Continuum beliefs of mental illness: a systematic review of measures.

PURPOSE: The continuum of mental health/illness has been subject to scientific debate for decades. While current research indicates that continuum belief interventions can reduce mental health stigma and improve treatment seeking in affected populations, no study has yet systematically examined measures of continuum beliefs. METHODS: This preregistered systematic review summarizes measures of continuum beliefs. Following the PRISMA statement, three scientific databases (PubMed, PsycInfo and PsycArticles via EBSCOhost, Web of Science) are searched, instruments are described and discussed regarding their scope, and methodological quality. RESULTS: Overall, 7351 records were identified, with 35 studies reporting relevant findings on 11 measures. Most studies examined general population samples and used vignette-based measures. Schizophrenia and depression were most commonly examined, few studies focused on dementia, ADHD, OCD, eating disorders, and problematic alcohol use, or compared continuum beliefs across disorders. Validity was very good for most measures, but reliability was rarely tested. Measures mostly assessed beliefs in the normality of mental health symptoms or the normality of persons with such symptoms but rarely nosological aspects (i.e., categorical v continuous conceptualization of mental disorders). CONCLUSIONS: Current research provides psychometrically sound instruments to examine continuum beliefs for a variety of mental disorders. While studies suggest utility for general population samples and mental health professionals, more research is necessary to corroborate findings, for instance, regarding age (e.g., in adolescents), gender, or type of mental disorder. Future research should also compare self-report ratings, and vignette-based measures, include measures of nosological concepts to fully grasp the continuum concept of mental illness. PREREGISTRATION: PROSPERO: CRD42019123606.

A Mini-Review: Leber Congenital Amaurosis: Identification of Disease-Causing Variants and Personalised Therapies.

Leber congenital amaurosis (LCA) encompasses a group of severe inherited retinal dystrophies (IRDs) responsible for early childhood blindness. There are currently 25 genes implicated in the pathogenesis of these diseases, and identification of disease-causing variants will be required for personalised therapies. Whole exome and whole genome sequencing is informative for detecting novel disease-causing genes, whilst next-generation sequencing has excelled at detecting novel variants in known disease-causing genes.A global effort will be required to identify patient populations for early intervention. At the Australian Inherited Retinal Disease Registry and DNA Bank, we seek to identify genetic variants in individuals with IRDs in the Australian population to identify potential candidates for clinical trials, to inform clinical management of patients including reproductive options and to expand existing knowledge of IRDs.Due to the diversity of genes implicated, personalised strategies are likely to be the benchmark for treating these diseases, and a combined approach of different therapies may be optimal in treating some of these diseases.

Autosomal recessive bestrophinopathy associated with angle-closure glaucoma.

PURPOSE: Abnormalities in the BEST1 gene have recently been recognised as causing autosomal recessive bestrophinopathy (ARB). ARB has been noted to have a variable phenotypic presentation, distinct from that of autosomal dominant Best vitelliform macular dystrophy (BVMD). Both conditions are associated with deposits in the retina, a reduced or absent electro-oculography (EOG) light rise, and the risk of developing angle-closure glaucoma. Herein, we describe the clinical and genetic characteristics of a young male diagnosed with ARB associated with angle-closure glaucoma resulting from a novel homozygous mutation in BEST1. METHODS: All research involved in this case adhered to the tenets of the Declaration of Helsinki. The proband underwent slitlamp examination, retinal autofluorescence imaging and optical coherence tomography after presenting with deteriorating vision. The findings prompted genetic testing with bi-directional DNA sequencing of coding and flanking intronic regions of BEST1. The proband's family members were subsequently screened. RESULTS: A provisional diagnosis of ARB was made based on the findings of subretinal and schitic lesions on fundoscopy and retinal imaging, together with abnormal EOG and electroretinography. Genetic testing identified a novel homozygous mutation in BEST1, c.636+1 G>A. Family members were found to carry one copy of the mutation and had no clinical or electrophysiological evidence of disease. The proband was additionally diagnosed with angle-closure glaucoma requiring topical therapy, peripheral iridotomies and phacoemulsification. CONCLUSIONS: Phenotypic overlap, reduced penetrance, variable expressivity and the ongoing discovery of new forms of bestrophinopathies add to the difficulty in distinguishing these retinal diseases. All patients diagnosed with ARB or BVMD should be examined for narrow angles and glaucoma, given their frequent association with these conditions.

Immediate postpartum neurological deficits in the lower extremity: a prospective observational study.

