tbuckley/cabot-search huggingface dataset:
Antimicrobial effect of alexidine and chlorhexidine against Enterococcus faecalis infection
Authors: Hyun-Shik Kim, Seok Woo Chang, Seung-Ho Baek, Seung Hyun Han, Yoon Lee, Qiang Zhu, Kee-Yeon Kum
Journal: International Journal of Oral Science (2013)

A previous study demonstrated that alexidine has greater affinity for the major virulence factors of bacteria than chlorhexidine. The aim of this study was to compare the antimicrobial activity of 1% alexidine with that of 2% chlorhexidine using Enterococcus faecalis-infected dentin blocks. Sixty bovine dentin blocks were prepared and randomly divided into six groups of 10 each. E. faecalis was inoculated on 60 dentin blocks using the Luppens apparatus for 24 h and then the dentin blocks were soaked in 2% chlorhexidine or 1% alexidine solutions for 5 and 10 min, respectively. Sterile saline was used as a control. The antimicrobial efficacy was assessed by counting the number of bacteria adhering to the dentin surface and observing the degradation of bacterial shape or membrane rupture under a scanning electron microscope. Significantly fewer bacteria were observed in the 2% chlorhexidine- or 1% alexidine-soaked groups than in the control group (P<0.05). However, there was no significant difference in the number of bacteria adhering to the dentinal surface between the two experimental groups or between the two soaking time groups (P>0.05). Ruptured or antiseptic-attached bacteria were more frequently observed in the 10-min-soaked chlorhexidine and alexidine groups than in the 5-min-soaked chlorhexidine and alexidine groups. In conclusion, 10-min soaking with 1% alexidine or 2% chlorhexidine can be effective against E. faecalis infection. The new antiseptic alexidine disinfects root canals as effectively as the commonly used chlorhexidine, a study by Kee-Yeon Kum of the Seoul National University School of Dentistry in South Korea and co-workers has shown. The root canal's complex anatomy is prone to infection following treatment, so is treated with combinations of antiseptics. Chlorhexidine interacts poorly with the ubiquitously used sodium hypochlorite. Kum and co-workers therefore tested the efficacy of alexidine — which interacts well with sodium hypochlorite — against Enterococcus faecalis, a major cause of persistent infections. The researchers soaked blocks of bovine root canal, infected with E. faecalis, in 1% alexidine or 2% chlorhexidine for 5 or 10 minutes. Visualization of intact cells using scanning electron microscopy showed that alexidine and chlorhexidine are equally effective against E. faecalis, and that 5 minutes of soaking is required.
Prevalence of Neutropenia in the U.S. Population: Age, Sex, Smoking Status, and Ethnic Differences
Authors: Matthew M. Hsieh, James E. Everhart, Danita D. Byrd-Holt, John F. Tisdale, Griffin P. Rodgers
Journal: Annals of Internal Medicine (2007)

Background: Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status. Objective: To determine differences in neutrophil counts in the U.S. population according to ethnicity, age, sex, and smoking status. Design: Population-based, cross-sectional study. Setting: Various locations in the United States. Participants: 25 222 participants in the 1999 to 2004 National Health and Nutrition Examination Survey who were 1 year of age or older. Measurements: Complete blood counts and comparison of means and the proportion of participants with neutropenia. Results: Relative to white participants, black participants had lower leukocyte counts (mean difference, 0.89 × 109 cells/L; P < 0.001), lower neutrophil counts (0.83 × 109 cells/L; P < 0.001), and similar lymphocyte counts (0.022 × 109 cells/L; P = 0.36), whereas Mexican-American participants had slightly higher mean leukocyte counts (0.16 × 109 cells/L; P = 0.014), higher neutrophil counts (0.11 × 109 cells/L; P = 0.026), and higher lymphocyte counts (0.095 × 109 cells/L; P < 0.001). The prevalence of neutropenia (neutrophil count <1.5 × 109 cells/L) was 4.5% among black participants, 0.79% among white participants, and 0.38% among Mexican-American participants. The prevalence of neutropenia was higher among males and children younger than 5 years of age. Neutrophil counts less than 1.0 × 109 cells/L were observed in fewer than 1% of the overall sample (0.57% in black participants, 0.11% in white participants, and 0.08% in Mexican-American participants). Smoking was associated with higher leukocyte and neutrophil counts but had a smaller effect among black and Mexican-American participants than among white participants. Limitation: Because estimates are based on single measures, fluctuations over time could not be determined. Conclusions: In the United States, neutrophil counts are lower in black persons than in white persons and neutropenia is more prevalent in black persons. Neutrophil counts are slightly higher in Mexican-American persons than in white persons, and neutropenia is uncommon in both groups. The clinical implications of these findings are unclear, but they suggest that when determining the need for a diagnostic evaluation for neutropenia, clinicians should consider the patient's age, sex, ethnicity, and smoking status.
Bevacizumab in recurrent high-grade pediatric gliomas
Authors: A. Narayana, S. Kunnakkat, J. Chacko-Mathew, S. Gardner, M. Karajannis, S. Raza, J. Wisoff, H. Weiner, D. Harter, J. Allen
Journal: Neuro-Oncology (2010)

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m2. Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.
Population Genetic Structure in Indian Austroasiatic Speakers: The Role of Landscape Barriers and Sex-Specific Admixture
Authors: G. Chaubey, M. Metspalu, Y. Choi, R. Magi, I. G. Romero, P. Soares, M. van Oven, D. M. Behar, S. Rootsi, G. Hudjashov, C. B. Mallick, M. Karmin, M. Nelis, J. Parik, A. G. Reddy, E. Metspalu, G. van Driem, Y. Xue, C. Tyler-Smith, K. Thangaraj, L. Singh, M. Remm, M. B. Richards, M. M. Lahr, M. Kayser, R. Villems, T. Kivisild
Journal: Molecular Biology and Evolution (2010)

The geographic origin and time of dispersal of Austroasiatic (AA) speakers, presently settled in south and southeast Asia, remains disputed. Two rival hypotheses, both assuming a demic component to the language dispersal, have been proposed. The first of these places the origin of Austroasiatic speakers in southeast Asia with a later dispersal to south Asia during the Neolithic, whereas the second hypothesis advocates pre-Neolithic origins and dispersal of this language family from south Asia. To test the two alternative models, this study combines the analysis of uniparentally inherited markers with 610,000 common single nucleotide polymorphism loci from the nuclear genome. Indian AA speakers have high frequencies of Y chromosome haplogroup O2a; our results show that this haplogroup has significantly higher diversity and coalescent time (17–28 thousand years ago) in southeast Asia, strongly supporting the first of the two hypotheses. Nevertheless, the results of principal component and “structure-like” analyses on autosomal loci also show that the population history of AA speakers in India is more complex, being characterized by two ancestral components—one represented in the pattern of Y chromosomal and EDAR results and the other by mitochondrial DNA diversity and genomic structure. We propose that AA speakers in India today are derived from dispersal from southeast Asia, followed by extensive sex-specific admixture with local Indian populations.
Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells
Authors: Jörg Schrader, Timothy T. Gordon-Walker, Rebecca L. Aucott, Mariëlle van Deemter, Alexander Quaas, Shaun Walsh, Daniel Benten, Stuart J. Forbes, Rebecca G. Wells, John P. Iredale
Journal: Hepatology (2010)

There is increasing evidence that the physical environment is a critical mediator of tumor behavior. Hepatocellular carcinoma (HCC) develops within an altered biomechanical environment, and increasing matrix stiffness is a strong predictor of HCC development. The aim of this study was to establish whether changes in matrix stiffness, which are characteristic of inflammation and fibrosis, regulate HCC cell proliferation and chemotherapeutic response. Using an in vitro system of “mechanically tunable” matrix-coated polyacrylamide gels, matrix stiffness was modeled across a pathophysiologically relevant range, corresponding to values encountered in normal and fibrotic livers. Increasing matrix stiffness was found to promote HCC cell proliferation. The proliferative index (assessed by Ki67 staining) of Huh7 and HepG2 cells was 2.7-fold and 12.2-fold higher, respectively, when the cells were cultured on stiff (12 kPa) versus soft (1 kPa) supports. This was associated with stiffness-dependent regulation of basal and hepatocyte growth factor-stimulated mitogenic signaling through extracellular signal-regulated kinase, protein kinase B (PKB/Akt), and signal transducer and activator of transcription 3. β1-Integrin and focal adhesion kinase were found to modulate stiffness-dependent HCC cell proliferation. Following treatment with cisplatin, we observed reduced apoptosis in HCC cells cultured on stiff versus soft (physiological) supports. Interestingly, however, surviving cells from soft supports had significantly higher clonogenic capacity than surviving cells from a stiff microenvironment. This was associated with enhanced expression of cancer stem cell markers, including clusters of differentiation 44 (CD44), CD133, c-kit, cysteine-X-cysteine receptor 4, octamer-4 (CXCR4), and NANOG. Conclusion: Increasing matrix stiffness promotes proliferation and chemotherapeutic resistance, whereas a soft environment induces reversible cellular dormancy and stem cell characteristics in HCC. This has implications for both the treatment of primary HCC and the prevention of tumor outgrowth from disseminated tumor cells. (HEPATOLOGY 2011;)
Serum Phosphate Levels and Mortality Risk among People with Chronic Kidney Disease
Authors: Bryan Kestenbaum, Joshua N. Sampson, Kyle D. Rudser, Donald J. Patterson, Stephen L. Seliger, Bessie Young, Donald J. Sherrard, Dennis L. Andress
Journal: Journal of the American Society of Nephrology (2004)

Elevated serum phosphate levels have been linked with vascular calcification and mortality among dialysis patients. The relationship between phosphate and mortality has not been explored among patients with chronic kidney disease (CKD). A retrospective cohort study was conducted from eight Veterans Affairs' Medical Centers located in the Pacific Northwest. CKD was defined by two continuously abnormal outpatient serum creatinine measurements at least 6 mo apart between 1999 and 2002. Patients who received chronic dialysis, those with a present or previous renal transplant, and those without a recent phosphate measurement were excluded. The primary end point was all-cause mortality. Secondary end points were acute myocardial infarction and the combined end point of myocardial infarction plus death. A total of 95,619 veterans with at least one primary care or internal medicine clinic contact from a Northwest VA facility and two or more outpatient measurements of serum creatinine, at least 6 mo apart, between January 1, 1999, and December 31, 2002, were identified. From this eligible population, 7021 patients met our definition of CKD. After exclusions, 6730 CKD patients were available for analysis, and 3490 had a serum phosphate measurement during the previous 18 mo. After adjustment, serum phosphate levels >3.5 mg/dl were associated with a significantly increased risk for death. Mortality risk increased linearly with each subsequent 0.5-mg/dl increase in serum phosphate levels. Elevated serum phosphate levels were independently associated with increased mortality risk among this population of patients with CKD.
De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study
Authors: Djamel Mokart, Géraldine Slehofer, Jérôme Lambert, Antoine Sannini, Laurent Chow-Chine, Jean-Paul Brun, Pierre Berger, Ségolène Duran, Marion Faucher, Jean-Louis Blache, Colombe Saillard, Norbert Vey, Marc Leone
Journal: Intensive Care Medicine (2013)
Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy
Authors: R. Jordan
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy. <b>Design:</b> Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment. <b>Participants:</b> Patients with any stage of HIV infection who had not received antiretroviral therapy. <b>Main outcome measures:</b> Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers). <b>Search strategy:</b> Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001. <b>Results:</b> 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality. <b>Conclusions:</b> Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs. <h3>What is already known on this topic</h3> Triple combination antiretroviral therapy is accepted by clinicians and patients as the usual treatment for HIV and has evolved through an incremental strategy in the numbers of drugs combined Guidance on treatment, however, has predominantly been based on early reports of research There are no published analyses that assess the effectiveness of the increasing numbers of drugs used in combination <h3>What this study adds</h3> The results of this systematic review support the use of triple therapy but there is inadequate evidence for quadruple or higher combinations Heterogeneity in the effect estimates seems to result from variable effectiveness of different drug combinations, trial duration, and problems with study quality
Plasma Osteoprotegerin Is Associated with Mortality in Hemodialysis Patients
Authors: Marion Morena, Nathalie Terrier, Isabelle Jaussent, Hélène Leray-Moragues, Lotfi Chalabi, Jean-Pierre Rivory, Franc[COMBINING CEDILLA]ois Maurice, Cécile Delcourt, Jean-Paul Cristol, Bernard Canaud, Anne-Marie Dupuy
Journal: Journal of the American Society of Nephrology (2005)

