tbuckley/cabot-search huggingface dataset:
Relative location of alpha- and beta-adrenoceptors to sites of release of sympathetic transmitter in the rabbit facial vein.
Authors: R J Winquist, J A Bevan
Journal: Circulation Research (1981)

We studied alpha- and beta-adrenoceptor-mediated responses of rabbit facial vein rings to adrenergic stimulation to determine the location of the two types of receptors in relation to the sympathetic nerve terminals. Transmural electrical nerve stimulation (TNS) at low frequency elicited large beta-receptor-mediated relaxation responses in rings pretreated with phentolamine (6 x 10(-7)M). These responses were significantly greater than the corresponding alpha-receptor-mediated contractions in rings pretreated with propranolol (10(-6)M). Blockade of neuronal uptake with desmethylimipramine (DMI, 10(-7)M) increased significantly the neurogenic relaxation but had little effect on neurogenic contractility. DMI pretreatment caused a shift to the left (x 5.6) in the relaxant dose-response curve to exogenous l-norepinephrine (NE). The NE contractile dose-response curve was also shifted to the left after DMI pretreatment but by a significantly smaller amount (x 3.1). Neurogenic activation of beta-receptors evoked almost maximal relaxations in facial vein rings (85% at 2 Hz), whereas the maximum neurogenic contraction was approximately half the maximum contraction with exogenous NE (40% at 6 Hz). These results imply that the beta-adrenoceptors in the rabbit facial vein are located in close proximity to sites of adrenergic transmitter release and neuronal reuptake, whereas the alpha-receptors are more distant.
Delayed diagnosis of dyskeratosis congenita in a 40-year-old woman with multiple head and neck squamous cell carcinomas
Authors: M. Castori, C. Ceccarini, D. Castiglia, S. Ruggeri, B. Dallapiccola, G. Zambruno
Journal: British Journal of Dermatology (2007)

Journal Article Delayed diagnosis of dyskeratosis congenita in a 40‐year‐old woman with multiple head and neck squamous cell carcinomas Get access M. Castori, M. Castori IRCCS‐CSS San Giovanni Rotondo and CSS‐Mendel Institute, Viale Regina Margherita 261, 00198 Rome, ItalyDepartment of Experimental Medicine and Pathology, University 'La Sapienza', Viale Regina Elena 324, 00161 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar C. Ceccarini, C. Ceccarini IRCCS‐CSS San Giovanni Rotondo and CSS‐Mendel Institute, Viale Regina Margherita 261, 00198 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar D. Castiglia, D. Castiglia Laboratory of Molecular and Cell Biology and Search for other works by this author on: Oxford Academic Google Scholar S. Ruggeri, S. Ruggeri VIII Division of Dermatology, Istituto Dermopatico dell'Immacolata, IRCCS, Via Monti di Creta 104, 00167 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar B. Dallapiccola, B. Dallapiccola IRCCS‐CSS San Giovanni Rotondo and CSS‐Mendel Institute, Viale Regina Margherita 261, 00198 Rome, ItalyDepartment of Experimental Medicine and Pathology, University 'La Sapienza', Viale Regina Elena 324, 00161 Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Zambruno G. Zambruno Laboratory of Molecular and Cell Biology and Correspondence: Giovanna Zambruno. E‐mail: g.zambruno@idi.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 2, 1 February 2007, Pages 406–408, https://doi.org/10.1111/j.1365-2133.2006.07661.x Published: 01 February 2007
Reversible De Novo Left Ventricular Trabeculations in Pregnant Women
Authors: Sabiha Gati, Michael Papadakis, Nikolaos D. Papamichael, Abbas Zaidi, Nabeel Sheikh, Matthew Reed, Rajan Sharma, Baskaran Thilaganathan, Sanjay Sharma
Journal: Circulation (2014)

