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.

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.

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.

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.

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.

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.

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.

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.

Predictors of survival in HIV-infected tuberculosis patients.

OBJECTIVE: To ascertain predictors of survival in HIV-infected tuberculosis (TB) patients. DESIGN: Retrospective cohort study. SETTING: New York City public hospital. PATIENTS: Fifty-four consecutive HIV-seropositive patients with newly diagnosed TB and no other AIDS-defining illnesses. MAIN OUTCOME MEASURES: CD4+ T-lymphocyte counts, completion of anti-TB therapy, repeat hospitalizations with TB, and survival. RESULTS: Forty-five (84%) of the 54 patients died a median of 15 months after TB diagnosis (range, 1-80 months), five (9%) were alive after a median of 81 months (range, 75-84 months), and four (7%) were lost to follow-up after a median of 42 months (range, 30-66 months). In univariate analyses, disseminated TB, intrathoracic adenopathy, oral candidiasis and CD4 count depletion were each associated with decreased survival. In a multivariate analysis, CD4 count depletion was the only independent predictor of decreased survival. Repeat hospitalization with TB occurred in 10 out of 15 patients who did not complete anti-TB therapy compared with one out of 21 patients who completed anti-TB therapy (P < 0.001). CONCLUSION: The clinical presentation of TB and CD4 count at TB diagnosis are each predictive of survival in HIV-seropositive TB patients. The CD4 count is the only independent predictor of survival.

The neurodevelopmental basis of schizophrenia: clinical clues from cerebro-craniofacial dysmorphogenesis, and the roots of a lifetime trajectory of disease.

A "read-back" analysis of schizophrenia, from chronic illness, through the first psychotic episode, to psychosocial and neurointegrative abnormalities of childhood and infancy, leads to the intrauterine period as a primary focus for etiological events. Evidence for a characteristic topography of cerebro-craniofacial dysmorphology in schizophrenia is reviewed, and interpreted to estimate: (i) the timing of dysmorphic event(s); (ii) the nature of early cellular and molecular mechanisms which might determine that topography of dysmorphogenesis; and (iii) the population homogeneity of these processes. It is argued that early cerebro-craniofacial dysmorphogenesis in schizophrenia should be conceptualized as a first stage not in a static but rather in a dynamic, lifetime trajectory of disease.

1H-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates.

Twenty eight schizophrenic patients and 20 normal volunteers underwent proton magnetic resonance spectroscopy (MRS) on the left temporal and frontal lobe regions. Male patients showed a significant reduction in frontal but not temporal n-acetylaspartate (an intraneuronally distributed metabolite) in comparison with either male controls or female patients; frontal choline was raised in male patients relative to these groups. Putative neurodevelopmental indices, including obstetric complications, family history of schizophrenia, and minor physical anomalies, proved unrelated to MRS resonances. However, multiple aspects of memory function in patients were related to temporal but not frontal creatine, a pattern that was not apparent among controls. These MRS findings complement some previous structural MRI studies and much clinical and epidemiological evidence of important gender differences in schizophrenia. The findings also suggest that memory dysfunction in patients with schizophrenia may be associated with a particular pattern of temporal lobe metabolism on MRS.

The relationship of minor physical anomalies and other putative indices of developmental disturbance in schizophrenia to abnormalities of cerebral structure on magnetic resonance imaging.

Minor physical anomalies, together with obstetric complications, family history, and handedness status, were assessed to explore putative neurodevelopmental disturbance(s) in patients with schizophrenia whose cerebral structure had been examined previously by magnetic resonance imaging. Minor physical anomalies were related to negative symptoms in males and to premorbid intellectual function in females, but not to ventricular volume; however, three patients with evident neurodevelopmental anomalies of the ventricular system showed prominent minor physical anomalies. In exploratory analyses, obstetric complications were associated with left ventricular asymmetry, and a positive family history with inverse profiles of asymmetry in males vs. females; non-right-handedness was associated with increased ventricular volume in males but with poorer premorbid intellectual function in females. This nexus of relationships and their gender specificities suggest early dysmorphogenesis in schizophrenia that is related to sexual dimorphism.

Familial, obstetric, and other clinical correlates of minor physical anomalies in schizophrenia.

OBJECTIVE: This study investigated possible antecedents of minor physical anomalies in schizophrenia, particularly in terms of obstetric and genetic factors, and demographic, clinical and cognitive correlates of such anomalies in schizophrenia. METHOD: Forty-one outpatients satisfying the DSM-III criteria for schizophrenia were examined for minor physical anomalies by using the Waldrop scale. These subjects were drawn from a group of 45 such patients whose cognitive function had been previously evaluated with Trail Making Tests A and B and whose biological mothers had been interviewed for any history of obstetric complications or family history of schizophrenia. RESULTS: Linear multiple regression analysis showed that higher scores for minor physical anomalies were associated with impaired cognitive flexibility on Trail Making Test B, family history of schizophrenia in a first-degree relative, maternal history of obstetric complications, smaller number of siblings, later position in the birth order, and male sex. A family history of schizophrenia was particularly associated with abnormalities of the mouth. The association between minor physical anomalies in the patients and obstetric complications in their mothers appeared to be confined to instances in which the mother had a history of bleeding in early pregnancy. CONCLUSIONS: Minor physical anomalies indicate early dysmorphogenesis in schizophrenia, particularly in males, which appears to be associated more reliably with genetic rather than obstetric factors and with cognitive impairment.

