Orientador: Ericson Bagatin / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T19:42:21Z (GMT). No. of bitstreams: 1 Publio_AlessandraZanovelli_D.pdf: 2461788 bytes, checksum: 790e1d83d8462e0845c03147e0388e54 (MD5) Previous issue date: 2008 / Resumo: A asma ocupacional, pneumoconioses e as doenças granulomatosas são consideradas as principais doenças respiratórias relacionadas com exposição ocupacional. Nos países desenvolvidos estão bem documentadas em bases de dados de vigilância epidemiológica que permitem uma análise detalhada da morbi-mortalidade. No Brasil são escassos os estudos sobre essas doenças e não há disponibilidade de bases para estimar a magnitude desse problema. Assim, tornou-se oportuno o estudo nesta área em uma região considerada pólo industrial do mobiliário, que pudesse proporcionar informações fundamentais para o entendimento dos sintomas respiratórios entre trabalhadores da indústria do mobiliário. O objetivo foi avaliar a prevalência de sintomas respiratórios entre trabalhadores formais das indústrias moveleiras, expostos à poeira de madeira, tintas e vernizes, da cidade de Votuporanga e região. Foi realizado um estudo transversal, em 499 trabalhadores das indústrias do setor mobiliário que estavam expostos à poeira de madeira, tintas e/ou vernizes por no mínimo um ano, sem infecções respiratórias referidas e que concordaram em participar da pesquisa após assinado consentimento livre e esclarecido. Foi aplicado o questionário inicial, InternationaL Study of Asthma and Allergies in Childhood (ISAAC) para a detecção de manifestações respiratórias e atopia, questionário complementar para consumo tabágico e história ocupacional. Nos sintomáticos foi aplicado o British Medical Research Council (MRC) e realizado espirometria com prova farmacológica e no grupo controle MRC e espirometria pré e pós broncodilatador e entre os controles sem a prova farmacodinâmica. Para comparação entre o grupo sintomático e o controle, foi utilizado teste t de Student para grupos independentes, correlação de Pearson para as variáveis espirométricas e tempo de exposição; qui-quadrado para observação de associação de tabagismo e sintomas, e entre função pulmonar e sintomas. Os trabalhadores tinham média de idade entre 32,8 ±9,44, e 77,2% eram do sexo masculino e 22,8% do sexo feminino, 351 não fumantes, 53 fumantes e 95 ex-fumantes; o tempo médio de exposição foi, em anos, de 8,42 ±8,09, quanto ao setor de exposição 331(66,3) trabalhavam na marcenaria, 97(19,4%) no acabamento e 71(14,2%) na pintura; do total de trabalhadores 5,6% referiram sintomas respiratórios atuais, 16% referiram rinoconjuntivites e 8,4% eczema de pele. Os sibilos e a dispnéia de grau leve foram observados no grupo sintomático quando aplicado o questionário MRC. A variável espirométrica FEF25-75% se correlacionou com o tempo de exposição do trabalhador e não houve associação entre função pulmonar e sintomas. A prevalência de sintomas respiratórios foi de 5,6% entre os trabalhadores do setor moveleiro e observou-se comprometimento das pequenas vias aéreas entre os sintomáticos / Abstract: The occupational asthma, pneumoconioses and granulomatosis diseases are considered the main respiratory illness related with occupational exposure. In developed countries, they are well documented in databases of epidemiological surveillance that allow a detailed analysis of the morbid-mortality. In Brazil, the researches about these diseases are rare and there is not availability of bases to estimate the magnitude of this problem. This way, it became appropriate research in this area and in a region considered important industrial center of furniture. It could provide essential information for the understanding of respiratory symptoms among those workers. Objective to evaluate the prevalence of respiratory symptoms among formal workers of the furniture industries; exposed to the wood dust, paints and varnish, from the city of Votuporanga and throughout the region. A cross-sectional study to evaluate workers from the furniture industries that were expose to wood dust, paints and-or varnish at least one year, without respiratory infections mentioned and they agreed in participate of the research after they have been explained. It was applied the initial questionnaire, ISAAC for