tbuckley/cabot-search huggingface dataset:
Preventing Diabetic Foot Ulcer Recurrence in High-Risk Patients
Authors: Lawrence A. Lavery, Kevin R. Higgins, Dan R. Lanctot, George P. Constantinides, Ruben G. Zamorano, Kyriacos A. Athanasiou, David G. Armstrong, C. Mauli Agrawal
Journal: Diabetes Care (2006)

The purpose of this study was to evaluate the effectiveness of a temperature monitoring instrument to reduce the incidence of foot ulcers in individuals with diabetes who have a high risk for lower extremity complications.In this physician-blinded, randomized, 15-month, multicenter trial, 173 subjects with a previous history of diabetic foot ulceration were assigned to standard therapy, structured foot examination, or enhanced therapy groups. Each group received therapeutic footwear, diabetic foot education, and regular foot care. Subjects in the structured foot examination group performed a structured foot inspection daily and recorded their findings in a logbook. If standard therapy or structured foot examinations identified any foot abnormalities, subjects were instructed to contact the study nurse immediately. Subjects in the enhanced therapy group used an infrared skin thermometer to measure temperatures on six foot sites each day. Temperature differences >4 degrees F (>2.2 degrees C) between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized.The enhanced therapy group had fewer foot ulcers than the standard therapy and structured foot examination groups (enhanced therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs. structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy and structured foot examination groups were 4.37 and 4.71 times more likely to develop ulcers than patients in the enhanced therapy group.Infrared temperature home monitoring, in serving as an "early warning sign," appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.
Self-reported Determinants of Access to Surgical Care in 3 Developing Countries
Authors: Joseph D. Forrester, Jared A. Forrester, Thaim B. Kamara, Reinou S. Groen, Sunil Shrestha, Shailvi Gupta, Patrick Kyamanywa, Robin T. Petroze, Adam L. Kushner, Sherry M. Wren
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Surgical care is recognized as a growing component of global public health. <h3>Objective</h3> To assess self-reported barriers to access of surgical care in Sierra Leone, Rwanda, and Nepal using the validated Surgeons OverSeas Assessment of Surgical Need tool. <h3>Design, Setting, and Participants</h3> Data for this cross-sectional, cluster-based population survey were collected from households in Rwanda (October 2011), Sierra Leone (January 2012), and Nepal (May and June 2014) using the Surgeons OverSeas Assessment of Surgical Need tool. <h3>Main Outcomes and Measures</h3> Basic demographic information, cost and mode of transportation to health care facilities, and barriers to access to surgical care of persons dying within the past year were analyzed. <h3>Results</h3> A total of 4822 households were surveyed in Nepal, Rwanda, and Sierra Leone. Primary health care facilities were commonly reached rapidly by foot (&gt;70%), transportation to secondary facilities differed by country, and public transportation was ubiquitously required for access to a tertiary care facility (46%-82% of respondents). Reasons for not seeking surgical care when needed included no money for health care (Sierra Leone: n = 103; 55%), a person dying before health care could be arranged (all countries: 32%-43%), no health care facility available (Nepal: n = 11; 42%), and a lack of trust in health care (Rwanda: n = 6; 26%). <h3>Conclusions and Relevance</h3> Self-reported determinants of access to surgical care vary widely among Sierra Leone, Rwanda, and Nepal, although commonalities exist. Understanding the epidemiology of barriers to surgical care is essential to effectively provide surgical service as a public health commodity in developing countries.
Microglial Physiology: Unique Stimuli, Specialized Responses
Authors: Richard M. Ransohoff, V. Hugh Perry
Journal: Annual Review of Immunology (2009)

Microglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases.
Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate <i>mir-34a, mir-34b,</i> and <i>mir-34c</i> Expression, and Induce Senescence
Authors: Kensuke Kumamoto, Elisa A. Spillare, Kaori Fujita, Izumi Horikawa, Taro Yamashita, Ettore Appella, Makoto Nagashima, Seiichi Takenoshita, Jun Yokota, Curtis C. Harris
Journal: Cancer Research (2008)

Abstract Nutlin-3, an MDM2 inhibitor, activates p53, resulting in several types of cancer cells undergoing apoptosis. Although p53 is mutated or deleted in ∼50% of all cancers, p53 is still functionally active in the other 50%. Consequently, nutlin-3 and similar drugs could be candidates for neoadjuvant therapy in cancers with a functional p53. Cellular senescence is also a phenotype induced by p53 activation and plays a critical role in protecting against tumor development. In this report, we found that nutlin-3a can induce senescence in normal human fibroblasts. Nutlin-3a activated and repressed a large number of p53-dependent genes, including those encoding microRNAs. mir-34a, mir-34b, and mir-34c, which have recently been shown to be downstream effectors of p53-mediated senescence, were up-regulated, and inhibitor of growth 2 (ING2) expression was suppressed by nutlin-3a treatment. Two candidates for a p53-DNA binding consensus sequence were found in the ING2 promoter regulatory region; thus, we performed chromatin immunoprecipitation and electrophoretic mobility shift assays and confirmed p53 binding directly to those sites. In addition, the luciferase activity of a construct containing the ING2 regulatory region was repressed after p53 activation. Antisense knockdown of ING2 induces p53-independent senescence, whereas overexpression of ING2 induces p53-dependent senescence. Taken together, we conclude that nutlin-3a induces senescence through p53 activation in normal human fibroblasts, and p53-mediated mir34a, mir34b, and mir34c up-regulation and ING2 down-regulation may be involved in the senescence pathway. [Cancer Res 2008;68(9):3193–203]
Dispatches: Public Service, Private Profit
Authors: Trevor Jackson
Journal: BMJ (2006)

