tbuckley/cabot-search huggingface dataset:
The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms
Authors: Shannon M. Nugent, Benjamin J. Morasco, Maya E. O'Neil, Michele Freeman, Allison Low, Karli Kondo, Camille Elven, Bernadette Zakher, Makalapua Motu'apuaka, Robin Paynter, Devan Kansagara
Journal: Annals of Internal Medicine (2017)

Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain.To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations.MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017.Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes.Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria.From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient.Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily.Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects.U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).
Mammary specific inactivation of pRb family: An in vivo and 3-D culture study
Authors: Malini Mukherjee, Terry Van Dyke
Journal: Cancer Research (2004)

5090  Breast cancer is a major cause of mortality among women worldwide. An understanding of molecular mechanisms regulating breast cancer formation and progression is important for developing new diagnostic tools to identify marker genes in breast cancer early. Our lab has generated a genetically engineered mouse model for breast cancer with a mutant of SV40 T antigen (T121) mediated inactivation of the pRb tumor suppressor family of proteins. We have shown in a WAP-T121 mammary tumor model that T121 is able to induce mammary adenocarcinomas. Most apoptosis in mammary epithelial (ME) cells has been shown to be p53 dependent and p53 heterozygosity results in a shorter tumor latency. The specific transgene for the mouse model of interest here is called MFT121 and has T121 downstream of the MMTV promoter with a floxed eGFP reporter gene upstream of T121. We are crossing these mice to WAP-Cre mice to generate mammary specific expression of T121 under the MMTV promoter. As MMTV is expressed in both virgin and lactating mammary glands unlike WAP (only expressed in lactating glands) this model will allow us to study mammary tumorigenesis in virgin females. We are developing a 3-D mammary epithelial culture using these mice to study T121 onset in these ME cells. We are using the 3D epithelial culture system to investigate mechanisms of T121 mammary tumorigenesis in parallel with genetic studies described above. The presence of a floxed eGFP will give a visual assay for T121 turn on upon Cre viral infection, by deleting GFP expression in the ME cells. To establish that the 3D system recapitulates effects seen in vivo, we are investigating T121 expression, cell proliferation and apoptosis. Confocal microscopy is being utilized to evaluate acinar structure and cellular properties. T121 expression is being detected by immunostaining, proliferation is being detected by immunofluorescence staining of Ki-67 while apoptosis is being detected by ethidium bromide fluorescence. We are determining if apoptosis is p53-dependent by performing parallel experiments with ME from MFT121p53-/- animals. In the future, to evaluate genetic pathways and cooperating lesions in T121 oncogenesis, we will combine T121 expression with dominant expression or suppression of additional genes. MFT121 cells will be infected with retroviruses that express potential cooperating oncogenes or repress transgenes using short hairpin RNAs for RNA interference. We anticipate that the 3D culture system will recapitulate T121-dependent effects on proliferation and apoptosis of ME, providing a powerful model for screening potential cooperating lesions. Such lesions should result in increased proliferation, decreased apoptosis, increased genomic instability or disruption of acinar structures. The increased accessibility of an in vitro system will also allow more careful examination of T121-induced phenotypes, possibly providing additional clues about the mechanism of tumorigenesis.
