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The importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms.
Thirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated.
Symptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use.
Using a longitudinal within-subjects design, we showed that hippocampal–amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or ‘load’), suggesting functional activation patterns in depression are not subject to functional ‘scarring’ although this hypothesis awaits future replication.
In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals suffering from schizophrenia-spectrum disorders. In contrast, however, positive psychotic symptoms (e.g., command hallucinations and persecutory delusions) often drive behavior which serves as the gateway to arrest and criminalization. Historically, the keystone of treatment for positive psychotic symptoms has been antagonism of dopamine D2 receptors in the mesolimbic tract. In this article, we review and explore the principles underlying dopamine antagonism for the treatment of psychosis; optimization of dopamine antagonists in treating positive psychotic symptoms; the advantages of depot dopamine antagonist antipsychotics in forensic settings; the concepts of pharmacokinetic and pharmacodynamic treatment failures; and the role of medication plasma concentrations in optimizing and managing treatment.
Background: Atrial fibrillation (AF) is associated with increased risk of ischemic stroke. In Canada, the contemporary burden of AF-related stroke is incompletely characterized. Our objective was to determine temporal trends in hospital admissions and in-hospital mortality for AF-related stroke in Canada from 2007 to 2015. Methods: We conducted a retrospective cohort study using Canadian national administrative data to identify admissions to hospital for stroke with comorbid AF between 2007 and 2015. We analyzed temporal trends in age- and sex-standardized proportion of admissions with comorbid AF and associated in-hospital mortality. Results: There were 222,100 admissions to hospital for ischemic (182,990) or hemorrhagic (39,110) stroke. The age-sex adjusted proportion of ischemic stroke admissions with comorbid AF increased from 16.2% to 20.5% (p for trend = 0.02) between 2007 and 2015, and was stable among hemorrhagic stroke. In-hospital mortality for ischemic stroke with comorbid AF decreased from 21.6% to 15.0% (p for trend = 0.001). Conclusions: Rates of hospital admission for ischemic stroke with comorbid AF have increased, while associated in-hospital mortality has decreased. These results identify AF as an important continued focus for stroke prevention. Our findings provide insight into current trends and highlight the need for continued focus on AF-related stroke.
Evidence suggests that skin picking disorder (SPD) could be a prevalent condition associated with comorbidity and psychosocial dysfunction. However, just a few studies have assessed the prevalence and correlates of SPD in samples from low- and middle-income countries. In addition, the impact of SPD on quality of life (QoL) dimension after multivariable adjustment to potential confounders remains unclear.
Data were obtained from a Brazilian anonymous Web-based research platform. Participants provided sociodemographic data and completed the modified Skin Picking–Stanford questionnaire, the Hypomania Checklist (HCL-32), the Patient Health Questionnaire-9 (PHQ-9), the Fagerström Test for Nicotine Dependence, Alcohol Use Disorder Identification Test (AUDIT), Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report–short form, and the World Health Organization quality of life abbreviated scale (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models.
For our survey, 7639 participants took part (71.3% females; age: 27.2±7.9 years). The prevalence of SPD was 3.4% (95% CI: 3.0–3.8%), with a female preponderance (P<0.001). In addition, SPD was associated with a positive screen for a major depressive episode, nicotine dependence, and alcohol dependence, as well as suicidal ideation. Physical and psychological QoL was significantly more impaired in participants with SPD compared to those without SPD, even after adjustment for comorbidity.
In this large sample, SPD was a prevalent condition associated with co-occurring depression, nicotine, and alcohol dependence. In addition, SPD was independently associated with impaired physical and psychological QoL. Public health efforts toward the early recognition and treatment of SPD are warranted.
For treatment of patients diagnosed with schizophrenia, comparative
long-term effectiveness of antipsychotic drugs to reduce relapses when
minimising adverse effects is of clinical interest, hence prompting this
To evaluate the comparative long-term effectiveness of antipsychotic
We systematically searched electronic databases for reports of randomised
controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing
relapse risks in schizophrenia. We conducted network meta-analysis of 18
antipsychotics and placebo.
Studies of 10 177 patients in 56 reports were included; treatment
duration averaged 48 weeks (range 4–156). Olanzapine was significantly
more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI
0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine
decanoate was more effective than chlorpromazine (OR=0.31, 95% CI
0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol,
haloperidol decanoate and trifluoperazine produced more extrapyramidal
adverse effects than olanzapine or quetiapine; and olanzapine was
associated with more weight gain than other agents.
