tbuckley/cabot-search huggingface dataset:
Notes from the Field: Outbreak of Cryptosporidiosis Among Veterinary Medicine Students — Philadelphia, Pennsylvania, February 2015
Authors: Lauren N. Drinkard, Ashlee Halbritter, Giang T. Nguyen, Patricia L. Sertich, Max King, Sallyann Bowman, Rebecca Huxta, Mary Guagenti
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

On February 20, 2015, a northeastern university's student health center was notified of five veterinary medicine students with gastrointestinal symptoms. An investigation was conducted to establish the existence of an outbreak, determine the etiology, evaluate risk factors, and recommend control measures.
Diseases of the Reticuloendothelial System and Hematology: Hematological Sciences
Authors: Gurth Carpenter
Journal: Annual Review of Medicine (1952)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Carboplatin Plus Paclitaxel in Unknown Primary Carcinoma: A Phase II Hellenic Cooperative Oncology Group Study
Authors: Evangelos Briasoulis, Haralambos Kalofonos, Dimitris Bafaloukos, Epaminondas Samantas, George Fountzilas, Nikolaos Xiros, Dimosthenis Skarlos, Christos Christodoulou, Paris Kosmidis, Nicholas Pavlidis
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the efficacy of the carboplatin/paclitaxel combination in patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS: Seventy-seven consecutive CUP patients (45 women and 32 men; median age, 60 years) were treated with carboplatin at target area under the curve 6 mg/mL/min followed by paclitaxel 200 mg/m 2 as a 3-hour infusion and granulocyte colony-stimulating factor from days 5 to 12. Treatment courses were repeated every 3 weeks to a maximum of eight cycles. Forty-seven patients had adenocarcinomas, 27 had undifferentiated carcinomas, and three had squamous cell carcinomas. Thirty-three patients presented with liver, bone, or multiple organ metastases, 23 with predominantly nodal/pleural disease, and 19 (16 women) with peritoneal carcinomatosis. RESULTS: The overall response rate by intent-to-treat analysis was 38.7% (95% confidence interval, 27.5% to 49.9%). There were no differences in response between adenocarcinomas and undifferentiated carcinomas, but efficacy varied among clinical subsets. The response rates and median survival times in the three clinically defined subsets were 47.8% and 13 months, respectively, for patients with predominantly nodal/pleural disease, 68.4% and 15 months, respectively, in women with peritoneal carcinomatosis, and 15.1% and 10 months, respectively, in patients with visceral or disseminated metastases. Chemotherapy was well-tolerated. CONCLUSION: Carboplatin plus paclitaxel combination chemotherapy is effective in patients with predominantly nodal/pleural metastases of unknown primary carcinoma and in women with peritoneal carcinomatosis. However, in patients with liver, bone, or multiple organ involvement, the combination offers limited benefit. The investigation of novel treatment approaches is highly warranted for this group of patients.
Adult Asthma Assessment in an Accident &amp; Emergency Department
Authors: A S Coonar, N Nayeem, C P Bonell, S E Shires
Journal: Journal of the Royal Society of Medicine (1994)

Poor initial assessment contributes to morbidity and mortality in acute severe asthma. We have audited this aspect of management in an A & E department over a single 6-month senior house officer employment cycle. The use of a cheap and simple stamp highlighting important clinical features of asthma was associated with a significant improvement in early assessment.
Fli1 deficiency contributes to the downregulation of endothelial protein C receptor in systemic sclerosis: a possible role in prothrombotic conditions
Authors: R. Saigusa, Y. Asano, T. Yamashita, T. Taniguchi, T. Takahashi, Y. Ichimura, T. Toyama, A. Yoshizaki, T. Miyagaki, M. Sugaya, S. Sato
Journal: British Journal of Dermatology (2015)

Endothelial protein C receptor (EPCR), expressed predominantly on endothelial cells, plays a critical role in the regulation of the coagulation system and also mediates various cytoprotective effects by binding and activating protein C. So far, the role of EPCR has not been studied in systemic sclerosis (SSc). To investigate the potential contribution of EPCR to the development of SSc. EPCR expression was examined in skin samples and cultivated dermal microvascular endothelial cells by immunostaining, immunoblotting and/or quantitative reverse‐transcription polymerase chain reaction. Fli1, binding to the PROCR promoter, was assessed by chromatin immunoprecipitation. Serum EPCR levels were determined by enzyme‐linked immunosorbent assay in 65 patients with SSc and 20 healthy subjects. EPCR expression was decreased in dermal small vessels of SSc lesional skin compared with those of healthy control skin. Transcription factor Fli1, deficiency of which is implicated in SSc vasculopathy, occupied the PROCR promoter, and EPCR expression was suppressed in Fli1 small interfering RNA‐treated endothelial cells and dermal small vessels of Fli1+/− mice. In patients with SSc, decreased serum EPCR levels were associated with diffuse skin involvement, interstitial lung disease and digital ulcers. Furthermore, serum EPCR levels inversely correlated with plasma levels of plasmin–α2‐plasmin inhibitor complex (PIC). Importantly, bosentan significantly reversed circulating EPCR and PIC levels in patients with SSc, and the expression of Fli1 and EPCR in dermal small vessels was elevated in patients treated with bosentan compared with untreated patients. Endothelial EPCR downregulation due to Fli1 deficiency may contribute to hypercoagulation status leading to tissue fibrosis and impaired peripheral circulation in SSc.
Protection against pulmonary O2 toxicity by N-acetylcysteine
Authors: P D Wagner, O Mathieu-Costello, D E Bebout, A T Gray, P D Natterson, C Glennow
Journal: European Respiratory Journal (1989)

N-acetylcysteine (NAC) is a known antioxidant. We therefore investigated NAC as an agent protective against O2 toxicity in the lung. Twelve dogs were anaesthetized with sodium pentobarbital and ventilated with 100% O2 for 54 h. Five were given diluent and 7 intravenous NAC (loading dose prior to 100% O2 ventilation of 150 mg.kg-1 and maintenance dose of 20 mg.kg-1.h-1). Every 6 h, physiological evaluation of the pulmonary circulation, mechanical properties, and gas exchange was performed. Post-mortem evaluation consisted of gross examination and weighing followed by light and electron microscopy. By both functional and structural criteria, NAC protected against the effects of 100% O2. The NAC group developed significantly less increase in pulmonary vascular resistance, arterial carbon dioxide tension (PaCO2) and lung wet weight, while dynamic compliance was greater. NAC also delayed the development of abnormal ventilation-perfusion relationships and was associated with reduced pulmonary white cell accumulation, with less evidence of alveolar and interstitial oedema. NAC may well be worthy of evaluation as a therapeutic agent in human diseases characterized by oxidant damage.
Modulation of Azaserine-Induced Pancreatic Foci by Phenolic Antioxidants in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. D. Roebuck, Denise L. MacMillan, Donna M. Bush, Thomas W. Kensler
Journal: JNCI Journal of the National Cancer Institute (1984)

Effects of the dietary phenolic antioxidants butylated hydroxyanisole [(BHA) CAS: 25013-16-5; (1,1-dimethylethyl)-4-methoxyphenol] and butylated hydroxytoluene [(BHT) CAS: 128-37-0; 2,6-di-tert-butyl-p-cresol] on pancreatic tumorigenesis were examined. Male LEW inbred rats were given injections of 30 mg azaserine [CAS: 115-02-6; diazoacetate (ester) serine] per kg body weight once a week for 3 weeks and maintained on either a control diet or 0.45% BHA- or 0.45% BHT-supplemented control diet throughout the initiation and post-initiation phases of the experiment. At 4 months post initiation, pancreatic tissue sections were quantitatively examined for the number and size of preneoplastic foci. BHT and BHA treatments reduced the number of acidophilic foci per pancreas by 32 and 48%, respectively, but were without effect on focal size. By contrast, basophilic foci were not subject to modulation by these antioxidants. A constellation of enzyme activities involved in carcinogen inactivation and known to be perturbed by antioxidant treatment was examined in liver and pancreas. The hepatic activities of glucose-6-phosphate dehydrogenase, glutathione reductase, and glutathione-S-transferases were markedly elevated while catalase and Superoxide dismutase activities were unchanged. Glutathione peroxidase activity was diminished. In the pancreas, only glutathione peroxidase activity was affected, and it was reduced in both the BHA and BHT treatment groups. Although the pancreas is refractory to the enzyme inductive effects of these antioxidants, morphometric analysis of foci demonstrated chemoprevention by BHA and BHT of azaserine-induced foci. Whether this reduction reflected inhibition of an initiation, postinitiation, or a combination of effects was not known.
Antibacterial Properties of Propolis (Bee Glue)
Authors: J M Grange, R W Davey
Journal: Journal of the Royal Society of Medicine (1990)

Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram-negative bacilli. These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content.
Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation
Authors: Matthew W. Sherwood, James D. Douketis, Manesh R. Patel, Jonathan P. Piccini, Anne S. Hellkamp, Yuliya Lokhnygina, Alex C. Spyropoulos, Graeme J. Hankey, Daniel E. Singer, Christopher C. Nessel, Kenneth W. Mahaffey, Keith A. A. Fox, Robert M. Califf, Richard C. Becker
Journal: Circulation (2014)

Background— During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results— In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P =0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P =0.32). Conclusions— TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00403767.
Gas exchange and inspiratory capacity during incremental shuttle and 6-min walk tests in obese women
Authors: Victor Zuniga Dourado, Ricardo Luís Fernandes Guerra
Journal: European Respiratory Journal (2013)

Field walking tests such as the incremental shuttle and 6-min walk tests (ISWT and 6MWT) are simple tools to assess exercise capacity. Although exercise limitation has been described during maximal exercise tests, whether the walking performance is impaired in obese subjects should be better investigated. We aimed to evaluate the walking performance of obese women older than 40 years using ISWT and 6MWT. Twenty-six obese and 17 non-obese women were submitted to the ISWT and 6MWT on alternate days. Oxygen uptake (VO 2 ), CO 2  production (VCO 2 ), ventilation (VE) and heart rate (HR) were continuously measured during the walking tests. The following rates of changes were assessed during the ISWT: ΔVO 2 /Δwalking-velocity (WV), ΔHR/ΔVO 2 , ΔVE/ΔVCO 2 , and linearized Δtidal-volume (VT)/ΔlnVE. Inspiratory capacity (IC) was assessed before and after each test. The obese participants showed significant walking limitation, presenting impaired results in both tests for the distance walked, peaks of VO 2 , HR, pulse O 2 , VCO 2 /VO 2 , VE/VO 2 , and VE/VCO 2 . During the ISWT, obese women presented shallower slopes of ΔVO 2 /ΔWV and ΔVT/ΔlnVE and steepest slopes of ΔHR/ΔVO 2  and ΔVE/ΔVCO 2 , representing worse aerobic, cardiovascular and ventilatory efficiencies, and breathing pattern throughout the exercise. There were no significant differences in IC and its changes between groups. We conclude that middle-aged and older obese women present reduced walking performance. The ISWT and 6MWT seem to be appropriate tests to assess this impairment. Our results suggest that walking-based physical exercise should be encouraged in this population.
Aggressive combined modality therapy for advanced local-regional breast carcinoma.
Authors: C L Loprinzi, P P Carbone, D C Tormey, P R Rosenbaum, W Caldwell, J C Kline, R A Steeves, G Ramirez
Journal: Journal of Clinical Oncology (1984)

Thirty-two women with advanced local regional breast carcinoma, including nine patients with histologically diagnosed inflammatory cancer, were entered on a prospective pilot study. They were treated aggressively with initial surgery, two courses of induction chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, +/- prednisone, +/- tamoxifen (CMF [P] [T]), local-regional radiotherapy, and then maintenance chemotherapy with CMF(P) (T) alternating with doxorubicin, vincristine, +/- tamoxifen (AV[T]). The patients have been followed for 19-70 months from the time of mastectomy and their actuarial three-year survival is 65% with a median survival that has not yet been reached. Median disease-free survival (time to progression) is currently 29.5 months. Women whose gross disease could not be totally resected surgically had shorter disease-free survivals than those rendered surgically free of disease (p = 0.01). Clinically evident cardiotoxicity was seen in 25% of the patients and was felt to be primarily due to the combination of doxorubicin and radiation therapy. It was significantly more common (Plt less than 0.05) in patients with left chest irradiation (seven of 18 women) as opposed to those with right-sided irradiation (one of 14).
Measuring response to antiangiogenic agents
Authors: Michael S. O'Reilly
Journal: Clinical Cancer Research (2006)

