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Protein-RNA interactions are central to numerous cellular processes. In this work, we present an easy and straightforward NMR-based approach to determine the RNA binding site of RNA binding proteins and to evaluate the binding of pairs of proteins to a single-stranded RNA (ssRNA) under physiological conditions, in this case in nuclear extracts. By incorporation of a 19 F atom on the ribose of different nucleotides along the ssRNA sequence, we show that, upon addition of an RNA binding protein, the intensity of the 19 F NMR signal changes when the 19 F atom is located near the protein binding site. Furthermore, we show that the addition of pairs of proteins to a ssRNA containing two 19 F atoms at two different locations informs on their concurrent binding or competition. We demonstrate that such studies can be done in a nuclear extract that mimics the physiological environment in which these protein-ssRNA interactions occur. Finally, we demonstrate that a trifluoromethoxy group (-OCF 3 ) incorporated in the 2'ribose position of ssRNA sequences increases the sensitivity of the NMR signal, leading to decreased measurement times, and reduces the issue of RNA degradation in cellular extracts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kara, Axer, Muskett, Bueno-Alejo, Paschalis, Taladriz-Sender, Tubasum, Vega, Zhao, Clark, Hudson, Eperon, Burley and Dominguez.)

Introduction: The use of drones in environment and health research is a relatively new phenomenon. A principal research activity drones are used for is environmental monitoring, which can raise concerns in local communities. Existing ethical guidance for researchers is often not specific to drone technology and practices vary between research settings. Therefore, this scoping review aims to gather the evidence available on ethical considerations surrounding drone use as perceived by local communities, ethical considerations reported on by researchers implementing drone research, and published ethical guidance related to drone deployment., Methods and Analysis: This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and the Joanna Briggs Institute (JBI) guidelines. The literature search will be conducted using academic databases and grey literature sources. After pilot testing the inclusion criteria and data extraction tool, two researchers will double-screen and then chart available evidence independently. A content analysis will be carried out to identify patterns of categories or terms used to describe ethical considerations related to drone usage for environmental monitoring in the literature using the R Package RQDA. Discrepancies in any phase of the project will be solved through consensus between the two reviewers. If consensus cannot be reached, a third arbitrator will be consulted., Ethics and Dissemination: Ethical approval is not required; only secondary data will be used. This protocol is registered on the Open Science Framework (osf.io/a78et). The results will be disseminated through publication in a scientific journal and will be used to inform drone field campaigns in the Wellcome Trust funded HARMONIZE project. HARMONIZE aims to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots in Latin America & the Caribbean and will use drone technology to collect data on fine scale landscape changes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoek Spaans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i. e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i. e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer., Methods: We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function., Results: From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P<0.001), identification of parathyroid glands at surgery (P<0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P<0.001) and parathyroid hormone (PTH) (P<0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis., Conclusion: In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases., (Copyright © 2020 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Genetic association studies have identified many factors associated with neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the way these genes shape neuroanatomical structure and connectivity is poorly understood. Recent research has focused on proteins that act as points of convergence for multiple factors, as these may provide greater insight into understanding the biology of neurodevelopmental disorders. USP9X, a deubiquitylating enzyme that regulates the stability of many ASD-related proteins, is one such point of convergence. Loss of function variants in human USP9X lead to brain malformations, which manifest as a neurodevelopmental syndrome that frequently includes ASD, but the underlying structural and connectomic abnormalities giving rise to patient symptoms is unknown. Here, we analyzed forebrain-specific Usp9x knockout mice (Usp9x-/y) to address this knowledge gap. Usp9x-/y mice displayed abnormal communication and social interaction behaviors. Moreover, the absence of Usp9x culminated in reductions to the size of multiple brain regions. Diffusion tensor magnetic resonance imaging revealed deficits in all three major forebrain commissures, as well as long-range hypoconnectivity between cortical and subcortical regions. These data identify USP9X as a key regulator of brain formation and function, and provide insights into the neurodevelopmental syndrome arising as a consequence of USP9X mutations in patients., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: To determine the body composition profile of forest firefighters. Data were collected from 701 forest firefighters., Methods: We have carried out this analysis using a bioimpedance scale BC-601 of the brand Tanita ISO 9001 Certified., Results: Obtained values of body mass index 24.85 in women and 27.83 in men. The visceral fat index was 5 in women and 9 in men. In both cases, taking as reference the values proposed by the WHO, women are within a low-moderate risk of cardiovascular or metabolic diseases. Men are at a moderate-high risk., Conclusions: The values obtained in the analysis show that forest firefighters have a moderate risk of cardiovascular and metabolic diseases in the future. It is effective to propose future works that elaborate specific physical activity plans to improve their health profile.