Except for apparent superiority of olanzapine and fluphenazine decanoate
over chlorpromazine, most agents showed intermediate efficacy for relapse
prevention and differences among them were minor. Typical antipsychotics
yielded adverse neurological effects, and olanzapine was associated with
weight gain. The findings may contribute to evidence-based treatment
selection for patients with chronic psychotic disorders.
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refined de novo P. knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the ‘MaHPIC Pk genome sequence’, includes manual annotation of the SICAvar gene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of the SICAvar repertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens.
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.
Faster eating rates are associated with increased energy intake, but little is known about the relationship between children’s eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children’s BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.
Background: The pathophysiology of subarachnoid hemorrhage (SAH) is complex and includes disruption of the blood-brain barrier (BBB). We freshly isolated BBB endothelial cells (BECs) by 2 distinct methods after experimental SAH and then interrogated their gene expression profiles with the goal of uncovering new therapeutic targets. Methods: SAH was induced using the prechiasmatic blood injection mouse model. BBB permeability studies were performed by administering intraperitoneal cadaverine dye injections at 24h and 48h. BECs were isolated either by sequential magnetic-based sorting for CD45-CD31+ cells or by fluorescence-activated cell sorting (FACS) for Tie2+Pdgfrb- cells. Total RNA was extracted and analyzed using Affymetrix Mouse Gene 2.0 ST Arrays. Results: BBB impairment occurred at 24h and resolved by 48h after SAH. Analysis of gene expression patterns in BECs at 24h reveal clustering of SAH and sham samples. We identified 707 (2.8%) significant differentially-expressed genes (403 upregulated, 304 downregulated) out of 24,865 interrogated probe sets. Many significantly upregulated genes were involved in inflammatory pathways. These microarray results were validated with real-time polymerase chain reaction (RT-PCR). Conclusions: This study is the first to investigate in an unbiased manner, whole genome expression profiling of freshly-isolated BECs in an SAH animal model, yielding targets for novel therapeutic intervention.
The Sun’s activity has been evolving in the ascending phase of Solar Cycle 23 since 1996. Similarly, the research on solar activity is also in the ascending phase of a new active period. Numerous new results have been obtained from a large amount of space and ground observations covering a wide spectral range. In particular, observations with YOHKOH, SOHO, and TRACE have revealed a multitude of phenomena and processes in the solar atmosphere which provide us a new picture of the Sun.
Association mapping based on linkage disequilibrium (LD) is a promising tool to identify genes responsible for quantitative variations underlying complex traits. The present paper presents an association mapping panel consisting of 172 upland cotton (Gossypium hirsutum L.) accessions. The panel was phenotyped for five cotton plant architecture traits across multiple environments and genotyped using 386 simple sequence repeat (SSR) markers. Of these markers, 101 polymorphic SSR markers were used in the final analysis. There were abundant phenotypic variations within this germplasm panel and a total of 267 alleles ranging from two to seven per locus were identified in all collections. The threshold of LD decay was set to r2 = 0·1 and 0·2, and the genome-wide LD extended up to about 13–14 and 6–7 cM, respectively, providing the potential for association mapping of agronomically important traits in upland cotton. A total of 66 marker–trait associations were detected based on a mixed linear model, of which 35 were found in more than one environment. The favourable alleles from 35 marker loci can be used in marker-assisted selection of target traits. Both the synergistic alleles and the negative alleles for some traits, especially plant height and fruit branch angle, can be utilized in plant architecture breeding programmes according to specific breeding objectives.
Background: Blood breakdown products such as bilirubin and bilirubin oxidation products damage cortex and white matter after intracerebral hemorrhage(ICH). Here, we tested whether albumin can antagonize axonal damage caused by bilirubin. Methods: The effect of albumin on white matter injury was investigated using brain slices in vitro. After CD-1 mice brain slices were cut using a vibratome, they were incubated in one of five solutions: artificial cerebral spinal fluid (ACSF), bilirubin ACSF, bilirubin and albumin ACSF, bilirubin ACSF that had albumin added 1 hour(h) later, and bilirubin and denatured albumin ACSF. All solutions were continuously aerated with 95% O2 and 5% CO2. Subsequently, electrophysiological recordings of axonal response to electrical stimulation were performed 8h after incubation of brain slices. Results: Bilirubin treatment profoundly damaged both myelinated and unmeylinated axons in brain slices, but had a greater effect on myelinated axons. Unmyelinated axons were found to be more susceptible to damage from denatured albumin. Albumin treatment at 0 h and 1 h significantly diminished bilirubin toxicity for both myelinated and unmyelinated axons, with 1 h delayed albumin treatment conferring greater neuroprotection. Conclusions: These results implicate the role of albumin in preventing bilirubin-induced axonal damage following ICH and its potential therapeutic value for hemorrhagic stroke.
Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.
The electronic properties of the interface between Rh clusters and CeO2 (111), (110) and (100) surfaces were studied using an isothermal-isobaric (NPT) ensemble at 773 K and 101.343 kPa using the tight binding-quantum chemical molecular dynamics (TB-QCMD) method. The amount of electronic exchange by interaction at the interface between the supported Rh55 clusters and each CeO2 surface was investigated quantitatively. A comparison of the mean square displacement (MSD) showed that the topmost oxygens on the Rh-supporting CeO2 surface exhibited higher mobility than those of the bare CeO2 surface. Although the mobility of the topmost oxygens on the bare CeO2 surface was in the order (100) > (110) > (111), this sequence was altered by the presence of Rh, so that the oxygen mobility for the more open (110) surface was the largest. The amount of electron exchange that occurred between Rh and the CeO2 (110) surface was also larger than for the (111) or (100) surface. The Ce 4f orbitals on the CeO2 (110) surface exhibited the strongest mixing with Rh 4d orbitals, which simultaneously caused restructuring and instability of the topmost Ce-O bonds. This enhancement of oxygen migration in the presence of Rh was occurred together with an increase in the number of oxygen vacancies on the ceria surface. This was because the topmost oxygens was shifted to have a stronger affinity with Rh and thus formed stronger bonds with Rh than with Ce.
Human infection with the emerging avian influenza A(H7N9) virus in China in 2013 has raised global concerns. We conducted a retrospective descriptive study of 27 confirmed human influenza A(H7N9) cases in Jiangsu Province, to elaborate poultry-related exposures and to provide a more precise estimate of the incubation periods of the illness. The median incubation period was 6 days (range 2–10 days) in cases with single known exposure and was 7·5 days (range 6·5–12·5 days) in cases with exposures on multiple days, difference between the two groups was not significant (Z = −1·895, P = 0·058). The overall median incubation period for all patients was estimated to be 7·5 days (range 2–12·5 days). Our findings further highlight the necessity for public health authorities to extend the period of medical surveillance from 7 days to 10 days.
Based on the researches on the temperature and microstructures dependent fracture strength and temperature dependent thermal shock resistance, the new thermal shock resistance models for ultra-high-temperature ceramics were proposed. The effect of density on the fracture strength of material was investigated. A damage term was introduced to reveal the effects of uncertain factors on fracture strength. The roles of residual stress and microstructure sizes at different initial thermal shock temperatures in the thermal shock resistance were studied using the models. The study showed that the models can reveal the relationships among the residual stress, microstructure sizes and the temperature dependent thermal shock resistance well. The better thermal shock resistance is found for ultra-high-temperature ceramics having small SiC grains and relatively large micro-cracks around SiC grains. Large enhancement in thermal shock resistance can be achieved through our studies.
We present the results of our systematic investigation of the RE dependency of superconductivity in the parent compounds T’-RE2CuO4 (RE = Pr, Nd, Sm, Eu, Gd, and Tb). Superconducting samples were prepared by metal organic decomposition (MOD). A stringent control of synthesis- and post-annealing-conditions is required to obtain superconducting samples. Superconductivity with a transition temperature (Tconset) ≥ 30 K is achieved for RE = Pr and Nd. By contrast, Tconset is at highest 20 K for RE = Gd. Our results indicate that the induction of superconductivity into T’-RE2CuO4 cuprates strongly depends on the RE3+ ionic size. This trend is discussed from the viewpoint of RE-dependent thermodynamic stability of T’-RE2CuO4. For smaller RE3+ ions, the thermodynamic boundary conditions become tighter.
Epitaxial InAs layers were grown by molecular beam epitaxy (MBE) on GaAs substrates. The initial stages of nucleation were studied by in situ reflection high energy electron diffraction (RHEED). Cross-sectional TEM examination was used to investigate the morphology of the growing layer, while plan-view examination revealed the generation of misfit dislocations. The growth mode was found to depend mainly on the conditions used to nucleate the epitaxial layer. In most cases, Stranski-Krastanov type of growth was observed.