Analysis of the effects of applying external fields and device dimensions alterations on GaAs/AlGaAs multiple quantum well slow light devices based on excitonic population oscillation.
This paper demonstrates the effects of applying magnetic and electric fields and physical dimensions alterations on AlGaAs/GaAs multiple quantum well (QW) slow light devices. Physical parameters include quantum well sizes and number of quantum wells. To the best of our knowledge, this is the first analysis of the effects of both applying magnetic/electric fields and physical parameters alterations and the first suggestion for matching the prefabrication and post fabrication tuning of the slow light devices based on excitonic population oscillations. The aim of our theoretical analysis is controlling the optical properties such as central frequency, bandwidth, and slow down factor (SDF) in slow light devices based on excitonic population oscillation to achieve better tuning. To reach these purposes, first we investigate the quantum well size and number of quantum wells alteration effects. Next, we analyze the effects of applying magnetic and electric fields to the multiple quantum well structure, separately. Finally, physical parameters and applied external fields are changed for measuring frequency shift and SDF for coherent population oscillation slow light devices. The results show the available central frequency shifts in about 1.6 THz at best. Also the SDF value improvement is about one order of magnitude. These results will be applicable for optical nonlinearity enhancements, all-optical signal processing, optical communications, all-optical switches, optical modulators, and variable true delays.


Electrochemical properties of CVD grown pristine graphene: monolayer- vs. quasi-graphene.
We report the electrochemical properties of pristine monolayer, double layer and few-layer (termed quasi-) graphene grown via CVD and transferred using PMMA onto an insulating substrate (silicon dioxide wafers). Characterisation has been performed by Raman spectroscopy, optical spectroscopy, Atomic Force Microscopy and X-ray Photoelectron Spectroscopy, revealing 'true' pristine single-layer graphene (O/C of 0.05) at the former and pristine quasi-graphene at the latter (O/C of 0.07); the term "quasi-graphene" is coined due to the surface comprising on average 4-graphene-layers. The graphene electrodes are electrochemically characterised using both inner-sphere and outer-sphere redox probes with electrochemical performances of the graphene electrodes compared to other available graphitic electrodes, namely that of basal- and edge- plane pyrolytic graphite electrodes constructed from Highly Ordered Pyrolytic Graphite (HOPG), with information on heterogeneous rate constants (k(o)) obtained. The electrochemical rate constants are predominantly influenced by the electronic properties of the graphene surfaces. Monolayer graphene is found to exhibit slow heterogeneous electron transfer (HET) kinetics towards the redox probes studied, with HET rates ca. 2 and 8 times faster at quasi-graphene and HOPG respectively, relative to that of the monolayer graphene electrode. Critically contrasting the performance of monolayer graphene to quasi-graphene and HOPG electrodes reveals that increasing the number of graphene layers results in improved electrochemical properties, where in terms of the electrochemical reversibility of the probes studied: monolayer-graphene < quasi-graphene < HOPG, as governed by the respective HET electrochemical rate constants. Given that edge plane sites are the predominant origin of fast electron transfer kinetics at graphitic materials, the slow HET rates at pristine single-layer graphene electrodes are likely due to graphene's fundamental geometry, which comprises a small edge plane and large basal plane contribution. In the case of quasi-graphene and HOPG, they possess increasing global coverage of electrochemically reactive edge plane sites (respectively) and thus exhibit superior electrochemical performances over that of monolayer graphene. Last, the case of a double-layer graphene electrode is considered, which as a result of its fabrication possesses a large global coverage of edge plane like- sites/defects. In agreement with the former conclusions, the double-layered defect-graphene electrode is found to exhibit fast/favourable electrochemical properties, which is attributed to its large edge plane content (i.e. defect abundant graphene) and thus is further evidence that the electrochemical response is dependent on the density of edge plane sites at graphene based electrodes (influenced by the coverage of graphene-defects and the number of graphene layers).


Comparing and evaluating the efficacy of the TOR18FG Leeds test X-ray phantom for T-rays.
The commercially available X-ray fluoroscopy quality assurance phantom, the Leeds test object TOR18FG, was found to be suitable to assess T-ray image quality in the range (0.1-0.4) THz at a depth of 0.5 cm. Previous to this only custom made phantoms, made especially for the T-ray region, assessed T-ray spatial resolution. However, if sub-wavelength techniques are used, the Leeds test phantom may be implemented to measure the T-ray systems spatial resolution, allowing us to directly compare X-ray and T-ray spatial resolution. The systems compared include a Gulmay Orthovoltage machine (X-ray), the On Board Imager (OBI) of a Varian linear accelerator (X-ray), a two-colour system (T-ray) and Terahertz Time Domain Spectroscopy (THz-TDS) system. X-rays were found to have a spatial resolution of 1.25 lp/mm using the On Board Imager of a Varian Linear Accelerator whilst T-rays imaged using a broadband source imaged through a spatial pinhole had a spatial resolution of 0.56 lp/mm. The TOR18FG background material was found to block, 90% and 99% of the broadband T-rays emitted from a THz-TDS photo-conductive emitter, at 0.4 THz and 0.53 THz respectively. Contrast sensitivity was found to be 3% for 25 cm × 25 cm X-ray field at 65 kV, whilst this value could not be established for T-rays using the TOR18FG. All contrast circles were found to be the same for T-rays i.e. all 40% at 0.1 THz. Images of the same leaf were taken with diagnostic X-rays and both broadband and continuous wave (CW) T-ray systems. T-rays proved superior in providing image contrast, for a hydrated leaf, over X-rays.


Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing.
The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.


Elimination of Transcoarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress After Intervention in Patients With Mild Coarctation.
This study sought to investigate the impact of transcatheter intervention on left ventricular function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak transcoarctation pressure gradient <20 mm Hg). Debate rages regarding the risk/benefit ratio of intervention versus long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function, and peripheral perfusion. We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (before and after intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the left ventricle in 34 patients with mild COA to make these correlations. Despite dramatic reduction in the transcoarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced by 75% and 47.3%, respectively), there was only modest effect on aortic flow and no significant impact on aortic shear stress (the maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve left ventricular function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%, respectively). Transcatheter intervention that successfully relieves mild COA pressure gradients does not translate to decreased myocardial strain. The effects of the intervention were determined to the greatest degree by ventricular-vascular coupling hemodynamics and provide a novel valuable mechanism to evaluate patients with COA that may influence clinical practice.


[Caring of the mental patient in the emergency room: feelings and attitudes of the nursing team members].
This work is based upon a day-by-day study of the services provide by a nurse team at a mentally impaired emergency room. Our aim is to study staff's reactions toward the patients as well as service itself. We could feel the dynamic relation among thinking, feeling and performance created strong conceptions on individuals based upon a common sense. The feelings noticed are: pity, scare and rage depending upon behavior. The assistance given to the mentally impaired is, at large, based exclusively on technical data resorted to organic/biological aspects.


Dental erosion in mice with impaired salivary gland function.
Objective: Salivary flow rate exerts an essential impact on the development and progression of dental erosion. In this work, the experimental dental erosion in non-obese diabetic (NOD) mice with reduced salivary flow rate was induced, and the erosive effect of acidic drinks on their dentition was studied.Material and methods: Three acidic drinks (sports drink, cola light drink and sugar containing cola drink) were given to adult NOD mice (groups: N = 11) as the only drink for 6 weeks. Two control groups were included; wild type and NOD control (groups: N = 9). Experimental and control (water) teeth were dissected out and observed by scanning electron microscopy (SEM). Mandibular first molars were subsequently embedded in Epon, ground transversely, observed again by SEM, and the enamel thickness and tooth height were measured.Results: Mandibular molars were considerably more eroded than maxillary molars. The erosive process started at the top of the cusps and subsequently extended in the cervical, mesio-distal, and pulpal direction. Erosive lesions were evident in increased succession from sports drink, cola light to cola drink exposed mandibular molars, with the lingual tooth height being approximately 23%, 26%, and 37% lower, respectively, compared to the control. The lingual enamel was approximately 48% thinner in sports drink molars and 62% thinner in cola light molars. In cola drink molars, the lingual enamel was totally eroded, and significant erosion of dentine was evident.Conclusion: Reduced salivary flow, together with a high consumption of acidic drinks, results in severe erosion of NOD mice molars.


Night shifts, sleep deprivation, and attention performance in medical students.
To determine attention performance of medical students after sleep deprivation due to night shift work. Prospective cohort design. All seventh, eighth and ninth semester students were invited to participate (n= 209). The effectiveness and concentration indices (d2 Test for attention, dependent variable) from 180 students at 3 evaluations during the semester were compared. Eighth and ninth semester students underwent their second evaluation after a night shift. The independent variables were nocturnal sleep measurements. No differences in nocturnal sleep hours during the previous week (p=0.966), sleep deprivation (p=0.703) or effectiveness in the d2 Test (p=0.428) were found between the groups at the beginning of the semester. At the beginning and the end of the semester, the d2 Test results were not different between groups (p=0.410, p=0.394) respectively. The second evaluation showed greater sleep deprivation in students with night shift work (p=0.001). The sleep deprived students had lower concentration indices (p=0.001).The differences were associated with the magnitude of sleep deprivation (p=0.008). Multivariate regression analysis showed that attention performance was explained by sleep deprivation due to night shift work, adjusting for age and gender. Students with sleep deprivation had worse concentration than those without. Sleep deprivation due to night shift work in medical students had a negative impact on their attention performance. Medical educators should address these potential negative learning and patient care consequences of sleep deprivation in medical students due to night shifts.


