The effect of cyclic compression on the mechanical properties of the inter-vertebral disc: an in vivo study in a rat tail model.
To assess the changes in the mechanical properties of inter-vertebral discs in vivo following static and cyclic compressive loading of different frequencies. An in vivo biomechanical study using a rat-tail model of the inter-vertebral disc.Background. Mechanical loading has been suggested as playing a major role in the etiology of disc degeneration, but the relationship is still not fully understood. Sixty Sprague-Dawley rats were subject to daily compressive stress via pins inserted in the 6th and 7th caudal vertebrae over a two-week loading period. Animals were randomly divided into a sham group (pin insertion, no loading), a static loading group, or cyclic loading groups of 0.5, 1.5, or 2.5 Hz. Loading was applied for 1 h each day from the 3rd to 17th day following pin insertion, and the angular compliance, angular laxity, and inter-pin distance were measured in vivo at days 0, 3, 10 and 17. Changes in the inter-vertebral disc height depended on the frequency of loading, with the decrease in disc height in the static compression group significantly greater than that in all other groups, whereas the decrease in the 1.5 Hz cyclic compression group was significantly smaller than that in all other compression groups. Changes in disc properties depend on both the total load exposure and the frequency of loading. Cyclic loading in general produced less marked changes than static loading, but loading at particular frequencies may result in more severe changes. Previous studies have shown the in vivo changes in the mechanical properties of inter-vertebral discs to depend on the magnitude and duration of loading. In this study, a frequency dependent response to cyclic loading is also demonstrated.


Volatile organic compounds and risk of asthma and allergy: a systematic review.
Volatile organic compounds (VOCs) are ubiquitous domestic pollutants. Their role in asthma/allergy development and exacerbations is uncertain. This systematic review investigated whether domestic VOC exposure increases the risk of developing and/or exacerbating asthma and allergic disorders. We systematically searched 11 databases and three trial repositories, and contacted an international panel of experts to identify published and unpublished experimental and epidemiological studies. 8455 potentially relevant studies were identified; 852 papers were removed after de-duplication, leaving 7603 unique papers that were screened. Of these, 278 were reviewed in detail and 53 satisfied the inclusion criteria. Critical appraisal of the included studies indicated an overall lack of high-quality evidence and substantial risk of bias in this body of knowledge. Aromatics (i.e. benzenes, toluenes and xylenes) and formaldehyde were the main VOC classes studied, both in relation to the development and exacerbations of asthma and allergy. Approximately equal numbers of studies reported that exposure increased risks and that exposure was not associated with any detrimental effects. The available evidence implicating domestic VOC exposure in the risk of developing and/or exacerbating asthma and allergy is of poor quality and inconsistent. Prospective, preferably experimental studies, investigating the impact of reducing/eliminating exposure to VOC, are now needed in order to generate a more definitive evidence base to inform policy and clinical deliberations in relation to the management of the now substantial sections of the population who are either at risk of developing asthma/allergy or living with established disease.


Renal function and solitary kidney disease: Wilms tumour survivors versus patients with unilateral renal agenesis.
To test the hypothesis that Wilms tumour survivors (WTs) experience increased disturbance in renal function, even after prompt treatment, compared to patients with unilateral renal agenesis (URA). To assess the renal function of 30 WTs and 17 individuals with URA, the estimated glomerular filtration rate (eGFR) was calculated using the Schwartz and Filler formulas as well as the new Schwartz equation for chronic kidney disease. To measure kidney damage, serum levels and urine excretion of β(2)-microglobulin (B2M), cystatin C (Cys C), neutrophil gelatinase-associated lipocalin (NGAL) were tested, N-acetyl-β-glucosaminidase (NAG), and albumin urine excretion and urine sediment were examined. Blood pressure was measured. No differences were found between the groups in terms of eGFR, serum Cys C, B2M and NGAL concentrations. The urine excretion of Cys C, NGAL and NAG was similar in both groups. URA patients had higher B2M excretion than WTs. Arterial hypertension was present in 7/30 (23%) WTs and 1/17 (6%) patients with URA. WTs have similar eGFR to individuals with URA and are more likely to have arterial hypertension. The patients with URA have signs of tubular damage. This study demonstrates the need for nephrological monitoring of individuals with a single kidney.


Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.
Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity.


Reporting and analysis of repeated measurements in preclinical animals experiments.
A common feature of preclinical animal experiments is repeated measurement of the outcome, e.g., body weight measured in mice pups weekly for 20 weeks. Separate time point analysis or repeated measures analysis approaches can be used to analyze such data. Each approach requires assumptions about the underlying data and violations of these assumptions have implications for estimation of precision, and type I and type II error rates. Given the ethical responsibilities to maximize valid results obtained from animals used in research, our objective was to evaluate approaches to reporting repeated measures design used by investigators and to assess how assumptions about variation in the outcome over time impact type I and II error rates and precision of estimates. We assessed the reporting of repeated measures designs of 58 studies in preclinical animal experiments. We used simulation modelling to evaluate three approaches to statistical analysis of repeated measurement data. In particular, we assessed the impact of (a) repeated measure analysis assuming that the outcome had non-constant variation at all time points (heterogeneous variance) (b) repeated measure analysis assuming constant variation in the outcome (homogeneous variance), (c) separate ANOVA at individual time point in repeated measures designs. The evaluation of the three model fitting was based on comparing the p-values distributions, the type I and type II error rates and by implication, the shrinkage or inflation of standard error estimates from 1000 simulated dataset. Of 58 studies with repeated measures design, three provided a rationale for repeated measurement and 23 studies reported using a repeated-measures analysis approach. Of the 35 studies that did not use repeated-measures analysis, fourteen studies used only two time points to calculate weight change which potentially means collected data was not fully utilized. Other studies reported only select time points (n = 12) raising the issue of selective reporting. Simulation studies showed that an incorrect assumption about the variance structure resulted in modified error rates and precision estimates. The reporting of the validity of assumptions for repeated measurement data is very poor. The homogeneous variation assumption, which is often invalid for body weight measurements, should be confirmed prior to conducting the repeated-measures analysis using homogeneous covariance structure and adjusting the analysis using corrections or model specifications if this is not met.


Clinician Attitudes Toward Adoption of Pediatric Emergency Telemedicine in Rural Hospitals.
Although there is growing evidence regarding the utility of telemedicine in providing care for acutely ill children in underserved settings, adoption of pediatric emergency telemedicine remains limited, and little data exist to inform implementation efforts. Among clinician stakeholders, we examined attitudes regarding pediatric emergency telemedicine, including barriers to adoption in rural settings and potential strategies to overcome these barriers. Using a sequential mixed-methods approach, we first performed semistructured interviews with clinician stakeholders using thematic content analysis to generate a conceptual model for pediatric emergency telemedicine adoption. Based on this model, we then developed and fielded a survey to further examine attitudes regarding barriers to adoption and strategies to improve adoption. Factors influencing adoption of pediatric emergency telemedicine were identified and categorized into 3 domains: contextual factors (such as regional geography, hospital culture, and individual experience), perceived usefulness of pediatric emergency telemedicine, and perceived ease of use of pediatric emergency telemedicine. Within the domains of perceived usefulness and perceived ease of use, belief in the relative advantage of telemedicine was the most pronounced difference between telemedicine proponents and nonproponents. Strategies identified to improve adoption of telemedicine included patient-specific education, clinical protocols for use, decreasing response times, and simplifying the technology. More effective adoption of pediatric emergency telemedicine among clinicians will require addressing perceived usefulness and perceived ease of use in the context of local factors. Future studies should examine the impact of specific identified strategies on adoption of pediatric emergency telemedicine and patient outcomes in rural settings.


Usefulness of intra-aortic balloon pump counterpulsation in patients with cardiogenic shock from acute myocardial infarction.
Although intra-aortic balloon pump (IABP) counterpulsation is increasingly being used for the treatment of patients with cardiogenic shock from acute myocardial infarction, data on the long-term outcomes are lacking. The aim of the present study was to evaluate the 30-day and long-term mortality and to identify predictors for 30-day and long-term all-cause mortality of patients with acute myocardial infarction complicated by cardiogenic shock who were treated with IABP. From January 1990 to June 2004, 300 consecutive patients treated with IABP were included. The mean age of the study population was 61 +/- 11 years, and 79% of the patients were men. The survival rate until IABP removal after successful hemodynamic stabilization was 70% (n = 211). The overall cumulative 30-day survival rate was 58%. The 30-day mortality rate decreased over time from 52% in 1990 to 1994 to 36% in 2000 to 2004 (p for trend <0.05). Follow-up ranged from 0 to 15 years. In patients who survived until IABP removal, the cumulative 1-, 5-, and 10-year survival rate was 69%, 58%, and 36%, respectively. The adjusted predictors of long-term mortality were arrhythmias during the intensive cardiac care unit stay (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2 to 2.9) and renal failure during the intensive cardiac care unit stay (HR 2.5, 95% CI 1.3 to 5.1). After adjustment, treatment with primary percutaneous coronary intervention (HR 0.5, 95% CI 0.3 to 0.9) and coronary artery bypass grafting (HR 0.4, 95% CI 0.2 to 0.8) were associated with lower long-term mortality. In conclusion, in patients with acute myocardial infarction complicated by cardiogenic shock treated with IABP, the 30-day survival improved with time and an encouraging number of patients survived in the long term.


Towards a crucial role for DC-SIGN in tuberculosis and beyond.
The C-type lectin DC-SIGN has recently received considerable attention in the context of tuberculosis and other infectious diseases. Clinical investigations, together with genetic association studies, strongly support the notion that variation in the level of expression of DC-SIGN - but not changes in the structure of the protein - might have a strong impact on the susceptibility to and pathogenesis of several infectious diseases, including tuberculosis. In addition, efforts to decipher the evolutionary history of the gene encoding DC-SIGN clearly demonstrated that this gene is under strong selective constraints that have prevented the accumulation of amino acid changes over time. Altogether, these findings suggest that DC-SIGN might play a crucial part in host immunity to pathogens and possibly beyond, at an early stage of human development.


Economic burden of neonatal sepsis in sub-Saharan Africa.
The third Sustainable Development Goal for child health, which aims to end preventable deaths of newborns and children less than 5 years of age by 2030, cannot be met without substantial reduction of infection-specific neonatal mortality in the developing world. Neonatal infections are estimated to account for 26% of annual neonatal deaths, with mortality rates highest in sub-Saharan Africa (SSA). Reliable and comprehensive estimates of the incidence and aetiology surrounding neonatal sepsis in SSA remain incompletely available. We estimate the economic burden of neonatal sepsis in SSA. Data available through global health agencies and in the medical literature were used to determine population demographics in SSA, as well as to determine the incidence, disease burden, mortality and resulting disabilities associated with neonatal sepsis. The disability-adjusted life years (DALY) associated with successful treatment or prevention of neonatal sepsis in SSA for 1 year were calculated. The value of a statistical life (VSL) methodology was estimated to evaluate the economic burden of untreated neonatal sepsis in SSA. We conservatively estimate that 5.29-8.73 million DALYs are lost annually in SSA due to neonatal sepsis. Corresponding VSL estimates predict an annual economic burden ranging from $10 billion to $469 billion. Our results highlight and quantify the scope of the public health and economic burden posed by neonatal sepsis in SSA. We quantify the substantial potential impact of more successful treatment and prevention strategies, and we highlight the need for greater investment in strategies to characterise, diagnose, prevent and manage neonatal sepsis and its long-term sequelae in SSA.


Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala.
Memory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered.


Evaluation of stepping stones as a tool for changing knowledge, attitudes and behaviours associated with gender, relationships and HIV risk in Karnataka, India.
Stepping Stones training aims to help individuals explore sexual relationships and recognize gender inequalities, the structural drivers of the HIV epidemic, in order to understand risk behaviours and to seek solutions to factors that increase HIV vulnerability. Despite earlier studies suggesting the success of Stepping Stones, little data exist to show diffusion to trainees' social networks or the wider community. A mixed-methods evaluation of this approach was undertaken using in-depth interviews of trainees and friends, and polling booth surveys in 20 villages where Stepping Stones training took place and in another 20 villages with no Stepping Stones intervention. The interview respondents and their friends reported significant changes in their relationships after training, and benefit from discussion of gender, sexuality, condom use and HIV vulnerability issues. However, though diffusion of this knowledge at the level of personal contacts was strong, the evaluation revealed that diffusion to the community level was limited. The qualitative part of this study reflects other studies in different settings, in that SS participants gained immensely from the training. Wider behaviour change is a challenging goal that many programmes fail to attain, with most interventions too limited in scope and intensity to produce larger community effects. This may have contributed to the fact that we observed few differences between interventions and non-intervention villages in this study. However, it is also possible that we had excessive expectations of individual change at the community level, and that it might have been more appropriate to have had broader community level rather than individual behavioural change indicators. We suggest that SS could be enhanced by efforts to better engage existing community opinion leaders, to empower and train participants as community change agents, and to support the development of village-level action plans that combat sexual stereotyping and risky behaviours that lead to unhealthy sexual relationships.


Prevalence of lower urinary tract symptoms among female elementary school teachers in Taipei.
The aim of this study was to estimate the prevalence of lower urinary tract symptoms (LUTS) among female elementary school teachers in Taipei. A total of 520 self-administered surveys were distributed to 26 elementary schools in Taipei City. Data analyses were based on 445 usable surveys. The prevalence rates for different types of LUTS ranged from 9.9 to 44.5%. The prevalence of urinary incontinence (UI; 26.7%) and nocturia (16.0%) fell within the prevalence estimates of these LUTS in North American and European women. Employed women in this study were more likely to experience LUTS than women in previous epidemiological or community studies. This study extended research on UI into other LUTS among employed women in Asia. Study results suggest that the working environment may affect LUTS in female elementary school teachers. This preliminary study is important for developing future behavioral interventions for female LUTS in the workplace.


Outfracture osteotomy on lateral maxillary wall as a modified sinus graft technique.
The purpose of this study was to provide feasibility of a new technique of sinus graft: outfracture osteotomy sinus graft. The author modified the window opening method from the original trapdoor technique to an outfracturing and readaptation technique. It provides a few advantages in dental implant treatment of atrophic maxillary posterior edentulous alveolar ridges: 1) in combined cases of height and width problems; 2) in cases with anatomic problems such as sinus septum, thick lateral sinus wall, and intrabony bleedings; 3) possible use of the outfractured bony segment as a covering membrane. The follow-up of 34 patients (40 cases; 6 bilateral cases) revealed good results without a case of graft failure and showed excellent survival and function of the dental implants. The sinus graft technique was modified as the author outfractured and readapted the bony lateral window, with several advantages as mentioned above. This new outfracture osteotomy sinus graft technique has excellent results as an alternative to the original trapdoor technique.


Role of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus.
Shiga-toxigenic Escherichia coli strains belonging to serotype O157 are important human pathogens, but the genetic basis of expression of the O157 antigen and the role played by the lipopolysaccharide O side chain in the adherence of this organism to epithelial cells are not understood. We performed TnphoA mutagenesis on E. coli O157:H7 strain 86-24 to identify a mutant (strain F12) deficient in O-antigen expression. Nucleotide sequence analysis demonstrated that the transposon inserted within an open reading frame with significant homology to rfbE of Vibrio cholerae O1 (U. H. Stroeher, L. E. Karageorgos, R. Morona, and P. A. Manning, Proc. Natl. Acad. Sci. USA 89:2566-2570, 1992), which is postulated to encode perosamine synthetase. This open reading frame was designated rfbE(EcO157:H7). The guanine-plus-cytosine fraction (0.35) suggests that rfbE(EcO157:H7) may have originated in a species other than E. coli. rfbE(EcO157:H7) is conserved in nontoxigenic E. coli O157 strains expressing a variety of other flagellar antigens but is not found in E. coli O55:H7 strains, which are more closely related to E. coli O157:H7. Strain F12 was significantly more adherent to HeLa cells in a quantitative adherence assay than was its E. coli O157:H7 parent, but they did not differ in other phenotypes. Restoration of the expression of the O side chain by complementation of the TnphoA mutation in strain F12 by a plasmid expressing intact rfbE(EcO157:H7) reduced the adherence of the hyperadherent strain F12. We conclude that rfbE(EcO157:H7) is necessary for the expression of the O157 antigen, that acquisition of E. coli rfb genes occurred independently in E. coli O157:H7 and unrelated O157 strains, and that the O side chain of E. coli O157:H7 lipopolysaccharide interferes with the adherence of E. coli O157:H7 to epithelial cells.


Localized rest and stress human cardiac creatine kinase reaction kinetics at 3 T.
Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed. We assess scanning in a supine position and validate the MR measurement against biopsy assay of CK activity. We report normal ranges of stress CK forward rate (kfCK ) for healthy volunteers and obese patients. TRiST measures kfCK in 40 min at 3 T. StreST extends the previously developed TRiST to also make a further kfCK measurement during <20 min of dobutamine stress. We test our TRiST implementation in skeletal muscle and myocardium in both prone and supine positions. We evaluate StreST in the myocardium of six healthy volunteers and 34 obese subjects. We validated MR-measured kfCK against biopsy assays of CK activity. TRiST kfCK values matched literature values in skeletal muscle (kfCK = 0.25 ± 0.03 s-1 vs 0.27 ± 0.03 s-1 ) and myocardium when measured in the prone position (0.32 ± 0.15 s-1 ), but a significant difference was found for TRiST kfCK measured supine (0.24 ± 0.12 s-1 ). This difference was because of different respiratory- and cardiac-motion-induced B0 changes in the two positions. Using supine TRiST, cardiac kfCK values for normal-weight subjects were 0.15 ± 0.09 s-1 at rest and 0.17 ± 0.15 s-1 during stress. For obese subjects, kfCK was 0.16 ± 0.07 s-1 at rest and 0.17 ± 0.10 s-1 during stress. Rest myocardial kfCK and CK activity from LV biopsies of the same subjects correlated (R = 0.43, p = 0.03). We present an independent implementation of TRiST on the Siemens platform using a commercially available coil. Our extended StreST protocol enables cardiac kfCK to be measured during dobutamine-induced stress in the supine position.


Interaction of recombinant myocilin with the matricellular protein SPARC: functional implications.
Myocilin is an extracellular glycoprotein with unknown function that is associated with glaucoma. Calpain II cleaves recombinant myocilin within the linker region of the protein, releasing the C-terminal olfactomedin domain from the N-terminal domain. The authors previously reported that myocilin interacts with the C-terminal region of hevin, a secretory glycoprotein belonging to the SPARC family of matricellular proteins. This study aims to investigate the interaction of myocilin with SPARC. Protein-protein interactions were evaluated by the yeast two-hybrid system. The positive interactions were confirmed by solid-phase binding assays using Ni-chelating HPLC purified recombinant proteins and coexpression of recombinant proteins in HEK-293T cells. Coexpression of myocilin, SPARC, and hevin in ocular tissues was identified by immunoflorescence microscopy, Western blot, and array-based gene profiling. Yeast two-hybrid analyses showed that myocilin interacted with the highly conserved C-terminal extracellular calcium binding (EC) domain within SPARC and hevin. Solid-phase binding assays confirmed these interactions and showed that both myocilin and its C-terminal olfactomedin fragment interacted noncovalently with SPARC and a peptide containing the EC domain of SPARC. Full-length myocilin interacted with higher affinity with SPARC and its EC domain than the myocilin C-terminal fragment. Coexpression of the two recombinant proteins in HEK-293T cells also indicated their intracellular interaction. Recombinant myocilin and SPARC interact through their C-terminal domains. The data suggest that the proteolytic processing of myocilin modulates this interaction as well as the interactions of myocilin with other extracellular matrix and matricellular proteins, further supporting a functional role for this proteolytic cleavage.


Functional Independence Measure for Children (WeeFIM): a preliminary study in nondisabled Japanese children.
The Functional Independence Measure for Children (WeeFIM) was developed based on the FIMSM instrument to assess disability in children aged six months to seven years. Its reliability and validity have been studied, and normative data are available for American children. The WeeFIM instrument is potentially an internationally useful instrument, but data from other countries are lacking. The objectives of this study are to examine whether the WeeFIM instrument is applicable to Japanese children and to describe preliminary normative data. To study interrater reliability, we had two examiners assess 20 nondisabled children and calculated weighted kappas for individual item scores and intraclass correlation coefficients for total scores and motor and cognitive subscores. We then assessed 110 nondisabled children ages six months to seven years to obtain normative data and compared them with the American data. In 51 of these healthy children, we compared total WeeFIM scores with developmental ages as obtained with the Tsumori test, a standardized developmental test widely used in Japan to assess its concurrent validity. The weighted kappas were greater than 0.8, and the intraclass correlation coefficients were greater than 0.98. Total scores and motor and cognitive subscores increased with age, reaching a plateau at 60 to 72 months, which is similar to the American data. There were three patterns of chronologic changes in individual item scores: items showing high correlations with age (Spearman's rho > 0.8; grooming, dressing, memory, etc.), moderate correlations (0.8 > rho > 0.7; eating, bladder, comprehension, etc.), and lower correlations (0.7 > rho > 0.6; locomotion and chair transfer). Total scores correlated significantly with developmental ages (Spearman's rho = 0.938), but there was a discrepancy between each item score and the pass-or-fail patterns of the Tsumori test. This study demonstrated the applicability of the WeeFIM instrument to Japanese children with satisfactory reliability and validity and provided preliminary normative data for future studies.


Pharmacologic prophylaxis: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery.
New-onset atrial fibrillation (AF) occurs frequently in patients after cardiac surgery. The purpose of this study was to review the published trials and to provide clinical practice guidelines for pharmacologic prophylaxis against postoperative AF. Trials of pharmacologic prophylaxis against AF after heart surgery were identified by searching MEDLINE, the Cochrane Controlled Trials Register, and the bibliographies of published reports. Evidence grades and clinical recommendation scores were assigned to each prophylactic drug based on published evidence. Ninety-one trials were identified. The primary study design was a randomized, controlled trial of one drug vs placebo/usual care. Pharmacologic therapies that are reviewed include Vaughan-Williams class II agents (ie, beta-receptor antagonists) [29 trials; 2,901 patients], Vaughan-Williams class III agents (ie, sotalol and amiodarone) [18 trials; 2,978 patients], Vaughan-Williams class IV agents (ie, verapamil and diltiazem) [5 trials; 601 patients], and Vaughan-Williams class I agents (ie, quinidine and procainamide) [3 trials; 246 patients], as well as digitalis (10 trials; 1,401 patients), magnesium (14 trials; 1,853 patients), dexamethasone (1 trial; 216 patients), glucose-insulin-potassium (3 trials; 102 patients), insulin (1 trial; 501 patients), triiodothyronine (2 trials; 301 patients), and aniline (1 trial; 32 patients). A consistent finding in this review is that antiarrhythmic drugs with beta-adrenergic receptor-blocking effects (ie, class II beta-blockers, sotalol, and amiodarone) demonstrated successful prophylaxis. Furthermore, those therapies that did not inhibit beta-receptors generally failed to demonstrate a decreased incidence in postoperative AF. While sotalol and amiodarone have been shown in some studies to be effective, their safety and the incremental prophylactic advantage in comparison with beta-blockers has not been conclusively demonstrated. On the basis of evidence that has been reviewed and graded for quality, it is recommended that strong consideration should be given to the prophylactic administration of Vaughan-Williams class II beta-blocking drugs as a means of lowering the incidence of new-onset post-cardiac surgery AF.


Assessing Risk Among Correctional Community Probation Populations: Predicting Reoffense With Mobile Neurocognitive Assessment Software.
We seek to address current limitations of forensic risk assessments by introducing the first mobile, self-scoring, risk assessment software that relies on neurocognitive testing to predict reoffense. This assessment, run entirely on a tablet, measures decision-making via a suite of neurocognitive tests in less than 30 minutes. The software measures several cognitive and decision-making traits of the user, including impulsivity, empathy, aggression, and several other traits linked to reoffending. Our analysis measured whether this assessment successfully predicted recidivism by testing probationers in a large urban city (Houston, TX, United States) from 2017 to 2019. To determine predictive validity, we used machine learning to yield cross-validated receiver-operator characteristics. Results gave a recidivism prediction value of 0.70, making it comparable to commonly used risk assessments. This novel approach diverges from traditional self-reporting, interview-based, and criminal-records-based approaches, and can also add a protective layer against bias, while strengthening model accuracy in predicting reoffense. In addition, subjectivity is eliminated and time-consuming administrative efforts are reduced. With continued data collection, this approach opens the possibility of identifying different levels of recidivism risk, by crime type, for any age, or gender, and seeks to steer individuals appropriately toward rehabilitative programs. Suggestions for future research directions are provided.


An extended π-system and enhanced electronic delocalization on symmetric [Ru3O(CH3COO)6(L)3]n complexes combined with azanaphthalene ligands.
We report on the investigation of a new series of symmetric trinuclear ruthenium complexes combined with azanaphthalene ligands: [Ru3O(CH3COO)6(L)3]PF6 where L = (1) quinazoline (qui), (2) 5-nitroisoquinoline (5-nitroiq), (3) 5-bromoisoquinoline (5-briq), (4) isoquinoline (iq), (5) 5-aminoisoquinoline (5-amiq), and (6) 5,6,7,8-tetrahydroisoquinoline (thiq). The crystal structure of complex 1, [Ru3O(CH3COO)6(qui)3]PF6, was determined by X-ray diffraction analysis, showing a high degree of co-planarity between the [Ru3O] plane and the azanaphthalene ligands. Spectroscopic (UV-visible, NMR and infra-red) and electrochemical (cyclic voltammetry and spectroelectrochemistry) data showed correlation with the pKa values of the azanaphthalene ligands and this dependence was rationalized in terms of the molecular orbital of the [Ru3O] unit and the structure of the ligands. By analysing the spectroscopic and electrochemical correlations, the ability of the azanaphthalene ligands to extend the electronic π-system of the [Ru3O] unit to the periphery of the compounds was demonstrated. This electronic effect accounts for the planarity of the structure of complex 1. It was also shown through molecular modeling results that, to explain the spectroscopic and electrochemical behaviour of these species, it is not possible to neglect the electronic mixing between the metallic and the acetate orbitals. Finally, this work revealed that electronic coupling is more pronounced in the azanaphthalene series of complexes than in pyridinic analogues and it is this coupling that determines the spectroscopic and electrochemical behaviour of the new species.


