bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of universal health coverage on urban–rural inequity in psychiatric service utilisation for patients with first admission for psychosis: a 10-year nationwide population-based study in Taiwan
Authors: Chiang Chih-Lin , Chen Pei-Chun , Huang Ling-Ya , Kuo Po-Hsiu , Tung Yu-Chi , Liu Chen-Chung , Chen Wei J
Published: March 2016

Objective

To examine the disparities in psychiatric service utilisation over a 10-year period for patients with first admission for psychosis in relation to urban–rural residence following the implementation of universal health coverage in Taiwan.

Design

Population-based retrospective cohort study.

Setting

Taiwan's National Health Insurance Research Database, which has a population coverage rate of over 99% and contains all medical claim records of a nationwide cohort of patients with at least one psychiatric admission between 1996 and 2007.

Participants

69 690 patients aged 15–59 years with first admission between 1998 and 2007 for any psychotic disorder.

Main exposure measure

Patients’ urban–rural residence at first admissions.

Main outcome measures

Absolute and relative inequality indexes of the following quality indicators after discharge from the first admission: all-cause psychiatric readmission at 2 and 4 years, dropout of psychiatric outpatient service at 30 days, and emergency department (ED) treat-and-release encounter at 30 days.

Results

Between 1998 and 2007, the 4-year readmission rate decreased from 65% to 58%, the 30-day dropout rate decreased from 18% to 15%, and the 30-day ED encounter rate increased from 8% to 10%. Risk of readmission has significantly decreased in rural and urban patients, but at a slower speed for the rural patients (p=0.026). The adjusted HR of readmission in rural versus urban patients has increased from 1.00 (95% CI 0.96 to 1.04) in 1998–2000 to 1.08 (95% CI 1.03 to 1.12) in 2005–2007, indicating a mild widening of the urban–rural gap. Urban–rural differences in 30-day dropout and ED encounter rates have been stationary over time.

Conclusions

The universal health coverage in Taiwan did not narrow urban–rural inequity of psychiatric service utilisation in patients with psychosis. Therefore, other policy interventions on resource allocation, service delivery and quality of care are needed to improve the outcome of rural-dwelling patients with psychosis.
Molecular interactions of polo-like kinase 1 in human cancers
Authors: Weng Ng Wayne Tiong , Shin Joo-Shik , Roberts Tara Laurine , Wang Bin , Lee Cheok Soon
Published: March 2016

Polo-like kinase 1 (PLK1) is an essential protein in communicating cell-cycle progression and DNA damage. Overexpression of PLK1 has been validated as a marker for poor prognosis in many cancers. PLK1 knockdown decreases the survival of cancer cells. PLK1 is therefore an attractive target for anticancer treatments. Several inhibitors have been developed, and some have been clinically tested to show additive effects with conventional therapies. Upstream regulation of PLK1 involves multiple interactions of proteins such as FoxM1, E2F and p21. Other cancer-related proteins such as pRB and p53 also indirectly influence PLK1 expression. With the high mutation rates of these genes seen in cancers, they may be associated with PLK1 deregulation. This raises the question of whether PLK1 overexpression is a cause or a consequence of oncogenesis. In addition, hypomethylation of the CpG island of the PLK1 promoter region contributes to its upregulation. PLK1 expression can be affected by many factors; thus, it is possible that PLK1 deregulation in each individual patient tumours could be due to different underlying mechanisms.
Australian women's attitudes towards and understandings of the subdermal contraceptive implant: a qualitative study of never-users
Authors: Inoue Kumiyo , Kelly Marguerite , Barratt Alexandra , Bateson Deborah , Rutherford Alison , Black Kirsten I , Stewart Mary , Richters Juliet
Published: March 2016

Objective

Few studies have explored Australian women's understandings of contraception. This study examined the attitudes towards, and understandings of, the subdermal contraceptive implant expressed by women living in New South Wales (NSW), Australia.

Study design

As part of a larger qualitative study using in-depth, open-ended interviews in 2012–2013 with women aged 16–49 years who had ever used contraception (n=94), 65 interviews from women who discussed or mentioned the subdermal implant, but had not previously used the device, were examined and analysed using thematic analysis.

Results

The emergent themes were: satisfaction with current method; weak personal opinions and ambivalence; uncertainty due to specific concerns; and strong negative reactions – fear and dislike. Although there were a few positive perceptions expressed by women who had never used the subdermal implant, for the majority of women the perception was predominantly negative.

Discussion and conclusion

Women tended to form negative impressions from the stories of other women about the subdermal implant. Interventions to enhance evidence-informed awareness of the relative advantages and disadvantages of the implant – for example, improved access to supportive contraceptive counselling – need investigation in the Australian context. Avenues to improve women's perceived control over the device could also be usefully investigated.
NADPH oxidase 4 attenuates cerebral artery changes during the progression of Marfan syndrome
Authors: Onetti Yara , Meirelles Thayna , Dantas Ana P. , Schröder Katrin , Vila Elisabet , Egea Gustavo , Jiménez-Altayó Francesc
Published: March 2016

Marfan syndrome (MFS) is a connective tissue disorder that is often associated with the fibrillin-1 ( Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alterations, potentially including neurovascular disorders. However, little is known about small-vessel pathophysiology in MFS. MFS is associated with hyperactivated transforming growth factor (TGF)-β signaling, which among numerous other downstream effectors, induces the NADPH oxidase 4 (Nox4) isoform of NADPH oxidase, a strong enzymatic source of H2O2. We hypothesized that MFS induces middle cerebral artery (MCA) alterations and that Nox4 contributes to them. MCA properties from 3-, 6-, or 9-mo-old Marfan ( Fbn1C1039G/+) mice were compared with those from age/sex-matched wild-type littermates. At 6 mo, Marfan compared with wild-type mice developed higher MCA wall/lumen (wild-type: 0.081 ± 0.004; Marfan: 0.093 ± 0.002; 60 mmHg; P < 0.05), coupled with increased reactive oxygen species production, TGF-β, and Nox4 expression. However, wall stiffness and myogenic autoregulation did not change. To investigate the influence of Nox4 on cerebrovascular properties, we generated Marfan mice with Nox4 deficiency (Nox4−/−). Strikingly, Nox4 deletion in Marfan mice aggravated MCA wall thickening (cross-sectional area; Marfan: 6,660 ± 363 μm2; Marfan Nox4−/−: 8,795 ± 824 μm2; 60 mmHg; P < 0.05), accompanied by decreased TGF-β expression and increased collagen deposition and Nox1 expression. These findings provide the first evidence that Nox4 mitigates cerebral artery structural changes in a murine model of MFS.
Cardiorespiratory fitness estimation using wearable sensors: Laboratory and free-living analysis of context-specific submaximal heart rates
Authors: Altini Marco , Casale Pierluigi , Penders Julien , ten Velde Gabrielle , Plasqui Guy , Amft Oliver
Published: March 2016

In this work, we propose to use pattern recognition methods to determine submaximal heart rate (HR) during specific contexts, such as walking at a certain speed, using wearable sensors in free living, and using context-specific HR to estimate cardiorespiratory fitness (CRF). CRF of 51 participants was assessed by a maximal exertion test (V̇o2 max). Participants wore a combined accelerometer and HR monitor during a laboratory-based simulation of activities of daily living and for 2 wk in free living. Anthropometrics, HR while lying down, and walking at predefined speeds in laboratory settings were used to estimate CRF. Explained variance ( R2) was 0.64 for anthropometrics, and increased up to 0.74 for context-specific HR (0.73-0.78 when including fat-free mass). Next, we developed activity recognition and walking speed estimation algorithms to determine the same contexts (i.e., lying down and walking) in free living. Context-specific HR in free living was highly correlated with laboratory measurements (Pearson's r = 0.71–0.75). R2for CRF estimation was 0.65 when anthropometrics were used as predictors, and increased up to 0.77 when including free-living context-specific HR (i.e., HR while walking at 5.5 km/h). R2varied between 0.73 and 0.80 when including fat-free mass among the predictors. Root mean-square error was reduced from 354.7 to 281.0 ml/min by the inclusion of context-specific HR parameters (21% error reduction). We conclude that pattern recognition techniques can be used to contextualize HR in free living and estimated CRF with accuracy comparable to what can be obtained with laboratory measurements of HR response to walking.
The Hippo signal transduction network for exercise physiologists
Authors: Gabriel Brendan M. , Hamilton D. Lee , Tremblay Annie M. , Wackerhage Henning
Published: March 2016

The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports.
Age-related differences in plasma BDNF levels after prolonged bed rest
Authors: Soavi Cecilia , Marušič Uroš , Sanz Juana Maria , Morieri Mario Luca , Dalla Nora Edoardo , Šimunič Bostjan , Pišot Rado , Zuliani Giovanni , Passaro Angelina
Published: March 2016

Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and has been implicated in brain resistance to insults. Murine studies have demonstrated increased hippocampal concentration after acute immobilization and decreased concentration after chronic immobilization. In humans, chronic stress and sedentary lifestyle result in decreased plasma BDNF levels, but there no data exist regarding acute immobilization. The aim of our study was to evaluate age-related responses [comparing 7 younger subjects (age 23 ± 3 yr) and 8 older subjects (age 60 ± 4 yr)] of plasma BDNF before (baseline data collection, BDC) and after 14 days (BR14) of horizontal bed rest (BR). At BDC, BDNF levels were not different between the two groups ( P = 0.101), although at BR14, BDNF levels were higher in older subjects (62.02 ± 18.31) than in younger subjects (34.36 ± 15.24 pg/ml) ( P = 0.002). A general linear model for repeated measures showed a significant effect of BR on BDNF ( P = 0.002). The BDC BDNF levels correlated with fat-free mass in both populations (ALL) ( R = 0.628, P = 0.012), (older, R = 0.753, P = 0.031; younger, R = 0.772, P = 0.042), and with total cholesterol in ALL ( R = 0.647, P = 0.009) and older study subjects ( R = 0.805, P = 0.016). At BR14, BDNF correlated with total cholesterol ( R = 0.579, P = 0.024) and age ( R = 0.647, P = 0.009) in ALL. With an increase in age, the brain could become naturally less resistant to acute stressors, including the detrimental effects of prolonged bed rest, and thus the increase in BDNF in the older study group might reflect a protective overshooting of the brain to counteract the negative effects in such conditions.
Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects
Authors: Zhang Xiaoyan , Marjani Sadie L. , Hu Zhaoyang , Weissman Sherman M. , Pan Xinghua , Wu Shixiu
Published: March 2016

Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing. Cancer Res; 76(6); 1305–12. ©2016 AACR.
The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women
Authors: Huh Sung Jin , Oh Hannah , Peterson Michael A. , Almendro Vanessa , Hu Rong , Bowden Michaela , Lis Rosina L. , Cotter Maura B. , Loda Massimo , Barry William T. , Polyak Kornelia , Tamimi Rulla M.
Published: March 2016

The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case–control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67+ cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12–48.0]. Conversely, the frequency of ER+ or p27+ cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER+: OR = 0.70, 95% CI, 0.33–1.50; p27+: OR = 0.89, 95% CI, 0.45–1.75). Notably, high Ki67+/low p27+ and high Ki67+/low ER+ cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67+/low p27+ and low Ki67+/low ER+ cell frequencies, respectively, among premenopausal women (Ki67hi/p27lo: OR = 5.08, 95% CI, 1.43–18.1; Ki67hi/ERlo: OR = 4.68, 95% CI, 1.63–13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926–34. ©2016 AACR.
Shift Work, Chronotype, and Melatonin Patterns among Female Hospital Employees on Day and Night Shifts
Authors: Leung Michael , Tranmer Joan , Hung Eleanor , Korsiak Jill , Day Andrew G. , Aronson Kristan J.
Published: March 2016

Background: Shift work-related carcinogenesis is hypothesized to be mediated by melatonin; however, few studies have considered the potential effect modification of this underlying pathway by chronotype or specific aspects of shift work such as the number of consecutive nights in a rotation. In this study, we examined melatonin patterns in relation to shift status, stratified by chronotype and number of consecutive night shifts, and cumulative lifetime exposure to shift work.

Methods: Melatonin patterns of 261 female personnel (147 fixed-day and 114 on rotations, including nights) at Kingston General Hospital were analyzed using cosinor analysis. Urine samples were collected from all voids over a 48-hour specimen collection period for measurement of 6-sulfatoxymelatonin concentrations using the Buhlmann ELISA Kit. Chronotypes were assessed using mid-sleep time (MSF) derived from the Munich Chronotype Questionnaire (MCTQ). Sociodemographic, health, and occupational information were collected by questionnaire.

Results: Rotational shift nurses working nights had a lower mesor and an earlier time of peak melatonin production compared to day-only workers. More pronounced differences in mesor and acrophase were seen among later chronotypes, and shift workers working ≥3 consecutive nights. Among nurses, cumulative shift work was associated with a reduction in mesor.

Conclusion: These results suggest that evening-types and/or shift workers working ≥3 consecutive nights are more susceptible to adverse light-at-night effects, whereas long-term shift work may also chronically reduce melatonin levels.

Impact: Cumulative and current exposure to shift work, including nights, affects level and timing of melatonin production, which may be related to carcinogenesis and cancer risk. Cancer Epidemiol Biomarkers Prev; 25(5); 830–8. ©2016 AACR.
Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models
Authors: Punnoose Elizabeth A. , Leverson Joel D. , Peale Franklin , Boghaert Erwin R. , Belmont Lisa D. , Tan Nguyen , Young Amy , Mitten Michael , Ingalla Ellen , Darbonne Walter C. , Oleksijew Anatol , Tapang Paul , Yue Peng , Oeh Jason , Lee Leslie , Maiga Sophie , Fairbrother Wayne J. , Amiot Martine , Souers Andrew J. , Sampath Deepak
Published: March 2016

