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There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system, which require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex we have directly compared the Ca2+ signalling mechanisms involved in NMDAR-LTD and mGluR-LTD. Whilst both forms of LTD involve Ca2+ release from intracellular stores the Ca2+ sensors involved are different; NMDAR-LTD involves calmodulin, whilst mGluR-LTD involves the neuronal Ca2+ sensor (NCS) protein NCS-1. In addition, there is a specific requirement for IP3 and PKC as well as protein interacting with C-kinase (PICK-1) in mGluR-LTD. NCS-1 binds directly to PICK1, via its BAR domain, in a Ca2+-dependent manner. Furthermore, the NCS-1-PICK1 association is stimulated by activation of mGluRs, but not NMDARs, and introduction of a PICK1 BAR domain fusion protein specifically blocks mGluR-LTD. Thus, NCS-1 is a component of a novel mechanism involved in mGluR-LTD.
Risperidone (RISP) may induce both elevated prolactin (PRL) levels and weight gain. the aim of this study was to evaluate body weight and mass index (BMI), and PRL modifications in schizophrenic patients treated for 1 year with long-acting risperidone (LAR).
Body weight and BMI (calculated as weight in kilograms divide by height in meter squared) were determined at baseline and at endpoint in 19 schizophrenic patients (9 men and 10 women; mean[SEM] age 33.4[2.9] years). PRL levels were determined at baseline, after oral risperidone treatment (mean length of treatment: 79 days; mean dose: 5.8[0.5] mg daily) and during a 12 month treatment with LAR (mean dose: 50 mg every 2 weeks; PRL levels were measured before each injection).
At endpoint, a significant weight gain (Δweight: 8,1[1,4] kg) and BMI (ΔBMI: 2,9[0,5] kg/m²) was observed (both p< 0.0002). Compared with baseline, PRL levels were significantly increased (p< 0.0007; mean ΔPRL: 33 ng/ml). There was an association between ΔBMI>1,5 kg/m² and ΔPRL>40 ng/ ml (p< 0.04). Moreover ΔBMI was linked to the length of treatment (rho=0.47; n=19; p< 0.05).
Our results suggest a link between weight gain and long term hyperprolactinemia in patients treated with LAR. It has been hypothesized that PRL may have a role in the regulation of food intake by increasing leptin synthesis and secretion.
Motor, perceptual, and cognitive functions affect driving competence. White matter hyperintensities (WMH) changes on brain MRI are associated structural brain changes along with cognitive and motor performance. The aim of this study was to investigate the association between WMH and driving ability in the elderly.
Participants (n = 540) were drawn from a nationwide, multicenter, hospital-based, longitudinal cohort study. Each participant underwent clinical evaluations, neuropsychological tests, and interview for caregiver including driving capacity, which was categorized as ‘now driving’, and ‘driving cessation (driving before, not now)’. A total 540 participants were divided into three groups (389 mild, 116 moderate, and 35 severe) depending on the degree of WMH. The same evaluations of them were followed after each year. The statistical analyses were performed using χ2 test, an analysis of variance (ANOVA), structured equation model (SEM), and generalized estimating equation (GEE).
In a SEM, greater baseline degree of WMH was directly associated with driving cessation regardless of cognitive and motor dysfunction (β = –0.110, P < 0.001). In GEE models controlling for age, sex, education, cognitive, and motor dysfunction, the more severe changes of the degree of WMH was associated with the faster change from ‘now driving’ state to ‘driving cessation’ state over time in the elderly (β = –0.508, P < 0.001).
In both cross-sectional and longitudinal aspects, the degree of WMH might be one of the predictive factors for driving cessation in the elderly, reflecting both motor and cognitive functions or independently.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Antipsychotic-induced hyperprolactinemia is associated with relevant side effects: short-term as hypogonadism, gynecomastia, amenorrhoea, sexual dysfunction and galactorrhoea; long-term as cardiovascular disease, bone demineralization and breast and prostate tumors.
To evaluate the effect of switching to long-acting injectable aripiprazole on long-lasting antypsychotic-induced hyperprolactinemia.
This was a prospective observational 1-year study carried out in 125 outpatients with schizophrenia who were clinically stabilized but a switching to another antipsychotic was indicated. We measured the basal prolactine at the start of the study and 1 year after switching to long acting injecatable (LAI) aripiprazole.
