Factors delaying non-metastatic breast cancer adjuvant therapy and impact on prognosis in a cohort of Brazilian women.

OBJECTIVE: To identify factors associated with delays in beginning adjuvant therapy and prognosis impacts on non-metastatic breast cancer patients. METHODS: This assessment comprised a prospective cohort study concerning breast cancer patients treated at a public oncology centre. A time interval of ≥60 days between surgery and the beginning of the first adjuvant treatment was categorised as a delay. Factors associated with delays were evaluated through logistic regression analysis and the prognosis effects were assessed by a Cox regression analysis. RESULTS: The median time interval between surgery and the first adjuvant treatment for the 401 women included in this study was of 57.0 days (37.0-93.0). Independent factors associated with delays comprised not presenting an overexpression of the HER-2 protein, not having undergone neoadjuvant chemotherapy, and having undergone chemotherapy or other therapeutic modalities other than hormone therapy and chemotherapy as the first adjuvant treatment. Delays did not affect recurrence, distant metastasis, or death risks. Factors associated with recurrence and distant metastasis risks comprised a clinical staging ≥2B, having undergone neoadjuvant chemotherapy, presenting the luminal molecular subtype B and triple-negative tumours, and having children. Factors associated with death comprised triple-negative molecular tumours and neoadjuvant chemotherapy. CONCLUSION: Delays in beginning adjuvant treatment did not affect the prognosis of non-metastatic breast cancer patients. Clinical and treatment-related factors, on the other hand, were associated with delays, and recurrence, distant metastasis, and death risks.

The journey of stage III and IV non-small cell lung cancer patients in the Brazilian private healthcare system: a retrospective study.

Non-small cell lung cancer (NSCLC) is still diagnosed at late stages in Brazil. The availability of newer treatment options has changed patient management, however, few real-world data have been published since then. This is a population-based retrospective cohort study that aims to evaluate the characteristics of stage III/IV NSCLC patients and their journey in the Brazilian private healthcare system. Patients aged ≥18 years, residing in Brazil who had their first medical appointment between 2016 and 2018 were included in the study. The sociodemographic and clinical characteristics of the patients and time intervals of interest were described. A total of 10,394 patients were analyzed. The majority of the patients were male (58.5%) with a median age of 64.0 (IQR = 58.0 - 71.0) years. In relation to characteristics of the disease, most of the tumors were characterized as adenocarcinomas (52.3%) and diagnosed at stage IV (72.2%). Most patients arrived at the hospital with an established NSCLC diagnosis, while 45.7% were diagnosed at the first medical appointment in the hospital or later. For patients who were diagnosed at the first medical appointment or later, a median interval of 15.0 (IQR = 6.0 - 33.0) days was observed between the first medical appointment and the diagnosis. The first treatment was given after a median of 25.0 (IQR = 6.0 - 49.0) days after diagnosis for patients without a prior diagnosis, and 57.0 (IQR: 33.0 - 98.0) days for patients with a prior diagnosis. The most common treatments were chemotherapy alone (33.8%), chemotherapy combined with radiotherapy (21.5%), radiotherapy alone (13.1%), adjuvant or neoadjuvant treatment (9.3%), surgery (3.3%), and immunotherapy (0.7%; alone or combined). At the end of follow-up (September, 2020), 52.3% of the patients had died. Despite having more treatment options in the private sector, data show that there is a need to improve access to technologies.

Body composition in pediatric patients.

Undernutrition is highly prevalent in children who are critically ill and is associated with increased morbidity and mortality, including a higher risk of infection due to transitory immunological disorders, inadequate wound healing, reduced gut function, longer dependency on mechanical ventilation, and longer hospital stays compared with eutrophic children who are critically ill. Nutrition care studies have proposed that early interventions targeting nutrition assessment can prevent or minimize the complications of undernutrition. Stress promotes an acute inflammatory response mediated by cytokines, resulting in increased basal metabolism and nitrogen excretion and leading to muscle loss and changes in body composition. Therefore, the inclusion of body composition assessment is important in the evaluation of these patients because, in addition to the nutrition aspect, body composition seems to predict clinical prognosis. Several techniques can be used to assess body composition, such as arm measurements, calf circumference, grip strength, bioelectrical impedance analysis, and imaging examinations, including computed tomography and dual-energy x-ray absorptiometry. This review of available evidence suggests that arm measurements seem to be well-established in assessing body composition in children who are critically ill, and that bioelectrical impedance analysis with phase angle, handgrip strength, calf circumference and ultrasound seem to be promising in this evaluation. However, further robust studies based on scientific evidence are necessary.

