Healthcare policy in developed countries has, in recent years, promoted self-management among people with long-term conditions. Such policies are underpinned by neoliberal philosophy, as seen in the ...promotion of greater individual responsibility for health through increased support for self-management. Yet still little is known about how self-management is understood by commissioners of healthcare services, healthcare professionals, people with long-term conditions and family care-givers. The evidence presented here is drawn from a two-year study, which investigated how self-management is conceptualised by these stakeholder groups. Conducted in the UK between 2013 and 2015, this study focused on three exemplar long-term conditions, stroke, diabetes and colorectal cancer, to explore the issue. Semi-structured interviews and focus groups were carried out with 174 participants (97 patients, 35 family care-givers, 20 healthcare professionals and 22 commissioners). The data is used to demonstrate how self-management is framed in terms of what it means to be a ‘good’ self-manager. The ‘good’ self-manager is an individual who is remoralised; thus taking responsibility for their health; is knowledgeable and uses this to manage risks; and, is ‘active’ in using information to make informed decisions regarding health and social wellbeing. This paper examines the conceptualisation of the ‘good’ self-manager. It demonstrates how the remoralised, knowledgeable and active elements are inextricably linked, that is, how action is knowledge applied and how morality underlies all action of the ‘good’ self-manager. Through unpicking the ‘good’ self-manager the problems of neoliberalism are also revealed and addressed here.
•Self-management is framed in terms of what it means to be the ‘good’ self-manager.•Neoliberal health discourse is evident in conceptualisations of self-management.•The ‘good’ self-manager is remoralised, knowledgeable and active.•These three aspects are linked-action is knowledge applied and morality underpins both.
For systemically administered monoclonal antibodies (mAbs) with pharmacological targets in the epithelial lining fluid (ELF), information on the partitioning of mAb between plasma and ELF is ...instrumental for dose predictions. Bronchoalveolar lavage (BAL) combined with measurements of urea as indicator of sample dilution is often used to estimate ELF concentrations of a drug. However, unbalanced extraction of mAb and urea could potentially lead to a systematic bias in the back-calculated ELF concentration. In the present study 0.5, 1, or 4 mL phosphate-buffered saline was instilled to lungs of rats to obtain lavage samples after systemic dosing of mAb and tool small molecule (n≥4/group). Furthermore, extraction of urea, mAb and the small molecule was assessed by repeatedly lavaging the lung (n = 4). There was no statistically significant difference in the calculated partitioning into ELF between the evaluated instillation volumes. Repeated BAL demonstrated that urea and the small molecule were extracted from other sources than the ELF. In contrast, there was limited to none in-flow of mAb into the lavage fluid. The unbalanced extraction of urea and mAb could theoretically result in underestimated ELF concentrations and the calculated partitioning of 0.17±0.062 might therefore constitute a lower boundary for the true partitioning.
Pulmonary drug disposition after inhalation is complex involving mechanisms, such as regional drug deposition, dissolution, and mucociliary clearance. This study aimed to develop a systems ...pharmacology approach to mechanistically describe lung disposition in rats and thereby provide an integrated understanding of the system. When drug‐ and formulation‐specific properties for the poorly soluble drug fluticasone propionate were fed into the model, it proved predictive of the pharmacokinetics and receptor occupancy after intravenous administration and nose‐only inhalation. As the model clearly distinguishes among drug‐specific, formulation‐specific, and system‐specific properties, it was possible to identify key determinants of pulmonary selectivity of receptor occupancy of inhaled drugs: slow particle dissolution and slow drug‐receptor dissociation. Hence, it enables assessment of factors for lung targeting, including molecular properties, formulation, as well as the physiology of the animal species, thereby providing a general framework for rational drug design and facilitated translation of lung targeting from animal to man.
