Assessment of dietary patterns, physical activity and obesity from a national survey: Rural-urban health disparities in older adults.
Obesity is a critical public health issue, affecting over one-third of all Americans, and is an underlying cause of numerous health issues across the lifespan. For older adults, obesity is linked to premature declines in physical and mental health and cognitive functioning. The occurrence of obesity and related health behaviors and chronic diseases are higher in rural areas than in urban areas. Furthermore, rural areas of the United States have a higher proportion of older adults than urban areas. Few studies, to date, have explored rural-urban differences in the relationships between dietary patterns and obesity among older adults. Therefore, the purpose of this study is to assess rural-urban differences in obesity rates in older adults, and the potential for the associations between obesity and physical activity and dietary patterns to vary by rural-urban status. Data were abstracted from respondents aged 65 and above from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) database linked to Census-based county-level information on rural-urban status and socioeconomic status. Generalized linear models were utilized to assess rural-urban disparities in obesity, and the potential for associations between obesity and known risk factors (fruit consumption, green vegetable consumption and physical activity) to vary by rural-urban status, accounting for complex sampling and confounders. Obesity rates were highest and fruit consumption was lowest in the most rural areas. However, for older adults in the most urban areas, there was a significant negative association between obesity and fruit and green vegetable consumption. This association was not observed in more rural older adults. These findings underscore the need to take into account place-based factors such as rural-urban status, when designing and implementing policies and interventions designed to reduce obesity through risk factor mitigation in older adults. To reduce rural-urban disparities in older adults, all policies, programs, and interventions should address the unique barriers and needs specific to rural and urban older adults.


Peroxisome-proliferator-activated receptor gamma coactivator 1 α contributes to dysmyelination in experimental models of Huntington's disease.
The peroxisome-proliferator-activated receptor gamma coactivator 1 α (PGC1α) has been implicated in the pathogenesis of several neurodegenerative disorders, including Huntington's disease (HD). Recent data demonstrating white matter abnormalities in PGC1α knock-out (KO) mice prompted us to examine the role of PGC1α in CNS myelination and its relevance to HD pathogenesis. We found deficient postnatal myelination in the striatum of PGC1α KO mice, accompanied by a decrease in myelin basic protein (MBP). In addition, brain cholesterol, its precursors, and the rate-limiting enzymes for cholesterol synthesis, HMG CoA synthase (HMGCS1) and HMG CoA reductase (HMGCR), were also reduced in PGC1α KO mice. Moreover, knockdown of PGC1α in oligodendrocytes by lentiviral shRNA led to a decrease in MBP, HMGCS1, and Hmgcr mRNAs. Chromatin immunoprecipitations revealed the recruitment of PGC1α to MBP promoter in mouse brain, and PGC1α over-expression increased MBP and SREBP-2 promoter activity, suggesting that PGC1α regulates MBP and cholesterol synthesis at the transcriptional level. Importantly, expression of mutant huntingtin (Htt) in primary oligodendrocytes resulted in decreased expression of PGC1α and its targets HmgcS1, Hmgcr, and MBP. Decreased expression of MBP and deficient myelination were found postnatally and in adult R6/2 mouse model of HD. Diffusion tensor imaging detected white matter abnormalities in the corpus callosum of R6/2 mice, and electron microscopy revealed thinner myelin sheaths and increased myelin periodicity in BACHD [bacterial artificial chromosome (BAC)-mediated transgenic model for Huntington's disease] mice expressing full-length mutant Htt. Together, these data suggest that PGC1α plays a role in postnatal myelination and that deficient PGC1α activity in oligodendrocytes may contribute to abnormal myelination in HD.


Contemplative neuroscience, self-awareness, and education.
Accumulating research in education shows that contemplative practices contribute to and foster well-being of individuals in sustainable ways. This bears special importance for teachers, as it affects not only them but also their students. Based on accumulating behavioral and neuroscientific findings, it has been suggested that a key process by which mindfulness meditation enhances self-regulation is the altering of self-awareness. Indeed, accumulated work shows that the underlying networks supporting various types of self-awareness are malleable following meditative practice. However, the field of education has developed independently from the study of the self and its relation to contemplative neuroscience thus far, and to date there is no systematic account linking this accumulating body of knowledge to the field of education or discussing how it might be relevant to teachers. Here we show how incorporating insights from contemplative neuroscience-which are built on the conceptualization and neuroscience of the self-into contemplative pedagogy can inform the field and might even serve as a core underlying mechanism tying together different empirical evidence. This review points to potential neural mechanisms by which mindfulness meditation helps teachers manage stress and promote supportive learning environments, resulting in improved educational outcomes, and thus it has significant implications for educational policy regarding teachers.


Established and potential therapeutic applications of cannabinoids in oncology.
Cannabis occurs naturally in the dried flowering or fruiting tops of the Cannabis sativa plant. Cannabis is most often consumed by smoking marihuana. Cannabinoids are the active compounds extracted from cannabis. Recently, there has been renewed interest in cannabinoids for medicinal purposes. The two proven indications for the use of the synthetic cannabinoid (dronabinol) are chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Other possible effects that may prove beneficial in the oncology population include analgesia, antitumor effect, mood elevation, muscle relaxation, and relief of insomnia. Two types of cannabinoid receptors, CB1 and CB2, have been detected. CB1 receptors are expressed mainly in the central and peripheral nervous system. CB2 receptors are found in certain nonneuronal tissues, particularly in the immune cells. Recent discovery of both the cannabinoid receptors and endocannabinoids has opened a new era in research on the pharmaceutical applications of cannabinoids. The use of cannabinoids should be continued in the areas indicated, and further studies are needed to evaluate other potential uses in clinical oncology.


Bayesian inference of the number of factors in gene-expression analysis: application to human virus challenge studies.
Nonparametric Bayesian techniques have been developed recently to extend the sophistication of factor models, allowing one to infer the number of appropriate factors from the observed data. We consider such techniques for sparse factor analysis, with application to gene-expression data from three virus challenge studies. Particular attention is placed on employing the Beta Process (BP), the Indian Buffet Process (IBP), and related sparseness-promoting techniques to infer a proper number of factors. The posterior density function on the model parameters is computed using Gibbs sampling and variational Bayesian (VB) analysis. Time-evolving gene-expression data are considered for respiratory syncytial virus (RSV), Rhino virus, and influenza, using blood samples from healthy human subjects. These data were acquired in three challenge studies, each executed after receiving institutional review board (IRB) approval from Duke University. Comparisons are made between several alternative means of per-forming nonparametric factor analysis on these data, with comparisons as well to sparse-PCA and Penalized Matrix Decomposition (PMD), closely related non-Bayesian approaches. Applying the Beta Process to the factor scores, or to the singular values of a pseudo-SVD construction, the proposed algorithms infer the number of factors in gene-expression data. For real data the "true" number of factors is unknown; in our simulations we consider a range of noise variances, and the proposed Bayesian models inferred the number of factors accurately relative to other methods in the literature, such as sparse-PCA and PMD. We have also identified a "pan-viral" factor of importance for each of the three viruses considered in this study. We have identified a set of genes associated with this pan-viral factor, of interest for early detection of such viruses based upon the host response, as quantified via gene-expression data.


Causes and consequences of limitations in visual working memory.
Recent methodological and conceptual advances have led to a fundamental reappraisal of the nature of visual working memory (WM). A large corpus of evidence now suggests that there might not be a hard limit on the number of items that can be stored. Instead, WM may be better captured by a highly limited--but flexible--resource model. More resource can be allocated to prioritized items but, crucially, at a cost of reduced recall precision for other stored items. Expectations may modulate resource distribution, for example, through neural oscillations in the alpha band increasing inhibition of irrelevant cortical regions. Our understanding of the neural architecture of WM is also undergoing radical revision. Whereas the prefrontal cortex has previously dominated research endeavors, other cortical regions, such as early visual areas, are now considered to make an essential contribution, for example holding one or more items in a privileged state or "focus of attention" within WM. By contrast, the striatum is increasingly viewed as crucial in determining why and how items are gated into memory, while the hippocampus, it has controversially been argued, might be critical in the formation of temporally resilient conjunctions across features of stored items in WM.


Effect of sex and sex steroids on brown adipose tissue heat production in humans.
Retrospective studies suggest that women have more active brown adipose tissue (BAT) than men, but little is known of the effect of fluctuating sex steroids across the menstrual cycle on thermogenesis in women. To characterise the effects of sex and sex steroids on BAT activity we recruited healthy weight men (n = 14) and women at two stages of the menstrual cycle (luteal, n = 9; follicular, n = 11). Infrared thermography measured supraclavicular temperature to index BAT thermogenesis in response to both cold (immersion of one hand in water at 15°C) and meal (Ensure, 10 kcal/kg body weight) stimuli. Adaptive BAT temperature responses were greater (P < 0.05) in women than men, irrespective of stage of menstrual cycle. Whereas during cold exposure, the increase in BAT temperature was abrogated (P < 0.05) in women during follicular phase compared to men and women during luteal phase. Plasma concentrations of progesterone, 17β-estradiol, testosterone and cortisol were measured. Regression analyses demonstrated that baseline BAT temperature was positively correlated (P < 0.05) with progesterone levels, but was inversely associated (P < 0.05) with cortisol concentration. Both cold- and meal-induced changes in BAT temperature mildly correlated (P = 0.07; P < 0.05) with 17β-estradiol levels, but not with testosterone concentrations. Baseline supraclavicular temperature is elevated in women during the luteal phase of the menstrual cycle, which correlated with elevated progesterone concentrations. Women exhibited greater thermogenic responses than men, irrespective of the state of the menstrual cycle, which was associated with plasma levels of 17β-estradiol. We conclude that sex steroids may regulate BAT thermogenesis in healthy adults.


Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study.
POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome. This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival. Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months. Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.


The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.
Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular filaments that gate hair cell mechano-electrical transduction channels in the inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cytoplasmic domains; they are thought to function redundantly in mechano-electrical transduction during hair-bundle development, but whether any of these isoforms composes the tip-link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15-cre+/-) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15 frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano-electrical transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects.


Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches.
Most cancer deaths are not caused by the primary tumor, but by secondary tumors formed through metastasis, a complex and poorly understood process. Cues from the tumor microenvironment, such as the biochemical composition, cellular population, extracellular matrix, and tissue (fluid) mechanics, have been indicated to play a pivotal role in the onset of metastasis. Dissecting the role of these cues from the tumor microenvironment in a controlled manner is challenging, but essential to understanding metastasis. Recently, cancer-on-a-chip models have emerged as a tool to study the tumor microenvironment and its role in metastasis. These models are based on microfluidic chips and contain small chambers for cell culture, enabling control over local gradients, fluid flow, tissue mechanics, and composition of the local environment. Here, we review the recent contributions of cancer-on-a-chip models to our understanding of the role of the tumor microenvironment in the onset of metastasis, and provide an outlook for future applications of this emerging technology.


Neurotensin-induced dopamine release in vivo and in vitro from substantia nigra and nucleus caudate.
We compared the dopamine (DA) releasing effects of neurotensin (NT) from cell bodies (substantia nigra) and nerve terminals (nucleus caudate). In rats implanted with push-pull cannula, NT induced DA release from substantia nigra and nucleus caudate. NT was more potent in releasing DA from the substantia nigra than from the nucleus caudate (EC50%, 1.1 microM in substantia nigra and 9.8 microM in nucleus caudate). In vitro, in superfused rabbit brain slices, NT enhanced the depolarization-evoked release of DA and exerted a direct releasing effect. The latter was greater in the substantia nigra, and the former in the nucleus caudate. The direct releasing effect of NT was not inhibited, but enhanced by nomifensine (3 microM). Sulpiride, a D2 DA receptor antagonist, failed to modify NT-induced DA release; in addition, NT did not affect the inhibition of DA and acetylcholine release produced by LY-171555, a D2 DA agonist. In both the substantia nigra and the nucleus caudate, desensitization to the releasing effect of NT was observed, either after 2.5, 5, or 10 min of exposure to the peptide. A synergistic interaction on DA release was observed between NT and potassium (K+), and between NT and electrical stimulation. Greater synergism was observed with high extracellular K+. Pretreatment of striatal slices with 15 mM K+ produced a 9-fold enhancement of NT-induced DA release. When K+ (25 mM, 2 min) was given together with NT there was a 2- to 3-fold increase in DA release compared to the release evoked by K+ in the absence of NT.(ABSTRACT TRUNCATED AT 250 WORDS)


QUANTUM ESPRESSO: a modular and open-source software project for quantum simulations of materials.
QUANTUM ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). The acronym ESPRESSO stands for opEn Source Package for Research in Electronic Structure, Simulation, and Optimization. It is freely available to researchers around the world under the terms of the GNU General Public License. QUANTUM ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively parallel architectures, and a great effort being devoted to user friendliness. QUANTUM ESPRESSO is evolving towards a distribution of independent and interoperable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes.


Redox-active pyocyanin secreted by Pseudomonas aeruginosa 7NSK2 triggers systemic resistance to Magnaporthe grisea but enhances Rhizoctonia solani susceptibility in rice.
Pseudomonas aeruginosa 7NSK2 induces resistance in dicots through a synergistic interaction of the phenazine pyocyanin and the salicylic acid-derivative pyochelin. Root inoculation of the monocot model rice with 7NSK2 partially protected leaves against blast disease (Magnaporthe grisea) but failed to consistently reduce sheath blight (Rhizoctonia solani). Only mutations interfering with pyocyanin production led to a significant decrease in induced systemic resistance (ISR) to M. grisea, and in trans complementation for pyocyanin production restored the ability to elicit ISR. Intriguingly, pyocyanin-deficient mutants, unlike the wild type, triggered ISR against R. solani. Hence, bacterial pyocyanin plays a differential role in 7NSK2-mediated ISR in rice. Application of purified pyocyanin to hydroponically grown rice seedlings increased H202 levels locally on the root surface as well as a biphasic H202 generation pattern in distal leaves. Co-application of pyocyanin and the antioxidant sodium ascorbate alleviated the opposite effects of pyocyanin on rice blast and sheath blight development, suggesting that the differential effectiveness of pyocyanin with respect to 7NSK2-triggered ISR is mediated by transiently elevated H202 levels in planta. The cumulative results suggest that reactive oxygen species act as a double-edged sword in the interaction of rice with the hemibiotroph M. grisea and the necrotroph R. solani.


Cloning and characterization of the 5'-upstream sequence governing the cell cycle-dependent transcription of mouse DNA polymerase alpha 68 kDa subunit gene.
We have isolated the genomic DNA fragment spanning the 5-end and the first four exons encoding the 68 kDa subunit (p68) of the mouse DNA polymerase alpha-primase complex [corrected]. The p68 promoter region lacks TATA and CAAT boxes, but contains a GC-rich sequence, two palindrome sequences and two putative E2F-binding sites [corrected]. A series of transient expression assays using a luciferase reporter gene indicated that a region from nucleotide position -89 to -30 (-89/-30) with respect to the transcription initiation site is crucial for basal transcription of the p68 gene in proliferating NIH 3T3 cells. In particular, part of the GC-rich sequence (-57/-46) and the palindrome (-81/-62) elements were necessary for promoter activity, both of which share homology with the E-box sequence. Gel mobility shift assays using NIH 3T3 nuclear extracts revealed that the upstream stimulatory factor, known as an E-box-binding protein, binds to these sites. Moreover, we observed binding of E2F to two sites near the transcription initiation site (-11/-3 and +9/+16). A transient luciferase expression assay using synchronized NIH 3T3 cells in G(0)phase revealed that these E2F sites are essential for transcription induction of the p68 gene after serum stimulation, but are dispensable for basal transcription. These results indicate that growth-dependent regulation of transcription of the mouse p68 and p180 genes is mediated by a common factor, E2F; however, basal transcription of the genes, interestingly, is regulated by different transcription factors.


Sequencing the genomic regions flanking S-linked PvGLO sequences confirms the presence of two GLO loci, one of which lies adjacent to the style-length determinant gene CYP734A50.
Primula vulgaris contains two GLOBOSA loci, one located adjacent to the style length determinant gene CYP734A50 which lies within the S -locus. Using a combination of BAC walking and PacBio sequencing, we have sequenced two substantial genomic contigs in and around the S-locus of Primula vulgaris. Using these data, we were able to demonstrate that two alleles of PvGlo P as well as PvGlo T can be present in the genome of a single plant, providing empirical evidence that these two forms of the MADS-box gene GLOBOSA are separate loci and not allelic as previously reported. We propose they should be renamed PvGLO1 and PvGLO2. BAC contigs extending from each GLOBOSA locus were identified and fully sequenced. No homologous genes were found between the contigs other than the GLOBOSA genes themselves, consistent with their identity as separate loci. Exons of the recently identified style-length determinant gene CYP734A50 were identified on one end of the contig containing PvGLO2 and these genes are adjacent in the genome, suggesting that PvGLO2 lies either within or at least very close to the S-locus. Current evidence suggests that both CYP734A50 and GLO2 are specific to the S-morph mating type and are hemizygous rather than heterozygous in the Primula genome. This finding contrasts classical models of the HSI locus, which propose that components of the S-locus are allelic, suggesting that these models may need to be reconsidered.


Optic Disc Pyogenic Granuloma.
The aim of this paper was to report a rare presentation of adenoid cystic carcinoma. This is a case report presenting clinical, radiographic, and histopathologic findings. A 72-year-old female with no reported ocular symptoms was found to have an incidental right orbital mass on imaging. Additional studies revealed multiple liver lesions, which were biopsied and found to be consistent with adenoid cystic carcinoma. She was then referred to the ophthalmology service, where ocular examination demonstrated 2.5 mm of right proptosis with elevation and abduction deficits. Diplopia could be elicited in extreme upgaze and right lateral gaze. An excisional biopsy of the orbital mass was performed, with histopathology confirming the diagnosis of primary adenoid cystic carcinoma of the lacrimal gland, thereby also supporting the initial suspicion that the hepatic adenoid cystic carcinoma lesions represented metastases. The authors describe a rare presentation of adenoid cystic carcinoma of the lacrimal gland, initially asymptomatic, with metastatic lesions restricted to the liver at the time of diagnosis. Three previous cases of adenoid cystic carcinoma with isolated metastatic hepatic lesions at the time of diagnosis have been reported; all of these cases localized the primary tumor to the salivary glands.


Older patient-physician discussions about exercise.
This cross-sectional observational study examined the frequency of older patient-physician discussions about exercise, who initiates discussions, and the quality of questioning, informing, and support about exercise. The study used a convenience sample of 396 follow-up visits at 3 community-based practice sites, with 376 community-dwelling older patients and 43 primary-care physicians. Audiotapes were analyzed using the Multi-Dimensional Interaction Analysis coding system. Results demonstrate that exercise was discussed in 13% of visits and the subject was raised equally by patients and physicians. Exercise was significantly more likely to be discussed in dyadic visits (14.7%) than in triadic visits (4.1%). Patient level of education, patient overall physical health, and the physician's being female were significant predictors of the occurrence of exercise discussion. Given the importance of exercise for maintaining health and independence in older adults, more clinical and research attention is needed to address barriers to effective discussions in this area.


Effectiveness of Perioperative Opioid Educational Initiatives: A Systematic Review and Meta-Analysis.
Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills. The MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases were systematically searched for randomized controlled trials (RCTs) assessing the impact of perioperative educational interventions (using either paper- or video-based instruments regarding pain management and drug-induced side effects) on postoperative opioid patterns compared to standard preoperative care among patients undergoing elective surgery. Our end points were opioid consumption (number of pills used), appropriate disposal of unused opioids, opioid cessation (defined as no use of opioids), and opioid refills within 15 days, 6 weeks, and 3 months. In total, 11 RCTs fulfilled the inclusion criteria, totaling 1604 patients (804 received opioid education, while 800 received standard care). Six trials followed patients for 15 days after surgery, and 5 trials followed patients up to 3 months. After 15 days, the opioid education group consumed a lower number of opioid pills than those in the control group (weighted mean difference [WMD], -3.39 pills; 95% confidence interval [CI], -6.40 to -0.37; P =.03; I2 = 69%) with no significant difference in overall opioid cessation (odds ratio [OR], 0.25; 95% CI, 0.04-1.56; P = .14; I2 = 83%). Likewise, perioperative opioid education did not have significant effects on opioid cessation at 6 weeks (OR, 0.69; 95% CI, 0.45-1.05; P = .10; I2 = 0%) and 3 months (OR, 0.59; 95% CI,0.17-2.01; P = .10; I2 = 0%) after surgery, neither reduced the need for opioid refills at 15 days (OR, 0.57; 95% CI, 0.28-1.15; P = .12; I2 = 20%) and 6 weeks (OR, 1.08; 95% CI, 0.59-1.98; P = .80; I2 = 37%). There was no statistically significant difference in the rate of appropriate disposal of unused opioids between both groups (OR, 1.99; 95% CI, 0.66-6.00; P = .22; I2 = 71%). Subgroup analysis by type of educational intervention showed a statistical reduction of opioid consumption at 15 days when implementing multimedia/audiovisual strategies (4 trials: WMD, -4.05 pills; 95% CI, -6.59 to -1.50; P = .002; I2 = 45%), but there was no apparent decrease when using only paper-based strategies (2 trials: WMD, -2.31 pills; 95% CI, -12.21 to 7.59; P = .65; I2 = 80%). Perioperative educational interventions reduced the number of opioid pills consumed at 15 days but did not demonstrate a significant effect on opioid cessation or opioid refills at 15 days, 6 weeks, and 3 months. Further randomized trials should focus on evidence-based educational interventions with strict homogeneity of material to draw a more definitive recommendation.


Predicting myocardial functional recovery after acute myocardial infarction: relationship between myocardial strain and coronary flow reserve.
The purpose of this study was to evaluate the relationship between myocardial strain and coronary flow reserve (CFR) in the prediction of myocardial functional recovery after acute myocardial infarction (AMI). Consecutive patients with anterior ST elevation AMI were analyzed. Left ventricular (LV) strain, determined by 2-dimensional speckle tracking imaging and CFR, determined by intracoronary flow measurement, were obtained on the same day, 3-5 days after primary percutaneous coronary intervention. A-strain was defined as the mean systolic longitudinal strain of 11 LV segments (out of 18) assumed to be supplied by the left anterior descending coronary artery (LAD). Functional recovery was defined as improved wall motion >1 grade seen in at least 2 contiguous dysfunctional segments by echocardiography at the 6-month follow-up. Of 20 patients, 8 patients had preserved CFR (>2.0) and 12 patients had impaired CFR (≤2.0). There were no differences between the 2 CFR groups in LV ejection fractions and wall motion score indices in the LAD territory. However, A-strain was greater in patients with preserved CFR than in patients with impaired CFR (-6.4±2.0% vs. -4.6±1.4%, p=0.03). A-strain and CFR correlated well with each other (r=-0.49, p=0.03). Ten of 20 patients showed functional recovery at 6 months. Of clinical and echocardiographic parameters, A-strain was the only predictor of recovery (odds ratio 2.02, 95% confidence interval=1.03-3.97, p=0.04). For predicting recovery, the sensitivity and specificity were 80.0% and 80.0%, respectively, for CFR (cutoff=1.60), and 60.0% and 90.0%, respectively, for A-strain (cutoff=-6.13%). Myocardial strain correlates well with the extent of microvascular integrity and can be used as a noninvasive method for predicting recovery after AMI.


Age-associated molecular changes are deleterious and may modulate life span through diet.
Transition through life span is accompanied by numerous molecular changes, such as dysregulated gene expression, altered metabolite levels, and accumulated molecular damage. These changes are thought to be causal factors in aging; however, because they are numerous and are also influenced by genotype, environment, and other factors in addition to age, it is difficult to characterize the cumulative effect of these molecular changes on longevity. We reasoned that age-associated changes, such as molecular damage and tissue composition, may influence life span when used in the diet of organisms that are closely related to those that serve as a dietary source. To test this possibility, we used species-specific culture media and diets that incorporated molecular extracts of young and old organisms and compared the influence of these diets on the life span of yeast, fruitflies, and mice. In each case, the "old" diet or medium shortened the life span for one or both sexes. These findings suggest that age-associated molecular changes, such as cumulative damage and altered dietary composition, are deleterious and causally linked with aging and may affect life span through diet.


The complex association of health insurance and maternal health services in the context of a premium exemption for pregnant women: a case study in Northern Ghana.
Health insurance premium exemptions for pregnant women are a strategy to increase coverage of maternal health services in sub-Saharan countries. We examine health insurance registration among pregnant women before or after the introduction of a premium exemption, and test whether registration increases utilization of maternal health services. Data were drawn from a retrospective cohort study of 1641 women having given birth between January 2008 and August 2010 in two impoverished districts of Northern Ghana. Among those, 1411 became pregnant after premium exemption was adopted in July 2008. We compared registration rates before and after the exemption. We used logistic regressions to measure the association between insurance registration and receipt of essential maternal health interventions in the context of the premium exemption. We tested whether this association varied across levels of the health system [e.g. hospitals and health centres (HCs) vs community health compounds (CHC)]. Health insurance registration increased significantly among pregnant women after adoption of the premium exemption. Coverage of clinical and diagnostic services was high, but antenatal care (ANC) clients received only partial counselling about safe motherhood (e.g. pregnancy-related danger signs). Three out of four clients who sought ANC in hospitals and HCs delivered at a health facility vs. slightly more than 50% among clients of CHC. In hospitals and HCs, National Health Insurance Scheme (NHIS) registration was associated with higher quality of services. In CHCs, NHIS registrants received fewer diagnostic tests, were less extensively counselled about safe motherhood and were less likely to be vaccinated against tetanus toxoid than non-registered clients. Among CHCs clients, being a NHIS registrant was however associated with an increased likelihood of delivering at a health facility. In the context of premium exemptions, association of health insurance with use of maternal health services, and quality of services received, depends on place where pregnant women seek ANC.


Folic acid supplementation alleviates reduced ureteric branching, nephrogenesis, and global DNA methylation induced by maternal nutrient restriction in rat embryonic kidney.
We previously reported that maternal nutrient restriction (NR) inhibited ureteric branching, metanephric growth, and nephrogenesis in the rat. Here we examined whether folic acid, a methyl-group donor, rescues the inhibition of kidney development induced by NR and whether DNA methylation is involved in it. The offspring of dams given food ad libitum (CON) and those subjected to 50% food restriction (NR) were examined. NR significantly reduced ureteric tip number at embryonic day 14, which was attenuated by folic acid supplementation to nutrient restricted dams. At embryonic day 18, glomerular number, kidney weight, and global DNA methylation were reduced by NR, and maternal folic acid supplementation again alleviated them. Among DNA methyltransferases (DNMTs), DNMT1 was strongly expressed at embryonic day 15 in CON but was reduced in NR. In organ culture, an inhibitor of DNA methylation 5-aza-2 '-deoxycytidine as well as medium lacking methyl donors folic acid, choline, and methionine, significantly decreased ureteric tip number and kidney size mimicking the effect of NR. In conclusion, global DNA methylation is necessary for normal kidney development. Folic acid supplementation to nutrient restricted dams alleviated the impaired kidney development and DNA methylation in the offspring.


An in vitro study of the effect of probiotics, prebiotics and synbiotics on the elderly faecal microbiota.
The use of dietary intervention in the elderly in order to beneficially modulate their gut microbiota has not been extensively studied. The influence of two probiotics (Bifidobacterium longum and Lactobacillus fermentum) and two prebiotics [isomaltooligosaccharides (IMO) and short-chain fructooligosaccharides (FOS)], individually and in synbiotic combinations (B. longum with IMO, L. fermentum with FOS) on the gut microbiota of elderly individuals was investigated using faecal batch cultures and three-stage continuous culture systems. Population changes of major bacterial groups were enumerated using fluorescent in situ hybridisation (FISH). B. longum and IMO alone significantly increased the Bifidobacterium count after 5 and 10 h of fermentation and their synbiotic combination significantly decreased the Bacteroides count after 5 h of fermentation. L. fermentum and FOS alone significantly increased the Bifidobacterium count after 10 h and 5, 10 and 24 h of fermentation respectively. B. longum with IMO as well as B. longum and IMO alone significantly increased acetic acid concentration during the fermentation in batch cultures. In the three-stage continuous culture systems, both synbiotic combinations increased the Bifidobacterium and Lactobacillus count in the third vessel representing the distal colon. In addition, the synbiotic combination of L. fermentum with scFOS resulted in a significant increase in the concentration of acetic acid. The results show that the elderly gut microbiota can be modulated in vitro with the appropriate pro-, pre- and synbiotics.


Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates.
The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with bronchopulmonary dysplasia (BPD) or respiratory disease in the first year of life and those without these conditions. Study subjects were part of the PROP (Prematurity and Respiratory Outcomes Program) study, a longitudinal cohort study of infants born at less than 29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week before anticipated hospital discharge. Infants were breathing spontaneously and were receiving less than or equal to 1 L/min nasal cannula flow at 21% to 100% fraction of inspired oxygen. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without BPD (oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. A total of 765 infants survived to 36 weeks postmenstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of postdischarge respiratory disease was 65.7%. Compared with a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no clinically significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared with those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. Extremely premature infants receiving less than 1 L/min nasal cannula support at 21% to 100% fraction of inspired oxygen have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).


Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease.
Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% CI 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% CI 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% CI 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% CI 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% CI 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur.


Treatment Strategies in Diffuse Midline Gliomas With the H3K27M Mutation: The Role of Convection-Enhanced Delivery in Overcoming Anatomic Challenges.
Diffuse midline gliomas harboring the H3 K27M mutation-including the previously named diffuse intrinsic pontine glioma (DIPG)-are lethal high-grade pediatric brain tumors that are inoperable and without cure. Despite numerous clinical trials, the prognosis remains poor, with a median survival of ~1 year from diagnosis. Systemic administration of chemotherapeutic agents is often hindered by the blood brain barrier (BBB), and even drugs that successfully cross the barrier may suffer from unpredictable distributions. The challenge in treating this deadly disease relies on effective delivery of a therapeutic agent to the bulk tumor as well as infiltrating cells. Therefore, methods that can enhance drug delivery to the brain are of great interest. Convection-enhanced delivery (CED) is a strategy that bypasses the BBB entirely and enhances drug distribution by applying hydraulic pressure to deliver agents directly and evenly into a target region. This technique reliably distributes infusate homogenously through the interstitial space of the target region and achieves high local drug concentrations in the brain. Moreover, recent studies have also shown that continuous delivery of drug over an extended period of time is safe, feasible, and more efficacious than standard single session CED. Therefore, CED represents a promising technique for treating midline tumors with the H3K27M mutation.


Drought-induced changes in anthesis-silking interval are related to silk expansion: a spatio-temporal growth analysis in maize plants subjected to soil water deficit.
The growth and emergence of maize silks has a considerable importance in yield determination under drought conditions. Spatial and temporal patterns of the rates of tissue expansion and of cell division were characterized in silks of plants subjected to different soil water potentials. In all cases, silk development consisted of four phases: (1) cell division and tissue expansion occurred together uniformly all along the silk; (2) cell division progressively ceased from tip to base, while expansion remained spatially uniform including during the phase (3) after the cessation of cell division; and (4) as the silk emerged from the husks, expansion ceased in the emerged portion, probably because of direct evaporative demand, while the relative growth rate progressively decreased in the enclosed part. The rates of tissue expansion and cell division were reduced with water deficit, resulting in delayed silk emergence. The duration of cell division was not affected, and in all cases, the end of cell division in the silk coincided with anther dehiscence. The duration of phase 3, between the end of cell division and the arrest of cell growth in silk apex, considerably increased with water deficit. It corresponded to the anthesis-silking interval used by breeders to characterize the response of cultivars to stress.


Resistance to extreme strategies, rather than prosocial preferences, can explain human cooperation in public goods games.
The results of numerous economic games suggest that humans behave more cooperatively than would be expected if they were maximizing selfish interests. It has been argued that this is because individuals gain satisfaction from the success of others, and that such prosocial preferences require a novel evolutionary explanation. However, in previous games, imperfect behavior would automatically lead to an increase in cooperation, making it impossible to decouple any form of mistake or error from prosocial cooperative decisions. Here we empirically test between these alternatives by decoupling imperfect behavior from prosocial preferences in modified versions of the public goods game, in which individuals would maximize their selfish gain by completely (100%) cooperating. We found that, although this led to higher levels of cooperation, it did not lead to full cooperation, and individuals still perceived their group mates as competitors. This is inconsistent with either selfish or prosocial preferences, suggesting that the most parsimonious explanation is imperfect behavior triggered by psychological drives that can prevent both complete defection and complete cooperation. More generally, our results illustrate the caution that must be exercised when interpreting the evolutionary implications of economic experiments, especially the absolute level of cooperation in a particular treatment.


Individualized texting for adherence building (iTAB): improving antiretroviral dose timing among HIV-infected persons with co-occurring bipolar disorder.
HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff's d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff's d = -0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff's d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation.


RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis.
Measles virus (MV), a member of the family Paramyxoviridae and an exclusively human pathogen, is among the most infectious viruses. A progressive fatal neurodegenerative complication, subacute sclerosing panencephalitis (SSPE), occurs during persistent MV infection of the CNS and is associated with biased hypermutations of the viral genome. The observed hypermutations of A-to-G are consistent with conversions catalyzed by the adenosine deaminase acting on RNA (ADAR1). To evaluate the role of ADAR1 in MV infection, we selectively disrupted expression of the IFN-inducible p150 ADAR1 isoform and found it caused embryonic lethality at embryo day (E) 11-E12. We therefore generated p150-deficient and WT mouse embryo fibroblast (MEF) cells stably expressing the MV receptor signaling lymphocyte activation molecule (SLAM or CD150). The p150(-/-) but not WT MEF cells displayed extensive syncytium formation and cytopathic effect (CPE) following infection with MV, consistent with an anti-MV role of the p150 isoform of ADAR1. MV titers were 3 to 4 log higher in p150(-/-) cells compared with WT cells at 21 h postinfection, and restoration of ADAR1 in p150(-/-) cells prevented MV cytopathology. In contrast to infection with MV, p150 disruption had no effect on vesicular stomatitis virus, reovirus, or lymphocytic choriomeningitis virus replication but protected against CPE resulting from infection with Newcastle disease virus, Sendai virus, canine distemper virus, and influenza A virus. Thus, ADAR1 is a restriction factor in the replication of paramyxoviruses and orthomyxoviruses.


ASPECTS decay during inter-facility transfer in patients with large vessel occlusion strokes.
Favorable imaging profile according to the Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast head CT is a key criterion for the selection of patients with ischemic stroke from large vessel occlusion (LVO) for IA revascularization therapies. To analyze factors associated with changes in ASPECTS during inter-hospital transfer and to determine how deterioration of ASPECTS affects eligibility for endovascular procedures. We analyzed factors associated with changes in ASPECTS during inter-hospital transfer and their potential impact on eligibility for IA stroke therapies in patients with anterior circulation ischemic strokes. Clinical and demographic characteristics between patients with favorable (ASPECTS ≥6) and unfavorable (ASPECTS <6) imaging on repeat CT were compared. Stroke evolution towards unfavorable ASPECTS occurred in 13/42 (31%) patients who initially had a favorable imaging profile at outside hospitals. A higher National Institutes of Health Stroke Scale (NIHSS) score was the only significant predictor of ASPECTS decay, whereas other clinical characteristics, such as the use of IV thrombolysis and site of LVO, were similar between the two groups. In our cohort, one out of three patients became ineligible for IA thrombectomy because of unfavorable ASPECTS 'decay' following inter-hospital transfer. Except for NIHSS severity, baseline clinical factors could not identify which patients were at risk for ASPECTS deterioration.


Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration.
Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.


Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification.
Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties.


When it comes to lifestyle recommendations, more is sometimes less: a meta-analysis of theoretical assumptions underlying the effectiveness of interventions promoting multiple behavior domain change.
A meta-analysis of 150 research reports summarizing the results of multiple behavior domain interventions examined theoretical predictions about the effects of the included number of recommendations on behavioral and clinical change in the domains of smoking, diet, and physical activity. The meta-analysis yielded 3 main conclusions. First, there is a curvilinear relation between the number of behavioral recommendations and improvements in behavioral and clinical measures, with a moderate number of recommendations producing the highest level of change. A moderate number of recommendations is likely to be associated with stronger effects because the intervention ensures the necessary level of motivation to implement the recommended changes, thereby increasing compliance with the goals set by the intervention, without making the intervention excessively demanding. Second, this curve was more pronounced when samples were likely to have low motivation to change, such as when interventions were delivered to nonpatient (vs. patient) populations, were implemented in nonclinic (vs. clinic) settings, used lay community (vs. expert) facilitators, and involved group (vs. individual) delivery formats. Finally, change in behavioral outcomes mediated the effects of number of recommended behaviors on clinical change. These findings provide important insights that can help guide the design of effective multiple behavior domain interventions.


Food authentication from shotgun sequencing reads with an application on high protein powders.
Here we propose that using shotgun sequencing to examine food leads to accurate authentication of ingredients and detection of contaminants. To demonstrate this, we developed a bioinformatic pipeline, FASER (Food Authentication from SEquencing Reads), designed to resolve the relative composition of mixtures of eukaryotic species using RNA or DNA sequencing. Our comprehensive database includes >6000 plants and animals that may be present in food. FASER accurately identified eukaryotic species with 0.4% median absolute difference between observed and expected proportions on sequence data from various sources including sausage meat, plants, and fish. FASER was applied to 31 high protein powder raw factory ingredient total RNA samples. The samples mostly contained the expected source ingredient, chicken, while three samples unexpectedly contained pork and beef. Our results demonstrate that DNA/RNA sequencing of food ingredients, combined with a robust analysis, can be used to find contaminants and authenticate food ingredients in a single assay.


Tumor-induced oxidative stress perturbs nuclear factor-kappaB activity-augmenting tumor necrosis factor-alpha-mediated T-cell death: protection by curcumin.
Cancer patients often exhibit loss of proper cell-mediated immunity and reduced effector T-cell population in the circulation. Thymus is a major site of T-cell maturation, and tumors induce thymic atrophy to evade cellular immune response. Here, we report severe thymic hypocellularity along with decreased thymic integrity in tumor bearer. In an effort to delineate the mechanisms behind such thymic atrophy, we observed that tumor-induced oxidative stress played a critical role, as it perturbed nuclear factor-kappaB (NF-kappaB) activity. Tumor-induced oxidative stress increased cytosolic IkappaBalpha retention and inhibited NF-kappaB nuclear translocation in thymic T cells. These NF-kappaB-perturbed cells became vulnerable to tumor-secreted tumor necrosis factor (TNF)-alpha (TNF-alpha)-mediated apoptosis through the activation of TNF receptor-associated protein death domain-associated Fas-associated protein death domain and caspase-8. Interestingly, TNF-alpha-depleted tumor supernatants, either by antibody neutralization or by TNF-alpha-small interfering RNA transfection of tumor cells, were unable to kill T cell effectively. When T cells were overexpressed with NF-kappaB, the cells became resistant to tumor-induced apoptosis. In contrast, when degradation-defective IkappaBalpha (IkappaBalpha super-repressor) was introduced into T cells, the cells became more vulnerable, indicating that inhibition of NF-kappaB is the reason behind such tumor/TNF-alpha-mediated apoptosis. Curcumin could prevent tumor-induced thymic atrophy by restoring the activity of NF-kappaB. Further investigations suggest that neutralization of tumor-induced oxidative stress and restoration of NF-kappaB activity along with the reeducation of the TNF-alpha signaling pathway can be the mechanism behind curcumin-mediated thymic protection. Thus, our results suggest that unlike many other anticancer agents, curcumin is not only devoid of immunosuppressive effects but also acts as immunorestorer in tumor-bearing host.


Parathyroid localization.
Twenty-nine consecutive patients with suspected primary hyperparathyroidism were examined preoperatively using ultrasound, sonographically guided fine needle aspiration, and aspirate immunostaining for PTH. In 25 patients, localization of enlarged parathyroid glands was successful. In 2 patients, the tumors were located retrosternally and, thus, could not be detected by ultrasound. One patient had a multinodular goiter which impeded localization. In 1 patient with renal osteodystrophy, 2 enlarged parathyroid glands in the neck were not visualized preoperatively. Cytology was not diagnostic, although some cytological features were suggestive of parathyroid cells. Immunostaining of the aspirated smears for PTH, however, correctly diagnosed all preoperatively localized lesions. Ultrasound should be the routine procedure of choice for preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism. Fine needle aspiration and immunocytochemistry can supply confirmation, if necessary.


First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases.
The main goals were to study the safety and tolerability of the alpha-emitter radium-223 (223Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated. Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1, 4, and 8 weeks after injection. Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection. Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance with pretreatment (99m)Tc-MDP scans, accumulation of 223Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months. 223Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.


Type of musical soundtrack affects behavior in gambling.
A long existing notion is that the presence of music might affect gambling behavior. In spite of this, little empirical research on the subject exists. The main aim of the present study was to corroborate and elaborate on the existing findings concerning gambling and music through a laboratory based experiment. A nonclinical sample of 101 undergraduate students (72 females, 29 males) played a computerized gambling task in which either a high-tempo or a low-tempo musical soundtrack was present. Persistence in gambling, reaction time and evaluation of the game comprised the outcome variables. Low-tempo music was associated with increased gambling persistence in terms of overall number of bets placed, whereas high-tempo music was associated with intensified gambling in terms of faster reaction time per placed bet. Type of soundtrack was not associated with game evaluation. Our findings add to the existing knowledge by showing that both low-tempo and high-tempo music can be associated with more risky gambling behavior, the former by increasing gambling persistence and the latter by reducing reaction time for bets placed. In sum, the existing studies provide compelling evidence that music can affect various aspects of gambling behavior. These findings may have clinical implications by educating gamblers on the effects of structural mechanisms in gambling on behavior.


Bi-directional solid fermentation products of Trametes robiniophila Murr with Radix Isatidis inhibit proliferation and metastasis of breast cancer cells.
The bi-directional solid fermentation product extract of Trametes robiniophila Murr (Huaier) with Radix Isatidis (TIF) has been shown to have good anti-tumor activity. However, the mechanisms of this activity are still unknown. In the present study, we aimed to investigate its inhibitory effect on both SK-BR-3 and MDA-MB-231 cells, and explore the possible mechanisms of its anti-cancer effect in vitro. The experiment comprised a control group, Radix Isatidis group, Huaier group, and TIF group. The cell viability was measured by MTT and the distribution of cell cycle and apoptosis levels were analyzed by flow cytometry. Cell scratch, Transwell, and adhesion assays were used to measure the effects of the test compounds on the migration, invasion, and adhesion capability of SK-BR-3 and MDA-MB-231 cells. The effects of TIF on the mRNA and protein expression related to apoptosis and migration were measured by using semi-quantitative RT-PCR and western blotting. TIF strongly inhibited the cell proliferation of the SK-BR-3 and MDA-MB-231 cells in a time-dependent manner and induced G2/M arrest and apoptosis. Furthermore, TIF significantly inhibited the proliferation, migration, invasion, and adhesion capabilities of SK-BR-3 and MDA-MB-231 cells. Compared with other treatments, the anticancer effect of TIF were stronger in MDA-MB-231 cells. Semi-quantitative RT-PCR suggested that TIF may upregulate the expression of p53 and caspase-3 to inhibit cell proliferation, and downregulate the expression of MMP-9/Snail and MMP-9/MMP-2 to inhibit the migration, invasion, and adhesion capabilities of SK-BR-3 and MDA-MB-231 cells. Western blotting results showed that TIF increased the expression of p53 protein and decreased the expression of MMP-9 protein in SK-BR-3 and MDA-MB-231 cells. The results indicated that the bi-directional solid fermentation may enhance the efficacy of Huaier in MDA-MB-231 cells and that TIF may be an effective complementary medicine for cancer treatment.


Fear conditioning in an abdominal pain model: neural responses during associative learning and extinction in healthy subjects.
Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS(+)) were paired with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition) and the amygdala (late acquisition) in response to the CS(+). During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS(-) was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain.


The air entrapment under a drop impacting on a nano-rough surface.
We study the impact of drops onto a flat surface with a nano-particle-based superhydrophobic coating, focusing on the earliest contact using 200 ns time-resolution. A central air-disc is entrapped when the drop impacts the surface, and when the roughness is appropriately accounted for, the height and radial extent of the air-disc follow the scaling laws established for impacts onto smooth surfaces. The roughness also modifies the first contact of the drop around the central air-disc, producing a thick band of micro-bubbles. The initial bubbles within this band coalesce and grow in size. We also infer the presence of an air-film residing inside the microstructure, at radial distances outside the central air-disc. This is manifest by the sudden appearance of microbubbles within a few microseconds after impact. The central air-disc remains pinned on the roughness, unless it is chemically altered to make it superhydrophilic.


Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.
We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.


The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients.
Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present in KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present in the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected in the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population.


[The influence of macrophytes on rotifer and microcrustacean assemblage in a tropical floodplain].
Most studies on zooplankton ecology have been conducted in open waters. However, it has been considered of great importance to extend such studies to other habitats, such as those generated of macrophytes. We studied the spatial and temporal variation of the microcrustacean and rotifer assemblage structures associated with macrophytes, and compare them with the variation exhibited in open waters. Integrated samples were collected for zooplankton and phytoplankton biomass using a Schindler bottle, in four open water sites and four other sites covered by macrophytes in the floodplain complex of Ayapel (Córdoba, Colombia) during different limnimetric levels. The significant differences in the structure were evaluated using Kruskal & Wallis and discriminant analyses, and the similarity among sampling sites was evaluated using Bray & Curtis analysis. Zooplanktonic richness was favored by macrophytes. However, we did not find a constant spatial pattern for density, and only particular trends apparently conditionated by flood pulses. The presence of Eichhornia azurea (Pontederiaceae) contributed in a significant way with an increase in the diversity and density of benthic taxa. The density of some zooplanktonic groups was related with environmental conditions and phytoplanktonic biomass.


Dual roles of Wnt signaling during chondrogenesis in the chicken limb.
Long bones of the appendicular skeleton are formed from a cartilage template in a process known as endochondral bone development. Chondrocytes within this template undergo a progressive program of differentiation from proliferating to postmitotic prehypertrophic to hypertrophic chondrocytes, while mesenchymal cells immediately surrounding the early cartilage template form the perichondrium. Recently, members of the Wnt family of secreted signaling molecules have been implicated in regulating chondrocyte differentiation. We find that Wnt-5a, Wnt-5b and Wnt-4 genes are expressed in chondrogenic regions of the chicken limb: Wnt-5a is expressed in the perichondrium, Wnt-5b is expressed in a subpopulation of prehypertrophic chondrocytes and in the outermost cell layer of the perichondrium, and Wnt-4 is expressed in cells of the joint region. Misexpression experiments demonstrate that two of these Wnt molecules, Wnt-5a and Wnt-4, have opposing effects on the differentiation of chondrocytes and that these effects are mediated through divergent signaling pathways. Specifically, Wnt-5a misexpression delays the maturation of chondrocytes and the onset of bone collar formation, while Wnt-4 misexpression accelerates these two processes. Misexpression of a stabilized form of beta-catenin also results in accelerated chondrogenesis, suggesting that a beta-catenin/TCF-LEF complex is involved in mediating the positive regulatory effect of Wnt-4. A number of the genes involved in Wnt signal tranduction, including two members of the Frizzled gene family, which are believed to encode Wnt-receptors, show very dynamic and distinct expression patterns in cartilaginous elements of developing chicken limbs. Misexpression of putative dominant-negative forms of the two Frizzled proteins results in severe shortening of the infected cartilage elements due to a delay in chondrocyte maturation, indicating that an endogenous Wnt signal does indeed function to promote chondrogenic differentiation.


Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.
Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.


Non-mechanical sub-pixel image shifter for acquiring super-resolution digital images.
A sub-pixel image shifter is presented, for use in enhancing the spatial resolution of digital image sensors by combining multiple displaced sub-images using a super-resolution (SR) algorithm. The device uses the walk-off phenomenon in birefringent crystals to separate images with opposite polarizations by a sub-pixel displacement. A liquid crystal (LC) waveplate plus a polarizer can then select the specific image to be exposed, with fast, non-mechanical control. This cascaded device, comprising two sapphire crystals, two LCs, and a single polarizer, is capable of 2-dimensional image shift with displacements of 0.5 pixels. The experimental results show that the image registration stability can be precisely controlled within 0.05 pixels and the contrast transfer function ratio of the SR image is enhanced by up to 1.36 times compared to the original captured image. Moreover, based on the fast transition time of LCs, the displaced sub-images can be recorded in video form with a frame rate of 40 fps.


Utilization of optimal study design for maternal and fetal sheep propofol pharmacokinetics study: a preliminary study.
Multiple blood samples are generally required for measurement of pharmacokinetic (PK) parameters. D-optimal design is a popular and frequently used approach for determination of sampling time points in order to minimize the number of samples, while optimizing the estimation of PK parameters. Optimal design utilizing ADAPT (v5, BSR, University of Southern California, Los Angeles) developed a sparse sampling strategy to determine measurement of propofol in pregnant sheep. Propofal was administered as supplemental anesthetic agent to inhalation anesthesia to mimic anesthesia for open fetal surgery. In our preliminary study, propofol 3 mg/kg was given as a bolus to the ewe, followed by propofol infusion at rate 450 mcg/kg/min for 60 minutes, then decreased to 75 mcg/kg/min for 90 more minutes and then ceased. A three compartment model described the PK parameters with the fetus assumed as the third compartment. Initially, sampling times were chosen from thirteen time points as previously stated in the literature. Using priori propofol PK estimates, the final 9 sample time points were proposed in an optimal design with a change in infusion rate occurring between 65 and 75 minutes and sampling proposed at 5, 15, 25, 65, 75, 100, 110, 150, and 180 minutes. D-optimal design optimized the number and timing of samplings, which led to a reduction of cost and man power in the study protocol while preserving the ability to estimate propofol PK parameters in the maternal and fetal sheep model. Initial evaluation of samples collected from three sheep using the optimal design strategy confirmed the performance of the design in obtaining effective PK parameter estimates.


Antiplasmodial activity of ethanolic extracts of some selected medicinal plants from the northwest of Iran.
The effectiveness of antimalarial drugs is declining at an ever accelerating rate, with consequent increase in malaria-related morbidity and mortality. The newest antiplasmodial drug from plants is needed to overcome this problem. The aim of this study was to assess antimalarial activity of the ethanolic extracts of 10 different medicinal plants from eight families against Plasmodium falciparum chloroquine-sensitive 3D7 strain. The selection of the hereby studied plants was based on the existing information on their local ethnobotanic history. Plants were dried, powdered, and macerated in a hydroalcoholic solution. Resulting extracts have been assessed for in vitro and in vivo antimalarial and brine shrimp toxicity activities. Of 10 plant species tested, four plants: Althea officinalis L. (Malvaceae), Myrtus communis Linn (Myrtaceae), Plantago major (Plantaginaceae), and Glycyrrhiza glabra L. (Papilionaceae) displayed promising antimalarial activity in vitro (50% inhibitory concentration values of 62.77, 42.18, 40.00, and 13.56 μg/mL, respectively) with no toxicity against brine shrimp larvae. The crude extracts of three active plants, G. glabra, M. communis, and A. officinalis, also significantly reduced parasitemia in vivo in female Swiss albino mice at a dose of 400 mg/kg compared to no treatment. Antiplasmodial activities of extracts of A. officinalis and M. communis are reported for the first time.


Mechanistic Characterization of Escherichia coli l-Aspartate Oxidase from Kinetic Isotope Effects.
l-Aspartate oxidase, encoded by the nadB gene, is the first enzyme in the de novo synthesis of NAD+ in bacteria. This FAD-dependent enzyme catalyzes the oxidation of l-aspartate to generate iminoaspartate and reduced flavin. Distinct from most amino acid oxidases, it can use either molecular oxygen or fumarate to reoxidize the reduced enzyme. Sequence alignments and the three-dimensional crystal structure have revealed that the overall fold and catalytic residues of NadB closely resemble those of the succinate dehydrogenase/fumarate reductase family rather than those of the prototypical d-amino acid oxidases. This suggests that the enzyme can catalyze amino acid oxidation via typical amino acid oxidase chemistry, involving the removal of protons from the α-amino group and the transfer of the hydride from C2, or potentially deprotonation at C3 followed by transfer of the hydride from C2, similar to chemistry occurring during succinate oxidation. We have investigated this potential mechanistic ambiguity using a combination of primary, solvent, and multiple deuterium kinetic isotope effects in steady state experiments. Our results indicate that the chemistry is similar to that of typical amino acid oxidases in which the transfer of the hydride from C2 of l-aspartate to FAD is rate-limiting and occurs in a concerted manner with respect to deprotonation of the α-amine. Together with previous kinetic and structural data, we propose that NadB has structurally evolved from succinate dehydrogenase/fumarate reductase-type enzymes to gain the new functionality of oxidizing amino acids while retaining the ability to reduce fumarate.


Feasibility of Concurrent Chemoradiation in Patients treated for Esophageal Carcinoma: A Single Institutional Experience.
Chemoradiation has shown superior overall survival when compared with radiation alone in esophageal carcinoma. Due to compromised nutritional status, radiation therapy in esophageal cancer patients itself is a challenge and addition of concurrent chemotherapy leads to severe side effects even when standard dose regimens are used. The tolerance of chemoradiation for carcinoma esophagus in Indian patients is still unclear. This study is an effort to know feasibility of chemoradiation in patients treated for esophageal carcinoma in our hospital. A total of 47 consecutive patients of histologically proven esophageal carcinoma who were treated in MS Ramaiah Hospital were reviewed retrospectively from January to August 2013. Out of 47 patients, 20 patients were treated with concurrent chemoradiotherapy. Patients were assessed for number of days of treatment interruptions in radiation schedule and number of planned vs executed cycles of chemotherapy. Out of the 20 patients treated with concurrent chemoradiotherapy, 13 patients were male (65%) and 7 (35%) were female. Median age of patients was 60 years (25-75 years). Squamous cell carcinoma was noted in majority of cases (19/20 cases). A total of 18 of 20 patients completed the planned dose of radiation and only 3/20 patients completed all planned cycles of chemotherapy. Mean number of days of interruption in radiation schedule in patients receiving chemoradiotherapy was 4.4 days. There was poor tolerance to chemoradiotherapy leading to reduction in the number of executed chemotherapy cycles as opposed to planned cycles, although there were no significant interruptions in radiation treatment.How to cite this article: Kannan RA. Feasibility of Concurrent Chemoradiation in Patients treated for Esophageal Carcinoma: A Single Institutional Experience. Euroasian J Hepato-Gastroenterol 2014;4(1):11-13.


Apoptosis predominates in nonmyocytes in heart failure.
The goal of this investigation was to determine the distribution of myocardial apoptosis in myocytes and nonmyocytes in primates and patients with heart failure (HF). Almost all clinical cardiologists and cardiovascular investigators believe that myocyte apoptosis is considered to be a cardinal sign of HF and a major factor in its pathogenesis. However, with the knowledge that 75% of the number of cells in the heart are nonmyocytes, it is important to determine whether the apoptosis in HF is occurring in myocytes or in nonmyocytes. We studied both a nonhuman primate model of chronic HF, induced by rapid pacing 2-6 mo after myocardial infarction (MI), and biopsies from patients with ischemic cardiomyopathy. Dual labeling with a cardiac muscle marker was used to discriminate apoptosis in myocytes versus nonmyocytes. Left ventricular ejection fraction decreased following MI (from 78% to 60%) and further with HF (35%, P < 0.05). As expected, total apoptosis was increased in the myocardium following recovery from MI (0.62 cells/mm(2)) and increased further with the development of HF (1.91 cells/mm(2)). Surprisingly, the majority of apoptotic cells in MI and MI + HF, and in both the adjacent and remote areas, were nonmyocytes. This was also observed in myocardial biopsies from patients with ischemic cardiomyopathy. We found that macrophages contributed the largest fraction of apoptotic nonmyocytes (41% vs. 18% neutrophils, 16% fibroblast, and 25% endothelial and other cells). Although HF in the failing human and monkey heart is characterized by significant apoptosis, in contrast to current concepts, the apoptosis in nonmyocytes was eight- to ninefold greater than in myocytes.


Diagnostic yield of nasal scrape biopsies in primary ciliary dyskinesia: a multicenter experience.
Examination of ciliary ultrastructure remains the cornerstone diagnostic test for primary ciliary dyskinesia (PCD), a disease of abnormal ciliary structure and/or function. Obtaining a biopsy with sufficient interpretable cilia and producing quality transmission electron micrographs (TEM) is challenging. Methods for processing tissues for optimal preservation of axonemal structures are not standardized. This study describes our experience using a standard operating procedure (SOP) for collecting nasal scrape biopsies and processing TEMs in a centralized laboratory. We enrolled patients with suspected PCD at research sites of the Genetic Disorders of Mucociliary Clearance Consortium. Biopsies were performed according to a SOP whereby curettes were used to scrape the inferior surface of the inferior turbinate, with samples placed in fixative. Specimens were shipped to a central laboratory where TEMs were prepared and blindly reviewed. Four hundred forty-eight specimens were obtained from 107 young children (0-5 years), 189 older children (5-18 years), and 152 adults (> 18 years), and 88% were adequate for formal interpretation. The proportion of adequate specimens was higher in adults than in children. Fifty percent of the adequate TEMs showed normal ciliary ultrastructure, 39% showed hallmark ultrastructural changes of PCD, and 11% had indeterminate findings. Among specimens without clearly normal ultrastructure, 72% had defects of the outer and/or inner dynein arms (IDA), while 7% had central apparatus defects with or without IDA defects. In summary, nasal scrape biopsies can be performed in the outpatient setting and yield interpretable samples, when performed by individuals with adequate training and experience according to an SOP.


Sequencing and analysis of full-length cDNAs, 5'-ESTs and 3'-ESTs from a cartilaginous fish, the elephant shark (Callorhinchus milii).
Cartilaginous fishes are the most ancient group of living jawed vertebrates (gnathostomes) and are, therefore, an important reference group for understanding the evolution of vertebrates. The elephant shark (Callorhinchus milii), a holocephalan cartilaginous fish, has been identified as a model cartilaginous fish genome because of its compact genome (∼910 Mb) and a genome project has been initiated to obtain its whole genome sequence. In this study, we have generated and sequenced full-length enriched cDNA libraries of the elephant shark using the 'oligo-capping' method and Sanger sequencing. A total of 6,778 full-length protein-coding cDNA and 10,701 full-length noncoding cDNA were sequenced from six tissues (gills, intestine, kidney, liver, spleen, and testis) of the elephant shark. Analysis of their polyadenylation signals showed that polyadenylation usage in elephant shark is similar to that in mammals. Furthermore, both coding and noncoding transcripts of the elephant shark use the same proportion of canonical polyadenylation sites. Besides BLASTX searches, protein-coding transcripts were annotated by Gene Ontology, InterPro domain, and KEGG pathway analyses. By comparing elephant shark genes to bony vertebrate genes, we identified several ancient genes present in elephant shark but differentially lost in tetrapods or teleosts. Only ∼6% of elephant shark noncoding cDNA showed similarity to known noncoding RNAs (ncRNAs). The rest are either highly divergent ncRNAs or novel ncRNAs. In addition to full-length transcripts, 30,375 5'-ESTs and 41,317 3'-ESTs were sequenced and annotated. The clones and transcripts generated in this study are valuable resources for annotating transcription start sites, exon-intron boundaries, and UTRs of genes in the elephant shark genome, and for the functional characterization of protein sequences. These resources will also be useful for annotating genes in other cartilaginous fishes whose genomes have been targeted for whole genome sequencing.


Taxonomic use of DNA G+C content and DNA-DNA hybridization in the genomic age.
The G+C content of a genome is frequently used in taxonomic descriptions of species and genera. In the past it has been determined using conventional, indirect methods, but it is nowadays reasonable to calculate the DNA G+C content directly from the increasingly available and affordable genome sequences. The expected increase in accuracy, however, might alter the way in which the G+C content is used for drawing taxonomic conclusions. We here re-estimate the literature assumption that the G+C content can vary up to 3-5 % within species using genomic datasets. The resulting G+C content differences are compared with DNA-DNA hybridization (DDH) similarities calculated in silico using the GGDC web server, with 70% similarity as the gold standard threshold for species boundaries. The results indicate that the G+C content, if computed from genome sequences, varies no more than 1% within species. Statistical models based on larger differences alone can reject the hypothesis that two strains belong to the same species. Because DDH similarities between two non-type strains occur in the genomic datasets, we also examine to what extent and under which conditions such a similarity could be <70% even though the similarity of either strain to a type strain was ≥ 70%. In theory, their similarity could be as low as 50%, whereas empirical data suggest a boundary closer (but not identical) to 70%. However, it is shown that using a 50% boundary would not affect the conclusions regarding the DNA G+C content. Hence, we suggest that discrepancies between G+C content data provided in species descriptions on the one hand and those recalculated after genome sequencing on the other hand ≥ 1% are due to significant inaccuracies of the applied conventional methods and accordingly call for emendations of species descriptions.


The Treatment Advocacy Program: a randomized controlled trial of a peer-led safer sex intervention for HIV-infected men who have sex with men.
Primary care may be an effective venue for delivering behavioral interventions for sexual safety among HIV-positive men who have sex with men (MSM); however, few studies show efficacy for such an approach. We tested the efficacy of the Treatment Advocacy Program (TAP), a 4-session, primary-care-based, individual counseling intervention led by HIV-positive MSM "peer advocates" in reducing unprotected sex with HIV-negative or unknown partners (HIV transmission risk). We randomized 313 HIV-positive MSM to TAP or standard care. HIV transmission risk was assessed at baseline, 6 months, and 12 months (251 participants completed all study waves). We conducted intent-to-treat analyses using general estimating equations to test the interaction of group (TAP vs. standard care) by follow-up period. At study completion, TAP participants reported greater transmission risk reduction than did those receiving standard care, χ2(2, N = 249) = 6.6, p = .04. Transmission risk among TAP participants decreased from 34% at baseline to about 20% at both 6 and 12 months: Transmission risk ranged from 23% to 25% among comparison participants. TAP reduced transmission risk among HIV-positive MSM, although results are modest. Many participants and peer advocates commented favorably on the computer structure of the program. We feel that the key elements of TAP-computer-based and individually tailored session content, delivered by peers, in the primary care setting-warrant further exploration.


[The scanner and the temporomandibular joint; anatomic-radiologic comparisons. Apropos of 26 cases of masticatory apparatus pain-dysfunction syndrome].
Among 500 CT scan of temporomandibular joint (TMJ), examined since 1982 by bilateral direct sagittal method (Department of Radiology, Pr. A. Treheux, C.H.U. Nancy-Brabois), the authors have retained 14 cases of patients with symptoms related to TMJ's dysfunction cured by surgery (Department of Maxillo Facial Surgery, Pr. Stricker, C.H.U. Nancy). These cases were chosen among a hundred of patients annually examined by CT scan, for various diseases (TMJ's dysfunctions, traumatisms, infections, inflammatory diseases...) These correlations between radiology and surgery about 26 TMJ (2 patients underwent surgery only on one side) were: an accuracy with surgical findings for 19 cases (76%); in 6 cases (23%), a meniscus anteriorly displaced, non detected by CT scan was found by surgery; 2 cases of meniscus perforations (one in the frontal plane, the other sagittal) were surgical findings; in 1 case, a displacement was under-valued by CT scan; in 3 cases, arthrotic changes (1 case of Reiter syndrome) were characterized by CT scan. The authors emphasize the value and the limits of evaluation of the internal derangements of the TMJ with direct sagittal CT.


Quantifying photothermal heating at plasmonic nanoparticles by scanning electrochemical microscopy.
Photothermal heating at metal nanoparticles results from the non-radiative decay of localized surface plasmons. The local heat generation enhances the mass transport rate of redox molecules and causes a shift in their formal potential, both of which can impact an electrochemical process at the nanoparticle interface. Here we present a methodology for probing the surface temperature at a plasmonic nanoparticle substrate using scanning electrochemical microscopy (SECM). Light is used to excite a plasmonic substrate electrode, while an ultramicroelectrode tip is positioned close to the substrate to read out both the mass transfer rate and concentration profile of the redox molecules. The measured mass transfer rate and the shift in the equilibrium potential provide a quantitative value of the temperature increase at the substrate surface, which is verified by simulations using a mass transfer model coupled with heat dissipation. The developed SECM approach is suitable for probing heat generation at a variety of both plasmonic and non-plasmonic nanostructures.


Dual origin of tissue-specific progenitor cells in Drosophila tracheal remodeling.
During Drosophila metamorphosis, most larval cells die. Pupal and adult tissues form from imaginal cells, tissue-specific progenitors allocated in embryogenesis that remain quiescent during embryonic and larval life. Clonal analysis and fate mapping of single, identified cells show that tracheal system remodeling at metamorphosis involves a classical imaginal cell population and a population of differentiated, functional larval tracheal cells that reenter the cell cycle and regain developmental potency. In late larvae, both populations are activated and proliferate, spread over and replace old branches, and diversify into various stalk and coiled tracheolar cells under control of fibroblast growth factor signaling. Thus, Drosophila pupal/adult tissue progenitors can arise both by early allocation of multipotent cells and late return of differentiated cells to a multipotent state, even within a single tissue.