Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery. We have recruited 209 individuals with a rare EHMT1 variant and performed comprehensive molecular in silico and in vitro testing alongside DNA methylation (DNAm) signature analysis for the identified variants. We (re)classified the variants as likely pathogenic/pathogenic (molecularly confirming Kleefstra syndrome) in 191 individuals. We provide an updated and broader clinical and molecular spectrum of Kleefstra syndrome, including individuals with normal intelligence and familial occurrence. Analysis of the EHMT1 variants reveals a broad range of molecular effects and their associated phenotypes, including distinct genotype-phenotype associations. Notably, we showed that disruption of the "reader" function of the ankyrin repeat domain by a protein altering variant (PAV) results in a KLEFS1-specific DNAm signature and milder phenotype, while disruption of only "writer" methyltransferase activity of the SET domain does not result in KLEFS1 DNAm signature or typical KLEFS1 phenotype. Similarly, N-terminal truncating variants result in a mild phenotype without the DNAm signature. We demonstrate how comprehensive variant analysis can provide insights into pathogenesis of the disorder and DNAm signature. In summary, this study presents a comprehensive overview of KLEFS1 and EHMT1, revealing its broader spectrum and deepening our understanding of its molecular mechanisms, thereby informing accurate variant interpretation, counseling, and clinical management.

Recurrent alcohol-associated hepatitis is common and is associated with increased mortality.

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

Amino acids as bio-organocatalysts in ring-opening copolymerization for eco-friendly synthesis of biobased oligomers from vegetable oils.

Herein, we present an innovative synthetic approach for producing a diverse set of biobased oligomers. This method begins with olive oil and employs a wide variety of commercially available amino acids (AAs) as bio-organocatalysts, in addition to tetrabutylammonium iodide (TBAI) as a cocatalyst, to synthesize various biobased oligomers. These biobased oligomers were strategically prepared starting from epoxidized olive oil (EOO) and a variety of cyclic anhydrides (phthalic, PA; maleic, MA; succinic, SA; and glutaric, GA). Among the amino acids tested as bio-organocatalysts, L-glutamic acid (L-Glu) showed the best performance for the synthesis of both poly(EOO-co-PA) and poly(EOO-co-MA), exhibiting 100% conversion at 80 °C in 2 hours, whereas the formation of poly(EOO-co-SA) and poly(EOO-co-GA) required more extreme reaction conditions (72 hours under toluene reflux conditions). Likewise, we have succeeded in obtaining the trans isomer exclusively for the MA based-oligomer within the same synthetic framework. The obtained oligomers were extensively characterized using techniques including NMR, FT-IR, GPC and TGA. A series of computational simulations based on density functional theory (DFT) and post-Hartree Fock (post-HF) methods were performed to corroborate our experimental findings and to obtain an understanding of the reaction mechanisms.

Reduced neutralization against Delta, Gamma, Mu, and Omicron BA.1 variants of SARS-CoV-2 from previous non-Omicron infection.

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein.

Predictors of Word and Pseudoword Reading in Languages with Different Orthographic Consistency.

This study analyzes the impact of certain cognitive processes on word and pseudoword reading in languages with different orthographic consistency (Spanish and Arabic) in the first year of Primary Education. The study was conducted with a group of 113 pupils from Algeria and another group of 128 pupils from Ecuador, from a middle-class background and without any special education needs. The participants were assessed in terms of their reading ability of words and pseudowords, knowledge of letters, phonological awareness, rapid automatized naming, and phonological memory. Using a correlational design, descriptive-exploratory, bivariate, and hierarchical multivariate regressions were applied to the different measures of reading in each language. The findings show that knowledge of letters, phonological awareness, rapid automatized naming, and phonological memory contribute differently to the explanation of reading ability in each group at the start of compulsory schooling. These results have important implications for the teaching of reading skills and the prevention of specific learning disabilities, as well as the theory of reading acquisition.

Solid-State Preparation of Metal and Metal Oxides Nanostructures and Their Application in Environmental Remediation.

