598 research outputs found
Pharmacological aspects of neonatal antidepressant withdrawal
Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary
A Current Induced Transition in atomic-sized contacts of metallic Alloys
We have measured conductance histograms of atomic point contacts made from
the noble-transition metal alloys CuNi, AgPd, and AuPt for a concentration
ratio of 1:1. For all alloys these histograms at low bias voltage (below 300
mV) resemble those of the noble metals whereas at high bias (above 300 mV) they
resemble those of the transition metals. We interpret this effect as a change
in the composition of the point contact with bias voltage. We discuss possible
explanations in terms of electromigration and differential diffusion induced by
current heating.Comment: 5 pages, 6 figure
Clinical and Pathological Findings in SARS-CoV-2 Disease Outbreaks in Farmed Mink (Neovison vison)
SARS-CoV-2, the causative agent of COVID-19, caused respiratory disease outbreaks with increased mortality in 4 mink farms in the Netherlands. The most striking postmortem finding was an acute interstitial pneumonia, which was found in nearly all examined mink that died at the peak of the outbreaks. Acute alveolar damage was a consistent histopathological finding in mink that died with pneumonia. SARS-CoV-2 infections were confirmed by detection of viral RNA in throat swabs and by immunohistochemical detection of viral antigen in nasal conchae, trachea, and lung. Clinically, the outbreaks lasted for about 4 weeks but some animals were still polymerase chain reaction–positive for SARS-CoV-2 in throat swabs after clinical signs had disappeared. This is the first report of the clinical and pathological characteristics of SARS-CoV-2 outbreaks in mink farms
Studies of the Anomalous Hall Effect and Magnetic Structure of Nd2Mo2O7 -Test of the Chirality Mechanism-
Neutron scattering studies have been carried out under the magnetic fields
H//[0_11] and H//[001] on a single crystal of Nd2Mo2O7, whose Hall
resistivity(rhoH) exhibits quite unusual H- and temperature(T)-dependences.
Material parameters such as the single ion anisotropies of the Mo- and Nd-
moments and exchange coupling constants among the Mo-Mo, Mo-Nd and Nd-Nd
moments, have been determined to reproduce various kinds of experimental data
taken as a function of H and T. For example, the neutron Bragg intensities,
magnetization curves and the magnetic specific heats have been reproduced by
the common parameters. By using the magnetic structure reproduced by these
parameters, the spin chirality (chi) of Mo spins or the fictitious magnetic
flux Phi proportional to chi has been calculated as a function of H and T by
using equation chi=, where the bracket means the statistical
average. (Note that we do not use the equation chi=x, because the
local nature of the chirality should be correctly considered.) Comparing the
calculated results with the observed rhoH, we can conclude that the unusual
behavior of rH cannot be understood consistently only by the chirality
mechanism.Comment: 16 pages, 12 fiures, submitted to J. Phys. Soc. Jp
The peptidylarginine deiminase gene is a conserved feature of Porphyromonas gingivalis
Periodontitis is an infective process that ultimately leads to destruction of the soft and hard tissues that support the teeth (the periodontium). Periodontitis has been proposed as a candidate risk factor for development of the autoimmune disease rheumatoid arthritis (RA). Porphyromonas gingivalis, a major periodontal pathogen, is the only known prokaryote expressing a peptidyl arginine deiminase (PAD) enzyme necessary for protein citrullination. Antibodies to citrullinated proteins (anti-citrullinated protein antibodies, ACPA) are highly specific for RA and precede disease onset. Objective of this study was to assess P. gingivalis PAD (PPAD) gene expression and citrullination patterns in representative samples of P. gingivalis clinical isolates derived from periodontitis patients with and without RA and in related microbes of the Porphyromonas genus. Our findings indicate that PPAD is omnipresent in P. gingivalis, but absent in related species. No significant differences were found in the composition and expression of the PPAD gene of P. gingivalis regardless of the presence of RA or periodontal disease phenotypes. From this study it can be concluded that if P. gingivalis plays a role in RA, it is unlikely to originate from a variation in PPAD gene expression
Divergences in Real-Time Classical Field Theories at Non-Zero Temperature
The classical approximation provides a non-perturbative approach to
time-dependent problems in finite temperature field theory. We study the
divergences in hot classical field theory perturbatively. At one-loop, we show
that the linear divergences are completely determined by the classical
equivalent of the hard thermal loops in hot quantum field theories, and that
logarithmic divergences are absent. To deal with higher-loop diagrams, we
present a general argument that the superficial degree of divergence of
classical vertex functions decreases by one with each additional loop: one-loop
contributions are superficially linearly divergent, two-loop contributions are
superficially logarithmically divergent, and three- and higher-loop
contributions are superficially finite. We verify this for two-loop SU(N)
self-energy diagrams in Feynman and Coulomb gauges. We argue that hot,
classical scalar field theory may be completely renormalized by local (mass)
counterterms, and discuss renormalization of SU(N) gauge theories.Comment: 31 pages with 7 eps figure
Automated causal inference in application to randomized controlled clinical trials
Randomized controlled trials (RCTs) are considered the gold standard for testing causal hypotheses in the clinical domain; however, the investigation of prognostic variables of patient outcome in a hypothesized cause–effect route is not feasible using standard statistical methods. Here we propose a new automated causal inference method (AutoCI) built on the invariant causal prediction (ICP) framework for the causal reinterpretation of clinical trial data. Compared with existing methods, we show that the proposed AutoCI allows one to clearly determine the causal variables of two real-world RCTs of patients with endometrial cancer with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remains consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis
Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD
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