THU0006 Trans-ethnic meta-analysis of genome-wide association studies identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis
Authors: C Terao, T Kawaguchi, P Dieude, J Varga, M Kuwana, M Hudson, Y Kawaguchi, M Matucci-Cerinic, K Ohmura, G Riemekasten, A Kawasaki, P Airo, T Horita, A Oka, E Hachulla, H Yoshifuji, P Caramaschi, N Hunzelmann, M Baron, T Atsumi, P Hassouns, A Tochimoto, N Ayuzawa, H Yanagida, H Furukawa, S Tohma, M Hasegawa, M Fujimoto, O Ishikawa, T Yamamoto, D Goto, Y Asano, M Jinnin, H Endo, H Takahashi, K Takehara, S Sato, H Ihn, S Raychaudhuri, K Liao, P Gregersen, N Tsuchiya, V Riccieri, I Melchers, G Valentini, A Cauvet, M Martinez, T Mimori, F Matsuda, Y Allanore
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and composed of two subtypes, limited and diffuse cutaneous forms. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. <h3>Objectives</h3> To expand the list of susceptibility genes and deepen biological insights for SSc. <h3>Methods</h3> We performed trans-ethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4,436 cases and 14,751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighboring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. <h3>Results</h3> We identified two significant SNP in two loci, <i>GSDMA</i> and <i>PRDM1</i>, both of which are related with immune functions and associated with other autoimmune diseases (p=1.4x10<sup>-10</sup> and 6.6x10<sup>-10</sup>, respectively). <i>GSDMA</i> also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, <i>TNFAIP3</i>. <i>PRDM1</i> encodes BLIMP1, a transcription factor regulating T cell proliferation and plasma cell differentiation. The top SNP in <i>GSDMA</i> was a missense variant and correlated with gene expression of neighboring genes, and this could explain the association in this locus. We found different HLA association patterns between the two populations or two subtypes. Enrichment analysis suggested the importance of CD4 naïve primary T cell. <h3>Conclusions</h3> <i>GSDMA</i> and <i>PRDM1</i> are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc. <h3>Disclosure of Interest</h3> None declared
Abstract 420: Delineating the Caspase-dependent Targets and Signal Pathways That Promote Pathological Cardiac Hypertrophy
Authors: Charis Putinski, Mohammad Abdul-Ghani, Rebecca Stiles, Steve Brunette, Sarah A Dick, Pasan Fernando, Lynn A Megeney
Journal: Circulation Research (2015)

Although cardiac hypertrophy is initially an adaptive response, chronic stress on the heart is a maladaptive process that inevitably leads to end-stage heart failure. Interestingly, this pathological process is also characterized by cell behaviors associated with apoptosis. We previously demonstrated the essential role of the intrinsic cell death pathway during cardiac hypertrophy; however, the caspase-dependent pathways and cleavage targets remain elusive. To this aim, we evaluated a myocyte enhancer factor 2 (MEF2) transcription factor inhibitor, histone deacetylase 3 (HDAC3), and gelsolin as potential caspase cleavage substrates involved in the induction and/or maintenance of cardiac hypertrophy. In vitro cleavage assays were completed with effector caspase and recombinant substrate protein which demonstrated caspase-dependent cleavage. HDAC3 cleavage was observed during early stages of hypertrophy and reduced in the presence of a caspase inhibitor. Luciferase assays demonstrated that the transcriptional activity of MEF2 is dependent on intact caspase function suggesting caspase-directed HDAC3 cleavage may serve as a novel regulatory mechanism to alleviate MEF2 suppression to engage the hypertrophy gene expression program. Unlike HDAC3, caspase mediated gelsolin cleavage occurs at latter stages and is coincident with the cytoskeletal alterations that occur during this process. As gelsolin is a potent actin capping/severing enzyme, we hypothesize that caspase-mediated gelsolin activation acts as a key regulatory step in the structural rearrangements that allow for hypertrophy to occur. We have generated adenoviral vectors containing caspase cleavage mutants and cleaved forms of HDAC3 and gelsolin and will discuss the impact of these modified substrates on the hypertrophy process in vitro and in vivo. Collectively, this work suggests that caspase signalling acts to engage both the transcriptional program and cytoskeletal accommodations that characterize cardiac hypertrophy. Importantly, these observations suggest that identification of inhibitors that suppress caspase activity and/or activity of its cognate substrates may offer novel therapeutic targets to limit the development of pathological hypertrophy.
骨形成の損傷とROS誘発細胞の抑制のためのキトサンカテコール複合体によるチタンインプラントの表面官能化【Powered by NICT】
Authors: Chen Weizhen, Shen Xinkun, Hu Yan, Xu Kui, Ran Qichun, Yu Yonglin, Dai Liangliang, Yuan Zhang, Huang Ling, Shen Tingting, Cai Kaiyong
Journal: Biomaterials (2017)
THU0759-HPR Does physiotherapy and rehabilitation program improve mobility and daily living activities in elderly inpatient with osteoporosis?
