Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists.

Vagus nerve stimulation is a well-established treatment option for patients with drug-resistant epilepsy and has an expanding range of other clinical indications. Side effects of vagus nerve stimulation therapy include: cough; voice changes; vocal cord adduction; rarely, obstructive sleep apnoea; and arrhythmia. Patients with implanted vagus nerve stimulation devices may present for unrelated surgery and critical care to clinicians who are unfamiliar with their function and safe management. These guidelines have been formulated by multidisciplinary consensus based on case reports, case series and expert opinion to support clinicians in the management of patients with these devices. The aim is to provide specific guidance on the management of vagus nerve stimulation devices in the following scenarios: the peri-operative period; peripartum period; during critical illness; and in the MRI suite. Patients should be aware of the importance of carrying their personal vagus nerve stimulation device magnet with them at all times to facilitate urgent device deactivation if necessary. We advise that it is generally safer to formally deactivate vagus nerve stimulation devices before general and spinal anaesthesia. During periods of critical illness associated with haemodynamic instability, we also advise cessation of vagus nerve stimulation and early consultation with neurology services.

Psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland: optimised methodological approach of a case-control psychological autopsy study.

BACKGROUND: Suicide has profound effects on families and communities, but is a statistically rare event. Psychological autopsies using a case-control design allow researchers to examine risk factors for suicide, using a variety of sources to detail the psychological and social characteristics of decedents and to compare them to controls. The Suicide Support and Information System Case Control study (SSIS-ACE) aimed to compare psychosocial, psychiatric and work-related risk factors across three groups of subjects: suicide decedents, patients presenting to hospital with a high-risk self-harm episode, and general practice controls. METHODS: The study design includes two inter-related studies; one main case-control study: comparing suicide cases to general practice (GP) controls, and one comparative study: comparing suicide cases to patients presenting with high-risk self-harm. Consecutive cases of suicide and probable suicide are identified through coroners' registration of deaths in the defined region (Cork City and County, Ireland) and are frequency-matched for age group and gender with GP patient controls recruited from the same GP practice as the deceased. Data sources for suicide cases include coroners' records, interviews with health care professionals and proxy informants; data sources for GP controls and for high-risk self-harm controls include interviews with control, with proxy informants and with health care professionals. Interviews are semi-structured and consist of quantitative and qualitative parts. The quantitative parts include a range of validated questionnaires addressing psychiatric, psychosocial and occupational factors. The study adopts several methodological innovations, including accessing multiple data sources for suicide cases and controls simultaneously, recruiting proxy informants to examine consistency across sources. CONCLUSIONS: The study allows for the investigation of consistency across different data sources and contributes to the methodological advancement of psychological autopsy research. The study will also inform clinical and public health practice. The comparison between suicide cases and controls will allow investigation of risk and protective factors for suicide more generally, while the comparison with high-risk self-harm patients will help to identify the factors associated specifically with a fatal outcome to a self-harm episode. A further enhancement is the particular focus on specific work-related risk factors for suicide.

Effects of long-term exposure to elevated temperature on Zea mays endosperm development during grain fill.

Cereal yields decrease when grain fill proceeds under conditions of prolonged, moderately elevated temperatures. Endosperm-endogenous processes alter both rate and duration of dry weight gain, but underlying mechanisms remain unclear. Heat effects could be mediated by either abnormal, premature cessation of storage compound deposition or accelerated implementation of normal development. This study used controlled environments to isolate temperature as the sole environmental variable during Zea mays kernel-fill, from 12 days after pollination to maturity. Plants subjected to elevated day, elevated night temperatures (38°C day, 28°C night (38/28°C])) or elevated day, normal night (38/17°C), were compared with those from controls grown under normal day and night conditions (28/17°C). Progression of change over time in endosperm tissue was followed to dissect contributions at multiple levels, including transcriptome, metabolome, enzyme activities, product accumulation, and tissue ultrastructure. Integrated analyses indicated that the normal developmental program of endosperm is fully executed under prolonged high-temperature conditions, but at a faster rate. Accelerated development was observed when both day and night temperatures were elevated, but not when daytime temperature alone was increased. Although transcripts for most components of glycolysis and respiration were either upregulated or minimally affected, elevated temperatures decreased abundance of mRNAs related to biosynthesis of starch and storage proteins. Further analysis of 20 central-metabolic enzymes revealed six activities that were reduced under high-temperature conditions, indicating candidate roles in the observed reduction of grain dry weight. Nonetheless, a striking overall resilience of grain filling in the face of elevated temperatures can be attributed to acceleration of normal endosperm development.

Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-ß and cognitive function in APP/PS1 mice.

Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impact on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity. Here, we examined the effect of the small molecule inhibitor of the NLRP3 inflammasome, MCC950, on microglia in vitro and in vivo. The findings indicate that MCC950 inhibited LPS+Aß-induced caspase 1 activation in microglia and this was accompanied by IL-1ß release, without inducing pyroptosis. We demonstrate that MCC950 also inhibited inflammasome activation and microglial activation in the APP/PS1 mouse model of AD. Furthermore, MCC950 stimulated Aß phagocytosis in vitro, and it reduced Aß accumulation in APP/PS1 mice, which was associated with improved cognitive function. These data suggest that activation of the inflammasome contributes to amyloid accumulation and to the deterioration of neuronal function in APP/PS1 mice and demonstrate that blocking assembly of the inflammasome may prove to be a valuable strategy for attenuating changes that negatively impact on neuronal function.

Significant reduction in alcohol-related admissions to an intensive care unit in Dublin.

BACKGROUND: In 2008, we conducted an audit in our general intensive care unit (ICU) which demonstrated a high workload from alcohol-related admissions which represented 12 % of total admissions and 16.8 % of total available bed days at that time. AIMS: To repeat the audit 5 years later in 2013 to assess the current workload from alcohol-related admissions and whether this had increased or decreased in the intervening time period. METHODS: We retrospectively collected data from every admission to our 17-bed general ICU for the 6-month period from June 1 2013 to November 30 2013. We identified all admissions that were related to alcohol misuse. Their admission diagnosis, age, gender, ICU length of stay, APACHE 2 score (Acute Physiology and Chronic Health Evaluation 2) and 30-day mortality were recorded. The results of the 2013 audit were then compared with data from the 2008 study. RESULTS: There were 30 % less alcohol-related admissions to our ICU in 2013 compared to the same period in 2008. The study group had a longer length of stay on average but a lower mortality than the control group. CONCLUSION: There has been a significant reduction in the ICU workload from alcohol-related admissions in our general ICU in the past 5 years.

Self-cutting versus intentional overdose: psychological risk factors.

Individuals who present to emergency departments with self-harm are at elevated risk of further self-harm and suicide, and these risks are yet higher among patients who self-cut. Repetitive self-injury has previously been explained using a behaviourist approach focussing on operant conditioning, but we propose that the increased risk of self-harm repetition among those who present with self-cutting is at least partly mediated by pre-existing psychological risk factors. Several studies show that those who present with self-cutting differ from intentional overdose patients on demographic, psychiatric and social factors, but, based on findings from community-based studies, we hypothesise that there may be additional psychological differences that may also be associated with increased repetition risk. We conducted a small-scale cohort study of 29 self-harm patients presenting to A&E and compared theoretically-derived psychological variables between 8 self-cutting and 21 overdose patients. Those presenting with self-cutting scored significantly higher on hopelessness and lower on non-reactivity to inner experience and generally had a more vulnerable profile than those presenting with overdose. These findings support our hypothesis that the association between self-cutting and prospective repetition is at least partly due to pre-existing psychological vulnerabilities that increase both the likelihood of engaging in self-cutting as a method of self-harm and the likelihood of subsequent repetition of self-harm. Existing evidence suggests that self-cutting is a risk factor for repetition of self-harm, and it is possible that reducing and preventing repetition among these patients can be achieved by implementing psychological interventions to reduce hopelessness and increase tolerance of emotional distress.

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.

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.

Cyclosporine in the management of esophageal lichen planus.

Lichen planus (LP) is an uncommon disorder of unknown etiology, mostly affecting patients in their fifth and sixth decade of life. It is believed to be an autoimmune process involving T cells directed against basal keratinocytes. It affects the skin, nails, oral pharynx and genitals. Esophageal involvement is quite rare and can cause strictures, ulcerations and squamous cell cancer. The present article describes the case of a 54-year-old woman who was referred for assessment of dysphagia that initially occurred with solids, which then progressed to soft foods but spared liquids. The patient reported a weight loss of 9.1 kg. An esophagogastroduodenoscopy was performed and she was subsequently diagnosed with pill esophagitis. At the same time, she was also diagnosed with oral LP, with no involvement of the esophagus. She was treated with a proton pump inhibitor that resolved her gastrointestinal symptoms. The symptoms returned one year later and a repeat esophagogastroduodenoscopy revealed white plaques due to LP. She was treated with intermittent glucocorticoids. Diagnosis of esophageal LP is crucial for the proper treatment. Some patients may require systemic immunosuppression and mechanical dilation to prevent weight loss. Surveillance endoscopies should be performed to monitor for squamous cell cancer. Cyclosporine has been used for genital and oral LP, but the present case is the first in which it has been used successfully to treat esophageal LP.

