Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection.
Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium triple-knockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis.


Assessment of the reporting quality of RCTs for novel oral anticoagulants in venous thromboembolic disease based on the CONSORT statement.
Randomized controlled trials (RCTs) are the cornerstone of evidence based medicine. Ιt is crucial that RCTs have transparent reporting to facilitate their interpretation. The purpose of the present study is the evaluation of the reporting quality of RCTs for novel oral anticoagulants (NOACs) in venous thromboembolism (VTE) based on the CONSORT statement. MEDLINE was meticulously searched, while quoted references by retrieved RCTs were manually screened. The primary objective was to establish the mean CONSORT compliance of RCTs for NOACs in VTE. Secondary objectives were the calculation of compliance per CONSORT item and the investigation for probable determining factors with regards to the reporting quality of RCTs. Reporting above 70% of the items was defined as adequate compliance to the CONSORT statement. A total of 83 articles were considered eligible. Mean adherence to the CONSORT statement was 61.84%, standard deviation (SD) = 18.72. Among retrieved studies, 35 (42.17%) reported above 70% of the items, while 48 (57.83%) described less than 70% of the items. Inter-rater agreement was satisfactory (Cohen's kappa ≥ 0.75). Items with respect to randomization and blinding were principally underreported, whereas the rest of the methodological features and results were more sufficiently reported. Logistic regression failed to demonstrate significant effect for any of the factors investigated. Impact factor [odds ratio (OR) = 1.347, 95% confidence interval (CI) (0.994, 1.826), p = 0.055], number of authors [OR = 1.277, 95% CI (0.975, 1.672), p = 0.076] and presentation of participant flow-diagram [OR = 55.358, 95% CI (0.914, 3351.765), p = 0.055], came closer to significance. Exploratory analysis revealed significant, strong, positive correlation between abstract and article adherence to the CONSORT guidelines (r = 0.851, p < 0.001). Reporting quality of RCTs for NOACs in VTE is moderate. A superior reporting quality is desirable, especially relating to randomization and blinding.


Effects of Four Weeks of Strength Training on the Corticomotoneuronal Pathway.
Neural adaptations to strength training have long been recognized, but knowledge of mechanisms remains incomplete. Using novel techniques and a design which limited experimental bias, this study examined if 4 wk of strength training alters voluntary activation and corticospinal transmission. Twenty-one subjects were randomized into strength training (n = 10; 7 females, 3 males; 23.5 ± 7.5 yr; mean ± SD) and control groups (n = 11; 2 females, 9 males; 23.0 ± 4.2 yr). Strength training involved 12 sessions of high-force isometric contractions of the elbow flexors. Before and after training, voluntary activation of the elbow flexors was assessed via transcranial magnetic stimulation. Also, for the first time, magnetic stimulation of corticospinal axons was used to examine spinal-level adaptations to training. The evoked responses, termed cervicomedullary motor-evoked potentials (CMEPs), were acquired in resting biceps brachii in three arm postures. Muscle adaptations were assessed via electrical stimulation of biceps. Compared with the control group, the strength training group exhibited greater increases in maximal strength (12.8% ± 6.8% vs 0.0% ± 2.7%; P < 0.001), biceps electromyographic activity (27.8% ± 25.9% vs -5.2% ± 16.8%; P = 0.002), and voluntary activation (4.7% ± 3.9% raw change vs -0.1% ± 5.2%; P = 0.034). Biceps CMEPs in all arm postures were unchanged after training. Biceps twitch characteristics were also unchanged. Four weeks of isometric strength training of the elbow flexors increased muscle strength and voluntary activation, without a change in the muscle. The improvement in activation suggests that voluntary output from the cortex was better able to recruit motoneurons and/or increase their firing rates. The lack of change in CMEPs indicates that neither corticospinal transmission nor motoneuron excitability was affected by training.


Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition.
The relation between vitamin D status and lymphoma risk is inconclusive. We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with ≥2 y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.


Bone formation on synthetic precursors of hydroxyapatite.
The aim of this study was to investigate the reaction of skeletal tissue to various synthetic calcium phosphate (Ca-P) compounds in vivo. Five synthetic Ca-P compounds were implanted into the subperiosteal area of the calvaria of 7-week-old BALB/c mice for one to 15 weeks. Synthetic compounds were dicalcium phosphate (DCP), octacalcium phosphate (OCP), amorphous calcium phosphate (ACP), Ca-deficient hydroxyapatite and hydroxyapatile (HA). Implanted DCP, OCP and ACP were found to be converted to apatitic phase by x-ray microdiffraction analysis using undecalcified specimens. Structure of bone was found out on all of Ca-P compounds eventually at late stage under the light microscope, but the rate of bone formation calculated from a number of experiments varied on respective synthetic Ca-P compound. It was high as 80% for DCP, OCP and ACP, but was low as 5.6% for Ca-deficient HA, and no reaction was found for HA at the stage of 3 weeks. Fine filaments and granular materials in the newly formed bone matrix were detected at 7 days around the remnants of OCP particles which already converted to apatitic phase by ultrastructural study of decalcified specimens. These structures were very similar to the components of bone nodules seen in intramembranous osteogenesis. It is postulated that the precursors of HA have an important role in intramembranous osteogenesis.


Explicitly correlated PNO-MP2 and PNO-CCSD and their application to the S66 set and large molecular systems.
We present our current progress on the combination of explicit electron correlation with the pair natural orbital (PNO) representation. In particular we show cubic scaling PNO-MP2-F12, and PNO-CCSD[F12] implementations. The PNOs are constructed using a hybrid scheme, where the PNOs are generated in a truncated doubles space, spanned by orbital specific virtuals obtained using an iterative eigenvector algorithm. We demonstrate the performance of our implementation through calculations on a series of glycine chains. The accuracy of the local approximations is assessed using the S66 benchmark set, and we report for the first time explicitly correlated CCSD results for the whole set and improved estimates for the CCSD/CBS limits. For several dimers the PNO-CCSD[F12] calculations are more accurate than the current reference values. Additionally, we present pilot applications of our PNO-CCSD[F12] code to host-guest interactions in a cluster model for zeolite H-ZSM-5 and in a calix[4]arene-water complex.


Shape Tracking with Occlusions via Coarse-to-Fine Region-Based Sobolev Descent.
We present a method to track the shape of an object from video. The method uses a joint shape and appearance model of the object, which is propagated to match shape and radiance in subsequent frames, determining object shape. Self-occlusions and dis-occlusions of the object from camera and object motion pose difficulties to joint shape and appearance models in tracking. They are unable to adapt to new shape and appearance information, leading to inaccurate shape detection. In this work, we model self-occlusions and dis-occlusions in a joint shape and appearance tracking framework. Self-occlusions and the warp to propagate the model are coupled, thus we formulate a joint optimization problem. We derive a coarse-to-fine optimization method, advantageous in tracking, that initially perturbs the model by coarse perturbations before transitioning to finer-scale perturbations seamlessly. This coarse-to-fine behavior is automatically induced by gradient descent on a novel infinite-dimensional Riemannian manifold that we introduce. The manifold consists of planar parameterized regions, and the metric that we introduce is a novel Sobolev metric. Experiments on video exhibiting occlusions/dis-occlusions, complex radiance and background show that occlusion/dis-occlusion modeling leads to superior shape accuracy.


Pars plana vitrectomy for vitreoretinal complications of Behçet uveitis.
Purpose. To evaluate the role of pars plana vitrectomy (PPV) for the treatment of vitreoretinal complications of ocular Behçet disease (BD). Methods. Retrospective review of the medical records of all patients who underwent PPV for vitreoretinal complications of Behçet uveitis in the Ophthalmology Department of the Hospital Clinic of Barcelona, Barcelona, Spain, from January 1994 until December 2011. Preoperative and postoperative best-corrected visual acuities (BCVA), ocular findings, treatments, surgical indications, and outcomes were evaluated in all patients. Results. Twelve patients (14 eyes) were included in the study. Indications for PPV were the following: vitreous hemorrhage in 4 eyes (28.5%), persistent vitreous opacities in 3 eyes (21.4%), rhegmatogenous retinal detachment in 2 eyes (14.3%), macular hole in 2 eyes (14.3%), persistent cystoid macular edema in 2 eyes (14.3%), and combined tractional and rhegmatogenous retinal detachment in 1 eye (7.1%). At last examination (median follow-up 105 months, range 6-209 months), BCVA increased 3 Snellen lines or more in 6 eyes (42.9%). Immunosuppressive treatment could be reduced in 5 patients (41.6%). No serious ocular inflammatory episodes presented during the follow-up in those operated patients. Conclusions. In this retrospective series with long-term follow-up, PPV can treat secondary vitreoretinal complications of Behçet uveitis, restoring or stabilizing vision without major adverse events.


Using Merged Clinical and Claims Registry Data to Identify High Utilizers of Surgical Inpatient Care 1 Year after Colectomy.
Under bundled payment initiatives, providers will be held financially responsible for patients' acute and post-acute care costs. Certain patients, termed high utilizers, use disproportionate shares of resources during 1 year. The aim of this study was to identify high utilizers, describe their costs, and determine whether preoperative characteristics predict high utilizer status. Colectomy patients with 1-year follow-up were identified in a linked clinical (American College of Surgeons NSQIP) and administrative (Medicare inpatient claims) dataset (2005 to 2008). Cost of inpatient care was calculated by multiplying patient Medicare charges in each cost center by cost-to-charge ratios from the Medicare cost reports. A mixed-effects logistic model quantified the association between preoperative characteristics and being a high utilizer after elective and emergent colectomies. One thousand and fifty-five of 10,561 colectomy patients accounted for >50% of the inpatient care cost of the entire cohort during 1 year postoperatively. This top decile of patients were labeled high utilizers and had substantially greater costs in the following cost centers: intensive care ($36,322 vs $0), respiratory ($2,875 vs $22), radiology ($649 vs $29), and cardiology ($5,057 vs $166) (all p < 0.001). High utilizers more frequently had emergent index colectomies (43% vs 17%; p < 0.001). Patients with American Society of Anesthesiologists class IV and V had 2-fold increased odds of being high utilizers after both elective (odds ratio = 2.72; 95% CI, 1.89-3.90) and emergent colectomies (odds ratio = 2.09; 95% CI, 1.23-3.55). Patients in the top cost decile account for the majority of costs in the year after colectomy, disproportionately accumulate those costs in particular cost centers, and can be identified preoperatively.


Cellular landmarks of Trypanosoma brucei and Leishmania mexicana.
The kinetoplastids Trypanosoma brucei and Leishmania mexicana are eukaryotes with a highly structured cellular organisation that is reproduced with great fidelity in each generation. The pattern of signal from a fluorescently tagged protein can define the specific structure/organelle that this protein localises to, and can be extremely informative in phenotype analysis in experimental perturbations, life cycle tracking, post-genomic assays and functional analysis of organelles. Using the vast coverage of protein subcellular localisations provided by the TrypTag project, an ongoing project to determine the localisation of every protein encoded in the T. brucei genome, we have generated an inventory of reliable reference organelle markers for both parasites that combines epifluorescence images with a detailed description of the key features of each localisation. We believe this will be a useful comparative resource that will enable researchers to quickly and accurately pinpoint the localisation of their proteins of interest and will provide cellular markers for many types of cell biology studies. We see this as another important step in the post-genomic era analyses of these parasites, in which ever expanding datasets generate numerous candidates to analyse. Adoption of these reference proteins by the community is likely to enhance research studies and enable better comparison of data.


Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors.
In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages.


Heterogeneous Colistin-Resistance Phenotypes Coexisting in Stenotrophomonas maltophilia Isolates Influence Colistin Susceptibility Testing.
The polymyxin antibiotic colistin shows in vitro activity against Stenotrophomonas maltophilia. However, an increased incidence of colistin-resistant isolates has been recently observed. In addition, in vitro evaluation of colistin susceptibility for this organism has been problematic. The aims of this study were to investigate the colistin-resistance phenotypes displayed by S. maltophilia and their potential association with the challenging determination of colistin susceptibilities for this organism by even the recommended method. Colistin-resistance phenotypes were inferred by use of the recommended broth microdilution method in different clinical isolates of S. maltophilia. Most of the strains showed non-interpretable minimum inhibitory concentrations (MICs) for colistin due to an incomplete growth inhibition in wells of the microdilution plate. In addition, the subpopulation of bacteria resistant to colistin showed an increased ability to form biofilms on the plastic surface of MIC plates. The observed incomplete growth inhibition in the microdilution plates is compatible with a progressive adaptation to colistin or a heterogeneous susceptibility to this antibiotic. Therefore, to determine the existence of heteroresistance or adaptive resistance, four colistin-resistant clinical isolates were subjected to serial Etest assays, growth rate analyses, and the population analysis profile test. The experiments indicated that these S. maltophilia isolates display a colistin-resistant sub-population that survives and multiplies in the presence of the antibiotic. Interestingly, this phenomenon might not be explainable by the natural background mutation rate alone since the development of a resistant sub-population occurred upon the contact with the antibiotic and it was reversible. This complex colistin-resistance phenotype is exhibited differently by the different isolates and significantly affected colistin susceptibility testing. Furthermore, it can coexist with adaptive resistance to colistin as response to pre-incubation with sub-inhibitory concentrations of the antibiotic. Overall, the combined action of heterogeneous colistin-resistance mechanisms in S. maltophilia isolates, including colistin-induced biofilm formation, may hamper the correct interpretation of colistin susceptibility tests, thus having potentially serious implications on antimicrobial-therapy decision making.


Interferon-beta mediates stromal cell rescue of T cells from apoptosis.
The resolution of immune responses is characterized by extensive apoptosis of activated T cells. However, to generate and maintain immunological memory, some antigen-specific T cells must survive and revert to a resting G0/G1 state. Cytokines that bind to the common gamma chain of the IL-2 receptor promote the survival of T cell blasts, but also induce proliferation. In contrast, soluble factors secreted by stromal cells induce Tcell survival in a resting G0/G1 state. We now report that interferon-beta is the principal mediator of stromal cell-mediated Tcell rescue from apoptosis. Interferon-alpha and -beta promote the reversion of blast Tcells to a resting G0/G1 configuration with all the characteristic features of stromal cell rescue; such as high Bcl-XL expression and low Bcl-2. Type I interferons and stromal cells stimulate apparently identical signaling pathways, leading to STAT-1 activation. We also show that this mechanism may play a fundamental role in the persistence of T cells at sites of chronic inflammation; suggesting that chronic inflammation is an aberrant consequence of immunological memory.


Diagnostic and prognostic value of delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) in early osteoarthritis of the hip.
Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) can detect glycosaminoglycan loss in the acetabular cartilage of asymptomatic individuals with cam morphology. The aims of this study were to explore the relationship between cam morphology and dGEMRIC values, and to explore whether baseline dGEMRIC can predict the development of radiographic hip osteoarthritis. Prospective cohort (SibKids) study with clinical, radiographic, and MRI assessment at baseline and five-year follow-up (n = 34). The dGEMRIC values of cartilage regions were correlated with measures of cam morphology. Receiver operating characteristic (ROC) analysis was applied to baseline variables to predict radiographic loss of joint space width. Superolateral acetabular cartilage dGEMRIC values were significantly lower in participants with cam morphology (P < 0.001), defined as an alpha angle greater than 60°. There was a negative correlation between alpha angle and the dGEMRIC value of adjacent acetabular cartilage. This relationship was strongest superoanteriorly (r = -0.697 P < 0.001). There was a positive correlation between baseline dGEMRIC and the magnitude of joint space width narrowing (r = 0.398 P = 0.030). ROC analysis of combined baseline variables (positive impingement test, alpha angle, dGEMRIC ratio) gave an Area Under the Curve (AUC) of 0.75 for predicting joint space width narrowing greater than 0.5 mm within 5 years. The size and position of cam morphology determines the severity and location of progressive cartilage damage, supporting the biomechanical aetiology of femoroacetabular impingement. Baseline dGEMRIC is able to predict the development of radiographic osteoarthritis. Compositional MRI offers the potential to identify patients who may benefit from early intervention to prevent the development of osteoarthritis.


Cancer risk elicitation and communication: lessons from the psychology of risk perception.
Cancer risk perceptions are a key predictor of risk-reduction practices, health behaviors, and processing of cancer information. Nevertheless, patients and the general public (as well as health care providers) exhibit a number of errors and biases in the way they think about risk, such that their risk perceptions and decisions deviate greatly from those prescribed by normative decision models and by experts in risk assessment. For example, people are more likely to engage in screening behaviors such as mammography when faced with loss-based messages than gain-framed messages, and they often ignore the base rate of a given disease when assessing their own risk of obtaining this disease. In this article, we review many of the psychological processes that underlie risk perception and discuss how these processes lead to such deviations. Among these processes are difficulties with use of numerical information (innumeracy), cognitive processes (eg, use of time-saving heuristics), motivational factors (eg, loss and regret aversion), and emotion. We conclude with suggestions for future research in the area, as well as implications for improving the elicitation and communication of personal cancer risk.


Human aging DNA methylation signatures are conserved but accelerated in cultured fibroblasts.
Aging is associated with progressive and site-specific changes in DNA methylation (DNAm). These global changes are captured by DNAm clocks that accurately predict chronological age in humans but relatively little is known about how clocks perform in vitro. Here we culture primary human fibroblasts across the cellular lifespan (~6 months) and use four different DNAm clocks to show that age-related DNAm signatures are conserved and accelerated in vitro. The Skin & Blood clock shows the best linear correlation with chronological time (r = 0.90), including during replicative senescence. Although similar in nature, the rate of epigenetic aging is approximately 62x times faster in cultured cells than in the human body. Consistent with in vivo data, cells aged under hyperglycemic conditions exhibit an approximately three years elevation in baseline DNAm age. Moreover, candidate gene-based analyses further corroborate the conserved but accelerated biological aging process in cultured fibroblasts. Fibroblasts mirror the established DNAm topology of the age-related ELOVL2 gene in human blood and the rapid hypermethylation of its promoter cg16867657, which correlates with a linear decrease in ELOVL2 mRNA levels across the lifespan. Using generalized additive modeling on twelve timepoints across the lifespan, we also show how single CpGs exhibit loci-specific, linear and nonlinear trajectories that reach rates up to -47% (hypomethylation) to +23% (hypermethylation) per month. Together, these high-temporal resolution global, gene-specific, and single CpG data highlight the conserved and accelerated nature of epigenetic aging in cultured fibroblasts, which may constitute a system to evaluate age-modifying interventions across the lifespan.


Managing clinical education through understanding key principles.
Traditionally, a practicum facilitated the integration of on-campus learning and practical workplace training. Over the past 3 decades, an educative practicum has evolved that promotes clinical reasoning, including analytical and evaluative abilities, through reflective practice. Anecdotal evidence indicates that the delivery of clinical education within medical radiation science entry-level programs continues to vacillate between traditional practicums and the new reflective practicums. To review the literature about clinical education within the medical radiation sciences and identify key principles for practitioners seeking to reflect upon and improve their approach to teaching and supporting students in the clinical environment. A search of 3 major journal databases, Internet searches, and hand searches of reference lists were conducted to identify literature about clinical education in the medical radiation sciences from January 1, 2000, to December 31, 2012. Twenty-two studies were included in this review. The 5 key elements associated with clinical education include the clinical support model and quality, overcoming the theory-practice gap, learning outcomes and reliable and valid assessment, preparing and supporting students, and accommodating differing teaching and learning needs. Many factors influence the quality of clinical education, including the culture of the clinical environment and clinical leadership roles. Several approaches can help students bridge the theory-practice gap, including simulators, role-playing activities, and reflective journals. In addition, clinical educators should use assessment strategies that objectively measure student progress, and they should be positive role models for their students. The successful clinical education of students in the medical radiation sciences depends upon the systems, structures, and people in the clinical environment. Clinical education is accomplished through the collaborative efforts of the clinical practitioner, the academic, and the student. Universities should include introductory material on clinical learning and teaching in their radiologic science curriculum.


A survey of the knowledge, attitudes and practices on Zika virus in new York City.
Over 900 travel-associated Zika virus cases have been identified in New York City (NYC), New York. A survey was administered in NYC adapted from the Knowledge, Attitudes, and Practices (KAP) survey on Zika virus developed by the World Health Organization (WHO). A standardized, self-administered, anonymous questionnaire was administered to a convenience sample in Manhattan and the Bronx from June 30th, 2016 to October 21st, 2016. Responses were grouped into six domains based on the content and structure of the questions and were summarized using descriptive statistics or converted into a continuous knowledge score and assessed for associations with pregnancy status and travel history using linear regression. There were 224 respondents with a mean age of 33 (SD ± 11.6) with 77% (170/224) female and 24% (51/224) pregnant. The majority (98% (213/217)) were unable to identify all of the symptoms associated with acute Zika virus infection and all modes of transmission (97% (213/219)). Most participants (85% (187/219)) identified mosquitoes as a mode of transmission. 95% (116/122) reported an association between Zika virus and microcephaly. The most concerning aspect of Zika virus in 46% (91/200) was the risk of disabilities to babies, and risk of sexual transmission (25% (49/200)). When asked what precautions pregnant persons should to reduce the risk of transmission when traveling to a Zika endemic region, only 27% (50/185) identified using condoms during intercourse or refraining from intercourse while pregnant. Knowledge of Zika transmission is significantly positively associated with pregnancy status, but not with travel history. Our results indicate an overall poor understanding of Zika virus symptoms and possible complications, transmission modes, and current recommended prevention guidelines. Pregnancy is positively associated with Knowledge of Zika Transmission, but not other knowledge scores. Reported travel history to Zika endemic regions is not significantly associated with Zika knowledge. There is a need for implementing future public health interventions that particularly focus on protection against Zika transmission, that Zika is sexually transmitted, and risks that the Guillain-Barré Syndrome poses a risk to adults.


Bivalve mollusks: fluid dynamics of burrowing.
When bivalves burrow into soft substrates the foot is first extended and then dilated to obtain a firm anchorage before retraction pulls the shell downward. Pedal dilation is principally caused by adduction of the valves. The hinged shell futnctions as a hydraulic machine in which the strength of the adductor muscles is transferred to the distal part of the foot by means of the body fluids.


Dietary Patterns and Fractures in Postmenopausal Women: Results From the Women's Health Initiative.
Considerable efforts have been undertaken to relate single nutrients to bone health. To this point, results are inconsistent. Suboptimal single nutrient intake does not occur in isolation but rather reflects a poor diet quality. To assess the association between adherence to a diet quality index constructed on the basis of dietary recommendations or existing healthy dietary patterns and fractures in postmenopausal women. Post hoc analysis was conducted of longitudinal data from 40 clinical centers throughout the United States included in the Women's Health Initiative (WHI) observational study. Participants in the prospective cohort included 93 676 women who were eligible for the WHI if they were aged 50 to 79 years. Recruitment was conducted from October 1, 1993, to December 31, 1998, with the study ending August 29, 2014. The WHI food frequency questionnaire was used to derive nutrient and food intake at baseline. Diet quality and adherence were assessed by scores on the alternate Mediterranean Diet (aMED), a 9-category measure of adherence to a Mediterranean dietary pattern; the Healthy Eating Index 2010 (HEI-2010), a 100-point measure of 12 food components; the 11-item Alternate Healthy Eating Index 2010 (AHEI-2010); or the 8-component Dietary Approaches to Stop Hypertension (DASH) diet score. Outcome measures included incident total and hip fractures. Hazard ratios (HRs) by quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses. Of the 93 676 participants, 90 014 were included in the analysis (mean [SD] age, 63.6 [7.4]) years. During a median follow-up time of 15.9 years, there were 2121 cases of hip fractures and 28 718 cases of total fractures. Women scoring in the highest quintile (Q5) of the aMED index had a lower risk for hip fractures (HR, 0.80; 95% CI, 0.66-0.97), with an absolute risk reduction of 0.29% and a number needed to treat of 342 (95% CI, 249-502). No association between the aMED score and total fractures was observed (Q5 HR, 1.01; 95% CI, 0.95-1.07). Higher HEI-2010 or DASH scores tended to be inversely related to hip fracture risk, but the results were nonsignificant (Q5 HR, 0.87; 95% CI, 0.75-1.02; and Q5 HR, 0.89; 95% CI, 0.75-1.06, respectively). The AHEI-2010 score was associated with neither hip nor total fractures. Higher adherence to a Mediterranean diet is associated with a lower risk for hip fractures. These results support that a healthy dietary pattern may play a role in maintaining bone health in postmenopausal women.


Long-term effectiveness of bee venom acupuncture and physiotherapy in the treatment of adhesive capsulitis: a one-year follow-up analysis of a previous randomized controlled trial.
An earlier randomized controlled trial (RCT) study showed that bee venom acupuncture (BVA) in combination with physiotherapy can be more effective in functional improvement and pain reduction in patients with adhesive capsulitis (AC). The objective of the current study was to examine the long-term effect of BVA in combination with physiotherapy on AC of the shoulder. Retrospective 1-year follow-up analysis of a previous RCT using a telephone interview method. Outpatient joint center at the Gang Dong Kyung Hee University Hospital of Seoul, Republic of Korea. A total of 192 patients had been enrolled in the previous study, and 124 of these were excluded from the current study. Sixty-eight patients who had been treated with combined BVA and physiotherapy for AC of the shoulder for 2 months were interviewed at approximately 1 year after treatment by telephone. Sixty of 68 patients were included in the follow-up analysis. Twenty received BV 1 treatment (1:10,000 concentration BVA plus physiotherapy), 22 received BV 2 treatment (1:30,000 concentration BVA plus physiotherapy), and 18 received control treatment (normal saline injection plus physiotherapy). The primary outcome measure was Shoulder Pain And Disability Index (SPADI) score. Secondary outcome measure was score on verbal rating scale for pain and patient satisfaction. Baseline characteristics of the groups did not significantly differ. SPADI scores at 1 year significantly differed between the BV 1 group and the control group (p=0.043). No significant differences were found in pain verbal rating scores after 1 year. Treatment satisfaction with therapy was also assessed, and the BV 1 and BV 2 groups showed significantly greater satisfaction compared with the control group. BVA combined with physiotherapy remains clinically effective 1 year after treatment and may help improve long-term quality of life in patients with AC of the shoulder.


Highly polymorphic mitochondrial DNA and deceiving haplotypic differentiation: implications for assessing population genetic differentiation and connectivity.
Hyperdiverse mtDNA with more than 5% of variable synonymous nucleotide sites can lead to erroneous interpretations of population genetic differentiation patterns and parameters (φST, DEST). We illustrate this by using hyperdiverse mtDNA markers to infer population genetic differentiation and connectivity in Melarhaphe neritoides, a NE Atlantic (NEA) gastropod with a high dispersal potential. We also provide a recent literature example of how mtDNA hyperdiversity may have misguided the interpretation of genetic connectivity in the crab Opecarcinus hypostegus. mtDNA variation surveyed throughout the NEA showed that nearly all M. neritoides specimens had haplotypes private to populations, suggesting at first glance a lack of gene flow and thus a strong population genetic differentiation. Yet, the bush-like haplotype network, though visually misleading, showed no signs of phylogeographic or other haplotype structuring. Coalescent-based gene flow estimates were high throughout the NEA, irrespective of whether or not mtDNA hyperdiversity was reduced by removing hypervariable sites. Melarhaphe neritoides seems to be panmictic over the entire NEA, which is consistent with its long-lived pelagic larval stage. With hyperdiverse mtDNA, the apparent lack of shared haplotypes among populations does not necessarily reflect a lack of gene flow and/or population genetic differentiation by fixation of alternative haplotypes (DEST ≈ 1 does not a fortiori imply φST ≈ 1), but may be due to (1) a too low sampling effort to detect shared haplotypes and/or (2) a very high mutation rate that may conceal the signal of gene flow. Hyperdiverse mtDNA can be used to assess connectivity by coalescent-based methods. Yet, the combined use of φST and DEST can provide a reasonable inference of connectivity patterns from hyperdiverse mtDNA, too.


[Rapid identification of Mycobacterium tuberculosis complex from broth cultures by immunochromatographic assay].
Recently, a simple and rapid commercial assay (BD MGIT TBc ID) has been developed using a monoclonal antibody anti-MPT64 for the differentiation of Mycobacterium tuberculosis complex from other mycobacteria by immunochromatography. We evaluate in this work the clinical usefulness of the test for the identification of 51 strains of M. tuberculosis complex and 24 strains of other mycobacteria belonging to 14 different species, compared with the method of hybridization with DNA probes. Immunochromatographic method performance was excellent, with sensitivity, specificity, positive and negative predictive values of 98, 100, 96.1, and 98.7%, respectively. These results indicate that immunochromatographic assay can be safely used for rapid identification of M. tuberculosis complex in combination with culture in liquid media. The test is extremely simple, provides results in just 15 minutes, requires no complex equipment or specialized personnel and may be a good alternative to molecular methods, especially in small laboratories.


Analysis of case series of milky urine: A single center and departmental clinical experience with emphasis on management perspectives: A prospective observational study.
Milky urine can be due to chyluria or lipiduria due to nephrotic syndrome. Filarial chyluria usually responds to medical management while non-filarial cases may require surgical intervention. To perform a prospective observational study in patients presenting with milky urine in our centre over a period of one year from July 2011 to June 2012, a complete biochemical work up and imaging to find out the site of leakage of lymph if it is a case of chyluria, its response to medical management and the requirement of surgical intervention. Routine blood and urine investigations, 24 hour urine protein excretion, USG abdomen, serum lipid profile and rapid filarial antigen test were done in all. MRI abdomen was done in affordable patients. Renal biopsy was done in some chyluria patients for academic purpose and in milky urine with negative urine ether test. Sclerotherapy was done with 50% dextrose and 0.2% povidone iodine. Patients were followed up with 24 hour urine protein and triglyceride estimation. 18 cases of milky urine were encountered. 8 were filarial chyluria, 9 non- filarial and 1 MCD. Mean urine TG level and median 24 hour urinary protein excretion were 37.2 ± 24.6 mg% and 4.96 g respectively. The mean age for filariasis (22.9 ± 4.5 years) was significantly different from that of non-filarial etiology (31.5 ± 4.8 years) (P = 0.005). The mean 24 hour urinary protein for normal MRI cases (4.64 ± 0.70 g) was significantly different from those with dilated lymphatics (8.15 ± 2.55 g) (P = 0.02). All the non- filarial and 4 filarial cases required sclerotherapy. One patient required a second sitting. Milky urine is most commonly due to chyluria and occasionally due to nephrotic syndrome. Nephrotic syndrome is managed in its own way while chyluria not amenable to pharmacological intervention is managed with sclerotherapy.


Why are you angry with me? Facial expressions of threat influence perception of gaze direction.
Gaze direction can influence the processing of facial expressions. Angry faces are judged more angry when displaying a direct gaze compared to an averted gaze. We investigated whether facial expressions have a reciprocal influence on the perception of gaze. Participants judged the gaze of angry, fearful and neutral faces across a range of gaze directions. Angry faces were perceived as looking at the observer over a wider range than were fearful or neutral faces, which did not significantly differ. This effect was eliminated when presenting inverted faces, suggesting these results cannot be accounted for by differences in visible eye information. Our findings suggest the existence of a reciprocal influence between gaze direction and angry expressions.


Clinical Management of Pediatric Achalasia: A Survey of Current Practice.
Pediatric achalasia is a rare neurodegenerative disorder of the esophagus that requires treatment. Different diagnostic and treatment modalities are available, but there are no data that show how children can best be diagnosed and treated. We aimed to identify current practices regarding the diagnostic and therapeutic approach toward children with achalasia. Information on the current practice regarding the management of pediatric achalasia was collected by an online-based survey sent to members of the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition involved in pediatric achalasia care. The survey was completed by 38 centers from 24 countries. Within these centers, 108 children were diagnosed with achalasia in the last year (median 2, range 0-15). Achalasia was primarily managed by a pediatric gastroenterologist (76%) and involved a multidisciplinary team in 84% of centers, also including a surgeon (87%), radiologist (61%), dietician (37%), speech pathologist (8%), and psychologist (5%). Medical history taking and physical examination were considered most important to establish the diagnosis (50%), followed by (a combination of) manometry (45%) or contrast swallow (21%). Treatment of first choice was Heller myotomy (58%), followed by pneumatic dilation (46%) and peroral endoscopic myotomy (29%). This study shows a great heterogeneity in the management of pediatric achalasia amongst different centers worldwide. These findings stress the need for well-designed intervention trials in children with achalasia. Given the rarity of this disease, we recommend that achalasia care should be managed in centers with access to appropriate diagnostic and treatment modalities.


Expression of D1 but not D2 dopamine receptors in striatal neurons producing neurokinin B in rats.
Neostriatal projection neurons are known to be largely divided into two groups, striatoentopeduncular/striatonigral and striatopallidal neurons, which mainly express D1 and D2 dopamine receptors, respectively. Recently, a small population of neostriatal neurons have been reported to produce neurokinin B (NKB), and send their axons mainly to the basal forebrain regions. To reveal which type of dopamine receptors were expressed by these NKB-producing neurons, we examined rat striatal neurons by combining immunofluorescence labeling for preprotachykinin B (PPTB), the precursor of NKB, and fluorescence in situ hybridization labeling for dopamine receptors. Fluorescent signals for D1 receptor mRNA were detected in 85-89% of PPTB-immunopositive neurons in the neostriatum, accumbens nucleus and lateral stripe of the striatum, whereas almost no signal for D2 receptor was observed in PPTB-positive striatal neurons. To further reveal intracellular signaling downstream of D1 receptor in PPTB-producing neurons, we used a double immunofluorescence labeling method to study the localization of some substrates for protein kinase A (PKA), which was known to be activated by D1 receptor. Although only 3-7% of PPTB-immunopositive striatal neurons displayed immunoreactivity for dopamine- and cAMP-regulated phosphoprotein of 32 kDa, a well-known PKA substrate expressed in the two major groups of neostriatal projection neurons, 60-64% of PPTB-positive striatal neurons exhibited immunoreactivity for striatal-enriched tyrosine phosphatase. These results suggest that NKB-producing neostriatal neurons are similar to striatoentopeduncular/striatonigral neurons in the usage of dopamine receptor subtypes, but different from the two major groups of neostriatal projection neurons in terms of the downstream signaling of dopamine receptors.


Image, eye, and retina (invited review).
Advances in understanding the initial stages of the visual process have been made over the centuries. This heritage will be reviewed with respect to the passage of light through the eye, as well as its gross anatomy and microscopic structure. The links between image formation in the camera and the eye were integrated with the anatomy of the eye in the seventeenth century. They drew attention to the problem of accommodation and to corrections for errors of refraction. Investigations of the structure of the retina were to await the invention of achromatic microscopes in the early nineteenth century. An armory of devices for examining vision and the eye were to follow later in the century. These transformed the study of vision from an observational to an experimental discipline.


Communication-and-resolution programs: the challenges and lessons learned from six early adopters.
In communication-and-resolution programs (CRPs), health systems and liability insurers encourage the disclosure of unanticipated care outcomes to affected patients and proactively seek resolutions, including offering an apology, an explanation, and, where appropriate, reimbursement or compensation. Anecdotal reports from the University of Michigan Health System and other early adopters of CRPs suggest that these programs can substantially reduce liability costs and improve patient safety. But little is known about how these early programs achieved success. We studied six CRPs to identify the major challenges in and lessons learned from implementing these initiatives. The CRP participants we interviewed identified several factors that contributed to their programs' success, including the presence of a strong institutional champion, investing in building and marketing the program to skeptical clinicians, and making it clear that the results of such transformative change will take time. Many of the early CRP adopters we interviewed expressed support for broader experimentation with these programs even in settings that differ from their own, such as systems that do not own and control their liability insurer, and in states without strong tort reforms.


The development of a parenting program for incarcerated mothers in Australia: a review of prison-based parenting programs.
The increasing population of children with an incarcerated parent is a significant public health issue. A literature search highlighted that children of incarcerated parents experience psychological stressors that may potentially impact on health and behavioural outcomes. Parenting programs for prisoners may be of benefit as early parenting experiences during childhood have a significant impact on a child's future experiences as an adolescent and adult. A review of identified evaluation-based studies of parenting programs for prisoners (N = 11), although varied in program delivery approaches and evaluation methods, suggest that such programs have the potential to improve the parenting skills, knowledge and confidence of incarcerated parents. Finally, this paper provides an outline of the development of an Australian based parenting program for incarcerated mothers and their young children.


Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis.
Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (Gzm) are proteases mainly found in cytotoxic lymphocytes that not only have a role in target cell death, but also as mediators of infection and inflammation. In this study we sought to analyse the intracellular expression of GzmA, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected intensive care unit (ICU) patients and 32 healthy controls. Additionally, we measured GzmA and B plasma levels. Both groups of patients presented decreased percentage of natural killer (NK) cells expressing GzmA, B and M relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing GzmB compared to controls. Expression of GzmK remained relatively unaltered between groups. Extracellular levels of GzmB were increased in non-infected ICU patients relative to sepsis patients and healthy controls. Our results show differential alterations in intracellular expression of Gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the Gzm.


Cadherin 6B induces BMP signaling and de-epithelialization during the epithelial mesenchymal transition of the neural crest.
The development of neural crest cells involves an epithelial-mesenchymal transition (EMT) associated with the restriction of cadherin 6B expression to the pre-migratory neural crest cells (PMNCCs), as well as a loss of N-cadherin expression. We find that cadherin 6B, which is highly expressed in PMNCCs, persists in early migrating neural crest cells and is required for their emigration from the neural tube. Cadherin 6B-expressing PMNCCs exhibit a general loss of epithelial junctional polarity and acquire motile properties before their delamination from the neuroepithelium. Cadherin 6B selectively induces the de-epithelialization of PMNCCs, which is mediated by stimulation of BMP signaling, whereas N-cadherin inhibits de-epithelialization and BMP signaling. As BMP signaling also induces cadherin 6B expression and represses N-cadherin, cadherin-regulated BMP signaling may create two opposing feedback loops. Thus, the overall EMT of neural crest cells occurs via two distinct steps: a cadherin 6B and BMP signaling-mediated de-epithelialization, and a subsequent delamination through the basement membrane.


High association of MOG-IgG antibodies in children with bilateral optic neuritis.
Bilateral optic neuritis (bilON) is a rare clinical presentation often thought to be associated with relapsing disorders such as neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS). To characterize the clinical, radiological phenotype and antibody status of children presenting with bilON. Retrospective multicenter study on children with bilON age <18 years with a first episode aquired demyelinating syndrome (ADS), cMRI, AQP4- and serum MOG-antibody status and follow-up data were collected. 30 patients (f:m = 15:15, median age 8.0y) with bilON met the inclusion criteria. 22/30 (73%) were MOG-positive (median: 1:1280, range: 1:160-1:1520). No patient showed AQP4-abs. 4/30 patients (13%), all with high MOG-abs titers, had recurrent episodes. No patient developed MS. Improvement after IVMP was observed in most patients (26/30; 87%). Outcome was favorable with no sequelae in 22/30 patients. Serial MOG-abs titers tested in 15/22 patients decreased to a median of 1:160 (range: 0-1:640) over a period of 31 months (range: 2-141 months) in 14/15 (93%) patients. MR imaging showed a predominantly anterior affection of the visual system in seropositive patients with bilateral intraorbital lesions in 68% (15/22), compared to 25% in MOG-negative patients (2/8). Pediatric bilON is associated with high MOG-abs titers in combination with anterior involvement of the visual system. Despite severe loss of vision, the majority of patients shows distinct recovery after IVMP.


Faculty practice: what do the data show? Findings from the NONPF Faculty Practice Survey. National Organization of Nurse Practitioner Faculties.
This article reports on the findings of the NONPF (National Organization of Nurse Practitioner Faculties) Faculty Practice Survey regarding promotion and tenure. Relevant issues related to tenure for practicing faculty are identified and discussed. Faculty practice has become an increasingly important and complex issue for academic institutions in relation to promotion and tenure. The purpose of this article is to examine the role and patterns of practice among tenured and nontenured faculty in academic nursing institutions and the variables associated with faculty promotion and tenure in these institutions. A survey was mailed to the membership of the National Organization of Nurse Practitioner Faculties to examine the differences between practicing faculty who were tenured and those who were nontenured and to identify predictors of tenure. A 50% response rate (N = 452) was obtained. Findings indicate that only 37% of the practicing faculty were tenured, and more than half (51%) reported that practice was not considered in promotion and tenure decisions at their institutions. The predictors of tenure included practice being considered in promotion and tenure and support for practice at the school of nursing level. Data on reasons faculty practice are also presented. Recommendations for including practice in promotion and tenure guidelines are discussed as well as the ramifications of administrative support for practice.


Histopathological prognostic factors influencing long-term prognosis after surgical resection for hepatic metastases from colorectal cancer.
We aimed to present new histopathological features of metastatic liver nodules as more reliable prognostic factors after surgical resection for colorectal metastatic cancer. Clinicopathological features, including newly proposed histopathological ones, of 63 consecutive patients were reviewed retrospectively to determine which most strongly correlated with long-term prognosis after hepatectomy for metastatic tumors from colorectal cancers, using univariate and multivariate analysis. The 1-, 3-, and 5-year cancer-related survival rates after hepatectomy were 87.8%, 55.2%, and 47.3%, respectively. New histopathological features we proposed, which are expansive growth, marginal fibrosis, and peritumorous lymphocytic infiltration of hepatic tumor, were significant prognostic factors for cancer-related survival after hepatectomy in an univariate analysis. Also in a multivariate analysis, i.e., a stepwise Cox regression analysis, infiltrative, i.e., not expansive, growth of hepatic tumor was one of significant and independent poor prognostic factors for survival after hepatectomy, with moderate to severe lymphatic vessel involvement of the primary colorectal lesion, microscopic cancer invasion at the surgical margin of hepatectomy, and extrahepatic distant metastases. Our results suggest that our proposed new histopathological features of hepatic metastases were good predictors of prognosis after surgical resection for hepatic metastases from colorectal cancer. Especially, infiltrative growth of hepatic tumor is strongly correlated with a poor prognosis after hepatectomy.


Evidence against a direct role for the induction of c-jun expression in the mediation of drug-induced apoptosis in human acute leukemia cells.
Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-beta-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the bcl-2 oncogene and overexpress p26BCL-2, although ara-C or mitoxantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonucleolytic DNA fragmentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression. These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.


Abalone withering syndrome: distribution, impacts, current diagnostic methods and new findings.
Withering syndrome (WS) is a fatal disease of abalone caused by a Rickettsiales-like organism (WS-RLO). The causative agent, 'Candidatus Xenohaliotis californiensis', occurs along the eastern Pacific margin of North America in California, USA, and Baja California, Mexico. However, as infected abalones have been transported to Chile, China, Taiwan, Iceland, Ireland, Israel, Spain, Thailand and Japan, the geographical range of the etiological agent is suspected to be broad, especially where California red abalones Haliotis rufescens are cultured or in areas where native species have been exposed to this species. Susceptibility varies among species, with up to 99% losses of black abalone H. cracherodii in laboratory and field studies in the USA to no losses among the small abalone H. diversicolor supertexta in Thailand. Some populations that have suffered catastrophic losses due to WS have developed resistance to the disease. In addition, a newly identified phage hyperparasite of the WS-RLO may reduce pathogenicity and dampen associated losses. Diagnosis of WS requires the identification of infection with the pathogen (WS-RLO detected via in situ hybridization or histology coupled with PCR and sequence analysis) accompanied by morphological changes that characterize this disease (e.g. pedal and digestive gland atrophy, and digestive gland metaplasia). A quantitative PCR assay was developed and may be useful in quantifying pathogen DNA. Confirmation of infection cannot be done by PCR analysis alone but can be used as a proxy for infection in areas where the agent is established and is recommended for inclusion in health examinations. Avoidance of WS is best accomplished by the establishment of a health history and multiple health examinations prior to movement of animals.


The acute pulmonary toxicity in mice induced by Staphylococcus aureus, particulate matter, and their combination.
Inhalation of pathogenic bacteria transported by particulate matter (PM) presents an important potential threat to human health. Therefore, the pulmonary toxicity in mice caused by Staphylococcus aureus (S. aureus) and PM as individual matter and mixtures was studied. PM and S. aureus were instilled intratracheally into Kunming mice at doses of 0.2 mg/mouse and 5.08 × 106 CFU /mouse, respectively, as individual matter and in combination two times at 5-day intervals. After the exposure period, oxidative stress markers and nitric oxide (NO) in the lung, cellular infiltration, neurotrophins, chemokines, and cytokines in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in sera were examined. Exposure to the combination of PM and S. aureus caused significant increases in malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and NO and significant decreases in total antioxidant capacity (T-AOC) and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in the lung. Meanwhile, the ratio of interleukin (IL)-4 to interferon (INF)-γ, the IL-4 level in BALF, and the IgE concentration in sera were significantly increased in the groups exposed to S. aureus or the combination of PM and S. aureus. Substance P and IL-8 in BALF were significantly increased in mice exposed to PM, S. aureus or their combination. In addition, PM, S. aureus, and their combination caused infiltration of leukocytes into the alveolar tissue spaces. The results suggested that exposure to the combination of PM and S. aureus induced a lung inflammatory response that was at least partly caused by oxidative stress and mediators from the activated eosinophils, neutrophils, alveolar macrophages, and epithelial cells.


Respiration characteristics in temperate rainforest tree species differ along a long-term soil-development chronosequence.
We measured the response of dark respiration (R(d)) to temperature and foliage characteristics in the upper canopies of tree species in temperate rainforest communities in New Zealand along a soil chronosequence (six sites from 6 years to 120,000 years). The chronosequence provided a vegetation gradient characterised by significant changes in soil nutrition. This enabled us to examine the extent to which changes in dark respiration can be applied across forest biomes and the utility of scaling rules in whole-canopy carbon modelling. The response of respiration to temperature in the dominant tree species differed significantly between sites along the sequence. This involved changes in both R(d) at a reference temperature (R(10)) and the extent to which R(d) increased with temperature (described by E(o), a parameter related to the energy of activation, or the change in R(d) over a 10 degrees C range, Q(10)). Site averaged E(o) ranged from 44.4 kJ mol(-1) K(-1) at the 60-year-old site to 26.0 kJ mol(-1) K(-1) at the oldest, most nutrient poor, site. Relationships between respiratory and foliage characteristics indicated that both the temperature response of respiration (E(o) or Q(10)) and the instantaneous rate of respiration increased with both foliar nitrogen and phosphorus content. The ratio of photosynthetic capacity (Whitehead et al. in Oecologia 2005) to respiration (A(max)/R(d)) attained values in excess of 15 for species in the 6- to 120-year-old sites, but thereafter decreased significantly to around five at the 120,000-year-old site. This indicates that shoot carbon acquisition is regulated by nutrient limitations in the retrogressing ecosystems on the oldest sites. Our findings indicate that respiration and its temperature response will vary according to soil age and, therefore, to soil nutrient availability and the stage of forest development. Thus, variability in respiratory characteristics for canopies should be considered when using models to integrate respiration at large spatial scales.


Different effect of two synthetic coumarin-stilbene hybrid compounds on phagocyte activity.
Activated phagocytes, generating a variety of powerful inflammatory mediators, such as oxygen and nitrogen species, may participate in oxidative stress-mediated inflammation and organ toxicity. At present, great attention is devoted to the important class of phenolic compounds - coumarins - due to their antiinflammatory/antioxidant activities. We compared two synthetic phenylcoumarins: 7-hydroxy-3-(4´-hydroxyphenyl) coumarin (HHC; 0.01-100 µmol/l) and its hydrogenated analogue: 7-hydroxy-3-(4´-hydroxyphenyl)-3,4-dihydrocoumarin (HHDC; 0.01-100 µmol/l) as their ability to inhibit reactive oxygen species (ROS) generation in human neutrophils and nitric oxide (NO) production by RAW 264.7 macrophages in vitro, with respect to some of their physicochemical characteristics. ROS production was measured with luminol-enhanced chemiluminescence (CL) in the microplate luminometer Immunotech LM-01T, nitrite formation was determined by the Griess reaction - spectrophotometrically. The radical scavenging assays were employed to assess the antiradical activity values. The relevant physico-chemical parameters of the compounds tested, electronic and hydrophobic, were determined experimentally as well as by suitable computational programmes. Both HHC and HHDC were found to decrease significantly (p<0.01) CL of whole blood stimulated with phorbol myristate acetate (PMA) from the concentration of 1 µmol/l. While HHC significantly inhibited CL stimulated by A23187 and opsonized zymosan (OpZ), HHDC was ineffective. Unlike HHDC, HHC in the concentrations of 10 and 100 µmol/l significantly (p<0.01) reduced NO formation in lipopolysaccharide (LPS) -stimulated murine macrophages RAW 264.7. HHC possessed the higher free radical reducing efficacy in accordance with its more favourable values of electronic parameters in comparison with HHDC. Our results show the different inhibitory effects of HHC and HHDC on phagocytic activity that might be the result of their diverse free radical scavenging properties and lipophilicity features.


A comparison of methods for differential expression analysis of RNA-seq data.
Finding genes that are differentially expressed between conditions is an integral part of understanding the molecular basis of phenotypic variation. In the past decades, DNA microarrays have been used extensively to quantify the abundance of mRNA corresponding to different genes, and more recently high-throughput sequencing of cDNA (RNA-seq) has emerged as a powerful competitor. As the cost of sequencing decreases, it is conceivable that the use of RNA-seq for differential expression analysis will increase rapidly. To exploit the possibilities and address the challenges posed by this relatively new type of data, a number of software packages have been developed especially for differential expression analysis of RNA-seq data. We conducted an extensive comparison of eleven methods for differential expression analysis of RNA-seq data. All methods are freely available within the R framework and take as input a matrix of counts, i.e. the number of reads mapping to each genomic feature of interest in each of a number of samples. We evaluate the methods based on both simulated data and real RNA-seq data. Very small sample sizes, which are still common in RNA-seq experiments, impose problems for all evaluated methods and any results obtained under such conditions should be interpreted with caution. For larger sample sizes, the methods combining a variance-stabilizing transformation with the 'limma' method for differential expression analysis perform well under many different conditions, as does the nonparametric SAMseq method.


Inoculum and zeolite synergistic effect on anaerobic digestion of poultry manure.
Poultry manure is an ammonia-rich substrate due to its high content of proteins and amino acids. Ammonia is the major inhibitor of anaerobic digestion (AD) process, affecting biogas production and causing great economic losses to the biogas plants. In this study, the effect of different natural zeolite dosages on the mesophilic AD of poultry manure inoculated with a non-acclimatized to ammonia inoculum (dairy manure) was investigated. Additionally, a comparative analysis was performed between the data extracted from this study and the results of a previous study, which has been conducted under the same experimental conditions but with the use of ammonia acclimatized inoculum (swine manure). At 5 and 10 g zeolite L(-1), the methane yield of poultry manure was 43.4% and 80.3% higher compared with the experimental set without zeolite addition. However, the ammonia non-acclimatized inoculum was not efficient in digesting poultry manure even in the presence of 10 g zeolite L(-1), due to low methane production (only 39%) compared with the maximum theoretical yield. Finally, ammonia acclimatized inoculum and zeolite have demonstrated a possible 'synergistic effect', which led to a more efficient AD of poultry manure. The results of this study could potentially been used by the biogas plant operators to efficiently digest poultry manure.


Monte Carlo modeling of the response of NRC's 90Sr/90Y primary beta standard.
The BEAMnrc/EGSnrc Monte Carlo code system is employed to develop a model of the National Research Council of Canada primary standard of absorbed dose to tissue in a beta radiation field, comprising an extrapolation chamber and 90Sr/90Y beta source. We benchmark the model against the measured response of the chamber in terms of absorbed dose to air, for three different experimental setups when irradiated by the 90Sr/90Y source. For the first setup, the chamber cavity depth is fixed at 0.2 cm and the source-to-chamber distance varied between 11 and 60 cm. In the other two cases, the source-to-chamber distance is fixed at 30 cm. In one case the response for different chamber depths is studied, while in the other case the chamber depth is fixed at 0.2 cm as different thicknesses of Mylar are added to the front surface of the extrapolation chamber. The agreement as a function of distance between the calculated and measured responses is within 0.37% for a variation in response of a factor of 29. In the case of dose versus chamber depth, the agreement is within 0.4% for the ISO-recommended nominal depths of 0.025-0.25 cm. Agreement between calculated and measured responses is very good (between 0.02% and 0.2%) for added Mylar foils of thicknesses up to 10.8 mg cm(-2). For larger Mylar thicknesses, deviations of 0.6%-1.2% are observed, which are possibly due to the systematic uncertainties associated with the restricted collisional stopping powers of air or Mylar used in the calculations. We conclude that our simulation model represents the extrapolation chamber and 90Sr/90Y source with adequate accuracy to calculate correction factors for accurate realization of dose rate to tissue at a depth of 7 mg cm(-2) in an ICRU tissue phantom, despite the fact that the uncertainties in the physical characteristics of the source leave some uncertainty in certain calculated quantities.


Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013.
Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5'-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5'UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.


Recovery of influenza A viruses from lake water and sediments by experimental inoculation.
Influenza A viruses (IAV) are zoonotic pathogens relevant to human, domestic animal and wildlife health. Many avian IAVs are transmitted among waterfowl via a faecal-oral-route. Therefore, environmental water where waterfowl congregate may play an important role in the ecology and epidemiology of avian IAV. Water and sediment may sustain and transmit virus among individuals or species. It is unclear at what concentrations waterborne viruses are infectious or remain detectable. To address this, we performed lake water and sediment dilution experiments with varying concentrations or infectious doses of four IAV strains from seal, turkey, duck and gull. To test for infectivity of the IAV strains in a concentration dependent manner, we applied cultivation to specific pathogen free (SPF) embryonated chicken eggs and Madin-Darby Canine Kidney (MDCK) cells. IAV recovery was more effective from embryonated chicken eggs than MDCK cells for freshwater lake dilutions, whereas, MDCK cells were more effective for viral recovery from sediment samples. Low infectious dose (1 PFU/200 μL) was sufficient in most cases to detect and recover IAV from lake water dilutions. Sediment required higher initial infectious doses (≥ 100 PFU/200 μL).


Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin.
A stable HeLa cell line expressing a dynamin mutant, dynts, exhibits a temperature-sensitive defect in endocytic clathrin-coated vesicle formation. Dynts carries a point mutation, G273D, corresponding to the Drosophila shibirets1 allele. The ts-defect in receptor-mediated endocytosis shows a rapid onset (< 5 min) and is readily reversible. At the nonpermissive temperature (38 degrees C) HRP uptake is only partially inhibited. Moreover, when cells are held at the nonpermissive temperature, fluid phase uptake fully recovers to wild-type levels within 30 min, while receptor-mediated endocytosis remains inhibited. The residual HRP uptake early after shift to the nonpermissive temperature and the induced HRP uptake that occurs after recovery are insensitive to cytosol acidification under conditions that potently inhibit receptor-mediated endocytosis of Tfn. Together, these results suggest that a dynamin- and clathrin-independent mechanism contributes to the total constitutive pinocytosis in HeLa cells and that dynts cells rapidly and completely compensate for the loss of clathrin-dependent endocytosis by inducing an alternate endocytic pathway.


Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR.
Steroid hormones modulate activity of the nuclear receptor constitutive active receptor (CAR, or constitutive androstane receptor) in mouse liver. Progesterone and testosterone repress the constitutive activity of mouse CAR (mCAR) in cell-mediated transfection assays, whereas estrogens activate the repressed receptor. This repression and activation is not observed with human CAR. To define the structural basis that confers the hormone responsiveness to mCAR, we constructed various chimeric and mutated receptors and examined their response to steroid hormones. The hormone responsiveness resided near or within AF-2 domain of mCAR. Moreover, a single mutation of threonine at position 350 to the corresponding methionine in the human counterpart abolished the repression of mCAR by steroid hormones. Coactivation by steroid receptor coactivator 1 (SRC-1) of mCAR did not depend on the threonine 350. However, overexpression of SRC-1 counteracted progesterone to repress mCAR activity. Thus, threonine 350 seems to regulate hormone responsiveness of mCAR by interfering indirectly an interaction of the receptor with a coactivator.


Genetic characterization of rabies field isolates from Venezuela.
Twenty samples from cases of rabies in humans and domestic animals diagnosed in Venezuela between 1990 and 1994 and one sample from a vampire bat collected in 1976 were characterized by reactivity to monoclonal antibodies against the viral nucleoprotein and by patterns of nucleotide substitution in the nucleoprotein gene. Three antigenic variants were found: 1, 3, and 5. Antigenic variant 1 included all samples from dogs and humans infected by contact with rabid dogs. Unique substitutions permitted identification of two separate outbreaks of dog rabies in the Maracaibo Depression and Los Llanos region and in the Andean region of Venezuela. Samples from the vampire bat and two head of cattle were characterized as antigenic variant 3 and showed a nucleotide sequence homology of 96 to 98% to each other and to samples of vampire bat-associated rabies throughout Latin America. Ten of the remaining 12 samples were characterized as antigenic variant 5. Genetic studies indicated that 11 of these samples formed a highly homologous and distinctive group but were closely related to samples of vampire bat-associated rabies. The 12th sample of variant 5 (from a cat) showed only 78 to 80% genetic homology to samples of rabies associated with vampire bats. The application of antigenic and genetic typing to rabies surveillance in Latin America is essential to improve control programs. Recognition of the source of outbreaks of dog rabies and identification of wildlife species maintaining sylvatic cycles of rabies transmission permit better utilization of public health resources.


Strong bound exciton-photon coupling in ZnO whispering gallery microcavity.
We report the cathodoluminescence (CL) study of bound-exciton-polaritons in ZnO whispering gallery (WG) microcavity. Thanks to the very high spatial resolution (: 100 nm) of CL technique, a scanning CL mapping along the tapered ZnO nanowire is achieved. We observe a clear anticrossing behavior which demonstrates the strong coupling between cavity mode and bound-excitons. Coupled oscillator model including both bound excitons and free excitons fits well with the experimental results. The energy splitting of bound-exciton-polaritons:2.6 meV is obtained.


The association between neighborhood socioeconomic status, cardiovascular and cerebrovascular risk factors, and cognitive decline in the Health and Retirement Study (HRS).
Background: A small but growing body of evidence supports a relationship between neighborhood socioeconomic status (NSES) and cognitive decline. Additional work is needed to characterize this relationship controlling for risk factors such as cardiovascular, cerebrovascular, and genetic risk factors.Methods: Cognitive decline was assessed in association with NSES, and cardiovascular and cerebrovascular risk factors (heart disease, diabetes, hypertension, and stroke) in 8,198 individuals from the 1992-2010 waves of the Health and Retirement Study (HRS). Latent class trajectory analysis determined the number of cognitive trajectory classes that best fit the data, and a multinomial logistic regression model in the latent class framework assessed the risk for cognitive classes conferred by NSES index score and heart disease, diabetes, hypertension, and stroke across three trajectory classes of cognitive function. The analyses controlled for genetic risk for cognitive decline (including APOE genotype) and demographic variables, including education.Results: The HRS sample was 57.6% female and 85.5% White, with a mean age of 67.5(3.5) years at baseline. The three-quadratic-class model best fit the data, where higher classes represented better cognitive function. Those with better cognitive function were mainly younger white females. Those in the highest quartile of NSES had 57% higher odds of being in the high cognitive function class. Heart disease, diabetes, hypertension, and stroke each increased the odds having of lower cognitive function.Conclusions: In examining the relationship of cognitive status with various variables, neighborhood socioeconomic status, cardiovascular risk, and cerebrovascular risk persisted across the cognitive trajectory classes.


Differences in providers' beliefs about benefits and risks of hormone replacement therapy in managed care.
Our objective was to determine if physician beliefs about the benefits and risks of hormone replacement therapy (HRT) differ by physician gender or specialty in a managed care setting. In a cross-sectional survey of providers in a health maintenance organization in North Carolina, 105 gynecologists, internists, and family physicians and physician assistants were surveyed, and 74 providers completed and returned the survey (70.5% response rate). Providers' beliefs about the benefits and risks of HRT differed by specialty and gender of physician. Gynecologists are significantly less concerned about the potential risks of HRT on breast cancer (p = 0.004) and thromboembolic events (p = 0.005) compared with family physicians and internists. Female providers across the three specialty categories were significantly different from their male colleagues in their beliefs about the benefits of HRT with regard to the reduction in risk of heart disease (79% versus 64%, p = 0.001), osteoporosis (83% versus 75%, p = 0.045), and Alzheimer's disease (45% versus 26%, p = 0.026). There was a trend toward female physicians being more convinced about the risks of breast cancer than their male colleagues (p = 0.08). Our results suggest that providers in a managed care setting vary in their beliefs about the benefits and risks of HRT, and this may affect provider-patient discussions about HRT.


Detection of dental fluorosis-associated quantitative trait Loci on mouse chromosomes 2 and 11.
Systemic exposure to greater than optimal fluoride (F) can lead to dental fluorosis (DF). Parental A/J (DF-susceptible) and 129P3/J (DF-resistant) inbred mice were used for histological studies and to generate F2 progeny. Mice were treated with 0 or 50 ppm F in their drinking water for 60 days. A clinical criterion (modified Thylstrup and Fejerskov categorical scale) was used to assess the severity of DF for each individual F2 animal. Parental strains were subjected to histological examination of maturing enamel. F treatment resulted in accumulation of amelogenins in the maturing enamel of A/J mice. Quantitative trait loci (QTL) detection was performed using phenotypic extreme F2 animals genotyped for 354 single nucleotide polymorphism-based markers distributed throughout the mouse genome followed by chi(2) analysis. Significant evidence of association was observed on chromosomes 2 and 11 for a series of consecutive markers (p < 0.0001). Further analyses were performed to examine whether the phenotypic effects were found in both male and female F2 mice or whether there was evidence for gender-specific effects. Analyses performed using the markers on chromosomes 2 and 11 which were significant in the mixed-gender mice were also significant when analyses were limited to only the male or female mice. The QTL detected on chromosomes 2 and 11 which influence the variation in response to fluorosis have their effect in mice of both genders. Finally, the QTL in both chromosomes appear to have an additive effect.


A systematic review of treatment outcomes for children with childhood apraxia of speech.
To present a systematic review of single-case experimental treatment studies for childhood apraxia of speech (CAS). A search of 9 databases was used to find peer-reviewed treatment articles from 1970 to 2012 of all levels of evidence with published communication outcomes for children with CAS. Improvement rate differences (IRDs) were calculated for articles with replicated (n > 1), statistically compared treatment and generalization evidence. Forty-two articles representing Phase I and II single-case experimental designs (SCEDs; n = 23) or case series or description studies ( n = 19) were analyzed. Six articles showed high CAS diagnosis confidence. Of the 13 approaches within the 23 SCED articles, treatments were primarily for speech motor skills ( n = 6), linguistic skills ( n = 5), or augmentative and alternative communication ( n = 2). Most participants responded positively to treatment, but only 7 of 13 approaches in SCED studies reported maintenance and/or generalization of treatment effects. Three approaches had preponderant evidence (Smith, 1981). IRD effect sizes were calculated for Integral Stimulation/Dynamic Temporal and Tactile Cueing, Rapid Syllable Transition Treatment, and Integrated Phonological Awareness Intervention. At least 3 treatments have sufficient evidence for Phase III trials and interim clinical practice. In the future, efficacy needs to be established via maintenance and generalization measures.


Intraocular pressure and its correlation with midnight plasma cortisol level in Cushing's disease and other endogenous Cushing's syndrome.
The purpose of this study is to measure intraocular pressure (IOP) and evaluate the correlation between IOP and midnight plasma cortisol (MPC) level in patients with Cushing's disease (CD) and other endogenous Cushing's syndrome (ECS). This is a cross-sectional study from a single center including newly diagnosed patients with CD or ECS. All patients underwent detailed ophthalmological evaluation. IOP was measured by Goldmann applanation tonometry in the morning and evening on two consecutive days. MPC value was obtained for each patient. The data were compared using paired and unpaired t-test, Mann-Whitney U-test, and Spearman's rank correlation coefficient. Among 32 patients, 22 were CD (68.75%) and 10 patients were other ECS (31.25%). A total of 25 patients (78.12%) in our study group had normal IOP (<22 mmHg), and seven patients (21.88%) had increased IOP (≥22 mmHg). The percentage of patients with normal IOP was found to be significantly higher compared to percentage of patients with high IOP (P = 0.001) using one-sample Chi-square test. Mean MPC value was 468.6 ± 388.3 nmol/L in patients having IOP ≥22 mmHg and 658.5 ± 584 nmol/L in those with IOP <22 mmHg from both CD and ECS groups, but the difference was not statistically significant. No correlation was found between IOP and MPC (Spearman's rank correlation rho = -0.16 [P = 0.38]). In CD and ECS patients, IOP elevation is an uncommon feature, and high IOP in either group does not correlate with MPC level.


PolySac3DB: an annotated data base of 3 dimensional structures of polysaccharides.
Polysaccharides are ubiquitously present in the living world. Their structural versatility makes them important and interesting components in numerous biological and technological processes ranging from structural stabilization to a variety of immunologically important molecular recognition events. The knowledge of polysaccharide three-dimensional (3D) structure is important in studying carbohydrate-mediated host-pathogen interactions, interactions with other bio-macromolecules, drug design and vaccine development as well as material science applications or production of bio-ethanol. PolySac3DB is an annotated database that contains the 3D structural information of 157 polysaccharide entries that have been collected from an extensive screening of scientific literature. They have been systematically organized using standard names in the field of carbohydrate research into 18 categories representing polysaccharide families. Structure-related information includes the saccharides making up the repeat unit(s) and their glycosidic linkages, the expanded 3D representation of the repeat unit, unit cell dimensions and space group, helix type, diffraction diagram(s) (when applicable), experimental and/or simulation methods used for structure description, link to the abstract of the publication, reference and the atomic coordinate files for visualization and download. The database is accompanied by a user-friendly graphical user interface (GUI). It features interactive displays of polysaccharide structures and customized search options for beginners and experts, respectively. The site also serves as an information portal for polysaccharide structure determination techniques. The web-interface also references external links where other carbohydrate-related resources are available. PolySac3DB is established to maintain information on the detailed 3D structures of polysaccharides. All the data and features are available via the web-interface utilizing the search engine and can be accessed at http://polysac3db.cermav.cnrs.fr.


Management of Postoperative Spondylodiscitis with and without Internal Fixation.
Postoperative spondylodiscitis is relatively uncommon. This complication is associated with increased cost, and long-term of inability to work, and even morbidity. Although the majority of postoperative spondylodiscitis cases can be well managed by conservative treatment, postoperative spondylodiscitis after internal fixation and those cases that are unresponsive to the conservative treatment present challenges to the surgeon. Here, a review was done to analyze the treatment of postoperative spondylodiscitis with/without internal fixation. This review article suggested that majority of postoperative spondylodiscitis without internal fixation could be cured by conservative treatment. Either posterior or anterior debridement can be used to treat postoperative spondylodiscitis without internal fixation when conservative treatment fails. In addition, minimally invasive debridement and drainage may also be an alternative treatment. In case of postoperative spondylodiscitis after internal fixation, surgical treatment was required. In the cervical spine, it can be well managed by anterior debridement, removal of internal fixation, and reconstruction of the spinal stability by using bone grafting/cage/anterior plate. Postoperative spondylodiscitis after internal fixation is successfully managed by combined anterior debridement, fusion with posterior approach and removal of pedicle screw or extension of pedicle screw beyond the lesion site, in the thoracic and lumbar spine.


What's in a norm? Sources and processes of norm change.
This reply to the commentary by E. Staub and L. A. Pearlman (2009) revisits the field experimental results of E. L. Paluck (2009). It introduces further evidence and theoretical elaboration supporting Paluck's conclusion that exposure to a reconciliation-themed radio soap opera changed perceptions of social norms and behaviors, not beliefs. Experimental and longitudinal survey evidence reinforces the finding that the radio program affected socially shared perceptions of typical or prescribed behavior-that is, social norms. Specifically, measurements of perceptions of social norms called into question by Staub and Pearlman are shown to correlate with perceptions of public opinion and public, not private, behaviors. Although measurement issues and the mechanisms of the radio program's influence merit further testing, theory and evidence point to social interactions and emotional engagement, not individual education, as the likely mechanisms of change. The present exchange makes salient what is at stake in this debate: a model of change based on learning and personal beliefs versus a model based on group influence and social norms. These theoretical models recommend very different strategies for prejudice and conflict reduction. Future field experiments should attempt to adjudicate between these models by testing relevant policies in real-world settings.


Occupational heat stress management: Does one size fit all?
Heat stress is a deadly occupational hazard that is projected to increase in severity with global warming. While upper limits for heat stress designed to protect all workers have been recommended by occupational safety institutes for some time, heat stress continues to compromise health and productivity. In our view, this is largely explained by the inability of existing guidelines to consider the inter-individual (age, sex, disease, others) and intra-individual (medication use, fitness, hydration, others) factors that cause extensive variability in physiological tolerance to a given heat stress. In conditions that do not exceed the recommended limits, this 'one size fits all' approach to heat stress management can lead to reductions in productivity in more heat-tolerant workers, while compromising safety in less heat-tolerant workers who may develop heat-related illness, even in temperate conditions. Herein, we discuss future directions in occupational heat stress management that consider this individual variability.


Chiropractic and rehabilitation management of a patient with extraforaminal entrapment of L4 nerve with balance problem.
Disc herniation is one of the most common causes of low back pain with radicular pain. Among various types of disc herniation, the extraforaminal disc herniation is a rare cause of lumbar radiculopathy. The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in the treatment of a rare case of extraforaminal L4 nerve entrapment causing severe L4 radiculopathy and chronic mild low back pain (LBP). The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in treatment of rare case of extraforaminal L4 nerve entrapment which caused severe L4 radiculopathy and chronic mild low back pain (LBP). A 45-year old female patient arrived at the clinic with chronic mild low back pain and right buttock pain, all of which had presented for two years' duration. During the preceding month, the radicular pain initiated in medium to high intensity, radiating to her right leg following the L4 dermatomal pattern with a periodic tingling sensation in her right foot. A neuro exam demonstrated a proprioception deficit in her right leg. A Romberg test was positive. The patient was treated by low amplitude high velocity spinal and extremity manipulation for 10 consecutive sessions (2 weeks), followed by rehabilitation and exercise therapy including advanced myofascial release therapy for an additional 12 sessions (4 weeks). After treatment, the patient reported a significant improvement in her low back pain and radiculopathy. In addition, she achieved some improvement in balance. It seems that Chiropractic care and rehabilitation therapy may be a safe and effective modality in treatment of an L4 radiculopathy in a patient with an extraforaminal L4 nerve entrapment. Although it is rare, an L4 extraforaminal disc herniation should be considered as a possible cause of symptoms in patients with chronic mild low back pain and severe L4 radiculopathy.