Prevalence of chronic diseases in private healthcare sector of South Africa: A threat to public health

Purpose: To evaluate the prevalence of patients suffering from registered chronic disease list (CDL) conditions in a section of the South African private health sector from 2008 - 2012. Methods: This study was a retrospective analysis of the medicine claims database of a nationally (South African) representative Pharmacy Benefit Management (PBM) company data between 2008 and 2012. Statistical analysis was used to analyse the data. Descriptive analysis was performed to calculate the prevalence of CDL conditions for the entire population, and stratified by age and gender. However, MIXED linear modelling was used to determine changes in the average number of CDL conditions per patient, adjusted for age and gender from 2008 - 2012. Results: An increase of 0.20 in chronic diseases was observed from 2008 - 2012 in patients having any CDL condition, with an average of 1.57 (1.57 - 1.58, 95 % CI) co-morbid CDL conditions in 2008 and 1.77 (1.77 - 1.78, 95 % CI) in 2012. This increase in average number of CDL conditions per patient between 2008 and 2012 was statistically significant (p < 0.05), but with no large practical significance (d < 0.8). Conclusion: Prevalence of patients with CDL conditions along with risk of co-morbidity has been increasing with time in the private health sector of South Africa. Risk of increased co-morbidity with age and among different genders was prevalent.

Public health implications of dietary fiber intake to reduce the cost of chronic diseases

Objective: To assess the epidemiological evidence on dietary fiber intake and chronic diseases and make public health recommendations for the population in Romania based on their consumption. Populations that consume more dietary fiber from cereals, fruits and vegetables have less chronic disease. Dietary Reference Intakes recommend consumption of 14 g dietary fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on epidemiologic studies showing protection against cardiovascular disease, stroke, hypertension, diabetes, obesity, metabolic syndrome, gastrointestinal disorders, colorectal -, breast -, gastric -, endometrial -, ovarian - and prostate cancer. Furthermore, increased consumption of dietary fiber improves serum lipid concentrations, lowers blood pressure, blood glucose leads to low glycemic index, aids in weight loss, improve immune function, reduce inflammatory marker levels, reduce indicators of inflammation. Dietary fibers contain an unique blend of bioactive components including resistant starches, vitamins, minerals, phytochemicals and antioxidants. Dietary fiber components have important physiological effects on glucose, lipid, protein metabolism and mineral bioavailability needed to prevent chronic diseases. Materials and methods: Data regarding diet was collected based on questionnaires. We used mathematical formulas to calculate the mean dietary fiber intake of Romanian adult population and compared the results with international public health recommendations. Results: Based on the intakes of vegetables, fruits and whole cereals we calculated the Mean Dietary Fiber Intake/day/person (MDFI). Our research shows that the national average MDFI was 9.8 g fiber/day/person, meaning 38% of Dietary Requirements, and the rest of 62% representing a “fiber gap” that we have to take into account. This deficiency predisposes to chronic diseases. Conclusions and recommendations:The poor control of relationship between dietary fiber intake and chronic diseases is a major issue that can result in adverse clinical and economic outcomes. The population in Romania is at risk to develop such diseases due to the deficient fiber consumption. A model of chronic diseases costs is needed to aid attempts to reduce them while permitting optimal management of the chronic diseases. This paper presents a discussion of the burden of chronical disease and its socio-economic implications and proposes a model to predict the costs reduction by adequate intake of dietary fiber.

On the etiology of cardiovascular diseases: a new framework for understanding literature results

The interpretative framework presented here provides a rationale for many well-known features of cardiovascular diseases. Prolonged acidemia with high blood levels of free fatty acids is proposed to shape the basic context for formation of fatty acid micelles and vesicles with an acidic core that fuse with the endothelia, disrupt vital cell processes, and initiate atherosclerotic plaque formation. It offers an explanation for the distributed localization of atherosclerotic lesions, and how mild cases of occurrence of fatty acids vesicles formed within the heart and the arteries close to the heart may cause such lesions. It provides a rationale for how acute events, namely heart attacks and strokes, may arise from stormy development of fatty acid vesicles within the heart. Additionally, a process is proposed for clot development from the existing fatty acid vesicles.