In basal analytic, 48% had hyperprolactinemia (21.8–306.2 ng/mL) and 66.5% of them described side effects: 78% sexual dysfunction (72% men), 11% galactorrhoea (100% women), 5.5% amenorrhoea and 5.5% bone pain (100% women). In 48% of patients with hyperprolactinemia, the previous antipsychotics comprised: LAI-paliperidone (65,7%), oral-risperidone (7%), oral-olanzapine (6.1%), oral-paliperidone (5.2%), LAI-risperidone (4%) and others (12%). One year after switching to LAI-aripiprazole, prolactine levels were lower in all patients and in 85% prolactine levels were normalized. Overall, 72% described a clinical improvement, especially in terms of sexual dysfunction.
Several studies have described an improvement of drug-induced hyperprolactinemia after switching to or adding oral aripiprazole. In our study, we observed that levels of prolactine were normalized in 85% of patients with a clinical improvement in almost all of cases. These findings suggest that switching to LAI aripiprazole may be an effective alternative for managing antipsychotic-induced hyperprolactinemia due to its partial agonism in D2 brain receptors, especially in tuberoinfundibular pathway.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Haemonchus contortus is a haematophagous gastrointestinal nematode (GIN) that causes severe anaemia and even death in small ruminants, negatively impacting the economic viability of farms. Traditionally, this parasite has been controlled with chemical compounds; however, inadequate use of these types of products has favoured the emergence of anthelmintic resistance. Therefore, it is necessary to search for alternatives for GIN control. Previous studies have reported the anthelmintic activity of edible mushroom extracts against H. contortus. A recent study reported that a fraction constituted of different fatty acids and β-sitosterol isolated from the basidiomata of the edible mushroom Pleurotus djamor ECS-123 has ovicidal and larvicidal activity against H. contortus. Thus, this study aimed to assess the anthelmintic activity of the pure molecules: pentadecanoic acid, palmitic acid, β-sitosterol, stearic acid and linoleic acid. For this purpose, an egg-hatching inhibition test was carried out in which the compounds were evaluated individually and in combination at a final concentration of 20 mg mL−1. Furthermore, larval mortality was assessed using a combination of the five commercial compounds previously mentioned at different concentrations (1.25–20 mg mL−1). Palmitic acid and stearic acid, in some combinations, inhibited H. contortus egg hatching by 100%. On the other hand, in the larval mortality test, the combination of the five compounds showed dose-dependent behaviour, and 100% mortality was obtained 24 h post-incubation. Pure molecules and their combinations have anthelmintic-like activity against the eggs and larvae of H. contortus.
In a tertiary-care hospital and affiliated long-term care facility, a stewardship intervention focused on patients with Clostridioides difficile infection (CDI) was associated with a significant reduction in unnecessary non-CDI antibiotic therapy. However, there was no significant reduction in total non-CDI therapy or in the frequency of CDI recurrence.
Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.
To determine whether central findings from vestibular tests predict abnormal findings on magnetic resonance imaging.
This study was a retrospective case series at a tertiary referral centre. The main outcome measure of this diagnostic intervention study was the positive predictive value of central vestibular findings in relation to magnetic resonance imaging abnormalities.
Central vestibular findings had a 50.9 per cent positive predictive value for magnetic resonance imaging abnormalities across all age groups although they varied according to age group. Optokinetic nystagmus (p < 0.05) and abnormal findings on videonystagmography tests (p < 0.05) were the main predictors of magnetic resonance imaging abnormalities. White matter lesions constituted the bulk of the central lesions on magnetic resonance imaging followed by cortical and cerebellar atrophy.
Central vestibular findings had a 50.9 per cent positive predictive value for magnetic resonance imaging abnormalities across all age groups. Magnetic resonance imaging is medically justified to further evaluate patients with central findings on vestibular studies. Therefore, it is reasonable to request magnetic resonance imaging in these patients.
To assess the feasibility of non-contrast T2-weighted magnetic resonance imaging as compared to T1-weighted post-contrast magnetic resonance imaging for detecting acoustic neuroma growth.
Adult patients with acoustic neuroma who underwent at least three magnetic resonance imaging scans of the internal auditory canals with and without contrast in the past nine years were identified. T1- and T2-weighted images were reviewed by three neuroradiologists, and tumour size was measured. Accuracy of the measurements on T2-weighted images was defined as a difference of less than or equal to 2 mm from the measurement on T1-weighted images.
