Mortality by avoidable causes in Brazil from 1990 to 2019: data from the Global Burden of Disease Study.

OBJECTIVES: The aim of this study was to analyse the trends of avoidable mortality in Brazil from 1990 to 2019 and its correlation with sociodemographic indexes (SDIs). STUDY DESIGN: Epidemiological mortality trends. METHODS: This study analysed data from the Global Burden of Disease database. The list of causes of avoidable death, as proposed by Nolte and McKee, was applied and included 32 causes. The current study used age-standardised mortality rates and the rates of change, in addition to a correlation analysis between avoidable death and the SDI. RESULTS: Mortality rates decreased from 343.90/100,000 inhabitants in 1990 to 155.80/100,000 inhabitants in 2019. Infectious diseases showed the largest decline in mortality rates, but notable decreases were also found for diarrhoeal diseases (-94.9%), maternal conditions (-66.5%) and neonatal conditions (-60.5%). Mortality rates for non-communicable diseases (NCDs) also decreased (-48%) but maintained a similar absolute number of deaths in 2019 compared with 1990. Decreased mortality rates were also found for ischaemic heart disease (-49.1%), stroke (-61.4%) and deaths due to adverse effects caused by medical treatments (-26.2%). Avoidable mortality rates declined in all of the 27 Brazilian states, and a high correlation was found between deaths and SDI (R = -0.74; P < 0.000001). CONCLUSIONS: A reduction in avoidable deaths was found throughout Brazil over the study period, although major regional inequalities were revealed. Richer states presented the best overall reduction in mortality rates. The biggest decreases in mortality were seen in maternal and paediatric infectious diseases in the poorest states due to the expansion of the Primary Health System and improvements in sanitation. Today, NCDs predominate and efforts should be made to formulate public policies for the prevention and control of NCDs.

Undernutrition, and overweight and obesity: the two faces of malnutrition in Brazil, analysis of the Global Burden of Disease, 1990 to 2019.

OBJECTIVES: The objective of this study was to analyse the global burden of disease attributable to undernutrition and high body mass index (BMI) in Brazil and its 27 states, as well as its association with the socio-demographic index (SDI) from 1990 to 2019. STUDY DESIGN: This is an epidemiological time-series study. METHODS: This study analysed the undernutrition and high BMI estimated by the Global Burden of Disease study conducted from 1990 to 2019 for Brazil and its states, using the following metrics: absolute number of deaths, standardised mortality rate, and disability-adjusted life years (DALYs). This study also analysed the correlation between the percentage variation of mortality rates and SDI. RESULTS: A decrease in the number of deaths (-75 %), mortality rate (-75.1 %), and DALYS (-72 %) attributable to undernutrition was found in Brazil and in all regions. As regarding the high BMI, an increase in the number of deaths was found (139.6 %); however, the mortality rate (-9.7) and DALYs (-6.4 %) declined in all regions, except in the North and Northeast regions, which showed an increase. A strong correlation was identified between undernutrition and high BMI with SDI. CONCLUSION: Our study observed a double burden of malnutrition in Brazil, with a reduction in the burden of diseases due to malnutrition in Brazil and variation in the burden due to high BMI according to the socioeconomic status of the region. Public policies are necessary in order to guarantee the human right to a healthy and sustainable diet, together with food and nutrition security and a diminishing of social inequality.

Sustainable Development Goals' health-related indicators for Brazil and Ecuador: an analysis for the period of 1990-2019.

