Mapping of spatiotemporal heterogeneous particle dynamics in living cells.
Colloidal particles embedded in the cytoplasm of living mammalian cells have been found to display remarkable heterogeneity in their amplitude of motion. However, consensus on the significance and origin of this phenomenon is still lacking. We conducted experiments on Hmec-1 cells loaded with about 100 particles to reveal the intracellular particle dynamics as a function of both location and time. Central quantity in our analysis is the amplitude (A) of the individual mean-squared displacement (iMSD), averaged over a short time. Histograms of A were measured, (1) over all particles present at the same time and (2) for individual particles as a function of time. Both distributions showed significant broadening compared to particles in Newtonian liquid, indicating that the particle dynamics varies with both location and time. However, no systematic dependence of A on intracellular location was found. Both the (strong) spatial and (weak) temporal variations were further analyzed by correlation functions of A . Spatial cross correlations were rather weak down to interparticle distances of 1 microm , suggesting that the precise intracellular probe distribution is not crucial for observing a dynamic behavior that is representative for the whole cell. Temporal correlations of A decayed at approximately 10 s , possibly suggesting an intracellular reorganization at this time scale. These findings imply (1) that both individual particle dynamics and the ensemble averaged behavior in a given cell can be measured if there are enough particles per cell and (2) that the amplitude and power-law exponent of iMSDs can be used to reveal local dynamics. We illustrate this by showing how superdiffusive and subdiffusive behaviors may be hidden under an apparently diffusive global dynamics.


Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature.
Epstein-Barr virus (EBV) is an important human pathogen; it infects >90% people globally and is linked to infectious mononucleosis and several types of cancer. Vaccines against EBV are in development. In this study we present the first systematic review of the literature on risk factors for EBV infection, and discuss how they differ between settings, in order to improve our understanding of EBV epidemiology and aid the design of effective vaccination strategies. MEDLINE, Embase, and Web of Science were searched on 6th March 2017 for observational studies of risk factors for EBV infection. Studies were excluded if they were published before 2008 to ensure relevance to the modern day, given the importance of influencing future vaccination policies. There were no language restrictions. After title, abstract and full text screening, followed by checking the reference lists of included studies to identify further studies, data were extracted into standardised spreadsheets and quality assessed. A narrative synthesis was undertaken. Seventy-seven papers met our inclusion criteria, including data from 31 countries. There was consistent evidence that EBV seroprevalence was associated with age, increasing throughout childhood and adolescence and remaining constant thereafter. EBV was generally acquired at younger ages in Asia than Europe/North America. There was also compelling evidence for an association between cytomegalovirus infection and EBV. Additional factors associated with EBV seroprevalence, albeit with less consistent evidence, included ethnicity, socioeconomic status, other chronic viral infections, and genetic variants of HLA and immune response genes. Our study is the first systematic review to draw together the global literature on the risk factors for EBV infection and includes an evaluation of the quality of the published evidence. Across the literature, the factors examined are diverse. In Asia, early vaccination of infants would be required to prevent EBV infection. In contrast, in Western countries a vaccine could be deployed later, particularly if it has only a short duration of protection and the intention was to protect against infectious mononucleosis. There is a lack of high-quality data on the prevalence and age of EBV infection outside of Europe, North America and South-East Asia, which are essential for informing effective vaccination policies in these settings.


Calcium modulates endopeptidase 24.15 (EC 18.104.22.168) membrane association, secondary structure and substrate specificity.
The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the extracellular environment as a secreted protein. Outside the cell, this enzyme degrades several neuropeptides containing from 5 to 17 amino acids (e.g. gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be stimulated linearly by reduced concentrations of extracellular calcium. In the present report we demonstrate that extracellular calcium concentration has no effect on the total amount of the extracellular (cell associated + medium) enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy suggested that the absence of calcium favors the enzyme shedding from the plasma membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and D159) were altered by site-directed mutagenesis to investigate their possible contribution to binding of the enzyme at the cell surface. These mutated recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. However, immunocytochemical analyses by confocal microscopy consistently show a reduced ability of the D93A mutant to associate with the plasma membrane of glioma C6 cells when compared with the wild-type enzyme. These data and the model of the enzyme's structure as determined by X-ray diffraction suggest that D93 is located at the enzyme surface and is consistent with membrane association of EP24.15. Moreover, calcium was also observed to induce a major change in the EP24.15 cleavage site on distinctive fluorogenic substrates. These data suggest that calcium may be an important modulator of ep24.15 cell function.


Role of the substantia nigra pars reticulata in sleep-wakefulness: A review of research progress.
Sleep is a complex physiological process that includes two main stages: non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. During mammalian sleep, especially REM sleep, skeletal muscles are suppressed to varying degrees, and corresponding movements are inhibited. The synchronous occurrence of sleep and motor inhibition suggests they may share the same neural circuits. Recently, the substantia nigra pars reticulata (SNr) has attracted attention for its potential dual role in regulating sleep-wake cycles and movement. In this review, the SNr's role is surveyed by examining existing research reports regarding its involvement in sleep-wake regulation and motor control. By focusing on the SNr, the goal is to shed light on its dual role intricacies and stimulate further inquiry into potential interactions between sleep and movement regulation, thus aiming to explore sleep-wake regulatory mechanisms and offer novel directions for subsequent scientific investigation.


Arthrographic distension for adhesive capsulitis (frozen shoulder).
Adhesive capsulitis (frozen shoulder or painful stiff shoulder) is characterised by spontaneous onset of shoulder pain accompanied by progressive stiffness and disability. It is usually self-limiting but often has a prolonged course over two to three years. To determine the effectiveness and safety of arthrographic distension of the glenohumeral joint in the treatment of adults with adhesive capsulitis. We searched the Cochrane Musculoskeletal Review Group Register, CENTRAL, MEDLINE, CINAHL, and EMBASE to November 2006, unrestricted by date or language. We included randomised controlled trials and controlled clinical trials comparing arthrographic distension with placebo or other interventions. Two review authors independently assessed study quality and extracted data. Five trials with 196 people were included. One three-arm trial (47 participants) compared arthrographic distension using steroid and air to distension using air alone and to steroid injection alone. One trial (46 participants) compared arthrographic distension using steroid and saline to placebo. Two trials (45 and 22 participants) compared arthrographic distension using steroid to steroid injection alone. One trial (36 participants) compared arthrographic distension using steroid and saline plus physical therapy to physical therapy alone. Trials included similar study participants, but quality and reporting of data were variable. Only one trial was at low risk of bias. No meta-analysis was performed.The trial with low risk of bias demonstrated that distension with saline and steroid was better than placebo for pain (number needed to treat to benefit (NNTB) = 2), function (NNTB = 3) and range of movement at three weeks. This benefit was maintained at six and 12 weeks only for one of two scores measuring function (NNT = 3). A second trial with high risk of bias also reported that distension combined with physical therapy improved range of movement and median percent improvement in pain (but not pain score) at eight weeks compared to physical therapy alone. Three further trials, all at high risk of bias, reported conflicting, variable effects of arthrographic distension with steroid compared to distension alone, and arthrographic distension with steroid compared to intra-articular steroid injection. The trials reported a small number of minor adverse effects, mainly pain during and after the procedure. There is "silver" level evidence that arthrographic distension with saline and steroid provides short-term benefits in pain, range of movement and function in adhesive capsulitis. It is uncertain whether this is better than alternative interventions.


Airborne contaminants and farmers health in swine farms with high and low prevalence of respiratory diseases in pigs.
The main purpose of this study was to investigate the relationship between prevalence of respiratory disease in swine and respiratory health of swine farmers. Fourteen farms were selected based on clinical history and slaughtercheck evidence of respiratory problems in pigs. The farms were divided into two groups with either high (n = 7) or low (n = 7) prevalence of respiratory disease in pigs. Airborne dust, endotoxin and peptidoglycan were measured once in farrowing, gestation, nursery and finishing of each farm. Respiratory health of farmers in participating farms was evaluated by questionnaire and pulmonary function test. A mean of 71% of the pigs in high prevalence farms had pneumonic lesions at slaughter, compared with 7% in low prevalence farms. No significant relationship was found between prevalence of respiratory disease in pigs and airborne dust, endotoxin or peptidoglycan. More farmers in high prevalence farms reported chest tightness (p = 0.038). The percentage predicted FEF 25%-75%; was lower (p = 0.046) in farmers working in high prevalence farms. Significant differences disappeared after adjusting for smoking status. Our study suggests that farmers working on farms with a high prevalence for respiratory disease in pigs may have more respiratory problems than farmers working in farms with low prevalence of such diseases.


The CD95/CD95L signaling pathway: a role in carcinogenesis.
Apoptosis is a fundamental process that contributes to tissue homeostasis, immune responses, and development. The receptor CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNF-R) superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance, and various lineages of malignant cells exhibit loss-of-function mutations in this pathway; therefore, CD95 was initially classified as a tumor suppressor gene. However, more recent data indicate that in different pathophysiological contexts, this receptor can transmit non-apoptotic signals, promote inflammation, and contribute to carcinogenesis. A comparison with the initial molecular events of the TNF-R signaling pathway leading to non-apoptotic, apoptotic, and necrotic pathways reveals that CD95 is probably using different molecular mechanisms to transmit its non-apoptotic signals (NF-κB, MAPK, and PI3K). As discussed in this review, the molecular process by which the receptor switches from an apoptotic function to an inflammatory role is unknown. More importantly, the biological functions of these signals remain elusive.


Simultaneous expression of salivary and pancreatic amylase genes in cultured mouse hepatoma cells.
The tissue-specific expression of two types of mouse amylase genes does not overlap in vivo; the Amy-1 locus is transcribed in the parotid gland and the liver, while expression of Amy-2 is limited to the pancreas. We identified a mouse hepatoma cell line, Hepa 1-6, in which both amylase genes can be simultaneously expressed. Amy-1 is constitutively active in these cells and is inducible by dexamethasone at the level of mRNA. We demonstrated that the liver-specific promoter of Amy-1 is utilized by the dexamethasone-treated hepatoma cells, and that glucocorticoid consensus sequences are present upstream of this promoter. Amy-2 is not detectable constitutively, but can be activated if the cells are cultured in serum-free medium containing dexamethasone. Expression of Amy-2 in a nonpancreatic cell type has not previously been observed. We speculate that induction of Amy-1 and activation of Amy-2 may involve different regulatory mechanisms. Hepa 1-6 cells provide an experimental system for molecular analysis of these events.


A Concept Analysis of Resilience Integrating Genetics.
Although clinicians and researchers are interested in the phenomenon of resilience, there is no agreed-upon definition of resilience. Scientific evidence suggests that resilience is influenced by intrapersonal (e.g. personality traits) and environmental (e.g. social support) variables. A concept analysis was conducted to better understand the meaning of resilience. In this analysis, the antecedent of resilience was a potentially traumatic event; the defining attributes were ego-resiliency, emotion regulation, social support, and heredity; and the consequences were none to mild psychopathological symptoms and positive adaptation. This analysis can help nurses better understand resilience and its relationships to both intrapersonal and environmental variables.


Effects of thermal processing on digestion stability and immunoreactivity of the Litopenaeus vannamei matrix.
Many types of shellfish, including shrimp, are sometimes cooked before ingestion. Hence, it is necessary to investigate how cooking (boiling, pressure treatment or none (raw)) affects the structure, digestibility and immunoreactivity of multi-component shrimp muscle. Protein extraction, simulated gastrointestinal digestion, immunoreactivity, immunoglobulin E (IgE)-mediated human mast cell degranulation, morphology, particle size and UV absorbance scanning were used to investigate changes in the shrimp muscle upon treatment. The extractability of proteins and allergens was highest with 0.5 mol L-1 NaCl. Pressure treatment increased the digestibility and reduced the immunoreactivity of shrimp edible portions. Thermal processing induced the production of regular fiber bundles, blue shifts of absorbance peaks and reduction of particle size in the complex food matrix. These changes in macro- and micro-structure can further affect gastrointestinal digestibility and immunoreactivity due to the interactions between multiple components in the whole food. In conclusion, the digestibility, immunoreactivity and structure were altered by thermal processing of the complex food matrix.


Da Vinci's yeast: Blastobotrys davincii f.a., sp. nov.
A new species of the yeast genus Blastobotrys was discovered during a worldwide survey of culturable xerophilic fungi in house dust. Several culture-dependent and independent studies from around the world detected the same species from a wide range of substrates including indoor air, cave wall paintings, bats, mummies, and the iconic self-portrait of Leonardo da Vinci from ca 1512. However, none of these studies identified their strains, clones, or OTUs as Blastobotrys. We introduce the new species as Blastobotrys davincii f.a., sp. nov. (holotype CBS H-24879) and delineate it from other species using morphological, phylogenetic, and physiological characters. The new species of asexually (anamorphic) budding yeast is classified in Trichomonascaceae and forms a clade along with its associated sexual state genus Trichomonascus. Despite the decade-old requirement to use a single generic name for fungi, both names are still used. Selection of the preferred name awaits a formal nomenclatural proposal. We present arguments for adopting Blastobotrys over Trichomonascus and introduce four new combinations as Blastobotrys allociferrii (≡ Candida allociferrii), B. fungorum (≡ Sporothrix fungorum), B. mucifer (≡ Candida mucifera), and Blastobotrys vanleenenianus (≡ Trichomonascus vanleenenianus). We provide a nomenclatural review and an accepted species list for the 37 accepted species in the Blastobotrys/Trichomonascus clade. Finally, we discuss the identity of the DNA clones detected on the da Vinci portrait, and the importance of using appropriate media to isolate xerophilic or halophilic fungi.


Surface-specific deposition of catalytic metal nanocrystals on hollow carbon nanospheres via galvanic replacement reactions of carbon-encapsulated MnO nanoparticles.
This paper reports the findings of our efforts toward gaining a more complete understanding and utilization of galvanic replacement reactions involving manganese oxide with noble metals. It was revealed that the site of metal deposition is significantly affected by the variable oxidation state of manganese oxide. The use of carbon-encapsulated MnO nanoparticles as a reaction template led to metal growth specifically on the outermost surfaces of the carbon shells rather than on the MnO cores, which allowed for the selective decoration of the external surfaces of hollow carbon nanospheres with catalytic nanocrystals of various noble metals, including Pt, Pd, Rh, and Ir. By rearranging the sequence between carbon-shell coating and galvanic replacement processes, the deposited metal nanocrystals could be placed on the interior surfaces of hollow carbon nanospheres and, moreover, separately on the internal and the external surfaces, which may enable the respective control of the catalytic functionalities of each specific surface.


Factors predicting doctors' reporting of performance change in response to multisource feedback.
Multi-source feedback (MSF) offers doctors feedback on their performance from peers (medical colleagues), coworkers and patients. Researchers increasingly point to the fact that only a small majority of doctors (60-70 percent) benefit from MSF. Building on medical education and social psychology literature, the authors identified several factors that may influence change in response to MSF. Subsequently, they quantitatively studied the factors that advance the use of MSF for practice change. This observational study was set in 26 non-academic hospitals in the Netherlands. In total, 458 specialists participated in the MSF program. Besides the collation of questionnaires, the Dutch MSF program is composed of a reflective portfolio and a facilitative interview aimed at increasing the acceptance and use of MSF. All specialists who finished a MSF procedure between May 2008 and September 2010 were invited to complete an evaluation form. The dependent variable was self-reported change. Three categories of independent variables (personal characteristics, experiences with the assessments and mean MSF ratings) were included in the analysis. Multivariate regression analysis techniques were used to identify the relation between the independent variables and specialists' reported change in actual practice. In total, 238 medical specialists (response rate 52 percent) returned an evaluation form and participated in the study. A small majority (55 percent) of specialists reported to have changed their professional performance in one or more aspects in response to MSF. Regression analyses revealed that two variables had the most effect on reported change. Perceived quality of mentoring positively influenced reported change (regression coefficient beta = 0.527, p < 0.05) as did negative scores offered by colleagues. (regression coefficient beta = -0.157, p < 0.05). The explained variance of these two variables combined was 34 percent. Perceived quality of mentoring and MSF ratings from colleagues seem to be the main motivators for the self-reported change in response to MSF by specialists. These insights could leverage in increasing the use of MSF for practice change by investing in the quality of mentors.


Multi-site study of surgical practice in neurosurgery based on surgical process models.
Surgical Process Modelling (SPM) was introduced to improve understanding the different parameters that influence the performance of a Surgical Process (SP). Data acquired from SPM methodology is enormous and complex. Several analysis methods based on comparison or classification of Surgical Process Models (SPMs) have previously been proposed. Such methods compare a set of SPMs to highlight specific parameters explaining differences between populations of patients, surgeons or systems. In this study, procedures performed at three different international University hospitals were compared using SPM methodology based on a similarity metric focusing on the sequence of activities occurring during surgery. The proposed approach is based on Dynamic Time Warping (DTW) algorithm combined with a clustering algorithm. SPMs of 41 Anterior Cervical Discectomy (ACD) surgeries were acquired at three Neurosurgical departments; in France, Germany, and Canada. The proposed approach distinguished the different surgical behaviors according to the location where surgery was performed as well as between the categorized surgical experience of individual surgeons. We also propose the use of Multidimensional Scaling to induce a new space of representation of the sequences of activities. The approach was compared to a time-based approach (e.g. duration of surgeries) and has been shown to be more precise. We also discuss the integration of other criteria in order to better understand what influences the way the surgeries are performed. This first multi-site study represents an important step towards the creation of robust analysis tools for processing SPMs. It opens new perspectives for the assessment of surgical approaches, tools or systems as well as objective assessment and comparison of surgeon's expertise.


Design of thermal wind sensor with constant power control and wind vector measurement method.
This paper presents a conceptual wind vector detector for measuring the velocity and direction of wind in enclosed or semi-enclosed large spaces. Firstly, a thermal wind sensor with constant power control was manufactured and then used as a wind velocity sensing unit. Secondly, a sensor bracket equipped with three thermal wind sensors was designed, the fluid dynamic response regularity of the measured wind field to the sensor bracket was analyzed using ANSYS Fluent CFD software, and then its structural parameters were optimized to improve measurement accuracy. The sensor bracket was fabricated via 3D printing. Finally, a unique wind vector measurement method was developed for the wind vector detector. Experimental results showed that the measured velocity range of the thermal wind sensor satisfied the requirements of being within 0-15 m/s with an accuracy of ±0.3 m/s, and the wind direction angle range of the wind vector detector was within 0-360° with an accuracy of ±5°. By changing the applied power control value of the thermal wind sensor and structural parameters of the sensor bracket, the measurement range and accuracy of the wind vector detector can be adjusted to suit different applications.


Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis.
The comparative risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving tenofovir disoproxil fumarate (TDF) vs. entecavir (ETV) remains controversial. In this individual patient data (IPD) meta-analysis, we aimed to compare HCC risk between the two drugs and identify subgroups who may benefit more from one treatment than the other. Published meta-analyses, electronic databases and congress proceedings were searched to identify eligible studies through January 2021. We compared HCC risk between the two drugs using a multivariable Cox proportional hazards model with anonymised IPD from treatment-naïve patients with CHB receiving TDF or ETV for ≥1 year. Treatment effect consistency was explored in propensity score matching (PSM), weighting (PSW) and subgroup analyses for age, sex, hepatitis B e-antigen (HBeAg) positivity, cirrhosis and diabetes status. We included 11 studies from Korea, Taiwan and Hong Kong involving 42,939 patients receiving TDF (n = 6,979) or ETV (n = 35,960) monotherapy. Patients receiving TDF had significantly lower HCC risk (adjusted hazard ratio [HR] 0.77; 95% CI 0.61-0.98; p = 0.03). Lower HCC risk with TDF was consistently observed in PSM (HR 0.73; 95% CI 0.59-0.88; p <0.01) and PSW (HR 0.83; 95% CI 0.67-1.03; p = 0.10) analyses and in all subgroups, with statistical significance in the ≥50 years of age (HR 0.76; 95% CI 0.58-1.00; p <0.05), male (HR 0.74; 95% CI 0.58-0.96; p = 0.02), HBeAg-positive (HR 0.69; 95% CI 0.49-0.97; p = 0.03) and non-diabetic (HR 0.79; 95% CI 0.63-1.00; p <0.05) subgroups. TDF was associated with significantly lower HCC risk than ETV in patients with CHB, particularly those with HBeAg positivity. Longer follow-up may be needed to better define incidence differences between the treatments in various subgroups. Previous aggregate data meta-analyses have reported inconsistent conclusions on the relative effectiveness of tenofovir disoproxil fumarate and entecavir in reducing hepatocellular carcinoma risk in patients with chronic hepatitis B (CHB). This individual patient data meta-analysis on 11 studies involving 42,939 patients from Korea, Taiwan and Hong Kong suggested that tenofovir disoproxil fumarate-treated patients have a significantly lower hepatocellular carcinoma risk than entecavir-treated patients, which was observed in all subgroups of clinical interest and by different analytical methodologies. These findings should be taken into account by healthcare providers when determining the optimal course of treatment for patients with CHB and may be considered in ensuring that treatment guidelines for CHB remain pertinent.


Alpha-band Activity Tracks the Zoom Lens of Attention.
Voluntary control over spatial attention has been likened to the operation of a zoom lens, such that processing quality declines as the size of the attended region increases, with a gradient of performance that peaks at the center of the selected area. Although concurrent changes in activity in visual regions suggest that zoom lens adjustments influence perceptual stages of processing, extant work has not distinguished between changes in the spatial selectivity of attention-driven neural activity and baseline shift of activity that can increase mean levels of activity without changes in selectivity. Here, we distinguished between these alternatives by measuring EEG activity in humans to track preparatory changes in alpha activity that indexed the precise topography of attention across the possible target positions. We observed increased spatial selectivity in alpha activity when observers voluntarily directed attention toward a narrower region of space, a pattern that was mirrored in target discrimination accuracy. Thus, alpha activity tracks both the centroid and spatial extent of covert spatial attention before the onset of the target display, lending support to the hypothesis that narrowing the zoom lens of attention shapes the initial encoding of sensory information.


Nimesulide for treatment of acute inflammation of the upper respiratory tract.
In a double-blind, parallel four-day trial with 51 patients, the anti-inflammatory, antiexudative, and antipyretic effects of nimesulide were compared with placebo in patients with acute inflammation of the upper respiratory tract. Patients who received nimesulide showed improvement in the signs and symptoms evaluated: pharyngeal redness, tonsillar redness, tonsillar swelling, hoarseness, sore throat, headache, and arthralgia. A statistically significant difference between nimesulide and placebo was evident for all parameters (P less than 0.01). The global use rating of the two drugs showed that nimesulide was useful in 22 (92%) of 24 patients and that placebo was useful in four (16%) of 25 patients (P less than 0.01). There were no side effects associated with nimesulide; one placebo-treated patient had diarrhea and withdrew from the study, and one nimesulide-treated patient withdrew for nonmedical reasons. No variations in laboratory tests were noted.


An association analysis between a silent C558T polymorphism at the pig vascular cell adhesion molecule 1 locus and sow reproduction and piglet survivability traits.
The vascular cell adhesion molecule 1 (VCAM1) has a strong influence on embryonic development and on the formation of the umbilical cord and placenta. These developmental processes are crucial to ensure the success of pregnancy. In this work, we have identified two T306A and C558T single nucleotide polymorphisms (SNP) at exons 2 and 3 of the pig VCAM1 locus, respectively. The T306A substitution involves a non conservative Asn to Lys replacement at amino acid position 102, whereas the C558T polymorphism is synonymous. An in silico prediction of the consequences of the Asn(102)-->Lys(102) mutation with the PolyPhen software revealed that it is not deleterious. The T306A SNP segregated in the Iberian, Piétrain, Duroc, Large White and Landrace breeds as well as in European wild boars. The C558T SNP also segregated and most of commercial standard breeds. The genotyping of the C558T SNP in an Iberian x Meishan intercross allowed to find a suggestive association (Bonferroni threshold, p < 0.004) between C558T genotype and time the newborn piglet needs to reach the udder (p = 0.013) as well as a significant one with time to make the first ingestion of colostrum (p = 0.003). The biological basis of these associations remains unclear and they should be interpreted with caution.


Detection of fusobacterium nucleatum and fadA adhesin gene in patients with orthodontic gingivitis and non-orthodontic periodontal inflammation.
Fusobacterium nucleatum is one of the most abundant gram-negative bacilli colonizing the subgingival plaque and closely associated with periodontal disease. However it is unclear whether F. nucleatum is involved in gingival inflammation under orthodontic appliance. A novel adhesin, FadA, which is unique to oral Fusobacteria, is required for F. nucleatum binding and invasion to epithelial cells and thus may play an important role in colonization of Fusobacterium in the host. In this study, we evaluated the prevalence of F. nucleatum and its virulence factor FadA adhesion gene (fadA) in 169 subgingival biofilm samples from 55 cases of gingivitis patients with orthodontic appliances, 49 cases of gingivitis patients without orthodontic treatment, 35 cases of periodontitis patients and 30 cases of periodontally healthy people via PCR. The correlations between the F. nucleatum/fadA and gingivitis index(GI)was also analyzed. The detection rate of F. nucleatum/fadA in periodontitis group and non-orthodontic gingivitis group was higher than the other two groups (p<0.01) while it was higher in orthodontic gingivitis group than in health people (p<0.05). An obviously positive correlation was observed between the prevalence of F. nucleatum/fadA and GI. F. nucleatum carrying fadA may be more closely related to the development of gingivitis and periodontal disease compared with orthodontic gingivitis.


Two different methods for numerical solution of the modified Burgers' equation.
A numerical solution of the modified Burgers' equation (MBE) is obtained by using quartic B-spline subdomain finite element method (SFEM) over which the nonlinear term is locally linearized and using quartic B-spline differential quadrature (QBDQM) method. The accuracy and efficiency of the methods are discussed by computing L 2 and L ∞ error norms. Comparisons are made with those of some earlier papers. The obtained numerical results show that the methods are effective numerical schemes to solve the MBE. A linear stability analysis, based on the von Neumann scheme, shows the SFEM is unconditionally stable. A rate of convergence analysis is also given for the DQM.


Diphyllobothrium nihonkaiense infection linked to chilled salmon consumption.
This is a case of a 40-year-old Japanese adult male who had acute onset watery diarrhoea with intermittent abdominal discomfort. Several days later, he found a 1 metre of tape-shaped object emerged from his anus and was eventually admitted to our hospital for further investigation. Stool examination revealed eggs of Diphyllobothrium with characteristic shape in his stool. After oral praziquantel administration, segments of proglottids were expelled from his anus. The proglottids were sent to the Infectious Disease Surveillance Centre of Japan, and DNA analysis of the proglottids proved to be those of Diphyllobothrium nihonkaiense. The patient confessed that he had an eating habit of chilled salmon. His diarrhoea and abdominal discomfort were completely diminished after 1 day of oral praziquantel administration. He was successfully discharged from the hospital a few days later admission without any complication of the disease and the side effect of treatment.


NACOB presentation Keynote lecture. Cancellous bone biomechanics. North American Congress on Biomechanics.
Cancellous bone is both a biological and a mechanical structure. The interaction between these two aspects of cancellous bone is sufficiently strong that understanding the mechanical properties of the tissue is not possible without consideration of the biology. This manuscript is a mathematical expansion of a portion of the first author's Keynote lecture at the 1998 NACOB presentation. The cellular activity of cancellous bone proceeds in part by the transport of metabolites between trabecular hard tissue and marrow. The anatomical observation is that human trabeculae are seldom internally served by a blood supply, suggesting that the transport mechanisms for trabecular survival are diffusion and a collection of mechanisms for active transport of metabolites independent of blood flow. It will be demonstrated that metabolite transport by diffusion can explain two notable empirical relationships for bone: (a) the close relationship between the bone surface and the bone volume, and (b) the exponential decline in the bone volume fraction during periods of mechanical disuse. A mathematical model is also developed showing how mechanical loading can effect bone volume fraction by increasing metabolite transport between the tissue compartments.


