Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Comparative Study of Automated Algorithms for Brain Arteriovenous Malformation Nidus Extent Identification Using 3DRA.

PURPOSE: When performing a brain arteriovenous malformation (bAVMs) intervention, computer-assisted analysis of bAVMs can aid clinicians in planning precise therapeutic alternatives. Therefore, we aim to assess currently available methods for bAVMs nidus extent identification over 3DRA. To this end, we establish a unified framework to contrast them over the same dataset, fully automatising the workflows. MATERIALS AND METHODS: We retrospectively collected contrast-enhanced 3DRA scans of patients with bAVMs. A segmentation network was used to automatically acquire the brain vessels segmentation for each case. We applied the nidus extent identification algorithms over each of the segmentations, computing overlap measurements against manual nidus delineations. RESULTS: We evaluated the methods over a private dataset with 22 3DRA scans of individuals with bAVMs. The best-performing alternatives resulted in [Formula: see text] and [Formula: see text] dice coefficient values. CONCLUSIONS: The mathematical morphology-based approach showed higher robustness through inter-case variability. The skeleton-based approach leverages the skeleton topomorphology characteristics, while being highly sensitive to anatomical variations and the skeletonisation method employed. Overall, nidus extent identification algorithms are also limited by the quality of the raw volume, as the consequent imprecise vessel segmentation will hinder their results. Performance of the available alternatives remains subpar. This analysis allows for a better understanding of the current limitations.

Clinical and Surgical Approach for Cerebral Cortical Dysplasia.

The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided.

Long-term seizure outcome and mobility after surgical treatment for Rasmussen encephalitis in children: A single-center experience.

OBJECTIVE: Rasmussen Encephalitis (RE) is a rare inflammatory neurodegenerative disease associated with refractory seizures, hemiparesis, and cognitive deterioration, due to lateralized cortical atrophy. Hemispheric surgery (hemispherotomy) is the mainstay of treatment, but its unavoidable motor deficits and lack of long-term data regarding seizure outcomes can make patients and families apprehensive to undergo this procedure. The present study aimed at analyzing the results of surgical treatment for RE from a motor and epilepsy standpoint, and mitigate such concerns. METHODS: Clinical and operative data were retrospectively collected from medical records of pharmacoresistant patients treated with functional hemispherectomy at a tertiary reference center for epilepsy surgery, during a 24-year period (1996-2020). Variables such as age of epilepsy onset, seizure semiology, seizure frequency, immunomodulatory therapy, age at surgery, duration of epilepsy, surgical procedures and complications, number of medications used preoperatively and postoperatively were described and statistically analyzed. RESULTS: Forty-three (43) patients were included in this study. Mean age of epilepsy onset was 6.14 years, the average interval between epilepsy onset and hemispherotomy was 2.21 years. and the mean age at surgery was 8.28 years. Thirty patients (69.7%) were Engel I at their last follow-up, of whom 23 (56.4%) were Engel Ia, within a mean follow-up of 11.3 years. Duration of epilepsy, seizure frequency, and age at surgery, among others, did not correlate with seizure outcome, except the use of immunotherapy which led to worse outcomes (p < .05). Also, after surgery, motor functionality was significantly recovered (i.e., most patients returned to their previous status) with time. SIGNIFICANCE: This study tackled some issues regarding the surgical treatment of this disease, particularly showing that hemispherotomy is safe and leads to potentially recoverable disability of motor functions while providing high rates of effective and long-lasting seizure control; therefore, early surgical indication should be warranted once medical refractoriness has been established.

3D Printing of Hybrid-Hydrogel Materials for Tissue Engineering: a Critical Review.

Purpose: Key natural polymers, known as hydrogels, are an important group of materials in design of tissue-engineered constructs that can provide suitable habitat for cell attachment and proliferation. However, in comparison to tissues within the body, these hydrogels display poor mechanical properties. Such properties cause challenges in 3D printing of hydrogel scaffolds as well as their surgical handling after fabrication. For this reason, the purpose of this study is to critically review the 3D printing processes of hydrogels and their characteristics for tissue engineering application. Methods: A search of Google Scholar and PubMed has been performed from 2003 to February 2022 using a combination of keywords. A review of the types of 3D printing is presented. Additionally, different types of hydrogels and nano-biocomposite materials for 3D printing application are critically reviewed. The rheological properties and crosslinking mechanisms for the hydrogels are assessed. Results: Extrusion-based 3D printing is the most common practice for constructing hydrogel-based scaffolds, and it allows for the use of varying types of polymers to enhance the properties and printability of the hydrogel-based scaffolds. Rheology has been found to be exceedingly important in the 3D printing process; however, shear-thinning and thixotropic characteristics should also be present in the hydrogel. Despite these features of extrusion-based 3D printing, there are limitations to its printing resolution and scale. Conclusion: Combining natural and synthetic polymers and a variety of nanomaterials, such as metal, metal oxide, non-metal, and polymeric, can enhance the properties of hydrogel and provide additional functionality to their 3D-printed constructs.

Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.

Hatchery tanks induce intense reduction in microbiota diversity associated with gills and guts of two endemic species of the São Francisco River.

The São Francisco River (SFR), one of the main Brazilian rivers, has suffered cumulative anthropogenic impacts, leading to ever-decreasing fish stocks and environmental, economic, and social consequences. Rhinelepis aspera and Prochilodus argenteus are medium-sized, bottom-feeding, and rheophilic fishes from the SFR that suffer from these actions. Both species are targeted for spawning and restocking operations due to their relevance in artisanal fisheries, commercial activities, and conservation concerns. Using high-throughput sequencing of the 16S rRNA gene, we characterized the microbiome present in the gills and guts of these species recruited from an impacted SFR region and hatchery tanks (HT). Our results showed that bacterial diversity from the gill and gut at the genera level in both fish species from HT is 87% smaller than in species from the SFR. Furthermore, only 15 and 29% of bacterial genera are shared between gills and guts in R. aspera and P. argenteus from SFR, respectively, showing an intimate relationship between functional differences in organs. In both species from SFR, pathogenic, xenobiont-degrading, and cyanotoxin-producer bacterial genera were found, indicating the critical pollution scenario in which the river finds itself. This study allowed us to conclude that the conditions imposed on fish in the HT act as important modulators of microbial diversity in the analyzed tissues. It also raises questions regarding the effects of these conditions on hatchery spawn fish and their suitability for restocking activities, aggravated by the narrow genetic diversity associated with such freshwater systems.

Direito da favela e política de exceção em territórios favelados / Favela law and policy of exception in favela territories

Esta pesquisa objetivou discutir situações em que grupos armados atuam como reguladores de relações sociais entre moradoras e moradores do Complexo da Maré. A partir de uma análise documental no banco de dados do Núcleo Interdisciplinar de Ações para Cidadania (Programa de Extensão da Universidade Federal do Rio de Janeiro), constatamos tal prática nos enunciados de usuários atendidos pelo programa. Usamos os relatos com a proposta de complexificar essa realidade em que grupos civis armados, majoritariamente ligados ao comércio de psicoativos no território, assumem o papel de promotores de justiça, garantindo direitos por vezes não acessados pela população pelas vias formais, quase sempre "classistas", sexistas e racistas. Colocamos em questão a produção da favela como território de exceção, uma das forças que sustentam a criminalização desta lógica resolutiva informal, contribuindo na manutenção da desigualdade social brasileira.

Photorepair of Either CPD or 6-4PP DNA Lesions in Basal Keratinocytes Attenuates Ultraviolet-Induced Skin Effects in Nucleotide Excision Repair Deficient Mice.

Ultraviolet (UV) radiation is one of the most genotoxic, universal agents present in the environment. UVB (280-315 nm) radiation directly damages DNA, producing cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs). These photolesions interfere with essential cellular processes by blocking transcription and replication polymerases, and may induce skin inflammation, hyperplasia and cell death eventually contributing to skin aging, effects mediated mainly by keratinocytes. Additionally, these lesions may also induce mutations and thereby cause skin cancer. Photolesions are repaired by the Nucleotide Excision Repair (NER) pathway, responsible for repairing bulky DNA lesions. Both types of photolesions can also be repaired by distinct (CPD- or 6-4PP-) photolyases, enzymes that specifically repair their respective photolesion by directly splitting each dimer through a light-dependent process termed photoreactivation. However, as photolyases are absent in placental mammals, these organisms depend solely on NER for the repair of DNA UV lesions. However, the individual contribution of each UV dimer in the skin effects, as well as the role of keratinocytes has remained elusive. In this study, we show that in NER-deficient mice, the transgenic expression and photorepair of CPD-photolyase in basal keratinocytes completely inhibited UVB-induced epidermal thickness and cell proliferation. On the other hand, photorepair by 6-4PP-photolyase in keratinocytes reduced but did not abrogate these UV-induced effects. The photolyase mediated removal of either CPDs or 6-4PPs from basal keratinocytes in the skin also reduced UVB-induced apoptosis, ICAM-1 expression, and myeloperoxidase activation. These findings indicate that, in NER-deficient rodents, both types of photolesions have causal roles in UVB-induced epidermal cell proliferation, hyperplasia, cell death and inflammation. Furthermore, these findings also support the notion that basal keratinocytes, instead of other skin cells, are the major cellular mediators of these UVB-induced effects.

Polimorfismo da região codante do gene NOS3 em idosos com Síndrome Metabólica / Polymorphism of the codante region of the NOS3 gene in the elderly with Metabolic Syndrome / Polimorfismo de la región codante del gen NOS3 en ancianos con Síndrome Metabólico

Objetivo: O presente estudo analisou se a presença do polimorfismo VNTR localizado no íntron 4 do gene NOS3 na região codante difere nos pacientes com Síndrome Metabólica e portadores de Hipertensão Arterial e/ou Diabetes Mellitus dos controles normotensos. Método: Neste estudo caso-controle, foi executada a técnica de PCR para identificar a presença dos genótipos em 94 pacientes idosas residentes do Distrito Federal. As associações com as manifestações clínicas foram feitas no programa SPSS. Foi analisada a probabilidade de equilíbrio de Hardy-Weinberg e Odds Ratio, considerando um intervalo de confiança de 95% e nível de significância de 5%. Resultados: Verificou-se que das 94 pacientes, 71 evidenciaram a presença de hipertensão e 23 a ausência da doença, o valor de p obtido foi de 0,218. Em relação a Diabetes Mellitus, 49 idosas possuem o problema e 45 não possuem, o valor de p obtido foi de 0,372. Conclusão: Não há associação entre os genótipos do polimorfismo do gene NOS3, e a manifestação de Hipertensão Arterial e Diabetes Mellitus em idosas portadoras da SM.

Objective: The present study analyzed whether the presence of VNTR polymorphism located in intron 4 of the NOS3 gene in the codante region differs in patients with Metabolic Syndrome and patients with Hypertension and/or Diabetes Mellitus from normotensive controls. Method: In this case-control study, the PCR technique was performed to identify the presence of genotypes in 94 elderly patients living in the Federal District. Associations with clinical manifestations were made in the SPSS program. The probability of Hardy-Weinberg equilibrium and Odds Ratio was analyzed, considering a confidence interval of 95% and significance level of 5%. Results: we found that of the 94 patients, 71 showed the presence of hypertension and 23 the absence of the disease, the p-value obtained was 0.218. Regarding Diabetes Mellitus, 49 old women have the problem and 45 do not have the p value obtained was 0.372. Conclusion: There is no association between nos3 gene polymorphism genotypes, and the manifestation of Arterial Hypertension and Diabetes Mellitus in elderly patients with MS.

Objetivo El presente estudio analizó si la presencia de polimorfismo VNTR localizado en el intrón 4 del gen NOS3 en la región codante difiere en pacientes con Síndrome Metabólico y pacientes con Hipertensión y/o Diabetes Mellitus de controles normotensos. Método: En este estudio de casos y controles, se realizó la técnica de PCR para identificar la presencia de genotipos en 94 pacientes ancianos residentes en el Distrito Federal. Las asociaciones con manifestaciones clínicas se realizaron en el programa SPSS. Se analizó la probabilidad de equilibrio de Hardy-Weinberg y Odds Ratio, considerando un intervalo de confianza del 95% y un nivel de significancia del 5%. Resultados: Se encontró que de los 94 pacientes, 71 mostraron la presencia de hipertensión arterial y 23 la ausencia de la enfermedad, el valor de p obtenido fue de 0,218. En cuanto a la Diabetes Mellitus, 49 ancianas tienen el problema y 45 no tienen el valor de p obtenido fue de 0,372. Conclusión: No existe asociación entre los genotipos de polimorfismo del gen nos3 y la manifestación de Hipertensión Arterial y Diabetes Mellitus en pacientes ancianos con SM

Atención Odontológica Durante el Estado de Alarma COVID-19 en el Hospital Comunitario de Achao, Chile: Un Estudio Observacional

RESUMEN: Conocer la prevalencia de las patologias odontológicas diagnósticas en la población adscrita en el Hospital comunitario de Achao ubicado en Achao, comuna de Quinchao, de mayo a diciembre de 2020. Se realizó un estudio observacional descriptivo a traves de la revisión de la totalidad de atenciones odontológicas realizadas en el Hospital comunitario de Achao, durante mayo a diciembre de 2020, registrando el sexo, la edad y el diagnóstico clínico según el motivo de consulta del paciente, realizado siempre por el mismo observador. Se revisaron 262 notificaciones que cumplieron con los criterios de inclusión. El sexo femenino fue el que consultó con mayor frecuencia. La edad del 76 % de la población fue entre 19 a 60 años. 159 notificaciones correspondieron a urgencias odontológicas ambulatorias GES, siendo los diagnósticos más prevalentes; Periodontitis apical sintomática y pulpitis. Por otra parte, se observaron consultas por desalojo de obturaciones y piezas con periodontits crónica severa. La pandemia ha generado una reorganización considerable en lo que respecta a las atenciones dentales, la literatura muestra que es recomendable suspender las atenciones electivas y restringuirse a la atención de urgencias, de pacientes críticos y procedimientos que no puedan ser postergados; En estos casos, se deben adoptar todas las medidas de protección antes, durante y despues de la atención dental.

ABSTRACT: The objective of this study was to know the prevalence of diagnostic dental pathologies in the population assigned to the Achao Community Hospital located in Achao, Quinchao commune, from May 2020 to December 2020. A descriptive observational study was carried out through the review of all dental care performed at the Achao Community Hospital, during May to December 2020, recording sex, age and clinical diagnosis according to the reason for consultation of the patient, always carried out by the same observer. 262 notifications that met the inclusion criteria were reviewed. It was noted that females consulted most frequently. The age of 76 % of the population was between 19 to 60 years. 159 notifications corresponded to GES outpatient dental emergencies, being the most prevalent diagnoses; Symptomatic apical periodontitis and pulpitis. On the other hand, consultations were observed due to the dislodgement of fillings and pieces with severe chronic periodontitis. The pandemic has generated a considerable reorganization with regard to dental care, the literature shows that it is advisable to suspend elective care and restrict it to outpatient dental emergencies, critical patients and procedures that cannot be postponed; in these cases, all protective measures must be taken before, during and after dental care.

Detection of DNA Adduct Formation in Rat Lungs by a Micro-HPLC/MS/MS Approach.

Aldehydes are abundantly present in tobacco smoke and in urban air pollution and are endogenously generated as products of the lipid peroxidation process. These molecules can react with DNA bases forming mutagenic exocyclic adducts, which have been used as biomarkers of aldehyde exposure and as potential tools for the study of inflammation, metal storage diseases, neurodegenerative disorders, and cancer. High-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) provides a highly precise, specific and ultrasensitive method for the detection of exocyclic DNA adducts. Here we present and describe a validated micro-HPLC-Electro Spray Ionization (ESI)-MS/MS method for the quantification of 1,N2-propanodGuo, an adduct produced following the reaction between 2'-deoxyguanosine and acetaldehyde or crotonaldehyde.

Monoclonal Antibodies Carried in Drug Delivery Nanosystems as a Strategy for Cancer Treatment.

