Assessment of Aspergillus fumigatus burden in pulmonary tissue of guinea pigs by quantitative PCR, galactomannan enzyme immunoassay, and quantitative culture.
Early diagnosis of invasive pulmonary aspergillosis is problematic in some patient groups due to the lack of rapid, sensitive, specific, and reliable diagnostic tests. Fungal burden and therapeutic efficacy were assessed by survival, quantitative culture (CFU counts), galactomannan enzyme immunoassay (GM-EIA), and quantitative PCR (qPCR) in a new guinea pig model of invasive pulmonary aspergillosis using an aerosol challenge. At 1 day postinfection, qPCR determined that the pulmonary fungal burden was 2 log(10) higher than that determined by CFU counting and increased significantly (P < 0.03) over time. In contrast, the tissue burden assessed by CFU counting did not rise over the course of the study. Therapy with the antifungal drug voriconazole produced statistically significant decreases in pulmonary fungal burden, as detected by CFU counting (P < 0.02), qPCR, and GM-EIA (both P < 0.0002). Daily assessment of the progression of fungal infection in serum was performed by qPCR and GM-EIA. GM-EIA demonstrated a statistically significant reduction in the fungal load on days 6 and 7 in voriconazole-treated animals compared to time-matched controls (P < 0.02). Confirmation of fungal tissue burden by two or more methods should provide a more precise account of the burden, allowing improved assessment of diagnostic and therapeutic strategies in invasive pulmonary aspergillosis.


A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats.
The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta(+) radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta(+) sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.


Transcriptome analysis of Aedes aegypti Aag2 cells in response to dengue virus-2 infection.
Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model. RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The transcriptome analysis generated 8866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed, and that the transcriptome sequencing data were reliable. This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.


Impact of Sprouting under Potassium Nitrate Priming on Nitrogen Assimilation and Bioactivity of Three Medicago Species.
Edible sprouts are rich in flavonoids and other polyphenols, as well as proteins, minerals, and vitamins. Increasing sprout consumption necessitates improving their quality, palatability, and bioactivity. The purpose of this study was to test how KNO3 priming affects the sprouting process species on three Medicago species (Medicago indicus, Medicago interexta, and Medicago polymorpha) and their nutritional values. Targeted species of Medicago were primed with KNO3, and the levels of different primary and secondary metabolites were determined. KNO3 induced biomass accumulation in the sprouts of the three species, accompanied by an increased content of total mineral nutrients, pigments, vitamins, and essential amino acids. Besides, our results showed that KNO3 enhanced the activity of nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine synthetase (GS) enzymes, which are involved in the nitrogen metabolism and GOGAT cycle, which, in turn, increase the nitrogen and protein production. KNO3 treatment improved the bioactive compound activities of Medicago sprouts by increasing total phenolic and flavonoid contents and enhancing the antioxidant and antidiabetic activities. Furthermore, species-specific responses toward KNO3 priming were noticeable, where Medicago interexta showed the highest antioxidant and antidiabetic activities, followed by Medicago polymorpha. Overall, this study sheds the light on the physiological and biochemical bases of growth, metabolism, and tissue quality improvement impact of KNO3 on Medicago sprouts.


A study to explore the risk factors for the early onset of cataract in India.
The aim of this study was to identify risk factors for the development of cataract in young patients. The study was undertaken at Iladevi Cataract and IOL Research Centre, Ahmedabad, Gujarat, India. In a clinic-based observational study, 340 consecutive patients in the age group of 30-45 years presenting with nuclear, cortical, posterior subcapsular (PSC), mixed, and posterior polar cataract were prospectively studied. A detailed history regarding sunlight exposure, atopy, diabetes, steroid intake, myopia, glaucoma, and uveitis was elicited. The mean age of the patients was 40.2+/-4.6 years; there were 202 men. The major risk factors were atopy (25.6%), idiopathic (19.1%), high myopia (12.4%), atopy with steroid intake (10.9%), steroid usage (7.4%), sunlight exposure (3.8%), and diabetes mellitus (3.2%). PSC was observed in 53.5% eyes. Multinomial logistic regression revealed that atopy (P=0.016), steroid usage (P=0.100), and diabetes mellitus (P=0.076) documented higher odds for PSC. High myopia (P<0.001) and sunlight exposure (P=0.003) documented higher odds for nuclear cataract. Atopy was found to be the most common risk factor associated with the development of cataract in young individuals. PSC was the predominant type of cataract prevalent in young patients.


[The clinical efficacy of ticarcillin/clavulanate in severe pneumonia].
Efficacy of ticarcillin/clavulanate was studied in the treatment of 11 patients with severe community- and hospital-acquired pneumonia in an open controlled trial. The drug was administered in a dose of 3.1 g every 4 or 6 hours depending on the infection severity. When pneumonia was due to Pseudomonas aeruginosa, amikacin was additionally used. The positive clinical effect of ticarcillin/clavulanate was stated in 73 per cent of the patients. The pathogen eradication was stated in all the patients. However, in 2 cases superinfection due to P.aeruginosa developed. Mild adverse effects were observed in 2 cases. It is concluded that ticarcillin/clavulanate is highly efficient in the treatment of patients with severe or complicated pneumonia. In cases with ventilator-associated pneumonia it is advisable to use ticarcillin/clavulanate in combination with an aminoglycoside.


MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer.
To investigate the mechanism by which miR-19a is up-regulated in gastric cancer (GC), which plays an oncogenic role. In the present study, we investigated the role of miR-19a in gastric tissues as well as two GC cell lines. In vivo, we detected the basal expression level of miR-19a using real-time reverse transcription-PCR (RT-PCR), and the relevance between expression of miR-19a and clinicopathological information was analyzed. In vitro, miR-19a was ectopically expressed using overexpression and knock-down strategies. Overexpression of miR-19a was significantly associated with metastasis of GC and inferior overall prognosis. However, no significant correlation was found between miR-19a expression and other characteristics such as age, gender, tobacco, alcohol or tumor size. Cell proliferation, migration and invasion assays showed that overexpression of miR-19a promoted the proliferation, migration and invasion, and that overexpression of miR-19a promoted the epithelial-mesenchymal transition through activating the PI3K/AKT pathway. Blocking the PI3K/AKT pathway could cancel the effect of miR-19a. All together, our results suggest that miR-19a could be used as a promising therapeutic target in the treatment of GC.


Monoclonal antibodies to the peplomer glycoprotein of coronavirus mouse hepatitis virus identify two subunits and detect a conformational change in the subunit released under mild alkaline conditions.
Monoclonal antibodies (MAbs) directed against the E2 glycoprotein of mouse hepatitis virus (MHV) have been classified according to their ability to bind to either of the two purified 90,000-molecular-weight subunits (90K subunits) of the 180K peplomeric glycoprotein E2. Correlation with previously reported information about these MAbs suggest that both of the subunits of E2 are important for viral infectivity and cell fusion. Incubation of trypsin-treated virions at pH 8.0 and 37 degrees C released only the E2N subunit from virions. The pattern of MAb reactions suggested that a conformational change occurred in the E2N subunit in association with its release from virions under mildly alkaline conditions at 37 degrees C, the same conditions which are optimal for coronavirus-induced cell fusion.


Detecting patterns of protein distribution and gene expression in silico.
Most biological information is contained within gene and genome sequences. However, current methods for analyzing these data are limited primarily to the prediction of coding regions and identification of sequence similarities. We have developed a computer algorithm, CoSMoS (for context sensitive motif searches), which adds context sensitivity to sequence motif searches. CoSMoS was challenged to identify genes encoding peroxisome-associated and oleate-induced genes in the yeast Saccharomyces cerevisiae. Specifically, we searched for genes capable of encoding proteins with a type 1 or type 2 peroxisomal targeting signal and for genes containing the oleate-response element, a cis-acting element common to fatty acid-regulated genes. CoSMoS successfully identified 7 of 8 known PTS-containing peroxisomal proteins and 13 of 14 known oleate-regulated genes. More importantly, CoSMoS identified an additional 18 candidate peroxisomal proteins and 300 candidate oleate-regulated genes. Preliminary localization studies suggest that these include at least 10 previously unknown peroxisomal proteins. Phenotypic studies of selected gene disruption mutants suggests that several of these new peroxisomal proteins play roles in growth on fatty acids, one is involved in peroxisome biogenesis and at least two are required for synthesis of lysine, a heretofore unrecognized role for peroxisomes. These results expand our understanding of peroxisome content and function, demonstrate the utility of CoSMoS for context-sensitive motif scanning, and point to the benefits of improved in silico genome analysis.


