined by symptoms, physical examination, and endoscopy using the St. Mark's index, and depressive symptoms and health anxiety were measured with self-report scales. Pearson correlations between disease activity and depressive symptoms and between disease activity and health anxiety were calculated., Results: In 74 pANCA negative subjects, the relationship between disease activity and measures of psychological distress was significant for disease activity-depression (partial correlation = 0.48, p < 0.001) and for disease activity-health anxiety (partial correlation = 0.64, p < 0.001), whereas in 74 pANCA positive subjects, no relationships were found (disease activity-depression: partial correlation = 0.18, p= 0.14; disease activity-health anxiety: partial correlation = 0.20, p= 0.09). The differences in the strength of correlation between pANCA positive and pANCA negative subjects were statistically significant for both disease activity-depression (z = 2.0, p= 0.02) and activity-health anxiety (z = 3.3, p < 0.001)., Conclusions: pANCA status demarcates psychobiologically distinct subtypes of UC, such that the absence of pANCA is associated with greater psychobiological interaction. These findings have implications for clinical care and understanding the pathophysiology of intestinal inflammation.

Purpose: In this initial study, we model the impact of crystalline lens movement and tilt, which we postulate are a potential consequence of scleral expansion surgery (SES). We demonstrate the possibility that these lead to an improvement in near vision with no concurrent restoration of lens accommodative function. With the implantation of scleral expansion bands (SEB), Schachar predicts an increase in the amplitude of accommodation not observed objectively. We postulate that the SEB implants cause the crystalline lens to be shifted forward and become misaligned. Using mathematical models of the optics of the human eye, we assess the effects of our postulate on the power of the eye, the depth of field, optical aberrations, and the appearance of the horizontal retinoscopic reflex., Methods: Using anatomically based models of the human eye, the postulated effects of SES are theoretically modeled and optically analyzed in Code V for unintentional lens anterior movement, tilts, and decentrations of up to 1 mm, +/- 3 degrees , and +/- 0.3mm, respectively. The transverse aberrations are calculated before and after SES. Because it has been reported that the appearance of the retinoscopic reflex is consistent with the presence of excess aberrations, we also predict the appearance of the one-dimensional retinoscopic reflex for our models. The change in refractive error is also determined. RESULTS.: Unintentional lens shift, tilt, and decentration, as might occur as a result of SES surgery, would result in an increase in the total power of the eye along with an increase in asymmetric aberrations and little change in symmetric aberrations. The calculated appearances of the retinoscopic reflexes pre- and postsurgery are consistent with observations in the literature., Conclusions: Scleral expansion surgery could produce an improvement in near vision through an unintentional anterior displacement of the crystalline lens in combination with excess tilts and decentrations rather than as a result of a restoration of lens accommodation. There is a need for measurements and further analysis of the optical and visual properties of SES patients postsurgery.

Understanding the control of eye growth may lead to the prevention of nearsightedness (myopia). Chicks develop refractive errors in response to defocusing lenses by changing the rate of eye elongation. Changes in optical image quality and the optical signal in lens compensation are not understood. Monochromatic ocular aberrations were measured in 16 chicks that unilaterally developed myopia in response to unilateral goggles with -15D lenses and in 6 chicks developing naturally. There is no significant difference in higher-order root mean square aberrations (RMSA) between control eyes of the goggled birds and eyes of naturally developing chicks. Higher-order RMSA for a constant pupil size exponentially decreases in the chick eye with age more slowly than defocus. In the presence of a defocusing lens, the exponential decrease begins after day 2. In goggled eyes, asymmetric aberrations initially increase significantly, followed by an exponential decrease. Higher-order RMSA is significantly higher in goggled eyes than in controls. Equivalent blur, a new measure of image quality that accounts for increasing pupil size with age, exponentially decreases with age. In goggled eyes, this decrease also occurs after day 2. The fine optical structure, reflected in higher-order aberrations, may be important in understanding normal development and the development of myopia.

Objective: The purpose of this study was to test predicted relationships between adult attachment and stress using subjective and physiological measures., Methods: Sixty-seven healthy adults completed measures of adult attachment and perceived chronic stress. Subjective stress and the high-frequency (HF) and low-frequency (LF) spectral bandwidths of heart rate variability (HRV) were measured during a standardized stress protocol., Results: Attachment anxiety is associated with between-subject differences in chronic perceived stress (P=.001) and subjective acute stress (P=.01). There is a main effect of attachment avoidance on between-subject differences in HF HRV (P=.004). Attachment avoidance is inversely associated with HF HRV, independent of age and variability in respiration., Conclusion: Attachment anxiety is associated with self-reported distress. Attachment avoidance is inversely associated with HF HRV, a marker of vagal influence on cardiac activity, but is not associated with subjective stress.

