bluuebunny/crossref_metadata_2025 huggingface dataset:
Computerized Cognitive Testing for Older Adults
Authors: Zygouris Stelios , Tsolaki Magda
Published: February 2014

Objective:

This article is a review of computerized tests and batteries used in the cognitive assessment of older adults.

Method:

A literature search on Medline followed by cross-referencing yielded a total of 76 citations.

Results:

Seventeen test batteries were identified and categorized according to their scope. Computerized adaptive testing (CAT) and the Cambridge Cognitive Examination CAT battery as well as 3 experimental batteries and an experimental test are discussed in separate sections. All batteries exhibit strengths associated with computerized testing such as standardization of administration, accurate measurement of many variables, automated record keeping, and savings of time and costs. Discriminant validity and test–retest reliability were well documented for most batteries while documentation of other psychometric properties varied.

Conclusion:

The large number of available batteries can be beneficial to the clinician or researcher; however, care should be taken in order to choose the correct battery for each application.
Cognitive Behavioral Therapy for Stress-Related Problems
Authors: Anclair Malin , Hiltunen Arto J.
Published: February 2014

Many parents who have children suffering from some form of chronic illness or mental disorder may experience chronic stress reactions of various types. Cognitive behavioral therapy (CBT) has been proved to be effective in reducing stress-related problems, but there seems to be no study to date in which CBT has been tested on this specific parent group. Two case studies were therefore performed. Case 1 centered on a 47-year-old married woman, who has lived in Sweden for 12 months. She described how she had become increasingly exhausted, and she wanted help to find strategies enabling her to cope with everyday life. Case 2 featured a 45-year-old single mother, who had been on part-time sick leave due to depression and stress. She described how she had always been anxious and worried and had had two episodes of depression. Both women had sons diagnosed with autism/Asperger syndrome. One of the women met the criteria for pathological burnout, while the other woman was just below the limit. The focus of the therapy for both women was on exhaustion, depression, and sleeping difficulties. In addition, therapy in Case 1 involved under-stimulation and in Case 2, anxiety. When the therapy ended, genuine improvements were registered for both clients. The results show that CBT can be an effective treatment of symptoms for this group of parents so that they can provide adequate support to their children, thus facilitating everyday life for a child with a chronic illness or disorder.
In Vitro and In Vivo Effects of Jia-Wei-Xiao-Yao-San in Human Breast Cancer MCF-7 Cells Treated With Tamoxifen
Authors: Chen Jiun-Liang , Chang Chun-Ju , Wang Jir-You , Wen Che-Sheng , Tseng Ling-Ming , Chang Wen-Chi , Noomhorm Nattanant , Liu Hui-Ju , Chen Wei-Shone , Chiu Jen-Hwey , Shyr Yi-Ming
Published: February 2014

Introduction. There is epidemiological evidence that Jia-Wei-Xiao-Yao-San (JWXYS) is the most common Chinese medicine decoction coprescribed with tamoxifen (Tam) when breast cancer is treated by hormonal therapy. However, whether there is interaction between JWXYS and Tam remains to be clarified. The aim of this study was to investigate the in vitro and in vivo effects of JWXYS on human breast cancer MCF-7 cells treated with Tam. Methods. In vitro cultured MCF-7 cells were cotreated with JWXYS and Tam. This was followed by MTT ([4,5-cimethylthiazol-2-yl]- 2,5-diphenyl tetrazolium bromide) assays and cell cycle analysis to assess cell proliferation; Western blot analysis was used to analyze the expression of various proteins involved in growth-related signal pathways. In addition, immunohistochemistry was used to detect autophagy among the cancer cells. In vivo analysis used female athymic nude mice implanted with MCF-7 cells; these mice were randomly assigned to 6 groups. All mice were killed humanely after 21 days of treatment; body weight, tumor volume, and tumor weight were then measured. Results. JWXYS was not cytotoxic to MCF-7 cells, based on the fact that there were no statistically significant changes between the JWXYS + Tam groups and the Tam-alone group in cell numbers, cell cycle progression, and cell proliferation signals, the latter including the expression levels of AKT, ERK, P38, p27(Kip1), and light chain (LC3)-I, II. Furthermore, using the MCF-7 xenograft mouse model, there were no significant changes between the JWXYS (1.3-3.9 gm/kg) + Tam groups and the Tam-alone group in terms of tumor weight and the protein expression levels of AKT, ERK, P38, and p27 (Kip1). However, there was a significant decrease in LC3-II protein expression with the low-dose JWXYS + Tam group but not with the middle- or high-dose JWXYS + Tam groups compared with the Tam-alone group. Conclusion. Based on in vitro studies and in vivo functional studies, there is no obvious interaction between JWXYS and Tam. However, the presence of interference at the molecular level in relation to LC3-II expression provides important information and may affect treatment strategies when physicians have patients with estrogen receptor-α(+) or progesterone receptor(+) breast cancers.
The Effects of Peroneal Nerve Functional Electrical Stimulation Versus Ankle-Foot Orthosis in Patients With Chronic Stroke
Authors: Bethoux Francois , Rogers Helen L. , Nolan Karen J. , Abrams Gary M. , Annaswamy Thiru M. , Brandstater Murray , Browne Barbara , Burnfield Judith M. , Feng Wuwei , Freed Mitchell J. , Geis Carolyn , Greenberg Jason , Gudesblatt Mark , Ikramuddin Farha , Jayaraman Arun , Kautz Steven A. , Lutsep Helmi L. , Madhavan Sangeetha , Meilahn Jill , Pease William S. , Rao Noel , Seetharama Subramani , Sethi Pramod , Turk Margaret A. , Wallis Roi Ann , Kufta Conrad
Published: February 2014

Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.
Association Between Leg Length Discrepancy and Posterior Tibial Tendon Dysfunction
Authors: Sanhudo Jose Antônio Veiga , Gomes Joao Luiz Ellera
Published: February 2014

Background. Leg length discrepancy (LLD) is associated with a variety of orthopaedic disorders and biomechanical gait changes that involve possible overload of the posterior tibial tendon (PTT). In view of the biomechanical disturbances induced by LLD, an association may exist between LLD and PTT dysfunction (PTTD). Purpose. To compare the frequency and magnitude of LLD between subjects with and without PTTD and ascertain whether associations exist between clinical features and presence of dysfunction. Study Design. Case–control study. Methods. A total of 118 patients with a diagnosis of PTTD were seen between January 2009 and September 2012 and compared with 118 gender-matched and race-matched volunteers. The frequency of LLD, the mean absolute LLD, and the mean relative LLD were measured by conventional (radiographic) or computed tomography scanography and compared between cases and controls. Results. The prevalence of LLD and mean absolute and relative LLD values were significantly greater in the case group (94.9%, 5.64 mm and 7.36%, respectively) than in the control group (79.7%, 3.28 mm and 4.18%, respectively) (P < .001). Conclusion. The findings of this study demonstrate a relationship between LLD and PTTD. In light of the major biomechanical changes it induces, LLD may be a predisposing factor for development of PTTD.

Level of Evidence: Prognostic, Level III: Case–control series, retrospective
Applicability of Cardoso and Faletto Model to Analyze the Current Latin American Reality
Authors: Silva Paulo Roberto
Published: February 2014

In 1966, sociologists Fernando Henrique Cardoso and Enzo Faletto wrote, on the request of Economic Commission for Latin America (ECLAC), the classic Dependence and Development in Latin America, in which they sought to underline social and economic fundamentals of what they called “national underdevelopment.” Almost half-century later, the Latin American reality is not the same, but the method adopted by Cardoso and Faletto can still be used to analyze it. A proof of its actuality is its resemblance with some methodological approaches that operate in the intersection between economics and social sciences by Anglo-Saxon scholars.
Asymmetric Hip Rotation in Professional Baseball Pitchers
Authors: McCulloch Patrick C. , Patel Jayesh K. , Ramkumar Prem N. , Noble Philip C. , Lintner David M.
Published: February 2014

Background:

There is a renewed interest in examining the association between hip range of motion and injury in athletes, and the data on baseball players are conflicting. Understanding whether asymmetrical hip rotation is a normal adaptation or a risk factor for injury will help therapists, trainers, and physicians develop rehabilitation programs to improve kinetic energy transfer and prevent injury. As our knowledge of hip pathology among baseball pitchers improves, establishing baselines for hip motion is critical in the further assessment of injury.

Hypothesis:

Because of the repetitive nature of throwing sports and the adaptive changes documented in the shoulder, elite baseball pitchers would have characteristic patterns of hip internal and external rotations on their dominant throwing side (stance) and their nondominant side (stride) in extension.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Computer software was used to measure passive internal and external rotations on digital photographs of 111 professional baseball pitchers.

Results:

In right-handed pitchers, there was significantly more internal rotation in the stance hip than the stride hip (32.2° ± 8.2° vs 30.8° ± 8.4°; P = .0349) and significantly more external rotation in the stride hip than the stance hip (36.3° ± 7.7° vs 30.8° ± 9.7°; P < .0001). While the mean difference in external rotation was 4.7°, 32% of the subjects had a >10° increase in external rotation on the stride hip relative to the stance hip. This population was statistically different from the remaining group for older age ( P = .0053), lower body mass index ( P = .0379), and more years in professional baseball ( P = .0328). In the smaller number of left-handed pitchers, side-to-side differences in hip rotation were found but were not statistically significant.

Conclusion:

Pitchers showed more internal rotation on their stance hip and more external rotation on their stride hip. Although the mean differences are small, there is a subset of pitchers with defined characteristics in whom larger differences exist.
Community-acquired lung respiratory infections in HIV-infected patients: microbial aetiology and outcome
Authors: Cilloniz Catia , Torres Antoni , Polverino Eva , Gabarrus Albert , Amaro Rosanel , Moreno Encarnacion , Villegas Santiago , Ortega Mar , Mensa Josep , Marcos Maria Angeles , Moreno Asuncion , Miro Jose M.
Published: February 2014

We describe the aetiology of community-acquired pneumonia (CAP) in HIV-infected patients, risk factors for bacterial orPneumocystis jiroveciiCAP and prognostic factors of 30-day mortality.

This was a prospective observational study of 331 consecutive adult CAP cases in HIV-infected patients (January 2007 to July 2012).

128 (39%) patients had CD4+cell counts <200 per mm3and 99 (43%) ha HIV RNA levels <200 copies per mL on antiretroviral therapy.Streptococcus pneumoniaewas the most frequent microorganism in the group with CD4+cell counts ≥200 per mm3;P. jiroveciiwas the most frequent microorganism in the group with CD4+cell counts <200 per mm3and in patients with HIV RNA ≥200 copies per mL. Predictors of bacterial CAP were: time with symptoms ≤5 days (OR 2.6, 95% CI 1.5–4.4), C-reactive protein level ≥22 mg·dL−1(OR 4.3, 95% CI 2.3–8.2) and hepatitis C virus co-infection (OR 2.3, 95% CI 1.4–3.9). White blood cell count ≤4×1012per L (OR 3.7, 95% CI 1.2–11.5), lactate dehydrogenase (LDH) level ≥598 U·L−1(OR 12.9, 95% CI 4.2–39.7) and multilobar infiltration (OR 5.8, 95% CI 1.9–19.5) were predictors ofP. jirovecii. Overall 30-day mortality was 7%. Appropriate antibiotic treatment (OR 0.1, 95% CI 0.03–0.4), LDH ≥598 U·L−1(OR 6.2, 95% CI 1.8–21.8) and mechanical ventilation (OR 22.0, 95% CI 6.2–78.6) were the variables independently associated with 30-day mortality.

The described predictors may help clinicians to distinguish between bacterial andP. jiroveciipneumonia in patients with suspected or confirmed HIV infection.
Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD
Authors: Thabut Gabriel , Mornex Jean-François , Pison Christophe , Cuvelier Antoine , Balduyck Malika , Pujazon Marie-Christine , Fournier Michel , AitIlalne Brahim , Porcher Raphaël
Published: February 2014

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD.

We assessed the prognostic value of the BODE index in 191 patients followed from 2006 to 2012 in a French prospective cohort of patients with α1-antitrypsin deficiency.

20 patients died during follow-up and 22 underwent lung transplantation. Survival (95% CI) was 93.0% (91.7–94.3%) at 3 years and 76.0% (72.9–79.1%) at 5 years. The 3-year survival was 97.4% (96.6–98.2%), 98.0% (96.7–99.3%), 87.7% (84.5–90.9%) and 75.3% (66.0–84.6%) for patients with BODE index 0–2, 3–4, 5–6 and 7–10, respectively. Survival discrimination of the BODE index was better than with both forced expiratory volume in 1 s and Global Initiative for Chronic Obstructive Lung Disease classification. Regarding calibration, expected survival by BODE index was noticeably lower than observed survival.

The BODE index showed very good survival discrimination in patients with α1-antitrypsin deficiency-related COPD. Larger studies are needed to support its use to drive patient referral for lung transplantation.
Classification and pharmacological treatment of preschool wheezing: changes since 2008
Authors: Brand Paul L.P. , Caudri Daan , Eber Ernst , Gaillard Erol A. , Garcia-Marcos Luis , Hedlin Gunilla , Henderson John , Kuehni Claudia E. , Merkus Peter J.F.M. , Pedersen Soren , Valiulis Arunas , Wennergren Göran , Bush Andrew
Published: February 2014

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.
Importance of concomitant local and systemic eosinophilia in uncontrolled asthma
Authors: Schleich Florence Nicole , Chevremont Anne , Paulus Virginie , Henket Monique , Manise Maité , Seidel Laurence , Louis Renaud
Published: February 2014

Systemic and airway eosinophilia are recognised features of asthma. There are, however, patients who exhibit discordance between local and systemic eosinophilia. In this study, we sought to determine the prevalence and characteristics of patients with concordant and discordant systemic and bronchial eosinophilia.

We conducted a retrospective study on 508 asthmatics with successful sputum induction. We assessed the relationship between blood and sputum eosinophils by breaking down the population into four groups according to blood (≥400 cells per mm3) and sputum (≥3%) eosinophils. Then, we prospectively reassessed the link between eosinophils and asthma control (Asthma Control Questionnaire (ACQ)) and exacerbation rate in a new cohort of 250 matched asthmatics.

In our retrospective cohort, asthmatics without eosinophilic inflammation were the largest group (49%). The group with isolated sputum eosinophilia (25%) was, compared with noneosinophilic asthma, associated with lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio and higher bronchial hyperresponsiveness and exhaled nitric oxide fraction (FeNO). Asthmatics exhibiting isolated systemic eosinophilia (7%) had similar characteristics as noneosinophilic asthmatics. The group with concordant systemic and airway eosinophilia (19%) showed remarkable male predominance, and had the lowest airway calibre, asthma control and quality of life, and the highest bronchial hyperresponsiveness,FeNOand exacerbation rate. The prospective cohort confirmed the different subgroup proportions and the higher ACQ and exacerbation rates in cases of diffuse eosinophilia compared with noneosinophilic asthmatics.

Concomitant systemic and bronchial eosinophilic inflammation contribute to poor asthma control.
Multimodal management of malignant pleural mesothelioma: where are we today?
Authors: Van Schil Paul E. , Opitz Isabelle , Weder Walter , De Laet Christophe , Domen Andreas , Lauwers Patrick , Hendriks Jeroen M. , Van Meerbeeck Jan P.
Published: February 2014

The prognosis of patients with malignant pleural mesothelioma remains poor and although it is clear that multimodal therapy is necessary to improve long-term results, precise treatment schemes have not yet been unequivocally established. Single-modality therapy does not have a major impact on long-term survival and combined-modality therapies are being further evaluated. However, the relative contributions of chemotherapy, radiotherapy and surgery have not been clearly determined at the present time. Moreover, the extent of resection and precise surgical procedure remain a highly debated topic. To better compare and combine results from different institutions and trials, uniform definitions of surgical procedures including extrapleural pneumonectomy and different forms of pleurectomy have recently been introduced. Due to the relatively higher morbidity and mortality of extrapleural pneumonectomy, there is currently a shift towards pleurectomy/decortication when a macroscopic complete resection of all tumour can be obtained by this procedure. In most recent trials, induction chemotherapy was administered to improve surgical resection rates but pathological complete responses are infrequently observed. The role of post-operative radiotherapy has to be further elucidated.

Further treatment options that are currently explored include hyperthermic intrapleural chemotherapy, immunotherapy, gene therapy and photodynamic therapy. However, no randomised comparisons are available yet.
Major aging-associated RNA expressions change at two distinct age-positions
Authors: Gheorghe Marius , Snoeck Marc , Emmerich Michael , Bäck Thomas , Goeman Jelle J , Raz Vered
Published: February 2014

Background

Genome-wide expression profiles are altered during biological aging and can describe molecular regulation of tissue degeneration. Age-regulated mRNA expression trends from cross-sectional studies could describe how aging progresses. We developed a novel statistical methodology to identify age-regulated expression trends in cross-sectional datasets.

Results

We studied six cross-sectional RNA expression profiles from different human tissues. Our methodology, capable of overcoming technical and genetic background differences, identified an age-regulation in four of the tissues. For the identification of expression trends, five regression models were compared and the quadratic model was found as the most suitable for this study. Afterk-meansclustering of the age-associated probes, expression trends were found to change at two major age-positions in brain cortex and inVastus lateralismuscles. The first age-position was found to occur during the fifth decade and a later one during the eighth decade. In kidney cortex, however, only one age-position was identified correlating with a late age-position. Functional mapping of genes at each age-position suggests that calcium homeostasis and lipid metabolisms are initially affected and subsequently, in elderly mitochondria, apoptosis and hormonal signaling pathways are affected.