detection of respiratory manifestation and atopic diseases; complementary questionnaire smoking consuptionto the history and nicotine charge and the final questionnaire of occupational history. To the symptomatic individuals was applied the MRC and realized spirometry pre and post Bd in the symptomatic grup and in the control group without pharmacologic teste. To comparison between the symptomatic group and the control group was used t test of Student to the independent groups, Pearson's correlation for the spirometric variables and time of exposure and qui-squared to observation of association of tobaccoism and symptoms and between pulmonary function and symptoms. 499 were evaluated worker, on average, the age of 32.8 ± 9.44, and 77.2% male and 22.8 female; 351 non-smoking, 53 smoke and 95 ex-smokers, the average of exposure time was of 8.42 ± 8.09 years, 331(66.3) worked in the carpentry, 97(19.4%) polishing and 71(14.2%) painting section; 5.6% of total workers reported present respiratory symptoms, 16% reported rhino-conjunctivitis and 8.4% reported eczema. A light whistle and dyspnea were observed in the symptomatic group when applied the MRC questionnaire. The spirometric variable FEF25-75% correlated with time of exposure and there was not association between pulmonary function and symptoms. The prevalence of respiratory symptoms was 5.6% among workers and was observed probable small airway diseases / Doutorado / Saude Coletiva / Mestre em Saude Coletiva

Sua história natural e o real risco à função renal foram pouco estudados. Objetivo: Avaliar o impacto do cálculo ureteral silencioso sobre a função renal antes a após o tratamento, procurando por fatores preditivos de uma melhor evolução. Material e Método: O cálculo ureteral silencioso foi definido como aquele em que o paciente não apresentava nenhum sintoma subjetivo ou objetivo a ele relacionado. Os pacientes com cálculo ureteral silencioso foram prospectivamente incluídos no estudo, sendo avaliados com 99mTc-DMSA, creatinina sérica (Cr), ritmo de filtração glomerular (RFG) e ultrassonografia (USG) no pré-tratamento, três e 12 meses após o mesmo. Pacientes que receberam tratamento fora de nossa instituição e aqueles com avaliação perioperatória incompleta foram excluídos. A análise estatística incluiu os testes de ANOVA, Qui-quadrado/Fisher, e regressão logística/múltipla. O nível de significância foi estabelecido em p<0,05. Resultados: Entre jan/2006 e jan/2014, 26 pacientes com cálculo ureteral silencioso, correspondendo a 2,1% de todos os cálculos ureterais tratados, preencheram os critérios de inclusão do estudo. Treze pacientes eram do sexo feminino, com idade média de 59,3 ± 11,3 anos. O diagnóstico do cálculo foi relacionado a uma causa urológica em 14 (53,8%) casos. O diâmetro e densidade média dos cálculos era de 11,8 ± 2,8 mm e 1201 ± 272 UH, respectivamente. Apenas dois pacientes não apresentavam hidronefrose ao USG inicial e a espessura média do parênquima renal era 10,7 ± 4,1 mm. Os valores médios pré-operatórios de Cr, RFG e 99mTc-DMSA foram 1,24 ± 0.87 mg/dl, 72,5 ± 25.2 mL/min e 33,4 ± 16,7%, respectivamente. Vinte (77%) pacientes apresentavam 99mTc-DMSA < 45% no exame inicial. Regressão múltipla revelou que idade (p=0,041) e espessura do parênquima renal (p=0,001) predizem o valor do 99mTc-DMSA inicial. Quando comparados com os valores pré-operatórios, a Cr (p=0,89), o RFG (p=0,48) e a função renal ao 99mTc-DMSA (p=0,19) permaneceram inalterados com três e 12 meses após o tratamento. A hidronefrose apresentou melhora três meses após o tratamento (p < 0,01), mas manteve-se inalterada no período entre três e 12 meses (p=0,06). Nenhuma variável pré-operatória foi capaz de prever uma variação > 5% do 99mTc-DMSA entre pré e pós-operatório, sendo que o tamanho do cálculo (p=0,12) e tempo para tratamento (p=0,15) tiveram influência marginal. Conclusão: O cálculo ureteral silencioso está associado à diminuição da função renal e algum grau de hidronefrose já ao diagnóstico. Idade, espessura do parênquima renal e grau de hidronefrose predizem o valor inicial do 99mTc-DMSA. Enquanto a hidronefrose regride após a remoção do calculo, a função renal se mantém inalterada. Nenhum fator conseguiu predizer significativamente a evolução da função renal ao 99mTc-DMSA doze meses após o tratamento / Introduction: Ureteral stones may be asymptomatic in 0.3-5.3% of patients. The natural history and the disease influence on renal function have been poorly studied. Objective: to evaluate the impact of silent ureteral stone on renal function before and after treatment, searching for predictive factor of better outcomes. Material and Method: A ureteral stone was defined as silent if the patient had no subjective/objective symptoms related to the calculus. Patients with a silent ureteral stone were prospectively enrolled in the study. Patients were evaluated with 99mTc-DMSA scintigraphy, serum creatinine (Cr), Cr clearance (CrCl) and ultrasound (USG) pre and post-operatively on months three and 12. Patients treated outside our institution or with incomplete perioperative evaluation were excluded. ANOVA, Chi-square/Fisher test, and regression analysis were used. Significance was set at p < 0.05. Results: Between Jan/06-Jan/14, 26 patients with silent ureteral stones met our inclusion criteria, comprising 2.1% of all ureteral stones treated at our institution. Half of patients were female, mean age was 59.3 ± 11.3 years-old. Stone diagnosis was related to a urological cause in 14 (53.8%) cases. Mean stone diameter and density were 11.8 ± 2.8 mm and 1201 ± 272 HU, respectively. Only two patients had no hydronephrosis at initial USG evaluation and mean renal parenchyma thickness was 10.7 ± 4.1mm. Mean preoperative Cr, CrCl and 99mTc-DMSA were 1.24 ± 0.87 mg/dL, 72.5 ± 25.2 mL/min and 33.4 ± 16.7%, respectively. Twenty (77%) patients had 99mTc-DMSA < 45% at initial examination. Multiple regression revealed age (p=0.041) and renal parenchyma thickness (p=0.001) to predict initial 99mTc-DMSA. When compared to preoperative values, Cr (p=0.89), CrCl (p=0.48) and 99mTc-DMSA (p=0.19) remained unaltered three and 12 months postoperatively. Hydronephrosis improved from before to three months after treatment (p < 0.01), but remained unchanged from three to 12 months (p=0.06). No preoperative variable was able to predict a > 5% variation on 99mTc-DMSA from pre to postoperative periods, though stone size (p=0.12) and time to treatment (p=0.15) had a marginal influence. Conclusion: Silent ureteral stones are associated with decreased renal function and hydronephrosis already at diagnosis. Age, renal parenchyma thickness and degree of hydronephrosis predict initial 99mTc-DMSA. Hydronephrosis tends to diminish after stone removal, while renal function remains stable. No preoperative factor significantly predicted renal function progression twelve months postoperatively

Orientador: Anita Liberalesso Neri / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T18:29:32Z (GMT). No. of bitstreams: 1 Pinto_JulianaMartins_M.pdf: 1927683 bytes, checksum: b8702e2320c8c9352c95804216817a08 (MD5) Previous issue date: 2012 / Resumo: Objetivo: Este estudo teve como objetivo estudar relações entre variáveis sociodemográficas, doenças crônicas, sinais e sintomas, força de preensão manual, velocidade da marcha, participação social e satisfação global e referenciada a domínios em idosos da comunidade. Métodos: 2.472 idosos sem déficit cognitivo sugestivo de demência foram entrevistados sobre características sociodemográficas, condições de saúde, atividades avançadas de vida diária de natureza social e satisfação, e foram submetidos a medidas objetivas de força de preensão palmar e velocidade de marcha. Resultados: A idade média foi 72,2 '+ ou -' 5,5 anos e a renda média, 3,9 '+ ou -' 4,9 SM; 65,7% dos idosos eram mulheres, que apresentaram mais doenças e pior desempenho funcional, assim como os octogenários e os mais pobres. Foi observada maior participação social entre as mulheres do que entre os homens. Houve correlação entre desempenho funcional e participação social. Maior renda relacionou-se à maior satisfação com a memória, com a capacidade de solucionar problemas, com os serviços de saúde e com os meios de transportes. Associaram-se à baixa satisfação global ter três ou mais doenças (OR=2,14), problemas de memória (OR=1,76), baixa participação social (OR=1,73), baixa força de preensão palmar, baixa velocidade da marcha (OR=1,69), incontinência urinária (OR=1,54) e quedas (OR=1,34). Conclusão: Condições de saúde, desempenho funcional e participação social interagem na velhice e influenciam o bem-estar subjetivo, de modo que é importante intervir nos aspectos modificáveis dessas relações para favorecer a qualidade de vida e o bem-estar dos idosos / Abstract: Objective: This study was aimed at investigating relationships between sociodemographic variables, chronic diseases, signs and symptoms, grip strength, gait speed, social participation and life satisfaction and domain referenced satisfaction. Methods: 2,472 elderly people without cognitive impairment suggestive of dementia were interviewed about sociodemographic characteristics, health conditions, social advanced activities of daily living, global and domain referenced satisfaction, and had their grip strength and gait speed submitted to objective measurement. Results: Mean age of the sample was 72.2 '+ or -' 5.5 years and mean income was 3.9 '+ or -' 4.9 SM; 67% of the participants were women, who had more diseases, worse functional performance and greater social participation than men. The octogenarian and the poorest had worse functional performance and reduced social participation. It was observed correlation between functional performance and social participation. Higher income was related to satisfaction with memory, functional ability, health services and transports. Low satisfaction was associated with having three or more chronic diseases (OR = 2.14), memory problems (OR = 1.76), low social participation (OR = 1.73), low grip strength, low gait speed (OR = 1.69), urinary incontinence (OR = 1.54) and falls (OR = 1.34). Conclusion: Health, functional performance and social participation interact with subjective well-being, so it is important to intervene on modifiable aspects of these relations to promote quality of life and well being of the elderly / Mestrado / Gerontologia / Mestra em Gerontologia

The purpose of this work was to examine biological mechanisms and symptom outcomes of illness uncertainty and psychological stress in Parkinson’s disease (PD). Parkinson’s disease is a chronic, progressive neurodegenerative disorder characterized by complex symptoms that fluctuate in onset, severity, level of disability, and responsiveness to treatment. In addition to characteristic motor symptoms of tremor, rigidity, bradykinesia, and postural instability, a considerable number of individuals with PD also experience debilitating pain, fatigue, and medication-induced motor complications of dyskinesia, dystonia, and on-off phenomena. The unpredictable nature of PD symptoms and motor complications coupled with the inability to halt or slow disease progression may result in uncertainty and psychological stress. Evidence is lacking regarding biological mechanisms and symptom outcomes of uncertainty and psychological stress in PD. As such, 80 men and women diagnosed with PD after the age of 49 were recruited to participate in this study. Data specific to characteristics that may contribute to uncertainty and psychobehavioral measures of uncertainty, appraisal, psychological stress, and symptom outcomes of motor symptoms, pain, and fatigue were collected. Biological measures of neuropeptide Y (NPY) and cytokines were obtained. The results revealed that participants perceived a moderate level of illness uncertainty. Uncertainty correlated significantly with motor symptoms, pain severity, and pain interference and predicted more severe pain severity and pain interference. Psychological stress correlated significantly with motor symptoms, pain severity, pain interference, and fatigue and predicted more severe symptoms across all outcomes. NPY was positively correlated with threat appraisals and psychological stress. Cytokines were below the level of detection in this sample, and not used beyond descriptive analyses. In summary, this study found uncertainty and psychological stress contributed to more severe symptom outcomes in PD. This knowledge may be used to guide future studies aimed at further elucidating biobehavioral symptom and health outcomes of uncertainty and psychological stress in PD. It will also facilitate the development of interventions specifically targeted to uncertainty and psychological stress for the ultimate purpose of improving symptom management, health outcomes, and disease progression in PD.

The opportunistic fungus, Aspergillus fumigatus, is a leading cause of morbidity and mortality among the immunocompromised population. Experimental and clinical findings have established that phagocytic defenses are critical in the recognition and clearance of A. fumigatus. Previous studies found that Toll-like receptors (TLRs), specifically TLR2 and TLR4, were essential in the detection of the mold. Furthermore, one study found that mice deficient in TLR9 lived longer than their wild-type counterparts following challenge with A. fumigatus. We sought to determine the role of TLR9 during A. fumigatus infection. Our results show that A. fumigatus contains unmethylated CpG DNA, the natural ligand of TLR9. Furthermore, A. fumigatus DNA stimulates a potent pro-inflammatory response in mouse bone marrow derived dendritic cells (BMDCs) and human plasmacytoid dendritic cells (pDCs). A genome wide analysis showed that A. fumigatus DNA contains 87 human and 23 mouse putative immunostimulatory motifs. The response to A. fumigatus DNA is TLR9-dependent, as BMDCs from TLR9-/- mice were unresponsive to the fungal DNA. In addition, HEK293 cells cotransfected with human TLR9 and NFκB driven Luciferase conferred responsiveness to A. fumigatus CpG-rich sequences found in the fungal DNA. Our results show that TLR9 detects A. fumigatus DNA, resulting in the secretion of proinflammatory cytokines. While pDCs secrete IFNα in response to A. fumigatus DNA, these cells have been mainly described to play critical roles in the antiviral responses. The role of pDCs during fungal infections remains to be elucidated. Our data show that CD304+ peripheral blood pDCs challenged with A. fumigatus hyphae secrete large concentrations of IFNα and TNFα in response to infection. Furthermore, the response appears to be TLR9- independent. However, pDCs spread over the hyphae and inhibit fungal growth. Furthermore, pDCs undergo cell lysis upon incubation with A. fumigatus. The antifungal activity of the pDCs was retained in the cell lysates, suggesting that this response was mediated by an intracellular factor. Addition of exogenous Zn2+, but not Fe3+, partially restores hyphal growth. In addition, western blot of pDC lysates show that these cells have the Zn2+-binding protein calprotectin. Over 60% cell death is observed in the pDC population following a 2 hour incubation with A. fumigatus. The observed pDC cell death can be partially attributed to gliotoxin, as pDCs challenged with A. fumigatus stains deficient in production of the mycotoxin result in decreased pDC cytotoxicity. Furthermore, pDC cell death occurs independent of contact with the mold, confirming that pDC cell death is mediated by a secreted fungal factor. In addition, our results show that pDCs are required for the host response against A. fumigatus. Mice depleted of their pDCs are more susceptible to A. fumigatus infection than the control counterparts, suggesting that pDCs play a role in the antifungal response. Also, we observe a 5-fold increase in the pDC population in the lungs of infected mice. Therefore, the possibility of these cells playing a role in recruiting and communicating with other immune cells cannot be eliminated. Upon maturation, pDCs acquire characteristics of conventional DCs (cDCs) such as upregulation of major histocompatability complex (MHC) and becoming more phagocytic. Whether mature pDCs are involved in the detection of and responses against fungal pathogens remains to be determined. Here we show that mature pDC secrete IFNα and TNFα in response to A. fumigatus conidia as early as 6 hours post-challenge. While cytokine secretion of mature pDCs against A. fumigatus does not require opsonization, it requires for A. fumigatus being alive and growing. Furthermore, supernatants from conidial growth induced cytokine secretion by the mature pDCs. The work presented in this thesis establishes that the nucleic acids in A. fumigatus serve as a pathogen associated molecular pattern (PAMP) that can induce a TLR9- dependent response. Furthermore, I show that pDCs secrete cytokines and induce an antifungal response against A. fumigatus conidia and hyphae. While the pDC population in the blood appears to be small, our work shows that these cells could be intimately involved in the antifungal responses against A. fumigatus.

Bakgrund: Sepsis är en sjukdom där en infektion ger ett systemiskt inflammationssvar i kroppen. Symtombilden kan vara varierande och även ospecifik. Både incidensen och mortaliteten är hög i världen. Sjukdomen innebär stort lidande för patienterna både under den akuta sjukdomsfasen och i efterförloppet för de överlevande. Framtagna bedömningsinstrumenten grundar sig främst på patientens vitalparametrar, vilka nödvändigtvis inte är avvikande initialt. Genom en ökad kunskap om både subjektiva och objektiva värden har ambulanssjuksköterskan goda möjligheter att identifiera fler patienter med misstänkt sepsis prehospitalt. Syfte: Att beskriva kännetecken och symtom hos patienter med sepsis inom ambulanssjukvården.   Metod: En systematisk litteraturstudie gjord med en integrativ metod enligt Whittemore &amp; Knafl (2005) och en induktiv ansats. Resultatet baseras på 15 vetenskapliga artiklar med kvantitativ, kvalitativ och mixad metod.  Resultat: Resultatet visade att de subjektiva kännetecknen och de objektiva symtomen alla var viktiga delar som gav en helhetsbild av sepsis. Åtta subkategorier gav de två kategorierna En känsla av sjukdom och att inte vara sig själv och En kropp som sviker. De bildade sedan huvudkategorin Helhetsbilden av sepsis – kännetecken och symtom av betydelse.  Slutsats: Symtombilden vid sepsis kunde vara komplex och varierande. Patienterna beskrevs kunna ha kännetecken och symtom från alla kroppens organsystem. Patienterna var ofta mycket påverkade, hade ett stort lidande samt stor risk att avlida i sin sjukdom. / Background: Sepsis is a disease in which an infection produces a systemic inflammatory response in the body. The presentation of signs and symptoms can be varied and non-specific. Both the incidence and mortality are high in the world. The disease leads to great suffering for the patients both during the acute phase of the disease but also in the aftermath for the survivors. The assessment tools are mainly based on the patient's vital signs, which are not necessarily deviating initially. Through an increased knowledge of both subjective and objective parameters, the ambulance clinicians have good possibilities to identify more patients with suspected sepsis in the prehospital setting. Aim: To describe the signs and symptoms in patients with sepsis in the ambulance services. Method: A systematic literature review done with an integrative method according to Whittemore &amp; Knafl (2005) and an inductive approach. The result is based on 15 scientific papers with a variety of quantitative, qualitative and mixed methods. Results: The results showed that subjective signs and objective symptoms were important pieces of the overall picture of sepsis. 8 subcategories formed two categories A feeling of illness and not being oneself and A body that fails. These shaped the main category The overall picture of sepsis – signs and symptoms of significance. Conclusion: The presentation of sepsis could be complex and varied. Patients were described as having signs and symptoms from all the body's organ systems. The patients were often very affected, had a great deal of suffering and a high risk of dying from their disease.

Background:Lower back pain is one of the most common health-related complaints in the adult population. Thirty percent of Americans 65 years and older reported symptoms of lower back pain in 2004. With an aging population, the proportion of people over the age of 65 is expected to reach 20% by the year 2030. Because of this increase in older adults, lumbar spinal stenosis (LSS) associated with arthritic changes will also likely increase. In older adults, lower back pain is most often caused by degenerative lumbar spinal stenosis. Stenosis is the narrowing ofthe spinal canal, causing pressure on the nerve roots and is frequently treated surgically. Lumbar spinal stenosis is one of the most common reasons for back surgery in patients 65 years and older 2. However, risks associated with surgery increase with age 3-5 and older patients may choose non-surgical treatment for their lower back pain, including injection treatment. Injection treatment, usually consisting of anti-inflammatory medications and analgesics, has improved since the mid-1990's when fluoroscopic guidance was developed. Information about injection treatment for lower back pain is limited, especially in the older population. An extensive review of published literature regarding injection treatment revealed a paucity of information about older adults diagnosed with lumbar spinal stenosis. In this study, three aims were designed to gain more information about the effectiveness of injection treatment in older patients with lumbar spinal stenosis. In the first (retrospective) study, information about receipt of second injections and time between injections was collected to examine injection usage. In the second and third (prospective) studies, information about pain relief and functional return following injection treatment was collected to examine the effectiveness of injection treatment in patients age 60 and older diagnosed with lumbar spinal stenosis. To our knowledge, such results have not been repolted for this population in the literature. Objective:Injection treatment is a commonly used non-surgical procedure to alleviate lower back pain in older adults. However, older patients do not have enough information about how long pain relief will last after treatment or the amount of pain relief and functional return they will experience. These studies focused on three topics: 1) usage of injection treatment; 2) effectiveness of injection treatment on pain relief; 3) effectiveness of injection treatment on functional return. In addition, the variations of the effectiveness were examined by selected patient attributes. Methods:In a retrospective study, medical records of patients aged 60 years or older from a high volume dedicated spine center at the University of Massachusetts Memorial Hospital were retrospectively reviewed. This study included those diagnosed with degenerative LSS, who had not received an injection for lower back pain within six months, and whom were treated between June I, 2006 and May 31, 2007. In two prospective studies, patients scheduled for lumbar injection treatment between January 1 and June 30, 2008 were selected from the University of Massachusetts Memorial Hospital Spine Center. Selection criteria included patients age 60 and over, diagnosed with degenerative lumbar spinal stenosis and no previous lumbar injection within 6 months or lumbar surgery within 2 years. The Pain sub-score of the SF-36 questionnaire was used to measure pain at baseline and at one and three months post injection. The Physical Component Score (PCS) of the SF-36 questionnaire and the Oswestry Disability Index (ODI) were used to measure function at baseline and at one and three months post injection. Variations in longitudinal changes in scores by patient characteristics were analyzed in both unadjusted (univariate) analyses using one-way analysis of variance (ANOVA), and adjusted (multiple regression) analyses using linear mixed effects models. Results: In the retrospective cohort, the mean age of the cohort was 68, 64% were female, 59% were married, with a mean Body Mass index of 32 kg/m2. Of 92 eligible patients, 57% returned for a second injection within six months of the first. The mean number of months between injections was 4.8 for all patients, ranging from 1 to 22 months. When patient characteristics were examined, the only variable that showed a statistically significant difference was age. Patients aged 70 years and older were found to be 67% less likely to return for a second injection when compared to patients age 60-69 (OR=0.33 (0.12 - 0.94)p In the prospective cohort, information was collected on 62 patients. Mean Pain scores improved significantly from baseline to one month (14.1 points), and from baseline to three months (8.3 points). Post injection changes in Pain scores varied by Body Mass Index (BMI) and baseline emotional health. Based on a linear mixed effects model analysis, higher baseline emotional health, as measured by the SF-36 Mental Component Score (MCS>50), was associated with greater reduction in pain over three months when compared to lower emotional health (MCS Conclusion: Patients over age 70 do not return for repeat injection as frequently as patients age 60-69. In addition, each year a patient ages over age 60, they are 10% less likely to return for a repeat injection. Lower back pain in older adults with LSS is clinically significantly alleviated after injection treatment. In addition, injection treatment for LSS is associated with return of lost function needed for daily living activities in older adults. Pain relief and functional return varies by patient personal and clinical characteristics. Higher emotional health was associated with more pain relief and more functional return experienced over three months following injection treatment. Additional information is needed about why older patients do not return for second injections at the same rate as younger patients and how emotional health affects response to injection treatment in older adults.

Host cell attachment by pathogenic bacteria can play very different roles in the course of infection. The pathogenic spirochetes Borrelia hermsii and Borrelia burgdorferi sensu lato which cause relapsing fever and Lyme disease, respectively, are transmitted by the bite of infected ticks. After transmission, these spirochetes can cause systemic infection. Relapsing fever spirochetes remain largely in the bloodstream causing febrile episodes, while Lyme disease will often colonize a variety of tissues, such as the heart, joint and nervous system, resulting in a chronic multisystemic disorder. Borrelia species have the ability to bind to various cell types, a process which plays a crucial role in pathogenesis and may influence spirochetal clearance from the bloodstream. Colonization of multiple tissues and cell types is likely promoted by the ability to bind to components found in target tissues, and many B. burgdorferi adhesins have been shown to promote attachment to a wide variety of cells and extracellular matrix components. Different Lyme disease strains have been shown to preferentially colonize certain tissues, although the basis of this tissue tropism is not well understood. In this study we found that among different Lyme disease strains, allelic variation of the adhesin DbpA contributes to variation in its in vitro binding activities raising the possibility that this variation contributes to tissue tropism in vivo. In studying B. hermsii infection, we found evidence by both histological and fluorescence in situ hybridization (FISH) analysis of tissues that indicated that red blood cells were removed by tissue resident macrophages in infected mice. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream. Our findings indicate that host cell attachment play a key role in the establishment of Lyme disease infection, and in contrast contributes to the clearance of relapsing fever infection.

Chronic intake of alcohol can result in a range of pathology in the liver. Whilst the earliest changes observed with chronic ethanol, including the accumulation of lipid, or steatosis, are readily reversible upon cessation of alcohol consumption, longer exposure to ethanol may achieve more complex disease states including steatohepatitis, fibrosis, and cirrhosis that can cause irreversible damage and progress to fulminant hepatic failure. A key concept in the pathogenesis of alcoholic liver disease is that chronic ethanol primes the liver to increased injury through an interplay between hepatocytes and non-parenchymal cells, chiefly immune cells, of the liver. These relationships between hepatocytes and non-parenchymal cell types in alcoholic liver disease are reviewed in Chapter 1A. The Hypoxia Inducible Factors are a set of transcription factors that classically have been described as affecting a homeostatic response to conditions of low oxygen tension. Alcoholic liver disease is marked by increased hepatic metabolic demands, and some evidence exists for increased hepatic tissue hypoxia and upregulation of hypoxia-inducible factor mRNA with chronic alcohol. However, the biological significance of these findings is unknown. In Chapter 1B, we review the literature on recent investigations on the role of hypoxia inducible factors in a broad array of liver diseases, seeking to find common themes of biological function. In subsequent chapters, we investigate the hypothesis that a member of the hypoxia inducible- factor family, HIF1α, has a role in the pathogenesis of alcoholic liver disease. In Chapter 2, we establish a mouse model of alcoholic liver disease and report data confirming HIF1α activation with chronic ethanol. We demonstrate that HIF1α protein, mRNA, and DNA binding activity is upregulated in ethanol-fed mice versus pair-fed mice, and that some upregulation of HIF2α protein is observable as well. In Chapter 3, we utilize a mouse model of hepatocyte-specific HIF1α activation and demonstrate that such mice have exacerbated liver injury, including greater triglyceride accumulation than control mice. Using cre-lox technology, we introduce a degradation resistant mutant of HIF1α in hepatocytes, and after four weeks of ethanol feeding, we demonstrate that mice with the HIF1α transgene have increased liver-weight to body weight ratio and higher hepatic triglyceride levels. Additionally, several HIF1α target genes are upregulated. In Chapter 4, we examine the relationship between HIF1α activation and hepatic lipid accumulation using a recently published in vitro system, in which lipid accumulation was observed after treating Huh7 cells with the chemokine Monocyte Chemoattractant Protein-1 (MCP-1). We report that MCP-1 treatment induces HIF1α nuclear protein accumulation, that HIF1α overexpression in Huh7 cells induces lipid accumulation, and finally, that HIF1α siRNA prevents MCP-1 induced lipid accumulation. In Chapter 5, we use mouse models to investigate the hypothesis that suppression of HIF1α in hepatocytes or cells of the myeloid lineage may have differing effects on the pathogenesis of alcoholic liver disease. We find that ethanol-fed mice expressing a hepatocyte-specific HIF1α deletion mutant exhibit less elevation in liver-weight body ratio and diminished hepatic triglycerides versus wild-type mice; furthermore, we find that challenging these mice with lipopolysaccharide (LPS) results in less liver enzyme elevation and inflammatory cytokine secretion than in wild-type mice. In Chapter 6, we offer a final summary of our findings and some directions for future work.

Teachers in a New Jersey suburban high school noticed an increase in students' stress and anxiety associated with high-stakes testing, and they were struggling to find strategies and interventions to help. The purpose of this study was to investigate high school English and mathematics teachers' current knowledge, experiences, and perceptions about students' preparation and responses to high-stakes testing and to explore teachers' perceptions about teaching strategies they needed to reduce student test anxiety. Liebert and Morris's bidimensional components of anxiety, emotionality, and worry form the conceptual framework that guided this study. The research questions focused on teachers' perceptions about students' high-stakes testing readiness, students' testing behaviors, and teachers' training needs. A case study design was used to capture the insights of 12 high school English and math teachers through semistructured interviews and a focus group interview; a purposeful sampling process was used to select the participants. Emergent themes were identified through open coding, and the findings were developed and checked for trustworthiness through member checking, rich descriptions, and researcher reflexivity. The findings revealed that teachers recognize that students react in different ways to testing, that students who are prepared for the tests demonstrate greater confidence and less anxiety, and that teachers want more professional development specific to reducing students' anxiety and stress. A professional development project was created to provide teachers with strategies and approaches to prepare students for high-stress testing situations. This study has implications for positive social change by creating a structure to provide teachers with strategies for managing students' test anxiety.