Intrinsic properties and reflex compensation in reinnervated triceps surae muscles of the cat: effect of movement history.
Effects of prior motion on ramp stretch responses of reflexive and areflexive muscles were measured in decerebrate cats. Soleus and gastrocnemius muscles were rendered areflexive by reinnervation a minimum of 9 mo before the terminal experiments. The introduction of a shortening phase prior to the ramp stretch increased the normalized initial stiffness of muscles and decreased the tendency to yield of the reinnervated muscles as compared with the case in which muscles contracted isometrically prior to stretch. Yielding was compensated by reflex action for all amplitudes of prior shortening in soleus and gastrocnemius muscles. The comparison of responses of untreated and reinnervated muscles indicated that the contribution of reflex action progressively declined with the amplitude of prior shortening as the extent of yielding diminished. In soleus muscle, during a variable delay period of isometric contraction interposed between shortening and lengthening force generation, initial stiffness and yielding returned to levels seen with isometric contractile history. However, these attributes recovered at different rates, suggesting that distinct processes are responsible for initial stiffness and yielding. Yielding was compensated for by reflex action regardless of the length of the interposed delay or of the amplitude of the prior shortening. These and previous findings indicate that the stretch reflex regulates muscular stiffness for a wide range of conditions. This regulation apparently arises from complementary mechanical properties of intrafusal and extrafusal muscle.


Psychological therapy for anxiety in bipolar spectrum disorders: a systematic review.
Comorbid anxiety is common in bipolar spectrum disorders [BPSD], and is associated with poor outcomes. Its clinical relevance is highlighted by the "anxious distress specifier" in the revised criteria for Bipolar Disorders in the Diagnostic and Statistical Manual 5th Edition [DSM-5]. This article reviews evidence for the effectiveness of psychological therapy for anxiety in adults with BPSD (bipolar I, II, not otherwise specified, cyclothymia, and rapid cycling disorders). A systematic search yielded 22 treatment studies that included an anxiety-related outcome measure. Cognitive behavioural therapy [CBT] for BPSD incorporating an anxiety component reduces anxiety symptoms in cyclothymia, "refractory" and rapid cycling BPSD, whereas standard bipolar treatments have only a modest effect on anxiety. Preliminary evidence is promising for CBT for post-traumatic stress disorder and generalised anxiety disorder in BPSD. Psychoeducation alone does not appear to reduce anxiety, and data for mindfulness-based cognitive therapy [MBCT] appear equivocal. CBT during euthymic phases has the greatest weight of evidence. Where reported, psychological therapy appears acceptable and safe, but more systematic collection and reporting of safety and acceptability information is needed. Development of psychological models and treatment protocols for anxiety in BPSD may help improve outcomes.


Low levels of plasma omega 3-polyunsaturated fatty acids are associated with cerebral small vessel diseases in acute ischemic stroke patients.
Cerebral small vessel diseases (SVDs) are related to stroke or cognitive dysfunction. n-3-polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) represent possible disease-modifying factors for cardiovascular disease or dementia. Our hypothesis was that a low proportion of plasma FAs would be associated with cerebral SVDs. We prospectively enrolled 220 patients with a first-episode cerebral infarction within 7 days after symptom onset. The composition of plasma FAs was analyzed by gas chromatography methods. The presence and burden of cerebral microbleeds (CMBs), high-grade white matter changes (HWCs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) were investigated. The mean proportion (± SD) was 2.0 ± 0.7 for EPA, 8.9 ± 1.5 for DHA, and 12.0 ± 2.1 for ∑ n-3-PUFAs. In total, 46 (20.9%) patients had CMBs, 64 (29.1 %) had HWCs, 57 (25.9%) had HPVSs, and 65 (29.5%) had ALIs. In univariate analyses, CMBs, HWCs, and HPVSs were each negatively correlated with the proportion of EPA, DHA, and ∑ n-3-PUFAs. In the multivariate analysis, a lower proportion of EPA, DHA and ∑ n-3-PUFAs was associated with the presence of CMBs, HWCs and HPVS, but not ALIs. Total SVDs score was inversely correlated with the proportion of EPA, DHA and ∑ n-3-PUFAs. Overall, we found an association between low proportions of plasma n-3-PUFAs and cerebral SVDs pathologies. Further studies are needed to explore the association and potential therapeutic role of FAs in cerebral SVDs.


Moderate-intensity physical activity and fasting insulin levels in women: the Cross-Cultural Activity Participation Study.
The purpose of this study was to determine the association between moderate-intensity physical activity (PA) and fasting insulin levels among African-American (n = 47), Native American (n = 46), and Caucasian women (n = 49), aged 40-83 years, enrolled in the Cross-Cultural Activity Participation Study. Associations by race/ethnicity, levels of central obesity, and cardiorespiratory fitness were also examined. Physical activity scores were obtained from detailed PA records that included all PA performed during two consecutive 4-day periods scheduled 1 month apart. Using MET intensity (the associated metabolic rate for a specific activity divided by a standard resting metabolic rate), PA was expressed as MET-min (the product of the minutes for each activity times the MET intensity level) per day of energy expended in moderate (3-6 METs) and moderate/vigorous (> or = 3 METs) PA. Fasting insulin levels were determined by radioimmunoassay. Data were analyzed by multiple linear regression analysis. After adjusting for race/ethnicity, age, educational attainment, and site, an increase of 30 min of moderate-intensity PA was associated with a 6.6% lower fasting insulin level (P < 0.05). The association was similar among races/ethnicities, centrally lean and centrally obese women, and women with low and high cardiorespiratory fitness levels. These findings lend support to the 1995 Centers for Disease Control and Prevention and American College of Sports Medicine recommendations for an accumulation of 30 min/day in moderate-intensity PA. They also contribute to the growing literature suggesting that moderate amounts of PA have a significant role in reducing the burden of hyperinsulinemia and diabetes among ethnic populations at highest risk for these conditions.


Hepatoprotective and antioxidant effects of lycopene in acute cholestasis.
Lycopene, which is suggested to be a potent antioxidant, may play a protective role in diseases related to oxidative stress. In order to understand the effects of lycopene in the pathogenesis of cholestasis, we investigated the effects of lycopene on oxidative stress parameters and DNA damage induced by experimental biliary obstruction in the liver tissues and the lymphocytes of Wistar albino rats. The animals were randomized into 3 groups. The sham group was subjected to a sham operation, the BDL group was subjected to bile duct ligation (BDL), and the BDL+L group was subjected to BDL and treated with 10 mg/kg body weight of lycopene. After 7 days of treatment, the liver functions, oxidative stress parameters, and DNA damage were evaluated. The lycopene treatment significantly ameliorated the liver function parameters in BDL rats. It significantly reduced malondialdehyde and nitric oxide levels and enhanced reduced glutathione levels and catalase, superoxide dismutase, and glutathione S transferase activities in the BDL rats. The lycopene treatment also decreased DNA damage as assessed by comet assay in the lymphocytes and hepatocytes of the BDL rats. These results suggest that lycopene might have protective effects on acute cholestasis.


Inequalities in perceived health in the Russian Federation, 1994-2012.
Individual characteristics and socioeconomic strata (SES) are important determinants of health differences. We examine health inequalities in Russia and estimate the association of demography (gender and age) and SES (working status, income, geography of residence, living standard, wealth possession, and durable asset-holding) with perceived health over the period 1994-2012. This study uses nationally representative datasets from the Russian Longitudinal Monitoring Survey (RLMS: 1994-2012). We apply a random effect GLS model to examine the association of individual characteristics and individual heterogeneity in explaining self-perceived health status. In addition, we estimate a regression-based concentration index, which we decompose into the determinants of health inequalities. The self-perceived health differences between the better-off and the worse-off is reduced over the 18 year period (1994 - 2012). The individual variances in self-perceived health status are higher compared to the variances between the individuals over the period. The measure of health inequality index (concentration index) indicates a change for better health for the better-off Russians. Being employed matters in perceiving a better health status for the Russians in 2012. Self-perceived health differences in the Russian Federation has changed over time. Such differences in changes are attributable to both changes in the distribution of the determinants of health as well as changes in the association between the determinants of health with the self-perceived health status. Though this study identifies the determinants of health inequalities for the Russians, the future research is to examine the in-country distribution of these determinants that produce health differences within the Russian Federation.


Using a representative sample of elementary school students to determine the statewide prevalence of childhood overweight and obesity in Utah.
Utah's Height and Weight Measurement Project was conducted with elementary school students periodically from 2002 to 2008. The 2002 pilot project was performed to establish variability rates between schools and within schools. It allowed us to accurately determine both the sample size and the number of schools that were required to calculate a reliable statewide estimate based on a random sample of schools and to establish sentinel grades. The sentinel grades identified were grades 1, 3, and 5. Use of randomly selected classes in the sentinel grades resulted in decreased sample size and less school disruption while maintaining sufficient precision. Standardized, calibrated equipment was purchased and given to school nurses for safekeeping. Lessons learned included establishing strong relationships with partners, especially school nurses, and obtaining support from upper management at the schools, school districts, and the Utah Department of Health. A significant difference in participation rates and obesity rates at the individual school level was observed depending on parental consent type; active consent was associated with lower student participation rates and lower observed obesity rates. Data were presented to both participating and nonparticipating schools, school nurses, district superintendents, and principals. For surveillance purposes, sampling is an efficient, cost-effective way to estimate childhood overweight and obesity rates.


Tra1p is a component of the yeast Ada.Spt transcriptional regulatory complexes.
The yeast Ada and TBP class of Spt proteins interact in multiple complexes that are required for transcriptional regulation. We have identified Tra1p as a component of these complexes through tandem mass spectrometry analysis of proteins that associate with Ngg1p/Ada3p. TRA1 is an essential gene and encodes a 3744-amino acid protein that is a member of a group of proteins including the catalytic subunit of DNA-dependent protein kinase, ATM and TRRAP, with carboxyl-terminal regions related to phosphatidylinositol 3-kinases. The interaction between Tra1p and Ada/Spt components was verified by the reciprocal coimmunoprecipitation of Ada2p and Tra1p from whole cell extracts in one or more complexes containing Spt7p. Tra1p cofractionated with Ngg1p and Spt7p through consecutive chromatography on Mono Q, DNA-cellulose, and Superose 6 columns. Binding of Tra1p to DNA-cellulose required Ada components. The association of Tra1p with two Ada.Spt complexes was suggested by its cofractionation with Ngg1p and Spt7p in two peaks on the Mono Q column. In the absence of Ada2p, the elution profile of Tra1p shifted to a distinct peak. Despite the similarity of Tra1p to a group of putative protein kinases, we have not detected protein kinase activity within immunoprecipitates of Tra1p or the Ada.Spt complexes.


Poverty, household chaos, and interparental aggression predict children's ability to recognize and modulate negative emotions.
The following prospective longitudinal study considers the ways that protracted exposure to verbal and physical aggression between parents may take a substantial toll on emotional adjustment for 1,025 children followed from 6 to 58 months of age. Exposure to chronic poverty from infancy to early childhood as well as multiple measures of household chaos were also included as predictors of children's ability to recognize and modulate negative emotions in order to disentangle the role of interparental conflict from the socioeconomic forces that sometimes accompany it. Analyses revealed that exposure to greater levels of interparental conflict, more chaos in the household, and a higher number of years in poverty can be empirically distinguished as key contributors to 58-month-olds' ability to recognize and modulate negative emotion. Implications for models of experiential canalization of emotional processes within the context of adversity are discussed.


Developing an innovative online medication calculator for patients with Parkinson's disease who are nil by mouth.
Missed Parkinson's disease (PD) medications when patients are admitted to hospital are associated with increased -morbidity and mortality. Swallowing difficulties in hospitalised PD patients are common and should prompt clinicians to -consider conversion of a patient's PD medications to a non-oral form - this is, however, recognised as a challenging area with potential for error. Northumbria Healthcare NHS Foundation Trust's PD service set out to address this patient safety issue through the development of an innovative online medication -calculator (pdmedcalc.co.uk). This article summarises the development process underpinning the calculator, presents numerical data on the usage of the calculator and presents survey data -relating to user experiences of the calculator. Lastly, we highlight how user feedback has been used to refine subsequent iterations of the calculator and how use of the calculator has rapidly spread beyond our trust because of it being freely accessible online.


Regioselective modification of unprotected glycosides.
Selective modification of unprotected carbohydrates is difficult due to the similar reactivity of the hydroxyl groups. In carbohydrate synthesis, therefore, even straightforward transformations often require multiple synthetic steps. The development of selective methods for carbohydrate modification is consequently highly desired. This review describes the methods for the regio- and chemoselective carbohydrate modification, with a focus on novel approaches that mainly apply transition metal catalysis and organocatalysis, and discusses the challenges and opportunities in this field.


Neural responses to maternal praise and criticism: Relationship to depression and anxiety symptoms in high-risk adolescent girls.
The parent-child relationship may be an important factor in the development of adolescent depressive and anxious symptoms. In adults, depressive symptoms relate to increased amygdala and attenuated prefrontal activation to maternal criticism. The current pilot study examined how depressive and anxiety symptoms in a high-risk adolescent population relate to neural responses to maternal feedback. Given previous research relating oxytocin to maternal behavior, we conducted exploratory analyses using oxytocin receptor (OXTR) genotype. Eighteen females (ages 12-16) listened to maternal praise, neutral, and critical statements during functional magnetic resonance imaging. Participants completed the Mood and Feelings Questionnaire and the Screen for Child Anxiety Related Emotional Disorders. The OXTR single nucleotide polymorphism, rs53576, was genotyped. Linear mixed models were used to identify symptom or allele (GG, AA/AG) by condition (critical, neutral, praise) interaction effects on brain activation. Greater symptoms related to greater right amygdala activation for criticism and reduced activation to praise. For left amygdala, greater symptoms related to reduced activation to both conditions. Anxiety symptoms related to differences in superior medial PFC activation patterns. Parental OXTR AA/AG allele related to reduced activation to criticism and greater activation to praise within the right amygdala. Results support a relationship between anxiety and depressive symptoms and prefrontal-amygdala responses to maternal feedback. The lateralization of amygdala findings suggests separate neural targets for interventions reducing reactivity to negative feedback or increasing salience of positive feedback. Exploratory analyses suggest that parents' OXTR genetic profile influences parent-child interactions and related adolescent brain responses.


Five-year rehospitalization outcomes in a cohort of patients with acute ischemic stroke: Medicare linkage study.
The purposes of this study were to track mortality and rehospitalizations over 5 years poststroke in a stroke cohort (SC) and compare long-term risks of complications to a matched nonstroke cohort (NSC). A cohort design with a matched NSC comparison was used. The SC constituted a validated database of acute ischemic stroke patients, ≥65 years, hospitalized across 19 Minnesota hospitals in the year 2000. The NSC was constructed from the year 2000 General Medicare Population by matching SC members on age, race, and sex. Both cohorts were tracked across 5 years of Medicare claims data to identify dates and causes of rehospitalization and death dates. Kaplan-Meier survival curves estimated cumulative incidence rates. Cox models calculated adjusted hazard ratios. Event rates and adjusted hazard ratios were: mortality: 1 year SC=24%, NSC=4%; 5 years SC=49%, NSC=24% (hazard ratio, 4.4; 95% CI, 3.6 to 5.5). Overall rehospitalization rates were: 1 year SC=49%, NSC=20%; 5 years SC=83%; NSC=63% (hazard ratio, 2.6; 95% CI, 2.2 to 3.0). Cause-specific 5-year rehospitalization rates were significantly higher in SC versus NSC for recurrent ischemic stroke, heart failure, cardiac events, any vascular events, pneumonia, and hip fractures. The excess risk of mortality and rehospitalizations in the SC persisted beyond the initial aftermath of the acute stroke (i.e., beyond 30 days poststroke) and persisted even after 1 year poststroke. Average acute care Medicare charges in SC were more than doubled those in NSC. The high rates of acute care poststroke readmissions indicate a need for trials to prevent long-term complications in stroke survivors.


Unraveling template-free fabrication of carbon nitride nanorods codoped with Pt and Pd for efficient electrochemical and photoelectrochemical carbon monoxide oxidation at room temperature.
The tailored synthesis of carbon nitrides (CNs) is of particular interest in multidisciplinary catalytic applications. However, their fabrication in the form of one-dimensional (1D) nanorods for electrocatalytic carbon monoxide (CO) oxidation is not hitherto reported. Herein, a facile roadmap is presented for the rational design of Pt- and Pd-codoped CN (PtPd/CNs) nanorods via protonation of melamine in an ethylene glycol solution containing Pt and Pd precursors using NaNO3 and HCl and subsequent annealing. The protonation induces the polymerization of melamine to melon nanosheets that consequently roll up to CN nanorods. This tailored the prompt high mass production of uniform 1D CN nanorods (94 ± 2 nm) with a high surface area (155.2 m2 g-1) and they were atomically codoped with Pt and Pd (1.5 wt%) without a template and/or multiple complicated steps. The electrocatalytic CO oxidation activity of PtPd/CNs is 2.01 and 23.41 times greater than that of the commercial Pt/C catalyst and metal-free CNs, respectively, at room temperature. Meanwhile, the UV-vis light irradiation enhanced the CO oxidation activity of PtPd/CNs nanorods by 1.48 fold compared to that in the dark, emanated from the coupling between the drastic inbuilt catalytic merits of PtPd and the inimitable physicochemical properties of CNs. The presented study may pave the way for using CN-based materials in gas conversion reactions.


