The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's ...antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.
In response to the emerging crisis and growing calls from patients and clinicians for guidance 5, a working group of clinical experts from the International College of Obsessive Compulsive Spectrum ...Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network of the European College of Neuropsychopharmacology (OCRN) have produced this consensus statement with the aim of delivering pragmatic guidance at the earliest opportunity to clinicians for managing this complex challenge. Based on the risks associated with exposure and response prevention (ERP) in the pandemic (see below), and uncertainty as to which of the two evidence-based treatments, pharmacotherapy or cognitive behaviour therapy (CBT), represents the most efficacious first line treatment modality 11, pharmacotherapy should be the first option for adults and children with OCD with contamination, washing or cleaning symptoms during the COVID-19 pandemic. Consider A) type of medication; most patients should receive an SSRI, or if not responsive, another SSRI and as a third choice clomipramine (for which an ECG may be required in certain patient groups); Note US Food and Drug Administration "black box" warnings or advice from equivalent national regulatory authorities regarding increased risk in young people and other vulnerable patient groups. Check for adverse effects and be available for any concerns related to "activation" or newly emergent or increased suicidal ideation, which in the young can be mitigated by starting treatment at a low dose and titrating more gradually; B) dosage; if the patient is on a suboptimal dose, consider increasing it, paying attention to any contraindications; C) SSRI-resistance; consider a low dose of adjunctive antipsychotic (aripiprazole, risperidone, quetiapine, olanzapine), especially if a tic is present; D) adherence; ensure the patient is able to obtain an adequate supply and is taking the treatment regularly.
Background
Frequent wheezing in original asthma predictive index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent ...wheezing in children, particularly aged over 3 years, has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records.
Methods
Among children who participated in a previous study (n = 427), all wheezing episodes documented in medical records were collected for children who had ≥2 wheezing episodes PLUS met one major criterion or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1 year) compared to those with longer interval (1 to 3 years).
Results
A total of 62 children met API at median age of 2.3 years. During follow‐up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1‐year interval (n = 40) vs 1‐ to 3‐year interval (n = 13) appeared to be similar in regard to the known risk factors for asthma.
Conclusions
Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (<3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding.
Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, ...an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibroblastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an α-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
Rationale
The practice of binge drinking is very common among adolescents of both sexes. It can have long-term consequences with respect to drug consumption during adulthood, but knowledge on these ...effects in females is limited.
Objectives
The long-lasting effects of intermittent exposure to ethanol (EtOH) during adolescence on different cocaine-elicited behaviours, including locomotor reactivity, conditioned place preference (CPP) and intravenous self-administration, were evaluated in male and female adult mice. It was hypothesized that an EtOH binge during adolescence would increase sensitivity to the effects of a sub-threshold dose of cocaine and has a differential impact on the drug’s effects in males and females.
Methods
Adolescent OF1 mice (postnatal day (PND) 26) underwent a 2-week pre-treatment schedule consisting of 16 doses of EtOH (2.5 g/kg) or saline (twice daily administrations separated by a 4-h interval i.p.) administered on two consecutive days separated by an interval of 2 days. Three weeks later (PND > 60), we assessed locomotor activity responses induced by an acute injection of different doses of cocaine in experiment 1 and the rewarding effects of cocaine on the CPP (1 mg/kg) and intravenous self-administration (1 mg/kg/infusion) paradigms in experiment 2.
Results
Pre-exposure to EtOH during adolescence altered motor reactivity to cocaine in a dose- and sex-dependent manner, increased sensitivity to cocaine in CPP and enhanced self-administration in adult mice.
Conclusions
The effects of intermittent exposure to ethanol during adolescence are evident in adulthood, during which greater sensitivity and intake of cocaine is observed and differ in each sex.
The objective of this research was to develop a direct artificial neural network with the ability to predict a corrosion rate of metals in different biodiesel. Experimental values were obtained by ...the electrochemical noise technique, EN, as well as, information reported in the literature. A backpropagation model was proposed with three layers; metal and biodiesel composition, blend biodiesel/diesel, total acid number (TAN), temperature and exposure time were considered as input variables in the model. The best fitting training data were acquired with 24:4:1, considering a Levenberg –Marquardt learning algorithm, a hyperbolic tangent and linear transfer functions in the hidden and output layer respectively. Experimental and simulated data were compared satisfactorily through the linear regression model with a correlation coefficient of 0.9885 and a mean square error, MSE, of 2.15 × 10−4 in the validation stage. Furthermore, the model agreed the requirements of the slope and the intercept statistical test with a 99% confidence. The obtained results indicated that the ANN model could be attractive as corrosion rate estimator.
•ANN model was applied to predict CR of metals in different biodiesel.•Database was collected by EN results and scientist available information.•Metal and environment composition, TAN, T and time were input variables.•ANN was successfully trained and validated by different database.•Unsaturated esters, metal ions and TAN greatly influenced the corrosion rate model.
