tbuckley/cabot-search huggingface dataset:
miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD
Authors: Chong He, Yan Shi, Ruijin Wu, Mingming Sun, Leilei Fang, Wei Wu, Changqin Liu, Maochun Tang, Zhong Li, Ping Wang, Yingzi Cong, Zhanju Liu
Journal: Gut (2015)

<h3>Objective</h3> MicroRNA (miR)-301a is known to be involved in the tumourigenesis and pathogenesis of several autoimmune diseases, but it remains unclear whether miR-301a is associated with the pathogenesis of IBD. <h3>Methods</h3> miR-301a expression was assessed in peripheral blood mononuclear cells (PBMC) and inflamed mucosa of patients with IBD by quantitative real-time-PCR. Peripheral blood CD4+ T cells were transduced with lentivirus-encoding pre-miR-301a (LV-miR-301a) or a reverse complementary sequence of miR-301a (LV-anti-miR-301a), and their differentiation and activation were investigated in vitro. Antisense miR-301a was administered into mice during trinitrobenzene sulphonic acid (TNBS)-induced colitis to determine its role in colitis. <h3>Results</h3> miR-301a expression was significantly upregulated in PBMC and inflamed mucosa of patients with IBD compared with healthy controls. Stimulation with tumour necrosis factor-α (TNF-α) significantly enhanced miR-301a expression in IBD CD4+ T cells, which was markedly reversed by anti-TNF-α mAb (Infliximab) treatment. Transduction of LV-miR-301a into CD4+ T cells from patients with IBD promoted the Th17 cell differentiation and TNF-α production compared with the cells with expression of LV-anti-miR-301a. SNIP1 as a functional target of miR-301a was reduced in miR-301a expression but increased in LV-anti-miR-301a expression. Knockdown of SNIP1 could enhance Th17 cell differentiation. Furthermore, intracolonical administration of antisense miR-301a in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A<sup>+</sup> cells and amounts of pro-inflammatory cytokines (eg, IL-17A, TNF-α) in inflamed colon. <h3>Conclusions</h3> Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD.
Total knee replacement is linked to reduced pain but with serious side effects, trial finds
Authors: Susan Mayor
Journal: BMJ (2015)

Total knee replacement is associated with greater pain relief and functional improvement than non-surgical treatment but also with more serious adverse events in people with osteoarthritis, a randomised controlled trial has shown. It also found that nearly three quarters of patients treated non-surgically did not require an operation in the following year.

The trial, reported in the New England Journal of Medicine ,1 randomised 100 patients with symptomatic osteoarthritis to undergo total knee replacement followed by a rigorous 12 week non-surgical treatment regimen or to …
Low public health risk of MERS-CoV in people returning from the Hajj
Authors: Gerry Waldron, Lorraine Doherty
Journal: BMJ (2015)

Kumar and colleagues do well to raise the possibility of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) arising in returning travellers from high risk areas.1 However, their assertions that “awareness of MERS in healthcare workers remains low” and “the risk of returning Hajj pilgrims contracting and spreading MERS-CoV . . . …
Part 4: Advanced Life Support
Authors: Clifton W. Callaway, Jasmeet Soar, Mayuki Aibiki, Bernd W. Böttiger, Steven C. Brooks, Charles D. Deakin, Michael W. Donnino, Saul Drajer, Walter Kloeck, Peter T. Morley, Laurie J. Morrison, Robert W. Neumar, Tonia C. Nicholson, Jerry P. Nolan, Kazuo Okada, Brian J. O’Neil, Edison F. Paiva, Michael J. Parr, Tzong-Luen Wang, Jonathan Witt, Lars W. Andersen, Katherine M. Berg, Claudio Sandroni, Steve Lin, Eric J. Lavonas, Eyal Golan, Mohammed A. Alhelail, Amit Chopra, Michael N. Cocchi, Tobias Cronberg, Katie N. Dainty, Ian R. Drennan, Michael Fries, Romergryko G. Geocadin, Jan-Thorsten Gräsner, Asger Granfeldt, Sarah Heikal, Peter J. Kudenchuk, Anthony T. Lagina, Bo Løfgren, Jill Mhyre, Koenraad G. Monsieurs, Allan R. Mottram, Tommaso Pellis, Joshua C. Reynolds, Giuseppe Ristagno, Fred A. Severyn, Markus Skrifvars, William C. Stacey, Jonathon Sullivan, Sarah L. Todhunter, Gino Vissers, Stephen West, Wolfgang A. Wetsch, Natalie Wong, Theodoros Xanthos, Carolyn M. Zelop, Janice Zimmerman
Journal: Circulation (2015)
Immunological Factors Influencing Renal Graft Survival
Authors: G Opelz, V Lenhard
Journal: Annual Review of Medicine (1983)

