Introduction: Analysis of urine from dogs and cats are an important method for diagnosingkidney and urinary tract diseases. Earlier studies have suggested that urine needs to be acidifiedbefore analysis of calcium and phosphorus to obtain a more reliable result. The acidification ismeant to dissolve urinary crystals which could affect the analysis. Aim: The aim of this study was to investigate if acidification of dog and cat urinary samples isnecessary for reliable analysis of calcium and phosphorus. The study also aimed to investigate ifacidification is possible after the freezing of urine, and also evaluate the stability of acidifiedurine and supernatant in -80 °C freezer. Material and method: Forty-four urinary samples, of which 38 were from dogs and 6 from cats,were collected. Each sample was divided into three aliquots; one aliquot was acidified directly,one aliquot was acidified after storage in the freezer, and the last aliquot was centrifuged and thesupernatant was collected. Calcium and phosphorus were analyzed with an automatic chemistryinstrument in all aliquots before and after storage in -80 °C. The presence of urinary crystals wasinvestigated through a microscope. Results and conclusion: The calcium and phosphorus concentration were not higher in acidifiedurine, so acidification does not seem to be required for analysis of calcium and phosphorus indog and cat urine. Acidification after storage of urine in the freezer gave similar results asacidification of fresh urine. Both supernatant and acidified urine were stable in -80 °C for at least 3 days.

Approved for public release, distribution is unlimited / The purpose of this thesis was to examine the feasibility of testing hair for illicit drug use in the United States Marines Corps. Specifically, the study determined the hair test's potential for detecting and deterring illicit drug use and abuse among Marines. In addition, the study estimated the potential costs of implementing hair tests and examined fairness concerns with regard to testing hair among ethnically diverse populations. The results indicate that the hair test would be more effective than the urinalysis at detecting a wide variety of illicit drugs, with the exception of marijuana. The increased effectiveness of the hair test is likely to enhance the level of deterrence currently sustained by the Marine Corps' urinalysis program. Costs associated with the implementation of hair test would be offset by the increase in detection of illicit drug use and drug dependence among enlisted recruits and officer candidates pursuing active duty military service. Enhanced deterrence levels among active duty personnel that are a consequence of implementing the hair test would result in additional cost savings. Finally, implementation of the hair test would not result in racial bias, but may amplify the existence of drug preferences among different races. / Major, United States Marine Corps

INTRODUÇÃO: O instrumento escolhido para coleta de informações em uma investigação científica tem de ser capaz de traduzir, com boa precisão, a realidade estudada. Neste estudo, foi analisado o desempenho de um questionário para avaliar o consumo de drogas na prisão confrontando o relato dos entrevistados com a análise toxicológica de urina. METODOLOGIA: Foi realizado um estudo observacional transversal em setembro de 2007, numa unidade prisional masculina, localizada no estado de São Paulo. Os detentos foram entrevistados e submetidos à coleta de urina para detecção qualitativa de canabinóides e de cocaína, utilizando análise por imunoensaio enzimático. Foram selecionadas duas questões; a primeira sobre uso de drogas e, a segunda, mais específica, que identifica o padrão de uso da maconha e da cocaína na prisão. Para avaliar a capacidade destas questões em identificar corretamente os indivíduos que usam drogas na prisão, foram comparadas as respostas com os resultados de exame de urina (padrão ouro) e calculadas a sensibilidade e a especificidade. Entrevistador, período em que foi realizada a entrevista, faixa etária dos entrevistados, tempo de presídio, situação prisional, relação existente entre o delito cometido e as drogas, duração da pena atual e o resultado das análises toxicológicas da urina foram escolhidos como fatores com potencial para interferir nos resultados. RESULTADOS: Participaram da pesquisa 337 detentos, com idade média de 30,4 anos, cumprindo pena média de 10,1 anos, que estão em média há 16,7 meses no presídio e que, em sua maioria não cometeram delitos relacionados a drogas (73,3%). A prevalência obtida pela análise toxicológica da urina foi de 61,4% para maconha e 7,7% para cocaína. Combinar as questões melhorou o desempenho do questionário. Dos 260 entrevistados identificados, pelo questionário, como usuários de drogas na prisão, 191 tiveram resultado positivo na análise toxicológica da urina e 69, resultado negativo. Dos 76 entrevistados identificados como não usuários de droga na prisão, 21 tiveram resultado positivo na análise toxicológica da urina e 55, resultado negativo (Sensibilidade=90,1% e Especificidade=44,1%). A prevalência para o uso de maconha na prisão, obtida a partir das entrevistas, foi de 77,4% e, para o de cocaína, de 8,8%. Os detentos que não cometeram crimes relacionados a drogas (p=0,011) e os com resultado positivo para a análise da urina para canabinóides (p=0,028) tiveram um desempenho melhor ao responder as questões relacionadas ao uso de cocaína. Os detentos mais novos consomem mais maconha na prisão (80,6%, p=0,000). Já os reincidentes (11,4%, p=0,017) e os que estão há mais tempo no presídio (17,3%, p=0,038) destacaram-se como os que consumem mais cocaína. Os detentos primários (11,3%, p=0,028) e os com resultado positivo na análise da urina para canabinóides (10,2%, p=0,009) apresentaram frequência maior de respostas dissociadas. Apresentaram frequência menor, os que cumprem pena entre 6,33 e 14,62 anos (3,4%, p=0,025). CONCLUSÕES: A concordância entre o relato de consumo de maconha e cocaína na prisão obtida pelo questionário e o resultado do exame toxicológico foi boa para as duas drogas. Combinar as respostas apareceu como uma forma de melhorar a sensibilidade do questionário. / INTRODUCTION: The instrument used for collection of information in scientific research must be able to translate with accuracy the reality under investigation. In this study, we investigated the performance of a questionnaire in assessing drug use in prison compared with toxicological analysis of urine. METHODS: A cross sectional observational study was conducted in September 2007, in a male inmate placed in the state of Sao Paulo. The prisoners were interviewed and underwent urine collection for the detection of cannabinoids and cocaine metabolites trough toxicological analysis (enzyme immunoassay). Two questions were selected, one about drug use in general, and a second one, which was more specific and used to identify the drug consumption pattern in prison. To assess the ability of these questions to correctly identify individuals who currently use drugs in prison, the responses were compared with the urine test (gold standard) and sensitivity and specificity rates were calculated. Interviewer characteristics, total period of interview, age of respondents, time in jail, penalties conditions, relationship between the offense and drug use, total penalty time and urinalysis were considered factors with the potential to affect the results. RESULTS: 337 prisoners completed the questionnaire and provided urine samples for the study. These subjects presented a mean age of 30.4 years, an average time spent in prison of 1 year and 16.7 months, 10.1 years of total penalty time and the majority of them have not committed crimes related to drugs (73.3%). The prevalence based on urine toxicological analysis was 61.4% for marijuana and 7.7% for cocaine. When the answers to the questions were combined to the toxicological results, the assessment for drug consumption trough the questionnaire was improved. Of the 260 respondents identified by the questionnaire as a drug user in prison, 191 presented positive results for toxicological analysis and 69 negative results. Of the 76 respondents identified as non-drug user in prison, 21 presented positive results for toxicological analysis and 55 negative (sensitivity=90.1% and specificity =44.1%). The prevalence of cannabis use in prison taking into account only the interviews was 77.4% and 8.8%, for marijuana and cocaine, respectively. Prisoners who have committed crimes related to drugs (p=0,011) and those with positive urinalysis for cannabinoids (p=0,028) performed better in answering questions related to cocaine use. The younger prisoners consumed more marijuana in prison (80.6%, p=0,000) than their older counterparts. Repeat offenders (11.4%, p=0,017) and those who are in prison for longer (17.3%, p=0,038) time stood out as those who consume more cocaine. First offenders (11.3%, p=0,028) and those with positive urinalysis for cannabinoids (10,2%, p=0,009) showed higher frequency of misleading answers and, less often, those who were serving time between 6.33 and 14.62 years (3.4%, p=0.025). CONCLUSIONS: The agreement between the reporting of marijuana and cocaine consumption in prison obtained by questionnaire with toxicological essay was adequate for both use in general and recent use. Combining responses appeared as a way to improve the sensitivity of the questionnaire.

Background The remarkably efficient mechanisms of the human body to maintain its core temperature of 37°C can be inadequate when harsh climatic conditions and excessive muscle movement lead to heat stress, dehydration and potential heat illness, ranging from minor symptoms such as fatigue to a potentially fatal heat stroke. Agricultural workers in the tropics are at high risk, which is expected to increase with climate change. Sugarcane harvesting in Costa Rica is largely done by cutting the cane with a machete, by temporary, sub-contracted workers who are often migrants and living in poverty. Sugarcane harvesters are known to be affected by an epidemic of chronic kidney disease of non-traditional origin, currently hypothesized to be related to working conditions. Objectives This work aimed to better understand and document sugarcane harvester exposure to heat and the health consequences of working under such conditions. Specific objectives were to 1) Document working conditions and heat in the Costa Rican sugarcane industry (Paper I); 2) Quantify heat stress exposures faced by sugarcane harvesters in Costa Rica (Paper II); and 3) Quantify the occurrence of heat stress symptoms and abnormal urinary parameters in sugarcane workers in Costa Rica (Papers III and IV). Methods This study took place over three harvests following a pilot assessment prior to the first harvest. Methods included direct observation, semi-structured interviews with 24 individuals and a participatory workshop with 8 harvesters about heat-related perceptions, exposures and coping strategies during the harvest and non-harvest season (Pilot). Researchers accompanied workers in the field during all three harvests, measured wet bulb globe temperature (WBGT) and conducted direct observation. Heat exposure assessment was conducted by calculating metabolic load, WBGT and corresponding limit values based on international guidelines (NTP and OSHA) (Harvest 1). Self-reported symptom data were collected using orally-administered questionnaires from 106 sugarcane harvesters and 63 non-harvesters from the same company (Harvest 2). Chi-square test and gamma statistic were used to evaluate differences in self-reported symptoms and trends over heat exposure categories. Finally, liquid consumption during the work shift was documented and urinalysis was conducted pre-and post-shift in 48 sugarcane harvesters on three days; differences were assessed with McNemar´s test on paired proportions (Harvest 3). Results Sugarcane workers in both the harvest and non-harvest seasons are exposed to heat, but particularly during the harvest season. Field workers have to carry their own water to the field and often have no access to shade. Some plantworkers are also exposed to intense heat. The metabolic load of sugarcane harvesting was determined to be 261 W/m2. The corresponding threshold value is 26 ◦C WBGT, above which workers should decrease work load or take breaks to avoid the risk of heat stress. Harvesters in this study were at risk of heat stress as early as 7:15 am on some mornings and by 9:00 am on all mornings. After 9:15 am, OSHA recommendations would require that harvesters only work at full effort 25% of each hour to avoid heat stress. Heat and dehydration symptoms at least once per week were experienced significantly more frequently among harvesters than non-harvesters (p<0.05): headache, tachycardia, fever, nausea, difficulty breathing, dizziness, and dysuria. Percentages of workers reporting heat and dehydration-related symptoms increased over increasing heat exposure categories. Total liquid consumed ranged from 1 to 9 L and differed over days (median 5.0, 4.0 and 3.25 on days 1, 2 and 3 respectively). On these same days, the two principle indicators of dehydration: high USG (≥1.025) and low pH (≤5), changed significantly from pre to post-shift (p=0.000 and p=0.012).Proportions of workers with proteinuria >30 mg/dL, and blood, leucocytes and casts in urine were also significantly different between pre and post-shift samples at the group level, but unlike USG and pH, these alterations were more frequent in the pre-shift sample. 