Boiling peanut Ara h 1 results in the formation of aggregates with reduced allergenicity.
Roasting rather than boiling and Maillard modifications may modulate peanut allergenicity. We investigated how these factors affect the allergenic properties of a major peanut allergen, Ara h 1. Ara h 1 was purified from either raw (N-Ara h 1) or roasted (R-Ara h 1) peanuts. Boiling (100°C 15 min; H-Ara h 1) resulted in a partial loss of Ara h 1 secondary structure and formation of rod-like branched aggregates with reduced IgE-binding capacity and impaired ability to induce mediator release. Glycated Ara h 1 (G-Ara h 1) formed by boiling in the presence of glucose behaved similarly. However, H- and G-Ara h1 retained the T-cell reactivity of N-Ara h 1. R-Ara h 1 was denatured, comprised compact, globular aggregates, and showed no evidence of glycation but retained the IgE-binding capacity of the native protein. Ara h 1 aggregates formed by boiling were morphologically distinct from those formed by roasting and had lower allergenic activity. Glycation had no additional effect on Ara h 1 allergenicity compared with heating alone. Taken together with published data on the loss of Ara h 2/6 from boiled peanuts, this supports the hypothesis that boiling reduces the allergenicity of peanuts.


Review of Arthroscopic and Histological Findings Following Knee Inlay Arthroplasty.
The phenomenon of cartilage rim loading in defects exceeding the threshold diameter of 10 mm is well documented. Contoured defect fill off-loads the perimeter and counteracts further delamination and progression of defects. When biological procedures have failed, inlay arthroplasty follows these concepts. The human biological response to contoured metallic surface implants has not been described. Four patients underwent non-implant-related, second-look arthroscopy following inlay arthroplasty for bi- (n=3) and tricompartmental (n=1) knee arthrosis without subchondral bone collapse. Arthroscopic probing of the implant-cartilage interface of nine prosthetic components did not show signs of implant-cartilage gap formation, loosening, or subsidence. The implant periphery was consistently covered by cartilage confluence leading to a reduction of the original defect size diameter. Femoral condyle cartilage flow appeared to have more hyaline characteristics. Trochlear cartilage flow showed greater histological variability and less organization with fibrocartilage and synovialized scar tissue. This review reconfirmed previous basic science results and demonstrated effective defect fill and rim off-loading with inlay arthroplasty.


New self-assembling polyaspartylhydrazide copolymer micelles for anticancer drug delivery.
A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C(16)) moieties on polymer backbone, and the structure of obtained PAHy-PEG(2000)-C(16) copolymer have been characterized by 2D (1)H/(13)C NMR experiments. PAHy-PEG(2000)-C(16) copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D (1)H NMR NOESY experiments. The presence of cross-peaks for protons of C(16) and PAHy portions, indicated that the two domains are in close proximity forming micelle core. The critical aggregation concentration (CAC) values of PAHy-PEG(2000)-C(16) amphiphilic graft copolymer was determined in water by fluorescence technique, and it was demonstrated that PAHy-PEG(2000)-C(16) micelles are well suited to be micellar vehicle of highly hydrophobic molecules. Therefore, anticancer drug tamoxifen, used as a model hydrophobic molecule, was loaded into PAHy-PEG(2000)-C(16) micelles obtaining an increase of drug solubility of about 3000 times. Transmission electron microscopy (TEM) observations showed the spherical morphology of micelles formed by PAHy-PEG(2000)-C(16) copolymer with a mean diameter of about 30nm, as confirmed also by dynamic light scattering (DLS) studies. Finally, in vitro cell viability studies were carried out on human breast cancer cells (MCF-7) testing the pharmacological activity of tamoxifen-loaded PAHy-PEG(2000)-C(16) micelles, in comparison with free tamoxifen at different drug concentrations, demonstrating that tamoxifen-loaded PAHy-PEG(2000)-C(16) micelles exhibited a concentration-dependent cytotoxic activity.


Deficits in reinforcement learning but no link to apathy in patients with schizophrenia.
Negative symptoms in schizophrenia have been linked to selective reinforcement learning deficits in the context of gains combined with intact loss-avoidance learning. Fundamental mechanisms of reinforcement learning and choice are prediction error signaling and the precise representation of reward value for future decisions. It is unclear which of these mechanisms contribute to the impairments in learning from positive outcomes observed in schizophrenia. A recent study suggested that patients with severe apathy symptoms show deficits in the representation of expected value. Considering the fundamental relevance for the understanding of these symptoms, we aimed to assess the stability of these findings across studies. Sixty-four patients with schizophrenia and 19 healthy control participants performed a probabilistic reward learning task. They had to associate stimuli with gain or loss-avoidance. In a transfer phase participants indicated valuation of the previously learned stimuli by choosing among them. Patients demonstrated an overall impairment in learning compared to healthy controls. No effects of apathy symptoms on task indices were observed. However, patients with schizophrenia learned better in the context of loss-avoidance than in the context of gain. Earlier findings were thus partially replicated. Further studies are needed to clarify the mechanistic link between negative symptoms and reinforcement learning.


The Discovery, Distribution, and Evolution of Viruses Associated with Drosophila melanogaster.
Drosophila melanogaster is a valuable invertebrate model for viral infection and antiviral immunity, and is a focus for studies of insect-virus coevolution. Here we use a metagenomic approach to identify more than 20 previously undetected RNA viruses and a DNA virus associated with wild D. melanogaster. These viruses not only include distant relatives of known insect pathogens but also novel groups of insect-infecting viruses. By sequencing virus-derived small RNAs, we show that the viruses represent active infections of Drosophila. We find that the RNA viruses differ in the number and properties of their small RNAs, and we detect both siRNAs and a novel miRNA from the DNA virus. Analysis of small RNAs also allows us to identify putative viral sequences that lack detectable sequence similarity to known viruses. By surveying >2,000 individually collected wild adult Drosophila we show that more than 30% of D. melanogaster carry a detectable virus, and more than 6% carry multiple viruses. However, despite a high prevalence of the Wolbachia endosymbiont--which is known to be protective against virus infections in Drosophila--we were unable to detect any relationship between the presence of Wolbachia and the presence of any virus. Using publicly available RNA-seq datasets, we show that the community of viruses in Drosophila laboratories is very different from that seen in the wild, but that some of the newly discovered viruses are nevertheless widespread in laboratory lines and are ubiquitous in cell culture. By sequencing viruses from individual wild-collected flies we show that some viruses are shared between D. melanogaster and D. simulans. Our results provide an essential evolutionary and ecological context for host-virus interaction in Drosophila, and the newly reported viral sequences will help develop D. melanogaster further as a model for molecular and evolutionary virus research.


Pharmacological and functional characterization of bradykinin receptors in rat cultured vascular smooth muscle cells.
The pharmacological properties of bradykinin receptors were characterized in rat cultured vascular smooth muscle cells (VSMCs) using [3H]-bradykinin as a ligand. Analysis of binding isotherms gave an apparent equilibrium dissociation constant (K(D)) of 1.2 +/- 0.2 nM and a maximum receptor density (Bmax) of 47.3 +/- 4.4 fmol/mg protein. The specific binding of [3H]-bradykinin to VSMCs was inhibited by the B2 receptor-selective agonists (bradykinin and kallidin) and antagonists ([D-Arg0, Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (Hoe 140) and [D-Arg0, Hyp3, Thi(5,8), D-Phe7]-bradykinin) with an order of potency as kallidin = bradykinin = Hoe 140 > [D-Arg0, Hyp3, Thi(5,8), D-Phe7]-bradykinin, but not by a B1 receptor-selective agonist (des-Arg9-bradykinin) and antagonist ([Leu8, des-Arg9]-bradykinin). Stimulation of VSMCs by bradykinin produced a concentration-dependent inositol phosphate (IP) accumulation, and initial transient peak of [Ca2+]i with half-maximal responses (pEC50) were 7.53 and 7.69, respectively. B2 receptor-selective antagonists (Hoe 140 and [D-Arg0, Hyp3, Thi(5,8), D-Phe7]-bradykinin) significantly antagonized the bradykinin-induced responses with pK(B) values of 8.3-8.7 and 7.2-7.9, respectively. Pretreatment of VSMCs with pertussis toxin (100 ng/ml, 24 h) did not alter the bradykinin-induced inositol phosphate accumulation and [Ca2+]i changes in VSMCs. Removal of external Ca2+ led to a significant attenuation of responses induced by bradykinin. Influx of external Ca2+ was required for the bradykinin-induced responses, since Ca2+-channel blockers, nifedipine, verapamil, and Ni2+, partially inhibited the bradykinin-induced IP accumulation and Ca2+ mobilization. These results demonstrate that bradykinin stimulates phosphoinositide hydrolysis and Ca2+ mobilization via a pertussis toxin-insensitive G-protein in rat VSMCs. Bradykinin B2 receptors may be predominantly mediating IP accumulation and subsequently induction of Ca2+ mobilization may function as the transducing mechanism for bradykinin-stimulated contraction of vascular smooth muscle.


Magnetofluidic platform for multidimensional magnetic and optical barcoding of droplets.
We present a concept of multidimensional magnetic and optical barcoding of droplets based on a magnetofluidic platform. The platform comprises multiple functional areas, such as an encoding area, an encoded droplet pool and a magnetic decoding area with integrated giant magnetoresistive (GMR) sensors. To prove this concept, penicillin functionalized with fluorescent dyes is coencapsulated with magnetic nanoparticles into droplets. While fluorescent dyes are used as conventional optical barcodes which are decoded with an optical decoding setup, an additional dimensionality of barcodes is created by using magnetic nanoparticles as magnetic barcodes for individual droplets and integrated micro-patterned GMR sensors as the corresponding magnetic decoding devices. The strategy of incorporating a magnetic encoding scheme provides a dynamic range of ~40 dB in addition to that of the optical method. When combined with magnetic barcodes, the encoding capacity can be increased by more than 1 order of magnitude compared with using only optical barcodes, that is, the magnetic platform provides more than 10 unique magnetic codes in addition to each optical barcode. Besides being a unique magnetic functional element for droplet microfluidics, the platform is capable of on-demand facile magnetic encoding and real-time decoding of droplets which paves the way for the development of novel non-optical encoding schemes for highly multiplexed droplet-based biological assays.


