tbuckley/cabot-search huggingface dataset:
Bioaerosol production by patients with tuberculosis during normal tidal breathing: implications for transmission risk
Authors: Fatima B Wurie, Stephen D Lawn, Helen Booth, Pam Sonnenberg, Andrew C Hayward
Journal: Thorax (2016)

<h3>Background</h3> The size and concentration of exhaled bioaerosols may influence TB transmission risk. This study piloted bioaerosol measurement in patients with TB and assessed variability in bioaerosol production during normal tidal breathing. Understanding this may provide a tool for assessing heterogeneity in infectivity and may inform mathematical models of TB control practices and policies. <h3>Methods</h3> Optical particle counter technology was used to measure aerosol size and concentration in exhaled air (range 0.3–20 µm in diameter) during 15 tidal breaths across four groups over time: healthy/uninfected, healthy/<i>Mycobacterium tuberculosis</i>-infected, patients with extrathoracic TB and patients with intrathoracic TB. High-particle production was defined as any 1–5 µm sized bioaerosol count above the median count among all participants (median count=2 counts/L). <h3>Results</h3> Data from 188 participants were obtained pretreatment (baseline). Bioaerosol production varied considerably between individuals. Multivariable analysis showed intrathoracic TB was associated with a 3½-fold increase in odds of high production of 1–5 µm bioaerosols (adjusted OR: 3.5; 95% CI 1.6 to 7.8; p=0.002) compared with healthy/uninfected individuals. <h3>Conclusions</h3> We provide the first evidence that intrathoracic TB increases bioaerosol production in a particle size range that could plausibly transport <i>M. tuberculosis</i>. There is substantial variation in production within patients with TB that may conceivably relate to the degree of infectivity. Further data is needed to determine if high bioaerosol production during tidal breathing is associated with infectiousness.
NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs
Authors: Zhenke Wen, Yasuhiro Shimojima, Tsuyoshi Shirai, Yinyin Li, Jihang Ju, Zhen Yang, Lu Tian, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Journal of Clinical Investigation (2016)

Immune aging results in progressive loss of both protective immunity and T cell-mediated suppression, thereby conferring susceptibility to a combination of immunodeficiency and chronic inflammatory disease. Here, we determined that older individuals fail to generate immunosuppressive CD8+CCR7+ Tregs, a defect that is even more pronounced in the age-related vasculitic syndrome giant cell arteritis. In young, healthy individuals, CD8+CCR7+ Tregs are localized in T cell zones of secondary lymphoid organs, suppress activation and expansion of CD4 T cells by inhibiting the phosphorylation of membrane-proximal signaling molecules, and effectively inhibit proliferative expansion of CD4 T cells in vitro and in vivo. We identified deficiency of NADPH oxidase 2 (NOX2) as the molecular underpinning of CD8 Treg failure in the older individuals and in patients with giant cell arteritis. CD8 Tregs suppress by releasing exosomes that carry preassembled NOX2 membrane clusters and are taken up by CD4 T cells. Overexpression of NOX2 in aged CD8 Tregs promptly restored suppressive function. Together, our data support NOX2 as a critical component of the suppressive machinery of CD8 Tregs and suggest that repairing NOX2 deficiency in these cells may protect older individuals from tissue-destructive inflammatory disease, such as large-vessel vasculitis.
The Bard’s Blunder—Debunking the Myth Around Rhinophyma
Authors: Aleksandra Augustynowicz, Eric L. Maranda, Joseph Zullo, Louis Cai, Joaquin Jimenez
Journal: JAMA Dermatology (2016)

While the eyes are commonly referred to as windows to the soul, studies suggest that the nose could be the door. This most conspicuous facial feature has been shown to influence body image, selfperception, and even personality. The American Society of Plastic Surgeons reports rhinoplasty to be one of the most commonly requested surgical procedures; positive outcomes of these procedures have been shown to ameliorate psychological suffering due to deformities of the nose, to have beneficial psychological implications, and even to allow patients to feel more comfortable with their identity. 1 The role of the nose in shaping one’s image in society is best exemplified through rhinophyma, an end-stage form of rosacea affecting primarily men ages 50 to 70 years, leads to enlargement, fibrosis, and telangiectasia of the nose, and has long been associated with a love of drink. Although alcohol and other substances, such as caffeine, cause local vasodilation that can exacerbate the symptoms, the cause has yet to be elucidated. 2 The common misconception involving alcohol and rhinophyma is illustrated and propagated throughout classical literature. In Macbeth, Shakespeare’s characters warn their readers, “Drink, sir, is a great provoker of three things…nose-painting, sleep, and urine. Lechery, sir, it provokes and unprovokes,” thus mercilessly linking a red nose to alcohol and shameful behavior. The Pardoner in Chaucer’s Canterbury Tales highlights the vices of alcohol through emphasizing its role in disfiguring the face and focuses on the snoring sound of the nose:
Syphilis, a Disfiguring Disease
Authors: Chu Hsiao, Samantha Hsieh, Eric L. Maranda, Victoria Lim, Joseph Zullo, Joaquin Jimenez
Journal: JAMA Dermatology (2016)

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Lethal Neonatal Deficiency of Carbamyl Phosphate Synthetase
Authors: Thomas D. Gelehrter, Philip J. Snodgrass
Journal: New England Journal of Medicine (1974)

A male infant, who appeared normal at birth, manifested hypothermia, irritability, and hypertonia 24 hours after beginning protein feedings. Increasing rigidity and coma ensued, and the child died at 75 hours of age. A male sibling had also died with an identical clinical picture. Laboratory studies on the proband demonstrated a blood ammonia of 1480 μg per 100 ml (normal <150 μg per 100 ml). Assay of the urea-cycle enzymes in liver obtained at autopsy revealed selective deficiency of carbamyl phosphate synthetase activity (<10 per cent of the lowest newborn autopsy control); activity of the other four urea-cycle enzymes was normal. The residual carbamyl phosphate synthetase activity was not dependent on N-acetylglutamate, suggesting that it represented cytoplasmic carbamyl phosphate synthetase II, and that mitochondrial carbamyl phosphate synthetase I was completely absent. Deficiency of this enzyme must now be added to the causes of lethal hyperammonemia in the newborn. (N Engl J Med 290:430–433, 1974)
COMMAND: A phase II randomized, double-blind, placebo-controlled, multicenter study of defactinib as maintenance therapy in subjects with malignant pleural mesothelioma that has not progressed on at least four cycles of pemetrexed/platinum therapy.
Authors: Dean Anthony Fennell, Paul Baas, Hedy Lee Kindler, Lee M. Krug, Anna Nowak, Marjorie Zauderer, Richard J. Gralla, Mitchell Keegan, Joanna Horobin
Journal: Journal of Clinical Oncology (2014)

TPS7611 Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor in the pleural lining of the lung usually caused by asbestos exposure. Median OS following frontline chemotherapy with pemetrexed/cisplatin (pem/cis) is ~12 months. There is no established second line therapy. 40-50% of MPM tumors exhibit disruption of the NF2 tumor suppressor gene by mutation and/or deletion resulting in lack of expression of functional merlin protein. Mesothelioma cell lines that lack merlin are more sensitive to focal adhesion kinase (FAK) inhibitors than those with wild type merlin. Furthermore, pem/cis enrich cancer stem cells (CSCs) in tumors, while FAK inhibitors have been found to decrease CSCs in mesothelioma models. Given the sensitivity of mesothelioma cells lacking merlin and the effect on CSCs, the use of a FAK inhibitor in a maintenance setting after first line chemotherapy may be an attractive strategy to extend survival of MPM patients. Defactinib (VS-6063) is an oral inhibitor of FAK. Methods: A multinational, randomized, double-blind, placebo controlled, clinical trial will determine if defactinib provides superior clinical benefit compared with placebo as a maintenance treatment in patients with MPM following frontline therapy with pem/platinum therapy. Approximately 370 eligible patients with PR or SD following at least 4 cycles of pem/cis or pem/carboplatin will be enrolled. Patients will receive defactinib 400mg BID or matched placebo (1:1). Patients will continue treatment until disease progression. Randomization will be stratified by merlin status (high vs low) as determined by immunohistochemistry on archival tumor tissue. Primary endpoints will include OS and PFS. An adaptive enrichment design at the interim analysis may restrict patients to those with low merlin protein expression if benefit is observed among the subpopulation. Secondary endpoints include patient-reported outcomes, objective response and safety and tolerability. Twenty-eight sites are actively recruiting patients across 8 countries. Clinical trial: NCT01870609.
The Methodologic Foundations of Studies of the Appropriateness of Medical Care
Authors: Charles E. Phelps
Journal: New England Journal of Medicine (1993)

As health care costs continue to increase rapidly, both health care providers and consumers have expressed concern that the additional resources used for health services do not provide commensurate increases in health benefits. Adding fuel to this concern, a number of disquieting studies have estimated the rates of “inappropriate” use in a variety of settings of a variety of procedures such as coronary angiography, carotid endarterectomy, endoscopy, and coronary-artery bypass graft surgery1–4. The estimated rates of inappropriate treatment have ranged from about 15 to 30 percent, reaching as high as 40 percent for particular procedures at individual institutions. . . .
Salivary cortisol levels and their correlation with plasma ACTH levels in depressed patients before and after the DST
Authors: R Galard, J M Gallart, R Catalan, S Schwartz, J M Arguello, J M Castellanos
Journal: American Journal of Psychiatry (1991)

The aim of this work was to study the clinical utility of salivary cortisol concentrations in a group of depressed patients undergoing the dexamethasone suppression test (DST) and the correlation of these concentrations with plasma ACTH levels.Twenty outpatients from the psychiatric department of a Barcelona hospital who were diagnosed as having nonendogenous (N = 9) or endogenous (N = 11) depression according to DSM-III criteria and the Newcastle scale participated in the study. The comparison group consisted of 12 healthy volunteers. Blood and saliva samples were taken before and after administration of 1 mg of dexamethasone Salivary cortisol and plasma ACTH concentrations were determined by direct iodine-125 radioimmunoassay with commercial kit reagents.Predexamethasone salivary cortisol concentrations were significantly higher in the group with endogenous depression than in the comparison group. A significant correlation was obtained between plasma ACTH and predexamethasone salivary cortisol levels in the group with nonendogenous depression and in the comparison subjects.These preliminary findings indicate that salivary cortisol could substitute for plasma cortisol in clinical studies in which the DST and hypercortisolemia are evaluated. The lack of correlation between ACTH and cortisol levels in saliva in the group of endogenously depressed patients could indicate a disturbance in the regulation of cortisol secretion in major depression.
Interleukin 2 (IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75.
Authors: H Asao, T Takeshita, M Nakamura, K Nagata, K Sugamura
Journal: The Journal of Experimental Medicine (1990)

We have recently established a mAb named TU11 mAb specific for the p75 subunit of human IL-2 receptor (IL-2R). The present study using TU11 mAb demonstrates the IL-2-induced phosphorylation of IL-2Rp75 on tyrosine residues in IL-2-dependent T cells. The tyrosine phosphorylation is mediated by the high affinity IL-2R, correlates with the IL-2-induced cell growth, and rapidly increases during the first 5 min of IL-2 stimulation. Phosphorylation of serine and threonine residues of IL-2Rp75 is also detected, but its IL-2 dependency is not significant during at least the first 5 min. These results suggest some roles of a tyrosine kinase associated with IL-2Rp75 in the IL-2-induced signal-transducing pathway.
Outbreak of Salmonella enterica serovar Typhimurium in Switzerland, May – June 2008, implications for production and control of meat preparations
Authors: H Schmid, H Hächler, R Stephan, A Baumgartner, K Boubaker
Journal: Eurosurveillance (2008)

An increased number of Salmonella Typhimurium cases were reported in Switzerland between May and June 2008. Investigations involved 72 cases. Results of PFGE typing identified several outbreak strains, the dominating one present in 43 of the 72 isolates. Strains affecting one third of the cases were also found in animal samples, in particular pork. However, no specific food source could be identified. Outbreaks described in this paper highlight the importance of food safety regulations such as those on minced meat and meat preparations issued by the European Commission and adopted by Switzerland into the national law.
M18 Knowledge and attitudes of secondary care staff toward giving advice on Smoking, Weight management, Alcohol and Physical activity
Authors: S Mendes, B Menezes, B Mallia, H Abusriwil
Journal: Thorax (2015)

<h3>Introduction</h3> It is well recognised that adopting a healthier lifestyle leads to better health, improved survival and reduced NHS costs. There are numerous missed opportunities within secondary care to identify high-risk patients and intervene early to prevent illness. The aim of this study was to examine knowledge, attitude and perceived barriers of members of staff to provide healthy lifestyle advise such as Smoking cessation, Weight management, Alcohol consumption and Physical activity (SWAP) and referral to appropriate services. <h3>Methods</h3> A questionnaire was distributed to all members of staff working at Sandwell and West Birmingham Hospitals NHS trust electronically and via paper copies. <h3>Results</h3> A total of 558 responses were secured from a wide breadth of staff (doctors (23%), Nurses/midwives (36.2%), allied health professionals (11.3%), Pharmacists (1.8%), Admin (8.1%), Domestic/porters (4.1%), clinical support staff (13.8%). Most respondents saw it as their role to encourage people to adopt a healthy lifestyle. Staff had limited knowledge of local resources, however significantly higher knowledge scores were seen for stopping smoking verses weight management (P &lt; 0.001) and physical activity (P &lt; 0.001). Most respondents knew how to refer patients for smoking cessation (66%) and alcohol services (63%), which was significantly higher compared to weight management (39%) and physical activity (36%) services (P &lt; 001). 56% participants had not given any life style advice within the previous week, 4% to at least 5 people and 3% to more than 10. 72% participants had not referred anyone to services. The top barriers identified included patient unreadiness to change, unclear referral pathways, lack of time and need for additional training. 82% of staff had no formal training. <h3>Conclusion</h3> It is encouraging that a large proportion of staff in secondary care see it as their role to give lifestyle advise, however the majority don’t do it due to barriers including lack of time, knowledge and training. We have therefore devised an electronic training package that has gone live on our trust intranet page giving very brief advise on SWAP as well as providing an electronic referral system that will ensure a ‘one click’ referral system to the appropriate service. We plan to re audit in a few months time.
A first-in-human dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of oral 2-hydroxyoleic acid (2-OHOA) in adult patients (pt) with advanced solid tumors including grade III/IV glioblastoma multiforme (GBM).
Authors: Desamparados Roda, Yvette Drew, Analia Azaro, Alan David Smith, Alastair Greystoke, Elisabet Sicart, Pablo V. Escriba, Xavier Busquets, Victoria LLado, Vicente Tur, Edwin Klumper, Jordi Rodon Ahnert, L Rhoda Molife, Ruth Plummer
Journal: Journal of Clinical Oncology (2015)

2513 Background: 2-OHOA, is a synthetic hydroxylated lipid that activates sphingomyelin synthase (SGMS) and regulates the lipid content of cell membranes resulting in translocation of Ras to the cytoplasm and inactivation of Ras/MAPK, PI3K/Akt and PKC/cyclin/CDK signaling pathways. 2-OHOA reduces tumor growth in xenograft mice models of prostate, leukemia, breast, colon, breast cancer, and GBM, and also crosses the blood brain barrier. This first-in-human trial was designed to determine the safety, tolerability, and recommended phase 2 dose (RP2D), alongside the PK, PD and anti-tumor profile of 2-OHOA. Methods: Eligible pts with advanced solid tumors or grade (G) III/IV GBM received 2-OHOA as a PO suspension, BID in 21-d cycles using a ‘3+3’ dose escalation design. Adverse events (AE) were assessed by Common Terminology Criteria for AE v4; tumor response was assessed every 2 cycles using RECIST 1.1/RANO criteria. Results: 17 pts (median age 59 years; range 19-71; 7 GBM and 10 solid tumors) were treated at 5 dose levels: 250-, 500-, 1000, 2000 and 4000-mg BID. Treatment was well tolerated with toxicities limited to grade 1-2 nausea (n = 4), vomiting (n = 6) and diarrhea (n = 6). The PK profile was dose-proportional with no accumulation up to 2000mg BID; t1/2 = 4h. No effect of food was observed. One pt with GBM treated at 500mg BID has a confirmed and ongoing partial response and is currently at cycle (C) 23 of treatment; a 2nd GBM pt has SD after 2 cycles and continues on study. A 3rd pt with progressive mesothelioma demonstrated SD lasting to C15. Conclusions: 2-OHOA can be safely administered up to doses of 4000mg BID. Clinical benefit was observed in 3 patients including 1 PR in a pt with GBM. Dose escalation continues to determine a RP2D, followed by a RP2D expansion in patients with both solid tumors and grade III/IV GBM. Clinical trial information: NCT01792310.
Leukemia Following Hodgkin's Disease
Authors: John M. Kaldor, Nicholas E. Day, E. Aileen Clarke, Flora E. Van Leeuwen, Michel Henry-Amar, Mario V. Fiorentino, Janine Bell, Dorthe Pedersen, Pierre Band, David Assouline, Maria Koch, Won Choi, Patricia Prior, Valerie Blair, Froydis Langmark, Vera Pompe Kirn, Frank Neal, David Peters, Rudolf Pfeiffer, Sakari Karjalainen, Jack Cuzick, Simon B. Sutcliffe, Reiner Somers, Brigitte Pellae-Cosset, Giovanni L. Pappagallo, Patricia Fraser, Hans Storm, Marilyn Stovall
Journal: New England Journal of Medicine (1990)

To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case–control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop.
Breast cancer carcinomatous meningitis: Differences in survival depending on biological subtype, performance status, and treatment methods.
Authors: A. M. Niwinska, H. Rudnicka, M. Murawska
Journal: Journal of Clinical Oncology (2011)

1073 Background: The aim of the study was to define biological subtypes of breast cancer that have the propensity to metastasize to the leptomeninges and to assess factors influencing survival from detection of CM. Methods: 118 consecutive breast cancer patients with CM were treated in one institution, between the years 1999 and 2009. Univariate and Cox multivariate analysis were performed in order to determine factors influencing survival from CM. Results: 27% of patients had lobular cancer. 40.5% of patients had triple-negative subtype, 37.5% had luminal A (ER/PgR-positive, HER2-negative) and 22% had HER2-positive biological subtype. Median survival from the detection of CM was 18 weeks and 1-year survival was 16%. Median survival of patients with good and poor performance status was 7 and 3 months, respectively (p<0.001). Median survival of patients treated and not treated systemically was 6 and 2 months, respectively (p<0.001). Cox multivariate analysis revealed that performance status and systemic treatment statistically significantly influenced survival of patients with CM. Conclusions: Lobular histological type and triple-negative biological subtype of breast cancer had the propensity to metastasize to the leptomeninges. Performance status was the main factor impacting survival. Systemic intravenous/oral therapy was the only treatment method prolonging survival of patients with CM.
Role Of PET/CT In The Management Of Burkitt Lymphoma
Authors: Estrella Carrillo, Fatima De la Cruz, Víctor Marín, María Solé, Isabel Borrego, Eduardo Quiroga, Marina Manzanares, Francisco Javier Capote, María José Ramirez, Ildefonso Espigado, Ricardo Vázquez, Pérez-Simón Jose Antonio
Journal: Blood (2013)
Money saved could be spent on patient education
Authors: J. Paris
Journal: BMJ (1995)

continue to have the right and opportunity to make a subsequent attempt at suicide.We do not suggest that any method of interpreting principles that may be relevant in a volunteer based organisation would be transferable to the clinical domain, but we believe that when in doubt we should err on the side of life.Each situation will be different and will need careful and sensitive assessment (in so far as time and the circumstances permit).Nobody, however, can escape from the fact that death is for ever.