bluuebunny/crossref_metadata_2025 huggingface dataset:
Management: The work that dares not speak its name
Authors: Brocklehurst Michael , Grey Chris , Sturdy Andrew
Published: November 2009

The status of management and managers has fluctuated over the years, arguably reaching its high point in the mid-20th century but since declining. This article explores how managers respond to this decline in status. It presents and discusses the findings of a study of managers (who are also Executive MBA students) who unanimously avoided describing themselves as ‘managers’. The article argues that this response reflects both the overuse of the designation ‘manager’ as well as derogatory connotations of the term. This derogation is rooted in the nature of managerial work and its associations with bureaucracy and inflexibility. But while features of bureaucracy such as hierarchy remain, then these managers find justification for their status in alternative self-descriptions such as ‘professional’, ‘entrepreneur’ and ‘project leader’. The article concludes by considering some of the implications for management education and learning.
Fatigue and quality of life in pediatric multiple sclerosis
Authors: MacAllister William S , Christodoulou Christopher , Troxell Regina , Milazzo Maria , Block Pamela , Preston Thomas E , Bender Heidi A , Belman Anita , Krupp Lauren B
Published: November 2009

Fatigue and quality of life are significant concerns in adult multiple sclerosis (MS) but little is known about these factors in pediatric MS. The present investigation evaluates fatigue and quality of life in 51 pediatric MS patients to determine the rate of fatigue and reduced quality of life and assesses the relations between these variables and clinical factors. Fatigue and quality of life were assessed by self- and parent-report via the PedsQL Multidimensional Fatigue Scale and the PedsQL Quality of Life Scale. One-sample t-tests determined if scores were below published data for healthy individuals. Moreover, scores falling one standard deviation from norms were considered mildly affected, with severe difficulties being defined as scores falling two or more standard deviations from norms. Associations between self- and parent-reported difficulties and clinical factors were examined via Pearson correlation analyses. In comparison with healthy samples, pediatric MS patients reported greater difficulties with respect to fatigue, sleep, cognition, physical limitations, and academics. In addition to significant difficulties on these factors, parents reported problems with respect to emotional functioning, and tended to report greater fatigue, sleep, and cognitive difficulties than were self-reported. Expanded Disability Status Scale score was the only neurologic variable significantly related to fatigue or quality of life scores. Fatigue was significantly correlated with reports of sleep difficulties, cognitive problems, and quality of life variables. These findings suggest that fatigue and poorer quality of life is a clear concern in pediatric MS, and is related to overall physical disability.
Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations
Authors: Wu Xiao-Mu , Chaodong Wang  , Zhang Kun-Nan , Lin Ai-Yu , Kira Jun-ichi , Hu Guo-Zhu , Qu Xin-Hui , Xiong Ying-Qiong , Cao Wen-Feng , Gong Lin-Yun
Published: November 2009

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MSassociated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) ( p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) ( p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) ( p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.
Influence of interferon-beta therapy switching on neutralizing antibody titres: results from the Austrian Switch Study
Authors: Gneiss Claudia , Koudouovoh-Tripp Pia-Maria , Ropele Stefan , Gotwald Thaddäus , Ehling Rainer , Lutterotti Andreas , Aichner Franz , Ladurner Gunther , Eggers Christian , Schautzer Franz , Künz Bettina , Millonig Alban , Aspeck Engelbert , Reindl Markus , Berger Thomas , Fazekas Franz , Deisenhammer Florian
Published: November 2009

Neutralizing antibodies against interferon-beta are associated with a reduction of the efficacy of this drug. Continuing treatment leads to a decline or even loss of neutralizing antibodies over years. No strategies are currently available to shorten the period of neutralizing antibody positivity. The objective of this study was to investigate the effect of switching between high and low immunogenic interferon-beta products on neutralising antibody titres. Twenty-four patients treated with the subcutaneously administered interferon-beta 1b or 1a and high titres of neutralizing antibodies were included. At baseline interferon-beta therapy was interrupted for 3 months and two pulses of high dose methylprednisolone were applied. Patients were then randomized to receive either the previous interferon-beta preparation or the low immunogenic intramuscular interferon-beta 1a. The primary end-point was the change of neutralizing antibody titres 12 months after randomization. Twelve patients were switched to interferon-beta 1a intramuscularly and 12 patients remained on previous treatment. Median neutralizing antibody titres were 846 NU at baseline and 196 NU at the end of the study. The median change of neutralizing antibody titres did not differ significantly between therapy switchers and non-switchers. Baseline and final neutralizing antibody titres correlated significantly. In conclusion, neither switching nor continuous therapy with any subcutaneous interferon-beta preparation significantly changed neutralizing antibody titres.
APOE-ε4 is not associated with cognitive impairment in relapsing—remitting multiple sclerosis
Authors: Portaccio Emilio , Goretti Benedetta , Zipoli Valentina , Nacmias Benedetta , Stromillo Maria Laura , Bartolozzi Maria Letizia , Siracusa Gianfranco , Guidi Leonello , Federico Antonio , Sorbi Sandro , De Stefano Nicola , Pia Amato Maria
Published: November 2009

The objective of this article was to assess the association between apolipoprotein E (APOE)-ε4 and cognitive impairment (CI) in relapsing—remitting multiple sclerosis (RRMS). The APOE genotype was assessed in 85 RRMS cases (58 females, mean age 43 ± 8.4 years, mean disease duration 15.8 ± 9.6 years, mean Expanded Disability Status Scale (EDSS) 1.7 ± 1.0). Cognitive functioning was evaluated in the whole sample using Rao’s Brief Repeatable Battery (BRB). Performance on each test was assessed by applying the normative values for the Italian population. In a subgroup of 50 patients, a brain magnetic resonance (MR) study was performed including measurement of T2 lesion volumes (T2LV), neocortical volume (NCV) and normalized brain volume (NBV). The relationship between APOE genotype, CI and MR variables was assessed through univariate and multivariate logistic regression models. CI, most commonly involving complex attention and verbal memory tasks, was found in 28 cases (33%). We identified a total of 19 ε4carriers (22.4%), who did not differ from non-carriers regarding clinical and demographic characteristics. The presence of the ε4 genotype was associated with neither CI (p = 0.28) nor impairment on each neuropsychological test (p > 0.32; corrected for age, gender, disease duration, EDSS, depression and fatigue). The APOE genotype and CI were also not related in the subgroup of younger patients (age < 45 years; p > 0.9). Moreover, CI was related to higher T2LV (p = 0.008) and lower NCV (p = 0.006). In conclusion, in our sample CI was associated with higher subcortical damage and cortical atrophy but not with APOE-ε4 genotype. The role of APOE-ε4 as a possible biomarker in multiple sclerosis is still questionable.
Association of anti-Helicobacter pylori neutrophil-activating protein antibody response with anti-aquaporin-4 autoimmunity in Japanese patients with multiple sclerosis and neuromyelitis optica
Authors: Wei Li  , Minohara Motozumi , Hua Piao  , Matsushita Takuya , Masaki Katsuhisa , Matsuoka Takeshi , Isobe Noriko , Jen Jen Su  , Ohyagi Yasumasa , Kira Jun-ichi
Published: November 2009

There are two distinct subtypes of multiple sclerosis (MS) in Asians: opticospinal (OSMS) and conventional (CMS). OSMS has similar features to neuromyelitis optica (NMO) and half of OSMS patients have the NMO-Immunoglobulin G (IgG)/ anti-aquaporin-4 (AQP4) antibody. We reported that Helicobacter pylori (H. pylori) infection was significantly less common in CMS patients than controls. To reveal the immune responses to the H. pylori neutrophil-activating protein (HP-NAP) in Japanese MS patients, according to anti-AQP4 antibody status, sera from 162 MS patients, 37 patients with other inflammatory neurological diseases (OIND), and 85 healthy subjects were assayed for anti-H. pylori antibodies, anti-HP-NAP antibodies, and myeloperoxidase (MPO) by enzyme immunoassays. H. pylori seropositivity rates were significantly higher in anti-AQP4 antibody-positive MS/NMO (AQP4 + /MS) patients (19/27, 70.4%) than anti-AQP4 antibody-negative CMS (AQP4 — /CMS) patients (22/83, 26.5%). Among H. pylori-infected individuals, the anti-HP-NAP antibody was significantly more common in AQP4 + /MS and AQP4 — /OSMS patients than healthy subjects (36.8%, 34.6% versus 2.8%). Among the AQP4 + /MS patients, a significant positive correlation between anti-HP-NAP antibody levels and the final Kurtzke’s Expanded Disability Status Scale scores was found, and MPO levels were higher in anti-HP-NAP antibody-positive patients than anti-HP-NAP antibody-negative ones. Therefore, HP-NAP may be associated with the pathology of anti-AQP4 antibody-related neural damage in MS/NMO patients.
Relationship between Barkhof criteria and the clinical features of multiple sclerosis in northern Japan
Authors: Nakamura M. , Houzen H. , Niino M. , Tanaka K. , Sasaki H.
Published: November 2009

We previously reported that the prevalence of multiple sclerosis (MS) in the Tokachi Province of Hokkaido increased from 8.6 to 13.1 per 100,000 individuals between 2001 and 2006. Here, we study the frequency of MS patients who fulfill the Barkhof criteria and identified their common features. All 47 subjects in our previous study, who fulfilled Poser’s criteria, were included in this study. Of these, 33 satisfied the Barkhof criteria. In 2006, 9.2 per 100,000 MS patients fulfilled the Barkhof criteria; the percentage of patients who fulfilled these criteria was significantly higher among patients born after 1960 than among those born before 1960 (84.3% and 40.0%, respectively). The proportion of patients with conventional MS (C-MS) who fulfilled the Barkhof criteria was higher than that of patients with opticospinal MS (OS-MS) who fulfilled these criteria (93.9% and 71.4%, respectively). Longitudinally extensive spinal cord lesions (LESCLs) were not associated with the brain lesions defined in the Barkhof criteria (Barkhof brain lesions). In Tokachi Province, the increased percentage of MS patients who fulfill the Barkhof criteria was associated with increased C-MS incidence and an increase in the proportion of C-MS patients with Barkhof brain lesions among people born after 1960.
Deep gray matter T2 hypointensity is present in patients with clinically isolated syndromes suggestive of multiple sclerosis
Authors: Ceccarelli Antonia , Rocca Maria A , Neema Mohit , Martinelli Vittorio , Arora Ashish , Tauhid Shahamat , Ghezzi Angelo , Comi Giancarlo , Bakshi Rohit , Filippi Massimo
Published: November 2009

Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p = 0.04). At the baseline, the T2 intensity of the left caudate nucleus was significantly lower (p = 0.01) in CIS patients with disease dissemination in space (DIS), but not in those without DIS, compared to the HC. The baseline T2 lesion volume, but not GM T2 hypointensity, was associated with evolution to CDMS (hazard ratio = 1.60, 95% confidence interval (CI) = 1.05—2.42; p = 0.02). In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.
Anxiety and depression in multiple sclerosis. A comparative population-based study in Nord-Trøndelag County, Norway
Authors: Dahl Ole-Petter , Stordal Eystein , Lydersen Stian , Midgard Rune
Published: November 2009

