Models of Recovery in Mental Illness

Background. Discourse on the possibility of recovery from serious mental illness has become increasingly dominant among mental health professionals. Mental health recovery has been conceptualized variously by researchers, practitioners, policy-makers, and persons with mental illness. Several systematic reviews have synthesized the experience of recovery from the perspective of persons with mental illness, and offer different models of recovery. This proposed overview aims to summarize the methodological characteristics of systematic reviews on mental health recovery and to synthesize models of recovery from the perspective of persons with mental illness. Design and analysis. The authors will use systematic review methods to identify and synthesize systematic reviews on the phenomenon of recovery in mental illness. A pre-specified search strategy will be used to search academic databases and libraries of the Campbell Collaboration, Cochrane Collaboration, and Joanna Briggs Institute for published and gray literature. Two authors will independently screen titles/abstracts and full texts. Authors will pilot the data extraction form before independently extracting data and appraising study quality. Reflexive thematic analysis, informed by a hermeneutic orientation towards the included texts, will be used to synthesize models of recovery presented in eligible studies. Discussion. This overview will synthesize systematic review evidence on consumer perspectives of mental health recovery. Findings could inform future research, clinical practice, and policy by elucidating similarities and differences in recovery models across demographic or diagnostic categories and identifying how environmental, interpersonal, and intrapersonal factors contribute to recovery. Systematic review registration: PROSPERO CRD4201914297

Struggling to Meditate: Contextualising Integrated Treatment of Traumatised Tibetan Refugee Monks

As a result of the recent resurgence of violence in the Tibetan Autonomous Region, the Boston Center for Refugee Health and Human Rights has an increased patient demographic: Tibetan refugee monks. Diagnosed by their amchis (traditional healers) as having a srog-rLung (life-wind) imbalance and presenting with posttraumatic stress disorder (PTSD), they struggle with their contemplative meditation, which—as a central focus of their daily lives— normally comes with ease. In this article, we consider the pathological implications of the highly relevant Buddhist context for this dual diagnosis. Specifically, we contextualize the classification of ‘religious impairment’ as well as the significance of ongoing persecution of the devoutly religious for trauma therapy. We then draw upon spiritually oriented Eastern therapies as well as the confluence of specific paradigmatic practices to properly address these intricacies in devising an effective holistic healing approach to the dual PTSD/srog-rLung diagnosis

Stat3 isoforms, α and β, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3β mapping to its unique C-terminal end

Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, alpha (p92) and beta (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3alpha is deleted in Stat3beta and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3alpha and Stat3beta into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3alpha or GFP-Stat3beta revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3alpha or GFP-Stat3beta. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3alpha, it was >180 min for GFP-Stat3beta. Furthermore, although the intranuclear mobility of GFP-Stat3alpha was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP-Stat3beta in unstimulated cells was slower than that of GFP-Stat3alpha in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3beta eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3beta

Quantitative Chemically-Specific Coherent Diffractive Imaging of Buried Interfaces using a Tabletop EUV Nanoscope

Characterizing buried layers and interfaces is critical for a host of applications in nanoscience and nano-manufacturing. Here we demonstrate non-invasive, non-destructive imaging of buried interfaces using a tabletop, extreme ultraviolet (EUV), coherent diffractive imaging (CDI) nanoscope. Copper nanostructures inlaid in SiO2 are coated with 100 nm of aluminum, which is opaque to visible light and thick enough that neither optical microscopy nor atomic force microscopy can image the buried interfaces. Short wavelength (29 nm) high harmonic light can penetrate the aluminum layer, yielding high-contrast images of the buried structures. Moreover, differences in the absolute reflectivity of the interfaces before and after coating reveal the formation of interstitial diffusion and oxidation layers at the Al-Cu and Al-SiO2 boundaries. Finally, we show that EUV CDI provides a unique capability for quantitative, chemically-specific imaging of buried structures, and the material evolution that occurs at these buried interfaces, compared with all other approaches.Comment: 12 pages, 8 figure

Androgen Receptor Mutations Associated with Androgen Insensitivity Syndrome: A High Content Analysis Approach Leading to Personalized Medicine

Androgen insensitivity syndrome (AIS) is a rare disease associated with inactivating mutations of AR that disrupt male sexual differentiation, and cause a spectrum of phenotypic abnormalities having as a common denominator loss of reproductive viability. No established treatment exists for these conditions, however there are sporadic reports of patients (or recapitulated mutations in cell lines) that respond to administration of supraphysiologic doses (or pulses) of testosterone or synthetic ligands. Here, we utilize a novel high content analysis (HCA) approach to study AR function at the single cell level in genital skin fibroblasts (GSF). We discuss in detail findings in GSF from three historical patients with AIS, which include identification of novel mechanisms of AR malfunction, and the potential ability to utilize HCA for personalized treatment of patients affected by this condition

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BackgroundScreening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions.MethodsOne hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information.ResultsPCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients.ConclusionWhile our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics

Feed-Forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

SummaryWe compared transcriptomes of terminally differentiated mouse 3T3-L1 and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3-L1. It is interesting that AR induction corresponded with dexamethasone activation of the glucocorticoid receptor (GR); however, when exposed to the differentiation cocktail required for adipocyte maturation, AR adopted an antagonist conformation and was transcriptionally repressed. To further explore effectors within the cocktail, we applied an image-based support vector machine (SVM) classification scheme to show that adipocyte differentiation components inhibit AR action. The results demonstrate human adipocyte differentiation, via GR activation, upregulates AR but also inhibits AR transcriptional activity

Cancer-Preventive Rexinoid Modulates Neutral Lipid Contents of Mammary Epithelial Cells through a Peroxisome Proliferator- Activated Receptor ␥-Dependent Mechanism

ABSTRACT Synthetic rexinoids effectively suppress both estrogen receptor-positive and estrogen receptor-negative mammary tumors in animal models, which makes them prime candidates for a novel class of cancer-preventive agents. When used in combination with chemotherapy for non-small-cell lung cancer, the rexinoid bexarotene was most effective for patients who developed hypertriglyceridemia as a side effect. Although serum triglycerides originate from the liver, the effect of bexarotene on lipogenesis in breast epithelial cells is not known. Gene expression studies with normal mammary epithelial cells indicated that rexinoids modulate lipid metabolism, particularly enzymes involved in triglyceride synthesis. High-content analysis revealed dose-dependent accumulation of neutral lipids within adipocyte differentiation-related protein-associated cytoplasmic lipid droplets after long-term bexarotene treatment. Bexarotene also induced mRNA and protein levels for peroxisome proliferator-activated receptor (PPAR) ␥, whereas selective knockdown of PPAR␥ attenuated the induction of both lipid droplets and adipocyte differentiation-related protein. Pharmacological activation of PPAR␥, but not PPAR␣ or retinoic acid receptors, effectively induced lipid accumulation. Furthermore, the combination of the PPAR␥ agonist rosiglitazone with bexarotene synergistically suppressed the growth of human mammary epithelial cells and revealed a strong, nonlinear, inverse correlation of cell growth with lipid droplet accumulation in the cell population. These findings indicate that rexinoids activate a lipogenic program in mammary epithelial cells through a retinoid X receptor/PPAR␥-mediated mechanism. It is noteworthy that combining low doses of bexarotene with the PPAR␥ agonist rosiglitazone provides effective growth suppression of mammary epithelial cells, potentially dissociating systemic adverse effects associated with standard bexarotene treatment from the antiproliferative effects on mammary epithelium

Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted