bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping with multimorbidity in old age – a qualitative study
Authors: Löffler Christin , Kaduszkiewicz Hanna , Stolzenbach Carl-Otto , Streich Waldemar , Fuchs Angela , van den Bussche Hendrik , Stolper Friederike , Altiner Attila
Published: May 2012

Background

Comparatively few studies address the problems related to multimorbidity. This is surprising, since multimorbidity is a particular challenge for both general practitioners and patients. This study focuses on the latter, analyzing the way patients aged 65–85 cope with multimorbidity.

Methods

19 narrative in-depth interviews with multimorbid patients were conducted. The data was analysed using grounded theory. Of the 19 interviewed patients 13 were female and 6 male. Mean age was 75 years. Participating patients showed a relatively homogeneous socio-economic status. Patients were recruited from the German city of Hamburg and the state of North Rhine-Westphalia.

Results

Despite suffering from multimorbidity, interviewees held positive attitudes towards life: At the social level, patients tried to preserve their autonomy to the most possible extent. At the emotional level, interviewees oscillated between anxiety and strength - having, however, a positive approach to life. At the practical level, patients aimed at keeping their diseases under control. The patients tended to be critical in regards to medication.

Conclusions

These findings might have implications for the treatment of multimorbid patients in primary care and further research: The generally presumed passivity of older individuals towards medical treatment, which can be found in literature, is not evident among our sample of older patients. In future, treatment of these patients might take their potential for pro-active cooperation more strongly into account than it is currently the case.
The effect of taping versus semi-rigid bracing on patient outcome and satisfaction in ankle sprains: a prospective, randomized controlled trial
Authors: Lardenoye Sacha , Theunissen Ed , Cleffken Berry , Brink Peter RG , de Bie Rob A , Poeze Martijn
Published: May 2012

Background

Functional treatment is a widely used and generally accepted treatment for ankle sprain. A meta-analysis comparing the different functional treatment options could not make definitive conclusions regarding the effectiveness, and until now, little was known about patient satisfaction in relation to the outcome.

Methods

Patients with acute ankle sprain received rest, ice, compression and elevation with an compressive bandage at the emergency department. After 5-7 days, 100 patients with grade II and III sprains were randomized into two groups: one group was treated with tape and the other with a semi-rigid ankle brace, both for 4 weeks. Post-injury physical and proprioceptive training was standardized. As primary outcome parameter patient satisfaction and skin complications were evaluated using a predefined questionnaire and numeric rating scale. As secondary outcome parameter the ankle joint function was assessed using the Karlsson scoring scale and range of motion.

Results

Patient-reported comfort and satisfaction during treatment with a semi-rigid brace was significantly increased. The rate of skin complication in this group was significantly lower compared to the tape group (14.6% versus 59.1%, P < 0.0001). Functional outcome of the ankle joint was similar between the two treatment groups, as well as reported pain.

Conclusion

Treatment of acute ankle sprain with semi-rigid brace leads to significantly higher patient comfort and satisfaction, both with similar good outcome.
Therapeutic effects of radix dipsaci, pyrola herb, and cynomorium songaricum on bone metabolism of ovariectomized rats
Authors: Liu Meijie , Xiao Gary Guishan , Rong Peijing , Zhang Zhiguo , Dong Jiazi , Zhao Hongyan , Li Honghong , Li Yan , Pan Jinghua , Liu Hong , Wang Wenlai , Zha Qinglin , Ju Dahong
Published: May 2012

Background

The objective of this study was to evaluate the effects of herbal medicines, such as Radix Dipsaci (RDD), Pyrola Herb (PHD), and Cynomorium songaricum decoction (CSD), on osteoporotic rats induced by ovariectomy (OVX).

Methods

OVX or sham operations were performed on 69 virgin Wistar rats that were divided into six groups: sham (sham, n = 12), OVX control group (OVX, n = 12), and OVX rats with treatments (diethylstilbestrol, E2, n = 12; RDD, n = 11, PHD, n = 11, and CSD, n = 11). Non-surgical rats served as normal control (NC, n = 12). The treatments began four weeks after surgery and lasted for 12 weeks. Bone mass and bone turnover were analyzed by histomorphometry. Levels of protein expression and mRNA of OPG and RANKL in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization.

Results

Compared to NC and sham rats, trabecular bone formation was significantly reduced in OVX rats, but restored in E2-treated rats. Treatment with either RDD or PHD enhanced trabecular bone formation remarkably. No significant change of bone formation was observed in CSD-treated rats. OPG expression of protein and mRNA was reduced significantly in OB and bMSC of OVX control rats. RANKL expression of protein and mRNA was increased significantly in OB and bMSC of OVX control rats. These effects were substantially reversed (increased in OPG and decreased in RANKL) by treatment with E2, RDD, or PHD in OB and bMSC of OVX rats. No significant changes in either OPG or RANKL expression were observed in OB and bMSC of OVX rats treated with CSD.

Conclusions

Our study showed that RDD and PHD increased bone formation by stimulating overexpression of OPG and downregulation of RANKL in OB and bMSC. This suggests that RDD and PHD may be used as alternative therapeutic agents for postmenopausal osteoporosis.
Impact on learning of an e-learning module on leukaemia: a randomised controlled trial
Authors: Morgulis Yuri , Kumar Rakesh K , Lindeman Robert , Velan Gary M
Published: May 2012

Background

e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources.

