Abstract Tobacco dependence is the most common substance use disorder in adults with mental illness. The prevalence rates for tobacco dependence are two to four times higher in these patients than in ...the general population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental health patients, and remains the leading preventable cause of death in this group. Despite these statistics, in some countries smokers with mental illness are disadvantaged in receiving intervention and support for their tobacco dependence, which is often overlooked or even tolerated. This statement from the European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco dependence and withdrawal in patients with mental illness and their treatment. It provides seven recommendations for the core components of diagnostics and treatment in this patient group. These recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7) relapse prevention. They aim to help clinicians improve the care, health and well-being of patients suffering from mental illness.
Controlled growth of nanowires is an important, emerging research field with many applications in, for example, electronics, photonics, and life sciences. Nanowires of zinc blende crystal structure, ...grown in the B direction, which is the favoured direction of growth, usually have a large number of twin-plane defects. Such defects limit the performance of optoelectronic nanowire-based devices. To investigate this defect formation, we examine GaP nanowires grown by metal-organic vapour-phase epitaxy. We show that the nanowire segments between the twin planes are of octahedral shape and are terminated by {111} facets, resulting in a microfaceting of the nanowires. We discuss these findings in a nucleation context, where we present an idea on how the twin planes form. This investigation contributes to the understanding of defect formation in nanowires. One future prospect of such knowledge is to determine strategies on how to control the crystallinity of nanowires.
Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for ...model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (
), Rat1 (
), Zebrafish1 (
), Fruitfly1 (
), and Worm1 (
). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer's disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.
Behavioural attraction of the malaria vector Anopheles coluzzii to human host odour increases during adult maturation. We have previously demonstrated that the onset of host seeking in An. coluzzii ...coincides with an increased sensitivity of the CO
-sensitive neurons and abundance of chemosensory receptor gene transcripts in the maxillary palp. In this study, we extend our analysis to the antenna. Functional characterisation of the near-complete repertoire of odorant receptors (Ors) expressed in this tissue, to fractioned human odour, reveals a subset of salient human odorants to be detected by Ors at physiological relevant concentrations. When presented as a blend in their ratio of natural emission, these odorants elicit attraction by host-seeking mosquitoes, emphasising that Ors alone can mediate this behaviour. However, the same blend inhibits attraction in teneral mosquitoes. This switch in behavioural response indicates a change in valence during adult maturation. Quantitative analysis of Or transcript abundance and in vivo electrophysiological analysis reveal that the olfactory system of female An. coluzzii undergoes concerted changes that correlate with the onset of host seeking. We conclude that changes in Or abundance modulate peripheral olfactory coding, resulting in ecologically relevant behavioural effects.
•Lumateperone had an antipsychotic-like effect in the CAR test.•Lumateperone facilitated NMDA and AMPA receptor-mediated currents in the rat mPFC.•NMDA and AMPA receptor-mediated currents were ...dopamine D1 dependent.•Lumateperone significantly increased dopamine and glutamate release in the rat mPFC.•Mechanisms help explain lumateperone's improvement of negative/depressive symptoms.
Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic- and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateperone, electrophysiology in vitro to study lumateperone's effects on NMDA- and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine- and glutamate release in the rat mPFC. Our results demonstrate that lumateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumateperone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations.
Septoria tritici blotch (STB) caused by the fungal pathogen
Zymoseptoria tritici
and powdery mildew (PM) caused by
Blumeria graminis
f.sp
tritici
(
Bgt
) are among the forefront foliar diseases of ...wheat that lead to a significant loss of grain yield and quality. Resistance breeding aimed at developing varieties with inherent resistance to STB and PM diseases has been the most sustainable and environment-friendly approach. In this study, 175 winter wheat landraces and historical cultivars originated from the Nordic region were evaluated for adult-plant resistance (APR) to STB and PM in Denmark, Estonia, Lithuania, and Sweden. Genome-wide association study (GWAS) and genomic prediction (GP) were performed based on the adult-plant response to STB and PM in field conditions using 7,401 single-nucleotide polymorphism (SNP) markers generated by 20K SNP chip. Genotype-by-environment interaction was significant for both disease scores. GWAS detected stable and environment-specific quantitative trait locis (QTLs) on chromosomes 1A, 1B, 1D, 2B, 3B, 4A, 5A, 6A, and 6B for STB and 2A, 2D, 3A, 4B, 5A, 6B, 7A, and 7B for PM adult-plant disease resistance. GP accuracy was improved when assisted with QTL from GWAS as a fixed effect. The GWAS-assisted GP accuracy ranged within 0.53–0.75 and 0.36–0.83 for STB and PM, respectively, across the tested environments. This study highlights that landraces and historical cultivars are a valuable source of APR to STB and PM. Such germplasm could be used to identify and introgress novel resistance genes to modern breeding lines.
While treatment for breast cancer has been refined and overall survival has improved, there is concern that the incidence of brain metastases has increased.
We identified patients in Sweden with ...incident breast cancer 1998-2006 in the National Cancer Register, and matched these to the National Patient Register to obtain information on hospital admissions for distant metastases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed with Cox regression as estimates of relative risk.
Among 50 528 breast cancer patients, 696 (1.4%) were admitted with brain metastases during median 3.5 years of follow-up. Admissions for other metastases were found in 3470 (6.9%) patients. Compared with the period 1998-2000, patients diagnosed with breast cancer 2004-2006 were at a 44% increased risk of being admitted with brain metastases (HR 1.44, 95% CI 1.13-1.85).
The incidence of admissions with brain metastases in breast cancer patients was increasing in the mid-2000s in Sweden. These findings support a true increase in incidence of brain metastases among breast cancer patients.
Growth of one-dimensional nanostructures in MOVPE Seifert, Werner; Borgström, Magnus; Deppert, Knut ...
Journal of crystal growth,
12/2004, Letnik:
272, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
The use of metal organic vapor-phase epitaxy (MOVPE) for growth of one-dimensional nanostructures in the material systems GaAs, GaP, InAs and InP is investigated. Some kinetic effects are discussed, ...especially the general finding that in MOVPE thinner whiskers grow faster than thicker whiskers. Effects of growth temperature on growth rate and shape of the whiskers, the effects of different growth directions on the perfection of the materials and the possibilities to grow heterostructures in axial and lateral directions are reported. Ways to overcome the randomness in whisker growth by controlled seeding of the Au particles and by using lithography for site control are demonstrated.
Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect ...changes in cognition.
To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE).
Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines.
The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups.
In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.