Childhood infection burden, recent antibiotic exposure and vascular phenotypes in preschool children.

BACKGROUND: Severe childhood infection has a dose-dependent association with adult cardiovascular events and with adverse cardiometabolic phenotypes. The relationship between cardiovascular outcomes and less severe childhood infections is unclear. AIM: To investigate the relationship between common, non-hospitalised infections, antibiotic exposure, and preclinical vascular phenotypes in young children. DESIGN: A Dutch prospective population-derived birth cohort study. METHODS: Participants were from the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort. We collected data from birth to 5 years on antibiotic prescriptions, general practitioner (GP)-diagnosed infections, and monthly parent-reported febrile illnesses (0-1 years). At 5 years, carotid intima-media thickness (CIMT), carotid artery distensibility, and blood pressure (BP) were measured. General linear regression models were adjusted for age, sex, smoke exposure, birth weight z-score, body mass index, and socioeconomic status. RESULTS: Recent antibiotic exposure was associated with adverse cardiovascular phenotypes; each antibiotic prescription in the 3 and 6 months prior to vascular assessment was associated with an 18.1 µm (95% confidence interval, 4.5-31.6, p = 0.01) and 10.7 µm (0.8-20.5, p = 0.03) increase in CIMT, respectively. Each additional antibiotic prescription in the preceding 6 months was associated with an 8.3 mPa-1 decrease in carotid distensibility (-15.6- -1.1, p = 0.02). Any parent-reported febrile episode (compared to none) showed weak evidence of association with diastolic BP (1.6 mmHg increase, 0.04-3.1, p = 0.04). GP-diagnosed infections were not associated with vascular phenotypes. CONCLUSIONS: Recent antibiotics are associated with adverse vascular phenotypes in early childhood. Mechanistic studies may differentiate antibiotic-related from infection-related effects and inform preventative strategies.

Antifungal activity of essential oils and their combinations against storage fungi.

We aimed to evaluate the fungicidal activity of essential oils (EOs) from Baccharis dracunculifolia (Asteraceae), Baccharis uncinella (Asteraceae), Mentha arvensis (Lamiaceae), Salvia officinalis (Lamiaceae), Melaleuca alternifolia (Myrtaceae), and Cymbopogon nardus (Poaceae) in the in vitro control of mycotoxin-producing strains of Aspergillus niger, Aspergillus nomius, Aspergillus flavus, and Fusarium graminearum. EOs' chemical composition was analyzed by gas chromatography-mass spectrometry, and a total of 19, 21, 18, 20, 17, and 15 compounds were identified in B. dracunculifolia, B. uncinella, S. officinalis, M. arvensis, M. alternifolia, and C. nardus EOs, respectively. Contact and volatilization bioassays were performed, for which M. alternifolia and C. nardus EOs had the greatest fungicidal effect (> 90%). Therefore, these EOs were evaluated for minimum inhibitory concentration, medium inhibitory concentration, and sporulation. Effects from the combined use of EOs were also evaluated. EOs interacted in combination, displaying an additive effect against F. graminearum and A. flavus and an antagonistic effect against the remaining isolates. We conclude that C. nardus EO was effective in the control of storage pathogens and that combined EOs can improve their antifungal effects.

Living with small fiber neuropathy: insights from qualitative focus group interviews.

OBJECTIVE: Small fiber neuropathy (SFN) is characterized by chronic neuropathic pain and autonomic dysfunction. Currently, symptomatic pharmacological treatment is often insufficient and frequently causes side effects. SFN patients have a reduced quality of life. However, little is known regarding whether psycho-social variables influence the development and maintenance of SFN-related disability and complaints. Additional knowledge may have consequences for the treatment of SFN. For example, factors such as thinking, feeling, and behavior are known to play roles in other chronic pain conditions. The aim of this study was to obtain further in-depth information about the experience of living with SFN and related chronic pain. METHODS: Fifteen participants with idiopathic SFN participated in a prospective, semi-structured, qualitative, focus group interview study. The focus groups were audio-recorded, transcribed, and analyzed cyclically after each interview. RESULTS: The following main themes were identified: "pain appraisal", "coping", "social, work, and health environment", and "change in identity". Catastrophic thoughts and negative emotions were observed. Living with SFN resulted in daily limitations and reduced quality of life. CONCLUSIONS: Given the results, it can be concluded that an optimal treatment should include biological, psychological, and social components.