Predictors of outcome in first-episode schizophrenia over the first 4 years of illness.

BACKGROUND: The outcome of schizophrenia appears to be more favourable than once thought. However, methodological issues, including the reliance on diagnosis at first presentation have limited the validity of outcome studies to date. METHOD: We conducted a first-episode follow-up study of 97 patients with DSM-IV schizophrenia over the first 4 years of illness. First presentation and follow-up assessments were compared using paired t tests and a forced-entry regression analysis was used to determine prognostic variables. RESULTS: There were significant improvements in positive and negative symptoms and global assessment of functioning between first presentation and follow-up. At first presentation, fewer negative symptoms (t=-3.40, p<0.01), more years spent in education (t=3.25, p<0.01), and a shorter duration of untreated psychosis (DUP) (t=-2.77, p<0.01) significantly predicted a better outcome at follow-up. CONCLUSIONS: The outcome of schizophrenia may not be as pessimistic as once thought and most patients did not display a downward deteriorating course of illness. This study supports the relationship between DUP and outcome beyond the early stages of illness.

A prospective evaluation of adherence to medication in first episode schizophrenia.

The aim of this study was to identify the features of first episode schizophrenia that predict adherence antipsychotic medication at six-month follow-up. We used validated instruments to assess clinical and socio-demographic variables in all patients with first episode schizophrenia from a defined geographical area admitted to a Dublin psychiatric hospital over a four-year period (N=100). At six-month follow-up (N=60) we assessed adherence to medication using the Compliance Interview. One third of patients with schizophrenia were non-adherent with medication within six months of their first episode of illness. High levels of positive symptoms at baseline, lack of insight at baseline, alcohol misuse at baseline and previous drug misuse predict non-adherence. These results indicate that an identifiable subgroup of patients with first episode schizophrenia is at high risk of early non-adherence to medication. While high positive symptom scores pre-date and predict non-adherence in most patients, reduced insight is the best predictor of non-adherence in patients who do not misuse alcohol or other drugs.

Antibiotic resistance of Campylobacter jejuni and Campylobacter coli isolated from hog, beef, and chicken carcass samples from provincially inspected abattoirs in Ontario.

Campylobacterjejuni is one of the most common causes of bacterial foodborne infection in the United States, and there are reports of resistance of Campylobacter spp. to antimicrobial agents used for the treatment of gastroenteritis. The purpose of this study was to determine the antimicrobial resistance patterns of Campylobacter spp. isolated from hog, beef, and chicken carcasses from provincially inspected abattoirs in Ontario. The agar dilution method was performed to measure antimicrobial resistance of the isolates. Antimicrobial resistance of Campylobacter isolates from hogs (n = 401), beef (n = 21), and chicken (n = 435) to ampicillin, azithromycin, chloramphenicol, ciprofloxacin, clindamycin, erythromycin, gentamicin, nalidixic acid, streptomycin, and tetracycline was determined. Resistance of chicken, hog, and beef isolates was 14.3, 18.2, and 9.5% to ampicillin; 17.9, 67.3, and 38.1% to azithromycin; 0, 0.5, and 0% to chloramphenicol; 3.7, 1.2, and 0% to ciprofloxacin; 2.3, 46.6, and 4.8% to clindamycin; 6.7, 43.6, and 4.8% to erythromycin; 0.2, 0, and 0% to gentamicin; 5.1, 10.7, and 0% to nalidixic acid; 13.6, 57.4, and 4.8% to streptomycin; and 52.6, 44.1, 42.9% to tetracycline, respectively. The hog isolates had the greatest resistance to seven of the ten antimicrobials tested. Results of this study confirm the existence of antimicrobial resistance of Campylobacter to various antimicrobial agents,especially ciprofloxacin and erythromycin, commonly used for treatment of campylobacteriosis in humans.

Early insight predicts depression and attempted suicide after 4 years in first-episode schizophrenia and schizophreniform disorder.

OBJECTIVE: To map the development of insight in the 4 years after presentation with first-episode schizophrenia and schizophreniform disorder and to determine the effects of evolving insight on depression and the likelihood of attempted suicide. METHOD: We assessed 101 individuals at presentation, 6 months and 4 years. We measured insight, including recognition of mental illness, recognition of need for treatment and ability to relabel psychotic symptoms. We measured depression and recorded all suicide attempts. RESULTS: Insight improved with time. Recognition of mental illness at 6 months predicted depression and attempted suicide at 4 years. CONCLUSION: Six months after presentation, the greater the acknowledgement by people that they had a mental illness, the more depressed they were at 4 years and the greater the likelihood that they would attempt suicide by 4 years. This may have implications for disclosure of diagnosis.