Background— Patients with heart failure and chronic anemia frequently demonstrate left ventricular (LV) trabeculations, which may be compatible with the diagnosis of LV noncompaction. We used the pregnancy model, which is characterized by a reversible increase in cardiac preload and other changes in cardiac function, to assess the development of de novo LV trabeculations in women with morphologically normal hearts. Methods and Results— One hundred two primigravida pregnant women were evaluated longitudinally with a series of echocardiograms in the first trimester, in the third trimester, and postpartum. Echocardiograms were analyzed according to established guidelines. Increased LV trabeculations and the presence of LV noncompaction were based on established criteria. Pregnancy was associated with an increased heart rate, stroke volume, and cardiac output, as well as increased LV volume and mass. During pregnancy, 26 women (25.4%) developed increased trabeculations. Eight women showed sufficient trabeculations to fulfill criteria for LV noncompaction. During the postpartum follow-up period of 24±3 months, 19 women (73%) demonstrated complete resolution of trabeculations, and 5 showed a marked reduction in the trabeculated layer. Conclusions— Pregnancy induces de novo LV trabeculations in a significant proportion of women. The results suggest that LV trabeculations occur in response to increased LV loading conditions or other physiological responses to pregnancy and are not specific for LV noncompaction. These factors should be considered in the assessment of individuals with LV trabeculations outside the context of symptoms of heart failure or familial cardiomyopathy.
Use of molecular beacons to verify that the serine hydroxymethyltransferase pseudogene SHMT-ps1 is unique to the order Primates.
Authors: Eric J Devor
Journal: Genome biology (2001)

The serine hydroxymethyltransferase processed pseudogene SHMT-ps1 has been suggested to be unique to the order Primates because of the failure to amplify this sequence by PCR from genomic DNAs of any non-primate mammal species. Here, 'molecular beacon' probes specific to SHMT-ps1 were used in an attempt to verify this suggestion.In a search for SHMT-ps1-specific sequences using molecular beacons across a range of mammalian species, SHMT-ps1 was only found in primates. The molecular beacon assays also showed that SHMT-ps1 is present in both Old World and New World species but not among prosimians.These results suggest that SHMT-ps1 originated close to the origin of the Anthropoidea, some 40 to 50 million years ago.
Differential Expression of Calcineurin A Isoforms in the Diabetic Kidney
Authors: Jennifer L. Gooch, Pablo E. Pe[Combining Grave Accent]rgola, Rebecca L. Guler, Hanna E. Abboud, Jeffrey L. Barnes
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Calcineurin is an important signaling molecule in mesangial cells in vitro and is involved in some manifestations of diabetic nephropathy in vivo. However, calcineurin acts in a cell-specific and tissue-specific manner in the kidney, and mechanisms of specificity are unknown. Three closely related isoforms of the calcineurin A (CnA) subunit are expressed in a tissue-specific manner. This study was undertaken to determine if specificity of calcineurin action is linked to regulation of CnA isoforms in the diabetic kidney. After induction of diabetes with streptozotocin, expression of all three CnA isoforms rapidly increased, primarily in the thick ascending limb of Henle (TAL). After prolonged diabetes, increase specifically of the α isoform was observed in collecting ducts (CD) and in endothelial cells of glomeruli. Aquaporin 2 (AQP2), a putative substrate of calcineurin phosphatase in the kidney, is also involved in diabetic nephropathy. Co-localization of CnA isoforms with AQP2 revealed that CnA-α is the predominant isoform that associates with AQP2 in the diabetic kidney. Furthermore, inhibition of calcineurin with cyclosporin A (CsA) alters AQP2 localization and phosphorylation in principal cells of CD. Alterations in subcellular localization of AQP2 were parallel with CnA-α. Similarly, CsA treatment results in a further increase in urine output compared with diabetes alone, suggesting a functional consequence of inhibiting calcineurin-mediated regulation of AQP2. In conclusion, all three isoforms of CnA are upregulated in the diabetic kidney. Increased expression of CnA-α, in particular, is observed in glomeruli and CD and participates in regulation of AQP2 expression, phosphorylation, and function.
Detection of Circulating miRNA Levels in Schizophrenia
Authors: Hui Wei, Yanbo Yuan, Sha Liu, Cheng Wang, Fude Yang, Zheng Lu, Chuanyue Wang, Hong Deng, Jinping Zhao, Yan Shen, Chenyu Zhang, Xin Yu, Qi Xu
Journal: American Journal of Psychiatry (2015)

Objective: Diagnosis of schizophrenia is currently dependent on symptom-based criteria and lacks objective indicators. In this study, the authors investigated whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia. Methods: Global plasma miRNAs were profiled in a test cohort of 164 schizophrenia patients and 187 control subjects, using Solexa sequencing, TaqMan Low Density Array, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The captured miRNAs were then validated by qRT-PCR assays in an independent cohort of 400 schizophrenia patients, 213 control subjects, and 162 patients with nonschizophrenia psychiatric disorders; the 400 schizophrenia patients underwent a 12-month follow up study of regular treatment with an atypical antipsychotic (risperidone and aripiprazole). Results: The global plasma miRNA screening revealed eight miRNAs that were up-regulated in schizophrenia, as revealed by both assay platforms. The qRT-PCR analysis showed the up-regulation of miR-130b and miR-193a-3p in schizophrenia but not in nonschizophrenia disorders. Conclusions: The up-regulation of miR-130b and miR-193a-3p is a state-independent biomarker for schizophrenia, and these two miRNAs could be used to develop a diagnostic tool for schizophrenia.
Blunt traumatic rupture of the thoracic oesophagus.
Authors: C P Young, S R Large, S J Edmondson
Journal: Thorax (1988)

A man with a crush injury of his upper abdomen developed bilateral pulmonary empyema after repair of tears of the oesophagus and liver. Attempts to withdraw chest drains led to recurrent septicaemia, treated by reinsertion of the drains plus administration of antibiotics. The communication of the empyema space with both the bronchial tree and the oesophagus was managed successfully with intermittent positive pressure ventilation and with a double lumen endobronchial tube isolating the right lung for 10 days. Traumatic rupture of the thoracic oesophagus carries a high mortality and prompt repair is vital.
Tasimelteon for non-24-hour sleep–wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials
Authors: Steven W Lockley, Marlene A Dressman, Louis Licamele, Changfu Xiao, Dennis M Fisher, Erin E Flynn-Evans, Joseph T Hull, Rosarelis Torres, Christian Lavedan, Mihael H Polymeropoulos
Journal: The Lancet (2015)
Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY)
Authors: Maxime Dougados, Karsten Kissel, Tom Sheeran, Paul P Tak, Philip G Conaghan, Emilio Martín Mola, Georg Schett, Howard Amital, Federico Navarro-Sarabia, Antony Hou, Corrado Bernasconi, TWJ Huizinga
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy. <h3>Methods</h3> Double-blind, 2-year study in which adults with active RA (DAS28 &gt;4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28–erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage. <h3>Results</h3> Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28–ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant–Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively. <h3>Conclusion</h3> No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.
How to read a paper: Statistics for the non-statistician. II: "Significant" relations and their pitfalls
Authors: T. Greenhalgh
Journal: BMJ (1997)