All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus-coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13-HEPAVIH Cohort.
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce. Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome. We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events. In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients.


Glacial lakes in the Indian Himalayas--from an area-wide glacial lake inventory to on-site and modeling based risk assessment of critical glacial lakes.
Glacial lake hazards and glacial lake distributions are investigated in many glaciated regions of the world, but comparably little attention has been given to these topics in the Indian Himalayas. In this study we present a first area-wide glacial lake inventory, including a qualitative classification at 251 glacial lakes >0.01 km(2). Lakes were detected in the five states spanning the Indian Himalayas, and lake distribution pattern and lake characteristics were found to differ significantly between regions. Three glacial lakes, from different geographic and climatic regions within the Indian Himalayas were then selected for a detailed risk assessment. Lake outburst probability, potential outburst magnitudes and associated damage were evaluated on the basis of high-resolution satellite imagery, field assessments and through the use of a dynamic model. The glacial lakes analyzed in the states of Jammu and Kashmir and Himachal Pradesh were found to present moderate risks to downstream villages, whereas the lake in Sikkim severely threatens downstream locations. At the study site in Sikkim, a dam breach could trigger drainage of ca. 16×10(6)m(3) water and generate maximum lake discharge of nearly 7000 m(3) s(-). The identification of critical glacial lakes in the Indian Himalayas and the detailed risk assessments at three specific sites allow prioritizing further investigations and help in the definition of risk reduction actions.


Treatment-related outcome of oropharyngeal cancer patients differentiated by HPV dictated risk profile: a tertiary cancer centre series analysis.
To date, no treatment modality has been identified as more effective for oropharyngeal cancer (OPC), and no predictive factors are known to guide treatment decision for this disease. This retrospective study evaluates the differential effects of diverse treatment options for OPC according to patient risk profiles. We considered two series of locally advanced squamous cell OPC patients treated with either surgery followed by radiotherapy (surgical series) or chemoradiation (CRT) with/without induction docetaxel, cisplatin and 5-fluorouracil (TPF) chemotherapy (CRT series). Smoking habits, tumor p16 expression/human papillomavirus (HPV) status and T and N stage were analyzed to stratify the patients according to Ang's risk profile (low, intermediate and high risk). Overall survival (OS) and disease-free survival were calculated with the Kaplan-Meier method. Globally, 171 patients were considered, 56 in surgical and 115 in CRT series. Patients were stratified in low- (20% of surgical and CRT groups), intermediate- (23% and 41%) and high-risk (57% and 39%) groups. In the surgical series, 5-year OS was 54.5%, 46.9% and 40.0% in low, intermediate and high Ang's risk profiles, respectively, whereas in the CRT series those were 100%, 78.9% and 46.7%, respectively. In the multivariable analyses, adjusting for inhomogeneity between the treatment group, the CRT effect was significantly higher in the low- and intermediate-risk groups (P-value for the interaction treatment risk group = 0.034 in the OS analysis). In this retrospective analysis, low- and intermediate-risk OPC patients had a better survival when treated with CRT compared with open surgery followed by radiation therapy. These data suggest that different treatment approaches might be essential in determining outcome results.


Sequence and comparative analysis of three Enterobacter cloacae ampC beta-lactamase genes and their products.
The sequences of three Enterobacter cloacae ampC beta-lactamase genes have been determined. The deduced amino acid sequences are very similar: out of a total of 361 residues, only eight positions were found to be variable, and several mutations yielded residues with very similar properties. The kinetic properties of two of the enzymes were not significantly different. The three enzymes also exhibited a high degree of homology (greater than 70%) with the ampC beta-lactamases of Escherichia coli K12 and Citrobacter freundii, confirming the homogeneity of class-C beta-lactamases.


Helicobacter pylori infection following partial gastrectomy for gastric cancer.
Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required.


Visual communication of how fabrics feel.
Although product photos and movies are abundantly present in online shopping environments, little is known about how much of the real product experience they capture. While previous studies have shown that movies or interactive imagery give users the impression that these communication forms are more effective, there are no studies addressing this issue quantitatively. We used nine different samples of jeans, because in general fabrics represent a large and interesting product category and specifically because jeans can visually be rather similar while haptically be rather different. In the first experiment we let observers match a haptic stimulus to a visual representation and found that movies were more informative about how objects would feel than photos. In a second experiment we wanted to confirm this finding by using a different experimental paradigm that we deemed a better general paradigm for future studies on this topic: correlations of pairwise similarity ratings. However, the beneficial effect of the movies was absent when using this new paradigm. In the third experiment we investigated this issue by letting people visually observe other people in making haptic similarity judgments. Here, we did find a significant correlation between haptic and visual data. Together, the three experiments suggest that there is a small but significant effect of movies over photos (Experiment 1) but at the same time a significant difference between visual representations and visually perceiving products in reality (Experiments 2 and 3). This finding suggests a substantial theoretical potential for decreasing the gap between virtual and real product presentation.


Music therapy may increase breastfeeding rates among mothers of premature newborns: a randomized controlled trial.
To evaluate the impact of music therapy on breastfeeding rates among mothers of premature newborns. In this open randomized controlled trial, mothers of premature neonates weighting ≤ 1,750 g were submitted to music therapy sessions three times a week for 60 minutes. The endpoints were breastfeeding rates at the moment of infant hospital discharge and at follow-up visits (7-15 days, 30 and 60 days after discharge). A total of 94 mothers (48 in the music therapy group and 46 in the comparison group) were studied. Breastfeeding was significantly more frequent in the music therapy group at the first follow-up visit [relative risk (RR) = 1.26; 95% confidence interval (95%CI) = 1.01-1.57; p = 0.03; number needed to treat (NNT) = 5.6]. Moreover, this group showed higher breastfeeding rates at the moment of infant discharge (RR = 1.22; 95%CI = 0.99-1.51; p = 0.06; NNT = 6.3) and at days 30 and 60 after discharge (RR = 1.21; 95%CI = 0.73-5.6; p = 0.13 and RR = 1.28; 95%CI = 0.95-1.71; p = 0.09, respectively), but those results were not statistically significant. This study demonstrated that music therapy had a significant effect in increasing breastfeeding rates among mothers of premature newborns at the first follow-up visit, and also a positive influence (although not significant) that lasted up to 60 days after infant discharge. Music therapy may be useful for increasing breastfeeding rates among mothers of premature newborns.


Correlation between soluble endoglin, vascular endothelial growth factor receptor-1, and adipocytokines in preeclampsia.
Recent reports have demonstrated that soluble endoglin (sEng), an antiangiogenic protein thought to impair TGF-beta binding to receptors, and soluble vascular endothelial growth factor receptor (sVEGFR)-1 play important roles in the pathophysiology of preeclampsia (PE). Moreover, insulin resistance, which is greatly influenced by adipocytokines, characterizes PE. We examined possible links between sEng, VEGF, sVEGFR, and adipocytokines in the pathophysiology of PE. We performed a cross-sectional study in 30 PE patients and controls matched for gestational age and body mass index. Blood samples were collected soon after disease onset. We measured serum concentrations of leptin, adiponectin, sEng, VEGF, placental growth factor (PlGF), and sVEGFR [soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble fetal liver kinase 1 (sFlk-1)], and examined the placental protein content of sEng and sFlt-1. sEng concentrations in PE patients (60.9 +/- 28.8 ng/ml) were significantly higher than those in controls (11.2 +/- 4.4 ng/ml). There was a significant correlation between sEng and sFlt-1 or PlGF. Moreover, there were significant differences in mean blood pressure between the high and low sEng groups, and in proteinuria between the high and low sFlt-1 groups, and significant differences in placental sEng and sFlt-1 contents between patients with and without severe hypertension or proteinuria. sEng was also correlated positively with adiponectin levels and negatively with the leptin to adiponectin ratio. Along with sFlt-1 and PlGF, sEng might play a role in the pathophysiology of PE, especially in elevating blood pressure, while the association with hypoadiponectinemia and the high leptin to adiponectin ratio in pregnancy seem to be risk factors for PE.


Dietary and weight-related behaviors and body mass index among Hispanic, Hmong, Somali, and white adolescents.
The population of the United States is becoming increasingly ethnically and racially diverse, much of it due to immigration patterns. However, little is known about dietary intake and weight-related concerns and behaviors of youth from some ethnic-minority groups, especially Hispanic, Hmong, and Somali adolescents. Our aim was to describe dietary intake and weight-related concerns and behaviors among Hispanic, Hmong, and Somali adolescents and compare them with white adolescents. We performed a cross-sectional analysis of data from Eating and Activity in Teens 2010, a population-based study in the Minneapolis/St Paul metropolitan area. Current analysis includes 1,672 adolescents (Hispanic: n=562 [33.6%]; Hmong: n=477 [28.5%]; Somali: n=113 [6.8%]; white: n=520 [31.1%]; mean age=15.0 years). Adolescents completed classroom surveys and had their height/weight measured during the 2009-2010 academic year. Multivariable regression models, adjusted for socioeconomic status, age, and school as a random effect were used to examine racial/ethnic differences for each outcome variable for boys and girls. There were numerous differences in the behaviors of Hispanic, Hmong, and Somali adolescents as compared with whites. Hispanic and Somali youth consumed fruit and fast food more frequently. Hmong adolescents consumed sugar-sweetened beverages less frequently, and Somali boys consumed energy and sport drinks more frequently than whites. Compared with white boys, overweight/obesity was higher among Hispanic and Hmong. A higher percentage of Hmong and Somali adolescents engaged in unhealthy weight control behaviors. Body satisfaction was lower for all Hmong adolescents compared with whites. There were varying areas of concern in dietary intake, weight, and weight-related concerns and behaviors among adolescents in all ethnic groups. Future nutrition and physical activity interventions that include adolescents from these ethnic and cultural groups can benefit from, for example, modifying intervention strategies to the specific priority behaviors within the target population.


