Use of simple kinetic and reaction-order measurements for the evaluation of the mechanism of surfactant-liposome interactions.
Surfactant-liposome interactions have been previously studied through different methods and techniques. We present here a classical physical chemistry study on liposome solutions added to destabilizing agents at concentrations well above the solubilization concentration, which enable us to draw useful and interesting conclusions about the mechanism of surfactant-induced liposomal breakdown by simply exploiting the kinetics and the reaction order of the liposomal content release. In such excess of surfactant, the mechanism of surfactant-induced rupture of the liposomes has been demonstrated to be different from that proposed for low surfactant concentrations. Thus, depending on the surfactant concentration, two prevailing processes have been evidenced: (i) a cooperative mechanism that implies the assembly of a critical number of surfactant molecules to trigger the formation of a channel and therefore the release of the liposomal content and (ii) a mechanism driven by direct interaction of the surfactant molecules with the lipids that causes the complete solubilization of the liposomes. The former mechanism occurs at low surfactant concentrations, whereas the latter occurs at higher concentrations and above the CMC of the surfactants. The effect of different guests embedded into the liposomal bilayer on the mechanism of surfactant-induced liposomal breakdown has been compared by using the second-order rate constants measured for the liposome breakdown process.


Getting the cost right in cost-effectiveness analyses.
The authors examined different ways of measuring unit costs and how methodological assumptions can affect the magnitude of cost estimates and the ratio of treatment costs in comparative studies of mental health interventions. Four methodological choices may bias cost estimates: study perspective, definition of the opportunity cost of resources, cost allocation rules, and measurement of service units. Unit costs for outpatient services, individual therapy, and group therapy were calculated under different assumptions for a single community mental health center (CMHC). Using hypothetical service utilization profiles, the authors used the unit costs to calculate the costs of mental health treatments provided by two programs of the CMHC. The unit costs for an hour of outpatient services ranged from $108 to $538. The unit costs for an hour of therapy varied by 156%; unit costs were lowest if the management perspective was assumed and highest if the economist perspective was assumed. The ratio of the outpatient costs in the two treatment programs ranged from 0.6 to 1.8. The potential errors introduced by methodological choices can bias cost-effectiveness findings based on randomized control trials. These errors go undetected because crucial methodological information is not reported.


Does a High Sugar High Fat Dietary Pattern Explain the Unequal Burden in Prevalence of Type 2 Diabetes in a Multi-Ethnic Population in The Netherlands? The HELIUS Study.
The risk for type 2 diabetes (T2D) in ethnic minorities in Europe is higher in comparison with their European host populations. The western dietary pattern, characterized by high amounts of sugar and saturated fat (HSHF dietary pattern), has been associated with a higher risk for T2D. Information on this association in minority populations is scarce. Therefore, we aimed to investigate the HSHF dietary pattern and its role in the unequal burden of T2D prevalence in a multi-ethnic population in The Netherlands. We included 4694 participants aged 18-70 years of Dutch, South-Asian Surinamese, African Surinamese, Turkish, and Moroccan origin from the HELIUS study. Dutch participants scored the highest on the HSHF dietary pattern, followed by the Turkish, Moroccan, African Surinamese, and South-Asian Surinamese participants. Prevalence ratios (PR) for T2D were then calculated using multivariate cox regression analyses, adjusted for sociodemographic, anthropometric, and lifestyle factors. Higher adherence to an HSHF diet was not significantly related to T2D prevalence in the total study sample (PR 1.04 high versus low adherence, 95% CI: 0.80-1.35). In line, adjustment for HSHF diet score did not explain the ethnic differences in T2D. For instance, the PR of the South-Asian Surinamese vs. Dutch changed from 2.76 (95% CI: 2.05-3.72) to 2.90 (95% CI: 2.11-3.98) after adjustment for HSHF. To conclude, a western dietary pattern high in sugar and saturated fat was not associated with T2D, and did not explain the unequal burden in prevalence of T2D across the ethnic groups.


Comprehensive analysis of clinico-pathological data reveals heterogeneous relations between atherosclerosis and cancer.
Atherosclerosis and cancer share common risk factors and involve similar molecular pathomechanisms. Most clinical and epidemiological studies show a positive correlation between atherosclerosis and smoking-related cancers and heterogeneous results for non-smoking-related cancers. However, up-to-date large-scale autopsy studies including a detailed analysis of cancer types are lacking. Therefore, we sought to investigate the relation between major cancer types and the grade of atherosclerosis in a recent well-powered autopsy cohort. In 2101 patients, both autopsy data and clinical data including demographics, disease groups, tumour type, cause of death and grade of atherosclerosis were reviewed and statistically analysed. We found cancer in general is associated with less atherosclerosis (OR 0.60, p<0.0001). In particular, haematological neoplasm and sarcomas were associated with much less atherosclerosis (OR=0.45, p<0.0001 and OR=0.43, p=0.087), while carcinomas were associated with moderately less atherosclerosis (OR=0.72, p=0.002). Furthermore, non-smoking-related cancers were associated with much less atherosclerosis (OR=0.41, p<0.0001), while possibly smoking-related cancer and smoking-related cancer showed no significant association. In a comprehensive analysis of 21 cancer types, biliary tract cancer, lymphomas/lymphoid leukaemias and kidney cancer were associated with much less atherosclerosis (OR=0.19, p<0.0001; OR=0.41, p<0.0001; and OR=0.48, p=0.029). In an exploratory analysis of treatment strategies, we found that tumours with a recommendation of oxazaphosphorines and pyrimidine antagonist treatment were significantly associated with less atherosclerosis (OR=0.33, p=0.0068 and OR=0.58, p=0.012). In conclusion, the study showed an inverse association between cancer and atherosclerosis postmortem that depends on the cancer type and suggests a possible impact of chemotherapy regimens.


Endemic treponemal diseases.
The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecological niche but all predominantly affect poor, rural communities. As with venereal syphilis, the clinical manifestations of the endemic treponemal diseases are variable and can be broken down in to early stage and late stage disease. Current diagnostic techniques are unable to distinguish the different causative species but newer molecular techniques are now making this possible. Penicillin has long been considered the mainstay of treatment for the endemic treponemal diseases but the recent discovery that azithromycin is effective in the treatment of yaws has renewed interest in these most neglected of the NTDs, and raised hopes that global eradication may finally be possible.


MICL controls inflammation in rheumatoid arthritis.
Myeloid inhibitory C-type lectin-like receptor (MICL, Clec12A) is a C-type lectin receptor (CLR) expressed predominantly by myeloid cells. Previous studies have suggested that MICL is involved in controlling inflammation. To determine the role of this CLR in inflammatory pathology using Clec12A(-/-) mice. Clec12A(-/-) mice were generated commercially and primarily characterised using the collagen antibody-induced arthritis (CAIA) model. Mechanisms and progress of disease were characterised by clinical scoring, histology, flow cytometry, irradiation bone-marrow chimera generation, administration of blocking antibodies and in vivo imaging. Characterisation of MICL in patients with rheumatoid arthritis (RA) was determined by immunohistochemistry and single nucleotide polymorphism analysis. Anti-MICL antibodies were detected in patient serum by ELISA and dot-blot analysis. MICL-deficient animals did not present with pan-immune dysfunction, but exhibited markedly exacerbated inflammation during CAIA, owing to the inappropriate activation of myeloid cells. Polymorphisms of MICL were not associated with disease in patients with RA, but this CLR was the target of autoantibodies in a subset of patients with RA. In wild-type mice the administration of such antibodies recapitulated the Clec12A(-/-) phenotype. MICL plays an essential role in regulating inflammation during arthritis and is an autoantigen in a subset of patients with RA. These data suggest an entirely new mechanism underlying RA pathogenesis, whereby the threshold of myeloid cell activation can be modulated by autoantibodies that bind to cell membrane-expressed inhibitory receptors.


General psychopathology links burden of recent life events and psychotic symptoms in a network approach.
Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that general symptoms would mediate between recent life events and psychotic symptoms. We analyzed baseline data of patients at clinical high risk for psychosis and with recent-onset psychosis (n = 547) from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. In a network analysis, we modeled links between the burden of recent life events and all individual symptoms of the Positive and Negative Syndrome Scale before and after controlling for childhood trauma. To investigate the longitudinal associations between burden of recent life events and symptoms, we analyzed multiwave panel data from seven timepoints up to month 18. Corroborating our hypothesis, burden of recent life events was connected to positive and negative symptoms through general psychopathology, specifically depression, guilt feelings, anxiety and tension, even after controlling for childhood trauma. Longitudinal modeling indicated that on average, burden of recent life events preceded general psychopathology in the individual. In line with the theory of an affective pathway to psychosis, recent life events may lead to psychotic symptoms via heightened emotional distress. Life events may be one driving force of unspecific, general psychopathology described as characteristic of early phases of the psychosis spectrum, offering promising avenues for interventions.