Conclusions

Our results suggest that age-associated temporal changes in human tissues progress at distinct age-positions, which differ between tissues and in their molecular composition.
Dynamic comparison between Daan real-time PCR and Cobas TaqMan for quantification of HBV DNA levels in patients with CHB
Authors: Cai Shao-hang , Lv Fang-fang , Zhang Yong-hong , Jiang Ye-gui , Peng Jie
Published: February 2014

Background

Hepatitis B virus (HBV) DNA levels are crucial for managing chronic hepatitis B (CHB). It was unclear whether Daan real-time polymerase chain reaction test (Daan test) or COBAS TaqMan HBV DNA Test (Cobas TaqMan) was superior in measuring different HBV DNA levels in clinical specimens.

Methods

We enrolled 67 treatment-naïve, HBV surface antigen-positive CHB patients (high baseline viral levels) who received either lamivudine/adefovir or entecavir. Serum samples were tested at baseline and treatment week 24 using the Daan test and Cobas TaqMan.

Results

In the 67-baseline samples, the HBV DNA levels with the Cobas TaqMan (7.90 ± 0.73 log10 IU/mL) were significantly greater than those of the Daan test (7.11 ± 0.44 log10 IU/mL; P < 0.001). Of the 67 24-week samples (low viral levels), the Cobas TaqMan detected 59 (88.1%; 8 undetected); the Daan test detected 33 (49.3%; 34 undetected; P < 0.001). The Cobas TaqMan detected HBV DNA in 26 of 34 samples undetectable by the Daan test (range, 1.4–3.7 log10 IU/mL) or 38% of samples (26/67). The reductions in viral load after 24 weeks of oral antiviral treatment in the 33 samples that were positive for both the Daan test and the Cobas TaqMan test were significantly different (3.59 ± 1.11 log10 IU/mL versus 4.87 ± 1.58 log10 IU/mL, respectively; P = 0.001). Spearman correlation analysis showed positive correlation between results from two tests (rp = 0.602,P<0.001). The HBV genotypes and the anti-viral treatment did not affect the measurements of the HBV DNA by the Daan assay and the Cobas Taqman assay.

Conclusion

The Cobas Taqman was more sensitive at low viral loads than the Daan test and the change from complete to partial virological response could affect clinical decisions. The Cobas Taqman may be more appropriate for detection of HBV DNA levels.
The innervation of the human acetabular labrum and hip joint: an anatomic study
Authors: Alzaharani Abdullah , Bali Kamal , Gudena Ravi , Railton Pamela , Ponjevic Dragana , Matyas John R , Powell James N
Published: February 2014

Background

The aim of the current study was to evaluate the innervation of the acetabular labrum in the various zones and to understand its potential role in nociception and proprioception in hips with labral pathology.

Methods

A total of twenty hip labrums were tagged and excised intraoperatively from patients undergoing a total hip replacement. After preparation, the specimens were cut to a thickness of 10 μm and divided into four quadrants (zones) using a clock face pattern. Neurosensory structure distribution was then evaluated using Hematoxylin and Eosin (H and E), and immunoreactivity to S-100.

Results

All specimens had abundant free nerve endings (FNEs). These were seen predominantly superficially and on the chondral side of the labrum. In addition, predominantly three different types of nerve end organs (NEOs) were identified in all twenty specimens. FNEs and NEOs were more frequently seen in the antero-superior and postero-superior zones. Four specimens had abundant vascularity and disorganised architecture of FNEs in the deeper zones of the antero-superior quadrant suggestive of a healed tear. Myofibroblasts were present in abundance in all the labral specimens and were distributed uniformly throughout all labral zones and depth.

Conclusions

The current study shows that the human acetabular labrum has abundant FNEs and NEOs. These are more abundant in the antero-superior and postero-superior zones. The labrum, by virtue of its neural innervation, can potentially mediate pain as well as proprioception of the hip joint, and be involved in neurosecretion that can influence connective tissue repair.
Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23
Authors: Ignesti Marilena , Barraco Marilena , Nallamothu Gouthami , Woolworth Julie A , Duchi Serena , Gargiulo Giuseppe , Cavaliere Valeria , Hsu Tien
Published: February 2014

Background

The Drosophila abnormal wing discs (awd) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, the Nm23 proteins, has not yet been clearly defined. Previous awd genetic analyses unraveled its endocytic role that is required for proper internalization of receptors controlling different signaling pathways. In this study, we analyzed the role of Awd in controlling Notch signaling during development.