Methods

A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period.

Results

Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive.

Conclusions

A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.
Production of 2,3-butanediol in Saccharomyces cerevisiae by in silico aided metabolic engineering
Authors: Ng ChiamYu , Jung Moo-young , Lee Jinwon , Oh Min-Kyu
Published: May 2012

Background

2,3-Butanediol is a chemical compound of increasing interest due to its wide applications. It can be synthesized via mixed acid fermentation of pathogenic bacteria such as Enterobacter aerogenes and Klebsiella oxytoca. The non-pathogenic Saccharomyces cerevisiae possesses three different 2,3-butanediol biosynthetic pathways, but produces minute amount of 2,3-butanediol. Hence, we attempted to engineer S. cerevisiae strain to enhance 2,3-butanediol production.

Results

We first identified gene deletion strategy by performing in silico genome-scale metabolic analysis. Based on the best in silico strategy, in which disruption of alcohol dehydrogenase (ADH) pathway is required, we then constructed gene deletion mutant strains and performed batch cultivation of the strains. Deletion of three ADH genes, ADH1, ADH3 and ADH5, increased 2,3-butanediol production by 55-fold under microaerobic condition. However, overproduction of glycerol was observed in this triple deletion strain. Additional rational design to reduce glycerol production by GPD2 deletion altered the carbon fluxes back to ethanol and significantly reduced 2,3-butanediol production. Deletion of ALD6 reduced acetate production in strains lacking major ADH isozymes, but it did not favor 2,3-butanediol production. Finally, we introduced 2,3-butanediol biosynthetic pathway from Bacillus subtilis and E. aerogenes to the engineered strain and successfully increased titer and yield. Highest 2,3-butanediol titer (2.29 g·l-1) and yield (0.113 g·g-1) were achieved by Δadh1 Δadh3 Δadh5 strain under anaerobic condition.

Conclusions

With the aid of in silico metabolic engineering, we have successfully designed and constructed S. cerevisiae strains with improved 2,3-butanediol production.
Factors explaining the gender disparity in lipid-lowering treatment goal attainment rate in Chinese patients with statin therapy
Authors: Zhang Rui , Zhao Liancheng , Liang Lirong , Xie Gaoqiang , Wu Yangfeng
Published: May 2012

Background

The lipid-lowering treatment goal attainment rate is lower for women than for men among Chinese patients, but the reasons for this disparity have not been fully explored yet.

Objectives

To elucidate the potential factors and the significance of their contributions towards the observed discrepancy in lipid-lowering treatment goal attainment rates between Chinese women and men.

Methods

We used data from 1808 patients from 21 tertiary and 6 secondary hospitals in China who received and maintained statin therapy treatment for at least 2 months. Lipid-lowering treatment goal attainment was defined as low-density lipoprotein cholesterol (LDL- C) reaching the treatment targets recommended by the Chinese Guidelines on Prevention and Control of Dyslipidemia in Adults. Logistic Regression was used to explore possible factors associated with gender disparity in goal attainment rates, and to what extent each factor contributes.

Results

A total of 674 women and 1134 men were enrolled in the study. Women had a significantly lower LDL-C goal attainment rate than that of men (46.0% vs 53.8%, P = 0.002), particularly in high and very high CVD risk groups. Among high and very high risk patients, approximately 35%, 7%, 5%, and 5% of gender disparity in LDL-C goal attainment rate was attributable to the gender difference in baseline LDL-C level, cardiovascular co-morbidities and associated risk factors, socioeconomic status, and the dosage of statin treatment, respectively. Approximately 50% of the gender disparity remained unexplained by these factors.

Conclusions

Although nearly half of the gender disparity in lipid-lowering treatment goal attainment rate can be explained by the gender differences in baseline lipid level, socioeconomic status, cardiovascular co-morbidities and associated risk factors, and the dosage of statin in high and very high CVD risk patients, the other half of the gender disparity remains unexplained and requires further study to fully understand what other factors are at play.
Left ventricular strain and peak systolic velocity: responses to controlled changes in load and contractility, explored in a porcine model
Authors: A’roch Roman , Gustafsson Ulf , Johansson Göran , Poelaert Jan , Haney Michael
Published: May 2012

Background

Tissue velocity echocardiography is increasingly used to evaluate global and regional cardiac function. Previous studies have suggested that the quantitative measurements obtained during ejection are reliable indices of contractility, though their load-sensitivity has been studied in different settings, but still remains a matter of controversy. We sought to characterize the effects of acute load change (both preload and afterload) and change in inotropic state on peak systolic velocity and strain as a measure of LV contractility.

Methods

Thirteen anesthetized juvenile pigs were studied, using direct measurement of left ventricular pressure and volume and transthoracic echocardiography. Transient inflation of a vena cava balloon catheter produced controlled load alterations. At least eight consecutive beats in the sequence were analyzed with tissue velocity echocardiography during the load alteration and analyzed for change in peak systolic velocities and strain during same contractile status with a controlled load alteration. Two pharmacological inotropic interventions were also included to generate several myocardial contractile conditions in each animal.

Results

Peak systolic velocities reflected the drug-induced changes in contractility in both radial and longitudinal axis. During the acute load change, the peak systolic velocities remain stable when derived from signal in the longitudinal axis and from the radial axis. The peak systolic velocity parameter demonstrated no strong relation to either load or inotropic intervention, that is, it remained unchanged when load was systematically and progressively varied (peak systolic velocity, longitudinal axis, control group beat 1-5.72 ± 1.36 with beat 8–6.49 ± 1.28 cm/sec, 95% confidence interval), with the single exception of the negative inotropic intervention group where peak systolic velocity decreased a small amount during load reduction (beat 1–3.98 ± 0.92 with beat 8–2.72 ± 0.89 cm/sec). Systolic strain, however, showed a clear degree of load-dependence.

Conclusions

Peak systolic velocity appears to be load-independent as tested by beat-to-beat load reduction, while peak systolic strain appears to be load-dependent in this model. Peak systolic velocity, in a controlled experimental model where successive beats during load alteration are assessed, has a strong relation to contractility. Peak systolic velocity, but not peak strain rate, is largely independent of load, in this model. More study is needed to confirm this finding in the clinical setting.
Altered glucose disposition and insulin sensitivity in peri-pubertal first-degree relatives of women with polycystic ovary syndrome
Authors: Raissouni Nouhad , Kolesnikov Andrey , Purushothaman Radhika , Sinha Sunil , Bhandari Sonal , Bhangoo Amrit , Malik Shahid , Mathew Revi , Baillargeon Jean-Patrice , Hernandez Maria Isabel , Rosenbaum Michael , Ten Svetlana , Geller David
Published: May 2012

Background

First-degree relatives (FDRs) of women with PCOS are at increased risk for impaired insulin sensitivity and diabetes mellitus. Glucose tolerant FDR have evidence of insulin resistance and hyperinsulinemia prior to emergence of frank PCOS.

Aim

To study insulin dynamics parameters in the early adolescent FDR of women with PCOS.

Methods

This is a cross-sectional study involving 18 adolescents whose mothers or sisters had been diagnosed with PCOS and 21 healthy, age-matched control adolescents without FDR. Subjects underwent anthropometric measurements, steroid profiling and frequently sampled Intravenous Glucose Tolerance Test (IVGTT), Homeostasis Model Assessment (HOMA) index, Glucose Disposal Index (GDI), Acute Insulin Response (AIR) and Quantitative insulin sensitivity check index (QUICKI) were derived from IVGTT results.

Results

FDRs showed significantly higher mean HOMA and lower GDI. There were no differences in mean age or BMI Z-score between the cohorts. No differences in sex steroids or AIR were identified between groups.

Conclusion

Female adolescent FDR of women with PCOS have higher HOMA index and lower QUICKI, reflecting altered insulin sensitivity and lower GDI reflecting poorer beta-cell function. The presence of multiple risk factors for type 2 diabetes suggests that aggressive screening of the early adolescent FDR of women with PCOS is indicated.
Tumor necrosis factor-α synthesis inhibitor 3,6′-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer’s disease
Authors: Tweedie David , Ferguson Ryan A , Fishman Kelly , Frankola Kathryn A , Van Praag Henriette , Holloway Harold W , Luo Weiming , Li Yazhou , Caracciolo Luca , Russo Isabella , Barlati Sergio , Ray Balmiki , Lahiri Debomoy K , Bosetti Francesca , Greig Nigel H , Rosi Susanna
Published: May 2012

Background

Neuroinflammation is associated with virtually all major neurodegenerative disorders, including Alzheimer’s disease (AD). Although it remains unclear whether neuroinflammation is the driving force behind these disorders, compelling evidence implicates its role in exacerbating disease progression, with a key player being the potent proinflammatory cytokine TNF-α. Elevated TNF-α levels are commonly detected in the clinic and animal models of AD.

Methods

The potential benefits of a novel TNF-α-lowering agent, 3,6′-dithiothalidomide, were investigated in cellular and rodent models of neuroinflammation with a specific focus on AD. These included central and systemic inflammation induced by lipopolysaccharide (LPS) and Aβ1–42 challenge, and biochemical and behavioral assessment of 3xTg-AD mice following chronic 3,6′-dithiothaliodmide.

Results

3,6′-Dithiothaliodmide lowered TNF-α, nitrite (an indicator of oxidative damage) and secreted amyloid precursor protein (sAPP) levels in LPS-activated macrophage-like cells (RAW 264.7 cells). This translated into reduced central and systemic TNF-α production in acute LPS-challenged rats, and to a reduction of neuroinflammatory markers and restoration of neuronal plasticity following chronic central challenge of LPS. In mice centrally challenged with Aβ1–42 peptide, prior systemic 3,6′-dithiothalidomide suppressed Aβ-induced memory dysfunction, microglial activation and neuronal degeneration. Chronic 3,6′-dithiothalidomide administration to an elderly symptomatic cohort of 3xTg-AD mice reduced multiple hallmark features of AD, including phosphorylated tau protein, APP, Aβ peptide and Aβ-plaque number along with deficits in memory function to levels present in younger adult cognitively unimpaired 3xTg-AD mice. Levels of the synaptic proteins, SNAP25 and synaptophysin, were found to be elevated in older symptomatic drug-treated 3xTg-AD mice compared to vehicle-treated ones, indicative of a preservation of synaptic function during drug treatment.

