Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

Involved-Field Radiation Therapy for Patients With Unresectable Pancreatic Adenocarcinomas: Failure Pattern Analysis.

Introduction Unresectable pancreatic tumors are frequently diagnosed. Initial treatment is carried out with chemotherapy. Eventually, in selected cases, radiotherapy may be used to improve local control rates and relieve the symptoms. The volume of radiotherapy treatment fields is the subject of controversy in the literature. The use of involved fields with the gross tumor volume encompassing the primary tumor and lymph nodes considered clinically positive is associated with a lower rate of side effects, but can lead to a higher rate of regional loco failures, especially in regional lymph nodes. The purpose of this article is to analyze the failure pattern of chemotherapy and involved-field radiation therapy (IFRT) for treating patients with unresectable pancreatic adenocarcinomas. Methods Clinical records of thirty consecutive patients treated from March 2016 to June 2020 for unresectable pancreatic adenocarcinoma were analyzed. The patients were treated with initial systemic chemotherapy (median: 6 cycles) with regimens based on gemcitabine or oxaliplatin-irinotecan (folfirinox/folfox) followed by radiotherapy (total dose of 50-54 Gy/with fractionation of 2 Gy/day). The patients were treated with IFRT. Local failure (LF) was defined as an increase in radiographic abnormality within the planning target volume (PTV). Elective nodal failure (ENF) was defined as recurrence in any lymph node region outside the PTV. Any other failure was defined as distant failure (DF). Results The median age of the patients was 68 years (range: 44-80 years); 20 patients (66.7%) were men, and 11 (36.6%) and 19 (63.4%) patients presented with tumors of stage II and III, respectively. Most patients (63.3%) had tumors in the pancreatic head. The median survival was 17.2 months. Tumor recurrences were classified as LF, DF, LF and DF in 7 (23.3%), 17 (56.7%), and 5 (16.7%) patients, respectively. Only one patient (3.3%) had both LF and ENF. No severe side effects related to radiotherapy were reported. Conclusion The use of IFRT did not cause a significant amount of ENF, besides presenting low morbidity, which is of special importance for patients with locally advanced tumors or low performance status. The predominant failure pattern was distant metastases.

Urea Hydrogen Peroxide and Ethyl Lactate, an Eco-Friendly Combo System in the Direct C(sp2)-H Bond Selenylation of Imidazo[2,1-b]thiazole and Related Structures.

Herein, we describe a urea hydrogen peroxide-mediated sustainable protocol for the synthesis of selenylated imidazo[2,1-b]thiazole by using half molar equivalent diorganyl diselenides in ethyl lactate as a greener solvent. The reaction features high yields, easy performance on gram scale, metal-free conditions, as well as applicability to imidazopyridine and imidazopyrimidine.

Catalyst- and metal-free C(sp2)-H bond selenylation of (N-hetero)-arenes using diselenides and trichloroisocyanuric acid at room temperature.

In this paper, we report an eco-friendly approach for the C(sp2)-H bond selenylation of imidazopyridines and other N-heteroarenes as well as simple arenes at ambient temperature. This new protocol consists of the reaction between (N-hetero)-arenes and the diorganyl-diselenides and trichloroisocyanuric acid (TCCA)-ethanol reagent system. In a short reaction time, the desired selenylated products were obtained regioselectively in good yields, with tolerance for a wide range of functional groups.

Pervasive gaps in Amazonian ecological research.

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%-18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost.

Stochastic epigenetic mutations as possible explanation for phenotypical discordance among twins with congenital hypothyroidism.

