bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release
Authors: Borutaite Vilmante , Morkuniene Ramune , Arandarcikaite Odeta , Jekabsone Aiste , Barauskaite Jurgita , Brown Guy C 
Published: August 2009

AbstractBackgroundHeart ischemia can rapidly induce apoptosis and mitochondrial dysfunction via mitochondrial permeability transition-induced cytochromecrelease. We tested whether nitric oxide (NO) can block this damage in isolated rat heart, and, if so, by what mechanisms.MethodsHearts were perfused with 50 μM DETA/NO (NO donor), then subjected to 30 min stop-flow ischemia or ischemia/reperfusion. Isolated heart mitochondria were used to measure the rate of mitochondrial oxygen consumption and membrane potential using oxygen and tetraphenylphosphonium-selective electrodes. Mitochondrial and cytosolic cytochromeclevels were measured spectrophotometrically and by ELISA. The calcium retention capacity of isolated mitochondria was measured using the fluorescent dye Calcium Green-5N. Apoptosis and necrosis were evaluated by measuring the activity of caspase-3 in cytosolic extracts and the activity of lactate dehydrogenase in perfusate, respectively.Results30 min ischemia caused release of mitochondrial cytochromecto the cytoplasm, inhibition of the mitochondrial respiratory chain, and stimulation of mitochondrial proton permeability. 3 min perfusion with 50 μM DETA/NO of hearts prior to ischemia decreased this mitochondrial damage. The DETA/NO-induced blockage of mitochondrial cytochromecrelease was reversed by a protein kinase G (PKG) inhibitor KT5823, or soluble guanylate cyclase inhibitor ODQ or protein kinase C inhibitors (Ro 32-0432 and Ro 31-8220). Ischemia also stimulated caspase-3-like activity, and this was substantially reduced by pre-perfusion with DETA/NO. Reperfusion after 30 min of ischemia caused no further caspase activation, but was accompanied by necrosis, which was completely prevented by DETA/NO, and this protection was blocked by the PKG inhibitor. Incubation of isolated heart mitochondria with activated PKG blocked calcium-induced mitochondrial permeability transition and cytochromecrelease. Perfusion of non-ischemic heart with DETA/NO also made the subsequently isolated mitochondria resistant to calcium-induced permeabilisation, and this protection was blocked by the PKG inhibitor.ConclusionThe results indicate that NO rapidly protects the ischemic heart from apoptosis and mitochondrial dysfunction via PKG-mediated blockage of mitochondrial permeability transition and cytochromecrelease.
Improvement in survival among HIV-infected individuals in the Republic of Korea: Need for an early HIV diagnosis
Authors: Kee Mee-Kyung , Lee Jin-Hee , Kim Eun-Jin , Lee Jiae , Nam Jeong-Gu , Yoo Byung-Hee , Kim Sung Soon 
Published: August 2009

Abstract

Background
There is little information describing survival in HIV-infected patients after primary diagnosis in Korea, and changes in survival over time. This study investigated survival times, survival characteristics, and changes in survival after initial HIV diagnosis. Survival was characterized by evaluation of the immune status at primary HIV diagnosis nationwide.

Methods
A total of 5,323 HIV-infected individuals were registered with the government and followed until the end of 2007. Survival following HIV diagnosis was estimated based on epidemiological characteristics. We examined 3,369 individuals with available initial CD4+ T-cell counts within 6 months of HIV diagnosis to estimate survival based on immune status at diagnosis. The association between epidemiological variables and survival times was analyzed with univariate and multivariate Cox's proportional hazards model.

Results
Individuals died during the study period (n = 980), and 45% of the individuals died within 6 months of HIV diagnosis. The median survival following HIV diagnosis was 16.7 years. Survival were longer in women, in younger persons, in individuals diagnosed at blood centers, and in individuals diagnosed later in the study period. Survival were shortest in individuals with CD4+ T-cell counts <200 cells/mm3 at HIV diagnosis. These results suggest that early HIV diagnosis in Korea is imperative to increase survival and to promote the quality of life for HIV-infected individuals with governmental support.