Comparison of mass isotopomer dilution methods used to compute VLDL production in vivo.
The recent development of mass isotopomer distribution methods represents an important new tool for quantifying synthetic rates. These methods allow precursor enrichment to be determined indirectly from the enrichment of the product, thus sidestepping the often difficult problem of measuring the precursor enrichment. Two different methods have been described to compute synthetic rates by this general approach in the laboratories of M. K. Hellerstein and J. K. Kelleher, and variations of these basic approaches have also been presented by W. N. Lee and by ourselves. A comparison between the different methods has never been reported. In this paper, we take a specific application, calculation of the fractional rate of incorporation of acetyl-CoA into very low density lipoprotein-bound palmitate, and compare the results obtained from all of the mass isotopomer methods using the same data set obtained in vivo in human subjects. We found that it is critical that the measured background isotopomer distribution of palmitate is used rather than the theoretical background isotopomer distribution. We also found that the different methods give comparable precursor enrichments and comparable fractional synthesis rates, provided that the enrichments in Kelleher's method are properly weighted. Thus the choice of method to use is a matter of personal preference.


Nasopharyngoscopy in palatopharyngeal prosthetic rehabilitation: A preliminary report.
Prosthetic rehabilitation of speech disorders related to palatopharyngeal dysfunction is accomplished through separation of the oral and nasal cavities. The ability to achieve this separation is challenged when the disorder or defect involves the soft palate. Prosthetic rehabilitation of soft palate disorders and defects has traditionally relied on functional contouring of a prosthesis using functionally adapted impression materials. However, there are limitations to this process, particularly in its inability to visualize function as it relates to the prosthesis in a 3-dimensional space. The aim of this study was to address this limitation by describing outcomes related to the use of nasopharyngoscopy (NPS) for visualization of the velopharyngeal port during assessment and treatment of palatopharyngeal dysfunction. A retrospective analysis of speech data was conducted for 5 patients who were assessed before treatment, after prosthetic intervention using conventional functional impression techniques, and after prosthetic intervention using NPS. Nasalance and velopharyngeal orifice area outcome measurements were collected for each patient at clinically predetermined intervals. Perceptual assessment of speech samples was performed as well. Improvements in speech function were observed for all patients after treatment with a prosthesis designed via a conventional functional impression technique; however, no patient showed normal values for nasalance or velopharyngeal orifice area. With the use of NPS to adjust the wax impression-derived prosthesis, both nasalance and velopharyngeal orifice area measurements for all patients were within normal limits. Similarly, perceptual judgment of speech found that normal resonance balance was obtained after use of NPS. The addition of NPS into prosthetic treatment for palatopharyngeal disorders shows promise for improved speech results.


Daptomycin antibiotic lock therapy for hemodialysis patients with Gram-positive bloodstream infections following use of tunneled, cuffed hemodialysis catheters: retrospective single center analysis.
Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis patients. We assessed the efficacy of systemic daptomycin (DPT) plus DPT antibiotic lock therapy (DPT-ALT) for catheter salvage in patients with Gram-positive CRBSIs. This is a retrospective study of hemodialysis patients with tunneled and cuffed hemodialysis catheters. All patients were from a single institution in Taipei and received systemic DPT plus DPT-ALT for the treatment of Gram-positive CRBSI. Successful resolution of CRBSI was implemented. Resolution of fever within 48 hours, negative result of repeated blood cultures after resolution of fever, no clinical evidence of CRBSI relapse and no need for catheter removal were measured. Fifteen hemodialysis patients received DPT-ALT for CRBSI, nine with coagulase-negative Staphylococcus (CONS), two with methicillin-resistant Staphylococcus aureus (MRSA), three with methicillin-sensitive Staphylococcus aureus (MSSA) and one with polymicrobial infections. Systemic DPT plus DPT-ALT cured 11 patients (73.3%). Treatment failed in all three MRSA cases (two with MRSA and one with MRSA + Enterococcus faecalis). Retrospective design and small sample size were the limitations of this study. Systemic DPT plus DPT-ALT appears to be a promising treatment for CRBSI from CONS and MSSA, but not for MRSA CRBSI. Systemic DPT plus DPT-ALT should be considered for patients with CRBSIs caused by certain species.


Statistical Approaches in the Studies Assessing Associations between Human Milk Immune Composition and Allergic Diseases: A Scoping Review.
A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets.


Identification and characterization of Snapin as a ubiquitously expressed SNARE-binding protein that interacts with SNAP23 in non-neuronal cells.
Members of the SNARE (soluble N -ethylmaleimide-sensitive fusion protein attachment protein receptor) superfamily [syntaxins, VAMPs (vesicle-associated membrane proteins) and SNAP25 (synaptosome-associated protein-25)-related proteins] are required for intracellular membrane-fusion events in eukaryotes. In neurons, assembly of SNARE core complexes comprising the presynaptic membrane-associated SNAREs syntaxin 1 and SNAP25, and the vesicle-associated SNARE VAMP2, is necessary for synaptic vesicle exocytosis. Several accessory factors have been described that associate with the synaptic SNAREs and modulate core complex assembly or mediate Ca2+ regulation. One such factor, Snapin, has been reported to be a brain-specific protein that interacts with SNAP25, and regulates association of the putative Ca2+-sensor synaptotagmin with the synaptic SNARE complex [Ilardi, Mochida and Sheng (1999) Nat. Neurosci. 2, 119-124]. Here we demonstrate that Snapin is expressed ubiquitously in neuronal and non-neuronal cells. Furthermore, using protein-protein-interaction assays we show that Snapin interacts with SNAP23, the widely expressed homologue of SNAP25, and that the predicted C-terminal helical domain of Snapin contains the SNAP23-binding site. Subcellular localization experiments revealed that Snapin is a soluble protein that exists in both cytosolic and peripheral membrane-bound pools in adipocytes. Moreover, association of Snapin with the plasma membrane was detected in cells overexpressing a Snapin-green fluorescent protein fusion protein. Finally, we show that Snapin is able to form a ternary complex with SNAP23 and syntaxin 4, suggesting that it is a component of non-neuronal SNARE complexes. An important implication of our results is that Snapin is likely to perform a general role in SNARE-mediated vesicle fusion events in non-neuronal cells in addition to its participation in Ca2+-regulated neurosecretion.


PLCgamma2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells.
B cells from phospholipase C (PLC)gamma2-deficient mice express reduced levels of the pro-survival protein Bcl-2 and show a defect in the development of transitional T3 and marginal zone (MZ) B cells that reflects reduced B cell survival. Introduction of a bcl-2 transgene restored the numbers of MZ, T3 and follicular B cells in PLCgamma2(-/-) mice. Restricting the B cell repertoire in PLCgamma2-deficient mice by the introduction of a BCR transgene resulted in a striking reduction in the number of IgM-positive B cells and a paucity of IgD-expressing cells in the spleen which was also rescued by the bcl-2 transgene. BCR-stimulated ERK and IkappaBalpha phosphorylation were PLCgamma2 dependent, while calcium flux was reduced, but not abrogated, in the absence of PLCgamma2, suggesting an ancillary role for PLCgamma1. The bcl-2 transgene rescued development of PLCgamma2(-/-) B cells and serum IgM levels but did not restore BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest that PLCgamma2 performs a critical role in B cell development through regulation of survival rather than differentiation.


[Detection of IgM against the dengue++ virus in whole blood absorbed on filter paper].
This paper presents a standardized procedure for the detection of IgM antibodies to dengue virus in blood samples taken from filter paper. The samples were obtained from 118 patients, of whom 91 had been clinically diagnosed with dengue and 27 with a viral infection unrelated to that disease. The first group of patients came from Costa Rica and Nicaragua and the second group from Cuba. All the samples were tested for IgM antibody against dengue virus by means of a capture enzyme immunoassay (EIA). Analysis of the results for patients from all three countries together yielded a sensitivity of 98.1% and a specificity of 98.5% for the test done on whole blood on filter paper stored at 4 degrees C; agreement between the results of that test and those of the EIA using serum samples was 96%. In a comparison of the results obtained with three samples from the same patient--whole blood on filter paper stored at room temperature, the same type of sample stored at 4 degrees C, and serum--the agreement was 86%. This study demonstrates the high diagnostic sensitivity and specificity achieved when whole blood absorbed on filter paper is processed in the manner described in detail in the article. The authors recommend the use of this method in the dengue surveillance programs in the Region.


Ozymandias: a biodiversity knowledge graph.
Enormous quantities of biodiversity data are being made available online, but much of this data remains isolated in silos. One approach to breaking these silos is to map local, often database-specific identifiers to shared global identifiers. This mapping can then be used to construct a knowledge graph, where entities such as taxa, publications, people, places, specimens, sequences, and institutions are all part of a single, shared knowledge space. Motivated by the 2018 GBIF Ebbe Nielsen Challenge I explore the feasibility of constructing a "biodiversity knowledge graph" for the Australian fauna. The data cleaning and reconciliation steps involved in constructing the knowledge graph are described in detail. Examples are given of its application to understanding changes in patterns of taxonomic publication over time. A web interface to the knowledge graph (called "Ozymandias") is available at https://ozymandias-demo.herokuapp.com.


CaseLog: semantic network interface to a student computer-based patient record system.
We have developed a computer program called CaseLog, which serves as an exemplary, computer-based patient record (CPR) system. The program allows for the introduction of the students to issues unique to patient record systems. These include record security, unique patient identifiers, and the use of controlled vocabularies. A particularly challenging aspect of the development of this program was allowing for student entry of controlled vocabulary terms. There were four goals we wished to achieve: students should be able to find the terms they are looking for; once a term has been found, it should be easy to find contextually related terms; it should be easy to determine that a sought-for term is not in the vocabulary; and the structure of the vocabulary should be dynamically altered by contextual information to allow its use for a variety of purposes. We chose a semantic network for our vocabulary structure. Within the processing power of the equipment we were working with, we achieved our goals. This paper will describe the development of the vocabulary, the design of the CaseLog program, and the feedback from student users of the program.


Is variation in susceptibility to Phytophthora ramorum correlated with population genetic structure in coast live oak (Quercus agrifolia)?
California coastal woodlands are suffering severe disease and mortality as a result of infection from Phytophthora ramorum. Quercus agrifolia is one of the major woodland species at risk. This study investigated within- and among-population variation in host susceptibility to inoculation with P. ramorum and compared this with population genetic structure using molecular markers. Susceptibility was assessed using a branch-cutting inoculation test. Trees were selected from seven natural populations in California. Amplified fragment length polymorphism molecular markers were analysed for all trees used in the trials. Lesion sizes varied quantitatively among individuals within populations, with up to an eightfold difference. There was little support for population differences in susceptibility. Molecular structure also showed a strong within-population, and weaker among-population, pattern of variation. Our data suggest that susceptibility of Q. agrifolia to P. ramorum is variable and is under the control of several gene loci. This variation exists within populations, so that less susceptible local genotypes may provide the gene pool for regeneration of woodlands where mortality is high.


Peer status in school and adult disease risk: a 30-year follow-up study of disease-specific morbidity in a Stockholm cohort.
Children have a social status position of their own, apart from that of the family, that may have an impact on short-term and long-term health. The aim of the present study was to analyse the associations between childhood social status in school (ie, peer status) and disease-specific morbidity in adulthood. Data were derived from a longitudinal study using a 1953 cohort born in Stockholm, Sweden: The Stockholm Birth Cohort Study (1953-2003). Peer status was sociometrically assessed in sixth grade (1966). Hazard ratios for adult disease-specific morbidity based on information on inpatient care (1973-2003) were calculated by peer status category for men and women separately, using Cox regression. The results indicate that the lower the childhood peer status, the higher the overall adult disease risk. There were, however, differences in the degree and magnitude to which disease-specific inpatient care varied with peer status. Some of the steepest gradients were found for mental and behavioural disorders (eg, alcohol abuse and drug dependence), external causes (eg, suicide) and various lifestyle-related diseases (eg, ischaemic heart disease and diabetes). The results were not explained by childhood social class. The present study underlines the importance of recognising children's social position, apart from that of their family, for later health. Not only psychologically related diseases but also those related to behavioural risk factors demonstrate some of the largest relative differences by peer status, suggesting that health-related behaviour may be one important mechanism in the association between peer status and morbidity.


Matrix stiffness regulates endothelial cell proliferation through septin 9.
Endothelial proliferation, which is an important process in vascular homeostasis, can be regulated by the extracellular microenvironment. In this study we demonstrated that proliferation of endothelial cells (ECs) was enhanced on hydrogels with high stiffness (HSG, 21.5 kPa) in comparison to those with low stiffness (LSG, 1.72 kPa). ECs on HSG showed markedly prominent stress fibers and a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber formation and proliferation of ECs on HSG, but had little effect on ECs on LSG; enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2, which are positive RhoA upstream effectors, were higher in ECs on HSG. The inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9), the negative upstream effector for RhoA, was significantly higher in ECs on LSG. The inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC proliferation on LSG, but showed minor effects on ECs on HSG. We further demonstrated that the inactivation of integrin α(v)β(3) caused an increase of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and inhibit RhoA-dependent EC proliferation. These results demonstrate that the SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the mechanical regulation of EC proliferation.


Exceptionally high δ15N values in collagen single amino acids confirm Neandertals as high-trophic level carnivores.
Isotope and archeological analyses of Paleolithic food webs have suggested that Neandertal subsistence relied mainly on the consumption of large herbivores. This conclusion was primarily based on elevated nitrogen isotope ratios in Neandertal bone collagen and has been significantly debated. This discussion relies on the observation that similar high nitrogen isotopes values could also be the result of the consumption of mammoths, young animals, putrid meat, cooked food, freshwater fish, carnivores, or mushrooms. Recently, compound-specific C and N isotope analyses of bone collagen amino acids have been demonstrated to add significantly more information about trophic levels and aquatic food consumption. We undertook single amino acid C and N isotope analysis on two Neandertals, which were characterized by exceptionally high N isotope ratios in their bulk bone or tooth collagen. We report here both C and N isotope ratios on single amino acids of collagen samples for these two Neandertals and associated fauna. The samples come from two sites dating to the Middle to Upper Paleolithic transition period (Les Cottés and Grotte du Renne, France). Our results reinforce the interpretation of Neandertal dietary adaptations as successful top-level carnivores, even after the arrival of modern humans in Europe. They also demonstrate that high δ15N values of bone collagen can solely be explained by mammal meat consumption, as supported by archeological and zooarcheological evidence, without necessarily invoking explanations including the processing of food (cooking, fermenting), the consumption of mammoths or young mammals, or additional (freshwater fish, mushrooms) dietary protein sources.


The primordium of a biological joint replacement: Coupling of two stem cell pathways in biphasic ultrarapid compressed gel niches.
The impaired temporomandibular joint might be the first to benefit from applied tissue engineering techniques because it is small and tissue growth in larger amounts is challenging. Bone and cartilage require different competing environmental conditions to be cultivated in vitro. But coupling both the osteogenic and cartilaginous pathways of mesenchymal stem cell differentiation in homeostasis will be a key essential to grow osteochondral constructs or even the first biological joint replacement in the future. The aim of this study was to test a single source biomaterial and a single source cell type to engineer a biphasic osteochondral construct in vitro for future in vivo implantation. Ultrarapid tissue engineering techniques were used to create the biphasic matrix and primary human mesenchymal stem cells (MSCs) preconditioned in osteogenic and chondrogenic media were then seeded in opposite portions of the hyper-hydrated collagen gel in order to further substantiate the respective bone-like and cartilage-like layers thus potentially customising the collagen scaffold according to patient needs in regards to future biological joint replacements. After incubation for 7 days to allow cell growth and differentiation, mineralization of the bone-like layer was demonstrated using von Kossa staining and biochemical bone markers. The cartilage-like layer was demonstrated using alcian blue staining and biochemical cartilage markers. Integration of the bone-like and cartilage-like layers to simulate a tidemark layer was achieved through partial setting of the gels. Cell tracking was used to further confirm the establishment of distinct cartilage-like and bone-like areas within the single construct. This is the first report of one homogeneous human MSC population differentiating into dissimilar "bone-like" and "cartilage-like" zones hosted in a biphasic ultrarapid compressed gel phase niche and mimicking a primordial joint-like structure.


Novel steroid inhibitors of glucose 6-phosphate dehydrogenase.
Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate. Improved potency was achieved by replacing the androstane nucleus with a pregnane nucleus, provided a ketone at C-20 is present. For pregnan-20-ones incorporation of a 21-hydroxyl group is often beneficial. The novel compounds generally have good physicochemical properties and satisfactory in vitro DMPK parameters. These derivatives may be useful for examining the role of G6PD inhibition in cells and will assist the future design of more potent steroid inhibitors with potential therapeutic utility.


Complete nucleotide and deduced amino acid sequence of human beta 2-glycoprotein I.
The nucleotide and complete amino acid sequence for the human beta 2-glycoprotein I (beta 2I) was derived by sequencing the cDNA clone pB2I-1. In addition to the 326 amino acid residues of the mature protein this clone codes for a putative leader peptide and contains sequence representing 5' and 3' untranslated regions. When this amino acid sequence was compared with the previously published primary sequence, three major amino acid substitutions were found, two involving cysteine residues. These substitutions lead to a new alignment of the complement control protein (CCP) repeats present in beta 2I and a prediction of the complete disulphide bond organization. Northern-blot analysis indicates that hepatocytes are a major site of biosynthesis for this protein. A transcription signal of about 1.5 kb was detected by using RNA from HepG2 cells.


A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya: comparison between Rotarix and RotaTeq vaccines.
Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.


