bluuebunny/crossref_metadata_2025 huggingface dataset:
φX216, a P2-like bacteriophage with broad Burkholderia pseudomallei and B. malleistrain infectivity
Authors: Kvitko Brian H , Cox Christopher R , DeShazer David , Johnson Shannon L , Voorhees Kent J , Schweizer Herbert P
Published: December 2012

Background

Burkholderia pseudomallei and B. mallei are closely related Category B Select Agents of bioterrorism and the causative agents of the diseases melioidosis and glanders, respectively. Rapid phage-based diagnostic tools would greatly benefit early recognition and treatment of these diseases. There is extensive strain-to-strain variation in B. pseudomallei genome content due in part to the presence or absence of integrated prophages. Several phages have previously been isolated from B. pseudomallei lysogens, for example φK96243, φ1026b and φ52237.

Results

We have isolated a P2-like bacteriophage, φX216, which infects 78% of all B. pseudomallei strains tested. φX216 also infects B. mallei, but not other Burkholderia species, including the closely related B. thailandensis and B. oklahomensis. The nature of the φX216 host receptor remains unclear but evidence indicates that in B. mallei φX216 uses lipopolysaccharide O-antigen but a different receptor in B. pseudomallei. The 37,637 bp genome of φX216 encodes 47 predicted open reading frames and shares 99.8% pairwise identity and an identical strain host range with bacteriophage φ52237. Closely related P2-like prophages appear to be widely distributed among B. pseudomallei strains but both φX216 and φ52237 readily infect prophage carrying strains.

Conclusions

The broad strain infectivity and high specificity for B. pseudomallei and B. mallei indicate that φX216 will provide a good platform for the development of phage-based diagnostics for these bacteria.
Caregiver burden in amyotrophic lateral sclerosis is more dependent on patients’ behavioral changes than physical disability: a comparative study
Authors: Lillo Patricia , Mioshi Eneida , Hodges John R
Published: December 2012

Background

Behavioral changes in patients with amyotrophic lateral sclerosis (ALS) mirror those found in frontotemporal dementia (FTD). Considering the high rate of neuropsychiatric symptoms found in ALS patients, this paper examines whether caregiver burden is associated with behavioral changes over and above the physical disability of patients with ALS, and if the presence of caregivers’ depression, anxiety and stress also impacts on caregiver burden.

Methods

140 caregivers of patients with ALS participated in a postal survey investigating patients’ neuropsychiatric symptoms (Cambridge Behaviour Inventory Revised CBI-R), motor function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised - ALSFRS-R), caregiver burden (Zarit Burden Interview), and caregiver mood (Depression, Anxiety and Stress Scale- DASS21). Seventy four percent of them were caregivers of patients with limb onset and 25.7% were caregivers of patients with bulbar onset.

Results

Moderate to severe behavioral changes were reported in 10-40% of patients with ALS. The levels of depression, anxiety and stress in the caregivers reached 20%. Burden was high in 48% of the caregivers. The strongest predictor of high caregiver burden was ALS patients’ abnormal behavior rather than physical disability, with an odds ratio of 1.4, followed by caregivers’ stress.

Conclusions

Our study has identified that behavioral changes (e.g. disinhibition, impulsivity) and caregiver stress have greater impact on caregiver burden than level and pattern of physical disability.
Risk factors for VIA positivity and determinants of screening attendances in Dar es Salaam, Tanzania
Authors: Kahesa Crispin , Kjaer Susanne Kruger , Ngoma Twalib , Mwaiselage Julius , Dartell Myassa , Iftner Thomas , Rasch Vibeke
Published: December 2012

Background

Tanzania is among the countries in the world where the cervical cancer incidence is estimated to be highest. Acknowledging an increase in the burden of cervical cancer, VIA was implemented as a regional cervical cancer screening strategy in Tanzania in 2002. With the aim of describing risk factors for VIA positivity and determinants of screening attendances in Tanzania, this paper present the results from a comparative analysis performed among women who are reached and not reached by the screening program”.