Conclusion
The median survival time of HIV-infected individuals following HIV diagnosis was 16.7 years in Korea. The survival was significantly lower in individuals with CD4+ T-cell counts <200 cells/mm3 at HIV diagnosis and higher by introduction of drugs and development of therapy.
Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention
Authors: Puts Martine TE , Monette Johanne , Girre Veronique , Wolfson Christina , Monette Michele , Batist Gerald , Bergman Howard 
Published: August 2009

Abstract

Background
There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.

Methods
Medical charts of all patients in the Segal Cancer Centre aged 65 and over were screened and evaluated for inclusion. Several strategies to facilitate recruitment and retention were implemented. Reasons for exclusion, refusal and loss to follow-up were recorded. Descriptive statistics were used to report the reasons for refusal and loss to follow-up. A non-response analysis using chi-square tests and t-tests was conducted to compare respondents to those who refused to participate and to compare those who completed the study to those who were lost to follow-up. A feedback form with open-ended questions was administered following the last interview to obtain patient's opinions on the length of the interviews and conduct of this pilot study.

Results
3060 medical charts were screened and 156 eligible patients were identified. Of these 112 patients participated for a response rate of 72%. Reasons for refusal were: feeling too anxious (40%), not interested (25%), no time (12.5%), too sick (5%) or too healthy (5%) or other reasons (5%). Ninety-one patients participated in the six-month follow-up (retention 81.3%), seven patients refused follow-up (6.2%) and fourteen patients died (12.5%) during the course of the study. The median time to conduct the baseline interview was 45 minutes and 57% of baseline interviews were conducted at home. Most patients enjoyed participation and only five felt that the interviews were too long.

Conclusion
It was feasible to recruit newly-diagnosed cancer patients prior to treatment although it required considerable time and effort. Once patients were included, the retention rate was high despite the fact that most were undergoing active cancer treatment.
Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda
Authors: Amuron Barbara , Namara Geoffrey , Birungi Josephine , Nabiryo Christine , Levin Jonathan , Grosskurth Heiner , Coutinho Alex , Jaffar Shabbar 
Published: August 2009

Abstract

Background
In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4–12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates.

Methods
HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4–6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression.

Results
4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport.

Conclusion
About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.
Prevalence of risk factors for non-communicable diseases in the Mekong Delta, Vietnam: results from a STEPS survey
Authors: Pham Luc H , Au Thuy B , Blizzard Leigh , Truong Nhan B , Schmidt Michael D , Granger Robert H , Dwyer Terence 
Published: August 2009

Abstract

Background
Despite the increasing burden of non-communicable diseases (NCD) in Vietnam, information on the prevalence of preventable risk factors for NCD is restricted to the main urban centres of Ha Noi, and Ho Chi Minh City (HCMC). This population-based survey aimed to describe the prevalence of risk factors for NCD in a rural Vietnamese sample.

Methods
This survey was conducted using the WHO "STEPwise approach to surveillance of non-communicable diseases" (STEPS) methodology. Participants (n = 1978) were residents of the Mekong Delta region selected by multi-stage sampling. Standardised international protocols were used to measure behavioural risk factors (smoking, alcohol consumption, fruit and vegetable consumption, physical activity), physical characteristics (weight, height, waist and hip circumferences, blood pressure – BP), fasting blood glucose (BG) and total cholesterol (TC). Data were analysed using complex survey analysis methods.

Results
In this sample, 8.8% of men and 12.6% of women were overweight (body mass index (BMI) ≥ 25 kg/m2) and 2.3% of men and 1.5% of women were obese (BMI ≥ 30 kg/m2). The prevalence of hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, or taking medication for hypertension) was 27.3% for men and 16.2% for women. There were 1.0% of men and 1.1% of women with raised BG (defined as capillary whole BG of at least 6.1 mmol/L).

Conclusion
We provide the first NCD risk factor profile of people living in the Mekong Delta of Vietnam using standardised methodology. Our findings for this predominantly rural sample differ from previous studies conducted in Ha Noi and HCMC, and suggest that it is inappropriate to generalise findings from the big-city surveys to the other 80% of the population.
Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients
Authors: Yamada Hidetaka , Shinmura Kazuya , Goto Masanori , Iwaizumi Moriya , Konno Hiroyuki , Kataoka Hideki , Yamada Masami , Ozawa Takachika , Tsuneyoshi Toshihiro , Tanioka Fumihiko , Sugimura Haruhiko 
Published: August 2009

Abstract

Background
Germline mono-allelic promoter hypermethylation of the MLH1 or MSH2 gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene CDH1 (E-cadherin) might cause predisposition to gastric cancer.

Methods
We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the CDH1 promoter by bisulfite sequencing of multiple clones.

Results
Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.

Conclusion
These results suggest that germline mono-allelic hypermethylation of the CDH1 promoter is not a major predisposing factor for gastric cancer.
Selective entrainment of the Drosophilacircadian clock to daily gradients in environmental temperature
Authors: Currie Jake , Goda Tadahiro , Wijnen Herman 
Published: August 2009

Abstract

Background

Circadian clocks are internal daily time keeping mechanisms that allow organisms to anticipate daily changes in their environment and to organize their behavior and physiology in a coherent schedule. Although circadian clocks use temperature compensation mechanisms to maintain the same pace over a range of temperatures, they are also capable of synchronizing to daily temperature cycles. This study identifies key properties of this process.

Results

Gradually ramping daily temperature cycles are shown here to synchronize behavioral and molecular daily rhythms in Drosophila with a remarkable efficiency. Entrainment to daily temperature gradients of amplitudes as low as 4°C persisted even in the context of environmental profiles that also included continuous gradual increases or decreases in absolute temperature. To determine which elements of daily temperature gradients acted as the key determinants of circadian activity phase, comparative analyses of daily temperature gradients with different wave forms were performed. The phases of ascending and descending temperature acted together as key determinants of entrained circadian phase. In addition, circadian phase was found to be modulated by the relative temperature of release into free running conditions. Release at or close to the trough temperature of entrainment consistently resulted in phase advances. Re-entrainment to daily temperature gradients after large phase shifts occurred relatively slowly and required several cycles, allowing flies to selectively respond to periodic rather than anecdotal signals. The temperature-entrained phase relationship between clock gene expression rhythms and locomotor activity rhythms strongly resembled that previously observed for light entrainment. Moreover, daily temperature gradient and light/dark entrainment reinforced each other if the phases of ascending and descending temperature were in their natural alignment with the light and dark phases, respectively.

Conclusion

The present study systematically examined the entrainment of clock-controlled behavior to daily environmental temperature gradients. As a result, a number of key properties of circadian temperature entrainment were identified. Collectively, these properties represent a circadian temperature entrainment mechanism that is optimized in its ability to detect the time-of-day information encoded in natural environmental temperature profiles. The molecular events synchronized to the daily phases of ascending and descending temperature are expected to play an important role in the mechanism of circadian entrainment to daily temperature cycles.
A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement
Authors: Xu Yuanyong , Zhang Chuanfu , Jia Leili , Wen Cuirong , Liu Huihui , Wang Yong , Sun Yansong , Huang Liuyu , Zhou Yusen , Song Hongbin 
Published: August 2009

AbstractBackgroundThe complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.Presentation of the hypothesisPrevious studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.Testing the hypothesisOur hypothesis was tested using cell-free HIV-1 virions cultivatedin vitroand assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.Implications of the hypothesisThe targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.
Promoting smoking cessation in Bangladeshi and Pakistani male adults: design of a pilot cluster randomised controlled trial of trained community smoking cessation workers
Authors: Begh Rachna A , Aveyard Paul , Upton Penney , Bhopal Raj S , White Martin , Amos Amanda , Prescott Robin J , Bedi Raman , Barton Pelham , Fletcher Monica , Gill Paramjit , Zaidi Qaim , Sheikh Aziz 
Published: August 2009