BCL-2 family proteins dictate survival of human multiple myeloma cells, making them attractive drug targets. Indeed, multiple myeloma cells are sensitive to antagonists that selectively target prosurvival proteins such as BCL-2/BCL-XL (ABT-737 and ABT-263/navitoclax) or BCL-2 only (ABT-199/GDC-0199/venetoclax). Resistance to these three drugs is mediated by expression of MCL-1. However, given the selectivity profile of venetoclax it is unclear whether coexpression of BCL-XL also affects antitumor responses to venetoclax in multiple myeloma. In multiple myeloma cell lines (n = 21), BCL-2 is expressed but sensitivity to venetoclax correlated with high BCL-2 and low BCL-XL or MCL-1 expression. Multiple myeloma cells that coexpress BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a BCL-XL–selective inhibitor (A-1155463). Multiple myeloma xenograft models that coexpressed BCL-XL or MCL-1 with BCL-2 were also resistant to venetoclax. Resistance to venetoclax was mitigated by cotreatment with bortezomib in xenografts that coexpressed BCL-2 and MCL-1 due to upregulation of NOXA, a proapoptotic factor that neutralizes MCL-1. In contrast, xenografts that expressed BCL-XL, MCL-1, and BCL-2 were more sensitive to the combination of bortezomib with a BCL-XL selective inhibitor (A-1331852) but not with venetoclax cotreatment when compared with monotherapies. IHC of multiple myeloma patient bone marrow biopsies and aspirates (n = 95) revealed high levels of BCL-2 and BCL-XL in 62% and 43% of evaluable samples, respectively, while 34% were characterized as BCL-2High/BCL-XLLow. In addition to MCL-1, our data suggest that BCL-XL may also be a potential resistance factor to venetoclax monotherapy and in combination with bortezomib. Mol Cancer Ther; 15(5); 1132–44. ©2016 AACR.
BRD4 Regulates EZH2 Transcription through Upregulation of C-MYC and Represents a Novel Therapeutic Target in Bladder Cancer
Authors: Wu Xinchao , Liu Dong , Tao Dan , Xiang Wei , Xiao Xingyuan , Wang Miao , Wang Liang , Luo Gang , Li Yawei , Zeng Fuqing , Jiang Guosong
Published: March 2016

People who develop bladder cancer frequently succumb to the intractable disease. Current treatment strategies are limited presumably due to the underlying molecular complexity and insufficient comprehension. Therefore, exploration of new therapeutic targets in bladder cancer remains necessary. Here, we identify that bromodomain-4 protein (BRD4), an important epigenome reader of bromodomain and extraterminal domain (BET) family member, is a key upstream regulator of enhancer of zeste homologue 2 (EZH2), and represents a novel therapeutic target in bladder cancer. We found that BRD4 was significantly overexpressed in bladder cancer cells and tissues. Inhibition of BRD4 decreased bladder cancer cell proliferation concomitantly with the accumulation of cell apoptosis in vitro and suppressed tumor growth in vivo. We further found that suppression of BRD4 decreased the mRNA and protein levels of EZH2, which was reversed by ectopic expression of C-MYC. In particular, individual silencing of BRD4 using shRNA or the BET inhibitor JQ1 strikingly diminished the recruitment of C-MYC to EZH2 promoter in bladder cancer. Briefly, our research reveals that BRD4 positively regulates EZH2 transcription through upregulation of C-MYC, and is a novel promising target for pharmacologic treatment in transcriptional program intervention against this intractable disease. Mol Cancer Ther; 15(5); 1029–42. ©2016 AACR.
Elevated Translation Initiation Factor eIF4E Is an Attractive Therapeutic Target in Multiple Myeloma
Authors: Li Shirong , Fu Jing , Lu Caisheng , Mapara Markus Y. , Raza Shahzad , Hengst Ulrich , Lentzsch Suzanne
Published: March 2016

eIF4E is the key regulator of protein translation and critical for translation. The oncogenic potential of tumorigenesis, which is highly contingent on cap-dependent eIF4E, also arises from the critical role in the nuclear export and cytosolic translation of oncogenic transcripts. Inhibition of Exportin1 (XPO1), which is the major nuclear export protein for eIF4E-bound oncoprotein mRNAs, results in decreased tumor cell growth in vitro and in vivo, suggesting that eIF4E is critical in multiple myeloma. Indeed, we found that eIF4E is overexpressed in myeloma cell lines and primary myeloma cells compared with normal plasma cells. Although stable overexpression of eIF4E in multiple myeloma cells significantly increases tumorigenesis, knockdown of eIF4E impairs multiple myeloma tumor progression in a human xenograft mouse model. Using a tet-on–inducible eIF4E-knockdown system, eIF4E downregulation blocks multiple myeloma tumor growth in vivo, correlating with decreased eIF4E expression. Further overexpression and knockdown of eIF4E revealed that eIF4E regulates translation of mRNAs with highly complex 5′-untranslated regions, such as c-MYC and C/EBPβ, and subsequently proliferation in multiple myeloma cells, but not in nonmalignant bone marrow stromal cells. Because many transcription factors that are critical for multiple myeloma proliferation exhibit a higher dependency on protein translation, eIF4E is an ideal and selective tool to target multiple myeloma cell growth. Mol Cancer Ther; 15(4); 711–9. ©2016 AACR.
Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance
Authors: Heinrich Anne-Kathrin , Lucas Henrike , Schindler Lucie , Chytil Petr , Etrych Tomáš , Mäder Karsten , Mueller Thomas
Published: March 2016

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA–doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA–doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging–based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998–1007. ©2016 AACR.
Use of antipsychotics and risk of venous thromboembolism in postmenopausal women
Authors: Liou Jun-Ting , Huang Yun-Wen , Lin Chen , Wu Gwo-Jang , Chu Che-Li , Yeh Chin-Bin , Wang Yun-Han , Wang Meng-Ting
Published: March 2016

Despite continued uncertainty of venous thromboembolism (VTE) caused from antipsychotic agents, this safety issue has not been examined in postmenopausal women, a population with high usages of antipsychotics and at high risk for VTE. We assessed whether antipsychotic use was associated with an increased VTE risk in women after menopause. We conducted a nested case-control study of all Taiwanese women aged ≥ 50 years (n = 316,132) using a nationwide healthcare claims database between 2000 and 2011. All newly diagnosed VTE patients treated with an anticoagulant or thrombectomy surgery were identified as cases (n = 2,520) and individually matched to select controls (n = 24,223) by cohort entry date, age, cancer diagnosis and major surgery procedure. The odds ratios (ORs) and 95 % confidence interval (CI) of VTE associated with antipsychotics were estimated by multivariate conditional logistic regressions. Current use of antipsychotics was associated with a 1.90-fold (95 % CI = 1.64–2.19) increased VTE risk compared with nonuse in postmenopausal women. The VTE risk existed in a dose-dependent fashion (test for trend, p<0.001), with a more than quadrupled risk for high-dose antipsychotics (adjusted OR = 4.60; 95 % CI = 2.88–7.33). Current parenteral administration of antipsychotics also led to a 3.46-fold increased risk (95 % CI = 2.39–5.00). Conversely, there was no increased VTE risk when antipsychotics were discontinued for > 30 days. In conclusion, current use of antipsychotics is significantly associated with a dose-dependent increased risk of VTE in postmenopausal women, especially for those currently taking high-dose or receiving parenteral antipsychotics.
Desafios e perspectivas da formação do terapeuta ocupacional no campo da saúde mental
Authors: Lins Sarah Raquel Almeida , Matsukura Thelma Simões
Published: March 2016

Este estudo objetivou identificar a opinião de docentes de cursos de graduação em Terapia Ocupacional acerca dos desafios e perspectivas implicados na formação acadêmica do terapeuta ocupacional no campo da saúde mental. Trata-se de estudo qualitativo realizado com 14 docentes de saúde mental vinculados a 10 cursos de graduação em Terapia Ocupacional do Estado de São Paulo. A coleta dos dados se deu através de Formulário de Identificação do Participante e de Roteiro de entrevistas semiestruturado que foram descritos e analisados através da identificação de categorias temáticas. Os principais desafios desta formação revelada pelos docentes envolvem a limitação da grade curricular e a distância existente entre o que preconizam as políticas públicas e a realidade observada no campo. Todos os docentes consideram a pertinência da formação generalista bem como da educação continuada para aquisição de conhecimentos mais específicos. Discute-se sobre os desafios e as potencialidades da formação e da integração ensino-serviço, a continuidade à formação, bem como o engajamento dos docentes na proposição de uma formação mais condizente com a realidade do campo. Considera-se que este estudo acrescenta ao conhecimento da área e contribui para o desenvolvimento de reflexões que contemplem a formação do terapeuta ocupacional em saúde mental.
Repertório funcional de crianças com paralisia cerebral nos contextos domiciliar e clínico: relato de cuidadores e profissionais.
Authors: Oliveira Alyne Kalyane Câmara , Matsukura Thelma Simões , Mancini Marisa Cotta
Published: March 2016

O objetivo do estudo foi avaliar a associação do perfil de funcionalidade de crianças com paralisia cerebral em casa e no contexto clínico nas áreas de autocuidado, mobilidade e função social, relatado por cuidadores e profissionais da reabilitação. Participaram 50 crianças, 50 cuidadores e 25 profissionais, fisioterapeutas e terapeutas ocupacionais, vinculados a instituições de saúde do interior Paulista. A instrumentação incluiu o Inventário de Avaliação Pediátrica de Incapacidade, uma ficha de identificação dos participantes e o Sistema de Classificação da Função Motora Grossa. Foi utilizado o teste de correlação de Spearman. Verificou-se associação significativa com índices de correlação de grande magnitude entre o perfil funcional das crianças nos dois contextos nas áreas investigadas, principalmente no que se refere às habilidades funcionais e a assistência dos cuidadores disponibilizada; associação mais fraca foi evidenciada nas modificações utilizadas. Resultados revelam coerência no repertório funcional das crianças em ambos contextos. A assistência disponibilizada por cuidadores e profissionais é relativamente semelhante, entretanto, os contextos se estruturam de forma a oferecerem modificações específicas, que dão suporte ao desempenho funcional dessas crianças em suas rotinas.
A interação durante as provas operatórias: considerações para a avaliação infantil
Authors: Silva Carla Regina , Silvestrini Marina Sanches
Published: March 2016

A teoria de Jean Piaget classifica o desenvolvimento infantil em estágios, de acordo com as estruturas cognitivas delineadas por idade e elabora o sistema de avaliação infantil - provas operatórias, conhecido e muitas vezes utilizado pelo terapeuta ocupacional. Serão apresentados os resultados relevantes de uma pesquisa que objetivou a análise crítica-reflexiva de variáveis durante a aplicação de provas operatórias de conservação; seriação; classificação e função simbólica em crianças nas fases pré-operatória, operatória e operatória concreta. As metodologias aplicadas e os materiais utilizados foram intencionalmente modificados em três etapas para cada prova: material e metodologia tradicionais, material diversificado e manuseio ativo e material personalizado e metodologia ativa. Após três meses de aplicações, registros imagéticos, instrumentos de pesquisa preenchidos e análises realizadas, temos como principais resultados que o manuseio ativo e a relação com os materiais diversificados contribuíram para respostas de maior maturidade intelectual da criança, em um número considerável de sessões.
CRISPR-Cas9 Targeting of
PCSK9
in Human Hepatocytes In Vivo—Brief Report
Authors: Wang Xiao , Raghavan Avanthi , Chen Tao , Qiao Lyon , Zhang Yongxian , Ding Qiurong , Musunuru Kiran
Published: March 2016

Objective—

Although early proof-of-concept studies of somatic in vivo genome editing of the mouse ortholog of proprotein convertase subtilisin/kexin type 9 (
Pcsk9
) in mice have established its therapeutic potential for the prevention of cardiovascular disease, the unique nature of genome-editing technology—permanent alteration of genomic DNA sequences—mandates that it be tested in vivo against human genes in normal human cells with human genomes to give reliable preclinical insights into the efficacy (on-target mutagenesis) and safety (lack of off-target mutagenesis) of genome-editing therapy before it can be used in patients.

Approach and Results—

We used a clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) 9 genome-editing system to target the human
PCSK9
gene in chimeric liver-humanized mice bearing human hepatocytes. We demonstrated high on-target mutagenesis (approaching 50%), greatly reduced blood levels of human PCSK9 protein, and minimal off-target mutagenesis.

Conclusions—

This work yields important information on the efficacy and safety of CRISPR-Cas9 therapy targeting the human
PCSK9
gene in human hepatocytes in vivo, and it establishes humanized mice as a useful platform for the preclinical assessment of applications of somatic in vivo genome editing.
miRNA Targeting of Oxysterol-Binding Protein-Like 6 Regulates Cholesterol Trafficking and Efflux
Authors: Ouimet Mireille , Hennessy Elizabeth J. , van Solingen Coen , Koelwyn Graeme J. , Hussein Maryem A. , Ramkhelawon Bhama , Rayner Katey J. , Temel Ryan E. , Perisic Ljubica , Hedin Ulf , Maegdefessel Lars , Garabedian Michael J. , Holdt Lesca M. , Teupser Daniel , Moore Kathryn J.
Published: March 2016

Objective—

Cholesterol homeostasis is fundamental to human health and is, thus, tightly regulated. MicroRNAs exert potent effects on biological pathways, including cholesterol metabolism, by repressing genes with related functions. We reasoned that this mode of pathway regulation could be exploited to identify novel genes involved in cholesterol homeostasis.

Approach and Results—

Here, we identify oxysterol-binding protein-like 6 (
OSBPL6
) as a novel target of 2 miRNA hubs regulating cholesterol homeostasis: miR-33 and miR-27b. Characterization of
OSBPL6
revealed that it is transcriptionally regulated in macrophages and hepatocytes by liver X receptor and in response to cholesterol loading and in mice and nonhuman primates by Western diet feeding.
OSBPL6
encodes the OSBPL-related protein 6 (ORP6), which contains dual membrane- and endoplasmic reticulum–targeting motifs. Subcellular localization studies showed that ORP6 is associated with the endolysosomal network and endoplasmic reticulum, suggesting a role for ORP6 in cholesterol trafficking between these compartments. Accordingly, knockdown of
OSBPL6
results in aberrant clustering of endosomes and promotes the accumulation of free cholesterol in these structures, resulting in reduced cholesterol esterification at the endoplasmic reticulum. Conversely, ORP6 overexpression enhances cholesterol trafficking and efflux in macrophages and hepatocytes. Moreover, we show that hepatic expression of
OSBPL6
is positively correlated with plasma levels of high-density lipoprotein cholesterol in a cohort of 200 healthy individuals, whereas its expression is reduced in human atherosclerotic plaques.

Conclusions—

These studies identify ORP6 as a novel regulator of cholesterol trafficking that is part of the miR-33 and miR-27b target gene networks that contribute to the maintenance of cholesterol homeostasis.
Beta-adrenergic Blockade at Memory Encoding, but Not Retrieval, Decreases the Subjective Sense of Recollection
Authors: Rimmele Ulrike , Lackovic Sandra F. , Tobe Russell H. , Leventhal Bennett L. , Phelps Elizabeth A.
Published: March 2016

Humans remember emotional events not only better but also exhibit a qualitatively distinct recollective experience—that is, emotion intensifies the subjective vividness of the memory, the sense of reliving the event, and confidence in the accuracy of the memory [Phelps, E. A., & Sharot, T. How (and why) emotion enhances the subjective sense of recollection. Current Directions in Psychological Science, 17, 147–152, 2008]. Although it has been demonstrated that activation of the beta-adrenergic system, linked to increases in stress hormone levels and physiological arousal, mediates enhanced emotional memory accuracy, the mechanism underlying the increased subjective sense of recollection is unknown. Behavioral evidence suggests that increased arousal associated with emotional events, either at encoding or retrieval, underlies their increased subjective sense of recollection. Using a double-blind, placebo-controlled, within-subject design, we showed that reducing arousal at encoding through oral intake of 80-mg of the beta-adrenergic receptor antagonist propranolol decreases the subjective sense of recollection for both negative and neutral stimuli 24 hr later. In contrast, administration of propranolol before memory retrieval did not alter the subjective sense of recollection. These results suggest that the neurohormonal changes underlying increased arousal at the time of memory formation, rather than the time of memory retrieval, modulate the subjective sense of recollection.
Cortical Integration of Contextual Information across Objects
Authors: Livne Tomer , Bar Moshe
Published: March 2016

Recognizing objects in the environment and understanding our surroundings often depends on context: the presence of other objects and knowledge about their relations with each other. Such contextual information activates a set of medial lobe brain regions, the parahippocampal cortex and the retrosplenial complex. Both regions are more activated by single objects with a unique contextual association than by objects not associated with any specific context. Similarly they are more activated by spatially coherent arrangements of objects when those are consistent with their known spatial relations. The current study tested how context in multiple-object displays is represented in these regions in the absence of relevant spatial information. Using an fMRI slow-event-related design, we show that the precuneus (a subpart of the retrosplenial complex) is more activated by simultaneously presented contextually related objects than by unrelated objects. This suggests that the representation of context in this region is cumulative, representing integrated information across objects in the display. We discuss these findings in relation to processing of visual information and relate them to previous findings of contextual effects in perception.
Whole-Body Reaching Movements Formulated by Minimum Muscle-Tension Change Criterion
Authors: Kudo Naoki , Choi Kyuheong , Kagawa Takahiro , Uno Yoji
Published: March 2016

It is well known that planar reaching movements of the human shoulder and elbow joints have invariant features: roughly straight hand paths and bell-shaped velocity profiles. The optimal control models with the criteria of smoothness or precision, which determine a unique movement pattern, predict such features of hand trajectories. In this letter on expanding the research on simple arm reaching movements, we examine whether the smoothness criteria can be applied to whole-body reaching movements with many degrees of freedom. Determining a suitable joint trajectory in the whole-body reaching movement corresponds to the optimization problem with constraints, since body balance must be maintained during a motion task. First, we measured human joint trajectories and ground reaction forces during whole-body reaching movements, and confirmed that subjects formed similar movements with common characteristics in the trajectories of the hand position and body center of mass. Second, we calculated the optimal trajectories according to the criteria of torque and muscle-tension smoothness. While the minimum torque change trajectories were not consistent with the experimental data, the minimum muscle-tension change model was able to predict the stereotyped features of the measured trajectories. To explore the dominant effects of the extension from the torque change to the muscle-tension change, we introduced a weighted torque change cost function. Considering the maximum voluntary contraction (MVC) force of the muscle as the weighting factor of each joint torque, we formulated the weighted torque change cost as a simplified version of the minimum muscle-tension change cost. The trajectories owing to the minimum weighted torque change criterion also showed qualitative agreement with the common features of the measured data. Proper estimation of the MVC forces in the body joints is essential to reproduce human whole-body movements according to the minimum muscle-tension change criterion.
Fluency, Satisfaction, Truth: Reassessing James in Light of Some Contemporary Psychology
Authors: Brunson Daniel J.
Published: March 2016

A notable feature of classical American pragmatism is its close association with the birth of experimental psychology. In particular, William James’ work as a psychologist influenced, and was influenced by, his pragmatism. This paper seeks to support this reading of the relation between Jamesian psychology and pragmatism, particularly through his “Sentiment of Rationality” and the later contention that the true is the satisfactory. In addition, James’ insights are tested and expanded through reference to contemporary research on processing fluency, as well as concepts of ecological rationality.
The Future of Pragmatism’s Second Life
Authors: Margolis Joseph
Published: March 2016

I view the revival of pragmatism, without manifesto, as a demand for fresh clues about the directives of its second life, and explore the prospects and possible gains of four proposals: (i) the primacy and artifactuality of persons; (ii) the mongrel nature of ordinary discourse; (iii) the discursivity of normativity; (iv) the abductive turn.
Kantianism and Pragmatism: A Response to Margolis
Authors: Levine Steven
Published: March 2016

In this piece I respond to Joseph Margolis’ article “The Future of Pragmatism’s Second Life.” I make two arguments. First, I argue that Margolis misinterprets the true contest between Kantianism and Pragmatism, and that his vision of Pragmatism’s second life is overly Kantian. Second, I question his conclusion that truths about our agential norms can only ever be ‘second best’.
A Synopsis of the family Pottiaceae in Brazil
Authors: COSTA DENISE PINHEIRO DA
Published: March 2016

The Pottiaceae are acrocarpous mosses, with South America being considered one of the centers of diversity. A revision of Brazilian species of the Pottiaceae resulted in 66 accepted species in the subfamilies Timmielloideae, Trichostomoideae, Barbuloideae, and Pottioideae. These species are found at elevations from sea level to 2700 m in Brazil. The family itself consists of 36 genera and 66 species, with only six taxa being considered endemic. Two new synonyms are designated for Weissia controversa: Weissia submicacea and Trichostomum exulatum. An illustrated key is presented for all the Brazilian species of the family Pottiaceae, as well as the vegetation types where they occur, there altitudinal ranges in Brazil, substrate types, world distributions, and additional comments.
Supplementary descriptive notes of the Sinella and Coecobrya (Collembola: Entomobryidae) species from North America, Hawaii and Japan
Authors: WU JUN , YAN QIBAO , ZHANG FENG
Published: March 2016

Many known collembolan species lack sufficient descriptive details so that further taxonomical comparison cannot be achieved. When sorting documents and materials from Prof. Jian-Xiu CHEN, Nanjing University, we found many old but valuable drafts on Sinella and Coecobrya species from North America, Hawaii and Japan. Supplementary descriptions, particularly chaetotaxy, were provided for the following species: S. agna Christiansen & Bellinger, 1980, S. alata Christiansen, 1960, S. baca Christiansen & Bellinger, 1980, S. barri Christiansen, 1960, S. hoffmani Wray, 1952, S. sexoculata (Schött, 1896), S. straminea (Folsom, 1899), S. yosiia Christiansen & Bellinger, 1992, C. akiyoshiana Yosii, 1956, C. borerae Christiansen & Bellinger, 1992, C. ishikawai Yosii, 1956, C. kukae Christiansen & Bellinger, 1992, C. lua Christiansen & Bellinger, 1992, C. nupa Christiansen & Bellinger, 1992, C. tibiotarsalis Yosii, 1964. Sinella cavernarum (Packard, 1888) was redescribed based on topotypes and more additional materials.
An explanation of honour-related killings of women in Europe through Bourdieu’s concept of symbolic violence and masculine domination
Authors: Grzyb Magdalena A
Published: March 2016

This article aims to explain the lethal violence against women observed in certain contexts in recent years. It analyses the phenomenon of female homicide victimization through the lens of Pierre Bourdieu’s theory of symbolic violence. The principal manifestation of homicide of female victims explored in this article are honour killings in migrant communities in Europe, a culturally specific form of gender-related homicide. The concept of symbolic violence partially explains the honour-related violence within the framework of patriarchal theories and emphasizes the function of direct violence against women as a patriarchal backlash in a situation of structural changes in gender relations. Applying Bourdieu’s theory to honour killings in Europe will explain the dynamics of violence against women in a situation where symbolic patriarchal power is undermined, due to new structural conditions, and offer guidelines on context and agent-focused approaches to tackling the phenomenon.
Injustice hurts, literally: The role of sleep and emotional exhaustion in the relationship between organizational justice and musculoskeletal disorders
Authors: Manville Caroline , Akremi Assâad El , Niezborala Michel , Mignonac Karim
Published: March 2016

The physical health consequences of perceived injustice at work are an important yet underexplored area of research. Using the job-stress recovery literature as an overarching framework, we argued that incomplete recovery because of sleep disorders and subsequent emotional exhaustion is a possible underlying mechanism through which organizational justice relates to employee musculoskeletal disorders (MSD). Using both self-administered questionnaires and medical examination to assess MSD, we tested our argument in two studies. Based on a randomly selected sample of employees from a variety of organizations, Study 1 found organizational justice to be negatively related to MSD through diminished sleep-related disorders. Using a sample of employees in nursing homes for the elderly, Study 2 extended these results by showing that the organizational justice–MSD relationship is sequentially mediated by sleep disorders and emotional exhaustion.