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Retinal vascular basement membrane (BM) thickening is an early structural abnormality of diabetic retinopathy (DR). Recent studies suggest that BM thickening contributes to the DR pathological cascade; however, much remains to be elucidated about the exact mechanisms by which BM thickening develops and subsequently drives other pathogenic events in DR. Therefore, we undertook a systematic analysis to understand how human retinal microvascular endothelial cells (hRMEC) and human retinal pericytes (hRP) change their expression of key extracellular matrix (ECM) constituents when treated with diabetes-relevant stimuli designed to model the three major insults of the diabetic environment: hyperglycemia, dyslipidemia, and inflammation. TNFα and IL-1β caused the most potent and consistent changes in ECM expression in both hRMEC and hRP. We also demonstrate that conditioned media from IL-1β-treated human Müller cells caused dose-dependent, significant increases in collagen IV and agrin expression in hRMEC. After narrowing our focus to inflammation-induced changes, we sought to understand how ECM deposited by hRMEC and hRP under inflammatory conditions affects the behavior of naïve hRMEC. Our data demonstrated that diabetes-relevant alterations in ECM composition alone cause both increased adhesion molecule expression by and increased peripheral blood mononuclear cell (PBMC) adhesion to naïve hRMEC. Taken together, these data demonstrate novel roles for inflammation and pericytes in driving BM pathology and suggest that inflammation-induced ECM alterations may advance other pathogenic behaviors in DR, including leukostasis.

Blood–retinal barrier (BRB) dysfunction represents one of the most significant changes occurring during diabetic retinopathy. We set up a high-reproducible human-based in vitro BRB model using retinal pericytes, retinal astrocytes, and retinal endothelial cells in order to replicate the human in vivo environment with the same numerical ratio and layer order. Our findings showed that high glucose exposure elicited BRB breakdown, enhanced permeability, and reduced the levels of junction proteins such as ZO-1 and VE-cadherin. Furthermore, an increased expression of pro-inflammatory mediators (IL-1β, IL-6) and oxidative stress-related enzymes (iNOS, Nox2) along with an increased production of reactive oxygen species were observed in our triple co-culture paradigm. Finally, we found an activation of immune response-regulating signaling pathways (Nrf2 and HO-1). In conclusion, the present model mimics the closest human in vivo milieu, providing a valuable tool to study the impact of high glucose in the retina and to develop novel molecules with potential effect on diabetic retinopathy.

Background Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. Methods The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples ( N  = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors’ and partners’ Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. Discussion The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that—if found efficacious—will improve access to much needed specialty care in prostate cancer survivorship. Trial registration Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

The envelope of straight lines normal to a plane curve \\documentclass{article}\\pagestyle{empty}\\begin{document}$C$\\end{document} is its evolute; the envelope of lines tangent to \\documentclass{article}\\pagestyle{empty}\\begin{document}$C$\\end{document} is the original curve, together with the entire tangent line at each inflexion of \\documentclass{article}\\pagestyle{empty}\\begin{document}$C$\\end{document} . We introduce some standard techniques of singularity theory and use them to explain how the first of these envelopes turns into the second, as the (constant) angle between the set of lines forming the envelope and the set of tangents to \\documentclass{article}\\pagestyle{empty}\\begin{document}$C$\\end{document} changes from \\documentclass{article}\\pagestyle{empty}\\begin{document}$\\frac{1}{2}\\pi$\\end{document} to 0. In particular, we explain how cusps disappear and what happens at inflexions, where the evolute goes to infinity. We also study the family of “wavefronts” or “parallels” associated with these envelopes.

Prescription-related opioid misuse, especially in chronic pain populations, is an ongoing problem and is related to increased mortality. The purpose of this study was to assess the utility of two restructured scales of the MMPI-2-RF: the Personality Psychopathology Five (PSY-5-RF) and the Higher-Order Scales to determine which of their subscales may be beneficial for identifying the risk of opioid misuse in a chronic pain population. A sample of 136 patients with chronic disabling occupational musculoskeletal disorders completed the MMPI-2-RF and the Current Opioid Misuse Measure (COMM) upon admission to a functional restoration program. The PSY-5-RF and H–O subscales were correlated with the baseline COMM scores. Correlation analyses, ROC curve analyses, and multiple binary logistic regression models were developed to determine which subscales were most associated with elevated COMM scores. The results of the regression analyses suggest that Scale elevations on two of the PSY-5-RF Scales and two Higher-Order Scales of the MMPI-2-RF demonstrated significant associations with elevated COMM scores, thus exhibiting the utility of these subscales in identifying the risk of opioid misuse among chronic pain patients. These findings are clinically meaningful in underscoring the importance of identifying specific personality traits as potential predictors of opioid misuse, and identifying those at risk through careful screening. Clinical implications based on each of the PSY-5-RF and H–O scales significantly associated with elevated COMM scores are discussed.

Chronic hyperglycemia is thought to be the major stimulator of retinal dysfunction in diabetic retinopathy (DR). Thus, many diabetes-related systemic factors have been overlooked as inducers of DR pathology. Cell culture models of retinal cell types are frequently used to mechanistically study DR, but appropriate stimulators of DR-like factors are difficult to identify. Furthermore, elevated glucose, a gold standard for cell culture treatments, yields little to no response from many primary human retinal cells. Thus, the goal of this project was to demonstrate the effectiveness of the free fatty acid, palmitic acid and compare its use alone and in combination with elevated glucose as a stimulus for human Müller cells, a retinal glial cell type that is activated early in DR pathogenesis and uniquely responsive to fatty acids. Using RNA sequencing, we identified a variety of DR-relevant pathways, including NFκB signaling and inflammation, intracellular lipid signaling, angiogenesis, and MAPK signaling, that were stimulated by palmitic acid, while elevated glucose alone did not significantly alter any diabetes-relevant pathways. Co-treatment of high glucose with palmitic acid potentiated the expression of several DR-relevant angiogenic and inflammatory targets, including PTGS2 (COX-2) and CXCL8 (IL-8).

Issue Title: Special Issue on Computational Vision at Brown University In this paper we explore the local geometry of the medial axis (MA) and shocks (SH), and their structural changes under deformations, by viewing these symmetries as subsets of the symmetry set (SS) and present two results. First, we establish that the local form of the medial axis must generically be one of three cases, which we denote by the A notation explained below (here, it merely serves as a reference to sections of the paper): endpoints (A^sub 3^), interior points (A^sub 1^^sup 2^), and junctions (A^sub 1^^sup 3^). The local form of shocks is then derived from a sub-classification of these points into six types. Second, we address the (classical) instabilities of the MA, i.e., abrupt changes in the representation arising from slight changes in shape, as when a new branch appears with slight protrusion. The identification of these 'transitions' is clearly crucial in robust object recognition. We show that for the medial axis only two such instabilities are generically possible: (i) when four branches come together (A^sub 1^^sup 4^), and (ii) when a new branch grows out of an existing one (A^sub 1^ A^sub 3^). Similarly, there are six cases of shock instabilities, derived as sub-classifications of the MA instabilities. We give an explicit example of a dent forming in an ellipse where many of the transitions described in the paper can be seen to appear.[PUBLICATION ABSTRACT]

Health care professionals (HCPs) working collaboratively can improve patient outcomes and also increase their understanding of each other's professional roles. This descriptive study aimed to explore dental hygienists' perceptions of collaboration with dentists and intraprofessional educational (IntraPE) experiences. A convenience sampling method was used to assess DHs perceptions of collaboration with dentists using the Interprofessional Collaboration Scale (ICS), a validated scale that measures perceptions of communication, accommodation, and isolation among HCPs. One open-ended question was added to explore IntraPE. Demographics, work characteristics and responses from the ICS were analyzed using frequency, mean, standard deviation, Pearson's correlation, t-test, ANOVA, and multivariable regression. Responses from the open-ended question were transcribed, organized, and coded. Themes were identified using the Delve Qualitative Analysis Tool. Of the 264 participants, the average age was 38.9, and most identified as female (98.9%). Data analysis revealed that DHs had positive perceptions of collaboration with dentists. Significant relationships were found between ICS factor accommodation and the average number of patients treated per day (r = -0.242, <0.001), dentists' age (r = -.145, <0.05). Isolation showed a significant negative correlation with the average number of patients treated per day (r = -0.156, <0.05). Most reported having no opportunities for IntraPE education experiences with dentists. Five categories of themes were identified from the open-ended question: shared academic setting, clinic dentist, externships, desire for more shared learning, and shared patient experiences. Dental hygienists in this study had an overall more positive than negative perception of collaboration with dentists. Dental and dental hygiene programs should focus on intraprofessional education experiences to continue to enhance collaboration.

En 1860, une collection d'objets issus des jardins impériaux de Chine (Yuánmingyuán) est arrivée à Paris. La saisie de ces artefacts, pillés à titre punitif à la fin de l'expédition franco-britannique en Chine, lors de la seconde guerre de l'opium, représentait une véritable conquête symbolique de la Chine et marqua un renouveau impérial français dans le Pacifique. Ces objets ont d'abord été exposés au public avant d‘être intégrés aux insignes du Second Empire. À travers l'institution du pillage, la démocratisation de la consommation et le legs royal, les relations franco-chinoises basculaient ainsi d'un système fondé sur le partenariat vers un modèle explicitement impérial, un modèle qui situait désormais la France comme l'héritière d'un empire universalisant s‘étendant de Rome à l'Extrême-Orient. In 1860, a collection of objects from the Chinese imperial gardens (Yuánmíngyuán) arrived in Paris. The artifacts had been pillaged as a punitive measure at the end of the Franco-British expedition to China during the Second Opium War. They were put on public display before being integrated into the regalia of the Second Empire. The ritual of pillage, popular consumption, and royal reimagining transformed the French relationship with China from partnership into an explicitly imperial paradigm. The seizure and display of objects from the Yuánmíngyuán attested to the symbolic conquest of China, and signaled a French imperial reawakening in the Pacific. It set the tone for an aggressive French occupation of other Asian territories, and asserted that the French were descendants of a universalizing empire ranging from Rome to the Far East.