85% of workers presented with proteinuria at least once and 52% had at least one post-shift USG indicative of dehydration. Conclusion Heat exposure is an important occupational health risk for sugarcane workers according to international standards. A large percentage of harvesters experience symptoms consistent with heat exhaustion throughout the harvest season. Pre and post-shift urine samples demonstrate dehydration and other abnormal findings. The results of this study demonstrate an urgent need to improve working conditions for sugarcane harvesters both under current conditions and in adaptation plans for future climate change.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-30T21:03:32Z No. of bitstreams: 1 Maria Goreth. Prevalência de Resistência a Antimicrobianos e.pdf: 781360 bytes, checksum: f2b7c7040f7e8670e3df7e6c9397283d (MD5) / Made available in DSpace on 2012-07-30T21:03:32Z (GMT). No. of bitstreams: 1 Maria Goreth. Prevalência de Resistência a Antimicrobianos e.pdf: 781360 bytes, checksum: f2b7c7040f7e8670e3df7e6c9397283d (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / Estimar a prevalência de resistência a antimicrobianos em isolados de Escherichia coli e avaliar o desempenho dos testes laboratoriais rápidos para diagnóstico das infecções não complicadas do trato urinário adquiridas na comunidade. Métodos: Este trabalho foi dividido em dois estudos, no primeiro para avaliar o perfil de susceptibilidade a antimicrobianos, foi avaliada uma amostra consecutiva de 411 isolados de E. coli procedentes de pacientes com Infecção do Trato Urinário (ITU) atendidos numa unidade de emergência de hospital privado no período de julho de 2008 a julho 2009. A identificação e os testes de susceptibilidade a antimicrobianos utilizou o sistema automatizado WalkAway – Microscan® (Siemens - Califórnia). No segundo estudo, para avaliar o desempenho dos testes rápidos para diagnóstico de ITU, além dos casos de ITU do primeiro estudo, foram incluídos 411 pacientes sem ITU atendidos no mesmo local e período. Os testes rápidos estudados, microscopia direta (Gram), teste de piúria e teste do nitrito, foram realizados conforme respectivos protocolos, realizando os controle de qualidade de todas as etapas. Resultados: A amostra de casos de ITU era formada por 342 (83%) adultos e 69 (17%) crianças. A distribuição por sexo entre adultos e crianças, mostrou predominância dos episódios no sexo feminino (85%). Dos 22 antibióticos testados, a maior prevalência de resistência foi encontrada para ampicilinasulbactam (41%), ampicilina (49%), cefalotina (33%) e sulfametoxazol-trimetoprim (36%), além disso, observamos uma inusitada taxa de resistência à ciprofloxacina (9%). Quarenta e dois por cento dos isolados de E. coli apresentaram resistência a três ou mais drogas. Houve um aumento na taxa de resistência à cefalotina, em comparação com estudo realizado na mesma cidade em 2001-2002. Não foram observadas variações significativas nas taxas de resistência para a maioria dos demais antimicrobianos. Dentre os testes rápidos avaliados a detecção de piúria apresentou a maior sensibilidade (95%; IC95%: 92-97%) e a menor especificidade (66%; IC95%: 61-70%). O teste de nitrito apresentou a maior especificidade (99%; IC95%: 98-100%) e a menor sensibilidade (45%; IC95%: 40-50%). No geral, o teste com maior acurácia foi a microscopia direta (84%; IC95%: 79-88%), seguido da detecção de piúria (80%; IC95%: 77-83%). O teste de nitrito teve o maior valor preditivo positivo (VPP) e o teste de piúria o maior valor preditivo negativo (VPN). Os testes rápidos apresentaram concordância modesta e a combinação de resultados positivos com maior VPP foi obtida com os testes de nitrito e microscopia direta (Gram). Enquanto a combinação de microscopia direta (Gram) e piúria negativos tiveram o maior VPN. Conclusão: Os isolados de E. coli apresentaram elevadas taxas de resistência a: ampicilina, ampicilina-sulbactam, sulfametoxazol-trimetoprim e cefalotina, limitando a indicação desses antibióticos para tratamento empírico das ITUs adquiridas na comunidade. Apesar da variação nos valores de sensibilidade e especificidade dos testes rápidos avaliados, o teste de nitrito positivo e o teste de piúria negativo apresentaram a melhor taxa de acerto para confirmar ou afastar o diagnóstico de ITU, respectivamente. Embora, os testes rápidos possam ser considerados úteis no diagnóstico das ITU-AC, a urocultura ainda é o teste laboratorial definitivo para diagnóstico de ITU. / To estimate the prevalence of antimicrobial resistance in Escherichia coli isolates Escherichia coli and evaluate the performance of laboratory tests for fast diagnosis of uncomplicated community acquired urinary tract infections. Methods: This work was divided into two studies; first to evaluate the profile of antimicrobial resistance we evaluated a consecutive sample of 411 isolates of E. coli from patients with urinary tract infection (UTI) attending an emergency unit of a private hospital from July 2008 to July 2009. The identification and antimicrobial susceptibility testing used the automated Walkaway - Microscan ® (Siemens - California). In the second study, to evaluate the performance of quick tests for diagnosis of UTI, apart from cases of UTI in the first study, we included 411 patients without UTI treated at the same place and period. The quick tests studied, direct microscopy (Gram), pyuria and nitrite were performed according to the respective protocols, quality control measures were performed in all stages. Results: The sample consisted of 342 (83%) adults and 69 (17%) children. The gender distribution showed that a greater number of episodes occurred in females (85%). Of 22 antibiotics tested, the highest prevalence of resistance was found for ampicillinsulbactam (41%), ampicillin (49%), cephalothin (33%) and trimethoprimsulfamethoxazole (36%), and we also noticed an unusual rate of resistance to ciprofloxacin (9%.) Forty-two percent of the isolates of E. coli were resistant to three or more drugs. There was an increase in the rate of resistance to cephalosporins, compared with a study conducted in the same city in 2001-2002. There were no significant variations in rates of resistance to most other antibiotics. Among the quick tests evaluated, the detection of pyuria had the highest sensitivity (95%, 95% CI: 92- 97%) and the lowest specificity (66%, 95% CI: 61-70%). The nitrite test had the highest specificity (99%, 95% CI: 98-100%) and the lowest sensitivity (45%, 95% CI: 40-50%). Overall, the most accurate test was the direct microscopy (84%, 95% CI: 79-88%), followed by the detection of pyuria (80%, 95% CI: 77-83%). The nitrite test had the highest positive predictive value (PPV) and the pyuria test the highest negative predictive value (NPV). Rapid tests showed modest agreement, the combination of positive results with the highest PPV was obtained from the tests of nitrite and direct microscopy (Gram), while the combination of direct microscopy (Gram) and negative pyuria had the highest NPV. Conclusion: E. coli isolates showed high rates of resistance to: ampicillin, ampicillinsulbactam, trimethoprim-sulfamethoxazole and cephalosporins, limiting the indication of these antibiotics for empirical treatment of community acquired UTIs. Despite the variation in sensitivity and specificity of the rapid tests evaluated, a positive nitrite test and a negative pyuria test showed the highest likelihood to confirm or exclude the diagnosis of UTI, respectively. Although rapid tests might be considered useful in the diagnosis of community acquired UTI, urine culture is still the definitive laboratory test for diagnosis of UTI.