The results of clinical renal transplantation are determined mainly by immunological factors, the most important of which are compatibility for the HLA chromosomes and pretransplant blood transfusions. Other factors include HLA matching in cadaver transplantation, compatibility for the Lewis blood group system, and sensitization to lymphocyte panels or to endothelial-monocyte antigens. Performance of the previous graft is the most reliable predictor of success in recipients of retransplants. Because several immunological factors may interact, multiple variables must be considered simultaneously.
AN INTERPRETATIVE STUDY OF INVOLUTIONAL DEPRESSION
Authors: Gerald H. J. Pearson
Journal: American Journal of Psychiatry (1928)

A study of the productions of four cases of depression, three of involutional melancholia and one in the involutional period with a seventh attack of manic-depressive psychosis is reported here. These productions seem to indicate that the following mechanism produces the attack of depression. A precipitating situation arises in the patient's life whereby his ego receives a wound and the carefully built up compensations over many years fail. This precipitating situation reactivates a similar childhood situation and causes a regression of the libido to a more infantile level—one of oral eroticism. At this level the differentiation between subject and object is vague. The object seems to have signified the ego ideal—the inhibitions—and this projection of the ego ideal on the object seems to have made it possible for the ego to incorporate it (devour it) into a subordinate position where the hate element in the libido strivings can be vented on it. The patient flees from the precipitating situation into the psychosis and in the psychosis can give full play to his infantile hate against the object, his ego ideal and his inhibitions, but by doing this he increases his guilt which he is able to satisfy by punishing his ego for its subordination of the ego ideal.
Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3
Authors: Janet D. Klein, Yanhua Wang, Abinash Mistry, Lauren M. LaRocque, Patrick A. Molina, Richard T. Rogers, Mitsi A. Blount, Jeff M. Sands
Journal: Journal of the American Society of Nephrology (2015)

Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability.
The G protein–coupled receptor P2RY8 and follicular dendritic cells promote germinal center confinement of B cells, whereas S1PR3 can contribute to their dissemination
Authors: Jagan R. Muppidi, Erick Lu, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2015)

The orphan Gα13-coupled receptor P2RY8 is mutated in human germinal center (GC)-derived lymphomas and was recently found to promote B cell association with GCs in a mouse model. Here we establish that P2RY8 promotes clustering of activated B cells within follicles in a follicular dendritic cell (FDC)-dependent manner. Although mice lack a P2RY8 orthologue, we show that mouse GC B cell clustering is also dependent on FDCs acting to support the function of a Gα13-coupled receptor. Mutations in GNA13 and its downstream effector ARHGEF1 are associated with the development of disseminated GC-derived lymphomas. We find that egress of Gna13 mutant GC B cells from lymph nodes in the mouse depends on sphingosine-1-phosphate receptor-3. These findings provide evidence that FDCs promote GC confinement of both human and mouse GC B cells via Gα13-dependent pathways, and they show that dissemination of Gα13-deficient GC B cells additionally requires an egress-promoting receptor.
Regulation of the Release of Coexisting Neurotransmitters
Authors: T Bartfai, K Iverfeldt, G Fisone, P Serfözö
Journal: The Annual Review of Pharmacology and Toxicology (1988)

The joy of neurobiologists at the discovery of the coexistence of several neuroactive substances within the same neuron terminals can be compared with the delight of a man who has bought a radio he thought would only receive AM broadcasts, but who then discovers that it also gets all the FM stations. The discovery that the given neuronal network has the possibility of transmitting several different signals at the same time, at many of its syn­ apses, lends new dimensions to the workings of this network. The pace of morphological discovery of ever new examples of the coexistencel colocalization of two or more neuroactive substances in the same neuron is very high, producing several hundred new examples of coexistence phe­ nomena in the periphery and eNS (cf. 1-6). The work on the functional implications of the possibility of multiple signalling through the same syn­ apse-using several coexisting neurotransmitters-has been much slower. In this review, we discuss some important questions concerning the release of coexisting neurotransmitters and through these get some insight into the functional implications of coexistence. These questions are as follows: (a) Will a neuron at every one of its processes (dendrites and axon
The Effect of a Psychiatric Residency Program on Admission and Discharge Rates and Patient Disposition
Authors: TOKSOZ B. KARASU, ROBERT PLUTCHIK, PHILIP HERSCHENFELD, BARBARA SIEGEL
Journal: American Journal of Psychiatry (1974)

This study examined the effect of a residency training program on the services delivered to patients on two psychiatric wards of a general hospital. Data obtained before and after the introduction of the program indicated that screening procedures and the relationship between ward and intake services improved, uninteresting cases were not "dumped." and treatment was focused on the more seriously ill patients.
Renal handling of low molecular weight proteins
Authors: R. Peter Mogielnick, Thomas A. Waldmann, Warren Strober
Journal: Journal of Clinical Investigation (1971)

