A new species of Liolaemus related to L. nigroviridis from the Andean highlands of Central Chile (Iguania, Liolaemidae)

Indexación: Web of Science; Scopus.The Liolaemus nigroviridis group is a clade of highland lizards endemic to Chile. These species are distributed from northern to central Chile, and currently there are no cases of sympatric distribution. This study describes a new species, Liolaemus uniformis sp. n., from this group, and provides a detailed morphological characterization and mitochondrial phylogeny using cytochrome-b. Liolaemus uniformis was found in sympatry with L. nigroviridis but noticeably differed in size, scalation, and markedly in the color pattern, without sexual dichromatism. This new species has probably been confused with L. monticola and L. bellii, both of which do not belong to the nigroviridis group. The taxonomic issues of this group that remain uncertain are also discussed.https://zookeys.pensoft.net/articles.php?id=601

Temporal dynamics and neuronal specificity of Grin3a expression in the mouse forebrain

GluN3A subunits endow N-Methyl-D-Aspartate receptors (NMDARs) with unique biophysical, trafficking, and signaling properties. GluN3A-NMDARs are typically expressed during postnatal development, when they are thought to gate the refinement of neural circuits by inhibiting synapse maturation, and stabilization. Recent work suggests that GluN3A also operates in adult brains to control a variety of behaviors, yet a full spatiotemporal characterization of GluN3A expression is lacking. Here, we conducted a systematic analysis of Grin3a (gene encoding mouse GluN3A) mRNA expression in the mouse brain by combining high-sensitivity colorimetric and fluorescence in situ hybridization with labeling for neuronal subtypes. We find that, while Grin3a mRNA expression peaks postnatally, significant levels are retained into adulthood in specific brain regions such as the amygdala, medial habenula, association cortices, and high-order thalamic nuclei. The time-course of emergence and down-regulation of Grin3a expression varies across brain region, cortical layer of residence, and sensory modality, in a pattern that correlates with previously reported hierarchical gradients of brain maturation and functional specialization. Grin3a is expressed in both excitatory and inhibitory neurons, with strong mRNA levels being a distinguishing feature of somatostatin interneurons. Our study provides a comprehensive map of Grin3a distribution across the murine lifespan and paves the way for dissecting the diverse functions of GluN3A in health and disease. circuit refinement, excitatory glycine receptors, high-order thalamus, neocortical maturation, somatostatin interneuron

Layperson perception of reflux-related symptoms

OBJECTIVE: To assess for differences of intended meaning in the description of reflux-related symptoms among otolaryngology patients and clinicians. STUDY DESIGN: Cross-sectional survey-based study. SETTING: Five tertiary, academic otolaryngology practices. METHODS: Between June 2020 and July 2022, a questionnaire consisting of 20 common descriptors of reflux-related symptoms within four domains (throat-, chest-, stomach-, and sensory-related symptoms) was completed by patients. Attending otolaryngologists at five academic medical centers then completed the same survey. The primary outcome was to assess differences in patient and clinician perceptions of reflux-related symptoms. Differences based on geographic location was a secondary outcome. RESULTS: A total of 324 patients and 27 otolaryngologists participated. Patients selected a median of six terms compared with 10.5 for otolaryngologists ( CONCLUSION: There are differences between otolaryngologists and their patients in the interpretation of the symptoms of reflux. Patients tended to have a narrower interpretation of reflux with symptoms primarily limited to classic stomach-related symptoms, while clinicians tended to have a broader definition of reflux that included extra-esophageal manifestations of disease. This has important counseling implications for the clinician, as patients presenting with reflux symptoms may not comprehend the relationship of those symptoms to reflux disease

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Deep Sequencing of Small RNAs in Tomato for Virus and Viroid Identification and Strain Differentiation

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution