Involuntary psychiatric hospitalisation, stigma stress and recovery: a 2-year study

AIMS Compulsory admission can be experienced as devaluing and stigmatising by people with mental illness. Emotional reactions to involuntary hospitalisation and stigma-related stress may affect recovery, but longitudinal data are lacking. We, therefore, examined the impact of stigma-related emotional reactions and stigma stress on recovery over a 2-year period. METHOD Shame and self-contempt as emotional reactions to involuntary hospitalisation, stigma stress, self-stigma and empowerment, as well as recovery were assessed among 186 individuals with serious mental illness and a history of recent involuntary hospitalisation. RESULTS More shame, self-contempt and stigma stress at baseline were correlated with increased self-stigma and reduced empowerment after 1 year. More stigma stress at baseline was associated with poor recovery after 2 years. In a longitudinal path analysis more stigma stress at baseline predicted poorer recovery after 2 years, mediated by decreased empowerment after 1 year, controlling for age, gender, symptoms and recovery at baseline. CONCLUSION Stigma stress may have a lasting detrimental effect on recovery among people with mental illness and a history of involuntary hospitalisation. Anti-stigma interventions that reduce stigma stress and programs that enhance empowerment could improve recovery. Future research should test the effect of such interventions on recovery

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

AbstractProper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes

Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure

Purpose: Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable. Methods: The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable. Results: Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups. Conclusions: Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients. Translational Relevance: Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies

So what do we really mean when we say that systems biology is holistic?

Background: An old debate has undergone a resurgence in systems biology: that of reductionism versus holism. At least 35 articles in the systems biology literature since 2003 have touched on this issue. The histories of holism and reductionism in the philosophy of biology are reviewed, and the current debate in systems biology is placed in context. Results: Inter-theoretic reductionism in the strict sense envisaged by its creators from the 1930s to the 1960s is largely impractical in biology, and was effectively abandoned by the early 1970s in favour of a more piecemeal approach using individual reductive explanations. Classical holism was a stillborn theory of the 1920s, but the term survived in several fields as a loose umbrella designation for various kinds of anti-reductionism which often differ markedly. Several of these different anti-reductionisms are on display in the holistic rhetoric of the recent systems biology literature. This debate also coincides with a time when interesting arguments are being proposed within the philosophy of biology for a new kind of reductionism. Conclusions: Engaging more deeply with these issues should sharpen our ideas concerning the philosophy of systems biology and its future best methodology. As with previous decisive moments in the history of biology, only those theories that immediately suggest relatively easy experiments will be winners

Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma

The precise transcriptional regulation of gene expression is essential for vertebrate development, but the role of posttranscriptional regulatory mechanisms is less clear. Cytoplasmic RNA granules (RGs) function in the posttranscriptional control of gene expression, but the extent of RG involvement in organogenesis is unknown. We describe two human cases of pediatric cataract with loss-of-function mutations in TDRD7 and demonstrate that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins (RNPs). TDRD7 coimmunoprecipitates with specific lens messenger RNAs (mRNAs) and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function. These findings demonstrate a role for RGs in vertebrate organogenesis

System approaches of Weiss and Bertalanffy and their relevance for systems biology today

System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or order, is equally important as the dynamics within systems and the interplay between different levels from molecules over cells to organisms. They also called for taking the intrinsic activity of living systems and the conservation of system states into account. We compare these notions with today's systems biology, which is often a bottom-up approach from molecular dynamics to cellular behaviour. We conclude that bringing together the early heuristics with recent formalisms and novel experimental set-ups can lead to fruitful results and understanding. © 2011 Elsevier Ltd.Revie