bluuebunny/crossref_metadata_2025 huggingface dataset:
Emotion Perception in Schizophrenia: Context Matters
Authors: Kring Ann M. , Campellone Timothy R.
Published: April 2012

Research on emotion perception in schizophrenia has focused primarily on the perception of static faces displaying different emotion signals or expressions. However, perception of emotion in daily life relies on much more than just the face. In this article, we review the role of context in emotion perception among people with and without schizophrenia. We argue that not only is context central to the perception of emotion, it in fact helps to construct the perception. Implications for future research on emotion perception are discussed.
Emotion as Personal Relatedness
Authors: Hobson R. Peter
Published: April 2012

In this article, I consider the structure of interpersonal emotional relations. I argue that current cognitive-developmental theory has overestimated the role of conceptual thinking, and underestimated the role of intrinsic social-emotional organization, in the early development of such feelings as jealousy, shame, and concern. I suggest that human forms of social experience are shaped by a process through which one individual identifies with the bodily expressed attitudes of other people, and stress the diversity of self–other relational states. I draw on studies in developmental psychopathology, and specifically research in autism and borderline personality disorder, to illustrate some implications of this viewpoint.
Time, Emotion, and Depression
Authors: Gallagher Shaun
Published: April 2012

I examine several aspects of the experience of time in depression and in the experience of different emotions. Both phenomenological and experimental studies show that depressed subjects have a slowed experience of time flow and tend to overestimate time spans. In comparison to patients in control conditions, depressed patients tend to be preoccupied with past events, and less focused on present and future events. Recent empirical findings in studies of emotion perception show different degrees of over- or underestimation of time in perception of faces showing different emotions compared with neutral faces. Clinical phenomenology predicts that the effects on time estimation would not be additive if these tests were conducted with depressed subjects.
Construction of a finite element model for collisions of a golf ball with a club during swing
Authors: Tanaka Katsumasa , Matsuoka Katsuya , Fujita Shogo , Teranishi Yukihiro , Ujihashi Sadayuki
Published: April 2012

The objective of this study was to construct a finite element model for simulating the mechanical behaviour of a golf club and ball from swing to impact. An experiment using a golf robot was conducted to obtain the motion of the shaft grip during the swing, and the behaviour of the club and ball during the swing and impact. The swing model was developed by inputting the positional coordinate data of the grip, which was obtained from an experiment, into the grip model. The simulation results generally matched the experimental results for the swing motion, the behaviour of the shaft during the swing and the clubhead velocity and orientation at impact. The modelling of the grip contributed to the accuracy of the simulation results by precisely representing swing motion and suppressing the generation of vibration in the shaft grip. This indicates that the components of the proposed modelling method may also be suitable for representing the swing using data obtained from the robot test, and that the model and the approach for modelling may have potential to be used as a predictable tool to supplement robot tests, reducing the dependency on prototypes.
My Brother’s Keeper?
Authors: Saslow Laura R. , Willer Robb , Feinberg Matthew , Piff Paul K. , Clark Katharine , Keltner Dacher , Saturn Sarina R.
Published: April 2012

Past research argues that religious commitments shape individuals’ prosocial sentiments, including their generosity and solidarity. But what drives the prosociality of less religious people? Three studies tested the hypothesis that, with fewer religious expectations of prosociality, less religious individuals’ levels of compassion will play a larger role in their prosocial tendencies. In Study 1, religiosity moderated the relationship between trait compassion and prosocial behavior such that compassion was more critical to the generosity of less religious people. In Study 2, a compassion induction increased generosity among less religious individuals but not among more religious individuals. In Study 3, state feelings of compassion predicted increased generosity across a variety of economic tasks for less religious individuals but not among more religious individuals. These results suggest that the prosociality of less religious individuals is driven to a greater extent by levels of compassion than is the prosociality of the more religious.
Positive conversion of negative signaling of CTLA4 potentiates antitumor efficacy of adoptive T-cell therapy in murine tumor models
Authors: Shin Jae Hun , Park Hyung Bae , Oh Yu Mi , Lim Dong Pyo , Lee Ji Eun , Seo Hae Hyun , Lee Sang Jin , Eom Hyeon Seok , Kim In-Hoo , Lee Seung Hoon , Choi Kyungho
Published: April 2012

Cytotoxic T lymphocyte–associated antigen 4 (CTLA4) has been known to be a strong tolerance-inducing inhibitory receptor on T-cell surface. Systemic blocking of CTLA4 function with blocking antibodies has been regarded as an attractive strategy to enhance antitumor immunity. However, this strategy accompanies systemic autoimmune side effects that are sometimes problematic. Therefore, we developed a novel CTLA4 mutant that could be expressed in tumor antigen-specific T cells to enhance antitumor effect without systemic autoimmunity. This mutant, named CTLA4-CD28 chimera, consists of extracellular and transmembrane domains of CTLA4, linked with cytoplasmic CD28 domain. Overexpression of CTLA4-CD28 chimera in T cells delivered stimulatory signals rather than inhibitory signals of CTLA4 and significantly enhanced T-cell reactivity. Although this effect was observed in both CD4 and CD8 T cells, the effect on CD4 T cells was predominant. CTLA4-CD28 chimera gene modification of CD4 T cells significantly enhanced antitumor effect of unmodified CD8 T cells. Nonetheless, the gene modification of CD8 T cells along with CD4 T cells further maximized antitumor effect of T cells in 2 different murine tumor models. Thus, CTLA4-CD28 chimera gene modification of both tumor antigen-specific CD4 and CD8 T cells would be an ideal way of modulating CTLA4 function to enhance tumor-specific T-cell reactivity.
Identification and expansion of highly suppressive CD8+FoxP3+ regulatory T cells after experimental allogeneic bone marrow transplantation
Authors: Robb Renee J. , Lineburg Katie E. , Kuns Rachel D. , Wilson Yana A. , Raffelt Neil C. , Olver Stuart D. , Varelias Antiopi , Alexander Kylie A. , Teal Bianca E. , Sparwasser Tim , Hammerling Gunter J. , Markey Kate A. , Koyama Motoko , Clouston Andrew D. , Engwerda Christian R. , Hill Geoffrey R. , MacDonald Kelli P. A.
Published: April 2012

FoxP3+ confers suppressive properties and is confined to regulatory T cells (Treg) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4+ Treg are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8+ population of FoxP3+ Treg that convert from CD8+ conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation. These CD8+ Treg undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGF-β. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4+FoxP3+ population and is more potent in exerting class I–restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8+FoxP3+ Treg are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by coadministering rapamycin and IL-2 antibody complexes. CD8+FoxP3+ Treg thus represent a new regulatory population with considerable potential to preferentially subvert MHC class I–restricted T-cell responses after bone marrow transplantation.
Prognostic irrelevance of ring sideroblast percentage in World Health Organization–defined myelodysplastic syndromes without excess blasts
Authors: Patnaik Mrinal M. , Hanson Curtis A. , Sulai Nanna H. , Hodnefield Janice M. , Knudson Ryan A. , Ketterling Rhett P. , Lasho Terra L. , Tefferi Ayalew
Published: April 2012

The presence of ≥ 15% bone marrow (BM) ring sideroblasts (RS) and < 5% blasts is required for a diagnosis of refractory anemia with ring sideroblasts. We examined the phenotypic and prognostic relevance of this “15%” RS threshold in 200 patients with myelodysplastic syndromes (MDS) without excess blasts and with ≥ 1% RS. The impact of RS% was assessed both as a continuous and categorical variable: < 5% (n = 56), 5%-14% (n = 32), 15%-50% (n = 79), and > 50% (n = 33). RS% correlated (P < .05) directly with age, platelet count, transfusion dependency, BM cellularity, and mutant SF3B1 and inversely with hemoglobin level, multilineage dysplasia, and high-risk karyotype; but did not correlate with IDH mutations. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Neither univariate nor multivariable analysis showed significant effect for RS% on overall or leukemia-free survival, suggesting the limited prognostic value of quantifying BM RS in MDS.
Does doctors’ workload impact supervision and ward activities of final-year students? A prospective study
Authors: Celebi Nora , Tsouraki Rodoula , Engel Corinna , Holderried Friederike , Riessen Reimer , Weyrich Peter
Published: April 2012

Background

Hospital doctors face constantly increasing workloads. Besides caring for patients, their duties also comprise the education of future colleagues. The aim of this study was to objectively investigate whether the workload arising from increased patient care interferes with student supervision and is associated with more non-medical activities of final-year medical students.

Methods

A total of 54 final-year students were asked to keep a diary of their daily activities over a three-week period at the beginning of their internship in Internal Medicine. Students categorized their activities – both medical and non-medical - according to whether they had: (1) only watched, (2) assisted the ward resident, (3) performed the activity themselves under supervision of the ward resident, or (4) performed the activity without supervision. The activities reported on a particular day were matched with a ward specific workload-index derived from the hospital information system, including the number of patients treated on the corresponding ward on that day, a correction factor according to the patient comorbidity complexity level (PCCL), and the number of admissions and discharges. Both students and ward residents were blinded to the study question.

Results

A total of 32 diaries (59 %, 442 recorded working days) were handed back. Overall, the students reported 1.2 ± 1.3 supervised, 1.8 ±1.6 medical and 3.6 ± 1.7 non-medical activities per day. The more supervised activities were reported, the more the number of reported medical activities increased (p < .0001). No relationship between the ward specific workload and number of medical activities could be shown.

Conclusions

There was a significant association between ward doctors’ supervision of students and the number of medical activities performed by medical students. The workload had no significant effect on supervision or the number of medical or non-medical activities of final-year students.
Temporal trends of sulphadoxine-pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya
Authors: Iriemenam Nnaemeka C , Shah Monica , Gatei Wangeci , van Eijk Anna M , Ayisi John , Kariuki Simon , Vanden Eng Jodi , Owino Simon O , Lal Ashima A , Omosun Yusuf O , Otieno Kephas , Desai Meghna , ter Kuile Feiko O , Nahlen Bernard , Moore Julie , Hamel Mary J , Ouma Peter , Slutsker Laurence , Shi Ya Ping
Published: April 2012

Background

Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited.

Methods

Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed.

Results

The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7 % in the first study (1996–2000) to 88 % in the third study (2008–2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4 % in 1998 to 44.4 % three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996–2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002–2008 and 2008–2009 studies. In addition, in the 2008–2009 study, 5.3 % of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples.

Conclusions

There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug-resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP.
A two-stage cluster sampling method using gridded population data, a GIS, and Google EarthTM imagery in a population-based mortality survey in Iraq
Authors: Galway LP , Bell Nathaniel , SAE Al Shatari , Hagopian Amy , Burnham Gilbert , Flaxman Abraham , Weiss Wiliam M , Rajaratnam Julie , Takaro Tim K
Published: April 2012

Background

Mortality estimates can measure and monitor the impacts of conflict on a population, guide humanitarian efforts, and help to better understand the public health impacts of conflict. Vital statistics registration and surveillance systems are rarely functional in conflict settings, posing a challenge of estimating mortality using retrospective population-based surveys.

Results

We present a two-stage cluster sampling method for application in population-based mortality surveys. The sampling method utilizes gridded population data and a geographic information system (GIS) to select clusters in the first sampling stage and Google EarthTMimagery and sampling grids to select households in the second sampling stage. The sampling method is implemented in a household mortality study in Iraq in 2011. Factors affecting feasibility and methodological quality are described.

Conclusion

Sampling is a challenge in retrospective population-based mortality studies and alternatives that improve on the conventional approaches are needed. The sampling strategy presented here was designed to generate a representative sample of the Iraqi population while reducing the potential for bias and considering the context specific challenges of the study setting. This sampling strategy, or variations on it, are adaptable and should be considered and tested in other conflict settings.
Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study
Authors: Zhou Yi-Li , Gao Er-li , Zhang Wei , Yang Han , Guo Gui-Long , Zhang Xiao-Hua , Wang Ou-Chen
Published: April 2012

Background

The optimal resection extent for papillary thyroid microcarcinoma (PTMC) remains controversial. The objective of the study was to investigate risk factors of bilateral PTMC and central lymph node metastasis (CLNM) to guide surgical strategies for PTMC patients.

Methods

We retrospectively reviewed 211 PTMC patients who underwent total thyroidectomy (TT) and 122 clinical lymph node-negative (cN0) cases that underwent prophylactic central lymph node dissection (CLND) between 2010 and 2011. The frequency, pattern, and predictive factors for bilateral PTMC and CLNM in these patients were studied using univariate and multivariate analysis with respect to the following variables: age, gender, extrathyroidal extension (ETE), T stage, with Hashimoto thyroiditis (HT), tumor size and multifocality based on final pathology, and preoperative evaluation using ultrasonography (US).

Results

Fifty-four of 211 (25.6%) patients had bilateral PTMC. In multivariate analysis, multifocality (P < 0.001, OR = 23.900) and tumor size ≥7 mm (P = 0.014, OR = 2.398) based on US were independent predictive factors for bilateral PTMC which was also independently associated with multifocality (P < 0.001, OR = 29.657) and tumor size ≥7 mm (P = 0.005, OR = 2.863) based on final pathology. Among 122 cN0 patients who underwent prophylactic CLND, we found 49.2% of patients had CLNM. CLNM was independently associated with men, age <50 years and tumor size ≥7 mm based on final pathology or preoperative US.

Conclusions

TT should be considered for PTMC patients who are found multifocality and tumor size ≥7 mm based on preoperative US. CLND need be considered in cN0 patients who are men, aged <50 years or tumor size ≥7 mm based on preoperative US.
Prognostic significance of tumor markers in T4a gastric cancer
Authors: Liu Xiaowen , Cai Hong , Wang Yanong
Published: April 2012

Background

The clinical importance of preoperative tumor markers remain elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of AFP, CEA, CA19-9, and CA50 in T4a stage gastric cancer.

Methods

Two hundred and seventy-three T4a gastric cancer patients who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. The correlation between tumor markers and clinicopathologic characteristics and prognostic value of preoperative tumor markers were investigated.

Results

Correlation analysis showed that AFP was associated with Borrmann type (P = 0.010); CEA with sex (P = 0.029), tumors site (P = 0.014), and N stage (P = 0.001); CA19-9 with age (P = 0.047), tumor site (P = 0.011), lymphovascular invasion (P = 0.004), and N stage (P = 0.000); CA50 with age (P = 0.017), tumor site (P = 0.004), tumor size (P = 0.014), and N stage (P = 0.000). Multivariate analysis showed that the positivity of preoperative CEA, CA19-9, and CA50 were major independent poor prognostic factors of patients with T4a stage gastric cancer.

Conclusions

Preoperative serum tumor marker might be a candidate for the staging system in addition to conventional factors.
GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology
Authors: Cota Ana Marcia M , Oliveira Joao Batista A , Petersen Claudia G , Mauri Ana L , Massaro Fabiana C , Silva Liliane FI , Nicoletti Andreia , Cavagna Mario , Baruffi Ricardo LR , Franco José G
Published: April 2012

Background

The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation.

Methods

A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed.

Results

Out of a total of 681 oocytes, 189 (27.8 %) were morphologically normal, 220 (32.3 %) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist-treated groups (P ≫ 0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P ≫ 0.05).

Conclusions

Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.
Mitogen Activated Protein Kinase Phosphatase-1 Prevents the Development of Tactile Sensitivity in a Rodent Model of Neuropathic Pain
Authors: Ndong Christian , Landry Russell P. , DeLeo Joyce A. , Romero-Sandoval Edgar Alfonso
Published: April 2012

Background:

Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK) family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs) limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression.

Results:

We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs) as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide). Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced proinflammatory cytokines and chemokines and the phosphorylated form of p38.

Conclusions:

Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.
Lamina I NK1 Expressing Projection Neurones are Functional in Early Postnatal Rats and Contribute to the Setting up of Adult Mechanical Sensory Thresholds
Authors: Man Sharon HW , Géranton Sandrine M , Hunt Stephen P
Published: April 2012

Background:

A small proportion of lamina I neurons of the spinal cord project upon the hindbrain and are thought to engage descending pathways that modulate the behavioural response to peripheral injury. Early postnatal development of nociception in rats is associated with exaggerated and diffuse cutaneous reflexes with a gradual refinement of responses over the first postnatal weeks related to increased participation of inhibitory networks. This study examined the postnatal development of lamina I projection neurons from postnatal day 3 (P3) until P48.

Results:

At P3, a subset of lamina I neurons were found to express the neurokinin 1 (NK1) receptor. Using fluorogold retrograde tracing, we found that the NK1 positive neurons projected upon the parabrachial nucleus (PB) within the hindbrain. Using c-fos immunohistochemistry, we showed that lamina I and PB neurons in P3 rats responded to noxious stimulation of the periphery. Finally, ablation of lamina I neurons with substance-P saporin conjugates at P3 resulted in increased mechanical sensitivity from P45 onwards compared to control animals of the same age.

Conclusions:

These results suggest that the lamina I pathway is present and functional at least from P3 and required for establishing and fine-tuning mechanical sensitivity in adult rats.
Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial
Authors: Jäger Susanne , Müller Kai W , Ruckes Christian , Wittig Tobias , Batra Anil , Musalek Michael , Mann Karl , Wölfling Klaus , Beutel Manfred E
Published: April 2012

Background

In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy.