Controle biológico de doenças de plantas no Brasil: história, pesquisa, comercialização e perspectivas=Biological control of plant diseases in Brazil: history, research, commercialization and perspectives.

2008

Probiotics for the prevention/treatment of human diseases and ecological study of the intestinal microbiota

The interest in human intestinal microbiota has increased in the last 20 years and significant advances have been achieved with regard to its composition and functions. The gut microbiota contributes to the maintenance of the host health status and, since alterations in the gut microbiota have been involved in the pathogenesis/progression of some diseases, several studies have focused on the manipulation of its composition. Probiotics are a strategy to maintain/restore the correct balance of gut microbial population and to prevent/treat diseases. The aim of this thesis was to explore the possibility of probiotic supplementation for the prevention/treatment of human diseases and the related study of the intestinal microbial environment. After reviewing studies concerning the use of Bifidobacterium breve as probiotic in paediatric diseases, the effectiveness of a probiotic formulation consisting of two strains of B. breve was assessed in paediatric subjects for the prevention or alleviation of gastrointestinal disorders, including coeliac disease and paediatric obesity. As the emerging role of gut microbiota in neurological diseases, the intestinal microbial environment in amyotrophic lateral sclerosis patients compared to healthy controls and the effects of a probiotic administration were examined. Considering the role of viruses in shaping gut microbiota, gut bacteriophages and bacterial community of preterm infants were investigated. The results evidenced differences in gut microbial composition of healthy controls and diseased subjects in coeliac and amyotrophic lateral sclerosis patients. The probiotic approach was effective in restoring the microbial composition in the former, whereas, in the latter, the influence was focused only on some microbial groups. The probiotic intervention was effective in improving the glyco-insulinemic profile in obese children and in preventing gastrointestinal disorders in healthy newborns. The study of the bacterial and phage composition in preterm infants suggested a transkingdom interplay between bacteria and viruses with a reciprocal influence on their composition.

Design and synthesis of (pro)electrophilic compounds for investigating the multifactorial nature of neurodegenerative diseases: focus on inflammation-driven events

Neuroinflammation constitutes a major player in the etiopathology of neurodegenerative diseases (NDDs), by orchestrating several neurotoxic pathways which in concert lead to neurodegeneration. A positive feedback loop occurs between inflammation, microglia activation and misfolding processes that, alongside excitotoxicity and oxidative events, represent crucial features of this intricate scenario. The multi-layered nature of NDDs requires a deepen investigation on how these vicious cycles work. This could further help in the search for effective treatments. Electrophiles are critically involved in the modulation of a variety of neuroprotective responses. Thus, we envisioned their peculiar ability to switch on/off biological activities as a powerful tool for investigating the neurotoxic scenario driven by inflammation in NDDs. In particular, in this thesis project, we wanted to dissect at a molecular level the functional role of (pro)electrophilic moieties of previously synthesized thioesters of variously substituted trans-cinnamic acids, to identify crucial features which could interfere with amyloid aggregation as well as modulate Nrf2 and/or NF-κB activation. To this aim, we first synthesized new compounds to identify bioactive cores which could specifically modulate the intended target. Then, we systematically modified their structure to reach additional pathogenic pathways which could in tandem contribute to the inflammatory process. In particular, following the investigation of the mechanistic underpinnings involving the catechol feature in amyloid binding through the synthesis of new dihydroxyl derivatives, we incorporated the identified antiaggregating nucleus into constrained frames which could contrast neuroinflammation also through the modulation of CB2Rs. In parallel, Nrf2 and/or NF-κB antinflammatory structural requirements were combined with the neuroprotective cores of pioglitazone, an antidiabetic drug endowed with MAO-B inhibitory properties, and memantine, which notably contrasts excitotoxicity. By acting as Swiss army knives, the new set of molecules emerge as promising tools to deepen our insights into the complex scenario regulating NDDs.

