tbuckley/cabot-search huggingface dataset:
Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial
Authors: M. J. Crawford, H. Killaspy, T. R. E. Barnes, B. Barrett, S. Byford, K. Clayton, J. Dinsmore, S. Floyd, A. Hoadley, T. Johnson, E. Kalaitzaki, M. King, B. Leurent, A. Maratos, F. A. O'Neill, D. P. Osborn, S. Patterson, T. Soteriou, P. Tyrer, D. Waller
Journal: BMJ (2012)

<b>Objectives</b> To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment. <b>Design</b> Three arm, rater blinded, pragmatic, randomised controlled trial. <b>Setting</b> Secondary care services across 15 sites in the United Kingdom. <b>Participants</b> 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study. <b>Interventions</b> Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue. <b>Main outcome measures</b> The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months. <b>Results</b> 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was −0.9 (95% confidence interval −3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (−3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months. <b>Conclusions</b> Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes. <b>Trial registration</b> Current Controlled Trials ISRCTN46150447.
Effect of Drastic Weight Loss after Bariatric Surgery on Renal Parameters in Extremely Obese Patients
Authors: Maruja Navarro-Díaz, Assumpta Serra, Ramón Romero, Josep Bonet, Beatriu Bayés, Mercé Homs, Noelia Pérez, Jordi Bonal
Journal: Journal of the American Society of Nephrology (2006)

Obesity is a health problem that is reaching epidemic proportions. Extreme obesity (body mass index [BMI] ≥40 kg/m2) is a type of obesity that usually does not respond to medical treatment, with surgery being the current treatment of choice. Extreme obesity is associated with cardiovascular disease, type 2 diabetes, dyslipidemia, and hypertension. Recently, obesity has been related with high rate of renal lesions, but renal function and renal parameters in extreme obesity scarcely are documented. The objective of this study was to evaluate the effect of weight loss after bariatric surgery (BS) on BP, renal parameters, and renal function in 61 extremely obese (EO) patients after 24 mo of follow-up. A total of 61 EO adults (37 women) were studied prospectively before and 24 mo after surgery. Control subjects were 24 healthy, normal-weight adults (15 women). Anthropometric, BP, and renal parameters were determined. Presurgery weight, BMI, GFR, 24-h proteinuria, and 24-h albuminuria were higher in the EO patients than in control subjects (P < 0.001). All parameters improved at 12 mo after BS. However, during the second year of follow-up, only 24-h albuminuria (P = 0.006) and BMI (P = 0.014) continued to improve. At 24 mo after BS, obesity-related renal alterations considerably improved. This improvement was observed mainly in the first year after surgery, when the majority of weight loss occurred. However, 24-h albuminuria still improves during the second year of follow-up. It is possible that this decrease in 24-h albuminuria is not GFR related but rather is attributable to the persistence of the decrease in BMI and to the improvement of other weight-related metabolic factors.
Is tendinopathy research at a crossroads?
Authors: Lorenzo Masci
Journal: British Journal of Sports Medicine (2015)

Imagine a medical condition that is relatively common in a group of people who share similar characteristics. This condition is a common cause of morbidity leading to varying degrees of physical impairment. There is disagreement regarding specific pathological pathways, and a divergence of opinion concerning the importance of imaging. And finally, there are differing views on management of this disease with a recent explosion of treatments that have tenuous evidence supporting use in clinical practice. Such a scenario, if present in medicine, would lead to desperate calls for more research. Welcome to the world of tendinopathy.

Tendinopathy, tendinosis or tendon disease—we cannot even agree on a suitable name—is common in active individuals. There is a general consensus that tendon disease involves a degenerative process,1 although recent studies have demonstrated evidence of inflammatory pathways that question this consensus.2 Source of tendon pain generation remains elusive with contradictory evidence supporting local3 and centrally mediated pathways.4 Although imaging demonstrates specific changes of tendon disease, a recent meta-analysis questions whether tendon imaging has …
Tempo and mode of synonymous substitutions in mitochondrial DNA of primates
Authors: J. Adachi, M. Hasegawa
Journal: Molecular Biology and Evolution (1996)

Nucleotide substitutions of the four-fold degenerate sites and the total third codon positions of mitochondrial DNA from human, common chimpanzee, bonobo, gorilla, and orangutan were examined in detail by three alternative Markov models; (1) Hasegawa, Kishino, and Yano's (1985) model, (2) Tamura and Nei's (1993) model, and (3) the general reversible Markov model. These sites are expected to be relatively free from constraint, and therefore their tempo and mode in evolution should reflect those of mutation. It turned out that, among the alternative models, the general reversible Markov model best approximates the nucleotide substitutions of the four-fold degenerate sites and the total third codon positions, while the maximum likelihood estimates of the numbers of nucleotide substitutions along each branch do not differ significantly among the three models. It was further shown that the transition rate of these sites during evolution, and therefore transitional mutation rate of mtDNA, are higher in humans than in chimpanzees and gorillas probably by about two times. However, transversional mutation rate and amino acid substitution rate do not differ significantly between humans and the African apes. These and additional observations suggest heterogeneity of the mutation rate as well as of the constraint operating on the mtDNA-encoded proteins among different lineages of Hominoidea.
Mucin Glycoprotein Content of Human Pigment Gallstones
Authors: Thomas J. Lamont, Allen S. Ventola, Bruce W. Trotman, Roger D. Soloway
Journal: Hepatology (1983)

Mucin glycoproteins, a secretory product of the gallbladder, are thought to contribute to the matrix or nucleus of gallstones. Human black pigment stones originate in the gallbladder and have as their major constituent calcium bilirubinate, as well as inorganic salts and small amounts of cholesterol. The object of this study was to estimate the amount of glycoprotein in black pigment stones and to isolate gallbladder mucin from dissolved stones. Black pigment stones containing 18 to 65% calcium bilirubinate were first dissolved in 12.5 mMEDTA/0.1 iVNaOH and decolorized, then subjected to glycoprotein assay. The mean glycoprotein content of eight stones was 12.4%. In separate experiments, pigment stones were partially dissolved by brief exposure to EDTA/NaOH to minimize glycoprotein breakdown, and the glycoproteins isolated by gel filtration and ultracen-trifugation. Pigment stones contained two glycoprotein fractions on Sepharose 4B; a high molecular weight mucin glycoprotein in the void volume and a lower molecular fraction in the included volume. Mucin was further purified by density gradient ultracentrifugation in cesium chloride. Three separate mucin fractions had an average buoyant density of 1.48 gm per ml which is typical for these glycoproteins. Bile pigment was associated with high molecular weight mucin even after extensive dialysis, gel filtration, and density gradient ultracentrifugation. The identity of mucin was further established by β-elimination of glycoproteins in alkaline borohydride which yielded galactosaminitol from cleavage of O-glycosidic bonds. Our results indicate that mucin glycoproteins are present in significant concentrations in human black pigment stones and can be purified from stones solubilized in EDTA/NaOH. The association of bile pigment with gallbladder mucin, even after extensive purification, is consistent with the hypothesis that mucin contributes to the matrix of pigment gallstones.
A psychosocial kinship model for family therapy
Authors: E M Pattison, D Defrancisco, P Wood, H Frazier, J Crowder
Journal: American Journal of Psychiatry (1975)

Family therapy has traditionally centered on the nuclear family and thus has been typically oriented toward urban white middle-class families. A variety of modifications in therapeutic technique has evolved for work with the many modern families whose structure consists of a functional psychosocial family kinship. The authors have developed a formal theoretical framework and model for family therapy that encompasses the total psychosocial network, i.e., the extended kinships of the nuclear family and the functional kin such as friends, neighbors, and associates.
The Roles of Specific Genes Implicated as Circulating Factors Involved in Normal and Disordered Phosphate Homeostasis: Frizzled Related Protein-4, Matrix Extracellular Phosphoglycoprotein, and Fibroblast Growth Factor 23
Authors: Kenneth E. White, Tobias E. Larsson, Michael J. Econs
Journal: Endocrine Reviews (2006)