A total of 107 magnetic resonance imaging scans of 26 patients were reviewed. Measurements on T2-weighted magnetic resonance imaging scans were 88 per cent accurate. Measurements on T2-weighted images differed from measurements on T1-weighted images by an average of 1.27 mm, or 10.4 per cent of the total size. The specificity of T2-weighted images was 88.2 per cent and the sensitivity was 77.8 per cent.
The T2-weighted sequences are fairly accurate in measuring acoustic neuroma size and identifying growth if one keeps in mind the caveats associated with the tumour characteristics or location.
This paper introduces GLINTS, a graphical tool for exploring variant narrowing computations in Maude. The most recent version of Maude, version 2.7.1, provides quite sophisticated unification features, including order-sorted equational unification for convergent theories modulo axioms such as associativity, commutativity, and identity. This novel equational unification relies on built-in generation of the set of variants of a term t, i.e., the canonical form of tσ for a computed substitution σ. Variant generation relies on a novel narrowing strategy called folding variant narrowing that opens up new applications in formal reasoning, theorem proving, testing, protocol analysis, and model checking, especially when the theory satisfies the finite variant property, i.e., there is a finite number of most general variants for every term in the theory. However, variant narrowing computations can be extremely involved and are simply presented in text format by Maude, often being too heavy to be debugged or even understood. The GLINTS system provides support for (i) determining whether a given theory satisfies the finite variant property, (ii) thoroughly exploring variant narrowing computations, (iii) automatic checking of node embedding and closedness modulo axioms, and (iv) querying and inspecting selected parts of the variant trees.
We investigated whether convenience sampling is a suitable method to generate a sample of older drivers representative of the older-Canadian driver population. Using equivalence testing, we compared a large convenience sample of older drivers (Candrive II prospective cohort study) to a similarly aged population of older Canadian drivers. The Candrive sample consists of 928 community-dwelling older drivers from seven metropolitan areas of Canada. The population data was obtained from the Canadian Community Health Survey – Healthy Aging (CCHS-HA), which is a representative sample of older Canadians. The data for drivers aged 70 and older were extracted from the CCHS-HA database, for a total of 3,899 older Canadian drivers. Two samples were demonstrated as equivalent on socio-demographic, health, and driving variables that we compared, but not on driving frequency. We conclude that convenience sampling used in the Candrive study created a fairly representative sample of Canadian older drivers, with a few exceptions.
We hypothesized that changes over time in cognitive performance are associated with changes in driver perceptions, attitudes, and self-regulatory behaviors among older adults. Healthy older adults (n = 928) underwent cognitive assessments at baseline with two subsequent annual follow-ups, and completed scales regarding their perceptions, attitudes, and driving behaviours. Multivariate analysis showed small but statistically significant relationships between the cognitive tests and self-report measures, with the largest magnitudes between scores on the Trails B cognitive task (seconds), perceptions of driving abilities (β = –0.32), and situational driving avoidance (β = 0.55) (p < 0.05). Cognitive slowing and executive dysfunction appear to be associated with modestly lower perceived driving abilities and more avoidance of driving situations over time in this exploratory analysis.
To date, associations between psychosocial driving variables and behaviour have been examined only cross-sectionally. Using three waves of data collected annually from 928 older drivers (mean age = 76.21 years; 62% male) enrolled in the Candrive II cohort, we examined in this study whether changes in attitudes and perceptions towards driving (decisional balance and day and night driving comfort) were associated with changes in older adults’ reported restrictions in driving practices and perceived driving abilities. Multi-level models revealed that older adults who showed an increase in negative attitudes towards driving over time were more likely to report more-restricted practices (greater avoidance of challenging driving situations) and perceived declines in driving abilities compared to individuals whose attitudes towards driving remained stable across two years. This work supports previous findings and offers a new understanding of how attitudes relate to driving perceptions (e.g., comfort) and self-regulation in older adults over time.