Ambulatory 24-hour blood pressure monitoring: correlation between blood pressure variability and left ventricular hypertrophy in untreated hypertensive patients.
Left ventricular hypertrophy (LVH) appears to be poorly correlated with clinical measurements of blood pressure: a better correlation may be observed with data from 24 h ambulatory blood pressure monitoring (ABPM). The aim of this study was to compare the results of non-invasive ABPM in a population of patients with essential hypertension who had never been treated, subdividing them based on the presence or absence of LVH in the transthoracic echocardiogram (LVMI, left ventricular mass index > 135 g/m2 in males and > 110 g/m2 in females). Eighty hypertensive patients with mild or moderate hypertension underwent routine blood tests, a 24 h ABPM and a transthoracic echocardiogram. Based on the ABPMs, we analyzed average 24 h systolic and diastolic blood pressure (BP), average daytime (6 a.m.-10 p.m.) and nighttime (10 p.m.-6 a.m.) systolic and diastolic BP, average morning (6-12 a.m.) BP and the number of dipper or non-dipper patients. The echocardiographic study included the calculation of left ventricular mass using Devereux's formula according to the Penn convention, analysis of the patterns of left ventricular geometry and a study of left ventricular diastolic function. Thirty-five (43.7%) patients had LVH at the echocardiographic study. In 52 subjects, the clinical history showed at least one BP measurement > 140/90 mmHg in the year prior to our observation. The average age was 48 +/- 11, without any significant correlation to LVMI (r = 0.13). The magnitude of the S-wave in V1 and the R-wave in V5 and the magnitude of the tallest R-wave and S-wave in the electrocardiogram analysis had a significant correlation with LVMI (r = 0.23 and r = 0.26, respectively). The echocardiogram revealed a normal left ventricular geometry in 43.8% of hypertensive patients, concentric remodeling in 13.8%, concentric hypertrophy in 16.2% and eccentric hypertrophy in 26.2%. The isovolumic relaxation time (IVRT) and A-wave were significantly correlated with LVMI (r = 0.49 and r = 0.33, respectively). LVMI had a significant correlation with systolic BP at ABPM (24 h systolic BP r = 0.34; daytime systolic BP r = 0.35; nighttime systolic BP r = 0.28; 6-12 systolic BP r = 0.29) but not with diastolic BP. Dipper patients represented 76.3% of the population, without any difference in LVMI between dippers and non-dippers (p = 0.09). Dipper patients had a higher prevalence of normal left ventricles as compared with non-dippers (p < 0.0001). White-coat hypertension was observed in 7.5% of hypertensive patients. The prevalence of LVH in our population was high (43.7%) and some parameters related to diastolic left ventricular function (IVRT, A-wave) were correlated with LVMI. Systolic ambulatory BP was significantly correlated with LVMI, while diastolic BP was not.


What Do Adults with Type 2 Diabetes Want from the "Perfect" App? Results from the Second Diabetes MILES: Australia (MILES-2) Study.
Background: We investigated what Australian adults with type 2 diabetes (T2D) want from the "perfect" diabetes self-management application. Methods: Adults with T2D completed a national online survey including an open-ended question: "If you were describing the perfect app to help you manage your diabetes, what would it do?" Qualitative responses were subjected to thematic analysis. Results: Of the 339 participants who provided usable responses, 153 (45%) were women, the mean age was 58 ± 10 years, and 139 participants (41%) managed their diabetes with insulin. Two primary themes emerged. First, participants expressed a desire for assistance with practical aspects of diabetes self-management to improve, and reduce the cognitive burden of, self-management; this included tracking and visualizing multiple sources of data, using data to inform automated, personalized coaching, reminders, and alarms, and automating upload and linking of data through connected devices. Second, they desired assistance with psychological and emotional aspects of diabetes self-management; this included ongoing encouragement and motivation, help with stress management or negative emotions, and complementing existing health care by facilitating interconnectivity with health professionals. Conclusions: Our findings suggest that the clear desire of people with type 2 diabetes is for the "perfect app" to reduce not only the practical, but also the cognitive and emotional burden of diabetes self-management. They provide further evidence that understanding the desires of people living with diabetes needs to be the first step in app development to ensure that apps provide features, support, and benefits that people with diabetes value.


Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors activated by fatty acids and derivatives. Although PPARalpha mediates the hypolipidemic action of fibrates, PPARgamma is the receptor for the antidiabetic glitazones. PPARalpha is highly expressed in tissues such as liver, muscle, kidney, and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPARgamma is predominantly expressed in adipose tissues, where it promotes adipocyte differentiation and lipid storage. PPARbeta/delta is expressed in a wide range of tissues, and recent findings indicate a role for this receptor in the control of adipogenesis. Pharmacological and gene-targeting studies have demonstrated a physiological role for PPARs in lipid and lipoprotein metabolism. PPARalpha controls plasma lipid transport by acting on triglyceride and fatty acid metabolism and by modulating bile acid synthesis and catabolism in the liver. All 3 PPARs regulate macrophage cholesterol homeostasis. By enhancing cholesterol efflux, they stimulate the critical steps of the reverse cholesterol transport pathway. As such, PPARs control plasma levels of cholesterol and triglycerides, which constitute major risk factors for coronary heart disease. Furthermore, PPARalpha and PPARgamma regulate the expression of key proteins involved in all stages of atherogenesis, such as monocyte and lymphocyte recruitment to the arterial wall, foam cell formation, vascular inflammation, and thrombosis. Thus, by regulating gene transcription, PPARs modulate the onset and evolution of metabolic disorders predisposing to atherosclerosis and exert direct antiatherogenic actions at the level of the vascular wall.


Differential response of bovine mammary epithelial cells to Staphylococcus aureus or Escherichia coli agonists of the innate immune system.
Mastitis caused by Escherichia coli and Staphylococcus aureus is a major pathology of dairy cows. To better understand the differential response of the mammary gland to these two pathogens, we stimulated bovine mammary epithelial cells (bMEC) with either E. coli crude lipopolysaccharide (LPS) or with S. aureus culture supernatant (SaS) to compare the transcriptomic profiles of the initial bMEC response. By using HEK 293 reporter cells for pattern recognition receptors, the LPS preparation was found to stimulate TLR2 and TLR4 but not TLR5, Nod1 or Nod2, whereas SaS stimulated TLR2. Biochemical analysis revealed that lipoteichoic acid, protein A and α-hemolysin were all present in SaS, and bMEC were found to be responsive to each of these molecules. Transcriptome profiling revealed a core innate immune response partly shared by LPS and SaS. However, LPS induced expression of a significant higher number of genes and the fold changes were of greater magnitude than those induced by SaS. Microarray data analysis suggests that the activation pathways and the early chemokine and cytokine production preceded the defense and stress responses. A major differential response was the activation of the type I IFN pathway by LPS but not by SaS. The higher upregulation of chemokines (Cxcl10, Ccl2, Ccl5 and Ccl20) that target mononuclear leucocytes by LPS than by SaS is likely to be related to the differential activation of the type I IFN pathway, and could induce a different profile of the initial recruitment of leucocytes. The MEC responses to the two stimuli were different, as LPS was associated with NF-κB and Fas signaling pathways, whereas SaS was associated with AP-1 and IL-17A signaling pathways. It is noteworthy that at the protein level secretion of TNF-α and IL-1β was not induced by either stimulus. These results suggest that the response of MEC to diffusible stimuli from E. coli and S. aureus contributes to the onset of the response with differential leucocyte recruitment and distinct inflammatory and innate immune reactions of the mammary gland to infection.


Permeability, cytotoxicity, and genotoxicity of chromium (V) and chromium (VI) complexes in V79 Chinese hamster lung cells.
The genotoxicity of Cr(V) complexes in mammalian cells (V79 Chinese hamster lung cells) has been studied for the first time using the in vitro micronucleus assay. Two complexes were investigated, [CrO(ehba)2]-, which undergoes ligand-exchange and disproportionation reactions in the cell growth medium, and [CrO(mampa)]-, which is chemically inert in the medium for the duration of the exposure period. Results of in vitro micronucleus assays show that both complexes are genotoxic and exhibit similar potencies to that of [Cr2O7]2-. The permeabilities of the Cr(V) complexes were also investigated for the first time using particle-induced X-ray emission (PIXE) analysis of individual cells. The Cr uptake increased in the order: [Cr(phen)2-(H2O)2]3+ < [CrO(ehba)2]- < [CrO(mampa)]- < [Cr2O7]2-. Clonal assays showed that Cr(VI) exhibits an expectedly higher cytotoxicity than the Cr(V) complexes. While the genotoxicities of the Cr(V) and Cr(VI) complexes increase according to their permeabilities, the genotoxicities of the Cr(V) complexes are equal to, if not greater than, that of Cr(VI) in terms of the amount of Cr entering the cell. This supports other evidence that Cr(V), produced as a metabolic intermediate from the intracellular reduction of Cr(VI), may be important in Cr-induced cancers.


The herpes simplex virus 1 Us11 protein cooperates with suboptimal amounts of human immunodeficiency virus type 1 (HIV-1) Rev protein to rescue HIV-1 production.
The human immunodeficiency virus type 1 (HIV-1) RNA-binding Rev protein governs the expression of structural and enzymatic viral proteins at a posttranscriptional level. Binding of Rev to the stem-loop IIB (SLIIB) sequence of the Rev-response element (RRE) within unspliced and singly spliced viral mRNAs and to the nuclear export signal-binding receptor, hCRM1 (or exportin 1), is required for the export of these transcripts to the cytoplasm. We have previously shown that herpes simplex virus type 1 (HSV-1) RNA-binding Us11 protein is able to bind the RRE and substitute for Rev in inducing the expression of HIV-1 envelope glycoproteins. We show here that Us11 cannot substitute for Rev in rescuing a rev-deleted HIV-1 provirus. However, HIV-1 production is observed when Us11 is expressed with suboptimal amounts of Rev. An in vivo RNA-protein binding assay indicates that Us11 is unable to directly interact with the SLIIB RNA but can bind Rev assembled on that stem-loop structure. This association of US11 with Rev, which was confirmed by in vivo coimmunoprecipitation and GST-pulldown assays, therefore underlies a biological Us11-Rev cooperation. Furthermore this cooperation was shown to remain susceptible to the effect of leptomycin B, which blocks the binding of hCRM1 to the nuclear export signal of Rev. These observations performed with intron-containing constructs provide evidence that HSV-1 Us11 protein is not directly involved in the cytoplasmic accumulation of viral mRNAs but may be rather acting as an auxiliary protein, thus allowing this retroviral protein to fulfill the nuclear export of these transcripts and to rescue HIV-1 production.


Habitat use, but not gene flow, is influenced by human activities in two ecotypes of Egyptian fruit bat (Rousettus aegyptiacus).
Understanding the ecological, behavioural and evolutionary response of organisms to changing environments is of primary importance in a human-altered world. It is crucial to elucidate how human activities alter gene flow and what are the consequences for the genetic structure of a species. We studied two lineages of the Egyptian fruit bat (Rousettus aegyptiacus) throughout the contact zone between mesic and arid Ecozones in the Middle East to evaluate the species' response to the growing proportion of human-altered habitats in the desert. We integrated population genetics, morphometrics and movement ecology to analyse population structure, morphological variation and habitat use from GPS- or radio-tagged individuals from both desert and Mediterranean areas. We classified the spatial distribution and environmental stratification by describing physical-geographical conditions and land cover. We analysed this information to estimate patch occupancy and used an isolation-by-resistance approach to model gene flow patterns. Our results suggest that lineages from desert and Mediterranean habitats, despite their admixture, are isolated by environment and by adaptation supporting their classification as ecotypes. We found a positive effect of human-altered habitats on patch occupancy and habitat use of fruit bats by increasing the availability of roosting and foraging areas. While this commensalism promotes the distribution of fruit bats throughout the Middle East, gene flow between colonies has not been altered by human activities. This discrepancy between habitat use and gene flow patterns may, therefore, be explained by the breeding system of the species and modifications of natal dispersal patterns.


ChipQA: No-Reference Video Quality Prediction via Space-Time Chips.
We propose a new model for no-reference video quality assessment (VQA). Our approach uses a new idea of highly-localized space-time (ST) slices called Space-Time Chips (ST Chips). ST Chips are localized cuts of video data along directions that implicitly capture motion. We use perceptually-motivated bandpass and normalization models to first process the video data, and then select oriented ST Chips based on how closely they fit parametric models of natural video statistics. We show that the parameters that describe these statistics can be used to reliably predict the quality of videos, without the need for a reference video. The proposed method implicitly models ST video naturalness, and deviations from naturalness. We train and test our model on several large VQA databases, and show that our model achieves state-of-the-art performance at reduced cost, without requiring motion computation.


Analgesic, Antiinflammatory, and Antipyretic Effects of S(+)-Ketoprofen In Vivo.
Many studies indicate that the S-enantiomers of arylpropionic (APA) nonsteroidal antiinflammatory drugs (NSAIDs) are the pharmacologically active enantiomers. S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX) in vitro but very little is known about the differential activity of ketoprofen enantiomers in vivo. We examined the analgesic, antiinflammatory, and antipyretic activities of S(+)-ketoprofen in rats and mice. First, we measured the antinociceptive action of S(+)-ketoprofen in abdominal pain models. After intravenous administration, 0.5 mg/kg S(+)-ketoprofen inhibited 92.1 ± 2.2% of writhing in mice. Stereoselectivity in the activity was detected; intravenous administration of the R(-)-enantiomer resulted in no statistically significant activity in a dose range of 0.15-1 mg/kg. Similar results were obtained after oral administration in mice. In the rat, S(+)-ketoprofen was a more potent analgesic than diclofenac by both intravenous and oral administration. There was no significant difference between the analgesic effect of S(+)-ketoprofen treatment and the twofold dose of the racemic form in both the mouse and rat models. Second, we measured the antiinflammatory activity of S(+)-ketoprofen using a carrageenan-induced paw edema model in the rat. Intravenous administration of 5 mg/kg of S(+)-ketoprofen almost completely inhibited edema formation. After oral administration, S(+)-ketoprofen is both more potent and effective than diclofenac. Third, we measured antipyretic activity. S(+)-ketoprofen showed a marked antipyretic action (ED50 = 1.6 mg/kg) and was the most potent of the NSAIDs tested. S(+)-ketoprofen is a potent antiinflammatory, analgesic, and antipyretic agent in vivo, consistent with its potent anti-COX activity.


Anti-angiogenic agents and cancer: current insights and future perspectives.
For sustained growth, tumors are dependent upon neovascularization to feed their massive demand for nutrients and oxygen. Cancer cells produce growth factors and activators that stimulate vessels in the surrounding tissue to form a new circulatory network around the tumor. Therapies aimed at reducing the blood flow to the cancer cells can slow down tumor growth and reduce metastasis. This review describes novel anti-angiogenic agents, including antibodies directed against vascular growth factors and angiotensin II, pharmaceutical compounds and natural metabolites derived from plants and microorganisms. The relevant patents are discussed. These agents may become valuable anti-cancer therapeutics in the future, as a supplement to chemo- and radiation-therapy.


[Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and β-asarone].
To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.


Development of malignant goiter by defatted soybean with iodine-free diet in rats.
Hyperplastic goiters were observed frequently in female rats of Wistar strain when given defatted soybean under iodine deficiency for 6 to 12 months. The findings in the thyroid were those of malignant tumors in which the features of thyroid carcinomas were seen, accompanied with metastasis in the lungs of some animals. Enlargement of the thyroid was completely inhibited in rats when a small amount of iodine was added to the diet. The role of soybean factor(s) which causes enlargment of the thyroid is discussed in relation to the development of malignant goiter, together with pathological findings in the animals.


Male rats fed methyl- and folate-deficient diets with or without niacin develop hepatic carcinomas associated with decreased tissue NAD concentrations and altered poly(ADP-ribose) polymerase activity.
Folate is an essential cofactor in the generation of endogenous methionine, and there is evidence that folate deficiency exacerbates the effects of a diet low in choline and methionine, including alterations in poly(ADP-ribose) polymerase (PARP) activity, an enzyme associated with DNA replication and repair. Because PARP requires NAD as its substrate, we postulated that a deficiency of both folate and niacin would enhance the development of liver cancer in rats fed a diet deficient in methionine and choline. In two experiments, rats were fed choline- and folate-deficient, low methionine diets containing either 12 or 8% casein (12% MCFD, 8% MCFD) or 6% casein and 6% gelatin with niacin (MCFD) or without niacin (MCFND) and were compared with folate-supplemented controls. Liver NAD concentrations were lower in all methyl-deficient rats after 2-17 mo. At 17 mo, NAD concentrations in other tissues of rats fed these diets were also lower than in controls. Compared with control values, liver PARP activity was enhanced in rats fed the 12% MCFD diet but was lower in MCFND-fed rats following a further reduction in liver NAD concentration. These changes in PARP activity associated with lower NAD concentrations may slow DNA repair and enhance DNA damage. Only rats fed the MCFD and MCFND diets developed hepatocarcinomas after 12-17 mo. In Experiment 2, hepatocarcinomas were found in 100% of rats fed the MCFD and MCFND diets. These preliminary results indicate that folic acid deficiency enhances tumor development. Because tumors developed in 100% of the MCFD-fed rats and because tissue concentrations of NAD in these animals were also low, further studies are needed to clearly define the role of niacin in methyl-deficient rats.


Acute exercise-related cognitive effects are not attributable to changes in end-tidal CO2 or cerebral blood velocity.
Cognition, cerebral blood flow (CBF) and its major regulator (i.e., arterial CO2), increase with submaximal exercise and decline with severe exercise. These responses may depend on fitness. We investigated whether exercise-related changes in cognition are mediated in part by concomitant changes in CBF and CO2, in ten active (26 ± 3 years) and ten inactive (24 ± 6 years) healthy adults. Participants completed two randomised sessions; exercise and a resting CO2-control-wherein end-tidal CO2 (PETCO2) was matched between sessions and clamped across conditions at exercise-associated increases (+ 3 mmHg) and hypercapnia (+ 10 mmHg). Exercise comprised inclined walking at submaximal and severe intensities. CBF was indexed using right middle cerebral artery blood velocity (MCAv). Cognition (visuomotor, switching and inhibitory response time) was measured before, during, and after exercise. MCAv and its inverted-U response to exercise were comparable between groups, whereas visuomotor performance improved during submaximal exercise in the active group only (p = 0.046). Submaximal, but not severe (p = 0.33), exercise increased MCAv (p ≤ 0.03). Hypercapnia increased MCAv during the CO2-control (27 ± 12%) and during submaximal exercise (39 ± 17%; p < 0.01). Despite the acute increases in MCAv, cognition was impaired during both levels of increased PETCO2 (3-6%; p ≤ 0.04), regardless of session. Overall, resting or exercise-related changes in PETCO2 and MCAv did not associate with changes in cognition (r ≤ 0.29 ± 0.34). Fitness ([Formula: see text]O2MAX) was associated with baseline cognition (r ≥ 0.50). Acute increases in PETCO2 and MCAv were not associated with improved cognition. In fact, cognitive performance was impaired at both levels of increased PETCO2, regardless of session. Finally, fitter people were found to have better cognition.


Hepatic portal venous gas: the ABCs of management.
To review the use of computed tomography (CT) and radiography in managing hepatic portal venous gas (HPVG) at a university-affiliated tertiary care center and in the literature. Hepatic portal venous gas is frequently associated with acute mesenteric ischemia, accounting for most of the HPVG-associated mortality. While early studies were necessarily dependent on plain abdominal radiography, modern high-resolution CT has revealed a host of benign conditions in which HPVG has been reported that do not require emergent surgery. Patient records from our institution over the last 10 years and relevant studies from BioMed Central, CENTRAL, PubMed, and PubMed Central. In addition, references cited in selected works were also used as source data. Patient records were selected if the CT or radiograph findings matched the term hepatic portal venous gas. Studies were selected based on the search terms hepatic portal venous gas or portal venous gas. Quantitative and qualitative data were quoted directly from cited work. Early studies of HPVG were based on plain abdominal radiography and a literature survey in 1978 found an associated mortality rate of 75%, primarily due to ischemic bowel disease. Modern abdominal CT has resulted in the detection of HPVG in more benign conditions, and a second literature survey in 2001 found a total mortality of only 39%. While the pathophysiology of HPVG is, as yet, unclear, changing abdominal imaging technology has altered the significance of this radiologic finding. Hepatic portal venous gas therefore predicts high risk of mortality (>50%) if detected by plain radiography or by CT in a patient with additional evidence of necrotic bowel. If detected by CT in patients after surgical or endoscopic manipulation, the clinician is advised that there is no evidence of increased risk. If HPVG is detected by CT in patients with active peptic ulcer disease, intestinal obstruction and/or dilatation, or mucosal diseases such as Crohn disease or ulcerative colitis, caution is warranted, as risk of death may approach 20% to 30%. The finding of HPVG alone cannot be an indication for emergency exploration, and we have developed an evidence-based algorithm to guide the clinician in management of patients with HPVG.


Diversity of conidia of aquatic hyphomycetes assessed by microscopy and by DGGE.
Water samples from a Canadian stream were passed through membrane filters between 22 July 2002 and 19 May 2003. Filters with trapped conidia of aquatic hyphomycetes were cut in half. One half was examined under a light microscope, and conidia were counted and identified. From the second half, DNA was extracted and amplified with fungal primers. The number of different ITS sequences (phylotypes) in the amplified DNA was assessed with DGGE. On average, the number of visually identified species per sample (12.4) was higher than the number of phylotypes (11.7), but the difference was nonsignificant (P = 0.36). However, the difference between species and phylotype numbers increased significantly with the number of species or conidia present on the filter, indicating that the sensitivity of DGGE decreases with sample size. When few conidia were present, phylotype numbers often exceeded species numbers, suggesting insufficient resolution of visual identification or the presence of DNA from nonconidial sources. A modification of the described method may be useful to check the accuracy of taxonomy and identification based on conidial morphology.


Glaucoma screening: current trends, economic issues, technology, and challenges.
Glaucoma is one of the leading causes of irreversible blindness worldwide. Early glaucoma detection and treatment are currently the only known methods for preventing blindness and low vision resulting from this frequently asymptomatic disease. New technologies for detecting early glaucomatous damage are important in diagnosing optic nerve disease, not only in community screening settings but also in clinics. Imaging of the optic nerve head and macula and retinal nerve fiber layer analysis can provide quick, automated, and quantitative measurements in agreement with clinical estimates of optic disc structure and visual function. In the area of perimetry, frequency-doubling technology is a promising and feasible mass-screening method with reasonable sensitivity for detecting visual field loss. Central corneal thickness has emerged as a new risk factor for the development and progression of glaucoma, thereby complicating the role of tonometry and measurement of intraocular pressure as screening parameters for glaucoma. Along with technological advances, strides are also being made with public policy and legislative efforts to bring glaucoma onto the national and global health care agenda. These initiatives incorporate vision-screening goals into national disease prevention programs emphasizing the need for early glaucoma detection and treatment. Glaucoma awareness needs to be increased through better education, and compliance with follow-up care needs to be improved to decrease the economic and social costs from glaucoma. In addition, screening models need to be developed that will be effective in developing countries where the risk of blindness from glaucoma is highest.


Alzheimer's disease, metal ions and metal homeostatic therapy.
Mounting evidences support the idea that endogenous 'biometals', such as copper, iron, zinc and exogenous ones such as aluminum, can be involved as factors or cofactors in the etiopathogenesis of a variety of neurodegenerative diseases. Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. In AD, the process of beta-amyloid (Abeta) misfolding and plaque aggregation is greatly influenced by alterations in the homeostasis of the aforementioned metal ions. Here, we discuss the most recent evidences that associate metal ion dyshomeostasis with the development of AD. As for aluminum, a role for this ion in AD pathogenesis is still controversial. Thus, here, we also critically review new findings that argue for and against the 'aluminum hypothesis'. Finally, it is discussed how therapeutic strategies aimed at restoring metal homeostasis can delay and modify the progression of AD-related neurodegeneration.


Association Between Surgeon-Specific Features and Number of Stages, Flaps, and Grafts in Mohs Micrographic Surgery: A Retrospective Observational Study of 59 Early-, Mid-, and Advanced-Career Mohs Surgeons.
There is limited data available to correlate Mohs surgeons' behavior and years of experience. Moreover, the recent standardization of Mohs surgery training programs may allow for the prediction of future trends in Mohs micrographic surgery surgery based on the current behavior of recently trained Mohs surgeons. To better understand the relationship between surgeon-specific characteristics and the number of Mohs micrographic surgery total cases, stages per case, number of grafts, and number of flaps performed by each surgeon. Procedure data of 59 early-career, mid-career, and advanced-career Mohs surgeons were obtained from the website of the Centers for Medicare & Medicaid services. No statistically significant differences were identified in the number of stages per case between the 3 groups. Two-proportion testing between advanced-career surgeons and early-career surgeons indicated a statistically significant difference in the number of surgeons performing flaps or grafts (p < .05). Similarly, a statistically significant difference was noticed between mid-career surgeons and early-career surgeons (p < .05). The result of this study showed that more years of experience was significantly associated with reported utilization of flaps or grafts in practice. Furthermore, no significant difference was observed between years in practice and number of stages per case.


Analysis of the nuclear-electronic orbital method for model hydrogen transfer systems.
Fundamental issues associated with the application of the nuclear-electronic orbital (NEO) approach to hydrogen transfer systems are addressed. In the NEO approach, specified nuclei are treated quantum mechanically on the same level as the electrons, and mixed nuclear-electronic wavefunctions are calculated with molecular orbital methods. The positions of the nuclear basis function centers are optimized variationally. In the application of the NEO approach to hydrogen transfer systems, the hydrogen nuclei and all electrons are treated quantum mechanically. Within the NEO framework, the transferring hydrogen atom can be represented by two basis function centers to allow delocalization of the proton vibrational wavefunction. In this paper, the NEO approach is applied to the [He-H-He]+ and [He-H-He]++ model systems. Analyses of technical issues pertaining to flexibility of the basis set to describe both single and double well proton potential energy surfaces, linear dependency of the hydrogen basis functions, multiple minima in the basis function center optimization, convergence of the number of hydrogen basis function centers, and basis set superposition error are presented. The accuracy of the NEO approach is tested by comparison to grid calculations for these model systems.


Melatonin in the biliary tract and liver: health implications.
Melatonin is a widely-produced and ubiquitously-distributed molecule with multiple critical functions in all organs and organisms. These functions are mediated by both receptor-mediated and receptor-independent actions of the indole. This survey reviews the reports documenting the presence and function of melatonin in the hepatobiliary system. The published data document the exceptionally high concentrations of melatonin in the bile; herein, we speculate on the significance of these high melatonin levels to the function of the biliary tree. Moreover, we suggest that the elevated concentrations of melatonin in the bile fluid may be a consequence of its recirculation in what is referred to as the enterohepatic circulation. The article also examines the published reports related to melatonin levels in hepatocytes, which appear to be independent of pineal-derived melatonin. In both the biliary system and liver, melatonin provides protection against free radicals in cells of these organs. This is particularly important in these organs since they are under constant assault by highly toxic agents/processes that could compromise their critical physiology. As in other tissues, melatonin provides hepatocytes and cholangiocytes with a buffer against free radicals that are persistently produced and thereby this indole protects against oxidative molecular damage and metabolic dysfunction. Melatonin achieves this protection via the diverse free radical scavenging mechanisms of it and its metabolites (known as the antioxidant cascade), due to its ability to reduce electron leakage from the respiratory complexes in the inner mitochondrial membrane (radical avoidance) and as a result of the stimulation of antioxidative enzymes.


Synthesis and stabilization of supported metal catalysts by atomic layer deposition.
Supported metal nanoparticles are among the most important catalysts for many practical reactions, including petroleum refining, automobile exhaust treatment, and Fischer-Tropsch synthesis. The catalytic performance strongly depends on the size, composition, and structure of the metal nanoparticles, as well as the underlying support. Scientists have used conventional synthesis methods including impregnation, ion exchange, and deposition-precipitation to control and tune these factors, to establish structure-performance relationships, and to develop better catalysts. Meanwhile, chemists have improved the stability of metal nanoparticles against sintering by the application of protective layers, such as polymers and oxides that encapsulate the metal particle. This often leads to decreased catalytic activity due to a lack of precise control over the thickness of the protective layer. A promising method of catalyst synthesis is atomic layer deposition (ALD). ALD is a variation on chemical vapor deposition in which metals, oxides, and other materials are deposited on surfaces by a sequence of self-limiting reactions. The self-limiting character of these reactions makes it possible to achieve uniform deposits on high-surface-area porous solids. Therefore, design and synthesis of advanced catalysts on the nanoscale becomes possible through precise control over the structure and composition of the underlying support, the catalytic active sites, and the protective layer. In this Account, we describe our advances in the synthesis and stabilization of supported metal catalysts by ALD. After a short introduction to the technique of ALD, we show several strategies for metal catalyst synthesis by ALD that take advantage of its self-limiting feature. Monometallic and bimetallic catalysts with precise control over the metal particle size, composition, and structure were achieved by combining ALD sequences, surface treatments, and deposition temperature control. Next, we describe ALD oxide overcoats applied with atomically precise thickness control that stabilize metal catalysts while preserving their catalytic function. We also discuss strategies for generation and control over the porosity of the overcoats that allow the embedded metal particles to remain accessible by reactants, and the details for ALD alumina overcoats on metal catalysts. Moreover, using methanol decomposition and oxidative dehydrogenation of ethane as probe reactions, we demonstrate that selectively blocking low coordination metal sites by oxide overcoats can provide another strategy to enhance both the durability and selectivity of metal catalysts.


Paracrine upregulation of monocyte cyclooxygenase-2 by mediators produced by T lymphocytes: role of interleukin 17 and interferon-gamma.
Cyclooxygenase (COX)-2 is an inducible eicosanoid-forming enzyme that is expressed at sites of inflammation. T lymphocytes and monocytes are found in close proximity at sites of inflammation, including synovitis. We investigated whether activated T lymphocytes express COX-2 and whether activated T cells upregulate monocyte COX-2 expression. Human T lymphocytes and monocytes were isolated from fresh buffy coats by density gradient separation followed by passage through either nylon wool columns (T lymphocytes) or counter-current elutriation (monocytes). T lymphocytes were stimulated using anti-CD3 and anti-CD28 in a co-culture system with monocytes using transwells, which prevents cell-cell contact, but allows diffusion of soluble mediators. Repeated examination of COX isotypes in resting and stimulated T cells revealed COX-1, but not COX-2. Activated T cells produced a soluble mediator(s) that upregulated monocyte COX-2. Mediator production was inhibited by cyclosporin A. Activated T cells produced interleukin 17 (IL-17) and interferon-g (IFN-g), and in the co-culture IL-17-neutralizing antibodies partially reduced monocyte COX-2 expression, whereas IFN-g-neutralizing antibodies had the opposite effect. Exogenous IL-17 upregulated monocyte COX-2, although concentrations were high compared with those generated by stimulated T cells. By contrast, monocyte COX-2 expression was downregulated when monocytes were treated with IFN-g prior to stimulation with lipopolysaccharide. Soluble mediators produced by activated T cells can influence induction of monocyte COX-2, with IL-17 acting as a positive paracrine regulator and IFN-g acting as a negative regulator. In rheumatoid joints, previously observed high concentrations of IL-17 and low concentrations of IFN-g could contribute to T cell-driven upregulation of monocyte COX-2.


Fuzzy modeling of electrical impedance tomography images of the lungs.
Aiming to improve the anatomical resolution of electrical impedance tomography images, we developed a fuzzy model based on electrical impedance tomography's high temporal resolution and on the functional pulmonary signals of perfusion and ventilation. Electrical impedance tomography images carry information about both ventilation and perfusion. However, these images are difficult to interpret because of insufficient anatomical resolution, such that it becomes almost impossible to distinguish the heart from the lungs. Electrical impedance tomography data from an experimental animal model were collected during normal ventilation and apnea while an injection of hypertonic saline was administered. The fuzzy model was elaborated in three parts: a modeling of the heart, the pulmonary ventilation map and the pulmonary perfusion map. Image segmentation was performed using a threshold method, and a ventilation/perfusion map was generated. Electrical impedance tomography images treated by the fuzzy model were compared with the hypertonic saline injection method and computed tomography scan images, presenting good results. The average accuracy index was 0.80 when comparing the fuzzy modeled lung maps and the computed tomography scan lung mask. The average ROC curve area comparing a saline injection image and a fuzzy modeled pulmonary perfusion image was 0.77. The innovative aspects of our work are the use of temporal information for the delineation of the heart structure and the use of two pulmonary functions for lung structure delineation. However, robustness of the method should be tested for the imaging of abnormal lung conditions. These results showed the adequacy of the fuzzy approach in treating the anatomical resolution uncertainties in electrical impedance tomography images.


Microcredit as a public health initiative? Exploring mechanisms and pathways to health and wellbeing.
The widening health gap between the best and worst-off in the UK requires innovative solutions that act upon the social, economic and environmental causes of ill-health. Initiatives such as microcredit have been conceptualised as having the potential to act on the social determinants of health. However, pathways that lead to this impact have yet to be empirically explored. People living on low incomes, who are financially-excluded, require access to credit to cope with everyday financial needs. While research shows the connections between debt and health, this link is often focused on over-indebtedness and negative health outcomes. In this paper, we investigate the impact of responsibly-delivered credit on the health and wellbeing of borrowers. In 2016-17, in-depth, semi-structured interviews were undertaken with fourteen borrowers from two microcredit providers offering personal and business microloans, operating in Glasgow, United Kingdom. Findings are presented, using social determinants of health as an analytic lens, and illustrated in a conceptual model explaining the loan mechanisms and pathways connecting microcredit to health and wellbeing. Microcredit, and the mechanisms through which it is delivered, were perceived by participants as positively impacting on their health and wellbeing. Access to flexible, responsibly-delivered, microloans enabled participants to plan and feel secure when faced with (un)expected financial events, reducing the associated stress, sustaining social relationships and empowering borrowers to take greater control over their lives. For some, receiving microcredit was stressful, as it is still a debt that needs to be repaid. Such stress can also be exacerbated by particular aspects of the lending model; for example, group lending. Our results contribute to growing evidence on the impact of financial inclusion approaches on health and wellbeing, highlighting the potential role of microcredit as a public health initiative and the need to support 'alternative' economic spaces in the UK to serve the financially-excluded.


Effects of stress and beta-blockade on platelet function.
Platelet function can be assessed by various techniques in vitro or in vivo, but methodological problems in the field are considerable. By use of the conventional in vitro technique (Born aggregometry), it has been shown that sympathoadrenal activation in vivo (e.g., mental stress, epinephrine infusions, exercise, and surgical stress) may result in either enhanced or reduced platelet aggregability in vitro. In vivo measures of platelet function (platelet counts, size distribution, and aggregability, as reflected by filtragometry ex vivo) more consistently indicate platelet activation during stress. Platelet-specific proteins in plasma are less readily affected by stress. Elevations of circulating epinephrine do not seem to explain proaggregatory effects of stress. Aggregatory responses to epinephrine may be enhanced by propranolol in vitro, because of unopposed alpha 2-stimulation (beta 2-stimulation attenuates aggregation). Other in vitro effects of beta-blockade seem to be related to nonspecific effects at very high concentrations. Studies of the effects of beta-blockade in vivo have yielded conflicting data. Some studies suggest that beta 2-blockade may reduce platelet cAMP and enhance aggregability in vitro; other studies show that propranolol attenuates platelet aggregability, particularly in patients with ischemic heart disease. There is, however, a need for well-conducted studies assessing platelet function in vivo during beta-blockade to evaluate whether platelet responses contribute to favorable effects of beta-blockade in unstable angina, for example, or after myocardial infarction. Methodological developments are needed to better understand platelet function in vivo in humans. Available data suggest that stress enhances and beta-blockade reduces platelet function. This may influence thrombus formation in the short term and atherosclerosis in the long term.


Tandem measurement of D-dimer and myeloperoxidase or C-reactive protein to effectively screen for pulmonary embolism in the emergency department.
The hypothesis was that the tandem measurement of D-dimer and myeloperoxidase (MPO) or C-reactive protein (CRP) could significantly decrease unnecessary pulmonary vascular imaging in emergency department (ED) patients evaluated for pulmonary embolism (PE) compared to D-dimer alone. The authors measured the sequential combinations of D-dimer and MPO and D-dimer and CRP in a prospective sample of ED patients evaluated for PE at two centers. Patients were followed for 90 days for venous thromboembolism (VTE, either PE or deep venous thrombosis [DVT]), which required the consensus of two of three blinded physician reviewers. The authors enrolled 304 patients, 22 with VTE (7%; 95% confidence interval [CI] = 5% to 10%). The sensitivity and specificity of a D-dimer alone (cutoff > or = 500 ng/mL) were 100% (95% CI = 85% to 100%) and 59% (95% CI = 53% to 65%), respectively, and was followed by pulmonary vascular imaging negative for PE in 38% (115/304; 95% CI = 32% to 44%). The combination of either a negative D-dimer, or MPO < 22 mg/dL, had a sensitivity of 100% and specificity of 73% (95% CI = 67% to 78%). Thus, tandem measurement of D-dimer and MPO would have decreased the frequency of subsequent negative pulmonary vascular imaging from 38% to 25% (95% CI of the difference of -13% = -5% to -20%). The combination of CRP and D-dimer would not have significantly improved the rate of negative imaging. The tandem measurement of D-dimer and MPO would have significantly decreased negative pulmonary vascular imaging compared with D-dimer alone and should be validated prospectively.


Oral Delivered Dexmedetomidine Promotes and Consolidates Non-rapid Eye Movement Sleep via Sleep-Wake Regulation Systems in Mice.
Dexmedetomidine, a highly selective α2-adrenergic agonist, is widely used in clinical anesthesia and ICU sedation. Recent studies have found that dexmedetomidine-induced sedation resembles the recovery sleep that follows sleep deprivation, but whether orally delivered dexmedetomidine can be a candidate for the treatment of insomnia remains unclear. In this study, we estimated the sedative effects of orally delivered dexmedetomidine by spontaneous locomotor activity (LMA), and then evaluated the hypnotic effects of dexmedetomidine on sleep-wake profiles during the dark and light phase using electroencephalography/electromyogram (EEG/EMG), respectively. Using c-Fos staining, we explored the effects of dexmedetomidine on the cerebral cortex and the sub-cortical sleep-wake regulation systems. The results showed that orally delivered dexmedetomidine at 2 h into the dark cycle reduced LMA and wakefulness in a dose-dependent manner, which was consistent with the increase in non-rapid eye movement sleep (NREM sleep). However, dexmedetomidine also induced a rebound in LMA, wake and rapid eye movement sleep (REM sleep) in the later stage. In addition, orally delivered dexmedetomidine 100 μg/kg at 2 h into the light cycle shortened the latency to NREM sleep and increased the duration of NREM sleep for 6 h, while decreased REM sleep for 6 h. Sleep architecture analysis showed that dexmedetomidine stabilized the sleep structure during the light phase by decreasing sleep-wake transition and increasing long-term NREM sleep (durations of 1024-2024 s and >2024 s) while reducing short-term wakefulness (duration of 4-16 s). Unlike the classic hypnotic diazepam, dexmedetomidine also increased the delta power in the EEG spectra of NREM sleep, especially at the frequency of 1.75-3.25 Hz, while ranges of 0.5-1.0 Hz were decreased. Immunohistochemical analysis showed that orally delivered dexmedetomidine 100 μg/kg at 2 h into the dark cycle decreased c-Fos expression in the cerebral cortex and sub-cortical arousal systems, while it increased c-Fos expression in the neurons of the ventrolateral preoptic nucleus. These results indicate that orally delivered dexmedetomidine can induce sedative and hypnotic effects by exciting the sleep-promoting nucleus and inhibiting the wake-promoting areas.


Pulmonary inflammation by ambient air particles is mediated by superoxide anion.
Lung inflammation is a key response to increased levels of particulate air pollution (PM); however, the cellular mechanisms leading to this response remain poorly understood. We have previously shown that oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles. Here we tested the possible role of a specific oxidant, superoxide anion, by using the membrane-permeable analog of superoxide dismutase, Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP). Adult Sprague-Dawley rats were instilled with either urban air particles (UAP) or saline. MnTBAP-treated rats received 10 mg/kg (ip) MnTBAP 2 h prior to exposure to UAP. Recruitment of inflammatory cells into bronchoalveolar lavage was evaluated 4 h after instillation. Rats exposed to UAP showed significant increases in the total cell number (8.9 +/- 0.6 x 10(6); sham: 5.1 +/- 0.6 x 10(6), p < .02), the numbers of polymorphonuclear leukocytes (26 +/- 4%; sham: 6 +/- 1%, p < .0001), protein levels (1.2 +/- 0.5 mg/ml, sham: 0.4 +/- 0.1 mg/ml, p < .001), and a trend of increase in myeloperoxidase levels (5 +/- 1; sham: 2 +/- 1 mU/ml) in bronchoalveolar lavage (BAL). Pretreatment with MnTBAP at a dose that prevented UAP-induced increases in oxidants effectively prevented increase in BAL cells (2.7 +/- 0.6 x 10(6), p < .0001 vs. UAP), PMN influx into the lungs (4 +/- 3%, p < .0001 vs. UAP), and increase in myeloperoxidase (2 +/- 1 mU/ml) and protein levels in BAL (0.1 +/- 0.1 mg/ml). These data indicate that superoxide anion is a critical mediator of the inflammatory response elicited by PM deposition in the lung.


Successful treatment of pure endodermal sinus tumors in adult men.
Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.


Suppression of Pitch Labeling: No Evidence for an Impact of Absolute Pitch on Behavioral and Neurophysiological Measures of Cognitive Inhibition in an Auditory Go/Nogo Task.
Pitch labeling in absolute pitch (AP), the ability to recognize the pitch class of a sound without an external reference, is effortless, fast, and presumably automatic. Previous studies have shown that pitch labeling in AP can interfere with task demands. In the current study, we used a cued auditory Go/Nogo task requiring same/different decisions to investigate both behavioral and electrophysiological correlates of increased inhibitory demands related to automatic pitch labeling. The task comprised two Nogo conditions: a Nogo condition with pitch differences larger than one semitone, and a second Nogo condition with pitch differences of only a quarter semitone. The first Nogo condition tested if auditory-related inhibition processes are generally altered in AP musicians. The second Nogo condition tested the suppressibility of the pitch labeling using a Stroop-like effect: the two tones belonged to the same pitch class but were not identical in terms of tone frequency. If pitch labeling cannot be suppressed, the conflicting information would be expected to increase the inhibitory load in AP musicians. Our data provided no evidence for an increased difficulty to inhibit a prepotent response or to suppress conflicting pitch-labeling information in AP: AP musicians showed similar commission error rates as non-AP musicians in both Nogo conditions. N2d and P3d amplitudes of AP musicians were also comparable to those of non-AP musicians. The event-related potentials (ERPs) were, however, modulated by the Nogo condition, probably indicating an effect of stimulus similarity. It is possible that, depending on the context, pitch labeling in AP musicians is not entirely automatic and can be suppressed.


Nucleosome stability measured in situ by automated quantitative imaging.
Current approaches have limitations in providing insight into the functional properties of particular nucleosomes in their native molecular environment. Here we describe a simple and powerful method involving elution of histones using intercalators or salt, to assess stability features dependent on DNA superhelicity and relying mainly on electrostatic interactions, respectively, and measurement of the fraction of histones remaining chromatin-bound in the individual nuclei using histone type- or posttranslational modification- (PTM-) specific antibodies and automated, quantitative imaging. The method has been validated in H3K4me3 ChIP-seq experiments, by the quantitative assessment of chromatin loop relaxation required for nucleosomal destabilization, and by comparative analyses of the intercalator and salt induced release from the nucleosomes of different histones. The accuracy of the assay allowed us to observe examples of strict association between nucleosome stability and PTMs across cell types, differentiation state and throughout the cell-cycle in close to native chromatin context, and resolve ambiguities regarding the destabilizing effect of H2A.X phosphorylation. The advantages of the in situ measuring scenario are demonstrated via the marked effect of DNA nicking on histone eviction that underscores the powerful potential of topological relaxation in the epigenetic regulation of DNA accessibility.


Skeletal muscle mitochondrial and metabolic responses to a high-fat diet in female rats bred for high and low aerobic capacity.
Rats selected artificially to be low-capacity runners (LCR) possess a metabolic syndrome phenotype that is worsened by a high-fat diet (HFD), whereas rats selected to be high-capacity runners (HCR) are protected against HFD-induced obesity and insulin resistance. This study examined whether protection against, or susceptibility to, HFD-induced insulin resistance in the HCR-LCR strains is associated with contrasting metabolic adaptations in skeletal muscle. HCR and LCR rats (generation 20; n = 5-6; maximum running distance approximately 1800 m vs. approximately 350 m, respectively (p < 0.0001)) were divided into HFD (71.6% energy from fat) or normal chow (NC) (16.7% energy from fat) groups for 7 weeks (from 24 to 31 weeks of age). Skeletal muscle (red gastrocnemius) mitochondrial-fatty acid oxidation (FAO), mitochondrial-enzyme activity, mitochondrial-morphology, peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), and peroxisome proliferator-activated receptor delta (PPARdelta) expression and insulin sensitivity (intraperitoneal glucose tolerance tests) were measured. The HFD caused increased adiposity and reduced insulin sensitivity only in the LCR and not the HCR strain. Isolated mitochondria from the HCR skeletal muscle displayed a 2-fold-higher rate of FAO on NC, but both groups increased FAO following HFD. PGC-1alpha mRNA expression and superoxide dismutase activity were significantly reduced with the HFD in the LCR rats, but not in the HCR rats. PPARdelta expression did not differ between strains or dietary conditions. These results do not provide a clear connection between protection of insulin sensitivity and HFD-induced adaptive changes in mitochondrial function or transcriptional responses but do not dismiss the possibility that elevated mitochondrial FAO in the HCR may play a protective role.


Expanding poliomyelitis and measles surveillance networks to establish surveillance for acute meningitis and encephalitis syndromes--Bangladesh, China, and India, 2006-2008.
Quality surveillance is critical to the control and elimination of vaccine-preventable diseases (VPDs). A key strategy for enhancing VPD surveillance, outlined in the World Health Organization (WHO) Global Framework for Immunization Monitoring and Surveillance (GFIMS), is to expand and link existing VPD surveillance systems (particularly those developed for polio eradication and measles elimination) to include other priority VPDs. Since the launch of the Global Polio Eradication Initiative in 1988, the incidence of polio has decrease by 99% worldwide. A cornerstone of this success is a sensitive surveillance system based on the rapid and timely reporting of all acute flaccid paralysis (AFP) cases in children aged <15 years, with confirmatory diagnostic testing performed by laboratories that are part of a global network. As countries achieve polio-free status, many have expanded syndromic surveillance to include persons with rash and fever, and have built measles diagnostic capacity in existing polio reference laboratories. Acute meningitis/encephalitis syndrome (AMES) and acute encephalitis syndrome (AES) are candidates for expanded surveillance because they are most often caused by VPDs of public health importance for which confirmatory laboratory tests exist. Vaccine-preventable cases of encephalitis include approximately 68,000 Japanese encephalitis (JE) cases, resulting in 13,000-20,000 deaths each year in Asia. Moreover, although bacterial meningitis incidence in Asia is not as well-documented, pneumococcal and meningococcal meningitis outbreaks have been reported in Bangladesh and China, and the incidence of Haemophilus influenzae type b (Hib) meningitis in children aged <5 years in India has been estimated to be 7.1 per 100,000 population, similar to that in European countries before the introduction of vaccine. This report describes a prototype for expanding existing polio and measles surveillance networks in Bangladesh, China, and India to include surveillance for viral and bacterial vaccine-preventable causes of AMES and AES and presents data from 2006-2008.


Lymphadenectomy along the left recurrent laryngeal nerve by a minimally invasive esophagectomy in the prone position for thoracic esophageal cancer.
A thoracoabdominal esophagectomy for esophageal cancer is a severely invasive procedure. A thoracoscopic esophagectomy may minimize injury to the chest wall and reduce surgical invasiveness. Conventional thoracoscopic procedures are performed in the left lateral-decubitus position. Recently, procedures performed in the prone position have received more attention because of improvements in operative exposure or surgeon ergonomics. However, the efficacy of the prone position in an aggressive thoracoscopic esophagectomy with an extensive lymphadenectomy has not been fully documented. We successfully performed a thoracoscopic esophagectomy with a three-field extensive lymphadenectomy in 43 esophageal carcinoma patients in the prone position from December 2007 to December 2009. We describe our procedures with the patients in the prone position, focusing especially on a lymphadenectomy along the left recurrent laryngeal nerve where the nodes are frequently involved and precise dissection is technically challenging. To determine further the advantages of this position, we retrospectively compared surgical outcomes in 43 patients to those of 34 patients who underwent a thoracoscopic esophagectomy in the left lateral decubitus position as a historical control from January 2006 to November 2007. It was easier to explore the operative field around the left recurrent laryngeal nerve during a thoracoscopic esophagectomy in the prone position. The mean duration of the aggressive thoracoscopic procedure in the prone position was 307 min, which was significantly longer than in the left lateral decubitus position, but the total estimated blood loss in the prone position was significantly lower. There was no difference in the incidence of postoperative complications between the two procedures. A thoracoscopic esophagectomy in the prone position is technically safe and feasible and provides better surgeon ergonomics and better operative exposure around the left recurrent laryngeal nerve during an aggressive esophagectomy.