Association of NOS1AP variants and depression phenotypes in schizophrenia

Background The nitric oxide synthase 1 adaptor protein gene (NOS1AP) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N-methyl-d-aspartate (NMDA) receptor and reduced NO levels have been observed in schizophrenia patients. However, association studies investigating NOS1AP and schizophrenia have produced inconsistent results, most likely because schizophrenia is a clinically heterogeneous disorder. This study aims to investigate the association between NOS1AP variants and defined depression phenotypes of schizophrenia. Methods Nine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression. Result One NOS1AP SNP (rs1858232) was associated with the broad diagnosis of schizophrenia and eight SNPs were associated with depression related phenotypes within schizophrenia. The rs1415259 SNP showed strong association with sleep dysregulation phenotypes of depression. Conclusion Results suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males. Limitation Schizophrenia is a clinically heterogeneous disease that can vary greatly between different ethnic and geographic populations so our observations should be viewed with caution until they are independently replicated, particularly in larger patient cohorts.

Initial prototype testing of Ray's Night Out: A new mobile app targeting risky drinking in young people

Background Risky single occasion drinking (RSOD; 4 or more drinks in <6 h) more than doubles the risk of injury in young people (15 - 25 years). The potential role of smartphone apps in reducing RSOD in young people is yet to be explored. Objective: To describe the initial prototype testing of ‘Ray's Night Out’, a new iPhone app targeting RSOD in young people. Method Quantitative and qualitative methods were used to evaluate the quality, perceived utility, and acceptability of the app among nine young people (19e23 years). Results Participants reported Ray's Night Out had good to excellent levels of functionality and visual appeal, acceptable to good levels of entertainment, interest and information, and acceptable levels of customization and interactivity. Young people thought the app had high levels of youth appeal, would prompt users to think about their alcohol use limits, but was unlikely to motivate a change in alcohol use in its current form. Qualitative data provided several suggestions for improving the app. Conclusion Following revision, Ray's Night Out could provide an effective intervention for RSOD in non help-seeking young people. A randomized controlled trial is currently underway to test the final prototype of the app.

Evaluation of hospital preparedness for public health emergencies in Sichuan (China)

The aim of this research was to develop a set of reliable, valid preparedness metrics, built around a comprehensive framework for assessing hospital preparedness. This research used a combination of qualitative and quantitative methods which included interview and a Delphi study as well as a survey of hospitals in the Sichuan Province of China. The resultant framework is constructed around the stages of disaster management and includes nine key elements. Factor Analysis identified four contributing factors. The comparison of hospitals' preparedness using these four factors, revealed that tertiary-grade, teaching and general hospitals performed better than secondary-grade, non-teaching and non-general hospitals.

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid, and; (c) the effect of coadministration of a liquid meal. Sixty-nine children (1.6 ± 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids, and; (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

Protein turnover in malnourished patients with cystic fibrosis: Effects of elemental and nonelemental nutritional supplements

To evaluate the relative efficacy of nonele-mental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [15N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study compar-ing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-110 h-1versus 0.33 g kg-110 h-1for Criticare and-0.59 g kg-110 h-1for MT), although this was significant (p < 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF. © 1990 Raven Press Ltd, New York.

Lavage treatment of distal intestinal obstruction syndrome in children with cystic fibrosis

The efficacy, adverse reactions, and long-term effects of intestinal lavage treatment with a balanced electrolyte solution (Golytely) was evaluated in patients with cystic fibrosis and distal intestinal obstruction syndrome. Twenty-two patients with cystic fibrosis (mean age 21.8 years, range 14 to 34 years, 15 boys or men) who sough medical attention because of abdominal pain and a mass in the right iliac fossa received Golytely, 5.6 ± 1.9 L (mean ± 1 SD), either orally (n = 14) or via nasogastric tube (n = 8) during 5.6 ± 2.4 hours. No serious side effects occurred. Serum electrolyte values remained within normal limits. Body weight did not change significantly. Minor adverse reactions included bloating (n = 12), nausea (n = 8), vomiting (n = 1), and chills (n = 3). All but one patient reported impressive relief of symptoms and remained pain free for an average of 3 months (range 1 to 19 months). Symptoms of abdominal pain and radiologic signs of fecal impaction assessed before and after lavage both decreased significantly (P < .0001). During follow-up (mean 15.2 months, range 4 to 26 months), 11 patients required a total of 38 (range one to nine) additional doses of Golytely. Seven patients drank the solution at home (21 treatments); only two patients chose a nasogastric tube. In ten patients with symptoms of recurrent distal intestinal obstruction syndrome prior to institution of therapy, duration of hospitalization was significantly reduced by this treatment (5.1 ± 7.6 v 2.3 ± 6.3 hospital days per annum, P < .02). It is concluded that intestinal lavage is a well-accepted, safe, and effective therapy for distal intestinal obstruction syndrome in patients with cystic fibrosis.