First principles study of photo-oxidation degradation mechanisms in P3HT for organic solar cells.
We present a theoretical study of degradation mechanisms for photoinduced oxidation in organic polymers in the condensed phase, using poly(3-hexylthiophene) (P3HT) as an example. Applying density functional theory with a hybrid density functional and periodic boundary conditions that account for steric effects and permit the modeling of interchain chemical reactions, we investigate reaction pathways that may lead to the oxidation of the thiophene backbone as a critical step toward disrupting the polymer conjugation. We calculate energy barriers for reactions of the P3HT backbone with oxidizing agents including the hydroxyl radical (OH˙), hydroperoxide (ROOH), and the peroxyl radical (ROO˙), following a UV-driven radical reaction starting at the α-carbon of the alkyl side chain as suggested by infrared (IR) and X-ray photoemission (XPS) spectrosocopy studies. The results strongly suggest that an attack of OH˙ on sulfur in P3HT is unlikely to be thermodynamically favored. On the other hand, an attack of a peroxyl radical on the side chain on the P3HT backbone may provide low barrier reaction pathways to photodegradation of P3HT and other polymers with side chains. The condensed phase setting is found to qualitatively affect predictions of degradation processes.


Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.
Nod2 activates the NF-kappaB pathway following intracellular stimulation by bacterial products. Recently, mutations in Nod2 have been shown to be associated with Crohn's disease, suggesting a role for bacteria-host interactions in the etiology of this disorder. We show here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptidoglycan motif common to all bacteria. Moreover, the 3020insC frameshift mutation, the most frequent Nod2 variant associated with Crohn's disease patients, fully abrogates Nod2-dependent detection of peptidoglycan and MDP. Together, these results impact on the understanding of Crohn's disease development. Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound.


Access to Care: Using eHealth to Limit Location-Based Barriers for Patients With Cancer.
Rural and urban communities may encounter barriers to care, which can lead to delays in timely screening, diagnosis, and treatment. eHealth interventions, such as televisits and remote patient monitoring, are being used increasingly to improve patient access to quality clinical cancer care and to support patient-provider communication. This article describes how eHealth can bridge gaps in patient access to cancer care and provides insight into successful eHealth program implementation. Articles that evaluate access to care and eHealth program implementation were summarized. Two case studies illustrate eHealth as a strategy to improve care delivery and access. Integrating eHealth into clinical practice can help to transform care delivery and improve patient access to quality cancer care by limiting barriers.


Optics in a hostile environment.
The hostile environment is defined for the purposes of this paper and modes of hostility due to physical, human, and economic factors are outlined. An account is given of some ways in which the optical methods can be defended against the inimical physical and human factors by the functional design of the apparatus with some examples which have proved successful in practice. The influence of economics is discussed, together with its implications for the designer of optical instruments.


Cranberries for preventing urinary tract infections.
Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in preventing such infections. To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptible populations. Electronic databases and the Internet were searched using English and non English language terms; companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of review articles and relevant trials were searched. Cochrane Central Register of Controlled Trials (CENTRAL - the Cochrane Library, issue 1, 2003) was searched in February 2003. All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of urinary tract infections in susceptible populations. Trials of men, women or children were included. Two reviewers independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic and asymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria. Seven trials met the inclusion criteria (four cross-over, three parallel group). The effectiveness of cranberry juice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness of cranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two good quality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91) compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave 1:30 concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIs between cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five trials were not included in the meta-analyses due to methodological flaws or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trials were high. There is some evidence from two good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly men and women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juice may not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method of administration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.


Phasic release of adenosine during steady state metabolic stimulation in the isolated guinea pig heart.
If adenosine is the major factor responsible for myocardial metabolic vasodilation, its release should be sustained as long as oxygen consumption and coronary flow are augmented. To see if adenosine meets this criterion, we examined the time course of its release during norepinephrine infusion in isolated, non-working guinea pig hearts (n = 8). During an 11-minute infusion period (steady state perfusate concentration = 6 X 10(-8) M), the coronary effluent was collected over 30-second intervals for measurements of coronary flow (ml/min per g), and adenosine and inosine release (pmol/min per g). Myocardial oxygen consumption (MVO2 = microliter O2/min per g) was measured at 1, 4, 6.5, and 11 minutes. Control values of coronary flow, myocardial oxygen consumption, and adenosine and inosine release were 7.5 +/- 0.4, 85 +/- 5, 22 +/- 5, and 431 +/- 39, respectively. During norepinephrine infusion, coronary flow, myocardial oxygen consumption, and adenosine release attained maximal levels within one minute (inosine within 2 minutes). These values were 10.6 +/- 0.4, 125 +/- 9, 849 +/- 110, and 2595 +/- 581, respectively. Thereafter, coronary flow and myocardial oxygen consumption values were sustained. In contrast, adenosine and inosine release significantly declined to nadirs by 9.5 minutes. Thereafter, steady state levels were maintained at 117 +/- 24 and 960 +/- 294, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Differences in microhabitat, abundance, biomass and body size between oxybiotic and thiobiotic free-living marine nematodes.
Analysis of samples from a 15 m deep sandy bottom in the northern part of Øresund, Denmark shows that the nematode fauna comprises 2.9 million individuals per m2 down to 20 cm depth which averages of 0.40 g organic carbon. Highest densities are found in the uppermost cm. Biomass attains its highest value at 1-2 cm depth. Three results are discussed: 1) nematodes in the uppermost cm are, on average, three times smaller than those between 1-8 cm depth (60 ng org. C vs. 200 ng org. C ind. weight); 2) a distinct abundance trough is found at 8 cm depth, which correlates with the physical space occupied by the gallery of the lugworm Arenicola marina as well as with its possibly unselective feeding on the interstitial meiofauna at that depth; 3) the thiobiotic (deeper-living) species are significantly more slender than the oxybiotic (surface-dwelling) species, suggesting surface-dependent adaptations to life in oxygen poor and sulphide rich sediments where large amounts of dissolved organic matter occur. This is in contrast to previous assumptions that the body length or body shape reflects adaptations to the physical constraints of interstitial space.


JNK pathway inhibition selectively primes pancreatic cancer stem cells to TRAIL-induced apoptosis without affecting the physiology of normal tissue resident stem cells.
Successful treatment of solid cancers mandates targeting cancer stem cells (CSC) without impact on the physiology of normal tissue resident stem cells. C-Jun N-terminal kinase (JNK) signaling has been shown to be of importance in cancer. We test whether JNK inhibition would sensitize pancreatic CSCs to induction of apoptosis via low-dose TNFα-related apoptosis-inducing ligand (TRAIL). Effects of JNK inhibition (JNKi) were evaluated in vitro in functional assays, through mRNA and protein expression analysis, and in in vivo mouse studies. CSCs were enriched in anoikis-resistant spheroid culture and analyzed accordingly. We confirmed that the JNK pathway is an important regulatory pathway in pancreatic cancer stem cells and further found that JNK inhibition downregulates the decoy receptor DcR1 through IL-8 signaling while upregulating pro-apoptotic death receptors DR4/5, thereby sensitizing cells - even with acquired TRAIL-resistance - to apoptosis induction. Treatment of orthotopic pancreatic cancer xenografts with either gemcitabine, JNKi or TRAIL alone for 4 weeks showed only modest effects compared to control, while the combination of JNKi and TRAIL resulted in significantly lower tumor burden (69%; p < 0.04), reduced numbers of circulating tumor cells, and less distant metastatic events, without affecting the general health of the animals. The combination of JNKi and TRAIL significantly impacts on CSCs, but leaves regular tissue-resident stem cells unaffected - even under hypoxic stress conditions. This concept of selective treatment of pancreatic CSCs warrants further evaluation.


Dietary Patterns during Pregnancy Are Associated with Risk of Gestational Diabetes Mellitus.
Maternal dietary patterns before and during pregnancy play important roles in the development of gestational diabetes mellitus (GDM). We aimed to identify dietary patterns during pregnancy that are associated with GDM risk in pregnant U.S. women. From a 24 h dietary recall of 253 pregnant women (16-41 years) included in the National Health and Nutrition Examination Survey (NHANES) 2003-2012, food items were aggregated into 28 food groups based on Food Patterns Equivalents Database. Three dietary patterns were identified by reduced rank regression with responses including prepregnancy body mass index (BMI), dietary fiber, and ratio of poly- and monounsaturated fatty acids to saturated fatty acid: "high refined grains, fats, oils and fruit juice", "high nuts, seeds, fat and soybean; low milk and cheese", and "high added sugar and organ meats; low fruits, vegetables and seafood". GDM was diagnosed using fasting plasma glucose levels ≥5.1 mmol/L for gestation <24 weeks. Multivariable logistic regression models were used to estimate adjusted odds ratio (AOR) and 95% confidence intervals (CIs) for GDM, after controlling for maternal age, race/ethnicity, education, family poverty income ratio, marital status, prepregnancy BMI, gestational weight gain, energy intake, physical activity, and log-transformed C-reactive protein (CRP). All statistical analyses accounted for the appropriate survey design and sample weights of the NHANES. Of 249 pregnant women, 34 pregnant women (14%) had GDM. Multivariable AOR (95% CIs) of GDM for comparisons between the highest vs. lowest tertiles were 4.9 (1.4-17.0) for "high refined grains, fats, oils and fruit juice" pattern, 7.5 (1.8-32.3) for "high nuts, seeds, fat and soybean; low milk and cheese" pattern, and 22.3 (3.9-127.4) for "high added sugar and organ meats; low fruits, vegetables and seafood" pattern after controlling for maternal sociodemographic variables, prepregnancy BMI, gestational weight gain, energy intake and log-transformed CRP. These findings suggest that dietary patterns during pregnancy are associated with risk of GDM after controlling for potential confounders. The observed connection between a high consumption of refined grains, fat, added sugars and low intake of fruits and vegetables during pregnancy with higher odds for GDM, are consistent with general health benefits of healthy diets, but warrants further research to understand underlying pathophysiology of GDM associated with dietary behaviors during pregnancy.


Ethnic differences and socio-demographic predictors of illness perceptions, self-management, and metabolic control of type 2 diabetes.
This study investigated ethnic differences in diabetes-specific knowledge, illness perceptions, self-management, and metabolic control among black-African, black-Caribbean,and white-British populations with type 2 diabetes. The study also examined associations between demographic/disease characteristics and diabetes-specific knowledge, illness perceptions, self-management, and metabolic control in each of the three ethnic groups. Cross-sectional. Diabetes/retinal screening clinics in Hackney and Brent, London. Black-African, black-Caribbean and white-British populations with type 2 diabetes were asked to participate. Questionnaires measuring demographic/disease characteristics, diabetes-specific knowledge, self-management, and illness perceptions were used for data collection. Data for glycated hemoglobin (HbA1c) and microvascular complications were obtained from medical records. Ethnic differences in diabetes-related measures were estimated using analysis of variance/covariance. Multiple regression techniques were used to determine relationships between demographic/disease characteristics and measured diabetes-related outcomes. Three hundred and fifty-nine patients participated in the study. White-British participants had high diabetes-specific knowledge compared to their black-African and black-Caribbean counterparts. Black-Africans reported better adherence to self-management recommendations than the other ethnic groups. Compared to the white-British patients, black-African and black-Caribbean participants perceived diabetes as a benign condition that could be cured. Educational status and treatment category were determinants of diabetes-specific knowledge in all three ethnic groups. However, different demographic/disease characteristics predicted adherence to self-management recommendations in each ethnic group. Clearly, there is disease (diabetes) knowledge-perception variation between different ethnic groups in the UK which may partly influence overall disease outcome. It is plausible to recommend screening, identifying, and dispelling misconceptions about diabetes among ethnic minority patients by health care professionals as well as emphasizing the importance of self-management in managing chronic diseases such as diabetes.


Charge-transfer-induced structural rearrangements at both sides of organic/metal interfaces.
Organic/metal interfaces control the performance of many optoelectronic organic devices, including organic light-emitting diodes or field-effect transistors. Using scanning tunnelling microscopy, low-energy electron diffraction, X-ray photoemission spectroscopy, near-edge X-ray absorption fine structure spectroscopy and density functional theory calculations, we show that electron transfer at the interface between a metal surface and the organic electron acceptor tetracyano-p-quinodimethane leads to substantial structural rearrangements on both the organic and metallic sides of the interface. These structural modifications mediate new intermolecular interactions through the creation of stress fields that could not have been predicted on the basis of gas-phase neutral tetracyano-p-quinodimethane conformation.


Incentive preferences for community health volunteers in Kenya: findings from a discrete choice experiment.
Community health volunteers (CHVs) play crucial roles in enabling access to healthcare at the community levels. Although CHVs are considered volunteers, programmes provide financial and non-financial incentives. However, there is limited evidence on which bundle of financial and non-financial incentives are most effective for their improved performance. We used a discrete choice experiment (DCE) to understand incentive preferences of CHVs with the aim to improve their motivation, performance and retention. Relevant incentive attributes were identified through qualitative interviews with CHVs and with their supervisors. We then deployed a nominal group technique to generate and rank preferred attributes among CHVs. We developed a DCE based on the five attributes and administered it to 211 CHVs in Kilifi and Bungoma counties in Kenya. We used mixed multinomial logit models to estimate the utility of each incentive attribute and calculated the trade-offs the CHWs were willing to make for a change in stipend. Transport was considered the incentive attribute with most relative importance followed by tools of trade then monthly stipend. CHVs preferred job incentives that offered higher monthly stipends even though it was not the most important. They had negative preference for job incentives that provided award mechanisms for the best performing CHVs as compared with jobs that provided recognition at the community level and preferred job incentives that provided more tools of trade compared with those that provided limited tools. A bundled incentive of both financial and non-financial packages is necessary to provide a conducive working environment for CHVs. The menu of options relevant for CHVs in Kenya include transport, tools of trade and monthly stipend. Policy decisions should be contextualised to include these attributes to facilitate CHW satisfaction and performance.


Genome-wide gene expression effects of sex chromosome imprinting in Drosophila.
Imprinting is well-documented in both plant and animal species. In Drosophila, the Y chromosome is differently modified when transmitted through the male and female germlines. Here, we report genome-wide gene expression effects resulting from reversed parent-of-origin of the X and Y chromosomes. We found that hundreds of genes are differentially expressed between adult male Drosophila melanogaster that differ in the maternal and paternal origin of the sex chromosomes. Many of the differentially regulated genes are expressed specifically in testis and midgut cells, suggesting that sex chromosome imprinting might globally impact gene expression in these tissues. In contrast, we observed much fewer Y-linked parent-of-origin effects on genome-wide gene expression in females carrying a Y chromosome, indicating that gene expression in females is less sensitive to sex chromosome parent-of-origin. Genes whose expression differs between females inheriting a maternal or paternal Y chromosome also show sex chromosome parent-of-origin effects in males, but the direction of the effects on gene expression (overexpression or underexpression) differ between the sexes. We suggest that passage of sex chromosome chromatin through male meiosis may be required for wild-type function in F1 progeny, whereas disruption of Y-chromosome function through passage in the female germline likely arises because the chromosome is not adapted to the female germline environment.


A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer's disease.
Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer's disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000 IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD.


Systematic review and meta-analysis of public hospital efficiency studies in Gulf region and selected countries in similar settings.
The assessment of hospital efficiency is attracting interest worldwide, particularly in Gulf Cooperation Council (GCC) countries. The objective of this study was to review the literature on public hospital efficiency and synthesise the findings in GCC countries and comparable settings. We systematically searched six scientific databases, references and grey literature for studies that measured the efficiency of public hospitals in appropriate countries, and followed PRISMA guidelines to present the results. We summarised the included studies in terms of samples, methods/technologies and findings, then assessed their quality. We meta-analysed the efficiency estimates using Spearman's rank correlations and logistic regression, to examine the internal validity of the findings. We identified and meta-analysed 22 of 1128 studies. Four studies were conducted in GCC nations, 18 came from Iran and Turkey. The pooled technical-efficiency (TE) was 0.792 (SE ± 0.03). There were considerable variations in model specification, analysis orientation and variables used in the studies, which influenced efficiency estimates. The studies lacked some elements required in quality appraisal, achieving an average of 73%. Meta-analysis showed negative correlations between sample size and efficiency scores; the odd ratio was 0.081 (CI 0.005: 1.300; P value = 0.07) at 10% risk level. The choice of model orientation was significantly influenced (82%) by the studied countries' income categories, which was compatible with the strategic plans of these countries. The studies showed methodological and qualitative deficiencies that limited their credibility. Our review suggested that methodology and assumption choices have a substantial impact on efficiency measurements. Given the GCC countries' strategic plans and resource allocations, these nations need further efficiency research using high-quality data, different orientations and developed models. This will establish an evidence-based knowledge base appropriate for use in public hospital assessments, policy- and decision-making and the assurance of value for money.


Past, present, and future climate at select INDEPTH member Health and Demographic Surveillance Systems in Africa and Asia.
Climate and weather affect human health directly and indirectly. There is a renewed interest in various aspects of environmental health as our understanding of ongoing climate change improves. In particular, today, the health effects in low- and middle-income countries (LMICs) are not well understood. Many computer models predict some of the biggest changes in places where people are equipped with minimal resources to combat the effects of a changing environment, particularly with regard to human health. This article documents the observed and projected climate profiles of select sites within the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) network of Health and Demographic Surveillance System sites in Africa and Asia to support the integration of climate research with health practice and policy. The climatology of four meteorological stations representative of a suite of INDEPTH Health and Demographic Surveillance Systems (HDSSs) was assessed using daily data of 10 years. Historical and future trends were analyzed using reanalysis products and global climate model projections. The climate characteristics of the HDSS sites investigated suggest vulnerability to different environmental stressors, and the changes expected over the next century are far greater in magnitude than those observed at many of the INDEPTH member sites. The magnitude of potential future climate changes in the LMICs highlights the need for improvements in collaborative climate-health research in these countries. Climate data resources are available to support such research efforts. The INDEPTH studies presented in this supplement are the first attempt to assess and document associations of climatic factors with mortality at the HDSSs.