OBJECTIVE: This article aims to analyse the evolution of 40 Sustainable Development Goals' (SDGs) health-related indicators in Brazil and Ecuador from 1990 to 2019. STUDY DESIGN: Epidemiological study of long-term trends in 40 SDGs' health-related indicators for Brazil and Ecuador from 1990 to 2019, using estimates from the Global Burden of Disease Study. METHODS: Forty SDGs' health-related indicators and an index from 1990 to 2017 for Brazil and Ecuador, and their projections up to 2030 were extracted from the Institute for Health Metrics and Evaluation's Global Burden of Disease website and analysed. The percent annual change (PC) between 1990 and 2019 was calculated for both countries. RESULTS: Both countries have made progress on child stunting (Brazil: PC = -38%; Ecuador: PC = -43%) and child wasting prevalences (Brazil: PC = -42%; Ecuador: PC = -41%), percent of vaccine coverage (Brazil: PC = +215%; Ecuador: PC = +175%), under-5 (Brazil: PC = -75%; Ecuador: PC = -60%) and neonatal mortality rates (Brazil: PC = -69%; Ecuador: PC = -51%), health worker density per 1000 population (Brazil: PC = +153%; Ecuador: PC = +175%), reduction of neglected diseases prevalences (Brazil: PC = -40%; Ecuador: PC = -58%), tuberculosis (Brazil: PC = -27%; Ecuador: PC = -55%) and malaria incidences (Brazil: PC = -97%; Ecuador: PC = -100%), water, sanitation and hygiene mortality rates (Brazil and Ecuador: PC = -89%). However, both countries did not show sufficient improvement in maternal mortality ratio to meet SDGs targets (Brazil: PC = -37%; Ecuador: PC = -40%). Worsening of indicators were found for violence, such as non-intimate partner violence for both countries (Brazil: PC = +26%; Ecuador: PC = +18%) and suicide mortality rate for Ecuador (PC = +66%), child overweight indicator for Brazil (PC = -67%), disaster mortality rates (Brazil: PC = +100%; Ecuador: PC = +325%) and alcohol consumption (Brazil: PC = +46%; Ecuador: PC = +35%). CONCLUSIONS: Significant improvements are necessary in both countries requiring the strengthening of health and other policies, particularly concerning the prevention and management of violence and alcohol consumption, and preparedness for dealing with environmental disasters.

Evaluating H295R steroidogenesis assay data for robust interpretation.

The in vitro H295R steroidogenesis assay (OECD TG 456) is used to determine a chemical's potential to interfere with steroid hormone synthesis/metabolism. As positive outcomes in this assay can trigger significant higher tiered testing, we compiled a stakeholder database of reference and test item H295R data to characterize assay outcomes. Information concerning whether a Level 5 reproductive toxicity study was triggered due to a positive outcome in the H295R assay was also included. Quality control acceptance criteria were not always achieved, suggesting this assay is challenging to conduct within the guideline specifications. Analysis of test item data demonstrated that pairwise significance testing to controls allowed for overly sensitive statistically significant positive outcomes, which likely contribute to the assay's high positive hit rate. Complementary interpretation criteria (e.g., 1.5-fold change threshold) markedly reduced the rate of equivocal and positive outcomes thus improving identification of robust positive effects in the assay. Finally, a case study (positive H295R outcome and no endocrine adversity in vivo) is presented, which suggests that stricter data interpretation criteria could refine necessary in vivo follow-up testing. Overall, the described additional criteria could improve H295R data interpretation and help inform on how to best leverage this assay for regulatory purposes.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

[Use of neurodevelopmental disorder screening tool in primary care : A multicenter observational study]. / Utilisation en soins primaires d'un outil de repérage des troubles du neurodéveloppement : étude multicentrique observationnelle.

INTRODUCTION: Neurodevelopmental disorders (NDD) affect 5 to 15% of the population. Improved management largely depends on early detection in primary care. A screening tool was developed by an expert consensus and its use has been recommended since 2019. This tool has never been evaluated to date. The aim of this study was to investigate the prevalence and factors associated with the identification of neurodevelopmental disorders in primary care in children aged 6 months to 5 years. METHOD: This work is a multicentric observational study carried out in general practice in two regions of France: Île-de-France and Auvergne-Rhône-Alpes. A multivariate analysis was performed to identify the factors associated with the presence of abnormal signs on the grid. RESULTS: Five hundred and sixty-four (564) children aged 6 months to 4 years were included. The prevalence of children identified on the grid was 3.9%. The factors associated with the neurodevelopmental disorders identified in multivariate analysis were: low socio-professional status of the mother, male gender and parental concern about the child's neurodevelopment. Factors associated with identifying a developmental trajectory gap were male gender (OR = 2.10 (1.22-3.62)) and low socio-professional status of the mother (OR = 2.23 [1.05-4.70]). CONCLUSION: This original work allowed us to carry out first-line testing of a tool for the identification of NDD in primary care and to evaluate the prevalence of identification of these disorders. A complementary cohort study will be necessary to evaluate the sensitivity and specificity of this identification tool.

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Comparison of cell invasion, macrophage survival and inflammatory cytokines profiles between Salmonella enterica serovars Enteritidis and Dublin from Brazil.

AIMS: This study compared the capacity of strains of Salmonella enterica serovars Enteritidis and Dublin isolated in Brazil to invade epithelial cells, to be internalized by and survive within macrophages, and to stimulate cytokine release in vitro. METHODS AND RESULTS: Both serovars infected 75 and 73% Caco-2 (human) and MDBK (bovine) epithelial cells respectively. Salmonella Dublin and S. Enteritidis (i) were internalized at the respective rates of 79·6 and 65·0% (P ≤ 0·05) by U937 (human) macrophages, and 70·4 and 66·9% by HD11 (chicken) macrophages; and (ii) multiplied at the respective rates of 3·2- and 2·7-fold within U937 cells, and 1·9- and 1·1-fold (P ≤ 0·05) within HD11 cells respectively. Seventy per cent of 10 S. Dublin strains stimulated IL-8 production, while 70% of S. Enteritidis strains enhanced production of IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF in Caco-2 cells. CONCLUSIONS: Compared with S. Enteritidis, S. Dublin had stronger ability to survive within macrophages and induced weak cytokine production, which may explain the higher incidence of invasive diseases caused by S. Dublin in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study compared S. enterica serovars Enteritidis and Dublin to provide comparative data about the profile of the two serovars in cells from humans, the common host and their respective natural animal hosts and vice versa in order to check the differences between these two phylogenetically closely related serovars that share antigenic properties but present different phenotypic behaviours.

Management and biosecurity practices by small to medium egg producers in Scotland.

1. Information about procedures and biosecurity practices used by small and medium egg producers (SMEPs) is scarce. Anecdotal evidence suggests that biosecurity in such enterprises may be poor, as personnel and equipment move freely between sites and this may be compounded by personnel working on commercial units who keep their own poultry.2. To fill this knowledge gap, a questionnaire was designed and implemented targeting SMEPs in Scotland. Small enterprises were defined as egg producers that have ≥50 laying hens but <350 laying hens; while medium enterprises were defined as egg producers that have ≥350 laying hens but ≤32 000 laying hens. The questionnaire consisted of a total of 56 questions divided into multiple sections, covering the characteristics of the primary keeper, location of the enterprise and size of the flocks, husbandry, marketing of products and health/biosecurity.3. The questionnaire was posted to 375 holdings at the beginning of March 2017 and the survey remained open until the end of May 2017. In total 90 questionnaires were received by the cut-off date of which 76 questionnaires were from SMEPs. Forty were small enterprises and 36 were medium enterprises. For three questionnaires, it was not possible to identify the enterprise type.4. Differences were observed between SMEPs in terms of reported biosecurity and management practices, with medium enterprises reporting the adoption of more biosecurity measures than small enterprises. Furthermore, SMEPs behave differently from backyard poultry keepers and large commercial companies in terms of disease risk.5. In conclusion, it is important to ensure that SMEPs are considered in contingency plans and disease control programmes and that engagement with them is promoted so that the uptake of relevant information, such as awareness of disease control programmes, is optimised.

Evaluation of the sensitivity of the Express View function in the Mirocam® capsule endoscopy software.

Background: A new computer algorithm called Express-View has recently been introduced by Mirocam, but data concerning its application and efficacy are scarce.Objective: To evaluate the lesion detection rate, per-patient sensitivity and the diagnostic accuracy using Express-View.Methods: All patients who performed CE between January 2018 and June 2019, whose indication was obscure gastrointestinal bleeding (OGIB) and with findings on CE, were included. Lesions identified in conventional reading were selected and considered as reference.Results: Eighty-nine patients were included, 50.6% male, with a mean age of 68.4 years-old (±12.3). The Express-View mode detected 85.5% of lesions previously detected by conventional reading (524 out of 613). There were 89 missed lesions, mainly erosions or ulcers (44.9%) and angioectasias (38.2%). The lesion detection rate was found to be lower in the jejunum and ileum compared to extra-small bowel locations and duodenum (p = .04). Although Express-View had a per-patient sensitivity for all lesions of 56.2% and a per-patient sensitivity for all clinically significant lesions of 83.1%, it achieved a diagnostic accuracy of 91%.Conclusions: The per-patient sensitivity for all lesions was shown to be below expectations, although the lesion detection rate, the per-patient sensitivity for all clinically significant lesions, and the diagnostic accuracy were shown to be higher.

A description and qualitative comparison of the elements of heterogeneous bovine viral diarrhea control programs that influence confidence of freedom.

For endemic infections in cattle that are not regulated at the European Union level, such as bovine viral diarrhea virus (BVDV), European Member States have implemented control or eradication programs (CEP) tailored to their specific situations. Different methods are used to assign infection-free status in CEP; therefore, the confidence of freedom associated with the "free" status generated by different CEP are difficult to compare, creating problems for the safe trade of cattle between territories. Safe trade would be facilitated with an output-based framework that enables a transparent and standardized comparison of confidence of freedom for CEP across herds, regions, or countries. The current paper represents the first step toward development of such a framework by seeking to describe and qualitatively compare elements of CEP that contribute to confidence of freedom. For this work, BVDV was used as a case study. We qualitatively compared heterogeneous BVDV CEP in 6 European countries: Germany, France, Ireland, the Netherlands, Sweden, and Scotland. Information about BVDV CEP that were in place in 2017 and factors influencing the risk of introduction and transmission of BVDV (the context) were collected using an existing tool, with modifications to collect information about aspects of control and context. For the 6 participating countries, we ranked all individual elements of the CEP and their contexts that could influence the probability that cattle from a herd categorized as BVDV-free are truly free from infection. Many differences in the context and design of BVDV CEP were found. As examples, CEP were either mandatory or voluntary, resulting in variation in risks from neighboring herds, and risk factors such as cattle density and the number of imported cattle varied greatly between territories. Differences were also found in both testing protocols and definitions of freedom from disease. The observed heterogeneity in both the context and CEP design will create difficulties when comparing different CEP in terms of confidence of freedom from infection. These results highlight the need for a standardized practical methodology to objectively and quantitatively determine confidence of freedom resulting from different CEP around the world.

Immunoexpression of bone resorption biomarkers in apical periodontitis in diabetics and normoglycaemics.

AIM: To compare the immunoexpression of RANK, MMP-9 and PTHrP in apical periodontitis lesions of diabetic and normoglycaemic individuals. METHODOLOGY: Primary chronic apical periodontitis lesions associated with teeth indicated for extraction in 13 type 2 diabetic individuals and 13 normoglycaemic individuals who were screened for the glycaemic index and glycated haemoglobin (HbA1c) were analysed. Individuals with other systemic diseases and users of anti-inflammatories and/or antibiotics in the previous 3 months were excluded. Silanized slides with paraffin sections were used for immunohistochemical reactions and stained with haematoxylin and eosin for histopathological classification. The images were analysed with an optical microscope, and the slides were subdivided into five large fields assigning scores (0-2), according to the number of positive markings for each antibody. Fisher's exact test evaluated the parameters: gender, type of lesion, location and position in the arch. Nonparametric Mann-Whitney test was used for age, HbA1c values and comparison of marker expression. The chi-squared test was used to associate the expression of the markers. And the Spearman's coefficient correlated the markers with the size of the periapical lesion. RESULTS: The samples consisted of 69% periapical granulomas and 31% periapical cysts in each group. RANK expression was considered weak/moderate and strong in, respectively, 62% and 38% of the cases in both groups. MMP-9 expression was weak/moderate and strong in, respectively, 38% and 62% of the cases from the diabetic group, in comparison with 38% and 38% in the normoglycaemics (24% cases from this group were negative). In contrast, PTHrP expression was negative, weak/moderate and strong in, respectively, 46%, 46% and 8% of the cases from the diabetic group, in comparison with 38% negative and 62% weak/moderate in normoglycaemics. Quantitative analysis revealed that there were no significant differences in the immunoexpression of RANK (P = 0.26), MMP-9 (P = 0.17) and PTHrP (P = 0.43) between the groups. There was no significant correlation between the expression of bone resorption markers and the macroscopic size of the periapical lesions (P > 0.05). CONCLUSIONS: The bone resorption mediators analysed had similar immunoexpression in the periapical lesions of diabetic and normoglycaemic individuals.

First report of the root-knot nematode, Meloidogyne morocciensis infecting peach in Southern Brazil.

The peach tree (Prunus persica) is the third most cultivated temperate fruit species in Brazil. In August 2017, peach seedling plants showing symptoms of stunting and multiple galls in the roots were detected in the municipality of Pelotas, state of Rio Grande do Sul, Brazil. Samples of peach roots were collected and they were subsequently processed to obtain eggs and second-stage juveniles (J2), to determine the number of nematodes per gram of roots and to proceed with morphological studies. Additionally, individual females were extracted from the peach roots and submitted to Meloidogyne species identification by electrophoresis using α-esterase (Est) and malate dehydrogenase (Mdh) phenotypes and perineal pattern. The nematode population density in the samples was 283 eggs + J2s per gram of fresh roots. The polymorphism analysis revealed the A3N1 phenotype, typical to Meloidogyne morocciensis. Perineal patterns of females showed oval squared shapes, with moderately high to high dorsal arches, streaks widely separated, generally continuous, sometimes broken; the phasmids were separate by 29.3 µm (25.43-31.94 µm), similar to M. arenaria and M. incognita, as observed by Hammah and Hirschmann (1990). The second-stage juveniles had the following morphometric characters: L = 389.3 ± 3.8 (377.5-425.1) µm, stylet = 13.9 ± 0.2 (12.7-14.9) µm, DGO = 3.6 ± 0.1 (3.3-4.2) µm, tail length 47.5 ± 0.6 (45.3-48.9) µm, hyaline tail terminus = 14.1 ± 0.3 (12.5-17.0) µm, a = 25.6 ± 0.4 (23.8-28.8) µm and c = 8.6 ± 0.1 (8.0-9.3). The known SCAR marker obtained for M. arenaria is the same as that amplified for M. morocciensis. Under greenhouse conditions, peach plants seedlings inoculated with 1,000 eggs (Pi) with M. morocciensis were evaluated 28 days after inoculation compared to non-inoculated plants. The inoculated peach plants showed a mean of 338 galls per root system, and a nematode reproduction factor of 10.3. Besides this plants exhibited a reduction in fresh weight of shoots and roots compared to the non-inoculated plants. These results confirm M. morocciensis pathogenicity on P. persica.The peach tree (Prunus persica) is the third most cultivated temperate fruit species in Brazil. In August 2017, peach seedling plants showing symptoms of stunting and multiple galls in the roots were detected in the municipality of Pelotas, state of Rio Grande do Sul, Brazil. Samples of peach roots were collected and they were subsequently processed to obtain eggs and second-stage juveniles (J2), to determine the number of nematodes per gram of roots and to proceed with morphological studies. Additionally, individual females were extracted from the peach roots and submitted to Meloidogyne species identification by electrophoresis using α-esterase (Est) and malate dehydrogenase (Mdh) phenotypes and perineal pattern. The nematode population density in the samples was 283 eggs + J2s per gram of fresh roots. The polymorphism analysis revealed the A3N1 phenotype, typical to Meloidogyne morocciensis. Perineal patterns of females showed oval squared shapes, with moderately high to high dorsal arches, streaks widely separated, generally continuous, sometimes broken; the phasmids were separate by 29.3 µm (25.43-31.94 µm), similar to M. arenaria and M. incognita, as observed by Hammah and Hirschmann (1990). The second-stage juveniles had the following morphometric characters: L = 389.3 ± 3.8 (377.5-425.1) µm, stylet = 13.9 ± 0.2 (12.7-14.9) µm, DGO = 3.6 ± 0.1 (3.3-4.2) µm, tail length 47.5 ± 0.6 (45.3-48.9) µm, hyaline tail terminus = 14.1 ± 0.3 (12.5-17.0) µm, a = 25.6 ± 0.4 (23.8-28.8) µm and c = 8.6 ± 0.1 (8.0-9.3). The known SCAR marker obtained for M. arenaria is the same as that amplified for M. morocciensis. Under greenhouse conditions, peach plants seedlings inoculated with 1,000 eggs (Pi) with M. morocciensis were evaluated 28 days after inoculation compared to non-inoculated plants. The inoculated peach plants showed a mean of 338 galls per root system, and a nematode reproduction factor of 10.3. Besides this plants exhibited a reduction in fresh weight of shoots and roots compared to the non-inoculated plants. These results confirm M. morocciensis pathogenicity on P. persica.

3D printing in the design of pharmaceutical dosage forms.

Three-dimensional (3D) printing technologies are manufacturing approaches with widespread use in industry (e.g. automotive, automobile, pharmaceutical industries). With regard to its use in pharmaceutical industry, 3D printing is demonstrating to be of added value attributed to the possibility of printing tailored pharmaceutical products, namely personalized medical devices, such as implants and other dosage forms. However, with the approval of the first 3D-printed drug-product in 2015, a new perspective has arisen, i.e. the use of this technology to produce solid oral dosage forms exhibiting complex drug release profiles and allowing for individual dosing. Technological hurdles and regulatory issues still have to be overcome before this technology can truly find its place in the healthcare sector, where it can certainly contribute to a personalized and patient-centered healthcare. This manuscript offers a comprehensive analysis of the most extensively used methods of 3D printing in the pharmaceutical field, with examples of solid oral dosage forms and other medical devices currently under development or already marketed.

Adenosine A2A receptor regulation of microglia morphological remodeling-gender bias in physiology and in a model of chronic anxiety.

Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, responsive to GCs and morphologically altered in stress-related disorders. These cells are regulated by adenosine A2A receptors, which are also involved in the pathophysiology of anxiety. We now compare animal behavior and microglia morphology in males and females prenatally exposed to the GC dexamethasone. We report that prenatal exposure to dexamethasone is associated with a gender-specific remodeling of microglial cell processes in the prefrontal cortex: males show a hyper-ramification and increased length whereas females exhibit a decrease in the number and in the length of microglia processes. Microglial cells re-organization responded in a gender-specific manner to the chronic treatment with a selective adenosine A2A receptor antagonist, which was able to ameliorate microglial processes alterations and anxiety behavior in males, but not in females.

Post hoc support vector machine learning for impedimetric biosensors based on weak protein-ligand interactions.

Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptors and target analytes are a challenge for detection electronics, particularly in field studies or in the analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but achieving accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show the use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrate two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on the measurement of acetone, an important biomarker related to the onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well as, or better, than the equivalent circuit analysis for characterizing weak/transient interactions between a model ligand (acetone) and a small chemosensory protein derived from the tsetse fly. In addition, the tool has a low computational requirement, facilitating use for mobile acquisition systems such as mobile phones. The protocol is deployed through Jupyter notebook (an open source computing environment available for mobile phone, tablet or computer use) and the code was written in Python. For each of the applications, we provide step-by-step instructions in English, Spanish, Mandarin and Portuguese to facilitate widespread use. All codes were based on scikit-learn, an open source software machine learning library in the Python language, and were processed in Jupyter notebook, an open-source web application for Python. The tool can easily be integrated with the mobile biosensor equipment for rapid detection, facilitating use by a broad range of impedimetric biosensor users. This post hoc analysis tool can serve as a launchpad for the convergence of nanobiosensors in planetary health monitoring applications based on mobile phone hardware.

Association between bacteria occurring in the apical canal system and expression of bone-resorbing mediators and matrix metalloproteinases in apical periodontitis.

AIM: To evaluate the association between the presence of selected bacterial species/groups in the apical root canal and expression of mediators of soft and bone tissue destruction in apical periodontitis lesions. Relationships between bacteria and some other features of apical periodontitis were also investigated. METHODOLOGY: Seventeen freshly extracted teeth with pulp necrosis and apical periodontitis were included. The apical root segment was sectioned and cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial species/groups using real-time polymerase chain reaction. Lesions were processed for histopathological and immunohistochemical analyses, which targeted matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target bacteria with expression of these mediators, presence of symptoms, lesion size and histopathological diagnosis were evaluated. Data were analysed using the chi-square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05 were considered significant. RESULTS: All pulverized apical root samples were positive for bacteria. The most prevalent taxa were Actinobacteria (53%), Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%). The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%; MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test). Actinobacteria were associated with granulomas, higher MMP-2 expression, lower OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test or Mann-Whitney test). No other significant associations were found. CONCLUSION: Actinobacteria may play an important role in the active phase of soft and bone tissue destruction in apical periodontitis.

Newcastle disease vaccination in captive-bred wild birds.

The breeding of wild birds in captivity assumes an increasingly important role in conservation due to the loss of species and their habitats. Providing the environmental and nutritional needs of species kept in captivity is the key for achieving success in such initiatives. Among the flock health practices, we highlight here wild bird vaccination, a scarcely studied subject. This study clinically and serologically evaluates the effect of applying a vaccination protocol against Newcastle disease in three groups of ornamental wild birds. The responses observed in 10 ornamental chickens were compared to those recorded in 12 ring-neck pheasants (Phasianus colchicus), 6 psittacines (2 cockatiels Nymphicus hollandicus, 2 lorikeets Trichoglossus haematodus molucanos, and 2 eastern rosellas Platycercus eximius), and 6 touracos (2 guinea Tauraco persa, 2 white-cheeked Tauraco leucotis, and 2 violet Musophaga violacea). One drop of each live Newcastle HB1 and La Sota vaccines were ocularly instilled on the 1st and 21st experimental days, respectively. On the 112th day, one shot of an inactivated oily Newcastle vaccine was intramuscularly injected. Serum samples were submitted to the Newcastle disease virus antibody Test Kit ELISA-BioChek. Except for the psittacines, other bird species showed a considerable increase in the antibody titers. However, their mean antibody titers differed significantly (P < 0.05) from that recorded in the chickens.