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

Home monitoring for infants at risk of the sudden infant death syndrome

This study evaluates the effectiveness and social implications of home monitoring of 31 infants at risk of sudden infant death syndrome (SIDS). Thirteen siblings of children dying of SIDS, nine near miss SIDS infants and nine preterm infants with apnoea persisting beyond 40 weeks post conceptual age were monitored from a mean age of 15 days to a mean of 10 months. Chest movement detection monitors were used in 27 and thoracic impedance monitors in four. Genuine apnoeic episodes were reported by 21 families, and 13 infants required resuscitation. Apnoeic episodes occurred in all nine preterm infants but in only five (38%) of the siblings of SIDS (P<0.05). Troublesome false alarms were a major problem occurring with 61% of the infants and were more common with the preterm infants than the siblings of SIDS. All but two couples stated that the monitor decreased anxiety and improved their quality of life. Most parents accepted that the social restrictions imposed by the monitor were part of the caring process but four couples were highly resentful of the changes imposed on their lifestyle. The monitors used were far from ideal with malfunction occurring in 17, necessitating replacement in six, repair in six and cessation of monitoring in three. The parents became ingenious in modifying the monitors to their own individual requirements Although none of these 31 ‘at risk’ infants died the study sample was far too small to conclude whether home monitoring prevented any cases of SIDS.

A subculture of mental toughness in an Australian Football League club

Objective The current study aimed to provide a subcultural analysis of mental toughness in a high-performance context in sport. Design Using Schein's (1990) framework of organisational culture, an exploratory qualitative analysis, employing focus group and individual interviews, was used to investigate mental toughness in an Australian Football League club. Method Nine senior coaches and players participated in focus group and individual interviews. Photo elicitation was used as a method to capture mental toughness through the identification of prominent club artefacts. Participants were considered to have significant subcultural knowledge of their football club and were willing to describe personal experiences and perceptions of mental toughness through this cultural lens. Deductive and inductive analyses were conducted to capture the core themes of mental toughness across the disparate levels of Schein's organisational framework. Results Mental toughness was found to be a socially derived term marked by unrelenting standards and sacrificial displays. These acts were underpinned by subcultural values emphasising a desire for constant improvement, a team first ethos, relentless effort, and the maintenance of an infallible image. At its core, mental toughness was assumed to be an internal concept, epitomised an idealised form of masculinity, elitist values, and was rhetorically depicted through metaphors of war. Conclusions It may be difficult to understand mental toughness without giving attention to the contextual norms related to the term. Appreciating how people promote, instil, and internalise prized ideals coveted as mental toughness could be intriguing for future research in sport psychology.

Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.

Visual demands in modern Australian primary school classrooms

BACKGROUND The visual demands of modern classrooms are poorly understood yet are relevant in determining the levels of visual function required to perform optimally within this environment. METHODS Thirty-three Year 5 and 6 classrooms from eight south-east Queensland schools were included. Classroom activities undertaken during a full school day (9 am to 3 pm) were observed and a range of measurements recorded, including classroom environment (physical dimensions, illumination levels), text size and contrast of learning materials, habitual working distances (distance and estimated for near) and time spent performing various classroom tasks. These measures were used to calculate demand-related minimum criteria for distance and near visual acuity, contrast and sustained use of accommodation and vergence. RESULTS The visual acuity demands for distance and near were 0.33 ± 0.13 and 0.72 ± 0.09 logMAR, respectively (using habitual viewing distances and smallest target sizes) or 0.33 ± 0.09 logMAR assuming a 2.5 times acuity reserve for sustained near tasks. The mean contrast levels of learning materials at distance and near were greater than 70 per cent. Near tasks (47 per cent) dominated the academic tasks performed in the classroom followed by distance (29 per cent), distance to near (15 per cent) and computer-based (nine per cent). On average, children engaged in continuous near fixation for 23 ± 5 minutes at a time and during distance-near tasks performed fixation changes 10 ± 1 times per minute. The mean estimated habitual near working distance was 23 ± 1 cm (4.38 ± 0.24 D accommodative demand) and the vergence demand was 0.86 ± 0.07Δ at distance and 21.94 ± 1.09Δ at near assuming an average pupillary distance of 56 mm. CONCLUSIONS Relatively high levels of visual acuity, contrast demand and sustained accommodative-convergence responses are required to meet the requirements of modern classroom environments. These findings provide an evidence base to inform prescribing guidelines and develop paediatric vision screening protocols and referral criteria.