Conclusions

Our data suggest a strong beneficial effect of 3,6′-dithiothalidomide in the setting of neuroinflammation and AD, supporting a role for neuroinflammation and TNF-α in disease progression and their targeting as a means of clinical management.
Analgesia effect of a fixed nitrous oxide/oxygen mixture on burn dressing pain: study protocol for a randomized controlled trial
Authors: Yuxiang Li , Lu Tang , Jianqiang Yu , Xiuying Dai , Wanfang Zhou , Wannian Zhang , Xiaoyan Hu , Shichu Xiao , Wen Ni , Xiuqiang Ma , Yinsheng Wu , Ming Yao , Guoxia Mu , Guangyi Wang , Wenjun Han , Zhaofan Xia , Hongtai Tang , Jijun Zhao
Published: May 2012

Background

Procedural burn pain is the most intense acute pain and most likely type of burn injury pain to be undertreated due to the physician’s fear of the adverse effect of analgesia and lack of anesthetist present. At our institution, in most of the cases, local burn detersion and debridement were performed at the ward level without any analgesics. This article describes a study designed to test the analgesia effect of a fixed nitrous oxide/oxygen mixture on burn dressing pain.

Methods/design

The experiment was carried out in three centers. The patients were given a number from 1 to 240. A randomization list was produced by a statistician according to our preliminary study. Due to the severity of the pain suffered, ethically it was decided to help as many as possible, so patients given the letters A, B or C were treated using a canister with the appropriate letter containing preprepared nitrous oxide/oxygen mixture (NOOM). Those with D were given oxygen only, from an identical-looking canister labeled D. Neither patients, nor doctors, nor nurses, nor data collector knew what was in each canister, thus they were all blind. The nursing officer who implemented the intervention handed the doctors envelopes containing the patients’ name and allocation of A, B, C or D. Thus, patients receiving NOOM or oxygen were in the ratio 3:1. Parameters, including pain severity, blood pressure, heart rate, digital oxygen saturation and the Chinese version of the burn specific pain anxiety scale (C-BSPAS), were taken before, during and after dressing for each group. A video and audio record was taken individually for later communication coding and outcome analysis. Rescue analgesic was recorded.

Discussion

Based on the findings from our previous qualitative study that physician’s reluctance to order narcotic analgesia is due to its adverse effect and from our pilot experiment, this study aims to test the hypothesis that a fixed nitrous oxide/oxygen mixture will promote better burn dressing pain alleviation and outcomes. Analyses will focus on the effects of the experimental intervention on pain severity during dressing (primary outcomes); physiological parameters, C-BSPAS and acceptance of both health care professionals and patients (secondary outcomes). If this model of analgesia for burn pain management implemented by nurses proves successful, it could potentially be implemented widely in hospital and prehospital settings and improve patients’ satisfaction and quality of life.

Trial registration

(Clinical Trials Identifier: CHICTR-TRC11001690).
The effects of exercise during pregnancy on the newborn’s brain: study protocol for a randomized controlled trial
Authors: LeMoyne Elise L , Curnier Daniel , St-Jacques Samuel , Ellemberg Dave
Published: May 2012

Background

It is generally accepted that an active lifestyle is beneficial for cognition in children, adults and the elderly. Recently, studies using the rat animal model found that the pups of mothers who exercised during pregnancy had increased hippocampal neurogenesis and better memory and learning abilities. The aim of this report is to present the experimental protocol of a study that is designed to verify if an active lifestyle during pregnancy in humans has an impact on the newborn's brain.

Methods

60 pregnant women will be included in a randomized controlled study. The experimental group will be asked to exercise a minimum of 20 minutes three times per week, at a minimal intensity of 55% of their maximal aerobic capacity. The control group will not be exercising. The effect of exercise during pregnancy on the newborn's brain will be investigated 8 to 12 days postpartum by means of the mismatch negativity, a neurophysiological brain potential that is associated to auditory sensory memory. We hypothesize that children born to mothers who exercised during their pregnancy will present shorter latencies and larger mismatch negativity amplitudes, indicating more efficient auditory memory processes.

Discussion

As of September 2011, 17 women have joined the study. Preliminary results show that the experimental group are active 3.1 ± 0.9 days per week while the control group only exercise 0.8 ± 0.6 days per week. The results of this study will present insight on fetal neuroplasticity and will be a valuable tool for health professionals who wish to encourage pregnant women to exercise.

Trial registration

ClinicalTrials.gov registration: NTC01220778
Survey of co-infection by Salmonellaand oxyurids in tortoises
Authors: Dipineto Ludovico , Capasso Michele , Maurelli Maria Paola , Russo Tamara Pasqualina , Pepe Paola , Capone Giovanni , Fioretti Alessandro , Cringoli Giuseppe , Rinaldi Laura
Published: May 2012

Background

Salmonella spp. and oxyurids are among the most prevalent bacterial and parasitic agents in reptiles. These organisms are routinely isolated in healthy tortoises, although heavy infections may cause significant pathology. Tortoises are considered a common source of reptile-associated salmonellosis, an important zoonosis reported worldwide. A survey of the prevalence of Salmonella spp. and oxyurids in 53 tortoises was conducted in southern Italy and a possible correlation between the two pathogens was therefore investigated.