Purpose: To model the feasibility of an accommodating intraocular lens (IOL) that allows near vision by means of an anterior translation within the capsular bag., Setting: University of Waterloo, Waterloo, Ontario, Canada., Methods: Model eyes were constructed and analyzed based on experimental data using Code V, a computerized optical design tool. The potential near vision of IOLs of different powers was calculated as they were moved anteriorly within the capsular bag. The conditions under which a spherical lens performs well and when an aspheric design should be considered were determined., Results: Accommodation (the dioptric change from the far to the near point) varies linearly with lens movement and is sensitive to corneal and IOL powers. Simple equations were derived and accurately predicted induced accommodation. Retinal image quality varies significantly with pupil size and IOL power. However, image quality is minimally affected by the amount of induced accommodation., Conclusions: From an optical standpoint accommodation with adequate image quality can be achieved by anterior movement of a spherical IOL within the capsular bag.

Background: Among people with ulcerative colitis, depression occurs more frequently when inflammation is active. We hypothesized that individual differences in interpersonal style affect the risk that active disease will be accompanied by depressive symptoms., Methods: In this study, disease activity, depressive symptoms, and 2 dimensions of interpersonal style, attachment anxiety and attachment avoidance, were measured in 146 ulcerative colitis outpatients at time 1 and in 99 of these patients at a second time-point, 7 to 37 months later. Test-retest correlations of attachment anxiety (r = 0.83, P < 0.001) and attachment avoidance (r = 0.76, P < 0.001) confirmed that these dimensions are stable., Results: There was a stepwise increase in the correlation between time 2 disease activity and depression from the lowest tercile of attachment anxiety (r = 0.00, P = 0.99), through the middle tercile (r = 0.36, P = 0.05), to the highest tercile (r = 0.52, P = 0.002). For attachment avoidance, disease activity and depression were only significantly correlated in the highest tercile (r = 0.49, P = 0.005)., Conclusions: Attachment anxiety meets all tested criteria as a moderator of the relationship between disease activity and depressive symptoms. Further attention to interpersonal style as a moderator of depressive risk in ulcerative colitis is warranted.

Melastatin 1 (MLSN1), originally identified as melanoma metastasis suppressor, represents a TRPM subfamily of transient receptor potential (TRP) proteins which serve diverse biological roles in a wide variety of cell types. Down-regulation of MLSN1 expression in human cutaneous melanoma, as indicated by in situ hybridization, appears to be a prognostic marker for melanoma metastasis. However, the exact physiological function(s) of MLSN1, the mechanism(s) involved in the regulation of its expression and its role in melanoma tumour progression are not yet clear. In this study, we identified a 654 bp upstream sequence of MLSN1, containing four E boxes (E1-E4), including an 11 bp M box (E4), that is sufficient for melanocyte-specific transcription and activation by the melanocyte transcription factor MITF (a bHLH-zip factor). Deletion analysis showed that the two distal E boxes (E3 and E4) in the MLSN1 promoter are required for both its activation by MITF and its constitutive activity in melanoma cells. Western blot analysis using polyclonal rabbit anti-human MLSN1 antibodies identified several polypeptides, presumably generated by both alternative splicing of MLSN1 messenger RNA (mRNA) and proteolytic cleavage, in both melanocytes and metastatic melanoma cells. Thus, multiple mechanisms appear to regulate MLSN1 expression in melanocytes and melanoma cells.

Objective: The object of this study was to evaluate the evidence linking attachment insecurity to illness. Attachment theory describes lifelong patterns of response to threat that are learned in the interaction between an infant and his or her primary caregiver. Despite its biopsychosocial domain, attachment theory has only recently been applied to psychosomatic medicine., Method: MEDLINE and PsychInfo databases were searched from 1966 to 2000 for English language papers with key words "attachment" and "object relations." Papers and their cited references were reviewed if they were directly related to physical illness, symptoms, or physiology. A hypothetical causal model was developed., Results: Direct and indirect evidence from survey studies supports an association between attachment insecurity and disease. Animal studies and human experiments suggest that attachment contributes to individual differences in physiological stress response. There is also less robust support for insecure attachment leading to symptom reporting and to more frequent health risk behaviors, especially substance use and treatment nonadherence. Evidence supports the prediction from attachment theory that the benefits of social support derive more from attachment relationships than nonattachment relationships., Conclusions: Although the available data are suggestive rather than conclusive, the data can be organized into a model that describe attachment insecurity leading to disease risk through three mechanisms. These are increased susceptibility to stress, increased use of external regulators of affect, and altered help-seeking behavior. This model warrants further prospective investigation.