Antibiotic resistance of Salmonella isolated from hog, beef, and chicken carcass samples from provincially inspected abattoirs in Ontario.

The emergence of antimicrobial-resistant Salmonella organisms, especially Salmonella Typhimurium DT104, has been reported in many countries, including the United States and Canada. The purposes of this study were to determine the antimicrobial resistance patterns of Salmonella isolated from hog, beef, and chicken carcasses from provincially inspected abattoirs in Ontario and to determine the agreement between the agar dilution method and the microbroth dilution method for measurement of antimicrobial resistance of the isolates. Antimicrobial resistance of Salmonella isolates from hogs (n = 71), beef (n = 24), and chicken (n = 295) to amikacin, ampicillin, cephalothin, chloramphenicol, ciprofloxacin, gentamicin, streptomycin, sulfamethoxazole, and tetracycline was determined using the two methods. None of the 390 isolates were resistant to ciprofloxacin at levels of 0.125 microg/ml. All chicken and hog isolates were sensitive to amikacin, whereas all beef isolates were sensitive to both amikacin and gentamicin. Multiple antimicrobial resistance (resistance to more than one antimicrobial) was found in 29% of bovine isolates and 42% of porcine isolates using both methods for testing and in 42% by the agar dilution and 33% by the microbroth dilution methods in the chicken isolates. Overall, there was good agreement between the two test methods for resistance to most of the antimicrobials, with disagreement found in the results in 1.3% of the isolates for ampicillin and sulfamethoxazole, 8.2% for streptomycin, 5.6% for cephalothin, and 1.0% of the isolates for tetracycline. The lack of agreement between the two test methods was found mostly among the chicken isolates.

Clinical predictors of admission status in first episode schizophrenia.

Having a diagnosis of schizophrenia is a risk factor for involuntary admission to psychiatric inpatient care, but we have a limited understanding of why some patients and not others require involuntary admission. We aimed to identify the predictors of involuntary admission in first episode schizophrenia. We used validated instruments to assess clinical and socio-demographic variables in all patients (n = 78) with first episode schizophrenia from a defined geographical area admitted to a Dublin psychiatric hospital over a 4-year period. Involuntary patients (n = 17) could not be distinguished from voluntary patients (n = 61) on the basis of age, gender, living status, marital status, drug abuse or duration of untreated psychosis. Neither positive nor negative symptoms were useful predictors of admission status. Lack of insight was a strong predictor of involuntary status.

Prospective evaluation of neurological soft signs in first-episode schizophrenia in relation to psychopathology: state versus trait phenomena.

BACKGROUND: Although patients with schizophrenia have increased rates of neurological soft signs, few studies have examined prospectively their trait or state characteristics in relation to psychopathology. METHOD: In a prospective study of 97 patients with first-episode schizophrenia (DSM-IV criteria) we assessed neurological soft signs and psychopathology at presentation and at 6 month follow-up for 73 cases. To establish whether soft signs were associated with variations in clinical state, neurological soft signs were measured using two validated examinations (Neurological Evaluation Scale and Condensed Neurological Examination); psychopathology was assessed using the Positive and Negative Syndrome Scale. RESULTS: There was significant improvement in overall neurological function, primarily in motor-related and cortical signs, which were associated with improvement in psychopathology. Conversely, 'harder' signs were unrelated to improvement in psychopathology. CONCLUSIONS: Neurological soft signs in schizophrenia are heterogenous. Motor and cortical signs evidence state-like characteristics and vary with clinical course, while 'harder' signs evidence more static, trait-like characteristics in accordance with a neurodevelopmental basis.

Phosphorylation of RIM1alpha by PKA triggers presynaptic long-term potentiation at cerebellar parallel fiber synapses.

Presynaptic activation of protein kinase A (PKA) induces LTP in cerebellar parallel fiber synapses. Presynaptic LTP is known to require the active zone protein RIM1alpha, but the underlying induction mechanism remains unclear. We now show that PKA directly phosphorylates RIM1alpha at two sites. Using paired recordings from cultured cerebellar granule and Purkinje neurons, we demonstrate that LTP is absent in neurons from RIM1alpha KO mice but is rescued by presynaptic expression of RIM1alpha. Mutant RIM1alpha lacking the N-terminal phosphorylation site is unable to rescue LTP in RIM1alpha knockout neurons but selectively suppresses LTP in wild-type neurons. Our findings suggest that PKA-mediated phosphorylation of the active zone protein RIM1alpha at a single N-terminal site induces presynaptic LTP.