H ow much does it cost to change a hospital light switch? If it's a hospital built under the government's private finance initiative (PFI), it could cost as much as £333 (€494; $629), according to Dispatches . The reason? The hospital cannot just call in a local electrician—it has to act in accordance with its contract with the private owner. Such contracts cover every possible maintenance task, however small, and to carry these out the private owner is likely to go through a host of middle men before sending in a contractor. Not surprisingly, the bill mounts. At one privately owned hospital, Darent Valley in Kent, the programme claimed that it cost £200 to hang a mirror and £420 to fit a plug socket.

None of this sounds like value for money. And according to Dispatches , it gets worse. Reporter Liam Halligan, economics …
Parity of esteem between mental and physical health
Authors: C. Millard, S. Wessely
Journal: BMJ (2014)

Means different things to different people, making it difficult to enforce

Although parity of esteem between mental and physical health has been a high profile political issue in the UK since 2011, debates about the relative esteem and provision for mental and physical health are long standing. For example, the report that preceded the 1959 Mental Health Act (which removed all restriction on mental health treatment in general hospitals) claimed—prematurely perhaps—that “most people are coming to regard mental illness and disability in much the same way as physical illness and disability.”1

The recent coinage of “parity of esteem” is uncertain. The term parity became enshrined in US law in 2006, when it was mandated that mental health and substance misuse problems should treated the same as medical and surgical conditions in health insurance coverage and not be excluded. It became a key part of the 2010 UK coalition government’s mental health strategy, No Health Without Mental Health, in 2011. The Health and Social Care Act 2012 was altered during its passage into law to include specific reference to mental health, and the NHS Constitution and NHS Mandate for 2014-2015 both include specific commitments in this area. Since 2012 there have …
Phase II Multicenter Study of Induction Chemotherapy Followed by Concurrent Efaproxiral (RSR13) and Thoracic Radiotherapy for Patients With Locally Advanced Non–Small-Cell Lung Cancer
Authors: Hak Choy, Abdenour Nabid, Baldassarre Stea, Charles Scott, Wilson Roa, Larry Kleinberg, Joseph Ayoub, Colum Smith, Luis Souhami, Solomon Hamburg, William Spanos, Harvey Kreisman, Adam P. Boyd, Pablo J. Cagnoni, Walter J. Curran
Journal: Journal of Clinical Oncology (2005)

Efaproxiral (RSR13) reduces hemoglobin oxygen-binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC).Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10.Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%).Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.
Ryanodine inhibits the release of calcium from intracellular stores in guinea pig aortic smooth muscle.
Authors: K Ito, S Takakura, K Sato, J L Sutko
Journal: Circulation Research (1986)

We have examined the effects of ryanodine, an inhibitor of the release of sarcoplasmic reticulum calcium in cardiac muscle, on contractile tension and calcium-45 movement in aortic smooth muscle of guinea pigs to learn whether this agent also modifies the release of stored calcium in vascular smooth muscle. Ryanodine (3-100 microM) suppressed the phasic contractions induced by caffeine and norepinephrine in calcium-free medium and prevented the stimulation of calcium-45 efflux by these agonists. Ryanodine did not significantly alter either the contractile response or the increased cellular influx of calcium-45 caused by high potassium in more than 1 mM calcium, suggesting that this agent does not affect depolarization-induced calcium entry into the cells. In a calcium-free, high potassium solution, the addition of calcium at concentrations of 1 mM and less resulted in a contraction which appeared to depend largely on the release of calcium from intracellular stores. This contraction was blocked by ryanodine. These data are consistent with the hypothesis that ryanodine causes a diminished release of calcium from the intracellular store in vascular smooth muscle, as it does in cardiac muscle. Moreover, our results indicate that a calcium-induced calcium release may exist in smooth muscle, and that this release is antagonized by ryanodine.
Age-specific population frequencies of cerebral β-amyloidosis and neurodegeneration among people with normal cognitive function aged 50–89 years: a cross-sectional study
Authors: Clifford R Jack, Heather J Wiste, Stephen D Weigand, Walter A Rocca, David S Knopman, Michelle M Mielke, Val J Lowe, Matthew L Senjem, Jeffrey L Gunter, Gregory M Preboske, Vernon S Pankratz, Prashanthi Vemuri, Ronald C Petersen
Journal: The Lancet Neurology (2014)
Circulating Carotenoids and Risk of Breast Cancer: Pooled Analysis of Eight Prospective Studies
Authors: A. Heather Eliassen, Sara J. Hendrickson, Louise A. Brinton, Julie E. Buring, Hannia Campos, Qi Dai, Joanne F. Dorgan, Adrian A. Franke, Yu-tang Gao, Marc T. Goodman, Göran Hallmans, Kathy J. Helzlsouer, Judy Hoffman-Bolton, Kerstin Hultén, Howard D. Sesso, Anne L. Sowell, Rulla M. Tamimi, Paolo Toniolo, Lynne R. Wilkens, Anna Winkvist, Anne Zeleniuch-Jacquotte, Wei Zheng, Susan E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2012)

Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER−) than for ER+ tumors (eg, β-carotene: ER−: top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER+: RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.
Multidrug Efflux Systems Play an Important Role in the Invasiveness of <i>Pseudomonas aeruginosa </i>
Authors: Yoichi Hirakata, Ramakrishnan Srikumar, Keith Poole, Naomasa Gotoh, Takashi Suematsu, Shigeru Kohno, Shimeru Kamihira, Robert E. W. Hancock, David P. Speert
Journal: The Journal of Experimental Medicine (2002)

Pseudomonas aeruginosa is an important opportunistic human pathogen. Certain strains can transmigrate across epithelial cells, and their invasive phenotype is correlated with capacity to cause invasive human disease and fatal septicemia in mice. Four multidrug efflux systems have been described in P. aeruginosa, however, their contribution to virulence is unclear. To clarify the role of efflux systems in invasiveness, P. aeruginosa PAO1 wild-type (WT) and its efflux mutants were evaluated in a Madin-Darby canine kidney (MDCK) epithelial cell monolayer system and in a murine model of endogenous septicemia. All efflux mutants except a ΔmexCD-oprJ deletion demonstrated significantly reduced invasiveness compared with WT. In particular, a ΔmexAB-oprM deletion strain was compromised in its capacity to invade or transmigrate across MDCK cells, and could not kill mice, in contrast to WT which was highly invasive (P &amp;lt; 0.0006) and caused fatal infection (P &amp;lt; 0.0001). The other mutants, including ΔmexB and ΔmexXY mutants, were intermediate between WT and the ΔmexAB-oprM mutant in invasiveness and murine virulence. Invasiveness was restored to the ΔmexAB-oprM mutant by complementation with mexAB-oprM or by addition of culture supernatant from MDCK cells infected with WT. We conclude that the P. aeruginosa MexAB-OprM efflux system exports virulence determinants that contribute to bacterial virulence.
Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system.
Authors: J Sprent, I Lefkovits
Journal: The Journal of Experimental Medicine (1976)

When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed.
On giving a more active and selective role to consciousness
Authors: Frederick Toates
Journal: Behavioral and Brain Sciences (1995)

Abstract An active role for conscious processes in the production of behaviour is proposed, involving top level controls in a hierarchy of behavioural control. It is suggested that by inhibiting or sensitizing lower levels in the hierarchy conscious processes can play a role in the organization of ongoing behaviour. Conscious control can be more or less evident, according to prevailing circumstances.
17 beta-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine.
Authors: J F Keaney, G T Shwaery, A Xu, R J Nicolosi, J Loscalzo, T L Foxall, J A Vita
Journal: Circulation (1994)

BACKGROUND Cardiovascular events are less prevalent in premenopausal women and women receiving estrogen replacement than in postmenopausal women or men. Endothelium-derived relaxing factor (EDRF) is an important local modulator of vascular tone, and abnormal endothelial function is related, in part, to the oxidative modification of low-density lipoprotein (LDL). Estrogens possess substantial antioxidant activity and inhibit LDL modification in vitro. METHODS AND RESULTS We investigated the effects of 17 beta-estradiol (E2) on endothelial vasomotor function in cholesterol-fed miniature swine. Animals underwent ovariectomy or a sham procedure and received E2 or placebo via implant yielding three groups: sham, ovariectomy (E2 placebo), and implant (E2 implant). After 16 weeks, coronary arteries were harvested and endothelial function was examined in vitro. Vessels from the sham and implant groups demonstrated preserved endothelium-dependent relaxation to bradykinin, substance P, and A23187. Vessels from the ovariectomy group exhibited impaired relaxation to bradykinin and substance P (P &lt; .05 versus sham and implant groups) but not to A23187. Plasma E2 levels were strongly correlated with the response to bradykinin (R = .82, P &lt; .001), substance P (R = .64, P &lt; .01), and A23187 (R = .65, P &lt; .01). Compared with the ovariectomy group, LDL derived from the sham and implant groups was markedly resistant to ex vivo oxidation (P &lt; .05), and this effect correlated with preserved endothelium-dependent relaxation to bradykinin (R = .62, P &lt; .03) and substance P (R = .61, P &lt; .03). CONCLUSIONS Thus, E2 preserves endothelial function in cholesterol-fed swine in association with protection of LDL against oxidative modification. These data suggest that E2 may, in part, favorably affect vascular function and coronary artery disease by virtue of its antioxidant properties.