Essential oils and hydrolates as potential tools for integrated prevention of bacterial diseases in plants

The present work aims to investigate the potential use of natural substances against bacterial plant pathogens. Microdilution tests were therefore carried out in vitro to identify the minimum inhibitory and bactericidal concentrations (MIC and MBC) of several EOs and Hys against selected bacterial pathogens. Commercial products based on a mixture of EOs were in addition assayed with macrodilution experiments against Erwinia amylovora (Ea-causal agent of fire blight). Subsequently, using selected EOs, Hys, and commercial products, ex vivo tests on disease incidence and Ea population dynamics were carried out; the latter experiment was followed by SEM observations. In addition, in vivo resistance induction test was carried out against bacterial leaf of tomato, caused by Xanthomonas vesicatoria (Xv). EOs and Hys showed high bactericidal activity in vitro (MBC <0.1 and <10% for the most active EOs and Hys: Origanum compactum and Thymus vulgaris EOs and Citrus aurantium var. amara Hy, respectively), but they were not effective ex vivo, while resulted very active when used in vivo as resistance inducers in the tomato-Xv pathosystem (relative protection >40%). Differently, commercial products resulted active in all tests, but not as resistance inducers against Xv. An open field trial with commercial products was carried out on strawberry plants naturally infected with Xanthomonas fragariae; the results showed discrete relative protection, concerning that provided by the conventional products based on copper; mostly, the disease severity reduction on those plants treated with EOs commercial products was significant when disease severity resulted high. The papers already published described in the present work investigate (1)the activity of Hys in comparison to EOs with respect to their active volatile content; (2) the potential use of EOs and Hys in cultural heritage; for the restoration of paintings; (3) the induction of resistance caused by plasma-activated water-based root treatments.

Development of functional MRI protocols in the study of neurodegenerative diseases: MRI study in patients with REM sleep behavior disorder, idiopathic Parkinson's disease and multisystem atrophy

In the central nervous system, iron in several proteins is involved in many important processes: oxygen transportation, oxidative phosphorylation, mitochondrial respiration, myelin production, the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation, modification of lipids, proteins, carbohydrates, and DNA, lead to neurotoxicity. Moreover increased levels of iron are harmful and iron accumulations are typical hallmarks of brain ageing and several neurodegenerative disorders particularly PD. Numerous studies on post mortem tissue report on an increased amount of total iron in the substantia nigra in patients with PD also supported by large body of in vivo findings from Magnetic Resonance Imaging (MRI) studies. The importance and approaches for in vivo brain iron assessment using multiparametric MRI is increased over last years. Quantitative MRI may provide useful biomarkers for brain integrity assessment in iron-related neurodegeneration. Particularly, a prominent change in iron- sensitive T2* MRI contrast within the sub areas of the SN overlapping with nigrosome 1 were shown to be a hallmark of Parkinson's Disease with high diagnostic accuracy. Moreover, differential diagnosis between Parkinson's Disease (PD) and atypical parkinsonian syndromes (APS) remains challenging, mainly in the early phases of the disease. Advanced brain MR imaging enables to detect the pathological changes of nigral and extranigral structures at the onset of clinical manifestations and during the course of the disease. The Nigrosome-1 (N1) is a substructure of the healthy Substantia Nigra pars compacta enriched by dopaminergic neurons; their loss in Parkinson’s disease and atypical parkinsonian syndromes is related to the iron accumulation. N1 changes are supportive MR biomarkers for diagnosis of these neurodegenerative disorders, but its detection is hard with conventional sequences, also using high field (3T) scanner. Quantitative susceptibility mapping (QSM), an iron-sensitive technique, enables the direct detection of Neurodegeneration

Neuro-ophthalmological and electrophysiological characterization of mitochondrial diseases.

