Modulation of Ca2+-dependent anion secretion by protein kinase C in normal and cystic fibrosis pancreatic duct cells

AbstractThe study investigated the role of protein kinase C (PKC) in the modulation of agonist-induced Ca2+-dependent anion secretion by pancreatic duct cells. The short-circuit current (ISC) technique was used to examine the effect of PKC activation and inhibition on subsequent ATP, angiotensin II and ionomycin-activated anion secretion by normal (CAPAN-1) and cystic fibrosis (CFPAC-1) pancreatic duct cells. The ISC responses induced by the Ca2+-mobilizing agents, which had been previously shown to be attributed to anion secretion, were enhanced in both CAPAN-1 and CFPAC-1 cells by PKC inhibitors, staurosporine, calphostin C or chelerythrine. On the contrary, a PKC activator, phorbol 12-myristate 13-acetate (PMA), was found to suppress the agonist-induced ISC in CFPAC-1 cells and the ionomycin-induced ISC in CAPAN-1 cells. An inactive form of PMA, 4αd-phorbol 12,13-didecanote (4αD), was found to exert insignificant effect on the agonist-induced ISC, indicating a specific effect of PMA. Our data suggest a role of PKC in modulating agonist-induced Ca2+-dependent anion secretion by pancreatic duct cells. Therapeutic strategy to augment Ca2+-activated anion secretion by cystic fibrosis pancreatic duct cells may be achieved by inhibition or down-regulation of PKC

Bayesian time-varying quantile forecasting for Value-at-Risk in financial markets

Recently, Bayesian solutions to the quantile regression problem, via the likelihood of a Skewed-Laplace distribution, have been proposed. These approaches are extended and applied to a family of dynamic conditional autoregressive quantile models. Popular Value at Risk models, used for risk management in finance, are extended to this fully nonlinear family. An adaptive Markov chain Monte Carlo sampling scheme is adapted for estimation and inference. Simulation studies illustrate favourable performance, compared to the standard numerical optimization of the usual nonparametric quantile criterion function, in finite samples. An empirical study generating Value at Risk forecasts for ten major financial stock indices finds significant nonlinearity in dynamic quantiles and evidence favoring the proposed model family, for lower level quantiles, compared to a range of standard parametric volatility models, a semi-parametric smoothly mixing regression and some nonparametric risk measures, in the literature

The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18– 60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18–60 years; (2) combine these data with those for healthy children (aged 0–12), adolescents (aged 12–18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population- based cross-sectional observational study of healthy Chinese subjects aged 0.5–89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5–89; 52% male). From previous studies, 1197 children (aged 0–12, 55% male), 590 adolescents (aged 12–18, 49% male), and 77 elderly (aged 60–89, 55% male) were included. New data were collected from 354 adults aged 18–60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly

Probabilistic Latent Semantic Analyses (PLSA) in Bibliometric Analysis for Technology Forecasting

Due to the availability of internet-based abstract services and patent databases, bibliometric analysis has become one of key technology forecasting approaches. Recently, latent semantic analysis (LSA) has been applied to improve the accuracy in document clustering. In this paper, a new LSA method, probabilistic latent semantic analysis (PLSA) which uses probabilistic methods and algebra to search latent space in the corpus is further applied in document clustering. The results show that PLSA is more accurate than LSA and the improved iteration method proposed by authors can simplify the computing process and improve the computing efficiencyDebido a la disponibilidad de servicios abstractos de internet y bases de datos de patentes, un análisis bibliométrico se ha transformado en una aproximación clave de sondeo de tecnologías. Recientemente, el Análisis Semántico Latente (LSA) ha sido aplicado para mejorar la precisión en el clustering de documentos. En el siguiente trabajo se muestra, un nuevo método LSA, el Análisis Semántico Probabilística Latente (PLSA), que utiliza métodos probabilísticas y álgebra para buscar espacio latente en el cuerpo generado por el clustering de documentos. Los resultados demuestran que PLSA es más preciso que LSA y mejora el método de iteración propuesto por autores que simplifican los procesos de computación y mejoran la eficiencia de cómputo.Due to the availability of internet-based abstract services and patent databases, bibliometric analysis has become one of key technology forecasting approaches. Recently, latent semantic analysis (LSA) has been applied to improve the accuracy in document clustering. In this paper, a new LSA method, probabilistic latent semantic analysis (PLSA) which uses probabilistic methods and algebra to search latent space in the corpus is further applied in document clustering. The results show that PLSA is more accurate than LSA and the improved iteration method proposed by authors can simplify the computing process and improve the computing efficienc

