Investigations into plant biochemical wound-response pathways involved in the production of aphid-induced plant volatiles.
Feeding damage to plants by insect herbivores induces the production of plant volatiles, which are attractive to the herbivores natural enemies. Little is understood about the plant biochemical pathways involved in aphid-induced plant volatile production. The aphid parasitoid Diaeretiella rapae can detect and respond to aphid-induced volatiles produced by Arabidopsis thaliana. When given experience of those volatiles, it can learn those cues and can therefore be used as a novel biosensor to detect them. The pathways involved in aphid-induced volatile production were investigated by comparing the responses of D. rapae to volatiles from a number of different transgenic mutants of A. thaliana, mutated in their octadecanoid, ethylene or salicylic acid wound-response pathways and also from wild-type plants. Plants were either undamaged or infested by the peach-potato aphid, Myzus persicae. It is demonstrated that the octadecanoid pathway and specifically the COI1 gene are required for aphid-induced volatile production. The presence of salicylic acid is also involved in volatile production. Using this model system, in combination with A. thaliana plants with single point gene mutations, has potential for the precise dissection of biochemical pathways involved in the production of aphid-induced volatiles.


The emergence of carbapenem resistant Klebsiella pneumoniae in Malaysia: correlation between microbiological trends with host characteristics and clinical factors.
Carbapenem resistant Enterobacteriaceae is a growing concern worldwide including Malaysia. The emergence of this pathogen is worrying because carbapenem is one of the 'last-line' antibiotics. The main objective of this study was to determine the prevalence of genetic mechanisms and clinical risk factors of carbapenem resistant Klebsiella pneumoniae (K. pneumoniae) in Malaysia. In this study, seventeen carbapenem resistant K. pneumoniae strains isolated from a tertiary teaching hospital in 2013 were studied. Minimal inhibitory concentration (MIC) of the bacterial strains was determined and genes associated with carbapenemases and extended-spectrum-beta-lactamases (ESBLs) were sequenced and compared with the closest representatives published in public domains. All strains were also sub-typed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Statistical analyses were performed to determine the correlation between risk factors for acquiring carbapenem resistant K. pneumoniae and in-hospital mortality. The predominant carbapenemase was blaOXA-48, detected in 12 strains (70.59%). Other carbapenemases detected in this study were blaKPC-2, blaIMP-8, blaNMC-A and blaNDM-1. Nine different pulsotypes were identified and nine strains which were affiliated with ST101, the predominant sequence type had similar PFGE patterns (similarity index of 85%). Based on univariate statistical analysis, resistance to imipenem and usage of mechanical ventilation showed a statistically significant effect separately to in-hospital mortality. The diverse genetic mechanisms harbored by these carbapenem resistant K. pneumoniae facilitates its spread and complicates its detection. Thus, correlation between microbiological trends with host characteristics and clinical factors will provide a better insight of rational treatment strategies and pathogen control.


Giant-cell pneumonia caused by measles and methotrexate in childhood leukaemia in remission.
Four children who had acurate lymphoblastic leukaemia in remission and developed pneumonia were studied. Investigations including electron microscopy and immunofluorescence of lung biopsy material disclosed measles, although there was no clinical evidence of the disease. Despite an identical presentation, two types of illness developed: two children died of giant-cell pneumonia, while the other two developed pneumonia indistinguishable from that associated with methotrexate treatment, recovering when treated with steroids and gammaglobulin. Measles infection is easily overlooked in the absence of rash. The diagnosis may be suggested by clinical and radiological features and confirmed by specific immunofluorescence staining of lung biopsy tissue.


Is the association of breastfeeding with child obesity explained by infant weight change?
Breastfeeding and infant weight change are both associated with adiposity. We examined the extent to which infant weight change mediates the association between breastfeeding and adiposity at age 3 years. We studied 884 children in a prospective cohort study. We determined breastfeeding status in the first 6 months. Our primary outcomes at 3 years were body mass index (BMI) z score and the sum of subscapular and triceps skinfold thicknesses (SS + TR); we also assessed obesity. We defined infant weight change as change in weight-for-age z score between birth and 6 months. We performed multivariable regression analyses. At age 6 months, 25.0% of infants were fully breastfed. At age 3 years, mean (standard deviation) BMI z score was 0.45 (1.03). In linear regression analyses adjusted for mother's educational level, race/ethnicity, smoking, BMI, pregnancy weight gain and birth weight (adjusted for gestational age), the BMI z score of fully breastfed children was 0.17 (95% CI: -0.43, 0.09) units lower than never breastfed children. After additional adjustment for infant weight change, the estimate was attenuated (-0.03, 95% CI: -0.27, 0.20). Adjustment for infant weight change only modestly attenuated estimates for SS + TR (from -1.48 mm [95% CI: -2.52, -0.44] to -1.16 mm [95% CI: -2.18, -0.14]), and for the odds of being obese (from 0.21 [95% CI: 0.07, 0.68] to 0.29 [95% CI: 0.08, 1.05]). Infant weight change between birth and 6 months mediates associations of breastfeeding with BMI, but only partially with indicators of child adiposity.


Disclosure of stuttering and quality of life in people who stutter.
This study investigated the disclosure practices of people who stutter, and the relationship between disclosure of stuttering and quality of life. Participants were 322 adults who stutter recruited from speech-language pathologists and support group leaders. Participants completed a survey that contained items measuring level of disclosure of stuttering, as well as a global measure of self-rated quality of life. Participants were grouped into low, average, and high quality of life subgroups. Analysis of variance tests compared disclosure levels among these subgroups. The low quality of life subgroup reported significantly lower levels of disclosure compared to both the average and high quality of life subgroups. Participants with self-help/support group experience for stuttering demonstrated significantly higher levels of disclosure of stuttering compared to individuals without such experience. In addition, a substantial number of participants in the overall sample reported that they more than rarely feel the need to conceal stuttering from others (40%), and that no one knows that they stutter in many areas of life (37%). Attempts to conceal stuttering in at least some life situations are not uncommon among adults who stutter. However, being involved in self-help support groups may be a helpful way of increasing disclosure of stuttering. Speech-language pathologists should become aware of the positive relationship between disclosure of stuttering and quality of life and its relevance in assessment and treatment when working with people who stutter.


Exploring gender perceptions of risk of HIV infection and related behaviour among elderly men and women of Ga-Rankuwa, Gauteng Province, South Africa.
The literature shows that there are important differences between women and men in the underlying mechanisms of transmission of HIV infection and AIDS, as well as in the social and economic consequences of HIV/AIDS. These stem from sexual behaviour and socially constructed 'gender' differences between women and men in roles and responsibilities. Despite the fact that numerous gender-related sociocultural factors influence HIV/AIDS protective behaviours, little gender specificity is included in HIV prevention among the elderly. In order to close this gap, this study explored gender-related perceptions of risk of HIV infection among elderly men and women of Ga-Rankuwa in Gauteng Province, South Africa. This qualitative study used purposive sampling to conduct three focus group interviews with 22 women and 10 men who were above 60 years of age. Findings revealed that both genders blame each other for the spreading of HIV/AIDS. Male participants displayed the tendency to have multiple partners, whereas females accepted that males are promiscuous. Mixed perceptions about disclosure of HIV status were found. Condom use was a challenge, as men did not know how to introduce it with their wives, and some female participants indicated that men are resistant to using condoms. The elderly men also believed that women will have sex in exchange for money. It is concluded that there is a need for substantial behaviour change among both elderly males and females, which should address gender power relations. More in-depth and extensive research in this area is recommended.


Design and performance of personal cooling garments based on three-layer laminates.
Personal cooling systems are mainly based on cold air or liquids circulating through a tubing system. They are weighty, bulky and depend on an external power source. In contrast, the laminate-based technology presented here offers new flexible and light weight cooling garments integrated into textiles. It is based on a three-layer composite assembled from two waterproof, but water vapor permeable membranes and a hydrophilic fabric in between. Water absorbed in the fabric will be evaporated by the body temperature resulting in cooling energy. The laminate's high adaptiveness makes it possible to produce cooling garments even for difficult anatomic topologies. The determined cooling energy of the laminate depends mainly on the environmental conditions (temperature, relative humidity, wind): heat flux at standard climatic conditions (20 degrees C, 65% R.H., wind 5 km/h) has measured 423.2 +/- 52.6 W/m(2), water vapor transmission resistance, R (et), 10.83 +/- 0.38 m(2) Pa/W and thermal resistance, R (ct), 0.010 +/- 0.002 m(2) K/W. Thermal conductivity, k, changed from 0.048 +/- 0.003 (dry) to 0.244 +/- 0.018 W/m K (water added). The maximum fall in skin temperature, Delta T (max), under the laminate was 5.7 +/- 1.2 degrees C, taken from a 12 subject study with a thigh cooling garment during treadmill walking (23 degrees C, 50% R.H., no wind) and a significant linear correlation (R = 0.85, P = 0.01) between body mass index and time to reach 67% of Delta T (max) could be determined.


Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.
In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. http://www.clinicaltrials.gov. Unique identifier: NCT00120289.