Nanomaterials have attracted much attention over the last decades due to their very different properties compared to those of bulk equivalents, such as a large surface-to-volume ratio, the size-dependent optical, physical, and magnetic properties. A number of solution fabrication methods have been developed for the synthesis of metal and metal oxides nanoparticles, but few solid-state methods have been reported. The application of nanostructured materials to electronic solid-state devices or to high-temperature technology requires, however, adequate solid-state methods for obtaining nanostructured materials. In this review, we discuss some of the main current methods of obtaining nanomaterials in solid state, and also we summarize the obtaining of nanomaterials using a new general method in solid state. This new solid-state method to prepare metals and metallic oxides nanostructures start with the preparation of the macromolecular complexes chitosan·Xn and PS-co-4-PVP·MXn as precursors (X = anion accompanying the cationic metal, n = is the subscript, which indicates the number of anions in the formula of the metal salt and PS-co-4-PVP = poly(styrene-co-4-vinylpyridine)). Then, the solid-state pyrolysis under air and at 800 °C affords nanoparticles of M°, MxOy depending on the nature of the metal. Metallic nanoparticles are obtained for noble metals such as Au, while the respective metal oxide is obtained for transition, representative, and lanthanide metals. Size and morphology depend on the nature of the polymer as well as on the spacing of the metals within the polymeric chain. Noticeably in the case of TiO2, anatase or rutile phases can be tuned by the nature of the Ti salts coordinated in the macromolecular polymer. A mechanism for the formation of nanoparticles is outlined on the basis of TG/DSC data. Some applications such as photocatalytic degradation of methylene by different metal oxides obtained by the presented solid-state method are also described. A brief review of the main solid-state methods to prepare nanoparticles is also outlined in the introduction. Some challenges to further development of these materials and methods are finally discussed.

Planar Elongated B12 Structure in M3B12 Clusters (M = Cu-Au).

Here, it is shown that the M3B12 (M = Cu-Au) clusters' global minima consist of an elongated planar B12 fragment connected by an in-plane linear M3 fragment. This result is striking since this B12 planar structure is not favored in the bare cluster, nor when one or two metals are added. The minimum energy structures were revealed by screening the potential energy surface using genetic algorithms and density functional theory calculations. Chemical bonding analysis shows that the strong electrostatic interactions with the metal compensate for the high energy spent in the M3 and B12 fragment distortion. Furthermore, metals participate in the delocalized π-bonds, which infers an aromatic character to these species.

[Effectiveness of a multidimensional therapeutic program for aged people attending senior centers]. / Efectividad a mediano plazo de un programa multidimensional en personas mayores en centros diurnos en Chile.

BACKGROUND: It is imperative to have effective programs to improve or maintain the health of aged people. AIM: To evaluate the effectiveness of an intervention based on a multidimensional program in Senior centers in Chile five months after its implementation, in the domains of physical and mental health, functionality and quality of life in aged people. MATERIAL AND METHODS: Sixty participants older than 60 years completed a multidimensional program for one month that included interventions of guided physical exercises, in addition to educational and social activities. They were evaluated at baseline and one and five months after the intervention. RESULTS: After the first and fifth months, significant improvements were observed in the five times sit to stand test (5TSTS) and gait speed (WST), in addition, significant improvements were observed in literacy measured by the Short Assessment of Health Literacy for Spanish-speaking Adults (SAHLSA). At the fifth month, slight improvements were observed in the Yesavage and short Falls efficacy scales, Barthel index, Unipodal Station and EuroQol five-dimensional quality of life tests. CONCLUSIONS: A multidimensional program for aged people lasting one month, improved the physical health dimension and literacy by the fifth month of evaluation.

Declines in Pneumonia Mortality Following the Introduction of Pneumococcal Conjugate Vaccines in Latin American and Caribbean Countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children < 5 years of age. METHODS: We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death. RESULTS: The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2-59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%-35%]), Ecuador (25% [95% CrI, 4%-41%]), Mexico (11% [95% CrI, 3%-18%]), Nicaragua (19% [95% CrI, 0-34%]), and Peru (35% [95% CrI, 20%-47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2-59 months since introduction. CONCLUSIONS: Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Prevalence in Blood in a Large School Community Subject to a Coronavirus Disease 2019 Outbreak: A Cross-sectional Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. METHODS: The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4-19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. RESULTS: The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2-11.8) for 1009 students and 16.6% (95% CI, 12.1-21.9) for 235 staff. Among students, positivity was associated with a younger age (P = .01), a lower grade level (P = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P = .03), and a history of contact with a confirmed case (P < .001). Among staff, positivity was higher in teachers (P = .01) and in those previously RT-PCR positive (P < .001). Excluding RT-PCR-positive individuals, antibody positivity was associated with fever in adults and children (P = .02 and P = .002, respectively), abdominal pain in children (P = .001), and chest pain in adults (P = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P = .01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.

Development of neutralizing antibody responses against SARS-CoV-2 in COVID-19 patients.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are new global problems. The understanding of the host immune response in COVID-19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID-19 patients. We followed up 117 COVID-19 confirmed patients from a reference health center for COVID-19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS-CoV-2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID-19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes-free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS-CoV-2 infection during severe COVID-19.

Effect of sugar-sweetened beverages on oral health: a systematic review and meta-analysis.

BACKGROUND: The impact of consumption of sugar-sweetened beverages (SSB) on health outcomes such as obesity have been studied extensively, but oral health has been relatively neglected. This study aims to assess the association between SSB consumption and dental caries and erosion. METHODS: Systematic review of observational studies. Search strategy applied to Medline, Embase, Cochrane Library, SciELO, LILACS, OpenGrey and HMIC. The risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cross-Sectional Studies and evidence certainty using Grading of Recommendation Assessment Development and Evaluation. Relationships between SSB consumption and caries and erosion were estimated using random-effects model meta- and dose-response analyses. RESULTS: A total of 38 cross-sectional studies were included, of which 26 were rated as high quality. Comparing moderate-to-low consumption, there was significantly increased risk of both caries [OR = 1.57, 95% CI: 1.28-1.92; decayed, missing and filled teeth weighted mean differences (DMFT WMD) = 0.82, 95% CI: 0.38-1.26] and erosion (OR = 1.43, 95% CI: 1.01-2.03). Comparing high-to-moderate consumption, there was further increased risk of caries (OR = 1.53, 95% CI: 1.17-1.99; DMFT WMD = 1.16, 95% CI: -0.59-2.91) and erosion (OR = 3.09, 95% CI: 1.37-6.97). A dose-response gradient and high certainty of evidence was observed for caries. CONCLUSIONS: Increasing SSB consumption is associated with increased risk of dental caries and erosion. Studies were cross-sectional, hence temporality could not be established, but the positive dose-response suggests this relationship is likely to be causal. These findings illustrate the potential benefits to oral health of policies that reduce SSB consumption, including sugar taxation.

Health-related quality of life in older people with functional independence or mild dependence.

BACKGROUND: The concept of Health-Related Quality of Life (HRQOL) has grown in importance in the elderly population (PM), which is due to the increase in life expectancy of contemporary societies and the desire of people to live the most advanced years in good condition. OBJECTIVE: To know the effect of the epidemiological dimensions, functional capacity, social and psychological well-being on the HRQL of a group of senior people from the Borough of Puente Alto intervened by the multidimensional model of the Integral Center for Happy Aging, CIEF, Universidad de los Andes. RESULTS: Correlation was observed between the dimensions mentioned above, as well as the improvement in the predictive models of HRQL in the extent to which social and psychological variables are incorporated into the morbidity and functional capacity dimension, the latter strongly related to HRQL according to the scientific literature. CONCLUSION: The study shows the relevance of incorporating measures of social and psychological well-being in the evaluation of HRQL, especially with a view to the design of multidimensional interventions that encompass individual content and the environment in which seniors develop.

Molecular and epidemiological characterization of imported malaria cases in Chile.

BACKGROUND: Chile is one of the South American countries certified as malaria-free since 1945. However, the recent increase of imported malaria cases and the presence of the vector Anopheles pseudopunctipennis in previously endemic areas in Chile require an active malaria surveillance programme. METHODS: Specimens from 268 suspected malaria cases-all imported-collected between 2015 and 2018 at the Public Health Institute of Chile (ISP), were diagnosed by microscopy and positive cases were included for epidemiological analysis. A photo-induced electron transfer fluorogenic primer real-time PCR (PET-PCR) was used to confirm the presence of malaria parasites in available blood samples. Sanger sequencing of drug resistance molecular markers (pfk13, pfcrt and pfmdr1) and microsatellite (MS) analysis were performed in confirmed Plasmodium falciparum samples and results were related to origin of infection. RESULTS: Out of the 268 suspected cases, 65 were Plasmodium spp. positive by microscopy. A total of 63% of the malaria patients were male and 37% were female; 43/65 of the patients acquired infections in South American endemic countries. Species confirmation of available blood samples by PET-PCR revealed that 15 samples were positive for P. falciparum, 27 for Plasmodium vivax and 4 were mixed infections. The P. falciparum samples sequenced contained four mutant pfcrt genotypes (CVMNT, CVMET, CVIET and SVMNT) and three mutant pfmdr1 genotypes (Y184F/S1034C/N1042D/D1246Y, Y184F/N1042D/D1246Y and Y184F). MS analysis confirmed that all P. falciparum samples presented different haplotypes according to the suspected country of origin. Four patients with P. vivax infection returned to the health facilities due to relapses. CONCLUSION: The timely detection of polymorphisms associated with drug resistance will contribute to understanding if current drug policies in the country are appropriate for treatment of imported malaria cases and provide information about the most frequent resistant genotypes entering Chile.

