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h the approaches. This suggests that utilizing a single approach may not give precise vulnerability status of an ecosystem. Use of combined approaches for construction of a composite vulnerability index covering different aspects impacted by climate change might present a better picture of the vulnerability status and aid in formulation of effective mitigation/management plan.This systematic review aims to give an overview of the diversity of research areas related to human biometeorology in Brazil. The main focus of this paper addresses research trends, represented by published papers with national and international authorship, main contributions and shortcomings, as well as challenges and prospects of research in this area of study. An extensive literature search was conducted in the Scopus, Web of Science, and Science Direct databases so as to identify relevant publication output up to July 2021 related to the research area. The screening resulted in 96 studies chosen for full-text reading. Overall, results indicated a reduced amount of articles on the subject matter published internationally, with noticeable gaps in research in some regions of the country, such as the Amazon region and in the Brazilian Midwest region. Research gaps in relevant areas have been identified with limited output in the climate dimensions of tourism, vector-borne diseases, mortality and morbidity in urban centers. Such gaps should further encourage researchers to engage in research focused on those areas.Nonpoint source pollution (NPSP) from human production and life activities causes severe destruction in river basin environments. In this study, three types of sediment samples (A, NPSP tributary samples; B, non-NPSP mainstream samples; C, NPSP mainstream samples) were collected at the estuary of the NPSP tributaries of the Jialing River. High-throughput sequencing of the fungal-specific internal transcribed spacer (ITS) gene region was used to identify fungal taxa. The impact of NPSP on the aquatic environment of the Jialing River was revealed by analysing the community structure, community diversity, and functions of sediment fungi. The results showed that the dominant phylum of sediment fungi was Rozellomycota, followed by Ascomycota and Basidiomycota (relative abundance > 5%). NPSP caused a significant increase in the relative abundances of Exosporium, Phialosimplex, Candida, Inocybe, Tausonia, and Slooffia, and caused a significant decrease in the relative abundances of Cercospora, Cladosporium, Dokmaia, biosynthesis from glycine, and adenine and adenosine salvage III metabolic circulation pathway functions (P  less then  0.05). Hence, NPSP causes changes in the community structure and functions of sediment fungi in Jialing River and has adversely affected for the stability of the Jialing River Basin ecosystem.Thrombin is a Na[Formula see text]-activated serine protease existing in two forms targeted to procoagulant and anticoagulant activities, respectively. There is one Na[Formula see text]-binding site that has been the focus of the study of the thrombin. However, molecular dynamics (MD) simulations suggest that there might be actually two Na[Formula see text]-binding sites in thrombin and that Na[Formula see text] ions can even bind to two sites simultaneously. In this study, we performed 12 independent 2-µs all-atom MD simulations for the wild-type (WT) thrombin and we studied the effects of the different Na[Formula see text] binding modes on thrombin. From the root-mean-square fluctuations (RMSF) for the [Formula see text]-carbons, we see that the atomic fluctuations mainly change in the 60s, 170s, and 220s loops, and the connection (residue 167 to 170). The correlation matrices for different binding modes suggest regions that may play an important role in thrombin's allosteric response and provide us a possible allosteric pathway for the sodium binding. Amorim-Hennig (AH) clustering tells us how the structure of the regions of interest changes on sodium binding. Principal component analysis (PCA) shows us how the different regions of thrombin change conformation together with sodium binding. Solvent-accessible surface area (SASA) exposes the conformational change in exosite I and catalytic triad. Finally, we argue that the double binding mode might be an inactive mode and that the kinetic scheme for the Na[Formula see text] binding to thrombin might be a multiple-step mechanism rather than a 2-step mechanism.Hereditary transthyretin-related amyloidosis (ATTRv) is a rare autosomal dominant disease and is fatal if left untreated. It is caused by mutations in the transthyretin gene. All known mutations induce misfolding of the tetrameric transthyretin molecule and protein deposits in multiple organs. In peripheral nerves this result in sensorimotor and autonomic polyneuropathy and in cardiac muscle it causes cardiomyopathy. Selleckchem Plinabulin Untreated ATTRv is characterized by an irreversible and progressive course and death 7-11 years after symptom onset. Treatment options consist of TTR stabilizing drugs, such as tafamidis and active agents that selectively interfere at the mRNA level, the so-called gene silencers patisiran and inotersen. All forms of treatment aim to prevent amyloid tissue deposition in tissues and organ dysfunction. Patisiran works by RNA interference on endogenous mechanisms of gene expression. It results in the cleavage of TTR-mRNA using the cytoplasmatic RNA-induced silencing complex. Inotersen, an antisense oligonucleotide, degrades TTR-mRNA via activation of nuclear RNase H. Both mechanisms result in a significant reduction of TTR protein serum levels. The efficacy could be demonstrated by slowing or improving neuropathy progression in the phase III study APOLLO (patisiran) or the NEURO-TTR study (inotersen). Furthermore, the use of both agents led to an improvement in the quality of life in patients with ATTRv. Both forms of treatment are approved in Germany since August 2018 for polyneuropathy stages 1 and 2 according to Coutinho. The choice of treatment should be carried out individually considering drug formulation, contraindications and the necessary safety monitoring controls.

