tbuckley/cabot-search huggingface dataset:
Understanding health care in the south Caucasus: examples from Armenia: Fig 1
Authors: Tido von Schoen-Angerer
Journal: BMJ (2004)

Along with sociopolitical and economic problems, the medical poverty trap in the south Caucasus region exacerbates its health problems Health care in the south Caucasus has suffered as a result of the socioeconomic decline that followed the collapse of the Soviet Union and the ensuing-still unresolved-conflicts between Armenia and Azerbaijan over Nagorno-Kharabakh and between Georgia and its breakaway republics Abkhazia and South Ossetia.As in most parts of the former Soviet Union, these places have increasing cardiovascular mortality, a high burden of mental illness, and spreading infectious diseases such as tuberculosis, sexually transmitted infections, and HIV. 1 2 However, the widespread underreporting in dysfunctional and collapsing health systems leaves considerable uncertainty about actual figures. 3 Collapse of healthcare servicesAccess to health care and the role of the state as healthcare provider are open questions in the south Caucasus.Instead of questioning and contributing funding to the extremely low government health budget of about US$10 (£5.4; €8.1) per capita-as low as in many sub-Saharan countries in Africa 2 -the World Bank has explicitly encouraged health reform that aims to contain healthcare spending and reduce the state's role in healthcare delivery. 4It promoted introduction of user fees for public services in Armenia Approach to medicine and public healthClinicians in the former Soviet Union have developed distinct treatment approaches and do not share the Western paradigm of evidence based medicine. 16iagnostic criteria are often different, and many drug treatments and physical therapies (x rays, electric fields, Stigma and isolation are two of the main problems for people with mental illness and their families: woman with psychotic disorder in her home (credit: German Avagyan 2003
Telomere Shortening in Kidneys with Age
Authors: ANETTE MELK, VIDO RAMASSAR, LISA M. H. HELMS, RON MOORE, DAVID RAYNER, KIM SOLEZ, PHILIP F. HALLORAN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The histology and function of the kidney deteriorates with age and age-related diseases, but the mechanisms involved in renal aging are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stresses that increase replication. This study explored the relationship between age and telomere length in surgical samples from 24 human kidneys, which were either histologically normal (17) or displayed histologic abnormalities (7). Telomere loss was assessed by two independent methods: Southern blotting of terminal restriction fragments (TRF) and slot blotting using telomere-specific probes. The results of these methods correlated with each other. The mean TRF length determined by Southern blotting in cortex was about 12 kb pairs (kbp) in infancy and was shorter in older kidneys. The slope of the regression line was about 0.029 kbp (0.24%, P = 0.023) per year. Telomere DNA loss in cortex by the slot blot method was 0.25% per year ( P = 0.011). By both methods, the telomere loss in medulla was not significant and was less than in cortex. Comparisons of TRF length from 20 paired samples from cortex and medulla showed that TRF was greater in cortex than medulla, with the differences being greater in young kidneys and lessening with age due to telomere loss in cortex. These findings indicate that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.
Implication of the Insulin-like Growth Factor-IR Pathway in the Resistance of Non–small Cell Lung Cancer Cells to Treatment with Gefitinib
Authors: Floriana Morgillo, Woo-Young Kim, Edward S. Kim, Fortunato Ciardiello, Waun Ki Hong, Ho-Young Lee
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been found to be effective against lung cancer in vitro, but clinical resistance to these agents has developed as their usage has increased. In this study, we determined whether the insulin-like growth factor I (IGF-I) signaling pathway induces resistance of non–small cell lung cancer (NSCLC) cells to the EGFR tyrosine kinase inhibitor gefitinib. Experimental Design: The effects of gefitinib and cetuximab on NSCLC cells, alone or with an IGF-I receptor (IGF-IR) inhibitor, were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the flow cytometry–based terminal nucleotidyl transferase–mediated nick end labeling assay, coimmunoprecipitation, and Western blot analysis. EGFR and IGFR expression in NSCLC tissues were examined by Western blot analysis. Results: Gefitinib inhibited NSCLC cell proliferation by inducing apoptosis when IGF-IR signaling was suppressed. Treatment with gefitinib, but not cetuximab, induced EGFR:IGF-IR heterodimerization and activation of IGF-IR and its downstream signaling mediators, resulting in increased survivin expression in NSCLC cell lines with high levels of IGF-IR expression. Inhibition of IGF-IR activation and knockdown of survivin expression led to increased apoptosis. In contrast, overexpression of survivin protected cells with low IGF-IR expression from gefitinib-induced apoptosis. Most NSCLC tissues with EGFR overexpression had associated high levels of IGF-IR expression. Conclusions: IGF-IR expression may be useful as a predictive marker for gefitinib treatment of NSCLC. Suppression of IGF-IR signaling pathways may prevent or delay development of gefitinib resistance in patients with NSCLC.
The Relationship among Previous Antimicrobial Use, Antimicrobial Resistance, and Treatment Outcomes for <i>Helicobacter pylori</i> Infections
Authors: Brian J. McMahon, Thomas W. Hennessy, J. Michael Bensler, Dana L. Bruden, Alan J. Parkinson, Julie M. Morris, Alisa L. Reasonover, Debby A. Hurlburt, Michael G. Bruce, Frank Sacco, Jay C. Butler
Journal: Annals of Internal Medicine (2003)

The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown.To determine whether previous use of antimicrobial agents predicts subsequent antibiotic resistance of H. pylori and whether resistance affects treatment outcome.Retrospective cohort analysis of adults recruited sequentially from a clinical practice.A referral hospital in Anchorage, Alaska.125 adults infected with H. pylori.Medical records were reviewed for antimicrobial agents prescribed in the 10 years before diagnosis with H. pylori infection. Antimicrobial susceptibility of H. pylori isolates obtained from endoscopic gastric biopsy was determined by using agar dilution. Cure was determined by using the urea breath test 2 months after antimicrobial treatment.Among the 125 patients, 37 (30%) were found to have H. pylori isolates resistant to clarithromycin and 83 (66%) were found to have H. pylori isolates resistant to metronidazole. Resistance to clarithromycin was associated with previous use of any macrolide antibiotic (P < 0.001), and resistance to metronidazole was associated with previous use of metronidazole (P < 0.001). The odds of isolates being resistant to clarithromycin increased in relation to the number of courses of macrolides received (P < 0.001). Among 53 persons treated with clarithromycin-based regimens, treatment failed in 77% of those carrying clarithromycin-resistant H. pylori (10 of 13) and 13% of those with clarithromycin-susceptible strains (5 of 40) (relative risk, 6.2 [95% CI, 1.9 to 37.1]; P < 0.001).Previous use of macrolides and metronidazole is associated with H. pylori resistant to these antimicrobial agents. Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based treatments.
High Temperature and Hospitalizations for Cardiovascular and Respiratory Causes in 12 European Cities
Authors: Paola Michelozzi, Gabriele Accetta, Manuela De Sario, Daniela D'Ippoliti, Claudia Marino, Michela Baccini, Annibale Biggeri, H. Ross Anderson, Klea Katsouyanni, Ferran Ballester, Luigi Bisanti, Ennio Cadum, Bertil Forsberg, Francesco Forastiere, Patrick G. Goodman, Ana Hojs, Ursula Kirchmayer, Sylvia Medina, Anna Paldy, Christian Schindler, Jordi Sunyer, Carlo A. Perucci
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Episode analyses of heat waves have documented a comparatively higher impact on mortality than on morbidity (hospital admissions) in European cities. The evidence from daily time series studies is scarce and inconsistent.To evaluate the impact of high environmental temperatures on hospital admissions during April to September in 12 European cities participating in the Assessment and Prevention of Acute Health Effects of Weather Conditions in Europe (PHEWE) project.For each city, time series analysis was used to model the relationship between maximum apparent temperature (lag 0-3 days) and daily hospital admissions for cardiovascular, cerebrovascular, and respiratory causes by age (all ages, 65-74 age group, and 75+ age group), and the city-specific estimates were pooled for two geographical groupings of cities.For respiratory admissions, there was a positive association that was heterogeneous between cities. For a 1 degrees C increase in maximum apparent temperature above a threshold, respiratory admissions increased by +4.5% (95% confidence interval, 1.9-7.3) and +3.1% (95% confidence interval, 0.8-5.5) in the 75+ age group in Mediterranean and North-Continental cities, respectively. In contrast, the association between temperature and cardiovascular and cerebrovascular admissions tended to be negative and did not reach statistical significance.High temperatures have a specific impact on respiratory admissions, particularly in the elderly population, but the underlying mechanisms are poorly understood. Why high temperature increases cardiovascular mortality but not cardiovascular admissions is also unclear. The impact of extreme heat events on respiratory admissions is expected to increase in European cities as a result of global warming and progressive population aging.
Enhancing the Predictive Value of Urinary Albumin for Diabetic Nephropathy
Authors: M. Luiza Caramori, Paola Fioretto, Michael Mauer
Journal: Journal of the American Society of Nephrology (2006)

Diabetic nephropathy (DN) is a growing cause of ESRD despite widely known recommendations for improved glycemic and BP control. Perhaps earlier identification of patients who have diabetes and are at high risk for DN could reverse these epidemiologic trends. Albumin excretion rate (AER), the mainstay of early detection of DN, is not a sufficiently precise predictor of DN risk. Careful family history, smoking history, consideration of absolute versus categorical AER values, more frequent AER measures, ambulatory BP monitoring, precise GFR measurements, diabetic retinopathy assessments, and plasma lipid levels all can add to predictive accuracy for DN. Thus, although further research in DN biomarkers and predictors is greatly needed, a careful integrated evaluation of currently available parameters can improve our ability to predict DN risk in individual patients.
Dupilumab Improves Patient-Reported Outcomes (PROs) in a Phase 2 Study in Adults with Moderate-to-Severe Atopic Dermatitis
Authors: Eric Simpson, Margitta Worm, Weily Soong, Andrew Blauvelt, Laurent Eckert, Richard Wu, Marius Ardeleanu, Neil Graham, Gianluca Pirozzi, E. Rand Sutherland, Vera Mastey
Journal: Journal of Allergy and Clinical Immunology (2015)
Rat glomerular epithelial cells in culture express characteristics of parietal, not visceral, epithelium.
Authors: T Weinstein, R Cameron, A Katz, M Silverman
Journal: Journal of the American Society of Nephrology (1992)

Glomerular epithelial cells (GEC) in culture are derived from intact isolated glomeruli. Although there is general agreement about distinguishing GEC from mesangial and endothelial cells, there is still uncertainty regarding the visceral versus parietal origin of cultured GEC. If these cells are to provide a useful model system, it is necessary to establish well-defined cell populations. The purpose of this study was to evaluate this important issue by comparing the characteristics of cultured GEC with glomerular epithelium from rat kidney sections. By electron microscopy, GEC were polygonal, with cilia and desmosomes between cells, similar to parietal cells in situ. Because intermediate filaments are specifically expressed in differentiated cells in the kidney, the expression of intermediate filaments in cultured GEC were compared with those of intact glomeruli. Cultured GEC are positive for cytokeratin and negative for vimentin and desmin, identical to parietal cells in situ. In contrast, podocytes are positive for vimentin and desmin and negative for cytokeratin. In vivo, podocytes express gp330 and puromycin-aminonucleoside (PAN) susceptibility, which are used as markers for cultured GEC. Immunoperoxidase staining of rat kidney sections with monoclonal anti-gp330 demonstrated gp330 localization to the cell surface and coated pits of the parietal cells, similar to its localization in podocytes. The presence of gp330 in cultured GEC was confirmed by immunoblot. PAN administration to rats induced vacuolization and detachment from the basement membrane in the parietal cells of Bowman's capsule, similar to the cytotoxicity observed in podocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacometrics in Pregnancy: An Unmet Need
Authors: Alice Ban Ke, Amin Rostami-Hodjegan, Ping Zhao, Jashvant D. Unadkat
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Pregnant women and their fetuses are orphan populations with respect to the safety and efficacy of drugs. Physiological and absorption, distribution, metabolism, and excretion (ADME) changes during pregnancy can significantly affect drug pharmacokinetics (PK) and may necessitate dose adjustment. Here, the specific aspects related to the design, execution, and analysis of clinical studies in pregnant women are discussed, underlining the unmet need for top-down pharmacometrics analyses and bottom-up modeling approaches. The modeling tools that support data analysis for the pregnancy population are reviewed, with a focus on physiologically based pharmacokinetics (PBPK) and population pharmacokinetics (POP-PK). By integrating physiological data, preclinical data, and clinical data (e.g., via POP-PK) to quantify anticipated changes in the PK of drugs during pregnancy, the PBPK approach allows extrapolation beyond the previously studied model drugs to other drugs with well-characterized ADME characteristics. Such a systems pharmacology approach can identify drugs whose PK may be altered during pregnancy, guide rational PK study design, and support dose adjustment for pregnant women.
The genetic basis of idiopathic pulmonary fibrosis
Authors: Jonathan A. Kropski, Timothy S. Blackwell, James E. Loyd
Journal: European Respiratory Journal (2015)

Throughout the past decade, there have been substantial advances in understanding the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recently, several large genome-wide association and linkage studies have identified common genetic variants in more than a dozen loci that appear to contribute to IPF risk. In addition, family-based studies have led to the identification of rare genetic variants in genes related to surfactant function and telomere biology, and mechanistic studies suggest pathophysiological derangements associated with these rare genetic variants are also found in sporadic cases of IPF. Current evidence suggests that rather than existing as distinct syndromes, sporadic and familial cases of IPF (familial interstitial pneumonia) probably reflect a continuum of genetic risk. Rapidly evolving bioinformatic and molecular biology techniques, combined with next-generation sequencing technologies, hold great promise for developing a comprehensive, integrated approach to defining the fundamental molecular mechanisms that underlie IPF pathogenesis.
Persistence of Prolonged C-peptide Production in Type 1 Diabetes as Measured With an Ultrasensitive C-peptide Assay
Authors: Limei Wang, Nicholas Fraser Lovejoy, Denise L. Faustman
Journal: Diabetes Care (2012)

OBJECTIVE To examine persistence of C-peptide production by ultrasensitive assay years after onset of type 1 diabetes and factors associated with preserving β-cell function. RESEARCH DESIGN AND METHODS Serum C-peptide levels, a marker of insulin production and surviving β-cells, were measured in human subjects (n = 182) by ultrasensitive assay, as was β-cell functioning. Twenty-two times more sensitive than standard assays, this assay’s lower detection limit is 1.5 pmol/L. Disease duration, age at onset, age, sex, and autoantibody titers were analyzed by regression analysis to determine their relationship to C-peptide production. Another group of four patients was serially studied for up to 20 weeks to examine C-peptide levels and functioning. RESULTS The ultrasensitive assay detected C-peptide in 10% of individuals 31–40 years after disease onset and with percentages higher at shorter duration. Levels as low as 2.8 ± 1.1 pmol/L responded to hyperglycemia with increased C-peptide production, indicating residual β-cell functioning. Several other analyses showed that β-cells, whose C-peptide production was formerly undetectable, were capable of functioning. Multivariate analysis found disease duration (β = −2.721; P = 0.005) and level of zinc transporter 8 autoantibodies (β = 0.127; P = 0.015) significantly associated with C-peptide production. Unexpectedly, onset at &amp;gt;40 years of age was associated with low C-peptide production, despite short disease duration. CONCLUSIONS The ultrasensitive assay revealed that C-peptide production persists for decades after disease onset and remains functionally responsive. These findings suggest that patients with advanced disease, whose β-cell function was thought to have long ceased, may benefit from interventions to preserve β-cell function or to prevent complications.
Monocyte Chemotactic Protein-1 Increases Collateral and Peripheral Conductance After Femoral Artery Occlusion
Authors: Wulf D. Ito, Margarete Arras, Bernd Winkler, Dimitri Scholz, Jutta Schaper, Wolfgang Schaper
Journal: Circulation Research (1997)

Abstract Monocytes are activated during collateral artery growth in vivo, and monocyte chemotactic protein-1 (MCP-1) has been shown to be upregulated by shear stress in vitro. In order to investigate whether MCP-1 enhances collateral growth after femoral artery occlusion, 12 rabbits were randomly assigned to receive either MCP-1, PBS, or no local infusion via osmotic minipump. Seven days after occlusion, isolated hindlimbs were perfused with autologous blood at different pressures, measuring flows at maximal vasodilation via flow probe and radioactive microspheres, as well as peripheral pressures. This allowed the calculation of collateral (thigh) and peripheral (lower limb) conductances from pressure-flow tracings (slope of the curve). Collateral growth on postmortem angiograms was restricted to the thigh and was markedly enhanced with MCP-1 treatment. Both collateral and peripheral conductances were significantly elevated in animals with MCP-1 treatment compared with the control group, reaching values of nonoccluded hindlimbs after only 1 week of occlusion (collateral conductance, 70.6±19.23 versus 25.1±2.59 mL/min per 100 mm Hg; P &lt;.01; peripheral conductance, 119.3±22.37 versus 45.4±6.80 mL/min per 100 mm Hg; P &lt;.05). These results suggest that activation of monocytes plays an important role in collateral growth as well as in capillary sprouting.
Comparison of expression of napsin A and surfactant protein D in bleomycin-induced pulmonary fibrosis mouse model
Authors: Takuya Samukawa, Tsutomu Hamada, Tomohiro Kumamoto, Go Tsukuya, Shingo Kubota, Masaki Watanabe, Hiromasa Inoue
Journal: European Respiratory Journal (2013)

Introduction :We have shown elevation of serum napsin A in patients with idiopathic pulmonary fibrosis (IPF), and suggest that napsin A may be a candidate biomarker for IPF. However, napsin A has not been confirmed as a marker for bleomycin-induced pulmonary fibrosis model.

Objective : To confirm expression of napsin A in bleomycin-induced pulmonary fibrosis mouse model compared with that of surfactant protein D (SP-D).

Methods : Pulmonary fibrosis was induced in C57BL/6J mice by intratracheal injection of 3.0 mg/kg of bleomycin. Five mice underwent bronchoalveolar lavage (BAL) and were sacrificed on 5 individual days, including before the injection (Day 0) and at 2, 7, 14, and 21 days after. The levels of napsin A and SP-D in BAL fluids and serum were measured by ELISA (Mouse Napsin-A kit, CUSABIO, China; Rat/Mouse SP-D kit YAMASA EIA, Yamasa, Japan). Lung tissues were used for immunohistochemistry (IHC) analysis.

Result : Napsin A levels in BAL fluids were 119.01 ± 23.63 pg/ml for Day 0, 561.86 ± 178.53 pg/ml for Day 7, and 571.70 ± 279.18 pg/ml for Day 21. Napsin A levels in BAL fluids in bleomycin-induced model were significantly increased after Day 7 and were still detected on Day 21 (p<0.001). However serum napsin A levels showed no significant elevation. SP-D was significantly elevated in BALF fluids and serum (p<0.001). IHC analysis of bleomycin-induced model revealed elevated napsin A and SP-D in lung epithelial cells.

Conclusion s: The present study demonstrated napsin A as a marker for bleomycin-induced pulmonary-fibrosis model in BAL fluids and lung tissues.
SASMA: happy to be ‘hip’, wary of being too ‘hip happy’
Authors: Jon Patricios, Phatho Zondi
Journal: British Journal of Sports Medicine (2014)

The slang term ‘to be hip’, meaning fashionably current and in the know, probably has its origins in African-American Vernacular English and became popularly used in the African-American dominated jazz scene of the 1930s and 1940s.1 This year's Fourth International Conference on Injury Prevention hosted by the IOC in Monaco was the place for ‘hip’ sport and exercise clinicians to be seen. Fireworks over the harbour, a reception at the palace and an opening address by the Prince may have left many star struck, but it was the networking with the ‘who's who’ of Sport and Exercise Medicine (SEM) during and in between the insightful sessions that would have had the most impact, especially with so many established faces mingling with young clinicians and up-and-coming researchers.

Somewhat lower in profile, but equally momentous, was the networking workshop hosted by BJSM the day before the IOC meeting. The 13 associate societies (whose members have free access to the journal as part of their association subscriptions) met to discuss successes and challenges in promoting SEM among their national and continental memberships. In addition, Claire Bower, BMJ's digital communications manager, provided great insight into how societies could tap into BMJ's array of social media platforms to communicate with members and access BMJ and BJSM's educational modules (follow @clairebower for great ideas …