Anxiety and depression are widely distributed symptoms among multiple sclerosis patients and in the general population. We assessed the prevalence of anxiety and depression in the multiple sclerosis population in Nord-Trøndelag County, Norway compared with Norway’s general population. The Hospital Anxiety and Depression Scale questionnaire was completed by 172 MS patients and 56,000 controls. A cut-off of ≥8 was used to define significant symptoms of anxiety and depression. Fatigue was measured using Krupp’s Fatigue Severity Scale, with a mean cut-off of >4. Among men, 31.1% of the multiple sclerosis patients reported anxiety, while only 12.1% of the control population reported this symptom ( p = 0.002). For women, the prevalence of anxiety was 29.7% versus 17.4% ( p < 0.001). Depression was reported by 26.2% of the men with multiple sclerosis compared with 10.8% of the controls ( p < 0.001). The corresponding figures for women were 25.2% versus 10.4% ( p < 0.001). Anxiety and depression were not correlated with duration of disease or disability measured by the Expanded Disability Status Scale. Among women, fatigue was associated with anxiety ( p ≤ 0.010) and depression ( p = 0.007). No such association was found among men. Anxiety and depression occur more frequently in multiple sclerosis patients than in the general population. Fatigue was associated with these neuropsychiatric manifestations in only women.
Very long chain fatty acid levels in patients diagnosed with multiple sclerosis
Authors: Wilkins Alastair , Ingram Gillian , Brown Anny , Jardine Philip , Steward Colin G , Robertson Neil P , Scolding Neil J
Published: November 2009

In clinical practice it is not uncommon for patients with adrenomyeloneuropathy or female carriers of adrenoleucodystrophy to have a presenting history and examination compatible with multiple sclerosis. This suggests that there may be an under-diagnosis of adrenoleucodystrophy and its variants in the multiple sclerosis population. We measured levels of very long chain fatty acids, which are typically elevated in the plasma of patients with adrenoleucodystrophy, in a large cohort of patients diagnosed clinically with multiple sclerosis. We tested serum samples from patients with either a first degree relative with multiple sclerosis or those with a primary progressive phenotype. No elevations in very long chain fatty acids were found in the cohort. This study suggests that the number of cases of adrenomyeloneuropathy or adrenoleucodystrophy amongst patients diagnosed clinically with multiple sclerosis is likely to be extremely low. This has important diagnostic implications.
Treatment manual for trauma-exposed youth: Case studies
Authors: Carrion Victor G. , Hull Katherine
Published: November 2009

Witnessing community violence and experiencing abuse in the home are two examples of interpersonal trauma that can have a devastating impact on children and adolescents. Recent research on the treatment of children exposed to interpersonal violence has focused on cognitive-behavioral interventions, often delivered in school settings. We describe the application of a new manual-based psychotherapy protocol for treating pediatric trauma in a middle school. Two case studies illustrate the protocol application to children from an inner-city neighborhood. The Stanford Cue-Centered Therapy (CCT) is a short-term, multimodal therapy for youths who have experienced trauma, focusing primarily on exposure to trauma-related cues. These cases provide early data on the feasibility and effectiveness of providing CCT for high-risk youth within a school setting and training of school mental-health personnel in the use of the Stanford CCT Manual.
Parental and child perspectives on adaptation to childhood chronic illness: A qualitative study
Authors: Gannoni Anne F. , Shute Rosalyn H.
Published: November 2009

This qualitative study aimed to gain an in-depth understanding of the adaptation of children and families to childhood chronic illness. Considering ecological theories and child empowerment, we departed from the usual practice of relying solely on parental report by also soliciting children’s views. Eighteen children aged 7—14 with cancer, chronic renal failure or type 1 diabetes, and 21 of their parents, participated. The inclusion of several conditions enabled the examination of data from a categorical versus non-categorical perspective. Focus groups supplemented by individual interviews explored participants’ views about challenges and the processes they considered important in enhancing adaptation to a chronic illness. Children, as well as parents, provided rich material. Thematic analysis revealed 11 main themes. Six concerned the impact of the illness on various aspects of life. The other main themes were the meaning of disease, stress-processing, social support, future concerns and psychosocial interventions. There were many similarities and some differences between parent and child reports. Many issues were common across illness groups, consistent with a non-categorical approach, though there were some illness-specific issues, especially for those with cancer. Positive as well as negative material emerged. Implications for clinical services are discussed.
Comparing two attachment classification methods applied to preschool strange situations
Authors: Spieker Susan , Mckinsey Crittenden Patricia
Published: November 2009

