tbuckley/cabot-search huggingface dataset:
Costs and Consequences of the US Centers for Disease Control and Prevention's Recommendations for Opt-Out HIV Testing
Authors: David R Holtgrave
Journal: PLoS Medicine (2007)

The United States Centers for Disease Control and Prevention (CDC) recently recommended opt-out HIV testing (testing without the need for risk assessment and counseling) in all health care encounters in the US for persons 13-64 years old. However, the overall costs and consequences of these recommendations have not been estimated before. In this paper, I estimate the costs and public health impact of opt-out HIV testing relative to testing accompanied by client-centered counseling, and relative to a more targeted counseling and testing strategy.Basic methods of scenario and cost-effectiveness analysis were used, from a payer's perspective over a one-year time horizon. I found that for the same programmatic cost of US$864,207,288, targeted counseling and testing services (at a 1% HIV seropositivity rate) would be preferred to opt-out testing: targeted services would newly diagnose more HIV infections (188,170 versus 56,940), prevent more HIV infections (14,553 versus 3,644), and do so at a lower gross cost per infection averted (US$59,383 versus US$237,149). While the study is limited by uncertainty in some input parameter values, the findings were robust across a variety of assumptions about these parameter values (including the estimated HIV seropositivity rate in the targeted counseling and testing scenario).While opt-out testing may be able to newly diagnose over 56,000 persons living with HIV in one year, abandoning client-centered counseling has real public health consequences in terms of HIV infections that could have been averted. Further, my analyses indicate that even when HIV seropositivity rates are as low as 0.3%, targeted counseling and testing performs better than opt-out testing on several key outcome variables. These analytic findings should be kept in mind as HIV counseling and testing policies are debated in the US.
Comparison of thoracoabdominal asynchrony estimated via optolectronic and inductive respiratory plethymographies
Authors: Mayra Caleffi Pereira, Desiderio Cano Porras, Renata Cléia Claudino, Letícia Cardenas, Renata Pletsch, Pauliane Santana, Vinícius Iamonti, Renan Maloni, Carlos R.R. Carvalho, Celso Carvalho, André L.P. Albuqueruqe
Journal: European Respiratory Journal (2014)

Thoracoabdominal asynchrony (TAA) is defined as the no coincident motion of ribcage (RC) and abdomen (AB) and considered as relevant clinically. TAA has been estimated through respiratory inductive plethysmography (RIP) and, more recently, optoelectronic plethysmography (OEP). However, the agreement of TAA measurements with both RIP and OEP remains unknown.  OBJECTIVE:  To compare TAA values during inspiration via OEP and RIP.  METHODS:  8 healthy subjects (4 male, 34.2±8.7yrs and FEV 1  91.8±7.2%pred) performed 2 cycle ergometer sessions with 30 minutes between them in a random order. TAA was evaluated in different phases of exercise, 3 minutes of each one: at rest, 40% (L 40 ), 60% (L 60 ) and 80% (L 80 ) of maximal workload obtained in a previous day. TAA was calculated between RC (upper RC in OEP) and AB through phase angle using the Lissajous approach (Agostini and Mognoni, 1966). The flow at the mouth was assessed with a pneumotacograph. It was analyzed a mean cycle of 5 last breaths of every phase.  RESULTS:  The minute ventilation (V e ) and the pattern of breathing were homogeneous in OEP and RIP for rest and all phases of exercise. TAA was very similar in both approaches not only at rest but also in L 40 , L 60  and L 80  [Table1].  CONCLUSION:  Thoracoabdominal asynchrony obtained by OEP or RIP results in similar values at rest and even for different exercise intensities.
Absence of Interleukin‐17 Receptor A Signaling Prevents Autoimmune Inflammation of the Joint and Leads to a Th2‐like Phenotype in Collagen‐Induced Arthritis
Authors: Odilia B. J. Corneth, Adriana M. C. Mus, Patrick S. Asmawidjaja, Roel G. J. Klein Wolterink, Menno van Nimwegen, Maarten D. Brem, Yara Hofman, Rudi W. Hendriks, Erik Lubberts
Journal: Arthritis & Rheumatology (2013)

Interleukin-17A (IL-17A) signals through the IL-17 receptor (IL-17R) A/C heterodimer. IL-17RA serves as a common receptor subunit for several IL-17 cytokine family members. Lack of IL-17RA signaling may therefore have additional effects beyond those of lack of IL-17A alone. The present study was undertaken to determine the role of IL-17RA signaling in autoimmune arthritis.Disease incidence and severity were scored in type II collagen-treated wild-type, IL-17RA-deficient, and IL-23p19-deficient mice. T helper cell profiles and humoral immune responses were analyzed at several time points. Pathogenicity of T cells and total splenocytes was determined by in vitro functional assay. IL-17RA signaling was blocked in vivo in mice with antigen-induced arthritis (AIA).Comparable to the findings in IL-23p19-deficient mice, IL-17RA-deficient mice were completely protected against the development of collagen-induced arthritis (CIA). However, IL-17RA-deficient mice exhibited an increased number of IL-4-producing CD4+ T cells, distinct from IL-17A+CD4+ T cells. This was associated with fewer plasma cells, lower production of pathogenic IgG2c antibody, and increased production of IgG1 antibody. Both isolated CD4+ T cells and total splenocytes from IL-17RA-deficient mice had a reduced ability to induce IL-6 production by synovial fibroblasts in the setting of CIA, in a functional in vitro assay. Furthermore, blocking of IL-17RA signaling in AIA reduced synovial inflammation.These results demonstrate that absence of IL-17RA leads to a Th2-like phenotype characterized by IL-4 production and suggest that IL-17RA signaling plays a critical role in the regulation of IL-4 in CIA and the development of autoimmune inflammation of the joint.
Heparanase Enhances Local and Systemic Osteolysis in Multiple Myeloma by Upregulating the Expression and Secretion of RANKL
Authors: Yang Yang, Yongsheng Ren, Vishnu C. Ramani, Li Nan, Larry J. Suva, Ralph D. Sanderson
Journal: Cancer Research (2010)

Excessive bone destruction is a major cause of morbidity in myeloma patients. However, the biological mechanisms involved in the pathogenesis of myeloma-induced bone disease are not fully understood. Heparanase, an enzyme that cleaves the heparan sulfate chains of proteoglycans, is upregulated in a variety of human tumors, including multiple myeloma. We previously showed that heparanase promotes robust myeloma tumor growth and supports spontaneous metastasis of tumor cells to bone. In the present study, we show, for the first time, that the expression of heparanase by myeloma tumor cells remarkably enhances bone destruction locally within the tumor microenvironment. In addition, enhanced heparanase expression in the primary tumor also stimulated systemic osteoclastogenesis and osteolysis, thus mimicking the systemic osteoporosis often seen in myeloma patients. These effects occur, at least in part, as the result of a significant elevation in the expression and secretion of receptor activator of NF-κB ligand (RANKL) by heparanase-expressing myeloma cells. Moreover, analysis of bone marrow biopsies from myeloma patients reveals a positive correlation between the level of expression of heparanase and RANKL. Together, these discoveries reveal a novel and key role for heparanase in promoting tumor osteolysis and show that RANKL is central to the mechanism of heparanase-mediated osteolysis in myeloma.
Raf Kinase Inhibitor RKIP Inhibits MDA-9/Syntenin-Mediated Metastasis in Melanoma
Authors: Swadesh K. Das, Sujit K. Bhutia, Upneet K. Sokhi, Belal Azab, Zhao-zhong Su, Habib Boukerche, Talha Anwar, Erika L. Moen, Devasis Chatterjee, Maurizio Pellecchia, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2012)

Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, functions as a positive regulator of melanoma progression and metastasis. In contrast, the Raf kinase inhibitor, RKIP, a negative modulator of RAF-stimulated MEKK activation, is strongly downregulated in metastatic melanoma cells. In this study, we explored a hypothesized inverse relationship between MDA-9 and RKIP in melanoma. Tumor array and cell line analyses confirmed an inverse relationship between expression of MDA-9 and RKIP during melanoma progression. We found that MDA-9 transcriptionally downregulated RKIP in support of a suggested cross-talk between these two proteins. Furthermore, MDA-9 and RKIP physically interacted in a manner that correlated with a suppression of FAK and c-Src phosphorylation, crucial steps necessary for MDA-9 to promote FAK/c-Src complex formation and initiate signaling cascades that drive the MDA-9-mediated metastatic phenotype. Finally, ectopic RKIP expression in melanoma cells overrode MDA-9-mediated signaling, inhibiting cell invasion, anchorage-independent growth, and in vivo dissemination of tumor cells. Taken together, these findings establish RKIP as an inhibitor of MDA-9-dependent melanoma metastasis, with potential implications for targeting this process therapeutically.
Malignant pleural effusion cells show aberrant glucose metabolism gene expression
Authors: C-C. Lin, L-C. Chen, V.S. Tseng, J-J. Yan, W-W. Lai, W-P. Su, C-H. Lin, C-Y.F. Huang, W-C. Su
Journal: European Respiratory Journal (2010)

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation. Three tissue sample cohorts, seven from healthy lungs, 18 from stage I–III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy. 20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell. Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.
Lipid Metabolism and Neuroinflammation in Alzheimer's Disease: A Role for Liver X Receptors
Authors: Jihong Kang, Serge Rivest
Journal: Endocrine Reviews (2012)

