Correction to: Assessment of Psychosocial Functioning in a Large Cohort of Patients with Schizophrenia

Psychiatric Quarterly -     

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes,Australia

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.     

Catabolic Properties of Microdissected Human Endosteal Bone Lining Cells

Bone lining cells cover >80% of endosteal surfaces of human cancellous bone. Current research assigns to them a dual role: (1) as a biological membrane regulating exchange of substrates between the bone fluid compartment and the extracellular fluid of bone marrow and (2) as a signaling link between the osteocytic network as mechanical receptor and the osteoclastic cell pool for local induction of bone resorption. Furthermore, a catabolic role has been considered. We therefore examined the presence of matrix-metalloproteinases (MMPs) and their physiological tissue inhibitors (TIMPs) as putative proteolytic elements. Firstly, human cancellous bone from 60 patients was examined by immunofluorescence with antibodies against MMPs and TIMPs. Secondly, we applied laser-assisted microdissection (LMD) to isolate bone lining cells from frozen sections of human trabecular bone. mRNA analysis was performed using a single-cell PCR protocol. Three laser microdissection systems were tested: the new generation of Leica LMD and P.A.L.M. laser pressure catapulting (LPC) were compared to P.A.L.M. laser microdissection and micromanipulation (LMM). In a few pooled cell profiles, mRNA of MMP13, MMP14, TIMP1, and CBFA-1 was clearly detected. By immunofluorescence MMP13 and -14 as well as TIMP1 and -2 were strongly present in lining cells, while MMP2, TIMP3, and TIMP4 showed weak or negative signals. Although the functional impact of these enzymatic components remains open, there is additional evidence for a catabolic function of lining cells. The new diode-laser microdissection with LMD and LPC proved to be especially suitable to gain new insights into the properties of bone lining cells.     

Animal models for neonatal diseases in humans

The development of vaccines for infants and young children requires the use of animal models at various stages of preclinical development. Animal models are being used to assess the quantity and quality of the immune response, onset and duration of the response, induction of systemic versus local immunity, protection against challenge infection for the assessment of vaccine efficacy, as well as safety and toxicity of the vaccine formulation itself. A variety of animal models are available, each with its own specific advantages and disadvantages. Here, we review the most common animal models for preclinical vaccine development for human infants.     

Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration

Human embryonic stem cells (hESCs) can be induced and differentiated to form a relatively homogeneous population of neuronal precursors in vitro. We have used this system to screen for genes necessary for neural lineage development by using a pooled human short hairpin RNA (shRNA) library screen and massively parallel sequencing. We confirmed known genes and identified several unpredicted genes with interrelated functions that were specifically required for the formation or survival of neuronal progenitor cells without interfering with the self-renewal capacity of undifferentiated hESCs. Among these are several genes that have been implicated in various neurodevelopmental disorders (i.e., brain malformations, mental retardation, and autism). Unexpectedly, a set of genes mutated in late-onset neurodegenerative disorders and with roles in the formation of RNA granules were also found to interfere with neuronal progenitor cell formation, suggesting their functional relevance in early neurogenesis. This study advances the feasibility and utility of using pooled shRNA libraries in combination with next-generation sequencing for a high-throughput, unbiased functional genomic screen. Our approach can also be used with patient-specific human-induced pluripotent stem cell-derived neural models to obtain unparalleled insights into developmental and degenerative processes in neurological or neuropsychiatric disorders with monogenic or complex inheritance.     

Trends in ophthalmology journals: a five-year bibliometric analysis (2009-2013)

AIM: To explore the trends in the ophthalmic literature over a 5-year period in relation to country, research expenditure and demographics. METHODS: Articles published between 2009 and 2013 by the 20highest-contributing countries in the 20 top-ranked ophthalmology journals were identified by their country of affiliation. The number of articles published and mean impact factor were measured per country for each year and trends explored using regression analysis with 5-year and 10-year forecasts calculated. Data on research expenditure was collected and tested for correlation with the number of articles and mean impact factor. RESULTS: The analysis included 19 338 articles. The USA, UK and Europe accounted for 60.2% of articles published, with the USA contributing 7388 articles (34.0%). The USA also demonstrated the highest mean impact factor (3.5). Research expenditure was significantly correlated with both research output (r=0.86, P<0.001) and scholarly impact (r=0.42, P<0.001). China (P<0.01), Korea (P<0.01) and India (P<0.02) demonstrated a significant growth in research output over the study period. The research contribution of these three countries combined is forecasted to overtake that of Europe within ten years, with China expected to be the second-largest contributor within five years. These countries were also among those demonstrating the greatest growth in research expenditure. CONCLUSION: While the USA and European countries are major contributors of ophthalmic research, the productivity of some Asian countries is growing impressively. The contribution of China, Korea and India is forecasted to outweigh that of Europe by 2023. Research expenditure is highly correlated with research productivity and these trends reflect the differing economic priorities across the world.     