Engineering of tomato for the sustainable production of ketocarotenoids and its evaluation in aquaculture feed.

Ketocarotenoids are high-value pigments used commercially across multiple industrial sectors as colorants and supplements. Chemical synthesis using petrochemical-derived precursors remains the production method of choice. Aquaculture is an example where ketocarotenoid supplementation of feed is necessary to achieve product viability. The biosynthesis of ketocarotenoids, such as canthaxanthin, phoenicoxanthin, or astaxanthin in plants is rare. In the present study, complex engineering of the carotenoid pathway has been performed to produce high-value ketocarotenoids in tomato fruit (3.0 mg/g dry weight). The strategy adopted involved pathway extension beyond ß-carotene through the expression of the ß-carotene hydroxylase (CrtZ) and oxyxgenase (CrtW) from Brevundimonas sp. in tomato fruit, followed by ß-carotene enhancement through the introgression of a lycopene ß-cyclase (ß-Cyc) allele from a Solanum galapagense background. Detailed biochemical analysis, carried out using chromatographic, UV/VIS, and MS approaches, identified the predominant carotenoid as fatty acid (C14:0 and C16:0) esters of phoenicoxanthin, present in the S stereoisomer configuration. Under a field-like environment with low resource input, scalability was shown with the potential to deliver 23 kg of ketocarotenoid/hectare. To illustrate the potential of this "generally recognized as safe" material with minimal, low-energy bioprocessing, two independent aquaculture trials were performed. The plant-based feeds developed were more efficient than the synthetic feed to color trout flesh (up to twofold increase in the retention of the main ketocarotenoids in the fish fillets). This achievement has the potential to create a new paradigm in the renewable production of economically competitive feed additives for the aquaculture industry and beyond.

Type of delivery and reading, writing, and arithmetic learning in twin births.

This study analyses, in children born in twin births, the relationship between reading, writing and arithmetic learning, on the one hand, and type of delivery, on the other, controlling for the effect of interaction and/or confusion of third variables (maternal age at delivery, gestational age, fetal position, birthweight, 1-min Apgar score). In the planned retrospective cohort design, the exposed cohort consisted of children born by caesarean section, and the non-exposed cohort was comprised of children born vaginally. One hundred and twenty-four children born of twin births were evaluated during their first year of primary school: K-BIT tests were used to measure intelligence; the Evalúa-1 battery was used to assess reading, writing, and arithmetic ability; and the children's clinical histories were analysed for obstetric and neonatal variables. After applying binary logistic regressions for each dependent variable, it was found that caesarean delivery in twin births appeared as a possible independent risk factor for specific learning disabilities (LDs) in reading, writing, and arithmetic. Based on these results, further research using larger samples and at more advanced ages is required in order to analyse the influence of obstetric and neonatal variables on the processes underlying specific LDs.

[Risk of infections associated with the use of biological medications; a review]. / Riesgo de infección en pacientes con enfermedades inmunológicas y oncológicas tratados con biológicos: revisión panorámica.

Biological medications are effective for the treatment of cancer and inflammatory diseases. The aim of this review is to summarize the available evidence in systematic reviews or meta-analyses about the risk of infection in patients with cancer, arthritis, psoriasis and inflammatory bowel disease who use biological medications. We included systematic reviews or meta-analyses of controlled clinical trials and case/control studies that analyze infections during and after treatment with FDA-approved biological medications for the treatment of cancer, arthritis, inflammatory bowel disease and psoriasis, both in adults and children. The following databases were consulted: PubMed, Epistemonikos, Crochrane reviews, JIB, and Prospero. A quality guideline (AMSTAR) was applied to the selected studies. We included 26 studies. The risk of infections in patients with solid organ cancer is consistent in the literature. In psoriasis there is a risk of non-serious infections. In arthritis and other inflammatory diseases there is a risk of serious infections. In inflammatory bowel disease there is a risk for opportunistic infections. In conclusion, in patients with cancer and inflammatory diseases use biological medications entails a risk of infection. The evidence is different depending on the underlying disease of each patient.

Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico.

BACKGROUND: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates. OBJECTIVES: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus. METHODS: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records. RESULTS: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.

[Impact of the ERA and GES health programs on mortality from community-acquired pneumonia in persons aged ≥65 years in ChileImpacto do programa de saúde ERA e do GES na mortalidade por pneumonia adquirida na comunidade em indivíduos com idade acima de 65 anos no Chile]. / Impacto de los programas de salud ERA y GES en la mortalidad por neumonía adquirida en la comunidad en personas de 65 años o más en Chile.

OBJECTIVE: Evaluate the impact of the Adult Respiratory Diseases (ERA) Program and the General System of Explicit Health Guarantees (GES) on mortality from community-acquired pneumonia (CAP) in persons aged ≥65 years in Chile. METHODS: In this ecological study, annual and quarterly mortality rates from CAP were calculated in persons aged 65 to 79 years and ≥80 years from 1990 to 2014. Information was gathered from the databases of Chile's Department of Health Statistics and Information and its National Statistics Institute. The ERA Program (implemented in 2001) and the inclusion of CAP in the GES (starting in 2005) were evaluated as interventions. Data were analyzed using the interrupted time-series method, following the Prais-Winsten model, with a 5% significance level. RESULTS: The analysis showed that after the ERA Program began, significant reductions in CAP mortality were observed in the two age groups studied, whereas after CAP was added to the GES program, no statistically significant changes were found in those rates. CONCLUSIONS: Implementation of the ERA Program helped to reduce CAP mortality in persons aged ≥65 years in Chile, whereas inclusion of CAP in the GES program did not.

OBJETIVO: Avaliar o efeito do Programa Enfermidades Respiratorias del Adulto (doenças respiratórias do adulto, ERA) e do Régimen General de Garantías Explícitas en Salud (regime geral de garantias explícitas em Saúde, GES) na mortalidade por pneumonia adquirida na comunidade (PAC) em indivíduos acima de 65 anos no Chile. MÉTODOS: Estudo ecológico em que foram calculadas as taxas anuais e trimestrais de mortalidade por PAC em indivíduos de 65 a 79 anos e acima de 80 anos no período entre 1990 e 2014. Os dados foram obtidos dos bancos de dados do Departamento de Estatística e Informação em Saúde e do Instituto Nacional de Estatística do Chile. As intervenções avaliadas foram o Programa ERA (implantado em 2001) e a inclusão da PAC no GES (a partir de 2005). Os dados foram analisados com o método de séries temporais interrompidas segundo o modelo de Prais-Winsten. O nível de significância foi de 5%. RESULTADOS: A análise demonstrou que, após a implantação do Programa ERA, houve uma redução significativa na taxa de mortalidade por PAC nas duas faixas etárias consideradas. Por outro lado, a inclusão da PAC no GES não teve efeito estatisticamente significativo na taxa de mortalidade. CONCLUSÕES: A implantação do Programa ERA contribuiu para reduzir a taxa de mortalidade por PAC em indivíduos acima de 65 anos no Chile, porém o mesmo não ocorreu com a inclusão da PAC no GES.

Affinity of Electrochemically Deposited Sol⁻Gel Silica Films towards Catecholamine Neurotransmitters.

Dopamine, norepinephrine, and epinephrine neurotransmitters can be detected by electrochemical oxidation in conventional electrodes. However, their similar chemical structure and electrochemical behavior makes a difficult selective analysis. In the present work, glassy carbon electrodes have been modified with silica layers, which were prepared by electroassisted deposition of sol⁻gel precursors. These layers were morphologically and compositionally characterized using different techniques, such as field emission scanning electron microscopy (FESEM), TEM, FTIR, or thermogravimetric analysis⁻mass spectrometry (TG-MS). The affinity of silica for neurotransmitters was evaluated, exclusively, by means of electrochemical methods. It was demonstrated that silica adsorbs dopamine, norepinephrine, and epinephrine, showing different interaction with silica pores. The adsorption process is dominated by a hydrogen bond between silanol groups located at the silica surface and the amine groups of neurotransmitters. Because of the different interaction with neurotransmitters, electrodes modified with silica films could be used in electrochemical sensors for the selective detection of such molecules.