bluuebunny/crossref_metadata_2025 huggingface dataset:
Malocclusion, psycho-social impacts and treatment need: A cross-sectional study of Tanzanian primary school-children
Authors: Mtaya Matilda , Astrom Anne N , Brudvik Pongsri
Published: May 2012

Background

studies on the relationship between children's malocclusion and its psycho-social impacts are so far largely unexplored in low-income countries. This study aimed to assess the prevalence of malocclusion, reported dental problems and dissatisfaction with dental appearance among primary school children in Tanzania. The relationship of dissatisfaction with socio-demographic characteristics, clinically defined malocclusion and psychosocial impacts of dental anomalies was investigated. Orthodontic treatment need was estimated using an integrated socio-dental approach.

Method

One thousand six hundred and one children (mean age 13 yr) attending primary schools in the districts of Kinondoni and Temeke completed face to face interviews and a full mouth clinical examination. The survey instrument was designed to measure a Kiswahili translated and culturally adapted Child Oral Impact on Daily Performance (Child-OIDP) frequency score, reported dental problems, dissatisfaction with dental appearance/function and socio-demographic characteristics.

Results

The prevalence of malocclusion varied from 0.9% (deep bite) to 22.5% (midline shift) with a total of 63.8% having at least one type of anomaly. Moderate proportions of children admitted dental problems; ranging from 7% (space position) to 20% (pain). The odds ratio of having problems with teeth position, spaces, pain and swallowing if having any malocclusion were, respectively 6.7, 3.9, 1.4 and 6.8. A total of 23.3% children were dissatisfied with dental appearance/function. Children dissatisfied with their dental appearance were less likely to be Temeke residents (OR = 0.5) and having parents of higher education (OR = 0.6) and more likely to reporting problem with teeth position (OR = 4.3) and having oral impacts (OR = 2.7). The socio-dental treatment need of 12% was five times lower than the normative need assessment of 63.8%.

Conclusion

Compared to the high prevalence of malocclusion, psycho social impacts and dissatisfaction with appearance/function was not frequent among Tanzanian schoolchildren. Subjects with malocclusion reported problems most frequently and malocclusion together with other psycho-social impact scores determined children's satisfaction with teeth appearance- and function.
Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats
Authors: Faddah Laila M , Baky Nayira A Abdel , Al-Rasheed Nouf M , Al-Rasheed Nawal M , Fatani Amal J , Atteya Muhammad
Published: May 2012

Background

Nanoparticles are small-scale substances (<100 nm) with unique properties. Therefore, nanoparticles pose complex health risk implications. The objective of this study was to detect whether treatment with quercetin (Qur) and/or arginine (Arg) ameliorated nephrotoxicity induced by two different doses of nano zinc oxide (n-ZnO) particles.

Method

ZnO nanoparticles were administered orally in two doses (either 600 mg or 1 g/Kg body weight/day for 5 conscutive days) to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed.

Results

Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); and C-reactive protein (CRP). Moreover, immunoglobulin (IGg), vascular endothelium growth factor (VEGF), and nitric oxide (NO) were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH) was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters.

Conclusions

The data show that Qur has a beneficial effect against n-ZnO oxidative stress and related vascular complications. Also, its combination with Arg proved to be even more effective in ameliorating nano zinc oxide nephrotoxicity.
Burnout syndrome in Cypriot physiotherapists: a national survey
Authors: Pavlakis Andreas , Raftopoulos Vasilios , Theodorou Mamas
Published: May 2012

Background

Burnout in the healthcare workers is formally defined as a state of physical, emotional and mental exhaustion caused by long-term involvement in situations that are emotionally demanding.

Methods

Using a random stratified sampling method and taking into account geographical location, specialty and type of employment, 172 physiotherapists working both in the private and public sectors completed an anonymous questionnaire that included several aspects related to burnout; the MBI scale, questions related to occupational stress, and questions pertaining to self image.

Results

Almost half (46%) of the 172 participants believed that their job is stressful. Approximately 57% of the physiotherapists who worked in the public sector and 40% of those who worked in the private sector (p = 0.038) reported that their job is stressful. In total, 21.1% of participants met Maslach's criteria for burnout. The point prevalence of burnout was as follows: (1) 13.8% of those who worked in the public sector and 25.5% of those in the private sector (2) 22.2% of males and 20% of females (3) 21.6% who were married, 18% who were single and 33.3% who were separated. Gender was found to be associated with the level of personal accomplishment (chi-squared test; p = 0.049), as 17.8% of men compared with 24.3% of women reported high personal accomplishment. The number of years of working as a physiotherapist correlated negatively (r = -0.229, p = 0.004) with the total depersonalization score. Regression analysis showed that the perception that the job is stressful (p < 0.001) and the low salary (p = 0.016) were significant predictors of high emotional exhaustion scores, while age group (p = 0.027) predicted high scores of depersonalization and the employment sector (p = 0.050) as well as the low salary predicted high personal accomplishment scores.

Conclusions

Burnout levels in physiotherapists in Cyprus ranged from low to moderate.
Severe disease in children hospitalized with a diagnosis of Plasmodium vivax in south-eastern Pakistan
Authors: Shaikh Salma , Memon Hafeezullah , Iohano Bhagchand , Shaikh Amna , Ahmed Imran , Baird J Kevin
Published: May 2012

Background

Infection by Plasmodium vivax has been considered rarely threatening to life, but recent studies challenge this notion. This study documented the frequency and character of severe illness in paediatric patients admitted to a hospital in south-eastern Pakistan with a laboratory-confirmed diagnosis of vivax malaria.

Methods

An observational study of all 180 paediatric patients admitted with any diagnosis of malaria during 2010 was conducted: 128 P. vivax; 48 Plasmodium falciparum; and four mixed infections of these species. Patients were classified as having severe illness with any of the following indicators: Glascow coma scale <11; ≥2 convulsions; haemoglobin <5g/dL; thrombocytes <50,000/mL; blood glucose <45mg%; >70 breaths/min; or intravenous anti-malarial therapy. Additionally, 64 patients with a diagnosis of vivax malaria were treated during 2009, and the 21 of these having severe illness were included in analyses of the frequency and character of severe illness with that diagnosis.

Results

During 2010, 39 (31%) or 37 (77%) patients with a diagnosis of P. vivax or P. falciparum were classified as having severe disease. Including the 2009 records of 64 patients having vivax malaria, a total of 60 (31%) patients with severe illness and a diagnosis of P. vivax were available. Altered mental status (Glascow coma scale score <11; or ≥2 convulsions) dominated at 54% of the 83 indicators of severe illness manifest among the patients with vivax malaria, as was true among the 37 children with a diagnosis of falciparum malaria and being severely ill; 58% of the 72 indicators of severe disease documented among them. No statistically significant difference appeared in frequencies of any other severe disease indicators between patients diagnosed with vivax or falciparum malaria. Despite such similarities, a diagnosis of falciparum malaria nonetheless came with 3.8-fold (95% CI = 1.8-8.1) higher risk of presenting with severe illness, and 8.0-fold (95% CI = 2.1-31) greater likelihood of presenting with three or more severe disease indicators. Two patients did not survive hospitalization, one each with a diagnosis of falciparum or vivax malaria.

Conclusions

Vivax malaria caused a substantial burden of potentially life-threatening morbidity on a paediatric ward in a hospital in south-eastern Pakistan.
Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum
Authors: Gill Jasmita , Kumar Anuj , Yogavel Manickam , Belrhali Hassan , Jain SK , Rug Melanie , Brown Monica , Maier Alexander G , Sharma Amit
Published: May 2012

Background

Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite Plasmodium falciparum contains two nucleosome assembly proteins termed PfNapL and PfNapS.

Methods

Three-dimensional crystal structure of PfNapS has been determined and analysed. Gene knockout and localization studies were also performed on PfNapS using transfection studies. Fluorescence spectroscopy was performed to identify histone-binding sites on PfNapS. Extensive sequence and structural comparisons were done with the crystal structures available for NAP/SET family of proteins.

Results

Crystal structure of PfNapS shares structural similarity with previous structures from NAP/SET family. Failed attempts to knock-out the gene for PfNapS from malaria parasite suggest essentiality in the parasite. GFP-fused PfNapS fusion protein targeting indicates cellular localization of PfNapS in the parasite nucleus. Fluorescence spectroscopy data suggest that PfNapS interacts with core histones (tetramer, octamer, H3, H4, H2A and H2B) at a different site from its interaction with linker histone H1. This analysis illustrates two regions on the PfNapS dimer as the possible sites for histone recognition.

Conclusions

This work presents a thorough analysis of the structural, functional and regulatory attributes of PfNapS from P. falciparum with respect to previously studied histone chaperones.
The acceptability of rat trap use over pesticides for rodent control in two poor urban communities in South Africa
Authors: Roomaney Rifqah , Ehrlich Rodney , Rother Hanna-Andrea
Published: May 2012

Background

Rodent infestations are a public health problem in poor urban communities. The use of illegal street pesticides to control rodent infestations with resulting poisonings is an additional public health concern receiving limited attention in many developing countries, including South Africa.