Monoclonal antibodies carried in nanosystems have been extensively studied and reported as a promising tool for the treatment of various types of cancers. Monoclonal antibodies have great advantages for the treatment of cancer because their protein structure can bind to the target tissue; however, it has some challenges such as denaturation following heat exposure and extreme values of pH, temperature and solvents, the ability to undergo hydrolysis, oxidation and deamination and the formation of non-native aggregates, which compromise drug stability to a large extent. In addition to these characteristics, they suffer rapid elimination when in the blood, which results in a short half-life and the production of neutralizing antibodies, rendering the doses ineffective. These challenges are overcome with encapsulation in nanosystems (liposomes, polymer nanoparticles, cyclodextrins, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers and micelles) due to the characteristics of improving solubility, permeability, and selectivity only with tumor tissue; with that, there is a decrease in side effects beyond controlled release, which is critical to improving the therapeutic efficacy of cancer treatment. The article was divided into different types of nanosystems, with a description of their definitions and applications in various types of cancers. Therefore, this review summarizes the use of monoclonal antibodies encapsulated in nanosystems and the description of clinical studies with biosimilars. Biosimilars are defined as products that are similar to monoclonal antibodies which are produced when the patent for the monoclonal antibodies expires.

Antimicrobial Resistance Dynamics in Chilean Shigella sonnei Strains Within Two Decades: Role of Shigella Resistance Locus Pathogenicity Island and Class 1 and Class 2 Integrons.

Shigellosis is an enteric infectious disease in which antibiotic treatment is effective, shortening the duration of symptoms and reducing the excretion of the pathogen into the environment. Shigella spp., the etiologic agent, are considered emerging pathogens with a high public health impact due to the increase and global spread of multidrug-resistant (MDR) strains. Since Shigella resistance phenotype varies worldwide, we present an overview of the resistance phenotypes and associated genetic determinants present in 349 Chilean S. sonnei strains isolated during the periods 1995-1997, 2002-2004, 2008-2009, and 2010-2013. We detected a great variability in antibiotic susceptibility patterns, finding 300 (86%) MDR strains. Mobile genetic elements (MGE), such as plasmids, integrons, and genomic islands, have been associated with the MDR phenotypes. The Shigella resistance locus pathogenicity island (SRL PAI), which encodes for ampicillin, streptomycin, chloramphenicol, and tetracycline resistance genes, was detected by PCR in 100% of the strains isolated in 2008-2009 but was less frequent in isolates from other periods. The presence or absence of SRL PAI was also differentiated by pulsed-field gel electrophoresis. An atypical class 1 integron which harbors the bla OXA-1 -aadA1-IS1 organization was detected as part of SRL PAI. The dfrA14 gene conferring trimethoprim resistance was present in 98.8% of the 2008-2009 isolates, distinguishing them from the SRL-positive strains isolated before that. Thus, it seems an SRL-dfrA14 S. sonnei clone spread during the 2008-2009 period and declined thereafter. Besides these, SRL-negative strains harboring class 2 integrons with or without resistance to nalidixic acid were detected from 2011 onward, suggesting the circulation of another clone. Whole-genome sequencing of selected strains confirmed the results obtained by PCR and phenotypic analysis. It is highlighted that 70.8% of the MDR strains harbored one or more of the MGE evaluated, while 15.2% lacked both SRL PAI and integrons. These results underscore the temporal dynamics of antimicrobial resistance in S. sonnei strains circulating in Chile, mainly determined by the spread of MGE conferring MDR phenotypes. Since shigellosis is endemic in Chile, constant surveillance of antimicrobial resistance phenotypes and their genetic basis is a priority to contribute to public health policies.

Transcription blockage by DNA damage in nucleotide excision repair-related neurological dysfunctions.

Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. This review presents much of the evidence on the mechanisms related to neurodegenerative processes associated with DNA damage responses. The primary focus is on the effects of the transcription machinery, including the accumulation of DNA•RNA hybrids (R-loops) that, in turn, influence DNA damage and repair metabolism. Moreover, several neuronal tissues present higher expression of long genes, a genomic subset more affected by DNA lesions, which may explain part of the neurological abnormalities in these patients. Also, neuronal tissues have different DNA repair capabilities that might result in different neurological consequences, as observed in patients and NER deficient animal models. The better understanding of how the accumulation of transcription blocking lesions can lead to neurological abnormalities and premature aging-like phenotypes may assist us in finding potential biomarkers and therapeutic targets that might improve the lives of these patients, as well as other neurological disorders in the general population.