Sotos syndrome is a developmental disorder characterized by a suite of clinical features. In children, the three cardinal features of Sotos syndrome are a characteristic facial appearance, learning disability and overgrowth (height and/or head circumference > 2 SDs above average). These features are also evident in adults with this syndrome. Over 90% of Sotos syndrome patients are haploinsufficient for the gene encoding nuclear receptor-binding Su(var)3-9, Enhancer-of-zesteand Trithorax domain-containing protein 1 (NSD1). NSD1 is a histone methyltransferase that catalyzes the methylation of lysine residue 36 on histone H3. However, although the symptomology of Sotos syndrome is well established, many aspects of NSD1 biology remain unknown. Here, we assessed the expression of Nsd1 within the mouse brain, and showed a predominantly neuronal pattern of expression for this histone-modifying factor. We also generated a mouse strain lacking one allele of Nsd1 and analyzed morphological and behavioral characteristics in these mice, showing behavioral characteristics reminiscent of some of the deficits seen in Sotos syndrome patients., (© 2020 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Background: The X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative., Methods: We used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology., Results: Twelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor β signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocampal-dependent learning and memory., Conclusions: Our data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor β signaling and hippocampal function., (Copyright © 2019 Society of Biological Psychiatry. All rights reserved.)

Purpose: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain., Methods: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study., Results: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism., Conclusions: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Toxic effects of the non-biodegradable drug chlorpromazine and its degradation products have been reported on microorganisms in aqueous media. Here, chlorpromazine degradation assays in forced and non-forced conditions have been done to know its persistence and degradation products in river water. Sunlight irradiation promotes the complete degradation of chlorpromazine (2 μg L(-1)) in less than 4 h, but if the exposure to sunlight is limited chlorpromazine is detected during 4 weeks in river water. Sixteen degradation products in surface water are described for first time after solid-phase extraction and analysis by ultra-pressure liquid chromatography/quadrupole time-of-flight/mass spectrometry; their structures are proposed from the molecular formulae of the fragment-ions observed in high-resolution tandem mass spectra. Hydroxylation and oxidation products such as chlorpromazine sulfoxide, 2-hydroxypromazine and 2-hydroxypromazine sulfoxide were predominant degradation products in the early stages; some benzo[1,4]thiazin-6-ol derivatives resulting from the breakdown of the phenothiazine core were the major and relatively stable products after 20 weeks under non-forced conditions. A degradation pathway of chlorpromazine in water is outlined. Moreover, it is shown that chlorpromazine is very strongly adsorbed on sediment while the degradation products that kept the promazine core have a notable capacity of sorption, too; sorption coefficients are calculated. Finally, a prediction about the toxicity of the degradation products in aquatic ecosystems suggests that some of them have toxicities similar, or even higher, than chlorpromazine., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Migraine has been considered a vascular risk factor especially in young women. Factors predisposing to endothelial damage in migraine are still being debated. The insufficiency of circulating endothelial precursor circulating cells (EPCs) suggested a link between migraine and cardiovascular risk. This research aimed to study a subtype of EPCs, those expressing e-selectin, to assess endothelial activation and, therefore, endothelial dysfunction in migraine., Methods: Consecutive headache patients (n = 99) and 35 adjusted controls were recruited. Total EPCs, defined as CD34+/KDR+ cells, and EPC colony-forming units (CFUs) were assayed. We identified as "early" EPCs those CD62E- EPCs, and "late" EPCs, CD62E+, a surrogate marker for endothelial damage. Plasmatic calcitonin-gene related protein (CGRP) and vascular-endothelial growth factor (VEGF) were analyzed., Results: We did not find differences in the total number of CFUs among clinical groups. Means of total CD34+/KDR+ and "early" EPCs were not significant among clinical groups. Nevertheless, the mean of "late" EPCs was lower (log(10)-transformed mean = 1.715; SD = 0.393) in the control group than in the migraine patients (log(10)-transformed mean = 2.167; SD = 0.685), even after adjustment by VEGF plasma level and other confounding factors. Linear regression analyses disclosed significant predictors for "late" EPCs for controls vs migraine (β = 0.452 SE ± 0.13; p = 0.001). We did not observe differences between migraine with or without aura., Conclusion: We observed higher number of activated EPCs in migraine patients than in controls. CD62E+ EPCs might be considered a marker for vascular damage in migraine patients.

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.