Requirement for the SLP-76 adaptor GADS in T cell development.
GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling.


[Model of the formation of nystagmic reactions to a set of caloric tests].
The model can furnish additional information about the vestibulary system, when evaluating caloric tests. The model has been built with certain assumptions being made. The nystagmus intensity (the slow component rate during maximum intensity) is assumed to be proportional to the difference between energy levels (EL) of the right and left vestibular nuclear complexes (NC). El of each NC is equal to the afferent flow (AF) plus its inherent activity (IA). During caloric (two warm and two cold) tests IA remains constant. AF at rest is equal to spontaneous activity of receptors and during stimulation it increases or decreases in a linear fashion. Parameters of the model are: difference between intensities of reactions to warm and cold tests, difference between EL of two (right and left) unstimulated NC, and ratio of nystagmus intensity to the stimulus for each labyrinth. The behavior of the model during vestibular dysfunctions of various origin (changes in one of AF characteristics or changes in IA of one NC) is discussed. The diagnostic application of the model is illustrated by the discussion of nystagmometric data. The conclusion about vestibular dysfunction and its etiology can be made on the basis of statistic analysis of parameters of the model in the norm.


Daytime systolic ambulatory blood pressure with a two-step switch from candesartan to olmesartan monotherapy and the fixed-dose combination of olmesartan/amlodipine in patients with uncontrolled essential hypertension (SEVICONTROL-2).
The objective of this study was to investigate the efficacy of the fixed-dose combination olmesartan/amlodipine 40/10 mg in patients with moderate essential hypertension not controlled on candesartan 32 mg. This was a prospective, single-arm, phase IV study. The primary endpoint was the change in mean daytime systolic blood pressure (BP). A total of 77 of 89 screened patients started candesartan 32 mg, 62 olmesartan 40 mg, and 57 olmesartan 40 mg/amlodipine 10 mg. Mean daytime systolic BP was reduced by 9.8±15.2 mm Hg (P<.001) vs candesartan monotherapy. Office BP reduction was 9.2±18.8/5.0±8.9 mm Hg (P<0.001). Treatment goals (<140/90 mm Hg for office and <135/85 mm Hg for ambulatory BP) were achieved in 58.2% and 78.4% of patients, respectively. There was one drug-related adverse event (edema) and no serious adverse events. Patients of Caucasian ethnicity with moderate essential hypertension uncontrolled on candesartan experienced a further drop in BP using olmesartan and amlodipine.


Copper stress response in yeast Rhodotorula mucilaginosa AN5 isolated from sea ice, Antarctic.
Heavy metal pollution in Antarctic is serious by anthropogenic emissions and atmospheric transport. To dissect the heavy metal adaptation mechanisms of sea-ice organisms, a basidiomycetous yeast strain AN5 was isolated and its cellular changes were analyzed. Morphological, physiological, and biochemical characterization indicated that this yeast strain belonged to Rhodotorula mucilaginosa AN5. Heavy metal resistance pattern of Cd > Pb = Mn > Cu > Cr > Hg was observed. Scanning electron microscopic (SEM) results exhibited altered cell surface morphology under the influence of copper metal compared to that with control. The determination of physiological and biochemical changes manifested that progressive copper treatment significantly increased antioxidative reagents content and enzymes activity in the red yeast, which quench the active oxygen species to maintain the intercellular balance of redox state and ensure the cellular fission and growth. Comparative proteomic analysis revealed that, under 2 mM copper stress, 95 protein spots were tested reproducible changes of at least 10-fold in cells. Among 95 protein spots, 43 were elevated and 52 were decreased synthesis. After MALDI TOF MS/MS analysis, 51 differentially expressed proteins were identified successfully and classified into six functional groups, including carbohydrate and energy metabolism, nucleotide and protein metabolism, protein folding, antioxidant system, signaling, and unknown function proteins. Function analysis indicated that carbohydrate and energy metabolism-, nucleotide and protein metabolism-, and protein folding-related proteins played central role to the heavy metal resistance of Antarctic yeast. Generally, the results revealed that the yeast has a great capability to cope with heavy metal stress and activate the physiological and protein mechanisms, which allow more efficient recovery after copper stress. Our studies increase understanding of the molecular resistance mechanism of polar yeast to heavy metal, which will be benefitted for the sea-ice isolates to be a potential candidate for bioremediation of metal-contaminated environments.