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.
P121 Cost-Effectiveness of Alpha-1 Antitrypsin (A1AT) Deficiency Case-Finding in Secondary Care: Abstract P121 TABLE 1.
Authors: L Dron, S Whiting, D Thorburn, M Pinzani, B Gooptu, DA Lomas, JR Hurst
Journal: Thorax (2013)

<h3>Background</h3> Screening for A1AT-deficiency at our institution involves serum protein assay, then phenotyping where A1AT≤1.1g/L. RT-PCR genotyping for S/Z variants is available for clarification. We recently established a multi-disciplinary respiratory/hepatology London A1AT Deficiency Service and re-examined the cost-effectiveness of our diagnostic algorithm. <h3>Method</h3> We studied all patients who had a serum A1AT request over the three years 1/1/2010–31/12/2012. We went on to examine all requests for phenotyping and/or genotyping over the ten years 1/1/2003–31/12/2012. <h3>Results</h3> From 4460 requests over 2010–2012, 240(5.4%) had serum A1AT≤1.1g/l. Of these, phenotyping was not available in 33 and of the remainder the following phenotype-prevalence data were observed (n,%): MM (75,36%), MZ (89,43%), MS (29,14%), ZZ (6,3%), SZ (6,3%), SS (1,1%), GM (1,1%). In error, 28 patients had phenotyping with A1AT&gt;1.1g/l: 27 were PiMM and 1 PiMS. Over 2003–2012, 525 phenotyping tests were performed. In 41 the result was unclear or there was evidence of <i>in vivo</i> degradation. The prevalence of the respective phenotypes and mean (SD) A1AT concentrations are reported in the Table. Over the same period, 24 equivocal samples were sent for genotyping. This confirmed 13 = PiMM, 4 = PiZZ, 3 = PiMZ, 2 = PiMS and 2 = PiSZ. The NHS costs of A1AT serum assay, phenotyping and genotyping are £2.45, £35.50 and £87.50. Using the 2010–2012 data, our mean annualised spend on A1AT serum, phenotyping and genotyping was £3,642 £3,170 and £376 respectively. The cost per ZZ/SZ case diagnosed was £1198. The highest A1AT serum concentration recorded in the ZZ/SZ patients were 0.4 and 1.0g/l respectively suggesting that the ≤1.1g/l cut-off is appropriate. The specificity, sensitivity and positive predictive values are 26.5%, 100% and 6.5%. <h3>Conclusion</h3> 5.4% of serum A1AT assays yielded results ≤1.1g/l. Of these, 6% were found to represent SZ/ZZ variants at risk of clinically relevant disease (0.27%, 1/372 requests). The ≤1.1g/l cut-off was 100% sensitive but only 26.5% specific for clinically relevant deficiency alleles. The ≤1.1g/l cut-off could be lowered with improved specificity and cost-saving if the desire was to detect only ZZ patients.
Energy Metabolism During Human Pregnancy
Authors: Elisabet Forsum, Marie Löf
Journal: Annual Review of Nutrition (2007)

This review summarizes information regarding how human energy metabolism is affected by pregnancy, and current estimates of energy requirements during pregnancy are presented. Such estimates can be calculated using either increases in basal metabolic rate (BMR) or increases in total energy expenditure (TEE). The two modes of calculation give similar results for a complete pregnancy but different distributions of energy requirements in the three trimesters. Recent information is presented regarding the effect of pregnancy on BMR, TEE, diet-induced thermogenesis, and physical activity. The validity of energy intake (EI) data recently assessed in well-nourished pregnant women was evaluated using information regarding energy metabolism during pregnancy. The results show that underreporting of EI is common during pregnancy and indicate that additional longitudinal studies, taking the total energy budget during pregnancy into account, are needed to satisfactorily define energy requirements during the three trimesters of gestation.
Levels of seven urinary phthalate metabolites in a human reference population.
Authors: B C Blount, M J Silva, S P Caudill, L L Needham, J L Pirkle, E J Sampson, G W Lucier, R J Jackson, J W Brock
Journal: Environmental Health Perspectives (2000)

Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates.