Direct marketing of parenting programs: comparing a promotion-focused and a prevention-focused strategy.
: For parenting programs to achieve a public health impact, it is necessary to develop more effective marketing strategies to increase public awareness of these programs and promote parental participation. In this article, we compared a promotion-focused and a prevention-focused strategy via two studies. : We designed two ads inviting parents to participate in a universal parenting program; one ad focused on the program increasing the likelihood of positive outcomes for children (promotion-focused) and the other on the program reducing the likelihood of negative outcomes (prevention-focused). In study I, the two ads were run online simultaneously. Those who clicked on an ad were directed to a website where they could read about and sign up for the program. In study II, a community sample of 706 parents answered a questionnaire about the ads. : In study I, over 85 days, the prevention ad generated more clicks. There was no difference in the number of pages visited on the website nor in the number of parents who signed up for the program. In study II, parents showed a preference for the promotion ad, perceiving it as more relevant and rating it as more effective in getting them interested in the program. : A prevention strategy may be more effective in drawing public attention, in general. However, a promotion strategy is more likely to reach parents, in particular, and inspire them to consider participating in parenting programs. These strategies should be developed further and tested in both general and clinical populations.


Long-term hypoxia modulates expression of key genes regulating adipose function in the late-gestation ovine fetus.
A major function of abdominal adipose in the newborn is nonshivering thermogenesis. Uncoupling protein (UCP) UCP1 and UCP2 play major roles in thermogenesis. The present study tested the hypothesis that long-term hypoxia (LTH) modulates expression of UCP1 and UCP2, and key genes regulating expression of these genes in the late-gestation ovine fetus. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dG); perirenal adipose tissue was collected from LTH and age-matched, normoxic control fetuses at 139-141 dG. Quantitative real-time PCR was used to analyze mRNA for UCP1, UCP2, 11beta hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2), glucocorticoid receptor (GR), beta3 adrenergic receptor (beta3AR), deiodinase type 1 (DIO1) and DIO2, peroxisome proliferator activated receptor (PPAR) alpha and gamma and PPARgamma coactivator 1 (PGC1alpha). Concentrations of mRNA for UCP1, HSD11B1, PPARgamma, PGC1, DIO1, and DIO2 were significantly higher in perirenal adipose of LTH compared with control fetuses, while mRNA for HSD11B2, GR, or PPARalpha in perirenal adipose did not differ between control and LTH fetuses. The increased expression of UCP1 is likely an adaptive response to LTH, assuring adequate thermogenesis in the event of birth under oxygen-limiting conditions. Because both glucocorticoids and thyroid hormone regulate UCP1 expression, the increase in HSD11B1, DIO1, and DIO2 implicate increased adipose capacity for local synthesis of these hormones. PPARgamma and its coactivator may provide an underlying mechanism via which LTH alters development of the fetal adipocyte. These findings have important implications regarding fetal/neonatal adipose tissue function in response to LTH.


[Effects of hypothermia on ATPase activity in the cerebral tissue of rats].
The hypothermia 20 degrees C of various periods of action stimulates greatly the activity of Na,K-ATF-ase and causes some insignificant changes in the process of Mg-ATF-ase in homogenates, synaptosomal and mitochondrial fractions, extracted from cortex of big hemispheres. The gained data testifies to some differences of the properties of membrane while cooling.


Ethics, public policy and behavioral genetics.
Behavioral genetics is the identification of behavioral traits that are genetically determined, the identification of the genes that are involved, and the discovery of modes of intervention to alter the expected course of the disease. Unlike the classical Mendelian traits, many specific aspects of behavior are, in part, determined by several genes. The corresponding abnormalities of behavior or deficiencies are therefore polygenic. New genetic techniques are leading to the discovery of these genes, and the techniques and knowledge developed in the Human Genome Project make it possible to screen the genome of any individual for the presence of known polymorphisms. This raises great hopes for diagnosis and the individualization of therapy. However, the genetic prediction of unacceptable behavior can further lead to social and occupational discrimination and enforced therapy. This raises serious concerns about how this information will be collected and who will have access to it.


Similar effects of the selective noradrenaline reuptake inhibitor atomoxetine on three distinct forms of impulsivity in the rat.
Atomoxetine is a noradrenaline-specific reuptake inhibitor used clinically for the treatment of childhood and adult attention deficit hyperactivity disorder (ADHD). Studies in human volunteers and patient groups have shown that atomoxetine improves stop-signal reaction time (SSRT) performance, an effect consistent with a reduction in motor impulsivity. However, ADHD is a heterogeneous disorder and it is of interest to determine whether atomoxetine is similarly effective against other forms of impulsivity, as well as the attentional impairment present in certain subtypes of ADHD. The present study examined the effects of atomoxetine on impulsivity using an analogous SSRT task in rats and two additional tests of impulsivity; delay discounting of reward and the five-choice serial reaction time task (5CSRTT), the latter providing an added assessment of sustained visual attention. Atomoxetine produced a significant dose-dependent speeding of SSRT. In addition, atomoxetine produced a selective, dose-dependent decrease in premature responding on the 5CSRTT. Finally, on the delay-discounting task, atomoxetine significantly decreased impulsivity by increasing preference for the large-value reward across increasing delay. These findings conclusively demonstrate that atomoxetine decreases several distinct forms of impulsivity in rats. The apparent contrast of these effects with stimulant drugs such as amphetamine and methylphenidate, which generally act to increase impulsivity on the 5CSRTT, may provide new insights into the mechanisms of action of stimulant and nonstimulant drugs in ADHD.


Development and validation of a 1-km cardio-trekking test to estimate cardiorespiratory fitness in healthy adults.
Maximum oxygen uptake (V̇O2max), the gold standard measure of cardiorespiratory fitness (CRF), supports cardiovascular risk assessment and is mainly assessed during maximal spiroergometry. However, for field use, submaximal exercise tests might be appropriate and feasible. There have been no studies attempting a submaximal test protocol involving uphill hiking. This study aimed to develop and validate a 1-km cardio-trekking test (CTT) controlled by heart rate monitoring and Borg's 6-20 rating of perceived exertion (RPE) scale to predict V̇O2max outdoors. Healthy participants performed a maximal incremental treadmill walking laboratory test and a submaximal 1-km CTT on mountain trails in Austria and Germany, and V̇O2max was assessed with a portable spirometry device. Borg's RPE scale was used to control the exercise intensity of the CTT. All subjects wore a chest strap to measure heart rate (HR). A total of 134 participants (median age: 56.0 years [IQR: 51.8-63.0], 43.3 % males) completed both testing protocols. The prediction model is based on age, gender, smoking status, weight, mean HR, altitude difference, duration, and the interaction between age and duration (R2 = 0.65, adj. R2 = 0.63). Leave-one-out cross-validation revealed small shrinkage in predictive accuracy (R2 = 0.59) compared to the original model. Submaximal exercise testing using uphill hiking allows for practical estimation of V̇O2max in healthy adults. This method may allow people to engage in physical activity while monitoring their CRF to avert unnecessary cardiovascular events.


Combined effects of night warming and light pollution on predator-prey interactions.
Interactions between multiple anthropogenic environmental changes can drive non-additive effects in ecological systems, and the non-additive effects can in turn be amplified or dampened by spatial covariation among environmental changes. We investigated the combined effects of night-time warming and light pollution on pea aphids and two predatory ladybeetle species. As expected, neither night-time warming nor light pollution changed the suppression of aphids by the ladybeetle species that forages effectively in darkness. However, for the more-visual predator, warming and light had non-additive effects in which together they caused much lower aphid abundances. These results are particularly relevant for agriculture near urban areas that experience both light pollution and warming from urban heat islands. Because warming and light pollution can have non-additive effects, predicting their possible combined consequences over broad spatial scales requires knowing how they co-occur. We found that night-time temperature change since 1949 covaried positively with light pollution, which has the potential to increase their non-additive effects on pea aphid control by 70% in US alfalfa. Our results highlight the importance of non-additive effects of multiple environmental factors on species and food webs, especially when these factors co-occur.


Transesophageal electrophysiological evaluation of children with a history of supraventricular tachycardia in infancy.
Supraventricular tachycardia (SVT) presenting in the neonatal period may resolve by 1 year of age. Predicting which patients require therapy beyond 1 year of age is desirable. Pediatric electrophysiology databases from two institutions were reviewed for patients with a history of infant SVT who underwent transesophageal electrophysiology study (TEEPS) after initial SVT and before 2 years of age. All patients were tested off medications and followed for clinical recurrence. Forty-two patients presented with SVT at median age of 4 days (0-300 days). Initial control was achieved with one drug in 31 patients and multiple drugs in 11 patients. Prior to TEEPS, nine patients had clinical recurrence in the first year of life after initial control had been previously achieved. For all patients, TEEPS was performed, without complications, at median 13 months (9-22 months) of age and at median of 13 months (6-22 months) following the initial SVT episode. SVT was inducible in 27/42: 8 atrio-ventricular nodal reentry tachycardia (AVNRT) and 19 atrio-ventricular reciprocating tachycardia (AVRT). Inducibility was not associated with age at presentation, age at TEEPS, ventricular dysfunction at presentation, presence of structural congenital heart disease, number of drugs required to initially control SVT, or SVT recurrence after initial control. Of 15 not inducible at TEEPS, none had known SVT recurrence off medications at median follow-up of 27 months (6-37 months). In conclusion, among patients having SVT in early infancy, (1) TEEPS results are not associated with clinical variables, (2) non-inducibility is a good indicator of lack of clinical recurrence at intermediate follow-up, and (3) AVNRT may be more prevalent in infancy than previously reported.


The development of culture-specific health education packages to increase case-finding of leprosy in Sarawak.
For any health education to succeed, the people's perception of the disease, their beliefs and cultural practices are of utmost importance as these have tremendous influence on their acceptance of new ideas. It is therefore essential to develop appropriate health education packages based on the understanding of the traditional and socio-cultural belief systems of the people. Thus on the basis of anthropological studies, health education packages were developed for the leprosy control programme in Sarawak, aimed at both adults and children. Newspaper articles, cartoon tape-slides, cartoon story books as well as posters were developed for both Chinese as well as other groups such as Malays, Ibans and Kayans. These were field tested and are now used in the Rejang Valley of Sarawak.


[Fosinopril in the treatment of cardiorenal syndrome in chronic cardiac failure].
Renal dysfunction is an independent risk factor of chronic cardiac failure (CCF) and death due to this disease. CCF patients are elderly patients with diabetes mellitus, arterial hypertension and long-term chronic cardiac insufficiency. CCF patients do not often have left ventricular systolic dysfunction, renal affection is not associated with low ejection syndrome. Renal affection in CCF is primarily caused by activation of the system rennin-angiotensin, inflammation, disturbed bioavailability of nitric oxide, hyperactivation of the sympathetic nervous system. ACE inhibitors correct pathophysiological disorders of renal flow in CCF. Fosinopril shows the highest efficacy and safety in management of cardiorenal syndrome in CCF patients. Fosinopril can also prevent renal dysfunction in CCF patients.


Mechanisms involved in calcium-mobilizing agonist responses.
Many hormones and neurotransmitters exert their biological effects by increasing the levels of Ca2+ and 1,2-diacylglycerol in their target cells. Major agonists that act in this way are epinephrine and norepinephrine, acetylcholine, vasopressin, cholecystokinin, and angiotensin II. These and other Ca2+-mobilizing agonists may also produce effects that are not mediated by Ca2+ or diacylglycerol, but involve separate receptors and an increase or decrease in cyclic AMP. The general mechanisms by which Ca2+-mobilizing agonists induce their physiological responses are depicted in Fig. 12. These responses appear to involve an initial mobilization of Ca2+ from endoplasmic reticulum and perhaps other intracellular Ca2+ stores, followed by alterations in the flux of Ca2+ across the plasma membrane. The Ca2+ changes are consistently associated with increased turnover of cellular phosphoinositides. The most rapid response is breakdown of phosphatidylinositol 4,5-P2 in the plasma membrane, and there is much evidence that this involves a guanine-nucleotide-binding regulatory protein similar to those involved in the regulation of adenylate cyclase. Myo-inositol 1,4,5-P3 produced by phosphatidylinositol 4,5-P2 breakdown rapidly releases Ca2+ from endoplasmic reticulum, and it is likely that it is the long-sought second message for the Ca2+-dependent hormones. 1,2-Diacylglycerol, the other product of phosphatidylinositol 4,5-P2 breakdown, also acts as a second message in that it activates protein kinase C, a Ca2+-phospholipid-dependent protein kinase, by lowering its requirement for Ca2+. The cellular substrates for protein kinase C and its role in the different physiological responses to the Ca2+-mediated agonists are currently being defined. The major intracellular target for Ca2+ is the Ca2+-dependent regulatory protein calmodulin. This binds Ca2+ with high affinity, and the resulting complex interacts with a variety of enzymes and other cellular proteins, modifying their activities. A major target is the multifunctional calmodulin-dependent protein kinase that phosphorylates and alters the activities of many proteins, for example, glycogen synthase and tyrosine hydroxylase. Calcium ions may also stimulate calmodulin-dependent protein kinases that are more specific, such as phosphorylase kinase and myosin light-chain kinase. Other important Ca2+-calmodulin targets are the microtubule-associated proteins, but it is likely that many more will be found.(ABSTRACT TRUNCATED AT 400 WORDS)


ERPs reveal atypical processing of subject versus object Wh-questions in children with specific language impairment.
Children with specific language impairment (SLI) show particular difficulty comprehending and producing object (Who did the bear follow?) relative to subject (Who followed the tiger?) wh-questions. To determine if school-age children with SLI, relative to children with typical development (TD), show a more distinct unevenness, or asymmetry, in the comprehension of these questions. In addition, this study examined whether the sustained left-anterior negativity (LAN) in event-related potentials (ERP) could be used as a marker for atypical processing of these questions in children with SLI. The LAN effect signals the greater working memory processes for maintaining in memory the dislocated object in object wh-questions and reflects working memory capacity in adults. It was predicted that the amplitude of the LAN would be greater in children with SLI, reflecting the characteristic low working memory capacity in this population. The concomitance of these behavioural and electrophysiological effects would suggest that the subject-object asymmetry in SLI should be investigated in relation to poor working memory skills. Groups including 13 children with SLI, 17 same-age TD children and 18 normal adults completed an auditory sentence comprehension task requiring button responses while continuous electroencephalography (EEG) was collected. Accuracy for subject and object questions was calculated. The mean amplitude values of the ERP data for the wh-questions were examined to identify differential processing of subject and object questions. TD children demonstrated asymmetrical comprehension of subject and object wh-questions, whereas children with SLI comprehended both question types poorly and adults did not show subject-object asymmetry. ERP waveforms spanning the wh-dependency revealed a large and widespread sustained anterior positivity for object relative to subject questions in the TD group, indicating differential processing of these questions. This effect was attenuated and non-significant in the SLI group. The adults' grand average waveforms showed the expected LAN effect, which was opposite in polarity relative to the children, although it only approached significance. The finding of less differential processing of subject and object wh-questions in SLI relative to TD children suggests inefficient maintenance of sentential information in working memory for object questions in SLI. Whereas behavioural methods did not identify subject-object asymmetry in SLI, the more fine-grained method of ERPs elucidated this effect. Further analysis of working memory as the basis for the subject-object asymmetry in SLI is critical for identifying appropriate intervention targets for this population.


Simulation of surface acoustic wave motor with spherical slider.
The operation of a surface acoustic wave (SAW) motor using spherical-shaped sliders was demonstrated by Kurosawa et al. (1994). It was necessary to modify the previous simulation models for usual ultrasonic motors because of this slider shape and the high frequency vibration. A conventional ultrasonic motor has a flat contact surface slider and a hundredth driving frequency; so, the tangential motion caused by the elasticity of the slider and stator with regard to the spherical slider of the SAW motor requires further investigation. In this paper, a dynamic simulation model for the SAW motor is proposed. From the simulation result, the mechanism of the SAW motor was clarified (i.e., levitation and contact conditions were repeated during the operation). The transient response of the motor speed was simulated. The relationships between frictional factor and time constant and vibration velocity of the stator and the slider speed were understood. The detailed research regarding the elastic deformation caused by preload would be helpful to construct an exact simulation model for the next work.


[DAPI-DNA cytofluorometric study of glioma cells--application of DAPI-DNA cytofluorometry to paraffin embedded archival glioma tissue for nuclear DNA content analysis].
Using DAPI-DNA cytofluorometry, the author analyzed nuclear DNA content of formalin fixed, paraffin embedded, glioma material obtained from 14 glioma cases at surgery. Sections of 10 microns were deparaffinized. Following simultaneous DAPI (4,6-diamidino-2-phenylindole dihydroporphyrin chloride)/HP (hematoporphyrin) staining, DAPI binds DNA and DNA-DAPI complexes emit blue fluorescence when exited by ultraviolet (UV) light. Through Zeiss fluorescence microscope, the author measured nuclear fluorescence intensity with histological verification of glioma cells. A DNA histogram was obtained with fluorescence intensity recorded on the abscissa and number of cells plotted on the ordinate. Samples of 20 normal non-neoplastic astrocytes taken from apparently normal brain tissue included in the histological slide were used as diploid (2 C) control. Based on DNA content, tumor cells were classified into 4 groups: N-group composed of cells with 2 C DNA content (normoploid), S-group with less than 2 C (hypoploid), L-group more than 4 C (hypertetraploid), I-group between 2 C and 4 C (intermediate ploidy). Intermediate ploidy was significantly higher and normoploid was significantly lower in glioblastoma compared with those of benign astrocytoma. Thus, DNA content and histological malignancy were well correlated. Due to limitation of measuring diaphragm of turret in the microscope, some extra large cell could not be included in it and was excluded from the measurement.(ABSTRACT TRUNCATED AT 250 WORDS)


Sociodemographic profile of undergraduate nursing students.
The College of Nursing at Ribeirão Preto, University of São Paulo, Brazil has been projected as a national reference with special appeal for students, which motivated this study on the profile of the school's applicants. The population of this exploratory-descriptive study is composed of alumni from 1999 to 2003. The data collection was performed through the university's registration forms and the analysis through the quantitative method. Results show a decreasing number of applications from Ribeirão Preto, a predominance of young, female and single applicants; few of them were employed at the time. Regarding their educational background, the data show an increasing number of applicants coming from private schools, while the majority of them entered the university within two years after concluding secondary school. Some of the students temporarily abandoned the course or lost one or more semesters, while most of them graduated within the expected term.


Acceleration forces on the human subject.
An overall view of the methodology of acceleration research, i.e. G-tolerance measuring devices and the peculiarities of each, general information on G tolerance and types of G stress, the methods of determining G tolerance, and the methods of modifying one's G tolerance, is presented. Some human factors aspects of G tolerance, as well as some physiologic changes under G, i.e. ECG changes, cardiac problems, and various other biochemical and hematological alterations, are discussed. Special emphasis is placed on the proven G-associated cardiac pathology found in various animal models, and its possible application to the human subject.


Identification of bacterial strains isolated from the Mediterranean Sea exhibiting different abilities of biofilm formation.
The Mediterranean Sea has rarely been investigated for the characterization of marine bacteria as compared to other marine environments such as the Atlantic or Pacific Ocean. Bacteria recovered from inert surfaces are poorly studied in these environments, when it has been shown that the community structure of attached bacteria can be dissimilar from that of planktonic bacteria present in the water column. The objectives of this study were to identify and characterize marine bacteria isolated from biofilms developed on inert surfaces immersed in the Mediterranean Sea and to evaluate their capacity to form a biofilm in vitro. Here, 13 marine bacterial strains have been isolated from different supports immersed in seawater in the Bay of Toulon (France). Phylogenetic analysis and different biological and physico-chemical properties have been investigated. Among the 13 strains recovered, 8 different genera and 12 different species were identified including 2 isolates of a novel bacterial species that we named Persicivirga mediterranea and whose genus had never been isolated from the Mediterranean Sea. Shewanella sp. and Pseudoalteromonas sp. were the most preponderant genera recovered in our conditions. The phenotypical characterization revealed that one isolate belonging to the Polaribacter genus differed from all the other ones by its hydrophobic properties and poor ability to form biofilms in vitro. Identifying and characterizing species isolated from seawater including from Mediterranean ecosystems could be helpful for example, to understand some aspects of bacterial biodiversity and to further study the mechanisms of biofilm (and biofouling) development in conditions approaching those of the marine environment.


Multidisciplinary managed care networks-Life-saving interventions for hepatitis C patients.
Successful hepatitis C virus (HCV) therapy depends on effective pathways of care. Over two decades, we have developed four sequential models of care latterly using a multidisciplinary managed care network to improve HCV testing, care and treatment. This was a cohort study to evaluate the effectiveness of care pathways, carried out using all HCV antibody-positive individuals tested in a geographical region between 1994 and 2014. The study involved 3122 HCV-positive patients. They were divided into four subgroups representing different care pathways defined by their date of HCV antibody diagnosis. The number who accessed treatment services within 1 year of diagnosis increased from 77 of 292 (26.3%) to 521 of 821 (72.9%). The rate of treatment starts within 1 year of diagnosis increased from 6 of 292 (2.0%) to 133 of 821 (16.2%), and the sustained viral response rate improved from 61.6% to 77.4%. All-cause mortality decreased from 232 of 688 (33.7%) in subgroup A to 55 of 1207 (4.5%) in subgroup D, and multivariate analysis showed that pathway type was an independent predictor of mortality irrespective of age, sex, SVR status or HIV co-infection with pathway in D having an odds ratio of 0.53(0.40-0.77; P<.001) compared to pathway in A. At study end, 78% (3122) of an estimated 4000 HCV positive had been diagnosed. In total, 97.5% of HCV caseload was referred to specialist services and 89% attended for assessment. The introduction of a managed care network increased access to care and reduced all-cause mortality.


Observations on muscle pain in man, with particular reference to pain during needle electromyography.
Muscle pain receptors have been studied in man. During the advance of an EMG needle pain is most regularly experienced as the muscle fascia is pierced. Further advancing the needle is usually quite painless. However, there are scantily distributed points within the muscle (`pain spots') which may give rise to pain if encountered by the advancing needle. The nature of the responsible receptors is obscure but it is likely that pain may sometimes be caused by activation of nerve fibres (presumably from these receptors) coursing through the muscle rather than by activation of the receptors themselves. Intramuscular bleeding is unlikely to contribute often to the pain of needle electromyography. Mechanically sensitive `pain spots' are more painful than other areas when stimulated electrically or injected with hypertonic (6%) saline. This suggests a common receptor. The high electrical threshold and relative invulnerability to pressure of afferent fibres from these receptors suggest that they are mainly of small diameter. These findings are discussed in relation to experimental work on pressure-pain receptors in animals.


Evaluation of Fourier deconvolution ion mobility spectrometer as high-performance gas chromatography detector for the analysis of plant extract flavors.
The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di‑tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.


Recollection and familiarity in hippocampal amnesia.
Currently, there is a general agreement that two distinct cognitive operations, recollection and familiarity, contribute to performance on recognition memory tests. However, there is a controversy about whether recollection and familiarity reflect different memory processes, mediated by distinct neural substrates (dual-process models), or whether they are the expression of memory traces of different strength in the context of a unitary declarative memory system (unitary-strength models). Critical in this debate is the status of recognition memory in hippocampal amnesia and, in particular, whether the various structures in the medial temporal lobe (MTL) contribute differentially to the recollection and familiarity components of recognition. The present study aimed to explore the relative contribution of recollection and familiarity to recognition of words that had been previously read or that had been previously generated in a group of severely amnesic patients with cerebral damage restricted to the hippocampus. A convergent pattern of results emerged when we used a subjective-based (remember/know; R/K) and an objective-based (process dissociation procedure; PDP) methods to estimate the contribution of recollection and familiarity to recognition performance. In both PDP and R/K procedures, healthy controls disclosed significantly higher recollection estimates for words that had been anagrammed than for words that had been read. Amnesic patients' recollection scores were not different for words that had been generated or that had been read, and the recollection estimate for words that had been generated was significantly reduced as compared to the group of healthy controls. For familiarity, both healthy controls and amnesic patients recognized as familiar more words that had been generated than words that had been read, and there was no difference between the two groups. These data support the hypothesis of a specific role of the hippocampus in recollection processes and suggest that other components of the MTL (e.g., perirhinal cortex) may be more involved in the process of familiarity.


Localization of dopamine carriers by BTCP, a dopamine uptake inhibitor, on nigral cells cultured in vitro.
BTCP, N-[1-(2-benzo(b)thiopenyl)cyclohexyl]piperidine, a derivative of phencyclidine, acted as a potent dopamine (DA) uptake blocking agent on primary cultures of dopaminergic neurons obtained from substantia nigra (IC50 = 70 nM). This value was closely related to IC50 determined for reference DA uptake inhibitors such as nomifensine (70 nM) or benztropine (50 nM), showing the specificity of BTCP towards the DA carrier. Thus, we used BTCP as a tool to visualize the DA uptake complexes on cultures, a model which preserves the integrity of the neurons. The [3H]BTCP binding sites directly visualized by radioautographical (RAG) labelling seemed to follow the fibres (axons or dendrites) of neurons in culture whereas the cell bodies were not labelled. The [3H]DA uptake visualized by RAG labelling, was inhibited either partially by BTCP at a concentration near its IC50 or totally by a high concentration of BTCP, all over the dopaminergic neurons (neurites and somas) immunostained with an anti-DA antiserum. Thus, the distribution of DA carriers can be investigated by a suitable tool, BTCP, a powerful and selective DA uptake blocker. These carriers have been visualized by radioautography with tritiated BTCP along the neurites, and the uptake can be totally blocked by a high concentration of BTCP all over DA neurons in vitro.


Ultrasound beamforming using compressed data.
The rapid advancements in electronics technologies have made software-based beamformers for ultrasound array imaging feasible, thus facilitating the rapid development of high-performance and potentially low-cost systems. However, one challenge to realizing a fully software-based system is transferring data from the analog front end to the software back end at rates of up to a few gigabits per second. This study investigated the use of data compression to reduce the data transfer requirements and optimize the associated trade-off with beamforming quality. JPEG and JPEG2000 compression techniques were adopted. The acoustic data of a line phantom were acquired with a 128-channel array transducer at a center frequency of 3.5 MHz, and the acoustic data of a cyst phantom were acquired with a 64-channel array transducer at a center frequency of 3.33 MHz. The receive-channel data associated with each transmit event are separated into 8 × 8 blocks and several tiles before JPEG and JPEG2000 data compression is applied, respectively. In one scheme, the compression was applied to raw RF data, while in another only the amplitude of baseband data was compressed. The maximum compression ratio of RF data compression to produce an average error of lower than 5 dB was 15 with JPEG compression and 20 with JPEG2000 compression. The image quality is higher with baseband amplitude data compression than with RF data compression; although the maximum overall compression ratio (compared with the original RF data size), which was limited by the data size of uncompressed phase data, was lower than 12, the average error in this case was lower than 1 dB when the compression ratio was lower than 8.


US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status.
In 2010, Surveillance, Epidemiology, and End Results (SEER) registries began collecting human epidermal growth factor 2 (HER2) receptor status for breast cancer cases. Breast cancer subtypes defined by joint hormone receptor (HR; estrogen receptor [ER] and progesterone receptor [PR]) and HER2 status were assessed across the 28% of the US population that is covered by SEER registries. Age-specific incidence rates by subtype were calculated for non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API), and Hispanic women. Joint HR/HER2 status distributions by age, race/ethnicity, county-level poverty, registry, stage, Bloom-Richardson grade, tumor size, and nodal status were evaluated using multivariable adjusted polytomous logistic regression. All statistical tests were two-sided. Among case patients with known HR/HER2 status, 36810 (72.7%) were found to be HR(+)/HER2(-), 6193 (12.2%) were triple-negative (HR(-)/HER2(-)), 5240 (10.3%) were HR(+)/HER2(+), and 2328 (4.6%) were HR(-)/HER2(+); 6912 (12%) had unknown HR/HER2 status. NH white women had the highest incidence rate of the HR(+)/HER2(-) subtype, and NH black women had the highest rate of the triple-negative subtype. Compared with women with the HR(+)/HER2(-) subtype, triple-negative patients were more likely to be NH black and Hispanic; HR(+)/HER2(+) patients were more likely to be NH API; and HR(-)/HER2(+) patients were more likely to be NH black, NH API, and Hispanic. Patients with triple-negative, HR(+)/HER2(+), and HR(-)/HER2(+) breast cancer were 10% to 30% less likely to be diagnosed at older ages compared with HR(+)/HER2(-) patients and 6.4-fold to 20.0-fold more likely to present with high-grade disease. In the future, SEER data can be used to monitor clinical outcomes in women diagnosed with different molecular subtypes of breast cancer for a large portion (approximately 28%) of the US population.


Joint position reproduction and joint position discrimination at the ankle are not related.
Purpose: Limited data in current literature can be found on the relation between the two commonly-used active proprioception assessment methods -active joint position reproduction (JPR) and active movement extent discrimination assessment (AMEDA). The current study compared the two active methods, JPR and AMEDA, to investigate their interrelationship over two studies that differed in task difficulty, using active ankle inversion movements made in weight-bearing to maximise ecological validity.Methods: 50 participants volunteered in this research, 20 of whom on a harder protocol and the other 30 on an easier protocol, were tested by both methods, JPR and AMEDA. Proprioceptive acuity was represented by absolute error (AE) and variable error (VE) for JPR and by AE and the area under the curve (AUC) for AMEDA.Results: Proprioceptive acuity scores are found to be significantly correlated within test methods but not between methods for either hard or easy tasks, where JPR AE and VE scores were not correlated with either AMEDA AE or AUC. Further, proprioceptive acuity scores were significantly higher on the easy task when tested with the AMEDA method, but not with JPR method.Conclusion: Scores obtained from the two active movement proprioception tests, movement extent discrimination and joint position reproduction, were not significantly correlated. Taken together with previous findings, these results show that for proprioception, scores from the three classical psychophysical methods for measuring sensitivity (adjustment, limits and constant stimuli) are not correlated with each other. This suggests that each proprioception measurement system assesses a different aspect of proprioception.


The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.
Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration.


Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4+ T Cells and Offers an Opportunity to Tackle Infection.
HIV persists in long-lived infected cells that are not affected by antiretroviral treatment. These HIV reservoirs are mainly located in CD4+ T cells, but their distribution is variable in the different subsets. Susceptibility to HIV-1 increases with CD4+ T cell differentiation. We evaluated whether the metabolic programming that supports the differentiation and function of CD4+ T cells affected their susceptibility to HIV-1. We found that differences in HIV-1 susceptibility between naive and more differentiated subsets were associated with the metabolic activity of the cells. Indeed, HIV-1 selectively infected CD4+ T cells with high oxidative phosphorylation and glycolysis, independent of their activation phenotype. Moreover, partial inhibition of glycolysis (1) impaired HIV-1 infection in vitro in all CD4+ T cell subsets, (2) decreased the viability of preinfected cells, and (3) precluded HIV-1 amplification in cells from HIV-infected individuals. Our results elucidate the link between cell metabolism and HIV-1 infection and identify a vulnerability in tackling HIV reservoirs.


Phospho-kinase profile of triple negative breast cancer and androgen receptor signaling.
The androgen receptor (AR) plays a central role in the oncogenesis of different tumors, as is the case in prostate cancer. In triple negative breast cancer (TNBC) a gene expression classification has described different subgroups including a luminal androgen subtype. The AR can be controlled by several mechanisms like the activation of membrane tyrosine kinases and downstream signaling pathways. However little is known in TNBC about how the AR is modulated by these mechanisms and the potential therapeutic strategists to inhibit its expression. We used human samples to evaluate the expression of AR by western-blot and phospho-proteomic kinase arrays that recognize membrane tyrosine kinase receptors and downstream mediators. Western-blots in human cell lines were carried out to analyze the expression and activation of individual proteins. Drugs against these kinases in different conditions were used to measure the expression of the androgen receptor. PCR experiments were performed to assess changes in the AR gene after therapeutic modulation of these pathways. AR is present in a subset of TNBC and its expression correlates with activated membrane receptor kinases-EGFR and PDGFRβ in human samples and cell lines. Inhibition of the PI3K/mTOR pathway in TNBC cell lines decreased notably the expression of the AR. Concomitant administration of the anti-androgen bicalutamide with the EGFR, PDGFRβ and Erk1/2 inhibitors, decreased the amount of AR compared to each agent given alone, and had an additive anti-proliferative effect. Administration of dihydrotestosterone augmented the expression of AR that was not modified by the inhibition of the PI3K/mTOR or Erk1/2 pathways. AR expression was posttranscriptionally regulated by PI3K or Erk1/2 inhibition. Our results describe the expression of the AR in TNBC as a druggable target and further suggest the combination of bicalutamide with inhibitors of EGFR, PDGFRβ or Erk1/2 for future development.


ColabFold predicts alternative protein structures from single sequences, coevolution unnecessary for AF-cluster.
Though typically associated with a single folded state, globular proteins are dynamic and often assume alternative or transient structures important for their functions 1,2 . Wayment-Steele, et al. steered ColabFold 3 to predict alternative structures of several proteins using a method they call AF-cluster 4 . They propose that AF-cluster "enables ColabFold to sample alternate states of known metamorphic proteins with high confidence" by first clustering multiple sequence alignments (MSAs) in a way that "deconvolves" coevolutionary information specific to different conformations and then using these clusters as input for ColabFold. Contrary to this Coevolution Assumption, clustered MSAs are not needed to make these predictions. Rather, these alternative structures can be predicted from single sequences and/or sequence similarity, indicating that coevolutionary information is unnecessary for predictive success and may not be used at all. These results suggest that AF-cluster's predictive scope is likely limited to sequences with distinct-yet-homologous structures within ColabFold's training set.


Genome sequencing and comparative genomics of tropical disease pathogens.
The sequencing of eukaryotic genomes has lagged behind sequencing of organisms in the other domains of life, archae and bacteria, primarily due to their greater size and complexity. With recent advances in high-throughput technologies such as robotics and improved computational resources, the number of eukaryotic genome sequencing projects has increased significantly. Among these are a number of sequencing projects of tropical pathogens of medical and veterinary importance, many of which are responsible for causing widespread morbidity and mortality in peoples of developing countries. Uncovering the complete gene complement of these organisms is proving to be of immense value in the development of novel methods of parasite control, such as antiparasitic drugs and vaccines, as well as the development of new diagnostic tools. Combining pathogen genome sequences with the host and vector genome sequences is promising to be a robust method for the identification of host-pathogen interactions. Finally, comparative sequencing of related species, especially of organisms used as model systems in the study of the disease, is beginning to realize its potential in the identification of genes, and the evolutionary forces that shape the genes, that are involved in evasion of the host immune response.


BHV-1-Specific CD4+, CD8+, and gammadelta T cells in calves vaccinated with one dose of a modified live BHV-1 vaccine.
Expression of the high-affinity interleukin 2 receptor alpha chain (CD25) was used to monitor antigen-specific activation of T lymphocyte subsets (CD4+, CD8+, and gammadelta T cells) from cattle immunized with modified live bovine herpesvirus-1 (BHV-1). Calves seronegative for BHV-1 were either vaccinated with one dose of modified live vaccine containing BHV-1 or not vaccinated to serve as negative controls. Two animals vaccinated 7 and 5 weeks before the start of the experiment with two doses of modified live vaccine containing BHV-1 served as positive controls. Blood samples were taken from the nonvaccinate group, the positive control group, and the vaccinate group at 0, 21, 35, 60, and 90 days postinoculation (PI). Isolated peripheral blood mononuclear cells from immunized and control animals were incubated for 5 days with and without live BHV-1 ISU99. Compared to the nonvaccinates, a significant (p < 0.05) increase in expression of CD25 by CD4+, CD8+, and gammadelta T lymphocytes from the vaccinate group was detected following in vitro exposure to live BHV-1 after vaccination. This is apparently the first report using live BHV-1 to stimulate lymphocytes in vitro and showing CD8+ T cell activation. Peripheral blood from the positive control animals was depleted of CD4+, CD8+, or gammadelta T lymphocytes prior to incubation with BHV-1 to assess bystander activation in the CD25 expression assay. When incubated with live BHV-1, depletion of CD4+ T cells depressed the expression of CD25 by CD8+ T cells, but not gammadelta T cells. Depleting CD8+ or gammadelta T cells prior to in vitro culture with BHV-1 did not affect the expression of CD25 by the remaining T lymphocyte subsets. Vaccinates were protected from challenge with virulent BHV-1 at 110 days postvaccination compared to nonvaccinates. Expression of CD25 appears to be a useful marker for evaluating induction of antigen-specific T lymphocyte subset responses following vaccination.


Appendiceal mucinous adenocarcinoma presenting as an enterocutaneous fistula in an incisional hernia.
A 68-year-old woman with a history of bone-graft harvesting from the right iliac crest presented with an incisional hernia and abscess at the graft donor site. Following incision and drainage of the abscess, CT demonstrated an enterocutaneous fistula between the appendix and bone-graft incision with appendicitis assumed to be the original cause of the abscess. At laparoscopy, the appendix was adherent to the hernia sac with mucinous material at the superficial orifice of the fistula site but not in the peritoneal cavity. Laparoscopic appendicectomy with fistula track excision was performed. Histological evaluation confirmed a well-to-moderately differentiated mucinous adenocarcinoma arising on a background of dysplastic villous adenoma. Tumour extended along the fistula track to involve the surface skin. A laparoscopic right hemicolectomy, lymph node dissection and wide local excision of the fistula track were carried out at a second procedure. Final histology confirmed pT4N1 tumour with clear resection margins.


Sphincter of Oddi motility.
Recent developments of manometric and endoscopic instrumentation have rekindled interest in sphincter of Oddi function. As a result of human and animal studies, our understanding of normal sphincter of Oddi physiology has increased and possible motility abnormalities are being identified. Manometric studies have shown that the sphincter of Oddi is characterized by prominent phasic contractions which are super-imposed on a low tonic pressure. The phasic contractions are orientated mainly in an antegrade direction; however, both simultaneous and retrograde contractions are registered. Cineradiography has demonstrated that the phasic contractions have a propulsive function, expelling small volumes of fluid from the common bile duct into the duodenum. Intravenously administered cholecystokinin-octapeptide normally inhibits the phasic contractions and reduces the sphincter tone. Motility abnormalities may occur if the sphincter of Oddi exhibits abnormally high tone, alteration in the direction of the phasic contractions, abnormal changes in the contraction frequency, or abnormal responses to hormonal stimulation. Preliminary human studies demonstrate disorders in sphincter of Oddi motility patterns, suggesting that motility abnormalities may be associated with choledocholithiasis, dyskinesia and idiopathic relapsing pancreatitis.


Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer.
To provide information and recommendations to women with a previous diagnosis of breast cancer and their physicians regarding hormone replacement therapy (HRT). Control of menopausal symptoms, quality of life, prevention of osteoporosis, prevention of cardiovascular disease, risk of recurrence of breast cancer, risk of death from breast cancer. Systematic review of English-language literature published from January 1990 to July 2001 retrieved from MEDLINE and CANCERLIT. * Routine use of HRT (either estrogen alone or estrogen plus progesterone) is not recommended for women who have had breast cancer. Randomized controlled trials are required to guide recommendations for this group of women. Women who have had breast cancer are at risk of recurrence and contralateral breast cancer. The potential effect of HRT on these outcomes in women with breast cancer has not been determined in methodologically sound studies. However, in animal and in vitro studies, the development and growth of breast cancer is known to be estrogen dependent. Given the demonstrated increased risk of breast cancer associated with HRT in women without a diagnosis of breast cancer, it is possible that the risk of recurrence and contralateral breast cancer associated with HRT in women with breast cancer could be of a similar magnitude. * Postmenopausal women with a previous diagnosis of breast cancer who request HRT should be encouraged to consider alternatives to HRT. If menopausal symptoms are particularly troublesome and do not respond to alternative approaches, a well-informed woman may choose to use HRT to control these symptoms after discussing the risks with her physician. In these circumstances, both the dose and the duration of treatment should be minimized. Internal validation within the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer; no external validation. The steering committee was convened by Health Canada. COMPLETION DATE: October 2001.


Weight of evidence approaches for the identification of endocrine disrupting properties of chemicals: Review and recommendations for EU regulatory application.
A Weight-of-evidence (WoE) evaluation should be applied in assessing all the available data for the identification of endocrine disrupting (ED) properties of chemicals. The European Commission draft acts specifying criteria under the biocidal products and plant protection products regulations require that WoE is implemented for the assessment of such products. However, only some general considerations and principles of how a WoE should be conducted are provided. This paper reviews WoE approaches to distil key recommendations specifically for the evaluation of potential ED properties of chemicals. In a manner, which is consistent with existing, published WoE frameworks, the WoE evaluation of ED properties can be divided into four phases: 1) Definition of causal questions and data gathering and selection, 2) Review of individual studies, 3) Data integration and evaluation, and 4) Drawing conclusions based on inferences. Recommendations are made on how to conduct each phase robustly and transparently to help guide the WoE evaluation of potential endocrine disrupting properties of chemicals within a European regulatory context.


Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor α and microbial translocation.
Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor α (IL-7Rα) gene were important for immune recovery. We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7Rα haplotypes and measured levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples collected before and after ART initiation. Levels of soluble IL-7Rα were measured in HIV-infected patients with IL-7Rα haplotype 2 (n = 11) and those without IL-7Rα haplotype 2 (n = 22). Multivariate analysis was used to identify variables associated with faster recovery to CD4(+) T cell counts of >500 and >200 cells/μL. Both LPS and soluble CD14 levels were significantly decreased with ART (P < .001, respectively) but remained elevated compared with uninfected controls. In a multivariate analysis, faster recovery to a CD4(+) T cell count of >500 cells/μL was significantly associated with higher baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre-ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7Rα haplotype 2 (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected patients with haplotype 2 had significantly lower soluble IL-7Rα levels compared with those of patients without haplotype 2 (P < .001). Both the extent of immune depletion prior to ART and IL-7Rα haplotype 2 are important determinants of time to CD4(+) T cell recovery to counts of >500 cells/μL.


Detection in BHK cells of a precursor form for lamin A.
Lamins are structural proteins found in the fibrous lamina underlining the nuclear envelope. In vitro translation of polyadenylated RNA or polysomes followed by immunoprecipitation with a serum raised against BHK nuclear matrix proteins showed that lamin A (72 kD) is synthesized as a high molecular weight precursor (74 kD) (Laliberté et al., J Cell Biol 98 (1984) 980) [23]. We have thus investigated the presence in BHK cells of this putative precursor by in vivo labelling with [35S]methionine and immunoprecipitation of lamin proteins. Short labelling times, ranging from 5 to 60 min reveal the presence of the 74 kD protein. Pulse-chase experiments indicate that the half-life of the precursor is about 60 min. On two-dimensional gel, the 74 kD protein is resolved in a cluster of isovariants between pH 7.4 and 6.6, which are generally slightly more alkaline than their counterparts in lamin A. These results indicate that lamin A is synthesized as a precursor of 74 kD; the long half-life further suggests that pre-lamin A might accumulate in some sort of cellular pool before undergoing post-transcriptional modification(s) to give the mature form of lamin A.


Wetting equilibrium in a rectangular channel.
When a capillary channel with corners is wetted by a fluid, there are regions where the fluid fills the whole cross-section and regions where only the corners are filled by the fluid. The fluid fraction of the partially-filled region, s*, is an important quantity related to the capillary pressure. We calculate the value of s* for channels with a cross-section slightly deviated from a rectangle: the height is larger in the center than those on the two short sides. We find that a small change in the cross-section geometry leads to a huge change of s*. This result is consistent with experimental observations.


Hospital-Wide Surveillance of Fracture Risk Assessment by Both FRAX and Medication Patterns in Acute Care Hospital.
To identify patients at a high risk for primary and secondary osteoporotic fractures using fracture risk assessments performed using the current method and the proposed method, in an acute care hospital and to identify departments where high-risk patients are admitted. This retrospective study included patients aged 40-90 years who were hospitalized at Fujita Health University Hospital. We collated the clinical data and prescriptions of all study participants. We also gathered data pertaining to risk factors according to Fracture Risk Assessment Tool (FRAX). Of the 1595 patients, the mean number of major osteoporotic fracture risk predicted using FRAX was 11.73%. The department of rheumatology showed the highest fracture risk (18.55 ± 16.81) and had the highest number of patients on medications that resulted in reduced bone mineral density (1.07 ± 0.98 medication). Based on the FRAX, the proportion of patients in the high-risk group in this department was significantly higher compared with those in the remaining departments with respect to glucocorticoid administration, rheumatoid arthritis, and secondary osteoporosis. However, the departments included in the high-risk group were not necessarily the same as the departments included in the top group, based on the administered medications. FRAX score is calculated based on various risk factors; however, only glucocorticoid corresponds to medications. We should focus on medication prescription patterns in addition to FRAX to improve fracture risk assessment in hospital-wide surveillance. Therefore, we recommend the use of FRAX along with the prescribed medications to identify departments that admit high-risk patients.


Regulation of Na+ transport in brown adipose tissue.
In order to test the hypothesis that Na+, K+-ATPase (Na+,K+-dependent ATPase) is involved in the noradrenaline-mediated stimulation of respiration in brown adipose tissue, the effects of noradrenaline on Na+,K+-ATPase in isolated brown-fat-cell membrane vesicles, and on 22Na+ and K+ (86Rb+) fluxes across the membranes of intact isolated cells, were measured. The ouabain-sensitive fraction of the K+-dependent ATPase activity in the isolated membrane-vesicle preparation was small and was not affected by the presence of noradrenaline in the incubation media. The uptake of 86Rb+ into intact hormone-sensitive cells was inhibited by 80% by ouabain, but it was insensitive to the presence of noradrenaline. 22Na+ uptake and efflux measured in the intact cells were 8 times more rapid than the 86Rb+ fluxes and were unaffected by ouabain. This indicated the presence of a separate, more active, transport system for Na+ than the Na+,K+-ATPase. This is likely to be a Na+/Na+ exchange activity under normal aerobic conditions. However, under anaerobic conditions, or conditions simulating anaerobiosis (2 mM-NaCN), the unidirectional uptake of Na+ increased dramatically, while efflux was unaltered.


Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180 spans the lamina lucida.
The BP180 antigen is a hemidesmosomal glycoprotein that is recognized by autoantibodies associated with three autoimmune disorders, bullous pemphigoid (BP), herpes gestationis (HG), and cicatricial pemphigoid (CP). BP and HG sera have been shown to recognize a common extracellular site located near the membrane-spanning domain of this protein, whereas CP sera react predominantly with a distinct site near the C terminus. In the current study, the main immunogenic sites on the BP180 ectodomain were ultrastructurally localized using six BP sera, four CP sera, and two rabbit antisera. The immunolocalization pattern of BP sera was largely restricted to the upper lamina lucida region immediately subjacent to the epidermal hemidesmosome and closely resembled that of a rabbit antiserum directed against the NC16A (membrane-proximal) domain of BP180. CP sera, on the other hand, exhibited a lower lamina lucida/lamina densa labeling pattern that was strikingly similar to that of rabbit antibodies to the BP180 C-terminal region. Finally, antibodies to the BP180 C-terminal region co-localized with an anti-laminin-5 antibody in the anchoring filament zone. These findings strongly suggest that the BP180 extracellular domain exists in an extended conformation, with the C terminus of this protein projecting into the lamina densa. These data support the hypothesis that BP180 contributes to the structure and function of the anchoring filaments. Differences in the ultrastructural mapping of BP and CP autoantibodies appear to correlate with epitope mapping data, which, together, may help to explain the clinical heterogeneity observed in this group of bullous disorders.


Dragon TF Association Miner: a system for exploring transcription factor associations through text-mining.
We present Dragon TF Association Miner (DTFAM), a system for text-mining of PubMed documents for potential functional association of transcription factors (TFs) with terms from Gene Ontology (GO) and with diseases. DTFAM has been trained and tested in the selection of relevant documents on a manually curated dataset containing >3000 PubMed abstracts relevant to transcription control. On our test data the system achieves sensitivity of 80% with specificity of 82%. DTFAM provides comprehensive tabular and graphical reports linking terms to relevant sets of documents. These documents are color-coded for easier inspection. DTFAM complements the existing biological resources by collecting, assessing, extracting and presenting associations that can reveal some of the not so easily observable connections among the entities found which could explain the functions of TFs and help decipher parts of gene transcriptional regulatory networks. DTFAM summarizes information from a large volume of documents saving time and making analysis simpler for individual users. DTFAM is freely available for academic and non-profit users at http://research.i2r.a-star.edu.sg/DRAGON/TFAM/.


Vibrational Structure in Magnetic Circular Dichroism Spectra of Polycyclic Aromatic Hydrocarbons.
Absorption and magnetic circular dichroism (MCD) spectroscopies are powerful and simple methods to discriminate among various compounds. Polycyclic aromatic hydrocarbons provide particularly strong signal, which, for example, facilitates their detection in the environment. However, interpretation of the spectra is often based on quantum-chemical simulations, providing a limited precision only. In the present work, we use time-dependent density functional theory and complete active space second-order perturbation theories to understand spectral features observed in a series of naphthalene, anthracene, phenanthrene, and three larger compounds. The electronic computations provided reasonable agreement with the experiment for the smaller molecules, while a large error persisted for the bigger ones. However, many discrepancies could be explained by vibrational splitting of the electronic transitions across the entire spectral range. Compared to plain absorption, MCD spectral bands and their vibrational splitting were more specific for each aromatic molecule. The computational tools allowing simulations of detailed vibrational features in the electronic spectra thus promise to open a qualitatively new chapter in the spectroscopy of aromatic compounds.


Subjective impact of osteoarthritis flare-ups on patients' quality of life.
Clinical trials on osteoarthritis (OA) flare-ups treatment usually focus only on objective measures of health status, albeit recent literature suggestions on the importance of patients' subjectivity. Aim of the study was to evaluate the effects of OA and of its different types of medical treatment(s) on Health Related Quality of Life (HRQoL) in terms of both subjective satisfaction and functional status. An observational study on prospective data collected from the Evaluation of Quality of life in OA (EQuO) clinical trial (April 1999-November 2000) was conducted; outpatients from 70 participating centers (Orthopedy or Rheumatology Departments in Italy) with a diagnosis of OA of the hip or knee were consecutively enrolled. Patients were observed at OA flare-ups (baseline) and at follow up 4 weeks after treatment. Patients' objective and subjective HRQoL were assessed by means of the SF-36 and the Satisfaction Profile (SAT-P, which focuses on subjective satisfaction); Present Pain at baseline and Pain Relief at follow up were also evaluated. Among the 1323 patients, 1138 (86%) were prescribed one drug/treatment of osteoarthritis, 169 (13%) 2 drugs/treatments, and 16 (1%) 3 drugs/treatments; most of treatments involved the prescription of NSAIDs; non-coxib, COX2 selective NSAIDs were prescribed in about 50% of patients. Follow-up visits were performed after 29.0 days on average (+/- 7.69 SD). For all SF-36 domains, all SAT-P items and factors, the differences between baseline and follow up scores resulted statistically significant (p < 0.001), enlighting an improvement both in health status and in subjective HRQoL. Besides the classic health status measures, the assessment of patients' subjective satisfaction provides important clues on treatments efficacy of OA within the patient-centered medicine model. In clinical practice this could lead to a better doctor-patient communication and to higher levels of treatment adherence.


A Multicenter Case-Historical Control Study on Short-Term Outcomes of Tele-Intensive Care Unit.
Aims: This study aimed to determine the impact of tele-intensive care unit (ICU) on ICU mortality rate (%), and to quantify association of the tele-ICU intervention with ICU length of stay (LOS, days), readmission rates (%), reintubation rates (%), hospital-acquired pressure ulcer (HAPU) rate (%), and discharge against medical advice (DAMA) rate (%) in five hospitals. Methods: A multicenter case-historical control study was conducted on short-term outcomes of tele-ICU program in five private hospitals within Arabian Gulf Region. Critically ill adult patients admitted into ICU without tele-ICU were recorded as control group (pre-tele-ICU), whereas those admitted to tele-ICU were grouped as treatment group (post-tele-ICU). The observed outcomes for each patient were then recorded, namely mortality, reintubation, readmission, HAPU, DAMA, and length of stay (LOS). Results: Chi-square test showed that there are significant differences in mortality rate (χ2 = 6.596, p = 0.010), readmission rate (χ2 = 4.315, p = 0.038), HAPU rate (χ2 = 10.445, p = 0.001), and DAMA rate (χ2 = 4.485, p = 0.034) between pre-tele-ICU and post-tele-ICU, at 0.05 significance difference level. Independent t-test showed that there is significant different in LOS (t = 43.63, p < 0.001) between pre-tele-ICU (mean = 6.72 days) and post-tele-ICU (mean = 5.79 days). Odds ratio showed that critically ill adult patients who admitted to post-tele-ICU have 19% less reduction in mortality rate, 23% less reduction in readmission rate, 43% less reduction in HAPU rate, and 11% less reduction in DAMA rate as compared with those admitted to pre-tele-ICU.Conclusion: Tele-ICU as a step to improve the quality of health care project has shown statistically significant improvement in the adult ICU patients' outcomes, which lead to lesser mortality rate, readmission rate, HAPU rate, DAMA rate, and shorter LOS.


Evolutionary game theory meets social science: is there a unifying rule for human cooperation?
Evolutionary game theory has shown that human cooperation thrives in different types of social interactions with a PD structure. Models treat the cooperative strategies within the different frameworks as discrete entities and sometimes even as contenders. Whereas strong reciprocity was acclaimed as superior to classic reciprocity for its ability to defeat defectors in public goods games, recent experiments and simulations show that costly punishment fails to promote cooperation in the IR and DR games, where classic reciprocity succeeds. My aim is to show that cooperative strategies across frameworks are capable of a unified treatment, for they are governed by a common underlying rule or norm. An analysis of the reputation and action rules that govern some representative cooperative strategies both in models and in economic experiments confirms that the different frameworks share a conditional action rule and several reputation rules. The common conditional rule contains an option between costly punishment and withholding benefits that provides alternative enforcement methods against defectors. Depending on the framework, individuals can switch to the appropriate strategy and method of enforcement. The stability of human cooperation looks more promising if one mechanism controls successful strategies across frameworks.


Immunosuppressive activity of adipose tissue-derived mesenchymal stem cells in a rat model of hind limb allotransplantation.
Many reports have shown that bone marrow-derived mesenchymal stem cells exhibit immunosuppressive effects in allogeneic transplantation. However, few reports have evaluated the immunosuppressive properties of adipose tissue-derived mesenchymal stem cells (ASCs) in vitro and in vivo. In this study, we investigated the immunosuppressive characteristics of ASCs, and investigated whether ASCs originating from donor rats prolong allotransplant survival in a rat hind limb allotransplantation model. T-cell proliferation stimulated by allogeneic stimuli or mitogen with or without ASCs originating from the donor was assessed in vitro. The effects of cellular contact or soluble factors on the inhibition of T-cell proliferation were also evaluated. In the in vivo study, cultured ASCs (1 × 10(5)) that originated from the donor were injected into recipient animals intravenously immediately after operation, followed by 1 dose per day for 3 consecutive days post-transplantation. When immune rejection occurred, the survival time of allotransplants was determined and rejected tissue was histologically and immunochemically assessed for determining regulatory T-cell infiltration. ASCs inhibited the T-cell proliferation stimulated by alloantigen or mitogen in a dose-dependent manner, and recipient T cells proliferated less in animals treated with ASCs than in controls. Although ASCs were separated from T cells, ASCs persisted to elicit a suppressive effect. ASC culture supernatants did not inhibit T-cell proliferation; however, supernatants obtained from the mixed lymphocyte reaction in the presence of ASCs suppressed T-cell proliferation. ASCs prolonged allotransplant survival time, reduced inflammatory cell infiltration, and induced regulatory T cells. In conclusion, ASCs can exhibit in vitro immunosuppressive properties and prolong allotransplant survival time in a rat hind limb composite tissue allotransplantation model, possibly through the induction of regulatory T cells.


The impaired nurse. Organizational and professional models of response.
1. Two models of response, organizational and professional, affect the impaired nurse, who is both an employee and a professional. 2. The organizational model of response uses an Employee Assistance Program (EAP) to detect and intervene with impaired employees. 3. The professional model of response involves mechanisms established through the board of nursing, including posttreatment monitoring. 4. When both models are available, linking mechanisms such as coordinators, policies, and reentry practices can combine the strengths of each model.


The interaction of gamma radiation with drugs used in cholinergic medications.
Purpose: Pharmacological medications can reduce the radiation damage in the organism when applied in the stage before or after exposure to radiation. Cholinergic drugs are a category of pharmaceutical agents acting on the neurotransmitter acetylcholine, the primary neurotransmitter in the parasympathetic nervous system. In this investigation, some gamma radiation interaction parameters namely mass attenuation coeffıcients (μρ), effective atomic number (Zeff) and electron densities (Nel) of 12 cholinergic system drugs have been calculated in the energy range 1 KeV-100 GeV. In addition, gamma-ray energy absorption (EABF) and exposure (EBF) of buildup factors have been computed using the five-parameter geometric progression (G-P) fitting formula for investigated drugs in the energy range 0.015-15 MeV, and for penetration depths up to 40 mean free path (mfp).Materials and methods: In order to perform these calculations, data obtained from WinXCom computer program were used. The computed μρ values were then used to calculate the effective atomic numbers and electron density of the investigated drugs. To compute the buildup factors, the G-P fitting parameters were determined by the method of interpolation from the equivalent atomic number, 'Zeq'Results and Conclusions: It has been concluded that effective atomic number and electron density of malathion is bigger than the other drugs and the variations in values of Zeff and Nel for all drugs depend on chemical compositions and photon energy where the K-absorption edge of elements may affect the energy dependence of Zeff and Nel. It should also be noted that the buildup of photons is less in malathion and carbachol and is more in tabun and parathion compared with other drugs. Photon interaction parameters evaluated in the present study may be beneficial in radiation dosimetry and therapy.


MALDI mass spectrometry imaging, from its origins up to today: the state of the art.
Mass Spectrometry (MS) has a number of features namely sensitivity, high dynamic range, high resolution, and versatility which make it a very powerful analytical tool for a wide spectrum of applications spanning all the life science fields. Among all the MS techniques, MALDI Imaging mass spectrometry (MALDI MSI) is currently one of the most exciting both for its rapid technological improvements, and for its great potential in high impact bioscience fields. Here, MALDI MSI general principles are described along with technical and instrumental details as well as application examples. Imaging MS instruments and imaging mass spectrometric techniques other than MALDI, are presented along with examples of their use. As well as reporting MSI successes in several bioscience fields, an attempt is made to take stock of what has been achieved so far with this technology and to discuss the analytical and technological advances required for MSI to be applied as a routine technique in clinical diagnostics, clinical monitoring and in drug discovery.


A 56-year-old man with sudden onset of portosystemic encephalopathy years after severe electrocution trauma.
A 56-year-old white male painter, with a history of major electrocution and deep thermal injury, developed mental status changes initially ascribed to an acute neurological event. Unexpectedly, magnetic resonance imaging (MRI) of the head showed areas of high signal intensity in the basal ganglia, which can be observed in advanced liver disease. An electroencephalogram (EEG) suggested metabolic encephalopathy and coexistent elevation of ammonia, indicative of significant liver disease. The patient had had a long history of right upper quadrant pain and fluctuation in liver tests following the electrocution trauma. For these symptoms, he underwent surgery 7 years prior to his current presentation of portosystemic encephalopathy, and was found to have a gangrenous acalculous cholecystitis. Intraoperative cholangiogram suggested possible strictures within the right hepatic ducts. Multiple liver biopsies, however, showed only steatosis. Current evaluation including liver biopsy, MRI, magnetic resonance angiography (MRA), and magnetic resonance cholangiopancreatography (MRCP), revealed progression to biliary cirrhosis with large bile duct obstruction, and hepatic artery thrombosis/occlusion with evidence of left lobe atrophy and right lobe compensatory hypertrophy. The pathobiology of ischemic bile duct injury is discussed herein. The case is an example of serious late sequelae of an occupational injury.


Local delivery of angiopoietin-2 into the preovulatory follicle terminates the menstrual cycle in rhesus monkeys.
The angiopoietin (ANGPT)-receptor (TEK) system plays a crucial role in blood vessel formation and stability. Because the endogenous agonist ANGPT1, antagonist ANGPT2, and TEK are expressed in the primate ovary, experiments were designed to investigate their role at a critical time during tissue remodeling/ angiogenesis in the menstrual cycle (i.e., at midcycle during maturation, ovulation, and luteinization of the dominant follicle). Either vehicle, 20 microg of ANGPT1, 2 microg of ANGPT2 (low-dose), or 20 microg of ANGPT2 (high-dose) was injected directly into the preovulatory follicle of monkeys around the day (-1 to 0) of the midcycle estradiol (E2)/LH peak. Ovaries were evaluated on Day 3 postinjection for follicle rupture, and serum samples were analyzed for levels of E2 and progesterone. Similar to controls, ANGPT1 treatment was followed by ovulation, and elevated progesterone levels during the luteal phase. In contrast, high-dose ANGPT2 treatment prevented follicle rupture, and progesterone levels never rose above baseline in the subsequent 12 days. However, an E2 peak typically occurred 12 days postinjection. Laparoscopy detected a preovulatory follicle on the contralateral (noninjected) ovary. Progesterone levels subsequently increased above baseline in these animals. Thus, exogenous ANGPT2 disrupted maturation of the preovulatory follicle, preventing its ovulation and conversion into the corpus luteum. ANGPT antagonism eliminated the dominant structure, thereby resetting the ovarian cycle, with selection and maturation of the next preovulatory follicle occurring in a timely manner. The data are consistent with a critical role of the ANGPT-TIE1/TEK system in the ovary, notably at the late stages of follicle maturation during the menstrual cycle.


Studies on the mode of uptake of blood triglycerides by the mammary gland of the lactating goat. The uptake and incorporation into milk fat and mammary lymph of labelled glycerol, fatty acids and triglycerides.
1. The mode of uptake of the precursors of milk fat by the mammary gland of the lactating goat has been examined by infusing radioactive fatty acids, glucerol or doubly labelled triglycerides into the mammary artery or jugular vein of animals surgically prepared to permit samples of arterial and venous blood to be withdrawn without disturbance to the animal. 2. Acetate was taken up by the mammary gland and incorporated into milk fat. The decrease in the specific radioactivity of blood acetate across the gland was evidence of acetate production, but there was no significant release of labelled lipid from the mammary gland. 3. When labelled long-chain fatty acids or glycerol were infused into the lactating goat, there was extensive transfer of radioactivity into milk in spite of the absence of net uptake of substrate by the mammary gland. The decrease in the specific radioactivity of each substrate across the mammary gland, however, showed that both fatty acids and glycerol were simultaneously taken up and released by mammary tissue. 4. The infusion of chylomicra and triglyceride emulsions labelled with (3)H and (14)C revealed that both glycerol and fatty acids were released during triglyceride uptake by mammary tissue. Changes in the (3)H/(14)C ratio during the transfer of triglyceride from blood into milk showed that at least 80% of the triglyceride was hydrolysed during uptake, but the potential re-utilization of both products of hydrolysis for triglyceride synthesis in mammary tissue implied that only a minimum value could be obtained from the change in the ratio. 5. The time-course of the transfer of (3)H and (14)C into milk and lymph were closely similar after the infusion of [2-(3)H]glycerol tri[1-(14)C]oleate or of a mixture of [2-(3)H]glycerol and [1-(14)C]oleate. 6. The results were consistent with the hypothesis that plasma triglycerides are extensively or completely hydrolysed during mammary uptake.


Carbon and chlorine isotope ratios of chlorinated ethenes migrating through a thick unsaturated zone of a sandy aquifer.
Compound-specific isotope analysis (CSIA) can potentially be used to relate vapor phase contamination by volatile organic compounds (VOCs) to their subsurface sources. This field and modeling study investigated how isotope ratios evolve during migration of gaseous chlorinated ethenes across a 18 m thick unsaturated zone of a sandy coastal plain aquifer. At the site, high concentrations of tetrachloroethene (PCE up to 380 μg/L), trichloroethene (TCE up to 31,600 μg/L), and cis-1,2-dichloroethene (cDCE up to 680 μg/L) were detected in groundwater. Chlorinated ethene concentrations were highest at the water table and steadily decreased upward toward the land surface and downward below the water table. Although isotopologues have different diffusion coefficients, constant carbon and chlorine isotope ratios were observed throughout the unsaturated zone, which corresponded to the isotope ratios measured at the water table. In the saturated zone, TCE became increasingly depleted along a concentration gradient, possibly due to isotope fractionation associated with aqueous phase diffusion. These results indicate that carbon and chlorine isotopes can be used to link vapor phase contamination to their source even if extensive migration of the vapors occurs. However, the numerical model revealed that constant isotope ratios are only expected for systems close to steady state.


The contamination levels of organochlorine pesticides in water and sediment samples in Uluabat Lake, Turkey.
The Uluabat Lake is a reservoir of 125 km2 surface area, in the boundaries of Bursa province, Turkey. The results showed that Uluabat Lake was still contaminated by organochlorine pesticides and their residues despite the existence of bans over a long time. Considerable amounts of organochlorine pesticides (HCB, p.p'-DDT, p.p'-DDE, alpha-, beta- and gamma-BHC, Aldrin, Heptachlor epoxide, Endrin, Endosulfan I and II) were detected in water and sediment samples during one-year study in this lake. Samples of water and sediment were collected in different regions, (6 sampling point) of the lake between February 2002 and November 2002. The mean levels of organochlorine pesticides in water and sediments were determined. According to results, it was found that various environs in Uluabat Lake were contaminated by 11 different organochlorine pesticides. Residue analyses showed that higher organochlorine pesticides and their residues were generally more accumulated in the sediment samples.


Complement-mediated production of plasma-membrane vesicles from rat fat-cells.
1. Rat isolated fat-cells were coated with rabbit anti-(rat erythrocyte) antibody and incubated with fresh guinea-pig serum for 25 min at 37 degrees C, which resulted in a more than 95% release of the cytosolic enzyme lactate dehydrogenase. 2. Under these conditions fragmentation of the plasma membrane was examined by following the plasma-membrane markers 5'-nucleotidase, adrenaline-sensitive adenylate cyclase and membrane-bound rabbit immunoglobulin G through a differential-centrifugation fractionation procedure. 3. Approx. 50% of the plasma-membrane markers remained associated with triacylglycerol. Of the remainder more than half was pelleted by centrifugation at 10 000 g for 30 min. 4. The 10 000 g supernatant was fractionated by centrifugation on a sucrose density gradient (15-50%, w/w). This procedure resulted in the production of two visible white bands on the density gradient. The bands consisted of vesicles derived from the plasma membrane, since they coincided with peaks of 5'-nucleotidase activity, contained membrane-bound immunoglobulin G and the denser one had adenylate cyclase activity. The phospholipid and protein contents of the vesicles were determined and compared with those in purified plasma membrane. 5. It is suggested that complement-mediated lysis of rat fat-cells caused the production of plasma-membrane vesicles that differ in composition from the whole plasma membrane.