A census of the Critically Endangered Bengal Florican Houbaropsis bengalensis was conducted between March and May 2012 on and surrounding the Tonle Sap floodplain in Cambodia, which supports the last extant population of the Indochinese subspecies blandini. We found a decline in the number of displaying males of 44–64% since a comparable estimate from the same sites in 2005 to 2007. The estimated population, including five individuals at one previously unsurveyed site, is now 216 (95% CI 156–275) displaying males, plus potential non-displaying males and an unknown number of females. If numbers continue to be lost at a similar rate, it is possible that blandini would become extinct within 10 years. Although the population faces multiple threats, this critical situation has primarily been caused by the recent, rapid conversion of the florican’s grassland habitat to intensive, industrial-scale, irrigated rice cultivation. To protect the Bengal Florican from extinction in South East Asia, existing Bengal Florican Conservation Areas (BFCAs) need expansion and improvements, including strengthened legal status by prime ministerial sub-decree and better demarcation, patrolling and management. As priorities, both irrigated rice and scrub encroachment within the BFCAs needs to be reversed, local communities better supported, and land outside the BFCAs monitored and strategically managed for florican conservation. Where possible, further BFCAs need to be established. Land purchase may also be an effective conservation measure; leasing land earmarked for cultivation would be cheaper, but less secure.
The success of central line-associated bloodstream infection (CLABSI) prevention programs in intensive care units (ICUs) has led to the expansion of surveillance at many hospitals. We sought to compare non-ICU CLABSI (nCLABSI) rates with national reports and describe methods of surveillance at several participating US institutions.
Design and Setting.
An electronic survey of several medical centers about infection surveillance practices and rate data for non-ICU Patients.
Ten tertiary care hospitals.
In March 2011, a survey was sent to 10 medical centers. The survey consisted of 12 questions regarding demographics and CLABSI surveillance methodology for non-ICU patients at each center. Participants were also asked to provide available rate and device utilization data.
Hospitals ranged in size from 238 to 1,400 total beds (median, 815). All hospitals reported using Centers for Disease Control and Prevention (CDC) definitions. Denominators were collected by different means: counting patients with central lines every day (5 hospitals), indirectly estimating on the basis of electronic orders (n = 4), or another automated method (n = 1). Rates of nCLABSI ranged from 0.2 to 4.2 infections per 1,000 catheter-days (median, 2.5). The national rate reported by the CDC using 2009 data from the National Healthcare Surveillance Network was 1.14 infections per 1,000 catheter-days.
Only 2 hospitals were below the pooled CLABSI rate for inpatient wards; all others exceeded this rate. Possible explanations include differences in average central line utilization or hospital size in the impact of certain clinical risk factors notably absent from the definition and in interpretation and reporting practices. Further investigation is necessary to determine whether the national benchmarks are low or whether the hospitals surveyed here represent a selection of outliers.
All-printed electronics is the key technology to ultra-low-cost, large-area electronics. As a critical step in this direction, we demonstrate that femtosecond laser processing (sintering and ablation) of solution deposited metal nanoparticles enables direct metal patterning at low-temperature with ultra high resolution (∼300nm) to overcome the resolution limitation of the current inkjet direct writing processes.
This could be explained by the combined effects of novel properties of metal nanoparticles such as melting temperature drop, strong absorption of the incident laser beam at surface plasmon mode, lower conductive heat transfer loss, and the relatively weak bonding between nanoparticles. Local thermal control of the laser sintering process could minimize the heat-affected zone and the thermal damage to the substrate and further enhance the resolution of the process. This local nanoparticle deposition and energy coupling enable an environmentally friendly and cost-effective process as well as a low-temperature manufacturing sequence to realize large-area, flexible electronics on polymer substrates.
This work reports on thermal and electrical conductivities and interface resistances for transport along aligned multiwalled carbon nanotubes (CNT) films grown on a nickel superalloy (Inconel) substrate. The measured specific thermal resistance of the combined Inconel–CNT and indium–CNT interfaces is of the same order as reported for CNT and silicon or SiO2 interfaces but much higher than theoretical predictions considering perfect contact between the tubes and substrate. Imperfect mechanical contact with the substrate and a large contribution caused by indium–CNT interface are thought to be mainly responsible for the high interface resistances and the low effective values of thermal and electrical conductivities. However, reported results represent an incentive for further research on CNT synthesis on metallic substrates for thermal management applications and pave the way for much easier integration of carbon nanotubes in electronic applications.
Tight control of defects is pivotal for semiconductor technology. However, even the basic defects are not entirely understood in silicon carbide. In the recent years significant advances have been reached in identification of defects by combining the experimental tools like electron paramagnetic resonance and photoluminescence with ab initio calculations. We summarize these results and their consequences in silicon carbide based technology. We show recent methodological developments making possible the accurate calculation of absorption and emission signals of defects.