BACKGROUND: Neurological deficits noted immediately after childbirth are usually various obstetric neuropathies, but prospective studies are limited. The main study aim was to quantify and describe immediate postpartum neurological deficits of the lower extremity, including the buttocks. METHODS: A prospective observational study of postpartum women delivering in a single maternity hospital during three months of 2016. Among 1147 eligible women, 1019 were screened for symptoms of lower extremity numbness or weakness within eight to 32hours of delivery. Consent to undergo a detailed neurological evaluation was sought from those reporting symptoms. Risk factors were identified using logistic regression. RESULTS: Thirty five women (3.4%) reported symptoms, 27 entered the study and 23 (2.0%) had objective signs of a neurological deficit. The most common injuries were mild lumbosacral plexopathies and cluneal nerve compression. Most deficits were sensory, half of these also having a motor deficit that did not impact functionally. Based on analysis of 22 cases involving a likely intrapartum deficit, no association was found with parity, body weight, duration of labour, mode of delivery or neuraxial block. A past history of a neurological condition or a back injury was associated with odds ratios of 7.98 and 4.82 respectively. There were no neurological deficits that were clinically concerning or that were likely a complication of a neuraxial block. CONCLUSION: Transient neurological complications after labour and delivery are infrequent, mainly sensory involving multiple lumbosacral nerve roots or specific sacral cutaneous nerves, and they typically resolve within a short time.

Detection of germ cell-derived proteins in testicular interstitial fluid: potential for monitoring spermatogenesis in vivo.

The aim of the present study was to assess whether proteins secreted by the seminiferous tubules (ST) can be detected in testicular interstitial fluid (IF) and testicular (TV), spermatic (SV), and peripheral venous (PV) plasma from adult rats. An antiserum was raised against seminiferous tubule-conditioned medium (STCM) prepared from adult rats and used in conjunction with Western blot analysis to screen IF and blood samples resolved by one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Samples of IF and PV were analyzed from control adult rats and rats exposed to scrotal heating (43 degrees C for 30 minutes) 24 hours earlier to ascertain whether damage to spermatogenesis would affect 'leakage' of proteins from the seminiferous tubules. In all control rats, the STCM antiserum specifically detected three proteins in testicular IF with molecular weights of 24, 16, and 14 kDa, respectively. Heat treatment increased the abundance of these proteins and induced the appearance of several other less-abundant proteins, all with molecular masses below 25 kDa. Two of the proteins present in IF were identified, the 24-kDa protein as phosphatidylethanolamine-binding protein (PEBP), and the 14-kDa protein as an androgen-regulated protein (ARP-2). Both of these proteins have been shown in previous studies to be secreted by round spermatids. Our results suggest that germ cell secretory products can gain access to the interstitium under both normal physiological conditions and more easily after induction of damage to spermatogenesis. The antiserum was unable to detect any ST-derived proteins in blood, although it is likely that this result may be due to insensitivity of the presently used techniques. The development of specific immunoassays for germ cell-secreted proteins (e.g., PEBP and ARP-2) should enable more definitive assessment of whether proteins secreted by the seminiferous epithellum can be measured in blood and thus provide a potential means of monitoring spermatogenesis.

Effect of age on seminiferous tubule protein secretion and the adverse effects of testicular toxicants in the rat.

This study has assessed the effect of age on protein secretion by seminiferous tubules (ST) isolated from rats and their response to Sertoli cell toxicants. ST were isolated from immature (aged 28 days), late pubertal (aged 45 days) and young adult (aged 70 days) rats and cultured in vitro for 24 h with 35S-methionine in the presence or absence of FSH (1 mg/ml), m-dinitrobenzene (m-DNB) or nitrobenzene (NB) (both at 10(-4)M). Incorporation of 35S-methionine into newly synthesized proteins in the culture medium (secreted proteins) was assessed and the pattern of protein secretion evaluated using two-dimensional sodium dodecylsulphate polyacrylamide gel electrophoresis (2-D SDS-PAGE). These data were compared with those obtained using cultures of immature rat Sertoli cells+germ cells (SC+GC). Addition of FSH, m-DNB or NB in vitro either had no effect (NB) or had a small stimulatory effect (FSH and m-DNB) on the incorporation of 35S-methionine into overall secreted proteins by ST isolated from immature rats. At the same doses, addition of either FSH, m-DNB or NB to SC+GC co-cultures resulted in increased incorporation of radiolabel into secreted proteins in all instances. In contrast, the same additions to ST isolated from adult rats resulted in a 20-34% decrease in the overall incorporation of 35S-methionine into secreted proteins. ST isolated from late pubertal rats showed a similar response to adult rats except that the decreases in incorporation induced by FSH, m-DNB and NB were smaller. Analysis by 2-D SDS-PAGE revealed considerable age-dependent differences in the proteins secreted by ST from immature and adult rats, of which 13 were identified as being of potential importance. Most of these proteins were prominent secretory products of ST from adult rats, but were minor or non-detectable products of cultures of ST or SC+GC from immature rats. Most of these proteins disappeared or decreased in abundance after culture of ST with m-DNB or NB. Two proteins showed the reverse pattern, being more prominent secretory products in immature than mature rats, and their secretion was unaffected or was increased by toxicant exposure. These results demonstrate that there are major age-dependent differences in the secretion of total and specific proteins by isolated ST and that these are probably related to changes in the germ cell complement with age.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of stage-specific changes in protein secretion by isolated seminiferous tubules from the rat following exposure to either m-dinitrobenzene or nitrobenzene.