In this work, nitrogen-doped graphene quantum dots (N-GQDs) were synthesized by pulsed laser ablation in liquid using Nd:YAG laser (532 nm). Graphite target was ablated in dimethylformamide, as ...solvent and nitrogen source, and the microstructure as well as optical properties of N-GQDs were studied. The N-GQDs structure consists of a graphitic core with oxygen and nitrogen functionalities and particle size about 3 nm, as demonstrated by X-ray photoelectron spectroscopy, Raman spectroscopy and transmission electron microscopy. The as-prepared N-GQDs structure was modified by solvothermal treatment at 65, 90 and 120 °C reducing the oxygen functional groups, adding nitrogen and restoring the π-conjugated structure of N-GQD. The N-GQDs exhibit UV–Vis absorption spectrum with the characteristic π-π* and n – π* electronic transitions of the GQDs with a large amount of oxygen and nitrogen functionalities. These N-GQDs exhibited a visible light photoluminescence centered at 486 nm upon an excitation of 410 nm and the photoluminescence intensity enhanced up to 4.05% of quantum yield after solvothermal treatment. The N-GQDs dispersion was used for selective detection of ascorbic acid, through a signal-off and signal-on system. The results show the use of N-GQDs as a competent photoluminescence sensor for metal ions and ascorbic acid.
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Worldwide the mosquito Aedes aegypti (L.) is the principal urban vector of dengue viruses. Currently 2.5 billion people are at risk for infection and reduction of Ae. aegypti populations is the most ...effective means to reduce the risk of transmission. Pyrethroids are used extensively for adult mosquito control, especially during dengue outbreaks. Pyrethroids promote activation and prolong the activation of the voltage gated sodium channel protein (VGSC) by interacting with two distinct pyrethroid receptor sites 1, formed by the interfaces of the transmembrane helix subunit 6 (S6) of domains II and III. Mutations of S6 in domains II and III synergize so that double mutants have higher pyrethroid resistance than mutants in either domain alone. Computer models predict an allosteric interaction between mutations in the two domains. In Ae. aegypti, a Ile1,016 mutation in the S6 of domain II was discovered in 2006 and found to be associated with pyrethroid resistance in field populations in Mexico. In 2010 a second mutation, Cys1,534 in the S6 of domain III was discovered and also found to be associated with pyrethroid resistance and correlated with the frequency of Ile1,016.
A linkage disequilibrium analysis was performed on Ile1,016 and Cys1,534 in Ae. aegypti collected in Mexico from 2000-2012 to test for statistical associations between S6 in domains II and III in natural populations. We estimated the frequency of the four dilocus haplotypes in 1,016 and 1,534: Val1,016/Phe1,534 (susceptible), Val1,016/Cys1,534, Ile1,016/Phe1,534, and Ile1,016/Cys1,534 (resistant). The susceptible Val1,016/Phe1,534 haplotype went from near fixation to extinction and the resistant Ile1,016/Cys1,534 haplotype increased in all collections from a frequency close to zero to frequencies ranging from 0.5-0.9. The Val1,016/Cys1,534 haplotype increased in all collections until 2008 after which it began to decline as Ile1,016/Cys1,534 increased. However, the Ile1,016/Phe1,534 haplotype was rarely detected; it reached a frequency of only 0.09 in one collection and subsequently declined.
Pyrethroid resistance in the vgsc gene requires the sequential evolution of two mutations. The Ile1,016/Phe1,534 haplotype appears to have low fitness suggesting that Ile1,016 was unlikely to have evolved independently. Instead the Cys1,534 mutation evolved first but conferred only a low level of resistance. Ile1,016 in S6 of domain II then arose from the Val1,016/Cys1,534 haplotype and was rapidly selected because double mutants confer higher pyrethroid resistance. This pattern suggests that knowledge of the frequencies of mutations in both S6 in domains II and III are important to predict the potential of a population to evolve kdr. Susceptible populations with high Val1,016/Cys1,534 frequencies are at high risk for kdr evolution, whereas susceptible populations without either mutation are less likely to evolve high levels of kdr, at least over a 10 year period.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human host genetic factors have been suggested to be determinants of the prevalence and clinical forms of Chagas disease. In this regard, IL-17A is believed to control parasitemia and protect against ...heart disease. In this work, we assessed whether IL17A gene polymorphisms are related to infection and/or development of the cardiac form of Chagas disease by genotyping for five IL17A SNPs (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) in 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n=595), seropositive asymptomatic (n=175) and chronic Chagas cardiomyopathy (n=401). Our results showed that SNP rs8193036, which is located upstream of the coding region of the gene, was slightly associated with protection against T. cruzi infection (P=0.0170, P(FDR)=0.0851, odds ratio (OR)=0.80, confidence interval (CI)=0.66-0.96) and associated with protection against the development of cardiomyopathy (P=0.0065, P(FDR)=0.0324, OR=0.75, CI=0.60-0.92). This finding suggests that this IL17A polymorphism could be associated with Trypanosoma cruzi infection and the development of chronic cardiomyopathy due to differential expression of cytokine IL-17A.
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