PURPOSE: The elevated frequency of discordance for congenital hypothyroidism (CH) phenotype between monozygotic twins suggests the involvement of non-mendelian mechanisms. The aim of the study was to investigate the role of epigenetics in CH pathogenesis. METHODS: A genome-wide DNA methylation analysis was performed on the peripheral blood of 23 twin pairs (10 monozygotic and 13 dizygotic), 4 concordant and 19 discordant pairs for CH at birth. RESULTS: Differential methylation analysis did not show significant differences in methylation levels between CH cases and controls, but a different methylation status of several genes may explain the CH discordance of a monozygotic twin couple carrying a monoallelic nonsense mutation of DUOX2. In addition, the median number of hypo-methylated Stochastic Epigenetic Mutations (SEMs) resulted significantly increased in cases compared to controls. The prioritization analysis for CH performed on the genes epimutated exclusively in the cases identified SLC26A4, FOXI1, NKX2-5 and TSHB as the genes with the highest score. The analysis of significantly SEMs-enriched regions led to the identification of two genes (FAM50B and MEG8) that resulted epigenetically dysregulated in cases. CONCLUSION: Epigenetic modifications may potentially account for CH pathogenesis and explain discordance among monozygotic twins.

A new DLK1 defect in a family with idiopathic central precocious puberty: elucidation of the male phenotype.

PURPOSE: We aimed to investigate a cohort of female and male patients with idiopathic central precocious puberty (CPP), negative for Makorin Ring Finger Protein 3 (MKRN3) defect, by molecular screening for Delta-like 1 homolog (DLK1) defects. DLK1 is an imprinted gene, whose mutations have been described as a rare cause of CPP in girls and adult women with precocious menarche, obesity and metabolic derangement. METHODS: We enrolled 14 girls with familial CPP and 13 boys with familial or sporadic CPP from multiple academic hospital centers. Gene sequencing of DLK1 gene was performed. Circulating levels of DLK1 were measured and clinical and biochemical characteristics were described in those with DLK1 defects. RESULTS: A novel heterozygous mutation in DLK1, c.288_289insC (p.Cys97Leufs*16), was identified in a male proband, his sister and their father. Age at onset of puberty was in line with previous reports in the girl and 8 years in the boy. The father with untreated CPP showed short stature. No metabolic derangement was present in the father except hypercholesterolemia. Undetectable Dlk1 serum levels indicated the complete lack of protein production in the three affected patients. CONCLUSION: A DLK1 defect has been identified for the first time in a boy, underscoring the importance of genetic testing in males with idiopathic or sporadic CPP. The short stature reported by his untreated father suggests the need for timely diagnosis and treatment of subjects with DLK1 defects.

Implicating factors in the increase in cases of central precocious puberty (CPP) during the COVID-19 pandemic: Experience of a tertiary centre of pediatric endocrinology and review of the literature.

Sexual development is a complex mechanism activated by the hypothalamic-pituitary-gonadal axis. Over the last one hundred years there has been a decline in the age at puberty onset in industrialised countries. Some Italian studies showed an increase in diagnoses of Central Precocious Puberty (CPP) during the COVID-19 pandemic. It is thus supposed that in this period there was an increased impact of factors that can influence pubertal development. Our retrospective monocentric study aimed to confirm the existence of this phenomenon and analysed possible related factors. We retrospectively evaluated clinical, laboratory, radiological and ultrasound (US) data of 154 girls referred to our Tertiary Centre of Paediatric Endocrinology from January 2019 to April 2021 for different forms of Precocious Puberty. We subdivided the cases into subgroups according to the final diagnosis: CPP, Early Puberty (EP), isolated thelarche and isolated pubarche. The observation period was subdivided into: Period 1, before lockdown (1 January 2019 - 8 March 2020) and Period 2, lockdown and the following months (9 March 2020 - 30 April 2021). Period 2 was further divided into "restrictive lockdown period" (Period 2.1) (March 2020 - 14 June 2020, in which the schools were closed) and "less restrictive lockdown period" (Period 2.2) (15 June 2020 - 30 April 2021). We analysed data regarding the use of electronic devices before and during lockdown in a group of girls with CPP diagnosed in Period 2 and we compared the data with that of a control group. Our data show an increase in the number of new diagnoses of CPP during lockdown and in the following months, compared with the previous period. We also detected a higher use of PCs and smartphones in girls with CPP diagnosed in Period 2, compared with the control group. The percentage of the presence of endometrial rhyme detected during the pelvic ultrasound was higher in girls with CPP in Period 2, compared with the previous period. Based on our data we assume there was an environmental effect on pubertal timing that calls our attention to factors such as food, use of electronic devices and stress. We will need further studies to better understand this data.

Transplantation to save the life, TSH screening to save the brain: A report and brief literature review of autoimmune thyroid disease after HSCT for severe combined immunodeficiency.

Autoimmune thyroid disease has been described as a complication of HSCT for different indications and as a manifestation of inborn errors of immunity, like SCID. A 1-month female was diagnosed with RAG1-mutated SCID and received allogenic HSCT. She developed autoimmune hypothyroidism 5 months after transplantation and was treated with levo-thyroxine with a good response. Autoimmune thyroid disease can develop after HSCT during the immune reconstitution phase, leading to potentially severe neurological and growth impairment, particularly in SCID patients, often transplanted during the first year of life. Recommendations regarding early and frequent vigilance for thyroid function are needed in these patients.

Clinical Prognostic Factors for Patients With Esophageal Cancer Treated With Definitive Chemoradiotherapy.

Background Treatment with definitive chemoradiotherapy (CRT) is the best option for patients with locally advanced esophageal tumors considered unresectable or for patients without clinical conditions to undergo surgical treatment. Technological advances in radiotherapy in the last decades have made treatment more accurate with less toxicity, and the association with more effective systemic treatment has been gradually improving survival rates. Aim Evaluate clinical prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients with esophageal cancer treated with definitive radiotherapy (RT) and chemotherapy (ChT). Material and methods The clinical records of 60 patients treated from April 2011 until December 2019 with esophageal cancer considered unresectable and/or without clinical conditions for surgery, treated with definitive CRT, were analyzed. All patients had upper digestive endoscopy (UDE) with positive biopsy, neck, chest, and abdominal CT scan, and 18F-fluorodeoxyglucose positron-emission tomography (PET-CT). Patients were followed with physical examination and CTs every three months in the first and second years and every six months from the third year of follow-up. UDE was made every three to six months after the end of the treatment or in suspicion of tumor recurrence. PET-CT was also performed in the follow-up when clinically necessary. Local and regional failure (LRF) was defined as abnormalities in the image tests within the planning target volume (PTV) and/or positive biopsy on UDE. Any other failure was defined as a distant failure (DF). PFS was defined in the record of the first tumor recurrence site and OS in the death record from the date of the start of treatment. Results The median age of the patients was 66 years (range: 33 to 83 years) and 46 patients (76.7%) were male. Squamous cell carcinoma (SCC) was the most frequent histological type (85%). Most patients had tumors located in the mid-thoracic esophagus (53.3%) and stage III or IV (59.9%). All patients were treated using 3D (76.7%) or intensity-modulated radiotherapy (IMRT; 23.3%). The median total dose was 50.4Gy (41.4-50.4). All patients received platinum-based ChT concomitant with RT. The most common regimen used was carboplatin and paclitaxel, with a median of five cycles. With a median follow-up of 19 months, the median PFS and OS were 10 and 20 months, respectively. LRF and DF as the first site of failure were observed in 22 (36.6%) and 26 (43.3%) patients, respectively. In the univariate analysis, tumor length lower than 2.6 cm, gross tumor volume (GTV) volume lower than 28 cm3, clinical tumor stages T1 and T2, clinical node stage N0, clinical prognostic stage groups I and II, and complete response to treatment, were statistically significant factors for better PFS and OS. In the multivariate analysis, the presence of clinical nodal stage N0 was related to better PFS (p=0.02). Conclusion Node clinical status was the most important clinical factor for PFS. Despite all the technical progress observed in radiotherapy, treatments concomitant with platinum-based chemotherapy are associated with high levels of LRF and DF. New strategies in systemic therapy and radiotherapy are necessary for improving outcomes.

Temperature and productivity distinctly affect the species richness of ectothermic and endothermic multitrophic guilds along a tropical elevational gradient.

The diversity of endotherms and ectotherms may be differently affected by ambient temperature and net primary productivity (NPP). Additionally, little is known about how these drivers affect the diversity of guilds of different trophic levels. We assessed the relative role of temperature and NPP in multitrophic guilds of ectothermic (arthropods: ants, ground beetles, spiders, and harvestmen) and endothermic (large mammals) animals along a tropical elevational gradient. We sampled arthropods at eight elevation belts and large mammals at 14 elevation belts in Atlantic rainforest (ranging from 600 to 2450 m.a.s.l.) of Itatiaia National Park, Southeast Brazil. Overall arthropod species richness was more associated with temperature than overall large-mammal species richness, while the latter was more associated with NPP. When separated into trophic guilds, we found that the species richness associated with NPP increased across arthropod trophic levels from herbivores to predators. Conversely, although NPP influenced large-mammal herbivore species richness, its effects did not seem to accumulate across large-mammal trophic levels since the species richness of large-mammal omnivores was more associated with temperature and none of the variables we studied influenced large-mammal predators. We suggest that thermal physiological differences between ectotherms and endotherms are responsible for the way in which arthropods and large mammals interact with or are constrained by the environment. Furthermore, the inconsistency regarding the role of temperature and NPP on species richness across multitrophic guilds of ectotherms and endotherms could indicate that thermal physiological differences might also interfere with energy use and flux in the food web.

Bioactive glass/poloxamer 407 hydrogel composite as a drug delivery system: The interplay between glass dissolution and drug release kinetics.

Since patients suffer pain in the post-surgery of bone repair interventions, bioactive glass/hydrogel drug delivery systems containing local anesthetics, such as ropivacaine, could improve patient life quality by combining bone regeneration with anesthetics. However, poloxamer-based hydrogel properties are sensitive to ions, temperature, and water contents and could be structurally influenced by the ionic dissolution products from bioactive glasses of different compositions. Therefore, this study evaluated the interplay between bioactive glass dissolution kinetics and poloxamer 407 properties, establishing a correlation between changes in the hydrogel and drug release kinetics. Three glass compositions were produced, yielding Ca-rich, Na-rich, and an intermediate glass composition. The influence of Ca/Na ratios on the glass structure and dissolution was investigated. Further, the glasses and ropivacaine were incorporated in the poloxamer hydrogel, and the self-assembly ability of poloxamer, the degradation rate, and the drug release kinetics of the composites were evaluated. The results suggested that glass connectivity affected the early-stage of glass dissolution, while sodium mobility influenced the long-term. The dissolution products from the glasses interact with the supramolecular structure of the poloxamer, causing structural changes responsible for hydrogel degradation. Consequently, by changing the Ca/Na ratio in the glasses, it is possible to modulate glass dissolution that, in turn, influences the ropivacaine release. Thus, we propose that the Ca/Na ratio in quaternary bioactive glasses can be used to modulate drug-delivery properties from systems based on bioactive glasses and poloxamer 407.

Drought-driven wildfire impacts on structure and dynamics in a wet Central Amazonian forest.

While the climate and human-induced forest degradation is increasing in the Amazon, fire impacts on forest dynamics remain understudied in the wetter regions of the basin, which are susceptible to large wildfires only during extreme droughts. To address this gap, we installed burned and unburned plots immediately after a wildfire in the northern Purus-Madeira (Central Amazon) during the 2015 El-Niño. We measured all individuals with diameter of 10 cm or more at breast height and conducted recensuses to track the demographic drivers of biomass change over 3 years. We also assessed how stem-level growth and mortality were influenced by fire intensity (proxied by char height) and tree morphological traits (size and wood density). Overall, the burned forest lost 27.3% of stem density and 12.8% of biomass, concentrated in small and medium trees. Mortality drove these losses in the first 2 years and recruitment decreased in the third year. The fire increased growth in lower wood density and larger sized trees, while char height had transitory strong effects increasing tree mortality. Our findings suggest that fire impacts are weaker in the wetter Amazon. Here, trees of greater sizes and higher wood densities may confer a margin of fire resistance; however, this may not extend to higher intensity fires arising from climate change.

Discrimination of bacteria using whole organism fingerprinting: the utility of modern physicochemical techniques for bacterial typing.

Rapid and accurate classification and discrimination of bacteria is an important task and has been highlighted recently for rapid diagnostics using real-time results. Coupled with a recent report by Jim O'Neill [] that if left unaddressed antimicrobial resistance (AMR) in bacteria could kill 10 million people per year by 2050, which would surpass current cancer mortality, this further highlights the need for unequivocal identification of microorganisms. Whilst traditional microbiological testing has offered insights into the characterisation and identification of a wide range of bacteria, these approaches have proven to be laborious and time-consuming and are not really fit for purpose, considering the modern day speed and volume of international travel and the opportunities it creates for the spread of pathogens globally. To overcome these disadvantages, modern analytical methods, such as mass spectrometry (MS) and vibrational spectroscopy, that analyse the whole organism, have emerged as essential alternative approaches. Currently within clinical microbiology laboratories, matrix assisted laser desorption ionisation (MALDI)-MS is the method of choice for bacterial identification. This is largely down to its robust analysis as it largely measures the ribosomes which are always present irrespective of how the bacteria are cultured. However, MALDI-MS requires large amounts of biomass and infrared spectroscopy and Raman spectroscopy are attractive alternatives as these physicochemical bioanalytical techniques have the advantages of being rapid, reliable and cost-effective for analysing various types of bacterial samples, even at the single cell level. In this review, we discuss the fundamental applications, advantages and disadvantages of modern analytical techniques used for bacterial characterisation, classification and identification.

Out of Sight, Out of Mind: Widespread Nuclear and Plastid-Nuclear Discordance in the Flowering Plant Genus Polemonium (Polemoniaceae) Suggests Widespread Historical Gene Flow Despite Limited Nuclear Signal.

Phylogenomic data from a rapidly increasing number of studies provide new evidence for resolving relationships in recently radiated clades, but they also pose new challenges for inferring evolutionary histories. Most existing methods for reconstructing phylogenetic hypotheses rely solely on algorithms that only consider incomplete lineage sorting (ILS) as a cause of intra- or intergenomic discordance. Here, we utilize a variety of methods, including those to infer phylogenetic networks, to account for both ILS and introgression as a cause for nuclear and cytoplasmic-nuclear discordance using phylogenomic data from the recently radiated flowering plant genus Polemonium (Polemoniaceae), an ecologically diverse genus in Western North America with known and suspected gene flow between species. We find evidence for widespread discordance among nuclear loci that can be explained by both ILS and reticulate evolution in the evolutionary history of Polemonium. Furthermore, the histories of organellar genomes show strong discordance with the inferred species tree from the nuclear genome. Discordance between the nuclear and plastid genome is not completely explained by ILS, and only one case of discordance is explained by detected introgression events. Our results suggest that multiple processes have been involved in the evolutionary history of Polemonium and that the plastid genome does not accurately reflect species relationships. We discuss several potential causes for this cytoplasmic-nuclear discordance, which emerging evidence suggests is more widespread across the Tree of Life than previously thought. [Cyto-nuclear discordance, genomic discordance, phylogenetic networks, plastid capture, Polemoniaceae, Polemonium, reticulations.].

