tbuckley/cabot-search huggingface dataset:
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Authors: Douglas J. Morrison, Tom Preston
Journal: Gut Microbes (2016)

The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.
World invests too little and is underprepared for disease outbreaks, report warns
Authors: Anne Gulland
Journal: BMJ (2016)

The world must invest £3bn (€3.98bn; $4.33bn) every year to prepare for future pandemics, a report has urged. The Commission on Creating a Global Health Risk Framework for the Future warned in its report that the yearly global cost of potential pandemics is around £40bn.1

The commission, sponsored by the Wellcome Trust in partnership with organisations including the Bill and Melinda Gates Foundation and the Rockefeller Foundation, said that governments and private and philanthropic bodies must increase their spending on pandemics. The World Bank has estimated that the Ebola epidemic cost around $2bn (£1.39bn; €1.84bn), and the commission’s own modelling suggests a 20% chance of four or more pandemics occurring over the next 100 years.

The commission said that the rate of …
Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families With Type 1 Diabetes
Authors: Caroline A. Brorsson, Flemming Pociot
Journal: Diabetes Care (2015)

Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim of this study was to investigate whether susceptibility loci identified in genome-wide association studies (GWAS) of T1D were also associated with autoantibody positivity in individuals with diabetes. Fifty single nucleotide polymorphisms (SNPs) were genotyped in 6,556 multiethnic cases collected by the Type 1 Diabetes Genetics Consortium (T1DGC). These were tested for association with three islet autoantibodies—against autoantibodies to GAD (GADA), IA-2 (IA-2A), and zinc transporter 8 (ZnT8A)—and autoantibodies against thyroid peroxidase (TPOA) in autoimmune thyroid disease, gastric parietal cells (PCA) in autoimmune gastritis, transglutaminase (TGA) in celiac disease, and 21-hydroxylase (21-OHA) in autoimmune hypoadrenalism. In addition to the MHC region, we identify SNPs in five susceptibility loci (IFIH1, PTPN22, SH2B3, BACH2, and CTLA4) as significantly associated with more than one autoantibody at a false discovery rate less than 5%. IFIH1/2q24 demonstrated the most unrestricted association, as significant association was demonstrated for PCA, TPOA, GADA, 21-OHA, and IA-2A. In addition, 11 loci were significantly associated with a single autoantibody.
Abstract 17644: Diagnostic Performance of Two-Dimensional Speckle Tracking Echocardiography for the Detection of Myocardial Infarction on Late Gadolinium Enhanced Magnetic Resonance Imaging
Authors: Shingo Kato, Noritaka Saito, Nao Ishii, Masashi Koga, Yuka Kusakawa, Ikuyoshi Kusama, Tatsuya Nakachi, Tsuyoshi Nakagawa, Kazuki Fukui, Kazuaki Uchino, Kazuo Kimura, Satoshi Umemura
Journal: Circulation (2012)

Purpose: Two-dimensional speckle tracking echocardiography (2D-STE) permits non-invasive and accurate quantification of regional myocardial strain on left ventricle. We assessed the hypothesis that...
Efficient therapy of ischaemic lesions with VEGF<sub>121</sub>-fibrin in an animal model of systemic sclerosis
Authors: Shadab Allipour Birgani, Marion Mailänder, Ines Wasle, Hermann Dietrich, Johann Gruber, Oliver Distler, Roswitha Sgonc
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF<sub>121</sub> variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF<sub>121</sub> leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions. <h3>Methods</h3> Ninety-one early and late ischaemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF<sub>121</sub>-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest. <h3>Results</h3> Overall, 79.3% of the lesions treated with VEGF<sub>121</sub>-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression. <h3>Conclusions</h3> Our findings in the avian model of SSc suggest that cell-demanded release of VEGF<sub>121</sub> from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers.
Exercise-based management versus surgery for multidirectional instability of the glenohumeral joint: a systematic review
Authors: Sarah A Warby, Tania Pizzari, Jon J Ford, Andrew J Hahne, Lyn Watson
Journal: British Journal of Sports Medicine (2015)