Results

To study the awd gene function we used genetic mosaic approaches to obtain cells homozygous for a loss of function allele. In awd mutant follicle cells and wing disc cells, Notch accumulates in enlarged early endosomes, resulting in defective Notch signaling. Our results demonstrate that awd function is required before γ-secretase mediated cleavage since over-expression of the constitutively active form of the Notch receptor in awd mutant follicle cells allows rescue of the signaling. By using markers of different endosomal compartments we show that Notch receptor accumulates in early endosomes in awd mutant follicle cells. A trafficking assay in living wing discs also shows that Notch accumulates in early endosomes. Importantly, constitutively active Rab5 cannot rescue the awd phenotype, suggesting that awd is required for Rab5 function in early endosome maturation.

Conclusions

In this report we demonstrate that awd is essential for Notch signaling via its endocytic role. In addition, we identify the endocytic step at which Awd function is required for Notch signaling and we obtain evidence indicating that Awd is necessary for Rab5 function. These findings provide new insights into the developmental and pathophysiological function of this important gene family.
HPTN 071 (PopART): Rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment – a study protocol for a cluster randomised trial
Authors: Hayes Richard , Ayles Helen , Beyers Nulda , Sabapathy Kalpana , Floyd Sian , Shanaube Kwame , Bock Peter , Griffith Sam , Moore Ayana , Watson-Jones Deborah , Fraser Christophe , Vermund Sten H , Fidler Sarah ,   The HPTN 071 (PopART) Study Team
Published: February 2014

Background

Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis.

Methods/Design

A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.

In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes.

Discussion

Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.

Trial registration

ClinicalTrials.gov NCT01900977.
Lignans from the bark of Eucommia ulmoides inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells
Authors: Li Zhen-yu , Deng Xiao-lan , Huang Wei-hua , Li Ling , Li Hui , Jing Xian , Tian Ying-ying , Lv Pei-yu , Yang Tian-lun , Zhou Hong-hao , Ouyang Dong-sheng
Published: February 2014

Background

Tree bark of Eucommia ulmoides Oliv., (commonly well-known as “Du-zhong” in China), has been used to treat hypertension, hypercholesterolemia, hyperglycemia, hepatic fibrosis and renal injury. This study aims to investigate the effects of lignans extracted from the bark of Eucommia ulmoides Oliv. on Ang II-induced proliferation and extracellular matrix biosynthesis in rat mesangial cells.

Methods

Rat mesangial cells (RMCs) were cultured in vitro and divided into six groups (control, Ang II, losartan, and low, middle and high concentration lignans groups). RMC proliferation was measured by MTT assay. RT-qPCR and western blotting were used to detect mRNA and protein expression of collagen type I (Col I), collagen type III (Col III), collagen type IV (Col IV), fibronectin and aldose reductase (AR).

Results

Cellular proliferation induced by Ang II was significantly suppressed by Eucommia lignans of different concentrations (P = 0.034, P < 0.001, and P < 0.001). Treatment of cells with Ang II increased Col I, Col III, Col IV, and fibronectin mRNA expression, which was observed at the protein level (P < 0.001, P < 0.001, P = 0.004, and P = 0.004, respectively). The increased mRNA expression and protein levels of Col I, Col III, Col IV, and fibronectin were diminished remarkably with by treatment Eucommia lignans, and elevated AR expression stimulated by Ang II was significantly inhibited by Eucommia lignans.

Conclusions

Eucommia lignans (Du-zhong) inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells.
Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma
Authors: Moinzadeh Pia , Fonseca Carmen , Hellmich Martin , Shah Ami A , Chighizola Cecilia , Denton Christopher P , Ong Voon H
Published: February 2014

Introduction

We assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis.

Methods

We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients.

Results

Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).

Conclusions

Our study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.
Anxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study
Authors: Pietrzak Robert H. , Scott J. Cobb , Neumeister Alexander , Lim Yen Ying , Ames David , Ellis Kathryn A. , Harrington Karra , Lautenschlager Nicola T. , Szoeke Cassandra , Martins Ralph N. , Masters Colin L. , Villemagne Victor L. , Rowe Christopher C. , Maruff Paul
Published: February 2014

Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.
Socioeconomic status and survival among older adults with dementia and depression
Authors: Chen Ruoling , Hu Zhi , Wei Li , Wilson Kenneth
Published: February 2014

Background

People from lower socioeconomic groups have a higher risk of mortality. The impact of low socioeconomic status on survival among older adults with dementia and depression remains unclear.

Aims

To investigate the association between socioeconomic status and mortality in people with dementia and late-life depression in China.

Method

Using Geriatric Mental Status – Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) we interviewed 2978 people aged ⩾60 years in Anhui, China. We characterised baseline socioeconomic status and risk factors and diagnosed 223 people with dementia and 128 with depression. All-cause mortality was followed up over 5.6 years.

Results

Individuals with dementia living in rural areas had a three times greater risk of mortality (multivariate adjusted hazard ratio (HR) = 2.96, 95% CI 1.45–6.04) than those in urban areas, and for those with depression the HR was 4.15 (95% CI 1.59–10.83). There were similar mortality rates when comparing people with dementia with lowv.high levels of education, occupation and income, but individuals with depression with lowv.high levels had non-significant increases in mortality of 11%, 50% and 55% respectively.

Conclusions

Older adults with dementia and depression living in rural China had a significantly higher risk of mortality than urban counterparts. Interventions should be implemented in rural areas to tackle survival inequality in dementia and depression.
Signaling Through FSH Receptors on Human Umbilical Vein Endothelial Cells Promotes Angiogenesis
Authors: Stilley Julie A. , Guan Rongbin , Duffy Diane M. , Segaloff Deborah L.
Published: February 2014

Context:

The FSH receptor (FSHR) is traditionally thought to play a role in female reproductive physiology solely within the context of ovarian FSHR. However, FSHR is also expressed in endothelial cells of the placental vasculature and human umbilical cord vessels, suggesting additional facets of female reproduction regulated by extragonadal FSHR.

Objective:

We sought to determine the functional role of FSHR on human umbilical cord endothelial cells (HUVECs), hypothesizing that activation of the FSHR would stimulate angiogenesis.

Design:

The ability of FSH to stimulate several angiogenic processes in HUVECs was determined.

Setting:

This was a laboratory-based study using commercially prepared HUVECs.

Results:

Tube formation, wound healing, cell migration, cell proliferation, nitric oxide production, and cell survival were stimulated in response to FSH. Quantitative comparisons between HUVECs incubated with maximally stimulatory concentrations of FSH vs vascular endothelial growth factor (VEGF), a well-characterized angiogenic factor, revealed that FSH is as efficacious as VEGF in promoting angiogenic processes. FSH did not provoke increased secretion of VEGF by HUVECs, suggesting the direct stimulation of angiogenic processes by FSH in endothelial cells. In contrast to gonadal cells, the FSHR on HUVECs did not mediate an FSH-stimulated increase in cAMP. However, increased phosphorylation of AKT in response to FSH was observed, suggesting that FSH stimulation of HUVEC FSHR stimulates the PI3K/AKT signaling pathway.

Conclusions:

Our studies reveal a novel role for FSHR in female reproductive physiology. Its ability to promote angiogenesis in placental endothelial cells suggests that the FSHR may have an influential role in pregnancy.
Bumblebees are not deterred by ecologically relevant concentrations of nectar toxins
Authors: Tiedeken Erin Jo , Stout Jane C. , Stevenson Philip C. , Wright Geraldine A.
Published: February 2014

Bees visit flowers to collect nectar and pollen that contain nutrients and simultaneously facilitate plant sexual reproduction. Paradoxically, nectar produced to attract pollinators often contains deterrent or toxic plant compounds associated with herbivore defence. The functional significance of these nectar toxins is not fully understood, but they may have a negative impact on pollinator behaviour and health, and ultimately plant pollination. This study investigates whether a generalist bumblebee, Bombus terrestris, can detect naturally occurring concentrations of nectar toxins. Using paired-choice experiments, we identified deterrence thresholds for five compounds found in the nectar of bee-pollinated plants: quinine, caffeine, nicotine, amygdalin, and grayanotoxin. The deterrence threshold was determined when bumblebees significantly preferred a sucrose solution over a sucrose solution containing the compound. Bumblebees had the lowest deterrence threshold for the alkaloid quinine (0.01 mM); all other compounds had higher deterrence thresholds, above the natural concentration range in floral nectar. Our data combined with previous work using honeybees suggest that generalist bee species have poor acuity for the detection of nectar toxins. The fact that bees do not avoid nectar relevant concentrations of these compounds is likely to indicate that it is difficult for them to learn to associate floral traits with the presence of toxins, thus, maintaining this trait in plant populations.
Olfactory foraging in temperate waters: Sensitivity to dimethylsulfide by shearwaters in the Atlantic Ocean and Mediterranean Sea
Authors: Dell'Ariccia Gaia , Celerier Aurelie , Gabirot Marianne , Palmas Pauline , Massa Bruno , Bonadonna Francesco
Published: February 2014

