Structures of SenB and SenA enzymes from Variovorax paradoxus provide insights into carbon-selenium bond formation in selenoneine biosynthesis.

Selenoneine, an ergothioneine analog, is important for antioxidation and detoxification. SenB and SenA are two crucial enzymes that form carbon-selenium bonds in the selenoneine biosynthetic pathway. To investigate their underlying catalytic mechanisms, we obtained complex structures of SenB with its substrate UDP-N-acetylglucosamine (UDP-GlcNAc) and SenA with N-α-trimethyl histidine (TMH). SenB adopts a type-B glycosyltransferase fold. Structural and functional analysis of the interaction network at the active center provide key information on substrate recognition and suggest a metal-ion-independent, inverting mechanism is utilized for SenB-mediated selenoglycoside formation. Moreover, the complex structure of SenA with TMH and enzymatic activity assays highlight vital residues that control substrate binding and specificity. Based on the conserved structure and substrate-binding pocket of the type I sulfoxide synthase EgtB in the ergothioneine biosynthetic pathway, a similar reaction mechanism was proposed for the formation of C-Se bonds by SenA. The structures provide knowledge on selenoneine synthesis and lay groundwork for further applications of this pathway.

Structural insights into a novel nonheme iron-dependent oxygenase in selenoneine biosynthesis.

Selenoneine (SEN) is a natural histidine derivative with radical-scavenging activity and shows higher antioxidant potential than its sulfur-containing isolog ergothioneine (EGT). Recently, the SEN biosynthetic pathway in Variovorax paradoxus was reported. Resembling EGT biosynthesis, the committed step of SEN synthesis is catalyzed by a nonheme Fe-dependent oxygenase termed SenA. This enzyme catalyzes oxidative carbon­selenium (C-Se) bond formation to conjugate N-α-trimethyl histidine (TMH) and selenosugar to yield selenoxide; the process parallels the EGT biosynthetic route, in which sulfoxide synthases known as EgtB members catalyze the conjugation of TMH and cysteine or γ-glutamylcysteine to afford sulfoxides. Here, we report the crystal structures of SenA and its complex with TMH and thioglucose (SGlc), an analog of selenoglucose (SeGlc) at high resolution. The overall structure of SenA adopts the archetypical fold of EgtB, which comprises a DinB-like domain and an FGE-like domain. While the TMH-binding site is highly conserved to that of EgtB, a various substrate-enzyme interaction network in the selenosugar-binding site of SenA features a number of water-mediated hydrogen bonds. The obtained structural information is beneficial for understanding the mechanism of SenA-mediated C-Se bond formation.

Children's Mental Health: Discrepancy between Child Self-Reporting and Parental Reporting.

(1) Background: Discrepancies between children's self-reports and their parents' reports on mental health indicators are associated with measurement errors or informant bias. However, they are a valuable tool in understanding the course of child psychopathology. This study aims to determine the level of discrepancies between parents' perceptions and children's self-reports in mental health indicators in Northern Chile. (2) Methods: A System of Evaluation of Children and Adolescents self-report (Sistema de Evaluación de Niños y Adolescentes, SENA) was responded to by 408 students between 8 and 13 years old and their parents. (3) Results: Children reported a significantly higher frequency of emotional problems, defiant behavior, and executive functions as compared to their parents' responses. (4) Conclusions: There is a disjunction between the report of parents and children, which could originate in poor family communication.

A CRISPR-Cas12a-based specific enhancer for more sensitive detection of SARS-CoV-2 infection.

BACKGROUND: Real-time reverse transcription-PCR (rRT-PCR) has been the most effective and widely implemented diagnostic technology since the beginning of the COVID-19 pandemic. However, fuzzy rRT-PCR readouts with high Ct values are frequently encountered, resulting in uncertainty in diagnosis. METHODS: A Specific Enhancer for PCR-amplified Nucleic Acid (SENA) was developed based on the Cas12a trans-cleavage activity, which is specifically triggered by the rRT-PCR amplicons of the SARS-CoV-2 Orf1ab (O) and N fragments. SENA was first characterized to determine its sensitivity and specificity, using a systematic titration experiment with pure SARS-CoV-2 RNA standards, and was then verified in several hospitals, employing a couple of commercial rRT-PCR kits and testing various clinical specimens under different scenarios. FINDINGS: The ratio (10 min/5 min) of fluorescence change (FC) with mixed SENA reaction (mix-FCratio) was defined for quantitative analysis of target O and N genes, and the Limit of Detection (LoD) of mix-FCratio with 95% confidence interval was 1.2≤1.6≤2.1. Totally, 295 clinical specimens were analyzed, among which 21 uncertain rRT-PCR cases as well as 4 false negative and 2 false positive samples were characterized by SENA and further verified by next-generation sequencing (NGS). The cut-off values for mix-FCratio were determined as 1.145 for positive and 1.068 for negative. INTERPRETATION: SENA increases both the sensitivity and the specificity of rRT-PCR, solving the uncertainty problem in COVID-19 diagnosis and thus providing a simple and low-cost companion diagnosis for combating the pandemic. FUNDING: Detailed funding information is available at the end of the manuscript.

Problemas de regulación emocional y salud mental en adolescentes del norte de Chile / Emotional regulation problems and mental health in adolescents in northern Chile

Resumen El propósito de este estudio fue evaluar la asociación entre los problemas de regulación emocional e indicadores de salud mental en adolescentes de la ciudad Arica al Norte de Chile, además de describir y comparar los niveles de problemas interiorizados y exteriorizados entre hombres y mujeres. Participaron 2331 estudiantes de 11 a 20 años provenientes de establecimientos educacionales. Para medir los problemas de regulación emocional y los indicadores de salud mental, se utilizó el Sistema de Evaluación de Niños y Adolescentes (SENA). Los resultados muestran que los problemas de regulación emocional poseen efectos grandes y significativos sobre los problemas interiorizados y exteriorizados. Asimismo, se observó que las mujeres presentan mayor sintomatología depresiva, ansiosa, de ansiedad social y problemas de regulación emocional que los hombres. Pareciera ser que los adolescentes que manifiestan problemas para regular sus emociones son más vulnerables a experimentar estados de ánimos disfóricos, preocupaciones recurrentes o comportamientos disruptivos.

Abstract The aim of this study was to assess the relationship between emotional regulation problems and mental health outcomes in adolescents from the city of Arica in northern Chile, in addition to describing and comparing the levels of internalized and externalized problems between men and women. A total of 2331 students from 11 to 20 years old from educational establishments participated in the study. To measure emotional regulation problems and mental health indicators, the System of Evaluation of Children and Adolescents (SENA) was used. The results show that emotional regulation problems have large and significant effects on both internalized and externalized problems. Likewise, it was observed that women show more depressive, anxious, social anxiety and emotional regulation problems than men. It seems that adolescents who manifest problems in regulating their emotions are more vulnerable to experience dysphoric moods, recurrent worries or disruptive behavior.

Avaliação comparativa de eficácia clínica e tolerabilidade para a combinação de Cassia fistula e Senna alexandrina Miller em pacientes com constipação intestinal funcional crônica / Comparative evaluation of clinical efficacy and tolerability for the combination of Cassia fistula and Senna alexandrina Miller in patients with chronic functional constipation

JUSTIFICATIVA E OBJETIVO: A constipação intestinal é um problema crônico, frequente, que afeta a Qualidade de Vida dos indivíduos. O objetivo deste estudo foi avaliar a eficácia clínica e a tolerabilidade da composição Cassia fistula e Senna alexandrina Miller, na apresentação geleia sem açúcar, em pacientes diagnosticados com constipação intestinal funcional crônica. MÉTODOS: Estudo envolvendo 96 voluntários com diagnóstico de constipação intestinal funcional crônica, conforme Critérios de Roma III, randomizados em grupos ativo e placebo. A avaliação da eficácia primária foi realizada por meio da frequência média de evacuações, consistência média das fezes e melhora global da constipação. Foram realizadas ainda avaliações secundárias, como número de dias seguidos sem evacuação, proporção de evacuações com dor, esforço, sensação de evacuação incompleta ou bloqueio, uso de manobras manuais, sujeitos de pesquisa que aderiram às recomendações de hábitos de vida, uso de fármacos de resgate e melhora da constipação segundo avaliação do sujeito de pesquisa. RESULTADOS: A proporção de sujeitos da pesquisa que apresentou melhora global da constipação foi de 65,1% no grupo ativo e de 22,0% grupo placebo (p<0,0001). Para a maioria das avaliações secundárias de eficácia, o grupo ativo apresentou melhor desempenho quando comparado ao grupo pesquisa. De acordo com a avaliação dos sujeitos de pesquisa sobre a melhora da constipação, o grupo ativo apresentou melhor desempenho do que o grupo pesquisa. Quanto à segurança, os dois grupos apresentaram resultados similares. CONCLUSÃO: A geleia sem açúcar composta de Cassia fistula e Senna alexandrina Miller apresentou um comportamento seguro e eficaz, sendo uma alternativa para tratamento da constipação intestinal funcional crônica.