Liver X receptors (LXR) are nuclear receptors that have emerged as key regulators of lipid metabolism. In addition to their functions as cholesterol sensors, LXR have also been found to regulate inflammatory responses in macrophages. Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive cognitive decline associated with inflammation. Evidence indicates that the initiation and progression of AD is linked to aberrant cholesterol metabolism and inflammation. Activation of LXR can regulate neuroinflammation and decrease amyloid-β peptide accumulation. Here, we highlight the role of LXR in orchestrating lipid homeostasis and neuroinflammation in the brain. In addition, diabetes mellitus is also briefly discussed as a significant risk factor for AD because of the appearing beneficial effects of LXR on glucose homeostasis. The ability of LXR to attenuate AD pathology makes them potential therapeutic targets for this neurodegenerative disease.
INJURIES AND RISK FACTORS IN PHYSICAL EDUCATION STUDENTS
Authors: AM van Beijsterveldt, S Bliekendaal, M Brink, J Stubbe
Journal: British Journal of Sports Medicine (2014)

Background Sports injuries are highly disadvantageous for Physical Education (PE) students, because they can lead to physical discomfort, and absence from sports classes resulting in higher study career costs. Objective To investigate the magnitude of the injury problem in PE students and to explore risk factors for sustaining an injury. Design A prospective cohort study with six months follow up. Participants and setting 280 Dutch freshmen PE students. Assessment of risk factors Prior to the start of the school year, all students underwent a medical examination to assess height, weight, percentage of body fat, blood pressure, visual acuity, muscle-skeletal functioning, and cardio-respiratory endurance. During the six months follow up, an online questionnaire was conducted on a weekly basis to monitor injuries and illnesses (OSTRC Overuse Injury Questionnaire). Furthermore, every two weeks an online questionnaire (POMS and RESTQ-Sports) was administered to measure mood and perceived stress and recovery of the students. Main outcome measures Frequencies and characteristics of injuries and illnesses. Results According to the OSTRC Overuse Injury Questionnaire, 22.5% of the students had physical problems regarding injuries during the first month of the school year, and 11.2% of the students were ill. Data collection will end in February 2014. We will perform a logistic regression analysis to test whether the injured students differ significantly from non injured students based on characteristics such as age, sex, body composition, and muscle-skeletal functioning. Conclusions Preliminary results showed that the risk of sustaining an injury and becoming ill is high for freshmen PE students. Screening at the start of the school year may play an important role in identifying the students at risk.
Dendritic cells and scavenger macrophages in chronic inflammatory bowel disease.
Authors: C A Seldenrijk, H A Drexhage, S G Meuwissen, S T Pals, C J Meijer
Journal: Gut (1989)

We used enzyme (acid phosphatase [AP]) and immunohistochemical techniques and a set of monoclonal antibodies (CD11, CD5, CD4, CD19, CD8, OKIa), including two recently developed antibodies--for example, HECA-452 (specific for an adhesion molecule on high endothelial venules) and RFD1 (specific for 'active' human dendritic cells) to analyse the composition of the gut wall infiltrate of 10 well defined cases of chronic inflammatory bowel disease (CIBD) (six Crohn's disease (CD), four ulcerative colitis (UC]. Two polar forms in a spectrum of gut mononuclear phagocyte types (CD11+) were identified: at the one extreme scavenger macrophages with blunted projections (AP+, Heca-452-, RFD1-) and at the other extreme, dendritic cells with long dendritic cytoplasmic projections (AP-, Heca-452+, RFD1+). Dendritic cells were mainly found in highly organised lymphoid tissue present at the deeper layers in the gut wall (normal gut: underneath the muscularis mucosae and T-cell areas of lymph follicles [25-30 per follicle]; surrounding the broad zone of scavenger macrophages at the bottom of ulcers (CIBD) and fissures (CD) and in the lymphoid aggregates [25-30 dendritic cells per aggregate] adjacent to granulomas (CD]. These observations can be taken as evidence that exaggerated antigen handling and presentation and stimulation of the immune response takes place at these foci. The observation that scavenger macrophages were localised more superficial, as band like zones (normal gut: subepithelial; mainly surrounding ulcers (CIBD) and fissures (CD] can be taken as evidence that at these spots the ingestion and degradation of foreign material takes place.
Systemic Delivery of γ134.5-Deleted Herpes Simplex Virus-1 Selectively Targets and Treats Distant Human Xenograft Tumors That Express High MEK Activity
Authors: Jula Veerapong, Kai A. Bickenbach, Michael Y. Shao, Kerrington D. Smith, Mitchell C. Posner, Bernard Roizman, Ralph R. Weichselbaum
Journal: Cancer Research (2007)