Methods/design

This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment.

Discussion

A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed.

Trial Registration

ClinicalTrials (NCT01434589)
A study of the effect of the FertilMate™ scrotum cooling patch on male fertility. SCOP trial (scrotal cooling patch) - study protocol for a randomised controlled trial
Authors: Osman M Waseem , Nikolopoulos llias , Haoula Zeina , Kannamannadiar Jayaprakasan , Atiomo William
Published: April 2012

Background

Male infertility is a significant contributor to the need for fertility treatment. Treatment currently involves correcting any identifiable adverse lifestyle factors in men with suboptimal sperm parameters, and if these measures are unsuccessful, assisted conception is offered, which can be quite expensive. Raised scrotal temperature is one of the least studied but easily corrected risk factors for male infertility. In a recent review of the literature, sperm count, motility and morphology improved with scrotal cooling devices. The devices used to achieve testicular cooling were, however, not practical for day-to-day use. A potentially more practical device for scrotal cooling has recently been developed. The Babystart® FertilMate™ Scrotum Cooling Patch is a hydrogel pad which allows for comfortable application. The aims of this study were to investigate whether exposing the scrotum to lower temperatures by means of these new patches could improve semen parameters, thereby improving fertility, and to assess the feasibility of a clinical trial.

Methods/design

This is a randomised controlled trial set in a university teaching hospital in the United Kingdom. The proposed sample size was 40 men with mild, moderate or severe oligoasthenospermia, of whom 20 would be randomised to wearing the scrotum cooling patch for 90 days and 20 men would be acting as controls and not wearing the patches. The primary outcome measure was the change in sperm concentration. Secondary outcome measures included the change in sperm volume, motility and morphology; endocrine parameters; metabolomic biomarkers; testicular volume and blood flow. Reasons for dropping out and non-compliance were also going to be noted and reported.

Discussion

The study started recruiting in October 2011 and as of November 2011 four men had been consented and were participating in the study. No operational challenges had been encountered at the time of the submission of this manuscript. Although the study also aimed to evaluate the feasibility of a definitive study, the change in sperm count after 90 days of wearing the scrotal cooling patches was made the primary outcome measure because a statistically significant improvement in sperm parameters with the scrotal patches would in itself be a definitive finding.

Trial registration

Current Controlled Trials ISRCTN94041896
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study
Authors: Bratton Daniel J , Nunn Andrew J , Wojnarowska Fenella , Kirtschig Gudula , Sandell Anna , Williams Hywel C
Published: April 2012

Background

The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus.

Methods

Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial.

Results

The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the ‘flexibility of the comparison intervention’ and ‘practitioner adherence’ domains (SD = 13). The trial team appeared to disagree most on the ‘eligibility criteria’ (SD = 35) and ‘participant compliance’ (SD = 31) domains, although the large standard deviations were a result of a single outlier in the two domains.

Conclusion

The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies.

Trial registration

Current Controlled Trials http://www.controlled-trials.com/ISRCTN13704604
Retracted: MyoD-dependent regulation of NF-κB activity couples cell-cycle withdrawal to myogenic differentiation
Authors: Parker Maura H , von Maltzahn Julia , Bakkar Nadine , Al-Joubori Ban , Ishibashi Jeff , Guttridge Denis , Rudnicki Michael A
Published: April 2012

Background

Mice lacking MyoD exhibit delayed skeletal muscle regeneration and markedly enhanced numbers of satellite cells. Myoblasts isolated from MyoD

-/-
myoblasts proliferate more rapidly than wild type myoblasts, display a dramatic delay in differentiation, and continue to incorporate BrdU after serum withdrawal.

Methods

Primary myoblasts isolated from wild type and MyoD

-/-
mutant mice were examined by microarray analysis and further characterized by cell and molecular experiments in cell culture.

Results

We found that NF-κB, a key regulator of cell-cycle withdrawal and differentiation, aberrantly maintains nuclear localization and transcriptional activity in MyoD

-/-
myoblasts. As a result, expression of cyclin D is maintained during serum withdrawal, inhibiting expression of muscle-specific genes and progression through the differentiation program. Sustained nuclear localization of cyclin E, and a concomitant increase in cdk2 activity maintains S-phase entry in MyoD

-/-
myoblasts even in the absence of mitogens. Importantly, this deficit was rescued by forced expression of IκBαSR, a non-degradable mutant of IκBα, indicating that inhibition of NF-κB is sufficient to induce terminal myogenic differentiation in the absence of MyoD.

Conclusion

MyoD-induced cytoplasmic relocalization of NF-κB is an essential step in linking cell-cycle withdrawal to the terminal differentiation of skeletal myoblasts. These results provide important insight into the unique functions of MyoD in regulating the switch from progenitor proliferation to terminal differentiation.
Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer
Authors: Kratz Harald , Haeckel Akvile , Michel Roger , Schönzart Lena , Hanisch Uli , Hamm Bernd , Schellenberger Eyk
Published: April 2012

Background

Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes.

Methods

Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5.

Results

The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5.

Conclusions

This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging.
Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathways
Authors: Liu Ju-Fang , Hou Sheng-Mou , Tsai Chun-Hao , Huang Chun-Yin , Yang Wei-Hung , Tang Chih-Hsin
Published: April 2012

Introduction

Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of osteoarthritis (OA). Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury. Here, we investigated the intracellular signaling pathways involved in thrombin-induced HO-1 expression in human synovial fibroblasts (SFs).

Methods

Thrombin-mediated HO-1 expression was assessed with quantitative real-time (q)PCR. The mechanisms of action of thrombin in different signaling pathways were studied by using Western blotting. Knockdown of protease-activated receptor (PAR) proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of Nrf2 to the HO-1 promoter. Transient transfection was used to examine HO-1 activity.

Results

Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of thrombin, and expression was higher than in normal SFs. OASFs stimulation with thrombin induced concentration- and time-dependent increases in HO-1 expression. Pharmacologic inhibitors or activators and genetic inhibition by siRNA of protease-activated receptors (PARs) revealed that the PAR1 and PAR3 receptors, but not the PAR4 receptor, are involved in thrombin-mediated upregulation of HO-1. Thrombin-mediated HO-1 expression was attenuated by thrombin inhibitor (PPACK), PKCδ inhibitor (rottlerin), or c-Src inhibitor (PP2). Stimulation of cells with thrombin increased PKCδ, c-Src, and Nrf2 activation.

Conclusion

Our results suggest that the interaction between thrombin and PAR1/PAR3 increases HO-1 expression in human synovial fibroblasts through the PKCδ, c-Src, and Nrf2 signaling pathways.
The renal urate transporter SLC17A1 locus: confirmation of association with gout
Authors: Hollis-Moffatt Jade E , Phipps-Green Amanda J , Chapman Brett , Jones Gregory T , van Rij Andre , Gow Peter J , Harrison Andrew A , Highton John , Jones Peter B , Montgomery Grant W , Stamp Lisa K , Dalbeth Nicola , Merriman Tony R
Published: April 2012

Introduction

Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets.

Methods

Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian.

Results

At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype.

Conclusion

We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.
Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel
Authors: Simonis Marieke , Atanur Santosh S , Linsen Sam , Guryev Victor , Ruzius Frans-Paul , Game Laurence , Lansu Nico , de Bruijn Ewart , van Heesch Sebastiaan , Jones Steven JM , Pravenec Michal , Aitman Tim J , Cuppen Edwin
Published: April 2012

Background

With the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression.

Results

We generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations.

Conclusions

We show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences.
Data error quantification in spectral induced polarization imaging
Authors: Orozco Adrián Flores , Kemna Andreas , Zimmermann Egon
Published: April 2012

Induced polarization (IP) imaging is being increasingly used in near-surface geophysical studies, particularly for hydrogeologic and environmental applications. However, the analysis of IP data error has received little attention, even though the importance of an adequate error parameterization has been demonstrated for electrical resistivity imaging. Based on the analysis of data sets measured in the frequency range from 1 Hz to 1 kHz, we proposed a model for the quantification of phase data errors in IP measurements. The analyzed data sets were collected on an experimental tank containing targets of different polarizability. Our study is based on the common practice that the discrepancy of measurements taken in normal and reciprocal configuration can be considered as a measure of data error. Statistical analysis of the discrepancies between normal and reciprocal measurements revealed that the phase error decreases with increasing resistance (i.e., signal strength). We proposed an inverse power-law model to quantify the phase error as a function of the measured resistances. We found that the adequate implementation of the proposed error model in an inversion scheme leads to improved IP imaging results in laboratory experiments. Application to a data set collected at the field-scale also demonstrated the superiority of the new model over previous assumptions.
Effects of home on the mental health of British forces serving in Iraq and Afghanistan
Authors: Mulligan Kathleen , Jones Norman , Davies Mark , McAllister Peter , Fear Nicola T. , Wessely Simon , Greenberg Neil
Published: April 2012

Background

Most studies of the mental health of UK armed forces focus on retrospective accounts of deployment and few sample personnel while they are deployed.

Aims

This study reports the results of a survey of deployed personnel, examining the perceived impact of events at home and military support for the family on current mental health during the deployment.

Method

Surveys were conducted with 2042 British forces personnel serving in Iraq and Afghanistan. Prevalence of common mental disorders was assessed with the 12-item General Health Questionnaire (GHQ-12) and post-traumatic stress disorder (PTSD) was assessed with the PTSD Checklist – Civilian version (PCL-C).

Results

The prevalence of common mental disorders was 17.8% and of probable PTSD was 2.8%. Perceived home difficulties significantly influenced the mental health of deployed personnel; the greater the perception of negative events in the home environment, the greater the reporting of adverse mental health effects. This finding was independent of combat exposure and was only partially mitigated by being well led and reporting subjectively good unit cohesion; however, the effect of the totality of home-front events was not improved by the latter. Poor perceived military support for the family had a detrimental impact on deployment mental health.

Conclusions

The armed forces offer many support services to the partners and families of deployed personnel and ensuring that the efforts being made on their behalf are well communicated might improve the mental health of deployed personnel.
Two novel mutations in the L ferritin coding sequence associated with benign hyperferritinaemia unmasked by glycosylated ferritin assay
Authors: Thurlow Vanessa , Vadher Bipin , Bomford Adrian , DeLord Corinne , Kannengiesser Caroline , Beaumont Carole , Grandchamp Bernard
Published: April 2012

Investigating persistent hyperferritinaemia without apparent iron overload is challenging. Even when inflammation, cirrhosis, Still's disease, fatty liver and malignancy are excluded, there remains a group of patients with unexplained hyperferritinaemia for whom rare forms of haemochromatosis (ferroportin disease) are a consideration. Preliminary results suggest that abnormal percentage glycosylation of serum ferritin is seen in some cases of genetically determined hyperferritinaemia. Serum ferritin is normally 50–81% glycosylated, but low glycosylation (20–42%) prevails in hereditary hyperferritinaemia cataract syndrome. This contrasts with hyperglycosylation (>90%) associated with the benign hyperferritinaemia related to missense L ferritin (p.Thr30Ile) mutation. Here, we describe two novel missense L ferritin variants also associated with hyperglycosylation, p.Gln26Ile and p.Ala27Val. Ferritin glycosylation, a comparatively simple measurement, can identify patients for DNA sequencing as hyperglycosylation (>90%) is associated with benign hyperferritinaemia and mutant L ferritin chain.
From molecular catalysts to nanostructured materials skeleton catalysts
Authors: Asao Naoki , Jin Tienan , Tanaka Shinya , Yamamoto Yoshinori
Published: April 2012

Molecular transformations using Au, Pd, and Cu nanoporous skeleton catalysts and the reactivity difference between those catalysts and the corresponding well-known homogeneous molecular catalysts are described. Nanoporous skeleton catalysts (e.g., PdNPore) can be fabricated through dealloying of the corresponding Pd-containing alloy PdxM1yM2z.
Marketing to the Base of the Pyramid: A Corporate Responsibility Approach with Case Inspired Strategies
Authors: Santos Nicholas J.C. , Laczniak Gene R.
Published: April 2012

The economic and political outcomes of market globalization continue to be complex. As international corporations engage developing markets, they increasingly find consumers who lack market sophistication, meaningful purchasing options and economic leverage. Such conditions are ripe for the exploitation of these market segments but also can be mitigated by enlightened managers willing to thoughtfully consider their ethical and professional obligations to vulnerable consumers. This paper builds on a normative ethical framework, labeled the integrative justice model (IJM) for impoverished markets that was introduced in the marketing and public policy literature. Specifically, the paper will extend the normative ethics of the IJM by proposing logically reasoned decision principles for managers, particularly in MNC subsidiaries, that might better shape ethical business strategy when targeting impoverished segments. Additionally, numerous case examples are given to illustrate how a number of these decision principles are already being applied by companies around the world. Such an approach can serve as a counterweight to the difficulty of crafting global regulations for market development.