An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported. Whether COVID-19 increases the risk of VTE in non-ICU ...wards remains unknown. We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.
In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS). The study was approved by the Institutional Ethics Committee.
The study comprised 156 patients (65.4% male). All but three patients received standard doses of thromboprophylaxis. Median days of hospitalization until CCUS was 9 (IQR 5–17). CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT. Seven patients (4.5%) had bilateral distal DVT. Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001. D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1–70.1). D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61–0.84).
In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series. Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.
In this work, we focus on (CH3)2NH2PbI3, a member of the AmineHPbI3 series of hybrid organic–inorganic compounds, reporting a very easy mechanosynthesis route for its preparation at room ...temperature. We report that this (CH3)2NH2PbI3 compound with 2H-perovskite structure experiences a first-order transition at ≈250 K from hexagonal symmetry P63/mmc (HT phase) to monoclinic symmetry P21/c (LT phase), which involves two cooperative processes: an off-center shift of the Pb2+ cations and an order–disorder process of the N atoms of the DMA cations. Very interestingly, this compound shows a dielectric anomaly associated with the structural phase transition. Additionally, this compound displays very large values of the dielectric constant at room temperature because of the appearance of a certain conductivity and the activation of extrinsic contributions, as demonstrated by impedance spectroscopy. The large optical band gap displayed by this material (E g = 2.59 eV) rules out the possibility that the observed conductivity can be electronic and points to ionic conductivity, as confirmed by density functional theory calculations that indicate that the lowest activation energy of 0.68 eV corresponds to the iodine anions, and suggests the most favorable diffusion paths for these anions. The obtained results thus indicate that (CH3)2NH2PbI3 is an electronic insulator and an ionic conductor, where the electronic conductivity is disfavored because of the low dimensionality of the (CH3)2NH2PbI3 structure.
Abstract Major depression is a mental disorder often preceded by exposure to chronic stress or stressful life events. Recently, animal models based on social conflict such as chronic social defeat ...stress (CSDS) are proposed to be more relevant to stress-induced human psychopathology compared to environmental models like the chronic mild stress (CMS). However, while CMS reproduces specifically core depressive symptoms such as anhedonia and helplessness, CSDS studies rely on the analysis of stress-induced social avoidance, addressing different neuropsychiatric disorders. Here, we study comparatively the two models from a behavioural and neurochemical approach and their possible relevance to human depression. Mice (C57BL/6) were exposed to CMS or CSDS for six weeks and ten days. Anhedonia was periodically evaluated. A battery of test applied during the fourth week after the stress procedure included motor activity, memory, anxiety, social interaction and helplessness. Subsequently, we examined glutamate, GABA, 5-HT and dopamine levels in the prefrontal cortex, hippocampus and brainstem. CMS induced a clear depressive-like profile including anhedonia, helplessness and memory impairment. CSDS induced anhedonia, hyperactivity, anxiety and social avoidance, signs also common to anxiety and posttraumatic stress disorders. While both models disrupted the excitatory inhibitory balance in the prefrontal cortex, CMS altered importantly this balance in the brainstem. Moreover, CSDS decreased dopamine in the prefrontal cortex and brainstem. We suggests that while depressive-like behaviours might be associated to altered aminoacid neurotransmission in cortical and brain stem areas, CSDS induced anxiety behaviours might be linked to specific alteration of dopaminergic pathways involved in rewarding processes.
In order to study which Bartonella genotypes are circulating among small mammals in Spain, we analyzed the spleens of 395 animals from three different areas--247 animals from the Basque Country ...(northern Spain), 121 animals from Catalonia (northeastern Spain), and 27 animals from Madrid (central Spain)--by a triplex PCR combined with a reverse line blot previously described by our group. The prevalence of Bartonella was 26.8% (106/395), and in 4.8% (19/395) of the animals more than one Bartonella genotype was detected. The study of gltA and the intergenic transcribed spacer in the positive samples demonstrated a large diversity, allowing the assignation of them into 22 genotypes. The most prevalent genotypes were 2 and 3, which are closely related to Bartonella taylorii. In addition, nine genotypes were associated with specific mammal species. Genotypes close to the zoonotic Bartonella grahamii, Bartonella elizabethae, and Bartonella rochalimae were also detected. Ten genotypes showed a percentage of similarity with known Bartonella species lower than 96%, suggesting the presence of potential new species. Further studies of the impact of these pathogens on human health and especially in cases of febrile illness in Spain are strongly recommended. Furthermore, our method has been updated with 21 new probes in a final panel of 36, which represents a robust molecular tool for clinical and environmental Bartonella studies.
Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation ...frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome.
One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples.
Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at -51 and -31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at -283 nt relative to the start site of the ADIPOQ promoter.
These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to predict and follow up the physiological changes associated with obesity and insulin resistance.
Rationale
Chronic social defeat stress (CSDS) has been proposed as a model of depression. However, most CSDS studies rely only on the analysis of stress-induced social avoidance. Moreover, the ...predictive validity of the model has been poorly analyzed, let alone its interaction with biological risk factors.
Objectives
Here, we explore the validity of CSDS as a depression model. Further, the effect of decreased vesicular glutamate transporter 1 (VGLUT1), as a potential factor enhancing a depressive-like phenotype, was studied.
Methods
Mice were exposed to CSDS (10 days) followed by saline, venlafaxine, fluoxetine, or tianeptine treatment (30 days). The battery of behaviors included motor activity, memory, anxiety, social interaction, helplessness, and anhedonic-like behavior. Moreover, the behavioral effect of CSDS in VGLUT1 heterozygous (VGLUT1+/−) mice was studied, as well as the regulation of VGLUT1 mRNA.
Results
CSDS induced anhedonia, helplessness, hyperactivity, anxiety, social avoidance, and freezing, as well as downregulation of VGLUT1 mRNA in the amygdala. Repeated venlafaxine showed antidepressant-like activity and both venlafaxine and tianeptine behaved as effective anxiolytics. CSDS-induced social avoidance was reverted by tianeptine. Fluoxetine failed to revert most of the behavioral alterations. VGLUT1+/− mice showed an enhanced vulnerability to stress-induced social avoidance.
Conclusion
We suggest that CSDS is not a pure model of depression. Indeed, it addresses relevant aspects of anxiety-related disorders. Firstly, CSDS-induced anhedonia and social avoidance are not associated in this model. Moreover, CSDS might be affecting brain areas mainly involved in the processing of social behavior, such as the amygdala, where the glutamatergic mechanism could play a key role.
Summary
Objective
To assess the risk of non‐fatal ischemic stroke associated with non‐steroidal anti‐inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, ...background cardiovascular (CV) risk and use of concomitant aspirin were studied.
Methods
We performed a population‐based case‐control study. Patients were considered exposed if they were on treatment within a 30‐day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression.
Results
Two thousand eight hundred and eighty‐eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90–1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19–1.97), in particular when used at high doses (OR = 1.62; 1.06–2.46), over long‐term periods (> 365 days; OR = 2.39; 1.52–3.76) and in patients with a high background CV risk (OR = 1.78; 1.23–2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05–2.67), in long‐term treatments (OR = 2.00; 1.14–3.53) and in patients with CV risk factors (OR = 2.33; 1.40–3.87). No association was found with ibuprofen (OR = 0.94; 0.76–1.17) or naproxen (OR = 0.68; 0.36–1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85–1.10) or in patients at high CV risk (OR = 0.94; 0.78–1.14).
Conclusions
Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.
5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can ...produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping
DPYD
gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of
DPYD
previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.
Aims. Our goal is to morphologically classify the sources identified in the images of the J-PLUS early data release (EDR) as compact (stars) or extended (galaxies) using a dedicated Bayesian ...classifier. Methods. J-PLUS sources exhibit two distinct populations in the r-band magnitude versus concentration plane, corresponding to compact and extended sources. We modelled the two-population distribution with a skewed Gaussian for compact objects and a log-normal function for the extended objects. The derived model and the number density prior based on J-PLUS EDR data were used to estimate the Bayesian probability that a source is a star or a galaxy. This procedure was applied pointing-by-pointing to account for varying observing conditions and sky positions. Finally, we combined the morphological information from the g, r, and i broad bands in order to improve the classification of low signal-to-noise sources. Results. The derived probabilities are used to compute the pointing-by-pointing number counts of stars and galaxies. The former increases as we approach the Milky Way disk, and the latter are similar across the probed area. The comparison with SDSS in the common regions is satisfactory up to r ~ 21, with consistent numbers of stars and galaxies, and consistent distributions in concentration and (g−i) colour spaces. Conclusions. We implement a morphological star/galaxy classifier based on probability distribution function analysis, providing meaningful probabilities for J-PLUS sources to one magnitude deeper (r ~ 21) than a classical Boolean classification. These probabilities are suited for the statistical study of 150 thousand stars and 101 thousand galaxies with 15 < r ≤ 21 present in the 31.7 deg2 of the J-PLUS EDR. In a future version of the classifier, we will include J-PLUS colour information from 12 photometric bands.
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