Cu(II) binding to the λ6aJL2-R24G antibody light chain protein associated with light chain amyloidosis disease: The role of histidines.

Light chain amyloidosis is a conformational disease caused by the abnormal proliferation and deposition of antibody light chains as amyloid fibers in organs and tissues. The effect of Cu(II) binding to the model recombinant protein 6aJL2-R24G was previously characterized in our group, and we found an acceleration of the aggregation kinetics of the protein. In this study, in order to confirm the Cu(II) binding sites, histidine variants of 6aJL2-R24G were prepared and the effects of their interaction with Cu(II) was analyzed by circular dichroism, fluorescence spectroscopy, isothermal calorimetry titrations, and molecular dynamics simulations. Confirming our earlier work, we found that His8 and His99 are the highest affinity Cu(II) binding sites, and that Cu(II) binding to both sites is a cooperative event.

Osmoprotectants play a major role in the Portulaca oleracea resistance to high levels of salinity stress-insights from a metabolomics and proteomics integrated approach.

Introduction: Purslane (Portulaca oleracea L.) is a non-conventional food plant used extensively in folk medicine and classified as a multipurpose plant species, serving as a source of features of direct importance to the agricultural and agri-industrial sectors. This species is considered a suitable model to study the mechanisms behind resistance to several abiotic stresses including salinity. The recently achieved technological developments in high-throughput biology opened a new window of opportunity to gain additional insights on purslane resistance to salinity stress-a complex, multigenic, and still not well-understood trait. Only a few reports on single-omics analysis (SOA) of purslane are available, and only one multi-omics integration (MOI) analysis exists so far integrating distinct omics platforms (transcriptomics and metabolomics) to characterize the response of purslane plants to salinity stress. Methods: The present study is a second step in building a robust database on the morpho-physiological and molecular responses purslane to salinity stress and its subsequent use in attempting to decode the genetics behind its resistance to this abiotic stress. Here, the characterization of the morpho-physiological responses of adult purslane plants to salinity stress and a metabolomics and proteomics integrative approach to study the changes at the molecular level in their leaves and roots is presented. Results and discussion: Adult plants of the B1 purslane accession lost approximately 50% of the fresh and dry weight (from shoots and roots) whensubmitted to very high salinity stress (2.0 g of NaCl/100 g of the substrate). The resistance to very high levels of salinity stress increases as the purslane plant matures, and most of the absorbed sodium remains in the roots, with only a part (~12%) reaching the shoots. Crystal-like structures, constituted mainly by Na+, Cl-, and K+, were found in the leaf veins and intercellular space near the stoma, indicating that this species has a mechanism of salt exclusion operating on the leaves, which has its role in salt tolerance. The MOI approach showed that 41 metabolites were statistically significant on the leaves and 65 metabolites on the roots of adult purslane plants. The combination of the mummichog algorithm and metabolomics database comparison revealed that the glycine, serine, and threonine, amino sugar and nucleotide sugar, and glycolysis/gluconeogenesis pathways were the most significantly enriched pathways when considering the total number of occurrences in the leaves (with 14, 13, and 13, respectively) and roots (all with eight) of adult plants; and that purslane plants employ the adaptive mechanism of osmoprotection to mitigate the negative effect of very high levels of salinity stress; and that this mechanism is prevalent in the leaves. The multi-omics database built by our group underwent a screen for salt-responsive genes, which are now under further characterization for their potential to promote resistance to salinity stress when heterologously overexpressed in salt-sensitive plants.

Extubation failure after cardiac surgery in children with Down syndrome.

Extubation failure (EF) after cardiac surgery is associated with poorer outcomes. Approximately 50% of children with Down syndrome (DS) have congenital heart disease. Our primary aim was to describe the frequency of EF and identify risk factors for its occurrence in a population of patients with DS after cardiac surgery. Secondary aims were to describe complications, length of hospital stay, and mortality rates. This report was a retrospective case-control study and was carried out in a national reference congenital heart disease repair center of Chile. This study includes all infants 0-12 months old with DS who were admitted to pediatric intensive care unit after cardiac surgery between January 2010 and November 2020. Patients with EF (cases) were matched 1:1 with children who did not fail their extubation (controls) using the following criteria: age at surgery, sex, and type of congenital heart disease. Overall, 27/226 (11.3%) failed their first extubation. In the first analysis, before matching of cases and controls was made, we found association between EF and younger age (3.8 months vs 5 months; p = 0.003) and presence of coarctation of the aorta (p = 0.005). In the case-control univariate analysis, we found association between an increased cardiothoracic ratio (CTR) (p = 0.03; OR 5 (95% CI 1.6-16.7) for a CTR > 0.59) and marked hypotonia (27% vs 0%; p = 0.01) with the risk of EF. No differences were found in ventilatory management. CONCLUSIONS: In pediatric patients with DS, EF after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting the degree of cardiomegaly and hypotonia. Recognition of these factors may be helpful when planning extubation for these patients. WHAT IS KNOWN: • Extubation failure after cardiac surgery is associated with higher morbidity and mortality rates. Some studies report higher rates of extubation failure in patients with Down syndrome. WHAT IS NEW: • In children with Down syndrome, extubation failure after cardiac surgery is associated with younger age, presence of aortic coarctation, higher CTR reflecting cardiomegaly and severe hypotonia.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

The early response of oil palm (Elaeis guineensis Jacq.) plants to water deprivation: Expression analysis of miRNAs and their putative target genes, and similarities with the response to salinity stress.

Oil palm (Elaeis guineensis Jacq.) is a oilseed crop of great economic importance drastically affected by abiotic stresses. MicroRNAs (miRNAs) play crucial roles in transcription and post-transcription regulation of gene expression, being essential molecules in the response of plants to abiotic stress. To better understand the molecular mechanisms behind the response of young oil palm plants to drought stress, this study reports on the prediction and characterization of miRNAs and their putative target genes in the apical leaf of plants subjected to 14 days of water deprivation. Then, the data from this study were compared to the data from a similar study that focused on salinity stress. Both, the drought-and salt-responsive miRNAs and their putative target genes underwent correlation analysis to identify similarities and dissimilarities among them. Among the 81 identified miRNAs, 29 are specific for oil palm, including two (egu-miR28ds and egu-miR29ds) new ones - described for the first time. As for the expression profile, 62 miRNAs were significantly differentially expressed under drought stress, being five up-regulated (miR396e, miR159b, miR529b, egu-miR19sds, and egu-miR29ds) and 57 down-regulated. Transcription factors, such as MYBs, HOXs, and NF-Ys, were predicted as putative miRNA-target genes in oil palm under water deprivation; making them the most predominant group of such genes. Finally, the correlation analysis study revealed a group of putative target genes with similar behavior under salt and drought stresses. Those genes that are upregulated by these two abiotic stresses encode lncRNAs and proteins linked to stress tolerance, stress memory, modulation of ROS signaling, and defense response regulation to abiotic and biotic stresses. In summary, this study provides molecular evidence for the possible involvement of miRNAs in the drought stress response in oil palm. Besides, it shows that, at the molecular level, there are many similarities in the response of young oil palm plants to these two abiotic stresses.

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review.

BACKGROUND: Hepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known. METHODS: We conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence. RESULTS: Of 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3-5 years for two-dose programs. Vaccine efficacy was >98% over 0.1-7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively. CONCLUSION: Experience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.

Expression analysis of miRNAs and their putative target genes confirm a preponderant role of transcription factors in the early response of oil palm plants to salinity stress.

BACKGROUND: Several mechanisms regulating gene expression contribute to restore and reestablish cellular homeostasis so that plants can adapt and survive in adverse situations. MicroRNAs (miRNAs) play roles important in the transcriptional and post-transcriptional regulation of gene expression, emerging as a regulatory molecule key in the responses to plant stress, such as cold, heat, drought, and salt. This work is a comprehensive and large-scale miRNA analysis performed to characterize the miRNA population present in oil palm (Elaeis guineensis Jacq.) exposed to a high level of salt stress, to identify miRNA-putative target genes in the oil palm genome, and to perform an in silico comparison of the expression profile of the miRNAs and their putative target genes. RESULTS: A group of 79 miRNAs was found in oil palm, been 52 known miRNAs and 27 new ones. The known miRNAs found belonged to 28 families. Those miRNAs led to 229 distinct miRNA-putative target genes identified in the genome of oil palm. miRNAs and putative target genes differentially expressed under salinity stress were then selected for functional annotation analysis. The regulation of transcription, DNA-templated, and the oxidation-reduction process were the biological processes with the highest number of hits to the putative target genes, while protein binding and DNA binding were the molecular functions with the highest number of hits. Finally, the nucleus was the cellular component with the highest number of hits. The functional annotation of the putative target genes differentially expressed under salinity stress showed several ones coding for transcription factors which have already proven able to result in tolerance to salinity stress by overexpression or knockout in other plant species. CONCLUSIONS: Our findings provide new insights into the early response of young oil palm plants to salinity stress and confirm an expected preponderant role of transcription factors - such as NF-YA3, HOX32, and GRF1 - in this response. Besides, it points out potential salt-responsive miRNAs and miRNA-putative target genes that one can utilize to develop oil palm plants tolerant to salinity stress.

Hepatitis A epidemiology in Latin American countries: a 2020 view from a systematic literature review.

INTRODUCTION: The World Health Organization recommends vaccination against hepatitis A virus (HAV) for children aged 1 year and older in areas where endemicity has shifted from high to intermediate. There are no recent comprehensive reviews of the epidemiology of HAV infection in Latin America, but seroprevalence and socioeconomic data suggest that, with improved clean water and sanitation systems, countries are transitioning to intermediate endemicity. AREAS COVERED: We conducted a systematic literature review of the epidemiology of HAV infection in 25 countries in the Latin American region, which included gray literature. We compiled data on HAV incidence and prevalence, including the identification of epidemiological changes observed in countries that established pediatric HAV vaccination programs. EXPERT OPINION: We identified 59 relevant articles, including 34 peer-reviewed seroprevalence studies (12 recent studies from Brazil), three incidence studies, and six vaccine impact studies (three from Argentina). Based on the estimated age at midpoint of population immunity in each country, most have a high-intermediate, intermediate, or low-intermediate level of HAV endemicity, suggesting that national childhood immunization may be an appropriate disease prevention strategy. However, recent data were lacking for most countries. Improved data quality and continued epidemiological surveillance are required for this region.

Máxime "Max" Kuczynski: Father of Peruvian Public Health and of the 66th President of Peru.

Máxime Kuczynski (1890-1967), a medical pioneer born in Poland, was renowned for his work in tropical medicine in the Peruvian jungle, especially on Bartonella baciliformis, the cutaneous form known as verruga peruana of deadly Oroya fever. His unique university training in anthropology, philosophy, and parasitology lead to a participatory observational method of practicing medicine. At the request of the Peruvian President, he ventured into the Peruvian Amazon in 1936 to establish a public health service in partnership with indigenous populations. In June 2016, his son Pedro Pablo Kuczynski, a former Prime Minister of Peru, was elected the 66th President of Peru.

Erythema ab igne: new technology rebounding upon its users?

Erythema ab igne (EAI) is a persistent, chronic skin condition resulting from prolonged exposure to infrared radiation, experienced as heat. Once associated with traditional warming sources like wood burning stoves or open fires, modern, infrared exposure originates also from newer sources like laptops and heating pads and may be creating a rebound of EAI. The epidemiology may be different too, with younger patients than previously seen. Localized EAI over an area of pain in the abdomen or lower back can be a sign of an underlying disorder, including cancer. Prognosis of EAI is good, with removal of the heat source resulting in complete remission. In chronic cases in which premalignant cutaneous dysplasia has resulted, additional treatments may be necessary including topical retinoids, 5-fluorouracil cream, and laser treatments. Rarely, cancers such as squamous cell carcinoma, Merkel cell carcinoma, and cutaneous marginal zone B cell lymphoma have been associated with longstanding EAI.

Programa de promoção da autorregulação da aprendizagem de ingressantes da educação superior / Program to promote self-regulated learning in higher education freshmen students / Programa de promoción de autorregulación del aprendizaje de ingresantes de la educación superior

O objetivo deste trabalho foi avaliar a eficácia de parte de um programa para promover a autorregulação da aprendizagem na educação superior. Participaram 26 ingressantes com idade média de 20,65 (DP = 3,35) provenientes de diferentes cursos de graduação de uma universidade pública, os quais participaram de uma atividade não obrigatória, organizada em seis encontros de 90 minutos cada um. Medidas de autorrelato foram aplicadas no pré e pós-teste a fim de comparar as variáveis dependentes: conhecimento das estratégias de aprendizagem, processos de autorregulação da aprendizagem, instrumentalidade percebida, autoeficácia para autorregular-se e para a formação superior. De acordo com a comparação entre o pré e pós-teste, os resultados são favoráveis no pós-teste para as variáveis conhecimento das estratégias de aprendizagem, autorregulação da aprendizagem e autoeficácia para autorregular-se. Esses resultados sugerem que a autorregulação da aprendizagem de ingressantes pode ser potencializada por meio do programa educacional "Cartas do Gervásio ao seu Umbigo". (AU)

The objective of this study was to assess the efficacy of part of a program aimed at promoting self-regulation learning in higher education. Participants included 26 freshmen with mean age 20.65 (SD=3.35), from several undergraduate courses in a public university. The program was a non-mandatory activity organized in six 90-minute meetings. Self-report measures were applied in the pre and post test in order to compare the dependent variables, which were: knowledge about learning strategies, self-regulation learning strategies, perceived instrumentality, self-efficacy to self-regulate and self-efficacy for higher education. Data from pre and post tests indicate that the results are favorable in the post test for the variables knowledge about learning strategies, self-regulation learning strategies, and self-efficacy to self-regulate. These results suggest that self-regulated learning by freshmen may be increased by the program named "Letters from Gervásio to his navel". (AU)

El objetivo de este trabajo fue evaluar la eficacia de parte de un programa, para promover la autoregulación del aprendizaje en la Educación Universitaria. El trabajo se realizó con 26 estudiantes con edad promedio entre 20,65 (DP=3,35) provenientes de diferentes cursos de graduación de una universidad pública, los cuales participaron de una actividad no obligatoria, organizada en seis encuentros de 90 minutos cada uno. Medidas de autoinforme fueron aplicadas en el pre y post test, a fin de comparar las variables dependientes: conocimiento de estrategias de aprendizaje, proceso de autoregulación de aprendizaje, instrumentalidad percibida, autoeficacia para autoregulación y para formación universitaria. De acuerdo con la comparación entre el pre y el post test, los resultados son favorables en el post test para las variables conocimiento de estrategias de aprendizaje, autoregulación de aprendizaje y autoeficacia para autoregulación. Estos resultados señalan que la autoregulación del aprendizaje de los ingresantes puede ser potencializada por medio del programa educacional "Cartas de Gervasio a su ombligo". (AU)

What's eating you? scabies in the developing world.

Scabies infestation is a major cause of impetigo and subsequent renal failure in the developing world, and efforts to eradicate widespread infestation are underway. Ivermectin, topical sulfur, and topical benzyl benzoate often are used to treat widespread outbreaks.

What's eating you? sticktight flea revisited.

The sticktight flea (Echidnophaga gallinacea) earns its name by embedding its head in the host's skin. It has been found in many species of birds and mammals, including humans. The sticktight flea is found worldwide in the tropics, subtropics, and temperate zones, and it is the only representative of this genus found in the United States. Bites from fleas cause irritation and itching for hosts including humans, typically resulting in clusters of firm, pruritic, erythematous papules. Treatment can be tricky, as the fleas can be difficult to remove, and any flea-infested environments should be properly treated to prevent further bites.

Shedding light on onychomadesis.

Onychomadesis is the proximal separation of the nail plate from the nail matrix due to a temporary cessation of nail growth. It can occur in children of all ages including neonates. Diagnosis is made clinically through palpation and inspection of the nail plate. Physicians should consider underlying associations. A review of the patient's history for any viral illnesses 1 to 2 months prior to nail changes often will help identify the causative disease. Onychomadesis typically is mild and self-limited. There is no specific treatment, but a conservative approach to management is recommended with treatment of any underlying causes and supportive care. Spontaneous nail regrowth usually occurs within 12 weeks and may occur faster in children. In this article, causes of onychomadesis are described, including the connection between hand-foot-and-mouth disease (HFMD) and onychomadesis. We also explore several theories of possible mechanisms for onychomadesis; however, the precise mechanism remains unclear and further investigation is needed.