Nanoparticle-encapsulated chlorhexidine against oral bacterial biofilms

Background: Chlorhexidine (CHX) is a widely used antimicrobial agent in dentistry. Herein, we report the synthesis of a novel mesoporous silica nanoparticle-encapsulated pure CHX (Nano-CHX), and its mechanical profile and antimicrobial properties against oral biofilms. Methodology/Principal Findings: The release of CHX from the Nano-CHX was characterized by UV/visible absorption spectroscopy. The antimicrobial properties of Nano-CHX were evaluated in both planktonic and biofilm modes of representative oral pathogenic bacteria. The Nano-CHX demonstrated potent antibacterial effects on planktonic bacteria and mono-species biofilms at the concentrations of 50-200 mu g/mL against Streptococcus mutans, Streptococcus sobrinus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Enterococccus faecalis. Moreover, Nano-CHX effectively suppressed multi-species biofilms such as S. mutans, F. nucleatum, A. actinomycetemcomitans and Porphyromonas gingivalis up to 72 h. Conclusions/Significance: This pioneering study demonstrates the potent antibacterial effects of the Nano-CHX on oral biofilms, and it may be developed as a novel and promising anti-biofilm agent for clinical use.published_or_final_versio

Diabetes incidence and prevalence in Hong Kong, China during 2006-2014

postprin

An investigation of the problem of optimizing a search tactic for a searchlight type sonar.

A searchlight type sonar is one of the systems that small navies use to counteract the danger which submarines present to their lines of supply and transport. In this paper, a standard search pattern for this type of sonar is compared with search patterns which are based on a consideration of the tactical value of detecting a submarine as a function of the relative location of the submarine. The results of the comparison suggest that is possible to increase the effectiveness of a searchlight type sonar by using a search pattern in which the sweep time allocated to a search sector is based on the sectors tactical importance.http://archive.org/details/investigationofp00llanCommander, Chilean NavyApproved for public release; distribution is unlimited

Visit-to-visit systolic blood pressure variability predicts all-cause and cardiovascular mortality after lacunar infarct

Background: Both blood pressure (BP) and its variability (BPV) are established risk factors for development of atherosclerotic disease and are associated with an increased risk for cardiovascular and all-cause mortality. The prognostic implications of out-patient clinic visit-to-visit BPV among patients with lacunar infarction are nevertheless unknown. Methods: We prospectively followed up the clinical outcome of 281 patients with lacunar infarction. The mean BP and BPV, as determined by the standard deviation of the systolic and diastolic BP, were recorded during a mean of 13 ± 6 out-patient clinic visits. Results: The mean age of the population was 70 ± 10 years. After a mean of 78 ± 18 month’s follow-up, 65 (23%) patients died, 31% (20/65) were due to cardiovascular causes. 14% and 7% developed recurrent stroke and acute coronary syndrome, respectively. After adjusting for age, sex, mean systolic and diastolic BP, cardiovascular risk factors and co-morbidities, patients with a systolic BPV of the third tertile had significantly higher risk of all-cause (hazard ratio [HR] = 1.97; 95% confidence interval [CI], 1.02-3.80; P = 0.04) and cardiovascular mortality (HR = 7.64; 95% CI, 1.65-35.41; P < 0.01) compared to those with systolic BPV of the first tertile. Nevertheless, systolic BPV did not predict recurrent stroke or acute coronary syndrome. Diastolic BPV did not predict various adverse clinical outcomes. Conclusions: Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality after lacunar infarct, independent of conventional risk factors including average BP control.published_or_final_versio

Long-term prognostic implications of visit-to-visit blood pressure variability in patients with ischaemic stroke

Background: Both blood pressure (BP) and its variability (BPV) are established risk factors for the development of atherosclerotic diseases and are associated with an increased risk of cardiovascular and all-cause mortality. The long-term prognostic implications of out-patient clinic visit-to-visit BPV among patients with ischaemic stroke are nevertheless unknown. Methods: We prospectively followed up the clinical outcome of 632 consecutive ischaemic stroke patients without atrial fibrillation. The mean BP and BPV, as determined by the coefficient of variation of the systolic and diastolic BP, were recorded during a mean of 12 ± 6 outpatient clinic visits. Results: The mean age of the patients was 71 ± 11 years. After a mean of 76 ± 18 month’s follow-up, 161 (26%) patients died, 35% (56/161) were due to cardiovascular causes. 16% and 5% developed recurrent stroke and acute coronary syndrome (ACS), respectively. After adjusting for mean systolic BP and confounding variables, patients with a high systolic BPV were at significantly greater risk of cardiovascular mortality (hazard ratio [HR] = 2.36; 95% confidence interval [CI], 1.02-5.49; P < 0.05). A high systolic BPV also predicted all-cause mortality after adjusting for mean systolic BP (HR = 1.79; 95% CI, 1.16-2.75; P < 0.05). There was no association between systolic BPV with non-fatal recurrent stroke nor non-fatal ACS. A raised diastolic BPV did not predict recurrent non-fatal stroke, non-fatal ACS nor mortality. Conclusions: Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality in patients with ischaemic stroke without atrial fibrillation, independent of other conventional risk factors including average BP control.published_or_final_versio

Combined Use of Serum Adiponectin and Tumor Necrosis Factor-Alpha Receptor 2 Levels Was Comparable to 2-Hour Post-Load Glucose in Diabetes Prediction

Background: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. Methods: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2), interleukin-6 (IL-6), adipocyte-fatty acid binding protein (A-FABP) and high-sensitivity C-reactive protein (hsCRP) were measured in baseline samples. Results: Seventy-six participants developed diabetes over 5.3 years (median). All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP) model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC) of the CDP model from 0.802 to 0.830 (P = 0.03), rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30). A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2), had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]). Conclusions: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT. © 2012 Woo et al.published_or_final_versio

Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years

Aims/hypothesis: Hypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years. Methods: In total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not. Results: Baseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status. Conclusions/interpretation: Adiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity

The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute to clinical heterogeneity. We hypothesized that genetically determined ABO histo-blood group antigen (ABH) differences in glycosylation may lead to differences in microbial binding by airway mucus, and thus predispose to early lung infection and more severe lung disease in a subset of patients with CF. infection in the severe or mild groups. Multivariate analyses of other clinical phenotypes, including gender, asthma, and meconium ileus demonstrated no differences between groups based on ABH type. infection, nor was there any association with other clinical phenotypes in a group of 808 patients homozygous for the ΔF508 mutation

Management of osteoporosis in patients hospitalized for hip fractures

Hip fracture is associated with high morbidity, mortality, and economic burden worldwide. It is also a major risk factor for a subsequent fracture. A literature search on the management of osteoporosis in patients with hip fracture was performed on the Medline database. Only one clinical drug trial was conducted in patients with a recent hip fracture. Further studies that specifically address post-fracture management of hip fracture are needed. The efficacy of anti-osteoporosis medication in older individuals and those at high risk of fall is reviewed in this paper. Adequate nutrition is vital for bone health and to prevent falls, especially in malnourished patients. Protein, calcium, and vitamin D supplementation is associated with increased hip BMD and a reduction in falls. Fall prevention, exercise, and balance training incorporated in a comprehensive rehabilitation program are essential to improve functional disability and survival. Exclusion of secondary causes of osteoporosis and treatment of coexistent medical conditions are also vital. Such a multidisciplinary team approach to the management of hip fracture patients is associated with a better clinical outcome. Although hip fracture is the most serious of all fractures, osteoporosis management should be prioritized to prevent deterioration of health and occurrence of further fracture

AAV Exploits Subcellular Stress Associated with Inflammation, Endoplasmic Reticulum Expansion, and Misfolded Proteins in Models of Cystic Fibrosis

Barriers to infection act at multiple levels to prevent viruses, bacteria, and parasites from commandeering host cells for their own purposes. An intriguing hypothesis is that if a cell experiences stress, such as that elicited by inflammation, endoplasmic reticulum (ER) expansion, or misfolded proteins, then subcellular barriers will be less effective at preventing viral infection. Here we have used models of cystic fibrosis (CF) to test whether subcellular stress increases susceptibility to adeno-associated virus (AAV) infection. In human airway epithelium cultured at an air/liquid interface, physiological conditions of subcellular stress and ER expansion were mimicked using supernatant from mucopurulent material derived from CF lungs. Using this inflammatory stimulus to recapitulate stress found in diseased airways, we demonstrated that AAV infection was significantly enhanced. Since over 90% of CF cases are associated with a misfolded variant of Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508-CFTR), we then explored whether the presence of misfolded proteins could independently increase susceptibility to AAV infection. In these models, AAV was an order of magnitude more efficient at transducing cells expressing ΔF508-CFTR than in cells expressing wild-type CFTR. Rescue of misfolded ΔF508-CFTR under low temperature conditions restored viral transduction efficiency to that demonstrated in controls, suggesting effects related to protein misfolding were responsible for increasing susceptibility to infection. By testing other CFTR mutants, G551D, D572N, and 1410X, we have shown this phenomenon is common to other misfolded proteins and not related to loss of CFTR activity. The presence of misfolded proteins did not affect cell surface attachment of virus or influence expression levels from promoter transgene cassettes in plasmid transfection studies, indicating exploitation occurs at the level of virion trafficking or processing. Thus, we surmised that factors enlisted to process misfolded proteins such as ΔF508-CFTR in the secretory pathway also act to restrict viral infection. In line with this hypothesis, we found that AAV trafficked to the microtubule organizing center and localized near Golgi/ER transport proteins. Moreover, AAV infection efficiency could be modulated with siRNA-mediated knockdown of proteins involved in processing ΔF508-CFTR or sorting retrograde cargo from the Golgi and ER (calnexin, KDEL-R, β-COP, and PSMB3). In summary, our data support a model where AAV exploits a compromised secretory system and, importantly, underscore the gravity with which a stressed subcellular environment, under internal or external insults, can impact infection efficiency