Methods

Participants in a household intervention in two poor urban areas of Cape Town, South Africa, received two high quality rat traps. Reported in this article are the results of a follow-up survey conducted six months after distribution to assess community perceived acceptability of using rat traps instead of toxic pesticides (N = 175).

Results

Of the 175 respondents that were followed up, 88% used the traps and only 35% continued using pesticides after the intervention. The analysis identified perceived effectiveness of the traps (prevalence odds ratio 18.00, 95% confidence interval 4.62 to 70.14), being male (prevalence odds ratio 8.86, 95% confidence interval 1.73 to 45.19), and the willingness to buy traps from an informal market (prevalence odds ratio 17.75, 95% confidence interval 4.22 to 74.57) as significantly associated with the acceptance of trap use.

Conclusions

Rat traps, when introduced to poor urban communities, are acceptable as an alternative to toxic pesticides for rodent control. Sustainability of trap use, however, needs to be researched, especially cost and cost-benefit.
Estrogen-like activity of seafood related to environmental chemical contaminants
Authors: Garritano Sonia , Pinto Barbara , Calderisi Marco , Cirillo Teresa , Amodio-Cocchieri Renata , Reali Daniela
Published: May 2012

Background

A wide variety of environmental pollutants occur in surface waters, including estuarine and marine waters. Many of these contaminants are recognised as endocrine disrupting chemicals (EDCs) which can adversely affect the male and female reproductive system by binding the estrogen receptor and exhibiting hormone-like activities. In this study the estrogenic activity of extracts of edible marine organisms for human consumption from the Mediterranean Sea was assayed.

Methods

Marine organisms were collected in two different areas of the Mediterranean Sea. The estrogenic activity of tissues was assessed using an in vitro yeast reporter gene assay (S. cerevisiae RMY 326 ER-ERE). Concentrations of polychlorinated biphenyls (PCBs) (congeners 28, 52, 101, 118, 138, 153, 180) in fish tissue was also evaluated.

Results

Thirty-eight percent of extracts showed a hormone-like activity higher than 10% of the activity elicited by 10 nM 17b-estradiol (E2) used as control.

Total PCB concentrations ranged from 0.002 up to 1.785 ng/g wet weight. Chemical analyses detected different levels of contamination among the species collected in the two areas, with the ones collected in the Adriatic Sea showing concentrations significantly higher than those collected in the Tyrrhenian Sea (p < 0.01).

Conclusion

The more frequent combination of chemicals in the samples that showed higher estrogenic activity was PCB 28, PCB 101, PCB 153, PCB 180.

The content of PCBs and estrogenic activity did not reveal any significant correlation.
Raisins and additional walking have distinct effects on plasma lipids and inflammatory cytokines
Authors: Puglisi Michael J , Vaishnav Ushma , Shrestha Sudeep , Torres-Gonzalez Moises , Wood Richard J , Volek Jeff S , Fernandez Maria Luz
Published: May 2012

Background

Raisins are a significant source of dietary fiber and polyphenols, which may reduce cardiovascular disease (CVD) risk by affecting lipoprotein metabolism and inflammation. Walking represents a low intensity exercise intervention that may also reduce CVD risk. The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on blood pressure, plasma lipids, glucose, insulin and inflammatory cytokines.

Results

Thirty-four men and postmenopausal women were matched for weight and gender and randomly assigned to consume 1 cup raisins/d (RAISIN), increase the amount of steps walked/d (WALK) or a combination of both interventions (RAISINS + WALK). The subjects completed a 2 wk run-in period, followed by a 6 wk intervention. Systolic blood pressure was reduced for all subjects (P = 0.008). Plasma total cholesterol was decreased by 9.4% for all subjects (P < 0.005), which was explained by a 13.7% reduction in plasma LDL cholesterol (LDL-C) (P < 0.001). Plasma triglycerides (TG) concentrations were decreased by 19.5% for WALK (P < 0.05 for group effect). Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN (P < 0.025 for time and group × time effect). All subjects had a reduction in plasma sICAM-1 (P < 0.01).