This study compared two methods for classifying preschool-age children’s behavior in the Strange Situation procedure, the MacArthur (MAC) and the Preschool Assessment of Attachment (PAA), to determine whether they operationalized converging or diverging approaches to attachment theory. Strange Situations of 306 randomly selected 3-year-old children and their mothers in the NICHD Study of Early Child Care and Youth Development were classified with the MAC and PAA. The methods showed 50% agreement. A block of seven demographic, child and family predictors was unrelated to MAC classifications, but accounted for 19% of the variance in PAA classifications. The MAC and PAA each had associations with some child outcomes in grades 1—5 (ages 6—10) totaling 5% and 12% of the variance respectively, but some of the MAC associations were counter to the hypothesis. The MAC and PAA were sufficiently different to reflect both different classificatory methods and different theoretical understandings of attachment. Results are discussed in terms of limitations of the sample and measures available to compare the two methods, and clinical implications.
Individual and group performance on insight problems: The effects of experimentally induced fixation
Authors: Smith Christine M. , Bushouse Emily , Lord Jennifer
Published: November 2009

Recent research has shown that the benefits associated with incubation periods during individual problem solving can be explained in terms of forgetting the material or of any strategy that serves to block progress toward success (e.g., Smith & Blankenship, 1991). While interacting groups reliably outperform individuals on both problem-solving and recall tasks, groups superior memory capacity may serve to hinder problem solving, especially when fixation has occurred. In the present study, individuals and three-person groups attempted to solve a set of 20 rebus puzzles on two different occasions. In the first session rebuses were accompanied by “clues, that were designed to either help or hinder problem solving. Following a 15-minute filled incubation period, the rebuses were again presented without the clues. As expected, groups recalled more of the clues than did individual problem solvers. Additionally, individual problem-solvers performance was improved following the incubation period on the misleading clue items but not the good clue items. Following incubation, groups improved on both the helpful and misleading clue items. The possibility that incubation effects may vary with task type in group problem-solving contexts is discussed.
Preserving positive identities: Public and private regard for one's ingroup and susceptibility to stereotype threat
Authors: Ho Arnold K. , Sidanius Jim
Published: November 2009

The current study examines the effect of racial regard—feelings of positivity or negativity toward African Americans—on stereotype threat. Forty participants at Harvard University responded to questions concerning their social attitudes and returned later to take a difficult verbal test. This study replicated the well-established stereotype threat effect, and found evidence that both public regard (judgments concerning how others view Blacks) and private regard (how one views Blacks and feels about being Black) moderate the effect. Specifically, Blacks high in public regard and high in private regard appear more susceptible to stereotype threat effects. The article discusses the possibility that African Americans in our study face an additional cognitive burden when confronted with the need to preserve a positive identity.
Racist or racism? Taxometric support for a dimensional latent structure of explicit prejudice
Authors: Denson Thomas F. , Iyer Ravi , Lickel Brian
Published: November 2009

Individual differences in explicit prejudice have long been a central concern in intergroup relations, yet no study has investigated the latent structure of prejudice. Whereas some media reports, lay classifications, and historical notions of prejudice focus on a prejudiced type of person, more recent conceptualizations of prejudice explain it as a dimension with any given individual falling along a continuum from low to high. In the first taxometric research to assess attitudes, two studies used taxometric methods to explore whether explicit prejudice is best considered dimensional (i.e., differing in degree) or taxonic (i.e., differing in kind). In Study 1, 130 undergraduates ( M age = 19.2 years, ranging from 18 to 26) completed measures of explicit prejudice toward Muslims. These results largely supported a dimensional latent structure. In Study 2, 448 non-Hispanic participants ( M age = 46.2 years, ranging from 18 to 86) completed three measures of explicit prejudice toward Hispanics (modern racism, social distance, and negative traits) via the internet. Results were consistent with a dimensional latent structure. Implications for promoting intergroup relations are discussed.
Respect for persons in the intergroup context: Self—other overlap and intergroup emotions as mediators of the impact of respect on action tendencies
Authors: Laham Simon M. , Tam Tania , Lalljee Mansur , Hewstone Miles , Voci Alberto
Published: November 2009

Two studies examined self—other overlap and intergroup emotions as mediators of the effects of respect for persons on action tendencies towards outgroup members. In contexts of both mild (Study 1) and more severe (Study 2) intergroup conflict, respect for persons predicted action tendencies towards outgroup members: those who value the intrinsic worth of others (high respect for persons) expressed less negative and more positive action tendencies towards outgroup members than did those with low respect for persons. These effects were obtained while controlling for Social Dominance Orientation and Agreeableness (Study 1). Further, the effects of respect for persons on action tendencies were shown to be partially mediated by self—other overlap and intergroup emotions. The findings support previous work in suggesting that respect for persons is an important predictor in intergroup contexts, and they highlight potential mechanisms through which respect might operate.
The uniquely human content of stereotypes
Authors: Vaes Jeroen , Paladino Maria Paola
Published: November 2009

The uniquely human content of stereotypes was measured in nine different inter-group comparisons that varied in terms of competence and warmth. Results indicated that the infrahumanization bias understood as people s tendency to see in-group relative to out-group stereotypes as more human occurred in almost all inter-group situations. Secondly, mainly out-groups that lack both warmth and competence were clearly infrahumanized as a result of a denial of out-group humanity. Finally, results suggested that among the different out-groups it was especially those high in competence, low in warmth that were seen as most uniquely human. As such, the current work extends previous research on infrahumanization to stereotypes, shows that group typology moderates the infrahumanization bias and demonstrates the affinity between the uniquely human and the competence dimension.
Interpersonal control, dehumanization, and violence: A self-determination theory perspective
Authors: Moller Arlen C. , Deci Edward L.
Published: November 2009

Interpersonally controlling approaches are often used to keep individuals in line, ostensibly in order to create a safer, more civilized society. Ironically, emerging research findings indicate that when people feel controlled, they often respond by behaving in a less civilized, more antisocial manner (Gagné, 2003; Knee, Neighbors, & Vietor, 2001; Mask, Blanchard, Amiot, & Deshaies, 2005; McHoskey, 1999). The present research investigation explored whether a process of mechanistic dehumanization might help to explain the observed relation between interpersonal control and antisocial behavior, specifically with regard to tendencies toward violence. The results indicated that a significant relation between interpersonal control and tendencies toward interpersonal violence was partially mediated by perceived mechanistic dehumanization.
Screening and treatment of latent tuberculosis in a cohort of asylum seekers in Norway
Authors: Harstad Ingunn , Heldal Einar , Steinshamn Sigurd L. , Garåsen Helge , Winje Brita A. , Jacobsen Geir W.
Published: November 2009

Aims: Asylum seekers are screened for tuberculosis at entry to Norway. We aimed to assess follow-up of screening results at different healthcare levels in relation to demographics, screening results and organizational factors, and how this influenced treatment of latent tuberculosis. Methods: All asylum seekers ≥18 years with a Mantoux test ≥6 mm or positive x-ray findings who arrived at the National Reception Centre from January 2005 to June 2006, were included. Data were collected from public health authorities in the municipality where the asylum seekers had moved, and from internists in case they had been referred to a specialist. Specialists are responsible for treating latent tuberculosis. Individual subjects were matched with the National Tuberculosis Register to which everybody who had started treatment for latent tuberculosis was reported. Results: Of 4,643 asylum seekers, 2,237 fulfilled the inclusion criteria. By May 2008, 30 persons had started treatment for latent TB, a median of 17 months (range 3—36) after arrival. A Mantoux test ≥15 mm on arrival was significantly associated with treatment. Demographic factors influenced follow-up in primary healthcare while screening results did not. Referral to specialist was related to screening results. Several specialists were reluctant to diagnose and treat latent tuberculosis and to treat persons without a permanent visa in particular. Conclusions: Just 1% of the study group received treatment for latent tuberculosis and with a long time delay. The reason for this may be organizational factors affecting follow-up and referral and specialists not following current guidelines.
Racial Environment and Political Participation
Authors: Matsubayashi Tetsuya
Published: November 2009

How does the racial environment influence mass political participation? The power—threat hypothesis predicts that a larger out-group population in the surrounding environment increases citizen participation, whereas the relational goods hypothesis predicts that it decreases participation. I attempt to reconcile these conflicting arguments into a single hypothesis positing that citizens’ decisions to participate in politics are simultaneously shaped by the power—threat and relational goods effects. I conclude that the racial environment plays a significant role as a determinant of mass participation but in ways more complicated than what simple models of contextual effects suggest.
Smoking Cessation
Authors: Greenhagen Robert M. , Johnson Adam R. , Bevilacqua Nicholas J.
Published: November 2009

Tobacco cigarette smoking causes many negative effects on the body, and it is the leading preventable cause of death in the United States. These negative effects are a concern for the foot and ankle surgeon, as smoking can increase the risk of diabetes and peripheral artery disease and delay healing of surgical incisions and ulcerations of the lower extremities. Tobacco cigarette smoking can also increase the risk of avascular necrosis and delayed union and nonunions of fractures and osteotomies. Smoking cessation is an important component in the overall treatment of conditions affecting the foot and ankle. Smoking cessation can be a difficult goal to achieve, but proper education and support can help patients reach this goal.
Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma
Authors: Chauhan Dharminder , Singh Ajita V. , Ciccarelli Bryan , Richardson Paul G. , Palladino Michael A. , Anderson Kenneth C.
Published: November 2009

Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus lenalidomide-induced apoptosis. Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low-dose combination of NPI-0052 and lenalidomide is well tolerated, significantly inhibits tumor growth, and prolongs survival. Taken together, our study provides the preclinical rationale for clinical protocols evaluating lenalidomide together with NPI-0052 to improve patient outcome in MM.
Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation
Authors: Aubin Éric , Lemieux Réal , Bazin Renée
Published: November 2009

Several clinical studies done with intravenous immunoglobulin (IVIg)–treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcγRIIb-independent, suggesting that IVIg must interfere with activating FcγRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.
ADAMTS13 gene deletion aggravates ischemic brain damage: a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion
Authors: Fujioka Masayuki , Hayakawa Kazuhide , Mishima Kenichi , Kunizawa Ai , Irie Keiichi , Higuchi Sei , Nakano Takafumi , Muroi Carl , Fukushima Hidetada , Sugimoto Mitsuhiko , Banno Fumiaki , Kokame Koichi , Miyata Toshiyuki , Fujiwara Michihiro , Okuchi Kazuo , Nishio Kenji
Published: November 2009

Reperfusion after brain ischemia causes thrombus formation and microcirculatory disturbances, which are dependent on the platelet glycoprotein Ib–von Willebrand factor (VWF) axis. Because ADAMTS13 cleaves VWF and limits platelet-dependent thrombus growth, ADAMTS13 may ameliorate ischemic brain damage in acute stroke. We investigated the effects of ADAMTS13 on ischemia-reperfusion injury using a 30-minute middle cerebral artery occlusion model in Adamts13−/− and wild-type mice. After reperfusion for 0.5 hours, the regional cerebral blood flow in the ischemic cortex was decreased markedly in Adamts13−/− mice compared with wild-type mice (P < .05), which also resulted in a larger infarct volume after 24 hours for Adamts13−/− compared with wild-type mice (P < .01). Thus, Adamts13 gene deletion aggravated ischemic brain damage, suggesting that ADAMTS13 may protect the brain from ischemia by regulating VWF-platelet interactions after reperfusion. These results indicate that ADAMTS13 may be a useful therapeutic agent for stroke.
gp96, an endoplasmic reticulum master chaperone for integrins and Toll-like receptors, selectively regulates early T and B lymphopoiesis
Authors: Staron Matthew , Yang Yi , Liu Bei , Li Janet , Shen Yuankai , Zúñiga-Pflücker Juan Carlos , Aguila Hector L. , Goldschneider Irving , Li Zihai
Published: November 2009

Integrins contribute to lymphopoiesis, whereas Toll-like receptors (TLRs) facilitate the myeloid replenishment during inflammation. The combined role of TLRs and integrin on hematopoiesis remains unclear. gp96 (grp94, HSP90b1) is an endoplasmic reticulum master chaperone for multiple TLRs. We report herein that gp96 is also essential for expression of 14 hematopoietic system-specific integrins. Genetic deletion of gp96 thus enables us to determine the collective roles of gp96, integrins, and TLRs in hematopoiesis. We found that gp96-null hematopoietic stem cells could support long-term myelopoiesis. B- and T-cell development, however, was severely compromised with transitional block from pro-B to pre-B cells and the inability of thymocytes to develop beyond the CD4−CD8− stage. These defects were cell-intrinsic and could be recapitulated on bone marrow stromal cell culture. Furthermore, defective lymphopoiesis correlated strongly with failure of hematopoietic progenitors to form close contact with stromal cell niche and was not the result of the defect in the assembly of antigen receptor or interleukin-7 signaling. These findings define gp96 as the only known molecular chaperone to specifically regulate T- and B-cell development.
Granzyme B is not required for regulatory T cell–mediated suppression of graft-versus-host disease
Authors: Cai Sheng F. , Cao Xuefang , Hassan Anjum , Fehniger Todd A. , Ley Timothy J.
Published: November 2009

Regulatory T (Treg) cells can suppress a wide variety of immune responses, including antitumor and alloimmune responses. The mechanisms by which Treg cells mediate their suppressive effects depend on the context of their activation. We previously reported that granzyme B is important for Treg cell–mediated suppression of antitumor immune responses. We therefore hypothesized that granzyme B may likewise be important for suppression of graft-versus-host disease (GVHD). We found that allogeneic mismatch induces the expression of granzyme B in mixed lymphocyte reactions and in a model of graft-versus-host disease (GVHD). However, wild-type and granzyme B–deficient Treg cells were equally able to suppress effector T (Teff) cell proliferation driven by multiple stimuli, including allogeneicantigen-presenting cells. Surprisingly, adoptive transfer of granzyme B–deficient Treg cells prevented GVHD lethality, suppressed serum cytokine production in vivo, and prevented target organ damage. These data contrast strikingly with our previous study, which demonstrated that granzyme B plays a nonredundant role in Treg cell–mediated suppression of antitumor responses. Taken together, these findings suggest that targeting specific Treg cell–suppressive mechanisms, such as granzyme B, may be therapeutically beneficial for segregating GVHD and graft-versus-tumor immune responses.
Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 Nuclear Bodies
Authors: Rajan Prabhakar , Dalgliesh Caroline , Bourgeois Cyril F , Heiner Monika , Emami Kaveh , Clark Emma L , Bindereif Albrecht , Stevenin James , Robson Craig N , Leung Hing Y , Elliott David J
Published: November 2009

Background

Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids.

Results

We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons.

Conclusion

Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs.
Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MRgene
Authors: Kanda Kyoko , Nozu Kandai , Yokoyama Naoki , Morioka Ichiro , Miwa Akihiro , Hashimura Yuya , Kaito Hiroshi , Iijima Kazumoto , Matsuo Masafumi
Published: November 2009

Background

Autosomal dominant pseudohypoaldosteronism type 1 (PHA1) is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR), but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD) and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations.

Methods and Results

We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products.

Conclusion

mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.
Placental malaria among HIV-infected and uninfected women receiving anti-folates in a high transmission area of Uganda
Authors: Newman Patrick M , Wanzira Humphrey , Tumwine Gabriel , Arinaitwe Emmanuel , Waldman Sarah , Achan Jane , Havlir Diane , Rosenthal Philip J , Dorsey Grant , Clark Tamara D , Cohan Deborah
Published: November 2009

Background

HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women.

Methods

This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP) in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR.

Results

Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW). Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used.

Conclusion

Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a considerable impact on the burden of LBW in this population.
Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines
Authors: Bredholt Therese , Dimba Elizabeth AO , Hagland Hanne R , Wergeland Line , Skavland Jørn , Fossan Kjell O , Tronstad Karl J , Johannessen Anne C , Vintermyr Olav K , Gjertsen Bjørn T
Published: November 2009

Background

An organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity.

Results

Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation.

Conclusion

Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.