The Early Effects of Alcohol Consumption on Functional Visual Acuity, Tear Functions, and the Ocular Surface.
We investigated the early effects of alcohol intake on tear functions and ocular surface health in this prospective controlled study. Forty-four eyes of 22 subjects (17 males, 5 females; mean age: 35.3 years) who drank 200 mL of 25% Japanese vodka and 44 eyes of age- and sex-matched 22 control subjects who drank water were investigated. Subjects were requested to refrain from alcohol consumption from the previous day and food ingestion 6 hr before the study. Each subject consumed exactly the same order prepared dinner and same quantity of alcohol over the same time frame. Subjects underwent breath alcohol level, tear evaporation and blink rate, tear lipid layer interferometry, tear film break-up time (BUT), fluorescein and Rose Bengal stainings, Schirmer test, and visual analog scale (VAS) evaluation of dry eye symptoms before, as well as 2 and 12 hr after alcohol intake. The mean breath alcohol level was significantly higher in the alcohol group compared to the water group at 2 and 12 hr (P<0.001). The mean tear evaporation increased significantly from 2.5×10-7 to 8.8×10-7 gr/cm2/sec 12 hr after alcohol intake (P<0.001). The mean BUT shortened significantly from 15.0±5.0 to 5.0±2.5 sec 12 hr after alcohol intake. Lipid layer interferometry showed signs of tear film thinning 12 hr after alcohol intake in all subjects of the alcohol intake group, which was not observed in the water group. The mean blink rates increased significantly from 10.6±1.5 blinks/min to 13.5±0.9 blinks/min and 15.1±1.2 blinks/min at 2 and 12 hr, respectively, in the alcohol group (P<0.001). The Schirmer test values decreased significantly 12 hr after alcohol intake (P<0.001). The mean VAS score for dryness increased from baseline significantly in the alcohol group at 12 hr (P<0.001). No significant time-wise changes in tear functions were observed in the water group. The tear film and ocular surface epithelia showed early and distinctive quantitative and qualitative changes associated with visual disturbances after alcohol intake.


Marital status and its effect on lung cancer survival.
The purpose of this study was to determine if marital status, including specific types of single status categories, is associated with length of survival in lung cancer patients. Data from the 1996-2007 Florida Cancer Data System were linked with Agency for Health Care Administration data and U.S. Census data. Patients with both small cell and non-small cell lung cancer were identified (n = 161,228). Marital status was characterized by married, widowed, separated/divorced, and never married. We compared median survival time and 1, 3, and 5-year post diagnosis survival rates. Overall, 54.6% were married, 19.1% were widowed, 13.5% were separated/divorced, and 12.7% had never married. Median survival in months was longest for married (9.9) and widowed (7.7) patients, and shortest for never married (4.9) and separated/divorced (4.1) patients. Five-year survival rates were 14.2% for married, 10.7% for widowed, 8.9% for separated/divorced, and 8.4% for never married. In univariate Cox regression, marital status was a significant predictor of better survival for married (HR = 0.70; p < 0.001) and widowed (HR = 0.81; p < 0.001) patients compared with never married patients, but worse for separated/divorced patients (HR = 1.03; p = 0.003). Multivariate models demonstrated sustained survival benefits for married (HR = 0.86; p < 0.001) and widowed (HR = 0.88; p < 0.001) patients, and detriments for separated/divorced patients (HR = 1.05; p < 0.001) after adjusting for extensive confounders including demographics; tumor stage, grade, and morphology; comorbidities; treatment; and smoking status. Our study demonstrated that married or widowed lung cancer patients have better survival compared to patients who were never married or separated/divorced. Research to understand the mechanism of this effect, and how the beneficial effect can be extended to those who have never married or have had the marital relationship severed through divorce or separation is needed.


UDP-glucose ceramide glucosyltransferase activates AKT, promoted proliferation, and doxorubicin resistance in breast cancer cells.
The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.


The future of poultry science research: things I think I think.
Much poultry research progress has occurred over the first century of the Poultry Science Association. During that time, specific problems have been solved and much basic biological knowledge has been gained. Scientific discovery has exceeded its integration into foundation concepts. Researchers need to be involved in the public's development of critical thinking skills to enable discernment of fact versus fiction. Academic, government, and private institutions need to hire the best people. Issues of insufficient research funding will be remedied by a combination of strategies rather than by a single cure. Scientific advocacy for poultry-related issues is critical to success. Two other keys to the future are funding for higher-risk projects, whose outcome is truly unknown, and specific allocations for new investigators. Diligent, ongoing efforts by poultry scientists will enable progress beyond the challenges.


Association between post-percutaneous coronary intervention bivalirudin infusion and net adverse clinical events: a post hoc analysis of the GLOBAL LEADERS study.
The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days. In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99-1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44-1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77-3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients. In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.


Evidence for the Validity of Pyridoxic Acid (PDA) as a Plasma-Based Endogenous Probe for OAT1 and OAT3 Function in Healthy Subjects.
Plasma pyridoxic acid (PDA) and homovanillic acid (HVA) were recently identified as novel endogenous biomarkers of organic anion transporter (OAT) 1/3 function in monkeys. Consequently, this clinical study assessed the dynamic changes and utility of plasma PDA and HVA as an initial evaluation of OAT1/3 inhibition in early-phase drug development. The study was designed as a single-dose randomized, three-phase, crossover study; 14 Indian healthy volunteers received probenecid (PROB) (1000 mg orally) alone, furosemide (FSM) (40 mg orally) alone, or FSM 1 hour after receiving PROB (40 and 1000 mg orally) on days 1, 8, and 15, respectively. PDA and HVA plasma concentrations remained stable over time in the prestudy and FSM groups. Administration of PROB significantly increased the area under the plasma concentration-time curve (AUC) of PDA by 3.1-fold (dosed alone; P < 0.05), and 3.2-fold (coadministered with FSM; P < 0.01), compared with the prestudy and FSM groups, respectively. The corresponding increase in HVA AUC was 1.8-fold (P > 0.05) and 2.1-fold (P < 0.05), respectively. The increases in PDA AUC are similar to those in FSM AUC, whereas those of HVA are smaller (3.1-3.2 and 1.8-2.1 vs. 3.3, respectively). PDA and HVA renal clearance (CL R) values were decreased by PROB to smaller extents compared with FSM (0.35-0.37 and 0.67-0.73 vs. 0.23, respectively). These data demonstrate that plasma PDA is a promising endogenous biomarker for OAT1/3 function and that its plasma exposure responds in a similar fashion to FSM upon OAT1/3 inhibition by PROB. The magnitude and variability of response in PDA AUC and CL R values between subjects is more favorable relative to HVA.


GPCR-mediated glucose sensing system regulates light-dependent fungal development and mycotoxin production.
Microorganisms sense environmental fluctuations in nutrients and light, coordinating their growth and development accordingly. Despite their critical roles in fungi, only a few G-protein coupled receptors (GPCRs) have been characterized. The Aspergillus nidulans genome encodes 86 putative GPCRs. Here, we characterise a carbon starvation-induced GPCR-mediated glucose sensing mechanism in A. nidulans. This includes two class V (gprH and gprI) and one class VII (gprM) GPCRs, which in response to glucose promote cAMP signalling, germination and hyphal growth, while negatively regulating sexual development in a light-dependent manner. We demonstrate that GprH regulates sexual development via influencing VeA activity, a key light-dependent regulator of fungal morphogenesis and secondary metabolism. We show that GprH and GprM are light-independent negative regulators of sterigmatocystin biosynthesis. Additionally, we reveal the epistatic interactions between the three GPCRs in regulating sexual development and sterigmatocystin production. In conclusion, GprH, GprM and GprI constitute a novel carbon starvation-induced glucose sensing mechanism that functions upstream of cAMP-PKA signalling to regulate fungal development and mycotoxin production.


Impaired driving from medical conditions: a 70-year-old man trying to decide if he should continue driving.
Some medical disorders can impair performance, increasing the risk of driving safety errors that can lead to vehicle crashes. The causal pathway often involves a concatenation of factors or events, some of which can be prevented or controlled. Effective interventions can operate before, during, or after a crash occurs at the levels of driver capacity, vehicle and road design, and public policy. A variety of systemic, neurological, psychiatric, and developmental disorders put drivers at potential increased risk of a car crash in the short or long term. Medical diagnosis and age alone are usually insufficient criteria for determining fitness to drive. Strategies are needed for determining what types and levels of reduced function provide a threshold for disqualification in drivers with medical disorders. Evidence of decreased mileage, self-restriction to driving in certain situations, collisions, moving violations, aggressive driving, sleepiness, alcohol abuse, metabolic disorders, and multiple medications may trigger considerations of driver safety. A general framework for evaluating driver fitness relies on a functional evaluation of multiple domains (cognitive, motor, perceptual, and psychiatric) that are important for safe driving and can be applied across many disorders, including conditions that have rarely been studied with respect to driving, and in patients with multiple conditions and medications. Neurocognitive tests, driving simulation, and road tests provide complementary sources of evidence to evaluate driver safety. No single test is sufficient to determine who should drive and who should not.


Keep calm and carry on: the 2009 NEHA sabbatical exchange ambassador report.
Sabbatical goal as an environmental health specialist working with the California Department of Public Health as an emergency planner, I was interested in the NEHA sabbatical exchange program for the opportunity it affords its awardees to see how Canada and the United Kingdom utilize their environmental health workforce. Specifically, I wanted to examine the role environmental health has in the preparations being made for the 2012 Olympic Games to be held in London. I had a special interest in the emergency preparedness efforts related to the games as my work involves promoting the integration of environmental health into the emergency response structure. In California, environmental health services are delivered by several state agencies as well as 62 local jurisdictions. This multifaceted system tends to diminish the important role environmental health plays in disaster response and recovery operations due to the lack of a central focus, and as a result, environmental health is often an overlooked resource. This situation is not unique to California, as the emergency management system in the U.S. has traditionally focused primarily on "blue light" first responders: police, fire, and emergency medical services. After an article caught my eye on involving environmental health in emergency planning, posted on the Chartered Institute of Environmental Health (CIEH) (NEHA's counterpart in the UK) Web site, I became intrigued and used it to form the basis of my sabbatical mission.


Persistent organic pollutants in Alaskan ringed seal (Phoca hispida) and walrus (Odobenus rosmarus) blubber.
Since 1987, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) has collected tissues from 18 marine mammal species. Specimens are archived in the National Institute of Standards and Technology's National Biomonitoring Specimen Bank (NIST-NBSB). AMMTAP has collected blubber, liver and/or kidney specimens from a number of ringed seals (Phoca hispida) from the areas near Nome and Barrow, Alaska and walruses (Odobenus rosmarus) from several locations in the Bering Sea. Thirty-three ringed seal and 15 walrus blubber samples from the NIST-NBSB were analyzed for persistent organic pollutants (POPs). The compounds determined included PCBs (28 congeners or congener groups), DDT and related compounds, hexachlorobenzene (HCB), hexachlorocyclohexane isomers (HCHs), chlordanes, dieldrin, and mirex. POP concentrations in ringed seal blubber were significantly higher in Barrow than in Nome when statistically accounting for the interaction of age and gender; HCB, however, was not statistically different between the two locations. Unlike males, POP concentrations and age were not significantly correlated in females probably as a result of lactational loss. POP concentrations in walrus blubber were lower than in ringed seal blubber for SigmaPCBs, chlordanes, and HCHs, but higher for dieldrin and mirex. POP concentrations in ringed seals and walrus from Alaska provide further evidence that the western Arctic tends to have lower or similar POP concentrations compared to the eastern Canadian Arctic.


Causes, diagnostic signs, and the utility of investigations of fever in dogs: 50 cases.
This study aimed to determine the distribution of diseases causing fever in dogs in France. Dogs with fever were reviewed and 50 dogs were retrospectively assigned to disease groups. Fever profile and intensity, the time taken to reach a diagnosis, and inflammatory status were compared among groups. Almost half the dogs (48%) were diagnosed with non-infectious inflammatory diseases. No final diagnosis was reached in 14 dogs, 13 of which belonged to owners who did not wish to pursue the investigations. No association was found between disease group and the intensity of fever, fever profile, or serum C-reactive protein concentration. Cytological examinations were most frequently found to be the most important determinant for diagnosis (55.7%). This study confirms the predominance of non-infectious inflammatory diseases as causes of fever. Neither clinical nor biological factors were found to be predictive of disease group.


Scientists@Home: what drives the quantity and quality of online citizen science participation?
Online citizen science offers a low-cost way to strengthen the infrastructure for scientific research and engage members of the public in science. As the sustainability of online citizen science projects depends on volunteers who contribute their skills, time, and energy, the objective of this study is to investigate effects of motivational factors on the quantity and quality of citizen scientists' contribution. Building on the social movement participation model, findings from a longitudinal empirical study in three different citizen science projects reveal that quantity of contribution is determined by collective motives, norm-oriented motives, reputation, and intrinsic motives. Contribution quality, on the other hand, is positively affected only by collective motives and reputation. We discuss implications for research on the motivation for participation in technology-mediated social participation and for the practice of citizen science.


A stochastic approach for automatic registration and fusion of left atrial electroanatomic maps with 3D CT anatomical images.
The integration of electroanatomic maps with highly resolved computed tomography cardiac images plays an important role in the successful planning of the ablation procedure of arrhythmias. In this paper, we present and validate a fully-automated strategy for the registration and fusion of sparse, atrial endocardial electroanatomic maps (CARTO maps) with detailed left atrial (LA) anatomical reconstructions segmented from a pre-procedural MDCT scan. Registration is accomplished by a parameterized geometric transformation of the CARTO points and by a stochastic search of the best parameter set which minimizes the misalignment between transformed CARTO points and the LA surface. The subsequent fusion of electrophysiological information on the registered CT atrium is obtained through radial basis function interpolation. The algorithm is validated by simulation and by real data from 14 patients referred to CT imaging prior to the ablation procedure. Results are presented, which show the validity of the algorithmic scheme as well as the accuracy and reproducibility of the integration process. The obtained results encourage the application of the integration method in post-intervention ablation assessment and basic AF research and suggest the development for real-time applications in catheter guiding during ablation intervention.


The rural allied health workforce study (RAHWS): background, rationale and questionnaire development.
The allied health professions form approximately 18% of the health workforce in Australia and are well placed to contribute to future multidisciplinary models of health care. There are many reports describing the health workforce in Australia for the medical and nursing professions but there is very little information available about the nature of the allied health workforce. Recent studies have highlighted the need for more current and detailed information about the rural allied health workforce to inform future workforce planning. National health policy reform requires that new healthcare models take into account future workforce requirements, the distribution and work contexts of existing practitioners, training needs, workforce roles and scope of practice. The absence of accurate data profiling the existing rural allied health workforce makes this impossible. The Rural Allied Health Workforce Study (RAHWS) aims to use a cross-sectional survey instrument with high validity to provide a large scale but detailed profile of the allied health workforce in regional, rural and remote Australia. The RAHWS survey instrument used in this study is the result of a comprehensive consultation with clinicians, academics and managers. The RAHWS survey instrument has been designed to provide uniform data across a wide range of healthcare settings. Good concurrent and face validity have been demonstrated and its design allows for data analysis using a wide range of variables. Cross-correlation of responses can answer a number of research questions in relation to rural recruitment and retention, professional education and service delivery models. This valid and feasible instrument will be used to explore the rural allied health workforce by implementing the RAHWS survey in rural regions on a state-by-state basis in Australia during 2009 and 2010.


Ferromagnetic contamination in the lungs and other organs of the human body.
Contaminating particles which are ferromagnetic have been found in the human body. Their distribution was measured by applying an external magnetic field to the torso for a short time, and then, in a shielded room, mapping the steady magnetic field around the torso due to the magnetized particles. Maps of subjects show various distributions, including particles in the stomach from food cans and in the lungs from are welding. The fields from these two sources are strong enough to be detected with a flux-gate magnetometer, without the need for a shielded room. This simplicity of detection of larger amounts of ferromagnetic contamination suggests that this method may be used in two applications: in detecting the presence of large amounts of asbestos (ferromagnetic and harmful) in the lungs of asbestos workers, and in tests of the condition of the lung where FE(3)O(4) dust (ferromagnetic and harmless) would be used as an inhaled tracer material.


Multi-Channel Optical Coherence Elastography Using Relative and Absolute Shear-Wave Time of Flight.
Elastography, the imaging of elastic properties of soft tissues, is well developed for macroscopic clinical imaging of soft tissues and can provide useful information about various pathological processes which is complementary to that provided by the original modality. Scaling down of this technique should ply the field of cellular biology with valuable information with regard to elastic properties of cells and their environment. This paper evaluates the potential to develop such a tool by modifying a commercial optical coherence tomography (OCT) device to measure the speed of shear waves propagating in a three-dimensional (3D) medium. A needle, embedded in the gel, was excited to vibrate along its long axis and the displacement as a function of time and distance from the needle associated with the resulting shear waves was detected using four M-mode images acquired simultaneously using a commercial four-channel swept-source OCT system. Shear-wave time of arrival (TOA) was detected by tracking the axial OCT-speckle motion using cross-correlation methods. Shear-wave speed was then calculated from inter-channel differences of TOA for a single burst (the relative TOA method) and compared with the shear-wave speed determined from positional differences of TOA for a single channel over multiple bursts (the absolute TOA method). For homogeneous gels the relative method provided shear-wave speed with acceptable precision and accuracy when judged against the expected linear dependence of shear modulus on gelatine concentration (R2 = 0.95) and ultimate resolution capabilities limited by 184μm inter-channel distance. This overall approach shows promise for its eventual provision as a research tool in cancer cell biology. Further work is required to optimize parameters such as vibration frequency, burst length and amplitude, and to assess the lateral and axial resolutions of this type of device as well as to create 3D elastograms.