PL-40   Angiogenesis is critical for a number of physiologic and pathophysiologic processes and several lines of direct evidence confirm that tumor growth is angiogenesis dependent. A number of antiangiogenic agents have been described and several are currently in clinical trials in cancer patients. Bevacizumab, an antibody that targets the proangiogenic molecule vascular endothelial growth factor (VEGF), is now approved for clinical use as part of combined modality therapy for patients with metastatic colorectal cancer and has also shown efficacy when combined with chemotherapy in Phase III clinical trials for breast and lung cancer patients. Orally available small molecules can also be used to target VEGF and other receptor tyrosine kinases involved in angiogenesis. Two of the most widely studied targets are epidermal growth factor (EGFR) and VEGFR. However, clinical trials of agents that target either of these pathways alone have been disappointing. Although antiangiogenic agents show great promise, their clinical use, particularly when administered as monotherapy, may be associated with a number of potential limitations including a delayed onset of antitumor activity and the potential for persistent microscopic residual disease even after prolonged high dose administration. Further, the specific organ microenvironment of a given malignancy may influence response to antiangiogenic, antivascular, and other biologic therapies. For patients with advanced malignancy, the limitations of antiangiogenic monotherapy will necessitate a combined modality approach and surrogates of response to therapy need to be developed and validated. To overcome the limitations of antiangiogenic monotherapy, angiogenesis inhibitors can and should be combined with radiation therapy, chemotherapy and/or other therapeutic modalities. In preclinical and clinical studies, antiangiogenic therapy enhances the effects of radiotherapy and chemotherapy although the degree of enhancement may be dependent upon the sequencing of each modality and upon the tumor microenvironment. By developing a rational basis for the combination of antiangiogenic agents with conventional therapies, improved efficacy and diminished toxicity in the treatment of cancer will be possible. The endothelial cell can now be considered as one gatekeeper capable of regulating tumor growth and it will be prudent to use angiogenesis inhibitors in combination with other modalities in order to overcome the limits of each. To accomplish this goal, a better understanding of the regulation of angiogenesis is needed and strategies for the use of antiangiogenic agents may need to be optimized on a site, disease, and perhaps patient specific basis. By doing so, cancer can be transformed into a chronic and controllable disease.
Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.
Authors: K Warzocha, G Salles, J Bienvenu, Y Bastion, C Dumontet, N Renard, E M Neidhardt-Berard, B Coiffier
Journal: Journal of Clinical Oncology (1997)

PURPOSE A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status &gt; or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, &gt; or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P &lt; .0001), and overall survival rates were 91%, 82%, and 51% (P &lt; .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.
SIRT6-induced activation of autophagy inhibits CSE-induced bronchial epithelial cell senescence
Authors: Naoki Takasaka, Jun Araya, Hiromichi Hara, Saburo Ito, Satoko Fujii, Kenichiro Shimizu, Makoto Kawaishi, Takanori Numata, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2013)

Introduction: Senescence is implicated in the pathogenesis of COPD, and cigarette smoke (CS) induces cellular senescence. SIRT6, a class III histone deacetylase (HDAC), has been demonstrated to antagonize cellular senescence, through the attenuation of IGF-Akt singaling. Autophagy is also regulated by IGF-Akt signaling through the mammalian target of rapamycin (mTOR). Autophagy plays a regulatory role in cellular senescence by eliminating damaged proteins, but a role for SIRT6 in autophagy activation has not been shown. Hence, we investigated the regulatory role for SIRT6 in autophagy activation in terms of CS-induced cellular senescence.

Methods: Using human bronchial epithelial cells (HBEC), senescence associated beta-galactosidase staining and western blotting of p21 were performed to evaluate senescence. SIRT6 expression vector and siRNA were transfected into HBEC using the Neon® Transfection System. To characterize autophagy, western blotting for LC3 and p62 were performed. Autophagy was inhibited by knock down of LC3 and ATG5 by siRNA transfection.

Results: CS extract (CSE)-induced HBEC senescence was inhibited by SIRT6 overexpression, while SIRT6 knock down and mutant SIRT6 (H133Y) without HDAC activity for H3K9 increased HBEC senescence. SIRT6 overexpression increased autophagy activation via attenuation of IGF-Akt-mTOR siginaling. Conversely, SIRT6 knock down and mutant SIRT6 (H133Y) inhibited autophagy activation. Autophagy inhibition attenuated the anti-senescent effect of SIRT6 overexpression.

Conclusion: Deacetylation mediated by SIRT6 is involved in CSE-induced HBEC senescence via autophagy regulation, which can be attributed to attenuation of IGF-Akt-mTOR siginaling.
Genetics of primary ovarian insufficiency: new developments and opportunities
Authors: Yingying Qin, Xue Jiao, Joe Leigh Simpson, Zi-Jiang Chen
Journal: Human Reproduction Update (2015)

BACKGROUNDPrimary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI.