1,927 research outputs found
A Group Intervention for Individuals With Obesity and Comorbid Binge Eating Disorder: Results From a Feasibility Study.
Purpose: A common challenge among a subgroup of individuals with obesity is binge eating, that exists on a continuum from mild binge eating episodes to severe binge eating disorder (BED). BED is common among bariatric patients and the prevalence of disordered eating and ED in bariatric surgery populations is well known. Conventional treatments and assessment of obesity seldom address the underlying psychological mechanisms of binge eating and subsequent obesity. This study, titled PnP (People need People) is a psychoeducational group pilot intervention for individuals with BED and obesity including patients with previous bariatric surgery. Design, feasibility, and a broad description of the study population is reported. Material and Methods: A total of 42 patients were from an obesity clinic referred to assessment and treatment with PnP in a psychoeducational group setting (3-hour weekly meetings for 10 weeks). Of these, 6 (14.3%) patients had a previous history of bariatric surgery. Feasibility was assessed by tracking attendance, potentially adverse effects and outcome measures including body mass index (BMI), eating disorder pathology, overvaluation of shape and weight, impairment, self-reported childhood difficulties, alexithymia, internalized shame as well as health related quality of life (HRQoL). Results: All 42 patients completed the intervention, with no adverse effects and a high attendance rate with a median attendance of 10 sessions, 95% CI (8.9,9.6) and 0% attrition. Extent of psychosocial impairment due to eating disorder pathology, body dissatisfaction and severity of ED symptoms were high among the patients at baseline. Additionally, self-reported childhood difficulties, alexithymia, and internalized shame were high among the patients and indicate a need to address underlying psychological mechanisms in individuals with BED and comorbid obesity. Improvement of HRQoL and reduction of binge eating between baseline and the end of the intervention was observed with a medium effect. Conclusion: This feasibility study supports PnP as a potential group psychoeducational intervention for patients living with BED and comorbid obesity. Assessments of BED and delivery of this intervention may optimize selection of candidates and bariatric outcomes. These preliminary results warrant further investigation via a randomized control trial (RCT) to examine the efficacy and effectiveness of PnP
The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds
The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds
Grounding knowledge and normative valuation in agent-based action and scientific commitment
Philosophical investigation in synthetic biology has focused on the knowledge-seeking questions pursued, the kind of engineering techniques used, and on the ethical impact of the products produced. However, little work has been done to investigate the processes by which these epistemological, metaphysical, and ethical forms of inquiry arise in the course of synthetic biology research. An attempt at this work relying on a particular area of synthetic biology will be the aim of this chapter. I focus on the reengineering of metabolic pathways through the manipulation and construction of small DNA-based devices and systems synthetic biology. Rather than focusing on the engineered products or ethical principles that result, I will investigate the processes by which these arise. As such, the attention will be directed to the activities of practitioners, their manipulation of tools, and the use they make of techniques to construct new metabolic devices. Using a science-in-practice approach, I investigate problems at the intersection of science, philosophy of science, and sociology of science. I consider how practitioners within this area of synthetic biology reconfigure biological understanding and ethical categories through active modelling and manipulation of known functional parts, biological pathways for use in the design of microbial machines to solve problems in medicine, technology, and the environment. We might describe this kind of problem-solving as relying on what Helen Longino referred to as “social cognition” or the type of scientific work done within what Hasok Chang calls “systems of practice”. My aim in this chapter will be to investigate the relationship that holds between systems of practice within metabolic engineering research and social cognition. I will attempt to show how knowledge and normative valuation are generated from this particular network of practitioners. In doing so, I suggest that the social nature of scientific inquiry is ineliminable to both knowledge acquisition and ethical evaluations
Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach
Introduction: Cigarette smoke contributes to a diverse
range of diseases including chronic obstructive
pulmonary disease (COPD), cardiovascular disorders
and many cancers. There currently is a need for
human challenge models, to assess the acute effects of
a controlled cigarette smoke stimulus, followed by
serial sampling of blood and respiratory tissue for
advanced molecular profiling. We employ precision
sampling of nasal mucosal lining fluid by absorption to
permit soluble mediators measurement in eluates.
Serial nasal curettage was used for transcriptomic
analysis of mucosal tissue.
Methods and analysis: Three groups of strictly
defined patients will be studied: 12 smokers with
COPD (GOLD Stage 2) with emphysema, 12 matched
smokers with normal lung function and no evidence of
emphysema, and 12 matched never smokers with
normal spirometry. Patients in the smoking groups are
current smokers, and will be given full support to stop
smoking immediately after this study. In giving a
controlled cigarette smoke stimulus, all patients will
have abstained from smoking for 12 h, and will smoke
two cigarettes with expiration through the nose in a
ventilated chamber. Before and after inhalation of
cigarette smoke, a series of samples will be taken from
the blood, nasal mucosal lining fluid and nasal tissue
by curettage. Analysis of plasma nicotine and
metabolites in relation to levels of soluble inflammatory
mediators in nasal lining fluid and blood, as well as
assessing nasal transcriptomics, ex vivo blood platelet
aggregation and leucocyte responses to toll-like
receptor agonists will be undertaken.