Equine hyperinsulinemia: Investigation of the enteroinsular axis during insulin dysregulation

Compared to other species insulin dysregulation in equids is poorly understood. Hyperinsulinemia causes laminitis, a significant and often lethal disease affecting the pedal bone/hoof wall attachment site. Until recently, hyperinsulinemia has been considered a counter-regulatory response to insulin resistance (IR), but there is growing evidence to support a gastrointestinal etiology. Incretin hormones released from the proximal intestine, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, augment insulin secretion in several species, but require investigation in horses. This study investigated peripheral and gut-derived factors impacting insulin secretion by comparing the response to intravenous (IV) and oral D-glucose. Oral and IV tests were performed in 22 ponies previously shown to be insulin dysregulated, of which only 15 were classified as IR (IV test). In a more detailed study, nine different ponies received four treatments: D-glucose orally, D-glucose IV, oats and Workhorse-mix. Insulin, glucose and incretin concentrations were measured before and after each treatment. All nine ponies showed similar IV responses, but five were markedly hyper-responsive to oral D-glucose and four were not. Insulin responsiveness to oral D-glucose was strongly associated with blood glucose concentrations and oral glucose bioavailability, presumably driven by glucose absorption/distribution, as there was no difference in glucose clearance rates. Insulin was also positively associated with active GLP-1 following D-glucose and grain. This study has confirmed a functional enteroinsular axis in ponies which likely contributes to insulin dysregulation that may predispose them to laminitis. Further, IV tests for IR are not reliable predictors of the oral response to dietary non-structural carbohydrate.

Effects of increasing neuromuscular electrical stimulation current intensity on cortical sensorimotor network activation: A time domain fNIRS study

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O₂Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O₂Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

A qualitative exploration of Internet-based treatment for comorbid depression and alcohol misuse

Background Many Internet-based treatments for depression and for alcohol misuse have a positive impact, yet little is known about how these treatments work. Most research on web-based interventions involves efficacy trials which, while important, offer little explanation about how people perceive and use online programs. Objective This study aimed to undertake a qualitative exploration of participants' experience, perceived impact and use of an integrated web-based program for comorbid depression and alcohol misuse. Specifically, it explored users' perspectives on the intensity of their treatment and the level of support they received. Methods Interviewees were drawn from participants in a randomised controlled trial of the OnTrack web-based treatment for depression and alcohol misuse, which compared Brief Self-Guided, Comprehensive Self-Guided and Comprehensive Therapist-Assisted versions of the program. Twenty-nine people (9–11 from each condition) completed semi-structured telephone interviews asking about their impressions and experiences with the program. Interview transcriptions were subject to a 6-step thematic analysis, employing a conceptual matrix to identify thematic differences across groups. Results Positive experiences and outcomes were more pronounced among participants receiving the comprehensive treatments than the brief one, but other responses were relatively consistent across conditions. A major theme was a wish for more individualisation and human contact, even in participants receiving emailed assistance. Some confused follow-up research assessments with therapist support. There was little correspondence between the perceived impact of the program and the amount reportedly completed, and some participants said they used strategies offline or completed exercises mentally. Conclusions This study highlighted discrepancies between how web-based treatments are intended to be used and how people actually engage with them. A challenge for the next wave of these interventions is the provision of individualised responses and coaching that retains an emphasis on self-management and constrains cost.

One device, two doses

Ms Breathless is a 59-year-old lady living with chronic obstructive pulmonary disease (COPD) for several years now, and quit smoking over 20 years ago. She sometimes experiences symptoms of breathlessness, and an unrelenting productive cough, particularly when she comes in contact with dusty places, second-hand smoke, or when her allergies and hay fever play up. Apart from these triggers, her symptoms are well maintained with her inhalers glycopyrronium bromide (Seebri) and indacaterol (Onbrez), and she has been using them for about nine months. Ms Breathless is otherwise healthy, and not taking any other medicines.