[The treatment of ductal carcinoma in situ (DCIS) of the breast].
Ductal carcinoma in situ (DCIS) of the breast is diagnosed more and more often in the Netherlands as a result of mammographic population screening and improved mammography techniques. Mastectomy and local excision, with or without radiotherapy, are used for the treatment of DCIS, but breast-conserving therapy seems a logical option in view of the favourable prognosis. Radiotherapy following total excision of DCIS reduces the local recurrence rate by half. Incomplete excision of DCIS is associated with a higher rate of local recurrence, which is invasive in about 50% of the cases and can therefore affect the prognosis adversely. There are conflicting opinions in the literature as to which patients with DCIS can be treated with breast-conserving therapy and whether local excision should be followed by radiotherapy, as is the case for breast-conserving treatment of invasive mammary carcinoma. The diagnosis and treatment of DCIS are therefore complex and require a multidisciplinary approach. Patients may be selected for breast-conserving therapy on the basis of diagnostic characteristics and risk factors.


Severe disease in adult dairy cattle in three UK dairy herds associated with BVD virus infection.
During 1993 outbreaks of diarrhoea in adult dairy cows in three geographically unrelated herds were found to be caused by bovine viral diarrhoea virus (BVDV). The affected animals showed signs of acute watery diarrhoea, agalactia and pyrexia (39.4 to 42 degrees C). Ulceration of the buccal mucosa, a mucoid nasal discharge and stiffness were inconsistent signs. The disease spread rapidly in each case. The diagnosis was confirmed by the isolation of non-cytopathic BVDV from blood and tissues and by the demonstration of significantly rising titres to BVDV by an ELISA. The highest morbidity recorded was 40 per cent with one herd experiencing a 10 per cent mortality. There was no increased incidence of abortion in any of the herds, either at the time of or subsequent to the outbreaks of diarrhoea. In one herd the purchase of a persistently viraemic heifer 14 days before the outbreak was thought to be the source of infection, but in the other two herds the source was not established.


Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach.
Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases.


CD1c restricts responses of mycobacteria-specific T cells. Evidence for antigen presentation by a second member of the human CD1 family.
Previous studies suggest that CD1 is a family of Ag-presenting molecules distantly related to those encoded by the MHC. However, of the four known human CD1 proteins, only CD1b has been shown to restrict Ag-specific T cell responses. In this study, we have shown that a second member of the human CD1 family, CD1c, could also mediate Ag presentation to T cells. Three T cell lines recognizing mycobacterial Ags in a CD1c-restricted manner were isolated from normal donor blood. These T cells were MHC unrestricted, and their recognition of Ag was independent of the products of the transporter associated with Ag presentation-1/2 and DMA/B genes that are generally required for Ag presentation by MHC-encoded Ag-presenting molecules. Furthermore, unlike MHC-restricted responses to peptides, the CD1c-restricted T cell lines recognized protease-resistant mycobacterial lipid Ags. These T cell lines also showed significant cytotoxicity toward CD1c-expressing target cells even in the absence of mycobacterial Ags, which was shown by clonal analysis to be mediated by a subpopulation of T cells directly reactive to CD1c molecules. Our findings establish the ability of a second member of the CD1 family to restrict responses of Ag-specific T cells, and thus support the general hypothesis that the CD1 family comprises a third lineage of Ag-presenting molecules that presents a novel class of foreign and self Ags to MHC-unrestricted T cells.


Effect of prenatal and postnatal photoperiod on spermatogenic development in the Djungarian hamster (Phodopus sungorus sungorus).
The effect of the pre- and postnatal daylength on the start of spermatogenesis and further testicular development from day 4 up to day 127 was investigated in Djungarian hamsters. Hamsters were either gestated under long (16 h light:8 h dark) photoperiod and reared under long or short (4 h light:20 h dark) photoperiod after birth (L/L and L/S hamsters, respectively), or gestated under short photoperiod and transferred to long photoperiod after birth (S/L hamsters). In L/L and L/S hamsters, spermatogenesis started between day 4 and day 5 (day of birth = day 1), when the first gonocytes entered the S-phase. A, Intermediate and B spermatogonia were first observed on days 6, 8 and 9, respectively. The proliferation pattern of gonocytes and Sertoli cells, studied between day 4 and day 9, did not differ between L/L and L/S hamsters. Hence, the duration of the postnatal photoperiod had no effect on the start of spermatogenesis. The first effect of postnatal photoperiod on spermatogenic development was observed on day 15, when testis weights and tubular diameters were reduced in L/S animals. From day 22 onwards, spermatogenesis was arrested mainly at the mid-pachytene stage, no tubular lumen was formed, and the number of preleptotene spermatocytes was reduced. The ultimate number of Sertoli cells per testis was not affected by postnatal short photoperiod. The duration of the prenatal photoperiod had a clear effect on spermatogenesis after birth. In S/L hamsters, the number of gonocytes per tubular cross-section was reduced on day 4 and 4.5. Gonocyte proliferation was reduced on day 5 and spermatogenesis started one day later. Consequently, A and Intermediate spermatogonia appeared on day 7 and 9, respectively. Sertoli cell proliferation was also shifted to later ages, but the ultimate number of Sertoli cells did not differ from L/L or L/S hamsters. From day 29 onwards, the number of preleptotene spermatocytes was increased in S/L hamsters, indicating that the Sertoli cells in these animals could support more germinal cells. In conclusion, a short postnatal photoperiod does not affect spermatogenesis before day 15 after birth, when further testicular development becomes arrested. A short prenatal photoperiod delays the start of spermatogenesis by one day, alters the proliferation pattern of Sertoli cells, and from day 29 onwards, enables the Sertoli cells to support more germinal cells. The duration of the pre- and postnatal photoperiod did not affect the ultimate number of Sertoli cells.


Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells.
Mitragyna speciosa Korth (M. speciosa) has been widely used as a recreational product, however, there are growing concerns on the abuse potentials and toxicity of the plant. Several poisoning and fatal cases involving kratom and mitragynine have been reported but the underlying causes remain unclear. The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit underlying cardiac rapidly delayed rectifier potassium current (IKr). Pharmacological blockade of the IKr can cause acquired long QT syndrome, leading to lethal cardiac arrhythmias. This study aims to elucidate the mechanisms of mitragynine-induced inhibition on hERG1a/1b current. Electrophysiology experiments were carried out using Port-a-Patch system. Quantitative RT-PCR, Western blot analysis, immunofluorescence and co-immunoprecipitation methods were used to determine the effects of mitragynine on hERG1a/1b expression and hERG1-cytosolic chaperones interaction. Mitragynine was found to inhibit the IKr current with an IC50 value of 332.70 nM. It causes a significant reduction of the fully-glycosylated (fg) hERG1a protein expression but upregulates both core-glycosylated (cg) expression and hERG1a-Hsp90 complexes, suggesting possible impaired hERG1a trafficking. In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.


How to cope in heterogeneous coastal environments: Spatio-temporally endogenous circadian rhythm of valve gaping by mussels.
Transitional coastal zones are subject to high degrees of temporal fluctuation in environmental conditions, with these patterns varying in space. Gaining an in depth understanding of how sessile organisms cope with and respond to such environmental changes at multiple scales is needed to i) advance fundamental knowledge, ii) predict how organisms may react to stressors and iii) support the management of halieutic resources in transitional coastal areas. We addressed this question using mussels (Mytilus galloprovincialis) as model system. Valve-gaping sensor were deployed at multiple sites within the southern Venice Lagoon over a period of 6 months, to investigate the existence of periodicity in valve-gaping and its relationship with environmental variables, such as temperature and chlorophyll-a. Gaping behaviour was found to have periodic rhythms, of ~12 h and ~ 24 h, which were most pronounced in the inner part of lagoon part and were strongest during summer months. In autumn, the dual periodicity became weaker and mostly the 12 h remained. Gaping was closely linked with tide, but the relationship in terms of phasing varied upon location. Surprisingly, no clear direct relationships were found with chlorophyll-a, but food delivery may be mediated by tide itself. The results highlight the heterogeneity of behaviour and the endogenic nature of circadian rhythms in space and time. These findings have important implications for management of transitional areas where tidal alteration may have impacts on key behaviours, and emphasize the importance of characterizing their rhythms before using these as stress indicator. Moreover, the described tidal relationships should be included in growth models of bivalves in these systems.


Learning to pronounce first words in three languages: an investigation of caregiver and infant behavior using a computational model of an infant.
Words are made up of speech sounds. Almost all accounts of child speech development assume that children learn the pronunciation of first language (L1) speech sounds by imitation, most claiming that the child performs some kind of auditory matching to the elements of ambient speech. However, there is evidence to support an alternative account and we investigate the non-imitative child behavior and well-attested caregiver behavior that this account posits using Elija, a computational model of an infant. Through unsupervised active learning, Elija began by discovering motor patterns, which produced sounds. In separate interaction experiments, native speakers of English, French and German then played the role of his caregiver. In their first interactions with Elija, they were allowed to respond to his sounds if they felt this was natural. We analyzed the interactions through phonemic transcriptions of the caregivers' utterances and found that they interpreted his output within the framework of their native languages. Their form of response was almost always a reformulation of Elija's utterance into well-formed sounds of L1. Elija retained those motor patterns to which a caregiver responded and formed associations between his motor pattern and the response it provoked. Thus in a second phase of interaction, he was able to parse input utterances in terms of the caregiver responses he had heard previously, and respond using his associated motor patterns. This capacity enabled the caregivers to teach Elija to pronounce some simple words in their native languages, by his serial imitation of the words' component speech sounds. Overall, our results demonstrate that the natural responses and behaviors of human subjects to infant-like vocalizations can take a computational model from a biologically plausible initial state through to word pronunciation. This provides support for an alternative to current auditory matching hypotheses for how children learn to pronounce.


Multimodal neuromarkers in schizophrenia via cognition-guided MRI fusion.
Cognitive impairment is a feature of many psychiatric diseases, including schizophrenia. Here we aim to identify multimodal biomarkers for quantifying and predicting cognitive performance in individuals with schizophrenia and healthy controls. A supervised learning strategy is used to guide three-way multimodal magnetic resonance imaging (MRI) fusion in two independent cohorts including both healthy individuals and individuals with schizophrenia using multiple cognitive domain scores. Results highlight the salience network (gray matter, GM), corpus callosum (fractional anisotropy, FA), central executive and default-mode networks (fractional amplitude of low-frequency fluctuation, fALFF) as modality-specific biomarkers of generalized cognition. FALFF features are found to be more sensitive to cognitive domain differences, while the salience network in GM and corpus callosum in FA are highly consistent and predictive of multiple cognitive domains. These modality-specific brain regions define-in three separate cohorts-promising co-varying multimodal signatures that can be used as predictors of multi-domain cognition.


Assessment of linear and nonlinear synchronization measures for analyzing EEG in a mild epileptic paradigm.
Epilepsy is one of the most common brain disorders and may result in brain dysfunction and cognitive disturbances. Epileptic seizures usually begin in childhood without being accommodated by brain damage and are tolerated by drugs that produce no brain dysfunction. In this study, cognitive function is evaluated in children with mild epileptic seizures controlled with common antiepileptic drugs. Under this prism, we propose a concise technical framework of combining and validating both linear and nonlinear methods to efficiently evaluate (in terms of synchronization) neurophysiological activity during a visual cognitive task consisting of fractal pattern observation. We investigate six measures of quantifying synchronous oscillatory activity based on different underlying assumptions. These measures include the coherence computed with the traditional formula and an alternative evaluation of it that relies on autoregressive models, an information theoretic measure known as minimum description length, a robust phase coupling measure known as phase-locking value, a reliable way of assessing generalized synchronization in state-space and an unbiased alternative called synchronization likelihood. Assessment is performed in three stages; initially, the nonlinear methods are validated on coupled nonlinear oscillators under increasing noise interference; second, surrogate data testing is performed to assess the possible nonlinear channel interdependencies of the acquired EEGs by comparing the synchronization indexes under the null hypothesis of stationary, linear dynamics; and finally, synchronization on the actual data is measured. The results on the actual data suggest that there is a significant difference between normal controls and epileptics, mostly apparent in occipital-parietal lobes during fractal observation tests.


The Swedish Regional Climate Modelling Programme, SWECLIM: a review.
The Swedish Regional Climate Modelling Programme, SWECLIM, was a 6.5-year national research network for regional climate modeling, regional climate change projections and hydrological impact assessment and information to a wide range of stakeholders. Most of the program activities focussed on the regional climate system of Northern Europe. This led to the establishment of an advanced, coupled atmosphere-ocean-hydrology regional climate model system, a suite of regional climate change projections and progress on relevant data and process studies. These were, in turn, used for information and educational purposes, as a starting point for impact analyses on different societal sectors and provided contributions also to international climate research.


Species differences in the expression of multiple tyrosine hydroxylase protein isoforms.
In subprimates, a single form of tyrosine hydroxylase (TH) is expressed, whereas two TH protein isoforms have been identified in monkeys and four isoforms have been demonstrated in humans. In order to establish the evolutionary pattern/emergence of these multiple TH isoforms, adrenal medullae from different mammalian species were analyzed by blot immunolabeling using pan-specific TH antibodies and antibodies specific to each of the four human TH isoforms. The expression of multiple TH isoforms was primate specific and restricted to anthropoids: only a single TH isoform was detected in adrenal medullae from several subprimate and prosimian species (six species from four families), while two TH isoforms were found in all of the anthropoid species studied. The presence of four TH isoforms could only be demonstrated in human specimens. Contrary to previous suggestions, only one TH protein isoform was found in rats and only four TH protein isoforms were found in humans.


Integrity of disposable nitrile exam gloves exposed to simulated movement.
Every year, millions of health care, first responder, and industry workers are exposed to chemical and biological hazards. Disposable nitrile gloves are a common choice as both a chemical and physical barrier to these hazards, especially as an alternative to natural latex gloves. However, glove selection is complicated by the availability of several types or formulations of nitrile gloves, such as low-modulus, medical grade, low filler, and cleanroom products. This study evaluated the influence of simulated movement on the physical integrity (i.e., holes) of different nitrile exam glove brands and types. Thirty glove products were evaluated out-of-box and after exposure to simulated whole-glove movement for 2 hr. In lieu of the traditional 1 L water-leak test, a modified water-leak test, standardized to detect a 0.15 ± 0.05 mm hole in different regions of the glove, was developed. A specialized air inflation method simulated bidirectional stretching and whole-glove movement. A worst-case scenario with maximum stretching was evaluated. On average, movement did not have a significant effect on glove integrity (chi-square; p=0.068). The average effect was less than 1% between no movement (1.5%) and movement (2.1%) exposures. However, there was significant variability in glove integrity between different glove types (p≤0.05). Cleanroom gloves, on average, had the highest percentage of leaks, and 50% failed the water-leak test. Low-modulus and medical grade gloves had the lowest percentages of leaks, and no products failed the water-leak test. Variability in polymer formulation was suspected to account for the observed discrepancies, as well as the inability of the traditional 1 L water-leak test to detect holes in finger/thumb regions. Unexpectedly, greater than 80% of the glove defects were observed in the finger and thumb regions. It is recommended that existing water-leak tests be re-evaluated and standardized to account for product variability.


Anticancer activities of alkaloids extracted from the Ba lotus seed in human nasopharyngeal carcinoma CNE-1 cells.
To investigate the anticancer activities of alkaloids from the Ba lotus seed (BLSA) in human nasopharyngeal carcinoma (NPC) CNE-1 cells, an MTT assay, flow cytometry, reverse transcription-polymerase chain reaction and western blotting were performed. BLSA was found to significantly reduce CNE-1 cell proliferation in a dose-dependent manner at all concentrations compared with the control (P<0.05). In addition, flow cytometry analysis identified that BLSA treatment significantly increased the sub-G1 content in CNE-1 cells (P<0.05). Following BLSA treatment, the mRNA and protein levels of a number of apoptosis-related factors, such as caspase family members (caspase-3, -8 and -9), B-cell lymphoma (Bcl)-2-associated X protein, Fas and Fas ligand were significantly increased compared with the control (P<0.05). This was accompanied by a significant decrease in anti-apoptotic Bcl-2 and Bcl-extra large protein expression compared with the control (P<0.05). Furthermore, BLSA treatment was determined to modulate CNE-1 cell expression of nuclear factor (NF)-κB and NF-κB inhibitor α. The results of the present study indicate that BLSA has anticancer activity through inducing cellular apoptosis. In addition, these results suggest that BLSA can be used as a therapeutic agent in NPC.


Phylogenetic comparison of the S3 gene of United States prototype strains of bluetongue virus with that of field isolates from California.
To better define the molecular epidemiology of bluetongue virus (BTV) infection, the genetic characteristics and phylogenetic relationships of the S3 genes of the five U.S. prototype strains of BTV, the commercially available serotype 10 modified live virus vaccine, and 18 field isolates of BTV serotypes 10, 11, 13, and 17 obtained in California during 1980, 1981, 1989, and 1990 were determined. With the exception of the S3 gene of the U.S. prototype strain of BTV serotype 2 (BTV 2), these viruses had an overall sequence homology of between 95 and 100%. Phylogenetic analyses segregated the prototype U.S. BTV 2 strain to a unique branch (100% bootstrap value), whereas the rest of the viruses clustered in two main monophyletic groups that were not correlated with their serotype, year of isolation, or geographical origin. The lack of consistent association between S3 gene sequence and virus serotype likely is a consequence of reassortment of BTV gene segments during natural mixed infections of vertebrate and invertebrate hosts. The prototype strain of BTV 13, which is considered an introduction to the U.S. like BTV 2, presents an S3 gene which is highly homologous to those of some isolates of BTV 10 and especially to that of the vaccine strain. This finding strongly suggests that the U.S. prototype strain of BTV 13 is a natural reassortant. The different topologies of the phylogenetic trees of the L2 and S3 genes of the various viruses indicate that these two genome segments evolve independently. We conclude that the S3 gene segment of populations of BTV in California is formed by different consensus sequences which cocirculate and which cannot be grouped by serotype.


Psychiatric aspects of women's health.
A number of psychiatric disorders are present exclusively or more commonly in women. Furthermore, within a particular disorder there may be significant gender differences across demographic and clinical variables, and neurobiological fluctuations across women's menstrual and life cycles may affect the psychobiology of disorders and the pharmacokinetics of pharmacotherapies. Indeed, exploration of gender may serve as a useful heuristic for advancing the field as a whole and for integrating epidemiological and psychobiological data. In this supplement, we highlight three issues that fall under the rubric of 'women's mental health'; premenstrual dysphoric disorder, pharmacotherapy during pregnancy and lactation, and violent trauma and post-traumatic stress disorder in women. Although further work across the range of basic, clinical, and sociopolitical fronts is needed, advances in the pharmacotherapy of premenstrual dysphoric disorder, recent safety data on certain agents in pregnancy, and progress in the management of post-traumatic stress disorder provides cause for clinical


Using appreciative inquiry to help students identify strategies to overcome handicaps of their learning styles.
In India, as in some other neighboring Asian countries, students and teachers are generally unaware of the differences in the learning styles among learners, which can handicap students with learning styles alien to the common teaching/learning modality within the institution. This study aims to find out whether making students aware of their learning styles and then using the Appreciative Inquiry approach to help them discover learning strategies that worked for them and others with similar learning styles within the institution made them perceive that this experience improved their learning and performance in exams. The visual, auditory, read-write, and kinesthetic (VARK) inventory of learning styles questionnaire was administered to all 100 first-year medical students of the Father Muller's Medical College in Mangalore India to make them aware of their individual learning styles. An Appreciate Inquiry intervention was administered to 62 student volunteers who were counseled about the different learning styles and their adaptive strategies. Pre and post intervention change in student's perception about usefulness of knowing learning styles on their learning, learning behavior, and performance in examinations was collected from the students using a prevalidated questionnaire. Post intervention mean scores showed a significant change (P < 0.0001) in student's self-perceptions about usefulness of knowing one's learning style and discovering strategies that worked within the institutional environment. There was agreement among students that the intervention helped them become more confident in learning (84%), facilitating learning in general (100%), and in understanding concepts (100%). However, only 29% of the students agreed that the intervention has brought about their capability improvement in application of learning and 31% felt it improved their performance in exams. Appreciate Inquiry was perceived as useful in helping students discover learning strategies that work for different individual learning styles and sharing them within the group helped students choose strategies to help overcome the handicap presented by the school's teaching methods.


Binding of SEC11 indicates its role in SNARE recycling after vesicle fusion and identifies two pathways for vesicular traffic to the plasma membrane.
SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins drive vesicle fusion in all eukaryotes and contribute to homeostasis, pathogen defense, cell expansion, and growth in plants. Two homologous SNAREs, SYP121 (=SYR1/PEN1) and SYP122, dominate secretory traffic to the Arabidopsis thaliana plasma membrane. Although these proteins overlap functionally, differences between SYP121 and SYP122 have surfaced, suggesting that they mark two discrete pathways for vesicular traffic. The SNAREs share primary cognate partners, which has made separating their respective control mechanisms difficult. Here, we show that the regulatory protein SEC11 (=KEULE) binds selectively with SYP121 to affect secretory traffic mediated by this SNARE. SEC11 rescued traffic block by dominant-negative (inhibitory) fragments of both SNAREs, but only in plants expressing the native SYP121. Traffic and its rescue were sensitive to mutations affecting SEC11 interaction with the N terminus of SYP121. Furthermore, the domain of SEC11 that bound the SYP121 N terminus was itself able to block secretory traffic in the wild type and syp122 but not in syp121 mutant Arabidopsis. Thus, SEC11 binds and selectively regulates secretory traffic mediated by SYP121 and is important for recycling of the SNARE and its cognate partners.


Automatic estimation of point-spread-function for deconvoluting out-of-focus optical coherence tomographic images using information entropy-based approach.
This paper proposes an automatic point spread function (PSF) estimation method to de-blur out-of-focus optical coherence tomography (OCT) images. The method utilizes Richardson-Lucy deconvolution algorithm to deconvolve noisy defocused images with a family of Gaussian PSFs with different beam spot sizes. Then, the best beam spot size is automatically estimated based on the discontinuity of information entropy of recovered images. Therefore, it is not required a prior knowledge of the parameters or PSF of OCT system for de-convoluting image. The model does not account for the diffraction and the coherent scattering of light by the sample. A series of experiments are performed on digital phantoms, a custom-built phantom doped with microspheres, fresh onion as well as the human fingertip in vivo to show the performance of the proposed method. The method may also be useful in combining with other deconvolution algorithms for PSF estimation and image recovery.


Comparative Genomic Analysis of Virulence, Antimicrobial Resistance, and Plasmid Profiles of Salmonella Dublin Isolated from Sick Cattle, Retail Beef, and Humans in the United States.
Salmonella enterica serovar Dublin is a host-adapted serotype associated with typhoidal disease in cattle. While rare in humans, it usually causes severe illness, including bacteremia. In the United States, Salmonella Dublin has become one of the most multidrug-resistant (MDR) serotypes. To understand the genetic elements that are associated with virulence and resistance, we sequenced 61 isolates of Salmonella Dublin (49 from sick cattle and 12 from retail beef) using the Illumina MiSeq and closed 5 genomes using the PacBio sequencing platform. Genomic data of eight human isolates were also downloaded from NCBI (National Center for Biotechnology Information) for comparative analysis. Fifteen Salmonella pathogenicity islands (SPIs) and a spv operon (spvRABCD), which encodes important virulence factors, were identified in all 69 (100%) isolates. The 15 SPIs were located on the chromosome of the 5 closed genomes, with each of these isolates also carrying 1 or 2 plasmids with sizes between 36 and 329 kb. Multiple antimicrobial resistance genes (ARGs), including blaCMY-2, blaTEM-1B, aadA12, aph(3')-Ia, aph(3')-Ic, strA, strB, floR, sul1, sul2, and tet(A), along with spv operons were identified on these plasmids. Comprehensive antimicrobial resistance genotypes were determined, including 17 genes encoding resistance to 5 different classes of antimicrobials, and mutations in the housekeeping gene (gyrA) associated with resistance or decreased susceptibility to fluoroquinolones. Together these data revealed that this panel of Salmonella Dublin commonly carried 15 SPIs, MDR/virulence plasmids, and ARGs against several classes of antimicrobials. Such genomic elements may make important contributions to the severity of disease and treatment failures in Salmonella Dublin infections in both humans and cattle.


Small bowel bacterial overgrowth in patients with alcoholic cirrhosis.
A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid.


Intra-abdominal Candida spp infection in acute abdomen in a quality assurance (QA)-certified academic setting.
To evaluate the contribution of light microscopy to detecting Candida spp infection in patients with complicated intra-abdominal infections (IAIs) admitted for acute abdomen to a quality assurance (QA)-certified surgical emergency ward. We conducted a retrospective study (2008-2012) of 809 abdominal intraoperative or biopsy tissue specimens obtained from patients admitted with acute abdomen and microbiological samples positive for Candida spp. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, antimicrobial therapy were collected and analysed. Any comments at the multidisciplinary team meeting was recorded in minutes of and approved. Sixty-six patients with complicated IAIs due to Candida spp were identified (39 male, 27 female, mean±SD age 75±20 years). Candida albicans was isolated in 35 cases and Candida non-albicans spp in 31 cases. Candida spp were isolated from blood in 50% of all selected microbiological specimens. Patients were stratified according to Candida spp (albicans vs non-albicans), underlying cancer disease and no previous antimicrobial administration, and a positive correlation with C. albicans isolation was found (p=0.009 and p=0.048, respectively). Out of 41 cases with microscopic evaluation, we identified yeast forms, pseudohyphae or both, indicative of Candida spp, in 23. Identification of Candida spp in histological specimens was higher in C. albicans cases than in C. non-albicans cases (73% vs 37.5%). Microscopy allowed prompt treatment of all patients. Light microscopy still has great diagnostic significance, being a solid QA step. It provides rapid information and clues in patients who may harbour impaired defence mechanisms, concurrent chronic conditions and/or cancer.


A biomechanical study of the Charleston brace for the treatment of scoliosis.
A biomechanical study of the Charleston brace. To model the nighttime Charleston brace treatment and study its biomechanical action. The Charleston brace has been proposed as an alternative to the traditional daytime thoracolumbosacral orthosis for the treatment of moderate scoliotic deformities. It is worn at night and imposes a supine side-bending to reduce the major scoliotic curve. The biomechanics of the Charleston brace is still poorly understood. The geometry of the spine, pelvis, rib cage, and of the external trunk surface of 2 scoliotic patients were acquired using a 3-dimensional multiview radiograph reconstruction technique and surface topography. A finite element model of each patient's trunk was created. Two sets of mechanical properties (stiff and normal) of the spine were tested. For each case, the transition from standing to supine position was first simulated by modifying the direction of the gravity forces acting on the patients' spine. Supine bending was simulated by applying a lateral displacement on the first thoracic vertebra. A custom-fit Charleston brace was modeled and positioned on the patient model. Tension was applied in the straps. Efficiency of the simulated Charleston braces was studied by computing geometrical corrections and effects on the internal stresses of the spine. The reduction of the major scoliotic curve varied between 58% and 97% and was in the range of published clinical data. Internal compressive stresses up to 1 MPa were generated on the convex side of the major scoliotic curve and tensile stresses up to 1 MPa on its concavity. In contrast, increased compressive stresses were exerted on the concavity of the secondary curves and added tensile stresses in their convexity. This study quantified the Charleston brace's biomechanical effect, which consists in inverting the asymmetrical compressive loading in the major scoliotic curve. It also highlighted that the Charleston brace worsens the asymmetrical compressive loading in the compensatory curves. The finite element model developed could help studying different brace designs and optimizing brace efficiency.


Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach.
With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects.


Clinical Relevance of Biomarkers of Oxidative Stress.
Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker.


Obesity promotes oxidative stress and exacerbates sepsis-induced brain damage.
Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. It is not novel that in sepsis the brain is one of the first organs affected which causes an increase in morbidity and mortality and its consequences may be exacerbated when associated with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of the present study is to evaluate the susceptibility to brain damage after sepsis in obese rats. During two months, Wistar rats, 60 days, 250-300g received hypercaloric nutrition to induce obesity. Sepsis was submitted to the cecal ligation and perforation (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into Sham + Eutrophic, Sham + Obesity, CLP + Eutrophic and CLP + Obesity. Twelve and twenty four hours after surgery the blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the hippocampus, cortex and prefrontal cortex. The data indicate that in obese rats subjected to sepsis occurs an increase of BBB permeability in different brain regions compared to eutrophic septic rats. This alteration reflected an increase of MPO activity, concentration of nitrite/nitrate, oxidative damage to lipids and proteins and an imbalance of SOD and CAT especially 24 hours after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate or accelerate the sepsis-induced damage in rat brain.


Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier.
Living in biofilms is probably the most common condition for bacteria and fungi and biofilm-related infections account for the majority of bacterial infectious diseases worldwide. Among others biofilm-related infections, those associated with implanted biomaterials have an enormous and still largely underestimated impact in orthopaedics and trauma, cardio-surgery and several other surgical disciplines. Given the limited efficacy of existing antibiotics in the prevention and treatment of bacterial biofilms, new strategies are needed to protect implants and host tissues, overcoming the striking ability of the microorganisms to adhere on different surfaces and to immediately protect themselves by forming the biofilm matrix. Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a potential target for new preventive and treatment approach. Among various polymers, tested as antibacterial coatings, hyaluronic acid and some of its composites do offer a well-established long-term safety profile and a proven ability to reduce bacterial adhesion and biofilm formation. Aim of the present review is to summarize the available evidence concerning the antiadhesion/antibiofilm activity of hyaluronic acid and some of its derivatives to reduce/prevent bacterial adhesion and biofilm formation in various experimental and clinical settings.


Large-scale virtual high-throughput screening for the identification of new battery electrolyte solvents: evaluation of electronic structure theory methods.
The performance of semi-empirical quantum mechanical (SQM), density functional theory (DFT) and wave function theory (WFT) methods is evaluated for the purpose of screening a large number of molecular structures with respect to their electrochemical stability to identify new battery electrolyte solvents. Starting from 100,000 database entries and based on more than 46,000 DFT calculations, 83 candidate molecules are identified and then used for benchmarking lower-level computational models (SQM, DFT) with respect to higher-level WFT reference data. A combination of SQM and WFT methods is suggested as a screening strategy at the electronic structure theory level. Using a subset of over 11,000 typical organic molecules and based on over 22,000 high-level WFT calculations, several simple models are tested for the prediction of ionization potentials (IPs) and electron affinities (EAs). Reference data are made available for the development of more sophisticated QSPR models.


Melatonin and the cardiovascular system.
Melatonin concentrations in serum, as well as urinary levels of its main metabolite, 6-sulphatoxymelatonin, decrease with age. In the course of aging, the frequency of heart diseases, both acute and chronic, systematically increases. The evidence from the last 10 years suggests that melatonin influences the cardiovascular system. The presence of vascular melatoninergic receptors/binding sites has been demonstrated; these receptors are functionally linked with vasoconstrictor or vasodilatory effects of melatonin. Melatonin can contribute in cardioprotection of the rat heart, following myocardial ischemia. It has been shown that patients with coronary heart disease have a low melatonin production rate, especially those with higher risk of cardiac infarction and/or sudden death. There are clinical data reporting some alterations of melatonin in human stroke and coronary heart disease. The suprachiasmatic nucleus and, possibly, the melatoninergic system may also modulate cardiovascular rhythmicity. Hypercholesterolemia and hypertension are the other age-related symptoms. People with high levels of LDL-cholesterol have low levels of melatonin. It has been shown that melatonin suppresses the formation of cholesterol by 38% and reduces LDL accumulation by 42%. A 10-20% reduction of cholesterol concentration in women using the B-oval pill has been observed. It is a very important because, even a 10-15% reduction in blood cholesterol concentration has bee shown to result in a 20 to 30% decrease in the risk of coronary heart disease. People with hypertension have lower melatonin levels than those with normal blood pressure. The administration of the hormone in question declines blood pressure to normal range. It has been observed that melatonin, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects. Melatonin may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus; 2) as an antioxidant which lowers blood pressure; 3) by decreasing the level of catecholamines, or 4) by relaxing the smooth muscle in the aorta wall.


Interactions of benzalkonium chloride with soft and hard contact lenses.
We measured the uptake and washout of benzalkonium chloride, using radioactive tracer, by representative hard and soft contact lenses. Uptake by soft contact lenses after 7 days of continuous exposure is high (30 to 56 micrograms/mg of lens weight), with a low percentage of washout in 24 hours (between 0.2% and 1.5% of total uptake). High-water content lenses absorb greater quantities of benzalkonium than do low-water content lenses. Hard lenses take up a much smaller quantity of benzalkonium but release between 30% and 60% of total uptake during washout for 24 hours. Fluorosilicone-acrylate polymer lenses adsorb and release the most preservative, while polymethylmethacrylate lenses (Paragon Optical Inc, Mesa, Ariz) adsorb and release the least. The released benzalkonium from either soft or hard lenses is of a sufficient concentration to be at or above the upper limits of safety.


[Norovirus outbreaks in hospitals and nursing homes in Catalonia, Spain].
The low infectious dose and multiple transmission routes favour the appearance of norovirus outbreaks. The objective of this study was to compare the incidence of norovirus outbreaks in hospitals and nursing homes in Catalonia. A descriptive study of norovirus outbreaks between 15/10/2004 and 30/10/2005 was carried out. An epidemiological survey was completed for each outbreak. Norovirus in clinical samples was determined by PCR techniques. The incidence in each centre and the annual incidence of outbreaks by centre were calculated. Differences were calculated using the chi-square test and the Student's t test, taking a p value of > 0.05 as significant. Seventeen outbreaks (6 in hospitals and 11 in nursing homes) were detected. The global attack rate was 33.4% (652/1951) and was slightly higher in nursing homes (35.2%) than in hospitals (31.4%). A total of 94.1% (16/17) of outbreaks were caused by person-to-person transmission and only 5.9% (1/17) by foods. The mean number of days between the first and last case was 11.4 (SD = 6.9). The mean duration of symptoms was 2.39 days (SD=1.6), and was higher hospitals, 2.63 (SD=1.7), than in nursing homes, 1.97 (SD=1.7) (p < 0.0001). Norovirus is responsible for a large number of outbreaks due to person-to-person transmission. Control should be standardized to reduce the number and duration of outbreaks.


Field-effect transistors based on self-organized molecular nanostripes.
Charge transport properties in organic semiconductors depend strongly on molecular order. Here we demonstrate field-effect transistors where drain current flows through a precisely defined array of nanostripes made of crystalline and highly ordered molecules. The molecular stripes are fabricated across the channel of the transistor by a stamp-assisted deposition of the molecular semiconductors from a solution. As the solvent evaporates, the capillary forces drive the solution to form menisci under the stamp protrusions. The solute precipitates only in the regions where the solution is confined by the menisci once the critical concentration is reached and self-organizes into molecularly ordered stripes 100-200 nm wide and a few monolayers high. The charge mobility measured along the stripes is 2 orders of magnitude larger than the values measured for spin-coated thin films.


Comparison of two face masks used to deliver early ventilation to laryngectomized patients.
Emergency airway management of laryngectomized patients is inherently complicated by the altered contours of their necks, by the presence of awkwardly placed tracheostomas, and by stomal strictures. Effective ventilation can also be compromised by the presence of hypertrophic peristomal scar tissue and by tumor recurrence. One common method of airway management involves the use of a pediatric face mask attached to a standard ventilation bag. We conducted a study of 20 laryngectomized patients to determine if they could be adequately ventilated through two commonly used pediatric face masks--the Laerdal mask and the Ambu mask. Ten of these patients had had an end tracheostoma in place for at least 1 year, and the remaining 10 had undergone stoma placement only recently. We found that all 20 patients achieved an adequate peristomal seal when using the Laerdal mask, whereas only 11 adequate seals were achieved with the Ambu mask. Therefore, we recommend that the Laerdal pediatric mask be used for early ventilation in laryngectomized patients.


Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.
Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.


Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species.
Leishmania braziliensis are intracellular parasites that cause unique clinical forms of cutaneous leishmaniasis. Previous studies with other leishmania species demonstrated that reactive oxygen species (ROS) control promastigotes, the infective stage of the parasite, but not the amastigote form that exists in the mammalian host. Here we show that ROS inhibits growth of L. braziliensis amastigotes in resting monocytes, and that classical monocytes are primarily responsible for this control. ROS, but not nitric oxide, also contributed to killing of L. braziliensis by IFN-γ activated monocytes. Furthermore, by gene expression profiling of human lesions we found greater expression of genes associated with ROS, but not nitric oxide, compared to normal skin. This study shows that ROS are important for control of L. braziliensis both at the initial stages of infection, as well as at later time points, and highlights that monocyte subsets may play different roles during leishmaniasis.


Social structural and behavioral underpinnings of hyperendemic hepatitis C virus transmission in drug injectors.
Hepatitis C virus (HCV) is hyperendemic in drug injectors, yet social structural and behavioral factors underlying transmission are not well established. We conducted a case-control study of HCV seroconversion in drug injectors, focusing on transmission within networks. Incident case subjects (n=17) and seronegative control subjects (n=42) reported injection and sex partners and referred as many as 5 for interviewing and blood testing. We performed nucleotide sequencing of HCV isolates from infected individuals. Seventy-eight percent of recent injection partnerships involved behavior that could transmit HCV. Case subjects and control subjects were similar demographically and behaviorally. Case subjects, however, had more HCV-infected partners and consequently engaged in injection risk behavior with more infected partners. The injection network was mostly connected, dense, and cyclic, but the sexual network was highly fragmented. Although participants generally injected with partners of similar age, most HCV-uninfected participants recently had injected with infected partners. In at least 1 of 4 pairs of genetically linked infections, transmission appeared to be due to sharing of injection equipment other than syringes. Except for transmission pairs, network distance between incident case subjects and genetic distance between their HCV variants were uncorrelated. Without dramatic reductions in injection risk behaviors, shattering of cohesive injection networks, and/or broad coverage of an effective vaccine, HCV will likely remain hyperendemic in drug injectors.


Evidence of disparities in the provision of the maternal postpartum 6-week check in primary care in England, 2015-2018: an observational study using the Clinical Practice Research Datalink (CPRD).
A maternal postpartum 6-week check (SWC) with a general practitioner (GP) is now considered an essential service in England, a recent policy change intended to improve women's health. We aimed to provide an up-to-date snapshot of the prevalence of SWC prior to the policy change as a baseline, and to explore factors associated with having a late or no check. We conducted a cohort study using primary care records in England (Clinical Practice Research Datalink (CPRD)). 34 337 women who gave birth between 1 July 2015 and 30 June 2018 and had ≥12 weeks of follow-up post partum were identified in the CPRD Pregnancy Register. The proportion who had evidence of an SWC with a GP was calculated, and regression analysis was used to assess the association between women's characteristics and risks of a late or no check. Sixty-two per cent (95% CI 58% to 67%) of women had an SWC recorded at their GP practice within 12 weeks post partum, another 27% had other consultations. Forty per cent had an SWC at the recommended 6-8 weeks, 2% earlier and 20% later. A late or no check was more common among younger women, mothers of preterm babies or those registered in more deprived areas. Nearly 40% of women did not have a postpartum SWC recorded. Provision or uptake was not equitable; younger women and those in more deprived areas were less likely to have a record of such check, suggesting postpartum care in general practice may be missing some women who need it most.


Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.
As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.


Single-photon pulsed-light indirect time-of-flight 3D ranging.
"Indirect" time-of-flight is one technique to obtain depth-resolved images through active illumination that is becoming more popular in the recent years. Several methods and light timing patterns are used nowadays, aimed at improving measurement precision with smarter algorithms, while using less and less light power. Purpose of this work is to present an indirect time-of-flight imaging camera based on pulsed-light active illumination and a 32 × 32 single-photon avalanche diode array with an improved illumination timing pattern, able to increase depth resolution and to reach single-photon level sensitivity.


Spontaneous eye blink rate (EBR) predicts poor performance in high-stakes situations.
Although the existence of 'choking under pressure' is well-supported by research, its biological underpinnings are less clear. In this research, we examined two individual difference variables that may predict whether people are likely to perform poorly in high-incentive conditions: baseline eye blink rate (EBR; reflecting dopamine system functioning) and baseline anterior hemispheric asymmetry (an indicator of goal-directed vs. stimulus driven processing). Participants conducted a switch task under control vs. incentive conditions. People low in EBR were generally capable of improving their performance when incentives were at stake, whereas people high in EBR were not. Hemispheric asymmetry did not predict performance. These findings are consistent with the idea that suboptimal performance in high-stakes conditions may stem from the neuromodulatory effects of dopamine.


Imported episodic rabies increases patient demand for and physician delivery of antirabies prophylaxis.
Imported cases threaten rabies reemergence in rabies-free areas. During 2000-2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). Annual data collected by the National Reference Center for Rabies NRCR (1989-2006) and the exhaustive database (2000-2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000-2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.


Quality criteria in bariatric surgery: Consensus review and recommendations of the Spanish Association of Surgeons and the Spanish Society of Bariatric Surgery.
Bariatric surgery has proven to be highly effective in controlling obesity and metabolic syndrome; the results of this surgery are not only expressed in terms of weight loss, but also in terms of resolution of comorbidities, improved quality of life and complications. The different parameters used to measure these outcomes require uniformity and reference patterns. Therefore, it is essential to identify those indicators and quality criteria that are helpful in defining the «best practice» principles in bariatric surgery. In this regard, the Section of Obesity of the Spanish Association of Surgeons, in collaboration with the Spanish Society for Bariatric Surgery (SECO), present as an objective to identify the key points that define «quality» in this type of surgery. We describe the main indicators based on the published literature as well as the criteria for referral of the main comorbidities according to the evidence found and grades of recommendation.


Instant Messaging in Dental Education.
Instant messaging (IM) is when users communicate instantly via their mobile devices, and it has become one of the most preferred choices of tools to communicate amongst health professions students. The aim of this study was to understand how dental students communicate via IM, faculty members' perspectives on using IM to communicate with students, and whether such tools are useful in the learning environment. After free-associating themes on online communication, two draft topic guides for structured interviews were designed that focussed on mobile device-related communication activities. A total of 20 students and six faculty members at the University of Birmingham School of Dentistry agreed to take part in the interviews. Students were selected from years 1-5 representing each year group. The most preferred communication tools were emails, social networking, and IM. Emails were used for more formal messages, and IM and social networking sites were used for shorter messages. WhatsApp was the most used IM app because of its popular features such as being able to check if recipients have read and received messages and group work. The students reported that changes were necessary to improve their communication with faculty members. The faculty members reported having mixed feelings toward the use of IM to communicate with students. The students wished to make such tools a permanent part of their learning environment, but only with the approval of faculty members. The faculty members were willing to accept IM as a communication tool only if it is monitored and maintained by the university and has a positive effect on learning.


Articulatory Fo perturbations and auditory feedback.
Singers are required to sing with a high degree of precision of fundamental frequency (Fo). Does this mean that they have learned to compensate for the change of pitch that has been described in speech during production of different vowels? Experienced choir singers sang sustained tones with a change of vowel in mid-tone. The fundamental frequency was measured, and the resulting Fo contours were evaluated with respect to Fo effects coincident with the vowel changes. The tasks were performed both with normal auditory feedback and with the auditory feedback masked by noise in headphones. The vowels (i) and (y) were found to be associated with higher Fo than other vowels. The irregularities in the Fo curves were somewhat larger in the absence of auditory feedback. This is consistent with findings during speech production. The instability in Fo, measured as the standard deviation over each tone, was also larger in the absence of feedback.


Female control of sexuality: illusion or reality? Use of vaginal products in south west Uganda.
This paper reports on a trial of vaginal products that were distributed and used by 131 women and 21 men in south west Uganda. It focuses specifically upon the issue of female control in heterosexual relationships and examines whether methods which are ostensibly under women's control, will in practice give women greater control of their sexual health. Participants were invited to select two from a range of vaginal products that included the female condom, contraceptive sponge, film, tablets, foam and gel, and use each for five weeks and their favourite product for a further three months. They were interviewed up to seven times over a five-month period. Although the women perceived that a major advantage of the products (with the exception of the female condom) was that they could be used secretly, less than 40% were using the products without their partner's knowledge after one week and this proportion declined over time with only 22% using the products secretly after ten weeks. In the main male partners were told as women felt it their duty to inform them. In general the women were very much more positive about the products than they were about the male condom, as were the men. A contributory factor to their popularity among women was the greater control they gave them. Even though, use of these products in practice often involved negotiation with male partners, the fact that use was contingent on women's action was empowering and increased somewhat their ability to control their sexual health.


A framework for effective management of change in clinical practice: dissemination and implementation of clinical practice guidelines.
Theories from social and behavioural science can make an important contribution to the process of developing a conceptual framework for improving use of clinical practice guidelines and clinician performance. A conceptual framework for guideline dissemination and implementation is presented which draws on relevant concepts from diffusion of innovation theory, the transtheoretical model of behaviour change, health education theory, social influence theory, and social ecology, as well as evidence from systematic literature reviews on the effectiveness of various behaviour change strategies. The framework emphasises the need for preimplementation assessment of (a) readiness of clinicians to adopt guidelines into practice, (b) barriers to change as experienced by clinicians, and (c) the level at which interventions should be targeted. It also incorporates the need for multifaceted interventions, identifies the type of barriers which will be addressed by each strategy, and develops the concept of progression through stages of guideline adoption by clinicians, with the use of appropriately targeted support strategies. The potential value of the model is that it may enable those involved in the process of guideline dissemination and implementation to direct strategies to target groups more effectively. Clearly, the effectiveness and utility of the model in facilitating guideline dissemination and implementation requires validation by further empirical research. Until such research is available, it provides a theoretical framework that may assist in the selection of appropriate guideline dissemination and implementation strategies.


Early effects of resident work-hour restrictions on patient safety: a systematic review and plea for improved studies.
since the inception of the eighty-hour work week, work hour restrictions have incited considerable debate. Work hour policies were designed to prevent medical errors and to reduce patient morbidity and mortality. It is unclear whether work hour restrictions have been helpful in medicine in general and in orthopaedic surgery specifically. This systematic review of the literature was designed to determine the success of these restrictions in terms of patient mortality, medical errors, and complications. a systematic review of the literature was performed to determine if work hour rules have improved patient and systems-based outcomes and reduced physician errors as measured by mortality, medical errors, and complications. A random effects model was utilized to determine whether patient mortality rates were improved under the new rules. the odds of patient death before implementation of the work hour rules were 1.12 (95% confidence interval, 1.07 to 1.17) times those after implementation. These differences were consistent across disciplines. The data concerning medical or surgical complications before and after the institution of the work hour rules were mixed. There was little information in these studies concerning direct medical errors. The odds of death in nonteaching cohorts were not significantly different from that in teaching cohorts. there appears to be a decrease in mortality following the institution of work hour rules. The difference seen in teaching cohorts is not significantly different from that in nonteaching cohorts. It is unclear whether this difference would have been observed even without work hour restrictions. No study has shown a reduction in mortality for orthopaedic patients in teaching cohorts that was greater than that observed in nonteaching cohorts. Because of methodological concerns and the lack of current literature linking physician fatigue and physician underperformance with patient mortality, it is unclear whether the goals of the work hour reductions have been achieved. Furthermore, because of a lack of a so-called dose-response relationship between work hour reduction and patient mortality, it is uncertain whether further reductions would be beneficial. therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.


The ERATO Systems Biology Workbench: enabling interaction and exchange between software tools for computational biology.
Researchers in computational biology today make use of a large number of different software packages for modeling, analysis, and data manipulation and visualization. In this paper, we describe the ERATO Systems Biology Workbench (SBW), a software framework that allows these heterogeneous application components--written in diverse programming languages and running on different platforms--to communicate and use each others' data and algorithmic capabilities. Our goal is to create a simple, open-source software infrastructure which is effective, easy to implement and easy to understand. SBW uses a broker-based architecture and enables applications (potentially running on separate, distributed computers) to communicate via a simple network protocol. The interfaces to the system are encapsulated in client-side libraries that we provide for different programming languages. We describe the SBW architecture and the current set of modules, as well as alternative implementation technologies.


Kinematic analysis of impairments and compensatory motor behavior during prosthetic grasping in below-elbow amputees.
After a major upper limb amputation, the use of myoelectric prosthesis as assistive devices is possible. However, these prostheses remain quite difficult to control for grasping and manipulation of daily life objects. The aim of the present observational case study is to document the kinematics of grasping in a group of 10 below-elbow amputated patients fitted with a myoelectric prosthesis in order to describe and better understand their compensatory strategies. They performed a grasping to lift task toward 3 objects (a mug, a cylinder and a cone) placed at two distances within the reaching area in front of the patients. The kinematics of the trunk and upper-limb on the non-amputated and prosthetic sides were recorded with 3 electromagnetic Polhemus sensors placed on the hand, the forearm (or the corresponding site on the prosthesis) and the ipsilateral acromion. The 3D position of the elbow joint and the shoulder and elbow angles were calculated thanks to a preliminary calibration of the sensor position. We examined first the effect of side, distance and objects with non-parametric statistics. Prosthetic grasping was characterized by severe temporo-spatial impairments consistent with previous clinical or kinematic observations. The grasping phase was prolonged and the reaching and grasping components uncoupled. The 3D hand displacement was symmetrical in average, but with some differences according to the objects. Compensatory strategies involved the trunk and the proximal part of the upper-limb, as shown by a greater 3D displacement of the elbow for close target and a greater forward displacement of the acromion, particularly for far targets. The hand orientation at the time of grasping showed marked side differences with a more frontal azimuth, and a more "thumb-up" roll. The variation of hand orientation with the object on the prosthetic side, suggested that the lack of finger and wrist mobility imposed some adaptation of hand pose relative to the object. The detailed kinematic analysis allows more insight into the mechanisms of the compensatory strategies that could be due to both increased distal or proximal kinematic constraints. A better knowledge of those compensatory strategies is important for the prevention of musculoskeletal disorders and the development of innovative prosthetics.


Potent inhibitory effect of Foeniculum vulgare Miller extract on osteoclast differentiation and ovariectomy-induced bone loss.
Inhibition of osteoclast differentiation and bone resorption is considered an effective therapeutic approach to the treatment of postmenopausal bone loss. To find natural compounds that may inhibit osteoclastogenesis, we screened herbal extracts on bone marrow cultures. In this study, we found that an aqueous extract of Foeniculum vulgare Miller seed (FvMs) at low concentration, which has traditionally been used as a treatment for a variety of ailments, inhibits the osteoclast differentiation and bone resorptive activity of mature osteoclasts. We further investigated the effects of FvMs on ovariectomy (OVX)-induced bone loss using microcomputed tomography, biomechanical tests and serum marker assays for bone remodeling. Oral administration of FvMs (30 mg or 100 mg/kg/day) for 6 weeks had an intermediary effect on the prevention of femoral bone mineral density (BMD), bone mineral content (BMC), and other parameters compared to OVX controls. In addition, FvMs slightly decreased bone turnover markers that were accelerated by OVX. The bone-protective effects of FvMs may be due to suppression of an OVX-induced increase in bone turnover. Collectively, our findings indicate that FvMs have potential in preventing bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function.


Relation between cognitive and behavioral strategies and future change in common mental health problems across 18 years.
Major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD), constitute common mental disorders that may have chronic and disabling courses. Cognitive and behavioral theories posit that lack of engagement in certain strategies (goal persistence, self-mastery, positive reappraisal) increases vulnerability toward these disorders. Further, scar effect theories assert that experiencing more of these disorders may diminish engagement in such strategies within individuals across time. However, dynamic longitudinal associations between cognitive-behavioral strategies (CBS) and disorder counts across adulthood are not well understood. Using bivariate latent difference score models, this study aimed to test the dynamic trajectories between disorder counts and each CBS across 18 years. Participants were 3,294 community-dwelling adults ages 45.62 years (SD = 11.41, range = 20-74; 54.61% female) who took part in 3 waves of measurement spaced 9 years apart. Self-mastery, disorder counts, and their change were not significantly related. However, higher within-subject increase in goal persistence (but not self-mastery or positive reappraisal) led to greater future decline in disorder counts, but not vice versa. Last, within individuals, greater prior levels of goal persistence and positive reappraisal predicted larger subsequent reduction in disorder counts, and vice versa. The reciprocal, bidirectional associations between specific CBS (goal persistence, positive reappraisal) and disorder counts support both vulnerability and scar models of depression and anxiety. Treatments for MDD, GAD, and PD should attempt to enhance perseverance and optimism. Theoretical and clinical implications are further discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Adipocytes contribute to resistance of human melanoma cells to chemotherapy and targeted therapy.
Epidemiological evidence has linked the development and progression of several cancers including melanoma with obesity. However, whether obesity impinges on responses of cancer cells to treatment remains less understood. Here we report that human adipocytes contribute to resistance of melanoma cells to various therapeutic agents. Exposure to media from adipocyte cultures (adipocyte media) increased cell proliferation and reduced sensitivity of melanoma cells to apoptosis induced by diverse chemotherapeutic drugs, including the DNA-damaging drug cisplatin, the microtubuletargeting agent docetaxel, and the histone deacetylase inhibitor SAHA. This was associated with increased activation of PI3K/Akt and MEK/ERK signaling, and was attenuated by a PI3K or MEK inhibitor. The effect of adipocyte media on melanoma cells was, at least in part, due to the interaction between the adipokine leptin and its long form receptor OB-Rb, in that immunodepletion of leptin in adipocyte media or siRNA knockdown of OB-Rb in melanoma cells reversed the increase in Akt and ERK activation, enhancement in cell proliferation, and importantly, protection of melanoma cells against the drugs. In support, recombinant leptin partially recapitulated the effect of adipocyte media on melanoma cells. Of note, OB-Rb was increased on the surface of melanoma cells compared to melanocytes, whereas leptin short form receptors appeared to be suppressed post-transcriptionally, suggesting that OB-Rb was selectively upregulated in melanoma cells. Collectively, these results indicate that adipocytes contribute to the resistance of melanoma cells to chemotherapeutic drugs and agents targeting the PI3K/Akt and MEK/ERK pathways, and suggest that inhibition of the leptin/ OB-Rb system may be useful to improve the efficacy of multiple therapeutic approaches in the treatment of melanoma.


Ultrastructural analyses of the attachment (bonding) zone between bone and implanted biomaterials.
This report presents transmission electron and high voltage transmission electron microscopic observations of bone and associated remodeling tissues directly interfacing with endosteal dental implants. Undecalcified interfacial tissues were serially sectioned from mandibular samples encasing 60 implants placed into 30 dogs. Two-dimensional ultrastructural analyses and three-dimensional stereology showed that osteogenesis adjacent to dental implants is a dynamic interaction of osseous cells and a collagenous fiber matrix. This study showed that the interfacial bone consists of a mineralized collagen fiber matrix associated with an inorganic (hydroxylapatite) matrix. This study suggested that an unmineralized collagen fiber matrix initially is laid down directly at the implant surface, and that this matrix then is mineralized. Osteoblasts interacted with this matrix, eventually becoming encased within developing lacunae during the remodeling process. This process formed the cellular (osteocyte) aspects of the developed bone. Osteocyte processes extended through canaliculi directly to the implant surface. Apparently, these processes also were entrapped within canaliculi during the mineralization events. At times, these processes paralleled the implant surface. The bone-implant interfacial zone was primarily fibrillar (both mineralized and unmineralized) in morphology, with an electron-dense, ruthenium positive deposition. This electron-dense material was approximately 20 to 50 nanometers in thickness, and only this thin layer separated the remodeled mineralized bone from the implant.


Preclinical cardiorenal interrelationships in essential hypertension.
A diseased heart causes numerous adverse effects on kidney function, and vice versa renal disease can significantly impair cardiac function. Beyond these heart-kidney interrelationships at the clinical level, a reciprocal association has been suggested to exist even in the early stages of those organs' dysfunction. The aim of the present review is to provide evidence of the presence of a preclinical cardiorenal syndrome in the particular setting of essential hypertension, focusing on the subsequent hypertensive sequelae on heart and kidneys. In particular, a plethora of studies have demonstrated not only the predictive role of kidney damage, as expressed by either decreased glomerular filtration or increased urine albumin excretion, for adverse left ventricular functional and structural adaptations but also preclinical heart disease, i.e. left ventricular hypertrophy that is associated with deterioration of renal function. Notably, these reciprocal interactions seem to exist even at the level of microcirculation, since both coronary flow reserve and renal hemodynamics are strongly related with clinical and preclinical renal and cardiac damage, respectively. In this preclinical setting, common pathophysiological denominators, including the increased hemodynamic load, sympathetic and renin-angiotensin system overactivity, increased subclinical inflammatory reaction, and endothelial dysfunction, account not only for the reported associations between overt cardiac and renal damage but also for the parallel changes that occur in coronary and renal microcirculation.


Randomised study within a trial (SWAT) to evaluate personalised versus standard text message prompts for increasing trial participant response to postal questionnaires (PROMPTS).
Use of a person's name in a text message has been shown to be effective in instigating behaviour change. We evaluated the effectiveness of a personalised text message (including the recipient's name) versus a standardised text message for prompting a response from trial participants to complete and return postal follow-up questionnaires. Using a randomised study within a trial (SWAT) embedded within the host GRASP (Getting it Right: Addressing Shoulder Pain) trial, participants who provided a mobile telephone number were randomised (1:1) by a central computer system to receive either (1) a personalised text message which included their name or (2) a standard text message. Text messages were sent by the trial office on the same day as the 6-month GRASP follow-up questionnaire. The primary outcome was questionnaire response rate, defined as the proportion of 6-month GRASP follow-up questionnaires returned by participants. Secondary outcomes included time to response, the proportion of participants sent a reminder follow-up questionnaire, and cost. Between March 2017 and May 2019 (recruitment period for GRASP trial), 618 participants were randomised to a personalised (n = 309) or standard (n = 309) text message and all were included in the analysis. The overall questionnaire response rate was 87% (n = 537/618); 90% (n = 277/309) of participants responded in the personalised text message group compared to 84% (n = 260/309) in the standard text message group (relative risk (RR) 1.07; 95% CI 1.00 to 1.13). Participants randomised to receive the personalised text message were more likely to return their initial postal questionnaire than those who received the standard text message (n = 185/309; 60% vs. n = 160/309; 52%) (RR 1.16; 95% CI 1.00 to 1.33); this represents an absolute percentage difference between intervention groups of 8%. Post hoc subgroup analysis showed that males under 65 years were the group most likely to return their initial questionnaire if they received a personalised text message. Overall, participants who received a personalised text message were more likely to return their questionnaire than those who received the standard text message. GRASP Trial ISRCTN16539266 ; SWAT Repository ID 35.


Use of exercise electrocardiography, technetium-99m-MIBI perfusion tomography, and two-dimensional echocardiography for coronary disease surveillance in a low-prevalence population of heart transplant recipients.
Coronary artery disease has been reported to be a significant cause of long-term morbidity and mortality after heart transplantation. However, the diagnosis of coronary disease by means of noninvasive procedures has shown disappointing accuracy, and many centers currently recommend an annual surveillance coronary angiogram. We prospectively studied the accuracy and feasibility of a symptom-limited upright bicycle exercise, combined with computerized electrocardiogram analysis, echocardiography, and perfusion scintigraphy in 37 consecutive heart transplant recipients at 2.8 +/- 1.4 years after transplantation for routine follow-up coronary angiography. No patient had any hemodynamically significant (> 50% diameter) coronary stenosis, but luminal irregularities were detectable in four patients. The exercise electrocardiogram was interpretable in only 22 patients (59%), and two of the remaining patients (9%) had false-positive results. The feasibility of perfusion tomography (100%) and two-dimensional echocardiography (97%) were greater than for stress electrocardiogram (p < 0.001 and p < 0.01 respectively). False-positive results were obtained at stress echocardiography in one patient (3%), and at scintigraphy in six patients (16%, p = not significant). None of these methods detected coronary artery stenoses of less than 50% diameter. Both exercise perfusion tomography and two-dimensional echocardiography are feasible and can be used with adequate specificity for the noninvasive diagnosis of coronary artery disease in heart transplant recipients. However further studies are needed to determine their respective sensitivity.


Immunochemical localization of tetrahydrocannabinol (THC) in cryofixed glandular trichomes of Cannabis (Cannabaceae).
Delta 9-tetrahydrocannabinol (THC) localization in glandular trichomes and bracteal tissues of Cannabis, prepared by high pressure cryofixation-cryosubstitution, was examined with a monoclonal antibody-colloidal gold probe by electron microscopy (EM). The antibody detected THC in the outer wall of disc cells during the presecretory cavity phase of gland development. Upon formation of the secretory cavity, the immunolabel detected THC in the disc cell wall facing the cavity as well as the subcuticular wall and cuticle throughout development of the secretory cavity. THC was detected in the fibrillar matrix associated with the disc cell and with this matrix in the secretory cavity. The antibody identified THC on the surface of secretory vesicles, but not in the secretory vesicles. Gold label also was localized in the anticlinal walls between adjacent disc cells and in the wall of dermal and mesophyll cells of the bract. Grains were absent or detected only occasionally in the cytoplasm of disc or other cells of the bract. No THC was detected in controls. These results indicate THC to be a natural product secreted particularly from disc cells and accumulated in the cell wall, the fibrillar matrix and surface feature of vesicles in the secretory cavity, the subcuticular wall, and the cuticle of glandular trichomes. THC, among other chemicals, accumulated in the cuticle may serve as a plant recognition signal to other organisms in the environment.


YPTB3816 of Yersinia pseudotuberculosis strain IP32953 is a virulence-related metallo-oligopeptidase.
Although bacterial peptidases are known to be produced by various microorganisms, including pathogenic bacteria, their role in bacterial physiology is not fully understood. In particular, oligopeptidases are thought to be mainly involved in degradation of short peptides e.g. leader peptides released during classical protein secretion pathways. The aim of this study was to investigate effects of inactivation of an oligopeptidase encoding gene opdA gene of Yersinia pseudotuberculosis on bacterial properties in vivo and in vitro, and to test dependence of the enzymatic activity of the respective purified enzyme on the presence of different divalent cations. In this study we found that oligopeptidase OpdA of Yersinia pseudotuberculosis is required for bacterial virulence, whilst knocking out the respective gene did not have any effect on bacterial viability or growth rate in vitro. In addition, we studied enzymatic properties of this enzyme after expression and purification from E. coli. Using an enzyme depleted of contaminant divalent cations and different types of fluorescently labelled substrates, we found strong dependence of its activity on the presence of particular cations. Unexpectedly, Zn2+ showed stimulatory activity only at low concentrations, but inhibited the enzyme at higher concentrations. In contrast, Co2+, Ca2+ and Mn2+ stimulated activity at all concentrations tested, whilst Mg2+ revealed no effect on the enzyme activity at all concentrations used. The results of this study provide valuable contribution to the investigation of bacterial peptidases in general, and that of metallo-oligopeptidases in particular. This is the first study demonstrating that opdA in Yersinia pseudotuberculsosis is required for pathogenicity. The data reported are important for better understanding of the role of OpdA-like enzymes in pathogenesis in bacterial infections. Characterisation of this protein may serve as a basis for the development of novel antibacterials based on specific inhibition of this peptidase activity.


α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1.
The Hippo pathway regulates contact inhibition of cell proliferation and, ultimately, organ size in diverse multicellular organisms. Inactivation of the Hippo pathway promotes nuclear localization of the transcriptional coactivator Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion of αE (α epithelial) catenin in the hair follicle stem cell compartment resulted in the development of skin squamous cell carcinoma in mice. Tumor formation was accelerated by simultaneous deletion of αE-catenin and the tumor suppressor-encoding gene p53. A small interfering RNA screen revealed a functional connection between αE-catenin and Yap1. By interacting with Yap1, αE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive nuclear localization in αE-catenin-null cells. We also found an inverse correlation between αE-catenin abundance and Yap1 activation in human squamous cell carcinoma tumors. These findings identify αE-catenin as a tumor suppressor that inhibits Yap1 activity and sequesters it in the cytoplasm.


Convergent and contingent community responses to grass source and dominance during prairie restoration across a longitudinal gradient.
Restoring prairie on formerly cultivated land begins by selecting propagule seed sources and the diversity of species to reintroduce. This study examined the effects of dominant grass propagule source (cultivar vs. non-cultivar) and sown propagule diversity (grass:forb sowing ratio) on plant community structure. Two field experiments were established in Kansas and Illinois consisting of identical split plot designs. Dominant grass source was assigned as the whole-plot factor, and sown dominance of grasses (five levels of seeded grass dominance) as the subplot factor. Species density, cover, and diversity were quantified for 5 years. The effect of dominant grass source on the cover of focal grasses, sown species, and volunteer species was contingent upon location, with variation between dominant grass sources observed exclusively in Kansas. Species density and diversity showed regionally convergent patterns in response to dominant grass source. Contrary to our hypotheses, total species density and diversity were not lower in the presence of grass cultivars, the grass source we had predicted would be more competitive. Sown grass dominance effects on the cover of the focal grass species were contingent upon location resulting from establishment corresponding better to the assigned treatments in Illinois. All other cover groups showed regionally convergent patterns, with lower cover of volunteers and higher cover of sown forbs, diversity, and species density in the lowest sown grass dominance treatment in both sites. Thus, decisions regarding the diversity of propagules to reintroduce had more consequence for plant community structure than cultivar or non-cultivar source of dominant grasses.


Association between self-reported household practices and body mass index of US children and adolescents, 2005.
Parents can set household practices that influence children's behaviors. The objective of this study was to determine whether children (children and adolescents aged 9-18 y) who live in a household that has healthful practices related to behaviors associated with obesity have a lower body mass index (BMI). We analyzed data from the 2005 Styles mail panel survey (N = 1,685 parents and children). We used multiple logistic regression to assess associations between 4 household practices and 3 children's behaviors: watching television, participating in vigorous physical activity, and purchasing sodas and snacks at school. Children watched more television if they had a television in their bedrooms, were less active as a family, and had no junk food restrictions at home. Children in less active families participated in about half as much VPA as children in more active families. Children purchased more sodas and snacks at school if they had a television in their bedrooms and their family consumed more meals at fast-food restaurants. Children whose families were less active were more likely to have a self-reported BMI at or above the 85th percentile. In addition, children who watched more television were more likely to have a self-reported BMI at or above the 85th percentile. Household practices were associated with children's behaviors and self-reported BMI. A household profile that includes being active as a family may counteract the increase in childhood obesity.


Cognition in breast cancer survivors: A pilot study of interval and continuous exercise.
The current study investigated the effects of two exercise interventions on cognitive function amongst breast cancer survivors. Pilot randomised-controlled trial. Seventeen female cancer survivors (mean: 62.9±7.8years) were randomised into three groups: high-intensity interval training (HIIT, n=6); moderate-intensity continuous training (MOD, n=5); or wait-list control (CON, n=6). The HIIT and MOD groups exercised on a cycle ergometer 3days/week for 12-weeks. Primary outcomes were cognitive function assessments utilising CogState. Secondary outcomes were resting middle cerebral artery blood flow velocity, cerebrovascular reactivity and aerobic fitness (VO2peak). Data were analysed with General Linear Mixed Models and Cohen's d effect sizes were calculated. All 17 participants who were randomised were available for follow-up analysis and adherence was similar for HIIT and MOD (78.7±13.2% vs 79.4±12.0%; p=0.93). Although there were no significant differences in the cognitive and cerebrovascular outcomes, HIIT produced moderate to large positive effects in comparison to MOD and CON for outcomes including episodic memory, working memory, executive function, cerebral blood flow and cerebrovascular reactivity. HIIT significantly increased VO2peak by 19.3% (d=1.28) and MOD had a non-significant 5.6% (d=0.72) increase, compared to CON which had a 2.6% decrease. This study provides preliminary evidence that HIIT may be an effective exercise intervention to improve cognitive performance, cerebrovascular function and aerobic fitness in breast cancer survivors. Considering the sample size is small, these results should be confirmed through larger clinical trials.