Interacting effects of maternal responsiveness, infant regulatory problems and dopamine D4 receptor gene in the development of dysregulation during childhood: A longitudinal analysis.
Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators.


Diurnal expression of transducin mRNA and translocation of transducin in rods of rat retina.
The messenger RNA (mRNA) that encodes alpha subunit of the guanosine triphosphate-binding protein transducin (T alpha) and T alpha immunoreactivity were localized and measured in the rat retina during the light-dark cycle with in situ hybridization and immunohistochemistry. Both T alpha mRNA and T alpha immunoreactivity were observed only in photoreceptors. Within the photoreceptor T alpha mRNA was present primarily in the inner segments and to a lesser extent in the outer nuclear layer at all times during the day and night. However, the distribution of T alpha immunoreactivity varied profoundly with the light-dark cycle; during the day, T alpha immunoreactivity was highest in the inner segments, and at night the outer segments were more immunoreactive. The amounts of T alpha mRNA and T alpha immunoreactivity also depended on the light-dark cycle. Levels of T alpha mRNA were high immediately before and after lights on; levels were low for the rest of the light-dark cycle. During the day, T alpha immunoreactivity increased in the inner segments following the increase in T alpha mRNA. After the lights were turned off, T alpha immunoreactivity decreased in the inner segments and increased in the outer segments. Thus, it appears that T alpha is synthesized in the inner segments after a morning increase in T alpha mRNA. Newly synthesized T alpha remains in the inner segments until it is transported to the outer segments at night, where it may be involved in the increase in the sensitivity of photoreceptor rods at night.


Comparison measurements of 0:45 radiance factor and goniometrically determined diffuse reflectance.
A comparison between the absolute gonioreflectometric scales at the Helsinki University of Technology (TKK) and the Physikalisch-Technische Bundesanstalt (PTB) has been accomplished. Six different reflection standards were measured for their 0:45 spectral radiance factor between 250 and 1650 nm in 10 nm intervals. Also, the 0:d reflectance factor between 400 and 1600 nm in 100 nm intervals was determined from goniometric reflectance measurements over polar angles with subsequent integration within the hemisphere above the sample. Goniometric comparisons covering such an extensive wavelength range and also several different sample materials are rarely implemented. For all but one sample, the difference between the results obtained at the TKK and the PTB was, with the exception of a couple of measurement points, within the expanded uncertainty (k = 2) of the comparison at least up to a wavelength of 1400 nm. All differences between the measurement results can be understood, except for one translucent sample in the visible wavelength range. The effect of sample translucency was found to be significant in the NIR wavelength region. Also, a general tendency of an increase of the TKK values relative to the PTB values in the UV region was observed. Possible causes for this phenomenon are discussed.


Methods for shortening patient-reported outcome measures.
Patient-reported outcome measures are widely used to assess patient experiences, well-being, and treatment response in clinical trials and cohort-based observational studies. However, patients may be asked to respond to many different measures in order to provide researchers and clinicians with a wide array of information regarding their experiences. Collecting such long and cumbersome patient-reported outcome measures may burden patients, increase research costs, and potentially reduce the quality of the data collected. Nonetheless, little research has been conducted on replicable, and reproducible methods to shorten these instruments that result in shortened forms of minimal length. This manuscript proposes the use of mixed integer programming through Optimal Test Assembly as a method to shorten patient-reported outcome measures. This method is compared to the existing standard in the field, which is selecting items based on having high discrimination parameters from an item response theory model. The method is then illustrated in an application to a fatigue scale for patients with Systemic Sclerosis.


Contribution of nitric oxide synthase (NOS) activity in blood-brain barrier disruption and edema after acute ischemia/reperfusion in aortic coarctation-induced hypertensive rats.
Nitric oxide synthase (NOS) activity is increased during hypertension and cerebral ischemia. NOS inactivation reduces stroke-induced cerebral injuries, but little is known about its role in blood-brain barrier (BBB) disruption and cerebral edema formation during stroke in acute hypertension. Here, we investigated the role of NOS inhibition in progression of edema formation and BBB disruptions provoked by ischemia/reperfusion injuries in acute hypertensive rats. Rats were made acutely hypertensive by aortic coarctation. After 7 days, the rats were randomly selected for the recording of carotid artery pressure, or regional cerebral blood flow (rCBF) using laser Doppler. Ishcemia induced by 60-min middle cerebral artery occlusion (MCAO), followed by 12-h reperfusion. A single i.p. dose of L-NAME (1 mg/kg) was injected before MCAO. After evaluation of neurological disabilities, rats were slaughtered under deep anesthesia to assess cerebral infarction volume, edema, or BBB disruption. A 75-85% reduction in rCBF was occurred during MCAO which returned to pre-occluded levels during reperfusion. Profound neurological disabilities were evidenced after MCAO alongside with severe cerebral infarctions (628 ± 98 mm3), considerable edema (4.05 ± 0.52%) and extensive BBB disruptions (Evans blue extravasation, 8.46 ± 2.03 mug/g). L-NAME drastically improved neurological disabilities, diminished cerebral infarction (264 ± 46 mm3), reduced edema (1.49 ± 0.47%) and BBB disruption (2.93 ± 0.66 mug/g). The harmful actions of NOS activity on cerebral microvascular integrity are intensified by ischemia/reperfusion injuries during acute hypertension. NOS inactivation by L-NAME preserved this integrity and diminished cerebral edema.


Interactions of grazing history, cattle removal and time since rain drive divergent short-term responses by desert biota.
Arid grasslands are used worldwide for grazing by domestic livestock, generating debate about how this pastoral enterprise may influence native desert biota. One approach to resolving this question is to experimentally reduce livestock numbers and measure the effects. However, a key challenge in doing this is that historical grazing impacts are likely to be cumulative and may therefore confound comparisons of the short-term responses of desert biota to changes in stocking levels. Arid areas are also subject to infrequent flooding rainfalls that drive productivity and dramatically alter abundances of flora and fauna. We took advantage of an opportunity to study the recent effects of a property-scale cattle removal on two properties with similarly varied grazing histories in central Australia. Following the removal of cattle in 2006 and before and after a significant rainfall event at the beginning of 2007, we sampled vegetation and small vertebrates on eight occasions until October 2008. Our results revealed significant interactions of time of survey with both grazing history and grazing removal for vascular plants, small mammals and reptiles. The mammals exhibited a three-way interaction of time, grazing history and grazing removal, thus highlighting the importance of careful sampling designs and timing for future monitoring. The strongest response to the cessation of grazing after two years was depressed reproductive output of plants in areas where cattle continued to graze. Our results confirm that neither vegetation nor small vertebrates necessarily respond immediately to the removal of livestock, but that rainfall events and cumulative grazing history are key determinants of floral and faunal performance in grassland landscapes with low and variable rainfall. We suggest that improved assessments could be made of the health of arid grazing environments if long-term monitoring were implemented to track the complex interactions that influence how native biota respond to grazing.


A resource-based perspective on retention strategies for nurse epidemiologists.
This paper is a report of a study to evaluate the intent of epidemiologists to remain in their chosen career and identify the variables that contributed to or predicted their intent to stay. Recently, emerging new infections, such as severe acute respiratory syndrome or bird flu, have placed significant occupational and psychological stress on epidemiologists, especially in South-East Asia, resulting in a high intent to change their career. In the light of possible staff shortages, retention strategies for epidemiologists have gained importance. A self-administered questionnaire survey and stratified sampling were used to collect data from 351 epidemiologists including nurse epidemiologists in Taiwan in 2005; response rate was 70.6%. Correlation analysis and hierarchical multiple regression analysis were used to examine relationships among occupational stress, psychological stress, human resources and intent to stay in their career. Occupational stress, psychological stress and human resources had an impact on epidemiologists' intent to stay in their career. Results show that the relationship between occupational stress (operation and personal safety hazard) and intent to stay could be influenced by organizational capital, and the relationship between emotional distress and intent to stay could be influenced by a broad spectrum of human resources (organizational, social and human capital). The severe acute respiratory syndrome epidemic raised worldwide attention and challenged epidemiologists' intent to stay. Results indicate that human resources play an important role in this issue. Managers should enhance human resources in organizations as much as possible to attenuate epidemiologists' stress, which may, in turn, strengthen their intent to stay.