Diphyllobothriasis: the first case report from Malaysia

Diphyllobothriasis is a disease caused by infection with adult tapeworms of the genus Diphyllobothrium. Humans acquire the infection by consuming the raw or inadequately cooked flesh, roe, liver, or other organs of infected fish. Diphyllobothrium latum infection has not been reported in Malaysia; we are reporting the first case. The patient was a 62 year old Chinese male seen at the outpatient clinic with complaints of watery stools and slight abdominal discomfort for four days. Physical examination was normal. He was treated for diarrhea. Two days after treatment, he passed out intact off-white proglottids in his stool. Diphyllobothriasis was confirmed by examination of these gravid proglottids; typical operculated eggs were seen after rupturing the gravid proglottids. The patient had a history of eating sashimi (Japanese raw fish). He was treated with a single dose of praziquantel and had been well since

Impact of a novel teaching method based on feedback, activity, individuality and relevance on students' learning

Objectives: This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students’ learning on clinical placement. Methods: This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Results: Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model. The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of “standard” clinical teaching. Conclusions: Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching

The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: a cohort study

Background: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. Methods: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for ≥2 years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. Results: A total of 20,252 eligible patients with an average age of 64.5 years (standard deviation 15.0) were included. The admission rate at 24 months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR] = 1.25, 95% CI 1.08 to 1.43, p = 0.002 at 12 months; AHR = 1.17, 95% CI 1.04 to 1.31, p = 0.009 at 24 months) and all causes (AHR = 1.12, 95% CI 1.05 to 1.19, p < 0.001 at 24 months) than perindopril users. Conclusions: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended

Association between statins and the risk of suicide attempt, depression, anxiety, and seizure: A population-based, self-controlled case series study

Background: Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows./ Methods: We identified patients aged 40–75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk./ Results: We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09–1.74) for suicide attempt, 1.29 (95 % CI, 1.15–1.45) for depression, 1.35 (95 % CI, 1.19–1.53) for anxiety, and 1.45 (95 % CI, 1.21–1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91–365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription./ Limitations: CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods./ Conclusions: Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed

Envelhecimento e doenças neurodegenerativas crônicas na Amazônia brasileira: implantação de novas metodologias de avaliação em pacientes com declínio cognitivo leve e doença de Alzheimer

