Influence of sire fertility status on conceptus-induced transcriptomic response of the bovine endometrium.

The aim was to examine the effect of sire fertility status on conceptus-induced changes in the bovine endometrial transcriptome. To generate elongated conceptuses, Day 7 blastocysts produced in vitro using frozen-thawed sperm from Holstein Friesian bulls (3 High fertility, HF and 3 Low fertility, LF) were transferred in groups of 5-10 into synchronized heifers (n = 7 heifers per bull) and recovered following slaughter on Day 15. Day 15 endometrial explants recovered from the uterine horn ipsilateral to the corpus luteum were recovered from synchronized cyclic heifers (n = 4). Explants from each heifer were co-cultured for 6 h in RPMI medium alone (Control) or with 100 ng/ml ovine recombinant interferon tau (IFNT) or with a single conceptus from each HF or LF bull. After 6 h, explants were snap frozen and stored at -80°C. Extracted mRNA was subjected to RNA-seq and the resulting data were analyzed with R software. The numbers of differentially expressed genes (DEG; FDR<0.05) were: HF vs. Control: 956; LF vs. Control: 1021; IFNT vs. Control: 1301; HF vs. LF: 2. Unsurprisingly, the majority of DEG (658) were common to all comparisons and were related to IFNT-induced changes in the endometrium. Prior to applying the adjusted p-value, there were 700 DEG between HF and LF, with 191 and 509 genes more expressed in HF or LF, respectively (p < 0.05). Overrepresentation analysis of KEGG pathways (FDR<0.05), revealed that DEG with higher expression in LF were involved in cell cycle and proteolysis, while those upregulated DEG by HF conceptuses were strongly associated with immune process pathways, such as TNF, NF-kappa B, cytokine-cytokine receptor interaction, and TLR signaling. These pathways were also enriched by DEG upregulated by IFNT compared to the Control. Furthermore, only the HF, and not the LF group, affected the expression of most genes in these pathways (p < 0.05) according to a negative binomial regression model. Finally, a weighted gene co-expression network analysis revealed two clusters of co-expressed genes associated with the HF conceptuses (p < 0.05), which were also enriched for the aforementioned pathways. In conclusion, HF conceptuses, similar to IFNT treatment, stimulated multiple pathways involved in immune response, which were apparently not affected by LF conceptuses.

Examination of the periaqueductal gray as a site for controlling arterial pressure in the conscious spontaneously hypertensive rat.

Our understanding of central nervous system regulation of the set-point of arterial pressure remains incomplete, especially in conditions of hypertension. The ventrolateral periaqueductal gray (vlPAG) is of particular interest given that its acute activation induces hypotension and sympatho-inhibition in anaesthetised, normotensive animals, and recent preliminary studies have shown that vlPAG stimulation can reduce blood pressure in refractory hypertensive patients. To assist our mechanistic understanding, we investigated whether electrical stimulation of the vlPAG had depressor actions in a model of neurogenic hypertension, the spontaneously hypertensive (SH) rat. We found that electrical stimulation of the lateral and vlPAG (2-6 V, 20-40 Hz, 0.18-0.2 ms pulse width) decreased arterial pressure (-19 ± 4 mm Hg, n = 8) and heart rate (median - 18 bpm) in anaesthetised SH rats. In contrast, in conscious freely-moving SH rats fitted with blood pressure telemetry, stimulation of this same region produced failed to evoked a hypotensive response (n = 13; either no change, n = 9; or an increase in arterial pressure of 23 ± 4 mm Hg, n = 4). The hypotensive action of the vlPAG observed in anaesthetised animals has been attributed to inhibition of pre-sympathetic neurones originating in the rostral ventrolateral medulla. We therefore used an un-anaesthetised, decerebrate SH rat preparation to investigate whether activation of vlPAG neurons produced sympatho-inhibition that might be below the threshold at which a peripheral vascular response could be observed. Only sympatho-excitatory responses to electrical and excitatory amino acid microinjections were observed, and these were evoked from both the dorsal and ventral PAG; no responses were evoked from the vlPAG. We conclude that the vlPAG is not a reliable antihypertensive locus in the awake SH rat. We discuss the potential importance of the state-dependency of the hypotensive response that can be evoked from the vlPAG, which has important implications for translating to humans.

Sire contribution to fertilization failure and early embryo survival in cattle.