Abdominal Wall Defects among Mexican American Infants: The Effect of Maternal Nativity.
US-born Mexican American women have greater rates of preterm birth and consequent overall infant mortality than their Mexico-born peers. However, the relation of Mexican American women's nativity to rates of congenital anomalies is poorly understood. Hispanic ethnicity and young maternal age are well-known risk factors for gastroschisis. To determine the extent to which nativity of Mexican American women is associated with abdominal wall defects. Stratified and multivariable logistic regression analyses were performed on the 2003-2004 National Center for Health Statistics linked live birth-infant death cohort. Only Mexican American infants were studied. Maternal variables examined included nativity, age, education, marital status, parity, and prenatal care usage. Infants with US-born Mexican American mothers (n=451,272) had an abdominal wall defect rate of 3.9/10,000 compared with 2.0/10,000 for those with Mexico-born mothers (n=786,878), RR=1.9 (1.5-2.4). Though a greater percentage of US-born (compared wtih Mexico-born) Mexican American mothers were teens, the nativity disparity was actually widest among women in their 20s. The adjusted (controlling for maternal age, education, marital status, parity, and prenatal care) odds ratio of abdominal wall defects among infants of US-born (compared with Mexico-born) Mexican American mothers was 1.6 (1.2-2.0). US-born Mexican American women have nearly a two-fold greater rate of delivering an infant with an abdominal wall defect than their Mexico-born counterparts. This phenomenon is only partially explained by traditional risk factors and highlights a detrimental impact of lifelong residence in the United States, or something closely related to it, on the pregnancy outcome of Mexican American women.


Response of day-to-day home blood pressure variability by antihypertensive drug class after transient ischemic attack or nondisabling stroke.
Visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of stroke and was reduced in randomized trials by calcium channel blockers and diuretics but not by renin-angiotensin system inhibitors. However, time of day effects could not be determined. Day-to-day variability on home BP readings predicts stroke risk and potentially offers a practical method of monitoring response to variability-directed treatment. SBP mean, maximum, and variability (coefficient of variation=SD/mean) were determined in 500 consecutive transient ischemic attack or minor stroke patients on 1-month home BP monitoring (3 BPs, 3× daily). Hypertension was treated to a standard protocol. Differences in SBP variability from 3 to 10 days before to 8 to 15 days after starting or increasing calcium channel blockers/diuretics versus renin-angiotensin system inhibitors versus both were compared by general linear models, adjusted for risk factors and baseline BP. Among 288 eligible interventions, variability in SBP was reduced after increased treatment with calcium channel blockers/diuretics versus both versus renin-angiotensin system inhibitors (-4.0 versus 6.9 versus 7.8%; P=0.015), primarily because of effects on maximum SBP (-4.6 versus -1.0 versus -1.0%; P=0.001), with no differences in effect on mean SBP. Class differences were greatest for early-morning SBP variability (3.6 versus 17.0 versus 38.3; P=0.002) and maximum (-4.8 versus -2.0 versus -0.7; P=0.001), with no effect on midmorning (P=0.29), evening (P=0.65), or diurnal variability (P=0.92). After transient ischemic attack or minor stroke, calcium channel blockers and diuretics reduced variability and maximum home SBP, primarily because of effects on morning readings. Home BP readings enable monitoring of response to SBP variability-directed treatment in patients with recent cerebrovascular events.


The quorum-sensing molecule autoinducer 2 regulates motility and flagellar morphogenesis in Helicobacter pylori.
The genome of the gastric pathogen Helicobacter pylori contains a homologue of the gene luxS, which has been shown to be responsible for production of the quorum-sensing signal autoinducer 2 (AI-2). We report here that deletion of the luxS gene in strain G27 resulted in decreased motility on soft agar plates, a defect that was complemented by a wild-type copy of the luxS gene and by the addition of cell-free supernatant containing AI-2. The flagella of the luxS mutant appeared normal; however, in genetic backgrounds lacking any of three flagellar regulators--the two-component sensor kinase flgS, the sigma factor sigma28 (also called fliA), and the anti-sigma factor flgM--loss of luxS altered flagellar morphology. In all cases, the double mutant phenotypes were restored to the luxS+ phenotype by the addition of synthetic 4,5-dihydroxy-2,3-pentanedione (DPD), which cyclizes to form AI-2. Furthermore, in all mutant backgrounds loss of luxS caused a decrease in transcript levels of the flagellar regulator flhA. Addition of DPD to luxS cells induced flhA transcription in a dose-dependent manner. Deletion of flhA in a wild-type or luxS mutant background resulted in identical loss of motility, flagella, and flagellar gene expression. These data demonstrate that AI-2 functions as a secreted signaling molecule upstream of FlhA and plays a critical role in global regulation of flagellar gene transcription in H. pylori.


Broadband Transient Absorption and Two-Dimensional Electronic Spectroscopy of Methylene Blue.
Broadband transient absorption and two-dimensional electronic spectroscopy (2DES) studies of methylene blue in aqueous solution are reported. By isolating the coherent oscillations of the nonlinear signal amplitude and Fourier transforming with respect to the population time, we analyzed a significant number of coherences in the frequency domain and compared them with predictions of the vibronic spectrum from density function theory (DFT) calculations. We show here that such a comparison enables reliable assignments of vibrational coherences to particular vibrational modes, with their constituent combination bands and overtones also being identified via Franck–Condon analysis aided by DFT. Evaluation of the Fourier transform (FT) spectrum of transient absorption recorded to picosecond population times, in coincidence with 2D oscillation maps that disperse the FT spectrum into the additional excitation axis, is shown to be a complementary approach toward detailed coherence determination. Using the Franck–Condon overlap integrals determined from DFT calculations, we modeled 2D oscillation maps up to two vibrational quanta in the ground and excited state (six-level model), showing agreement with experiment. This semiquantitative analysis is used to interpret the geometry change upon photoexcitation as an expansion of the central sulfur/nitrogen containing ring due to the increased antibonding character in the excited state.


Alzheimer disease-associated cystatin C variant undergoes impaired secretion.
CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.


In search of antiepileptogenic treatments for post-traumatic epilepsy.
Post-traumatic epilepsy (PTE) is diagnosed in 20% of individuals with acquired epilepsy, and can impact significantly the quality of life due to the seizures and other functional or cognitive and behavioral outcomes of the traumatic brain injury (TBI) and PTE. There is no available antiepileptogenic or disease modifying treatment for PTE. Animal models of TBI and PTE have been developed, offering useful insights on the value of inflammatory, neurodegenerative pathways, hemorrhages and iron accumulation, calcium channels and other target pathways that could be used for treatment development. Most of the existing preclinical studies test efficacy towards pathologies of functional recovery after TBI, while a few studies are emerging testing the effects towards induced or spontaneous seizures. Here we review the existing preclinical trials testing new candidate treatments for TBI sequelae and PTE, and discuss future directions for efforts aiming at developing antiepileptogenic and disease-modifying treatments.


Fate of DNA targeted to the liver by asialoglycoprotein receptor-mediated endocytosis in vivo. Prolonged persistence in cytoplasmic vesicles after partial hepatectomy.
After intravenous injection, DNA complexed with asialoglycoprotein-polylysine conjugates is endocytosed by hepatocytes via asialoglycoprotein receptors and is expressed transiently. Long term persistence and expression occurs when partial hepatectomy is performed after gene delivery. To determine the intracellular location of the persisting DNA, we transferred a plasmid expressing bacterial chloramphenicol acetyltransferase into the liver of rats in vivo by asialoglycoprotein receptor-mediated endocytosis. The internalized DNA was measured by Southern blot. Twenty min after administration, 80-85% of the plasmid appeared in the liver, 80% of which was within hepatocytes (12,000-18,000 copies/hepatocyte). In sham-operated control rats, the transgene concentration decreased to 8-12 and 2-4% of the initial levels in 4 and 24 h, respectively, and became undetectable at 7 days. In rats subjected to 66% hepatectomy 20 min after DNA administration, 20, 9, and 7% of the plasmid in the residual liver persisted at 4 h, 24 h, and 7 days, respectively. Liver homogenates were fractionated by differential centrifugation and Percoll gradient centrifugation. In 66% hepatectomized rats, the plasmid persisted in an undegraded, transfection-competent form in plasma membrane/endosome-enriched fractions throughout the duration of the experiment (7 days), indicating that cytoplasmic vesicles are the main site of persistence of the endocytosed DNA.


Mossbauer spectroscopy of moon samples.
Lunar bulk sample 10084,85 (< 1 mm size dust), and samples from rocks 10017,17 (fine grained, vesicular), 10046,17 (breccia), 10057,59 (fine grained, vesicular, top surface), 10057,60 (fine grained, vesicular, interior), and 10058,24 (medium grained, not vesicular) have been investigated by (57)Fe Mössbauer spectroscopy. Iron metal and the Fe(2+) minerals ilmenite, pyroxene, troilite, and iron containing glass have been identified. An iron line of sample 10084,85 (originally sealed in nitrogen) showed no significant intensity change when the sample was exposed to air. The antiferromagnetic transition in several lunar ilmenites at 57(0) +/- 2 degrees K corresponds to stoichiometric FeTiO,. Magneticallv separated 10057 showed troilite and somne metallic iron.


The ideological divide in public perceptions of self-driving cars.
Applications in artificial intelligence such as self-driving cars may profoundly transform our society, yet emerging technologies are frequently faced with suspicion or even hostility. Meanwhile, public opinions about scientific issues are increasingly polarized along the ideological line. By analyzing a nationally representative panel in the United States, we reveal an emerging ideological divide in public reactions to self-driving cars. Compared with liberals and Democrats, conservatives and Republicans express more concern about autonomous vehicles and more support for restrictively regulating autonomous vehicles. This ideological gap is largely driven by social conservatism. Moreover, both familiarity with driverless vehicles and scientific literacy reduce respondents' concerns over driverless vehicles and support for regulation policies. Still, the effects of familiarity and scientific literacy are weaker among social conservatives, indicating that people may assimilate new information in a biased manner that promotes their worldviews.


Reasons for non-response in observational pharmacogenetic research.
In epidemiological studies, non-response may introduce bias and limit generalizability. In genetic pharmacoepidemiological research, collection of DNA might be a major reason for non-response. We determined reasons for non-response and compared characteristics of non-responders and responders in a pharmacogenetic case-control study. Myocardial infarction (MI) cases and controls, who were antihypertensive drug users, were recruited through community pharmacies that participate in the Pharmaco-Morbidity-Record-Linkage-System (PHARMO). The PHARMO database comprises drug dispensing histories of about 2 000 000 subjects from a representative sample of Dutch community pharmacies linked to the national registry of hospital discharges. Independent samples t-test and ANOVA-statistics were used to analyse the differences in continuous variables between responders and non-responders. chi2 statistics and logistic regression were used to compare categorical variables. We approached 1871 cases and 14 102 controls of whom 794 MI cases (42.4%) and 4997 controls (35.4%) responded. We could not approach 2194 patients of whom 63.1% had died and 31.2% moved to another pharmacy. Main reasons for non-response were health problems or hospital stays (16.2%, OR 1.47; 95%CI: 1.00-2.16). Other reasons were old age or dementia (16.9%, OR 1.82; 95%CI: 1.24-2.65). Only a small percentage (1.1%, OR 1.43; 95%CI: 0.41-5.03) mentioned DNA sampling as a reason. About 30% of the non-responders did not give a reason. Women were statistically significantly (p < 0.0005) less willing to participate than men (38.8% versus 31.3%). An association with age was also found (mean age 64.6 versus 66.5 yrs) (p < 0.0005). In a pharmacogenetic case-control study fear for genetic screening was not a major reported reason for non-response. Females were less willing to participate than males.


TREM2 expression in the brain and biological fluids in prion diseases.
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.


Determination of daytime clenching events in subjects with and without self-reported clenching.
To confirm the validity of self-awareness of daytime clenching, specific electromyogram (EMG) characteristics of clenching behaviour were determined using surface EMG recordings. Temporal muscle EMGs were recorded for 5 h in 13 subjects with self-reported clenching (clenching group: 27·5 ± 3·8 years old) and 12 subjects without self-reported clenching (control group: 28·6 ± 7·1 years old). All EMG data were recorded and stored on a portable EMG apparatus. The device was similar in size to a hearing aid, and suitable to record daytime EMG without restriction of daily activities. A clenching event was defined as muscle activity exceeding 10% of the maximum voluntary contraction. Furthermore, simultaneous voice recording was also performed to identify the corresponding EMG event as functional or parafunctional. The mean number of clenching events was 192·8 ± 228·8 and 24·8 ± 26·5 in the clenching and the control groups, respectively (P < 0·05, Mann-Whitney U-test); the number of functional events was not significantly different between the groups. Because there was a significant difference in the number of clenching events between the groups, self-reported daytime clenching is considered to be a reliable screening parameter for awake bruxism.


Using porous magnetic iron oxide nanomaterials as a facile photoporation nanoplatform for macromolecular delivery.
The intracellular delivery of exogenous macromolecules such as functional proteins, antibodies, polysaccharides and nucleic acids into living cells for biomedical applications is of great interest. Even though great efforts have been devoted to this task, universal delivery systems that provide excellent intracellular delivery performance combined with easy cell recovery are urgently needed. Magnetic iron oxide nanoparticles show promising potential for various biomedical applications because of their advantages such as high biocompatibility and cost-effectiveness. Herein, a new facile platform for macromolecular delivery was developed based on the photothermal properties of porous magnetic iron oxide nanoparticles (P-MNPs). The near-infrared radiation (NIR) absorption behavior of P-MNPs remarkably facilitates the delivery of macromolecules into cells while maintaining high cell viability. Furthermore, the assistance of polycationic polyethylenimine improves the efficiency of DNA delivery. Most importantly, the cells could be easily recovered after macromolecular delivery by trypsinization, which is of great significance for further practical application of the delivery system. The facile and cost-effective platform proposed in this work provides a new avenue for the utilization of P-MNPs in macromolecular delivery.


Single all-fiber-based nanosecond-pulsed supercontinuum source for multispectral photoacoustic microscopy and optical coherence tomography.
We report the usefulness of a single all-fiber-based supercontinuum (SC) source for combined photoacoustic microscopy (PAM) and optical coherence tomography (OCT). The SC light is generated by a tapered photonic crystal fiber pumped by a nanosecond pulsed master oscillator power amplifier at 1064 nm. The spectrum is split into a shorter wavelength band (500-800 nm) for single/multi-spectral PAM and a longer wavelength band (800-900 nm) band for OCT. In vivo mouse ear imaging was achieved with an integrated dual-modality system. We further demonstrated its potential for spectroscopic photoacoustic imaging by doing multispectral measurements on retinal pigment epithelium and blood samples with 15-nm linewidth.


Organometallic manganese complexes as scaffolds for potential molecular wires.
This article reviews recent work in the area of organomanganese chemistry designing organometallic based molecular wires for potential applications in molecular electronics utilising the bottom-up approach. The field of molecular electronics has recently received much attention in the pursuit of continued miniaturization of electronics. Molecular wires that can allow a through-bridge exchange of an electron/electron hole between its remote ends/terminal groups are the basic motifs of single electron devices. Our recent work in this field has been the design and development of transition-metal complexes with a special emphasis on the half sandwich dinuclear manganese complexes and the bis dmpe dinuclear Mn(II)/Mn(II). In this review, we would like to highlight the importance of the nature of the transition metal and their significant effect on the redox process, which is of paramount importance for the design of systems that could be ultimately wired into circuits for various applications.


The amphioxus genome illuminates vertebrate origins and cephalochordate biology.
Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.


What contribution has cardiac surgery made to the decline in mortality from coronary heart disease?
The number of deaths from coronary artery disease is declining in New Zealand as in some other Western countries. It has been estimated that in 1981 in the Auckland metropolitan area there were 126 fewer deaths than would have been expected from the data in 1974. The contribution made by cardiac surgery to this decline was assessed from the known numbers of patients who were operated on, from their survival rate, and from the predicted mortality of the surgical cohort had they not undergone operation. Such mortality was predicted from past studies of patients with similar symptoms, exercise data, studies of unstable angina, and the coronary artery surgical study registry. From this method it was estimated that coronary surgery accounted for 26% to 42% of the reduction in coronary deaths. Two previous studies estimated, from calculations based on the European study of patients with modest symptoms, that the contribution of cardiac surgery was much lower. Extrapolating data from one subset of patients to a second subset with quite different characteristics is a conceptual fallacy.


Demonstration of a novel apamin-insensitive calcium-activated K+ channel in mouse pancreatic B cells.
The whole-cell configuration of the patch-clamp technique was used to characterize the biophysical and pharmacological properties of an oscillating K(+)-current that can be induced by intracellular application of GTP[gamma S] in mouse pancreatic B cells (Ammälä et al. 1991). These K+ conductance changes are evoked by periodic increases in the cytoplasmic Ca2+ concentration ([Ca2+]i) and transiently repolarize the B cell, thus inhibiting action-potential firing and giving rise to a bursting pattern. GTP[gamma S]-evoked oscillations in K+ conductance were reversibly suppressed by a high (300 microM) concentration of carbamylcholine. By contrast, alpha 2-adrenoreceptor stimulation by 20 microM clonidine did not interfere with the oscillatory behaviour but evoked a small sustained outward current. At 0 mV membrane potential, the oscillating K(+)-current elicited by GTP[gamma S] was highly sensitive to extracellular tetraethylammonium (TEA; 70% block by 1 mM). The TEA-resistant component, which carried approximately 80% of the current at -40 mV, was affected neither by apamin (1 microM) nor by tolbutamide (500 microM). The current evoked by internal GTP[gamma S] was highly selective for K+, as demonstrated by a 51-mV change in the reversal potential for a sevenfold change in [K+]o. Stationary fluctuation analysis indicated a unitary conductance of 0.5 pS when measured with symmetric (approximately 140 mM) KCl solutions. The estimated single-channel conductance with physiological ionic gradients is 0.1 pS. The results indicate the existence of a novel Ca(2+)-gated K+ conductance in pancreatic B cells. Activation of this K+ current may contribute to the generation of the oscillatory electrical activity characterizing the B cell at intermediate glucose concentrations.


Nutrition literacy status and preferred nutrition communication channels among adults in the Lower Mississippi Delta.
The objective of this cross-sectional study was to examine the nutrition literacy status of adults in the Lower Mississippi Delta. Survey instruments included the Newest Vital Sign and an adapted version of the Health Information National Trends Survey. A proportional quota sampling plan was used to represent educational achievement of residents in the Delta region. Participants included 177 adults, primarily African Americans (81%). Descriptive statistics, chi2 analysis, analysis of variance, and multivariate analysis of covariance tests were used to examine survey data. Results indicated that 24% of participants had a high likelihood of limited nutrition literacy, 28% had a possibility of limited nutrition literacy, and 48% had adequate nutrition literacy. Controlling for income and education level, the multivariate analysis of covariance models revealed that nutrition literacy was significantly associated with media use for general purposes (F = 2.79, P = .005), media use for nutrition information (F = 2.30, P = .04), and level of trust from nutrition sources (F = 2.29, P = .005). Overall, the Internet was the least trusted and least used source for nutrition information. Only 12% of participants correctly identified the 2005 MyPyramid graphic, and the majority (78%) rated their dietary knowledge as poor or fair. Compared with other national surveys, rates of limited health literacy among Delta adults were high. Nutrition literacy status has implications for how people seek nutrition information and how much they trust it. Understanding the causes and consequences of limited nutrition literacy may be a step toward reducing the burden of nutrition-related chronic diseases among disadvantaged rural communities.


A non-invasive technique for continuous monitoring of left ventricular function using a new solid state mercuric iodide radiation detector.
A miniature solid-state mercuric iodide (HgI2) nuclear probe detector has been developed in conjunction with a computerized nuclear probe (Nuclear Stethoscope) to enable continuous non-invasive monitoring of left ventricular function using 99Tc-labelled equilibrium blood pool techniques. Left ventricular ejection fraction was measured in 54 patients undergoing radionuclide angiography with a gamma-camera and with the Nuclear Stethoscope and a good correlation was obtained between both techniques (r = 0.94, n = 54, P less than 0.001). The prototype mercuric iodide detector was compared with the sodium iodide detector of the Nuclear Stethoscope and a study in 41 consecutive patients demonstrated a good correlation for the measurement of ejection fraction, ejection rate, peak filling rate and time to peak filling rate (r = 0.94, 0.89, 0.90 and 0.78 respectively). It may be possible to adapt the mercuric iodide detector for continuous non-invasive monitoring of left ventricular performance in critically ill patients and during physiological or pharmacological interventions.


Highlights from occupational safety and health continuing education needs assessment.
There is a lack of trained Occupational Safety and Health (OSH) professionals able to meet the current and future demand for such expertize in the United States. Many OSH professionals are required to perform duties, which are outside of their primary area of expertize; thus, expansion of continuing education (CE) may be necessary to properly train individuals for new OSH responsibilities. The National Institute for Occupational Safety and Health-funded Education and Research Centers collectively developed and distributed an internet-based survey to gauge the CE needs and interests of the OSH workforce. A total of 2064 responses were received. The most common primary professions represented were safety (28%), occupational health nursing (18%), and industrial hygiene (12%). The majority of respondents (61%) reported that they perform work activities outside of those associated with their primary OSH profession. The CE offerings with the highest interest among respondents were related to safety. Other courses with high levels of interest included topics such as legal issues in OSH (88%), compliance (88%), risk management (85%), OSH management (83%), risk communication (83%), and communication in accident prevention (81%). Health and safety leadership (82%), health and safety culture (78%) and total worker health (74%) were also significant interests. It is important to be responsive to the evolving needs of the OS&H community. Developing relevant courses will help ensure that OS&H professionals have access to the training they need to perform essential job functions and keep employees healthy and safe.


Use of circular cylinders as surrogates for hexagonal pristine ice crystals in scattering calculations at infrared wavelengths.
We investigate the errors associated with the use of circular cylinders as surrogates for hexagonal columns in computing the optical properties of pristine ice crystals at infrared (8-12-microm) wavelengths. The equivalent circular cylinders are specified in terms of volume (V), projected area (A), and volume-to-area ratio that are equal to those of the hexagonal columns. We use the T-matrix method to compute the optical properties of the equivalent circular cylinders. We apply the finite-difference time-domain method to compute the optical properties of hexagonal ice columns smaller than 40 microm. For hexagonal columns larger than 40 microm we employ an improved geometric optics method and a stretched scattering potential technique developed in previous studies to calculate the phase function and the extinction (or absorption) efficiency, respectively. The differences between the results for circular cylinders and hexagonal columns are of the order of a few percent. Thus it is quite reasonable to use a circular cylinder geometry as a surrogate for pristine hexagonal ice columns for scattering calculations at infrared (8-12-microm) wavelengths. Although the pristine ice crystals can be approximated as circular cylinders in scattering calculations at infrared wavelengths, it is shown that optical properties of individual aggregates cannot be well approximated by those of individual finite columns or cylinders.


Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study.
Whether the intake of dietary fiber can protect against colorectal cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been inconsistent. The objective was to investigate the relation between dietary fiber and whole-grain food intakes and invasive colorectal cancer in the prospective National Institutes of Health-AARP Diet and Health Study. The analytic cohort consisted of 291 988 men and 197 623 women aged 50-71 y. Diet was assessed with a self-administered food-frequency questionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up. The Cox proportional hazards model was used to estimate the relative risks (RRs) and 95% CIs. Total dietary fiber intake was not associated with colorectal cancer. The multivariate RR for the highest compared with the lowest intake quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In analyses of fiber from different food sources, only fiber from grains was associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86; 95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79 (95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association with whole grain was stronger for rectal than for colon cancer. In this large prospective cohort study, total dietary fiber intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.


Determination of antioxidative properties of herbal extracts: Agrimonia herba, Cynare folium, and Ligustri folium.
Hyaluronan (HA) molecules were exposed to free radical-mediated degradation performed by the reaction mixture Cu(II) and ascorbate, the so-called Weissberger biogenic oxidative system, which mimics the situation of acute inflammation. To achieve protection of HA from degradation, herbal extracts such as Agrimonia herba, Cynare folium, and Ligustri folium were selected. Time- and dose-dependent changes of dynamic viscosity of the HA solutions in the presence and absence of the herbal extracts were recorded by rotational viscometry (RV). Radical scavenging capacity of the extracts was investigated by the spectrocolorimetric ABTS and DPPH assays. The results of RV revealed that the extracts of Agrimonia herba and Cynare folium were effective in inhibiting the degradation of HA. On the other hand, the extract of Ligustri folium increased the rate of HA degradation. The highest radical scavenging capacity of ABTS(*+) and DPPH(*) was observed in Agrimonia herba extract followed by the extracts of Ligustri folium and Cynare folium.


Infectious delivery and expression of a 135 kb human FRDA genomic DNA locus complements Friedreich's ataxia deficiency in human cells.
Friedreich's ataxia (FA) is the most common recessive ataxia, affecting 1-2 in 50,000 Caucasians, and there is currently no effective cure or treatment. FA results from a deficiency of the mitochondrial protein frataxin brought about by a repeat expansion in intron 1 of the FRDA gene. The main areas affected are the central nervous system (particularly the spinocerebellar system) and cardiac tissue. Therapies aimed at alleviating the neurological degeneration have proved unsuccessful to date. Here, we describe the construction and delivery of high capacity herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the entire 80 kb FRDA genomic locus, driven by the endogenous FRDA promoter and including all introns and flanking regulatory sequences within a 135 kb genomic DNA insert. FA patient primary fibroblasts deficient in frataxin protein and exhibiting sensitivity to oxidative stress were transduced at high efficiency by FRDA genomic locus vectors. Following vector transduction, expression of FRDA protein by immunofluorescence was shown. Finally, functional complementation studies demonstrated restoration of the wild-type cellular phenotype in response to oxidative stress in transduced FA patient cells. These results suggest the potential of the infectious bacterial artificial chromosome-FRDA vectors for gene therapy of FA.


Markov model assessment of subjects' clinical skill using the E-Pelvis physical simulator.
Inherent difficulties evaluating clinical competence of physicians has led to the widespread use of subjective skill assessment techniques. Inspired by an analogy between spoken language and surgical procedure, a generalized methodology using Markov models (MMs), independent of the modality under study, was developed. The methodology applied to an endoscopic experiment in "Generalized approach for modeling minimally invasive surgery as a stochastic process using a discrete Markov model" by J. Rosen et al. (IEEE Trans. Biomed. Eng., Vol. 53, No. 3, pp. 399-413, Mar. 2006) is modified and applied to data collected with the E-Pelvis physical simulator. The simulator incorporates five contact pressure sensors located in key anatomical landmarks. Two 32-state fully connected MMs are used, one for each skill level. Each state corresponds to a unique five-dimensional signature of contact pressures. Statistical distances measured between models representing subjects with different skill levels are sensitive enough to provide an objective measure of medical skill level. The method was tested with 41 expert subjects and 41 novice subjects in addition to the 30 subjects used for training the MM. Of the 82 subjects, 76 (92%) were classified correctly. Unique state transitions as well as pressure magnitudes for corresponding states were found to be skill dependent. The "white box" nature of the model provides insight into the examination process performed.