Results

Salmonella spp. and oxyurids were detected with a prevalence of 49.1 and 81.1%, respectively. A significant positive correlation between Salmonella spp. and oxyurids was demonstrated. However, confounding factors related to husbandry could have been involved in determining this correlation.

Conclusions

Our results suggest that caution should be exercised in translocation, husbandry, and human contact with tortoises and other exotic pets. Further studies on the epidemiology, molecular characterization and pathogenesis of Salmonella and oxyurids are needed to assess the actual impact of these organisms, as single or associated infections, on tortoises and on other exotic pets.
Exacerbated metastatic disease in a mouse mammary tumor model following latent gammaherpesvirus infection
Authors: Chauhan Vinita S , Nelson Daniel A , Roy Lopamudra Das , Mukherjee Pinku , Bost Kenneth L
Published: May 2012

Background

Controversy exists as to the ability of human gammaherpesviruses to cause or exacerbate breast cancer disease in patients. The difficulty in conducting definitive human studies can be over come by investigating developing breast cancer in a mouse model. In this study, we utilized mice latently infected with murine gammaherpesvirus 68 (HV-68) to question whether such a viral burden could exacerbate metastatic breast cancer disease using a mouse mammary tumor model.

Results

Mice latently infected with HV-68 had a similar primary tumor burden, but much greater metastatic disease, when compared to mock treated mice given the transplantable tumor, 4 T1. This was true for lung lesions, as well as secondary tumor masses. Increased expression of pan-cytokeratin and VEGF-A in tumors from HV-68 infected mice was consistent with increased metastatic disease in these animals. Surprisingly, no viral particles could be cultured from tumor tissues, and the presence of viral DNA or RNA transcripts could not be detected in primary or secondary tumor tissues.

Conclusions

Latent HV-68 infection had no significant effect on the size of primary 4 T1 mammary tumors, but exacerbated the number of metastatic lung lesions and secondary tumors when compared to mock treated mice. Increased expression of the tumor marker, pan-cytokeratin, and VEGF-A in tumors of mice harboring latent virus was consistent with an exacerbated metastatic disease. Mechanisms responsible for this exacerbation are indirect, since no virus could be detected in cancerous tissues.
Bovine serum albumin further enhances the effects of organic solvents on increased yield of polymerase chain reaction of GC-rich templates
Authors: Farell Eric M , Alexandre Gladys
Published: May 2012

Background

While being a standard powerful molecular biology technique, applications of the PCR to the amplification of high GC-rich DNA samples still present challenges which include limited yield and poor specificity of the reaction. Organic solvents, including DMSO and formamide, have been often employed as additives to increase the efficiency of amplification of high GC content (GC > 60%) DNA sequences. Bovine serum albumin (BSA) has been used as an additive in several applications, including restriction enzyme digestions as well as in PCR amplification of templates from environmental samples that contain potential inhibitors such as phenolic compounds.

Findings

Significant increase in PCR amplification yields of GC-rich DNA targets ranging in sizes from 0.4 kb to 7.1 kb were achieved by using BSA as a co-additive along with DMSO and formamide. Notably, enhancing effects of BSA occurs in the initial PCR cycles with BSA additions having no detrimental impact on PCR yield or specificity. When a PCR was set up such that the cycling parameters paused after every ten cycles to allow for supplementation of BSA, combining BSA and organic solvent produced significantly higher yields relative to conditions using the solvent alone. The co-enhancing effects of BSA in presence of organic solvents were also obtained in other PCR applications, including site-directed mutagenesis and overlap extension PCR.

Conclusions

BSA significantly enhances PCR amplification yield when used in combination with organic solvents, DMSO or formamide. BSA enhancing effects were obtained in several PCR applications, with DNA templates of high GC content and spanning a broad size range. When added to the reaction buffer, promoting effects of BSA were seen in the first cycles of the PCR, regardless of the size of the DNA to amplify. The strategy outlined here provides a cost-effective alternative for increasing the efficiency of PCR amplification of GC-rich DNA targets over a broad size range.
XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by occupational chromium exposure
Authors: Zhang Xuhui , Zhang Xuan , Zhang Lei , Chen Qing , Yang Zhangping , Yu Jingmin , Fu Hong , Zhu Yimin
Published: May 2012

Background

Occupational chromium exposure may induce DNA damage and lead to lung cancer and other work-related diseases. DNA repair gene polymorphisms, which may alter the efficiency of DNA repair, thus may contribute to genetic susceptibility of DNA damage. The aim of this study was to test the hypothesis that the genetic variations of 9 major DNA repair genes could modulate the hexavalent chromium (Cr (VI))-induced DNA damage.

Findings

The median (P25-P75) of Olive tail moment was 0.93 (0.58–1.79) for individuals carrying GG genotype of XRCC1 Arg399Gln (G/A), 0.73 (0.46–1.35) for GA heterozygote and 0.50 (0.43–0.93) for AA genotype. Significant difference was found among the subjects with three different genotypes (P = 0.048) after adjusting the confounding factors. The median of Olive tail moment of the subjects carrying A allele (the genotypes of AA and GA) was 0.66 (0.44–1.31), which was significantly lower than that of subjects with GG genotype (P = 0.043). The A allele conferred a significantly reduced risk of DNA damage with the OR of 0.39 (95% CI: 0.15–0.99, P = 0.048). No significant association was found between the XRCC1Arg194Trp, ERCC1 C8092A, ERCC5 His1104Asp, ERCC6 Gly399Asp, GSTP1 Ile105Val, OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln and DNA damage.

Conclusion

The polymorphism of Arg399Gln in XRCC1 was associated with the Cr (VI)- induced DNA damage. XRCC1 Arg399Gln may serve as a genetic biomarker of susceptibility for Cr (VI)- induced DNA damage.
Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system
Authors: Swift-Gallant Ashlyn , Niel Lee , Monks D Ashley
Published: May 2012

Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.
Technical Advance: Decreased helper T cells and increased natural killer cells in chronic periodontitis analyzed by a novel method for isolating resident lymphocytes
Authors: Muthukuru Manoj
Published: May 2012

A novel oral mucosal gingival explant culture facilitates isolation of tissue resident mononuclear cells that represent tissue resident population, and are functional.

During CP, the gingival environment is primed to recruit and activate homing lymphocytes. However, detailed phenotypic and functional characterization of gingival tissue resident lymphocytes has been challenging as a result of limitations associated with available isolation methods and limited availability of human samples. This study aimed to develop a novel explant culture technique for effectively isolating human gingival lymphocytes. This technique takes advantage of the natural tendency of MNCs to migrate toward a chemokine gradient generated by the gingival fibroblasts. The explant system allowed isolation of MNCs with ∼95× higher yield relative to conventional approaches. The MNC yield correlates directly with wet weights of the tissues, and maximal MNCs are isolated during the 2nd day of the culture. The explant culture method and conventional approach produce similar MNC subpopulations such as Th, Tc, and B cells. Chemokines associated with MNC migration but not cytokines associated with MNC proliferation and differentiation were produced in the explant culture. Moreover, MNC migration in response to the secreted chemokines was inhibited by PTX. T cells did not undergo proliferation during the culture. However, the isolated T cells responded to mitogenic stimulation ex vivo. A statistically, significantly decreased Th cell with reduced CD25 expression along with increased NK and NKT cells in CP are shown. However, the number of naïve NK cells was decreased significantly in MNCs, suggesting activation of NK cells in CP.
Hypoxia-Induced MicroRNA-20a Expression Increases ERK Phosphorylation and Angiogenic Gene Expression in Endometriotic Stromal Cells
Authors: Lin Shih-Chieh , Wang Chih-Chuan , Wu Meng-Hsing , Yang Shang-Hsun , Li Yo-Hua , Tsai Shaw-Jenq
Published: May 2012

Context:

Aberrant activation of MAPK has been implicated to play important roles in pathological processes of endometriosis. However, how MAPK are constitutively activated in endometriotic tissues remains largely unknown. microRNA are small noncoding RNA that regulate the stability or translational efficiency of target mRNA by interacting with the 3′ untranslated region. Thus, miRNA are thought to be modulators of the transcriptional response, fine-tuning gene expression.

Objective:

The aim of this study was to evaluate the functional roles of microRNA-20a (miR20a) in MAPK activation and the pathogenesis of endometriosis.

Design:

miR20a expression was analyzed in nonpaired (endometrium = 17; endometriosis = 37) and paired (n = 12) endometriotic tissues by quantitative RT-PCR. Overexpression of miR20a in eutopic endometrial stromal cells or inhibition of miR20a in ectopic endometriotic stromal cells was used to evaluate its impact on ERK phosphorylation and subsequently angiogenesis- and proliferation-related gene expression.

Results:

Levels of miR20a were up-regulated in endometriotic stromal cells. Elevation of miR20a was up-regulated by hypoxia inducible factor-1α. The up-regulation of miR20a causes the down-regulation of dual-specificity phosphatase-2, which leads to prolonged ERK phosphorylation and an increase in the expression of several angiogenic genes. Furthermore, the up-regulation of miR20a enhances the prostaglandin E2-induced expression of fibroblast growth factor-9, a potent mitogen that stimulates both endothelial and endometrial cell proliferation.

Conclusion:

Our findings provide the novel mechanism that not only functionally links together hypoxic stress, miR20a expression, aberrant ERK phosphorylation, and angiogenesis but also demonstrates that miR20a is an important modulator in the development of endometriosis.
The Risk of All-Cause Mortality Is Inversely Related to Serum 25(OH)D Levels
Authors: Saliba Walid , Barnett Ofra , Rennert Hedy S. , Rennert Gad
Published: May 2012

Context and Objectives:

Vitamin D plays a key role in maintaining bone health, but evidence for its nonskeletal effects is inconsistent. This study aims to examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and all-cause mortality in a large general population cohort.

Design, Participants, and Setting:

Using the computerized database of the largest health care provider in Israel, we identified a cohort of subjects 20 years old or older with serum 25(OH)D levels measured between January 2008 and December 2009. Vital status was ascertained through August 2011.