AMP-activated protein kinase (AMPK)α2 plays a role in determining the cellular fate of glucose in insulin-resistant mouse skeletal muscle.
We determined whether: (1) an acute lipid infusion impairs skeletal muscle AMP-activated protein kinase (AMPK)α2 activity, increases inducible nitric oxide synthase (iNOS) and causes peripheral insulin resistance in conscious, unstressed, lean mice; and (2) restoration of AMPKα2 activity during the lipid infusion attenuates the increase in iNOS and reverses the defect in insulin sensitivity in vivo. Chow-fed, 18-week-old C57BL/6J male mice were surgically catheterised. After 5 days they received: (1) a 5 h infusion of 5 ml kg(-1) h(-1) Intralipid + 6 U/h heparin (Lipid treatment) or saline (Control); (2) Lipid treatment or Control, followed by a 2 h hyperinsulinaemic-euglycaemic clamp (insulin clamp; 4 mU kg(-1) min(-1)); and (3) infusion of the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) (1 mg kg(-1) min(-1)), or saline during Lipid treatment, followed by a 2 h insulin clamp. In a separate protocol, mice producing a muscle-specific kinase-dead AMPKα2 subunit (α2-KD) underwent an insulin clamp to determine the role of AMPKα2 in insulin-mediated muscle glucose metabolism. Lipid treatment decreased AMPKα2 activity, increased iNOS abundance/activation and reduced whole-body insulin sensitivity in vivo. AICAR increased AMPKα2 activity twofold; this did not suppress iNOS or improve whole-body or tissue-specific rates of glucose uptake during Lipid treatment. AICAR caused a marked increase in insulin-mediated glycogen synthesis in skeletal muscle. Consistent with this latter result, lean α2-KD mice exhibited impaired insulin-stimulated glycogen synthesis even though muscle glucose uptake was not affected. Acute induction of insulin resistance via lipid infusion in healthy mice impairs AMPKα2, increases iNOS and causes insulin resistance in vivo. However, these changes do not appear to be interrelated. Rather, a functionally active AMPKα2 subunit is required for insulin-stimulated muscle glycogen synthesis.


Phthalates, Pesticides, and Bisphenol-A Exposure and the Development of Nonoccupational Asthma and Allergies: How Valid Are the Links?
Phthalates, pesticides, and bisphenol-A (BPA) are three groups of chemicals, implicated in endocrine disruption and commonly found in the local environment, that have been implicated in the pathogenesis of asthma and allergies [1-3]. Multiple observational studies have demonstrated an association between exposure to phthalates and the development of asthma and allergies in humans. Associations with exposure to pesticides and BPA and the development of respiratory disease are less clear. However, recent evidence suggests that prenatal or early postnatal exposure to BPA may be deleterious to the developing immune system. Future cohort-driven epidemiological or translational research should focus on determining whether these ubiquitous chemicals contribute to the development of asthma and allergies in humans, and attempt to establish the routes and mechanisms by which they operate. Determining dose-response relationships will be important to establishing safe levels of these chemicals in the environment and in consumer products. Attempts to reduce exposures to chemicals such as phthalates, pesticides, and BPA may have environmental repercussions as well as public health impact for the developing child.


The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome.
Molecular mimicry of Campylobacter jejuni lipo-oligosaccharides (LOS) with gangliosides in nervous tissue is considered to induce cross-reactive antibodies that lead to Guillain-Barre syndrome (GBS), an acute polyneuropathy. To determine whether specific bacterial genes are crucial for the biosynthesis of ganglioside-like structures and the induction of anti-ganglioside antibodies, we characterized the C. jejuni LOS biosynthesis gene locus in GBS-associated and control strains. We demonstrated that specific types of the LOS biosynthesis gene locus are associated with GBS and with the expression of ganglioside-mimicking structures. Campylobacter knockout mutants of 2 potential GBS marker genes, both involved in LOS sialylation, expressed truncated LOS structures without sialic acid, showed reduced reactivity with GBS patient serum, and failed to induce an anti-ganglioside antibody response in mice. We demonstrate, for the first time, to our knowledge, that specific bacterial genes are crucial for the induction of anti-ganglioside antibodies.


[Predictors of operative blood loss in patients undergoing small incision radical prostatectomy].
We performed 82 cases of small incision radical prostatectomy from July, 2003 to September, 2009. There were 38 cases of cT1c, 41 cases of cT2, and 3 cases of cT3. Mean operative time was 222 +/- 31.7 (min.). Mean operative blood loss was 1,232 +/- 583 (ml). We evaluated factors predicting operative blood loss, such as prostate volume, body mass index (BMI), age, and preoperative PSA level. Group with smaller prostate volume and group with lower BMI showed significantly less blood loss compared to that of a higher group (p = 0.0009, p = 0.0014, respectively). Multivariate analysis showed that prostate volume and BMI were significant predictors for operative blood loss (p = 0.0005, p = 0.0122, respectively). Prostate volume and BMI may be a useful predictor for operative blood loss.


Dermatrophye test medium: evaluation with nondermatophytic pathogens.
The growth and color change produced on dermatophyte test medium (DTM) by 25 strains of zoopathogenic fungi associated with human skin lesions were evaluated quantitatively. DTM only partially suppressed the development of nondermatophytes, with total growth in most instances comparable with that observed with dermatophytes. Whereas all dermatophytes induced a rapid color change on DTM, several nondermatophytic pathogens induced an equally intense and almost as rapid conversion. The rapidity of this color change and the colonial morphology of these forms on DTM could cause their misidentification as dermatophytes under clinical conditions.


Involvement of local renin-angiotensin system in immunosuppression of tumor microenvironment.
To improve current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSC) which were shown to be negative factors in immune-checkpoint blockade therapy, need to be developed. In the present study, we evaluated the role of the local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Giving angiotensin II receptor blockers (ARB) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells. ARB administration did not change the numbers of CD11b+ myeloid cells in tumors, but significantly reduced their T-cell inhibitory ability along with decreased production of various immunosuppressive factors including interleukin (IL)-6, IL-10, vascular endothelial growth factor (VEGF), and arginase by CD11b+ cells in tumors. ARB also decreased expression of immunosuppressive factors such as chemokine ligand 12 and nitric oxide synthase 2 in cancer-associated fibroblasts (CAF). Last, combination of ARB and anti-programmed death-ligand 1 (PD-L1) antibodies resulted in significant augmentation of anti-tumor effects in a CD8+ T cell-dependent way. These results showed that RAS is involved in the generation of an immunosuppressive tumor microenvironment caused by myeloid cells and fibroblasts, other than the previously shown proliferative and angiogenetic properties of cancer cells and macrophages, and that ARB can transform the immunosuppressive properties of MDSC and CAF and could be used in combination with PD-1/PD-L1 immune-checkpoint blockade therapy.


Keeping Up with Insect Pollinators in Paris.
There is growing interest in urban pollinator communities, although they may be subject to biotic homogenization in densely artificial landscapes. Paris (France) is one of the densest cities in the world, yet over the years many insect pollinator species have been reported there. We conducted in-depth surveys of Parisian green spaces for two years, in order to improve our knowledge of these assemblages. We explored several types of green spaces, monitoring pollinators throughout their activity season. We listed 118 species of wild bees and 37 species of hoverflies, updating pre-existing lists with 32 additional species. Bee assemblages showed functional diversity with 18.5% parasitic species and 17.7% oligolectic species. We also found several bee and hoverfly species under special conservation status. Over the study period, we observed seasonal succession of species, with diversified phenological niches. The greatest taxonomic and functional diversity was found in green spaces combining several habitats with ecological management. Despite its very dense urbanism, Paris is home to diverse pollinator communities. As a result, nearly half of the wild bee species of the wider Ile-de-France administrative region can be found within the city. This highlights the need to also consider dense urban environments in insect pollinator conservation strategies.


The relationship between nursing home quality and costs: Evidence from the VA.
Ensuring quality of care in nursing homes is a public health priority, yet how nursing home quality relates to cost is not well understood. This paper addresses this relationship for 132 VA community living centers (nursing homes), for fiscal years 2014 and 2015. We estimated cost models using the VA Decision Support System which tracks total direct costs and nursing direct costs for individual resident segments of care. We summed residents' total costs and nursing costs to the community living center level for each year. Annual facility costs then were regressed on quality of care measured with composite scores based on 13 distinct adverse events. Results indicated that higher quality was associated with higher predicted cost. However, we did not find evidence that higher costs were driven by high nurse staffing levels.


Leadership Training in Endocrinology Fellowship? A Survey of Program Directors and Recent Graduates.
There is growing recognition that more physician leaders are needed to navigate the next era of medicine. To determine current opinions about leadership training in endocrinology fellowship programs. Twenty-seven-question survey addressing various aspects of leadership training to current nationwide fellowship program directors (PDs) and fellowship graduates since 2010. In partnership with the Endocrine Society, the electronic survey was advertised primarily via direct e-mail. It was open from March through July 2016. The survey addressed leadership traits, importance of leadership training, preferred timing, and content of leadership training. Forty-six of 138 PDs (33.3%) and 147 of 1769 graduates (8.3%) completed the survey. Among PDs and graduates, there was strong agreement (>95%) about important leadership characteristics, including job knowledge, character traits, team-builder focus, and professional skills. PDs (64.5%) and graduates (60.8%) favored teaching leadership skills during fellowship, with PDs favoring mentoring/coaching (75.0%), direct observation of staff clinicians (72.5%), and seminars (72.5%). Graduates favored a variety of approaches. Regarding topics to include in a leadership curriculum, PDs responded that communication skills (97.5%), team building (95.0%), professional skills (90.0%), clinic management (87.5%), strategies to impact the delivery of endocrinology care (85.0%), and personality skills (82.5%) were most important. Graduates responded similarly, with >80% agreement for each topic. Finally, most PDs (89%) expressed a desire to incorporate more leadership training into their programs. Our survey suggests a need for leadership training in endocrinology fellowships. More work is needed to determine how best to meet this need.