Spontaneous abnormal involuntary movements in first-episode schizophrenia and schizophreniform disorder: baseline rate in a group of patients from an Irish catchment area.

OBJECTIVE: This study investigated the rate of spontaneous abnormal involuntary movements in a group of patients presenting with a first episode of schizophrenia or schizophreniform psychosis. METHOD: Seventy-nine patients with a first episode of schizophrenia or schizophreniform psychosis who presented to a catchment area psychiatric service over a 3-year period, and who were neuroleptic-naive or had been medicated for less than 1 month, were examined for the presence of involuntary movements with use of the Abnormal Involuntary Movement Scale. RESULTS: Six patients (7.6%) had spontaneous dyskinesia as defined by the criteria of Schooler and Kane, and nine other patients had mild orofacial involuntary movements. The patients with spontaneous dyskinesia had completed significantly fewer years of education than the patients without dyskinesia. Spontaneous involuntary movements were unrelated to age at presentation for treatment. CONCLUSIONS: Spontaneous abnormal involuntary movements were evident among a proportion of patients with first-episode schizophrenia or schizophreniform psychosis at baseline presentation and were associated with reduced educational attainment. This finding supports previous suggestions that abnormal involuntary movements in schizophrenia may be related to the pathophysiology of the illness and therefore cannot be attributed entirely to the adverse effects of neuroleptic medication.

Magnetic resonance imaging of schizophrenia-like psychoses associated with cerebral trauma: clinicopathological correlates.

Three patients with schizophrenia-like psychosis and two with schizoaffective-like psychosis who experienced cerebral trauma before the onset of their illness underwent clinical and magnetic resonance imaging evaluation. Each patient with a schizophrenia-like psychosis, but neither of those with a schizoaffective-like psychosis, showed abnormalities confined to or including the left temporal lobe. These observations complement recent findings in schizophrenia.

Further evidence for anomalies in the hand-prints of patients with schizophrenia: a study of secondary creases.

Finger and palm prints from 46 ICD-9 schizophrenic patients and 43 age and sex matched normal controls were examined independently and blind to diagnosis, by four raters. Seven prints were judged to have very high densities of secondary creases. These abnormal prints were all from the schizophrenic group. Patients with high densities of creases were more severely ill, having had more than five admissions to hospital and higher doses of neuroleptic medication. There was a trend for such patients to have had a complicated obstetric history and an earlier onset of their illness.

Dermatoglyphic fluctuating asymmetry and atypical handedness in schizophrenia.

Atypical handedness and dermatoglyphic abnormalities are hypothesized to reflect a neurodevelopmental disturbance in schizophrenia. Developmental instability, indexed by dermatoglyphic fluctuating asymmetry (FA), reflects the degree to which an individual's ontogenetic program is maintained and provides a useful framework in which to consider atypical handedness in schizophrenia. Thirty patients diagnosed with schizophrenia were compared with 37 matched healthy controls on levels of dermatoglyphic FA, a demonstration task determining hand preference and a test of relative hand skill. Multivariate analyses established that patients demonstrated greater FA and more atypical hand skill compared with controls. In patients, but not in controls, there was a strong positive association between a measure of FA and a measure of atypical hand skill, suggesting that these markers of neurodevelopmental disturbance are related in schizophrenia. On a measure of hand preference, patients were more likely than controls to be classified as mixed handed than either right or left handed. Results from the present study support the conjecture of greater developmental instability in schizophrenia affecting neurodevelopmental processes, including those conferring manual dominance.

Does prenatal exposure to influenza in mice induce pyramidal cell disarray in the dorsal hippocampus?

Epidemiological studies point to an association between prenatal exposure to influenza and later schizophrenia. Such studies are consistent with neuropathologic reports demonstrating cytoarchitectural abnormalities in the hippocampus and parahippocampal gyrus suggestive of second trimester developmental anomalies. The hypothesis that prenatal exposure to influenza in the second trimester may induce hippocampal pyramidal cell disarray in mice was investigated. Between days 9-16 of pregnancy, 35 Balb/c mice were intranasally inoculated with either a mouse-adapted or non mouse-adapted pool of Influenza A/Singapore/1/57 (H2N2), and 10 controls were inoculated with normal saline. Offspring were sacrificed on day 21 postpartum. Microscopic examination of the CA1-CA2 junctional areas in the offspring of mice exposed to influenza failed to demonstrate excess pyramidal cell disarray when compared with influenza-free, age matched controls. There was evidence that disarray was greater among those exposed on day 13 of pregnancy. Analyses of the data by sex and severity of maternal infection failed to reveal any significant effects.

Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.

Although the seasonal patterns of admissions of affective disorder have been extensively studied, less attention has been given to the seasonal admission patterns of schizophrenia. The traditional method of aggregating the data over a study period, rather than analysing by year of admission may obscure potentially relevant fluctuations in the seasonal pattern. We examined the year-to-year variation in the admission patterns of schizophrenia and affective disorder in Ireland. Using the National Psychiatric Inpatient Reporting System (NPIRS), individuals admitted with an ICD-9/10 diagnosis of a first episode of schizophrenia or affective disorder during the 6-year period 1989-1994 were identified. Seasonal variations in their admission patterns were examined statistically and graphically. There was a significant seasonal variation in the monthly admission patterns of both schizophrenia and affective disorder. This pattern was more marked for individuals with affective disorder. However, the seasonal pattern was not constant from year to year, particularly for schizophrenia.