tbuckley/cabot-search huggingface dataset:
The impact of psychological readiness to return to sport and recreational activities after anterior cruciate ligament reconstruction
Authors: Clare L Ardern, Annika Österberg, Sofi Tagesson, Håkan Gauffin, Kate E Webster, Joanna Kvist
Journal: British Journal of Sports Medicine (2014)

Background This cross-sectional study aimed to examine whether appraisal of knee function, psychological and demographic factors were related to returning to the preinjury sport and recreational activity following anterior cruciate ligament (ACL) reconstruction. Method 164 participants completed a questionnaire battery at 1–7 years after primary ACL reconstruction. The battery included questionnaires evaluating knee self-efficacy, health locus of control, psychological readiness to return to sport and recreational activity, and fear of reinjury; and self-reported knee function in sport-specific tasks, knee-related quality of life and satisfaction with knee function. The primary outcome was returning to the preinjury sport or recreational activity. Results At follow-up, 40% (66/164) had returned to their preinjury activity. Those who returned had more positive psychological responses, reported better knee function in sport and recreational activities, perceived a higher knee-related quality of life and were more satisfied with their current knee function. The main reasons for not returning were not trusting the knee (28%), fear of a new injury (24%) and poor knee function (22%). Psychological readiness to return to sport and recreational activity, measured with the ACL-Return to Sport after Injury scale (was most strongly associated with returning to the preinjury activity). Age, sex and preinjury activity level were not related. Conclusions Less than 50% returned to their preinjury sport or recreational activity after ACL reconstruction. Psychological readiness to return to sport and recreation was the factor most strongly associated with returning to the preinjury activity. Including interventions aimed at improving this in postoperative rehabilitation programmes could be warranted to improve the rate of return to sport and recreational activities.
Progressive Resistance to Apoptosis in a Cell Lineage Model of Human Proliferative Breast Disease
Authors: S. L. Starcevic, C. Elferink, R. F. Novak
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Proliferative breast disease (PBD) may increase a woman's risk of developing breast cancer, perhaps by decreasing cellular sensitivity to apoptosis. To determine whether resistance to apoptosis develops during PBD, we investigated apoptosis initiated through the Fas pathway in a series of cell lines that recapitulates the morphologic changes of PBD in nude/beige mice. Methods: The series of cell lines used was MCF-10A cells (parental preneoplastic human breast epithelial cells), MCF-10AT cells (transformed with T24 Ha-ras), and MCF-10ATG3B cells (derivative cells that progress to carcinoma). Fas-mediated apoptosis, induced when a Fas monoclonal antibody bound to and activated the Fas receptor on these cells, was assessed morphologically and by flow cytometry. Levels of proteins involved in Fas-mediated apoptosis and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP), an end product of caspase activation, were determined by immunoblotting. Bcl-2 and Bax heterodimerization was examined by coimmunoprecipitation. All statistical tests were two-sided. Results: Sensitivity to Fas-mediated apoptosis decreased with the tumorigenic potential of cells: MCF-10A cells were extremely susceptible, MCF-10AT cells were less susceptible, and MCF-10ATG3B cells were resistant. The percentage of apoptotic cells declined, from 24% to 8% to 6%, respectively. All lines produced Fas ligand (FasL) and had comparable levels of Fas receptor, FasL, Fas-associated death-domain protein, and caspases 3 and 6. Levels of caspase 8 were similar in MCF-10A and MCF-10AT cells but about 30% lower in MCF-10ATG3B cells (P>.01 but <.05). Levels of caspase 10 were about 20% lower in MCF-10AT cells (P>.005 but <.01) and about 59% lower in MCF-10ATG3B cells than in MCF-10A cells (P>.01 but <.05). PARP cleavage was detected in MCF-10A and MCF-10AT cells but not in MCF-10ATG3B cells. Levels of Bax, Bid, and Bak proteins were similar in all lines, but levels of Bcl-2 were lower in MCF-10AT and MCF-10ATG3B cells than in MCF-A cells, and Bcl-2–Bax heterodimerization progressively declined in the series. Conclusion: Resistance to Fas-mediated apoptosis appears to develop progressively in the MCF-10AT cell series.
Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes
Authors: James F. List, Vincent Woo, Enrique Morales, Weihua Tang, Fred T. Fiedorek
Journal: Diabetes Care (2008)

