Introduction: Epidemiological studies suggest that at least 1 in 29 South African women will be diagnosed with breast cancer in their lifetime. Breast cancer is not a single disease. The heterogeneity of breast cancer results in four distinct molecular subtypes including aggressive human epidermal growth factor receptor-2 (Her-2) positive, where Her-2 receptors are overexpressed. Trastuzumab (Herceptin®), is a recombinant, humanized, anti-Her-2 monoclonal antibody that specifically targets subdomain IV of the extracellular domain of the Her-2 receptor and has dramatically altered the prognosis of Her-2 positive breast cancer. Trastuzumab is, however, associated with problems such as primary and acquired resistance, which has prompted investigation into improving its efficacy. Aim: To investigate the ability of selected therapeutic agents to alter in-vitro cell viability, cell cycling, apoptosis and Her-2 expression in models of Her-2-positive and oestrogen receptor positive, Her-2 negative breast adenocarcinoma and bring about an alteration in the efficacy of trastuzumab. Methods: MCF-7 cells which retain the ability to process oestrogen, and SK-Br-3 cells which overexpress Her-2 gene products were used. Cells were exposed to trastuzumab, aspirin, calcipotriol, doxorubicin, epidermal growth factor (EGF-human), geldanamycin, heregulin-β1 and β-oestradiol as single agents and in combination with trastuzumab. Research methodologies included tetrazolium conversion assay for cell viability, AMC-substrate cleavage and annexin-V for apoptosis, propidium iodide staining for cell cycle analysis and anti-Her-2 affibody molecule for relative Her-2 receptor density. Results: Cell survival of 95.39% (±2.69) for MCF-7 cells and 74.17% (±1.60) for SK-Br-3 cells was observed following trastuzumab (100 μg/ml) exposure. Trastuzumab resulted in statistically significant G1 phase accumulation in MCF-7 cells at 72 hours and in SK-Br-3 cells from 24 hours. Furthermore, trastuzumab decreased relative Her-2 receptor density in SK-Br-3 cells by approximately 35% by 24 hours but had no effect in MCF-7 cells. The anti-proliferative effects of trastuzumab were abrogated by EGF, a Her-1 ligand and heregulin-β1, a Her-3 and Her-4 ligand. Most agents altered distribution throughout the phases of cell cycle to a certain degree, with the G1 phase accumulation observed for trastuzumab being potentiated in some combinations. Most of the agents, with the exception of doxorubicin and geldanamycin, did not promote apoptosis and appeared instead to be anti-proliferative. Geldanamycin had the greatest effect on Her-2 receptor density (approximately 80% by 24 hours) followed by EGF, heregulin and trastuzumab, with the biological molecules in combination with trastuzumab producing a further significant reduction. Conclusion: Endogenous Her-receptor ligands (EGF and heregulin) differentially altered the viability parameters for trastuzumab which could play a role in the emergence of clinical resistance to targeted therapy. Doxorubicin with concurrent trastuzumab significantly reduced cell viability compared to each single agent in both cell lines. Furthermore, the cytostatic and cytotoxic abilities of each of the other agents either mimicked trastuzumab alone or the selected agent alone when exposed concurrently. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / Unrestricted

O objetivo do presente estudo foi realizar um estudo epidemiológico das condições de saúde bucal em crianças de 12 anos de idade, em escolas públicas na cidade de Quito, Equador, e verificar a relação entre maloclusão e fatores associados trata-se de um estudo transversal com amostragem complexa. Seis examinadores passaram por um treinamento e processo de calibração. Os dados foram analisados no pacote estatístico Stata 15.0. Os dados foram apresentados de forma descritiva e analítica, foram realizadas regressões de Poisson Bivariada, Múltipla e Complexa. O nível de significância utilizado foi de 5%. Por se tratar de levantamento epidemiológico de análise complexa, os dados foram apresentados com e sem ajustes da amostragem complexas e o desvio padrão das variâncias dos dois modos apresentados (DEFT). O projeto foi submetido ao Comitê de Ética em Pesquisa da FOUSP (Parecer 1825111), e também ao Comitê de Ética em Pesquisa da UCE e foram aprovados. Os responsáveis assinaram o Termo de Consentimento Livre e Esclarecido (TCLE) e as crianças preencheram o termo de assentimento. Participaram do estudo 998 escolares de 12 anos de idade da cidade de Quito Equador, sendo 55,51% do gênero feminino e 44,49% do masculino. Em relação aos dados socioeconômicos, podemos dar destaque a renda familiar, que 45,21% dos escolares vivem em lares que recebem até um salário mínimo. Sendo a porcentagem ponderada de 49,97%. O maior DEFT apresentado foi para a variável escolaridade da mãe. Foi verificada associação entre a prevalência de maloclusão e renda e aglomeração, quando a prevalência foi agrupada em moderada e severa não foi verificada associação a nenhuma situação. Verificou-se também associação entre a maloclusão e a qualidade de vida em saúde bucal. Devemos considerar ademais que as crianças de Quito, Equador, investigadas possuem uma alta prevalência de maloclusão em seus diferentes níveis de gravidade. Estudos futuros devem considerar a possível influencia, características contextuais como a disponibilidade de serviços e profissionais especializados no tratamento desse agravo e sua influência nos desfechos em saúde, em términos da maloclusão. Também devem ser considerados estudos epidemiológicos comportamentos prévios adotados durante a infância por parte das crianças e responsáveis, que possam representar fatores de risco para este desfecho. / The aim of the present study was to conduct an epidemiological study of oral health conditions in 12-year-old children in public schools in the city of Quito, Ecuador, and to verify the