Automatic detection of alignment errors in cryo-electron tomography.

Cryo-electron tomography is an imaging technique that allows the study of the three-dimensional structure of a wide range of biological samples, from entire cellular environments to purified specimens. This technique collects a series of images from different views of the specimen by tilting the sample stage in the microscope. Subsequently, this information is combined into a three-dimensional reconstruction.

A multi-orbital Hund's rules-based ionic Hamiltonian for transition metal atoms: high-order equation of motion method approach and Kondo resonances.

A multi-orbital ionic Hamiltonian is presented to analyze the many-body properties of the d-transition metal atoms. This Hamiltonian considers all the atomic states obeying the first Hund's rule and also includes all orbital degeneracy, as well as the interaction of the atom with a metal. We analyze the solution of this ionic Hamiltonian by means of the equation of Motion method up to the fourth order,, in the atom-metal interaction.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated.

Evolution and long‑term respiratory sequelae after severe COVID-19 pneumonia: nitric oxide diffusion measurement value.

Introduction: There are no published studies assessing the evolution of combined determination of the lung diffusing capacity for both nitric oxide and carbon monoxide (DL and DL) 12 months after the discharge of patients with COVID-19 pneumonia.

Methods: Prospective cohort study which included patients who were assessed both 3 and 12 months after an episode of SARS-CoV-2 pneumonia. Their clinical status, health condition, lung function testings (LFTs) results (spirometry, DL-DL analysis, and six-minute walk test), and chest X-ray/computed tomography scan images were compared.

Promising Molecular Targets in Pharmacological Therapy for Neuronal Damage in Brain Injury.

The complex etiopathogenesis of brain injury associated with neurodegeneration has sparked a lot of studies in the last century. These clinical situations are incurable, and the currently available therapies merely act on symptoms or slow down the course of the diseases. Effective methods are being sought with an intent to modify the disease, directly acting on the properly studied targets, as well as to contribute to the development of effective therapeutic strategies, opening the possibility of refocusing on drug development for disease management.

Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis.

What Is This Summary About?: This plain language summary describes the main findings from a trial in people with idiopathic pulmonary fibrosis (also called IPF) that was recently published in the . IPF is a rare disease, where the lungs become more and more scarred, with breathing and oxygen uptake becoming increasingly difficult. This trial looked at the medication BI 1015550 as a potential treatment for IPF.

Novel Germline TET2 Mutations in Two Unrelated Patients with Autoimmune Lymphoproliferative Syndrome-Like Phenotype and Hematologic Malignancy.

Somatic mutations in the ten-eleven translocation methylcytosine dioxygenase 2 gene (TET2) have been associated to hematologic malignancies. More recently, biallelic, and monoallelic germline mutations conferring susceptibility to lymphoid and myeloid cancer have been described. We report two unrelated autoimmune lymphoproliferative syndrome-like patients who presented with T-cell lymphoma associated with novel germline biallelic or monoallelic mutations in the TET2 gene.

Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis.

Background: Phosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.

Methods: In this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomly assigned in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo.

Interstitial lung disease before and after COVID-19: a double threat?

https://bit.ly/3jWBPCG

Alterations in Respiratory Function Test Three Months after Hospitalisation for COVID-19 Pneumonia: Value of Determining Nitric Oxide Diffusion.

Unlabelled: Three to four months after hospitalisation for COVID-19 pneumonia, the most frequently described alteration in respiratory function tests (RFTs) is decreased carbon monoxide transfer capacity (DL).

Methods: This is a prospective cohort study that included patients hospitalised because of SARS-CoV-2 pneumonia, three months after their discharge. A clinical evaluation, analytical parameters, chest X-ray, six-minute walk test, spirometry and DL-DL analysis were performed.

Congenital hypopituitarism in two brothers with a duplication of the 'acrogigantism gene' GPR101: clinical findings and review of the literature.

Purpose: Congenital hypopituitarism (CH) can cause significant morbidity or even mortality. In the majority of patients, the etiology of CH is unknown. Understanding the etiology of CH is important for anticipation of clinical problems and for genetic counselling.

DpgC-Catalyzed Peroxidation of 3,5-Dihydroxyphenylacetyl-CoA (DPA-CoA): Insights into the Spin-Forbidden Transition and Charge Transfer Mechanisms*.

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O at room temperature because O is a diradical whereas most organic molecules are closed-shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non-relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate.