Mechanobiology of the meniscus.
The meniscus plays a critical biomechanical role in the knee, providing load support, joint stability, and congruity. Importantly, growing evidence indicates that the mechanobiologic response of meniscal cells plays a critical role in the physiologic, pathologic, and repair responses of the meniscus. Here we review experimental and theoretical studies that have begun to directly measure the biomechanical effects of joint loading on the meniscus under physiologic and pathologic conditions, showing that the menisci are exposed to high contact stresses, resulting in a complex and nonuniform stress-strain environment within the tissue. By combining microscale measurements of the mechanical properties of meniscal cells and their pericellular and extracellular matrix regions, theoretical and experimental models indicate that the cells in the meniscus are exposed to a complex and inhomogeneous environment of stress, strain, fluid pressure, fluid flow, and a variety of physicochemical factors. Studies across a range of culture systems from isolated cells to tissues have revealed that the biological response of meniscal cells is directly influenced by physical factors, such as tension, compression, and hydrostatic pressure. In addition, these studies have provided new insights into the mechanotransduction mechanisms by which physical signals are converted into metabolic or pro/anti-inflammatory responses. Taken together, these in vivo and in vitro studies show that mechanical factors play an important role in the health, degeneration, and regeneration of the meniscus. A more thorough understanding of the mechanobiologic responses of the meniscus will hopefully lead to therapeutic approaches to prevent degeneration and enhance repair of the meniscus.


miRNA-dis: microRNA precursor identification based on distance structure status pairs.
MicroRNA precursor identification is an important task in bioinformatics. Support Vector Machine (SVM) is one of the most effective machine learning methods used in this field. The performance of SVM-based methods depends on the vector representations of RNAs. However, the discriminative power of the existing feature vectors is limited, and many methods lack an interpretable model for analysis of characteristic sequence features. Prior studies have demonstrated that sequence or structure order effects were relevant for discrimination, but little work has explored how to use this kind of information for human pre-microRNA identification. In this study, in order to incorporate the structure-order information into the prediction, a method called "miRNA-dis" was proposed, in which the feature vector was constructed by the occurrence frequency of the "distance structure status pair" or just the "distance-pair". Rigorous cross-validations on a much larger and more stringent newly constructed benchmark dataset showed that the miRNA-dis outperformed some state-of-the-art predictors in this area. Remarkably, miRNA-dis trained with human data can correctly predict 87.02% of the 4022 pre-miRNAs from 11 different species ranging from animals, plants and viruses. miRNA-dis would be a useful high throughput tool for large-scale analysis of microRNA precursors. In addition, the learnt model can be easily analyzed in terms of discriminative features, and some interesting patterns were discovered, which could reflect the characteristics of microRNAs. A user-friendly web-server of miRNA-dis was constructed, which is freely accessible to the public at the web-site on http://bioinformatics.hitsz.edu.cn/miRNA-dis/.


Association of trauma from occlusion with localized gingival recession in mandibular anterior teeth.
There have been passing references in history that excessive occlusal forces might be a causative factor in gingival recession. The purpose of the present cross-sectional study was to explore the role of trauma from occlusion on the development of gingival recession. Three hundred patients reporting to the department of Periodontics were screened for the presence of gingival recession in the lower incisors. A single trained examiner carried out clinical examination for signs of trauma from occlusion, such as fremitus test, presence of wear facets and mobility. The data were analyzed by chi square test. No statistically significant relationship was observed between the presence of a positive fremitus and wear facets with gingival recession. However, a significant association was observed between patients who experienced mobility and gingival recession. There does appear to be a relationship between fremitus and tooth wear with gingival recession based on the results of the present study, though not conclusive. However, the sign of tooth mobility, which is a feature of trauma from occlusion, appeared to be a predictor of positive association with gingival recession.


Anterior mandibular rehabilitation causing chronic obstructive sialadenitis: ?A series of sialo-CBCT cases and literature review.
The aim of this study was to assess and present, using sialo-cone beam computed tomography (sialo-CBCT) examination, cases of submandibular gland (SM) chronic obstructive sialadenitis (COS) caused by dental rehabilitation. Clinical and radiographic data of all patients referred for SM sialo-CBCT imaging in the Oral and Maxillofacial Imaging Unit with recurrent SM swelling between January 2012 and July 2015 were reviewed. Cases with suggested iatrogenic cause were selected and described. A literature review of similar cases was also performed. Seventy-one patients with salivary gland (SG) swelling were referred for SM sialo-CBCT. Of these, 16 had implant-supported fixed partial prostheses and seven had full mandibular overdentures. In five patients, COS was diagnosed and a causal relationship between their dental rehabilitation and symptoms was suggested. A literature search revealed 11 cases of SM COS secondary to anterior mandibular rehabilitation. Clinicians rehabilitating the anterior edentulous mandibular region should be aware that both fixed and removable devices may block the orifices of the SM, causing COS.