Background The most commonly recommended treatment for multidirectional instability (MDI) is exercise-based management, followed by surgery if exercise management fails. We aimed to evaluate the effectiveness of exercise-based management compared with surgery in patients with MDI. Secondary aims were to identify effective protocols and any adverse effects associated with exercise or surgery. Method The Cochrane database of systematic reviews, MEDLINE, EMBASE, CINAHL, PEDro, Current Contents, AMED, AMI, Ausport and Clinical Trials Registers were searched for published and unpublished studies from inception date to August 2014, using the key words multidirectional instability, and glenohumeral and exercise and surgery. Selection criteria included all study designs (except case reports and case series) and participants with MDI where both exercise-based management and surgery were compared in the same study. Inclusion criteria were not limited by outcomes. Risk of bias was assessed using Cochrane criteria. The GRADE approach was used to synthesise the evidence. Results 4 non-randomised studies met the inclusion criteria. Risk of bias was high in all 4 studies. GRADE assessment revealed very low-quality evidence that surgery was superior to exercise therapy for impairment outcome measures, and exercise was favoured over surgery for patient-reported outcome measures. Summary The effect of exercise-based management compared with surgery for MDI is difficult to determine due to participant heterogeneity and a high level of bias across included studies.
IL-33 amplifies an innate immune response in the degenerating retina
Authors: Hongkang Xi, Kenneth J. Katschke, Yun Li, Tom Truong, Wyne P. Lee, Lauri Diehl, Linda Rangell, Jianhua Tao, Rommel Arceo, Jeffrey Eastham-Anderson, Jason A. Hackney, Antonio Iglesias, Javier Cote-Sierra, Justin Elstrott, Robby M. Weimer, Menno van Lookeren Campagne
Journal: The Journal of Experimental Medicine (2016)

Age-related macular degeneration (AMD), a leading cause of vision impairment in the ageing population, is characterized by irreversible loss of retinal pigment epithelial (RPE) cells and photoreceptors and can be associated with choroidal neovascularization. Mononuclear phagocytes are often present in AMD lesions, but the processes that direct myeloid cell recruitment remain unclear. Here, we identify IL-33 as a key regulator of inflammation and photoreceptor degeneration after retina stress or injury. IL-33(+) Müller cells were more abundant and IL-33 cytokine was elevated in advanced AMD cases compared with age-matched controls with no AMD. In rodents, retina stress resulted in release of bioactive IL-33 that in turn increased inflammatory chemokine and cytokine expression in activated Müller cells. Deletion of ST2, the IL-33 receptor α chain, or treatment with a soluble IL-33 decoy receptor significantly reduced release of inflammatory mediators from Müller cells, inhibited accumulation of mononuclear phagocytes in the outer retina, and protected photoreceptor rods and cones after a retina insult. This study demonstrates a central role for IL-33 in regulating mononuclear phagocyte recruitment to the photoreceptor layer and positions IL-33 signaling as a potential therapeutic target in macular degenerative diseases.
Neofunctionalization of a Duplicate<i>dachshund</i>Gene Underlies the Evolution of a Novel Leg Segment in Arachnids
Authors: Natascha Turetzek, Matthias Pechmann, Christoph Schomburg, Julia Schneider, Nikola-Michael Prpic
Journal: Molecular Biology and Evolution (2015)

The acquisition of a novel function, or neofunctionalization, protects duplicated genes from redundancy and subsequent loss, and is a major force that drives adaptive evolution. Neofunctionalization has been inferred for many duplicated genes based on differences in regulation between the parental gene and its duplicate. However, only few studies actually link the new function of a duplicated gene to a novel morphological or physiological character of the organism. Here we show that the duplication of dachshund (dac) in arachnids (spiders and allies) is linked with the evolution of a novel leg segment, the patella. We have studied dac genes in two distantly related spider species, the entelegyne spider Parasteatoda tepidariorum and the haplogyne spider Pholcus phalangioides. Both species possess two paralogous dac genes that duplicated before the split between entelegyne and haplogyne spiders. In contrast to the evolutionarily highly conserved dac1, its duplicate dac2 is strongly expressed in the patella leg segment during embryogenesis in both species. Using parental RNA interference in P. tepidariorum we show that dac2 is required for the development of the patella segment. If dac2 function is impaired, then the patella is fused with the tibia into a single leg segment. Thus, removing the function of dac2 experimentally reverts P. tepidariorum leg morphology into a stage before the duplication of dac and the evolution of the patella segment. Our results indicate that the origin of the patella is the result of the duplication and subsequent neofunctionalization of dac in the arachnid lineage.
Editorial
Authors: T Opthof
Journal: Cardiovascular Research (1998)