GWAS identified 63 QTLs for resistance to downy mildew. Though QTLs were distributed across all chromosomes, the genomic regions frequently associated with resistance were located on chromosomes 4 and 5. Lettuce downy mildew is one of the most economically important diseases of cultivated lettuce worldwide. We have applied the genome-wide association mapping (GWAS) approach to detect QTLs for field resistance to downy mildew in the panel of 496 accessions tested in 21 field experiments. The analysis identified 131 significant marker-trait associations that could be grouped into 63 QTLs. At least 51 QTLs were novel, while remaining 12 QTLs overlapped with previously described QTLs for lettuce field resistance to downy mildew. Unlike race-specific, dominant Dm genes that mostly cluster on three out of nine lettuce chromosomes, QTLs (qDMR loci) for polygenic resistance are randomly distributed across all nine chromosomes. The genomic regions frequently associated with lettuce field resistance to downy mildew aially used for marker-assisted selection, or in combination with other markers in the genome, for a combined genomic and marker-assisted selection. Up to date this is the most comprehensive study of QTLs for field resistance to downy mildew and the first study that uses GWAS for mapping disease resistance loci in lettuce.Insomnia symptoms are frequent during peripartum and are considered risk factors for peripartum psychopathology. Assessing and treating insomnia and related conditions of sleep loss during peripartum should be a priority in the clinical practice. The aim of this paper was to conduct a systematic review on insomnia evaluation and treatment during peripartum which may be useful for clinicians. The literature review was carried out between January 2000 and May 2021 on the evaluation and treatment of insomnia during the peripartum period. The PubMed, PsycINFO, and Embase electronic databases were searched for literature published according to the PRISMA guidance with several combinations of search terms "insomnia" and "perinatal period" or "pregnancy" or "post partum" or "lactation" or "breastfeeding" and "evaluation" and "treatment." Based on this search, 136 articles about insomnia evaluation and 335 articles on insomnia treatment were found and we conducted at the end a narrative review. According to the inclusion/exclusion criteria, 41 articles were selected for the evaluation part and 22 on the treatment part, including the most recent meta-analyses and systematic reviews. Evaluation of insomnia during peripartum, as for insomnia patients, may be conducted at least throughout a clinical interview, but specific rating scales are available and may be useful for assessment. Cognitive behavioral therapy for insomnia (CBT-I), as for insomnia patients, should be the preferred treatment choice during peripartum, and it may be useful to also improve mood, anxiety symptoms, and fatigue. Pharmacological treatment may be considered when women who present with severe forms of insomnia symptoms do not respond to nonpharmacologic therapy.Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis.

Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases.

This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency.

The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001).

These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.