relationship between malocclusion and associated factors. complex sampling. Six examiners underwent a training and calibration process. The data were analyzed in Stata 15.0 statistical package. Data were presented in a descriptive and analytical way, and Bivariate, Multiple and Complex Poisson regressions were performed. The level of significance was 5%. Due to the fact that this was an epidemiological survey of complex analysis, the data were presented with and without complex sampling adjustments and the standard deviation of the variances of the two modes presented (DEFT) were presented. The project was submitted to the Research Ethics Committee of FOUSP (Opinion 1825111), and also to the Research Ethics Committee of the UCE and were approved. Those responsible signed the Term of Free and Informed Consent (TCLE) and the creation completed the term of assent. A total of 998 12-year-old schoolchildren from the city of Quito Ecuador participated in the study, 55.51% female and 44.49% male. Regarding socioeconomic data, we can highlight the family income, which 45.21% of schoolchildren live in homes that receive up to a minimum wage. The weighted percentage being 49.97%. The highest DEFT presented was for the mother\'s educational variable. It was verified association between the prevalence of malocclusion and income and agglomeration, when the prevalence was grouped in moderate and severe, no association was verified to any situation. There was also an association between malocclusion and quality of life in oral health. We must also consider that the children of Quito, Ecuador, investigated have a high prevalence of malocclusion in their different levels of severity. Future studies should consider the possible influence, contextual characteristics such as the availability of specialized services and professionals in the treatment of this condition and its influence on health outcomes, in terms of malocclusion. Pre-existing behaviors adopted during childhood by children and caregivers that may represent risk factors for this outcome should also be considered as epidemiological studies.

There is substantial evidence from cellular, animal and epidemiological studies in support of a role for calcium, and in particular, dairy foods in the regulation of weight (McCarron, 1983; Davies et al. 2000; Heaney, 2003a; Jacqmain et al. 2003; Parikh & Yanovski, 2003; Soares et al. 2004a; Azadbakht et al. 2005). These studies suggest, but do not provide, a causal link between increased calcium intake and reduced adiposity. In contrast, randomised controlled trails (RCT) are limited and their outcomes, to date, are conflicting in their findings (Zemel et al. 2004b; Harvey-Berino et al. 2005; Thompson et al. 2005; Zemel et al. 2005a; 2005b). The primary mechanism involves the control of intracellular calcium by calcitrophic hormones, vitamin D3 and PTH. It is proposed that a higher calcium intake lowers the calcitrophic hormones, thus reducing intracellular calcium and attenuating lipid storage (Zemel et al. 2000). Other flow through effects may include the greater utilisation of fat as a fuel source, increased thermogenesis, increased fat excretion, improved satiety and reduced food intake. (Melanson et al. 2003; Sun & Zemel, 2004; Boon et al. 2005a; Gunther et al. 2005b; Jacobsen et al. 2005b; Melanson et al. 2006). In this thesis we demonstrate that the acute ingestion of calcium, increased postprandial fat oxidation in overweight and obese humans. The results were consistent between the two sources of calcium tested (dairy and calcium citrate). Circulating levels of non-esterified fatty acids (NEFA) were less suppressed, while glycerol tended to be higher following both high calcium meals (Cummings et al. 2006). / There was no evidence of a modulation of subjective feelings of hunger, or satiety, nor immediate food intake (buffet) or 24 hour food intake. A prolongation of the inter-meal interval was however observed in subjects consuming the high calcium meals. A single-blind 12 week RCT, with a 12 week wash out period, compared two energy restricted (ER) diets either high (HC 1200 mg/d) or low in calcium (LD 600 mg/d). Forty overweight/obese male and female subjects were recruited for the study with 29 subjects completing both arms of the study. Anthropometric data and body composition from DEXA were measured before, during and following each diet. There was no difference between the diets in the loss of body weight, total fat mass or trunk fat mass. A greater reduction in waist circumference of 1.23 cm was observed when subjects had consumed the HC diet; this however was just short of significance (P=0.052). There was a smaller reduction of resting energy expenditure on the hypocaloric HC diet with a trend for a greater fat oxidation at week 10 of intervention. No differences were observed between the treatment groups for fasting levels of glucose, insulin, Hba1c, LDL-C, HDL-C or TC. We also found an inverse relationship between resting metabolic rate at the start of ER and body fat lost when subjects consumed the LC diet, but not the HC diet. / This is a novel finding in that it would be expected to see an inverse relationship between initial RMR and the amount of fat lost; however, the HC diet seems to achieve the same fat loss as the LC diet by taking away the effect of initial body size/composition. Overall, the ingestion of a single meal containing 500 mg of dietary and elemental calcium has some benefits for the obese individual. Six hours post-prandially fat oxidation is stimulated following the consumption of the dietary and elemental calcium breakfast meals. During a 12-week weight loss period, a higher calcium intake did not result in a greater weight loss compared to a low calcium diet. The HC diet did result in a trend for a greater reduction in waist circumference; however, this did not transcribe into an increased loss of total or regional body fat.

Introduction: Faravelli et al. [1, 2] present findings on the lifetime, point and 1-year prevalence of mental disorders from their recent Sesto Fiorentino community survey in Italy. The publication of these study findings occurs at a time where some researchers and journal editors seem to have come to the conclusion that there is currently no further need for such cross-sectional studies on the prevalence of mental disorders. In fact, there have been pleas for a pause of such studies [3]. Highlighting several noteworthy features and findings from the survey of Faravelli et al. [1, 2], this editorial will challenge this attitude. The status, past and recent progress in the field of epidemiology of mental disorders will be critically discussed, in an attempt to underline the continued core role of descriptive epidemiological studies for our field and to identify future research needs.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O objetivo deste trabalho foi determinar a freqÃÃncia e o perfil epidemiolÃgico do traumatismo dentÃrio em escolares, na faixa etÃria entre 6 e 12 anos, matriculados na rede pÃblica municipal de Fortaleza-CearÃ-Brasil, no ano de 2007. Foram examinados 500 escolares divididos proporcionalmente entre as seis secretarias executivas regionais e os dados como idade, sexo, elemento dentÃrio acometido pelo trauma, tipo de trauma, perda em razÃo de trauma, presenÃa de fÃstula, descoloraÃÃo, restauraÃÃo relacionada ao dente traumatizado e fatores predisponentes foram anotados em uma ficha clÃnica. Os dados foram agrupados e, para cada categoria avaliada, empregou-se o teste estatÃstico do qui-quadrado. Os resultados mostraram que, dos 500 escolares examinados, 130 apresentaram dentes traumatizados (25,7%), sendo 14 em dentes decÃduos (2,9%) e 116 em dentes permanentes (22,8%). A idade mais acometida por traumatismo dentÃrio foi dez anos (20,9%). O gÃnero feminino foi o mais prevalente (61,4%). O incisivo central superior esquerdo (8,4%) e o incisivo central superior direito (6,8%) foram os dentes mais envolvidos em traumatismos dentÃrios. A fratura foi o tipo de trauma mais prevalente, com 23,7% dos casos. A perda decorrente de trauma representou no presente estudo apenas 0,4% dos casos. A descoloraÃÃo apresentou-se ausente em 97% dos pacientes examinados. A fratura mais prevalente foi a fratura de esmalte (17,7%), seguida pela fratura de esmalte e dentina (4,4%). Neste estudo, 99,8% dos escolares que apresentaram dentes fraturados por trauma nÃo receberam tratamento adequado. Os traumas combinados sà ocorreram em 0,4% dos casos, como tambÃm a presenÃa de fÃstula (0,1%). Quanto aos fatores predisponentes, observou-se alteraÃÃo de sobressaliÃncia em 33,7% dos pacientes examinados, e selamento labial inadequado em 17,3% dos casos. Os resultados permitiram concluir que familiares, autoridades educacionais e cuidadores de crianÃas em geral deveriam ser portadores de conhecimentos suficientes para desenvolver um ambiente seguro e cuidados adequados no momento do traumatismo dentÃrio e assim prevenir e minimizar as seqÃelas de traumatismo dentÃrio. / The purpose of this study was to determine the frequency and epidemiological profile of dental trauma among 6-12-year-old schoolchildren regularly attending the municipal public schools of Fortaleza, CE, Brazil, in 2007. Five hundred schoolchildren proportionally divided among the six regional executive educational bureaus were examined and data referring to age, gender, traumatized tooth/teeth, type of trauma, tooth loss due to trauma, presence of fistula, discoloration, restoration related to the traumatized tooth/teeth and predisposing factors were recorded on clinical forms. The data were grouped and each category was analyzed statistically by the chi-square test. The results revealed that among the 500 examined children, 130 (25.7%) had suffered dental trauma to either primary teeth (14 children - 2.9%) or permanent teeth (116 children - 22.8%). The age of 10 years had the most frequency of dental trauma (20.9%). The female gender was more prevalent (61.4%). The maxillary left central incisor (8.4%) and the maxillary right central incisor (6.8%) were the most frequently traumatized teeth. Fracture was the most prevalent type of dental trauma, corresponding to 23.7% of the cases. Tooth loss due to traumatic injury occurred in only 0.4% of the cases. Discoloration was absent in 97% of the patients. Enamel fracture was the most prevalent of all types of fractures (17.7%) followed by enamel/dentin fracture (4.4%). The data showed that 99.8% of the schoolchildren who presented fractured teeth did not receive adequate dental treatment. Composite traumas and fistulae occurred in only 0.4% and 0.1% of the patients, respectively. Regarding the predisposing factors, alterations in the overjet was observed in 33.7% of the children and inadequate lip coverage was present in 17.3%. The findings of the present study allowed concluding that, in general, family, educational authorities and caregivers should have sufficient knowledge to provide a safe environment and adequate care at the moment of a dental trauma in such a way that its sequelae can be prevented or minimized.

Made available in DSpace on 2014-08-20T14:30:17Z (GMT). No. of bitstreams: 1 Dissertacao_Fabiana_Chiapinotto.pdf: 2959787 bytes, checksum: 637ef42043b24eb57bc0d4a7a20e6df3 (MD5) Previous issue date: 2011-07-08 / Periodontal disease in its destructive form is characterized as a public health problem due to its high incidence and prevalence worldwide, and may cause a negative impact on the quality of life of individuals, depending on its severity. However, few population-based studies were conducted to measure the nondestructive form of periodontal disease, gingivitis, and the factors associated with it. The aim of this study is to estimate the prevalence and severity of gingivitis in schoolchildren and test its association with demographic, socioeconomic and behavioral factors. The study had a cross-sectional school based in the city of Pelotas, Brazil. The sample consisted of children between the ages of 8 and 12 years of both sexes, attending public and private schools, randomly selected through a process of conglomerate in two stages. Data were obtained through semi-structured questionnaire directed to parents or guardians and interview and clinical oral examination performed on schoolchildren. The diagnosis of gingivitis was achieved by the Gingival Bleeding Index (GBI). The dependent variable was the presence of gingival bleeding and gingivitis and the independent variables consisted of demographic, family socioeconomic status and the behavior of children towards oral health, use of dental services, and clinical variables. For statistical analysis the data were organized into a database using Epi-Data 6.0 and the description of absolute and relative frequencies being held later. Soon after, the associations between exposures and outcomes were tested using bivariate analysis, estimating prevalence ratios and confidence intervals at 95%. Multivariate analysis was performed using Poisson regression with robust variance and a significance level of 5%. The prevalence of bleeding on probing was 78.4% (95% CI: 76.1 to 81.0), the mean and median number of sites with gingival bleeding was 3.10 and 2 (SD ± 3.22), respectively. In multivariable adjusted analysis, the presence of a greater number of sites with plaque was significantly associated with gingivitis [PR 1.89 (95% CI: 1.50 to 2.37)]. Children whose mothers had less education, were 55% more likely to have gingivitis than mothers with more years of schooling ≥ 8. Mulatto children had a 39% lower chance of having gingivitis [PR 0.61 (95% CI: 0.43 to 0.85)] compared to children of white skin. This association was observed after adjusting for other variables such as gender, skin color and age. The reported high prevalence of gingivitis among schoolchildren and the socioeconomic and behavioral factors associated whit it confirm the need for dental care as a priority in preventive measures at earlier ages, when this condition is reversible and healthy oral hygiene habits are better understood and strengthened, taking into account the role of the mother in this process / O objetivo do presente estudo é estimar a prevalência de gengivite em escolares e testar a associação com fatores demográficos, socioeconômicos e comportamentais. O estudo apresentou delineamento transversal de base escolar, realizado na cidade de Pelotas, RS, Brasil. A amostra foi formada por crianças entre 8 a 12 anos de idade de ambos os sexos, de escolas públicas e privadas, selecionadas aleatoriamente através de um processo de conglomerado em duplo estágio. Os dados foram obtidos por meio de aplicação de questionário semi-estruturado direcionado aos pais e/ou responsáveis e de entrevista e exame clínico odontológico nos escolares. O diagnóstico de gengivite foi obtido através do Índice de Sangramento Gengival (ISG). Os desfechos foram sangramento gengival e gengivite. As variáveis independentes foram constituídas por características demográficas, socioeconômicas da família e comportamentais das crianças como os cuidados com a saúde bucal, utilização de serviços odontológicos, além das variáveis clínicas. Para a análise estatística os dados foram organizados em um banco de dados, utilizando-se o programa Epi-Data 6.0 sendo, posteriormente, realizada a descrição das freqüências absolutas e relativas. Logo após, as associações entre desfecho e exposições foram testadas utilizando-se análise bivariada, estimando-se as razões de prevalência e seus intervalos de confiança em 95%. A análise multivariada foi realizada pela Regressão de Poisson com variância robusta e um nível de significância de 5%. A prevalência de sangramento gengival foi de 78,4% (IC95%: 76,1;81,0), a média e a mediana do número de sítios com sangramento gengival foi de 3,10 e 2 (±DP 3,22), respectivamente. A prevalência de gengivite foi de 44,5% (IC95%: 42,3;46,4). Na análise multivariada ajustada, a presença de maior número de sítios com placa teve associação significativa com gengivite [RP 1,89 (IC95%: 1,50;2,37)], crianças cujas mães não tinham estudado, tiveram 55% maior probabilidade de gengivite em relação às mães com ≥ 8 anos de estudo. Crianças pardas apresentaram 39% menor risco de apresentar gengivite [RP 0,61 (IC95%: 0,43;0,85)] comparado às crianças de cor da pele branca. Essas associações foram verificadas após ajuste para outras variáveis como sexo, cor da pele e idade. A considerável prevalência de gengivite relatada nos escolares e os fatores sociais e clínicos associados confirmam a necessidade de haver prioridade no atendimento odontológico quanto às medidas preventivas em idades mais precoces, quando o agravo é reversível e os hábitos saudáveis de higiene bucal são mais bem entendidos e reforçados, levando em conta o papel fundamental que a mãe desempenha neste processo.

Made available in DSpace on 2016-03-15T19:40:26Z (GMT). No. of bitstreams: 1 Sabrina Helena Bandini Ribeiro.pdf: 1303394 bytes, checksum: 3a8cdbfd1b0402b1d1f30c8f17251513 (MD5) Previous issue date: 2007-08-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Pervasive Developmental Disorders (PDD) are characterized by impairments in reciprocal social interaction, language, and communication and by the presence of repetitive and stereotypic patterns of behavior and interests. The prevalence of PDD has increased in recent years; currently frequencies are 30 to 60 per 10,000. There are no epidemiological studies of PDD prevalence in developing countries. The aim of this study was to verify the feasibility of our approach and of the protocol for a PDD prevalence study in Atibaia. It also describes the PDD prevalence found. Methods: To develop this pilot study, it was selected one urban neighborhood with 1470 children, ages 7 to 12. All the PDD services, all public schools in this neighborhood and the PSF team were identified and special meetings were organized with lectures and discussions about PDD. 99 children were indicated; 76 suspects cases between 07 to 12 years old children were evaluated. All suspected cases were evaluated based on PDD (ASQ) and mental health (SDQ and SRQ) screenings. Results: A PDD prevalence of 0.88% was found, with ratio of males to female 3:1. Conclusion: This is the first study reporting the prevalence of PDD in Latin American countries. The prevalence rates found was similar with others studies, although up to this moment, only the screening phase was done. It was important to use multiple informant sources. / Os Transtornos Invasivos do Desenvolvimento (TID) são caracterizados por uma tríade de comprometimentos em três áreas do desenvolvimento: interação social, comunicação e comportamentos restritos e estereotipados. Estudos epidemiológicos dos TIDs ao redor do mundo apontam um aumento do número de casos a partir da década de 90, sendo as taxas atualmente consideradas entre 30 a 60 para 10000. Não existem estudos de prevalência dos TIDs em países em desenvolvimento. O Objetivo deste trabalho foi testar a viabilidade metodológica de um estudo piloto de prevalência de TIDs e analisar a taxa de prevalência encontrada. Método: Foi eleito um bairro representativo da cidade, com 1470 crianças entre 7 e 12 anos. Todos os serviços de referência da cidade, as escolas do bairro e as equipes do PSF receberam orientações por meio de palestras e guidelines. Um total de 99 crianças foram indicadas; 76 crianças foram avaliadas com suspeita para TID. Foram aplicados questionários de rastreamento para TID (ASQ) e para saúde mental (SDQ e SRQ). Resultados: A prevalência de TID encontrada neste estudo foi de 0,88 %, com uma razão de 3:1 meninos para cada menina. Conclusão: Este é o primeiro estudo de prevalência de TID na América Latina. Apenas a fase de triagem dos casos foi realizada, os dados encontrados corroboram com os estudos de prevalência publicados. Observou-se a importância da utilização de várias fontes de informação para a busca dos casos.

Les infections dues aux bactéries gram-négatif multi résistantes en particulier la résistance aux carbapénèmes, représentent un problème majeur de santé publique. La hausse des taux de résistance à ces antibiotiques a conduit à la réutilisation de la colistine, comme alternative thérapeutique de dernier recours. Notre travail de thèse s'est concentré sur l'étude épidémiologique de la résistance aux antibiotiques d’isolats cliniques au Liban. Nos travaux se sont scindés en 4 chapitres, avec trois objectifs principaux; (i) l'étude des bactéries résistantes aux carbapénèmes, (ii) l'élucidation des mécanismes moléculaires de la résistance à la colistine (iii) l'émergence de bactéries à Gram-positif résistantes à la vancomycine. Initialement, une revue de la littérature sur l'épidémiologie et les facteurs de risque associés à l'infection bactérienne au cours de conflits armés et catastrophes naturelles en Asie et au Moyen Orient a été rédigée. Dans le deuxième chapitre nous avons cherché à voir l'effet du changement de traitement de la combinaison colistine-carbapénème à la colistine en monothérapie sur la résistance d’A. baumannii, en plus de la détection du blaVIM-2 codé par plasmide. Dans le troisième chapitre, nous avons détecté la propagation de bactéries gram-négatif résistantes à la colistine en raison de la mutation des (pmrA /pmrB, phoP/phoQ), ou mgrB. Enfin, nous détectons l'émergence du gène vanA d'E. faecium. Il serait nécessaire de mettre en place des enquêtes de surveillance de l’usage des antibiotiques pour éviter la propagation de souches résistantes à ces antibiotiques au Liban. / Infections due to multidrug-resistant gram-negative bacteria especially the resistance to carbapenems, have become a major public health problem. This increase in resistance to antibiotics has led to the resuscitation of colistin, as a last-resort treatment option. Our PhD work focused on the epidemiological study of the antibiotic resistance of clinical isolates in Lebanon. This thesis is divided into 5 chapters with three main objectives; (1) the investigation of carbapenem-resistant bacteria in Lebanese hospitals. (2) the Elucidation of the molecular mechanisms of colistin-resistant bacteria in Lebanese patients, and (3) the emergence of vancomycin-resistant gram-positive bacteria in Lebanon. At the start of this thesis, we have prepared a literature review on the epidemiology and the risk factors associated with bacterial infection in conflict wounded and natural disaster in Asia and the Middle East. The second chapter aimed to see the effect of the shift of treatment from colistin-carbapenem combination to colistin monotherapy on the prevalence and resistance of A. baumannii, in addition to the detection of the plasmid-encoded blaVIM-2 gene. In the third chapter, we have detected the spread of colistin-resistant gram-negative bacteria due to mutation of the two-component systems (pmrA /pmrB, phoP/phoQ), or mgrB. We detect the emergence of vanA of Enterococcus faecium resistant to vancomycin. This observation confirms that colistin resistance in Gram-negative bacteria is indeed increasing. In conclusion, it appears necessary and urgent to set up surveys to monitor the use of antibiotics to prevent the spread of resistant strains in Lebanon.

Introduction: Faravelli et al. [1, 2] present findings on the lifetime, point and 1-year prevalence of mental disorders from their recent Sesto Fiorentino community survey in Italy. The publication of these study findings occurs at a time where some researchers and journal editors seem to have come to the conclusion that there is currently no further need for such cross-sectional studies on the prevalence of mental disorders. In fact, there have been pleas for a pause of such studies [3]. Highlighting several noteworthy features and findings from the survey of Faravelli et al. [1, 2], this editorial will challenge this attitude. The status, past and recent progress in the field of epidemiology of mental disorders will be critically discussed, in an attempt to underline the continued core role of descriptive epidemiological studies for our field and to identify future research needs.

Introdução: Apesar das estratégias mundiais de saúde propostas para promover a saúde infantil, mais de 200 milhões de crianças menores de cinco anos não conseguem atingir o seu potencial máximo de desenvolvimento em decorrência de pobreza, más condições de saúde, nutrição e cuidados deficientes. No Brasil, os poucos estudos conduzidos buscam encontrar associação entre diversos fatores de risco e atrasos no desenvolvimento infantil, mas com dificuldade na identificação das raízes sociais desse processo. Além disso, apesar do acompanhamento do desenvolvimento infantil integrar a assistência à criança na Atenção Básica desde a década de 80, ainda são necessários avanços no seu acompanhamento. Justifica-se, pois, aprofundar os conhecimentos na rede de determinantes sociais relacionados a prováveis problemas no desenvolvimento de crianças cadastradas na atenção básica. Objetivos: Analisar a evolução história do acompanhamento do desenvolvimento infantil na atenção primária e os instrumentos propostos para orientar essa ação no Brasil; analisar associação entre prováveis problemas de desenvolvimento infantil e determinantes sociais em município do estado de São Paulo; e analisar os domínios do desenvolvimento infantil (maturativo, psicomotor, social e psíquico) e sua associação com grupos sociais e características maternas/paternas e infantis. Métodos: Análise documental de instrumentos oficiais referentes ao acompanhamento do desenvolvimento infantil, realizada mediante comparação com testes de triagem utilizados para detectar desvio/alteração no desenvolvimento infantil. Estudo transversal que analisou dados da 1ª fase de investigação mais ampla, aprovada por Comitê de Ética em Pesquisa. Etapa empírica foi desenvolvida em Itupeva, SP, Brasil, em amostra representativa de 348 crianças menores de 3 anos de idade, cadastradas nas 12 unidades básicas de saúde do município. Os dados foram coletados por entrevistas realizadas com as mães no período de fevereiro a abril de 2013. Dados do desenvolvimento infantil foram obtidos por meio da Ficha de Acompanhamento do Desenvolvimento proposto pelo Ministério da Saúde em 2002, que para cada uma das 11 faixas etárias, apresenta quatro marcos relativos aos domínios do desenvolvimento (maturativo, psicomotor, social e psíquico). Considerou-se Desenvolvimento Esperado para Idade, crianças com todos os marcos do desenvolvimento presentes e Provável Problema de Desenvolvimento, crianças com falha em alcançar algum marco do desenvolvimento. Utilizou-se Índice de Reprodução Social para classificar as famílias em quatro grupos sociais. A partir de uma base teórico-metodológica-operacional foram formados grupos sociais homogêneos segundo formas semelhantes de trabalhar e viver. Análises univariada e múltipla foram realizadas com o programa STATA 14.0. Na análise múltipla, foi utilizada regressão logística, tendo como base um modelo teórico definido a priori, respeitando a hierarquia do processo de determinação existente. Resultados: Foram apresentados três manuscritos em resposta aos objetivos: Manuscrito 1: Análise da Ficha de Acompanhamento do Desenvolvimento de 2002 e do Instrumento de Vigilância do Desenvolvimento da Criança de 0 a 3 anos, de 2010, mostrou 44 marcos de desenvolvimento, sendo que apenas 14 mantiveram-se iguais de 2002 para 2010. Os dois instrumentos trazem um marco para cada domínio por faixa etária, os quais em 2002 eram classificados como maturativo, psicomotor, social e psíquico, mas que em 2010 não foram especificados, apesar de adaptados de 2002. Em comparação com Denver II e ASQ-3, observou-se que 5 marcos de 2002 não se encontram em nenhum deles: Começa a diferenciar dia e noite, Distancia-se da mãe sem perdê-la de vista, Aceita a companhia de outras crianças, mas brinca isoladamente, Começa o controle esfincteriano e Altera momentos agressivos com cooperativos, o que foi ajustado no Instrumento de 2010. Ter o Instrumento de Vigilância do Desenvolvimento em documento que fica em posse dos cuidadores é um ganho, pois facilita o acesso a informações dos estágios de desenvolvimento da criança, porém é fundamental a incorporação dessa avaliação na prática profissional. Manuscrito 2: Constatou-se elevada prevalência de Provável Problema de Desenvolvimento (29%), que se distribuiu heterogeneamente nos diferentes Grupos Sociais, sendo que o grupo social dos menos favorecidos apresentou maior chance (OR:2,64; IC:1,18-5,91) em relação aos demais grupos, após ajuste para variáveis de confusão. Manuscrito 3: O Grupo Social dos menos favorecidos concentrou maior proporção de crianças com provável problema de desenvolvimento nos domínios maturativo (OR:3,05; IC:1,08-8,56), psicomotor (OR:3,11; IC:1,05-9,17) e social (OR:2,44; IC:1,02-5,84). Considerações finais: Os resultados confirmaram as hipóteses iniciais de que crianças dos grupos sociais menos favorecidos são as que apresentam maior chance para alterações no desenvolvimento infantil. Como implicações para a prática, destaca-se a necessidade de continuar a se investir na utilização dos instrumentos propostos pelo Ministério da Saúde, no âmbito da atenção básica, sendo imprescindível sua valorização pelos profissionais e gestores de saúde. No ensino, ressalta-se a importância de disciplinas que abordem o desenvolvimento infantil, na teoria e na prática, para a formação de profissionais aptos a consolidarem o acompanhamento do DI em sua prática, para identificação precoce de possíveis problemas de atraso no desenvolvimento e consequente intervenção efetiva. Aponta-se a necessidade de pesquisas que ampliem a compreensão dos motivos que levam os profissionais a não preencherem o instrumento de acompanhamento do desenvolvimento infantil. Por fim, espera-se que os resultados contribuam para sensibilizar profissionais e gestores para a importância da consolidação dos cuidados relacionados ao desenvolvimento infantil. / Introduction: Despite the global health strategies proposed to promote child health, more than 200 million children under the age of five are unable to reach their full development potential because of poverty, poor health, poor nutrition and nurturing care. In Brazil, the few studies conducted seek to find an association between several risk factors and delays in child development, but with difficulty in identifying the social roots of this process. In addition, although the monitoring of child development has integrated childcare in Primary Care since the 1980s, progress is still needed in its follow-up. It is therefore justified to deepen the knowledge in the network of social determinants related to probable problems in the development of children enrolled in primary care. Objectives: To analyze the evolution of the history of childhood development monitoring in primary care and the instruments proposed to guide this action in Brazil; to analyze the association between probable child development problems and social determinants in a municipality in the state of São Paulo; and analyze the domains of child development (maturative, psychomotor, social and psychic) and association with social groups and maternal/paternal and child characteristics. Methods: Documental analysis of official instruments related to the monitoring of child development, performed through comparison with screening tests used to detect diversion/alteration in child development. A cross-sectional study that analyzed data from the first phase of the broader research, approved by the Research Ethics Committee. The empirical phase was developed in Itupeva, SP, Brazil, in a representative sample of 348 children under 3 years of age, enrolled in the 12 basic health units of the municipality. Data were collected through interviews conducted with mothers from February to April 2013. Data on infant development were collected through the \"Development Follow-up Report\" proposed by the Ministry of Health in 2002, which for each of the 11 tracks (developmental, psychomotor, social and psychic). It was considered Development Expected to Age, children with all developmental milestones present and Probable Developmental Problem, children failing to achieve some milestone of development. The Social Reproduction Index was used to classify the families into four social groups. From a theoretical-methodological-operational base were formed homogenous social groups according to similar ways of working and living. Univariate and multiple analyzes were performed with the STATA 14.0 program. In the multiple analysis, logistic regression was used, based on a theoretical model defined a priori, respecting the hierarchy of the existing determination process. Results: Three manuscripts were presented in response to the objectives: Manuscript 1: Analysis of the \"Development Follow-up Report\" of 2002 and the \"Instrument for Surveillance of Child Development from 0 to 3 years of 2010\", showed 44 development milestones , with only 14 remaining the same from 2002 to 2010. The two instruments bring a milestone for each domain by age group, which in 2002 were classified as maturative, psychomotor, social and psychic, but in 2010 were not specified, although adapted from 2002. Compared with Denver II and ASQ-3, it was observed that 5 of 2002 marks are not found in any of them: \"It begins to differentiate day and night\", \"Distance from the mother without losing it of view, \"\" Accept the company of other children, but play alone, \"\" Start sphincter control \"and\" Change aggressive moments with cooperatives, \"which was adjusted in the Instrument of 2010. Have the instrument in a document that is in the hands of caregivers is a gain, since it facilitates access to information on the stages of development of the child, but it is fundamental to incorporate this evaluation into professional practice. Manuscript 2: There was a high prevalence of Probable Development Problem (29%), which was heterogeneously distributed among the different Social Groups, and the social group of the less privileged presented a greater chance (OR: 2.64, CI 1.18 -5.91) in relation to the other groups, after adjusting for confounding variables. Manuscript 3: The Social Group of the less favored concentrated a larger proportion of children with a probable developmental problem in the maturative (OR: 3.05, CI: 1.08-8.56), psychomotor (OR: 3.11, CI: 1.05-9.17) and social (OR: 2.44; CI: 1.02-5.84). Final considerations: The results confirmed the initial hypotheses that children from the less favored social groups are the ones with the greatest chance for changes in child development. As implied.