This article continues the checklist of questions that will help you to appraise the statistical validity of a paper. The first of this pair of articles was published last week.1 Has correlation been distinguished from regression, and has the correlation coefficient ( r value) been calculated and interpreted correctly? For many non-statisticians, the terms "correlation" and "regression" are synonymous, and refer vaguely to a mental image of a scatter graph with dots sprinkled messily along a diagonal line sprouting from the intercept of the axes. You would be right in assuming that if two things are not correlated, it will be meaningless to attempt a regression. But regression and correlation are both precise statistical terms which serve quite different functions.1 The r value (Pearson's product-moment correlation coefficient) is among the most overused statistical instrument. Strictly speaking, the r value is not valid unless the following criteria are fulfilled: #### Summary points An association between two variables is likely to be causal if it is strong, consistent, specific, plausible, follows a logical time sequence, and shows a dose-response gradient A P value of <0.05 means that this result would have arisen by chance on less than one occasion in 20 The confidence interval around a result in a clinical trial indicates the limits within which the "real" difference between the treatments is likely to lie, and hence the strength of the inference that can be drawn from the result A statistically significant result may not be clinically significant. The results of intervention trials should be expressed in terms of the likely benefit an individual could expect (for example, the absolute risk reduction)
The complexity of the cardio–renal link: taxonomy, syndromes, and diseases
Authors: Carmine Zoccali, David Goldsmith, Rajiv Agarwal, Peter J. Blankestijn, Danilo Fliser, Andrzej Wiecek, Gultekin Suleymanlar, Alberto Ortiz, Ziad Massy, Adrian Covic, Alberto Martinez-Castelao, Kitty J. Jager, Friedo W. Dekker, Bengt Lindholm, Gerard London
Journal: Kidney International Supplements (2011)
Error, stress, and teamwork in medicine and aviation: cross sectional surveys
Authors: J B Sexton, E J Thomas, R L Helmreich
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To survey operating theatre and intensive care unit staff about attitudes concerning error, stress, and teamwork and to compare these attitudes with those of airline cockpit crew. <b>Design:</b> Cross sectional surveys. <b>Setting:</b> Urban teaching and non-teaching hospitals in the United States, Israel, Germany, Switzerland, and Italy. Major airlines around the world. <b>Participants:</b> 1033 doctors, nurses, fellows, and residents working in operating theatres and intensive care units and over 30 000 cockpit crew members (captains, first officers, and second officers). <b>Main outcome measures:</b> Perceptions of error, stress, and teamwork. <b>Results:</b> Pilots were least likely to deny the effects of fatigue on performance (26% <i>v</i>70% of consultant surgeons and 47% of consultant anaesthetists). Most pilots (97%) and intensive care staff (94%) rejected steep hierarchies (in which senior team members are not open to input from junior members), but only 55% of consultant surgeons rejected such hierarchies. High levels of teamwork with consultant surgeons were reported by 73% of surgical residents, 64% of consultant surgeons, 39% of anaesthesia consultants, 28% of surgical nurses, 25% of anaesthetic nurses, and 10% of anaesthetic residents. Only a third of staff reported that errors are handled appropriately at their hospital. A third of intensive care staff did not acknowledge that they make errors. Over half of intensive care staff reported that they find it difficult to discuss mistakes. <b>Conclusions:</b> Medical staff reported that error is important but difficult to discuss and not handled well in their hospital. Barriers to discussing error are more important since medical staff seem to deny the effect of stress and fatigue on performance. Further problems include differing perceptions of teamwork among team members and reluctance of senior theatre staff to accept input from junior members.
First nicastrin mutation in <scp>PASH</scp> (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome
Authors: S. Duchatelet, S. Miskinyte, O. Join‐Lambert, M.‐N. Ungeheuer, C. Francès, A. Nassif, A. Hovnanian
Journal: British Journal of Dermatology (2015)

Funding sources: This work was supported by Fondation pour la Recherche Médicale (ROXANNE project, LMV20100519581). Conflicts of interest: none declared. Dear Editor, PASH (pyoderma gangrenosum, acne and suppurative hidradenitis) syndrome is a new clinical entity associating pyoderma gangrenosum (PG), severe acne and hidradenitis suppurativa (HS).1 The absence of pyogenic sterile arthritis (PA) distinguishes PASH syndrome from PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa) and PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndromes, which exhibit PA in combination with PG, severe acne with or without HS, respectively.2 3 Mutations in the coding region of the proline‐serine‐threonine‐phosphatase interacting protein 1 gene (PSTPIP1) were identified in patients with PAPA and PAPASH syndromes, although PAPA syndrome is genetically heterogenous.2 3 HS (OMIM#142690) is a chronic skin disease characterized by nodules, cysts and abscesses in apocrine gland‐bearing sites. Loss‐of‐function mutations in the γ‐secretase genes, nicastrin (NCSTN), presenilin enhancer gamma secretase subunit (PSENEN) and presenilin 1 (PSEN1), have been reported in a small number of HS cases.4 5 Furthermore, γ‐secretase is an intramembranous protease complex capable of cleaving transmembrane proteins, including Notch receptors.6 Mutations in the γ‐secretase genes may impair Notch signalling, which plays a crucial role in epidermal homeostasis.5 7
Left main coronary artery stenosis: the influence of aortocoronary bypass surgery on survival.
Authors: L Campeau, F Corbara, D Crochet, R Petitclerc
Journal: Circulation (1978)

A retrospective study was carried out in 114 unoperated and 197 operated patients having left main coronary artery (LMCA) stenosis greater than or equal to 50%. Including the operative mortality of 9.1%, survival at seven years was significantly greater following pure aortocoronary bypass graft surgery, 77.5% as compared to 48.5% for the unoperated patients (P less than 0.01). The surgical mortality was significantly less during the last five years (1972-1976), 6.2% as compared to 17% during 1969-1971 (P less than 0.025). The three year survival in patients operated since 1972 was 90.2% as compared to 60.4% for unoperated patients. Survival remained significantly higher in the operated patients when studied as subsets on the basis of the severity of the LMCA stenosis (less than 70% as opposed to greater than or equal to 70%), and on the extent of associated obstructive disease of major coronary arteries (0-1 versus 2-3 arteries). It was significantly higher, however, only in operated patients with associated stenosis greater than or equal to 70% of the right coronary artery. Survival was higher following surgery only when the ejection fraction was at least 0.45, or the left ventricular end-diastolic pressure below 20 mm Hg.
Leptin signalling reduces the severity of cardiac dysfunction and remodelling after chronic ischaemic injury
Authors: Kenneth R. McGaffin, Cheuk-Kwan Sun, Jennifer J. Rager, Lia C. Romano, Baobo Zou, Michael A. Mathier, Robert M. O'Doherty, Charles F. McTiernan, Christopher P. O'Donnell
Journal: Cardiovascular Research (2007)

Leptin is elevated under conditions of both obesity and heart failure (HF), and activation of leptin receptor (ObR) signalling is known to increase in vivo cardiac contractility and to have anti-hypertrophic effects on the left ventricle (LV). However, it is unknown whether ObR signalling is altered in cardiomyocytes after myocardial infarction (MI) leading to HF, or if a deficiency in ObR signalling leads to worse HF.In separate experimental protocols, C57BL/6J and leptin-deficient (ob/ob) mice underwent open-chest surgery to induce permanent left coronary artery ligation (CAL) or had a sham operation. Subgroups of ob/ob mice examined were lean (food-restricted), obese (food-ad libitum), and leptin repleted. Four weeks post-surgery, cardiac structure and function was examined by echocardiography, and the activation of cardiac leptin signalling was characterized through quantitative PCR, western blotting, and DNA-binding activities. CAL produced echocardiographic evidence of HF in C57BL/6J mice, elevated circulating leptin, increased cardiomyocyte leptin and ObR expression, and activated myocardial signal transducer and activator of transcription-3 (STAT3). In leptin-deficient ob/ob mice, whether lean or obese, CAL caused increased hypertrophy and dilation, decreased contractility of the LV, and worsened survival relative to wildtype or leptin-repleted mice after CAL. In ob/ob mice, activation of cardiac STAT3 signalling after CAL is enhanced in the presence of leptin and parallels the induction of the STAT3-responsive genes, tissue-inhibitor of metalloproteinase-1 and heat shock protein-70.These data demonstrate that HF increases ObR signalling in cardiomyocytes and that activation of ObR signalling improves functional outcomes in chronic ischaemic injury leading to HF.
Hypertrophy of the external and sphincter in haemorrhoids: a histometric study.
Authors: T Teramoto, A G Parks, M Swash
Journal: Gut (1981)

Biopsies of the external and sphincter taken from 24 male patients with haemorrhoids were subjected to examination using histochemical techniques. Fibre size (type 1 mean: 33 micrometers +/- 11.0 SD and type 2 mean: 47.9 micrometers +/- 15.0 SD) was increased when compared with control subjects. The distribution of muscle fibre types in these patients showed markedly greater type 1 fibre predominance (92%) than in control subjects. These abnormalities of the external sphincter did not show any clear relationship with age, degree of haemorrhoidal change, length of history of haemorrhoids, history of straining or of constipation, or perineal descent; however, increasing length of history up to 10 years was associated with increasing type 1 fibre predominance. We suggest that the external and sphincter in patients with haemorrhoids is in a state of increase tonic contraction, which causes work induced muscle hypertrophy and may contribute to increased resting pressure in the anal canal in patients with haemorrhoids.