Gas lasers.
A review is given of the present status of gas discharge lasers, with particular attention to developments reported in 1965 and early 1966. Following a brief history, gas lasers are classified by types-neutral atom, ion, and molecular-and a comparison is given of the properties of the various types. A short discussion is given of noise and coherence properties. Detailed descriptions are given of three recent developments of particular interest-the CO(2) laser, the argon-ion laser, and pulsed self-terminating lasers. Finally, brief mention is made of the most important present applications of gas lasers.


Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.
Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.


Effective uses of social media in public health and medicine: a systematic review of systematic reviews.
Research examining the effective uses of social media (SM) in public health and medicine, especially in the form of systematic reviews (SRs), has grown considerably in the past decade. To our knowledge, no comprehensive synthesis of this literature has been conducted to date. To conduct a systematic review of systematic reviews of the benefits and harms ("effects") of SM tools and platforms (such as Twitter and Facebook) in public health and medicine. To perform a synthesis of this literature and create a 'living systematic review'. Forty-two (42) high-quality SRs were examined. Overall, evidence of SM's effectiveness in public health and medicine was judged to be minimal. However, qualitative benefits for patients are seen in improved psychosocial support and psychological functioning. Health professionals benefited from better peer-to-peer communication and lifelong learning. Harms on all groups include the impact of SM on mental health, privacy, confidentiality and information reliability. A range of negatives and positives of SM in public health and medicine are seen in the SR literature but definitive conclusions cannot be made at this time. Clearly better research designs are needed to measure the effectiveness of social technologies. For ongoing updates, see the wiki "Effective uses of social media in health: a living systematic review of systematic reviews". http://hlwiki.slais.ubc.ca/index.php/Effective_uses_of_social_media_in_healthcare:_a_living_systematic_review_of_reviews.


A novel simian virus 40 early-region domain mediates transactivation of the cyclin A promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays.
At least three regions of the simian virus 40 small-t antigen (small-t) contribute to the protein's ability to enhance cellular transformation. As we showed previously for rat F111 cells, one region includes sequences from residues 97 to 103 that are involved in the binding and inhibition of protein phosphatase 2A. In the present study, the role of the protein phosphatase 2A binding region was confirmed in two additional small-t-dependent transformation systems. Second, small-t was found to provide a function previously identified as a large-T transformation domain. Mutations in residues 19 to 28 of large-T affected its transforming ability, but these mutations were complemented by a wild-type small-t. A third region of small-t was also required for efficient transformation. This region, the 42-47 region, is shared by large-T and small-t and contains a conserved HPDKGG hexapeptide. The 42-47 region function could be provided by either small-t or large-T in small-t-dependent systems. Mutations in the 42-47 region reduced the ability of small-t to transactivate the cyclin A promoter, of interest because small-t increased endogenous cyclin A mRNA levels in both human and monkey cells, as well as transactivating the promoter in transient assays.


Does adding antibiotics to cement reduce the need for early revision in total knee arthroplasty?
There is considerable debate about whether antibiotic-loaded bone cement should be used for fixation of TKAs. While antibiotics offer the theoretical benefit of lowering early revision due to infection, they may weaken the cement and thus increase the likelihood of aseptic loosening, perhaps resulting in a higher revision rate. We (1) compared the frequency of early knee revision arthroplasty in patients treated with antibiotic-loaded or non-antibiotic-loaded cement for initial fixation, (2) determined effects of age, sex, comorbidities, and surgeons' antibiotic-loaded cement usage patterns on revision rate, and (3) compared causes of revision (aseptic or septic) between groups. Our study sample was taken from the Canadian Joint Replacement Registry and Canada's Hospital Morbidity Database and included cemented TKAs performed between April 1, 2003, and March 31, 2008, including 20,016 TKAs inserted with non-antibiotic-loaded cement and 16,665 inserted with antibiotic-loaded cement. Chi-square test was used to compare the frequency of early revisions between groups. Cox regression modeling was used to determine whether revision rate would change by age, sex, comorbidities, or use of antibiotic-loaded cement. Similar Cox regression modeling was used to compare cause of revision between groups. Two-year revision rates were similar between the groups treated with non-antibiotic-loaded cement and antibiotic-loaded cement (1.40% versus 1.51%, p = 0.41). When controlling for age, sex, comorbidities, diabetes, and surgeons' antibiotic-loaded cement usage patterns, the revision risk likewise was similar between groups. Revision rates for infection were similar between groups; however, there were more revisions for aseptic loosening in the group treated with non-antibiotic-loaded cement (p = 0.02). The use of antibiotic-loaded cement in TKAs performed for osteoarthritis has no clinically significant effect on reducing revision within 2 years in patients who received perioperative antibiotics. Longer followup and confirmation of these findings with other national registries are warranted.


Tailored surface birefringence by femtosecond laser assisted wet etching.
Surface texturing is demonstrated by the combination of wet etching and ultrafast laser nanostructuring of silica glass. Using potassium hydroxide (KOH) at room temperature as an etchant of laser modified glass, we show the polarization dependent linear increase in retardance reaching a threefold value within 25 hours. The dispersion control of birefringence by the etching procedure led to achromatic behaviour over the entire visible spectral range. The mechanism of enhanced KOH etching selectivity after femtosecond laser exposure is discussed and correlated to the formation of various laser-induced defects, such as silicon-rich oxygen deficiency and color centers.


P2X4 receptor regulation of transient receptor potential melastatin type 6 (TRPM6) Mg2+ channels.
The transient receptor potential melastatin type 6 (TRPM6) ion channel regulates the body Mg(2+) homeostasis by mediating transcellular Mg(2+) absorption in kidney and intestine. Here, the P2X4 receptor was established as a novel regulator of TRPM6 activity. Using RT-qPCR on a mouse tissue panel, P2x4 and P2x6 were shown to be expressed in the epithelium of the colon and of the kidney, two major sites of Mg(2+) reabsorption. While P2x4 was highly expressed in the colon, both P2x4 and P2x6 mRNA were prominently expressed in the distal convoluted tubule segment of the kidney, a segment with high Trpm6 expression. Using whole-cell patch clamp, an inhibitory role of P2X4 on TRPM6 activity was determined. Expression of P2X6, which does not form functional channels in mammalian cells, did not affect the function of TRPM6. The inhibition was dependent on the activity of P2X4, since a P2X4 mutant with altered ATP sensitivity was not able to inhibit TRPM6. Additionally, P2X4 was unable to inhibit TRPM7, a close homologue of TRPM6, suggesting that the inhibition is specific for TRPM6. To identify the intracellular signaling molecules that mediate the P2X4-dependent inhibition of TRPM6, the cells were treated with inhibitors of protein kinase c, protein kinase a, and phosphoinositide 3-kinase. However, none of these inhibitors prevented the inhibition of TRPM6 by P2X4. In conclusion, we propose that P2X4 receptor mediated purinergic signaling is a new regulatory mechanism of TRPM6 Mg(2+) channels.


Transcriptome-wide analysis of trypanosome mRNA decay reveals complex degradation kinetics and suggests a role for co-transcriptional degradation in determining mRNA levels.
African trypanosomes are an excellent system for quantitative modelling of post-transcriptional mRNA control. Transcription is constitutive and polycistronic; individual mRNAs are excised by trans splicing and polyadenylation. We here measure mRNA decay kinetics in two life cycle stages, bloodstream and procyclic forms, by transcription inhibition and RNASeq. Messenger RNAs with short half-lives tend to show initial fast degradation, followed by a slower phase; they are often stabilized by depletion of the 5'-3' exoribonuclease XRNA. Many longer-lived mRNAs show initial slow degradation followed by rapid destruction: we suggest that the slow phase reflects gradual deadenylation. Developmentally regulated mRNAs often show regulated decay, and switch their decay pattern. Rates of mRNA decay are good predictors of steady state levels for short mRNAs, but mRNAs longer than 3 kb show unexpectedly low abundances. Modelling shows that variations in splicing and polyadenylation rates can contribute to steady-state mRNA levels, but this is completely dependent on competition between processing and co-transcriptional mRNA precursor destruction.


The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group.
HIV infection often results in neuropsychological (NP) impairment. In order to assess the impact that HIV-related NP deficits may have on automobile driving, we evaluated 68 HIV-seropositive drivers using an NP battery and two PC-based driving simulations. Thirty-two participants were classified as NP impaired; most (72%) evidenced only mild impairment, and none met criteria for HIV-associated dementia. After controlling for degree of immunosuppression and disease stage, NP-impaired participants failed a previously validated driving simulation at a much higher rate than cognitively intact participants [OR = 5.3, 95% CI (1.7, 17.0), p = .006]. Similarly, on a simulation of city driving, NP impaired participants were more likely to fail based upon the number of accidents [OR = 6.1, 95% CI (1.5, 24.6), p = .01]. Simulator performance was predicted by functioning in a number of NP domains, with NP tests accounting for 13-30% of the variance on the simulations. Although it would be premature to extrapolate these findings to impairment in on-the-road driving, they do argue for greater attention to the impact that even mild HIV-related NP deficits may have on driving skills.