Highly water-soluble and biocompatible hyaluronic acid functionalized upconversion nanoparticles as ratiometric nanoprobes for label-free detection of nitrofuran and doxorubicin.
Antibiotic detection is crucial and challenging because the widespread consumption of antibiotics has shown extensive harmful effects on food, environment and human health. Here, we propose highly water-soluble and biocompatible hyaluronic acid (HYA) functionalized upconversion nanoparticles (UCNPs) for ratiometric detection of multiple antibiotics. The ultraviolet upconversion luminescence (UCL) from UCNPs was significantly quenched by nitrofurazone (NFZ)/nitrofurantoin (NFT), and blue UCL was quenched by doxorubicin (DOX), while red UCL remained unchanged for internal reference. The UCNPs-HYA nanoprobes exhibit excellently sensitive and selective NFZ, NFT and DOX detection in linear range of 2.5-100 μM, 2.5-80 μM, and 2.5-200 μM with the LOD at 0.28 μM (55 μg/kg), 0.20 μM (48 μg/kg) and 0.17 μM (97 μg/kg), respectively. The nanoprobes achieved detecting real samples of NFZ in lake water, liquid milk and chicken meat with satisfactory results, and UCL bioimaging of DOX in HeLa cells. The UCNPs-HYA ratiometric nanoprobes are promising for food samples detection and potential biosensing in the cellular environment.


Modulation of Adipose-Derived Mesenchymal Stem/Stromal Cell Transcriptome by G-CSF Stimulation.
Mesenchymal stem/stromal cells (MSCs) exhibit multidifferentiation potential, paralleled with immunomodulatory and trophic properties that make them viable alternative tools for the treatment of degenerative disorders, allograft rejection, autoimmune diseases, and tissue regeneration. MSC functional attributes can be modulated by exposing them to inflammatory-stimulating microenvironments (i.e., priming) before their therapeutic use. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that plays key roles in immune response and hematopoiesis modulation through direct effects on hematopoietic progenitors' proliferation, survival, and mobilization. Despite the established roles of MSCs supporting hematopoiesis, the effects of G-CSF on MSCs biology have not been thoroughly explored. This study reveals that G-CSF has also direct effects on adipose-derived MSCs (ADSCs), modulating their functions. Herein, microarray-based transcriptomic analysis shows that G-CSF stimulation in vitro results in modulation of various signaling pathways including ones related with the metabolism of hyaluronan (HA), conferring a profile of cell mobilization to ADSCs, mediated in a cell-intrinsic fashion in part by reducing CD44 expression and HA synthesis-related genes. Collectively, these data suggest a direct modulatory effect of G-CSF on ADSC function, potentially altering their therapeutic capacity and thus the design of future clinical protocols.


How do health care professionals assess patients when initiating insulin therapy? A qualitative study.
To explore how health care professionals (HCPs) assess patients when initiating insulin therapy in type 2 diabetes. Focus group discussions and in-depth interviews were conducted with 41 health care professionals in Malaysia in 2010-2011. A semi-structured topic guide was used for the interview. The interviews were transcribed verbatim and analysed using the Nvivo9 software based on a thematic approach. HCPs were less likely to initiate insulin therapy in patients who were older, with irregular dietary patterns and poor financial status. They also assessed patients' knowledge, views and misconceptions of insulin. However, there was a variation in how doctors assessed patients' comorbidities before starting insulin therapy. Medical officers were more likely to initiate insulin therapy in patients with comorbidities and complications, whereas family medicine specialists were more cautious. In addition, most HCPs considered patients' psychosocial status, including self-care ability, social support and quality of life. HCPs' assessment of patients' need to start insulin therapy depends on their perception rather than objective evaluation of patients' background, knowledge, perception and abilities. The background and the type of practice of HCPs influence their assessment.


Finding the most powerful measures of the effectiveness of tissue plasminogen activator in the NINDS tPA stroke trial.
We sought to identify the most powerful binary measures of the treatment effect of tissue plasminogen activator (tPA) in the National Institute of Neurological Disorders and Stroke (NINDS) rTPA Stroke Trial. Using the Classification and Regression Tree (CART) algorithm, we evaluated binary cut points and combination of binary cut points with the 4 clinical scales and head CT imaging measures in the NINDS tPA Stroke Trial at 4 times after treatment: 2 hours, 24 hours, 7 to 10 days, and 3 months. The first analysis focused on detecting evidence of "early activity" of tPA with the use of outcome measures derived from the 2-hour and 24-hour clinical and radiographic measures. The second analysis focused on longer-term outcome and "efficacy" and used outcome measures derived from 7- to 10-day and 3-month measures. After identifying the cut points with the ability to classify patients into the tPA and placebo groups using part I data from the trial, we then used data from part II of the trial to validate the results. Of the 5 most powerful outcome measures for early activity of tPA, 4 involved the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours or changes in the NIHSS score from baseline to 24 hours. The best overall single outcome measure was an NIHSS score </=2 at 24 hours, which provided an odds ratio of 5.4 (95% CI, 2.4 to 12.1) and a projected sample size of 58 per treatment group assuming an alpha of 0.05 (2-sided test) and a power of 80% using part I data. The top 2 and 3 of the top 5 outcome measures for detecting the longer-term efficacy of tPA also involved the NIHSS score. A Rankin score of 0 or 1 at 3 months was the third most powerful outcome measure. Outcome measures identified by CART from part I data were not as sensitive in detecting the effectiveness of tPA when applied to part II data. Measures using the NIHSS and a Rankin score </=1 were the most sensitive discriminators of the effectiveness of tPA in the NINDS tPA Stroke Trial compared with the other clinical and radiological measures. The outcome measures identified in this exploratory analysis (eg, NIHSS score </=2 at 24 hours) would be best used as an outcome measure in future phase II trials of recanalization begun within the first 3 hours after stroke onset, with inclusion and exclusion criteria similar to those in the NINDS tPA Stroke Trial.


The Administrative Burden Framework: A New Horizon for Research and Practice in Social Work?
Social work is widely recognized as a human rights profession. The commitment to protect and advocate for social and economic rights has been incorporated into official definitions and codes of ethics of the profession globally, undergirding social work models and services. However, despite the overwhelming recognition of the importance of social work advocacy, a unified framework for research and practice has not been agreed upon, and new challenges to welfare states have somewhat contested the existing, primarily European advocacy framework built on the literature on take-up of social and economic rights. The purpose of this integrative context review is to introduce the administrative burden (AB) literature as a potential framework for meeting social work advocacy challenges by emphasizing a subjective viewpoint, a multifaceted understanding of the bureaucratic encounter, and the secondary effects of burden. The article concludes by identifying directions for future research and practice concerning the nexus between AB and social work.


Lung Cancer (LC) in HIV Positive Patients: Pathogenic Features and Implications for Treatment.
: The human immunodeficiency virus (HIV) infection continues to be a social and public health problem. Thanks to more and more effective antiretroviral therapy (ART), nowadays HIV-positive patients live longer, thus increasing their probability to acquire other diseases, malignancies primarily. Senescence along with immune-system impairment, HIV-related habits and other oncogenic virus co-infections increase the cancer risk of people living with HIV (PLWH); in the next future non-AIDS-defining cancers will prevail, lung cancer (LC) in particular. Tumor in PLWH might own peculiar predictive and/or prognostic features, and antineoplastic agents' activity might be subverted by drug-drug interactions (DDIs) due to concurrent ART. Moreover, PLWH immune properties and comorbidities might influence both the response and tolerability of oncologic treatments. The therapeutic algorithm of LC, rapidly and continuously changed in the last years, should be fitted in the context of a special patient population like PLWH. This is quite challenging, also because HIV-positive patients have been often excluded from participation to clinical trials, so that levels of evidence about systemic treatments are lower than evidence in HIV-uninfected individuals. With this review, we depicted the epidemiology, pathogenesis, clinical-pathological characteristics and implications for LC care in PLWH, offering a valid focus about this topic to clinicians.


Diet and health outcomes in vulnerable populations.
Good nutritional health is essential to physical and cognitive function, prevention or management of chronic health conditions, and prevention of disability. Poor nutritional health describes dietary intakes of inadequate amounts of energy, protein, and individual or multiple micronutrients. Homebound older adults are considered the most vulnerable for poor nutritional health; many are poor and experience persistent food insufficiency. This chapter discusses the importance of dietary intakes, especially for homebound older adults, and presents resource-related factors that influence food choice and food acquisition. These factors include limited household income, food insufficiency, and utilization of community nutrition assistance programs. Of importance is that low dietary intakes influence balance, gait speed, leg strength, and overall lower extremity physical performance (LEP). This is crucial since decreased LEP is associated with increased disability over time. It is time to review policies and programs that influence dietary intake of homebound older adults.