Immunoglobulin L-chain metabolism was studied in normal mice, mice with sodium maleate-induced renal tubular disease but normal glomerular filtration rate (GFR), and mice with both tubular disease and decreased GFR. The proteinuric rate of L-chain was increased twofold in mice with tubular disease alone though there was no alteration in the over-all rate at which L-chain disappeared from the circulation in these animals. This was in sharp contrast to findings in mice with tubular disease and a decreased glomerular filtration rate in which L-chain disappearance rates were markedly reduced. These findings demonstrate that in the normal state, L-chain and presumably other proteins of similar size pass through the glomerulus and are avidly taken up and catabolized by the convoluted tubular cells. In tubular proteinuric states this linked uptake-catabolic function fails, resulting in elevated urinary excretion but normal serum levels and turnover rates of these proteins. In uremic states with decreased glomerular filtration, less small protein is delivered into the tubular lumen and the processes of excretion and catabolism are reduced. This results in prolongation of the survival of small proteins and explains the elevated serum concentrations of these proteins observed in uremia.
Microvascular count and prognosis in colorectal cancer.
Authors: L Y Dirix, P B Vermeulen, A T Van Oosterom, G Gasparini
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.8.2400 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708734 Microvascular count and prognosis in colorectal cancer. L Y DirixxL Y DirixSearch for articles by this author , P B VermeulenxP B VermeulenSearch for articles by this author , A T Van OosteromxA T Van OosteromSearch for articles by this author , G GasparinixG GaspariniSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2400 First Page PDF © 1996 by American Society of Clinical Oncology
REPRINT
Authors: Joseph Broderick, Sander Connolly, Edward Feldmann, Daniel Hanley, Carlos Kase, Derk Krieger, Marc Mayberg, Lewis Morgenstern, Christopher S. Ogilvy, Paul Vespa, Mario Zuccarello
Journal: Circulation (2007)

The aim of this statement is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage.A formal literature search of Medline was performed through the end date of August 2006. The results of this search were complemented by additional articles on related issues known to the writing committee. Data were synthesized with the use of evidence tables. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 5 expert peer reviewers and by the members of the Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years' time.Evidence-based guidelines are presented for the diagnosis of intracerebral hemorrhage, the management of increased arterial blood pressure and intracranial pressure, the treatment of medical complications of intracerebral hemorrhage, and the prevention of recurrent intracerebral hemorrhage. Recent trials of recombinant factor VII to slow initial bleeding are discussed. Recommendations for various surgical approaches for treatment of spontaneous intracerebral hemorrhage are presented. Finally, withdrawal-of-care and end-of-life issues in patients with intracerebral hemorrhage are examined.
Abstract P149: The Effect of Alcohol Consumption on Insulin Sensitivity and Glycemic Status: A Systematic Review and Meta-analysis of Intervention Studies
Authors: Ilse C Schrieks, Annelijn L Heil, Henk F Hendriks, Kenneth J Mukamal, Joline W Beulens
Journal: Circulation (2014)

Introduction: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes, but this relation appears stronger for women than men. The reduced risk of diabetes could be explained by improved insulin sensitivity or glycemic status, but results of intervention studies on this relation are inconsistent. Our aim was to conduct a systematic review and meta-analysis of intervention studies investigating the effect of alcohol consumption on insulin sensitivity and glycemic status. Design: Systematic review and meta-analysis of intervention studies. Data sources: PubMed and Embase were searched until May 2013 using a pre-specified search string. Methods: Intervention studies on the effect of more than 2 weeks alcohol consumption on biological markers of insulin sensitivity or glycemic status were identified and assessed on their quality. Pooled standardized mean differences (SMD) were calculated using either fixed or random effects models. Gender-stratified analyses and sensitivity analyses excluding studies with high doses of alcohol (&gt; 40 g/day). In a meta-regression the influence of dosage and duration of intervention was tested. Results: We included 14 intervention studies in a meta-analysis on 6 glycemic endpoints. Alcohol consumption did not influence insulin sensitivity (SMD=0.06 [-0.13 to 0.26]) or fasting glucose (SMD=0.09 [-0.09 to 0.27]). Alcohol consumption reduced HbA1c (SMD=-0.62 [-1.01 to -0.23], P=0.002) and insulin concentrations (SMD=-0.17 [-0.34 to 0.00] P=0.049) compared with the control group. In women, alcohol consumption reduced fasting insulin (SMD=-0.23 [-0.41 to -0.04], P=0.019) and improved insulin sensitivity (SMD=0.19 [-0.03 to 0.41], P=0.087), but no significant differences were observed among men. Results were similar when only studies with moderate alcohol dosages were analysed and were not influenced by dosage and duration of the intervention. Conclusions: This study showed that moderate alcohol consumption may reduce fasting insulin and improve insulin sensitivity among women, but not among men. These effects may provide an explanation for the relation between alcohol consumption and type 2 diabetes. Furthermore, moderate alcohol consumption may reduce HbA1c levels among both men and women.
Intein Clustering Suggests Functional Importance in Different Domains of Life
Authors: Olga Novikova, Pradeepa Jayachandran, Danielle S. Kelley, Zachary Morton, Samantha Merwin, Natalya I. Topilina, Marlene Belfort
Journal: Molecular Biology and Evolution (2015)

Inteins, also called protein introns, are self-splicing mobile elements found in all domains of life. A bioinformatic survey of genomic data highlights a biased distribution of inteins among functional categories of proteins in both bacteria and archaea, with a strong preference for a single network of functions containing replisome proteins. Many nonorthologous, functionally equivalent replicative proteins in bacteria and archaea carry inteins, suggesting a selective retention of inteins in proteins of particular functions across domains of life. Inteins cluster not only in proteins with related roles but also in specific functional units of those proteins, like ATPase domains. This peculiar bias does not fully fit the models describing inteins exclusively as parasitic elements. In such models, evolutionary dynamics of inteins is viewed primarily through their mobility with the intein homing endonuclease (HEN) as the major factor of intein acquisition and loss. Although the HEN is essential for intein invasion and spread in populations, HEN dynamics does not explain the observed biased distribution of inteins among proteins in specific functional categories. We propose that the protein splicing domain of the intein can act as an environmental sensor that adapts to a particular niche and could increase the chance of the intein becoming fixed in a population. We argue that selective retention of some inteins might be beneficial under certain environmental stresses, to act as panic buttons that reversibly inhibit specific networks, consistent with the observed intein distribution.
Athletic groin pain: a systematic review and meta-analysis of surgical versus physical therapy rehabilitation outcomes
Authors: E King, J Ward, L Small, E Falvey, A Franklyn-Miller
Journal: British Journal of Sports Medicine (2015)

Background Athletic groin pain (AGP) is an encompassing term for the multitude of chronic conditions presenting as pain in the inguinal region. The purpose of this review was to compare the return to play rates (RTPrate) and return to play times (RTPtime) between surgical and rehabilitation interventions in the treatment of AGP. Methods A systematic review of English language peer review journals was carried out between 1980 to June 2013 using PubMed, Embase, CINHAL and Google Scholar searching for all papers relating to AGP (and its various pseudonyms) and all surgical and rehabilitative interventions which reported RTPrate and/or RTPtime. AGP literature has been subdivided by many eponymous diagnoses but anatomical diagnostic groupings of (1) abdominal wall, (2) adductor and (3) pubic related pain were used in this review. Meta-analysis was then carried out on the data to compare results between the surgical and rehabilitation groups. Results Fifty-six papers out of the 561 discovered in the initial search were included in the review with 3332 athletes included. Evidence was mostly level IV. Using the Black and Downs checklist we found poor study quality overall with a high risk of bias especially among surgical studies. The results showed comparable RTPrate between surgical and rehabilitative interventions within the three diagnostic groups. Rehabilitation had significantly quicker RTPtime for pubic related groin pain compared to surgery (10.5 weeks and 23.1 weeks respectively). The abdominal group had the fastest return of the three groups for the rehabilitation and surgery. Conclusions The review suggested better outcomes with rehabilitation for pubic-related groin pain with no difference between the adductor and abdominal groups. The review highlighted the poor quality and risk of bias in the literature making accurate comparison difficult.
Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor
Authors: Aanchal Kakkar, Kavneet Kaur, Tarun Kumar, Libin Babu Cherian, Rohit Kaushal, Mehar Chand Sharma, Anita Dhar, Amlesh Seth, Deepali Jain
Journal: Endocrine Pathology (2015)
Health committee backs sugar tax on soft drinks in fight against child obesity
Authors: Adrian O’Dowd
Journal: BMJ (2015)

MPs have called for a sugar tax of 20% on full sugar soft drinks as one of many measures needed to tackle the growing “crisis” of childhood obesity in the United Kingdom.

In a report1 by the parliamentary health committee published on 30 November MPs said that the sheer scale of childhood obesity demanded that the government take “bold and urgent” action on many fronts. The Department of Health is due to publish its “plans for action” on the issue in the next few months in a childhood obesity strategy.

MPs said that various measures were needed to deal with the problem, including the sugar tax; stronger controls on price promotions, marketing, and advertising of unhealthy food and drink; universal school food standards; clearer labelling of products; and a national reformulation …