Authors: M Karapinar, T Firat, N Kirdi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoporosis (OP) is a generalized skeletal disorder characterized by compromised bone strength and deterioration of bone quality, often leading to fragility. Elderly osteoporosis is being public health problem that highly affects people especially above 65 years. Physiotheraphy and rehabilitation programs are important in the prevention and management of osteoporosis. Exercises improve mobility in elder inpatient by increasing activity, muscular strength, flexibility, and reducing the risk of falls and length of stay in hospital. <h3>Objectives</h3> The aim of our study was to investigate the effects of physiotherapy and rehabilitation program on mobility, physical activity and quality of life in elderly inpatient. <h3>Methods</h3> A hundred and twenty four patient with OP (mean age: 73,03±5,9) participated in this study. A total of patients who were randomized as study and control group followed by Hacettepe University Faculty of Medicine Department of Internal Medicine, Division of Geriatric Medicine Department of Physiotheraphy and Rehabiltation, Geriatric Rehabilitation Unit were, were included to the study. Assessment for cognitive function (Mini Mental State Test), functional mobility (De Morton Mobility Index), activities of daily living (Katz Index of Independence in Activities of Daily Living), quality of life (EuroQol-5D) were used at admission and discharge in hospital. Thirty minutes physiotherapy and rehabilitation program including breathing, balance and coordination and strengthening exercises was performed by the intervention group under supervision of physiotherapist during the stay in hospital. Control group did not special exercise, they continued their activities of daily living. exercise. Length of stay in hospital of all participant was recorded. <h3>Results</h3> Sixty two patients were randomly assigned to the each group.The groups were similar in sociodemographical feature (p&gt;0.05). Improvements in mobility, quality of life and daily physical activity levels were found in the study group (p&lt;0.05). There were no significant differences between control and intervention group in length of stay in hospital (p&gt;0.05). <h3>Conclusions</h3> These results revealed the necessity of physiotherapy and rehabilitation program to prevent negative effects of the hospitalization process of the geriatric patients with osteoporosis. <h3>References</h3> Muche, J., McCarty, S., &amp; Kishner, S. (2015). Geriatric Rehabilitation. Curran, E., Clifford, S., Forman, S., &amp; Power, D. (2014, September). Screening of Osteoporosis Treatment in Patients Presenting with Fragility Fractures in a Geriatric Active Rehab Unit. In Irish Journal Of Medical Science (Vol. 183, Pp. S334-S335). 236 Grays Inn Rd, 6th Floor, London Wc1x 8hl, England: Springer London Ltd. <h3>Disclosure of Interest</h3> None declared
Heredity of supraglottic exercise-induced laryngeal obstruction
Authors: Emil Schwarz Walsted, Jeppe Hvedstrup, Hans Eiberg, Vibeke Backer
Journal: European Respiratory Journal (2017)

Respiratory symptoms on exertion, such as shortness of breath and wheezing, are commonly associated with asthma, but might also arise from the larynx [1–3]. In recent years, the emergence of exercise laryngoscopy [4] has led to a better understanding of laryngeal movement during exercise, and inspiratory supraglottic collapse on exertion has been established as a common cause of exertional breathlessness [5] that is correlated with exercise intensity [6]. Both glottic and supraglottic inspiratory closure are more commonly seen in females and most often in adolescents or young adults [7–11]. This predominance has yet to be explained; however, gender differences in larynx size/growth and consequently higher "Bernoulli forces" in females for a given respiratory demand could be a contributing factor [5]. Thus, an inherited disorder affecting laryngeal growth could also explain why the condition usually presents in adolescence [12, 13]. A recent study by Hilland and colleagues [14] describing an association between congenital laryngomalacia and (mainly supraglottic) laryngeal closure in adolescence, points out a likely predisposition for supraglottic exercise-induced laryngeal obstruction (EILO), whereas case studies have demonstrated that congenital laryngomalacia can be inherited [15, 16]. Supraglottic EILO could be inherited. Different modes of inheritance can explain the results of this study. <http://ow.ly/5XAv30csDRa>
Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria
Authors: Ana Sousa, Ricardo S. Ramiro, João Barroso-Batista, Daniela Güleresi, Marta Lourenço, Isabel Gordo
Journal: Molecular Biology and Evolution (2017)

The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut.
Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells
Authors: Steven A. Sloan, Spyros Darmanis, Nina Huber, Themasap A. Khan, Fikri Birey, Christine Caneda, Richard Reimer, Stephen R. Quake, Ben A. Barres, Sergiu P. Paşca
Journal: Neuron (2017)
The UK Royal College of Paediatrics and Child Health’s Policy on Funding From Commercial Organizations
Authors: Neena Modi, Judith Ellis, Mary Marsh
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
THU0469 Comparative effectiveness of tai chi versus aerobic exercise for fibromyalgia: a randomized controlled trial
Authors: C Wang, C Schmid, R Fielding, W Harvey, K Reid, LL Price, J Driban, R Kalish, R Rones, T McAlindon
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fibromyalgia is a complex disorder with strong psychological and pain components. Tai Chi is an integrated mind-body approach that enhances both physical and mental health and has great potential to treat fibromyalgia (1–2). <h3>Objectives</h3> We aimed to investigate whether Tai Chi is more effective with longer lasting effects than aerobic exercise. <h3>Methods</h3> We conducted a 52-week, single-blind, randomized trial of Tai Chi vs. aerobic exercise for fibromyalgia (ACR 1990 and 2010 diagnostic criteria). Participants were randomized to 1 of 4 Tai Chi interventions: 12 or 24 weeks of Tai Chi once or twice per week, or aerobic exercise held twice per week for 24 weeks. The primary endpoint was change in the Revised Fibromyalgia Impact Questionnaire (FIQR) score at 24 weeks. Secondary endpoints included change in patient9s global assessment, the Hospital Anxiety and Depression scale (HADS), Sleep Quality Index (PSQI), arthritis self-efficacy scale (ASES-8), and quality of life. The comparative efficacy of the five groups was determined using longitudinal models based on the intent-to-treat principal. <h3>Results</h3> The mean age of subjects was 52 years (SD 12), mean years of body pain of 9 years (SD 8), 92% were women, and 61% were white. Treatment groups did not differ in baseline outcome expectation. The average of all 4 Tai Chi groups, compared to aerobic exercise, showed significant improvements in FIQR scores, patient9s global, anxiety, and self-efficacy. All other outcomes favored Tai Chi over aerobic exercise (Table 1). The Tai Chi treatment with the same dosage as the aerobic group demonstrated an even larger effect for FIQR and for most other outcomes. The benefit of Tai Chi was consistent across instructors. <h3>Conclusions</h3> Tai Chi is more effective than aerobic exercise and can be considered as an important therapeutic option for patients with fibromyalgia. <h3>References</h3> Jones KD. Recommendations for resistance training in patients with fibromyalgia. Arthritis Res Ther 2015;17:258. Wang C, Schmid CH, Rones R, et al. A randomized trial of tai chi for fibromyalgia. N Engl J Med 2010;363:743–54. <h3>Disclosure of Interest</h3> None declared
Dosing immunotherapy combinations: Analysis of 3,526 patients in cancer clinical trials.
Authors: Mina Nikanjam, Harsh Patel, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

e14620 Background: Immunotherapy combinations are used to improve outcomes in metastatic cancer, but knowledge of appropriate starting doses for novel combinations is lacking. Methods: Phase I-III adult combination clinical trials (≥1 drug was immunotherapy; anti-PD1, PDL1, or CTLA4) were reviewed (PubMed Jan 1, 2010 to Sep 1, 2016; ASCO 2014-2016, ASH/ESMO 2014-2015 abstracts). The safe dose used in each combination was divided by the single agent recommended dose to calculate dose percentage. Additive dose percentage was the sum of each dose percentage. Results: 84 studies (N=3,526 patients, 60 combinations) were analyzed (see Table). Eight studies had unacceptable safety: ipilimumab with cytoxan, vemurafenib, dacarbazine, dabrafenib/trametinib, or carboplatin/etoposide; nivolumab or pembrolizumab with pazopanib; and tremelimumab with sunitinib. Lowest additive dose percentages evaluated in these studies were: 160, 175, 175, 217, 300, 167, 175, and 167%; it is unclear if lower doses would have been tolerable. Combinations with ipilimumab had lower additive dose percentages. Response rates (median [interquartile range]) were higher for 3 than 2 drug combinations (53% [33%-63%] (N = 23 studies) vs. 23% [14%-39%]) (N = 60 studies) with similar rates seen for targeted, cytotoxic, or dual immunotherapy combinations. Conclusions: In 63% of studies not including ipilimumab, full doses of combinations could be given. Triplet combinations had median response rates of 53 vs. 23% for doublets (p&lt;0.001). These findings can help inform safe starting doses for novel immunotherapy combinations in clinical trials and practice. [Table: see text]