BACKGROUND AND OBJECTIVE: Intestinal constipation is a chronic and frequent problem that affects Quality of Life. The aim of this study was to evaluate the efficacy and tolerability of the composition Cassia fistula and Senna alexandrina Miller, as sugar free jelly, in patients diagnosed with chronic functional constipation. METHODS: We evaluated 96 volunteers diagnosed with functional constipation according to Rome III criteria. Volunteers were randomized into active and placebo groups. Primary efficacy endpoint was evaluated by mean frequency of bowel movements, consistency of stools and global improvement of constipation. Secondary endpoints were evaluated, such as number of days without bowel movements, proportion of bowel movements with pain, with strain, sensation of incomplete or blocked bowel movement, use of, manual maneuvers to facilitate defecation, subjects who adhered to the diet recommendation, use of rescue medication, and level of constipation improvement, according to subject evaluation. RESULTS: Global improvement of constipationwas observed in 65.1% of subjects enrolled in active group versus 22% in placebo group (p<0.0001). For most secondary efficacy evaluations, the active group performed better when compared to placebo group. According to the evaluation of the subjects on the improvement of constipation, the active group performed better than the placebo group. As for security, the two groups showed similar results. CONCLUSION: Cassia fistula and Senna alexandrina Miller sugar free jelly demonstrated to be safe and effective and it can be used as an alternative for the treatment of functional constipation.

Uso de protetor físico na semeadura direta para recuperação de áreas degradadas / Use of physical protector in tillage for recovery of degraded areas

A semeadura direta apresenta-se como uma técnica viável economicamente e de fácil implantação para recuperação de áreas degradadas, no entanto problemas na emergência e crescimento inicial das plântulas são fatores limitantes para sua aplicação. Portanto, o presente trabalho teve como objetivo avaliar a eficiência do uso de protetor físico na emergência e crescimento inicial de três espécies arbóreas, Anadenanthera colubrina, Leucaena leucocephala e Sena pendula. Para a proteção das espécies foram utilizados copos plásticos de 400 mL com o fundo removido, sendo que, no período de 45 dias foram avaliadas a emergência, sobrevivência e altura das plântulas. Observou-se que, a utilização de protetor físico não foi significativo para a sobrevivência e emergência das espécies estudadas, porém o crescimento inicial em altura das plantas apresentou melhores resultados nas sementes com protetores quando comparadas às sem proteção, para as espécies L. leucocephala e A. colubrina. Pode-se concluir que, dispensa-se o uso de protetor para aumentar a emergência e sobrevivência das espécies em estudo, mas este é indicado quando deseja-se obter um maior incremento em altura.

The direct seeding is presented as an economically viable technique for easy deployment and recovery of degraded areas, however problems in the emergence and early seedling growth are limiting factors for their application. Therefore, this study aimed to evaluate the effectiveness of using physical protector in the emergence and early growth of three tree species, Anadenanthera colubrine, Leucaena leucocephala e Sena pendula. For the protection of the species used were 400 mL plastic cups with the bottom removed, and, within 45 days were examined emergence, survival and seedling height. It was observed that the use of physical protector was not significant for the survival and emergence of the species, but the initial growth of plant height showed the best results with floating seeds when compared to no protection for the species L. leucocephala and A. colubrina. It can be concluded that dismissal is the use of protective emergency and to increase the survival of the species studied, but this is indicated when it is desired to obtain a greater increase in height.

A comparison of the efficacy, adverse effects, and patient compliance of the sena-graph®syrup and castor oil regimens for bowel preparation.

Sena-Graph syrup has recently been formulated by an Iranian pharmaceutical company for being used in bowel evacuation before radiography, colonoscopy and surgery. This study compares the efficacy, adverse effects and patient compliance of two bowel preparation regimens with castor oil and Sena-Graph syrup in of outpatients for Intravenous Urography (IVU). One hundred and fourteen consecutive outpatients were randomized to receive either the standard bowel preparation with 60 mL of castor oil or the test method with 60 mL of Sena-Graph syrup before IVU examination. Demographic data of patients and their prior bowel preparation experience were collected before the examination. Two radiologists, blinded to the method of bowel preparation, reviewed the radiographs and graded the bowel preparation. The compliance and acceptability of both regimens were assessed by using structured questionnaires filled by the patients. The Numbers, ages, weights and gender distribution of patients and their prior bowel preparation experience in the two groups did not differ significantly. The cleanliness scores for the castor oil and Sena-Graph group were 3.97 ± 0.971 and 4.87 ± 0.917, respectively. The results indicated that Sena-Graph syrup causes a better bowel cleansing compared castor oil. Adverse effects in Sena-Graph groups were significantly lower than the castor oil group. Acceptability of the regimen in patients who used Sena-Graph was higher than the other group. The Sena-Graph regimen is significantly more effective and better tolerated than of Castor oil regimen in bowel cleansing. The incidence and severity of the adverse effects from Castor oil was higher than Sena-Graph.