Despite passing routine laboratory tests of semen quality, bulls used in artificial insemination (AI) exhibit a significant range in field fertility. The objective of this study was to determine whether subfertility in AI bulls is due to issues of sperm transport to the site of fertilization, fertilization failure, or failure of early embryo or conceptus development. In experiment 1, Holstein-Friesian bulls (3 high fertility, HF, and 3 low fertility, LF) were selected from the national population of AI bulls based on adjusted fertility scores from a minimum of 500 inseminations (HF: +4.37% and LF: -12.7%; mean = 0%). Superovulated beef heifers were blocked based on estimated number of follicles at the time of AI and inseminated with semen from HF or LF bulls (n = 3-4 heifers per bull; total 19 heifers). Following slaughter 7 d later, the number of corpora lutea was counted and the uteri were flushed. Recovered structures (oocytes/embryos) were classified according to developmental stage and stained with 4',6-diamidino-2-phenylindole to assess number of cells and accessory sperm. Overall recovery rate (total structures recovered/total corpora lutea) was 52.6% and was not different between groups. Mean (± standard error of the mean) number of embryos recovered per recipient was 8.7 ± 5.2 and 9.4 ± 5.5 for HF and LF, respectively. Overall fertilization rate of recovered structures was not different between groups. However, more embryos were at advanced stages of development (all blastocyst stages combined), reflected in a greater mean embryo cell number on d 7 for HF versus LF bulls. Number of accessory sperm was greater for embryos derived from HF than for LF bulls. The aim of experiment 2 was to evaluate the effect of sire fertility on survival of bovine embryos to d 15. Day 7 blastocysts were produced in vitro using semen from the same HF (n = 3) and LF (n = 3) bulls and transferred in groups of 5-10 to synchronized heifers (n = 7 heifers per bull; total 42 heifers). Conceptus recovery rate on d 15 was higher in HF (59.4%,) versus LF (45.0%). Mean length of recovered conceptuses for HF bulls was not affected by fertility status. In conclusion, while differences in field fertility among AI sires used in this study were not reflected in fertilization rate, differences in embryo quality were apparent as early as d 7. These differences likely contributed to the higher proportion of conceptuses surviving to d 15 in HF bulls.

RS-1 enhances CRISPR-mediated targeted knock-in in bovine embryos.

Targeted knock-in (KI) can be achieved in embryos by clustered regularly interspaced short palindromic repeats (CRISPR)-assisted homology directed repair (HDR). However, HDR efficiency is constrained by the competition of nonhomologous end joining. The objective of this study was to explore whether CRISPR-assisted targeted KI rates can be improved in bovine embryos by exposure to the HDR enhancer RS-1. In vitro produced zygotes were injected with CRISPR components (300 ng/µl Cas9 messenger RNA and 100 ng/µl single guide RNA against a noncoding region) and a single-stranded DNA (ssDNA) repair template (100 ng/µl). ssDNA template contained a 6 bp XbaI site insert, allowing targeted KI detection by restriction analysis, flanked by 50 bp homology arms. Following microinjection, zygotes were exposed to 0, 3.75, or 7.5 µM RS-1 for 24 hr. No differences were noted between groups in terms of development or genome edition rates. However, targeted KI rates were doubled in the group exposed to 7.5 µM RS-1 compared to the others (52.8% vs. 25% and 23.1%, for 7.5, 0, and 3.75 µM, respectively). In conclusion, transient exposure to 7.5 µM RS-1 enhances targeted KI rates resulting in approximately half of the embryos containing the intended mutation, hence allowing direct KI generation in embryos.

The cell adhesion molecule EphA4 is involved in circadian clock functions.

Circadian (∼24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analyzed circadian wheel-running behavior of EphA4 knockout (EphA4-/- ) mice under different light conditions and upon photic resetting, as well as their light-induced protein response in the SCN. EphA4-/- mice exhibited reduced wheel-running activity, longer endogenous periods under constant darkness and shorter periods under constant light conditions, suggesting an effect of EphA4 on SCN function. Moreover, EphA4-/- mice exhibited suppressed phase delays of their wheel-running activity following a light pulse during the beginning of the subjective night (CT15). Accordingly, light-induced c-FOS (FBJ murine osteosarcoma viral oncogene homolog) expression was diminished. Our results suggest a circadian role for EphA4 in the SCN neuronal network, affecting the circadian system and contributing to the circadian response to light.