Results:

Median follow-up was 28.5 months (interquartile range 23.8–33.5 months); 7,247 of 182,152 participants (4.0%) died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8 ± 24.2 nmol/liter) than those alive at the end of follow-up (51.0 ± 23.2 nmol/liter), P < 0.001. After adjustment for age, gender, ethnicity, and seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 [95% confidence interval (CI) 1.89–2.15] for the lowest serum 25(OH)D quartile (<33.8 nmol/liter) compared with the highest. After further adjustment for comorbidity, use of vitamin D supplements and statins, smoking, socioeconomic status, and body mass index, the HR was 1.81 (95% CI 1.69–1.95). This remained, even after adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium level (corrected for serum albumin levels), and glomerular filtration rate, 1.85 (95% CI 1.70–2.01). The fully adjusted HR associated with being in the second 25(OH)D quartile (33.8–49.4 nmol/liter) was 1.25 (95% CI 1.16–1.34).

Conclusions:

All-cause mortality is independently and inversely associated with serum 25(OH)D levels at levels less than 50 nmol/liter.
The New Old Rush
Authors: Salvato Nick
Published: May 2012

Nick Salvato examines the collision between “old” and “new” media staged by the actorless performance piece Bonanza, produced by German multimedia collective Berlin.
Artificial mirtron-mediated gene knockdown: Functional DMPK silencing in mammalian cells
Authors: Seow Yiqi , Sibley Christopher R. , Wood Matthew J.A.
Published: May 2012

Mirtrons are introns that form pre-miRNA hairpins after splicing to produce RNA interference (RNAi) effectors distinct from Drosha-dependent intronic miRNAs. Here we present a design algorithm for artificial mirtrons and demonstrate, for the first time, efficient gene knockdown of myotonic dystrophy protein kinase (DMPK) target sequences inRenillaluciferase 3′ UTR and subsequently pathogenic DMPK mRNA, causative of Type I myotonic dystrophy, using artificial mirtrons cloned as eGFP introns. Deep sequencing of artificial mirtrons suggests that functional mature transcripts corresponding to the designed sequence were produced in high abundance. They were further shown to be splicing-dependent, Drosha-independent, and partially dependent on exportin-5, resulting in the precise generation of pre-miRNAs. In a murine myoblast line containing a pathogenic copy of human DMPK with more than 500 CUG repeats, the DMPK artificial mirtron corrected DM1-associated splicing abnormalities of the Serca-1 mRNA, demonstrating the therapeutic potential of mirtron-mediated RNAi. Thus, further development and exploitation of the unique properties of mirtrons will benefit future research and therapeutic RNAi applications as an alternative to conventional RNAi strategies.
Bypassing the Greatwall–Endosulfine Pathway: Plasticity of a Pivotal Cell-Cycle Regulatory Module in Drosophila melanogaster and Caenorhabditis elegans
Authors: Kim Min-Young , Bucciarelli Elisabetta , Morton Diane G , Williams Byron C , Blake-Hodek Kristina , Pellacani Claudia , Von Stetina Jessica R , Hu Xiaoqian , Somma Maria Patrizia , Drummond-Barbosa Daniela , Goldberg Michael L
Published: May 2012

In vertebrates, mitotic and meiotic M phase is facilitated by the kinase Greatwall (Gwl), which phosphorylates a conserved sequence in the effector Endosulfine (Endos). Phosphorylated Endos inactivates the phosphatase PP2A/B55 to stabilize M-phase-specific phosphorylations added to many proteins by cyclin-dependent kinases (CDKs). We show here that this module functions essentially identically in Drosophila melanogaster and is necessary for proper mitotic and meiotic cell division in a wide variety of tissues. Despite the importance and evolutionary conservation of this pathway between insects and vertebrates, it can be bypassed in at least two situations. First, heterozygosity for loss-of-function mutations of twins, which encodes the Drosophila B55 protein, suppresses the effects of endos or gwl mutations. Several types of cell division occur normally in twins heterozygotes in the complete absence of Endos or the near absence of Gwl. Second, this module is nonessential in the nematode Caenorhaditis elegans. The worm genome does not contain an obvious ortholog of gwl, although it encodes a single Endos protein with a surprisingly well-conserved Gwl target site. Deletion of this site from worm Endos has no obvious effects on cell divisions involved in viability or reproduction under normal laboratory conditions. In contrast to these situations, removal of one copy of twins does not completely bypass the requirement for endos or gwl for Drosophila female fertility, although reducing twins dosage reverses the meiotic maturation defects of hypomorphic gwl mutants. These results have interesting implications for the function and evolution of the mechanisms modulating removal of CDK-directed phosphorylations.
Nucleolar Dominance of the Y Chromosome in Drosophila melanogaster
Authors: Greil Frauke , Ahmad Kami
Published: May 2012