Abstract Δγ134.5 mutant herpes simplex type 1 viruses are under active clinical investigation as oncolytic therapy for cancer. Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) activity has been shown to suppress protein kinase R and thereby confer oncolytic susceptibility to some human tumors by R3616, a virus deleted for both copies of γ134.5. We report that systemic delivery of R3616 can selectively target and destroy human xenograft tumors that overexpress MEK activity compared with tumors that express lower MEK activity. These results suggest systemic delivery of R3616 may be effective in the treatment of some human tumors. [Cancer Res 2007;67(17):8301–6]
Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count
Authors: A M Li
Journal: Thorax (2003)

<b>Background:</b> A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. <b>Methods:</b> Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5–13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. <b>Results:</b> Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV<sub>1</sub>) and eNO were 88.5% (IQR 79.5–98) and 23.9 ppb (IQR 11.4–41.5), respectively. The median number of cough episodes was 14 (IQR 7.0–24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1–10.5), p&lt;0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0–9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's <i>r</i> =0.781, p&lt;0.001) but not with FEV<sub>1</sub> or sputum eosinophil count (<i>r</i> =−0.270, p=0.157; <i>r</i> =0.173, p=0.508, respectively). <b>Conclusions:</b> Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.
EARLY AND DISCRETE CHANGES IN PERMEABILITY OF <i>ESCHERICHIA COLI</i> AND CERTAIN OTHER GRAM-NEGATIVE BACTERIA DURING KILLING BY GRANULOCYTES
Authors: Susan Beckerdite, Carolyn Mooney, J. Weiss, R. Franson, Peter Elsbach
Journal: The Journal of Experimental Medicine (1974)

Rapid killing of Escherichia coli by intact or disrupted rabbit granulocytes or by granulocyte fractions was found to be accompanied by an equally rapid increase in permeability of the E.coli envelope. This increase in permeability was detected by determining entry of substances that normally do not cross E.coli's permeability barrier, namely actinomycin D and o-nitrophenyl-ß-D-galactopyranoside (ONPG), a substrate for cytoplasmic ß-galactosidase. Because E.coli continue to incorporate radioactively labeled precursors into bacterial RNA and protein for at least 1 h, despite rapid killing by granulocytes, entry of actinomycin D could be measured by its inhibitory effect on macromolecular synthesis. Entry was evident within minutes after exposure to granulocytes or granulocyte fractions and is independent of pH over a range of 6.5–9.0. The effect of disrupted granulocytes or partially purified fractions on susceptibility of E.coli to actinomycin D and entry of ONPG is dose dependent. That the entry of actinomycin D and ONPG was not caused by gross destruction of the envelope is indicated by two sets of observations: (a) net influx of 42K was maintained for at least 15 min, even though efflux of potassium was immediately accelerated upon addition of bactericidal concentrations of granulocyte fractions; (b) ß-galactosidase did not leak out of E.coli under conditions that produce maximal inhibition by actinomycin D. Different species of gram-negative bacteria exhibited different susceptibilities to the bactericidal and permeability effects of granulocyte fractions. Thus, three strains of E.coli and one strain of Salmonella typhimurium were highly susceptible to both the bactericidal and the permeability enhancing effects of granulocyte fractions, whereas two strains of Serratia marcescens and one strain of Pseudomonas aeruginosa were resistant to both effects. Another strain of P. aeruginosa was rendered susceptible to actinomycin D without being killed and two strains of S. typhimurium remained insensitive to actinomycin D while being killed by granulocytes.
Therapeutic Biliary Endoscopy
Authors: M. Mutignani, A. Tringali, G. Costamagna
Journal: Endoscopy (2004)

Almost all biliary diseases are now amenable to endoscopic treatment. Progress in therapeutic biliary endoscopy is currently focusing on identifying the best treatment options to be used in each case in relation to the available evidence: how should a malignant stricture of the common bile duct or hilum be drained? How should an external biliary fistula be treated? What should one do with the gallbladder after extraction of common bile duct stones? Should sedation or general anesthesia be offered? Progress has been made in the technique of endoscopic ampullectomy and in developing new devices to improve the success rate of endoscopic retrograde cholangiopancreatography.
Preventing RhD haemolytic disease of the newborn
Authors: B. van Dijk
Journal: BMJ (1997)

In 1994 we saw the 25th anniversary year of the worldwide introduction of anti-rhesus (D) immunoglobulin prophylaxis, one of the most successful prophylactic programmes in medical history. In 1977, 110 cases of stillbirth or neonatal death due to RhD haemolytic disease were registered in Britain; by 1992, this figure seemed to have dropped to nine cases.1 In this issue of the BMJ , however, Whitfield and colleagues show that this is a serious underestimation (p 1504).2 Extrapolation of their Scottish figures suggests that there are 50 deaths a year due to RhD haemolytic disease in Britain. They conclude that the discrepancy is due to underreporting because deaths due to early abortion (before 24 weeks) and late neonatal death (second to fourth week of life) are not included in official figures.

The policy introduced in 1969 was to give anti-D immunoglobulin to RhD negative women only after the birth of …