Temperature and productivity distinctly affect the species richness of ectothermic and endothermic multitrophic guilds along a tropical elevational gradient

The diversity of endotherms and ectotherms may be differently affected by ambient temperature and net primary productivity (NPP). Additionally, little is known about how these drivers affect the diversity of guilds of different trophic levels. We assessed the relative role of temperature and NPP in multitrophic guilds of ectothermic (arthropods: ants, ground beetles, spiders, and harvestmen) and endothermic (large mammals) animals along a tropical elevational gradient. We sampled arthropods at eight elevation belts and large mammals at 14 elevation belts in Atlantic rainforest (ranging from 600 to 2450 m.a.s.l.) of Itatiaia National Park, Southeast Brazil. Overall arthropod species richness was more associated with temperature than overall large-mammal species richness, while the latter was more associated with NPP. When separated into trophic guilds, we found that the species richness associated with NPP increased across arthropod trophic levels from herbivores to predators. Conversely, although NPP influenced large-mammal herbivore species richness, its effects did not seem to accumulate across large-mammal trophic levels since the species richness of large-mammal omnivores was more associated with temperature and none of the variables we studied influenced large-mammal predators. We suggest that thermal physiological differences between ectotherms and endotherms are responsible for the way in which arthropods and large mammals interact with or are constrained by the environment. Furthermore, the inconsistency regarding the role of temperature and NPP on species richness across multitrophic guilds of ectotherms and endotherms could indicate that thermal physiological differences might also interfere with energy use and flux in the food web.

The Role of Radiation Therapy as an Adjuvant Treatment in Nodal Metastasis of Malignant Chondroid Syringoma.

Malignant chondroid syringomas (MCSs) are extremely rare and aggressive skin tumors, and wide surgical excision is the main treatment. They can progress with local recurrence and nodal and distant metastasis. The role of radiotherapy is uncertain, but may enhance local control after surgical approach. We report a case of a 60-year-old female with this disease that, four years after surgical resection, presented with nodal metastasis and was managed with surgery and adjuvant radiotherapy.

Nomenclatural and taxonomic updates in Rourea subgen. Rourea sect. Multifoliolatae (Connaraceae).

The pantropical genus Rourea Aubl. (Connaraceae) is composed of ca. 70 species, most of which occur in the Neotropics. Rourea is currently subdivided into three subgenera, with the American taxa included in Rourea subgen. Rourea. Forero (1976) recognised six sections for the species of the New World, with Rourea subgen. R. sect. Multifoliolatae being exclusive to Brazil, characterised by multifoliolate leaves, relatively small leaflets and the staminal tube (0.8-)1-1.5 mm long. Following Forero's (1976) treatment, additional botanical collections have become available in Brazilian herbaria, allowing re-evaluation of species concepts. This work recognises and revises 12 species in this section, mainly restricted to southeastern Brazil and southern Bahia. A nomenclatural and taxonomic study of these species is here presented, including an identification key, morphological descriptions, illustrations and geographic distribution maps. A new species is also described.

Optimization of Wood Supply: The Forestry Routing Optimization Model.

The main purpose of this paper was to present the Forestry Routing Optimization Model (FRoM) as a version of the classical Vehicle Routing Problem (VRP). This work approaches for wood logistic problems consisting of simple displacement and multiple displacements of trucks toward the stands. The FRoM encompasses both steps into one single integer mixed linear programming model, considering cranes and trucks schedule, fleet reduction, reduction of overtime, reduction of half-load transportation, and approaching the minimum distance traveled along a fixed planning horizon. Some technique constraints were implemented to provide accurate model function. An executed real problem data was used to compare the outcomes. The objective was to carry and transport 21,881.82 tons of lumber from 10 stands using a total of 48 trucks and 5 cranes in a planning horizon of 6 days, which each day has 20 hours of effective work. The FRoM has performed a fleet reduction of 72.92%, eliminating overtime. It has reduced the half-load trips to the order of 3.17% of all routes. The crane's analysis allowed catching points of inefficiency due to operational idleness. The FRoM provided savings of 49.12% at all logistic costs. FRoM has shown to be a good option as a route optimizer for forestry logistics.