Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning

Determinación espectrofotométrica sensible del peróxido de hidrógeno en muestras de agua procedentes de procesos de oxidación avanzada : Evaluación de posibles interferencias

RESUMEN: La determinación de peróxido de hidrógeno (H2O2) en muestras de agua real se llevó a cabo de una manera sencilla y sensible. Las condiciones óptimas de funcionamiento resultantes de un diseño experimental factorial completo fueron 450 nm, 50 mm y 6 x 10-3 M de longitud de onda de absorción, longitud de trayectoria de la celda de cuarzo y concentración final de la solución de monovanadato de amonio, respectivamente; permitiendo la cuantificación de 2.94x10-3 mM de H2O2. Se validó el método analítico propuesto y se investigó el efecto de la matriz obteniendo un método selectivo. Además, se aplicó el método analítico desarrollado para estudiar la evolución de H2O2 en la descontaminación de agua que contenía 6,73x10-5 mM de antraceno y 1,19x10-5 mM de benzo[a]pireno utilizando el sistema UV/H2O2. Se encontró que el nivel óptimo de H2O2 que permitía cerca del 45% de mineralización y una eliminación de los hidrocarburos aromáticos policíclicos objeto de estudio superior al 99% fue de 2,94x10-1 mM, permaneciendo aproximadamente 1,47x10-1 mM de H2O2 después de 90 min de tratamiento.ABSTRACT: Hydrogen peroxide (H2O2) determination in real water samples was carried out in a simple and sensitive way. The resulting optimal operating conditions from a 23 full factorial experimental design were 450 nm, 50 mm and 6x10-3 M for the absorption wavelength, the quartz cell path length and the final concentration of the ammonium monovanadate solution, respectively; allowing the quantification of H2O2 up to 2.94x10-3 mM. The proposed analytical method was validated and the effect of the background matrix was investigated, obtaining a selective method. Additionally, the developed analytical method was applied for studying the evolution of H2O2 in the decontamination of water containing 6.73x10-5 mM of anthracene and 1.19x10-5 mM of benzo[a]pyrene using the UV/H2O2 system. It was found that the optimal H2O2 level enabling about 45% of mineralisation and a removal of the target polycyclic aromatic hydrocarbons higher than 99% was 2.94x10-1 mM, remaining approximately 1.47x10-1 mM of H2O2 after 90 min of treatment

Efetividade da suplementacao de sulfato ferroso na prevencao da anemia em criancas: revisao sistematica da literatura e metanalise

Abstract and Keywords published in English and Portuguese. English title: Effectiveness of ferrous sulfate supplementation in the prevention of anemia in children: A systematic literature review and meta-analysis. Erratum included at the end of the PDF article.Revisão sistemática e metanálise de estudos que avaliaram a efetividade da suplementação de sulfato ferroso na prevenção da anemia em crianças menores de cinco anos de idade. Foram pesquisadas as bases PubMed, Scopus, SciELO e LILACS e incluídos artigos publicados entre 1980-2011 em espanhol, inglês ou português, utilizando os unitermos: criança, pré-escolar, lactente, anemia, prevenção, suplementação e ferro. Foram selecionados 13 estudos, que mostraram que independentemente da dose e do tempo de suplementação, o esquema diário foi mais consistente na melhoria dos níveis de hemoglobina (efeito combinado 0,56mg/dL, IC95%: 0,31; 0,81, p < 0,001) do que o semanal (efeito combinado 0,28mg/dL, IC95%: -0,22; 0,78, p = 0,273). Não houve efeito da suplementação na redução da prevalência de anemia, mesmo com doses diárias, e a administração conjunta com outros micronutrientes não trouxe benefícios adicionais em comparação com a administração exclusiva do suplemento. A suplementação diária de sulfato ferroso mostrou-se mais efetiva do que doses semanais na melhoria dos níveis de hemoglobina. = This was a systematic review and meta-analysis of studies evaluating the effectiveness of ferrous sulfate supplementation in the prevention of anemia in children under five. The database search included PubMed, Scopus, LILACS, and SciELO. Articles published between 1980 and 2011 in Spanish, English, or Portuguese were included, using the keywords child, preschool, infant, anemia, prevention, and iron supplementation. The authors selected 13 studies, which showed that regardless of dose and duration of supplementation, daily regimen was more consistently related to improvement in hemoglobin levels (pooled effect 0.56mg/dL, 95%CI: 0.31; 0.81, p < 0.001) as compared to weekly intervention (pooled effect 0.28mg/dL, 95%CI: -0.22; 0.78, p = 0.273). Iron supplementation was not associated with decreased prevalence of anemia, even with daily doses, and administration with other micronutrients did not bring additional benefits compared to the exclusive administration of iron supplement. Daily supplementation of ferrous sulfate was more effective than weekly doses in improving hemoglobin levels.Francieli Cembranel, Camila Dallazen, David Alejandro González-Chic