Methods

14 107 women aged 25–59 enrolled in a cervical cancer screening program in Dar es Salaam in the period 2002 – 2008. The women underwent VIA examination and took part in a structured questionnaire interview. Socioeconomic characteristics, sexual behavior, HIV status and high-risk (HR) HPV infection were determined in a subpopulation of 890 who participated and 845 who did not participate in the screening.

Results

Being widowed/separated OR=1.41 (95% CI: 1.17-1.66), of high parity OR=3.19 (95% CI: 1.84-5.48) of low education OR= 4.30 (95% CI: 3.50-5.31) and married at a young age OR=2.17 (95% CI: 1.37-3.07) were associated with being VIA positive. Women who participated in the screening were more likely to be HIV positive OR= 1.59 (95% CI. 1.14-2.25) in comparison with women who had never attended screening, while no difference was found in the prevalence of HR-HPV infection among women who had attended screening and women who had not attended screening.

Conclusion

Women who are widowed/separated, of high parity, of low education and married at a young age are more likely to be VIA positive and thus at risk of developing cervical cancer. The study further documents that a referral linkage between the HIV care and treatment program and the cervical cancer screening program is in place in the setting studied, where HIV positive were more likely to participate in the cervical cancer screening program than HIV negative women.
Lack of MMP-9 expression is a marker for poor prognosis in Dukes’ B colorectal cancer
Authors: Koskensalo Selja , Hagström Jaana , Linder Nina , Lundin Mikael , Sorsa Timo , Louhimo Johanna , Haglund Caj
Published: December 2012

Background

Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer.

Methods

We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens.

Results

Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p < 0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p = 0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p = 0.034).

Conclusion

Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.
The effect of community-based health management on the health of the elderly: a randomized controlled trial from China
Authors: Chao Jianqian , Wang Yimin , Xu Hui , Yu Qing , Jiang Lili , Tian Lin , Xie Wenyuan , Liu Pei
Published: December 2012

Background

An aging population poses significant challenges to health care in China. Health management has been implemented to reduce the costs of care, raise health service utilization, increase health knowledge and improve quality of life. Several studies have tried to verify the effectiveness of health management in achieving these goals worldwide. However, there have been insufficient randomized control trials (RCTs) to draw reliable conclusions. The few small-scale studies conducted in China include mostly the general population rather than the elderly. Our study is designed to evaluate the impact of community-based health management on the health of the elderly through an RCT in Nanjing, China.

Methods

Two thousand four hundred participants, aged 60 or older and who gave informed consent, were randomly allocated 1:1 into management and control groups, the randomization schedule was concealed from community health service center staff until allocation. Community-based health management was applied in the former while the latter was only given usual care. After 18 months, three categories of variables (subjective grading health indices, objective health indices and health service utilization) were measured based on a questionnaire, clinical monitoring and diagnostic measurements. Differences between the two groups were assessed before and after the intervention and analyzed with t-test, χ2-test, and multiple regression analysis.

Results

Compared with the control group, the management group demonstrated improvement on the following variables (P<0.01): health knowledge score, self-evaluated psychological conditions, overall self-evaluated health conditions, diet score, physical activity duration per week, regular blood pressure monitoring, waist-to-hip ratio, systolic blood pressure and fasting blood sugar. The number of outpatient clinic visits did not differ significantly (P=0.60) between the two groups before intervention, while after intervention it was smaller in the management group than in the control group (P<0.01). However, the number of hospital admissions in the preceding 6 months was not different between the two groups even after intervention (P=0.36). Multiple regression analysis showed that gender, age, education level, chronic disease status and self-evaluated psychological conditions were important factors affecting health knowledge score, BMI, and waist-to-hip ratio.

Conclusion

Community-based health management improved both subjective grading health indices, objective health indices and decreased the number of outpatient clinic visits, demonstrating effectiveness in improving elderly health.

Trial registration

ChiCTR-OCH-11001716
Reduction of multiplicity of infections but no change in msp2 genetic diversity in Plasmodium falciparum isolates from Congolese children after introduction of artemisinin-combination therapy
Authors: Ibara-Okabande Rod , Koukouikila-Koussounda Felix , Ndounga Mathieu , Vouvoungui Jeannhey , Malonga Vladimir , Casimiro Prisca Nadine , Ibara Jean Rosaire , Sidibe Anissa , Ntoumi Francine
Published: December 2012

Background

In this first study conducted after the introduction of artemisinin-combination therapy (ACT), the major objective was to evaluate Plasmodium falciparum genetic diversity and multiplicity of infection in isolates from Congolese children between one and nine years of age enrolled and followed up for one year. The secondary objective was to characterize the msp2 profiles of P. falciparum isolates collected from successive malaria episodes in ten children who had four or more clinical episodes during the follow up.

Methods

Three-hundred and thirteen children residing in southern part of Brazzaville participated in this study. Blood samples were obtained from all children at enrollment and checked for P. falciparum infection. Based on the one year follow-up data, two clinical groups were considered according to the number of malaria episodes presented over the follow up period: “protected”(children who did not experience any episode) and “unprotected” (those who experienced more that two episodes). Therefore, the msp2 genetic diversity of P. falciparum isolates collected at enrollment in the two groups was characterized by allele-specific nested PCR and compared. The msp2 profiles of P. falciparum isolates collected from successive malaria episodes was also characterized by allele-specific nested PCR.

Results

Forty-three percent of FC27 and fifty-seven percent of 3D7 in protected vs fifty-six percent of FC27 and forty-four percent of 3D7 in isolates from unprotected children were detected. Seven and two alleles belonging to the FC27, and six and three alleles belonging to 3D7 families were distinguished in isolates from protected and unprotected children respectively. The mean multiplicity of infection (MOI) values at inclusion for the msp2 locus was 1.29 and 1.43 for protected and unprotected children respectively. 43 isolates were obtained from the ten children who had four or more clinical episodes during the follow up. A total of 63 alleles or fragments corresponding to 57% (36/63) FC27 and 43% (27/63) 3D7 were detected. The variant 400bp of FC27 was the most prevalent. 46% (20/43), 42% (18/43), 2% (1/43) and 2% (1/43) of isolates were found to have 1, 2, 3 and 4 parasite genotypes respectively and the mean MOI was 1.78.

Conclusion

This study shows that the introduction of ACT in the Republic of Congo has reduced the MOI but not the genetic diversity of P. falciparum isolates from children living in Southern districts of Brazzaville.
Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in Rat sepsis syndrome induced by cecal puncture and ligation
Authors: Chang Chia-Lo , Leu Steve , Sung Hsin-Ching , Zhen Yen-Yi , Cho Chung-Lung , Chen Angela , Tsai Tzu-Hsien , Chung Sheng-Ying , Chai Han-Tan , Sun Cheuk-Kwan , Yen Chia-Hung , Yip Hon-Kan
Published: December 2012

Background

We tested whether apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) were superior to healthy (H)-ADMSCs at attenuating organ damage and mortality in sepsis syndrome following cecal ligation and puncture (CLP).

Methods

Adult male rats were categorized into group 1 (sham control), group 2 (CLP), group 3 [CLP + H-ADMSC administered 0.5, 6, and 18 h after CLP], group 4 [CLP + A-ADMSC administered as per group 3].

Results

Circulating peak TNF-α level, at 6 h, was highest in groups 2 and 3, and higher in group 4 than group 1 (p < 0.0001). Immune reactivity (indicated by circulating and splenic helper-, cytoxic-, and regulatory-T cells) at 24 and 72 h exhibited the same pattern as TNF-α amongst the groups (all p < 0.0001). The mononuclear-cell early and late apoptosis level and organ damage parameters of liver (AST, ALT), kidney (creatinine) and lung (arterial oxygen saturation) also displayed a similar pattern to TNF-α levels (all p < 0.001). Protein levels of inflammatory (TNF-α, MMP-9, NF-κB, ICAM-1), oxidative (oxidized protein) and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than group 1, whereas anti-apoptotic (Bcl-2) biomarker was lower in groups 2 and 3 than in group 1 but anti-oxidant (GR, GPx, HO-1, NQO-1) showed an opposite way of Bcl-2; these patterns were reversed for group 4 (all p < 0.001). Mortality was highest in group 3 and higher in group 2 than group 4 than group 1 (all p < 0.001).

Conclusions

A-ADMSC therapy protected major organs from damage and improved prognosis in rats with sepsis syndrome.
Stability of toxin gene proportion in red-pigmented populations of the cyanobacterium Planktothrix during 29 years of re-oligotrophication of Lake Zürich
Authors: Ostermaier Veronika , Schanz Ferdinand , Köster Oliver , Kurmayer Rainer
Published: December 2012

Background

Harmful algal blooms deteriorate the services of aquatic ecosystems. They are often formed by cyanobacteria composed of genotypes able to produce a certain toxin, for example, the hepatotoxin microcystin (MC), but also of nontoxic genotypes that either carry mutations in the genes encoding toxin synthesis or that lost those genes during evolution. In general, cyanobacterial blooms are favored by eutrophication. Very little is known about the stability of the toxic/nontoxic genotype composition during trophic change.

Results

Archived samples of preserved phytoplankton on filters from aquatic ecosystems that underwent changes in the trophic state provide a so far unrealized possibility to analyze the response of toxic/nontoxic genotype composition to the environment. During a period of 29 years of re-oligotrophication of the deep, physically stratified Lake Zürich (1980 to 2008), the population of the stratifying cyanobacterium Planktothrix was at a minimum during the most eutrophic years (1980 to 1984), but increased and dominated the phytoplankton during the past two decades. Quantitative polymerase chain reaction revealed that during the whole observation period the proportion of the toxic genotype was strikingly stable, that is, close to 100%. Inactive MC genotypes carrying mutations within the MC synthesis genes never became abundant. Unexpectedly, a nontoxic genotype, which lost its MC genes during evolution, and which could be shown to be dominant under eutrophic conditions in shallow polymictic lakes, also co-occurred in Lake Zürich but was never abundant. As it is most likely that this nontoxic genotype contains relatively weak gas vesicles unable to withstand the high water pressure in deep lakes, it is concluded that regular deep mixing selectively reduced its abundance through the destruction of gas vesicles.

Conclusions

The stability in toxic genotype dominance gives evidence for the adaptation to deep mixing of a genotype that retained the MC gene cluster during evolution. Such a long-term dominance of a toxic genotype draws attention to the need to integrate phylogenetics into ecological research as well as ecosystem management.
Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-κB activity: a comparative study with the HTLV-1 Tax-1 protein
Authors: Turci Marco , Lodewick Julie , Di Gennaro Gianfranco , Rinaldi Anne Sophie , Marin Oriano , Diani Erica , Sampaio Carla , Bex Françoise , Bertazzoni Umberto , Romanelli Maria Grazia
Published: December 2012

Background

Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway.

Results

The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1.

Conclusions

Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway.
A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains
Authors: Lu Lu , Pan Chungen , Li Yuan , Lu Hong , He Wu , Jiang Shibo
Published: December 2012

Background

Most currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4) can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell.

Results

We engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI), but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT.

Conclusion

This bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.
Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome
Authors: Cinar Nese , Harmanci Ayla , Aksoy Duygu Yazgan , Aydin Kadriye , Yildiz Bulent Okan
Published: December 2012

Background

Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women.

Methods

The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured.

Results

T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol.

Conclusion

PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.
Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes
Authors: Smith Logan B , Belanger Janelle M , Oberbauer Anita M
Published: December 2012

Background

Fibroblast growth factor receptor 3 (FGFR3) inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone (T3) plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase (TERT) and RNA component of telomerase (TR), and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response.