Neighbourhood characteristics and the incidence of first-episode psychosis and duration of untreated psychosis.

BACKGROUND: The incidence of psychotic disorders varies between geographical areas and it has been hypothesized that neighbourhood-level factors may influence this variation. It is also plausible that the duration of untreated psychosis (DUP) is associated with neighbourhood characteristics. The aims of this study were to determine whether the incidence of first-episode psychosis (FEP) and the DUP are associated with the level of social deprivation, fragmentation, social capital and population density. METHOD: All individuals with a FEP from a geographical defined catchment area over a 5-year period were included. Age-standardized incidence rates were calculated for each neighbourhood factor. RESULTS: A total of 292 cases of FEP were included in the study and 45% had a diagnosis of a schizophrenia-spectrum disorder. The age standardized incidence rate of FEP in the most deprived area was 72.4 [95% confidence interval (CI) 26.4-162.7] per 100 000 person-years compared with 21.5 (95% CI 17.6-26.0) per 100 000 person-years in the most affluent areas. This represents a 3.4-fold increase in FEP incidence in the most deprived areas. The incidence of FEP was also increased in neighbourhoods that were more socially fragmented [incidence rate ratio (IRR) = 2.40, 95% CI 1.05-5.51, p = 0.04] and there was a trend for the incidence to be increased in neighbourhoods with lower social capital (IRR = 1.43, 95% CI 0.99-2.06, p = 0.05). The median DUP was 4 months and was higher in more socially fragmented neighbourhoods. CONCLUSIONS: The incidence of psychotic disorders is related to neighbourhood factors and it may be useful to consider neighbourhood factors when allocating resources for early intervention services.

An exploration of the views of Australian mothers on promoting child oral health.

BACKGROUND: An important role for parents and caregivers in the prevention of dental caries in children is the early establishment of health promoting behaviours. This study aimed to examine mothers' views on barriers and facilitators to promoting child and family oral health. METHODS: Semi-structured interviews were undertaken with a purposive sample of mothers (n = 32) of young children. Inductive thematic analysis was conducted. RESULTS: Parental knowledge and beliefs, past experiences and child behaviour emerged as major influences on children's oral health. Child temperament and parental time pressures were identified as barriers to good oral health with various strategies reported for dealing with uncooperative children at toothbrushing time. Parental oral health knowledge and beliefs emerged as positive influences on child oral health; however, while most mothers were aware of the common causes of dental caries, very few knew of other risk factors such as bedtime feeding. Parents' own oral health experiences were also seen to positively influence child oral health, regardless of whether these were positive or negative experiences. CONCLUSIONS: Understanding parental oral health beliefs is essential to overcoming barriers and promoting enablers for good child oral health. Improving child oral health also requires consideration of child behaviour, family influences, and increasing awareness of lesser-known influencing factors.

Transition from milks to the introduction of solid foods across the first 2 years of life: findings from an Australian birth cohort study.

BACKGROUND: The current literature regarding the transition from milks to solid foods across the first 2 years of life is limited despite the important influence of early dietary intake on children's growth and development. The present study describes dietary intake from birth to 2 years across four developmental relevant time-points within an Australian birth cohort. METHODS: Dietary data from 466 infants was collected at four time-points in the first 2 years of life via parent-reported questionnaire, including a 45-item food and beverage frequency questionnaire. Subsample analyses of children who were aged 1-3, 6-8, 12-14 and 18-20 months at the time of data collection were conducted. RESULTS: Infant formula remained consistently consumed by over 75% of children from the 6-8- to 18-20 months old age groups. Mean (SD) age of introduction to solid foods was 5.2 (1.3) months. Almost 20% and 10% of children were introduced before 16 and after 32 weeks, respectively. The highest consumption of core foods, recommended for a healthy diet, daily was seen in the 12-14 months old age group with lower proportions in the 18-20 months old age group coinciding with an increased proportion of children eating discretionary choice foods, not recommended for a healthy diet. Discretionary choice foods/beverages presented in children's diets as early as in the 6-8 months old age group. By 18-20 months, at least 20% of children were consuming savoury biscuits, sweet biscuits, muesli bars and luncheon meats at least twice a week. CONCLUSIONS: The present study identified a number of findings outside the recommendations of the Australian Dietary and Infant Feeding Guidelines. Further work is warranted to explore these outcomes.

Validation of the completeness and accuracy of the Northern Ireland Cancer Registry.

BACKGROUND: It has been suggested that inaccuracies in cancer registries are distorting UK survival statistics. This study compared the Northern Ireland Cancer Registry (NICR) database of living patients, with independent data held by Northern Ireland's General Practitioners (GPs) to compare and validate the recorded diagnoses and dates held by the registry. METHODS: All 387 GP practice managers were invited to participate. 100 practices (25.84%) responded. Comparisons were made for 17,102 patients, equivalent to 29.08% of the living patients (58,798) extracted from the NICR between 1993 and 2010. RESULTS: There were no significant differences (p>0.05) between the responding and nonresponding GP patient profiles for age, marital status or deprivation score. However, the responding GPs included more female patients (p=0.02). NICR data accuracy was high, 0.08% of GP cancer patients (n=15) were not included in registry records and 0.02% (n=2) had a diagnosis date which varied more than 2 weeks from GP records (3 weeks and 5 months). The NICR had recorded two different tumour types and three different tumour statuses (benign vs. malignant) to the GPs. CONCLUSION: This comparison demonstrates a high level of accuracy within the NICR and that the survival statistics based on this data can be relied upon.

Illness characteristics and symptoms in an Irish early intervention for psychosis service.

OBJECTIVES: Study of illness characteristics and symptoms in a young population with psychosis can assist for understanding of their needs, and can inform service planning strategies. The aims of the current study were to describe illness characteristics and symptoms of a first episode psychosis (FEP) sample aged 25 years and under, and compare with a sample aged over 25 years. METHODS: Interviews were conducted for 437 individuals aged 16-65 years presenting with suspected psychosis between 2005 and 2012 in a defined catchment area (population of 390 000) using the Structured Clinical Interview for DSM IV to determine the presence of a psychosis diagnosis. Individuals with confirmed psychosis were assessed using standardised instruments to determine illness characteristics at first presentation. RESULTS: Among the 25 years, and under FEP sample, 23.9% had their first onset of symptoms (prodromal or psychotic) before 18 years of age. After controlling for confounders, the sample aged 25 years and under had a significantly shorter log transformed duration of untreated psychosis (p=0.002), more negative symptoms (p=0.045) and greater frequency of comorbid cannabis abuse diagnosis (p=0.027). CONCLUSIONS: Symptom onset in a youth FEP sample frequently occurs before age 18 years. Certain illness characteristics differed across the age categories, such as greater negative symptoms and cannabis abuse in the youth sample. Overall, the findings support the provision of adequate strategies for management of negative symptom deficits and substance abuse across all ages in FEP.

Tracheal stenosis following percutaneous dilatational tracheostomy using the single tapered dilator: an MRI study.

Despite widespread adoption of percutaneous dilatational tracheostomy within the critical care setting, there is still uncertainty regarding long-term complications, particularly in relation to missed or subclinical tracheal stenosis. In this study, all patients underwent tracheostomy using a single tapered dilator ≥ three months prior to enrollment and were evaluated using magnetic resonance imaging, spirometry and questionnaire. Tracheal area was recorded and deemed to be stenotic if a reduction of ≥10% was found. Fifty patients underwent magnetic resonance imaging and 49 attended for interview. Five patients were diagnosed with tracheal stenosis-none were symptomatic. Six of the 50 tracheostomies were technically difficult. Spirometry was not predictive of stenosis. A post critical care exercise tolerance of less than 100 metres was found in four tracheal stenosis patients. The prevalence of subclinical tracheal stenosis following percutaneous tracheostomy is low, with limited clinical significance. No patients required corrective surgery for tracheal stenosis. Routine airway follow-up in asymptomatic patients appears to be unwarranted.

Do psychosis prodrome onset negative symptoms predict first presentation negative symptoms?

BACKGROUND: Negative symptoms have been previously reported during the psychosis prodrome, however our understanding of their relationship with treatment-phase negative symptoms remains unclear. OBJECTIVES: We report the prevalence of psychosis prodrome onset negative symptoms (PONS) and ascertain whether these predict negative symptoms at first presentation for treatment. METHODS: Presence of expressivity or experiential negative symptom domains was established at first presentation for treatment using the Scale for Assessment of Negative Symptoms (SANS) in 373 individuals with a first episode psychosis. PONS were established using the Beiser Scale. The relationship between PONS and negative symptoms at first presentation was ascertained and regression analyses determined the relationship independent of confounding. RESULTS: PONS prevalence was 50.3% in the schizophrenia spectrum group (n=155) and 31.2% in the non-schizophrenia spectrum group (n=218). In the schizophrenia spectrum group, PONS had a significant unadjusted (χ(2)=10.41, P<0.001) and adjusted (OR=2.40, 95% CI=1.11-5.22, P=0.027) association with first presentation experiential symptoms, however this relationship was not evident in the non-schizophrenia spectrum group. PONS did not predict expressivity symptoms in either diagnostic group. CONCLUSION: PONS are common in schizophrenia spectrum diagnoses, and predict experiential symptoms at first presentation. Further prospective research is needed to examine whether negative symptoms commence during the psychosis prodrome.

Diagnostic trajectory, interplay and convergence/divergence across all 12 DSM-IV psychotic diagnoses: 6-year follow-up of the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

BACKGROUND: The boundaries of psychotic illness and the extent to which operational diagnostic categories are distinct in the long term remain poorly understood. Clarification of these issues requires prospective evaluation of diagnostic trajectory, interplay and convergence/divergence across psychotic illness, without a priori diagnostic or other restrictions. METHOD: The Cavan-Monaghan First Episode Psychosis Study (CAMFEPS), conducted using methods to attain the closest approximation to epidemiological completeness, incepts all 12 DSM-IV psychotic diagnoses. In this study we applied methodologies to achieve diagnostic reassessments on follow-up, at a mean of 6.4 years after first presentation, for 196 (97%) of the first 202 cases, with quantification of prospective and retrospective consistency. RESULTS: Over 6 years, the 12 initial psychotic diagnoses were characterized by numerous transitions but only limited convergence towards a smaller number of more stable diagnostic nodes. In particular, for initial brief psychotic disorder (BrP), in 85% of cases this was the harbinger of long-term evolution to serious psychotic illness of diagnostic diversity; for initial major depressive disorder with psychotic features (MDDP), in 18% of cases this was associated with mortality of diverse causality; and for initial psychotic disorder not otherwise specified (PNOS), 31% of cases continued to defy DSM-IV criteria. CONCLUSIONS: CAMFEPS methodology revealed, on an individual case basis, a diversity of stabilities in, and transitions between, all 12 DSM-IV psychotic diagnoses over 6 years; thus, psychotic illness showed longitudinal disrespect to current nosology and may be better accommodated by a dimensional model. In particular, a first episode of BrP or MDDP may benefit from more vigorous, sustained interventions.

Mood congruent psychotic symptoms and specific cognitive deficits in carriers of the novel schizophrenia risk variant at MIR-137.

OBJECTIVE: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. METHOD: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). RESULTS: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. CONCLUSION: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted.

Schizophrenia: a five-year follow-up of patient outcome following psycho-education for caregivers.

INTRODUCTION: There is evidence that psycho-education courses for caregivers of individuals with schizophrenia improve the short-term outcome of the condition. However, most of the outcome studies are limited to two-year follow-up. MATERIALS AND METHODS: This study is a five-year retrospective case-control follow-up of an original cohort of 63 patients and their 101 caregivers who completed a six-week Caregiver Psycho-education Programme (CPP) for schizophrenia and psychosis between 2002 and 2005, and 60 controls, matched for age, gender and severity of their psychotic illness. RESULTS: Patients whose caregivers learned more from the six-week psycho-education course had a significantly longer time to relapse (P = 0.04) and a significantly shorter length of stay during their first relapse (P < 0.05). Patients whose caregivers attended the six-week psycho-education course (regardless of how much the caregivers learned) had a significantly better outcome than controls. This included a significantly smaller number of relapses (P < 0.01), longer time to relapse (P < 0.01), shorter length of stay during their first relapse (P < 0.01) and smaller number of bed days over five years (P < 0.01). The odds ratio of controls relapsing, although insignificant at one year, was 4.13 (1.85-9.21) at five years. Outcome was not affected by either the numbers of caregivers attending for each patient, or caregiver gender. DISCUSSION AND CONCLUSIONS: This study, which is among the first to examine outcome over five years, supports the efficacy of psycho-education for caregivers in improving outcome for patients. Caregivers should be encouraged to take up psycho-education where it is available.

The relationship between insight and neurological dysfunction in first-episode psychosis.

PURPOSE: Impaired insight is commonly seen in psychosis and some studies have proposed that is a biologically based deficit. Support for this view comes from the excess of neurological soft signs (NSS) observed in patients with psychoses and their neural correlates which demonstrate a degree of overlap with the regions of interest implicated in neuroimaging studies of insight. The aim was to examine the relationship between NSS and insight in a sample of 241 first-episode psychosis patients. METHOD: Total scores and subscale scores from three insight measures and two NSS scales were correlated in addition to factors representing overall insight and NSS which we created using principal component analysis. RESULTS: There were only four significant associations when we controlled for symptoms. "Softer" condensed neurological evaluation (CNE) signs were associated with our overall insight factor (r = 0.19, P = 0.02), with total Birchwood (r = -0.24, P < 0.01), and the Birchwood subscales; recognition of mental illness (r = -0.24, P < 0.01) and need for treatment (r = -0.18, P = 0.02). Total neurological evaluation scale (NES) and recognition of the achieved effects of medication were also weakly correlated (r = 0.14, P = 0.04). CONCLUSION: This study does not support a direct link between neurological dysfunction and insight in psychosis. Our understanding of insight as a concept remains in its infancy.

A randomised controlled trial of carer-focussed multi-family group psychoeducation in bipolar disorder.

In a RCT of family psychoeducation, 47 carers of 34 patients were allocated to one of three groups; Multifamily Group Psychoeducation, Solution Focussed Group Therapy or Treatment as Usual. Carers in both the MFGP intervention and the SFGP arm demonstrated greater knowledge and reduction in burden than those in the TAU arm.

Regulation of angiotensinogen by angiotensin II in mouse primary astrocyte cultures.

Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin-angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological and pathological manipulations alter expression of angiotensinogen in brain. Surprisingly, little is known about the factors that regulate astrocytic expression of angiotensinogen. There is evidence that angiotensinogen production in both hepatocytes and cardiac myocytes can be positively regulated via the angiotensin type 1 receptor, but this effect has not yet been studied in astrocytes. Therefore, the aim of this project was to establish whether angiotensin II modulates angiotensinogen production in brain astrocytes. Primary astrocyte cultures, prepared from neonatal C57Bl6 mice, expressed angiotensinogen measured by immunocytochemistry and real-time PCR. Using a variety of approaches we were unable to identify angiotensin receptors on cultured astrocytes. Exposure of cultured astrocytes to angiotensin II also did not affect angiotensinogen expression. When astrocyte cultures were transduced with the angiotensin type 1A receptor, using adenoviral vectors, angiotensin II induced a robust down-regulation (91.4% ± 1.8%, p < 0.01, n = 4) of angiotensinogen gene expression. We conclude that receptors for angiotensin II are present in extremely low levels in astrocytes, and that this concurs with available data in vivo. The signaling pathways activated by the angiotensin type 1A receptor are negatively coupled to angiotensinogen expression and represent a powerful pathway for decreasing expression of this protein, potentially via signaling pathways coupled to Gα(q/11) .

Physical coercion, perceived pressures and procedural justice in the involuntary admission and future engagement with mental health services.

OBJECTIVES: We sought to determine the level of procedural justice experienced by individuals at the time of involuntary admission and whether this influenced future engagement with the mental health services. METHODS: Over a 15-month period, individuals admitted involuntarily were interviewed prior to discharge and at one-year follow-up. RESULTS: Eighty-one people participated in the study and 81% were interviewed at one-year follow-up. At the time of involuntary admission, over half of individuals experienced at least one form of physical coercion and it was found that the level of procedural justice experienced was unrelated to the use of physical coercive measures. A total of 20% of participants intended not to voluntarily engage with the mental health services upon discharge and they were more likely to have experienced lower levels of procedural justice at the time of admission. At one year following discharge, 65% of participants were adherent with outpatient appointments and 18% had been readmitted involuntarily. Insight was associated with future engagement with the mental health services; however, the level of procedural justice experienced at admission did not influence engagement. CONCLUSIONS: This study demonstrates that the use of physical coercive measures is a separate entity from procedural justice and perceived pressures.