Summary Objective Acetabular chondral lesions are common in patients with femoroacetabular impingement (FAI) syndrome. The aim of this study was (1) to evaluate the proliferation potential of primary ...human chondrocytes (hC) derived from both acetabular and femoral site and (2) to validate cellular differentiation during three-dimensional (3D) cultivation as a prerequisite for autologous matrix-assisted cartilage regeneration of the hip joint. Methods hC were isolated from cartilage samples obtained from N = 6 patients during offset reconstruction. Proteoglycan content was assessed by Safranin-O staining. Proliferation and cell viability were quantified by microscopic cell counting and Trypan Blue exclusion. Messenger ribonucleic acid (mRNA) expression levels of collagen type 1 and 2, aggrecan (ACAN), and interleukin-1β (IL-1β) genes were assessed upon monolayer cultivation, after 48 h/4–10°C – transport simulation and after 14 days of 3D hydrogel cultivation. Results Primary hC from acetabular and femoral damaged sites were viable. No significant intergroup differences were observed concerning cell viability (>95%) after monolayer cultivation and transport simulation. Harvest yields from acetabular and femoral cartilage samples were comparable to that known from knee joints (mean ± standard deviation (SD), 13.4 × 106 ± 5 × 106 cells per culture vs 20 × 106 cells). Redifferentiation was induced during 3D hydrogel cultivation as observed by increased levels of collagen II (1000-fold) and ACAN (10-fold) gene vs monolayer cultivation ( P < 0.001). Conclusion hC derived from damaged acetabular and femoral site are qualified for autologous matrix-assisted cartilage transplantation paving the way for cell-based cartilage regeneration in FAI patients.
Mutations of the gene encoding unconventional myosin XVa are associated with sensorineural deafness in humans (DFNB3) and shaker (Myo15sh2) mice. In deaf Myo15sh2/sh2mice, stereocilia are short, ...nearly equal in length, and lack myosin XVa immunoreactivity. We previously reported that myosin XVa mRNA and protein are expressed in cochlear hair cells. We now show that in the mouse, rat, and guinea pig, endogenous myosin XVa localizes to the tips of the stereocilia of the cochlear and vestibular hair cells. Myosin XVa localization overlaps with the barbed ends of actin filaments and extends to the apical plasma membrane of the stereocilia. Gene gun-mediated transfection of mouse inner ear sensory epithelia explants shows selective accumulation of myosin XVa-GFP at the tips of stereocilia, confirming the localization of native myosin XVa. Expression in COS7 cells also reveals targeting of myosin XVa-GFP to the dynamic actin region at the tips of filopodia. In a wild-type mouse, during auditory and vestibular hair cell development, myosin XVa appears at the tips of stereocilia at the time when the hair bundle begins to develop its characteristic staircase pattern. We propose that myosin XVa is essential for the graded elongation of stereocilia during their functional maturation.
Summary Objective In vitro expansion is an important step to acquire sufficient cells in human tissue engineering technologies. The high number of chondrocytes needed for human articular cartilage ...implants requires in vitro expansion of the primary cells, bearing a theoretical risk of in vitro induced changes in the genomes. To gain more insights into this situation, model cultures were prepared and analyzed. Design 25 chondrocyte cell DNA samples from nine donors were analyzed by array comparative genomic hybridization (aCGH) on whole genome level and 28 chondrocyte cell samples from 16 individuals were analyzed by fluorescence in situ hybridization (FISH) on single cell level. The expanded cells were further characterized upon the chondrocytic mRNA phenotype by reverse-transciptase polymerase chain reaction (RT-PCR). Results The molecular karyotyping results revealed autosomal stability, but all male samples analyzed by aCGH displayed a variable loss of the Y-chromosome. These data were confirmed by FISH-experiments and suggest an age dependant effect toward the loss of the Y-chromosome in cultured chondrocytes. RT-PCR data for the mRNAs from collagen types I, II, and aggrecan and the pro-inflammatory cytokine interleukin-1ß (IL-1ß) did not reveal any correlation of transcriptional activity in cultures with Y-chromosome losses, nor were there statistically significant differences between cells from female and male donors. Conclusions While cells of male origin may suffer from an age-related loss of the Y-chromosome, there was no indication of a functional impairment. The data suggest some caution toward applying proliferative steps when considering chondrocytes from elderly male patients for tissue engineering approaches.
We ascertained a large North American family, LMG2, segregating progressive, non‐syndromic, sensorineural hearing loss. A genome‐wide scan identified significant evidence for linkage (maximum ...logarithm of the odds (LOD) score = 4.67 at θ = 0 for D4S398) to markers in a 5.7‐cM interval on chromosome 4q12‐13.1. The DFNA27 interval spans 8.85 Mb and includes at least 61 predicted and 8 known genes. We sequenced eight genes and excluded them as candidates for the DFNA27 gene.
The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding ...genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.
Measurements of the center-of-mass energies at BESIII via the di-muon process 麦迪娜 M. N. Achasov X. C. Ai O. Albayrak M. Albrecht D. J. Ambrose A. Amoroso 安芬芬 安琪 白景芝 R. Baldini Ferroli 班勇 D. W. Bennett J. V. Bennett M. Bertani D. Bettoni 边渐鸣 F. Bianchi E. Boger I. Boyko R. A. Briere 蔡浩 蔡啸 O. Cakir A. Calcaterra 曹国富 S. A. Cetin 常劲帆 G. Chelkov 陈刚 陈和生 陈海云 陈江川 陈玛丽 陈申见 谌炫 陈旭荣 陈元柏 程和平 褚新坤 G. Cibinetto 代洪亮 代建平 A. D beyssi D. Dedovich 邓子艳 A. Denig I. Denysenko M Destefanis F. De Mori 丁勇 董超 董静 董燎原 董明义 杜书先 段鹏飞 范荆州 方建 房双世 方馨 方易 L. Fava F. Feldbauer G. Felici 封常青 E. Fioravanti M. Fritsch 傅成栋 高清 高鑫磊 高旭阳 高原宁 高榛 I. Garzia K. Goetzen 龚文煊 W. Gradl M. Greco 顾旻皓 顾运厅 管颖慧 郭爱强 郭立波 郭玥 郭玉萍 Z. Haddadi A. Hafner 韩爽 郝喜庆 F. A. Harris 何康林 T. Held 衡月昆 侯治龙 胡琛 胡海明 胡继峰 胡涛 胡誉 黄光明 黄光顺 黄金书 黄性涛 黄勇 T. Hussain 纪全 姬清平 季晓斌 季筱璐 姜鲁文 江晓山 蒋兴雨 焦健斌 焦铮 金大鹏 金山 T. Johansson A. Julin N. Kalantar-Nayestanaki 康晓琳 康晓珅 M. Kavatsyuk B. C. Ke P.Kiese R. Kliemt B. Kloss O. B. Kolcu B. Kopf M. Kornicer W. Kuhn A. Kupsc J. S. Lange M. Lara P. Larin C. Leng 李翠 李澄 李德民 李飞 李峰云 李刚 李海波 李家才 李瑾 李康 李科 李蕾 李培荣 李腾 李卫东 李卫国 李晓玲 李小梅 李小男 李学潜 李志兵 梁昊 梁勇飞 梁羽铁 廖广睿 D. X. Lin 刘北江 刘春秀 刘栋 刘福虎 刘芳 刘峰 刘宏邦 刘欢欢 刘汇慧 刘怀民 刘杰 刘建北 刘觉平 刘晶译 刘凯 刘魁勇 刘兰雕 刘佩莲 刘倩 刘树彬 刘翔 刘玉斌 刘振安 刘智清 H. Loehner 娄辛丑 吕海江 吕军光 卢宇 卢云鹏 罗成林 罗民兴 T. Luo 罗小兰 吕晓睿 马凤才 马海龙 马连良 马秋梅 马天 马旭宁 马骁妍 F. E. Maas M. Maggiora 冒亚军 毛泽普 S. Marcello J. G. Messchendorp 闵建 R. E. Mitchell 莫晓虎 莫玉俊 C. Morales Morales K. Moriya N. Yu. Muchnoi H. Muramatsu y. Nefedov F. Nerling I. B. Nikolaev 宁哲 S．Nisar 牛顺利 牛讯伊 马鹏 欧阳群 S. Pacetti 潘越 P．Patteri M. Pelizaeus 彭海平 K．Peters J. Pettersson 平加伦 平荣刚 R. Poling V. Prasad 祁鸣 钱森 乔从丰 秦丽清 覃拈 秦小帅 秦中华 邱进发 K. H. Rashid C. F. Redmer M. Ripka 荣刚 Ch. Rosner 阮向东 V. Santoro A. Sarantsev M. Savrie K. Schoennin S. Schumann 单葳 邵明 沈成平 沈培迅 沈肖雁 盛华义 宋维民 宋欣颖 S. Sosio S. Spataro 孙功星 孙俊峰 孙胜森 孙勇杰 孙永昭 孙志嘉 孙振田 唐昌建 唐晓 I. Tapan E. H. Thorndike M. Tiemens M. Ullrich I. Uman G. S. Varner 王斌 王东 王大勇 王科 王亮亮 王灵淑 王萌 王平 王佩良 王思广 王炜 王维平 王雄飞 王雅迪 王贻芳 王亚乾 王铮 王志刚 王志宏 王至勇 T. Weber 魏代会 韦江波 P. Weidenkaff 文硕频 U. Wiedner M. Wolke 伍灵慧 吴智 夏磊 夏力钢 夏宇18 肖栋 肖浩 肖振军 谢宇广 修青磊 许国发 徐雷 徐庆君 徐新平 严亮 鄢文标 闫文成 颜永红 杨海军 杨洪勋 杨柳 杨迎 杨永栩 叶梅 叶铭汉 殷俊昊 俞伯祥 喻纯旭 俞浩晟 苑长征 袁文龙 袁野 A. Yuncu A. A. Zafar A.Zallo 曾云 曾哲 张丙新 张炳云 张弛29 张长春 张达华 张宏浩 章红宇 张佳佳 张杰磊 张敬庆 张家文 张建勇 张景芝 张坤 张磊 张学尧 张瑶 张宇宁 张银鸿 张亚腾 张宇 张正好 张子平 张振宇 赵光 赵京伟 赵静宜 赵京周 赵雷 赵玲 赵明刚 赵强 赵庆旺 赵书俊 赵天玲 赵天池 赵豫斌 赵政国 A. Zhemchugov 郑波 郑建平 郑文静 郑阳恒 钟彬 周莉 周详 周晓康 周小蓉 周注玉 朱凯 朱科军 朱帅 朱世海 朱相雷 朱莹春 朱永生 朱自安 庄建 L．Zotti 邹冰松 邹佳恒