Results

Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity (p < 0.05). Chondrocytes treated with T3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity (p < 0.05); TERT and TR were not significantly reduced. The action of T3 at the growth plate may be partially mediated through the FGFR3 pathway.

Conclusions

The results suggest that FGFR3 inhibits chondrocyte proliferation by down-regulating TERT expression and reducing telomerase activity indicating an important role for telomerase in sustaining chondrocyte proliferative capacity during bone elongation.
Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study
Authors: Davidson Julie E , Lockhart Andrew , Amos Leslie , Stirnadel-Farrant Heide A , Mooser Vincent , Sollberger Marc , Regeniter Axel , Monsch Andreas U , Irizarry Michael C
Published: December 2012

Introduction

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 mass and dementia or Alzheimer's disease (AD) was detected in the Framingham study. The objectives of the current study were to explore the relationship of plasma Lp-PLA2 activity with cognitive diagnoses (AD, amnestic mild cognitive impairment (aMCI), and cognitively healthy subjects), cardiovascular markers, cerebrospinal fluid (CSF) markers of AD, and apolipoprotein E (APOE) genotype.

Methods

Subjects with mild AD (n = 78) and aMCI (n = 59) were recruited from the Memory Clinic, University Hospital, Basel, Switzerland; cognitively healthy subjects (n = 66) were recruited from the community. Subjects underwent standardised medical, neurological, neuropsychological, imaging, genetic, blood and CSF evaluation. Differences in Lp-PLA2 activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA2 and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients.

Results

There was no significant difference in plasma Lp-PLA2 activity between AD (197.1 (standard deviation, SD 38.4) nmol/min/ml) and controls (195.4 (SD 41.9)). Gender, statin use and low-density lipoprotein cholesterol (LDL) were independently associated with Lp-PLA2 activity in multiple regression models. Lp-PLA2 activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-ε4 had higher Lp-PLA2 activity (207.9 (SD 41.2)) than AD subjects lacking APOE-ε4 (181.6 (SD 26.0), P = 0.003) although this was attenuated by adjustment for LDL (P = 0.09). No strong correlations were detected for Lp-PLA2 activity and CSF markers of AD.

Conclusion

Plasma Lp-PLA2 was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA2 activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.
Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis
Authors: Toonen Erik JM , Barrera Pilar , Fransen Jaap , de Brouwer Arjan PM , Eijsbouts Agnes M , Miossec Pierre , Marotte Hubert , Scheffer Hans , van Riel Piet LCM , Franke Barbara , Coenen Marieke JH
Published: December 2012

Introduction

The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).

Methods

A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.

Results

Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.

Conclusions

Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.
Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus
Authors: Cortés-Hernández Josefina , Ávila Gabriela , Vilardell-Tarrés Miquel , Ordi-Ros Josep
Published: December 2012

Introduction

Cutaneous lupus erythematosus (CLE) is a chronic disease characterized by disfigurement and a relapsing course. Thalidomide has proven its efficacy in refractory cutaneous lupus disease, although it is not exempt from significant side effects and frequent relapses after withdrawal. New thalidomide analogues have been developed but lack clinical experience. The aim of this preliminary phase II study was to evaluate the efficacy and safety of lenalidomide in patients with refractory CLE.

Methods

Fifteen patients with refractory cutaneous lupus disease were enrolled in this single-center, open-label, non-comparative pilot trial between January 2009 and December 2010. Oral lenalidomide (5 to 10 mg/day) was administered and tapered according to clinical response. Patients were followed up for a mean of 15 months (range: 7 to 30). Primary efficacy endpoint was the proportion of patients achieving complete response, defined by a Cutaneous Lupus Erythematosus Disease Area and Severity index (CLASI) activity score of 0. Other secondary endpoints included development of side effects, evaluation of cutaneous and systemic flares, and impact on the immunological parameters.