The rDNA genes are transcribed by RNA polymerase I to make structural RNAs for ribosomes. Hundreds of rDNA genes are typically arranged in an array that spans megabase pairs of DNA. These arrays are the major sites of transcription in growing cells, accounting for as much as 50% of RNA synthesis. The repetitive rDNA arrays are thought to use heterochromatic gene silencing as a mechanism for metabolic regulation, since repeated sequences nucleate heterochromatin formation in eukaryotes. Drosophila melanogaster carries an rDNA array on the X chromosome and on the Y chromosome, and genetic analysis has suggested that both are transcribed. However, using a chromatin-marking assay, we find that the entire X chromosome rDNA array is normally silenced in D. melanogaster males, while the Y chromosome rDNA array is dominant and expressed. This resembles “nucleolar dominance,” a phenomenon that occurs in interspecific hybrids where an rDNA array from one parental species is silenced, and that from the other parent is preferentially transcribed. Interspecies nucleolar dominance is thought to result from incompatibilities between species-specific transcription factors and the rDNA promoters in the hybrid, but our results show that nucleolar dominance is a normal feature of rDNA regulation. Nucleolar dominance within D. melanogaster is only partially dependent on known components of heterochromatic gene silencing, implying that a distinctive chromatin regulatory system may act at rDNA genes. Finally, we isolate variant Y chromosomes that allow X chromosome array expression and suggest that the large-scale organization of rDNA arrays contribute to nucleolar dominance. This is the first example of allelic inactivation in D. melanogaster.
Avaliação da memória de trabalho em crianças com transtorno do déficit de atenção e hiperatividade
Authors: Messina Lucinete de Freitas , Tiedemann Klaus Bruno
Published: May 2012

Esse projeto investigou as habilidades cognitivas da Memória de Trabalho de crianças e adolescentes com o “Transtorno do Déficit de Atenção e Hiperatividade” (TDAH). Foi aplicado teste TIHC - Teste Infantil de Habilidades Cognitivas informatizado, avaliando principalmente cinco habilidades cognitivas Raciocínio Indutivas (RI), Memória de Armazenamento Auditiva (MAA) e Visual e Memória de Trabalho Auditiva (MTA) e Visual (MTV) usando o modelo de Cattell-Horn-Carroll. O teste foi aplicado em 62 sujeitos sendo 32 com TDAH do Hospital das Clínicas-SEPIA-USP e 30 sujeitos controle “normal” do Ensino Fundamental da rede municipal de 1ª à 8ª séries com idades entre 7 e 15 anos, de ambos os sexos. As análises executadas indicaram a existência de diferenças em diversos aspectos relacionados à memória nos tipos peculiares de crianças com TDAH. Verificou-se que as crianças com TDAH obtiveram bom desempenho nas provas de memória visual em detrimento as provas de memória auditiva. A correlação dos resultados do TIHC verificara que o tempo de reação da prova de memória de armazenamento visual manteve uma correlação significativa com a prova de cálculo.
Small-strain behaviour of cemented soils
Authors: TRHLíKOVá J. , MAšíN D. , BOHáč J.
Published: May 2012

The shear modulus of cemented soils at very small strain (G0) was studied. For artificially cemented clay, G0was found to be independent of the mean effective stress until the yield stress. After yield, a significant effect of structure degradation on G0was observed. The experimental data were interpreted by an equation, which relates G0of cemented soils to mean stress, apparent overconsolidation ratio and the state of structure (sensitivity). The equation was also found to represent G0of cemented sands.
Translating stem cell research to the clinic: A constant crosstalk between basic and applied research
Authors: Raineteau Olivier
Published: May 2012

Pluripotent stem cells hold great promise for the generation of patient-specific cells for disease modeling and regenerative medicine. Focusing on a recent study reporting the successful generation of midbrain dopaminergic neurons and their efficient grafting in animal models of Parkinson’s disease, I discuss how crosstalk between basic and applied stem cell research more generally paves the road toward clinical translation.
Repetitive transcanial magnetic stimulation (RTMS) modulates event-related potential (ERP) indices of attention in autism
Authors: Casanova Manuel , Baruth Joshua , El-Baz Ayman , Tasman Allan , Sears Lonnie , Sokhadze Estate
Published: May 2012

Individuals with autism spectrum disorder (ASD) have previously been shown to have significantly augmented and prolonged event-related potentials (ERP) to irrelevant visual stimuli compared to controls at both early and later stages (e.g., N200, P300) of visual processing and evidence of an overall lack of stimulus discrimination. Abnormally large and indiscriminative cortical responses to sensory stimuli may reflect cortical inhibitory deficits and a disruption in the excitation/inhibition ratio. Low-frequency (≤ 1HZ) repetitive transcranial magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated cortex by the activation of inhibitory circuits. It was our prediction that after 12 sessions of low-frequency rTMS applied bilaterally to the dorsolateral prefrontal cortices in individuals with ASD there would be a significant improvement in ERP indices of selective attention evoked at later (i.e., 200–600 ms) stages of attentional processing as well as an improvement in motor response error rate. We assessed 25 participants with ASD in a task of selective attention using illusory figures before and after 12 sessions of rTMS in a controlled design where a waiting-list group of 20 children with ASD performed the same task twice. We found a significant improvement in both N200 and P300 components as a result of rTMS as well as a significant reduction in response errors. We also found significant reductions in both repetitive behavior and irritability according to clinical behavioral questionnaires as a result of rTMS. We propose that rTMS has the potential to become an important therapeutic tool in ASD research and treatment.