Intervention and prevention of steroid use in adolescents.
Athletes with a higher intent to use anabolic steroids were similar to students who indicated no predisposition to use steroids on economic, academic, and physical measures. They had similar understandings of anabolic steroid effects, and their self-rated understandings of how to weight train and of sports nutrition were similar. In addition, the influence of the coaches and the media and the perceived prevalence of anabolic steroid use were not different between the higher- and lower-intent students. These results demonstrated several significant differences. Higher-intent students had higher levels of alcohol and marijuana use, which suggest that those items might be tackled concurrently. These athletes had higher hostility, impulsivity, and a win-at-all-costs attitude. Despite similar physical measures, they had a high body image, but were less satisfied with their current weight. These findings underscored the importance of using nutrition and appropriate training as effective alternatives to anabolic steroids. Higher-intent students had greater peer tolerance of drug use and less parental influence not to use drugs, which implies that a peer-led small group format might be important to dispel the perceived peer tolerance. Including a parent-based component, one that emphasizes a disapproval of drug use also could be effective. Higher-intent athletes had less ability to refuse an offer of steroids. The dynamics of turning down steroids may differ from that of other illicit substances so that training in refusal skills specific to steroids is needed. These differences provide a needs assessment to identify curricular components for an intervention to permit anabolic steroid use. The sports team may be a unique educational setting because it can capitalize on peer ties, the coach's influence, and an athletes' motivation to improve, to prevent drug use, and to promote healthy behaviors.


Enhanced duck hepatitis B virus gene expression following aflatoxin B1 exposure.
Epidemiological studies have suggested synergistic interactions between chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure in the etiology of hepatocellular carcinoma (HCC), although the molecular mechanisms of their interactions are still not understood. The aim of this study was to use the Pekin duck model to investigate the impact of AFB1 exposure on duck hepatitis B virus (DHBV) replication during the early stages of virus-carcinogen interactions. Six-week-old chronic DHBV-carrier or uninfected ducks were exposed to AFB1 for 5 weeks or treated with dimethylsulfoxide (DMSO) as a control. Animals were observed for 6 to 13 weeks after AFB1 treatment to study the influence of AFB1 exposure on DHBV replication and liver pathologies. Histological analysis showed more marked changes in the livers of AFB1-treated ducks, and these were enhanced by DHBV infection. A significant increase in serum and liver DHBV DNA level was observed in AFB1-treated ducks as compared with DMSO-treated controls. In addition, viral RNAs, in particular the pregenomic RNA that is the template of viral replication, and intrahepatic DHBV DNA replicative intermediates, were significantly increased by AFB1 treatment. Moreover, an overexpression and accumulation of DHBV large envelope (L) protein was observed in the hepatocytes of AFB1-exposed animals. The in vitro study has further confirmed an increase in intracellular viral DNA and in virus release in AFB1-treated primary duck hepatocytes. Taken together, our results indicate that AFB1 exposure leads to an increase in virus gene expression associated with intrahepatic accumulation of DHBV L protein and enhanced liver pathology.


Women, HIV infection, and AIDS: tapestries of life, death, and empowerment.
Women, the minority population in the human immunodeficiency virus (HIV) pandemic, are fast becoming one of the highest subgroups to be infected and affected by the disease. In the United States, most of these women are black or Hispanic, poor and urban dwellers, and addicted to drugs. This paper discusses the physical, psychological, and social manifestations of HIV disease in women, such as diminished activity tolerance, neurologic or cognitive changes, occupational and social role imbalance, and stigma and discrimination, and describes the sociocultural aspects of women's lives for assessment and treatment of women with HIV. Health promotion, education, and AIDS prevention and wellness programming are emphasized as strategies toward facilitation of self-empowerment for women with HIV disease. These health promotion and wellness strategies include learning of new and adaptation of current roles; learning strategies for self-care that include care for one's physical, psychosocial, spiritual, and sexual health; and learning and developing action plans toward healthy living and self-empowerment.


Isolation and structural characterisation of rhamnogalacturonan oligomers generated by controlled acid hydrolysis of sugar-beet pulp.
Controlled acid hydrolysis was applied to a deesterified beet pulp and the resulting soluble fraction was fractionated on a Biorad AG 1X8 column eluted by ammonium acetate pH 6 from 0.05 to 2 M. Eight retained fractions were obtained, containing almost exclusively GalA and Rha. Three types of oligomers could be identified: homogalacturonans, of which mono-,di- and tri-GalA were isolated as individual components, and two series of rhamnogalacturonan (RG) oligomers. One RG oligomer, isolated after ion-exchange chromatography, was identified as alpha-D-GalAp-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalA p-(1-->2)-L-Rhap. The major peak contained oligomers of dp 6 to more than 20, of which dp 6 to 16 could be isolated on Bio-Gel P-6 + P-4. NMR of the oligomers of dp 6 to 10 showed the following structure: alpha-D-GalAp-(1[-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalA p-(1]n-->2)-L-Rhap. A second, quantitatively minor, series of RG oligomers eluted at higher ionic strength. These oligomers, which could be hydrolysed by RG-hydrolase and RG-lyase, were based on the alternating RG structure. Their non-reducing end was GalA, susceptible to hydrolysis by RG-galacturonohydrolase, and their reducing end might have more than one consecutive GalA.


Stress fracture of the tarsal middle cuneiform bone. A case report.
The authors have presented what they believe is the only reported case of a stress fracture of the tarsal middle cuneiform bone. Stress fracture pathogenesis, as well as diagnosis and treatment, were reviewed. It has been proposed that the middle cuneiform may be subject to increased stress in the runner during the propulsive phase, as this is the midfoot bone that transmits weight proximally in the medial column. This is evident by studying the cancellous structure of the tarsal bones. The ligamentous and osseous architecture of this region also can produce a midfoot buckling when the foot is plantarflexed against resistance. Prompt diagnosis and treatment is the key in preventing the stress fracture from becoming a chronic source of discomfort.


Arthroscopic repair of SLAP lesions with a bioknotless suture anchor.
The diagnosis and treatment of SLAP tears have improved with the development of arthroscopic shoulder surgery techniques. With types 2 and 4 tears, the goal is to restore stability to the labrum and biceps anchor and achieve healing to the glenoid. Suture repair with anchors is currently the repair technique of choice. The purpose of this article is to report a fast and simple method for arthroscopic SLAP repair that uses knotless suture anchors and obviates complex suture management and arthroscopic knot tying.


A 10-Year Review of Surgical Management of Complicated Peptic Ulcer Disease From a Single Center: Is Laparoscopic Approach the Future?
The discovery of Helicobacter pylori (H. pylori) as the culprit in peptic ulcer disease (PUD) has revolutionized its management. Despite the presence of effective drug treatments and an increased understanding of its etiology, the percentage of patients who require emergent surgery for complicated disease remains constant at 7% of hospitalized patients. This study aims at reviewing the incidence of complicated PUD and analyze changes in surgical management. From January 2002 to September 2012, records of all patients with a clinical or radiologic diagnosis of perforated PUD were evaluated. Short-term and long-term results were assessed with regard to type of surgical intervention. The primary end point was adverse events. Other end points were length of hospital stay, complications, and deaths. Included were 400 patients with a median age of 56 years (range, 17 to 89 y). Of these, males made up 70% (n=280), were older and had more comorbidities. Majority of perforations were located in the prepyloric region (80%) and duodenal bulb (20%). Nonsteroidal anti-inflammatory drug alone was involved in 50% of cases and in combination with H. pylori in 84%. H. pylori alone occurred in 40% of cases.Laparoscopic treatment was performed in 48 patients (12%) who remained hemodynamically stable. In the remaining 88% of patients, open approach was used. Simple closure with omentoplasty was performed in 98% and in 2%; definitive anti ulcer procedure was performed. Major complications occurred in 6% with an overall 30-day mortality rate of 2%. Most postoperative morbidity occurred after open approach. One patient who had laparoscopic repair died of other causes unrelated to the gastroduodenal perforation. Among the laparoscopic group, mean hospital stay was 4 days (range, 3 to 7 d), compared with 6 days (5 to 14 d) after open approach. Although the incidence of PUD is decreasing, it appears that among our patients, the incidence of complication is rising. Laparoscopic approach offers an alternative treatment with less pain, shorter hospital stay, and improved complications rate.


COVID-19 Vaccination Acceptance in the Context of the Health Belief Model: Comparative Cross-Sectional Study in Punjab, Pakistan.
One of the models that could be used to understand the adoption of vaccine uptake is the Health Belief Model (HBM). The aim of this study is to assess the role of HBM constructs and Perceived Health Status (PHS) on the vaccination status of individuals and to understand the role of socio-demographic variables on HBM scoring. A comparative cross-sectional telephone survey was conducted among 1325 vaccinated (60.0%) and non-vaccinated (40.0%) individuals aged 40 years and above in July 2021 in Punjab province, Pakistan. A higher level of education was the strongest predictor of positive HBM. All constructs of HBM, PHS and cues-to-action were significant predictors of COVID-19 vaccination uptake, with perceived benefits as the strongest predictor. In order to expand the vaccination coverage, double-pronged interventions utilizing both information and communication technology and human resources should be designed that address each barrier perceived by individuals and understandably communicate the benefits of COVID-19 vaccination to the broader population.


Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling.
In the Drosophila ovary, bone morphogenetic protein (BMP) ligands maintain germline stem cells (GSCs) in an undifferentiated state. The activation of the BMP pathway within GSCs results in the transcriptional repression of the differentiation factor bag of marbles (bam). The Nanos-Pumilio translational repressor complex and the miRNA pathway also help to promote GSC self-renewal. How the activities of different transcriptional and translational regulators are coordinated to keep the GSC in an undifferentiated state remains uncertain. Data presented here show that Mei-P26 cell-autonomously regulates GSC maintenance in addition to its previously described role of promoting germline cyst development. Within undifferentiated germ cells, Mei-P26 associates with miRNA pathway components and represses the translation of a shared target mRNA, suggesting that Mei-P26 can enhance miRNA-mediated silencing in specific contexts. In addition, disruption of mei-P26 compromises BMP signaling, resulting in the inappropriate expression of bam in germ cells immediately adjacent to the cap cell niche. Loss of mei-P26 results in premature translation of the BMP antagonist Brat in germline stem cells. These data suggest that Mei-P26 has distinct functions in the ovary and participates in regulating the fates of both GSCs and their differentiating daughters.


Characterization of myo-inositol hexakisphosphate deposits from larval Echinococcus granulosus.
The abundant metabolite myo-inositol hexakisphosphate (InsP6) can form vesicular deposits with cations, a widespread phenomenon in plants also found in the cestode parasite, Echinococcus granulosus. In this organism, the deposits are exocytosed, accumulating in a host-exposed sheath of extracellular matrix termed the laminated layer. The formation and mobilization of InsP6 deposits, which involve precipitation and solubilization reactions, respectively, cannot yet be rationalized in quantitative chemical terms, as the solids involved have not been formally described. We report such a description for the InsP6 deposits from E. granulosus, purified as the solid residue left by mild alkaline digestion of the principal mucin component of the laminated layer. The deposits are largely composed of the compound Ca5H2L.16H2O (L representing fully deprotonated InsP6), and additionally contain Mg2+ (6-9% molar ratio with respect to Ca2+), but not K+. Calculations employing recently available chemical constants show that the precipitation of Ca5H2L.16H2O is predicted by thermodynamics in secretory vesicle-like conditions. The deposits appear to be similar to microcrystalline solids when analysed under the electron microscope; we estimate that each crystal comprises around 200 InsP6 molecules. We calculate that the deposits increase, by three orders of magnitude, the surface area available for adsorption of host proteins, a salient ability of the laminated layer. The major inositol phosphate in the deposits, other than InsP6, is myo-inositol (1,2,4,5,6) pentakisphosphate, or its enantiomer, inositol (2,3,4,5,6) pentakisphosphate. The compound appears to be a subproduct of the intracellular pathways leading to the synthesis and vesicular accumulation of InsP6, rather than arising from extracellular hydrolysis of InsP6.


Investigating the influence of African American and African Caribbean race on primary care doctors' decision making about depression.
This paper explores differences in how primary care doctors process the clinical presentation of depression by African American and African-Caribbean patients compared with white patients in the US and the UK. The aim is to gain a better understanding of possible pathways by which racial disparities arise in depression care. One hundred and eight doctors described their thought processes after viewing video recorded simulated patients presenting with identical symptoms strongly suggestive of depression. These descriptions were analysed using the CliniClass system, which captures information about micro-components of clinical decision making and permits a systematic, structured and detailed analysis of how doctors arrive at diagnostic, intervention and management decisions. Video recordings of actors portraying black (both African American and African-Caribbean) and white (both White American and White British) male and female patients (aged 55 years and 75 years) were presented to doctors randomly selected from the Massachusetts Medical Society list and from Surrey/South West London and West Midlands National Health Service lists, stratified by country (US v.UK), gender, and years of clinical experience (less v. very experienced). Findings demonstrated little evidence of bias affecting doctors' decision making processes, with the exception of less attention being paid to the potential outcomes associated with different treatment options for African American compared with White American patients in the US. Instead, findings suggest greater clinical uncertainty in diagnosing depression amongst black compared with white patients, particularly in the UK. This was evident in more potential diagnoses. There was also a tendency for doctors in both countries to focus more on black patients' physical rather than psychological symptoms and to identify endocrine problems, most often diabetes, as a presenting complaint for them. This suggests that doctors in both countries have a less well developed mental model of depression for black compared with white patients.


Color Lens: Adaptive Color Scale Optimization for Visual Exploration.
Visualization applications routinely map quantitative attributes to color using color scales. Although color is an effective visualization channel, it is limited by both display hardware and the human visual system. We propose a new interaction technique that overcomes these limitations by dynamically optimizing color scales based on a set of sampling lenses. The technique inspects the lens contents in data space, optimizes the initial color scale, and then renders the contents of the lens to the screen using the modified color scale. We present two prototype implementations of this pipeline and describe several case studies involving both information visualization and image inspection applications. We validate our approach with two mutually linked and complementary user studies comparing the Color Lens with explicit contrast control for visual search.


Population-based values and abnormalities of the electrocardiogram in the general Dutch population: The LifeLines Cohort Study.
Our aim is to present average values and prevalence of electrocardiographic (ECG) abnormalities among the general Dutch population in the LifeLines Cohort. The ECG values previously studied in the Caucasian population of smaller cohorts will be confirmed with ECG data from LifeLines. ECG data of 152 180 individuals age 18 to 93 years were available. Individuals with cardiovascular risk factors were excluded to analyze the healthy population. Average values of the ECG for the healthy population were presented as means with 95% and 99% confidence intervals and as medians with first and 99th percentiles. Median heart rate was highest in the youngest and oldest individuals of the healthy population. Median duration of P wave, PQ interval, and QRS duration were longer in males compared with females. In contrast, median QT interval corrected for heart rate was higher in females. In general, the above-mentioned parameters increased with age. The prevalences of ECG abnormalities adjusted for the Dutch population were 0.9% for atrial fibrillation or flutter, 1.4% for premature atrial complexes, 0.5% for myocardial infarction, 2.1% for ventricular premature complexes, 1.0% for left ventricular hypertrophy, 8.1% for P-R interval >200 ms, and 0.8% for bundle branch block. Our study provides an overview of average values and ECG abnormalities and confirms data of previous smaller studies. In addition, we evaluate the age- and sex-dependent normal limits of the P wave and QRS duration and confirm in detail the frontal plane QRS-T angle on the ECG.


A longitudinal perspective on violence in the lives of South African children from the Birth to Twenty Plus cohort study in Johannesburg-Soweto.
Violence against children is a significant cause of personal suffering and long-term ill health, poor psychological adjustment, and a range of social difficulties, including adverse effects intergenerationally. Using a large corpus of longitudinal data collected in the Birth to Twenty Plus cohort, to give an overview of exposure to and experience of violence, as well as perpetration of violence, across childhood, reported contemporaneously by several informants. This overcomes limitations of retrospectively recalled information collected from one person at one point in time. We identified 280 data points relating to exposure to and perpetration of violence in 14 of the 21 waves of data collection from birth to 22 years of age. Data were classified into four developmental stages (preschool, primary school years, adolescence and young adulthood) and seven categories (exposure to violence in the community, home and school; exposure to peer violence; being a victim of violence, excluding sexual violence; sexual violence; and perpetration of violence). Both descriptive and inferential statistics were employed to analyse the data. Over the past two decades, only 1% of the sample had not been exposed to or experienced violence in their home, school and/or community. Two-thirds of children of schoolgoing age were reported as having been exposed to community violence, and more than half of all children to violence in their home. Reports of sexual violence increased from 10% among primary school-aged children to ~30% among adolescents and young adults. Over the course of their lives, ~40% of children were reported as having been exposed to or being victims of five or six of the categories of violence coded in this analysis. High levels of violence perpetration were reported across childhood. Age and gender differences in exposure to and experience and perpetration of violence were evident, and all categories of violence were more prevalent among poorer and more disadvantaged groups. Very high levels of violence were reported in all the settings of urban South African children's lives: home, community, school, among peers and in their intimate relationships. Children and youth were also reported to perpetrate high levels of violence. The personal and social costs of violence are very high, resulting in major public health problems due to its avoidable effects on short- and long-term mental and physical health and social adjustment, and intergenerationally.


Tobacco policy in American prisons, 2007.
To examine current tobacco policy in US prisons and explore changes in prison tobacco policies over time. Telephone survey of the 52 US departments of correction. Current tobacco policy; distribution of free tobacco; availability of smoking cessation programming and cessation aids. Complete responses were received from 51 of 52 (98%) departments, while one provided partial information. The majority of correctional systems (60%) reported total tobacco bans on prison grounds, with most remaining facilities (27%) having an indoor ban on tobacco use. No prisons distributed free tobacco. No major violence was reported relating to the implementation of stricter tobacco policies; however many respondents noted that tobacco became a major contraband item following the implementation of a total ban. While most prison systems with an indoor tobacco ban (86%) reported having tobacco cessation programmes, few of those with total bans (39%) continued such programmes after the initial transition period. Total tobacco bans have often been accompanied by the termination of tobacco cessation programmes. Such actions undermine efforts to promote long-term cessation resulting in a missed public health opportunity.


The benefit of tissue contact monitoring with an electrical coupling index during ablation of typical atrial flutter--a prospective randomised control trial.
We sought to investigate the use of tissue contact monitoring by means of the electrical coupling index (ECI) in a prospective randomised control trial of patients undergoing cavotricuspid isthmus (CTI) ablation for atrial flutter. Patients with ECG-documented typical flutter undergoing their first CTI ablation were randomised to ECI™-guided or non-ECI™-guided ablation. An irrigated-tip ablation catheter was used in all cases. Consecutive 50-W, 60-s radiofrequency lesions were applied to the CTI, from the tricuspid valve to inferior vena cava, with no catheter movement permitted during radiofrequency (RF) delivery. The ablation endpoint was durable CTI block at 20 min post-ablation. Patients underwent routine clinic follow-up post-operatively. A total of 101 patients (79 male), mean age 66 (+/-11), 50 ECI-guided and 51 control cases were enrolled in the study. CTI block was achieved in all. There were no acute complications. All patients were alive at follow-up. CTI block was achieved in a single pass in 36 ECI-guided and 30 control cases (p = 0.16), and at 20 min post-ablation, re-conduction was seen in 5 and 12 cases, respectively (p = 0.07). There was no significant difference in total procedure time (62.7 ± 33 vs. 62.3 ± 33 min, p = 0.92), RF requirement (580 ± 312 vs. 574 ± 287 s, p = 0.11) or fluoroscopy time (718 ± 577 vs. 721 ± 583 s, p = 0.78). After 6 ± 4 months, recurrence of flutter had occurred in 1 (2 %) ECI vs. 8 (16 %) control cases (OR 0.13, 95 % CI 0.01-1.08, p = 0.06). ECI-guided CTI ablation demonstrated a non-statistically significant reduction in late recurrence of atrial flutter, at no cost to procedural time, radiation exposure or RF requirement.


Phosphorylation of the herpes simplex virus type 1 tegument protein VP22.
The herpes simplex virus type 1 tegument protein VP22 is known to be highly phosphorylated during infection. Here we show that two electrophoretic forms of VP22 can be identified in infected cell extracts and that this heterogeneity is accounted for by phosphorylation. Furthermore, the nonphosphorylated form of VP22 appears to be specifically incorporated into virions. We also show that the phosphorylated form of VP22 is the only form detected during transient transfection and as such that VP22 can act as a substrate for a cellular kinase. Phospho-amino acid and phospho-peptide analyses of in vivo labeled VP22 were utilized to demonstrate that the phosphorylation profiles of VP22 synthesized during transfection and infection are the same. In both cases VP22 was modified solely on serine residues located in the N-terminal 120 residues of the protein. Moreover, in vitro phosphorylation was utilized to show that the constitutive cellular kinase, casein kinase II, which has four serine consensus recognition sites at the N-terminus of VP22, phosphorylates VP22 in the same manner as observed in vivo. This kinase also phosphorylates VP22 at the N-terminus in intact capsid-tegument structures. Casein kinase II is therefore likely to be the major kinase of VP22 during infection.


Timing jitter measurement of transmitted laser pulse relative to the reference using type II second harmonic generation in two nonlinear crystals.
A new method is proposed and analyzed for measuring the timing jitter of the transmitted pulse relative to the reference pulse using two type II phase-matched nonlinear crystals for second harmonic generation (SHG). The polarizations of the two pulses are exchanged in two crystals and the difference between two detected second harmonic signals can reflect the transmitted jitter. This new method provides a high sensitivity and timing resolution compared with the conventional RF (radio frequency) method. Since the overlapping levels in the two crystals are the same, the final output is zero when there is no time delay between the two pulses. Thus no offset is necessary to be subtracted from the final output and no time delay adjustment is required between the two pulses, compared with the previous optical method using one crystal and two dichroic beamsplitters. The jitter measuring performance is studied theoretically using non-stationary nonlinear wave-coupled equations for type II SHG of two pulses. The theoretical computation and analysis show that the sensitivity and the dynamic range of this new method depend on pulse width, crystal pulses and group velocity difference between two fundamental pulses.


Diet fatty acid profile, membrane composition and lifespan: an experimental study using the blowfly (Calliphora stygia).
The membrane pacemaker theory of ageing proposes that the polyunsaturated fatty acid (PUFA) composition of membrane lipids of a species is an important determinant of its maximum lifespan. We report three experiments using the blowfly Calliphora stygia, where this theory was tested by manipulation of dietary fat profile. Although the fat profile of the larval diet resulted in small alterations of individual membrane fatty acids, it had no effect on the peroxidation index (PI) of membrane lipids and furthermore had no effect on maximum lifespan. Similarly, manipulation of the fat profile of the adult diet resulted in small changes in individual fatty acids, but had no effect on the PI of membrane lipids. There was a small increase in maximum lifespan when adult diet was supplemented with PUFA in form of vegetable oils but no effect when diet was supplemented with pure PUFA. This difference is possibly due to antioxidant content of vegetable oils. The relative refractoriness of membrane PI to dramatic changes in response to diet is similar to the situation in the rat. These results also indicate the blowfly is unable to convert 18-carbon PUFA to more highly polyunsaturated 20- and 22-carbon PUFA.


Phase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313.
Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival in preclinical models. The activity of PEGPH20 with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated in patients with metastatic pancreatic cancer (mPC). Patients had untreated mPC, a performance status of 0 to 1, and adequate organ function. Tumor HA status was not required for eligibility. After a phase Ib dose-finding study of mFOLFIRINOX plus PEGPH20, the phase II open-label study randomly assigned patients (1:1) to the combination arm or to mFOLFIRINOX alone (n = 138). The primary end point was overall survival (OS). PEGPH20 dosages of 3 µg/kg every 2 weeks were more tolerable than twice-weekly dosages used in the phase I study, so 3 µg/kg every 2 weeks was the phase II dosage. An amendment instituted enoxaparin prophylaxis in the PEGPH20 combination arm as a result of increased thromboembolic (TE) events. The planned interim futility analysis when 35 deaths (of 103 analyzable patients) occurred resulted in an OS hazard ratio (HR) of 2.07 that favored the control arm, and the study was closed to accrual. The treatment-related grade 3 to 4 toxicity was significantly increased in the PEGPH20 combination arm relative to control (odds ratio, 2.7; 95% CI, 1.1 to 7.1). The median OS in the mFOLFIRINOX arm was 14.4 months (95% CI, 10.1 to 15.7 months) versus 7.7 months (95% CI, 4.6 to 9.3 months) in the PEGPH20 combination arm. Addition of PEGPH20 to mFOLFIRINOX seems to be detrimental in patients unselected for tumor HA status. This combination caused increased toxicity (mostly GI and TE events) and resulted in decreased treatment duration compared with mFOLFIRINOX alone. The median OS in the mFOLFIRINOX control arm (14.4 months) is, to our knowledge, the longest yet reported and can be considered for patients with good PS.


Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses.
Expression of the adhesion molecules CD44, L-selectin (CD62L), and integrin alpha 4 beta 7 by antibody-secreting cells (ASC) was examined in human volunteers after oral, rectal, intranasal, or systemic immunization with cholera toxin B subunit. Almost all blood ASC, irrespective of immunization route, isotype (IgG and IgA), and immunogen, expressed CD44. On the other hand, marked differences were observed between systemically and intestinally induced ASC with respect to expression of integrin alpha 4 beta 7 and L-selectin, adhesion molecules conferring tissue specificity for mucosal tissues and peripheral lymph nodes, respectively. Thus, most ASC induced at systemic sites expressed L-selectin, whereas only a smaller proportion of ASC expressed alpha 4 beta 7. In contrast, virtually all IgA- and even IgG-ASC detected after peroral and rectal immunizations expressed alpha 4 beta 7, with only a minor fraction of these cells expressing L-selectin. Circulating ASC induced by intranasal immunization displayed a more promiscuous pattern of adhesion molecules, with a large majority of ASC coexpressing L-selectin and alpha 4 beta 7. These results demonstrate that circulating ASC induced by mucosal and systemic immunization express different sets of adhesion molecules. Furthermore, these findings provide for the first time evidence for differential expression of adhesion molecules on circulating ASC originating from different mucosal sites. Collectively, these results may explain the anatomical division of mucosal and systemic immune responses in humans as well as the compartmentalization of mucosal immune responses initiated in the upper vs. the lower aerodigestive tract.


Versatile stamps in microcontact printing: transferring inks by molecular recognition and from ink reservoirs.
Microcontact printing is a heavily used surface modification method in materials and life science applications. This concept article focuses on the development of versatile stamps for microcontact printing that can be used to bind and release inks through molecular recognition or through an ink reservoir, the latter being used for the transfer of heavy inks, such as biomolecules and particles. Conceptually, such stamp properties can be introduced at the stamp surface or by changing the bulk stamp material; both lines of research will be reviewed here. Examples include supramolecular stamps with affinity properties, polymer-layer-grafted PDMS stamps, and porous multilayer-grafted PDMS stamps for the first case, and hydrogel stamps and porous stamps made by phase-separation micromolding for the second. Potential directions for future advancement of this field are also discussed.


Fine-tuning polyoxometalate non-linear optical chromophores: a molecular electronic "Goldilocks" effect.
A new aryl-imido polyoxometalate non-linear optical chromophore (POMophore) with a diphenylamino donor group attains the highest βzzz, 0 value (196 × 10-30 esu by Hyper-Rayleigh Scattering, HRS), and best transparency/non-linearity trade off yet for such materials. Stark spectroscopic and DFT investigation of this compound, plus NMe2 and carbazole analogues, show that its high performance results from a combination of strongly dipolar electronic transitions, and strong electronic communication across the π-system.


A single amino acid defines cross-species reactivity of tree shrew (Tupaia belangeri) CD1d to human invariant natural killer T (iNKT) cells.
The non-classical major histocompatibility complex (MHC) class I molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells, which are an important part of the innate immune system. CD1d/iNKT systems are highly conserved in evolution, and cross-species reactivity has been suggested to be a common feature of different animals based on research in humans and mice. However, we found that CD1d from the tree shrew (Tupaia belangeri), a close evolutionary relative of primates, failed to stimulate human iNKT cells, despite being more homologous to human CD1d than that of mouse. Sequence comparison and molecular modelling showed that two of the key amino acid residues in human CD1d proposed to be in direct contact with T-cell receptors were mutated in tree shrew CD1d. Substitution of one of the residues, but not the other, with the human residue enabled tree shrew CD1d to regain the ability to present lipid antigen to human iNKT cells. These results indicate that CD1d/iNKT recognition is species-specific, and that cross-species reactivity may be less common than currently proposed. Also, a naturally occurring CD1d mutation(s) that confers inability to stimulate iNKT cell function may have implications for future studies on CD1d/iNKT-associated diseases.


[Dysautonomic syncope. Diagnosis and treatment].
Inappropriate activation or disbalance of vasomotor reflexes may have a close relationship with the pathogenesis of disautonomic syndromes, a frequent underlying cause of recurrent syncope. A combined approach of meticulous historical data, physical examination and selected laboratory procedures may delineate the most common causes of recurrent syncope. Tests of autonomic function may be particularly helpful in the diagnosis of this entity. They include some non-invasive maneuvers such as stimulation of carotid sinus, Valsalva maneuver or tilt-table test. Therapy for this syndrome includes pharmacologic agents, surgical and radiotherapeutic maneuvers and atrioventricular sequential pacing. In this work we will present an overall formulation of the diagnostic evaluation and a therapy approach of the patient presenting with this complaint.


Gene regulation of plasmid- and chromosome-determined inorganic ion transport in bacteria.
Regulation of chromosomally determined nutrient cation and anion uptake systems shows important similarities to regulation of plasmid-determined toxic ion resistance systems that mediate the outward transport of deleterious ions. Chromosomally determined transport systems result in accumulation of K+, Mg2+, Fe3+, Mn2+, PO4(3-), SO4(2-), and additional trace nutrients, while bacterial plasmids harbor highly specific resistance systems for AsO2-, AsO4(3-), CrO4(2-), Cd2+, Co2+, Cu2+, Hg2+, Ni2+, SbO2-, TeO3(2-), Zn2+, and other toxic ions. To study the regulation of these systems, we need to define both the trans-acting regulatory proteins and the cis-acting target operator DNA regions for the proteins. The regulation of gene expression for K+ and PO4(3-) transport systems involves two-component sensor-effector pairs of proteins. The first protein responds to an extracellular ionic (or related) signal and then transmits the signal to an intracellular DNA-binding protein. Regulation of Fe3+ transport utilizes the single iron-binding and DNA-binding protein Fur. The MerR regulatory protein for mercury resistance both represses and activates transcription. The ArsR regulatory protein functions as a repressor for the arsenic and antimony(III) efflux system. Although the predicted cadR regulatory gene has not been identified, cadmium, lead, bismuth, zinc, and cobalt induce this system in a carefully regulated manner from a single mRNA start site. The cadA Cd2+ resistance determinant encodes an E1(1)-1E2-class efflux ATPase (consisting of two polypeptides, rather than the one earlier identified). Cadmium resistance is also conferred by the czc system (which confers resistances to zinc and cobalt in Alcaligenes species) via a complex efflux pump consisting of four polypeptides. These two cadmium efflux systems are not otherwise related. For chromate resistance, reduced cellular accumulation is again the resistance mechanism, but the regulatory components are not identified. For other toxic heavy metals (with few exceptions), there exist specific plasmid resistances that remain relatively terra incognita for future exploration of bioinorganic molecular genetics and gene regulation.


Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.
Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures.


Results From Japan's 2016 Report Card on Physical Activity for Children and Youth.
The Report Card on Physical Activity for Children and Youth aims to consolidate existing evidence, encourage greater evidence-informed physical activity, and improve surveillance of physical activity. The Japan report card followed the methodology of the Canadian and Scottish report cards, but was adapted to reflect the Japanese context. Nationally representative data were used to score each of the respective indicators. The 2016 Japan Report Card on Physical Activity for Children and Youth consists of Health Behaviors and Outcomes (7 indicators), and Influences on Health Behaviors (4 indicators). Three Health Behaviors and Outcomes received C grades (Participation in Sport; Sedentary Behavior; Recreational Screen Time; Physical Fitness), while 2 indicators could not be graded (Overall Physical Activity, and Active Play). The indicators Active Transportation (B) and Weight Status were favorable (A). In the Influences domain, Family Influence and Community and the Built Environment were graded as D, while School and Government Strategies and Investments were favorable (B). The Japan report card illustrated some favorable health behaviors, health outcomes, and influences. There is a need for more evidence especially on overall physical activity levels, active play, and community and the built environment.


Atrial fibrillation requiring urgent medical care. Approach and outcome in the various departments of admission. Data from the atrial Fibrillation/flutter Italian REgistry (FIRE).
The atrial Fibrillation/flutter Italian REgistry (FIRE) study was designed to obtain updated information regarding the clinical characteristics of and medical approach to patients requiring urgent medical care for atrial fibrillation (AF) or atrial flutter in a nationwide and representative series of hospitals. 4570 consecutive patients admitted to the emergency room for AF/atrial flutter were enrolled in 207 hospitals. Of these, 2838 (61.9%) were hospitalized (median 6 days, 43% in cardiology and 57% in internal medicine departments), and constitute the population of this study. AF/atrial flutter represented 1.5% of all emergency room admissions and 3.3% of all hospitalizations. The mean age was 70 +/- 12 years; 89.9% had AF and 10.1% atrial flutter. In 31% of the hospitalized patients no cardiac disease was present, and in 18% no disease (either cardiac or non-cardiac) could be detected. Predictors of no attempt of cardioversion (37.5% of patients) included: onset of AF > 48 hours, heart failure, increasing age, syncope, admission to a non-cardiology department, stroke or transient ischemic attack (TIA). Predictors of in-hospital mortality (2.2%) included: age, heart failure, diabetes, admission to a non-cardiology department, and stroke or TIA. Predictors of the absence of sinus rhythm at discharge (35.6% of patients) included: no attempt of cardioversion, heart failure, chronic anticoagulation, AF duration > 48 hours, increasing age, stroke or TIA, and admission to a non-cardiology department. Transesophageal echocardiography was performed in only 6% of patients. AF/atrial flutter represent a significant burden on the health care system with a higher than expected hospitalization rate from the emergency room. One out of three discharged patients is not in sinus rhythm. There is still a wide gap between evidence-based medicine and real practice in the treatment of patients with AF.


Honey compared with silver sulphadiazine in the treatment of superficial partial-thickness burns.
Burn injury is associated with a high incidence of death and disability; yet, its management remains problematic and costly. We conducted this clinical study to evaluate the efficacy of honey in the treatment of superficial and partial-thickness burns covering less than 40% of body surface area and compared its results with those of silver sulphadiazine (SSD). In this randomised comparative clinical trial, carried out Burn Center of POF Hospital, Wah Cantt, Pakistan, from May 2007 to February 2008, 150 patients of all ages having similar types of superficial and partial-thickness burns at two sites on different parts of body were included. Each patient had one burn site treated with honey and one treated with topical SSD, randomly. The rate of re-epithelialization and healing of superficial and partial-thickness burns was significantly faster in the sites treated with honey than in the sites treated with SSD (13·47 ± 4·06 versus 15·62 ± 4·40 days, respectively: P < 0·0001). The site treated with honey healed completely in less than 21 days versus 24 days for the site treated with SSD. Six patients had positive culture for Pseudomonas aeroginsa in honey-treated site, whereas 27 patients had positive culture in SSD-treated site. The results clearly showed greater efficacy of honey over SSD cream for treating superficial and partial-thickness burns.


Psychosocial aspects of childhood obesity.
Rates of childhood obesity are increasing at alarming rates worldwide. This is especially alarming as obesity is associated with many physical and psychological consequences. A great number of studies indicate that obese children have an impaired psychological well-being (e.g., depression, self-esteem, and quality of life) compared to their non-overweight peers. There has been an overwhelming amount of research conducted in this area over the past few decades, and as such, this paper provides a summarized overview of the vast trove of available information on the psychosocial aspects of childhood obesity. In this paper we provide a summarized overview of: 1) psychosocial aspects that contribute to the onset of childhood obesity; 2) psychosocial consequences of childhood obesity; and 3) familial-based lifestyle behavior modification interventions for treating childhood obesity and its treatment success. Although it seems obvious that obese children and adolescents would likely be at higher risk for psychological problems, the mediating factors in the relationship between psychological problems and obesity are still not well established. Obesity is a complex disorder with an equally complex etiology, and is thus associated with complex behaviors and outcomes that make it difficult to study in children. It has been indicated that family-based lifestyle interventions can improve psychological well-being in obese children; however, not all children profit from these interventions. Interventions aimed at improving treatment results need further investigation. For example, interventions targeted specifically at groups that tend to be less successful in weight-loss programs and interventions providing long-term support to these individuals are recommended.


Unique prokaryotic consortia in geochemically distinct sediments from Red Sea Atlantis II and discovery deep brine pools.
The seafloor is a unique environment, which allows insights into how geochemical processes affect the diversity of biological life. Among its diverse ecosystems are deep-sea brine pools - water bodies characterized by a unique combination of extreme conditions. The 'polyextremophiles' that constitute the microbial assemblage of these deep hot brines have not been comprehensively studied. We report a comparative taxonomic analysis of the prokaryotic communities of the sediments directly below the Red Sea brine pools, namely, Atlantis II, Discovery, Chain Deep, and an adjacent brine-influenced site. Analyses of sediment samples and high-throughput pyrosequencing of PCR-amplified environmental 16S ribosomal RNA genes (16S rDNA) revealed that one sulfur (S)-rich Atlantis II and one nitrogen (N)-rich Discovery Deep section contained distinct microbial populations that differed from those found in the other sediment samples examined. Proteobacteria, Actinobacteria, Cyanobacteria, Deferribacteres, and Euryarchaeota were the most abundant bacterial and archaeal phyla in both the S- and N-rich sections. Relative abundance-based hierarchical clustering of the 16S rDNA pyrotags assigned to major taxonomic groups allowed us to categorize the archaeal and bacterial communities into three major and distinct groups; group I was unique to the S-rich Atlantis II section (ATII-1), group II was characteristic for the N-rich Discovery sample (DD-1), and group III reflected the composition of the remaining sediments. Many of the groups detected in the S-rich Atlantis II section are likely to play a dominant role in the cycling of methane and sulfur due to their phylogenetic affiliations with bacteria and archaea involved in anaerobic methane oxidation and sulfate reduction.


Feedback inhibition of insulin secretion in type 2 diabetes.
1. The purpose of the present study was to examine the ability of insulin to inhibit its own secretion in type 2 diabetes independently of the prevailing plasma glucose concentration. 2. The responses of the plasma C-peptide concentration to sustained hyperinsulinaemia were assessed during a 200 min isoglycaemic clamp study in 14 patients with type 2 diabetes and seven age- and weight-matched control subjects. The arterialized venous plasma glucose concentration was clamped at approximately 0.3 mmol/l below each subject's own basal level and was not permitted to rise above the basal level. 3. In the fasting state, the plasma C-peptide concentration was slightly, but not significantly, higher in the diabetic patients than in the control subjects (667 versus 413 pmol/l, respectively, P = 0.07), but it remained significantly higher in the diabetic patients during the clamp studies in absolute terms (minimum plasma C-peptide concentration 400 pmol/l in diabetic patients versus 151 pmol/l in control subjects, P less than 0.05) and was suppressed to a lesser extent when expressed as a percentage change from basal (35.8% in diabetic patients versus 59.4% in control subjects, P less than 0.01). 4. In order to investigate whether a high plasma glucose concentration was maintaining the plasma C-peptide concentration in the diabetic patients, six of these patients underwent a second clamp study at euglycaemia (plasma glucose concentration 5.2 mmol/l). Under these conditions, the plasma C-peptide concentration was suppressed to the same extent as in the control subjects (from 623 to 195 pmol/l, a change of 62.7%).(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic dissection of the central pair microtubules of the flagella of Chlamydomonas reinhardtii.
Mutations at two loci, which cause an altered mobility of the flagella, affected the central pair microtubule complex of Chlamydomonas reinhardtii flagella. The mutations at both loci primarily affected the C1 microtubule of the complex. Three alleles at the PF16 locus affected the stability of the C1 microtubule in isolated axonemes. This phenotype has allowed us to determine that at least ten polypeptides of the central pair complex are unique to the C1 microtubule. The motility defect was correlated with the failure to assemble three of these ten polypeptides in vivo. The structural gene product of the PF16 locus was a polypeptide with molecular weight 57,000 as shown by analysis of five intragenic revertants and by analysis of axonemes from dikaryon rescue experiments. Three alleles at the PF6 locus affected the assembly of one of the two projections of the C1 microtubule and this projection was formed by at least three polypeptide components, which are a subset of polypeptides missing in isolated pf16 axonemes. No structural gene product has been identified for the PF6 locus. The gene product is probably not one of the identified projection constituents as shown by analysis of dikaryon rescue experiments. Chemical extraction of isolated wild-type axonemes suggests that at least seven polypeptide components are unique to the C2 microtubule.


Adult neurogenesis in crayfish: Origin, expansion, and migration of neural progenitor lineages in a pseudostratified neuroepithelium.
Two decades after the discovery of adult-born neurons in the brains of decapod crustaceans, the deutocerebral proliferative system (DPS) producing these neural lineages has become a model of adult neurogenesis in invertebrates. Studies on crayfish have provided substantial insights into the anatomy, cellular dynamics, and regulation of the DPS. Contrary to traditional thinking, recent evidence suggests that the neurogenic niche in the crayfish DPS lacks self-renewing stem cells, its cell pool being instead sustained via integration of hemocytes generated by the innate immune system. Here, we investigated the origin, division and migration patterns of the adult-born neural progenitor (NP) lineages in detail. We show that the niche cell pool is not only replenished by hemocyte integration but also by limited numbers of symmetric cell divisions with some characteristics reminiscent of interkinetic nuclear migration. Once specified in the niche, first generation NPs act as transit-amplifying intermediate NPs that eventually exit and produce multicellular clones as they move along migratory streams toward target brain areas. Different clones may migrate simultaneously in the streams but occupy separate tracks and show spatio-temporally flexible division patterns. Based on this, we propose an extended DPS model that emphasizes structural similarities to pseudostratified neuroepithelia in other arthropods and vertebrates. This model includes hemocyte integration and intrinsic cell proliferation to synergistically counteract niche cell pool depletion during the animal's lifespan. Further, we discuss parallels to recent findings on mammalian adult neurogenesis, as both systems seem to exhibit a similar decoupling of proliferative replenishment divisions and consuming neurogenic divisions.


The low-recombining pericentromeric region of barley restricts gene diversity and evolution but not gene expression.
The low-recombining pericentromeric region of the barley genome contains roughly a quarter of the genes of the species, embedded in low-recombining DNA that is rich in repeats and repressive chromatin signatures. We have investigated the effects of pericentromeric region residency upon the expression, diversity and evolution of these genes. We observe no significant difference in average transcript level or developmental RNA specificity between the barley pericentromeric region and the rest of the genome. In contrast, all of the evolutionary parameters studied here show evidence of compromised gene evolution in this region. First, genes within the pericentromeric region of wild barley show reduced diversity and significantly weakened purifying selection compared with the rest of the genome. Second, gene duplicates (ohnolog pairs) derived from the cereal whole-genome duplication event ca. 60MYa have been completely eliminated from the barley pericentromeric region. Third, local gene duplication in the pericentromeric region is reduced by 29% relative to the rest of the genome. Thus, the pericentromeric region of barley is a permissive environment for gene expression but has restricted gene evolution in a sizeable fraction of barley's genes.


Chemical Modification of Influenza CD8+ T-Cell Epitopes Enhances Their Immunogenicity Regardless of Immunodominance.
T cells are essential players in the defense against infection. By targeting the MHC class I antigen-presenting pathway with peptide-based vaccines, antigen-specific T cells can be induced. However, low immunogenicity of peptides poses a challenge. Here, we set out to increase immunogenicity of influenza-specific CD8+ T cell epitopes. By substituting amino acids in wild type sequences with non-proteogenic amino acids, affinity for MHC can be increased, which may ultimately enhance cytotoxic CD8+ T cell responses. Since preventive vaccines against viruses should induce a broad immune response, we used this method to optimize influenza-specific epitopes of varying dominance. For this purpose, HLA-A*0201 epitopes GILGFVFTL, FMYSDFHFI and NMLSTVLGV were selected in order of decreasing MHC-affinity and dominance. For all epitopes, we designed chemically enhanced altered peptide ligands (CPLs) that exhibited greater binding affinity than their WT counterparts; even binding scores of the high affinity GILGFVFTL epitope could be improved. When HLA-A*0201 transgenic mice were vaccinated with selected CPLs, at least 2 out of 4 CPLs of each epitope showed an increase in IFN-γ responses of splenocytes. Moreover, modification of the low affinity epitope NMLSTVLGV led to an increase in the number of mice that responded. By optimizing three additional influenza epitopes specific for HLA-A*0301, we show that this strategy can be extended to other alleles. Thus, enhancing binding affinity of peptides provides a valuable tool to improve the immunogenicity and range of preventive T cell-targeted peptide vaccines.


Embodied Synaptic Plasticity With Online Reinforcement Learning.
The endeavor to understand the brain involves multiple collaborating research fields. Classically, synaptic plasticity rules derived by theoretical neuroscientists are evaluated in isolation on pattern classification tasks. This contrasts with the biological brain which purpose is to control a body in closed-loop. This paper contributes to bringing the fields of computational neuroscience and robotics closer together by integrating open-source software components from these two fields. The resulting framework allows to evaluate the validity of biologically-plausibe plasticity models in closed-loop robotics environments. We demonstrate this framework to evaluate Synaptic Plasticity with Online REinforcement learning (SPORE), a reward-learning rule based on synaptic sampling, on two visuomotor tasks: reaching and lane following. We show that SPORE is capable of learning to perform policies within the course of simulated hours for both tasks. Provisional parameter explorations indicate that the learning rate and the temperature driving the stochastic processes that govern synaptic learning dynamics need to be regulated for performance improvements to be retained. We conclude by discussing the recent deep reinforcement learning techniques which would be beneficial to increase the functionality of SPORE on visuomotor tasks.


Animal models for studying microglia: the first, the popular, and the new.
Microglia, the resident phagocytes of brain, have been intensively studied since their discovery in the 1920s. There is no doubt that the possibility of culturing microglia in vitro has advanced enormously our understanding of these cells. However, as we know today, that microglia react to even small changes in the brain, it is crucial to also study these cells by preserving as much as possible their natural environment. Nowadays, advances in imaging technologies and transgenic cell labeling methods allow the direct observation of cells at work. These in vivo approaches have already changed our view on microglia by showing that these cells are active even in the healthy adult brain. As today, there is upcoming evidence that microglia can directly influence neuronal activity, understanding their roles and, in particular, their interactions with neurons is of great importance. The aim of this review is to illustrate three animal models that are currently used for microglial research and to discuss their characteristics and advantages by presenting recent achievements in microglial research. In our view the availability of different systems for studying microglia will lead to a more comprehensive understanding of their functions.


Antiurolithic effect of lupeol and lupeol linoleate in experimental hyperoxaluria.
The present study was undertaken to explore the efficiency of the pentacyclic triterpene lupeol (1) and its ester derivative, lupeol linoleate (2), in experimental hyperoxaluria. Hyperoxaluria was induced in male Wistar rats with 0.75% ethylene glycol (EG) in drinking water for 28 days. Hyperoxaluric animals were supplemented orally with 1 and 2 (50 mg/kg body wt/day) throughout the experimental period of 28 days. The renal enzymes were assayed as markers of renal tissue integrity. The redox status and oxalate metabolism in animals under oxalate overloading was also assessed. Microscopic analysis was done to investigate the abnormalities associated with oxalate exposure in renal tissues. Increase in oxidative milieu in hyperoxaluria was evident by increased lipid peroxidation (LPO) and decreased enzymic and nonenzymic antioxidants. Decrease in the activities of renal enzymes exemplified the damage induced by oxalate, which correlated positively with increased LPO and increased oxalate synthesis. Renal microscopic analysis further emphasized the oxalate-induced damage. These abnormal biochemical and histological aberrations were attenuated with test compound treatment, with 2 more effective than 1. From the present study, it can be concluded that 1 and 2 may serve as candidates for alleviating oxalate toxicity.


The Sensitivity of the cVEMP Test in Detecting A Superior Semicircular Canal Dehiscence and the Influence of a Coexisting Incudal Lysis: A Case Report.
In this case report, the air-conducted cervical vestibular evoked myogenic potentials (AC cVEMP) test was only sensitive for the left superior semicircular canal dehiscence (SCD), even though the contralateral SCD was of equal length (2.5 mm). Furthermore, a lysis of the processus lenticularis incudis caused a real conductive hearing loss in the left ear. A diminished left AC cVEMP was thus expected, but the opposite was shown (increased corrected amplitude, lowered detection threshold). The patient only experienced hearing loss, so middle ear surgery was performed to repair the lysis. The postoperative AC cVEMP showed a further "uncovering" of the SCD with increased corrected amplitude on the left but no vestibular symptoms. The significance of an SCD should be interpreted with caution, even when the AC cVEMP and the imaging are significant. Furthermore, AC cVEMPs should not be considered as evidence for the absence or presence of conductive hearing loss.


Clinical and economic evaluation of first-line therapy with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer.
Recently, significant progress in treatment of metastatic colorectal cancer has been achieved. Either FOLFIRI (fluorouracil, leucovorin and irinotecan) or modified FOLFOX6 (fluorouracil, leucovorin and oxaliplatin, oxaliplatin dose 85 mg/m(2)) is selected as first-line therapy in clinical practice in Japan. However, economic burden of colorectal cancer is considerable. Analysis was made for all patients who were treated with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer. Regimen of FOLFIRI was compared with modified FOLFOX6 under consideration from clinical and economic standpoints. Progression free survival, response, toxicity and cancer care cost in patients with metastatic colorectal cancer was analyzed. Direct costs based on the fee schedule of the Japanese national health insurance were calculated. Median progression free survival was 7.7 months for FOLFIRI versus 8.4 months for modified FOLFOX6 (P = 0.48). Overall cost for first four cycles was yen756 284 for FOLFIRI and yen1 081 162 for modified FOLFOX6 (P < 0.0001). All grade alopecia was significantly more frequent with FOLFIRI than with modified FOLFOX6 (P = 0.04). All grade neuropathy was more observed with modified FOLFOX6 than FOLFIRI (P = 0.0002). FOLFIRI is inexpensive in the initial stage of treatment which a number of patients can receive chemotherapy than modified FOLFOX6 as first-line therapy for metastatic colorectal cancer in Japanese national insurance system.


Essential role for NFI-C/CTF transcription-replication factor in tooth root development.
The mammalian tooth forms by a series of reciprocal epithelial-mesenchymal interactions. Although several signaling pathways and transcription factors have been implicated in regulating molar crown development, relatively little is known about the regulation of root development. Four genes encoding nuclear factor I (NFI) transcription-replication proteins are present in the mouse genome: Nfia, Nfib, Nfic, and NFIX: In order to elucidate its physiological role(s), we disrupted the Nfic gene in mice. Heterozygous animals appear normal, whereas Nfic(-/-) mice have unique tooth pathologies: molars lacking roots, thin and brittle mandibular incisors, and weakened abnormal maxillary incisors. Feeding in Nfic(-/-) mice is impaired, resulting in severe runting and premature death of mice reared on standard laboratory chow. However, a soft-dough diet mitigates the feeding impairment and maintains viability. Although Nfic is expressed in many organ systems, including the developing tooth, the tooth root development defects were the prominent phenotype. Indeed, molar crown development is normal, and well-nourished Nfic(-/-) animals are fertile and can live as long as their wild-type littermates. The Nfic mutation is the first mutation described that affects primarily tooth root formation and should greatly aid our understanding of postnatal tooth development.


Role of U.S. animal control agencies in equine neglect, cruelty, and abandonment investigations.
Every state in the United States has regulations prohibiting acts of neglect and cruelty against animals. Local law enforcement and animal control agencies are responsible in many communities to enforce these statutes. As society's perception of horses has changed from their origin as livestock to companion animals in modern times, owners have transitioned their care and management. The goal of this study was to identify the role and capacities of local animal control services in the United States that investigate equine neglect, cruelty, and abandonment investigations and to identify challenges and outcomes of the investigations. A 128-question online survey was accessible for animal agencies to complete. Comprehensive questions included their capacity for investigating equine cases, funding, housing for horses, and causes and outcomes of investigations. Respondents also were asked to select a single case and provide detailed information on the condition of horses, seizure and custody procedures, costs, and prosecution proceedings. A total of 165 respondents from 26 states completed all or the majority of the questions. A total of 6,864 equine investigations were initiated between 2007 and 2009 by 90 agencies, which extrapolates to 38 investigations annually per agency. A typical agency has an average annual budget of $740,000, employs 7 animal control officers, and spends about $10,000 annually on equine cases. Neglect was ranked as the most common reason for investigation. Owner ignorance, economic hardship, and lack of responsibility were the highest ranked causes of neglect and cruelty. Individual cases were provided by 91 agencies concerning 749 equines. The physical condition of the horse was the primary factor of investigation, and low body condition, parasite infestation, and compromised dental condition were present in most seized horses. Over half of the equine owners previously had been investigated or charged with neglect or cruelty of animals or were identified with cruelty or abuse offenses to people. Less than 3% of the cases advanced to adjudication, and these were likely to be decided by a judge rather than a jury. Judgments of guilty verdicts and pleas were 9 times more common than acquittal. Challenges for equine investigations cases included lack of funding, limited availability of facilities for horses, and providing educational materials for horse owners to aid in prevention and resolution of neglect cases.


Open Access Dataset for EEG+NIRS Single-Trial Classification.
We provide an open access dataset for hybrid brain-computer interfaces (BCIs) using electroencephalography (EEG) and near-infrared spectroscopy (NIRS). For this, we con-ducted two BCI experiments (left vs. right hand motor imagery; mental arithmetic vs. resting state). The dataset was validated using baseline signal analysis methods, with which classification performance was evaluated for each modality and a combination of both modalities. As already shown in previous literature, the capability of discriminating different mental states can be en-hanced by using a hybrid approach, when comparing to single modality analyses. This makes the provided data highly suitable for hybrid BCI investigations. Since our open access dataset also comprises motion artifacts and physiological data, we expect that it can be used in a wide range of future validation approaches in multimodal BCI research.


Tough adults, frail babies: an analysis of stress sensitivity across early life-history stages of widely introduced marine invertebrates.
All ontogenetic stages of a life cycle are exposed to environmental conditions so that population persistence depends on the performance of both adults and offspring. Most studies analysing the influence of abiotic conditions on species performance have focussed on adults, while studies covering early life-history stages remain rare. We investigated the responses of early stages of two widely introduced ascidians, Styela plicata and Microcosmus squamiger, to different abiotic conditions. Stressors mimicked conditions in the habitats where both species can be found in their distributional ranges and responses were related to the selection potential of their populations by analysing their genetic diversity. Four developmental stages (egg fertilisation, larval development, settlement, metamorphosis) were studied after exposure to high temperature (30°C), low salinities (26 and 22‰) and high copper concentrations (25, 50 and 100 µg/L). Although most stressors effectively led to failure of complete development (fertilisation through metamorphosis), fertilisation and larval development were the most sensitive stages. All the studied stressors affected the development of both species, though responses differed with stage and stressor. S. plicata was overall more resistant to copper, and some stages of M. squamiger to low salinities. No relationship was found between parental genetic composition and responses to stressors. We conclude that successful development can be prevented at several life-history stages, and therefore, it is essential to consider multiple stages when assessing species' abilities to tolerate stress. Moreover, we found that early development of these species cannot be completed under conditions prevailing where adults live. These populations must therefore recruit from elsewhere or reproduce during temporal windows of more benign conditions. Alternatively, novel strategies or behaviours that increase overall reproductive success might be responsible for ensuring population survival.