Conclusion

This research shows that simple lifestyle modifications such as adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk.
Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels
Authors: Khalyfa Abdelnaby , Bhushan Bharat , Hegazi Mohamed , Kim Jinkwan , Kheirandish-Gozal Leila , Bhattacharjee Rakesh , Capdevila Oscar Sans , Gozal David
Published: May 2012

Introduction

Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity.

Methods

A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65) and non-obese (NOB). Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135), corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped.

Results

Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values.

Conclusions

Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.
A case of metastatic leptomeningeal carcinomatosis from early gastric carcinoma
Authors: Park Kwang-Kuk , Yang Song-I , Seo Kyung-Won , Kim Young-Ok , Yoon Ki-Young
Published: May 2012

Metastatic leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of solid carcinomas. The most common causes of leptomeningeal carcinomatosis are breast cancer, lung cancer and malignant melanoma. Leptomeningeal carcinomatosis associated with gastric cancer, especially in its early stages, is exceedingly rare. Its presenting symptoms include headache, nauseaand seizures. In this report, we describe a case of leptomeningeal metastasis that presented with early-stage gastric cancer. A 67-year-old woman with a history of early-stage gastric cancer in remission was admitted to our hospital with 3 days of headache and nausea. Her gastric cancer had been treated 29 months prior to presentation by a radical subtotal gastrectomy with a Billroth I anastomosis. She had an uneventful recovery until she was diagnosed with metastases to the left axilla and neck 26 months after surgery. Her presenting symptoms of headache and nausea prompted cytologic examination of the cerebrospinal fluid and measurement of tumor markers, which revealed metastatic leptomeningeal carcinomatosis from her gastric cancer. This report aims to raise awareness of the possibility that even early-stage gastric cancer can lead to leptomeningeal carcinomatosis.
Effect of pretreatment clinical factors on overall survival in glioblastoma multiforme: a Surveillance Epidemiology and End Results (SEER) population analysis
Authors: Thumma Sudheer R , Fairbanks Robert K , Lamoreaux Wayne T , Mackay Alexander R , Demakas John J , Cooke Barton S , Elaimy Ameer L , Hanson Peter W , Lee Christopher M
Published: May 2012

Background

Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors and is associated with a dismal prognosis. The median survival after the primary diagnosis remains poor, even after multimodal treatment approaches. However, a few patients have been reported to have long term survival greater than three years. A number of studies have attempted to define factors capable of predicting long term outcomes in specific patient groups. This article reports the outcomes of a very large group of patients diagnosed with GBM, and analyzes specific prognostic factors known to influence survival in these patients.

Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) to investigate various patient-related and treatment- related factors that could influence the long term survival in patients diagnosed with glioblastoma. A total of 34,664 patients aged 20 years or older with a diagnosis of GBM during the years 1973 to 2008 were studied. Overall survival outcomes were examined with Kaplan-Meier survival analysis and Cox hazard models.

Results

Asian/Pacific Islanders had a better survival compared to the white population (P = <0.001). Patients diagnosed with GBM during the years 2000 to 2008 had a superior survival rate when compared with earlier decades (P = <0 .001). Statistically significant improvements in overall survival were also found for patients who received surgical resections, and adjuvant radiation treatment versus no radiation (P-values <0.001). Young age was also found to be highly predictive of improved overall survival rates when separated into age groups as well as when studied as a continuous variable.

Conclusions

Clinical pretreatment and treatment factors, including young age at diagnosis, Asian/Pacific Islander ethnicity, recent year of diagnosis, surgical resection and the use of adjuvant radiation therapy favorably influence survival in patients diagnosed with glioblastoma.

Trial Registration

All data were obtained from the United States Surveillance Epidemiology and End Results (SEER) database.
The impact on clinical outcome of high prevalence of diabetes mellitus in Taiwanese patients with colorectal cancer
Authors: Huang Ching-Wen , Sun Li-Chu , Shih Ying-Ling , Tsai Hsiang-Lin , Chen Chao-Wen , Yeh Yung-Sung , Ma Cheng-Jen , Huang Che-Jen , Wang Jaw-Yuan
Published: May 2012

Background

Both colorectal cancer (CRC) and diabetes mellitus (DM) are important public health problems worldwide. As there are controversies about survival impact on CRC patients with preexisting DM, the purpose of the present study is to evaluate the incidence and the survival impact of preexisting DM on the long-term outcomes of patients with CRC in Taiwan.

Methods

From January 2002 to December 2008, 1,197 consecutive patients with histologically proven primary CRC, who received surgical treatment at a single institution, were enrolled. The clinicopathologic features between these patients with and without DM were retrospectively investigated. Moreover, we intended to analyze the impact of DM on overall survival (OS) and cancer-specific survival (CSS) rates.

Results

Of 1,197 CRC patients, 23.6% of patients had either a reported history of DM or were currently taking one or more diabetes-controlling medications. CRC patients with DM were significantly older than those without DM (P< 0.001), and had a higher incidence of cardiac disease and higher body mass index than those without DM (bothP < 0.001). There were no significant differences in gender, tumor size, tumor location, histological type, AJCC/UICC cancer stage, vascular invasion, perineural invasion, comorbidity of pulmonary disease or renal disease, and OS, and CSS between two groups. Additionally, DM patients had a higher incidence of second malignancy than patients without DM (9.54%vs6.01%,P = 0.040).

Conclusions

A considerably high prevalence of DM in CRC patients but no significant impact of DM on survival was observed in the single-institution retrospective study, regardless of cancer stages and tumor locations. Therefore, treatment strategies for CRC patients with DM should be the same as patients without DM.
Bridging the gaps among research, policy and practice in ten low- and middle-income countries: Development and testing of a questionnaire for health-care providers
Authors: Guindon G Emmanuel , Lavis John N , Boupha Boungnong , Shi Guang , Sidibe Mintou , Turdaliyeva Botagoz ,   Research to Policy and Practice Study Team (RPPST)
Published: May 2012

Background

The reliability and validity of instruments used to survey health-care providers' views about and experiences with research evidence have seldom been examined.

Methods

Country teams from ten low- and middle-income countries (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal and Tanzania) participated in the development, translation, pilot-testing and administration of a questionnaire designed to measure health-care providers' views and activities related to improving their clinical practice and their awareness of, access to and use of research evidence, as well as changes in their clinical practice that they attribute to particular sources of research evidence that they have used. We use internal consistency as a measure of the questionnaire's reliability and, whenever possible, we use explanatory factor analyses to assess the degree to which questions that pertain to a single domain actually address common themes. We assess the questionnaire's face validity and content validity and, to a lesser extent, we also explore its criterion validity.

Results

The questionnaire has high internal consistency, with Cronbach's alphas between 0.7 and 0.9 for 16 of 20 domains and sub-domains (identified by factor analyses). Cronbach's alphas are greater than 0.9 for two domains, suggesting some item redundancy. Pre- and post-field work assessments indicate the questionnaire has good face validity and content validity. Our limited assessment of criterion validity shows weak but statistically significant associations between the general influence of research evidence among providers and more specific measures of providers' change in approach to preventing or treating a clinical condition.

Conclusion

Our analysis points to a number of strengths of the questionnaire - high internal consistency (reliability) and good face and content validity - but also to areas where it can be shortened without losing important conceptual domains.
Bridging the gaps among research, policy and practice in ten low- and middle-income countries: Development and testing of a questionnaire for researchers
Authors: Cameron David , Lavis John N , Guindon G Emmanuel , Akhtar Tasleem , Becerra Posada Francisco , Ndossi Godwin D , Boupha Boungnong ,   Research to Policy and Practice Study Team
Published: May 2012

Background

A questionnaire could assist researchers, policymakers, and healthcare providers to describe and monitor changes in efforts to bridge the gaps among research, policy and practice. No questionnaire focused on researchers' engagement in bridging activities related to high-priority topics (or the potential correlates of their engagement) has been developed and tested in a range of low- and middle-income countries (LMICs).

Methods

Country teams from ten LMICs (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal, and Tanzania) participated in the development and testing of a questionnaire. To assess reliability we calculated the internal consistency of items within each of the ten conceptual domains related to bridging activities (specifically Cronbach's alpha). To assess face and content validity we convened several teleconferences and a workshop. To assess construct validity we calculated the correlation between scales and counts (i.e., criterion measures) for the three countries that employed both and we calculated the correlation between different but theoretically related (i.e., convergent) measures for all countries.

Results

Internal consistency (Cronbach's alpha) for sets of related items was very high, ranging from 0.89 (0.86-0.91) to 0.96 (0.95-0.97), suggesting some item redundancy. Both face and content validity were determined to be high. Assessments of construct validity using criterion-related measures showed statistically significant associations for related measures (with gammas ranging from 0.36 to 0.73). Assessments using convergent measures also showed significant associations (with gammas ranging from 0.30 to 0.50).

Conclusions

While no direct comparison can be made to a comparable questionnaire, our findings do suggest a number of strengths of the questionnaire but also the need to reduce item redundancy and to test its capacity to monitor changes over time.
Identification of subpopulations in mesenchymal stem cell-like cultures from human umbilical cord
Authors: Majore Ingrida , Moretti Pierre , Hass Ralf , Kasper Cornelia
Published: May 2012

Background

A variety of cell types can be identified in the adherent fraction of bone marrow mononuclear cells including more primitive and embryonic-like stem cells, mesenchymal stem cells (MSC), lineage-committed progenitors as well as mature cells such as osteoblasts and fibroblasts. Different methods are described for the isolation of single bone marrow stem cell subpopulations – beginning from ordinary size sieving, long term cultivation under specific conditions to FACS-based approaches. Besides bone marrow-derived subpopulations, also other tissues including human umbilical cord (UC) have been recently suggested to provide a potential source for MSC. Although of clinical importance, these UC-derived MSC populations remain to be characterized. It was thus the aim of the present study to identify possible subpopulations in cultures of MSC-like cells obtained from UC. We used counterflow centrifugal elutriation (CCE) as a novel strategy to successfully address this question.

Results

UC-derived primary cells were separated by CCE and revealed differentially-sized populations in the fractions. Thus, a subpopulation with an average diameter of about 11 μm and a small flat cell body was compared to a large sized subpopulation of about 19 μm average diameter. Flow cytometric analysis revealed the expression of certain MSC stem cell markers including CD44, CD73, CD90 and CD105, respectively, although these markers were expressed at higher levels in the small-sized population. Moreover, this small-sized subpopulation exhibited a higher proliferative capacity as compared to the total UC-derived primary cultures and the large-sized cells and demonstrated a reduced amount of aging cells.

Conclusion

Using the CCE technique, we were the first to demonstrate a subpopulation of small-sized UC-derived primary cells carrying MSC-like characteristics according to the presence of various mesenchymal stem cell markers. This is also supported by the high proliferative capacity of these MSC-like cells as compared to whole primary culture or other UC-derived subpopulations. The accumulation of a self-renewing MSC-like subpopulation by CCE with low expression levels of the aging marker senescence-associated β-galactosidase provides a valuable tool in the regenerative medicine and an alternative to bone-marrow-derived MSC.
A decentralized spectrum allocation and partitioning scheme for a two-tier macro-femtocell network with downlink beamforming
Authors: Ryoo Sunheui , Joo Changhee , Bahk Saewoong
Published: May 2012

This article examines spectrum allocation and partitioning schemes to mitigate cross-tier interference under downlink beamforming environments. The enhanced SIR owing to beamforming allows more femtocells to share their spectrum with the macrocell and accordingly improves overall spectrum efficiency. We first design a simplified centralized scheme as the optimum and then propose a practical decentralized algorithm that determines which femtocells to use the full or partitioned spectrum with acceptable control overhead. To exploit limited information of the received signal strength efficiently, we consider two types of probabilistic femtocell base station (HeNB) selection policies. They are equal selection and interference weighted selection policies, and we drive their outage probabilities for a macrocell user. Through performance evaluation, we demonstrate that the outage probability and the cell capacity in our decentralized scheme are significantly better than those in a conventional cochannel deployment scheme. Furthermore, we show that the cell utility in our proposed scheme is close to that in the centralized scheme and better than that in the spectrum partitioning scheme with a fixed ratio.
MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency
Authors: Grupping Katrijn , Selhorst Philippe , Michiels Johan , Vereecken Katleen , Heyndrickx Leo , Kessler Pascal , Vanham Guido , Martin Loïc , Ariën Kevin K
Published: May 2012

Background

Binding of the viral envelope protein (Env), and particularly of its gp120 subunit, to the cellular CD4 receptor is the first essential step of the HIV-1 entry process. The CD4 binding site (CD4bs) of gp120, and especially a recessed cavity occupied by the CD4 Phe43 residue, are known to be highly conserved among the different circulating subtypes and therefore constitute particularly interesting targets for vaccine and drug design. The miniCD4 proteins are a promising class of CD4bs inhibitors. Studying virus evolution under pressure of CD4bs inhibitors could provide insight on the gp120-CD4 interaction and viral entry.

