Is a tiered restrictions system an effective intervention for COVID-19 control? Results from Portugal, November-December 2020.

BACKGROUND: In November 2020, similar to other European countries, Portugal implemented a tiered restrictions system to control the COVID-19 pandemic. We aimed to compare the COVID-19 growth rate across tiers to assess the effect of a tiered restrictions system in Portugal, using models with different times between tiers assessment. Our hypothesis was that being in a higher tier brings a faster deceleration in the growth rate than being in a lower tier. METHODS: The national database of notified COVID-19 cases and publicly available data were used to analyse the effect of the tiered restrictions system on the COVID-19 incidence growth rate. The tiers were based on the European Centre for Disease Control risk classification: moderate, high, very and extremely high. We used a generalised mixed-effects regression model to estimate the growth rate ratio (GRR) for each tier, comparing the growth rates of higher tiers using moderate tier as reference. Three models were fitted using different times between tiers assessment, separated by 14 days. RESULTS: We included 156 034 cases. Very high tier was the most frequent combination in all the three moments assessed (21.2%), and almost 50% of the municipalities never changed tier during the study period. Immediately after the tiers implementation, a reduction was identified in the municipalities in high tier (GRR high tier: 0.90 [95%CI: 0.79; 1.02]) and very high tier (GRR very high tier: 0.68 [95%CI: 0.61; 0.77]), however with some imprecision in the 95% confidence interval for the high tier. A reduction in very high tier growth rate was identified two weeks (GRR: 0.79 [95%CI: 0.71; 0.88]) and four weeks (GRR: 0.77 [95%CI: 0.74; 0.82]) after the implementation, compared to moderate tier. In high tier, a reduction was also identified in both times, although smaller. CONCLUSIONS: We observed a reduction in the growth rate in very high tier after the tiered restriction system was implemented, but we also observed a lag between tiered restriction system implementation and the onset of consequent effects. This could suggest the importance of early implementation of stricter measures for pandemic control. Thus, studies analysing a broader period of time are needed.

Interprofessional education in undergraduate courses in health in Brazil: integrative review.

This integrative review aimed to synthesize the evidence regarding interprofessional education (IPE) in undergraduate health courses in Brazil. This article included original articles published between 2005 and 2020 addressing IPE in undergraduate health courses in Brazilian higher education institutions. Our search captured 333 articles in Medline, PubMed, Cochrane Library, Embase (Elsevier), Web Of Science (Main Collection), Scopus (Elsevier), Science Direct (Elsevier), ERIC, and LILACS via BVS. After applying the exclusion and inclusion criteria, the study corpus covered 34 original manuscripts. It was identified that a network is developed at the national level, and with international support, supports discussions and research on IPE. However, there is a concentration of partnerships between researchers from the Northeast, Southeast and South regions, with the need to expand studies on the country's experiences in the North and Midwest regions. There is also consistent publication of experiences concerning the implementation of IPE in undergraduate healthcare courses in Brazil. However, the uniprofessional characteristics and the lack of uniformity in the curricula are still significant, which represent essential obstacles to further IPE strengthening in Brazil. In the Brazilian literature, there is a dearth of longitudinal studies and mixed methods that assess changes in organizational practices. There remains a need for IPE studies with more rigorous designs to generate more impactful evidence.

Investigating the role of symptom valorisation in tuberculosis patient delay in urban areas in Portugal.

BACKGROUND: Diagnosis delay contributes to increased tuberculosis (TB) transmission and morbimortality. TB incidence has been decreasing in Portugal, but median patient delay (PD) has risen. Symptom valorisation may determine PD by influencing help-seeking behaviour. We aimed to analyse the association between symptom valorisation and PD, while characterising individuals who disregarded their symptoms. METHODS: A cross-sectional study was conducted among TB patients in Lisbon and Oporto in 2019 - 2021. Subjects who delayed seeking care because they did not value their symptoms or thought these would go away on their own were considered to have disregarded their symptoms. PD was categorised using a 21-day cut-off, and a 30-day cut-off for sensitivity analysis. We estimated the effect of symptom valorisation on PD through a directed acyclic graph. Then, a multivariable regression analysis characterised patients that disregarded their symptoms, adjusting for relevant variables. We fitted Poisson regression models to estimate crude and adjusted prevalence ratios (PR). RESULTS: The study included 75 patients. Median PD was 25 days (IQR 11.5-63.5), and 56.0% of participants had PD exceeding 21 days. Symptom disregard was reported by 38.7% of patients. Patients who did not value their symptoms had higher prevalence of PD exceeding 21 days compared to those who valued their symptoms [PR 1.59 (95% CI 1.05-2.42)]. The sensitivity analysis showed consistent point estimates but wider confidence intervals [PR 1.39 (95% CI 0.77-2.55)]. Being a smoker was a risk factor for symptom disregard [PR 2.35 (95% CI 1.14-4.82)], while living in Oporto [PR 0.35 (95% CI 0.16-0.75)] and having higher household incomes [PR 0.39 (95% CI 0.17-0.94)] were protective factors. CONCLUSIONS: These findings emphasise the importance of symptom valorisation in timely TB diagnosis. Patients who did not value their symptoms had longer PD, indicating a need for interventions to improve symptom recognition. Our findings also corroborate the importance of the socioeconomic determinants of health, highlighting tobacco as a risk factor both for TB and for PD.

A temporal analysis on patient and health service delays in pulmonary tuberculosis in Portugal: inter and intra­regional differences and in(equalities) between gender and age.

BACKGROUND: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient's first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender. METHODS: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system. RESULTS: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay. CONCLUSIONS: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation.

Hematological and histopathological evaluation of meat-type quails fed Madagascar cockroach meal.

Aiming at the sustainability of meat production, insects can replace traditional ingredients in the diet of poultry. Studies evaluating performance in birds have emerged to ensure this ability, but few address the health parameters of animals. This study was carried out to evaluate the effects of the inclusion of Madagascar cockroach meal in traditional diets on hematological and histopathological traits of meat-type quails. The inclusion of Madagascar cockroach meal in the diet was evaluated in four levels: 0%, 6%, 12%, and 18%. Observations for hematological and histopathological traits from 6 repetitions on each group were recorded for both sexes at 35 days of age. Hematological parameters were not influenced by Madagascar cockroach inclusion on diet and quail's sex. Red and white blood cells count were within the normal range for poultry. No significant findings were observed during the histopathological evaluation of the pancreas, duodenum, jejunum, and ileum. Liver fatty degeneration was visualized in all treatments in the same intensity. Quail's diets containing up to 18% insect meal during the growth period did not affect the studied health parameters, so the Madagascar cockroach meal could be considered as an alternative to a protein ingredient for poultry production.

Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use.

RATIONALE: Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies. METHODS: A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed. RESULTS: 10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10-6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found. CONCLUSIONS: The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.

ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis.

BACKGROUND: The polymorphism Arg16 in ß2 -adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long-acting ß2 -agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27. OBJECTIVE: We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA. METHODS: The study was undertaken using data from 10 independent studies (n = 5903) participating in the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma-related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta-analysed using the inverse variance weighting method assuming random-effects. RESULTS: In subjects treated with ICS and LABA (n = 832, age: 3-21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05-1.87, I2  = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05-1.94, I2  = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71-1.39, I2  = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as-required short-acting ß2 -agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686). CONCLUSION AND CLINICAL RELEVANCE: The ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype-guided treatment which might improve clinical outcomes in asthmatic patients.

Tuberculosis amongst foreign-born and nationals: different delays, different risk factors.

BACKGROUND: Delay in Tuberculosis (TB) diagnosis affects foreign-born and nationals in different ways, especially in low-incidence countries. This study characterises total delay and its components amongst foreign-born individuals in Portugal. Additionally, we identify risk factors for each type of delay and compare their effects between foreign-born and nationals. METHODS: We analysed data from the Portuguese TB surveillance system and included individuals with pulmonary TB (PTB), notified between 2008 and 2017. We described patient, healthcare, and total delays. Cox regression was used to identify factors associated with each type of delay. All analyses were stratified according to the origin country: nationals (those born in Portugal) and foreign-born. RESULTS: Compared with nationals, foreign-born persons presented statistically significant and longer median total and patient delays (Total: 67 vs. 63; Patient: 44 vs. 36 days), and lower healthcare services delays (7 vs. 9 days). Risk factors for delayed diagnosis differed between foreign-born and nationals. Being unemployed, having drug addiction, and having comorbidities were identified as risk factors for delayed diagnosis in national individuals but not in foreigners. Alcohol addiction was the only factor identified for healthcare delay for both populations: foreign-born (Hazard Ratio 1.34 [95% confidence interval 1.17;1.53]); nationals (Hazard Ratio 1.20 [95% confidence interval 1.13;1.27]). CONCLUSIONS: Foreign-born individuals with PTB take longer to seek health care. While no specific risk factors were identified, more in-depth studies are required to identify barriers and support public health intervention to address PTB diagnosis delay in foreign-born individuals.

Double jeopardy from the COVID-19 pandemic: risk of exposure and income loss in Portugal.

BACKGROUND: Increasing evidence indicates that the first wave of the COVID-19 pandemic had immediate health and social impact, disproportionately affecting certain socioeconomic groups. Assessing inequalities in risk of exposure and in adversities faced during the pandemic is critical to inform targeted actions that effectively prevent disproportionate spread and reduce social and health inequities. This study examines i) the socioeconomic and mental health characteristics of individuals working in the workplace, thus at increased risk of COVID-19 exposure, and ii) individual income losses resulting from the pandemic across socioeconomic subgroups of a working population, during the first confinement in Portugal. METHODS: This study uses data from 'COVID-19 Barometer: Social Opinion', a community-based online survey in Portugal. The sample for analysis comprised n = 129,078 workers. Logistic regressions were performed to estimate the adjusted odds ratios (AOR) of factors associated with working in the workplace during the confinement period and with having lost income due to the pandemic. RESULTS: Over a third of the participants reported working in the workplace during the first confinement. This was more likely among those with lower income [AOR = 2.93 (2.64-3.25)], lower education [AOR = 3.17 (3.04-3.30)] and working as employee [AOR = 1.09 (1.04-1.15)]. Working in the workplace was positively associated with frequent feelings of agitation, anxiety or sadness [AOR = 1.14 (1.09-1.20)] and perception of high risk of infection [AOR = 11.06 (10.53-11.61)]. About 43% of the respondents reported having lost income due to the pandemic. The economic consequences affected greatly the groups at increased risk of COVID-19 exposure, namely those with lower education [AOR = 1.36 (1.19-1.56)] and lower income [AOR = 3.13 (2.47-3.96)]. CONCLUSIONS: The social gradient in risk of exposure and in economic impact of the pandemic can result in an accumulated vulnerability for socioeconomic deprived populations. The COVID-19 pandemic seems to have a double effect in these groups, contributing to heightened disparities and poor health outcomes, including in mental health. Protecting the most vulnerable populations is key to prevent the spread of the disease and mitigate the deepening of social and health disparities. Action is needed to develop policies and more extensive measures for reducing disproportionate experiences of adversity from the COVID-19 pandemic among most vulnerable populations.

Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry.

OBJECTIVES: To evaluate the effectiveness and safety of pembrolizumab use in advanced melanoma in a real-life context; and to explore the existence of an efficacy-effectiveness gap, comparing registry data with the reference clinical trial. METHODS: This study followed the guidelines for good pharmacoepidemology practice. An ambispective cohort was constituted, initiating the observation upon drug approval (17/07/2015) and following exposed patients until death or cut-off date (15/11/2019). The primary outcome was overall survival (OS); secondary outcomes comprised progression-free survival (PFS), overall response rate (ORR) and the occurrence of adverse events (AE). For all survival analyses, the Kaplan-Meier estimator was used, considering a 95% confidence interval (CI), aside with one-year survival rates. RESULTS: A total of 125 patients constituted the cohort, originating from 16 hospitals in Portugal. Median OS was estimated to be 16.9 months (CI95% 11.3-25.5) and the probability of survival after 1 year was 57.5% (CI95% 48.4%-65.6%). Median PFS was estimated to be 4.8 months (CI95% 3.9-6.7) and the probability of remaining progression-free after 1 year was 32.8% (CI95% 24.8-41.1). ORR was 30.4% (CI95% 22.5%-39.3%). AEs were experienced by 82% of patients, and 27% experienced AE≥ grade 3. CONCLUSIONS: Our data suggest lower effectiveness in a real-life context than the efficacy reported in the clinical trial. Safety data seems, however, quite comparable to KEYNOTE-006.

Delayed diagnosis of active pulmonary tuberculosis - potential risk factors for patient and healthcare delays in Portugal.

BACKGROUND: Early diagnosis and treatment of pulmonary tuberculosis (PTB) is essential for an effective control of the tuberculosis (TB) epidemic. Delayed diagnosis and treatment of TB increases the chance of complications and mortality for the patients, and enhances TB transmission in the population. Therefore, the aim of this study was to characterize patient, healthcare and total delay in diagnosing PTB and assess the effect of clinical and sociodemographic factors on the time until first contact with healthcare or reaching a PTB diagnosis. METHODS: Retrospective cohort study that included active PTB patients notified in the National Tuberculosis Surveillance System (SVIG-TB), between 2008 and 2017. Descriptive statistics, Kaplan-Meier estimates, logrank test and Cox proportional hazards model were used to characterize patient, healthcare and total delay and estimate the effect of clinical and sociodemographic variables on these delays. Significance level was set at 0.05. RESULTS: Median patient, healthcare and total delays was 37 days (Interquartile range (IQR): 19-71), 8 days (IQR: 1-32) and 62 days (IQR: 38-102), respectively. The median patient delay showed a constant increase, from 33 days in 2008 to 44 days in 2017. The median total delay presented a similar trend, increasing from 59 days in 2008 to 70 days in 2017. Healthcare delay remained constant during the study period. More than half of the PTB cases (82.9%) had a delay > 1 month between symptom onset and diagnosis. In the final Cox model, alcohol abuse, unemployment and being from a high TB incidence country were factors significantly associated with longer patient delay, while being female, having more than 45 years, oncologic and respiratory diseases were associated with longer healthcare delay. Being female, having more than 45 years and being from a high TB incidence country were associated with longer total delay. CONCLUSIONS: Patient delay and total delay have increased in recent years. Older patients, patients with alcohol problems, other comorbidities, unemployed or from countries with high TB incidence would benefit from the development of specific public health strategies that could help reduce the delay in TB diagnosis observed in our study. This study emphasizes the need to promote awareness of TB in the general population and among the healthcare community, especially at ambulatory care level, in order to reduce the gap between beginning of symptoms and TB diagnosis.

Evolution of inequalities in the coronavirus pandemics in Portugal: an ecological study.

BACKGROUND: Previous literature shows systematic differences in health according to socioeconomic status (SES). However, there is no clear evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be different across SES in Portugal. This work identifies the coronavirus disease 2019 (COVID-19) worst-affected municipalities at four different time points in Portugal measured by prevalence of cases, and seeks to determine if these worst-affected areas are associated with SES. METHODS: The worst-affected areas were defined using the spatial scan statistic for the cumulative number of cases per municipality. The likelihood of being in a worst-affected area was then modelled using logistic regressions, as a function of area-based SES and health services supply. The analyses were repeated at four different time points of the COVID-19 pandemic: 1 April, 1 May, 1 June, and 1 July, corresponding to two moments before and during the confinement period and two moments thereafter. RESULTS: Twenty municipalities were identified as worst-affected areas in all four time points, most in the coastal area in the Northern part of the country. The areas of lower unemployment were less likely to be a worst-affected area on the 1 April [adjusted odds ratio (AOR) = 0.36 (0.14-0.91)], 1 May [AOR = 0.03 (0.00-0.41)] and 1 July [AOR = 0.40 (0.16-1.05)]. CONCLUSION: This study shows a relationship between being in a worst-affected area and unemployment. Governments and public health authorities should formulate measures and be prepared to protect the most vulnerable groups.

Effect of Different Resin Cements on the Bond Strength of Custom-made Reinforced Glass Fiber Posts-A Push-out Study.

AIM AND OBJECTIVE: This study aims to evaluate the effect of different resin cements on the bond strength (BS) of custom-made glass fiber posts (GFPs) using the push-out test. MATERIALS AND METHODS: Twenty-four uniradicular bovine teeth were selected. The crowns were sectioned at the cementoenamel junction, and the root canals were treated. The post spaces of the teeth were prepared to a length of 12 mm to receive a GFP. The specimens were randomly assigned to three experimental groups (n = 8), according to the resin cement used to fix the GFPs: RelyX U200 (U200), Allcem Core (ACC), and Allcem Dual (ACD). Each specimen was sectioned into six slices per root third (cervical, middle, and apical), which were subjected to the push-out test. BS values were calculated and compared using the Kruskal-Wallis and Friedman tests. RESULTS: There were significant differences in the middle third, according to the resin cement type used (p < 0.05). ACD showed lower BS values (p < 0.05). Significant differences were observed for ACD among the thirds of the slices, with the lowest values also observed for the middle third (p < 0.05). CONCLUSION: The present study shows that ACC and U200 showed higher BS values compared with ACD, and were also less influenced by the depth of the root dentin. CLINICAL SIGNIFICANCE: The restoration of endodontically treated teeth is a challenge in dentistry, and, in most cases, will require installation of fiberglass pins. In this respect, several types of resin cements are indicated for cementation of these pins; for this reason, their adhesiveness must be adequately investigated. Conventional cements and self-adhesive cements have shown satisfactory performance in cementing the custom-made GFPs, thereby making these cements satisfactory clinical choices. The present study suggests that ACD had lower performance than the other two cements evaluated.

Real-world effectiveness of pembrolizumab in previously treated non-small cell lung cancer: A population-based cohort study.

PURPOSE: Immunotherapy is promising for lung cancer treatment, although at significant financial impact. The aim of this study was to evaluate the effectiveness and the efficacy-effectiveness gap of pembrolizumab in previously treated non-small cell lung cancer (NSCLC). METHODS: A population-based ambispective cohort study was conducted. Cases of interest were identified through the National Cancer Registry database and additional data sources. Patients aged ≥18 years, diagnosed with NSCLC and exposed to pembrolizumab, between 23 June 2016 and 31 October 2018, as second or later lines of treatment for advanced disease were included. Patients were followed-up until death or cut-off date (30 April 2019). Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), event-free survival (EFS), and adverse events (AEs) leading to treatment discontinuation. The efficacy-effectiveness gap was evaluated comparing results with clinical trial data. RESULTS: A total of 181 patients were included. Median age was 63 years (range 33-94); 74.6% were male. Median treatment duration was 5.6 months (interquartile range: 1.4-10.4) and, at cut-off date, treatment had been discontinued in 141 patients, mainly due to disease progression. Median OS was 13.0 months (95% confidence interval [CI] 9.3-15.9) and 1-year OS was 53.1% (95% CI 45.2%-60.3%). Median PFS was 5.6 months (95% CI 4.6-7.2), median EFS was 4.7 months (95% CI 3.2-6.0), and treatment was discontinued due to AE in 8.3% of cases (n = 15). The efficacy-effectiveness gap seems to favor pembrolizumab use in clinical practice. CONCLUSION: Real-world data suggest the performance of pembrolizumab to reflect the clinical trial outcomes in previously treated NSCLC.

Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response. OBJECTIVE: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings. METHODS: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10-6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations. RESULTS: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10-6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10-3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10-3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.

Outbreak of Glomerulonephritis Caused by Streptococcus zooepidemicus SzPHV5 Type in Monte Santo de Minas, Minas Gerais, Brazil.

Streptococcus zooepidemicus is an emerging and opportunistic zoonotic pathogen which plays an important role in the development of severe and life-threatening diseases and is potentially capable of triggering large glomerulonephritis outbreaks. Between December 2012 and February 2013, 175 cases of glomerulonephritis were confirmed in the town of Monte Santo de Minas, MG, Brazil. During the outbreak, 19 isolates of S. zooepidemicus were recovered, 1 from ice cream, 2 from the oropharynx of food handlers, and 16 from patients affected by acute poststreptococcal glomerulonephritis (APSGN). All S. zooepidemicus isolates involved in the outbreak amplified the same sequence of the hypervariable region of the SzP protein (SzPHV5) and presented indistinguishable banding patterns with high similarity (>99%) to each other by the repetitive element sequence-based PCR (rep-PCR) technique. Inspection programs on the milk supply chain should be strengthened and continuously encouraged so that the health of consumers is preserved.

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet.

PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.