Implications: Development of acute cigarette smoke
challenge models has promise for the study of
molecular effects of smoking in a range of pathological
processes.This study was funded by the Wellcome Trust and Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan. Supported by: Dainippon Sumitomo Pharma Co Ltd, Osaka, Japan National Institute of Healthcare Research (Grant No: R3101002), NIHR Imperial Biomedical Research Centre (NIHR BMRC), Imperial Academic Health Science Centre (AHSC), Imperial Centre for Respiratory Infection (CRI, Grant No: 083567/Z/07/Z), Wellcome Trust (Grant No: 083429/Z/07/Z)
Scalar and tensor spherical harmonics expansion of the velocity correlation in homogeneous anisotropic turbulence
The Two Faces of Anomaly Mediation
Anomaly mediation is a ubiquitous source of supersymmetry (SUSY) breaking
which appears in almost every theory of supergravity. In this paper, we show
that anomaly mediation really consists of two physically distinct phenomena,
which we dub "gravitino mediation" and "Kahler mediation". Gravitino mediation
arises from minimally uplifting SUSY anti-de Sitter (AdS) space to Minkowski
space, generating soft masses proportional to the gravitino mass. Kahler
mediation arises when visible sector fields have linear couplings to SUSY
breaking in the Kahler potential, generating soft masses proportional to beta
function coefficients. In the literature, these two phenomena are lumped
together under the name "anomaly mediation", but here we demonstrate that they
can be physically disentangled by measuring associated couplings to the
goldstino. In particular, we use the example of gaugino soft masses to show
that gravitino mediation generates soft masses without corresponding goldstino
couplings. This result naively violates the goldstino equivalence theorem but
is in fact necessary for supercurrent conservation in AdS space. Since
gravitino mediation persists even when the visible sector is sequestered from
SUSY breaking, we can use the absence of goldstino couplings as an unambiguous
definition of sequestering.Comment: 21 pages, 1 table; v2, references added, extended discussion in
introduction and appendix; v3, JHEP versio
Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.This work was supported by a Sir Henry Dale Fellowship (J.R.J.) jointly funded by the Wellcome Trust and the Royal Society (grant number: 099966/Z/12/Z). PhD studentships (S.A.M. and M.J.H.) were funded by the Wellcome Trust (grant number: 102195/Z/13/Z)
Multiple FadD Acyl-CoA Synthetases Contribute to Differential Fatty Acid Degradation and Virulence in Pseudomonas aeruginosa
A close interconnection between nutrient metabolism and virulence factor expression contributes to the pathophysiology of Pseudomonas aeruginosa as a successful pathogen. P. aeruginosa fatty acid (FA) degradation is complicated with multiple acyl-CoA synthetase homologs (FadDs) expressed in vivo in lung tissue during cystic fibrosis infections. The promoters of two genetically linked P. aeruginosa fadD genes (fadD1 and fadD2) were mapped and northern blot analysis indicated they could exist on two different transcripts. These FadDs contain ATP/AMP signature and FA-binding motifs highly homologous to those of the Escherichia coli FadD. Upon introduction into an E. coli fadD-/fadR- double mutant, both P. aeruginosa fadDs functionally complemented the E. coli fadD-/fadR- mutant, allowing degradation of different chain-length FAs. Chromosomal mutagenesis, growth analysis, induction studies, and determination of kinetic parameters suggested that FadD1 has a substrate preference for long-chain FAs while FadD2 prefers shorter-chain FAs. When compared to the wild type strain, the fadD2 mutant exhibited decreased production of lipase, protease, rhamnolipid and phospholipase, and retardation of both swimming and swarming motilities. Interestingly, fadD1 mutant showed only increased swarming motility. Growth analysis of the fadD mutants showed noticeable deficiencies in utilizing FAs and phosphatidylcholine (major components of lung surfactant) as the sole carbon source. This defect translated into decreased in vivo fitness of P. aeruginosa in a BALB/c mouse lung infection model, supporting the role of lipids as a significant nutrient source for this bacterium in vivo
The alpha-kinase family: an exceptional branch on the protein kinase tree
The alpha-kinase family represents a class of atypical protein kinases that display little sequence similarity to conventional protein kinases. Early studies on myosin heavy chain kinases in Dictyostelium discoideum revealed their unusual propensity to phosphorylate serine and threonine residues in the context of an alpha-helix. Although recent studies show that some members of this family can also phosphorylate residues in non-helical regions, the name alpha-kinase has remained. During evolution, the alpha-kinase domains combined with many different functional subdomains such as von Willebrand factor-like motifs (vWKa) and even cation channels (TRPM6 and TRPM7). As a result, these kinases are implicated in a large variety of cellular processes such as protein translation, Mg2+ homeostasis, intracellular transport, cell migration, adhesion, and proliferation. Here, we review the current state of knowledge on different members of this kinase family and discuss the potential use of alpha-kinases as drug targets in diseases such as cancer
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