The objective of this study was to identify effects of two known Sertoli cell toxicants on the secretion of proteins by seminiferous tubules (ST) isolated from adult rats at different stages of the spermatogenic cycle and cultured in vitro for 24 hr with [35S]methionine. Adult rats received a single oral dose of 50 mg/kg metadinitrobenzene (m-DNB) or 300 mg/kg nitrobenzene (NB). Long lengths of ST at stages II-V, VI-VIII or IX-XII were then isolated from control and treated rats at 1 or 3 days post-treatment; selection of stages was based on the stage specificity of the early (24-72 hr) adverse effects of m-DNB and NB on spermatogenesis in vivo. In addition, ST at the same stages were isolated from untreated rats and cultured in the presence or absence of m-DNB or NB (10(-4)M). Incorporation of [35S]methionine into secreted proteins was assessed and the pattern of protein secretion evaluated using two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-D SDS-PAGE). ST isolated from rats pretreated 24 hr earlier with NB in vivo showed a significant decrease in the overall incorporation of [35S]methionine into secreted proteins at stages VI-VIII and IX-XII, whereas ST at stages II-V showed no such change; comparable protein changes were observed when 10(-4) M NB was added in vitro for 24 hr to ST isolated at the same stages from untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of stage-specific changes in protein secretion by isolated seminiferous tubules from rats following exposure to short-term local testicular heating.

The objective of this study was to identify the early (after 4 and 24 h) effects of short-term local testicular heating (43 degrees C for 30 min) on the secretion of proteins by seminiferous tubules isolated from adult rats at stages II-V, VI-VIII or IX-XII of the spermatogenic cycle, and cultured in vitro for 24 h with [35S]methionine. Incorporation of [35S]methionine into secreted and intracellular proteins was assessed and the pattern of protein secretion was evaluated using two-dimensional SDS-PAGE. Seminiferous tubules isolated from control rats exhibited the characteristic, androgen-dependent increase in protein secretion at stages VI-VIII. At 4 h after exposure to local testicular heating, seminiferous tubules at these stages showed a significant increase (P < 0.001) in the overall incorporation of [35S]methionine into secreted proteins, whereas seminiferous tubules at stages II-V and IX-XII showed no significant change. In marked contrast, seminiferous tubules isolated from rats 24 h after local testicular heating showed a significant decrease in the incorporation of [35S]methionine into secreted proteins at stages VI-VIII (P < 0.001) and to a lesser extent at IX-XII (P < 0.05), whereas seminiferous tubules at stages II-V showed no change in incorporation. Prior treatment to maintain normal intratesticular concentrations of testosterone in heat-exposed rats failed to prevent these changes. Similar results were obtained when incorporation of [35S]methionine into intracellular proteins was evaluated 4 and 24 h after exposure to local testicular heating.(ABSTRACT TRUNCATED AT 250 WORDS)

A retinitis pigmentosa register for western Australia.

This paper describes the main elements of the Western Australian retinitis pigmentosa register including details of the data stored on the register, aspects of the coding systems used and some description of the tests employed in diagnosis of retinitis pigmentosa. The register is family based and contains data on affected individuals and on their unaffected relatives. As at November 1991, the register contained data for 391 individuals from 207 separate families. Of the 391 individuals, 240 had definite or probable retinitis pigmentosa and 26 were possibly affected. The remainder were unaffected family members. In many cases, both affected and unaffected family members are being studied serially and the register is designed to store and easily retrieve serial data to allow study of disease progression for individuals and within families.