Unraveling the Prevalence of Antibiotic Resistance in Stenotrophomonas maltophilia: Insights into an Emerging Nosocomial Pathogen

Introduction: stenotrophomonas maltophilia is a clinically relevant opportunistic and nosocomial pathogen with increasing concerns regarding antibiotic resistance. Accurate diagnosis and identification are crucial for effective treatment, and misidentification can occur, thereby emphasizing the need for appropriate laboratory testing and surveillance. This review aimed to evaluate the epidemiology, pathogenesis, diagnosis, treatment, and antimicrobial resistance of Stenotrophomonas spp. Materials and Methods. A systematic literature review was conducted using the PubMed Central Database. Inclusion criteria included studies published in open-access scientific journals within the last five years, reporting information on Stenotrophomonas spp. epidemiology, pathogenesis, diagnosis, treatment, and/or antimicrobial resistance. The synthesis of the results involved a narrative synthesis of the findings from the included studies. Results. A total of 25 articles met the inclusion criteria and provided valuable insights into Stenotrophomonas spp. infections. The distribution of reported cases by country, sample type, and antimicrobial resistance patterns was summarized. The prevalence of resistance to various antibiotics was also assessed, highlighting the need for continuous surveillance. Conclusion. This analysis revealed the presence of antimicrobial resistance in Stenotrophomonas spp., particularly in S. maltophilia. The high prevalence of antibiotic resistance underscores the importance of ongoing surveillance and control measures to combat antibiotic resistance. The diverse distribution of S. maltophilia across different sample types emphasizes the need for accurate diagnosis and identification. Addressing antimicrobial resistance in Stenotrophomonas spp. is essential for global public health

“Who Cares?”: the acceptance of decentralized wastewater systems in regions without water problems

There is a growing interest in decentralized wastewater treatment systems, especially in regions with water scarcity problems or water management issues. This study aims to determine whether the perceived advantages and disadvantages (leading to acceptance) of decentralized wastewater plants in such regions are the same in regions where the population is not aware of these water issues. Firstly, this study systematically reviews previous findings on public perceptions of the acceptance of decentralized wastewater treatment systems. Then, the study details the results of a focus group study to determine whether the elements identified in the literature are also relevant in a region where people are unaware of water problems. The results show that a lack of awareness of water issues seems to be a critical factor influencing acceptance. Reframing the usefulness of these systems by focusing on other aspects, such as environmental sustainability, is key.info:eu-repo/semantics/publishedVersio

Impact of long‐term management with sleep medications on blood pressure: An Australian national study

OnlinePublBackground: There is mixed evidence about the impact of long-term management with hypnotic medications on blood pressure (BP). Aim: To estimate the effect of short- and long-term management with benzodiazepine and z-drugs (BZD) on BP. Method: Open cohort study using deidentified electronic health records of 523,486 adult regular patients (42.3% males; mean age 59.0 ± 17.0 years) annually attending 402 Australian general practices between 2016 to 2018 (MedicineInsight database). Average treatment effects (ATE) of recorded incident BZD prescriptions in 2017 on systolic (SBP) and diastolic (DBP) BP after starting these prescriptions were computed using augmented inverse probability weighting (AIPW). Results: In 2017, 16,623 new cases of short-term management with BZD and 2532 cases of long-term management with BZD were identified (incidence 3.2% and 0.5%, respectively). The mean BP among those not treated with BZD (reference group) was 130.9/77.3 mmHg. Patients prescribed short-term BZD showed a slightly higher SBP (ATE 0.4; 95% CI 0.1, 0.7) and DBP (ATE 0.5; 95% CI 0.3, 0.7), while those on long-term BZD prescriptions showed lower SBP (ATE -1.1; 95% CI −2.0, −0.2), but no effect on DBP (ATE −0.1; 95% CI −0.8, 0.5). However, long-term BZD prescriptions showed a stronger BP-lowering effect among patients aged 65+ years (SBP ATE −2.5 [95% CI −3.8, −1.3]; DBP ATE −1.0 [95% CI −1.7, −0.2]), but almost no effect was observed among younger patients. Conclusion: Long-term management with BZD had a BP-lowering effect among older patients. These findings add new evidence to current recommendations on limiting long-term BZD management in the elderly.Mumtaz Begum, David Gonzalez-Chica, Carla Bernardo, Nigel Stock

Maternal depression and anxiety predicts the pattern of offspring symptoms during their transition to adulthood

Background. Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood. Method. Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated. Results. Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers. Conclusions. Maternal D&A is associated with persistent D&A during the daughter’s transition to adulthood. Intervention strategies should consider the mother’s mental health