By 2025, the number of elderly people in the world will double and by 2050 will reach around two billion individuals, with the majority of them in developing countries. Alzheimer's disease (AD) is the fourth disease that most compromises the quality of life in elderly. This work aims to suggest new methodologies for evaluating elderly people with mild cognitive impairment and Alzheimer‟s disease, introducing a Brazilian version of the TSM-"Test Your Memory" and showing the performance fo this people in tests from CANTAB. It is an analytical, retrospective, longitudinal case-control study, performed at the Laboratory of Neurodegeneration and Infection, University Hospital João de Barros Barreto, from January 2009 to January 2011. Ninety five individuals 65 years old or older were divided in three groups: Alzheimer's disease (AD, n = 21), mild cognitive impairment (DCL, n = 31) and control (n = 43). Patients with previous stroke, primary depression, head injury, other dementias and other neuropsychiatric disorders, and serious visuo-auditory deficits were excluded. The participants were submitted to an initial assessment, screening with GDS-5 and DSM-IV, the International Physical Activity Questionnaire (IPAQ), CERAD neuropsychological test battery and the TSM - Test Your Memory (Brazilian version).Statistical analysis was performed using one-way ANOVA, defining the p-value<0.05 to detect significant differences. Female individuals of mixed ethnicity, aged 70 to 79 years predominated in all groups. The average MMSE score between the three groups was significantly different (control: 26.6± 2.2; DCL: 25.1 ± 2.6, DA: 17.3 ± 4.9, p <0.05), however, the TSM proved to be a more sensitive test to distinguish DCL patients from AD (control: 42.4± 5; DCL: 35.5 ± 7.7, DA: 25.7 ± 8, p <0.01 ). The three groups had different mean scores. In the CERAD word list, clock test, TNBr and phonological verbal fluency. The performance in TSM was significantly lower in DCL and AD groups than in the control group. And DA group was worse in this test than the DCL group too. The tests and measurements of CANTAB that best separate the three groups from the performance obtained were RVP A‟, PAL-trials to success and PAL-total errors in 6 patterns phase. Good correlations were found between the TSM and other tests, especially with the MMSE (Pearson‟s coefficient r = 0.79, p <0.0001) and clock test (r = 0.76, p <0.0001), as well as good correlations between the measures of PAL and TSM and MMSE. Physical activity level, in the control group was higher than in all other groups. When the level of physical activity and performance on cognitive tests were correlated, there were no significant differences in the different groups, except by a better performance in word recall test from CERAD, and word list in DCL group (DCL "active":4.7 ± 1.8; DCL"not active": 3 ± 1.5,p <0.01). Taken as a Whole, these results suggest that the application of automated automated neuropsychological tests associated with routine clinical tests and TYM, improve the clinical assessment´s sensitivity and reliability, especially in the early stages of dementia where the precoceous and accurate diagnosis are essential to guide therapeutic actions, drugs or behavioral modifications.Em 2025 o número de idosos no mundo irá dobrar e por volta de 2050 alcançará dois bilhões de indivíduos, estando a maioria em países desenvolvidos. A doença de Alzheimer (DA) é a quarta doença que mais compromete a qualidade de vida dos idosos. Este trabalho pretende sugerir novas metodologias de avaliação de pacientes com declínio cognitivo e doença de Alzheimer, apresentando uma versão brasileira a partir da versão original em língua inglesa intitulada “Test Your Memory” TYM (“teste sua memória- TSM), bem como mostrar os resultados do desempenho dos idosos na bateria de testes neuropsicológicos de Cambridge (CANTAB). Trata-se de estudo analítico, transversal retrospectivo do tipo caso-controle, realizado em pacientes do ambulatório de Geriatria do Hospital Universitário João de Barros Barreto, e em voluntários da comunidade no período de janeiro de 2009 a janeiro de 2011. Participaram 95 indivíduos com 65 ou mais anos de idade, divididos em 3 grupos: Alzheimer (DA, n=21), declínio cognitivo (DCL, n=31) e controle (n=43). Foram excluídos pacientes com história de acidente vascular encefálico (AVE), depressão primária, trauma cranioencefálico, outras demências, outras patologias neuropsiquiátricas e déficits visuo-auditivos limitantes. Os participantes foram submetidos à avaliação inicial, triagem com GDS-5 e DSM-IV, ao Questionário Internacional de Atividades Físicas (IPAQ), testes neuropsicológicos da bateria CERAD, teste do relógio, TSM (versão adaptada para o Português) e a bateria de Alzheimer do CANTAB. A análise estatística foi realizada empregando-se ANOVA, um critério, definindo-se o valor p<0,05 como significante. Houve predomínio em todos os grupos de indivíduos do gênero feminino, de cor parda, na faixa etária de 70 a 79 anos. A média de pontuação do MEEM entre os três grupos foi diferente (controle: 26,6±2,2; DCL: 25,1±2,6; DA: 17,3±4,9; p<0,05), entretanto o TSM mostrou ser uma ferramenta de triagem mais confiável para distinguir os pacientes DCL dos DA (controle: 42,4±5; DCL: 35,5±7,7; DA: 25,7±8; p<0,01). Na lista de palavras do CERAD, teste do relógio, TNBR e na fluência verbal fonológica os três grupos apresentaram diferenças significantes na média de pontos obtidos. A média da pontuação total no TSM foi significativamente menor nos grupos DCL e DA do que no grupo controle, e no grupo DA em relação ao DCL. Os testes e medidas do CANTAB que separam os três grupos pelo desempenho obtido são: RVP A‟, número de tentativas para o sucesso e total de erros na fase de 6 figuras do PAL. Foram encontradas boas correlações entre o TSM e outros testes, principalmente com o MEEM (Coeficiente de Pearson, r = 0,79; p<0,0001) e teste do relógio (r = 0,76; p<0,0001), bem como boa correlação entre as medidas do PAL e a pontuação do TSM e o MEEM. O nível de atividade física no grupo controle foi maior do que em todos os outros grupos. Ao ser correlacionado o nível de atividade física e o desempenho nos testes cognitivos, não foram observadas diferenças significativas nos diferentes grupos, exceto pela evocação de palavras no grupo DCL. Tomados em conjunto os resultados sugerem que a aplicação de testes neuropsicológicos automatizados associados aos testes da rotina clínica e ao TSM aumentam a resolução e a confiabilidade das análises particularmente no estágio inicial das síndromes demenciais onde a precocidade e a precisão diagnóstica são fundamentais para orientar as ações terapêuticas, sejam elas medicamentosas e/ou comportamentais