Differential signaling via the same axon of neocortical pyramidal neurons.
The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto the same morphological class differed in the numbers and dendritic locations of synaptic contacts, their absolute synaptic strengths, as well as their rates of synaptic depression and recovery from depression. The same axon of a pyramidal neuron innervating another pyramidal neuron and an interneuron mediated frequency-dependent depression and facilitation, respectively, during high frequency discharges of presynaptic action potentials, suggesting that the different natures of the target neurons underlie qualitative differences in synaptic properties. Facilitating-type synaptic connections established by three pyramidal neurons of the same class onto a single interneuron, were all qualitatively similar with a combination of facilitation and depression mechanisms. The time courses of facilitation and depression, however, differed for these convergent connections, suggesting that different pre-postsynaptic interactions underlie quantitative differences in synaptic properties. Mathematical analysis of the transfer functions of frequency-dependent synapses revealed supra-linear, linear, and sub-linear signaling regimes in which mixtures of presynaptic rates, integrals of rates, and derivatives of rates are transferred to targets depending on the precise values of the synaptic parameters and the history of presynaptic action potential activity. Heterogeneity of synaptic transfer functions therefore allows multiple synaptic representations of the same presynaptic action potential train and suggests that these synaptic representations are regulated in a complex manner. It is therefore proposed that differential signaling is a key mechanism in neocortical information processing, which can be regulated by selective synaptic modifications.


Evaluation of mindfulness-based cognitive therapy for life and a cognitive behavioural therapy stress-management workshop to improve healthcare staff stress: study protocol for two randomised controlled trials.
Healthcare workers experience higher levels of work-related stress and higher rates of sickness absence than workers in other sectors. Psychological approaches have potential in providing healthcare workers with the knowledge and skills to recognise stress and to manage stress effectively. The strongest evidence for effectiveness in reducing stress in the workplace is for stress-management courses based on cognitive behavioural therapy (CBT) principles and mindfulness-based interventions (MBIs). However, research examining effects of these interventions on sickness absence (an objective indicator of stress) and compassion for others (an indicator of patient care) is limited, as is research on brief CBT stress-management courses (which may be more widely accessible) and on MBIs adapted for workplace settings. This protocol is for two randomised controlled trials with participant preference between the two trials and 1:1 allocation to intervention or wait-list within the preferred choice. The first trial is examining a one-day CBT stress-management workshop and the second trial an 8-session Mindfulness-Based Cognitive Therapy for Life (MBCT-L) course, with both trials comparing intervention to wait-list. The primary outcome for both trials is stress post-intervention with secondary outcomes being sickness absence, compassion for others, depression symptoms, anxiety symptoms, wellbeing, work-related burnout, self-compassion, presenteeism, and mindfulness (MBCT-L only). Both trials aim to recruit 234 staff working in the National Health Service in the UK. This trial will examine whether a one-day CBT stress-management workshop and an 8-session MBCT-L course are effective at reducing healthcare staff stress and other mental health outcomes compared to wait-list, and, whether these interventions are effective at reducing sickness absence and presenteeism and at enhancing wellbeing, self-compassion, mindfulness and compassion for others. Findings will help inform approaches offered to reduce healthcare staff stress and other key variables. A note of caution is that individual-level approaches should only be part of the solution to reducing healthcare staff stress within a broader focus on organisational-level interventions and support. ISRCTN Registry, ISRCTN11723441 . Registered on 16 June 2017. Protocol Version 1: 24 April 2017. Trial Sponsor: Sussex Partnership NHS Foundation Trust (email@example.com).


Patellar instability factors in isolated medial patellofemoral ligament reconstructions--what does the literature tell us? A systematic review.
Many studies have demonstrated good results after medial patellofemoral ligament (MPFL) reconstruction for patients with patellar instability. The applicability of published studies to the clinical decision-making process for the individual patient with patellar instability, however, is not well elucidated. There is inconsistency in the reporting of preoperative and postoperative variables, which limits the applicability of current studies to patients with patellar instability. Systematic review. A systematic review of the literature was conducted using the search term medial patellofemoral ligament reconstruction to identify studies with cohorts of patients with isolated MPFL reconstruction. A combination of inclusion and exclusion criteria resulted in 24 studies being reviewed for a variety of preoperative demographics, physical examination findings, and imaging findings, as well as postoperative outcomes, including redislocation and responses to subjective questionnaires. A physical examination of lateral patellar translation was reported in 42% of studies, by reporting an apprehension sign (n = 9), reporting quadrant translation (n = 7), or both. For patellar instability factors on imaging, patellar height was reported as a preoperative variable in 75% of studies, and trochlear dysplasia was reported in 83% of studies. The tibial tubercle-trochlear groove distance was reported as a preoperative variable in 42% of studies. The rate of redislocation after index surgery was reported in 92% of studies. Patient-related outcome measures were reported in all of the studies; the Kujala score was the most common. A homogeneous population was selected as part of the authors' surgical indications for "isolated" MPFL in 67% of studies, and a heterogeneous population was selected in 33% of studies. Current literature on MPFL reconstruction contains diverse methods of recording preoperative and postoperative variables. Most studies report on a homogeneous population, with inconsistent applicability to the broad spectrum of patients with patellar instability. Outcomes reporting in our current literature needs more clarity and consistency regarding reporting methodology to be of value for the treating clinician.


Optimal Bayesian point estimates and credible intervals for ranking with application to county health indices.
It is fairly common to rank different geographic units, e.g. counties in the USA, based on health indices. In a typical application, point estimates of the health indices are obtained for each county, and the indices are then simply ranked as if they were known constants. Several authors have considered optimal rank estimators under squared error loss on the rank scale as a default method for general purpose ranking, e.g. situations where ranking units across the full spectrum of performance (low, medium, high) is important. While computationally convenient, squared error loss on the rank scale may not represent the true inferential goals of rank consumers. We construct alternative loss functions based on three components: (1) the inferential goal (rank position or pairwise comparisons), (2) the scale (original, log-transformed or rank) and (3) the (positional or pairwise) loss function (0/1, squared error or absolute error). We can obtain optimal ranks for loss functions based on rank positions and nearly optimal ranks for loss functions based on pairwise comparisons paired with highest posterior density (HPD) credible intervals. We compare inferences produced by the various ranking methods, both optimal and heuristic, using low birth weight data for counties in the Midwestern United States, from 2006 to 2012.


The association between hospital department, medical treatment and outcome in acute myocardial infarction.
Although the preferred management of a patient presenting with an acute myocardial infarction is in a coronary care unit, data based on discharge diagnoses in Israel indicate that many of these patients are treated outside of such units. To compare the demographic and clinical characteristics, treatment and mortality of AMI patients treated inside and outside a CCU. We compiled a registry of all patients admitted to three general hospitals in Haifa, Israel during January, March, May, July, September and November 1996. The non-CCU admission rate was 22%. CCU patients were younger (61.6 vs. 65.5 years), less likely to report a past AMI (18% vs. 34%), and arrived earlier at the emergency room. Non-CCU patients were more likely to present with severe heart failure (30 vs. 11%). Non-CCU patients received less aspirin (81 vs. 95%) and betablockers (62 vs. 80%). Upon discharge, these patients were less frequently prescribed beta-blockers and cardiac rehabilitation programs. CCU-treated patients had lower unadjusted mortality rates at both 30 days (odds ratio = 0.35) and in the long term (hazards ratio = 0.57). These ratios were attenuated after controlling for gender, age, type of AMI, and degree of heart failure (OR = 0.91 and HR = 0.78, respectively). A relatively high proportion of AMI patients were treated outside a CCU, with older and sicker patients being denied admission to a CCU. The process of evidence-based care by cardiologists was preferable to that of internists both during the hospital stay and at discharge. In Israel a significant proportion of all AMI admissions are initially treated outside a CCU. Emphasis on increasing awareness in internal medicine departments to evidence-based care of AMI is indicated.


Developing a standardised approach to the aggregation of inpatient episodes into person-based spells in all specialties and psychiatric specialties.
Electronic health record (EHR) data are available for research in all UK nations and cross-nation comparative studies are becoming more common. All UK inpatient EHRs are based around episodes, but episode-based analysis may not sufficiently capture the patient journey. There is no UK-wide method for aggregating episodes into standardised person-based spells. This study identifies two data quality issues affecting the creation of person-based spells, and tests four methods to create these spells, for implementation across all UK nations. Welsh inpatient EHRs from 2013 to 2017 were analysed. Phase one described two data quality issues; transfers of care and episode sequencing. Phase two compared four methods for creating person spells. Measures were mean length of stay (LOS, expressed in days) and number of episodes per person spell for each method. 3.5% of total admissions were transfers-in and 3.1% of total discharges were transfers-out. 68.7% of total transfers-in and 48.7% of psychiatric transfers-in had an identifiable preceding transfer-out, and 78.2% of total transfers-out and 59.0% of psychiatric transfers-out had an identifiable subsequent transfer-in. 0.2% of total episodes and 4.0% of psychiatric episodes overlapped with at least one other episode of any specialty. Method one (no evidence of transfer required; overlapping episodes grouped together) resulted in the longest mean LOS (4.0 days for all specialties; 48.5 days for psychiatric specialties) and the fewest single episode person spells (82.4% of all specialties; 69.7% for psychiatric specialties). Method three (evidence of transfer required; overlapping episodes separated) resulted in the shortest mean LOS (3.7 days for all specialties; 45.8 days for psychiatric specialties) and the most single episode person spells; (86.9% for all specialties; 86.3% for psychiatric specialties). Transfers-in appear better recorded than transfers-out. Transfer coding is incomplete, particularly for psychiatric specialties. The proportion of episodes that overlap is small but psychiatric episodes are disproportionately affected. The most successful method for grouping episodes into person spells aggregated overlapping episodes and required no evidence of transfer from admission source/method or discharge destination codes. The least successful method treated overlapping episodes as distinct and required transfer coding. The impact of all four methods was greater for psychiatric specialties.


Malignant fibrous histiocytoma of the abdominal cavity: report of a case.
Malignant fibrous histiocytoma (MFH) is a soft-tissue sarcoma originating from fibroblast cells, characterized by a high rate of metastasis or recurrence. This tumor rarely develops in the gastrointestinal tract, with no more than 30 cases described in the literature. We report a case of MFH of the abdominal cavity in a 45-year-old woman who presented with epigastric pain, anorexia, and weight loss. A computed tomography (CT) scan of the abdomen revealed multiple solid tumors in the peritoneal cavity. We performed exploratory laparotomy and found at least 15 solid whitish tumors attached to the wall of the small intestine, as well as to the parietal peritoneum. There were three metastases in the liver. All of the tumors were excised, most of which were about 10 cm in diameter. Histopathological findings indicated a stromal tumor consisting of spindle cells, and immunohistochemical examination of the resected specimens established the definite diagnosis of a pleomorphic MFH. The patient had an uneventful postoperative course and was given adjuvant chemotherapy. She is currently well 2 years after her operation. We review the clinical picture of this tumor in the abdominal cavity, and discuss its diagnosis, pathogenesis, and treatment.


Hybridization and polyploidy enable genomic plasticity without sex in the most devastating plant-parasitic nematodes.
Root-knot nematodes (genus Meloidogyne) exhibit a diversity of reproductive modes ranging from obligatory sexual to fully asexual reproduction. Intriguingly, the most widespread and devastating species to global agriculture are those that reproduce asexually, without meiosis. To disentangle this surprising parasitic success despite the absence of sex and genetic exchanges, we have sequenced and assembled the genomes of three obligatory ameiotic and asexual Meloidogyne. We have compared them to those of relatives able to perform meiosis and sexual reproduction. We show that the genomes of ameiotic asexual Meloidogyne are large, polyploid and made of duplicated regions with a high within-species average nucleotide divergence of ~8%. Phylogenomic analysis of the genes present in these duplicated regions suggests that they originated from multiple hybridization events and are thus homoeologs. We found that up to 22% of homoeologous gene pairs were under positive selection and these genes covered a wide spectrum of predicted functional categories. To biologically assess functional divergence, we compared expression patterns of homoeologous gene pairs across developmental life stages using an RNAseq approach in the most economically important asexually-reproducing nematode. We showed that >60% of homoeologous gene pairs display diverged expression patterns. These results suggest a substantial functional impact of the genome structure. Contrasting with high within-species nuclear genome divergence, mitochondrial genome divergence between the three ameiotic asexuals was very low, signifying that these putative hybrids share a recent common maternal ancestor. Transposable elements (TE) cover a ~1.7 times higher proportion of the genomes of the ameiotic asexual Meloidogyne compared to the sexual relative and might also participate in their plasticity. The intriguing parasitic success of asexually-reproducing Meloidogyne species could be partly explained by their TE-rich composite genomes, resulting from allopolyploidization events, and promoting plasticity and functional divergence between gene copies in the absence of sex and meiosis.


Multifunctional structural design of graphene thermoelectrics by Bayesian optimization.
Materials development often confronts a dilemma as it needs to satisfy multifunctional, often conflicting, demands. For example, thermoelectric conversion requires high electrical conductivity, a high Seebeck coefficient, and low thermal conductivity, despite the fact that these three properties are normally closely correlated. Nanostructuring techniques have been shown to break the correlations to some extent; however, optimal design has been a major challenge due to the extraordinarily large degrees of freedom in the structures. By taking graphene nanoribbons (GNRs) as a representative thermoelectric material, we carried out structural optimization by alternating multifunctional (phonon and electron) transport calculations and Bayesian optimization to resolve the trade-off. As a result, we have achieved multifunctional structural optimization with an efficiency more than five times that achieved by random search. The obtained GNRs with optimized antidots significantly enhance the thermoelectric figure of merit by up to 11 times that of the pristine GNR. Knowledge of the optimal structure further provides new physical insights that independent tuning of electron and phonon transport properties can be realized by making use of zigzag edge states and aperiodic nanostructuring. The demonstrated optimization framework is also useful for other multifunctional problems in various applications.


Proinflammatory Vδ2+ T cells populate the human intestinal mucosa and enhance IFN-γ production by colonic αβ T cells.
In nonhuman primates, Vγ9Vδ2(+) (Vδ2)T cells proliferate and accumulate in mucosal tissues following microbial activation. Human Vδ2T cells produce proinflammatory cytokines in response to bacterial species that colonize the gut, but the role played by Vδ2T cells in intestinal immunity is unknown. We hypothesized that circulating Vδ2T cells can populate the human intestine and contribute to mucosal inflammation. Cell suspensions prepared from peripheral blood and intestinal biopsies were stimulated with microbial phosphoantigen (1-hydroxy-2-methyl-2-buten-4-yl 4-diphosphate [HDMAPP]) and analyzed by flow cytometry to determine Vδ2T cell phenotype, cytokine production, and proliferative potential. Circulating Vδ2T cells expressed gut-homing integrin α4β7 (>70%), which was coexpressed with skin-associated cutaneous leukocyte Ag by up to 15% of the total population. However, Vδ2T cell activation with HDMAPP and exposure to retinoic acid (signaling via retinoic acid receptor α) increased α4β7 expression and enhanced binding to mucosal addressin cell adhesion molecule-1 in vitro while simultaneously suppressing cutaneous leukocyte Ag, thereby generating a committed gut-tropic phenotype. Confocal microscopy and flow cytometry identified frequent Vδ2T cells that migrated out of human intestinal biopsies and comprised both CD103(+) and CD103(-) subsets that produced TNF-α and IFN-γ upon phosphoantigen exposure, with more frequent cytokine-producing cells in the CD103(-) population. Activated intestinal Vδ2T cells expressed CD70 and HLA-DR but were unable to drive the proliferation of allogeneic naive CD4(+) T cells. Instead, phosphoantigen-activated CD103(-) Vδ2T cells increased T-bet expression and enhanced IFN-γ production by autologous colonic αβ T cells via an IFN-γ-dependent mechanism. These data demonstrate that circulating Vδ2T cells display enhanced gut-homing potential upon microbial activation and populate the human intestinal mucosa, generating functionally distinct CD103(+) and CD103(-) subsets that can promote inflammation by colonic αβ T cells.


Risk factors for vitamin D deficiency in patients with Crohn's disease.
Although the pathogenesis of osteopenia in Crohn's disease is not established, vitamin D deficiency is thought to be an important risk factor. However, little is known about the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan. This study aimed to clarify the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan and to examine the possible causes of the deficiency. We investigated serum 25-hydroxyvitamin D (25-OHD) levels, various laboratory parameters, and patient histories in 33 outpatients (25 men, 8 women; median age, 37 years; range, 26-57 years) and 15 age- and sex-matched healthy controls (8 men, 7 women; median age, 37 years; range, 24-57 years) and assessed risk factors for vitamin D deficiency. Although patients with Crohn's disease did not have significantly lower serum concentrations of 25-OHD than controls, 9 of 33 patients (27.3%) were considered vitamin D deficient (serum 25-OHD level </=10 ng/ml) compared with only 1 of 15 (6.7%) controls. Serum 25-OHD levels were significantly related to disease duration ( r = 0.46, P = 0.003), Crohn's Disease Activity Index (CDAI) score ( r = 0.44, P = 0.005), International Organization for the Study of Inflammatory Bowel Disease score ( r = 0.30, P < 0.05), and serum values of ferritin ( r = 0.34, P = 0.03), C-reactive protein ( r = 0.34, P = 0.03), total cholesterol ( r = 0.31, P = 0.04), and intact parathyroid hormone ( r = 0.23, P < 0.05). A logistic regression analysis was performed to investigate the ability of variables to predict low or normal 25-OHD values. Results showed that disease duration ( P = 0.03) and CDAI score ( P = 0.04) could predict the occurrence of vitamin D deficiency ( r(2) = 0.472, P = 0.0004). Vitamin D deficiency exists in patients with Crohn's disease in Japan. 25-OHD levels should be assessed in patients who have had Crohn's disease for a long time (>15 years) and who have been in the active stage of the disease for long periods.