Normal serum phosphate (Pi) concentrations are relatively tightly controlled by endocrine mediators of Pi balance. Recent data involving several disorders of Pi homeostasis have shed new light on the regulation of serum Pi balance. It has been hypothesized that circulating phosphaturic factors, or phosphatonins, exist that, when present at high serum concentrations, directly act on the kidney to induce renal Pi wasting. This review will focus upon recently discovered factors that are overexpressed in tumors associated with tumor-induced osteomalacia and have reported activity consistent with effecting Pi balance in vivo. Currently, the best-characterized group of phosphatonin-like polypeptides includes secreted frizzled related protein-4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor-23. Our understanding of these factors will, in the short term, aid us in understanding normal Pi balance and, in the future, help to design novel therapeutic strategies for disorders of Pi handling.
Downmodulation of the Inflammatory Response to Bacterial Infection by γδ T Cells Cytotoxic for Activated Macrophages
Authors: Paul J. Egan, Simon R. Carding
Journal: The Journal of Experimental Medicine (2000)

Although γδ T cells are involved in the regulation of inflammation after infection, their precise function is not known. Intraperitoneal infection of T cell receptor (TCR)-δ−/− mice with the intracellular bacterium Listeria monocytogenes resulted in the development of necrotic foci in the livers. In contrast, the peritoneal cavities of infected TCR-δ−/− mice contained an accumulation of low density activated macrophages and a reduced percentage of macrophages undergoing apoptosis. γδ T cell hybridomas derived from mice infected with Listeria were preferentially stimulated by low density macrophages from peritoneal exudates of infected mice. Furthermore, primary splenic γδ T cells isolated from Listeria-infected mice were cytotoxic for low density macrophages in vitro, and cytotoxicity was inhibited in the presence of antibodies to the γδ TCR. These results demonstrate a novel interaction between γδ T cells and activated macrophages in which γδ T cells are stimulated by terminally differentiated macrophages to acquire cytotoxic activity and which, in turn, induce macrophage cell death. This interaction suggests that γδ T cells regulate the inflammatory response to infection with intracellular pathogens by eliminating activated macrophages at the termination of the response.
Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up
Authors: J M Vonk
Journal: Thorax (2003)

<b>Background:</b> Childhood asthma is generally believed to be a disorder with a good prognosis. However, some asthmatics develop irreversible airway obstruction, probably as a result of airway remodelling. <b>Methods:</b> After 21–33 years, 228 adults (aged 13–44 years at baseline) with a history of asthma were re-examined to assess risk factors for the development of irreversible airway obstruction (IAO, forced expiratory volume in 1 second (FEV<sub>1</sub>) &lt;80% predicted and reversibility &lt;9% predicted) and a reduced postbronchodilator transfer coefficient (carbon monoxide transfer factor/alveolar volume, &lt;80% predicted), both characteristics of COPD. <b>Results:</b> At follow up, 41% did not have airway obstruction (NAO), 43% had reversible airway obstruction (RAO), and 16% had IAO; 23% had a reduced transfer coefficient. Patients with RAO had asthma-like characteristics (wheezing, asthma attacks, bronchial hyperresponsiveness (BHR)) while patients with IAO had COPD-like symptoms (cough, phlegm, dyspnoea) at follow up. The development of IAO is determined by a lower FEV<sub>1</sub>, less reversibility of airway obstruction and, surprisingly, less severe BHR at initial screening. Eighty percent of the patients with asthma who used anti-inflammatory medication still had airway obstruction, but IAO developed less frequently. Smoking was associated with a reduced transfer coefficient but not with the development of IAO. Female sex was associated with a reduced transfer coefficient, whereas corticosteroid use was not. <b>Conclusions:</b> Although IAO and a low transfer coefficient are both characteristics of COPD, they represent distinct entities in adult asthmatics in terms of symptomatology, aetiology, and probably in therapeutic approaches and disease prevention.
Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile
Authors: Karin Lundberg, Camilla Bengtsson, Nastya Kharlamova, Evan Reed, Xia Jiang, Henrik Kallberg, Iskra Pollak-Dorocic, Lena Israelsson, Christoph Kessel, Leonid Padyukov, Rikard Holmdahl, Lars Alfredsson, Lars Klareskog
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, were investigated. <h3>Methods</h3> 1985 patients with RA and 2252 matched controls from the EIRA case-control cohort were used in the study. Serum samples were assayed by ELISA for the presence of anticyclic citrullinated peptides (anti-CCP) antibodies and four different ACPA fine specificities. Cross-reactivity between ACPAs was examined by peptide absorption experiments. Genotyping was performed for <i>HLA-DRB1</i> shared epitope (SE) alleles and the <i>PTPN22</i> gene, while information regarding smoking was obtained by questionnaire. The association of genetic and environmental risk factors with different subsets of RA was calculated by logistic regression analysis. <h3>Results</h3> Limited cross-reactivity was observed between different ACPA fine specificities. In total, 17 RA subsets could be identified based on their different ACPA fine specificity profiles. Large differences in association with genetic and environmental determinants were observed between subsets. The strongest association of <i>HLA-DRB1</i> SE, <i>PTPN22</i> and smoking was identified for the RA subset which was defined by the presence of antibodies to citrullinated α-enolase and vimentin. <h3>Conclusion</h3> This study provides the most comprehensive picture to date of how <i>HLA-DRB1</i> SE, <i>PTPN22</i> and smoking are associated with the presence of specific ACPA reactivities rather than anti-CCP levels. The new data will form a basis for molecular studies aimed at understanding disease development in serologically distinct subsets of RA.
VHL-Regulated MiR-204 Suppresses Tumor Growth through Inhibition of LC3B-Mediated Autophagy in Renal Clear Cell Carcinoma
Authors: Olga Mikhaylova, Yiwen Stratton, Daniel Hall, Emily Kellner, Birgit Ehmer, Angela F. Drew, Catherine A. Gallo, David R. Plas, Jacek Biesiada, Jarek Meller, Maria F. Czyzyk-Krzeska
Journal: Cancer Cell (2012)
eIF2α Kinase PKR Modulates the Hypoxic Response by Stat3-Dependent Transcriptional Suppression of HIF-1α
Authors: Andreas I. Papadakis, Efrosyni Paraskeva, Philippos Peidis, Hala Muaddi, Suiyang Li, Leda Raptis, Kostas Pantopoulos, George Simos, Antonis E. Koromilas
Journal: Cancer Research (2010)

Abstract Hypoxia within the tumor microenvironment promotes angiogenesis, metabolic reprogramming, and tumor progression. In addition to activating hypoxia-inducible factor-1α (HIF-1α), cells also respond to hypoxia by globally inhibiting protein synthesis via serine 51 phosphorylation of translation eukaryotic initiation factor 2α (eIF2α). In this study, we investigated potential roles for stress-activated eIF2α kinases in regulation of HIF-1α. Our investigations revealed that the double-stranded RNA–dependent protein kinase R (PKR) plays a significant role in suppressing HIF-1α expression, acting specifically at the level of transcription. HIF-1α transcriptional repression by PKR was sufficient to impair the hypoxia-induced accumulation of HIF-1α and transcriptional induction of HIF-1α–dependent target genes. Inhibition of HIF-1A transcription by PKR was independent of eIF2α phosphorylation but dependent on inhibition of the signal transducer and activator of transcription 3 (Stat3). Furthermore, HIF-1A repression required the T-cell protein tyrosine phosphatase, which acts downstream of PKR, to suppress Stat3. Our findings reveal a novel tumor suppressor function for PKR, which inhibits HIF-1α expression through Stat3 but is independent of eIF2α phosphorylation. Cancer Res; 70(20); 7820–9. ©2010 AACR.
Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
Authors: F Fais, F Ghiotto, S Hashimoto, B Sellars, A Valetto, S L Allen, P Schulman, V P Vinciguerra, K Rai, L Z Rassenti, T J Kipps, G Dighiero, H W Schroeder, M Ferrarini, N Chiorazzi
Journal: Journal of Clinical Investigation (1998)

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.
Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models
Authors: E F Murphy, P D Cotter, S Healy, T M Marques, O O'Sullivan, F Fouhy, S F Clarke, P W O'Toole, E M Quigley, C Stanton, P R Ross, R M O'Doherty, F Shanahan
Journal: Gut (2010)

<h3>Background and Aims</h3> Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased <i>Firmicutes</i> and decreased <i>Bacteroidetes</i>), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (<i>ob/ob</i>) for changes in microbiota and energy harvesting capacity over time. <h3>Methods</h3> Seven-week-old male <i>ob/ob</i> mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing). <h3>Results</h3> A progressive increase in <i>Firmicutes</i> was confirmed in both HF-fed and <i>ob/ob</i> mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in <i>Bacteroidetes</i> were also found in <i>ob/ob</i> mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the <i>ob/ob</i> mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both <i>ob/ob</i> and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers. <h3>Conclusion</h3> The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.