OBJECTIVE Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks. The primary objective was to compare mean change from baseline in A1C. Other objectives included comparison of changes in fasting plasma glucose (FPG), weight, adverse events, and laboratory measurements. RESULTS After 12 weeks, dapagliflozin induced moderate glucosuria (52–85 g urinary glucose/day) and demonstrated significant glycemic improvements versus placebo (ΔA1C −0.55 to −0.90% and ΔFPG −16 to −31 mg/dl). Weight loss change versus placebo was −1.3 to −2.0 kg. There was no change in renal function. Serum uric acid decreased, serum magnesium increased, serum phosphate increased at higher doses, and dose-related 24-h urine volume and hematocrit increased, all of small magnitude. Treatment-emergent adverse events were similar across all groups. CONCLUSIONS Dapagliflozin improved hyperglycemia and facilitates weight loss in type 2 diabetic patients by inducing controlled glucosuria with urinary loss of ∼200–300 kcal/day. Dapagliflozin treatment demonstrated no persistent, clinically significant osmolarity, volume, or renal status changes.
The Evolution of Type 1 Diabetes
Authors: Jay S. Skyler, Jay M. Sosenko
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Microfibrillar elements in the synovial joint: presence of type VI collagen and fibrillin-containing microfibrils.
Authors: A D Waggett, C M Kielty, C A Shuttleworth
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--The aims were to isolate and positively identify the microfibrillar elements which have been observed in the synovial lining. In addition, synovial fluid was examined for these elements to improve the understanding of the role of these structures in health and disease. METHODS--Bacterial collagenase digestion of bovine synovial linings and human and bovine synovial fluids was used to release intact, non-denatured microfibrillar elements. The microfibrils were isolated by Sepharose CL-2B chromatography and viewed by rotary shadowing. They were characterised by immunogold labelling with specific antibodies. RESULTS--Intact type VI collagen microfibrils and fibrillin-containing microfibrils were isolated and positively identified in the synovial lining from bovine ankle joints by immunogold labelling. Type VI collagen microfibrils were also present in the synovial fluid. CONCLUSIONS--The role of the microfibrillar elements in vivo is not fully understood, but their distribution in the synovial lining suggests they have an important role in the mechanical and physical properties of this tissue. The presence of type VI collagen microfibrils in synovial fluid poses the intriguing possibility that it may represent a product of microfibril turnover and a potential early marker for rheumatoid arthritis. Alternatively, type VI collagen may be specifically secreted into the synovial fluid to interact with hyaluronan and form part of the structure of synovial fluid.
Survivin Mediates Renal Proximal Tubule Recovery from AKI
Authors: Jianchun Chen, Jian-Kang Chen, Edward M. Conway, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2013)

AKI induces the renoprotective upregulation of survivin expression in kidney epithelial cells, but the underlying mechanisms have not been identified. To determine the role of survivin in renal recovery from AKI, we generated mice with renal proximal tubule-specific deletion of survivin (survivinptKO). Renal survivin expression increased substantially in response to ischemia-reperfusion (I/R) injury in control littermates but remained minimal in survivinptKO mice. Functional and histologic data indicated similar degrees of renal injury in survivinptKO and control mice 24 hours after reperfusion, but recovery was markedly delayed in survivinptKO mice. In MCT cells, a mouse renal proximal tubule cell line, ATP depletion by antimycin A treatment upregulated survivin expression through a phospho-STAT3–dependent pathway. In wild-type mice, inhibition of STAT3 kinase diminished I/R-induced upregulation of STAT3 phosphorylation and survivin expression and delayed recovery. Furthermore, I/R injury activated Notch-2 signaling, and a γ-secretase inhibitor suppressed I/R-induced Notch-2 signaling, STAT3 phosphorylation, and survivin expression and delayed recovery. In MCT cells, inhibition of γ-secretase similarly attenuated antimycin A-induced Notch-2 activation, upregulation of survivin, and phosphorylation of STAT3, but STAT3 kinase inhibition did not prevent Notch-2 activation. Therefore, these data suggest that STAT3 phosphorylation and subsequent upregulation of survivin expression mediated by Notch-2 signaling in renal proximal tubule epithelial cells aid in the functional and structural recovery of the kidney from AKI.
ELECTRICAL SYNAPSES IN THE MAMMALIAN BRAIN
Authors: Barry W. Connors, Michael A. Long
Journal: Annual Review of Neuroscience (2004)

Many neurons in the mammalian central nervous system communicate through electrical synapses, defined here as gap junction-mediated connections. Electrical synapses are reciprocal pathways for ionic current and small organic molecules. They are often strong enough to mediate close synchronization of subthreshold and spiking activity among clusters of neurons. The most thoroughly studied electrical synapses occur between excitatory projection neurons of the inferior olivary nucleus and between inhibitory interneurons of the neocortex, hippocampus, and thalamus. All these synapses require the gap junction protein connexin36 (Cx36) for robust electrical coupling. Cx36 appears to interconnect neurons exclusively, and it is expressed widely along the mammalian neuraxis, implying that there are undiscovered electrical synapses throughout the central nervous system. Some central neurons may be electrically coupled by other connexin types or by pannexins, a newly described family of gap junction proteins. Electrical synapses are a ubiquitous yet underappreciated feature of neural circuits in the mammalian brain.
In Benign Barrett's Epithelial Cells, Acid Exposure Generates Reactive Oxygen Species That Cause DNA Double-Strand Breaks
Authors: Hui Ying Zhang, Kathy Hormi-Carver, Xi Zhang, Stuart J. Spechler, Rhonda F. Souza
Journal: Cancer Research (2009)

Abstract Cells that sustain double-strand breaks (DSB) can develop genomic instability, which contributes to carcinogenesis, and agents that cause DSBs are considered potential carcinogens. We looked for evidence of acid-induced DNA damage, including DSBs, in benign Barrett's epithelial (BAR-T) cell lines in vitro and in patients with Barrett's esophagus in vivo. In BAR-T cells, we also explored the mechanisms underlying acid-induced DNA damage. We exposed BAR-T cells to acid in the presence of a fluorescent probe for reactive oxygen species (ROS) and in the presence or absence of disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (which prevents intracellular acidification) and N-acety-l-cysteine (a scavenger of ROS). DSBs were detected by Western blotting and immunofluorescence for histone H2AX phosphorylation and by CometAssay. During endoscopy in patients with Barrett's esophagus, we took biopsy specimens from the metaplastic mucosa before and after esophageal perfusion with 0.1 N HCl for 3 min and sought DSBs by Western blotting for histone H2AX phosphorylation. In BAR-T cells, acid exposure resulted in ROS production and caused a time-dependent increase in levels of phospho-H2AX that continued for at least 48 h. Pretreatment with disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate or N-acety-l-cysteine prevented the acid-induced increase in phospho-H2AX levels. DSBs also were detected in biopsy specimens of Barrett's metaplasia following esophageal acid perfusion in all of 6 patients with Barrett's esophagus. Acid exposure causes DSBs in Barrett's epithelial cells through ROS produced as a consequence of intracellular acidification. These findings suggest that acid can be considered a carcinogen in Barrett's esophagus. [Cancer Res 2009;69(23):9083–9]
Ageing and social rank effects on the reproductive system of free-ranging yellow baboons (Papio cynocephalus) at Mikumi National Park, Tanzania
Authors: S. Wasser
Journal: Human Reproduction Update (1998)

Ageing and social status effects on reproductive condition are examined in 106 wild female baboons from 1974 to 1997. The mean duration of each reproductive state (follicular and luteal phase components, pregnancy and lactation) was examined per female, using a repeated measures analysis of variance across each of four age classes (3-6, 7-10, 11-14, and 15-20+ year olds) and dominance rank quartiles. The sex-skin swelling portion of the follicular phase increased whereas the fully swollen portion decreased in duration with advancing age and with low dominance rank. The detumescing portion of the luteal phase increased with advancing age, being most pronounced in lowest ranking females. The number of cycles to conception decreased with age, with no dominance rank effect. However, owing to variation in lactation duration, the interbirth interval was unaffected by age but was shorter in high ranking females. The miscarriage rate was unaffected by age but increased as female rank declined. Age and rank effects became significantly more pronounced in response to a crash in the study population between 1987 and 1993. In conclusion, age- and rank-related reproductive changes in baboons, like those in humans, appear to represent attempts to compensate endocrinologically for accelerated ovarian atresia and increased environmental hardship.
Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest
Authors: Michael P.W. Grocott, Daniel S. Martin, Denny Z.H. Levett, Roger McMorrow, Jeremy Windsor, Hugh E. Montgomery
Journal: New England Journal of Medicine (2009)

The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest.We obtained samples of arterial blood from 10 climbers during their ascent to and descent from the summit of Mount Everest. The partial pressures of arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)), pH, and hemoglobin and lactate concentrations were measured. The arterial oxygen saturation (SaO(2)), bicarbonate concentration, base excess, and alveolar-arterial oxygen difference were calculated.PaO(2) fell with increasing altitude, whereas SaO(2) was relatively stable. The hemoglobin concentration increased such that the oxygen content of arterial blood was maintained at or above sea-level values until the climbers reached an elevation of 7100 m (23,294 ft). In four samples taken at 8400 m (27,559 ft)--at which altitude the barometric pressure was 272 mm Hg (36.3 kPa)--the mean PaO(2) in subjects breathing ambient air was 24.6 mm Hg (3.28 kPa), with a range of 19.1 to 29.5 mm Hg (2.55 to 3.93 kPa). The mean PaCO(2) was 13.3 mm Hg (1.77 kPa), with a range of 10.3 to 15.7 mm Hg (1.37 to 2.09 kPa). At 8400 m, the mean arterial oxygen content was 26% lower than it was at 7100 m (145.8 ml per liter as compared with 197.1 ml per liter). The mean calculated alveolar-arterial oxygen difference was 5.4 mm Hg (0.72 kPa).The elevated alveolar-arterial oxygen difference that is seen in subjects who are in conditions of extreme hypoxia may represent a degree of subclinical high-altitude pulmonary edema or a functional limitation in pulmonary diffusion.
Patterns of Expression of Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase and Phospholamban mRNAs During Rat Heart Development
Authors: Antoon F. M. Moorman, Jacqueline L. M. Vermeulen, Maren U. Koban, Ketty Schwartz, Wouter H. Lamers, Kenneth R. Boheler
Journal: Circulation Research (1995)

Abstract This study reports the clonal analysis and sequence of rat phospholamban (PLB) cDNA clones and the temporal appearance and patterns of distribution of the mRNAs encoding sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA2) and PLB in the developing rat heart determined by in situ hybridization. Both proteins play a critical role in the contraction-relaxation cycle of the heart. SERCA2 mRNA is already abundantly present in the first stage studied, in the cardiogenic plate of the 9-day-old presomite embryo, before the occurrence of the first contractions. This very early expression makes it an excellent marker for the study of early heart development. Subsequently, SERCA2 mRNA becomes expressed in a craniocaudal gradient, being highest at the venous pole and decreasing in concentration toward the arterial pole of the heart. PLB mRNA can be detected in hearts from 12 days of development onward in a virtually opposite gradient. In essence, these patterns do not change during further development. PLB mRNA levels remain highest in the ventricle and outflow tract, whereas SERCA2 mRNA prevails in the inflow tract and atrium, although the difference between atrium and ventricle becomes less pronounced. These observations are compatible with a model in which the upstream part of the heart (inflow tract and atrium) would have a greater capacity to clear calcium and hence would have a longer duration of the diastole than the downstream compartments (atrioventricular canal, ventricle, and outflow tract), similar to the observed pattern of contraction of the embryonic heart. The sinoatrial and atrioventricular nodes do not reveal an expression pattern of SERCA2 and PLB mRNA that allows one to distinguish them from the surrounding atrial working myocardium. However, the ventricular part of the conduction system, comprising atrioventricular bundle and bundle branches, are almost devoid of SERCA2 mRNA.
Procoagulant and proinflammatory activity in acute coronary syndromes
Authors: A Manten
Journal: Cardiovascular Research (1998)

Objectives: Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes. Methods: Thrombin–antithrombin III (TAT), prothrombin fragments F1+2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA). Results: FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p=0.0015 and p<0.0001), and were higher in patients with AMI than UA (p=0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p=0.0020 and p<0.001), and again were higher in AMI than UA (p=0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1+2 and IL-8 levels were not different between the three groups. Conclusions: IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA+AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.
Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes
Authors: Maria Rosaria Rizzo, Michelangela Barbieri, Raffaele Marfella, Giuseppe Paolisso
Journal: Diabetes Care (2012)

Evaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, known to have different efficacy on mean amplitude of glycemic excursions (MAGE), on oxidative stress, and on systemic inflammatory markers in patients with type 2 diabetes.A prospective, randomized, open-label PROBE design (parallel group with a blinded end point) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin. The study assigned 45 patients to receive sitagliptin (100 mg once daily; sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice daily; vildagliptin group) for 12 weeks. MAGE, evaluated during 48 h of continuous subcutaneous glucose monitoring, allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients. Assessment of oxidative stress (nitrotyrosine) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients.HbA(1c), fasting and postprandial glucose, MAGE, and inflammatory and oxidative stress markers were similar between the groups at baseline. After 12 weeks, MAGE (P < 0.01) was lower in the vildagliptin group than in the sitagliptin group. After treatment, HbA(1c) and postprandial glucose evidenced similar changes between the groups (P = NS). Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine (P < 0.01), IL-6 (P < 0.05), and IL-18 (P < 0.05) than sitagliptin treatment. Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA(1c).MAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients. These effects were greater in the vildagliptin group than in the sitagliptin group.