Clustering of trauma patients based on longitudinal data and the application of machine learning to predict recovery.

Predicting recovery after trauma is important to provide patients a perspective on their estimated future health, to engage in shared decision making and target interventions to relevant patient groups. In the present study, several unsupervised techniques are employed to cluster patients based on longitudinal recovery profiles. Subsequently, these data-driven clusters were assessed on clinical validity by experts and used as targets in supervised machine learning models. We present a formalised analysis of the obtained clusters that incorporates evaluation of (i) statistical and machine learning metrics, (ii) clusters clinical validity with descriptive statistics and medical expertise. Clusters quality assessment revealed that clusters obtained through a Bayesian method (High Dimensional Supervised Classification and Clustering) and a Deep Gaussian Mixture model, in combination with oversampling and a Random Forest for supervised learning of the cluster assignments provided among the most clinically sensible partitioning of patients. Other methods that obtained higher classification accuracy suffered from cluster solutions with large majority classes or clinically less sensible classes. Models that used just physical or a mix of physical and psychological outcomes proved to be among the most sensible, suggesting that clustering on psychological outcomes alone yields recovery profiles that do not conform to known risk factors.

Diffuse large B-cell lymphoma: morphologic and immunohistochemical analysis of bone marrow for staging, with emphasis on lymphoid aggregates.

Diffuse large B-Cell lymphoma (DLBCL) may infiltrate bone marrow (BM) and evaluation of BM plays an important role in DLBCL staging. This study used BM samples from DLBCL patients for staging and analyzed the use of immunohistochemistry in the diagnostic management of these cases by the pathologist. Patients with DLBCL submitted to BM biopsy/aspiration for staging were studied according to clinical aspects, morphologic aspects, and expression of CD20 and CD3. The characteristics of lymphoid aggregates in the bone marrow and the power of histopathological diagnosis were studied, with immunohistochemistry as the gold standard for the decision of a neoplastic infiltration definition. An isolated morphological analysis showed low sensitivity (42.9%) for lymphoma detection in BM, which is disadvantageous. The median of three lymphoid aggregates in the BM (p-value = 0.02) and the presence of increased reticulin fibers (grade 2) in the lymphoid aggregate (p-value = 0.01) had significant associations with neoplastic infiltration. A morphological analysis must be accompanied by an immunohistochemical analysis in all cases, or when this is not possible, in cases with two or more lymphoid aggregates or an increase of reticulin within them.

Histomorphometric analysis of the lung of Swiss mice treated with a fibrinolytic protease.

Fibrinolytic enzymes are considered promising alternative in the treatment of cardiovascular diseases by preventing fibrin clots. A protease from Mucor subtilissimus UCP 1262 was obtained by solid state fermentation and purified by ion exchange chromatography. The purified extract was administered at an acute dose of 2000 mg/mL to evaluate its toxic effects to the lungs of mice. After 14 days of treatment, a histomorphometric study was performed by the type 1 and 2 pneumocyte count and the evaluation of the lung area. As result, the experimental group showed a significant decrease of type 2 pneumocyte and although a decrease in the alveolar area was observed in relation to the control group, no significant pulmonary toxicity, emphysema, and fibrosis characteristics were detected. The in vitro tests suggest possible clinical applications for the enzyme.

Enfermagem de Saúde Comunitária, de Saúde Pública e de Saúde Familiar / Community Health, Public Health and Family Health Nursing