In this issue Uta C. Hoppe and Dirk J. Beuckelmann describe the presence of I channels in human atrial cells f w x 1 .The cells were isolated from small segments of the right atrial appendage obtained at the time of open heart surgery in 96 patients.About 80% of those patients underwent a coronary bypass procedure.The same group recently published a paper on I in human ventricular myf ocytes.Those cells were isolated from explanted hearts from patients with endstage heart failure and from donor hearts not suitable for transplantation, the latter serving as w x controls 2 .This Editorial will focus on the implications of the presence of I current in atrial and ventricular f w x muscle in heart failure 3-5 . Role of I in normal pacemaking function fThe membrane current I , often described as 'the' f
The impact of circulating regulatory T cells number and their subpopulations on risk of lymph node metastasis
Authors: Jerzy Wydmanski, Agata Chwieduk, Agnieszka Gdowicz-Klosok, Magdalena Glowala-Kosinska, Tomasz Latusek, Agnieszka Namysl-Kaletka, Malgorzata Kraszkiewicz, Andrzej Tukiendorf
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Regulatory T cells (Tregs) suppress the induction of immune response to cancer cells. An increased number of Tregs have been observed in many solid tumors. The aim of this study was to evaluate whether the number and percentage of circulating Tregs and their subpopulations differ
Functional Studies Of Hsp70 Gene Expression In Multiple Myeloma Cell Lines Suggest That This Gene Inhibition Can Be a Potential Therapeutic Target, Independent Of 17p/p53 Status
Authors: Veruska Lia Fook Alves, Walter Moises Tobias Braga, Daniela Bertolli Zanatta, Fabricio de Carvalho, Maria de Lourdes Chauffaille, Bryan E. Strauss, Gisele Wally Braga Colleoni
Journal: Blood (2013)
Fluctuations in lower urinary tract symptoms in women
Authors: S. Hunskaar
Journal: BMJ (2000)

Urinary symptoms are common in both men and women. Traditionally “prostatism” has been used to describe the symptoms in men, while urinary incontinence and dysuria were used for women.1 For some years the term lower urinary tract symptoms (LUTS) has been used to describe any constellation of symptoms occurring in patients of either sex at any age. The symptoms are not disease specific and the term does not suggest any cause for the symptoms. It has been shown that instruments developed to score symptoms in men (for example, the international prostate symptom score scale) are not sex specific, as the symptoms are as prevalent in women as in men.2 3

In this issue Moller et al (p 1429) present data on the incidence and rates of remission at one year of lower urinary tract symptoms in 2284 Danish women aged 40-60.4 The prevalence was 29%, the incidence …
Abstract 18477: Outcome of Anatomical Approach of Radiofrequency Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia: 15 years experience
Authors: Jaemin Shim, Jin Wi, Hee-Sun Mun, Jae-Sun Uhm, Hye Jin Hwang, Jong Youn Kim, Boyoung Joung, Hui-Nam Pak, Sung Soon Kim, Moon-Hyoung Lee
Journal: Circulation (2012)

BACKGROUND: Even though the anatomical approach as the radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) has been introduced long ago, large population based outcome of this approach remains unclear. Moreover, electrophysiologic characteristics between different successful target sites have not been identified as well. The purpose of this study was to investigate outcome and electrophysiologic characteristics according to successful target site. METHODS: A total of 1391consecutive patients (mean age 45±16 years, female 63%) who underwent RF catheter ablation based on anatomical approach for AVNRT between 1996 and 2010 were enrolled in this study. The tricuspid annulus between the coronary sinus ostium and the His bundle recording site was divided into posterior (P), medial (M), and anterior (A) regions. Serial RF energy applications were delivered from P site to superior side until junctional rhythm was inducible. RESULTS: Dual AV nodal physiology was documented in 91.9 %, typical AVNRT was 92.4 %. The mean procedure time, fluoroscopic time, and the ablation time was 63±28 min, 12±7 min, and 226±176 sec, respectively. Successful target site was P in 46.7% (n=684), M in 47.9% (n=701), and A in 0.7% (n=5). Long-term recurrence rate was 1.8% (n=25). AV nodal block requiring pacemaker occurred in 0.2 % (n=3). When divided into two groups, A (successful ablation at P site) and B (successful ablation at M and A sites), there was no difference between two groups in age, gender, tachycardia cycle length, atrial effective refractory period (ERP), AV block cycle length (BCL), ERP of fast and slow pathway, ventricular ERP, temperature, RF power, and long-term recurrence (all p values &gt; 0.05). However, group A had more atypical form (9.4% vs. 6.0%, p=0.019), longer shortest VA interval (30.0±1.35 vs. 24.5±1.13 msec, p=0.002), longer VA BCL (376±102 vs. 361±88 msec, p=0.007), and shorter RF time (180±121 vs. 317±226 sec, p&lt;0.001) than group B. CONCLUSION: Anatomical approach of RF ablation for AVNRT showed excellent long-term outcome. The electrophysiologic characteristics were different according to successful ablation site.
HIV-1 outbreak among injecting drug users in Greece, 2011: a preliminary report
Authors: D Paraskevis, G Nikolopoulos, C Tsiara, D Paraskeva, A Antoniadou, M Lazanas, P Gargalianos, M Psychogiou, M Malliori, J Kremastinou, A Hatzakis
Journal: Eurosurveillance (2011)