Comparative study on anti-proliferative potentials of zinc oxide and aluminium oxide nanoparticles in colon cancer cells.
Use of commercial products containing nanoparticles formulated from zinc oxide (ZnO) and aluminium oxide (Al2O-3) has increased significantly. These nanoparticles are widely used as ingredient in cosmetics, and also in food packaging industry although their toxicity status is yet to be studied. Here, we aimed to explore the effect of zinc oxide nanoparticles (ZnO-NPs) and aluminium oxide nanoparticles (ANPs) in human HT29 colon cancer cell line. In this study, ZnO-NPs were synthesized by chemical method and ANPs synthesized by sol-gel method and were characterized using UV-Vis spectroscopy, X ray diffraction and Transmittance electron microscopy. The effects of ZnO-NPs and ANPs was determined by cell viability, membrane integrity and colony formation potentials. ZnO-NPs and ANPs inhibit HT29, colon cancer cell proliferation in a dose dependent manner, and affect the membrane potentials and also prevent the colony formation. The results suggest that ZnO NPs are found to be more effective than ANPs in reducing colon cancer cell proliferation.


Reduced efficacy of fluazinam against Phytophthora infestans in the Netherlands.
Phytophthora infestans is the causal organism of potato late blight, the most important disease in potato, the second most important arable crop in Europe. The P. infestans population in Europe is well known for its sudden changes in composition. Currently it is composed of a wide variety of genotypes, some of which are dominant clonal lines while others are rare or even unique to a year or location. Fungicides play a crucial role in the integrated control of late blight. Since its introduction in the Netherlands in 1992, fluazinam has been used in late blight control strategies in ware and starch potatoes. It has a broad spectrum of activity and is effective against a range of diseases including potato late blight. Fluazinam interrupts the pathogen cell's energy production process by an uncoupling effect on oxidative phosphorylation. It is considered to have a low resistance risk. Until recently, reduced efficacy against fluazinam was not detected in P. infestans surveys in Europe. In this paper we present the finding of a new clonal lineage (EU_33_A2) of P. infestans in the Netherlands and the reduced efficacy of fluazinam to control one of the EU_33_A2 isolates in field experiments carried out in 2011 and 2015 under high disease pressure. The potential effects of this finding on practical late blight control strategies are discussed.


Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.
Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort, and its association with clinical endpoints and functional relevance are unclear. We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored. Amplification of the 7q21 region was observed in 35% of tumors with a focal, minimal amplicon containing six genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified cyclin-dependent kinase 6 (CDK6) as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low-level amplification (10%) was observed at the 12q13 region containing the CDK6 homologue cyclin-dependent kinase 4 (CDK4). Both amplification and expression of CDK4 correlated with poor survival. A combined model of both CDK6 and CDK4 expressions is a superior predictor of survival than either alone. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage independence of EAC cells through activation of the pRB pathway. We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Targeting these molecules may constitute a viable new therapy for this disease.


Monocytes and vascular endothelial cells apoptosis. Role of p-HSP27.
The aim of this study was to find out whether stimulated monocytes could trigger apoptosis of vascular endothelial cells. Human umbilical vein endothelial cells (HUVEC) (EC) were co-cultured for 24 h and 48 h with monocytes isolated from peripheral blood (peripheral blood monocytes) or MonoMac6 cell line activated previously with proinflammatory cytokines. Real-time PCR was conducted to investigate p53 up-regulated modulator of apoptosis (PUMA), heat shock protein HSP70 and HSP27 genes expression. Changes in the level of PUMA, HSP70, HSP27 and phospho-heat shock protein 27 (p-HSP27) proteins were analyzed by means of immunoprecipitation. Apoptosis was determined by TUNEL and poli-(ADP ribose) polymerase ( PARP ) cleavage assay. In HUVEC cells stimulated with monocytes hardly any increase of PUMA mRNA was observed, but the PUMA protein level was significantly up regulated especially after 24 h. Heat shock proteins (HSP70 and HSP27) mRNA expression was elevated after 24 h and 48h and confirmatory up regulation of these proteins was observed in HUVEC cells stimulated with peripheral blood monocytes but not with MonoMac6 cells. Interestingly, in nuclear compartment of HUVECs exposed to the monocytic line and native monocytes, a significant increase of p-HSP27 level has appeared. TUNEL and PARP cleavage assay did not show any apoptotic HUVEC cells after stimulation with monocytes. The main observations of this study indicate that monocytes do not trigger apoptosis of vascular endothelial cells. Proapoptotic activation mediated by PUMA that was observed seemed to be counterbalanced by significant increase of antiapoptotic HSP70, HSP27 and especially phospho-HSP27 proteins level.


Leukocyte- and platelet-derived microvesicle interactions following in vitro and in vivo activation of toll-like receptor 4 by lipopolysaccharide.
Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood.


The role of adherence in the relationship between self-efficacy and self-management in diabetic patients undergoing CABG in Taiwan.
To determine the role of adherence and its significance in the relationship between self-efficacy and self-management of diabetic patients undergoing coronary artery bypass graft (CABG) in Taiwan. Descriptive and correlational survey design. Three outpatient clinics in Taiwan. Patients diagnosed with diabetes undergoing CABG at least 6 months before the study, 18 years of age or older, able to communicate verbally without any psychiatric problems, and with a life expectancy longer than 1 year. Self-management assessment (self-efficacy for managing disease and adherence to guidelines and medication measured on a scale of 0-8), the higher aspects of self-management (keeping appointments, taking medication properly and keeping follow-up appointments) and the lower aspects of self-management (inability to share decisions with primary physician, inability to take correct actions when symptoms worsen and inability to adapt habits to improve health). The mean score obtained for self-management among the 166 participants was 6.48, with 57 (34.3%) of them showing non-adherent behaviour. Self-efficacy accounts for 38% (R(2)=0.380, F(1,103)=63.124, p < 0.001), and 54% of good self-management was explained by self-efficacy and adherence in managing disease (R(2)=0.540, F(2,102)=56.937, p<0.001). Adherence accounts for 16% of better self-management, age and education combined account for 4.9% (R(2)=0.589, F(6.98)=23.399, p<0.001), and lifestyle items account for 5.2% (R(2)=0.641, F(14,90)=11.457, p<0.001). Disease-related variables contribute 3.4% (R(2)=0.674, F(17,87)=10.599, p<0.001). Thus self-efficacy, adherence, age, education, primary care provider and systolic pressure are considered significant predictors of self-management. With the exception of adherence, none of the variables had a statistically significant mediating effect. The results confirm strong relationships between self-efficacy, adherence and self-management, with adherence having a significant mediating effect in post-CABG patients with diabetes in Taiwan.


Diversity Arrays Technology (DArT) for whole-genome profiling of barley.
Diversity Arrays Technology (DArT) can detect and type DNA variation at several hundred genomic loci in parallel without relying on sequence information. Here we show that it can be effectively applied to genetic mapping and diversity analyses of barley, a species with a 5,000-Mbp genome. We tested several complexity reduction methods and selected two that generated the most polymorphic genomic representations. Arrays containing individual fragments from these representations generated DArT fingerprints with a genotype call rate of 98.0% and a scoring reproducibility of at least 99.8%. The fingerprints grouped barley lines according to known genetic relationships. To validate the Mendelian behavior of DArT markers, we constructed a genetic map for a cross between cultivars Steptoe and Morex. Nearly all polymorphic array features could be incorporated into one of seven linkage groups (98.8%). The resulting map comprised approximately 385 unique DArT markers and spanned 1,137 centimorgans. A comparison with the restriction fragment length polymorphism-based framework map indicated that the quality of the DArT map was equivalent, if not superior, to that of the framework map. These results highlight the potential of DArT as a generic technique for genome profiling in the context of molecular breeding and genomics.


Down-regulation of pan-T-cell antigens, particularly CD7, in acute infectious mononucleosis.
Multiparameter flow cytometric analysis was performed on the peripheral blood samples from 25 patients with acute infectious mononucleosis. Phenotypic results were matched with those for patients without viral symptomatology. Samples from all patients with infectious mononucleosis exhibited an activated (HLA-DR+, CD38+) CD8+ cytotoxic-suppressor T-cell population with aberrant down-regulation of CD7, and samples from 2 (8%) of 25 patients also showed down-regulation of CD5. The CD8+ cells also were slightly larger than normal T cells by forward scatter characteristics. None of the control samples showed down-regulation of either antigen. Aberrant pan-T-cell antigenic expression is a criterion in the immunophenotypic diagnosis of T-cell lymphoproliferative disorders. Acute Epstein-Barr virus infection should be considered in the differential diagnosis when down-regulation of CD7 is present, especially in conjunction with an activated CD8+ T-cell population.


Clinical utility and cost of non-invasive prenatal testing with cfDNA analysis in high-risk women based on a US population.
Evaluate the clinical and economic consequences of fetal trisomy 21 (T21) screening with non-invasive prenatal testing (NIPT) in high-risk pregnant women. Using a decision-analytic model, we estimated the number of T21 cases detected, the number of invasive procedures performed, corresponding euploid fetal losses and total costs for three screening strategies: first trimester combined screening (FTS), integrated screening (INT) or NIPT, whereby NIPT was performed in high-risk patients (women 35 years or older or women with a positive conventional screening test). Modeling was based on a 4 million pregnant women cohort in the US. NIPT, at a base case price of $795, was more clinically effective and less costly (dominant) over both FTS and INT. NIPT detected 4823 T21 cases based on 5330 invasive procedures. FTS detected 3364 T21 cases based on 108 364 procedures and INT detected 3760 cases based on 108 760 procedures. NIPT detected 28% and 43% more T21 cases compared to INT and FTS, respectively, while reducing invasive procedures by >95% and reducing euploid fetal losses by >99%. Total costs were $3786M with FTS, $3919M with INT and $3403M with NIPT. NIPT leads to improved T21 detection and reduction in euploid fetal loss at lower total healthcare expenditures.


Pharmacokinetics and tissue distribution of 2-fluoro-beta-alanine in rats. Potential relevance to toxicity pattern of 5-fluorouracil.
Clinical pharmacokinetic studies in our laboratory demonstrated that 2-fluoro-beta-alanine (FBAL), the major catabolite of fluorouracil (FUra), has a prolonged elimination with an approximately 150-fold longer half-life than that of the unchanged drug in humans [Heggie et al.: Cancer Res. 47, 2203-2206 (1987)]. Recent studies have suggested that FUra catabolites, such as FBAL, may have a role in neurotoxicity and cardiotoxicity that may occur during FUra chemotherapy [Okada et al.: Acta Neuropathol. 81, 66-73 (1990)]. This study was undertaken to determine the kinetics and tissue distribution of FBAL in rats following iv bolus administration of radiolabeled FBAL. Plasma disappearance curves for FBAL could be described by the sum of three exponentials, with half-lives of 0.26, 12.1, and 8426 min. Radioactivity, consisting mainly of FBAL-bile acid conjugates, was excreted in bile within 30 sec of iv bolus administration of FBAL and continued throughout the experimental period at concentrations 10-100-fold higher than that of the corresponding plasma level. Urinary excretion, consisting mainly of free FBAL, represented the major pathway of elimination of FBAL, with 40% of the administered dose excreted within 24 hr and approximately 70% over 192 hr. Fecal excretion was a minor pathway of elimination of FBAL, with approximately 10% of the administered dose excreted over 192 hr. During the initial 30 min, the highest levels of tissue radioactivity were found in the kidneys, liver, spleen, lungs, and heart. Radioactivity was retained over longer time periods in the enterohepatic circulation, central nervous system, heart, and skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


The association between indwelling urinary catheter use in the elderly and urinary tract infection in acute care.
The use of indwelling urinary catheters (IUCs) is thought to be the most significant risk factor for developing nosocomial urinary tract infections (UTIs). However, it is unclear how many elderly patients have preexisting bacteriuria prior to IUC placement. The purpose of this study was to determine 1) the frequency and appropriateness of IUC use in the Emergency Department (ED) in elderly patients admitted to our acute care hospital, 2) the percentage of elderly patients with an IUC who were discharged from the hospital with a diagnosis of UTI, 3) the percentage of patients with IUCs who were diagnosed and treated for UTI in the ED or who had admission bacteriuria > or =105 organisms/ml indicating preexisting UTI, and 4) the percentage of patients with no indication of UTI on admission who had inappropriately placed IUCs and subsequently were diagnosed with a UTI. Retrospective chart review. Chi square used to test significance of differences in proportions. Seventy three percent of patients who received an IUC in the ED were elderly (> or =65 years old). During the study period, 277 elderly patients received an IUC prior to admission. Of these, 77 (28%) were diagnosed with UTI during their hospitalization. Fifty three (69%) of those diagnosed with a UTI by discharge either had the UTI diagnosed in the ED or had bacteriuria > or =105 organisms/ml prior to IUC placement. Of the 24 elderly patients who developed a catheter-associated UTI (i.e., 9% of the elderly population who received an IUC), 11 of the IUCs were placed inappropriately. Thus, 4% of elderly patients with no indication of UTI on admission who received an inappropriate IUC in the ED had a primary or secondary diagnosis of UTI by discharge. The overall rate of nosocomial UTI due to an inappropriately placed IUC was the same in males and females. This study indicates that the strong association between IUC use and UTI may be partly explained by the high prevalence of preexisting UTI prior to IUC placement. Further prospective studies are needed to clarify the true risk vs benefit ratio for IUC use in acutely ill elderly patients.


Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats.
This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets. Rats were killed 20 weeks after the first AOM. Colon tissues and tumours were examined for histopathology by H&E, gene/protein expression by PCR and immunohistochemistry and digesta for analyses of fermentation products and microbiota populations. RS and RS + GTE (but not GTE) diets significantly (P< 0.05) decreased tumour multiplicity and adenocarcinoma formation, relative to the control diet. Effects of RS + GTE were not different from RS alone. RS diet caused significant shifts in microbial composition/diversity, with increases in Parabacteroides, Barnesiella, Ruminococcus, Marvinbryantia and Bifidobacterium as primary contributors to the shift. RS-containing diets increased short chain fatty acids (SCFA) and expression of the SCFA receptor GPR43 mRNA, and reduced inflammation (COX-2, NF-kB, TNF-α and IL-1β mRNA) and cell proliferation P< 0.05. GTE had no effect. This is the first study that demonstrates chemopreventive effects of RS (but not GTE) in a rodent CAC model, suggesting RS might have benefit to patients with ulcerative colitis who are at an increased risk of developing CRC.


Dengue virus and the complement alternative pathway.
Dengue disease is an inflammatory-driven pathology, and complement overactivation is linked to disease severity and vascular leakage. Additionally, dysregulation of complement alternative pathway (AP) components has been described, such as upregulation of complement factor D and downregulation of complement factor H (FH), which activate and inhibit the AP, respectively. Thus, the pathology of severe dengue could in part result from AP dysfunction, even though complement and AP activation usually provide protection against viral infections. In dengue virus-infected macrophages and endothelial cells (ECs), the site of replication and target for vascular pathology, respectively, the AP is activated. The AP activation, reduced FH and vascular leakage seen in dengue disease in part parallels other complement AP pathologies associated with FH deficiency, such as atypical haemolytic uraemic syndrome (aHUS). aHUS can be therapeutically targeted with inhibitors of complement terminal activity, raising the idea that strategies such as inhibition of complement or delivery of FH or other complement regulatory components to EC may be beneficial to combat the vascular leakage seen in severe dengue.


Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers.
Cell-free hemoglobin's (CFH) high affinity for nitric oxide (NO) could limit CFH's use as an oxygen-carrying blood replacement fluid because it scavenges NO, causing vasoconstriction and hypertension. However, the extent to which perivascular NO levels change following intravascular administration of hemoglobin (Hb) with different molecular dimensions correlates with vasoconstrictive responses in the microcirculation is unknown. The study objective was to determine vasoconstrictive effects following bolus infusions of (1) alphaalpha cross-linked Hb; (2) polymerized bovine Hb; or (3) polyethylene glycol-decorated Hb (PEG-Hb), by measurements of in vivo microvessel diameter, blood flow, perivascular NO concentration, and systemic hemodynamic parameters. All CFHs caused reductions in perivascular NO levels, not correlated to microvascular responses. PEG-Hb (largest molecular volume) maintained blood flow, while the others caused vasoconstriction and reduced perfusion. All solutions increased mean arterial pressure due to vasoconstriction and blood volume expansion, except for PEG-Hb, which increased blood pressure due to blood volume expansion and maintenance of cardiac output. In conclusion, perivascular NO reduction is similar for all Hb solutions because NO binding affinities are similar; however, effects on vascular resistance are related to the type of molecular modification, molecular volume, and oxygen affinity.


Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36.
We examined whether, in human obesity and type 2 diabetes, long chain fatty acid (LCFA) transport into skeletal muscle is upregulated and contributes to an excess intramuscular triacylglycerol accumulation. In giant sarcolemmal vesicles prepared from human skeletal muscle, LCFA transport rates were upregulated approximately 4-fold and were associated with an increased intramuscular triacylglycerol content in obese individuals and in type 2 diabetics. In these individuals, the increased sarcolemmal LCFA transport rate was not associated with an altered expression of FAT/CD36 or FABPpm. Instead, the increase in the LCFA transport rate was associated with an increase in sarcolemmal FAT/CD36 but not sarcolemmal FABPpm. Rates of fatty acid esterification were increased threefold in isolated human muscle strips obtained from obese subjects, while concomitantly rates of fatty acid oxidation were not altered. Thus, the increased rate of fatty acid transport may contribute to the increased rates of triacylglycerol accumulation in human skeletal muscle. The altered FAT/CD36 trafficking in muscle from obese subjects and type 2 diabetics juxtaposes the known alterations in GLUT4 trafficking, i.e., GLUT4 is known to be retained in its intracellular depots while FAT/CD36 is retained at the sarcolemma. This redistribution of FAT/CD36 to the sarcolemma may contribute to the etiology of insulin resistance in human muscle, and hence, FAT/CD36 provides another potential therapeutic target for the prevention and/or treatment of insulin resistance.