O presente relatório de estágio é realizado em duas áreas: Enfermagem de Saúde Comunitária e de Saúde Pública e Enfermagem de Saúde Familiar. Este estágio decorre do Estágio I, onde foi elaborado o Diagnóstico de Situação de Saúde da Cova da Beira, procurando dar resposta aos objetivos da Unidade Curricular do Estágio com Relatório Final. No relatório de estágio preconiza-se a fundamentação, a análise crítico-reflexiva e a visibilidade das intervenções especializadas nas áreas de Enfermagem Comunitária e de Saúde Pública e Enfermagem de Saúde Familiar. Pretende-se que seja revelador de aprendizagens numa perspetiva de enfermagem avançada, utilizando uma metodologia de pesquisa-ação, e refletindo no agir em contexto de prática clínica desenvolvendo competências no âmbito da prática baseada na evidência. Na área de Enfermagem de Saúde Comunitária e de Saúde Pública, foi elaborado o programa de Intervenção Comunitária "Sem Resistência", que decorreu do Diagnóstico de Situação de Saúde da Cova da Beira. Foi realizada uma ação de formação para apresentação do Programa "Sem Resistência", dirigida aos profissionais de saúde do Agrupamento de Centros de Saúde da Cova da Beira, os quais se sentiram, na sua maioria, muito satisfeitos com a organização da ação, inovação e pertinência da temática, e com os métodos utilizados. Foi também realizada uma sessão designada "Resiste à gripe e às constipações", na associação Quero Ser Mais E7G, para crianças e jovens, os quais obtiveram conhecimento sobre a prevenção das gripes e constipações. Com base neste programa, foi desenvolvido o projeto individual de IC "Vacinação: as gotas da proteção", tendo sido realizadas sessões sobre a importância da vacinação, dirigidas aos pais, durante as consultas de saúde infantil até aos 18 meses de idade. Tendo em conta os resultados obtidos, verificou-se um aumento da literacia dos pais sobre a importância da vacinação na saúde infantil. Na área de Enfermagem Saúde Familiar, foi aplicado o Modelo Dinâmico de Avaliação e Intervenção Familiar, a uma família nuclear com diabetes Mellitus tipo 2, com filhos adultos, classe média baixa, com habitação classificada como grau 2, muito equilibrada, muito ligada, muito flexível e altamente funcional. Apresenta baixa probabilidade de incidência de doenças no seio familiar. Verificou-se falta de conhecimento sobre as vacinas do animal doméstico, que não estavam atualizadas. Foram realizadas intervenções de enfermagem tendo a família a demonstrado conhecimento, após a realização das mesmas. Com a realização do estágio foram adquiridas competências comuns e específicas do Enfermeiro Especialista em Enfermagem Comunitária, na área de Enfermagem de Saúde Comunitária e de Saúde Pública e na área de Enfermagem de Saúde Familiar.

This internship report is carried out in two areas: Community Health Nursing and Public Health and Family Health Nursing. This internship stems from Internship I, where the Health Situation Diagnosis of Cova da Beira was prepared, seeking to respond to the objectives of the Internship Curricular Unit with a Final Report. The internship report advocates the foundation, critical-reflective analysis and visibility of specialized interventions in the areas of Community Nursing and Public Health and Family Health Nursing. It is intended to reveal learning from an advanced nursing perspective, using an action-research methodology, and reflecting on acting in the context of clinical practice, developing skills in the context of evidence-based practice. In the area of Community Health and Public Health Nursing, the Community Intervention program "Without Resistance" was developed, which resulted from the Cova da Beira Health Situation Diagnosis. A training action was held to present the "Without Resistance" Program, aimed at health professionals from the Cova da Beira Health Centers Group, who felt, for the most part, very satisfied with the organization of the action, innovation and relevance of the theme, and with the methods used. A session called "Resist the flu and colds" was also held at the Quero Ser Mais E7G association, for children and young people, who gained knowledge about the prevention of flu and colds. Based on this program, the individual CI project "Vaccination: the drops of protection" was developed, with sessions on the importance of vaccination, aimed at parents, during child health consultations up to 18 months of age. Taking into account the results obtained, there was an increase in parents' literacy on the importance of vaccination in children's health. In the area of Family Health Nursing, the Dynamic Model of Family Assessment and Intervention was applied to a nuclear family with type 2 diabetes mellitus, with adult children, lower middle class, housing classified as grade 2, very balanced, very connected, very flexible and highly functional. It has a low probability of disease incidence within the family. There was a lack of knowledge about pet vaccines were not up to date. Nursing interventions were carried out, with the family demonstrating knowledge after they were carried out. With the completion of the internship, common and specific competences of the Specialist Nurse in Community Nursing were acquired, in the area of Community Health and Public Health Nursing and in the area of Family Health Nursing

Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome.

BACKGROUND: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. METHODS: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. RESULTS: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. CONCLUSIONS: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

Genetic variability in COVID-19-related genes in the Brazilian population.

SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane serine protease (TMPRSS2) to infect human lung cells. Previous studies have suggested that different host ACE2 and TMPRSS2 genetic backgrounds might contribute to differences in the rate of SARS-CoV-2 infection or COVID-19 severity. Recent studies have also shown that variants in 15 genes related to type I interferon immunity to influenza virus might predispose patients toward life-threatening COVID-19 pneumonia. Other genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, IL6, CTSL, ABO, and FURIN) and HLA alleles have also been implicated in the response to infection with SARS-CoV-2. Currently, Brazil has recorded the third-highest number of COVID-19 cases worldwide. We aimed to investigate the genetic variation present in COVID-19-related genes in the Brazilian population. We analyzed 27 candidate genes and HLA alleles in 954 admixed Brazilian exomes. We used the information available in two public databases (http://www.bipmed.org and http://abraom.ib.usp.br/) and additional exomes from individuals born in southeast Brazil, the region of the country with the highest number of COVID-19 patients. Variant allele frequencies were compared with the 1000 Genomes Project phase 3 (1KGP) and gnomAD databases. We detected 395 nonsynonymous variants; of these, 325 were also found in the 1KGP and/or gnomAD. Six of these variants were previously reported to influence the rate of infection or clinical prognosis of COVID-19. The remaining 70 variants were identified exclusively in the Brazilian sample, with a mean allele frequency of 0.0025. In silico analysis revealed that seven of these variants are predicted to affect protein function. Furthermore, we identified HLA alleles previously associated with the COVID-19 response at loci DQB1 and DRB1. Our results showed genetic variability common to other populations and rare and ultrarare variants exclusively found in the Brazilian population. These findings might lead to differences in the rate of infection or response to infection by SARS-CoV-2 and should be further investigated in patients with this disease.

Diversity and regional distribution of harmful algal events along the Atlantic margin of Europe.

The IOC-ICES-PICES Harmful Algal Event Database (HAEDAT) was used to describe the diversity and spatiotemporal distribution of harmful algal events along the Atlantic margin of Europe from 1987 - 2018. The majority of events recorded are caused by Diarrhetic Shellfish Toxins (DSTs). These events are recorded annually over a wide geographic area from southern Spain to northern Scotland and Iceland, and are responsible for annual closures of many shellfish harvesting areas. The dominant causative dinoflagellates, members of the morphospecies 'Dinophysis acuminata complex' and D. acuta, are common in the waters of the majority of countries affected. There are regional differences in the causative species associated with PST events; the coasts of Spain and Portugal with the dinoflagellates Alexandrium minutum and Gymnodinium catenatum, north west France/south west England/south Ireland with A. minutum, and Scotland/Faroe Islands/Iceland with A. catenella. This can influence the duration and spatial scale of PST events as well as the toxicity of shellfish. The diatom Pseudo-nitzschia australis is the most widespread Domoic Acid (DA) producer, with records coming from Spain, Portugal, France, Ireland and the UK. Amnesic Shellfish Toxins (ASTs) have caused prolonged closures for the scallop fishing industry due to the slow depuration rate of DA. Amendments to EU shellfish hygiene regulations introduced between 2002 and 2005 facilitated end-product testing and sale of adductor muscle. This reduced the impact of ASTs on the scallop fishing industry and thus the number of recorded HAEDAT events. Azaspiracids (AZAs) are the most recent toxin group responsible for events to be characterised in the ICES area. Events associated with AZAs have a discrete distribution with the majority recorded along the west coast of Ireland. Ciguatera Poisoning (CP) has been an emerging issue in the Canary Islands and Madeira since 2004. The majority of aquaculture and wild fish mortality events are associated with blooms of the dinoflagellate Karenia mikimotoi and raphidophyte Heterosigma akashiwo. Such fish killing events occur infrequently yet can cause significant mortalities. Interannual variability was observed in the annual number of HAEDAT areas with events associated with individual shellfish toxin groups. HABs represent a continued risk for the aquaculture industry along the Atlantic margin of Europe and should be accounted for when considering expansion of the industry or operational shifts to offshore areas.

Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders.

We recently reported a deviation of local ancestry on the chromosome (ch) 8p23.1, which led to positive selection signals in a Brazilian population sample. The deviation suggested that the genetic variability of candidate genes located on ch 8p23.1 may have been evolutionarily advantageous in the early stages of the admixture process. In the present work, we aim to extend the previous work by studying additional Brazilian admixed individuals and examining DNA sequencing data from the ch 8p23.1 candidate region. Thus, we inferred the local ancestry of 125 exomes from individuals born in five towns within the Southeast region of Brazil (São Paulo, Campinas, Barretos, and Ribeirão Preto located in the state of São Paulo and Belo Horizonte, the capital of the state of Minas Gerais), and compared to data from two public Brazilian reference genomic databases, BIPMed and ABraOM, and with information from the 1000 Genomes Project phase 3 and gnomAD databases. Our results revealed that ancestry is similar among individuals born in the five Brazilian towns assessed; however, an increased proportion of sub-Saharan African ancestry was observed in individuals from Belo Horizonte. In addition, individuals from the five towns considered, as well as those from the ABRAOM dataset, had the same overrepresentation of Native-American ancestry on the ch 8p23.1 locus that was previously reported for the BIPMed reference sample. Sequencing analysis of ch 8p23.1 revealed the presence of 442 non-synonymous variants, including frameshift, inframe deletion, start loss, stop gain, stop loss, and splicing site variants, which occurred in 24 genes. Among these genes, 13 were associated with obesity, type II diabetes, lipid levels, and waist circumference (PRAG1, MFHAS1, PPP1R3B, TNKS, MSRA, PRSS55, RP1L1, PINX1, MTMR9, FAM167A, BLK, GATA4, and CTSB). These results strengthen the hypothesis that a set of variants located on ch 8p23.1 that result from positive selection during early admixture events may influence obesity-related disease predisposition in admixed individuals of the Brazilian population. Furthermore, we present evidence that the exploration of local ancestry deviation in admixed individuals may provide information with the potential to be translated into health care improvement.

The Aß(1-38) peptide is a negative regulator of the Aß(1-42) peptide implicated in Alzheimer disease progression.

The pool of ß-Amyloid (Aß) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for Aß peptides. We examined how a naturally occurring variant, e.g. Aß(1-38), interacts with the AD-related variant, Aß(1-42), and the predominant physiological variant, Aß(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that Aß(1-38) interacts differently with Aß(1-40) and Aß(1-42) and, in general, Aß(1-38) interferes with the conversion of Aß(1-42) to a ß-sheet-rich aggregate. Functionally, Aß(1-38) reverses the negative impact of Aß(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an Aß(1-42) phenotype in Caenorhabditis elegans. Aß(1-38) also reverses any loss of MTT conversion induced by Aß(1-40) and Aß(1-42) in HT-22 hippocampal neurons and APOE ε4-positive human fibroblasts, although the combination of Aß(1-38) and Aß(1-42) inhibits MTT conversion in APOE ε4-negative fibroblasts. A greater ratio of soluble Aß(1-42)/Aß(1-38) [and Aß(1-42)/Aß(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that Aß(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant Aß(1-42).

Water contamination with atrazine: is nitric oxide able to improve Pistia stratiotes phytoremediation capacity?

Atrazine is an herbicide commonly used in several countries. Due to its long half-life, associated with its use in large scales, atrazine residues remain as environmental pollutants in water bodies. Phytoremediation is often pointed out as an interesting approach to remove atrazine from the aquatic environment, but its practical application is limited by the high toxicity of this herbicide. Here, we characterize the damages triggered by atrazine in Pistia stratiotes, evaluating the role of nitric oxide (NO), a cell-signaling molecule, in increasing the tolerance to the pollutant and the phytoremediation potential of this species. Pistia stratiotes plants were exposed to four treatments: Control; Sodium nitroprusside (SNP) (0.05 mg L-1); Atrazine (ATZ) (150 µg L-1) and ATZ + SNP. The plants remained under those conditions for 24 h for biochemical and physiological analysis and 3 days for the evaluation of relative growth rate. The presence of atrazine in plant cells triggered a series of biochemical and physiological damages, such as the increase in the generation of reactive oxygen species, damages to cell membranes, photosynthesis impairment, and negative carbon balance. Despite this, the plants maintained greater growth rates than other aquatic macrophytes exposed to atrazine and showed high bioconcentration and translocation factors. The addition of SNP, a NO donor, decreased the herbicide toxicity, with an increase of over 60% in the IC50 value (Inhibitor Concentration). Indeed, the NO signaling action was able to increase the tolerance of plants to atrazine, which resulted in increments in pollutant uptake and translocation, with the maintenance of overall cell (e.g. membranes) and organs (root system) structure, and the functioning of central physiological processes (e.g. photosynthesis). These factors allowed for more quickly and efficient removal of the pollutant from the environment, reducing costs, and increasing the viability of the phytoremediation process.

Physicochemical Characteristics and Superficial Damage Modulate Persimmon Infestation by Drosophila suzukii (Diptera: Drosophilidae) and Zaprionus indianus.

Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) and Zaprionus indianus Gupta (Diptera: Drosophilidae) were recently observed co-infesting persimmons in Brazil. We evaluate the infestation susceptibility of persimmons at different ripening stages (unripe, UN; early ripe, ER; orange ripe, OR, and overripe, OV) by D. suzukii and Z. indianus in the field and laboratory conditions. Additionally, we determined the influence of physicochemical characteristics (e.g., resistance to penetration force, fruit skin color, acidity (pH), TSS concentration, total titratable acidity [TTA]) and the type of damage that facilitates infestation by D. suzukii or Z. indianus. In the field, the natural infestation capacity and biological development of D. suzukii and Z. indianus were verified in whole fruits at the ripening stages ER, OR, and OV. The natural infestation was directly related to the physicochemical characteristics of the fruits (resistance to penetration force, pH, and total soluble solids). In the no-choice bioassay, the oviposition rate of D. suzukii did not differ between the ripening stages of the fruit. However, in the choice bioassay, there was a higher preference for oviposition in OV fruits. Regarding Z. indianus, the highest preference for oviposition was observed in OR and OV fruits in both bioassays. The presence of mechanical damage did not increase the susceptibility of the fruits to D. suzukii. However, it favored the oviposition of Z. indianus in OR and OV fruits. The damage caused by D. suzukii or mechanical damage favored the infestation by Z. indianus. This is the first report of the capacity of D. suzukii to infest whole persimmons in Brazil.

Larvicidal Activity of Essential Oils Against Aedes aegypti (Diptera: Culicidae).

The Aedes aegypti is responsible for the transmission of arboviruses, which compromise public health. In the search for synthetic product alternatives, essential oils (OEs) have been highlighted by many researchers as natural insecticides. This systematic review (SR) was performed according to PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and its objective was to evaluate studies addressing OEs with larvicidal properties against Ae. aegypti, through electronic database searches (Pubmed, Science Direct and Scielo), covering an overview of the plant sources OEs, which plant parts were used, the extraction methods, analytical techniques, major and/or secondary constituents with greater percentages, as well as the LC50s responsible for larval mortality. Following study analysis, plants distributed across 32 families, 90 genera and 175 species were identified. The Lamiaceae, Myrtaceae, Piperaceae, Asteraceae, Rutaceae, Euphorbiaceae and Lauraceae families obtained the highest number of species with toxic properties against larvae from this vector. Practically all plant parts were found to be used for OE extraction. Hydrodistillation and steam distillation were the main extraction methods identified, with GC-MS/GC-FID representing the main analytical techniques used to reveal their chemical composition, especially of terpene compounds. In this context, OEs are promising alternatives for the investigation of natural, ecologically correct and biodegradable insecticides with the potential to be used in Ae. aegypti control programs.

Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis.

BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study. CONCLUSIONS: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

Clinical Course and Management of Dengue in Children Admitted to Hospital: A 5 Years Prospective Cohort Study in Jakarta, Indonesia.

BACKGROUND: Dengue incidence is rising globally which was estimated 100 million per year, whereas in Indonesia was estimated 7.5 million per year. Dengue clinical course varies from mild dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Patients, clinicians and care facilities would benefit if reliable predictors can determine at admission which cases with clinically suspected dengue will progress to DHF or DSS. METHODS: From 2009 through 2013, a cohort of 494 children admitted with clinically suspected dengue at a tertiary care hospital in Jakarta, Indonesia, was followed until discharge. We evaluated the clinical course and disease outcome of admitted patients and estimated the burden of dengue cases hospitalized over time. RESULTS: Of all 494 children, 185 (37%) were classified at admission as DF, 158 (32%) as DHF and 151 (31%) as DSS. Of DF patients, 52 (28%) progressed to DHF or DSS, 10 (5%) had other viral diseases. Of DHF patients, 9(6%) progressed to DSS. Of 33 routinely collected parameters at admission, duration of fever ≤4 days was the only significant predictor of disease progression (P = 0.01). Five cases (3%) admitted with DSS died. Between 2009 and 2013, annual dengue admissions declined, while distribution of disease severity remained stable. CONCLUSIONS: Almost a third of children admitted to tertiary care with clinically suspected DF progress to DHF or DSS. Among routinely collected parameters at admission, only fever duration was significantly associated with clinical progression, emphasizing unpredictability of dengue disease course from parameters currently routinely collected.