Study of age dependence of epiphyseal ossification of the hand skeleton

Radiological analysis of the hand skeleton is a key pillar of forensic age diagnostics in living subjects undergoing criminal proceedings. The present study investigated whether ossification stage classification of selected epiphyses of the hand could provide added value to hand radiograph analysis. Hand radiographs from 265 male and 164 female subjects aged 10–18years old who had been X-rayed due to traumatological indications were therefore assessed. Epiphyseal ossification of selected elements of the hand skeleton (ulna, radius and third metacarpal, basal phalanx, mesophalanx and telephalanx) was graded based on the criteria of the five-stage classification system of Schmeling et al. (Int J Legal Med, 118:5–8, 2004) for clavicular epiphyseal cartilage. Stage 5 (absence of the epiphyseal scar) does not occur in the radius of men before the age of 18. Stage 5 can therefore be regarded as a potential parameter for valid determination of a minimum age of 18 years for forensic age estimation in criminal proceedings.     

The transitory bone marrow edema syndrome of the hip

AIM OF THE STUDY: Since MRI-studies had begun to establish the diagnosis of transitory bone marrow edema syndrome of the hip orthopedic surgeons have tried to integrate this new syndrome into the internationally accepted system of musculoskeletal diseases. Particularly, the relation to non-traumatic osteonecrosis of the femoral head and the possibilities in therapy were investigated in our clinical trial. METHODS: Our clinical trial encompassed 106 patients suffering from the transitory bone marrow edema syndrome diagnosed in our department between the years 1985 and 2000. In order to confirm this diagnosis we used the patients' histories, their clinical courses, MRI studies, scintigraphic bone scans, intraosseal pressure measurements, phlebographies, laboratory data, and histologic specimens. One half of our collective positive for transient bone marrow edema of the hip underwent core-decompression surgery (50 patients), the other half (56 patients) was treated conservatively by analgesic medication combined with restriction of weight-bearing in the affected extremity. RESULTS: Patients positive for transitory bone marrow edema syndrome of the hip are middle-aged individuals with a male to female predominance of 60 : 40. This group has no or only few risk factors usually associated with osteonecrosis of the femoral head. Thus, the missing alcoholic abuse is striking. All patients suffering from transitory bone marrow edema syndrome of the hip recovered completely independent of the therapy we initiated and none of them showed any signs of osteonecrosis. The one half undergoing surgical decompression of the edema by using a 4.5 mm drill experienced an markedly accelerated relief of their clinical symptoms as well as their signal changes on MRI studies. Conventional X-ray pictures and scintigraphic bone scans are not useful for early differentiation between early stages of osteonecrosis and bone marrow edemas. This also accounts for the historical measurements of intraosseal pressure determinations and phlebographies. In contrast to that, MRI studies are effective in early differentiation between osteonecrosis and bone marrow edema syndrome of the hip, especially when contrast medium (gadolinium) is administrated intravenously and fat-suppressed MRI-sequences find use. Beginning osteonecrosis of the femoral head shows a segmental loss of contrast medium, a "double line sign" interface to the intact bone marrow, and only in a few cases they are associated with a huge symptomatic edema. The histologic examination of specimens obtained from 43 patients with transitory bone marrow edema syndrome of the hip revealed no signs of osteonecrosis. CONCLUSION: MRI studies are useful in differentiation between bone marrow edema syndrome of the hip and non-traumatic osteonecrosis of the femoral head in each stage of these two diseases. The thorough differentiation between these two diseases is of extraordinary importance for the clinical work-up of the patients as well as for scientific reasons. The course of primary bone marrow edema is benign as it results in entire recovery. The core decompression surgery offers the chance to shorten the course of the disease.