INTRODUÇÃO: O instrumento escolhido para coleta de informações em uma investigação científica tem de ser capaz de traduzir, com boa precisão, a realidade estudada. Neste estudo, foi analisado o desempenho de um questionário para avaliar o consumo de drogas na prisão confrontando o relato dos entrevistados com a análise toxicológica de urina. METODOLOGIA: Foi realizado um estudo observacional transversal em setembro de 2007, numa unidade prisional masculina, localizada no estado de São Paulo. Os detentos foram entrevistados e submetidos à coleta de urina para detecção qualitativa de canabinóides e de cocaína, utilizando análise por imunoensaio enzimático. Foram selecionadas duas questões; a primeira sobre uso de drogas e, a segunda, mais específica, que identifica o padrão de uso da maconha e da cocaína na prisão. Para avaliar a capacidade destas questões em identificar corretamente os indivíduos que usam drogas na prisão, foram comparadas as respostas com os resultados de exame de urina (padrão ouro) e calculadas a sensibilidade e a especificidade. Entrevistador, período em que foi realizada a entrevista, faixa etária dos entrevistados, tempo de presídio, situação prisional, relação existente entre o delito cometido e as drogas, duração da pena atual e o resultado das análises toxicológicas da urina foram escolhidos como fatores com potencial para interferir nos resultados. RESULTADOS: Participaram da pesquisa 337 detentos, com idade média de 30,4 anos, cumprindo pena média de 10,1 anos, que estão em média há 16,7 meses no presídio e que, em sua maioria não cometeram delitos relacionados a drogas (73,3%). A prevalência obtida pela análise toxicológica da urina foi de 61,4% para maconha e 7,7% para cocaína. Combinar as questões melhorou o desempenho do questionário. Dos 260 entrevistados identificados, pelo questionário, como usuários de drogas na prisão, 191 tiveram resultado positivo na análise toxicológica da urina e 69, resultado negativo. Dos 76 entrevistados identificados como não usuários de droga na prisão, 21 tiveram resultado positivo na análise toxicológica da urina e 55, resultado negativo (Sensibilidade=90,1% e Especificidade=44,1%). A prevalência para o uso de maconha na prisão, obtida a partir das entrevistas, foi de 77,4% e, para o de cocaína, de 8,8%. Os detentos que não cometeram crimes relacionados a drogas (p=0,011) e os com resultado positivo para a análise da urina para canabinóides (p=0,028) tiveram um desempenho melhor ao responder as questões relacionadas ao uso de cocaína. Os detentos mais novos consomem mais maconha na prisão (80,6%, p=0,000). Já os reincidentes (11,4%, p=0,017) e os que estão há mais tempo no presídio (17,3%, p=0,038) destacaram-se como os que consumem mais cocaína. Os detentos primários (11,3%, p=0,028) e os com resultado positivo na análise da urina para canabinóides (10,2%, p=0,009) apresentaram frequência maior de respostas dissociadas. Apresentaram frequência menor, os que cumprem pena entre 6,33 e 14,62 anos (3,4%, p=0,025). CONCLUSÕES: A concordância entre o relato de consumo de maconha e cocaína na prisão obtida pelo questionário e o resultado do exame toxicológico foi boa para as duas drogas. Combinar as respostas apareceu como uma forma de melhorar a sensibilidade do questionário. / INTRODUCTION: The instrument used for collection of information in scientific research must be able to translate with accuracy the reality under investigation. In this study, we investigated the performance of a questionnaire in assessing drug use in prison compared with toxicological analysis of urine. METHODS: A cross sectional observational study was conducted in September 2007, in a male inmate placed in the state of Sao Paulo. The prisoners were interviewed and underwent urine collection for the detection of cannabinoids and cocaine metabolites trough toxicological analysis (enzyme immunoassay). Two questions were selected, one about drug use in general, and a second one, which was more specific and used to identify the drug consumption pattern in prison. To assess the ability of these questions to correctly identify individuals who currently use drugs in prison, the responses were compared with the urine test (gold standard) and sensitivity and specificity rates were calculated. Interviewer characteristics, total period of interview, age of respondents, time in jail, penalties conditions, relationship between the offense and drug use, total penalty time and urinalysis were considered factors with the potential to affect the results. RESULTS: 337 prisoners completed the questionnaire and provided urine samples for the study. These subjects presented a mean age of 30.4 years, an average time spent in prison of 1 year and 16.7 months, 10.1 years of total penalty time and the majority of them have not committed crimes related to drugs (73.3%). The prevalence based on urine toxicological analysis was 61.4% for marijuana and 7.7% for cocaine. When the answers to the questions were combined to the toxicological results, the assessment for drug consumption trough the questionnaire was improved. Of the 260 respondents identified by the questionnaire as a drug user in prison, 191 presented positive results for toxicological analysis and 69 negative results. Of the 76 respondents identified as non-drug user in prison, 21 presented positive results for toxicological analysis and 55 negative (sensitivity=90.1% and specificity =44.1%). The prevalence of cannabis use in prison taking into account only the interviews was 77.4% and 8.8%, for marijuana and cocaine, respectively. Prisoners who have committed crimes related to drugs (p=0,011) and those with positive urinalysis for cannabinoids (p=0,028) performed better in answering questions related to cocaine use. The younger prisoners consumed more marijuana in prison (80.6%, p=0,000) than their older counterparts. Repeat offenders (11.4%, p=0,017) and those who are in prison for longer (17.3%, p=0,038) time stood out as those who consume more cocaine. First offenders (11.3%, p=0,028) and those with positive urinalysis for cannabinoids (10,2%, p=0,009) showed higher frequency of misleading answers and, less often, those who were serving time between 6.33 and 14.62 years (3.4%, p=0.025). CONCLUSIONS: The agreement between the reporting of marijuana and cocaine consumption in prison obtained by questionnaire with toxicological essay was adequate for both use in general and recent use. Combining responses appeared as a way to improve the sensitivity of the questionnaire.

Diabetic nephropathy (DN) is one of the leading causes of end stage renal disease (ESRD) in western world and has a trend to spread in developing countries. Pathogenesis of DN is not fully elucidated. Studies of recent years showed that podocyte loss and activation of the rennin-angiotensin system (RAS), especially intra-renal RAS, played important roles in this process. Although renal biopsy is currently the most common way used to determine the expression pattern of podocyte and RAS associated molecules in DN, this invasive procedure has its own risk and is not practical for serial monitoring. We hypothesized that measurement of messenger ribonucleic acid (mRNA) expression of related genes in the urinary sediment might be a useful way to assess the severity of DN. / Firstly, we found that urinary mRNA expressions of podocyte-associated molecules nephrin, podocin, synaptopodin, Wilm's tumor-1 (WT-1) and alpha-actinin-4 were higher in patients with DN than in healthy controls, and urinary nephrin, podocin and synaptopodin expression was related to proteinuria and baseline renal function. In addition, there was a close relationship between urinary mRNA expression of type 2 angiotensin converting enzyme (ACE2), a key element of RAS, and the degrees of proteinuria, renal function and rate of decline of glomerular filtration rate (GFR). Urinary mRNA expression of ACE also inversely correlated with the rate of renal function decline. / In the next step, we studied the change in urinary mRNA expression of nephrin, podocin, synaptopodin, ACE and ACE2 in patients with DN treated with angiotensin converting enzyme inhibitor (ACEI) and addition of angiotensin receptor blocker (ARB). We found that urinary mRNA expression of podocin, synaptopodin and propably nephrin increased with disease progression, and percentage change in urinary podocin expression negatively correlated with rate of decline of GFR. Furthermore, serial measurement of urinary expression of nephrin and possibly synaptopodin may reflect therapeutic response to ARB in these patients. Urinary mRNA expression of ACE and ACE2, however, remained unchanged during the study duration and did not correlate with therapeutic response. / In this series of work, we investigated (i) the relation between the gene expression profile of podocyte-associated molecules and RAS related molecules in the urinary sediment and the severity of DN, including clinically defined parameter of disease severity, histological scarring, and the degree of intra-renal podocyte loss, (ii) the relation between urinary and intra-renal gene expression of patients with DN, (iii) the application of urinary gene expression on the monitoring of disease progression and therapy response of DN. The urinary mRNA expression of related genes was quantified by real-time quantitative polymerase chain reaction (RT Q-PCR). The intra-renal mRNA expression of related genes was studied from the histologic specimens of kidney biopsy by laser catapult microdissection (LCM) and RT Q-PCR. The degree of renal scarring was determined by morphometric analysis. Glomerular podocyte number was determined by stereological study on serial sections of renal biopsy specimen. / Taken together, our results suggest that although urinary mRNA expression of podocyte and RAS associated molecules is not related to intra-renal expression, urinary expression has the potential to be used as a non-invasive tool to assess the severity and progression of DN, and serial measurements of urinary gene expression of podocyte associated molecules may be used to reflect therapy response for patients with DN. Our findings also indicate that the information from urinary gene expression is supplementary to, but not a surrogate of, the data obtained from renal biopsy. / We then examined the relation between urinary gene expression and histological changes in the kidney. We found that urinary WT-1 expression correlated with the degree of kidney fibrosis. Unlike intra-renal expression, urinary mRNA expression of podocyte associated molecules did not correlate with glomerular podocyte number. There was also no association between urinary and intra-renal mRNA expression. / Wang, Gang. / Adviser: Cheuk Chen Szeto. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3423. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 156-180). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

This was a retrospective study of a community-based methadone maintenance treatment (MMT) program in Toronto. Participants (N = 170) were federally sentenced adult male offenders admitted to this voluntary program between 1997 and 2009 while subject to community supervision following incarceration. The primary investigation examined correlates of treatment responsivity, with principal outcome measures including MMT clients’ rates of: (i) illicit drug use; and (ii) completion of conditional (parole) or statutory release (SR). For a subset (n = 74), recidivism rates were examined after a 9-year interval. Findings included strong convergent evidence from logistic regression and ROC analyses that an empirically and theoretically derived set of five variables was a stable and highly significant (p <.001) predictor of release outcome. Using five factors related to risk (work/school status, security level of releasing institution, total PCL-R score, history of institutional drug use, and days at risk), release outcome was predicted with an overall classification accuracy of 88%, with high specificity (86%) and sensitivity (89%). The logistic regression model generated an R2 of .55 and the accompanying AUC was .89, both substantial. Work/school status had an extremely large positive association with successful completion of community supervision, accounting for > half of the total variance explained by the five-factor model and increasing the estimated odds of successful release outcome by > 15-fold. Also, when in the MMT program, clients' risk taking behaviour was significantly moderated, with low overall base rates of illicit drug use, yet the rate of parole/SR revocation (71%) was high. The 9-year follow-up showed a high mortality rate (15%) overall. Revocation of release while in the MMT program was associated with a significantly higher rate and more violent recidivism at follow-up. Results are discussed within the context of: (a) Andrews' and Bonta's psychology of criminal conduct; (b) the incompatibility of a harm reduction treatment model with an abstinence-based parole decision-making model; (c) changing drug use profiles among MMT clients; (d) a strength-based approach to correctional intervention focusing on educational and vocational retraining initiatives; and (e) creation of a user friendly case-based screening algorithm for prediction of release outcome for new releases.

This was a retrospective study of a community-based methadone maintenance treatment (MMT) program in Toronto. Participants (N = 170) were federally sentenced adult male offenders admitted to this voluntary program between 1997 and 2009 while subject to community supervision following incarceration. The primary investigation examined correlates of treatment responsivity, with principal outcome measures including MMT clients’ rates of: (i) illicit drug use; and (ii) completion of conditional (parole) or statutory release (SR). For a subset (n = 74), recidivism rates were examined after a 9-year interval. Findings included strong convergent evidence from logistic regression and ROC analyses that an empirically and theoretically derived set of five variables was a stable and highly significant (p <.001) predictor of release outcome. Using five factors related to risk (work/school status, security level of releasing institution, total PCL-R score, history of institutional drug use, and days at risk), release outcome was predicted with an overall classification accuracy of 88%, with high specificity (86%) and sensitivity (89%). The logistic regression model generated an R2 of .55 and the accompanying AUC was .89, both substantial. Work/school status had an extremely large positive association with successful completion of community supervision, accounting for > half of the total variance explained by the five-factor model and increasing the estimated odds of successful release outcome by > 15-fold. Also, when in the MMT program, clients' risk taking behaviour was significantly moderated, with low overall base rates of illicit drug use, yet the rate of parole/SR revocation (71%) was high. The 9-year follow-up showed a high mortality rate (15%) overall. Revocation of release while in the MMT program was associated with a significantly higher rate and more violent recidivism at follow-up. Results are discussed within the context of: (a) Andrews' and Bonta's psychology of criminal conduct; (b) the incompatibility of a harm reduction treatment model with an abstinence-based parole decision-making model; (c) changing drug use profiles among MMT clients; (d) a strength-based approach to correctional intervention focusing on educational and vocational retraining initiatives; and (e) creation of a user friendly case-based screening algorithm for prediction of release outcome for new releases.