An eye-tracking investigation into readers' sensitivity to actual versus expected utility in the comprehension of conditionals.
The successful comprehension of a utility conditional (i.e., an "if p, then q" statement where p and/or q is valued by one or more agents) requires the construction of a mental representation of the situation described by that conditional and integration of this representation with prior context. In an eye-tracking experiment, we examined the time course of integrating conditional utility information into the broader discourse model. Specifically, the experiment determined whether readers were sensitive, during rapid heuristic processing, to the congruency between the utility of the consequent clause of a conditional (positive or negative) and a reader's subjective expectations based on prior context. On a number of eye-tracking measures we found that readers were sensitive to conditional utility-conditionals for which the consequent utility mismatched the utility that would be anticipated on the basis of prior context resulted in processing disruption. Crucially, this sensitivity emerged on measures that are accepted to indicate early processing within the language comprehension system and suggests that the evaluation of a conditional's utility informs the early stages of conditional processing.


HIPK2 phosphorylates ΔNp63α and promotes its degradation in response to DNA damage.
Homeodomain-interacting protein kinase 2 (HIPK2) is an emerging player in cell response to genotoxic agents that senses damage intensity and contributes to the cell's choice between cell cycle arrest and apoptosis. Phosphorylation of p53 at S46, an apoptosis-specific p53 posttranslational modification, is the most characterized HIPK2 function in response to lethal doses of ultraviolet (UV), ionizing radiation or different anticancer drugs, such as cisplatin, roscovitine and doxorubicin (DOX). Indeed, like p53, HIPK2 has been shown to contribute to the effectiveness of these treatments. Interestingly, p53-independent mechanisms of HIPK2-induced apoptosis were described for UV and tumor growth factor-β treatments; however, it is unknown whether these mechanisms are relevant for the responses to anticancer drugs. Because of the importance of the so-called 'p53-independent apoptosis and drug response' in human cancer chemotherapy, we asked whether p53-independent factor(s) might be involved in HIPK2-mediated chemosensitivity. Here, we show that HIPK2 depletion by RNA interference induces resistance to different anticancer drugs even in p53-null cells, suggesting the involvement of HIPK2 targets other than p53 in response to chemotherapy. In particular, we found that HIPK2 phosphorylates and promotes proteasomal degradation of ΔNp63α, a prosurvival ΔN isoform of the p53 family member, p63. Indeed, effective cell response to different genotoxic agents was shown to require phosphorylation-induced proteasomal degradation of ΔNp63α. In DOX-treated cells, we show that HIPK2 depletion interferes with ΔNp63α degradation, and expression of a HIPK2-resistant ΔNp63α-Δ390 mutant induces chemoresistance. We identify T397 as the ΔNp63α residue phosphorylated by HIPK2, and show that the non-phosphorylatable ΔNp63α-T397A mutant is not degraded in the face of either HIPK2 overexpression or DOX treatment. These results indicate ΔNp63α as a novel target of HIPK2 in response to genotoxic drugs.


Knowledge and Attitudes towards Handling Eggs in the Home: An Unexplored Food Safety Issue?
Foodborne illness is a global public health issue, with food handling in the home identified as an underestimated source. In Australia, there has been a significant increase in the incidence of salmonellosis with the majority of outbreaks linked to eggs. This study investigated Australian eggs consumer attitudes, behaviours and risk perceptions associated with the handling of raw eggs in the home. It was identified that 67% of participants chose free range eggs, 11% kept poultry, 7% did not have any preference, 7% cage eggs, 4% barn eggs, 2% organic eggs and 1% pasteurized eggs. The majority of participants (91%) reported they stored eggs in the fridge. It was identified that there is an underestimation of "risky behaviour" associated with the consumption of raw eggs in the home, as 84% of participants indicated that they did not consume raw eggs, but subsequently 86% indicated that they had eaten mixture/batter containing raw eggs. Participants' responses relating to food safety were also examined in relation to their profession and gender. Safer food handling practices were identified by Environmental Health Officers (EHO) and Food handlers compared to all other professions (p < 0.05). However, the gender of participants did not significantly affect (p > 0.05) their responses.


The further development and validation of the Liverpool Oral Rehabilitation Questionnaire: a cross-sectional survey of patients attending for oral rehabilitation and general dental practice.
Since the first version of the Liverpool Oral Rehabilitation Questionnaire (LORQ) was first published in 2004, the questionnaire has been modified to include more detail on chewing and appearance, and also details of denture, dental and implant status. The aim of this study is to report the ongoing development and validation of the LORQ version3. A postal survey of the LORQv3 and OHIP-14 questionnaires was performed in April 2004 of 164 patients who had attended the oral rehabilitation clinic from February 2000. In addition The LORQv3 was administered to 349 patients attending six General Dental Practices, based in Liverpool, attending for routine care. Patients attending GDP scored appreciably better on most items in the LORQv3. The questionnaire discriminated between cancer and non-cancer oral rehabilitation patients in items such as swallowing, chewing, trismus, drooling and food clearance. There was no significant difference between rehabilitation groups for any of the seven OHIP-14 domains. The LORQv3 demonstrated good criterion validity when compared to the OHIP-14 with social items in the LORQv3 correlating well with items of the OHIP-14. Conversely various LORQv3 items did not have strong correlates within the OHIP-14 thus endorsing the additional items in the LORQv3.


The Role of Adherence on the Impact of a School-Based Water, Sanitation, and Hygiene Intervention in Mali.
AbstractStudies assessing the impacts of school-based water, sanitation, and hygiene (WASH) interventions have revealed inconsistent improvements in pupils' health and educational outcomes. This may be in part due to suboptimal project fidelity or adherence. As part of a matched-control trial of a comprehensive school-based WASH project in Mali, we measured the degree to which schools met four prespecified WASH targets, comprised of 15 criteria, 0-3 years after program implementation. We compared achievement of the targets and criteria between beneficiary and matched control schools, and compared achievement within beneficiary schools at baseline and at follow-up visits. We assessed the "as-treated" associations between WASH target achievement and pupil diarrhea, respiratory symptoms, and absence. Between 44% and 81% of beneficiary schools achieved each target. Although adherence was inconsistent across schools, beneficiary schools, on average, met more WASH targets than matched control schools, and beneficiary schools also met more WASH targets at follow-up than at baseline. Very few of the targets were individually associated with health and absenteeism outcomes. Increasing achievement of multiple WASH targets together was associated with a lower odds of pupils having diarrhea (P trend < 0.01) and having respiratory symptoms (P trend < 0.01), but was not associated with roll-call absence (P trend = 0.14) or pupil-reported absence (P trend = 0.41). These results indicate that a comprehensive WASH intervention and a focus on increasing adherence may help maximize the health effects of school WASH programs, but that WASH alone might not be sufficient to decrease pupils' absenteeism.


Pre-travel health advice-seeking behavior among US international travelers departing from Boston Logan International Airport.
Globally mobile populations are at higher risk of acquiring geographically restricted infections and may play a role in the international spread of infectious diseases. Despite this, data about sources of health information used by international travelers are limited. We surveyed 1,254 travelers embarking from Boston Logan International Airport regarding sources of health information. We focused our analysis on travelers to low or low-middle income (LLMI) countries, as defined by the World Bank 2009 World Development Report. A total of 476 survey respondents were traveling to LLMI countries. Compared with travelers to upper-middle or high income (UMHI) countries, travelers to LLMI countries were younger, more likely to be foreign-born, and more frequently reported visiting family as the purpose of their trip. Prior to their trips, 46% of these travelers did not pursue health information of any type. In a multivariate analysis, being foreign-born, traveling alone, traveling for less than 14 days, and traveling for vacation each predicted a higher odds of not pursuing health information among travelers to LLMI countries. The most commonly cited reason for not pursuing health information was a lack of concern about health problems related to the trip. Among travelers to LLMI countries who did pursue health information, the internet was the most common source, followed by primary care practitioners. Less than a third of travelers to LLMI countries who sought health information visited a travel medicine specialist. In our study, 46% of travelers to LLMI countries did not seek health advice prior to their trip, largely due to a lack of concern about health issues related to travel. Among travelers who sought medical advice, the internet and primary care providers were the most common sources of information. These results suggest the need for health outreach and education programs targeted at travelers and primary care practitioners.


Predator-induced synchrony in population oscillations of coexisting small mammal species.
Comprehensive analyses of long-term (1977-2003) small-mammal abundance data from western Finland showed that populations of Microtus voles (field voles M. agrestis and sibling voles M. rossiaemeridionalis) voles, bank (Clethrionomys glareolus) and common shrews (Sorex araneus) fluctuated synchronously in 3 year population cycles. Time-series analyses indicated that interspecific synchrony is influenced strongly by density-dependent processes. Synchrony among Microtus and bank voles appeared additionally to be influenced by density-independent processes. To test whether interspecific synchronization through density-dependent processes is caused by predation, we experimentally reduced the densities of the main predators of small mammals in four large agricultural areas, and compared small mammal abundances in these to those in four control areas (2.5-3 km(2)) through a 3 year small-mammal population cycle. Predator reduction increased densities of the main prey species, Microtus voles, in all phases of the population cycle, while bank voles, the most important alternative prey of predators, responded positively only in the low and the increase phase. Manipulation also increased the autumn densities of water voles (Arvicola terrestris) in the increase phase of the cycle. No treatment effects were detected for common shrews or mice. Our results are in accordance with the alternative prey hypothesis, by which predators successively reduce the densities of both main and alternative prey species after the peak phase of small-mammal population cycles, thus inducing a synchronous low phase.


Oncology Nurse Retreat: A Strength-Based Approach to Self-Care and Personal Resilience .
Oncology nurses are at high risk for burnout and compassion fatigue. Self-care is an essential element that oncology nurses should incorporate into their daily lives but, instead, is often deprioritized. As a result, nurses do not seek out educational opportunities that focus on self-care or personal growth. This article describes the curriculum that was developed for an oncology nurse retreat that promoted self-care and building personal resilience using tools that could be adapted for use with patients and families. .


75% success rate after open debridement, exchange of tibial insert, and antibiotics in knee prosthetic joint infections.
Prosthetic joint infection (PJI) is a leading cause of early revision after total knee arthroplasty (TKA). Open debridement with exchange of tibial insert allows treatment of infection with retention of fixed components. We investigated the success rate of this procedure in the treatment of knee PJIs in a nationwide material, and determined whether the results were affected by microbiology, antibiotic treatment, or timing of debridement. 145 primary TKAs revised for the first time, due to infection, with debridement and exchange of the tibial insert were identified in the Swedish Knee Arthroplasty Register (SKAR). Staphylococcus aureus was the most common pathogen (37%) followed by coagulase-negative staphylococci (CNS) (23%). Failure was defined as death before the end of antibiotic treatment, revision of major components due to infection, life-long antibiotic treatment, or chronic infection. The overall healing rate was 75%. The type of infecting pathogen did not statistically significantly affect outcome. Staphylococcal infections treated without a combination of antibiotics including rifampin had a higher failure rate than those treated with rifampin (RR = 4, 95% CI: 2-10). In the 16 cases with more than 3 weeks of symptoms before treatment, the healing rate was 62%, as compared to 77% in the other cases (p = 0.2). The few patients with a revision model of prosthesis at primary operation had a high failure rate (5 of 8). Good results can be achieved by open debridement with exchange of tibial insert. It is important to use an antibiotic combination including rifampin in staphylococcal infections.


Facilitation May Buffer Competitive Effects: Indirect and Diffuse Interactions among Salt Marsh Plants.
Direct interactions among plant species may be highly modified by indirect or diffuse effects within a multispecies community. We investigated the direct and diffuse effects of two salt marsh perennials, Monanthechloe littoralis and Arthrocnemum subterminale, on winter annuals and the perennial herb Limonium californicum in a salt marsh in central California. In permanent plots, Monanthechloe had expanded substantially in the upper marsh over the past 13 yr, while Arthrocnemum and all annual species had decreased. These dynamics suggest that Monanthechloe may directly outcompete most other species in the upper marsh. In contrast, Arthrocnemum is known to facilitate some annual species. In our field experiments, Monanthechloe strongly suppressed Arthrocnemum, all four common annual species, and Limonium in direct interactions. In contrast, Arthrocnemum directly facilitated the winter annuals Parapholis incurva and Lasthenia glabrata, competed with Spergularia marina, and did not have a significant effect on Limonium. However, when the combined effects of Monanthechloe and Arthrocnemum were tested, Arthrocnemum ameliorated the negative effect of Monanthechloe on all four species. Although isolated Arthrocnemum competed with Spergularia and had no direct effects on Limonium, Arthrocnemum in the presence of Monanthechloe facilitated both species. We hypothesize that Arthrocnemum buffered the strong competitive effects of Monanthechloe on Lasthenia and Parapholis via direct positive effects and benefited Spergularia and Limonium through its competitive effect on Monanthechloe. These findings add to the growing body of literature emphasizing the importance of diversity and interdependence in the functioning of plant communities.


Small-molecule inhibitors of carboxylesterase Notum.
Notum has recently been identified as a negative regulator of Wnt signaling through the removal of an essential palmitoleate group from Wnt proteins. There are emerging reports that Notum plays a role in human disease, with published data suggesting that targeting Notum could represent a new therapeutic approach for treating cancer, osteoporosis and neurodegenerative disorders. Complementary hit-finding strategies have been applied with successful approaches that include high-throughput screening, activity-based protein profiling, screening of fragment libraries and virtual screening campaigns. Structural studies are accelerating the discovery of new inhibitors of Notum. Three fit-for-purpose examples are LP-922056, ABC99 and ARUK3001185. The application of these small-molecule inhibitors is helping to further advance an understanding of the role Notum plays in human disease.


Acute care utilization and rehospitalizations for sickle cell disease.
Published rates of health care utilization and rehospitalization by people with sickle cell disease have had limited generalizability and are not population based. To provide benchmark data for rates of acute care utilization and rehospitalizations for patients with sickle cell disease. Retrospective cohort of sickle cell disease-related emergency department (ED) visits and hospitalizations from select states in the 2005 and 2006 Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases and State Emergency Department Databases. Eight geographically dispersed states (Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee) that provide encrypted identifiers and have sufficient numbers of patients with sickle cell disease; together these states have 33% of the US population with sickle cell disease. A total of 21,112 patients with sickle cell-related treat-and-release ED visits or inpatient hospitalizations. Rates of acute care utilization and rehospitalizations. Population-based utilization rates were also calculated. The 21,112 people with sickle cell disease had 109,344 encounters, a mean of 2.59 (95% confidence interval [CI], 2.53-2.65) encounters per patient per year, 1.52 (95% CI, 1.48-1.55) encounters for hospitalizations and 1.08 (95% CI, 1.04-1.11) for treat-and-release ED visits. Utilization was highest for 18- to 30-year-olds, 3.61 (95% CI, 3.47-3.75) encounters per patient per year, and those with public insurance, 3.22 (95% CI, 3.13-3.31) encounters per patient per year. Publicly insured 18- to 30-year-olds had 4.80 (95% CI, 4.58-5.02) encounters per patient per year. Approximately 29% of the population had no encounters while 16.9% had 3 or more encounters per year. The 30-day and 14-day rehospitalization rates were 33.4% (95% CI, 33.0%-33.8%) and 22.1% (95% CI, 21.8%-22.4%), respectively. The rehospitalization rate was highest for 18- to 30-year-olds, with 41.1% (95% CI, 40.5%-41.7%) rehospitalized within 30 days and 28.4% (95% CI, 27.8%-29.0%) within 14 days. Rehospitalizations were also highest for publicly insured patients. Among patients with sickle cell disease, acute care encounters and rehospitalizations were frequent, particularly for 18- to 30-year-olds.


Covalently linked multimers of gold nanoclusters Au102(p-MBA)44 and Au∼250(p-MBA)n.
We present the synthesis, separation, and characterization of covalently-bound multimers of para-mercaptobenzoic acid (p-MBA) protected gold nanoclusters. The multimers were synthesized by performing a ligand-exchange reaction of a pre-characterized Au102(p-MBA)44 nanocluster with biphenyl-4,4'-dithiol (BPDT). The reaction products were separated using gel electrophoresis yielding several distinct bands. The bands were analyzed by transmission electron microscopy (TEM) revealing monomer, dimer, and trimer fractions of the nanocluster. TEM analysis of dimers in combination with molecular dynamics simulations suggest that the nanoclusters are covalently bound via a disulfide bridge between BPDT molecules. The linking chemistry is not specific to Au102(p-MBA)44. The same approach yields multimers also for a larger monodisperse p-MBA-protected cluster of approximately 250 gold atoms, Au∼250(p-MBA)n. While the Au102(p-MBA)44 is not plasmonic, the Au∼250(p-MBA)n nanocluster supports localized surface plasmon resonance (LSPR) at 530 nm. Multimers of the Au∼250(p-MBA)n exhibit additional transitions in their UV-vis spectrum at 630 nm and 810 nm, indicating the presence of hybridized LSPR modes. Well-defined structures and relatively small sizes make these systems excellent candidates for connecting ab initio theoretical studies and experimental quantum plasmonics. Moreover, our work opens new possibilities in the controlled synthesis of advanced monodisperse nanocluster superstructures.


Wage, work environment, and staffing: effects on nurse outcomes.
Research has shown that hospitals with better nurse staffing and work environments have better nurse outcomes-less burnout, job dissatisfaction, and intention to leave the job. Many studies, however, have not accounted for wage effects, which may confound findings. By using a secondary analysis with cross-sectional administrative data and a four-state survey of nurses, we investigated how wage, work environment, and staffing were associated with nurse outcomes. Logistic regression models, with and without wage, were used to estimate the effects of work environment and staffing on burnout, job dissatisfaction, and intent to leave. We discovered that wage was associated with job dissatisfaction and intent to leave but had little influence on burnout, while work environment and average patient-to-nurse ratio still have considerable effects on nurse outcomes. Wage is important for good nurse outcomes, but it does not diminish the significant influence of work environment and staffing on nurse outcomes.


Tetracycline-regulated transactivators driven by the involucrin promoter to achieve epidermal conditional gene expression.
To achieve conditional gene expression in the differentiated layers of the epidermis, we generated transgenic mice with the tetracycline-regulated transactivator proteins, tTA (tetracycline transactivator) and rtTA (reverse tetracycline transactivator), expressed from the human involucrin promoter. Interaction with tetracycline turns off or turns on the tTA and rtTA molecules, respectively, allowing for regulation of downstream target genes during development and postnatally. These transactivator lines were crossed with reporter mice driving LacZ expression from a tetracycline response element to analyze the specificity and levels of target gene expression. Quantitative beta-galactosidase experiments demonstrate a 30-fold induction, specific to epithelial tissues. Immunohistochemistry results illustrate that the beta-galactosidase staining follows that of endogenous involucrin expression. Induction initiates at embryonic day 14.5 with expression over the entire epidermal surface by E16.5. Together with other driver lines, expressing tetracycline transactivators in the mitotically active layers of the epidermis, these mice will allow investigators to specifically modulate expression of target genes to specific stages of epidermal differentiation.


Spatiotemporal sub-wavelength near-field light localization.
The control and localization of light at sub-wavelength scale are theoretically demonstrated with a very simple sub-wavelength dimension structure. This is demonstrated through a peculiar structure that can support localized modes which are not linked to any plasmon resonance. It is based on the acronym "FEMTO" that is designed using 26 sub-wavelength rectangular apertures engraved into perfectly conducting metal screen. A polarization-sensitive guided mode through these nano-apertures is at the origin of the light localization. Consequently, sub-wavelength light spots can be achieved with very simple structures illuminated by temporally shaped plane waves. Three parameters are temporally controlled for this purpose: the polarization, the wavelength and the amplitude of the incident beam. It is also demonstrated that replacing the perfect conductor by a real metal with dispersion leads to accentuate both the light confinement and its localization. These results open the path to the conception of optical nano-structures dedicated to sub-wavelength light addressing.


No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue.
Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.


Reinfection following initial cerebrospinal fluid shunt infection.
Significant variation exists in the surgical and medical management of CSF shunt infection. The objectives of this study were to determine CSF shunt reinfection rates following initial CSF shunt infection in a large patient cohort and to determine management, patient, hospital, and surgeon factors associated with CSF shunt reinfection. This retrospective cohort study included children who were in the Pediatric Health Information System (PHIS) database, who ranged in age from 0 to 18 years, and who underwent uncomplicated initial CSF shunt placement in addition to treatment for initial CSF shunt infection between January 1, 2001, and December 31, 2008. The outcome was CSF shunt reinfection within 6 months. The main predictor variable of interest was surgical approach to treatment of first infection, which was determined for 483 patients. Covariates included patient, hospital, surgeon, and other management factors. The PHIS database includes 675 children with initial CSF shunt infection. Surgical approach to treatment of the initial CSF shunt infection was determined for 483 children (71.6%). The surgical approach was primarily shunt removal/new shunt placement (in 286 children [59.2%]), but a substantial number underwent externalization (59 children [12.2%]), of whom a subset went on to have the externalized shunt removed and a new shunt placed (17 children [3.5% overall]). Other approaches included nonsurgical management (64 children [13.3%]) and complete shunt removal without shunt replacement (74 children [15.3%]). The 6-month reinfection rate was 14.8% (100 of 675 patients). The median time from infection to reinfection was 21 days (interquartile range [IQR] 5-58 days). Children with reinfection had less time between shunt placement and initial infection (median 50 vs 79 days, p = 0.06). No differences between those with and without reinfection were seen in patient factors (patient age at either shunt placement or initial infection, sex, race/ethnicity, payer, indication for shunt, number of comorbidities, distal shunt location, and number of shunt revisions at first infection); hospital volume; surgeon volume; or other management factors (for example, duration of intravenous antibiotic use). Nonsurgical management was associated with reinfection, and complete shunt removal was negatively associated with reinfection. However, reinfection rates did not differ between the 2 most common surgical approaches: shunt removal/new shunt placement (44 [15.4%] of 286; 95% CI 11.4%-20.1%) and externalization (total 12 [20.3%] of 59; 95% CI 11.0%-32.8%). Externalization followed by shunt removal/new shunt placement (5 [29.4%] of 17; 95% CI 10.3%-56.0%) and nonsurgical management (15 [23.4%] of 64; 95% CI 13.8%-35.7%) had higher, but nonstatistically significant, reinfection rates. The length of stay was shorter for nonsurgical management. Surgical approach to treatment of initial CSF shunt infection was not associated with reinfection in this large cohort of patients.


Nutritional potential of metabolic remodelling of white adipose tissue.
Recent findings in animals suggest that diet-related factors can programme adipose tissue features in early life and remodel white adipose tissue (WAT) towards a brown adipose tissue (BAT)-like phenotype in adulthood, while impacting on body fat content and susceptibility to obesity. The purpose of this review is to address the significance of these results and their applicability in humans. Nutritional conditions in the perinatal period influence sympathetic innervation to WAT and WAT cellularity in rodents. Leptin intake during the suckling period prevents obesity and other metabolic alterations in later life in rats through mechanisms that include increased sensitivity of adipose tissues to leptin. Recent data support the thermogenic functionality of inducible brown-like cells in rodent WAT and functional thermogenic beige adipogenesis from human progenitor cells. Diet-related factors and exercise can promote BAT activation and/or WAT-to-BAT remodelling (WAT browning) in animals. Animal studies suggest that adipose tissue health and whole body adiposity might be influenced by early life nutrition and lifestyle factors in adulthood impacting energy metabolism in adipose tissues. For this knowledge to be translated to humans, biomarkers allowing early detection of the programming status of the individual and technologies allowing measuring of the thermogenic activity of adipose tissue depots in vivo are required.


Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma.
The authors compared gemcitabine and carboplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) or mitomycin, vinblastine, and cisplatin (MVP) in patients with advanced nonsmall cell lung carcinoma (NSCLC). The primary objective was survival. Secondary objectives were time to disease progression, response rates, evaluation of toxicity, disease-related symptoms, World Health Organization performance status (PS), and quality of life (QoL). Three hundred seventy-two chemotherapy-naïve patients with International Staging System Stage III/IV NSCLC who were ineligible for curative radiotherapy or surgery were randomized to receive either 4 cycles of gemcitabine (1000 mg/m(2) on Days 1, 8, and 15) plus carboplatin (area under the serum concentration-time curve, 5; given on Day 1) every 4 weeks (the GC arm) or MIC/MVP every 3 weeks (the MIC/MVP arm). There was no significant difference in median survival (248 days in the MIC/MVP arm vs. 236 days in the GC arm) or time to progression (225 days in the MIC/MVP arm vs. 218 days in the GC arm) between the 2 treatment arms. The 2-year survival rate was 11.8% in the MIC/MVP arm and 6.9% in the GC arm. The 1-year survival rate was 32.5% in the MIC/MVP arm and 33.2% in the GC arm. In the MIC/MVP arm, 33% of patients responded (4 complete responses [CRs] and 57 partial responses [PRs]) whereas in the GC arm, 30% of patients responded (3 CRs and 54 PRs). Nonhematologic toxicity was comparable for patients with Grade 3-4 symptoms, except there was more alopecia among patients in the MIC/MVP arm. GC appeared to produce more hematologic toxicity and necessitated more transfusions. There was no difference in performance status, disease-related symptoms, or QoL between patients in the two treatment arms. Fewer inpatient stays for complications were required with GC. The results of the current study failed to demonstrate any difference in efficacy between the newer regimen of GC and the older regimens of MIC and MVP. Cancer 2003;98:542-53.


Influence of Constraints within a Cyclic Polymer on Solution Properties.
Cyclic polymers with internal constraints provide new insight into polymer properties in solution and bulk and can serve as a model system to explain the stability and mobility of cyclic biomacromolecules. The model system used in this work consisted of cyclic polystyrene structures, all with a nearly identical molecular weight, designed with 0-3 constraints located at strategic sites within the cyclic polymer, with either 4 or 6 branch points. The total number of branch points (or arms) within the cyclic ranged from 0 to 18. Molecular dynamic (MD) simulations showed that as the number of arms increased within the cyclic structure, the radius of gyration and the hydrodynamic radius generally decreased, suggesting the greater number of constraints resulted in a more compact polymer chain. The simulations further showed that the excluded volume was much greater for the cyclics compared to a linear polymer at the same molecular weight. The spirocyclic, a structure consisting of three rings joined in series, showed significant excluded volume effects in agreement with experimental data; the reason for which is unclear at this stage. Interestingly, under a size exclusion chromatography flow, the radius of hydration for all the cyclic structures increased compared with the DLS data, and could be explained from the greater swelling of the rings perpendicular to the flow found from previous simulations on rings. This data suggests that the greater compactness, greater excluded volume and structural rearrangements under flow of constrained cyclic polymers could be used to provide a physical basis for understanding greater stability and activity of cyclic biological macromolecules.


Production of solar chemicals: gaining selectivity with hybrid molecule/semiconductor assemblies.
Research on the production of solar fuels and chemicals has rocketed over the past decade, with a wide variety of systems proposed to harvest solar energy and drive chemical reactions. In this Feature Article we have focused on hybrid molecule/semiconductor assemblies in both powder and supported materials, summarising recent systems and highlighting the enormous possibilities offered by such assemblies to carry out highly demanding chemical reactions with industrial impact. Of relevance is the higher selectivity obtained in visible light-driven organic transformations when using molecular catalysts compared to photocatalytic materials.


Anatomy, pathophysiology and classification of posterior tibial tendon dysfunction.
Adult acquired flatfoot deformity is generally associated with a collapsing medial longitudinal arch and a progressive loss of strength of the posterior tibial tendon (PTT). This condition is commonly associated with PTT dysfunction or rupture, which can have an arthritic or a traumatic etiology. Several causes have been proposed to explain the clinical evidence of tendon degeneration observed at the time of surgery including trauma, anatomical, mechanical, inflammatory and ischemic factors. In this review, we analyzed anatomy, pathophysiology and existing classifications of posterior tibial tendon dysfunction. Anatomical features, and in particular vascularization, expose PTT to major degenerative disorders until rupture. A literature overview showed that a low blood supply of the gliding part of the tendon is linked to a dysfunction and/or a rupture of the PTT in the region located behind the medial malleolus. PTT low blood supply causes a dysfunction resulting in an abnormal loading of the foot's medial structures. This may be the reason why PTT dysfunction leads to an acquired flatfoot deformity. Conversely, flatfoot deformity may be a predisposing factor for the onset of PTT dysfunction.


A small dose of whey protein co-ingested with mixed-macronutrient breakfast and lunch meals improves postprandial glycemia and suppresses appetite in men with type 2 diabetes: a randomized controlled trial.
Large doses of whey protein consumed as a preload before single high-glycemic load meals has been shown to improve postprandial glycemia in type 2 diabetes. It is unclear if this effect remains with smaller doses of whey co-ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed whey offers further benefit under these conditions is unclear. The aim of this study was to investigate postprandial glycemic and appetite responses after small doses of intact and hydrolyzed whey protein co-ingested with mixed-nutrient breakfast and lunch meals in men with type 2 diabetes. In a randomized, single-blind crossover design, 11 men with type 2 diabetes [mean ± SD age: 54.9 ± 2.3 y; glycated hemoglobin: 6.8% ± 0.3% (51.3 ± 3.4 mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control) immediately before mixed-macronutrient breakfast and lunch meals, separated by 3 h. Blood samples were collected periodically and were processed for insulin, intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), leptin, peptide tyrosine tyrosine (PYY3-36), and amino acid concentrations. Interstitial glucose was measured during and for 24 h after each trial. Subjective appetite was assessed with the use of visual analog scales. Total postprandial glycemia area under the curve was reduced by 13% ± 3% after breakfast following the intact whey protein when compared with control (P < 0.05). Hydrolyzed whey attenuated early glucose after breakfast when compared with control (P < 0.05). Glycemia was improved postlunch after the intact whey protein only when compared with control (P < 0.05). Greater satiety was observed after the intact whey protein only after both meals when compared with control (P < 0.05). Insulin concentrations increased after both the intact and hydrolyzed whey protein, showing strong positive correlations with increases in valine and isoleucine (P < 0.05). Incretin and appetite regulatory hormone responses were similar across trials (P > 0.05). The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes. This trial was registered at www.clinicialtrials.gov as NCT02903199.


Metabolic dependence of fast axoplasmic transport in nerve.
Fast axoplasmic transport, shown in cat sciatic nerves by a crest of labeled activity after injection of the L7 ganglion with [(3)H]-leucine or [ (3)H]-lysine, was stopped within 15 minutes after death of the animals by bleeding. If the sciatic nerves were removed from the animals and placed in a chamber supplied with oxygen at 38 degrees centigrade, fast transport was sustained. Transport was rapidly blocked in similar in vitro preparations when the nerves were kept in a nitrogen environment. Fast axoplasmic transport is closely dependent upon oxibdative metabolism.


Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.
Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients. In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete. Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up. Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP. American College of Gastroenterology.


Molecular simulations of glycolipids: Towards mammalian cell membrane models.
Glycolipids are key components of mammalian cell membranes, influencing a diverse range of cellular functions. For example, a number of receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR), are allosterically regulated by the glycolipid monosialodihexosylganglioside (GM3). Recent advances in molecular dynamics methods, especially the development of coarse-grained models, have enabled simulations of increasingly complex models of cell membranes. We demonstrate these methodological developments via a case study of a coarse-grained model for the ganglioside GM3. This glycolipid is included in simulations of a mixed lipid bilayer model reflecting the compositional complexity of a mammalian cell membrane. The resultant membrane model is used to simulate the interactions of GM3 with the transmembrane domain of the EGFR.


Involvement of the Escherichia coli folate-binding protein YgfZ in RNA modification and regulation of chromosomal replication initiation.
The Escherichia coli hda gene codes for a DnaA-related protein that is essential for the regulatory inactivation of DnaA (RIDA), a system that controls the initiation of chromosomal replication. We have identified the ygfZ gene, which encodes a folate-binding protein, as a suppressor of hda mutations. The ygfZ null mutation suppresses an hda null mutation. The over-initiation and abortive elongation phenotypes conferred by the hda mutations are partially suppressed in an hda ygfZ background. The accumulation of the active form of DnaA, ATP-DnaA, in the hda mutant is suppressed by the disruption of the ygfZ gene, indicating that YgfZ is involved in regulating the level of ATP-DnaA. Although ygfZ is not an essential gene, the ygfZ disruptant grows slowly, especially at low temperature, demonstrating that this gene is important for cellular proliferation. We have identified mnmE (trmE) as a suppressor of the ygfZ disruption. This gene encodes a GTPase involved in tRNA modification. Examination of RNA modification in the ygfZ mutant reveals reduced levels of 2-methylthio N(6)-isopentenyladenosine [corrected] indicating that YgfZ participates in the methylthio-group formation of this modified nucleoside in some tRNAs. These results suggest that YgfZ is a key factor in regulatory networks that act via tRNA modification.


Utility of PDL progenitors for in vivo tissue regeneration: a report of 3 cases.
Periodontal disease is an inflammatory disorder with widespread morbidities involving both oral and systemic health. The primary goal of periodontal treatment is the regeneration of the lost or diseased periodontium. In this study, we retrospectively examined feasibility and safety of reconstructing the periodontal intrabony defects with autologous periodontal ligament progenitor (PDLP) implantation in three patients. In this retrospective pilot study, we treated 16 teeth with at least one deep intrabony defect of probing depth (PD) > OR = 6 mm with PDLP transplantation and evaluated clinical outcome measures in terms of probing depth, gingival recession and attachment gain for a duration of 32-72 months. Furthermore, we compare PDLPs with standard PDL stem cells (PDLSCs) and confirmed that PDLPs possessed progenitor characters. Clinical examination indicated that transplantationof PDLPs may provide therapeutic benefit for the periodontal defects. All treated patients showed no adverse effects during the entire course of follow up. We also found that PDLPs were analogous to PDLSCs in terms of high proliferation, expression of mesenchymal surface molecules, multipotent differentiation, and in vivo tissue regain. However, PDLPs failed to express scleraxis, a marker of tendon, as seen in PDLSCs. This study demonstrated clinical and experimental evidences supporting a potential efficacy and safety of utilizing autologous PDL cells in the treatment of human periodontitis.


Cardiovascular effects of 8 h of isocapnic hypoxia with and without beta-blockade in humans.
This study seeks to confirm the progressive changes in cardiac output and heart rate previously reported with 8 h exposures to constant hypoxia, and to examine the role of sympathetic mechanisms in generating these changes. Responses of ten subjects to four 8 h protocols were compared: (1) air breathing with placebo; (2) isocapnic hypoxia (end-tidal PO2 = 50 mm Hg) with placebo; (3) isocapnic hypoxia with beta-blockade; and (4) air breathing with beta -blockade. Regular measurements of heart rate and cardiac output (using ultrasonography and N2O rebreathing techniques) were made with subjects seated in the upright position. The sensitivity of heart rate to rapid variations in hypoxia (GHR) and heart rate in the absence of hypoxia were measured at times 0, 4 and 8 h. No significant progressive effect of hypoxia on cardiac output was detected. There was a gradual rise in heart rate with hypoxia of 11+/-2 beats min(-1) in the placebo protocol and of 10+/-2 beats min(-1) in the beta-blockade protocol over 8 h, compared to the air breathing protocols. The rise in heart rate was progressive (P<0.001) and accompanied by progressive increases in both GHR (P<0.001) and heart rate measured in the absence of hypoxia (P<0.05). No significant effect of beta-blockade was detected on any of these progressive changes. We conclude that sympathetic mechanisms that act via beta -receptors play little role in the progressive changes in heart rate observed over 8 h of moderate hypoxia.


CellNOptR: a flexible toolkit to train protein signaling networks to data using multiple logic formalisms.
Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce. Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities. Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.


Signals involved in the effects of bisphenol A (BPA) on proliferation and motility of Leydig cells: a comparative proteomic analysis.
Recent studies indicated that bisphenol A (BPA) can disrupt spermatogenesis and then cause male infertility. The present study revealed that BPA greater than 10-6 M inhibited the proliferation of Leydig TM3 cells via a concentration dependent manner. The proteomic study revealed that 50 proteins were modulated in TM3 cells following exposure to BPA, which was relevant to structure, motility, cell metabolism, protein and nucleotide processing, and cell proliferation. Furthermore, BPA increased the in vitro migration and invasion of Leydig TM3 cells, which might be due to the BPA's modulation of proteins related to cell structure and motility such as actin and heat shock protein (HSP). Silencing of galectin-1, which was up regulated by BPA, significantly abolished the BPA-induced migration of TM3 cells. BPA treatment obviously increased the phosphorylation of ERK1/2 and Akt, while only PD98509 (ERK1/2 inhibitor) significantly attenuated BPA induced up regulation of galectin-1. Furthermore, PD98509 also reversed BPA induced migration of TM3 cells. Our study demonstrated that xenoestrogen BPA at micromolar or greater concentrations can modulate protein profiles, inhibit cell proliferation, and promote the in vitro migration and invasion of Leydig TM3 cells. It provided new insight into the mechanisms responsible for BPA induced male infertility.


Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences.
Herbal medicines are currently in high demand, and their popularity is steadily increasing. Because of their perceived effectiveness, fewer side effects and relatively low cost, they are being used for the management of numerous medical conditions. However, they are capable of affecting the pharmacokinetics and pharmacodynamics of coadministered conventional drugs. These interactions are particularly of clinically relevance when metabolizing enzymes and xenobiotic transporters, which are responsible for the fate of many drugs, are induced or inhibited, sometimes resulting in unexpected outcomes. This article discusses the general use of herbal medicines in the management of several ailments, their concurrent use with conventional therapy, mechanisms underlying herb-drug interactions (HDIs) as well as the drawbacks of herbal remedy use. The authors also suggest means of surveillance and safety monitoring of herbal medicines. Contrary to popular belief that "herbal medicines are totally safe," we are of the view that they are capable of causing significant toxic effects and altered pharmaceutical outcomes when coadministered with conventional medicines. Due to the paucity of information as well as sometimes conflicting reports on HDIs, much more research in this field is needed. The authors further suggest the need to standardize and better regulate herbal medicines in order to ensure their safety and efficacy when used alone or in combination with conventional drugs.


County-level effects of green space access on physical activity.
Parks and other forms of green space are among the key environmental supports for recreational physical activity. Measurements of green space access have provided mixed results as to the influence of green space access on physical activity. This cross-sectional study uses a geographical information system (GIS) to examine the relationships between the amount of and distance to green space and county-level (n = 67) moderate and vigorous physical activity (MVPA) in the state of Florida. The gross amount of green space in a county (P < .05) and the amount of green space within defined distances of where people live (1/4 mile, P < .01; 1/2 mile, P < .05; 1 mile, P < .01) were positively associated with self-reported levels of MVPA. Distance to the nearest green space and the amount of green space furthest from where people live (10 miles) were not significantly associated with MVPA. All measures were weighted by the population living in census tracts. The results suggest that there is an association between the accessibility created by having more green space closer to home and MVPA, but this holds only for areas up to and including 1 mile from home.


Mindfulness in primary school children as a route to enhanced life satisfaction, positive outlook and effective emotion regulation.
Mindfulness programmes as a potential avenue of enhancing pupil wellbeing are beginning to show great promise. However, research concerning the effectiveness of mindfulness training for primary aged school children (7-11 years of age) has been neglected. Building on methodological limitations of prior research, this study employed an active controlled design to assess the longer term wellbeing and emotion regulation outcomes after a 6 week mindfulness programme (Living Mindfully Programme, UK), for a group of school children aged between 9 and 10. The programme was delivered by class teachers as part of their normal curriculum entitlement. One hundred and eight children took part from across three schools in North East of England. Participants formed a treatment group (n = 64), active control (n = 19) and wait list control (n = 25). Self-report measures of wellbeing, mindfulness and emotion regulation were collected at pre and post training as well as at 3 months follow up. Reliable findings, judged by medium to large effect sizes across both post intervention, follow-up and between both controls, demonstrated enhancement in a number of domains. Immediately after training and follow up, when compared with the wait list control, children who received mindfulness training showed significant improvements in mindfulness (d = .76 and .77), Positive Outlook (d = .55 and .64) and Life Satisfaction (d = .65 and 0.72). Even when compared to an active control, the effects remained although diminished reflecting the positive impact of the active control condition. Furthermore, a significant positive relationship was found between changes in mindfulness and changes in cognitive reappraisal. Taken together, this study provides preliminary evidence that the Living Mindfully Primary Programme is feasibly delivered by school staff, enjoyed by the children and may significantly improve particular components of wellbeing. Importantly, higher levels of mindfulness as a result of training may be related to effective emotional regulatory and cognitive reappraisal strategies.


An In Vitro Study on Mitochondrial Compensatory Response Induced by Gliadin Peptides in Caco-2 Cells.
Dietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in combination with the antioxidant 2,6-di-tbutyl-p-cresol (BHT), and the effects on mitochondrial biogenesis and mtDNA were studied. Cells ability to recover from stress was determined after 24 h and 48 h of incubation in the culture medium. Gliadin-induced oxidative stress evoked a compensatory response. The stressor triggered a rapid and significant increase of Peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and Peroxiredoxin III (PrxIII) proteins, and mtDNA amount. As for the effects of gliadin on mtDNA integrity, strand breaks, abasic sites, and modified bases were analyzed in three mtDNA regions. D-loop appeared a more fragile target than Ori-L and ND1/ND2. The temporal trend of the damage at D-loop paralleled that of the amount of mtDNA. Overall, a trend toward control values was shown 48 h after gliadin exposure. Finally, BHT was able to counteract the effects of gliadin. Results from this study highlighted the effects of gliadin-induced oxidative stress on mitochondria, providing valuable evidence that might improve the knowledge of the pathophysiology of gluten-related disorders.


Coupling single quantum dots to plasmonic nanocones: optical properties.
Coupling a single quantum emitter, such as a fluorescent molecule or a quantum dot (QD), to a plasmonic nanostructure is an important issue in nano-optics and nano-spectroscopy, relevant for a wide range of applications, including tip-enhanced near-field optical microscopy, plasmon enhanced molecular sensing and spectroscopy, and nanophotonic amplifiers or nanolasers, to mention only a few. While the field enhancement of a sharp nanoantenna increasing the excitation rate of a very closely positioned single molecule or QD has been well investigated, the detailed physical mechanisms involved in the emission of a photon from such a system are, by far, less investigated. In one of our ongoing research projects, we try to address these issues by constructing and spectroscopically analysing geometrically simple hybrid heterostructures consisting of sharp gold cones with single quantum dots attached to the very tip apex. An important goal of this work is to tune the longitudinal plasmon resonance by adjusting the cones' geometry to the emission maximum of the core-shell CdSe/ZnS QDs at nominally 650 nm. Luminescence spectra of the bare cones, pure QDs and hybrid systems were distinguished successfully. In the next steps we will further investigate, experimentally and theoretically, the optical properties of the coupled systems in more detail, such as the fluorescence spectra, blinking statistics, and the current results on the fluorescence lifetimes, and compare them with uncoupled QDs to obtain a clearer picture of the radiative and non-radiative processes.


Clinical trials of drugs used off-label in neonates: ethical issues and alternative study designs.
The use of drugs for indications unapproved by the Food and Drug Administration (FDA), often called "off label use, "is widespread in children, including neonates. The widespread off-label use of drugs in neonates presents ethical and safety challenges. Since the passage of the Best Pharmaceuticals for Children Act (BPCA) in 2002, both the FDA and National Institutes of Health (NIH) have taken initiatives to facilitate and encourage research to achieve the necessary labeling for drugs routinely used in infants and children. Federal regulations provide broad rules and guidance for the protection of human subjects in research. However, there are ethical issues that a physician may face when designing clinical trials of drugs in neonates that are routinely used off-label and widely believed to be beneficial. We attempt to describe these ethical challenges and provide recommendations, including alternative study designs, to resolve them in an ethical framework that takes into account the Belmont Report, the statement of the World Medical Association (WMA), and federal regulations.