Chinese physics C,
06/2016, Letnik:
40, Številka:
6
Journal Article
Recenzirano
Odprti dostop
From 2011 to 2014, the BESIII experiment collected about 5 fb^-1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing ...the di-muon process e＋e- →yma/Fsμ^＋μ^-, the center-of-mass energies of the data samples are measured with a precision of 0.8 MeV. The center-of-mass energy is found to be stable for most of the time during data taking.
Two structurally related triterpenoids 1 and 2 from pink peppercorn (berries of Schinus terebinthifolius) are identified and characterized as active site-directed specific competitive inhibitors of ...the three classes of secreted 14 kDa phospholipase A2. The inhibitors not only protect the active site histidine from alkylation but also inhibit the action of secreted phospholipase A2 from pig pancreas, human synovial fluid, and bee venom. Detailed X-ray crystallographic results on the structures of the inhibitors are provided. By physical methods and X-ray crystallography the triterpenoids were identified as masticadienoic acid and masticadienolic acid (schinol). Several other triterpenoids were ineffective as inhibitors of phospholipase A2; however certain ganoderic acid derivatives showed noticeable inhibition. Results show that the side chain of these acidic tetracyclic terpenoids can access the catalytic-site region of phospholipase A2, whereas the acyclic nucleus is at the interfacial recognition region. The selectivity of the assay protocol used here is demonstrated by the fact that the original screen of ethyl acetate extracts of 60 commercially available spices and herbs was carried out with phospholipase A2 from pig pancreas, and only one extract showed inhibitory action on the hydrolytic activity in the scooting mode. Under such assay conditions the enzyme remains tightly bound to the surface of the substrate vesicles. In this way, nonspecific effects of additives that promote desorption of the enzyme from the substrate vesicle surface, under conditions in which the binding of the enzyme to the vesicle is weak, are avoided. The assay protocol is useful for the kinetic characterization of the inhibitors of phospholipase A2, and it does not give false positive results with amphiphilic and hydrophobic compounds, as is the case with virtually all assay systems in use.
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