Abstract

Background
The prevalence of smoking is higher among Pakistani and Bangladeshi males than among the general population. Smokers who receive behavioural support and medication quadruple their chances of stopping smoking, but evidence suggests that these populations do not use National Health Service run stop smoking clinics as frequently as would be expected given their high prevalence of smoking. This study aims to tackle some of the main barriers to use of stop smoking services and adherence to treatment programmes by redesigning service delivery to be more acceptable to these adult male populations. The study compares the effectiveness of trained Pakistani and Bangladeshi smoking cessation workers operating in an outreach capacity ('clinic + outreach') with standard care ('clinic only') to improve access to and success of National Health Service smoking cessation services.

Methods/design
This is a pilot cluster randomised controlled trial based in Birmingham, UK. Super output areas of Birmingham will be identified in which more than 10% of the population are of Pakistani and/or Bangladeshi origin. From these areas, 'natural geographical communities' will be identified. Sixteen aggregated agglomerations of super output areas will be identified, separating areas from each other using buffer regions in order to reduce potential contamination. These natural communities will be randomised to 'clinic + outreach' (intervention) or 'clinic only' (control) arms. The use of stop smoking services and the numbers of people quitting smoking (defined as prolonged self-reported abstinence at four weeks, three months and six months) will be assessed in each area. In addition, we will assess the impact of the intervention on adherence to smoking cessation treatments and patient satisfaction.

Trial registration
Current Controlled Trials ISRCTN 82127540.
Modeling genetic imprinting effects of DNA sequences with multilocus polymorphism data
Authors: Wen Sheron , Wang Chenguang , Berg Arthur , Li Yao , Chang Myron M , Fillingim Roger B , Wallace Margaret R , Staud Roland , Kaplan Lee , Wu Rongling 
Published: August 2009

Abstract
Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T), OPRKA843G (with alleles A and G), and OPRKC846T (with alleles C and T), at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008). With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance.
The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties
Authors: Bennett Robert M , Friend Ronald , Jones Kim D , Ward Rachel , Han Bobby K , Ross Rebecca L 
Published: August 2009

Abstract
Introduction
The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia (FM) patients. Over the last 18 years, since the publication of the original FIQ, several deficiencies have become apparent and the cumbersome scoring algorithm has been a barrier to widespread clinical use. The aim of this paper is to describe and validate a revised version of the FIQ: the FIQR.

Methods
The FIQR was developed in response to known deficiencies of the FIQ with the help of a patient focus group. The FIQR has the same 3 domains as the FIQ (that is, function, overall impact and symptoms). It differs from the FIQ in having modified function questions and the inclusion of questions on memory, tenderness, balance and environmental sensitivity. All questions are graded on a 0–10 numeric scale. The FIQR was administered online and the results were compared to the same patient's online responses to the 36-Item Short Form Health Survey (SF-36) and the original FIQ.

Results
The FIQR was completed online by 202 FM patients, 51 rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients (31 RA and 20 SLE), 11 patients with major depressive disorder (MDD) and 213 healthy controls (HC). The mean total FIQR score was 56.6 ± 19.9 compared to a total FIQ score of 60.6 ± 17.8 (P < 0.03). The total scores of the FIQR and FIQ were closely correlated (r = 0.88, P < 0.001). Each of the 3 domains of the FIQR correlated well with the 3 related FIQ domains (r = 0.69 to 0.88, P < 0.01). The FIQR showed good correlation with comparable domains in the SF-36, with a multiple regression analysis showing that the three FIQR domain scores predicted the 8 SF-36 subscale scores. The FIQR had good discriminant ability between FM and the 3 other groups; total FIQR scores were HC (12.1 ± 11.6), RA/SLE (28.6 ± 21.2) and MDD (17.3 ± 11.8). The patient completion time was 1.3 minutes; scoring took about 1 minute.

Conclusions
The FIQR is an updated version of the FIQ that has good psychometric properties, can be completed in less than 2 minutes and is easy to score. It has scoring characteristics comparable to the original FIQ, making it possible to compare past FIQ results with future FIQR results.