Many procellariiforms use olfactory cues to locate food patches over the seemingly featureless ocean surface. In particular, some of them are able to detect and are attracted by dimethylsulfide (DMS), a volatile compound naturally occurring over worldwide oceans in correspondence with productive feeding areas. However, current knowledge is restricted to sub-Antarctic species, and to only one study realized under natural conditions at sea. Here, for the first time, we investigated the response to DMS in parallel in two different environments in temperate waters, the Atlantic Ocean and the Mediterranean Sea, employing Cory's (Calonectris borealis) and Scopoli's shearwaters (Calonectris diomedea) as models. To test whether these birds can detect and respond to DMS, we presented them with this substance in a Y-maze. Then, to determine if they use this molecule in natural conditions, we tested the response to DMS at sea. The number of birds that chose the DMS in the Y-maze and that were recruited at DMS-scented slicks at sea suggest that these shearwaters are attracted to DMS in both non-foraging and natural contexts. Our findings show that the use of DMS as a foraging cue may be a strategy used by procellariiforms across oceans but that regional differences may exist, giving a worldwide perspective to previous hypotheses concerning the use of DMS as chemical cue.
Octopaminergic modulation of the visual flight speed regulator ofDrosophila
Authors: van Breugel Floris , Suver Marie P. , Dickinson Michael H.
Published: February 2014

Recent evidence suggests that flies’ sensitivity to large field optic flow is increased by the release of octopamine during flight. This increase in gain presumably enhances visually-mediated behaviors such as the active regulation of forward speed, a process that involves the comparison of a vision-based estimate of velocity with an internal set point. To determine where in the neural circuit this comparison is made, we selectively silenced the octopamine neurons in the fruit fly, Drosophila, and examined the effect on vision-based velocity regulation in free flying flies. We found that flies with inactivated octopamine neurons accelerated more slowly in response to visual motion than control flies, but maintained nearly the same baseline flight speed. Our results are parsimonious with a circuit architecture in which the internal control signal is injected into the visual motion pathway upstream of the interneuron network that estimates groundspeed.
Fueling the engine: induction of AMP-activated protein kinase in trout skeletal muscle by swimming
Authors: Magnoni Leonardo J. , Palstra Arjan P. , Planas Josep V.
Published: February 2014

AMP-activated protein kinase (AMPK) is well known to be induced by exercise and to mediate important metabolic changes in the skeletal muscle of mammals. Despite the physiological importance of exercise as a modulator of energy use by locomotory muscle, the regulation of this enzyme by swimming has not been investigated in fish. We found that sustained swimming (40 days at 0.75 BLs-1) increased AMPK activity in red and white trout skeletal muscle (3.9 and 2.2 fold, respectively) as well as the expression of AMPK target genes involved in energy use: LPL and CS in red and white muscle and CPT1β1b and PGC-1α in red muscle. Furthermore, electrical pulse stimulation of cultured trout myotubes increased AMPK activity and glucose uptake (1.9 and 1.2 fold, respectively) in an AMPK-dependent manner. These results suggest that AMPK may play an important mediatory role in the metabolic adaptation to swimming in fish skeletal muscle.
Electron-Transfer Processes in Highly-Correlated Electron Systems of Thiazyl Radicals
Authors: Awaga Kunio , Nomura Kenji , Kishida Hideo , Fujita Wataru , Yoshikawa Hirofumi , Matsushita Michio M , Hu Laigui , Shuku Yoshiaki , Suizu Rie
Published: February 2014

Heterocyclic thiazyl radicals possess unique chemical and physical properties as building blocks for molecule-based conductors and magnetic materials. They do not need protecting groups on their molecular skeletons, and the lack of such substituents permits close packing in the solid state. Moreover, thiazyl radical solids often involve a multidimensional network consisting of π–π overlaps and S···N contacts. The electronic structures of the thiazyl radicals can be compared to highly-correlated electron systems. In this account, we describe various electron-transfer processes in the solids of the thiazyl radicals, which manifest themselves by external stimuli such as temperature change, electric field, and photoillumination.
Preparation of siRNA Carrier Based on Boronic Acid-functionalized Amphiphilic Poly(γ-glutamic acid) Nanoparticles
Authors: Shima Fumiaki , Shudo Manami , Akagi Takami , Akashi Mitsuru
Published: February 2014

Boronic acid-grafted amphiphilic poly(γ-glutamic acid) was successfully synthesized with carbodiimide. These copolymers could form 200-nm-sized monodispersed nanoparticles (NPs). These NPs were stable in saline and could efficiently load small interfering RNA (siRNA) in a dose-dependent manner at about 80% efficiency. These results demonstrated that the polymer chemistry could contribute to the development of siRNA-based gene therapies.