Effects of three anthozoan neuropeptides, Antho-RWamide I, Antho-RWamide II and Antho-RFamide, on slow muscles from sea anemones.
Antho-RWamide I (less than Glu-Ser-Leu-Arg-Trp-NH2) and Antho-RWamide II (less than Glu-Gly-Leu-Arg-Trp-NH2), the second and third anthozoan neuropeptides to be identified, both induced slow contractions of several endodermal muscles in four species of sea anemone. In a fifth species, Protanthea simplex, Antho-RWamide II, but not Antho-RWamide I, evoked contractions of body wall muscles. Isolated, trimmed sphincter muscle preparations of Calliactis parasitica contracted at a threshold concentration of 10(-9) mol l-1 Antho-RWamide II. Antho-RWamide II was more potent than Antho-RWamide I. Unlike the responses to Antho-RFamide (the first anthozoan neuropeptide described), these were simple contractions with no change in spontaneous activity. The Antho-RWamides did not excite electrical activity in any of the three known conducting systems (the through-conducting nerve net and the slow systems 1 and 2), indicating that they may be acting directly on endodermal muscles. Application of peptides to smooth muscle cells, isolated from the sphincter of C. parasitica, confirmed that Antho-RWamide I and II act directly on the muscle. We conclude that the Antho-RWamides may be neurotransmitters at some neuromuscular synapses in sea anemones.


Chronic infection of nude mice by murine K papovavirus.
Nude (nu/nu) mice were inoculated intracranially with 10(6.5) newborn mouse 50% lethal doses of K virus and were studied over a period of 28 weeks using serological methods, virus assay and immunohistological staining for viral antigens. K virus infection of nude mice, although clinically asymptomatic, was slowly progressive despite prompt IgM and IgG antibody response. The highest titres of K virus infectivity were reached in spleens, kidneys and intestines. Vascular endothelial cells represented the major site of viral replication, as has been shown to be the case in immunologically normal mice, with extensive involvement of intestinal capillaries. In addition, however, unlike immunologically normal mice, nude mice inoculated with K virus developed multifocal infection of renal tubular epithelial cells. Nude mice did not develop histologically detectable evidence of central nervous system involvement by K virus, and K virus infection did not result in neoplasia. Infected vascular endothelial cells and renal tubular epithelial cells in animals studied at 16 and 27 weeks after inoculation were grouped in scattered clusters, suggesting local spread of infection. The present study indicates that nude mice with preserved B cell function but impaired T cell-mediated immunity are able to limit systemic dissemination of K virus but are unable to prevent local progression of infection by cell-to-cell spread. K virus is capable of altering its cellular tropism during chronic infection.


Production of a Potentially Probiotic Product for Animal Feed and Evaluation of Some of Its Probiotic Properties.
Nowadays, probiotics have been proposed for substituting antibiotics in animal feed since the European Union banned the latter compounds in 2006 to avoid serious side effects on human health. Therefore, this work aimed to produce a probiotic product for use in animal feed by fed-batch fermentation of whey with a combination of kefir grains, AGK1, and the fermented whole milk used to activate these kefir grains. The probiotic culture obtained was characterized by high levels of biomass (8.03 g/L), total viability (3.6 × 108 CFU/mL) and antibacterial activity (28.26 Activity Units/mL). Some probiotic properties of the probiotic culture were investigated in vitro, including its survival at low pH values, under simulated gastrointestinal conditions, after freezing in skim milk at -20 °C, and in the commercial feed during storage at room temperature. The viable cells of lactic and acetic acid bacteria and yeasts exhibited higher tolerance to acidic pH and simulated gastrointestinal conditions when the cells were protected with skim milk and piglet feed, compared with washed cells. The results indicated the feasibility of producing a probiotic product at a low cost with a potential application in animal feed.


The red cell distribution width in sickle cell disease--is it of clinical value?
The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with sickle cell beta 0 thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in S beta + thalassaemia and SC disease and markedly increased in S beta 0 thalassaemia and SS disease. In SS, SC and S beta 0 thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume, and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration, and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia, and a more mild clinical course.


Strong plasmon-molecule coupling at the nanoscale revealed by first-principles modeling.
Strong light-matter interactions in both the single-emitter and collective strong coupling regimes attract significant attention due to emerging applications in quantum and nonlinear optics as well as opportunities for modifying material-related properties. Exploration of these phenomena is theoretically demanding, as polaritons exist at the intersection between quantum optics, solid state physics, and quantum chemistry. Fortunately, nanoscale polaritons can be realized in small plasmon-molecule systems, enabling treatment with ab initio methods. Here, we show that time-dependent density-functional theory calculations access the physics of nanoscale plasmon-molecule hybrids and predict vacuum Rabi splitting. By considering a system comprising a few-hundred-atom aluminum nanoparticle interacting with benzene molecules, we show that cavity quantum electrodynamics holds down to resonators of a few cubic nanometers in size, yielding a single-molecule coupling strength exceeding 200 meV due to a massive vacuum field of 4.5 V · nm-1. In a broader perspective, ab initio methods enable parameter-free in-depth studies of polaritonic systems for emerging applications.


Precision and neuronal dynamics in the human posterior parietal cortex during evidence accumulation.
Primate studies show slow ramping activity in posterior parietal cortex (PPC) neurons during perceptual decision-making. These findings have inspired a rich theoretical literature to account for this activity. These accounts are largely unrelated to Bayesian theories of perception and predictive coding, a related formulation of perceptual inference in the cortical hierarchy. Here, we tested a key prediction of such hierarchical inference, namely that the estimated precision (reliability) of information ascending the cortical hierarchy plays a key role in determining both the speed of decision-making and the rate of increase of PPC activity. Using dynamic causal modelling of magnetoencephalographic (MEG) evoked responses, recorded during a simple perceptual decision-making task, we recover ramping-activity from an anatomically and functionally plausible network of regions, including early visual cortex, the middle temporal area (MT) and PPC. Precision, as reflected by the gain on pyramidal cell activity, was strongly correlated with both the speed of decision making and the slope of PPC ramping activity. Our findings indicate that the dynamics of neuronal activity in the human PPC during perceptual decision-making recapitulate those observed in the macaque, and in so doing we link observations from primate electrophysiology and human choice behaviour. Moreover, the synaptic gain control modulating these dynamics is consistent with predictive coding formulations of evidence accumulation.


Aberrant methylation of the HIC1 promoter is a frequent event in specific pediatric neoplasms.
To determine the role of methylation of HIC1, a candidate tumor suppressor gene on 17p13.3, in various types of pediatric tumors. We examined the methylation status of the HIC1 promoter by methylation specific PCR in 157 pediatric tumors and 27 nonmalignant tissues. We correlated methylation with mRNA expression by reverse transcription-PCR in eight tumor-derived cell lines. HIC1 methylation was frequent in medulloblastomas (80%, 12 of 15), retinoblastomas (67%, 6 of 9), rhabdomyosarcomas (59%, 13 of 22), germ cell tumors (55%, 6 of 11), and neurouroblastic tumors (36%, 14 of 39); neuroblastomas (43%, 12 of 28); ganglioneuromas (17%, 1 of 6); and ganglioneuroblastomas (20%, 1 of 5). In contrast, a low incidence of methylation was observed in osteosarcomas (17%, 2 of 12), Ewing's tumors (9%, 1 of 11), Wilms' tumors (3%, 1 of 31), and hepatoblastomas (0%, 0 of 7). HIC1 methylation was more frequent in the aggressive alveolar subtype of rhabdomyosarcomas (100%, 8 of 8) than the embryonal subtype (33%, 4 of 12; P < 0.005) and was rare in the nonmalignant tissues examined. Methylation was also demonstrated by sequencing in nine randomly selected tumor samples. Seven of eight pediatric tumor cell lines examined were methylated and showed loss or reduced HIC1 mRNA. Expression was strongly induced in all cell lines by treatment with the demethylating agent 5-aza 2'deoxycytidine. Our data suggest that aberrant methylation of HIC1 may play a role in the pathogenesis of specific pediatric tumors.


Quantum equations for vibrational dynamics on metal surfaces.
A first principles treatment of the vibrational dynamics of molecular chemisorbates on metal surfaces is presented. It is shown that the mean field quantum evolution of the vibrational position operator is determined by a quantum Langevin equation with an electronic friction. In the mean field limit, the quantum noise and friction are related by the quantum fluctuation-dissipation theorem. The classical limit of this model is shown to agree with previously proposed models. A criterion is presented to describe the validity of the weak-coupling approximation and equations of motion for the dynamics in the presence of strong nonadiabatic coupling to electron-hole pairs are presented.


Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats.
Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to enhance mitochondrial antioxidant status in liver, heart and brain tissues in rodents. Whether or not long-term Sch B treatment can protect against oxidative stress-induced cerebral damage remains unclear. In the present study, the effect of long-term Sch B treatment (1-30 mg/kg/dx15) on cerebral ischemia/reperfusion (I/R) injury was examined in rats. Sch B treatment protected against I/R-induced cerebral damage, as evidenced by the significant increase in the percentage of 2,3,5-triphenyl tetrazolium chloride (TTC)-stained tissues in representative brain slices, when compared with the Sch B-untreated and I/R control. The cerebroprotection was associated with an enhancement in cerebral mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial structural integrity, as assessed by the extents of malondialdehyde production, Ca(2+) loading and cytochrome c release, as well as the sensitivity to Ca(2+)-induced permeability transition, in control and I/R-challenged rats. In conclusion, long-term Sch B treatment could enhance cerebral mitochondrial antioxidant status as well as improve mitochondrial structural integrity, thereby protecting against I/R injury.


Human myeloma in vitro colony growth: interrelationships between drug sensitivity, cell kinetics, and patient survival duration.
Ninety-seven patients with multiple myeloma evaluated serially had both a tritiated thymidine labeling index of bone marrow plasma cells (LI%) and in vitro myeloma stem cell culture performed. Thirty-three patients with myeloma colony growth had in vitro drug sensitivity testing carried out, 18 having in addition in vitro thymidine suicide determinations. The LI% and the likelihood of in vitro myeloma colony growth were highly correlated: the higher the LI%, the more likely was colony or cluster growth (p less than 0.001). The tritiated thymidine suicide of myeloma stem cells was usually very high. There was excellent correlation between in vitro and in vivo drug sensitivity. Both pretreatment drug resistance and selective sensitivity (e.g., interferon, bisantrene, methotrexate, vinblastine) at the time of relapse were accurately detected and correlated well with survival duration (p = 0.01 Wilcoxan). Although LI% and in vitro sensitivity were clearly independent variables, a high LI% (greater than 3%) plus in vitro resistance were associated with a subsequent survival duration of less than 6 mo. The studies allowed dissection of the complex interrelationship between cell kinetics and drug sensitivity.


Fertility outcomes in asthma: a clinical study of 245 women with unexplained infertility.
Evidence is increasing of an association between asthma and aspects of female reproduction. However, current knowledge is limited and furthermore relies on questionnaire studies or small populations. In a prospective observational cohort study to investigate whether time to pregnancy, the number of fertility treatments, and the number of successful pregnancies differ significantly between women with unexplained infertility with and without asthma.245 women with unexplained infertility (aged 23-45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. 96 women entering the study had either a former doctor's diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended.The likelihood of achieving pregnancy was lower in women with asthma compared with those without asthma: median total time to pregnancy was 32.3 months in non-asthmatic women versus 55.6 months in those with asthma, hazard ratio 0.50 (95% confidence interval 0.34-0.74) p<0.001.Women with asthma had fewer successful pregnancies during fertility treatment, 39.6 versus 60.4% (p=0.002). Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women (interaction between age and asthma on time to pregnancy, p=0.001). Female asthmatics had a longer time to pregnancy and less often became pregnant than non-asthmatic women. Increasing age reduced the chances of conceiving especially among asthmatic women. The causal relationship between asthma and subfertility remains unclear.


Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death.
Patients with chronic kidney disease (CKD) experience increased rates of hospitalization and death. Depressive disorders are associated with morbidity and mortality. Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown. To determine whether the presence of a current major depressive episode (MDE) is associated with poorer outcomes in patients with CKD. Prospective cohort study of 267 consecutively recruited outpatients with CKD (stages 2-5 and who were not receiving dialysis) at a VA medical center between May 2005 and November 2006 and followed up for 1 year. An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. The primary outcome was event-free survival defined as the composite of death, dialysis initiation, or hospitalization. Secondary outcomes included each of these events assessed separately. Among 267 patients, 56 had a current MDE (21%) and 211 did not (79%). There were 127 composite events, 116 hospitalizations, 38 dialysis initiations, and 18 deaths. Events occurred more often in patients with an MDE compared with those without an MDE (61% vs 44%, respectively, P = .03). Four patients with missing dates of hospitalization were excluded from survival analyses. The mean (SD) time to the composite event was 206.5 (19.8) days (95% CI, 167.7-245.3 days) for those with an MDE compared with 273.3 (8.5) days (95% CI, 256.6-290.0 days) for those without an MDE (P = .003). The adjusted hazard ratio (HR) for the composite event for patients with an MDE was 1.86 (95% CI, 1.23-2.84). An MDE at baseline independently predicted progression to dialysis (HR, 3.51; 95% CI, 1.77-6.97) and hospitalization (HR, 1.90; 95% CI, 1.23-2.95). The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis, independent of comorbidities and kidney disease severity.


Combinations of Spok genes create multiple meiotic drivers in Podospora.
Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74-167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.


Efficacy of Garcinia kola 0.5% Aqueous Eye Drops in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension.
To evaluate the intraocular pressure (IOP) lowering efficacy of Garcinia kola 0.5% aqueous solution eye drops in patients with newly diagnosed primary open-angle glaucoma or ocular hypertension (POAG/OH). A randomized, double-masked, multicenter, active-controlled prospective study. Patients who met the inclusion criteria were randomly assigned in equal numbers to receive Timolol 0.5% eye drops as a control medication (A = Group 1 eyes) or Garcinia kola 0.5% eye drops as the study medication (B = Group 2 eyes). All drops were instilled at 6 am and 6 pm daily. Goldman applanation tonometry was performed at 9 am, 12 pm and 3 pm at baseline, week-6, week-12 and week-24 visits. Voluntary and actively elicited reports of adverse events were documented. The mean change in IOP over 24 weeks was the primary outcome measure. Both groups were compared for statistically significant differences at all visits. A P < 0.05 was considered statistically significant. A total of 178 patients were randomly assigned to G. kola and Timolol groups. At baseline there were no differences in mean IOP between groups, based on age, sex, or diagnosis. At the end of the study period (24(th) week), the mean (+/- SD) reduction in IOP was 12.93 +/- 2.3 mmHg (47.8% +/- 0.8% reduction) in G. Kola group and 13.09 +/- 2.8 mm Hg (48.2% +/- 1.03% reduction) in the Timolol group (P > 0.05). Adverse events were mild in nature with no statistically significant differences between groups (P > 0.05). Garcinia kola ophthalmic solution significantly reduces IOP as compared to baseline. The IOP lowering effect of both treatments was equivalent.


Platelets from patients on haemodialysis show impaired responses to nitric oxide.
1. Platelets from patients on haemodialysis showed a loss of sensitivity to nitric oxide, reflected by a reduction in the ability of nitric oxide both to inhibit thrombin-induced aggregation and to increase intraplatelet cyclic GMP levels. Responses of platelets from patients on continuous ambulatory peritoneal dialysis were slightly, but not significantly, impaired. Platelets from both groups of uraemic patients showed normal sensitivity to the cyclic AMP-dependent inhibitor prostacyclin. 2. Reduced levels of cyclic GMP in response to nitric oxide in platelets from patients on haemodialysis were due to a defect in its generation, rather than to accelerated breakdown. 3. Basal levels of intra-platelet cyclic GMP were significantly increased in both patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis. 4. The activity of nitric oxide was more stable in plasma than in buffer; its survival in plasma from patients on haemodialysis was similar to that in plasma from healthy control subjects.


Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy.
Temple-Baraitser syndrome (TBS) is a multisystem developmental disorder characterized by intellectual disability, epilepsy, and hypoplasia or aplasia of the nails of the thumb and great toe. Here we report damaging de novo mutations in KCNH1 (encoding a protein called ether à go-go, EAG1 or KV10.1), a voltage-gated potassium channel that is predominantly expressed in the central nervous system (CNS), in six individuals with TBS. Characterization of the mutant channels in both Xenopus laevis oocytes and human HEK293T cells showed a decreased threshold of activation and delayed deactivation, demonstrating that TBS-associated KCNH1 mutations lead to deleterious gain of function. Consistent with this result, we find that two mothers of children with TBS, who have epilepsy but are otherwise healthy, are low-level (10% and 27%) mosaic carriers of pathogenic KCNH1 mutations. Consistent with recent reports, this finding demonstrates that the etiology of many unresolved CNS disorders, including epilepsies, might be explained by pathogenic mosaic mutations.


Sinusoidal phase modulating Fizeau interferometer.
Sinusoidal phase modulating interferometry is possible with Fizeau interferometers. The sinusoidal phase modulation is easily produced by vibrating the reference plate glass in a Fizeau interferometer. Since we can measure the amplitude and phase of the phase modulation with the interferometer itself, the exact phase modulation is obtained. The usefulness of the sinusoidal phase modulating Fizeau interferometer is made clear through surface profile measurements of 80-mm diam plate glasses and integrated circuit wafers and movement measurements of integrated circuit wafers.


Estimating reduction in occupational disease burden following reduction in exposure.
Many occupational exposures causing disease cannot feasibly be eliminated entirely, but policies that reduce the exposures may be under consideration. This paper sets out to clarify how to estimate the reduction in occupational disease following a reduction in exposure, and shows a real-data illustration for doing this. Modest extensions of standard expressions for attributable fractions permit estimation of fractions by which cases would be reduced by policies that do not eliminate exposure but change exposure distributions. However, this requires information on the exposure-response relation and on distribution of exposures. From hypothetical scenarios and a real example this paper explores how attributable cases are distributed by exposure level and, in particular, the proportion by which attributable cancers are reduced by eliminating exposures above a limit (the classic occupational limit regulation). It shows how this depends on the shape of the exposure-response relation and to some extent the shape of the exposure distribution, as well as on the proportion exposed above the limit. For linear no-threshold relations and left-skewed exposure distributions, the majority of the burden may be in a large number of people experiencing small relative risks, and thus may not be tackled by a strategy to reduce exposures above a certain limit. With appropriate data, estimating the disease burden in terms of the distribution of exposure is straightforward and can help to clarify the likely outcome of an intervention.


Symbiotic Nitrogen Fixation and the Challenges to Its Extension to Nonlegumes.
Access to fixed or available forms of nitrogen limits the productivity of crop plants and thus food production. Nitrogenous fertilizer production currently represents a significant expense for the efficient growth of various crops in the developed world. There are significant potential gains to be had from reducing dependence on nitrogenous fertilizers in agriculture in the developed world and in developing countries, and there is significant interest in research on biological nitrogen fixation and prospects for increasing its importance in an agricultural setting. Biological nitrogen fixation is the conversion of atmospheric N2 to NH3, a form that can be used by plants. However, the process is restricted to bacteria and archaea and does not occur in eukaryotes. Symbiotic nitrogen fixation is part of a mutualistic relationship in which plants provide a niche and fixed carbon to bacteria in exchange for fixed nitrogen. This process is restricted mainly to legumes in agricultural systems, and there is considerable interest in exploring whether similar symbioses can be developed in nonlegumes, which produce the bulk of human food. We are at a juncture at which the fundamental understanding of biological nitrogen fixation has matured to a level that we can think about engineering symbiotic relationships using synthetic biology approaches. This minireview highlights the fundamental advances in our understanding of biological nitrogen fixation in the context of a blueprint for expanding symbiotic nitrogen fixation to a greater diversity of crop plants through synthetic biology.


Surveying a New Multi-Institution Clinical Data Research Network.
Cultivated by the Patient-Centered Outcomes Research Network (PCORnet), thirteen regional clinical data research networks (CDRNs) are taking shape across the U.S. The PCORnet common data model was carefully planned, and the data marts assembled by the more than 80 data-contributing institutions (nodes) are undergoing, in 2016-2017, a series of data characterization cycles. PCORnet will adjudge each node's-and thereby, in a significant way, each CDRN's-readiness or unreadiness for multi-institution research. Certifying each node's quality and fidelity is of course essential. But in understanding network readiness there is an additional, vital dimension-one that has received too little attention. It is the development of knowledge about the nature of a CDRN's data, in its federated sense. With visualizations, how might one grasp the meta-data of a CDRN? We outline an approach that builds upon the HealthLNK Data Repository, a forerunner to the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) CDRN.


Postoperative low-molecular-weight heparin bridging is associated with an increase in wound hematoma following surgery for pacemakers and implantable defibrillators.
The perioperative management of patients receiving oral anticoagulation therapy (OAC) who undergo pacemaker (PM) and defibrillator (ICD) surgery remains controversial. Low-molecular-weight heparin (LMWH) is often used; however, wound hematoma is a common complication. At a single academic Canadian center, between July 2003 and June 2005, details of perioperative OAC bridging and the rate of wound hematoma requiring reoperation or interruption of OAC were reviewed for all patients receiving LMWH bridging for PM or ICD surgery. A total of 148 PM/ICD patients underwent perioperative bridging with LMWH. A significant hematoma occurred in 23 patients, requiring reoperation in three patients. No patient died, developed infection, or stroke. The initial bridging regimen included LMWH (enoxaparin 1 mg/kg BID) given until evening prior to surgery, and reinitiated on postoperative day 3. In response to high rates of postoperative hematoma, subsequent protocols omitted the LMWH on the evening before surgery, all postoperative LMWH, or both. The use of LMWH the night before surgery had no effect on hematoma rates (12% vs 17%, P = 0.62); however, the use of any postoperative LMWH increased hematoma rates (23% vs 8%, P = 0.01). Hematoma rates were not increased in patients receiving acetylsalicylic acid (19% vs 16%, P = 0.62) or clopidogrel (25% vs 17%, P = 0.54). In a multivariate analysis, independent predictors of significant wound hematoma included postoperative LMWH (P = 0.001), a higher international normalized ratio on the day of surgery (P = 0.03), and male sex (P = 0.05). Elimination of postoperative LMWH was associated with a substantial reduction in hematoma rates following PM and ICD surgery.


Surgical removal of a microchip from a puppy's spinal canal.
A 1.6 kg, six-week-old Tibetan Terrier was admitted with a 12-hours history of acute onset of progressive tetraparesis following insertion of a microchip to the dorsal cervical region. Neurological examination indicated a lesion to the Ce(1) to Ce(5) spinal cord segments. Radiographic examination confirmed the intra-spinal location of a microchip foreign body at the level of the second cervical vertebra. Microchip removal was achieved following dorsal hemi-laminectomy; significant intra-operative haemorrhage was encountered. The puppy was ambulatory at day seven. Follow-up telephone interview 18 months postoperatively confirmed that the patient had made a good recovery although it had a mild residual right- sided torticollis.


Covered Stents for the Prevention and Treatment of Carotid Blowout Syndrome.
Carotid blowout syndrome (CBS) is a life-threatening emergency resulting from compromise of the carotid artery caused by malignancy in the head and neck. To report our experience with covered stents for the prevention or treatment of carotid blowout syndrome secondary to head and neck cancer to ascertain the safety and efficacy of this technique. We reviewed the characteristics and outcome of all patients who underwent covered stent placement in the extracranial carotid artery in the setting of head and neck malignancy between 2006 and 2013 at the University of Miami. Patient demographics, presenting symptoms, devices used, perioperative complications, imaging, and follow-up data were reviewed. Seventeen carotids in 15 patients, whose ages ranged from 20 to 84 years (mean, 70.4 years), were treated with 20 covered nitinol (Viabahn Endoprosthesis, Gore, Flagstaff, Arizona) stents. Three patients were treated acutely for bleeding from carotid blowout, and 12 were treated prophylactically for threatened carotid blowout. All patients were given periprocedural dual antiplatelet therapy. No thromboembolic or ischemic complications were noted. Hemorrhage after treatment occurred in 4 patients. In 2 patients, the hemorrhage was from a source not covered by the stent. The use of covered stents is a simple, safe, and effective method for treating or preventing carotid blowout syndrome in patients with head and neck malignancy. Carotid artery reconstruction with covered stents may minimize the risk of ischemic complications associated with endovascular or surgical carotid sacrifice.


Neuropsychological evidence for a competitive bias against contracting stimuli.
Two experiments examined extinction to stimuli presented either with contracting or expanding motion. Experiment 1 used solid shapes which either increased or decreased in size rapidly, consistent with looming motion. Experiment 2 employed random dots so that stimulus size was not confounded with type of motion. In both experiments extinction was modulated by the type of motion presented, with extinction most evident when a contracting object was in the weaker visual field. In addition, in Experiment 2 there was evidence for grouping modulating extinction, when there were looming stimuli in both fields. The results suggest that looming motion is a powerful determinant of stimulus salience in selective attention.


Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide during Keratinocyte Differentiation.
The lipid lamellae in the stratum corneum is important for the epidermal permeability barrier. The lipid lamellae component ceramide (CER), comprising an ultra long-chain (ULC) fatty acid (FA) of ≥26 carbons (ULC CER), plays an essential role in barrier formation. ULC acyl-CoAs, produced by the FA elongase ELOVL4, are converted to ULC CERs by the CER synthase CERS3. In the presented study, we observed that ELOVL4 and CERS3 mRNAs increased during keratinocyte differentiation in vivo and in vitro. We also determined that peroxisome proliferator-activated receptor β/δ is involved in the up-regulation of the mRNAs. Knockdown of CERS3 caused a reduction in the elongase activities toward ULC acyl-CoAs, suggesting that CERS3 positively regulates ULCFA. Thus, we reveal that the two key players in ULC CER production in epidermis, CERS3 and ELOVL4, are coordinately regulated at both the transcriptional and enzymatic levels.


Campylobacter infection in humans.
Campylobacter jejuni and Campylobacter coli are now recognized as common bacterial cause of enteritis in humans. They infect the healthiest of persons resulting in a self-limiting diarrhoea often accompanied by mucus and blood in the stool. On the other hand C. fetus subsp fetus attacks otherwise debilitated persons whose body defences have been weakened by underlying conditions, and causes extragastrointestinal campylobacteriosis. C. pylori, which is able to survive in the stomach acid environment, is now widely considered to be associated with gastritis, peptic ulcer, duodenal ulcer and non-duodenal ulcer, although its aetiologic role in the causation of the disease has not yet been established.