Aims and methods: 1) characterization of patients with Dominant Optic Atrophy (DOA) associated with mutations in AFG3L2 and ACO2 genes in comparison with classical OPA1-DOA; 2) characterization of patients with mtDNA mutations causing MELAS and MERRF syndromes and correlation with heteroplasmy; 3) longitudinal evaluation of subacute m.11778G>A/MTND4 Leber’s Hereditary Optic Neuropathy (LHON) patients co-treated with rAAV2/2-ND4 gene therapy and idebenone. We performed a comprehensive neuro-ophthalmological assessment coupled with electrophysiological examination. Results: 1) We described and compared 23 ACO2 and 13 AFG3L2 patients with 72 OPA1 patients. All patients presented temporally predominant optic atrophy, with ACO2 showing higher RNFL and GCL thicknesses at OCT, while AFG3L2 was virtually-indistinguishable from OPA1. 2) Retinopathy was the most common manifestation in 17/33 MELAS patients, conversely, optic atrophy was the most common finding in 7/8 MERRF patients. Correlation of heteroplasmy with neuro-ophthalmological parameters failed to disclose any significance in MELAS, while it negatively correlated with OCT parameters in MERRF. 3) We compared modifications in visual acuity, OCT and electrophysiological parameters at 3 timepoints in 9 LHON patients. We observed significant decrease of RNFL thickness and reduction of PhNR amplitude. Visual acuity improved of about -0.37 LogMAR, correlating significantly with time from onset and from injection, but not with idebenone therapy duration. Discussion: 1) ACO2 seems associated to better preservation of retinal ganglion cells, depending on a different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2 which is involved in OPA1 processing. 2) MELAS and MERRF patients presented with a clearly distinct ocular phenotype, possibly reflecting a selective susceptibility of different retinal cell types to global energy defect or oxidative stress. 3) Follow up of LHON patients treated with gene therapy confirmed the deterioration in OCT and electrophysiological parameters, while the amount of visual improvement was similar to the one observed in recent clinical trials.

Doenças respiratórias associadas à atividade de mineração no município de Parelhas, região do seridó norte-riograndense

This work aims to characterize the workers in mineral activities exposed to lung injuries in Parelhas Municipality, Rio Grande do Norte State, seeking to relate respiratory diseases to the mining activity. The studied area (Parelhas City), with about 19,700 inhabitants, is located in the Serido region, approximately 232 km far from Natal City. The number of people involved in informal mining activity (garimpo) in the Seridó region reaches about 5,000. These workers generally do not use any kind of individual protection equipments and develop, at early ages of greater productivity, severe forms of diseases, which end up disabling them to professional activities, family and social life. Deceases by respiratory problems (e.g. silicosis) have been reported in very young adults. A descriptive observational study was conducted based on information from the records found in Dr. José Augusto Dantas Hospital, between the years 1996- 2006. The occupational and socio-economic features of the population, which was selected by using the hospital records, were achieved through individually answered forms. The purpose was to link the occupational activities with the respiratory diseases. The next stage of the research was an observational case-control study, in the 1:1 proportion. The achieved data allowed confirming the central hypothesis of the research, which states that the pneumoconiosis cases are due to the mineral-based activities in the studied area. The final step of the investigation tried to assess the knowledge of relatives of students in public and private elementary and high schools from Parelhas City, regarding silicosis. About 15.4% of urban schools were analyzed through application of a structured questionnaire. The results show distinct socio-economic levels and a difference in the perception of the relatives of students in public and private schools, concerning silicosis. It was possible to identify the characteristics of the population economically involved with mineral-based activities and to define the group that deserves preferential attention in preventive actions. The work indicates some environmental problems caused by inadequate mining operations in the region

Fatores associados à doença pulmonar em idosos

OBJETIVO: Investigar a prevalência de doença pulmonar referida entre idosos segundo características sociodemográficas, econômicas, estilo de vida, mobilidade física e condições de saúde. MÉTODOS: Trata-se de um estudo transversal, de base populacional, do qual participaram 1.957 idosos (60 anos ou mais). As informações foram coletadas por meio de entrevistas. Os participantes foram selecionados a partir de amostragem probabilística, estratificada, por conglomerados e obtida em dois estágios em seis municípios do Estado de São Paulo, no período de 2001 a 2002. Foram utilizadas estatísticas descritivas, testes de associação pelo chi2, razões de prevalência e intervalos de confiança de 95%. A análise ajustada foi conduzida por meio de regressão de Poisson. RESULTADOS: Dos entrevistados, cerca de 7% referiram doença pulmonar. Não houve associação entre doença pulmonar referida e vacinação contra influenza. A partir da análise ajustada foi possível identificar os seguintes fatores independentemente associados à referência da doença: tabagismo (RP=2,03; IC 95%: 1,39-2,97); uso de medicamentos (RP=2,05; IC 95%: 1,11-3,79); auto-avaliação do estado de saúde atual como ruim ou muito ruim (RP=1,89; IC 95%:1,20-2,96); e depressão, ansiedade ou problemas emocionais (RP=1,86; IC 95%: 1,11-3,10). CONCLUSÕES: Os achados do presente estudo reforçam a importância das doenças respiratórias em idosos, particularmente em grupos mais vulneráveis, justificando medidas preventivas e assistenciais específicas.