Influence of hair treatments on detection of antiretrovirals by mass spectrometry imaging.
Analysis of drugs in hair by mass spectrometry imaging (MSI) has great potential as an objective, long-term measure of medication adherence. However, the fidelity of the chemical record in hair may be compromised by any cosmetic hair treatments. Here, we investigate infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI response to multiple antiretrovirals (ARVs) in cosmetically treated hair. Hair strands from patients on different ARV regimens were mechanically treated with dye, bleach, and relaxer. The treatments had little or no effect relative to untreated controls for cobicistat, abacavir, dolutegravir, maraviroc, efavirenz, and darunavir, but all three treatments removed emtricitabine (FTC) to undetectable levels from patient hair strands. We also evaluated hair strands by IR-MALDESI MSI from 8 patients on FTC-based regimens who reported a range of hair treatments at varying recency prior to hair collection. While FTC was undetectable in the treated portion of these hair strands, ARVs coadministered with FTC remained detectable in hair strands after treatment. We conclude that IR-MALDESI MSI can be used when measuring adherence to ARV therapy, provided that ARVs other than FTC are targeted in people using hair treatments.


Successful management of an intracranial phaeohyphomycotic fungal granuloma in a dog.
A 12-month-old castrated male Boxer was examined because of signs of acute, progressive intracranial disease. Cytologic and histologic findings were consistent with an intracranial fungal granuloma in the right cerebral hemisphere. Fungal culture yielded a Cladophialophora sp. The granuloma was surgically debulked to remove infected brain tissue and the avascular purulent core. Postoperatively, the patient was treated with fluconazole (2.3 mg/kg [1 mg/lb], PO, q 12 h) for 4 months, followed by voriconazole (3.4 mg/kg [1.5 mg/lb], PO, q 12 h) for a further 10 months. The outcome was considered excellent on the basis of resolution of neurologic signs and a lack of evidence of recurrence of the granuloma during magnetic resonance imaging and CSF analysis 8 months after surgery. Magnetic resonance imaging and CSF analysis 9 weeks after administration of antifungal medications was discontinued (16 months after surgery) confirmed resolution. Intracranial phaeohyphomycosis in small animals is rare and is most commonly associated with Cladophialophora infection. Phaeohyphomycosis frequently causes a focal granuloma, whereas other fungal infections typically cause diffuse meningoencephalitis. In all previous reports of phaeohyphomycosis of the CNS in dogs, treatment has been limited to medical management with conventional antifungal drugs and had failed to prevent death. The present report suggested that combined management of granulomas with surgery and newer triazole medications such as voriconazole may represent a novel strategy that improves the prognosis for this disease.


Global quantitative proteomics reveals novel factors in the ecdysone signaling pathway in Drosophila melanogaster.
The ecdysone signaling pathway plays a major role in various developmental transitions in insects. Recent advances in the understanding of ecdysone action have relied to a large extent on the application of molecular genetic tools in Drosophila. Here, we used a comprehensive quantitative SILAC MS-based approach to study the global, dynamic proteome of a Drosophila cell line to investigate how hormonal signals are transduced into specific cellular responses. Global proteome data after ecdysone treatment after various time points were then integrated with transcriptome data. We observed a substantial overlap in terms of affected targets between the dynamic proteome and transcriptome, although there were some clear differences in timing effects. Also, downregulation of several specific mRNAs did not always correlate with downregulation of their corresponding protein counterparts, and in some cases there was no correlation between transcriptome and proteome dynamics whatsoever. In addition, we performed a comprehensive interactome analysis of EcR, the major target of ecdysone. Proteins copurified with EcR include factors involved in transcription, chromatin remodeling, ecdysone signaling, ecdysone biosynthesis, and other signaling pathways. Novel ecdysone-responsive proteins identified in this study might link previously unknown proteins to the ecdysone signaling pathway and might be novel targets for developmental studies. To our knowledge, this is the first time that ecdysone signaling is studied by global quantitative proteomics. All MS data have been deposited in the ProteomeXchange with identifier PXD001455 (http://proteomecentral.proteomexchange.org/dataset/PXD001455).


Two-stage combined endovascular and surgical approach for recurrent thoracoabdominal aortic aneurysm.
To present a 2-stage combined endovascular and surgical approach for recurrent thoracoabdominal aortic aneurysm (TAAA). A 78-year-old man with previous surgical repairs of infrarenal abdominal and descending thoracic aortic aneurysms was referred for dysphagia due to an enlarging 9-cm aneurysm extending from the mid thoracic to the suprarenal aorta. Because no suitable endograft was available, an open repair was attempted, but the presence of a "frozen" chest made the redo procedure extremely difficult. A 2-stage treatment was thus decided upon. First, a retrograde bifurcated bypass graft was implanted from the abdominal aortic graft to the superior mesenteric and celiac arteries. Twenty days later, the TAAA was successfully excluded with a stent-graft, during which spinal fluid drainage was performed to prevent paraplegia. At 6 months, computed tomography showed patency of the endoprosthesis and visceral grafts. At 1 year, the patient remains asymptomatic. This case illustrates that a 2-stage combined endovascular and surgical approach may be a safe and effective alternative to reoperation for recurrent TAAA.


Efficacy of Electrocuting Devices to Catch Tsetse Flies (Glossinidae) and Other Diptera.
The behaviour of insect vectors has an important bearing on the epidemiology of the diseases they transmit, and on the opportunities for vector control. Two sorts of electrocuting device have been particularly useful for studying the behaviour of tsetse flies (Glossina spp), the vectors of the trypanosomes that cause sleeping sickness in humans and nagana in livestock. Such devices consist of grids on netting (E-net) to catch tsetse in flight, or on cloth (E-cloth) to catch alighting flies. Catches are most meaningful when the devices catch as many as possible of the flies potentially available to them, and when the proportion caught is known. There have been conflicting indications for the catching efficiency, depending on whether the assessments were made by the naked eye or assisted by video recordings. Using grids of 0.5m2 in Zimbabwe, we developed catch methods of studying the efficiency of E-nets and E-cloth for tsetse, using improved transformers to supply the grids with electrical pulses of ~40kV. At energies per pulse of 35-215mJ, the efficiency was enhanced by reducing the pulse interval from 3200 to 1ms. Efficiency was low at 35mJ per pulse, but there seemed no benefit of increasing the energy beyond 70mJ. Catches at E-nets declined when the fine netting normally used became either coarser or much finer, and increased when the grid frame was moved from 2.5cm to 27.5cm from the grid. Data for muscoids and tabanids were roughly comparable to those for tsetse. The catch method of studying efficiency is useful for supplementing and extending video methods. Specifications are suggested for E-nets and E-cloth that are ~95% efficient and suitable for estimating the absolute numbers of available flies. Grids that are less efficient, but more economical, are recommended for studies of relative numbers available to various baits.


Differences in Activity of the Brain Networks During Voluntary Motor Tasks Engaging the Local and Global Muscular Systems of the Lower Trunk.
Low back pain constitutes a multidimensional problem of largely unknown origin. One of the recent theories explaining its frequent occurrence includes speculative statements on patterns of central nervous system activity associated with the control of so-called local and global muscles of the lower trunk. The objective of the study was to verify whether there is a difference in the activity of the brain during selective, voluntary contraction of the local and global abdominal muscles as assessed by functional MRI. Twenty healthy subjects participated. An experimental design was applied with repeated measurements of the blood-oxygen-level-dependent signal from the brain during voluntary contraction of the local and global abdominal muscles, performed in random order. Prior to registration, a 2-week training period was introduced, aiming to master the experimental motor tasks. The magnetic resonance imaging (MRI) data were processed using the FMRIB Software Library (Oxford, UK). Brain areas showing significant activations/deactivations were identified and averaged across all participants, and intercondition differential maps were computed. Areas of significant intercondition differences were linked to the corresponding anatomical structures and ascribed to the default mode functional brain network and to the sensorimotor network. Contraction of the local abdominal muscles elicited more pronounced activity of the brain cortex, basal ganglia, and cerebellum. This suggests that motor control of the abdominal musculature consists of two modes of brain activity and that control of the local muscles may be a more challenging task for the brain. Moreover, contraction of the local muscles elicited more distinct deactivation of the default mode network, which may have implications for diagnostics and therapy of low back pain.


Production of thermostable direct hemolysin by Vibrio parahaemolyticus enhanced by conjugated bile acids.
The effects of conjugated bile acids, glycocholic acid, and taurocholic acid (TC) on production of thermostable direct hemolysin (TDH) by Vibrio parahaemolyticus were determined by a reversed passive latex agglutination assay against TDH. The amount of TDH excreted in growth medium containing either glycocholic acid or taurocholic acid (5 mM/liter) was, on a per-cell basis, 4- to 16-fold greater than that excreted in medium without the bile acids. The amounts of TDH released from lysed cells grown with the bile acids (5 mM/liter) were 4- to 32-fold greater than those from lysed cells grown without, suggesting that the bile acids enhanced synthesis of TDH within bacterial cells. These data imply that the conjugated bile acids play a key role in the pathogenicity of V. parahaemolyticus.


Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey.
Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.