Risk factors for the development of acute lung injury in patients with infectious pneumonia

ABSTRACT: INTRODUCTION: Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia. METHODS: A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner. RESULTS: The study included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development. CONCLUSIONS: The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.     

Design and Development of Acetylthiocholine Electrochemical Biosensor Based on Zinc Oxide–Cerium Oxide Nanohybrid Modified Platinum Electrode

Acetylcholinesterase (AChE) enzyme has been predominantly used for the detection of pesticides and metal ions. But, these sensors respond to pesticides as well as metal ions at certain concentration, which results in poor selectivity. Hence in this work, the amount of thiocholine produced during AChE inhibition has been estimated to detect the residual activity of AChE enzyme in-turn to enhance the efficiency of the biosensor. In this context, Pt/ZnO–CeO₂/AChE/Chitosan based biosensor has been developed for sensitive voltammetric quantification of thiocholine in AChE. The sensor exhibited enhanced electron transfer rate, good conductivity and biocompatibility. Both the intrinsic and extrinsic parameters were simultaneously optimized using second order polynomial regression to get the best conditions for ATCh determination. Under optimized experimental conditions, the redox peak current was linear over the concentration range of 0.1–1.5 mM with detection and quantification limit of 0.05 and 0.15 μM respectively and the sensitivity of 1.47 μA mM^?1.     

Long term outcome of elective day case percutaneous coronary intervention in patients with stable angina

Patients undergoing elective PCI are traditionally admitted overnight, however day case PCI cuts costs and has been proposed as a safe method for selected patients. We evaluated the success and long term clinical outcomes of day case percutaneous coronary intervention (PCI) for outpatients with stable angina.In total, 484 consecutive patients treated over a five year period with planned day case PCI were studied and followed up for 12 months. Successful PCI with same day discharge was performed in 463 patients (95.7%). There were 21 patients (4.3%) who required hospital admission. Reasons for failed discharge were hematoma formation (n = 7, 1.4%), coronary dissection (n = 4, 0.8%), post-procedural chest pain (n = 3, 0.6%), prolonged procedure (n = 2, 0.4%), and 1 each of acute stent thrombosis, coronary perforation, anaphylaxis, minor drug reaction and a functional study for untreated disease. One year follow up was complete for 439/484 (90.7%). At 12 months there were 6 hospitalizations for angina (1.2%, 95% CI 0.6–3.0%), 20 repeat revascularisations (4.1%, 95% CI 2.7–6.3%), 3 myocardial infarctions (0.6%, 95% CI 0.2–2.1%) and 2 deaths (0.4%, 95% CI 0.1–1.6%). Event free survival at 1 year follow up was 93.6% (95% CI 90.7–95.6%).Selecting patients for day case PCI is safe, and can achieve a high rate of success with excellent long term outcomes.     

Structural basis for substrate discrimination by E. coli repair enzyme,AlkB

E. coli AlkB, a repair enzyme of the dioxygenase family, catalyses the removal of mutagenic methylated nucleotides from the genome. Known for substrate promiscuity, AlkB''s catalytic mechanism and conformational changes accompanying substrate binding have been extensively dissected. However, the structural parameters of various substrates governing their recognition by AlkB still remain elusive. In this work, through solution-state vibrational spectra of methylated substrates bound to AlkB in combination with computational analysis, we show that the recognition specificity is dictated by the protonation states of the substrates. Specificity is conferred predominantly through hydrogen bonding and cation–π interactions. Furthermore, we report on the interaction of AlkB with normal, unmodified nucleotides, wherein the presence of an exocyclic amino group serves as an essential criterion for the initial process of substrate recognition. Taken together, these results provide a rationale for structural determinants of substrate specificity as well as mode of lesion discrimination employed by AlkB.

Positive charge on methylated nucleotides is a prime criterion for substrate recognition by E. coli AlkB.     

Changes in Caries Experience,Untreated Caries,Sealant Prevalence,and Preventive Behavior Among Third-Graders in New York State, 2002–2004 and 2009–2012

ObjectiveThis study assessed changes in caries experience, untreated caries, sealant prevalence, and preventive behavior among third-grade children in New York State to monitor progress toward state health objectives.MethodsWe analyzed children''s data from the 2002–2004 (n=10,865) and 2009–2012 (n=6,758) New York State Oral Health Survey. We calculated differences in weighted percentages and 95% confidence intervals for caries experience, untreated caries, sealant prevalence, and preventive behavior. We used logistic regression procedures to assess the independent effects and interaction terms on dental caries experience.ResultsThe percentage of children with dental caries and untreated caries decreased from 54.1% and 33.0% in 2002–2004 to 45.2% and 23.6% in 2009–2012, respectively. While this decrease was not uniform across income subgroups, the prevalence of sealants, a key measure of the use of preventive services, increased significantly from 16.7% to 36.0% among lower-income children.ConclusionsMeasurable improvement in reducing dental caries prevalence among third-grade children has been made in New York State, but this improvement was not uniform across subgroups. Specifically, disease prevalence among lower-income children remained high, underscoring the need to strengthen existing programs and identify additional policy and programmatic interventions.Researchers generally agree that the prevalence and severity of dental caries among U.S. and New York State (NYS) school-age children declined steadily from the 1970s to the 1990s. Although this trend has continued for older children in more recent years, this trend is uncertain among younger children aged 2–8 years.^1–3 Findings from analyses of 1988–1994 and 1999–2004 national surveys show that declines in dental caries observed in earlier decades among younger children may have plateaued or dental caries may even be increasing among subgroups of younger children.⁴ Because of the persistent higher disease rate, especially in low-income groups, prevention of tooth decay among children has become the focus of many prevention efforts.^5,6 Since 2001, the Centers for Disease Control and Prevention (CDC) and the Health Resources and Services Administration have provided grants and technical assistance to NYS to strengthen the infrastructure and capacity to promote fluoridation and improve its quality, as well as to strengthen school-based preventive and early treatment programs.Changes have also been made to increase insurance coverage for dental services and improve annual dental visits.^7,8 Child Health Plus, the state Children''s Health Insurance Program (CHIP), was implemented in 1997 to provide public health insurance for near-poor children from families previously not eligible for Medicaid. According to a U.S. Government Accounting Office report, nationally, Medicaid and CHIP beneficiaries, children in particular, showed increases in the use of dental services (from 28% in 1996 to 37% in 2010), but still visited the dentist less frequently than privately insured children (58% in 2010).⁹ In NYS, the Medicaid program enhanced the fee structure for dental procedures in 2000. In addition, professional organizations, advocacy groups, and foundations have made a concerted effort to promote prevention and access to care. The professional recommendation to initiate first dental visit shifted from age 3 to age 1 around 2003.¹⁰ To assess the collective effect of these and other efforts in NYS, we examined data on caries experience, untreated caries, sealant prevalence, and preventive behavior among third-grade children from the 2002–2004 and 2009–2012 NYS Oral Health Survey.     

Endothelial caveolar hub regulation of adenosine triphosphate-induced endothelial nitric oxide synthase subcellular partitioning and domain-specific phosphorylation

ATP leads to endothelial NO synthase (eNOS)/NO-mediated vasodilation, a process hypothesized to depend on the endothelial caveolar eNOS partitioning and subcellular domain-specific multisite phosphorylation state. We demonstrate herein that, in both the absence and presence of ATP, the uterine artery endothelial caveolae contain specific protein machinery related to subcellular partitioning and act as specific focal "hubs" for NO- and ATP-related proteins. ATP-induced eNOS regulation showed a complex set of multisite posttranslational phosphorylation events that were closely associated with the enzyme's partitioning between caveolar and noncaveolar endothelial subcellular domains. The comprehensive model that we present demonstrates that ATP repartitioned eNOS between the caveolar and noncaveolar subcellular domains; specifically, the stimulatory (PSer635)eNOS was substantially higher in the caveolar pool with subcellular domain-independent increased levels on ATP treatment. The stimulatory (PSer1179)eNOS was not altered by ATP treatment. However, the inhibitory (PThr495)eNOS was regulated predominantly in the caveolar domain with decreased levels on ATP action. In contrast, the agonist-specific (PSer114)eNOS was localized in the noncaveolar pool with increased levels on ATP stimulation. Thus, the endothelial caveolar membrane system plays a pivotal role(s) in ATP-associated subcellular partitioning and possesses the relevant protein machinery for ATP-induced NO regulation. Furthermore, these subcellular domain-specific phosphorylation/dephosphorylation events provide evidence relating to eNOS spatio-temporal dynamics.     

Diabetes and Tooth Loss: An analysis of data from the National Health and Nutrition Examination Survey, 2003–2004

BackgroundThe authors conducted an analysis of data from the National Health and Nutrition Examination Survey (NHANES) to understand the association between diabetes and tooth loss in the United States.MethodsThe authors analyzed the oral examination and self-reported diabetes data obtained from the NHANES 2003–2004 cycle and included 2,508 participants representing a civilian, noninstitutionalized U.S. population 50 years and older. The authors calculated the prevalence of edentulism and the number of missing teeth among dentate people, and they used multiple regression analyses to assess the association between diabetes and tooth loss.ResultsThe prevalence of edentulism was 28 percent and 14 percent among people with and without diabetes, respectively. The multiple logistic regression analysis revealed that people with diabetes were more likely to be edentulous than were those without diabetes (adjusted odds ratio = 2.25; 95 percent confidence interval, 1.19–4.21). Among dentate adults, those with diabetes had a higher number of missing teeth than did adults without diabetes (mean [standard error {SE}] = 9.8 [0.67]), mean [SE] = 6.7 [0.29]); P < .01).ConclusionsThese study results revealed that adults with diabetes are at higher risk of experiencing tooth loss and edentulism than are adults without diabetes. One of every five cases of edentulism in the United States is linked to diabetes.Practical ImplicationsAlthough the association between diabetes and periodontal disease is well established, health care professionals also need to recognize the risk of tooth loss and its effect on quality of life among people with diabetes.