Challenges of interpreting epidemiologic surveillance pertussis data with changing diagnostic and immunization practices: the case of the state of São Paulo, Brazil

Abstract\ud \ud Background\ud A significant increase in pertussis incidence occurred in Brazil, from 2011 to 2014, despite high coverage of childhood immunization with whole-cell-pertussis (wP) containing vaccines. This study presents pertussis surveillance data from São Paulo state and discusses the challenges to interpret them considering pertussis cyclic epidemic behavior, the introduction of new diagnostic techniques and new vaccination strategies, and enhanced disease awareness during epidemics.\ud \ud \ud Methods\ud Observational study including pertussis cases reported to the Surveillance System in São Paulo state, from January 2001 to December 2015. Pertussis cases data were retrieved from the National Notifiable Diseases Information System (SINAN) website and from São Paulo state Epidemiological Surveillance Center (CVE/SP) database. Vaccination coverage and homogeneity data were collected from the Unified Health System Department of Informatics (DATASUS). We presented cases distribution by year, age group and diagnostic criteria and calculated pertussis incidence rates. The proportions of cases among different age groups were compared using chi-square test for trend.\ud \ud \ud Results\ud Infants less than 1 year of age were the most affected during the whole period, but the proportions of cases in this age group had a significant decreasing trend, with significant increase in the proportions of cases reported among older age groups (1–4, 5–10 and ≥20 years). Cases among infants aged less than 6 months represented ≥90% of all cases in children less than 1 year of age in all but 2 years (2012 and 2015). A non-significant decrease in the proportion of cases among infants aged < 2 months was observed in parallel to a significant increase in the proportion of cases in infants aged 6–11 months.\ud \ud \ud Conclusions\ud A pertussis outbreak has occurred in a state with universal use of wP vaccine. The disease cyclic behavior has probably had a major role in the increased incidence rates registered in São Paulo state, from 2011 to 2014, as well as in the decreased incidence in 2015. Maternal vaccination cannot explain the drop in the number of cases among all age groups, in 2015, as herd protection is not expected, but may have had an impact on the number of cases in infants aged < 2 months

Epidemiology of gastrointestinal symptoms in young and middle-aged Swiss adults: prevalences and comorbidities in a longitudinal population cohort over 28 years

Abstract Background Although subacute and chronic gastrointestinal symptoms are very common in primary care, epidemiological date are sparse. The aim of the study was to examine and quantify the prevalence of subacute and chronic gastrointestinal symptoms and their associations with somatic and mental disorders in the general population. Methods Data were collected prospectively between 1981 (age m = 22, f = 23) and 2008 (age 49/50) from the Zurich Cohort Study (n = 292 men, 299 women), a representative general population survey. The participants were assessed using a semi-structured interview, the “Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology” (SPIKE). Prevalence rates were computed to be representative of the general population aged 22–50. Associations were quantified by odds ratios (ORs) and their 99% confidence intervals (CI). Results The prevalences of intestinal and of gastric symptoms were significantly higher among women in all categories examined. For example, any gastric symptoms: f. 26.4% vs m.15.2%; any intestinal symptoms: 27.6% vs 14.6%; nausea/vomitus: 19.1% vs 4.5%; constipation: 15.8% vs 6.5% (all p < 0.001). Strong associations (all p < 0.0001) were found between fatigue (1 month) and chronic stomach (OR = 9.96, 99%-CI: 5.53–17.94) and chronic intestinal symptoms (OR = 9.02, 99%-CI: 4.92–16.54). Panic attacks were associated with subacute intestinal symptoms (OR = 4.00, 99%-CI: 2.43–6.59). Anxiety was more strongly associated with subacute intestinal symptoms (OR = 3.37, 99%-CI: 2.23–5.08) than with subacute stomach symptoms (OR = 1.85, 1.20–2.86). Bipolar disorders were associated with subacute stomach symptoms (OR = 1.83, 1.18–2.17) and unipolar depression with subacute intestinal symptoms (OR = 2.05, 1.34–3.15). Conclusions Remarkably high prevalence rates of gastric and intestinal complaints were observed in women (over 1/4; men 1/7). Fatigue/neurasthenia was the strongest co-factor in both conditions. Various syndromes related to anxiety, phobia, and panic disorders showed further significant associations. The integration of psychiatric and/or psychological treatment could help address the functional part of gastric and intestinal syndromes

EX-MET study: exercise in prevention on of metabolic syndrome – a randomized multicenter trial: rational and design

Abstract\ud \ud Background\ud Metabolic syndrome substantially increases risk of cardiovascular events. It is therefore imperative to develop or optimize ways to prevent or attenuate this condition. Exercise training has been long recognized as a corner-stone therapy for reducing individual cardiovascular risk factors constituting the metabolic syndrome. However, the optimal exercise dose and its feasibility in a real world setting has yet to be established.\ud The primary objective of this randomized trial is to investigate the effects of different volumes of aerobic interval training (AIT) compared to the current exercise guideline of moderate-intensity continuous training (MICT) on the composite number of cardiovascular disease risk factors constituting the metabolic syndrome after a 16 week, 1-year, and 3-year follow-up.\ud \ud \ud Methods\ud This is a randomized international multi-center trial including men and women aged ≥30 years diagnosed with the metabolic syndrome according to the International Diabetes Federation criteria. Recruitment began in August 2012 and concluded in December 2016. This trial consists of supervised and unsupervised phases to evaluate the efficacy and feasibility of different exercise doses on the metabolic syndrome in a real world setting. This study aims to include and randomize 465 participants to 3 years of one of the following training groups: i) 3 times/week of 4 × 4 min AIT at 85–95% peak heart rate (HRpeak); ii) 3 times/week of 1 × 4 min AIT at 85–95% HRpeak; or iii) 5–7 times/week of ≥30 min MICT at 60–70% HRpeak. Clinical examinations, physical tests and questionnaires are administered to all participants during all testing time points (baseline, 16 weeks and after 1-, and 3-years).\ud \ud \ud Discussion\ud This multi-center international trial indeed aims to ease the burden in healthcare/economic cost arising from treating end-stage CVD related conditions such as stroke and myocardial infarction, that could eventually emerge from the metabolic syndrome condition.\ud \ud \ud Trial registration\ud Clinical registration number: \ud NCT01676870\ud \ud , ClinicalTrials.gov (August 31, 2012).The study received two peer – review funding’s from the Joint Research\ud Committee between St. Olavs Hospital and the Faculty of Medicine and\ud Health sciences, Norwegian University of Science and Technology (NTNU

Palmitoleic acid (16:1n7) increases oxygen consumption, fatty acid oxidation and ATP content in white adipocytes

Abstract\ud \ud Background\ud We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes.\ud \ud \ud Methods\ud For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 μM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes.\ud \ud \ud Results\ud Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0.\ud \ud \ud Conclusions\ud Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.This work was supported by grants from FAPESP (2011/51627–8 and\ud 2011/51701–3)

Pulmonary interstitial emphysema in fatal asthma: case report and histopathological review

Abstract\ud \ud Background\ud Mortality related to asthma has decreased worldwide since the introduction of inhaled corticosteroid therapy in the past decades. However, there are still some asthma fatalities identified mainly in populations with less access to regular treatment. Pulmonary interstitial emphysema due to alveolar rupture has been rarely described as a complication of an acute severe asthma attack, and its identification in pathological analysis can be difficult. Previous studies reported the association of pulmonary interstitial emphysema and bronchial ductal gland ectasia in asthma.\ud \ud \ud Case presentation\ud We present the case of a 42-year- old man that died due to a fatal asthma attack. Postmortem computed tomography revealed the unusual finding of acute Pulmonary Interstitial Emphysema, confirmed by pathological analysis. We reviewed 28 cases of fatal asthma tissue and identified the presence of pulmonary interstitial emphysema in 10% of the cases.\ud \ud \ud Conclusions\ud Postmortem computed tomography is a useful complimentary diagnostic tool for autopsies. Pulmonary Interstitial Emphysema in acute exacerbations of asthma seems to be more frequent than reported. Alveolar hyperdistension and bronchial duct gland ectasia causing tissue rupture are possible mechanisms involved in the formation of Pulmonary Interstitial Emphysema. The clinical impact of Pulmonary Interstitial Emphysema in asthma is unknown.São Paulo Research Foundation (FAPESP), National Council for Scientific and\ud Technological Development (CNPq)

Techno-economic analysis of the industrial production of a low-cost enzyme using E. coli: the case of recombinant β-glucosidase

Abstract\ud \ud Background\ud The enzymatic conversion of lignocellulosic biomass into fermentable sugars is a promising approach for producing renewable fuels and chemicals. However, the cost and efficiency of the fungal enzyme cocktails that are normally employed in these processes remain a significant bottleneck. A potential route to increase hydrolysis yields and thereby reduce the hydrolysis costs would be to supplement the fungal enzymes with their lacking enzymatic activities, such as β-glucosidase. In this context, it is not clear from the literature whether recombinant E. coli could be a cost-effective platform for the production of some of these low-value enzymes, especially in the case of on-site production. Here, we present a conceptual design and techno-economic evaluation of the production of a low-cost industrial enzyme using recombinant E. coli.\ud \ud \ud Results\ud In a simulated baseline scenario for β-glucosidase demand in a hypothetical second-generation ethanol (2G) plant in Brazil, we found that the production cost (316 US$/kg) was higher than what is commonly assumed in the literature for fungal enzymes, owing especially to the facility-dependent costs (45%) and to consumables (23%) and raw materials (25%). Sensitivity analyses of process scale, inoculation volume, and volumetric productivity indicated that optimized conditions may promote a dramatic reduction in enzyme cost and also revealed the most relevant factors affecting production costs.\ud \ud \ud Conclusions\ud Despite the considerable technical and economic uncertainties that surround 2G ethanol and the large-scale production of low-cost recombinant enzymes, this work sheds light on some relevant questions and supports future studies in this field. In particular, we conclude that process optimization, on many fronts, may strongly reduce the costs of E. coli recombinant enzymes, in the context of tailor-made enzymatic cocktails for 2G ethanol production.This work received fnancial support from Fundação de Amparo à Pesquisa\ud do Estado de São Paulo—FAPESP (São Paulo, Brazil, Grants 2014/13974-6\ud and 2010/08089-2) and Conselho Nacional de Desenvolvimento Científco e\ud Tecnológico—CNPq (Brazil, Grant 400803/2013-5)

Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement

Abstract\ud \ud Background\ud Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells.\ud \ud \ud Methods\ud L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed.\ud \ud \ud Results\ud Chronic and acute palmitate exposure significantly reduced GLUT4 protein (~ 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (~ 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (~ 45%, P < 0.05).\ud \ud \ud Conclusion\ud Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells.This research was supported by grants from FAPESP (São Paulo State\ud Foundation for Research): 2010/09984-5, 2013/18841-1 and 2016/15603-1

Quality of life scores differs between genotypic groups of patients with suspected hereditary hemochromatosis

Abstract\ud \ud Background\ud Hereditary hemochromatosis (HH) encompasses a group of autosomal recessive disorders mainly characterized by enhanced intestinal absorption of iron and its accumulation in parenchymal organs. HH diagnosis is based on iron biochemical and magnetic resonance imaging (MRI) assessment, and genetic testing. Questionnaires, such as SF-36 (short form health survey), have been increasingly used to assess the impact of diseases on the patient’s quality of life (QL). In addition, different genotypes are identified as results of genetic tests in patients with suspected primary iron overload. In the present study, our aim was to evaluate whether domains of QL are different according to genotypic groups in patients suspected of HH.\ud \ud \ud Methods\ud Seventy-nine patients with primary iron overload were included and two genotypic groups were formed (group 1: homozygous genotype for the HFE p.Cys282Tyr mutation; group 2: other genotypes).\ud \ud \ud Results\ud Group 1 had higher means of plasma transferrin saturation (86 ± 19%) and serum ferritin (1669 ± 1209 ng/mL) compared to group 2 (71 ± 12%, 1252 ± 750 ng/mL, respectively; p = 0.001). Four domains were significantly different among groups 1 and 2: physical functioning (p = 0.03), bodily pain (p = 0.03), vitality (p = 0.02) and social functioning (p = 0.01).\ud \ud \ud Conclusions\ud Our main finding was that patients with p.Cys282Tyr homozygosity had a worse QL scenario assessed by SF-36, compared with patients with iron overload without the same genotype. Being aware of this relationship between genotypes and QL might be helpful in the overall management of patients suspected of hereditary hemochromatosis.PFS Fonseca and PCJL Santos are recipients of fellowships from\ud Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and\ud Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil\ud (Proc. 2013/09295–3 and Proc. 2013/20614–3, respectively)

Augmentative and alternative communication in children with Down’s syndrome: a systematic review

Abstract\ud \ud Background\ud The use of technology to assist in the communication, socialization, language, and motor skills of children with Down’s syndrome (DS) is required. The aim of this study was to analyse research findings regarding the different instruments of ‘augmentative and alternative communication’ used in children with Down’s syndrome.\ud \ud \ud Methods\ud This is a systematic review of published articles available on PubMed, Web of Science, PsycInfo, and BVS using the following descriptors: assistive technology AND syndrome, assistive technology AND down syndrome, down syndrome AND augmentative and alternative communication. Studies published in English were selected if they met the following inclusion criteria: (1) study of children with a diagnosis of DS, and (2) assistive technology and/or augmentative and alternative communication analysis in this population.\ud \ud \ud Results\ud A total of 1087 articles were identified. Thirteen articles met the inclusion criteria. The instruments most used by the studies were speech-generating devices (SGDs) and the Picture Exchange Communication System (PECS).\ud \ud \ud Conclusion\ud Twelve instruments that provided significant aid to the process of communication and socialization of children with DS were identified. These instruments increase the interaction between individuals among this population and their peers, contributing to their quality of life and self-esteem.The authors would like to thank CAPES (Higher Education Personnel Training\ud Coordination). Call Notice No. 59/2014 – PGPTA and the UNIEDU-SC postgraduate\ud programme