A significant increase (more than 10-fold) in the number of newly diagnosed HIV-1 infections among injecting drug users (IDUs) was observed in Greece during the first seven months of 2011. Molecular epidemiology results revealed that a large proportion (96%) of HIV-1 sequences from IDUs sampled in 2011 fall within phylogenetic clusters suggesting high levels of transmission networking. Cases originated from diverse places outside Greece supporting the potential role of immigrant IDUs in the initiation of this outbreak.
Denosumab compared with zoledronic acid for the treatment of bone disease in adults with newly diagnosed multiple myeloma: An international, randomized, double-blind trial.
Authors: Noopur S. Raje, Evangelos Terpos, Brian G. Durie, Ramon Garcia-Sanz, Kazuyuki Shimizu, Wolfgang Willenbacher, Li Zhu, Douglas J Warner, Antonio Palumbo
Journal: Journal of Clinical Oncology (2015)

TPS8611 Background: A characteristic feature of multiple myeloma (MM) is osteoclast-mediated breakdown of the bone. Patients with MM and bone lesions often experience debilitating pain and skeletal complications including pathologic fractures, need for radiotherapy or surgery to bone, and spinal cord compression, collectively termed skeletal-related events (SREs). RANKL is the key mediator of osteoclast activity. Denosumab, a fully human monoclonal antibody specific to RANKL, inhibits the formation, function, and survival of osteoclasts, thus decreasing cancer-mediated bone destruction. The primary endpoint of this trial is to determine whether denosumab is noninferior to zoledronic acid (ZA) in delaying the time to 1st on-study SRE in patients with MM. Secondary endpoints include superiority of denosumab vs ZA in delaying the time to 1st on-study SRE and time to 1st-and-subsequent SRE and overall survival. Safety endpoints will be assessed. This trial is registered (ClinicalTrials.gov NCT01345019) and sponsored by Amgen Inc. Methods: Targeted enrollment is ~1520 adults with newly diagnosed MM and ≥ 1 bone lesion receiving first-line treatment. Patients with ≤ 30 days of anti-myeloma therapy, ≤ 1 prior dose of IV bisphosphonate, an ECOG status ≤ 2, and adequate organ function are eligible. Use of any approved anti-myeloma treatment is permitted. Enrolled patients are stratified by whether they intend to undergo autologous stem cell transplant; use of novel vs non-novel anti-myeloma agents as first-line therapy; stage at diagnosis per the International Staging System (I, II, or III); SRE at time of presentation; and geographic region. Randomized (1:1) patients receive either SC denosumab 120 mg + IV placebo or IV ZA 4 mg (adjusted for CrCl) + SC placebo once every 4 weeks. Daily calcium ( ≥ 500 mg) and vitamin D ( ≥ 400 IU) supplements are strongly recommended. The primary analysis is planned when ~800 patients experience an on-study SRE. Enrollment is currently ongoing and enrollment rates are as planned.
ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk
Authors: Tabea Brick, Yvonne Schober, Christian Böcking, Juha Pekkanen, Jon Genuneit, Georg Loss, Jean-Charles Dalphin, Josef Riedler, Roger Lauener, Wolfgang Andreas Nockher, Harald Renz, Outi Vaarala, Charlotte Braun-Fahrländer, Erika von Mutius, Markus Johannes Ege, Petra Ina Pfefferle, A. Karvonen, P. Tiittanen, M.-L. Dalphin, B. Schaub, M. Depner, S. Illi, M. Kabesch
Journal: Journal of Allergy and Clinical Immunology (2016)
Decision support systems for personalized and participative radiation oncology
Authors: Philippe Lambin, Jaap Zindler, Ben G.L. Vanneste, Lien Van De Voorde, Daniëlle Eekers, Inge Compter, Kranthi Marella Panth, Jurgen Peerlings, Ruben T.H.M. Larue, Timo M. Deist, Arthur Jochems, Tim Lustberg, Johan van Soest, Evelyn E.C. de Jong, Aniek J.G. Even, Bart Reymen, Nicolle Rekers, Marike van Gisbergen, Erik Roelofs, Sara Carvalho, Ralph T.H. Leijenaar, Catharina M.L. Zegers, Maria Jacobs, Janita van Timmeren, Patricia Brouwers, Jonathan A. Lal, Ludwig Dubois, Ala Yaromina, Evert Jan Van Limbergen, Maaike Berbee, Wouter van Elmpt, Cary Oberije, Bram Ramaekers, Andre Dekker, Liesbeth J. Boersma, Frank Hoebers, Kim M. Smits, Adriana J. Berlanga, Sean Walsh
Journal: Advanced Drug Delivery Reviews (2016)
Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease
Authors: J P Fuld
Journal: Thorax (2005)

Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD.Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25).No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)).Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.