Fosfomicina en el tratamiento de la infección urinaria baja en niños mayores de 6 años. Evolución clínico-microbiológica / Fosfomycin for low urinary-tract infections in children of over 6 years of age. Clínical-microbiological evolution / Fosfomicina no tratamento da infecção do trato urinário baixo em crianças maiores de 6 anos de idade. Evolução clínico-microbiológica

Resumen: Introducción: fosfomicina trometamol (FT) representa una alternativa al tratamiento de la infección del tracto urinario (ITU) baja. Uruguay no dispone de información acerca de su uso en niños. Objetivo: describir la evolución clínica y microbiológica de una cohorte de niños mayores de 6 años con ITU baja tratados con FT. Material y método: se incluyeron niños mayores de 6 años con ITU baja de dos prestadores de salud de Montevideo, entre 1/2/2018 - 30/6/2019. A todos se indicó FT 2 g monodosis y urocultivo de control. Se realizó seguimiento telefónico. Se evaluó: clínica, antecedentes de ITU, microorganismo, susceptibilidad antimicrobiana y evolución: tiempo de resolución clínica, resolución microbiológica, efectos adversos, recurrencia en los primeros tres meses. Resultados: se incluyeron 46 niños, mediana de edad 9,4 años, antecedentes de ITU 13. Presentaron disuria 44, tenesmo 33, polaquiuria 31. Microorganismo aislado: E. coli 43, S. saprophyticus 2, Proteus sp 1. Todos susceptibles a FT, excepto S. saprophyticus naturalmente resistente. Resolución clínica en 48 horas: 42. Se obtuvo urocultivo de control en 31/46 niños: resolución microbiológica 22, no resolución 5 y contaminado 4. Presentaron efectos adversos 9: vómitos 1, diarrea 8 y cefalea 1. Seguimiento telefónico a 40/46 pacientes: reinfecciones al mes de tratamiento: 6. Conclusiones: no se registró resistencia adquirida en los microorganismos. Se observó resolución clínica en las primeras 48 horas en la mayoría de los casos. Los efectos adversos fueron leves. Ocurrieron reinfecciones en una proporción pequeña. Los resultados avalan a FT como alternativa terapéutica para ITU baja en mayores de 6 años.

Summary: Introduction: fosfomycin tromethamine (FT) is an alternative to the treatment of low urinary tract infection (UTI). Uruguay does not have information about its use in children. Objective: to describe the clinical and microbiological evolution of a cohort of children older than 6 years of age with low UTI treated with FT. Materials and methods: we included children of over 6 years of age with low UTI from two health providers in Montevideo between 2/1/2018 and 6/30/2019. We prescribed a single dose of FT 2 g and a control urine culture to all patients. We carried out a telephone follow-up and assessed their clinical record, history of UTI, microorganisms, antimicrobial susceptibility and evolution: time of clinical resolution, microbiological resolution, adverse effects, and recurrence during the first 3 months. Results: 46 children were included, median age 9.4 years, history of UTI 13. 44 presented dysuria, 33 tenesmus, 31 pollakiuria. Isolated microorganism: E. coli 43, S. saprophyticus 2, Proteus sp 1. All susceptible to FT, except S. saprophyticus, naturally resistant. Clinical resolution in 48 hours: 42. Control urine culture was obtained in 31/46 children: microbiological resolution 22, no resolution 5 and contaminated 4. Adverse effects 9: vomiting 1, diarrhea 8, and headache 1. Telephone follow-up carried out for 40 / 46 patients: reinfections after one month of treatment: 6. Conclusions: microorganisms had not acquired resistance. Most cases showed clinical resolution during the first 48 hours. Adverse effects were mild. Reinfections occurred in a small proportion. The results support FT as a therapeutic alternative for low UTI for the case of children of over 6 years of age.

Resumo: Introdução: A fosfomicina trometamina (FT) é uma alternativa ao tratamento da infecção do trato urinário baixo (ITU). O Uruguai não possui informações sobre seu uso em crianças. Objetivo: Descrever a evolução clínica e microbiológica de uma coorte de crianças maiores de 6 anos de idade com ITU baixa tratada com TF. Materiais e métodos: Foram incluídas crianças maiores de 6 anos de com ITU baixa de dois provedores de saúde em Montevidéu; no período 1/2 / 2018 e 30/06/2019. Todos os pacientes receberam indicação de FT 2 g em dose única, cultura de urina e controle. Realizou-se um rastreamento por telefone. Se avaliou: prontuário clínico, história de ITU, microrganismos, suscetibilidade a antimicrobianos e evolução: tempo de resolução clínica, resolução microbiológica, efeitos adversos, recorrência nos primeiros 3 meses. Resultados: Incluíram-se 46 crianças, mediana de idade 9,4 anos, história de ITU 13. 44 delas apresentaram disúria, tenesmo 33, polaciúria 31. Microrgoanismo isolado: E. coli 43, S. saprophyticus 2, Proteus sp 1. Todas suscetíveis a FT, exceto S. saprophyticus, naturalmente resistente. Resolução clínica em 48 horas: 42. Obtivemos cultura de urina controle em 31/46 crianças: resolução microbiológica 22, sem resolução 5 e contaminada 4. 9 delas apresentaram efeitos adversos 9: vômito 1, diarreia 8 e dor de cabeça 1. Realizamos acompanhamento telefônico em 40 / 46 pacientes: reinfecções um mês após tratamento, 6. Conclusões: Os microrganismos não adquiriram resistência. Na maioria dos casos observou-se resolução clínica nas primeiras 48 horas. Os efeitos adversos foram leves. As reinfecções ocorreram em pequena proporção. Os resultados apoiam o TF como uma alternativa terapêutica para ITU baixa para casos de crianças maiores de 6 anos de idade.

Complete genome sequence and analysis of Alcaligenes faecalis strain Mc250, a new potential plant bioinoculant.

Here we present and analyze the complete genome of Alcaligenes faecalis strain Mc250 (Mc250), a bacterium isolated from the roots of Mimosa calodendron, an endemic plant growing in ferruginous rupestrian grasslands in Minas Gerais State, Brazil. The genome has 4,159,911 bp and 3,719 predicted protein-coding genes, in a single chromosome. Comparison of the Mc250 genome with 36 other Alcaligenes faecalis genomes revealed that there is considerable gene content variation among these strains, with the core genome representing only 39% of the protein-coding gene repertoire of Mc250. Mc250 encodes a complete denitrification pathway, a network of pathways associated with phenolic compounds degradation, and genes associated with HCN and siderophores synthesis; we also found a repertoire of genes associated with metal internalization and metabolism, sulfate/sulfonate and cysteine metabolism, oxidative stress and DNA repair. These findings reveal the genomic basis for the adaptation of this bacterium to the harsh environmental conditions from where it was isolated. Gene clusters associated with ectoine, terpene, resorcinol, and emulsan biosynthesis that can confer some competitive advantage were also found. Experimental results showed that Mc250 was able to reduce (~60%) the virulence phenotype of the plant pathogen Xanthomonas citri subsp. citri when co-inoculated in Citrus sinensis, and was able to eradicate 98% of juveniles and stabilize the hatching rate of eggs to 4% in two species of agricultural nematodes. These results reveal biotechnological potential for the Mc250 strain and warrant its further investigation as a biocontrol and plant growth-promoting bacterium.

Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells.

The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

2018 Chilean Physical Activity Report Card for Children and Adolescents: Full Report and International Comparisons.

BACKGROUND: The study summarizes the findings of the 2018 Chilean Report Card (RC) on Physical Activity (PA) for Children and Adolescents and compares the results with the first Chilean RC and with other countries from the Global Matrix 3.0. METHODS: A Research Work Group using a standardized methodology from the Global Matrix 3.0 awarded grades for 13 PA-related indicators based on the percentage of compliance for defined benchmarks. Different public data sets, government reports, and papers informed the indicators. RESULTS: The grades assigned were for (1) "behaviors that contribute to overall PA levels": overall PA, D-; organized sport participation, D-; active play, INC; and active transportation, F; (2) "factors associated with cardiometabolic risk": sedentary behavior, C-; overweight and obesity, F; fitness, D; sleep, INC; and (3) "factors that influence PA": family and peers, F; school, D; inclusion, INC; community and built environment, B; government strategies and investments, B-. CONCLUSIONS: Chile's grades remained low compared with the first RC. On the positive side, Chile is advancing in environmental and policy aspects. Our findings indicate that the implementation of new strategies should be developed through collaboration between different sectors to maximize effective investments for increasing PA and decreasing sedentary time among children and adolescents in Chile.