Caracterização da criança com infecção por H1N1 e da intervenção fisioterapêutica: relato de casos em série

A infecção por influenza A, subtipo H1N1, é considerada uma doença viral aguda e importante causa de doença respiratória. As crianças foram consideradas como um dos grupos de risco, devido à imaturidade do sistema imunológico. A fisioterapia pode atuar na prevenção e no tratamento das doenças respiratórias em crianças, utilizando-se de diversas técnicas e procedimentos terapêuticos. Assim, o presente estudo teve como objetivo descrever o atendimento de fisioterapia em crianças internadas em um hospital-escola com diagnóstico/suspeita de infecção por H1N1. Estudo do tipo descritivo de relato de casos em série realizado por meio de análise de prontuário. Investigados 14 prontuários de crianças com mediana de idade de 1 ano e 5 meses, 10 do sexo masculino e 4 do feminino. A manifestação clínica mais frequente foi esforço respiratório, seguida por tosse, febre, coriza, vômitos e dor no corpo. As técnicas de fisioterapia mais realizadas foram respiratórias, seguidas de cinesioterapia, orientações para os pais, suporte de oxigênio e estímulo ao (DNPM). O tempo médio de internação foi de 4,57 dias. Algumas crianças somavam ao diagnóstico/suspeita de infecção por H1N1 diagnósticos e doenças associadas. A fisioterapia realizada foi principalmente no sentido de melhorar a mecânica respiratória por meio de técnicas desobstrutivas e outras condutas respiratórias, porém preocupação com mobilizações, orientações para os pais e desenvolvimento motor também foi destacada.

Doenças respiratórias em aves atendidas no laboratório de oriento- Patologia da FMVZ-UNESP/Botucatu-SP, Brasil, nos anos de 2005 A 2006

The respiratory tract of birds shows anatomical and physiological characteristics that facilitates the occurrence of disease, mainly those of microbiological origin. This article analyzes the frequency of respiratory diseases in domestic and wild birds treated during the years 2005-2006 at the Ornitopathology Laboratory of the Veterinary Hospital, Faculty of Veterinary Medicine and Zootecnics, São Paulo State University (FMVZUNESP). Diagnoses were obtained through clinical and radiographic exams as well as haemogram, microbiological culture, parasitological tests and necropsy, being septicemic processes, aspergillosis and mycoplasmosis the most diagnosed diseases. No zoonotic threats were identified, so the entities were described as of low-impact on public health. However, the above mentioned agents can provoke death of birds and difficult for treating and eradication as well.

Doenças respiratórios em aves atendidas no Laboratório de Ornitopatologia da FMVZ-UNESP/Botucatu-SP, Brasil, nos anos de 2005 a 2006

The respiratory tract of birds shows anatomical and physiological characteristics that facilitates the occurrence of disease, mainly those of microbiological origin. This article analyzes the frequency of respiratory diseases in domestic and wild birds treated during the years 2005-2006 at the Ornitopathology Laboratory of the Veterinary Hospital, Faculty of Veterinary Medicine and Zootecnics, São Paulo State University (FMVZ-UNESP). Diagnoses were obtained through clinical and radiographic exams as well as haemogram, microbiological culture, parasitological tests and necropsy, being septicemic processes, aspergillosis and mycoplasmosis the most diagnosed diseases. No zoonotic threats were identified, so the entities were described as of low-impact on public health. However, the above mentioned agents can provoke death of birds and difficult for treating and eradication as well.

Análise do sistema respiratório dos suínos por radiografia, broncoscopia e toracoscopia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)