Linking LOXL2 to Cardiac Interstitial Fibrosis.

Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension.

Design of the β3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial.

Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH.

Cation and anion effect on the biodegradability and toxicity of imidazolium- and choline-based ionic liquids.

This work studies the effect of the cation and anion on the biodegradability and inhibition of imidazolium- and choline-based ionic liquids (ILs) using activated sludge. Six commercial ILs, formed by combination of 1-Butyl-3-methylimidazolium (Bmim) and N,N,N-trimethylethanolammonium (Choline) cations and chloride (Cl), acetate (Ac) and bis(trifluoromethanesulfonyl)imide (NTf) anions were evaluated, all representative counter-ions with markedly different toxicity and biodegradability. Inherent and fast biodegradability tests were used to evaluate both the microorganism inhibition and the IL biodegradability.

Perinatal free-choice of a high-calorie low-protein diet affects leptin signaling through IRS1 and AMPK dephosphorylation in the hypothalami of female rat offspring in adulthood.

Aim: We aimed to investigate whether a dysregulated maternal diet during gestation and lactation induces long-lasting changes in the hypothalamic control of feeding behavior in the offspring and whether this effect is sex specific.

Methods: The study included an analysis of appetite-regulating metabolic hormones and hypothalamic signaling in male and female offspring in adulthood after exposure to a free-choice high-calorie palatable low-protein (P) diet or standard chow (C) during (pre)gestation/lactation (maternal) and/or postweaning (offspring).

Results: Maternal exposure to the P diet resulted in decreased protein intake and body weight gain in dams and decreased body weight gain in offspring during lactation.

Arterial Stiffness and Blood Pressure in a Multicultural Child Sample (Angola, Brazil, and Spain).

Background: To analyze the relationship between early-life indicators, blood pressure (BP), and arterial stiffness in childhood, in three samples with different bio-cultural characteristics.

Methods: The total sample included 520 schoolchildren 9-10 years of age from Madrid (Spain), Vitória (Brazil), and Luanda (Angola). Height and weight, BP, and carotid-femoral pulse wave velocity (cf-PWV) were measured, all by one observer in each site, and body mass index (BMI) was calculated.

Validation of electron microscopy initial models via small angle X-ray scattering curves.

Motivation: Cryo electron microscopy (EM) is currently one of the main tools to reveal the structural information of biological macromolecules. The re-construction of three-dimensional (3D) maps is typically carried out following an iterative process that requires an initial estimation of the 3D map to be refined in subsequent steps. Therefore, its determination is key in the quality of the final results, and there are cases in which it is still an open issue in single particle analysis (SPA).

Assessment the ecotoxicity and inhibition of imidazolium ionic liquids by respiration inhibition assays.

The ecotoxicity and inhibition of 12 imidazolium ionic liquids (ILs) with alkyl chain from C4 to C10 and chloride (Cl), tetrafluoroborate (BF) and bis(trifluoromethanesulfonyl)imide (NTf) anions have been studied by means of respiration inhibition assays using activated sludge collected from a wastewater treatment plant. This test represents an alternative easy, economic and quick way to evaluate the true impact of ILs on activated sludge-based wastewater treatment. For comparison purposes, the EC values were also determined by the Microtox test (Vibrio fischeri).

Enhanced anaerobic degradability of highly polluted pesticides-bearing wastewater under thermophilic conditions.

This work presents a sustainable and cost-competitive solution for hardly biodegradable pesticides-bearing wastewater treatment in an anaerobic expanded granular sludge bed (EGSB) reactor at mesophilic (35°C) and thermophilic (55°C). The reactor was operated in continuous mode during 160days, achieving an average COD removal of 33 and 44% under mesophilic and thermophilic conditions, respectively. The increase of temperature improved the biomass activity and the production of methane by 35%.

Occurrence of pharmaceutical, recreational and psychotropic drug residues in surface water on the northern Antarctic Peninsula region.

Human presence in the Antarctic is increasing due to research activities and the rise in tourism. These activities contribute a number of potentially hazardous substances. The aim of this study is to conduct the first characterisation of the pharmaceuticals and recreational drugs present in the northern Antarctic Peninsula region, and to assess the potential environmental risk they pose to the environment.

Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices.

Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats.

Strategies to design clinical studies to identify predictive biomarkers in cancer research.

The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated.

IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months.