Results

One patient discontinued treatment due to side effects. All remaining patients saw clinical improvement and this was already noticeable after 2 weeks of treatment. Twelve of those patients (86%) achieved complete response but clinical relapse was frequent (75%), usually occurring 2 to 8 weeks after lenalidomide's withdrawal. No influence on systemic disease, immunological parameters or CLASI damage score was observed. Side effects including insomnia, grade 2 neutropenia and gastrointestinal symptoms, were minor (13%). These resolved after withdrawing medication. Neither polyneuropathy nor thrombosis was observed.

Conclusion

Lenalidomide appears to be efficacious and safe in patients with refractory CLE, but clinical relapse is frequent after its withdrawal.

Trial registration

ClinicalTrials.gov: NCT01408199.
Students Fail to Transfer Knowledge of Chromosome Structure to Topics Pertaining to Cell Division
Authors: Newman Dina L. , Catavero Christina M. , Wright L. Kate
Published: December 2012

Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and in-depth interviews under the theory of knowledge transfer to explain student difficulties with concepts related to chromosomal behavior. In this paper, we show that students typically understand basic chromosome structure but do not activate cognitive resources that would allow them to explain macromolecular phenomena (e.g., homologous pairing during meiosis). To improve understanding of topics related to genetic information flow, we suggest that instructors use pedagogies and activities that prime students for making connections between chromosome structure and cellular processes.
Linguistic Analysis of Project Ownership for Undergraduate Research Experiences
Authors: Hanauer D. I. , Frederick J. , Fotinakes B. , Strobel S. A.
Published: December 2012

We used computational linguistic and content analyses to explore the concept of project ownership for undergraduate research. We used linguistic analysis of student interview data to develop a quantitative methodology for assessing project ownership and applied this method to measure degrees of project ownership expressed by students in relation to different types of educational research experiences. The results of the study suggest that the design of a research experience significantly influences the degree of project ownership expressed by students when they describe those experiences. The analysis identified both positive and negative aspects of project ownership and provided a working definition for how a student experiences his or her research opportunity. These elements suggest several features that could be incorporated into an undergraduate research experience to foster a student's sense of project ownership.
Collaborative Testing Improves Performance but Not Content Retention in a Large-Enrollment Introductory Biology Class
Authors: Leight Hayley , Saunders Cheston , Calkins Robin , Withers Michelle
Published: December 2012

Collaborative testing has been shown to improve performance but not always content retention. In this study, we investigated whether collaborative testing could improve both performance and content retention in a large, introductory biology course. Students were semirandomly divided into two groups based on their performances on exam 1. Each group contained equal numbers of students scoring in each grade category (“A”–“F”) on exam 1. All students completed each of the four exams of the semester as individuals. For exam 2, one group took the exam a second time in small groups immediately following the individually administered test. The other group followed this same format for exam 3. Individual and group exam scores were compared to determine differences in performance. All but exam 1 contained a subset of cumulative questions from the previous exam. Performances on the cumulative questions for exams 3 and 4 were compared for the two groups to determine whether there were significant differences in content retention. Even though group test scores were significantly higher than individual test scores, students who participated in collaborative testing performed no differently on cumulative questions than students who took the previous exam as individuals.
Education Catching Up with Science: Preparing Students for Three-Dimensional Literacy in Cell Biology
Authors: Kramer IJsbrand M. , Dahmani Hassen-Reda , Delouche Pamina , Bidabe Marissa , Schneeberger Patricia
Published: December 2012

The large number of experimentally determined molecular structures has led to the development of a new semiotic system in the life sciences, with increasing use of accurate molecular representations. To determine how this change impacts students’ learning, we incorporated image tests into our introductory cell biology course. Groups of students used a single text dealing with signal transduction, which was supplemented with images made in one of three iconographic styles. Typically, we employed realistic renderings, using computer-generated Protein Data Bank (PDB) structures; realistic-schematic renderings, using shapes inspired by PDB structures; or schematic renderings, using simple geometric shapes to represent cellular components. The control group received a list of keywords. When students were asked to draw and describe the process in their own style and to reply to multiple-choice questions, the three iconographic approaches equally improved the overall outcome of the tests (relative to keywords). Students found the three approaches equally useful but, when asked to select a preferred style, they largely favored a realistic-schematic style. When students were asked to annotate “raw” realistic images, both keywords and schematic representations failed to prepare them for this task. We conclude that supplementary images facilitate the comprehension process and despite their visual clutter, realistic representations do not hinder learning in an introductory course.
Radioiodine Therapy in Benign Thyroid Diseases: Effects, Side Effects, and Factors Affecting Therapeutic Outcome
Authors: Bonnema Steen Joop , Hegedüs Laszlo
Published: December 2012

Radioiodine (131I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after 131I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to 131I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the 131I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of 131I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of 131I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from 131I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from 131I therapy. Above all, the impact of 131I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid 131I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of 131I therapy in patients with nontoxic nodular goiter.
Phosphorylation network dynamics in the control of cell cycle transitions
Authors: Fisher Daniel , Krasinska Liliana , Coudreuse Damien , Novák Béla
Published: December 2012

Fifteen years ago, it was proposed that the cell cycle in fission yeast can be driven by quantitative changes in the activity of a single protein kinase complex comprising a cyclin – namely cyclin B – and cyclin dependent kinase 1 (Cdk1). When its activity is low, Cdk1 triggers the onset of S phase; when its activity level exceeds a specific threshold, it promotes entry into mitosis. This model has redefined our understanding of the essential functional inputs that organize cell cycle progression, and its main principles now appear to be applicable to all eukaryotic cells. But how does a change in the activity of one kinase generate ordered progression through the cell cycle in order to separate DNA replication from mitosis? To answer this question, we must consider the biochemical processes that underlie the phosphorylation of Cdk1 substrates. In this Commentary, we discuss recent findings that have shed light on how the threshold levels of Cdk1 activity that are required for progression through each phase are determined, how an increase in Cdk activity generates directionality in the cell cycle, and why cell cycle transitions are abrupt rather than gradual. These considerations lead to a general quantitative model of cell cycle control, in which opposing kinase and phosphatase activities have an essential role in ensuring dynamic transitions.
Lost in Transit: Product Replacement Bias and Pricing to Market
Authors: Nakamura Emi , Steinsson Jón
Published: December 2012

In the microdata underlying US trade price indexes, 40 percent of products are replaced before a single price change is observed and 70 percent are replaced after two price changes or fewer. A price index that focuses on price changes for identical items may, therefore, miss an important component of price adjustment occurring at the time of product replacements. We provide a model of this “product replacement bias” and quantify its importance using US data. Accounting for product replacement bias, long-run exchange rate “pass-through” is substantially higher than conventional estimates suggest, and the terms of trade are substantially more volatile. (JEL F14, F31)
Risk Preferences Are Not Time Preferences
Authors: Andreoni James , Sprenger Charles
Published: December 2012

Risk and time are intertwined. The present is known while the future is inherently risky. This is problematic when studying time preferences since uncontrolled risk can generate apparently present-biased behavior. We systematically manipulate risk in an intertemporal choice experiment. Discounted expected utility performs well with risk, but when certainty is added common ratio predictions fail sharply. The data cannot be explained by prospect theory, hyperbolic discounting, or preferences for resolution of uncertainty, but seem consistent with a direct preference for certainty. The data suggest strongly a difference between risk and time preferences. (JEL C91 D81 D91)
Married with Children: A Collective Labor Supply Model with Detailed Time Use and Intrahousehold Expenditure Information
Authors: Cherchye Laurens , Rock Bram De , Vermeulen Frederic
Published: December 2012

We propose a collective labor supply model with household production that generalizes a model of Blundell, Chiappori, and Meghir (2005). Adults' preferences depend not only on own leisure and individual private consumption of market goods. They also depend on the consumption of domestic goods, which are produced by combining market goods with individuals' time. A new identification result, which uses production shifters, is developed. We apply our model to unique data on Dutch couples with children. Our application uses a novel estimation strategy that builds upon the familiar two-stage allocation representation of the collective model. (JEL D12, J12, J22)
Political Aid Cycles
Authors: Faye Michael , Niehaus Paul
Published: December 2012

Researchers have scrutinized foreign aid's effects on poverty and growth, but anecdotal evidence suggests that donors often use aid for other ends. We test whether donors use bilateral aid to influence elections in developing countries. We find that recipient country administrations closely aligned with a donor receive more aid during election years, while those less aligned receive less. Consistent with our interpretation, this effect holds only in competitive elections, is absent in US aid flows to non-government entities, and is driven by bilateral alignment rather than incumbent characteristics.
Human Capital Investment and the Gender Division of Labor in a Brawn-Based Economy
Authors: Pitt Mark M , Rosenzweig Mark R , Hassan Mohammad Nazmul
Published: December 2012

A model of human capital investment and activity choice is used to explain facts describing gender differentials in the levels and returns to human capital investments and occupational choice. These include the higher return to and level of schooling, the small effect of healthiness on wages, and the large effect of healthiness on schooling for females relative to males. The model incorporates gender differences in the level and responsiveness of brawn to nutrition in a Roy-economy setting in which activities reward skill and brawn differentially. Evidence from rural Bangladesh provides support for the model and the importance of the distribution of brawn.
Who Gets the Job Referral? Evidence from a Social Networks Experiment
Authors: Beaman Lori , Magruder Jeremy
Published: December 2012

We use recruitment into a laboratory experiment in Kolkata, India to analyze how social networks select individuals for jobs. The experiment allows subjects to refer actual network members for casual jobs as experimental subjects under exogenously varied incentive contracts. We provide evidence that some workers, those who are high ability, have useful information about the abilities of members of their social network. However, the experiment also shows that social networks provide incentives to refer less qualified workers, and firms must counterbalance these incentives in order to effectively use existing employees to help overcome their screening problem.
The Effect of Evaluation on Teacher Performance
Authors: Taylor Eric S , Tyler John H
Published: December 2012

Teacher performance evaluation has become a dominant theme in school reform efforts. Yet, whether evaluation changes the performance of teachers, the focus of this paper, is unknown. Instead, evaluation has largely been studied as an input to selective dismissal decisions. We study mid-career teachers for whom we observe an objective measure of productivity—value-added to student achievement—before, during, and after evaluation. We find teachers are more productive in post-evaluation years, with the largest improvements among teachers performing relatively poorly ex-ante. The results suggest teachers can gain information from evaluation and subsequently develop new skills, increase long-run effort, or both.
The Impact of Pollution on Worker Productivity
Authors: Zivin Joshua Graff , Neidell Matthew
Published: December 2012

This paper assesses the impact of pollution on worker productivity by relating exogenous daily variations in ozone with productivity of agricultural workers as recorded under piece rate contracts. We find robust evidence that ozone levels well below federal air quality standards have a significant impact on productivity. These results suggest that, in contrast to common characterizations of environmental protection as a tax on producers, environmental protection can also be viewed as an investment in human capital, and thus a tool for promoting economic growth.
The Economic Impacts of Climate Change: Evidence from Agricultural Output and Random Fluctuations in Weather: Reply
Authors: Deschênes Olivier , Greenstone Michael
Published: December 2012

Fisher et al. (2012)––henceforth, FHRS––have uncovered coding and data errors in our paper, Deschênes and Greenstone (2007), henceforth, DG. We acknowledge and are embarrassed by these mistakes. We are grateful to FHRS for uncovering them. We hope that this Reply will also contribute to advancing the literature on the vital question of the impact of climate change on the US agricultural sector.