Results

The present study reports on the resistance induction of two subtype B HIV-1 against the most active miniCD4, M48U1, and its ancestor, M48, and how these mutated positions affect CD4bs recognition, entry efficiency, and sensitivity to other CD4bs inhibitors. Resistance against M48U1 was always associated with S375R/N substitution in both BaL and SF162; M48 resistance was associated with D474N substitution in SF162 and with H105Y substitution in BaL. In addition, some other mutations at position V255 and G471 were of importance for SF162 resistant viruses. Except for 474, all of these mutated positions are conserved, and introducing them into an SF162 Env expressing infectious molecular clone (pBRNL4.3 SF162) resulted in decreased entry efficiency. Furthermore, resistant mutants showed at least some cross-resistance towards other CD4bs inhibitors, the V3 monoclonal antibody 447-52D and some even against the monoclonal antibody 17b, of which the epitope overlaps the co-receptor binding site.

Conclusions

The mutations H105Y, V255M, S375R/N, G471R/E, and D474N are found to be involved in resistance towards M48 and M48U1. All mutated positions are part of, or in close proximity to, the CD4bs; most are highly conserved, and all have an impact on the entry efficiency, suggesting their importance for optimal virus infectivity.
Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism
Authors: Wang Tzu-Yun , Lee Sheng-Yu , Chen Shiou-Lan , Chang Yun-Hsuan , Chen Shih-Heng , Chu Chun-Hsien , Huang San-Yuan , Tzeng Nian-Sheng , Wang Chen-Lin , Lee I Hui , Yeh Tzung Lieh , Yang Yen Kuang , Lu Ru-Band
Published: May 2012

Background

Several studies have hypothesized that genes regulating the components of the serotonin system, includingserotonin transporter(5-HTTLPR) andserotonin 1 B receptor (5-HT1B),may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the5-HTTLPRgene and5-HT1BgeneG861Cpolymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan.

Methods

We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n = 120) and antisocial non-alcoholism (AS-N-ALC) group (n = 153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP.

Results

There were no significant differences in the genotypic frequency of the5-HT1B G861Cpolymorphism between the 3 groups. Although AS-ALC group members more frequently carried the5-HTTLPR S/S, S/LG,andLG/LGgenotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the5-HTTLPR S/S, S/LG,andLG/LGgenotypes may have interacted with the5-HT1B G861C C/Cpolymorphism and increased the risk of becoming antisocial alcoholism.

Conclusion

Our study suggests that neither the5-HTTLPRgene nor the5-HT1B G861Cpolymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.
Research into practice: Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Nottinghamshire, Derbyshire, Lincolnshire (NDL)
Authors: Rowley Emma , Morriss Richard , Currie Graeme , Schneider Justine
Published: May 2012

Background

To address the problem of translation from research-based evidence to routine healthcare practice, the Collaboration for Leadership in Applied Health Research and Care for Nottinghamshire, Derbyshire, and Lincolnshire (CLAHRC-NDL) was funded by the National Institute for Health Research as one of nine CLAHRCs across England. This paper outlines the underlying theory and its application that CLAHRC-NDL has adopted, as a case example that might be generalised to practice outside the CLAHRC, in comparison to alternative models of implementation.

Discussion

Conventional approaches to health research frequently generate evidence in isolation from the environment in which it is intended for use. The premise of the CLAHRC-NDL model is that barriers to implementation can be overcome if knowledge is co-produced by academic and clinical service staff, taking account of the organisational context in which it is to be applied. This approach is founded on organisational learning theory, recognising that change is a social and political phenomenon. Evidence is produced in real time, taking full account of the environment in which it is to be implemented. To support this process, senior health service staff are seconded to the CLAHRC as ‘diffusion fellows’ (DFs) to actively bridge the research to practice gap by being a full member of both the research team and their area of clinical practice. To facilitate innovation and embed change in the local health community, existing communities of practice are enhanced and new ones are fostered around specific themes. Our approach has been adopted by 16 clinical research studies in the areas of mental health, children and young people, primary care, and stroke rehabilitation.

The CLAHRC-NDL model of implementation applies organisational learning theory by addressing the social and situational barriers and enablers to implementation, and adopting a philosophy of co-production. Two key mechanisms for translation of innovation have been utilised: DFs, to actively bridge the research to practice gap, and communities of practice, to underpin and sustain improvements in healthcare. The model shows promising results in putting research into practice, which may be transferable to other healthcare contexts.
Lysosomal Membrane Permeabilization is an Early Event in Sigma-2 Receptor Ligand Mediated Cell Death in Pancreatic Cancer
Authors: Hornick John R , Vangveravong Suwanna , Spitzer Dirk , Abate Carmen , Berardi Francesco , Goedegebuure Peter , Mach Robert H , Hawkins William G
Published: May 2012

Background

Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer.

Results

Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43.

Conclusions

Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death following LMP protected by DEVD-FMK and α-toco, which is also known to stabilize the mitochondrial membrane during apoptotic stimuli. These differences in mechanism are likely dependent on the structural class of the compounds versus the inherent sigma-2 binding affinity. As resistance of pancreatic cancers to specific apoptotic stimuli from chemotherapy is better appreciated, and patient-tailored treatments become more available, ligands with high sigma-2 receptor affinity should be chosen based on sensitivities to apoptotic pathways.
A new vision of definition, commentary, and understanding in clinical and translational medicine
Authors: Wang Xiangdong
Published: May 2012

There is growing evidence to the importance of translational science and medicine in the improvement of patient outcome, even though the definitions of translational science, translational medicine, and clinical and translational medicine need to be further clarified. In the present perspective, we collected commentaries and descriptions about clinical and translational medicine from some members of Clinical and Translational Medicine editorial board to stimulate the discussion and help the understanding better.
ATP-binding cassette transporters in immortalised human brain microvascular endothelial cells in normal and hypoxic conditions
Authors: Lindner Christian , Sigrüner Alexander , Walther Franziska , Bogdahn Ulrich , Couraud Pierre O , Schmitz Gert , Schlachetzki Felix
Published: May 2012

Background

Rapid reperfusion following ischemia is the most effective therapy in stroke therapy. However, the success may be compromised by ischemia & reperfusion (I/R) injury and at the human blood–brain barrier (BBB), therefore the effects on transendothelial transport are of special interest. Current studies suggest the ATP-binding cassette (ABC) transporters to be regulated upon ischemic stroke in a way that impedes the effects of drug therapy. The immortalised human brain microvascular endothelial cell line hCMEC/D3 provides most of the unique properties of the BBB with respect to transport and might be a reliable in vitro model to study transendothelial transport after I/R.

Methods

We exposed hCMEC/D3 cells to 24 hours of hypoxia alone and to hypoxia followed by 60 min of reoxygenisation as an in vitro model for I/R. Western blot showed mild upregulation of hypoxia inducible factor (HIF-1α) after hypoxia alone and RNA lysates were analysed with a well-established real-time RT-PCR-based TaqMan low-density array detecting 47 of 48 known human ABC transporters.

Results

No significant increases of ABC mRNA expression levels were detected neither in hypoxic nor in I/R samples. However, slight decrease of ABCC1 in hypoxic and I/R samples and of ABCA10 and ABCD3 in I/R samples was observed.

Conclusion

Our data suggests that hCMEC/D3 cell line and – at the moment – in vitro models in general are a poor basis for stroke research but may be enhanced by co-culturing more cells of the neurovascular unit inducing an overall ischemic response at the BBB.
The effects of oxygen tension and antiaging factor Klothoon Wnt signaling in nucleus pulposus cells
Authors: Hiyama Akihiko , Arai Fumiyuki , Sakai Daisuke , Yokoyama Katsuya , Mochida Joji
Published: May 2012

Introduction

The goals of this study were to examine the oxemic regulation of Wnt signaling to explore whether Wnt signaling accelerates the age-related degeneration of nucleus pulposus cells, and if so, to define the mechanism underlying this effect. We investigated the expression of Klotho, a newly identified antiaging gene, and whether its regulation is attributable to the suppression of Wnt signaling.

Methods

Rat nucleus pulposus cells were cultured under normoxic (21% O2) or hypoxic (2% O2) conditions, and the expression and promoter activity of Wnt signaling and Klotho were evaluated. The effect of Klotho protein was examined with transfection experiments, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, senescence-associated β-galactosidase staining, and cell-cycle analysis. To determine the methylation status of the Klotho promoter region, bisulfite genomic sequencing analysis was performed. Its relation with the activation of Wnt signaling was assessed. We also examined whether the expression of Klotho could block the effects of pathological Wnt expression in nucleus pulposus cells.

Results

Nucleus pulposus cells exhibited increased β-catenin mRNA and protein under the hypoxic condition. Klotho protein was expressed in vivo, and protein and messenger RNA expression decreased under the hypoxic condition. Klotho treatment decreased cell proliferation and induced the quiescence of nucleus pulposus cells. In addition, Klotho treatment inhibited expression of β-catenin gene and protein compared with untreated control cells.

Conclusions

These data indicate that Wnt signaling and Klotho form a negative-feedback loop in nucleus pulposus cells. These results suggest that the expression of Klotho is regulated by the balance between upregulation and downregulation of Wnt signaling.