Olfactory system-inspired electronic nose system using numerous low-cost homogenous and hetrogenous sensors.
This paper presents an electronic nose system inspired by the biological olfactory system. When comparing the human olfactory system to that of a dog, it's worth noting that dogs have 30 times more olfactory receptors and three times as many types of olfactory receptors. This implies that the number of olfactory receptors could be a more important parameter for classifying chemical compounds than the number of receptor types. Instead of using expensive precision sensors, the proposed electronic nose system relies on numerous low-cost homogeneous and heterogeneous sensors with poor cross-interference characteristics due to their low gas selectivity. Even if the same type of sensor shows a slightly different output for the same chemical compound, this variation becomes a unique signal for the target gas being measured. The electronic nose system comprises 30 sensors, the e-nose had 6 differing sensors with 5 replicates of each type. The characteristics of the electronic nose system are evaluated using three different volatile alcoholic compounds, more than 99% of which are the same. Liquid samples are supplied to the sensor chamber for 60 seconds using an air bubbler, followed by a 60-second cleaning of the chamber. Sensor signals are acquired at a sampling rate of 100 Hz. In this experimental study, the effects of data preprocessing methods and the number of sensors of the same type are investigated. By increasing the number of sensors of the same type, classification accuracy exceeds 99%, regardless of the deep learning model. The proposed electronic nose system, based on low-cost sensors, demonstrates similar results to commercial expensive electronic nose systems.


Inpatient management of women with gestational and pregestational diabetes in pregnancy.
For women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM), poor maternal glycemic control can significantly increase maternal and fetal risk for adverse outcomes. Outpatient medical and nutrition therapy is recommended for all women with diabetes in order to facilitate euglycemia during the antepartum period. Despite intensive outpatient therapy, women with diabetes often require inpatient diabetes management prior to delivery as maternal hyperglycemia can significantly increase neonatal risk of hypoglycemia. Consensus guidelines recommend maternal glucose range of 80-110 mg/dL in labor. The most optimal inpatient strategies for the prevention of hyperglycemia and hypoglycemia proximate to delivery remain unclear and will depend upon factors such as maternal diabetes diagnosis, her baseline insulin resistance, duration and route of delivery etc. Low dose intravenous insulin and dextrose protocols are necessary to achieve optimal predelivery glycemic control for women with T1DM and T2DM. For most with GDM however, euglycemia can be maintained without intravenous insulin. Women treated with a subcutaneous insulin pump during the antepartum period represent a unique challenge to labor and delivery staff. Strategies for self-managed subcutaneous insulin infusion (CSII) use prior to delivery require intensive education and coordination of care with the labor team in order to maintain patient safety. Hospitalization is recommended for most women with diabetes prior to delivery and in the postpartum period despite appropriate outpatient glycemic control. Women with poorly controlled diabetes in any trimester have an increased baseline maternal and fetal risk for adverse outcomes. Common indications for antepartum hospitalization of these women include failed outpatient therapy and/or diabetic ketoacidosis (DKA). Inpatient management of DKA is a significant cause of maternal and fetal morbidity and remains a common indication for hospitalization of the pregnant woman with diabetes. Changes in maternal physiology increase insulin resistance and the risk for DKA. A systematic approach to its management will be reviewed.


Contribution of rpoB2 RNA polymerase beta subunit gene to rifampin resistance in Nocardia species.
Nocardia species are gram-positive environmental saprophytes, but some cause the infectious disease nocardiosis. The complete genomic sequence of Nocardia farcinica IFM 10152 has been determined, and analyses indicated the presence of two different RNA polymerase beta subunit genes, rpoB and rpoB2, in the genome (J. Ishikawa, A. Yamashita, Y. Mikami, Y. Hoshino, H. Kurita, K. Hotta, T. Shiba, and M. Hattori, Proc. Natl. Acad. Sci. USA 101:14925-14930, 2004). These genes share 88.8% identity at the nucleotide level. Moreover, comparison of their amino acid sequences with those of other bacterial RpoB proteins suggested that the nocardial RpoB protein is likely to be rifampin (RIF) sensitive, whereas RpoB2 protein contains substitutions at the RIF-binding region that are likely to confer RIF resistance. Southern analysis indicated that rpoB duplication is widespread in Nocardia species and is correlated with the RIF-resistant phenotype. The introduction of rpoB2 by using a newly developed Nocardia-Escherichia coli shuttle plasmid vector and transformation system conferred RIF resistance to Nocardia asteroides IFM 0319T, which has neither RIF resistance nor rpoB duplication. Furthermore, unmarked rpoB2 deletion mutants of N. farcinica IFM 10152 showed no significant resistance to RIF. These results indicated the contribution of rpoB2 to RIF resistance in Nocardia species. Since this is the first example of genetic engineering of the Nocardia genome, we believe that this study, as well as our determination of the N. farcinica genome sequence, will be a landmark in Nocardia genetics.


A Cross-species Model of Dual-Task Walking in Young and Older Humans and Rats.
Introduction: Dual-task walking is common in daily life but becomes more difficult with aging. Little is known about the neurobiological mechanisms affecting competing cognitive demands. Translational studies with human and animal models are needed to address this gap. This pilot study investigated the feasibility of implementing a novel cross-species dual-task model in humans and rats and aimed to establish preliminary evidence that the model induces a dual-task cost. Methods: Young and older humans and rats performed an object discrimination task (OD), a baseline task of typical walking (baseline), an alternation turning task on a Figure 8 walking course (Alt), and a dual-task combining object discrimination with the alternation task (AltOD). Primary behavioral assessments including walking speed and correct selections for object discrimination and turning direction. In humans, left prefrontal cortex activity was measured with functional near-infrared spectroscopy (fNIRS). Results: Human subjects generally performed well on all tasks, but the older adults exhibited a trend for a slowing of walking speed immediately before the turning decision for Alt and AltOD compared to baseline. Older adults also had heightened prefrontal activity relative to young adults for the Alt and AltOD tasks. Older rodents required more training than young rodents to learn the alternation task. When tested on AltOD with and without a 15-s delay between trials, older rodents exhibited a substantial performance deficit for the delayed version on the initial day of testing. Old rats, however, did not show a significant slowing in walking speed with increasing task demand, as was evident in the young rats. Discussion: This study demonstrates the feasibility and challenges associated with implementing a cross-species dual-task model. While there was preliminary evidence of dual-task cost in both humans and rats, the magnitude of effects was small and not consistent across species. This is likely due to the relative ease of each task in humans and the walking component in rats not being sufficiently challenging. Future versions of this test should make the cognitive tasks more challenging and the motor task in rats more complex.


Prevalence of tooth transpositions and associated dental anomalies in a Turkish population.
The aims of this study were to determine the prevalence of tooth transposition in a Turkish population, possibly associated dental anomalies and whether side laterality, gender expression or genetic influence exist or not. Panoramic radiographs of 5486 patients referred to Department of Oral Diagnosis and Radiology, University of Suleyman Demirel between April 2003 and March 2004 were examined retrospectively. All patients with tooth transpositions were recalled for detailed clinical examination and medical history. Age, sex, history (trauma), location of transposition, and associated congenital dental anomalies were recorded with details. 22 transpositions were found in 21 of 5486 (0.38%) patients. The most frequently seen transposition was maxillary canine-lateral incisor (1.64/1000), secondly maxillary canine-first premolar (0.91/1000) and maxillary canine-second premolar (0.18/1000) was the least frequently seen one. The frequencies of right and left side occurrence were equal (11/11). Each sex was affected similarly (11 males, 10 females). The prevalence of tooth transposition was 0.38% in a Turkish population. Maxillary canine-lateral incisor transposition was found to have a higher frequency than maxillary canine-first premolar transposition. Maxillary canine-second premolar transposition that had not been previously reported in the literature was observed in one of our cases. Transpositions had similar frequencies in both sexes.


Screening procedures in the asymptomatic adult. Comparison of physicians' recommendations, patients' desires, published guidelines, and actual practice.
To assess attitudes and practices regarding screening tests and preventive procedures, we surveyed 83 physicians in a hospital-based ambulatory care practice and compared their recommendations with the recommendations in published guidelines, the desires of 188 of their own patients, and the physicians' actual practice patterns on the surveyed patients. The surveyed physicians recommended screening procedures more frequently than the published guidelines in 48 situations and less frequently in 18 situations. Physicians at earlier levels of training tended to recommend more procedures than those who had completed training. Patients desired far more frequent screening than recommended either by their physicians or by the published guidelines. Physicians did not live up to their own recommendations for four of 14 procedures or to published guidelines for five of 14 procedures, with such failure occurring principally in situations where the test or procedure would normally be done personally by the physician.


Determination of true digestive utilization of phosphorus and the endogenous phosphorus outputs associated with soybean meal for growing pigs.
The objectives of this study were to determine true P digestibility, the gastrointestinal endogenous P outputs associated with soybean meal (SBM), and the role of the large intestine in P digestion in growing pigs. Four Yorkshire barrows, with average initial and final BW of 40 and 58 kg, were fitted with a simple T-cannula at the distal ileum and fed four diets according to a 4 x 4 Latin square design. The diets were cornstarch-based and contained four levels of P (0.098, 0.196, 0.293, and 0.391% on a DM basis) from solvent-extracted conventional SBM. Chromic oxide (3.5 g/kg of diet, as-fed basis) was included as a digestibility marker. Each experimental period consisted of 8 d with a 4-d adaptation period and a 4-d collection of representative ileal digesta (2 d) and fecal (2 d) samples. True ileal and fecal P digestibility values and the ileal and fecal endogenous P outputs associated with SBM were determined by the regression analysis technique. There were no differences (P > 0.05) in true P digestibility values (ileal, 59.0 +/- 8.3 vs. fecal, 51.3 +/- 7.9%, n = 16) and endogenous P outputs (ileal, 0.59 +/- 0.18 vs. fecal, 0.45 +/- 0.21 g/kg of DMI, n = 16) between the ileal and the fecal levels. The endogenous fecal P loss accounted for 8.1 and 17.6% of the NRC (1998) recommended total and available P requirements in growing pigs, respectively. In conclusion, approximately 51% of the total P in conventional SBM is digested in growing pigs. The large intestine does not play an important role in the digestion of P associated with SBM in the growing pig. The fecal loss of the gastrointestinal endogenous P is an important route of P excretion in the growing pig.


Isolation of S-adenosyl-3-thiopropylamine from the eye of the sea catfish (Arius felis).
A method is reported for the separation of S-adenosyl-3-methylthiopropylamine and other basic compounds in the eye of the sea catfish (Arius felis) by ion-exchange chromatography on CM-Sephadex. One of the basic compounds was isolated in crystalline form and was shown to be S-adenosyl-3-thiopropylamine by chemical and spectroscopic characterizations and by comparison with a synthetic sample.


The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil.
The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and ≥1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity of facilitating HIV diagnosis.


Lethality and pathogenesis of airborne infection with filoviruses in A129 α/β -/- interferon receptor-deficient mice.
Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 α/β -/- interferon receptor-deficient KO mice, strain A129 IFN-α/β -/-, were used to determine the lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV) and Côte d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or aerosol routes of infection. One hundred percent mortality was observed in all groups of KO mice that were administered with a range of challenge doses of MARV and ZEBOV by either IP or aerosol routes. Mean time to death for both routes was dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and from 10.2 to 13 days in the aerosol challenge. The lethal dose (50 % tissue culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1) when administered by either the IP or aerosol route of infection; for MARV the lethal dose was <1 TCID(50) ml(-1) by the IP route of infection and <10 TCID(50) ml(-1) by the aerosol route. In contrast, there was no mortality after infection with SEBOV or REBOV by either IP or aerosol routes of infection; all the mice lost weight (~15 % loss of group mean body weight with SEBOV and ~7 % with REBOV) but recovered to their original weights by day 14 post-challenge. There was no mortality in mice administered with CIEBOV via the IP route of infection and no clinical signs of infection were observed. The progression of disease was faster following infection with ZEBOV than with MARV but ultimately both viruses caused widespread infection with high titres of the infectious viruses in multiple organs. Histopathological observations were consistent with other animal models and showed widespread organ damage. This study suggests that MARV and ZEBOV are more virulent when administered via the IP route rather than by aerosol infection, although both are highly virulent by either route. The KO mouse may provide a useful model to test potential antiviral therapeutics against wild-type filoviruses.


Clonidine analgesia and suppression of operant responding: dissociation of mechanism.
In the rat the effects of clonidine and xylazine were compared on a measure of analgesia (tail-withdrawal from hot water) and on operant responding maintained by a fixed-ratio 20-response schedule of food presentation. Clonidine (2--8 mg/kg) produced dose-dependent increase in tail-withdrawal latency and was approximately twice as potent as xylazine (8--16 mg/kg) in this test. This analgesic effect of 8 mg/kg of clonidine was antagonized by phenoxybenzamine (10 mg/kg), and high doses of yohimbine (5--10 mg/kg), whereas the effect of 2 mg/kg of clonidine was potentiated by a nonanalgesic dose of nisoxetine (10 mg/kg). Clonidine (0.0063--0.2 mg/kg) and xylazine (0.25--8 mg/kg) produced a dose-dependent suppression of fixed-ratio responding. The potency of clonidine in this task was approximately 40 times greater than that of xylazine. The suppression of responding produced by both drugs was antagonized by low doses of yohimbine (0.5--2 kg/mg), which was maximally effective at a dose of 1 mg/kg. The data suggest that when using this type of assay for analgesia, the antinociceptive effects of clonidine which are measured are a result of stimulation of alpha-adrenergic receptors or noradrenergic neurons or by adrenergic receptors which inhibit noradrenergic neurons.


Epithelial mesenchymal transition and cancer stem cells in esophageal adenocarcinoma originating from Barrett's esophagus.
Carcinomas comprise cohesive epithelial cells linked to one another by E-cadherin-based cell-cell junctions. Epithelial mesenchymal transition (EMT) enables carcinoma cells to migrate from the original tissue and invade into stromal components. The E-cadherin promoter is frequently repressed by specific transcriptional repressors including Snail, Slug and Twist. CD133 is known to be a marker of tumor-initiating cells in human cancers. This is the first study to characterize the transcriptional factors for E-cadherin and the representative cancer stem cell marker in specimens of early esophageal adenocarcinoma (EAC) originating from Barrett's esophagus. Ten surgically treated patients were analyzed in the present study. Immunohistochemistry was performed to determine the expression of Snail, Slug, Twist and CD133, and the results were scored. Unlike previous studies of advanced stage esophageal cancers showing the overexpression of each specific transcriptional protein, the invading edges of the tumor were found to abundantly express Snail, Slug, Twist and CD133 in our cohort. Therefore, results of this study suggest that early stage cancers predominantly comprise cells with metastatic potential and this evidence adds legitimacy to the complete removal of early EAC.


Collective cloaking of a cluster of electrostatically defined core-shell quantum dots in graphene.
We study cloaking of aclusterof electrostatically defined core-shell quantum dots in graphene. Guided by the generalized multiparticle Mie theory, the Dirac electron scattering from a cluster of quantum dots is addressed. Indeed distant quantum dots may experience a sort of individual cloaking. But despite the multiple scattering of an incident electron from a set of adjacent quantum dots,collective cloakingmay happen. Via a proper choice of the radii and bias voltages of shells, two most important scattering coefficients and hence the scattering efficiency of the cluster dramatically decrease. Energy-selective electron cloaks are realizable. More importantly, clusters simultaneously transparent to electrons of different energies, are achievable. Being quite sensitive to applied bias voltages, clusters of core-shell quantum dots may be used to develop switches with high on-off ratios.


Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children.
Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.


Lifestyle Vaccines and Public Health: Exploring Policy Options for a Vaccine to Stop Smoking.
Experimental vaccines are being developed for the treatment of 'unhealthy lifestyles' and associated chronic illnesses. Policymakers and other stakeholders will have to deal with the ethical issues that this innovation path raises: are there morally justified reasons to integrate these innovative biotechnologies in future health policies? Should public money be invested in further research? Focusing on the case of an experimental nicotine vaccine, this article explores the ethical aspects of 'lifestyle vaccines' for public health. Based on findings from a qualitative study into a vaccine for smoking cessation, the article articulates possible value conflicts related to nicotine vaccination as an intervention in tobacco control. The 'vaccinization' of lifestyle disease piggybacks on the achievements of classic vaccines. Contrary to expectations of simplicity and success, quitting smoking with a vaccine requires a complex supportive network. Social justice and public trust may become important ethical challenges when deciding whether to use further public funds for research or whether to implement these innovative vaccines in the future.


Food addiction as a proxy for eating disorder and obesity severity, trauma history, PTSD symptoms, and comorbidity.
Food addiction (FA) is a newly defined yet still controversial condition that has important etiological, developmental, treatment, prevention, and social policy implications. In this review, the case is made that FA (or high scores on the Yale Food Addiction Scale) may be used as a proxy measure for a matrix of interrelated clinical features, including greater eating disorder severity, greater obesity severity, more severe trauma histories, greater symptoms of posttraumatic stress disorder (PTSD), greater psychiatric comorbidity, as well as greater medical morbidity and mortality. A Medline search was undertaken using the following terms: food addiction cross-referenced with eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder, and binge eating), obesity, trauma, posttraumatic stress disorder, and comorbidity. The thesis is that the identification and acknowledgment of the concept of FA, when integrated into an overall, trauma-focused and transdiagnostic treatment approach, are supported and can be useful in understanding clinically the "big picture." Food addiction (FA) may be used as a proxy for (1) bulimic eating disorder severity, (2) complex trauma histories, (3) severity of PTSD and PTSD symptoms, (4) intensity of psychiatric comorbidity, (5) severity of obesity, as well as (6) their combination. Implications for developing treatment strategies are discussed. The case for a comprehensive management that requires careful attention to medical and psychiatric assessment and integrated care that incorporates trauma-focused treatment is made.


Young adults' favorable perceptions of snus, dissolvable tobacco products, and electronic cigarettes: findings from a focus group study.
We explored young adults' perceptions of snus (spitless moist snuff packed in porous bags), dissolvable tobacco products, and electronic cigarettes and intention to try these products. We conducted 11 focus group discussions involving a total of 66 young adults (18-26 years old) on these new tobacco products (e.g., harmfulness, potential as quit aids, intention to try) held between July and December 2010. We analyzed discussions using a thematic approach. Participants generally reported positive perceptions of the new products, particularly because they came in flavors. Few negative perceptions were reported. Although some participants believed these products were less harmful than cigarettes and helpful in quitting smoking, others thought the opposite, particularly regarding electronic cigarettes. Participants also commented that these products could be gateways to cigarette smoking. Half of the participants, including a mix of smokers and nonsmokers, admitted they would try these products if offered by a friend. Young adults perceive the new tobacco products positively and are willing to experiment with them. Eliminating flavors in these products may reduce young adults' intentions to try these products.


Microporous titanosilicates Cu2+- and Co2+-ETS-4 for storage and slow release of therapeutic nitric oxide.
Although nitric oxide (NO) is very toxic in low concentrations it plays a key role in the regulation of several biological systems of the human body. The potential of copper and cobalt ion-exchanged microporous titanosilicate ETS-4 for therapeutic storage and release of nitric oxide was assessed. Materials were characterized by powder X-ray diffraction, nitrogen adsorption at -196 °C and chemical analysis. Cation-exchanged materials showed an increased surface area and minor structural changes, relative to the parent Na-ETS-4. The NO storage and release kinetics was studied in the gas and liquid phases. NO loaded materials were also studied by diffuse reflectance infrared Fourier transform spectroscopy. The NO amounts released in the liquid phase were within the physiological range (nanomolar), while the release kinetics was slow (0.023 min-1 for 85% release). The NO loading and release from ETS-4 were affected by the presence of Cu2+ and Co2+ cations. Assays with HeLa cells indicated that the materials have low cytotoxicity, which depends on the ion-exchanged cation. The performance of ETS-4 improved when the extra-framework Na+ cations were exchanged by Cu2+ and Co2+.


A panel of 74 AISNPs: Improved ancestry inference within Eastern Asia.
Many ancestry informative SNP (AISNP) panels have been published. Ancestry resolution in them varies from three to eight continental clusters of populations depending on the panel used. However, none of these panels differentiates well among East Asian populations. To meet this need, we have developed a 74 AISNP panel after analyzing a much larger number of SNPs for Fst and allele frequency differences between two geographically close population groups within East Asia. The 74 AISNP panel can now distinguish at least 10 biogeographic groups of populations globally: Sub-Saharan Africa, North Africa, Europe, Southwest Asia, South Asia, North Asia, East Asia, Southeast Asia, Pacific and Americas. Compared with our previous 55-AISNP panel, Southeast Asia and North Asia are two newly assignable clusters. For individual ancestry assignment, the likelihood ratio and ancestry components were analyzed on a different set of 500 test individuals from 11 populations. All individuals from five of the test populations - Yoruba (YRI), European (CEU), Han Chinese in Henan (CHNH), Rondonian Surui (SUR) and Ticuna (TIC) - were assigned to their appropriate geographical regions unambiguously. For the other test populations, most of the individuals were assigned to their self-identified geographical regions with a certain degree of overlap with adjacent populations. These alternative ancestry components for each individual thus help give a clearer picture of the possible group origins of the individual. We have demonstrated that the new AISNP panel can achieve a deeper resolution of global ancestry.


Understanding the structure and processes of primary health care for young indigenous children.
INTRODUCTION Primary health care organisations need to continuously reform to more effectively address current health challenges, particularly for vulnerable populations. There is growing evidence that optimal health service structures are essential for producing positive outcomes. AIM To determine if there is an association between process of care indicators (PoCIs) for important young indigenous child health and social issues and: (i) primary health-care service and child characteristics; and (ii) organisational health service structures. METHODS This was a cross-sectional study of 1554 clinical child health audits and associated system assessments from 74 primary care services from 2012 to 2014. Composite PoCIs were developed for social and emotional wellbeing, child neurodevelopment and anaemia. Crude and adjusted logistic regression models were fitted, clustering for health services. Odds ratios and 95% confidence intervals were derived. RESULTS Overall, 32.0% (449) of records had a social and emotional wellbeing PoCI, 56.6% (791) had an anaemia PoCI and 49.3% (430) had a child neurodevelopment PoCI. Children aged 12-23 months were significantly more likely to receive all PoCIs compared to children aged 24-59 months. For every one point increase in assessment scores for team structure and function (aOR 1.14, 95% CI 1.01-1.27) and care planning (aOR 1.14, 95% CI 1.01-1.29) items, there was a 14% greater odds of a child having an anaemia PoCI. Social and emotional wellbeing and child neurodevelopment PoCIs were not associated with system assessment scores. DISCUSSION Ensuring young indigenous children aged 24-59 months are receiving quality care for important social and health indicators is a priority. Processes of care and organisational systems in primary care services are important for the optimal management of anaemia in indigenous children.


[Interelement correlations in the lungs and the liver in alimentary obesity].
Using a high-fat diet in experiment on rats received model alimentary obesity (AO). Adding zinc to the diet did not affect the severity of the AO. The concentration of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, Sr in the liver and lungs of rats with obesity in both groups did not differ from that of healthy animals. As in the liver and lungs in rats of both groups with obesity has been a redistribution of interelement correlation (COP) and during physiological hunger and soon after consumption of pork fat. Redistribution of interelement COP in a state of physiological hunger reflects the strong changes of metabolic processes of the body. The nature of rearrangements of the COP in the liver and lungs were significantly different in each group of rats. Soon after intake of fatty foods in control rats and rats AO not receiving zinc, found an increase in the total number interelement COP in the lungs and major decline in the liver, which indirectly indicates the active participation of the lungs in the metabolism of dietary fat, over-expressed in control animals. In rats receiving more zinc, the increase in the total number of correlations after eating found in both bodies.


Abdominal Physical Signs and Medical Eponyms: Movements and Compression.
Prior to the advent of modern imaging techniques, maneuvers were performed as part of the physical examination to further assess pathological findings or an acute abdomen and to further improve clinicians' diagnostic acumen to identify the site and cause of disease. Maneuvers such as changing the position of the patient, extremity, or displacing through pressure a particular organ or structure from its original position are typically used to exacerbate or elicit pain. Some of these techniques, also referred to as special tests, are ascribed as medical eponym signs. PubMed, Medline, online Internet word searches, textbooks and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. These active and passive maneuvers of the abdomen, reported as medical signs, have variable performance in medical practice. The lack of diagnostic accuracy may be attributed to confounders such as the position of the organ, modification of the original technique, or lack of performance of the maneuver as originally intended.


Functional characterization of an eosinophil-specific galectin, ovine galectin-14.
Across mammalian species, human galectin-10 and ovine galectin-14 are unique in their expression in eosinophils and their release into lung and gastrointestinal tissues following allergen or parasite challenge. Recombinant galectin-14 is active in carbohydrate binding assays and has been used in this study to unravel the function of this major eosinophil constituent. In vitro cultures revealed that galectin-14 is spontaneously released by eosinophils isolated from allergen-stimulated mammary gland lavage, but not by resting peripheral blood eosinophils. Galectin-14 secretion from peripheral blood eosinophils can be induced by the same stimuli that induce eosinophil degranulation. Flow cytometric analysis showed that recombinant galectin-14 can bind in vitro to eosinophils, neutrophils and activated lymphocytes. Glycan array screening indicated that galectin-14 recognizes terminal N-acetyllactosamine residues which can be modified with alpha1-2-fucosylation and, uniquely for a galectin, prefers alpha2- over alpha2-sialylation. Galectin-14 showed the greatest affinity for lacto-N-neotetraose, an immunomodulatory oligosaccharide expressed by helminths. Galectin-14 binds specifically to laminin in vitro, and to mucus and mucus producing cells on lung and intestinal tissue sections. In vivo, galectin-14 is abundantly present in mucus scrapings collected from either lungs or gastrointestinal tract following allergen or parasite challenge, respectively. These results suggest that in vivo secretion of eosinophil galectins may be specifically induced at epithelial surfaces after recruitment of eosinophils by allergic stimuli, and that eosinophil galectins may be involved in promoting adhesion and changing mucus properties during parasite infection and allergies.


Orthopaedic implant infections: current management strategies.
Orthopaedic joint replacement and spinal stabilisation surgery has provided pain relief and functional improvement for millions. Postoperative infections involving the implanted hardware can have devastating functional, emotional and financial consequences. Implementation of relevant preoperative patient preparation, utilisation of appropriate prophylactic antimicrobials and intraoperative infection control measures have combined to diminish orthopaedic implant infection frequency significantly. Our adeptness at establishing the presence of an implant-related infection with certainty is not as well advanced. Similarly, treatment guidelines, while useful, remain somewhat anecdotal. The pathogenesis, risk factors, diagnosis, management and prevention of hip arthroplasty infection and spinal stabilisation with instrumentation infection are reviewed.


The effect of sodium citrate on the stimulation of polymorphonuclear leukocytes.
Topical administration of sodium citrate reduces the incidence of corneal ulceration and perforation following an alkali burn to the eye. The specific mechanism by which sodium citrate prevents the ulceration is not understood, although citrate does inhibit the infiltration of polymorphonuclear leukocytes (PMNs) into the cornea following an alkali burn. In the present study, the effects of sodium citrate and another calcium chelator, ethylene glycol bis (beta-aminoethylether)-N,N'tetraacetic acid (EGTA), upon PMN oxygen consumption and lysosomal enzyme release were determined. Oxygen consumption was measured polarographically using a Clark-type oxygen electrode, and lysosomal enzyme release was determined by intra- and extra-cellular measurements of myeloperoxidase activity. Opsonized zymosan and N-formylmethionylleucylphenylalanine (FMLP) were used to stimulate neutrophil oxygen consumption and lysosomal release. Both sodium citrate and EGTA inhibited PMN oxygen consumption and lysosomal enzyme release in response to opsonized zymosan. In contrast, neither sodium citrate nor EGTA reduced PMN oxygen consumption or lysosomal enzyme release in response to FMLP. Therefore, the ability of sodium citrate (and EGTA) to inhibit PMN stimulation is dependent upon the choice of stimulus. Until the inflammatory mediators involved in the ulcerative process following an alkali burn to the eye are delineated, the impact of sodium citrate upon PMN stimulation in vivo cannot be resolved.


Testability and the Refutation and Corroboration of Cladistic Hypotheses.
Both refutationist and verificationist philosophies and practices are becoming increasingly evident in phylogenetic inference. Refutation and verification are fundamentally different epistemologies, and it seems unlikely that they can continue to coexist as the basis for inferring species history. The refutationist nature of cladistics is explored in terms of Popperian testability, in order to understand better the alternatives and to predict the outcome of the expected revolution. Testability concerns the logical relationship between a hypothesis (h, such as a cladogram), evidence (e, such as synapomorphy), and background knowledge (b). Of particular importance is the direct relationship between the logical improbability ofhand its potential to be tested, because foreto corroborateh,eshould be improbable givenbalone. Simplicity and boldness, amount of empirical content, and logical improbability all refer to the potential to be tested. Thathmust be testable by severe tests is the same as saying that those tests have greater probability of failing, given onlyb. Descent with modification is sufficient as background knowledge (b) in phylogenetic inference, and such a minimal assumption explains the generality of cladistics. Also of interest to the refutationist position is total evidence. In terms of testability, a statement describing the results of multiple tests is less probable than a statement describing only some of the tests, the multiple test result being more improbable, and accordingly more severe, than its component tests. All other cladistic principles and practices considered in this review are also understandable in terms of Popperian testability, refutation and corroboration. These include minimizing ad hoc hypotheses of homoplasy and minimizing explanatory power, and choosing tentatively among cladograms according to their degree of corroboration (support). Differential character weighting is determined to be unacceptable in terms of testability. Also, testability does not provide a basis for assessing the accuracy of hypotheses, but then that is of no consequence to cladists, because they are not preoccupied with knowing the absolute truth, unlike verificationists.


Turnover of the methyl moiety of 5-methyltetrahydropteroylglutamic acid in the cobalamin-inactivated rat.
The metabolism of the methyl group of 5-methyltetrahydrofolate was studied in rats in which cobalamin had been inactivated by exposure to nitrous oxide and in air-breathing control animals. Methylfolate labeled with [14C] in the methyl group and with [3H] in the pteridine-PABA portion was injected and the disappearance of [14C]H3- relative to [3H]folate was measured in liver. The half-time of the methyl group in the livers of control rats was two hours. There was no turnover of the methyl group for the first 72 hours after cobalamin inactivation. After 72 hours, there was a slow turnover of the methyl group, with a half-time of 43 hours. In control rats, it is assumed that the methyl group was metabolized by transfer to homocysteine to form methionine. In cobalamin-inactivated rats, it was shown that methylfolate was used as the substrate for forming folate polyglutamate, and analogues with 3, 4, and 5 glutamic acid residues were present. It is likely that oxidation of the methyl group by methylene tetrahydrofolate reductase occurs from folate polyglutamate containing six and seven glutamic acid residues, (Brody et al, Biochemistry 21: 276, 1982), since we were unable to demonstrate labeled methyl in longer chain analogues.


Neural precursor cell proliferation is disrupted through activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Neurogenesis involves the proliferation of multipotent neuroepithelial stem cells followed by differentiation into lineage-restricted neural precursor cells (NPCs) during the embryonic period. Interestingly, these progenitor cells express robust levels of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates expression of genes important for growth regulation, and xenobiotic metabolism. Upon binding 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a pervasive environmental contaminant and potent AhR ligand, AhR, is activated and disrupts gene expression patterns to produce cellular toxicity. Because of its widespread distribution in the brain during critical proliferative phases of neurogenesis, it is conceivable that AhR participates in NPC expansion. Therefore, this study tested the hypothesis that AhR activation by TCDD disrupts signaling events that regulate NPC proliferation. The C17.2 NPC line served as a model system to (1) assess whether NPCs are targets for TCDD-induced neurotoxicity and (2) characterize the effects of TCDD on NPC proliferation. We demonstrated that C17.2 NPCs express an intact AhR signaling pathway that becomes transcriptionally active after TCDD exposure. (3)H-thymidine and alamar blue reduction assays indicated that TCDD suppresses NPC proliferation in a concentration-dependent manner without the loss of cell viability. Cell cycle distribution analysis by flow cytometry revealed that TCDD-induced growth arrest results from an impaired G1 to S cell cycle transition. Moreover, TCDD exposure altered p27( kip1) and cyclin D1 cell cycle regulatory protein expression levels consistent with a G1 phase arrest. Initial studies in primary NPCs isolated from the ventral forebrain of embryonic mice demonstrated that TCDD reduced cell proliferation through a G1 phase arrest, corroborating our findings in the C17.2 cell line. Together, these observations suggest that the inappropriate or sustained activation of AhR by TCDD during neurogenesis can interfere with signaling pathways that regulate neuroepithelial stem cell/NPC proliferation, which could adversely impact final cell number in the brain and lead to functional impairments.


Rare occurrence of heart lesions in Pacific oysters Crassostrea gigas caused by an unknown bacterial infection.
On rare occasions, small cream-coloured cysts have been observed in the heart and pericardial cavity of Pacific oysters Crassostrea gigas from British Columbia, Canada. Histopathology revealed the presence of large colonies of bacteria (up to 800 µm in diameter) causing significant host response and hypertrophy of the heart epithelium. The causative bacteria were characterized as follows: Gram-negative, coccoid to small rod-shaped, typically <1.5 µm in size, cell walls highly endowed with surface fimbriae and division via binary fission. Although these bacteria shared some morphological characteristics with the order Rickettsiales, they did not require an intracellular existence for multiplication. Unfortunately, a cultured isolate was not available, and a retrospective attempt to further characterize the bacteria using DNA sequence analysis of a fragment from the 16S rDNA region proved to be uninformative.


The effects of spatial discretization on performances and parameters of urban hydrological model.
Selecting a proper spatial resolution for urban rainfall runoff modeling was not a trivial issue because it could affect the model outputs. Recently, the development of remote sensing technology and increasingly available data source had enabled rainfall runoff process to be modeled at detailed and microscales. However, the models with less complexity might have equally good performance with less model establishment and computation time. This study attempted to explore the impact of model spatial resolution on model performance and parameters. Models with different discretization degree were built up on the basis of actual drainage networks, urban parcels and specific land use. The results showed that there was very little difference in the total runoff volumes while peak flows showed obvious scale effects which could be up to 30%. Generally, model calibration could compensate the scale effect. The calibrated models with different resolution showed similar performances. The consideration of effective impervious area (EIA) as a calibration parameter marginally increased performance of the calibration period but also slightly decreased performance in the validation period which indicated the importance of detailed EIA identification.


Phenotypic variation associated with molecular alterations at a cluster of thymidine kinase genes.
Genetic variation was studied in several mouse L cell lines containing tandemly repeated herpes simplex virus thymidine kinase (TK) genes introduced by DNA-mediated gene transfer. Variants were obtained after alternate positive and negative selection for TK expression. Three classes of molecular alteration are described. One class consisted of a concerted wave of hypermethylation affecting many sites in all or nearly all of the TK genes. This resulted in genetically stable TK- variants. Of five TK+ transformants from independent transfer experiments, only one, named HM, showed this class of methylation. Hypermethylation was a reproducible phenomenon in HM, yielding TK- variants after selection with either bromodeoxyuridine or acycloguanosine [Acyclovir or 9-(2-hydroxyethy-oxymethyl)guanine]. A second class of alteration consisted of methylation affecting some, but not all, genes in the cluster. This happened in all TK+ (HAT [hypoxanthine-aminopterin-thymidine]-resistant) cell lines investigated, and this second class of methylation was incapable of generating TK- variants. Neither type of methylation was accompanied by genomic rearrangements. The third class of molecular alteration was found among TK+ (HAT-resistant) back revertants of hypermethylated HM TK- derivatives. It consisted of a 10-fold amplification of the hypermethylated TK genes. Demethylation of hypermethylated HM variants was not observed. Thus, hypermethylation in this system can be compensated for by amplification but cannot be reversed.


Sustainable pathway towards large scale melt processing of the new generation of renewable cellulose-polyamide composites.
Modern society's growing demands for accountable high-performance and more environmentally friendly materials is leading to increased interest and fast development of sustainable polymeric composite materials. New generations of "greener" products originating from renewable resources fulfil emerging requirements of low environmental and health & safety impacts and contribute to diminishing global dependence on fossil feedstock. The preparation of sustainable polymeric composites via reliable and reproducible melt-compounding methods is still challenging but has the potential to yield applicable and market competitive products. This literature survey reviews the current state of research involving the use of cellulosic materials, as bio-sourced and sustainable reinforcement in melt-processed polyamides and focuses on the main hurdles that prevent their successful large-scale melt-compounding. Particular emphasis is dedicated to emerging bio-sourced polyamides fitting the performance of engineering materials and at the same time offering additional interesting properties for advanced applications such as piezoelectricity for transducers, sensors, actuators and energy harvesters.


[Deficiencies of the müllerian ducts induced by norethindrone in the female chick embryo].
Norethindrone produces two effects on müllerian ducts (MD) of female chick embryos. It induces the loss of the lower end of both ducts, as a result of a stop in their development, before 8 days. After 12 days NET causes regressions of the upper part of the MD particularly of the oviduct. NET like estrogens are the only known substances which present these both properties.


Toxic effects of hydroperoxide injections on rat lung. A light microscopical and ultrastructural study.
Intravenous administration of methyl linoleate hydroperoxide (MLH) uniformly resulted in extensive damage to septal wall components of the rat lung; the severity of these changes paralleled the administered dosage. The target cell of injury appeared to be the capillary endothelial cell. Destructive changes within the plasma membrane suggested that the major toxic effect of MLH was directed against membranous structures. Ultrastructural analysis showed that these effects were more severe in the vitamin E-deficient animals. Secondary changes were characterized by interstitial and alveolar edema, and degenerative changes within alveolar pneumocytes. Reparative proliferation of type 2 pneumocytes first became evident in animals that survived two days. These observations provide an insight into the susceptibility and sequential damage to pulmonary tissue by hydroperoxides and serve as a guide for investigations of the toxic effects of other oxidants on lung.


Association of specific genotypes in metastatic suppressor HTPAP with tumor metastasis and clinical prognosis in hepatocellular carcinoma.
The phosphatidic acid phosphatase HTPAP has been defined as a metastatic suppressor of hepatocellular carcinoma (HCC), but little is known about its function or potential applications as a prognostic marker. In this study, we analyzed patterns of HTPAP genetic variation and gene expression in 864 patients who underwent HCC resection, assessing these patterns for correlations to tumor metastasis potential. Focusing on two tagSNPs that were selected (+357G/C and +1838A/G), we found that only the +357G/C genotype was significantly associated with HTPAP mRNA and protein expression levels and the probability of metastasis. In an independent cohort of 665 HCC patients, we determined that the +357G/C genotype was associated with shorter time to recurrence and overall survival. Together, these results indicated that the HTPAP tagSNP +357 GG+GC genotypes may influence HCC metastatic potential and clinical prognosis by down-regulating HTPAP expression. Extending these results, a global expression profiling analysis identified 41 genes including the pro-inflammatory genes IL-8 and TLR2 that were significantly overexpressed in the +357 GG+GC group, as possible coregulated markers with HTPAP. Together, our findings identify an HTPAP genotype and associated gene expression pattern that favors metastasis progression and that could be used to predict tumor metastasis and prognosis in HCC patients.


The Assessment of Motor Fatigability in Persons With Multiple Sclerosis: A Systematic Review.
Persons with multiple sclerosis (PwMS) are often characterized by increased motor fatigability, which is a performance change on an objectively measured criterion after any type of voluntary muscle contractions. This review summarizes the existing literature to determine which protocols and outcome measures are best to detect or study motor fatigability and the underlying mechanisms in MS. Two electronic databases, PubMed and Web of Science, were searched for relevant articles published until August 2016 with a combination of multiple sclerosis, fatigability, muscle fatigue, and motor fatigue. A total of 48 articles were retained for data extraction. A variety of fatigability protocols were reported; protocols showed differences in type (isometric vs concentric), duration (15 to 180 s), and number of contractions (fixed or until exhaustion). Also, 12 articles reported motor fatigability during functional movements, predominantly assessed by changes in walking speed; 11 studies evaluated the mechanisms underlying motor fatigability, using additional electrical nerve or transcranial magnetic stimulation. Three articles reported psychometrics of the outcomes. The disparity of protocols and outcome measures to study different aspects of motor fatigability in PwMS impedes direct comparison between data. Most protocols use maximal single-joint isometric contractions, with the advantage of high standardization. Because there is no head-to-head comparison of the different protocols and only limited information on psychometric properties of outcomes, there is currently no gold standard to assess motor fatigability. The disability level, disease phenotype, and studied limb may influence the assessment of motor fatigability in PwMS.


Cost-analysis of an oral health outreach program for preschool children in a low socioeconomic multicultural area in Sweden.
The aim was to calculate the total and the net costs per child included in a 3-year caries preventive program for preschool children and to make estimates of expected lowest and highest costs in a sensitivity analysis. The direct costs for prevention and dental care were applied retrospectively to a comprehensive oral health outreach project for preschool children conducted in a low-socioeconomic multi-cultural urban area. The outcome was compared with historical controls from the same area with conventional dental care. The cost per minute for the various dental professions was added to the cost of materials, rental facilities and equipment based on accounting data. The cost for fillings was extracted from a specified per diem list. Overhead costs were assumed to correspond to 50% of salaries and all costs were calculated as net present value per participating child in the program and expressed in Euro. The results revealed an estimated total cost of 310 Euro per included child (net present value) in the 3-year program. Half of the costs were attributed to the first year of the program and the costs of manpower constituted 45% of the total costs. When the total cost was reduced with the cost of conventional care and the revenue of avoided fillings, the net cost was estimated to 30 Euro. A sensitivity analysis displayed that a net gain could be possible with a maximal outcome of the program. In conclusion, the estimated net costs were displayed and available to those considering implementation of a similar population-based preventive program in areas where preschool children are at high caries risk.


Type II restriction endonucleases: structure and mechanism.
Type II restriction endonucleases are components of restriction modification systems that protect bacteria and archaea against invading foreign DNA. Most are homodimeric or tetrameric enzymes that cleave DNA at defined sites of 4-8 bp in length and require Mg2+ ions for catalysis. They differ in the details of the recognition process and the mode of cleavage, indicators that these enzymes are more diverse than originally thought. Still, most of them have a similar structural core and seem to share a common mechanism of DNA cleavage, suggesting that they evolved from a common ancestor. Only a few restriction endonucleases discovered thus far do not belong to the PD...D/ExK family of enzymes, but rather have active sites typical of other endonuclease families. The present review deals with new developments in the field of Type II restriction endonucleases. One of the more interesting aspects is the increasing awareness of the diversity of Type II restriction enzymes. Nevertheless, structural studies summarized herein deal with the more common subtypes. A major emphasis of this review will be on target site location and the mechanism of catalysis, two problems currently being addressed in the literature.


Relationship between the shape and density distribution of the femur and its natural frequencies of vibration.
It has been recently suggested that mechanical loads applied at frequencies close to the natural frequencies of bone could enhance bone apposition due to the resonance phenomenon. Other applications of bone modal analysis are also suggested. For the above-mentioned applications, it is important to understand how patient-specific bone shape and density distribution influence the natural frequencies of bones. We used finite element models to study the effects of bone shape and density distribution on the natural frequencies of the femur in free boundary conditions. A statistical shape and appearance model that describes shape and density distribution independently was created, based on a training set of 27 femora. The natural frequencies were then calculated for different shape modes varied around the mean shape while keeping the mean density distribution, for different appearance modes around the mean density distribution while keeping the mean bone shape, and for the 27 training femora. Single shape or appearance modes could cause up to 15% variations in the natural frequencies with certain modes having the greatest impact. For the actual femora, shape and density distribution changed the natural frequencies by up to 38%. First appearance mode that describes the general cortical bone thickness and trabecular bone density had one of the strongest impacts. The first appearance mode could therefore provide a sensitive measure of general bone health and disease progression. Since shape and density could cause large variations in the calculated natural frequencies, patient-specific FE models are needed for accurate estimation of bone natural frequencies.


A Phase Variable Approach for Improved Rhythmic and Non-Rhythmic Control of a Powered Knee-Ankle Prosthesis.
Although there has been recent progress in control of multi-joint prosthetic legs for rhythmic tasks such as walking, control of these systems for non-rhythmic motions and general real-world maneuvers is still an open problem. In this article, we develop a new controller that is capable of both rhythmic (constant-speed) walking, transitions between speeds and/or tasks, and some common volitional leg motions. We introduce a new piecewise holonomic phase variable, which, through a finite state machine, forms the basis of our controller. The phase variable is constructed by measuring the thigh angle, and the transitions in the finite state machine are formulated through sensing foot contact along with attributes of a nominal reference gait trajectory. The controller was implemented on a powered knee-ankle prosthesis and tested with a transfemoral amputee subject, who successfully performed a wide range of rhythmic and non-rhythmic tasks, including slow and fast walking, quick start and stop, backward walking, walking over obstacles, and kicking a soccer ball. Use of the powered leg resulted in clinically significant reductions in amputee compensations for rhythmic tasks (including vaulting and hip circumduction) when compared to use of the take-home passive leg. In addition, considerable improvements were also observed in the performance for non-rhythmic tasks. The proposed approach is expected to provide a better understanding of rhythmic and non-rhythmic motions in a unified framework, which in turn can lead to more reliable control of multi-joint prostheses for a wider range of real-world tasks.


[Allelopathy effects of ferulic acid and coumarin on Microcystis aeruginosa].
The inhibitory effects and allelopathy mechanism of ferulic acid and coumarin on Microcystis aeruginosa were investigated by measuring the D680 value, the content of chlorophyll-a, the electrical conductivity (EC) and superoxide anion radical O*- value. Ferulic acid and coumarin had allelopathic effects on the growth of M. aeruginosa and promoted the physiological metabolism at low concentrations while inhibited the metabolism at high concentrations. Obvious inhibitory effects were observed when the concentration of ferulic acid or coumarin was over 100 mg x L(-1). The average inhibitory rates reached 80.3% and 58.0% after six days when the concentration of ferulic acid or coumarin was 200 mg x L(-1). The content of chlorophyll-a was decreased while the EC value and O2*- concentration were promoted by higher concentrations of ferulic acid or coumarin, suggesting that the growth of algae was inhibited probably by the damage of cell membrane, increase in the content of O2*- and decrease in the content of chlorophyll-a. In addition, seed germination test elucidated that Ferulic acid was safer than Coumarin.


The Hearing Voices Movement as Postmodern Religion-Making: Meaning, Power, Sacralization, Identity.
Over the past 40 or 50 years, scholars of religion have frequently attempted to use the tools of social science to analyse, describe, and explain the relevance and persistence of religion in the modern world. With the bold predictions of the secularization thesis as their stimuli, many sociologists and anthropologists preferred to focus on the under-explored, marginalized, or otherwise unexpected expressions of religion within those ostensibly secularizing contexts. Such studies have led to an abundance of theories and accompanying terms: "implicit religion," "vernacular religion," "vicarious religion," "lived religion," "popular religion," and "folk religion." Without choosing any one of these, but owing much to their shared-arguably postmodern-themes of commonplace sacrality and personal empowerment, this paper seeks to explore the possibility of the Hearing Voices Movement (HVM) as an example of religion-making. HVM is a growing force of "voice-hearers" from at least 28 countries who have formed user-led networks for activism and mental health recovery. More importantly, it is argued that HVM blends meaning-making, postmodern notions of identity in relation to power structures, and ritual embodiment, resulting in a striking example of sociologist Hans Mol's notion of religion as a sacralizing process.


Role of Group 1 CD1-Restricted T Cells in Infectious Disease.
The evolutionarily conserved CD1 family of antigen-presenting molecules presents lipid antigens rather than peptide antigens to T cells. CD1 molecules, unlike classical MHC molecules, display limited polymorphism, making CD1-restricted lipid antigens attractive vaccine targets that could be recognized in a genetically diverse human population. Group 1 CD1 (CD1a, CD1b, and CD1c)-restricted T cells have been implicated to play critical roles in a variety of autoimmune and infectious diseases. In this review, we summarize current knowledge and recent discoveries on the development of group 1 CD1-restricted T cells and their function in different infection models. In particular, we focus on (1) newly identified microbial and self-lipid antigens, (2) kinetics, phenotype, and unique properties of group 1 CD1-restricted T cells during infection, and (3) the similarities of group 1 CD1-restricted T cells to the closely related group 2 CD1-restricted T cells.


Comparison of the Diagnostic Performances of Same-session Endoscopic Ultrasound- and Endoscopic Retrograde Cholangiopancreatography-guided Tissue Sampling for Suspected Biliary Strictures at Different Primary Tumor Sites.
Determining the cause of suspected biliary stricture is often challenging in clinical practice. We aimed to compare the diagnostic yields of endoscopic ultrasound-guided tissue sampling (EUS-TS) and endoscopic retrograde cholangiopancreatography-guided tissue sampling (ERCP-TS) in patients with suspected biliary stricture at different primary lesions. We enrolled patients who underwent same-session EUS- and ERCP-TS for the evaluation of suspected biliary stricture. Forceps biopsy and/or brush cytology of intraductal lesions and fine-needle aspiration for solid mass lesions were performed during ERCP and EUS, respectively. One hundred and twenty-five patients treated at our institution between January 2011 and September 2016, were initially considered for the study. However, 32 patients were excluded due to loss of follow-up (n=8) and ERCP-TS on the pancreatic duct (n=20) or periampullary lesions (n=4). Of the 93 patients included, 86 had a malignant tumor including cholangiocarcinoma (n=39), pancreatic cancer (n=37), and other malignancies (n=10). Seven patients had benign lesions. EUS-TS had higher rate of overall diagnostic accuracy than ERCP-TS (82.8% vs. 60.2%, p=0.001), and this was especially true for patients with a pancreatic lesion (84.4% vs. 51.1%, p=0.003). EUS-TS was found to be superior to ERCP-TS for evaluating suspected biliary strictures, especially those caused by pancreatic lesions.


Single-molecule discrimination of discrete perisynaptic and distributed sites of actin filament assembly within dendritic spines.
Within dendritic spines, actin is presumed to anchor receptors in the postsynaptic density and play numerous roles regulating synaptic transmission. However, the submicron dimensions of spines have hindered examination of actin dynamics within them and prevented live-cell discrimination of perisynaptic actin filaments. Using photoactivated localization microscopy, we measured movement of individual actin molecules within living spines. Velocity of single actin molecules along filaments, an index of filament polymerization rate, was highly heterogeneous within individual spines. Most strikingly, molecular velocity was elevated in discrete, well-separated foci occurring not principally at the spine tip, but in subdomains throughout the spine, including the neck. Whereas actin velocity on filaments at the synapse was substantially elevated, at the endocytic zone there was no enhanced polymerization activity. We conclude that actin subserves spatially diverse, independently regulated processes throughout spines. Perisynaptic actin forms a uniquely dynamic structure well suited for direct, active regulation of the synapse.


Estimating the global conservation status of more than 15,000 Amazonian tree species.
Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict that most of the world's >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century.


[New treatments in respiratory medicine in 2018 : asthma, cystic fibrosis and nocturnal positive pressure (CPAP or NIV)].
In this review of novel therapies in pulmonary disorders in 2018, we cover 3 different entities. In GINA stage 1 and 2 asthma, new strategies allow a more individualized treatment. In more severe asthma, there is an increasing interest in biotherapies, with dupilumab, an anti-IL-4 receptor, completing the already available panel which includes anti-IgE, anti-IL-5 and anti-IL-5 receptor antibodies. In cystic fibrosis, a better understanding of the pathogenesis and the genetics of the disease is leading to new treatments acting directly on the function of the CFTR (Cystic fibrosis transmembrane conductance regulator), which, when used in combination, show very promising results. Finally, nocturnal positive pressure treatment (either CPAP or non invasive ventilation : NIV) is used more and more frequently. Recent studies have clarified therapeutic algorithms for the most frequent indications for NIV : COPD and obesity-hypoventilation.


Association of psychopathology with quality of life in acute phase of schizophrenia; an experience from east India.
To find the association of patient characteristic and psychopathology with quality of life in acute phase of schizophrenia. Socio-demographic variables of patient, psychopathology and quality of life were assessed. Spearman's Correlation coefficients were measured using SPSS version 15.0. Quality of life of the patients varied in different domains. Male gender, unmarried status and higher educational status predicted a poorer quality of life. The domains of physical and psychological well-being of WHO-QOL were correlated with PANSS general and total scores whereas environmental and social health showed no correlation with PANSS scores. Domains of subjective quality of life in acute phase of schizophrenia are associated variedly with socio-demographic variables and symptomatology.


Cancer in World Trade Center responders: Findings from multiple cohorts and options for future study.
Three longitudinal studies of cancer incidence in varied populations of World Trade Center responders have been conducted. We compared the design and results of the three studies. Separate analyses of these cohorts revealed excess cancer incidence in responders for all cancers combined and for cancers of the thyroid and prostate. Methodological dissimilarities included recruitment strategies, source of cohort members, demographic characteristics, overlap between cohorts, assessment of WTC and other occupational exposures and confounders, methods and duration of follow-up, approaches for statistical analysis, and latency analyses. The presence of three cohorts strengthens the effort of identifying and quantifying the cancer risk; the heterogeneity in design might increase sensitivity to the identification of cancers potentially associated with exposure. The presence and magnitude of an increased cancer risk remains to be fully elucidated. Continued long-term follow up with minimal longitudinal dropout is crucial to achieve this goal.


Tetrahydrobiopterin in nitric oxide synthesis: a novel biological role for pteridines.
Ever since the discovery that (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) is a cofactor of NOS, its function has been the object of intense research and occasional controversy. Only in the last couple of years a consensus has been reached on what constitutes the main role of BH4 in NO synthesis. In this review we aim to provide an outline of the various ways in which BH4 affects NOS catalysis. First we give a brief general description of the structure and catalytic mechanism of NOS, with special emphasis on those aspects of catalysis that are actively debated, and that directly or indirectly involve BH4. Foremost among those issues is uncoupled catalysis, i.e. the NOS-catalyzed oxidation of NADPH in the absence of substrate or pterin that does not result in NO production. We also shortly discuss the ongoing debate on whether NO is the actual reaction product of NOS catalysis, as well as the phenomenon of NO-mediated autoinhibition. We describe the function of BH4 in aromatic amino acid hydroxylation, and discuss the allosteric and structural effects that BH4 exerts on NOS. Next we turn our attention to what is now becoming accepted as the central function of BH4: its capacity to act as a 1-electron donor during reductive activation of the oxyferrous complex of the heme. Finally, we illustrate how BH4 might transform the NOS dimer into an efficient S-nitrosoglutathione synthase,and briefly touch on some more speculative aspects of the role of BH4 in NO synthesis.


Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality.
Biological methylation is a fundamental enzymatic reaction for a variety of substrates in multiple cellular processes. Mammalian N6amt1 was thought to be a homologue of bacterial N(6)-adenine DNA methyltransferases, but its substrate specificity and physiological importance remain elusive. Here, we demonstrate that N6amt1 functions as a protein methyltransferase for the translation termination factor eRF1 in mammalian cells both in vitro and in vivo. Mass spectrometry analysis indicated that about 70% of the endogenous eRF1 is methylated at the glutamine residue of the conserved GGQ motif. To address the physiological significance of eRF1 methylation, we disrupted the N6amt1 gene in the mouse. Loss of N6amt1 led to early embryonic lethality. The postimplantation development of mutant embryos was impaired, resulting in degeneration around embryonic day 6.5. This is in contrast to what occurs in Escherichia coli and Saccharomyces cerevisiae, which can survive without the N6amt1 homologues. Thus, N6amt1 is the first glutamine-specific protein methyltransferase characterized in vivo in mammals and methylation of eRF1 by N6amt1 might be essential for the viability of early embryos.


Greater variability in chimpanzee (Pan troglodytes) brain structure among males.
Across the animal kingdom, males tend to exhibit more behavioural and morphological variability than females, consistent with the 'greater male variability hypothesis'. This may reflect multiple mechanisms operating at different levels, including selective mechanisms that produce and maintain variation, extended male development, and X chromosome effects. Interestingly, human neuroanatomy shows greater male variability, but this pattern has not been demonstrated in any other species. To address this issue, we investigated sex-specific neuroanatomical variability in chimpanzees by examining relative and absolute surface areas of 23 cortical sulci across 226 individuals (135F/91M), using permutation tests of the male-to-female variance ratio of residuals from MCMC generalized linear mixed models controlling for relatedness. We used these models to estimate sulcal size heritability, simulations to assess the significance of heritability, and Pearson correlations to examine inter-sulcal correlations. Our results show that: (i) male brain structure is relatively more variable; (ii) sulcal surface areas are heritable and therefore potentially subject to selection; (iii) males exhibit lower heritability values, possibly reflecting longer development; and (iv) males exhibit stronger inter-sulcal correlations, providing indirect support for sex chromosome effects. These results provide evidence that greater male neuroanatomical variability extends beyond humans, and suggest both evolutionary and developmental explanations for this phenomenon.


Passive immunization of channel catfish Ictalurus punctatus with anti-Flavobacterium columnare sera.
Passive immunization of channel catfish Ictalurus punctatus (Rafinesque) was conducted to determine if anti-Flavobacterium columnare serum was protective when injected intraperitoneally (i.p.) into channel catfish. The anti-F. columnare serum was produced by actively immunizing (i.p. injection) channel catfish with sonicated whole cells or purified lipopolysaccharide (LPS) of F. columnare in Freund's adjuvant. Serum anti-F. columnare activity was verified by Western blotting and ELISA of serum. Normal serum and sterile culture broth were used as controls. Complement was inactivated in all sera by heating. After 48 h, passively immunized fish were challenged with virulent F. columnare by i.p. injection. A group of unchallenged fish served as controls. The immune response of catfish to the antigenic fractions was different when examined by Western blotting. Antibody produced with whole-cell antigen responded to a broad range of molecular weight components, while LPS antigens were restricted to a pair of bands near 20 kDa. Control fish injected with culture medium experienced 100% mortality 14 d post-challenge. Relative percent survival was 77 and 73 for catfish passively immunized with anti-LPS and anti-whole-cell serum, respectively. Results suggest that antibodies in the serum are involved in the protective immune response against columnaris disease in channel catfish.


Comparison of sitting height measurement using three anthropometric measuring techniques.
Accurate, reproducible, anthropometric measurements are essential in the aviation community. Three methodologies were evaluated to determine how they compared with respect to variability and accuracy. One of the methods, an anthropometric chair, is currently used to screen naval aviation candidates. Another method, employing anthropometers (calipers), has been widely used for anthropometric surveys. A third method, referred to as the digital anthropometric video imaging device (DAVID), is a computer-based technique that digitizes a video image for the purpose of determining anthropometric measurements. For this comparison study, sitting height was measured by 15 subjects using the 3 cited methods. An evaluation of sitting height was used because of its importance to aviation and because it requires attention to both posture and measurement technique. Statistical analysis showed no statistical difference between the three methodologies.


Recognizing delirium superimposed on dementia: assessing nurses' knowledge using case vignettes.
Delirium is a serious and prevalent problem that occurs in many hospitalized older adults. Delirium superimposed on dementia (DSD) occurs when a delirium occurs concurrently with a pre-existing dementia. DSD is typically underrecognized by medical and nursing staff. The current study measured nursing identification of DSD using standardized case vignettes, and the Mary Starke Harper Aging Knowledge Exam (MSHAKE). Results revealed that the nurses in this study had a high level of general geropsychiatric nursing knowledge as measured by the MSHAKE, yet had difficulty recognizing DSD compared to dementia alone and delirium alone. Only 21% were able to correctly identify the hypoactive form of DSD, and 41% correctly identified hypoactive delirium alone in the case vignettes. Interventions and educational programs designed to increase nursing awareness of DSD symptoms could help to decrease this gap in nursing knowledge.


The three genetics (nuclear DNA, mitochondrial DNA, and gut microbiome) of longevity in humans considered as metaorganisms.
Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between nDNA/mtDNA and the environment is most likely involved in phenomena such as ageing and longevity. To this scenario we have to add another level of complexity represented by the microbiota, that is, the whole set of bacteria present in the different part of our body with their whole set of genes. In particular, several studies investigated the role of gut microbiota (GM) modifications in ageing and longevity and an age-related GM signature was found. In this view, human being must be considered as "metaorganism" and a more holistic approach is necessary to grasp the complex dynamics of the interaction between the environment and nDNA-mtDNA-GM of the host during ageing. In this review, the relationship between the three genetics and human longevity is addressed to point out that a comprehensive view will allow the researchers to properly address the complex interactions that occur during human lifespan.


Orbital Hanle Magnetoresistance in a 3d Transition Metal.
The Hanle magnetoresistance is a telltale signature of spin precession in nonmagnetic conductors, in which strong spin-orbit coupling generates edge spin accumulation via the spin Hall effect. Here, we report the existence of a large Hanle magnetoresistance in single layers of Mn with weak spin-orbit coupling, which we attribute to the orbital Hall effect. The simultaneous observation of a sizable Hanle magnetoresistance and vanishing small spin Hall magnetoresistance in BiYIG/Mn bilayers corroborates the orbital origin of both effects. We estimate an orbital Hall angle of 0.016, an orbital relaxation time of 2 ps and diffusion length of the order of 2 nm in disordered Mn. Our findings indicate that current-induced orbital moments are responsible for magnetoresistance effects comparable to or even larger than those determined by spin moments, and provide a tool to investigate nonequilibrium orbital transport phenomena.


Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer. We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery). Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival. Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)