Oral infection of Aedes aegypti with yellow fever virus: geographic variation and genetic considerations.
Twenty-eight populations representing a worldwide distribution of Aedes aegypti were tested for their ability to become orally infected with yellow fever virus (YFV). Populations had been analyzed for genetic variations at 11 isozyme loci and assigned to one of 8 genetic geographic groups of Ae. aegypti. Infection rates suggest that populations showing isozyme genetic relatedness also demonstrate similarity to oral infection rates with YFV. The findings support the hypothesis that genetic variation exists for oral susceptibility to YFV in Ae. aegypti.


Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae.
Eukaryotic chaperonins, the Cct complexes, are assembled into two rings, each of which is composed of a stoichiometric array of eight different subunits, which are denoted Cct1p-Cct8p. Overexpression of a single CCT gene in Saccharomyces cerevisiae causes an increase of the corresponding Cct subunit, but not of the Cct complex. Nevertheless, overexpression of certain Cct subunits, especially CCT6, suppresses a wide range of abnormal phenotypes, including those caused by the diverse types of conditional mutations tor2-21, lst8-2 and rsp5-9 and those caused by the concomitant overexpression of Sit4p and Sap155p. The examination of 73 altered forms of Cct6p revealed that the cct6-24 mutation, containing GDGTT --> AAAAA replacements of the conserved ATP-binding motif, was unable to suppress any of these traits, although the cct6-24 allele was completely functional for growth. These results provide evidence for functional differences among Cct subunits and for physiological properties of unassembled subunits. We suggest that the suppression is due to the competition of specific Cct subunits for activities that normally modify various cellular components. Furthermore, we also suggest that the Cct subunits can act as suppressors only in certain states, such as when associated with ATP.


Effects of Self-breast Pumping in Primiparous Women after Cesarean Delivery.
This study was done to identify the effects of self-breast pumping on breastfeeding rates and, the degree of breast milk fullness among primiparous women giving birth by cesarean section. The study design was a non-synchronized posttest control group experiment with repeated measures. The participants were 60 women, 31 in the experimental group who used a manual pump 5 times a day after exclusive breastfeeding and 29 in the control group who breastfed exclusively with no other interventions. While self-breast pumping did not improve breastfeeding rates or the degree of breast milk fullness at any of the time points studied, breastfeeding rates continued to remain high till 12 weeks postpartum in both groups. Although some modifications in research methods will be required to identify the effects of breast pumping and exclusive breastfeeding, both these approaches can be used as interventions to improve breastfeeding rates and breast milk quantity.


Little Egrets (Egretta garzetta) and trace-metal contamination in wetlands of China.
The rapidly developing Asian countries may face threatening environmental contamination, that however remains largely unassessed. We studied persistent trace elements in three wetlands, Poyang Lake, relatively unpolluted, and Tai Lake, and Pearl River Delta, selected as hotspots of pollution in Central China. We adopted as indicator the Little Egret, a widespread colonial waterbird, and during 1999 and 2000 we collected and analysed the same samples as for a parallel study we conducted in Pakistan, e.g. eggs, body feathers of chicks, prey spontaneously regurgitated by the chicks, and sediments at the areas most used by foraging egrets. The levels of trace-metals at our three study areas were similar, or within the range, of those found in the few other studies for East Asia, with few exceptions. The concentrations of the various elements were below the threshold that may affect the survival or reproduction of the birds, and even the highest concentrations relative to background, i.e. Se in eggs, and Hg in feathers at Pearl Delta, do not pose toxic hazards. In sediments, the levels of trace elements were lower than the critical levels assumed for contaminated soil, except for alarming high levels of As at Poyang. These results do not confirm our expectation, that Poyang was relatively uncontaminated, while Tai and Pearl were polluted. Although trace metal concentration differed significantly among the three study areas, these differences were minor and were not consistent among elements and samples. The bioaccumulation ratios from sediments through prey, feather and egg, were consistent with our previous findings for Pakistan. Only Hg exhibited high bioaccumulation, while Se and Zn had low accumulation, and the other elements no accumulation. This reasserts that feathers of predators such as egrets, may be more sensitive indicators of environmental contamination for the elements subject to bioaccumulation, whereas the sediments or the organisms low in the food chain are better indicators for the other elements.


Depressive Symptoms and Category Learning: A Preregistered Conceptual Replication Study.
We present a fully preregistered, high-powered conceptual replication of Experiment 1 by Smith, Tracy, and Murray (1993). They observed a cognitive deficit in people with elevated depressive symptoms in a task requiring flexible analytic processing and deliberate hypothesis testing, but no deficit in a task assumed to require more automatic, holistic processing. Specifically, they found that individuals with depressive symptoms showed impaired performance on a criterial-attribute classification task, requiring flexible analysis of the attributes and deliberate hypothesis testing, but not on a family-resemblance classification task, assumed to rely on holistic processing. While deficits in tasks requiring flexible hypothesis testing are commonly observed in people diagnosed with a major depressive disorder, these deficits are much less commonly observed in people with merely elevated depressive symptoms, and therefore Smith et al.'s (1993) finding deserves further scrutiny. We observed no deficit in performance on the criterial-attribute task in people with above average depressive symptoms. Rather, we found a similar difference in performance on the criterial-attribute versus family-resemblance task between people with high and low depressive symptoms. The absence of a deficit in people with elevated depressive symptoms is consistent with previous findings focusing on different tasks.


Trends in centralization of cancer surgery.
The association between procedure volume and clinical outcomes has led many to advocate centralization of cancer procedures at high-volume centers (HVCs). Regional studies show practice patterns changing with increasing centralization of esophageal and pancreatic procedures at HVCs but little change for colorectal procedures. We hypothesize that similar trends are occurring nationwide. Secondary data analysis was performed by means of the National Inpatient Sample. We examined trends in hospital procedure volume from 1999 to 2007 for all extirpative esophageal, pancreatic, and colorectal cancer procedures. Survey-weighted multivariate logistic regressions were used to examine the likelihood of surgery at a low-volume center (LVC) over time as well as to determine sociodemographic factors associated with surgery at LVCs. A total of 351,164 cases met the inclusion criteria (6,345 esophagus, 17,658 pancreas, 255,753 colon, 71,408 rectum). The likelihood of surgery at a LVC in 2007 compared to 1999 was as follows: esophagus odds ratio [OR] 0.42 (95% confidence interval [95% CI], 0.34, 0.53), pancreas OR 0.40 (95% CI, 0.35, 0.46), colon OR 0.88 (95% CI, 0.85, 0.91), rectum OR 0.83 (95% CI, 0.78, 0.89). Admission through an emergency department was associated with a higher likelihood of surgery at a LVC, even after adjusting for clinical and sociodemographic factors. Volume was also associated with race and payer; black patients and the uninsured were particularly likely to remain at LVCs. Practice patterns have changed substantially to follow national recommendations for centralization of complex cancer surgery. Despite this, disparities remain with regard to access to HVCs.


An X-ray fluorescence microscopic analysis of the tissue surrounding the multi-channel cochlear implant electrode array.
The aim of this study was to analyse the tissue surrounding the University of Melbourne's (UOMs) multi-channel cochlear implant electrode array and cochlear limited replacements, after long-term implantations. In particular, it aimed to identify the particulate material in the fibrous tissue capsule of the arrays implanted in 1978, 1983, and 1998, by using the Australian Synchrotron for X-ray fluorescence microscopy (XFM) to reveal the characteristic spectrum of metal, in particular platinum. This also helped to determine its format and chemical state. Tissue was retrieved following the recipient's death in 2007. Tissue was fixed and sections taken across the UOM and Cochlear Corporation (CI-22 and CI-24) electrode tracks. These were stained with Masson's trichrome. The Australian Synchrotron enabled XFM to accurately identify platinum from its characteristic fluorescence spectrum. There was a fibrous tissue capsule (about 100-µm thick) and small regions of calcification around the UOM and CI-22 arrays, but a thinner capsule (40-60-µm thick) around CI-24, and a greater degree of calcification. Dark particulate matter was observed within macrophages and especially in fibrous tissue in proximity to the UOM and CI-22 arrays. This was identified as platinum using X-ray fluorescence. There was also diffusion of platinum into the tissue surrounding the UOM and CI-22 electrodes and fine particles had penetrated the spiral ligament. The larger particulate matter in the tissue around the UOM and CI-22 arrays suggested that it had flaked off in the manufacturing of the UOM electrodes. The more diffuse spread of platinum in the tissue around the UOM and CI-22 electrodes was likely due to electrolysis, probably from charge imbalance with the bipolar pulses from the UOM implant. This did not occur with the Cochlear CI-24 device. Furthermore, the widespread fine particles of platinum could have also been due to corrosion, especially from the UOM electrodes.


The structure of the PERK kinase domain suggests the mechanism for its activation.
The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK's N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the α-subunit of translation initiation factor 2 (eIF2α), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK's kinase domain has been determined to 2.8 Å resolution. The structure resembles the back-to-back dimer observed in the related eIF2α kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix αG in the C-terminal lobe, preparing the latter for eIF2α binding. The structure suggests conservation in the mode of activation of eIF2α kinases and is consistent with a `line-up' model for PERK activation triggered by oligomerization of its luminal domain.


The effects of ant nests on soil fertility and plant performance: a meta-analysis.
Ants are recognized as one of the major sources of soil disturbance world-wide. However, this view is largely based on isolated studies and qualitative reviews. Here, for the first time, we quantitatively determined whether ant nests affect soil fertility and plant performance, and identified the possible sources of variation of these effects. Using Bayesian mixed-models meta-analysis, we tested the hypotheses that ant effects on soil fertility and plant performance depend on the substrate sampled, ant feeding type, latitude, habitat and the plant response variable measured. Ant nests showed higher nutrient and cation content than adjacent non-nest soil samples, but similar pH. Nutrient content was higher in ant refuse materials than in nest soils. The fertilizer effect of ant nests was also higher in dry habitats than in grasslands or savannas. Cation content was higher in nests of plant-feeding ants than in nests of omnivorous species, and lower in nests from agro-ecosystems than in nests from any other habitat. Plants showed higher green/root biomass and fitness on ant nests soils than in adjacent, non-nest sites; but plant density and diversity were unaffected by the presence of ant nests. Root growth was particularly higher in refuse materials than in ant nest soils, in leaf-cutting ant nests and in deserts habitats. Our results confirm the major role of ant nests in influencing soil fertility and vegetation patterns and provide information about the factors that mediate these effects. First, ant nests improve soil fertility mainly through the accumulation of refuse materials. Thus, different refuse dump locations (external or in underground nest chambers) could benefit different vegetation life-forms. Second, ant nests could increase plant diversity at larger spatial scales only if the identity of favoured plants changes along environmental gradients (i.e. enhancing β-diversity). Third, ant species that feed on plants play a relevant role fertilizing soils, which may balance their known influence as primary consumers. Fourth, the effects of ant nests as fertility islands are larger in arid lands, possibly because fertility is intrinsically lower in these habitats. Overall, this study provide novel and quantitative evidence confirming that ant nests are key soil modifiers, emphasizing their role as ecological engineers.


Oral health care in CSHCN: state Medicaid policy considerations.
Low dental care service utilization among Medicaid-enrolled children has often been attributed to low Medicaid reimbursement levels. The purpose of this study was to provide estimates of preventive dental care utilization by Medicaid-enrolled children with special health care needs (CSHCN) and investigate the association of Medicaid preventive dental care reimbursement levels with the receipt of preventive dental care. We analyzed data for 40256 CSHCN (1-17 years of age). Unadjusted estimates of not needing, needing and receiving, and needing but not receiving preventive dental care are presented. Multilevel logistic regression models were fitted to examine associations between state Medicaid dental-procedure reimbursement and receipt of preventive dental care. Some significant associations were found between state-level Medicaid dental-procedure reimbursements and receipt of preventive dental care. The strongest individual-level factor associated with not receiving needed preventive dental care was not receiving needed preventive medical care. Parents of Medicaid-enrolled CSHCN were less likely to report receiving needed preventive dental care and more likely to report not needing or not receiving preventive dental care than non-Medicaid-enrolled CSHCN. Medicaid-enrolled CSHCN received less needed preventive dental care than non-Medicaid-enrolled CSHCN. An important link to receiving appropriate dental care may be the primary care provider. Raising the level of preventive dental care reimbursement along with other policy changes should increase the frequency of CSHCN receiving preventive dental services. State Medicaid agencies must develop models of medical-dental care management for CSHCN in their programs to ensure the most appropriate care.


Removal of thallium by deferasirox in rats as biological model.
The present research aimed to characterize the potential efficiency of deferasirox in removing thallium after its administration for 30 days following two dose levels of 20 and 160 μm of thallium (III) chloride to male Wistar rats every day. After thallium administration some abnormal clinical signs such as red staining around the eyes, greenish mottling on the liver, weakness, loss of hair and weight, were observed in animals. Deferasirox was given orally to different groups of rats for a period of one week immediately after thallium administration. After chelation therapy, animals were killed by exsanguination from the abdominal aorta, and then thallium and iron concentrations in various tissues were determined by standard addition method. The chelation therapy results showed that deferasirox was able to remove thallium ions from the body and clinical symptoms were also reduced.


Additional anthropometric measures may improve the predictability of basal metabolic rate in adult subjects.
The most commonly used predictive equation for basal metabolic rate (BMR) is the Schofield equation, which only uses information on body weight, age and sex to derive the prediction. However, because body composition is a key influencing factor, there will be error in calculating an individual's basal requirements based on this prediction. To investigate whether adding additional anthropometric measures to the standard measures can enhance the predictability of BMR and to cross-validate this within a separate subgroup. Cross-sectional study of 150 Caucasian adults from Scotland, with a body mass index range of 16.7-49.3 kg/m(2). All subjects underwent measurement of BMR, body composition, and 148 also had basic skinfold and circumference measures taken. The resultant equation was tested in a subgroup of 39 obese males. The average difference between the predicted (Schofield equation) and measured BMR was 502 kJ/day. There was a slight systematic bias in this error, with the Schofield equation underestimating the lowest values. The average discrepancy between predicted and actual BMR was reduced to 452 kJ/day, with the addition of fat mass, fat-free mass, an overall 10% improvement on the Schofield equation (P=0.054). Using an equation derived from principal components analysis of anthropometry measurements similarly decreased the difference to 458 kJ/day (P=0.039). Testing the equation in a separate group indicated a 33% improvement in predictability of BMR, compared to the Schofield equation. In the absence of detailed information on body composition, utilizing anthropometric data provides a useful alternative methodology to improve the predictability of BMR beyond that achieved from the standard Schofield prediction equation. This should be confirmed in more individuals, both within the obese and normal weight category.


GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression.
Major depression, persistent low mood, is one of common psychiatric diseases. Chronic stressful life is believed to be a major risk factor that leads to dysfunctions of the limbic system. However, a large number of the individuals with experiencing chronic stress do not suffer from major depression, called as resilience. Endogenous mechanisms underlying neuronal invulnerability to chronic stress versus major depression are largely unknown. As GABAergic neurons are vulnerable to chronic stress and their impairments is associated with major depression, we have examined whether the invulnerability of GABAergic neurons in the limbic system is involved in resilience. GABAergic neurons in the nucleus accumbens from depression-like mice induced by chronic unpredictable mild stress appear the decreases in their GABA release, spiking capability and excitatory input reception, compared with those in resilience mice. The levels of decarboxylase and vesicular GABA transporters decrease in depression-like mice, but not resilience. Mice were treated by chronic unpredictable mild stress for three weeks. Depression-like behaviors or resilience was confirmed by seeing whether their behaviors change significantly in sucrose preference, Y-maze and forced swimming tests. Mice from controls as well as depression and resilience in response to chronic unpredictable mild stress were studied in terms of GABAergic neuron activity in the nucleus accumbens by cell electrophysiology and protein chemistry. The impairment of GABAergic neurons in the nucleus accumbens is associated with major depression. The invulnerability of GABAergic neurons to chronic stress may be one of cellular mechanisms for the resilience to chronic stress.


Altitudinal gradients in Magellanic sub-Antarctic lagoons: the effect of elevation on freshwater macroinvertebrate diversity and distribution.
The study of altitudinal gradients provides insights about species diversity, distribution patterns and related drivers. The Magellanic sub-Antarctic ecoregion has a steep elevational gradient, peaking at around 1,000 m a.s.l., and marked changes in temperature and landscape composition can be observed over relatively short distances. This study assessed freshwater macroinvertebrate diversity associated with lakes and ponds along the altitudinal gradient of a Magellanic sub-Antarctic watershed. A monotonic decline in species richness was observed with increasing elevation, with simpler and more even community composition at higher altitude. This pattern differs from the mid-peak trend found in streams of the same watershed. Functional feeding group structure also diminished with increasing elevation. The study provides a descriptive baseline of macroinvertebrate community structure associated with lentic freshwater ecosystems in the Magellanic sub-Antarctic ecoregion, and confirms that elevation has substantial effects on community structure, function and environmental features, even in these relatively low elevation mountain ranges. The harsh environmental conditions of this ecoregion increase freshwater macroinvertebrate development time, as well as decreasing habitat availability and food supply, supporting simple but well adapted communities. In conjunction with previous research, this study provides a watershed-scale platform of information underpinning future long-term research in the region.


Interaction of branch migration translocases with the Holliday junction-resolving enzyme and their implications in Holliday junction resolution.
Double-strand break repair involves the formation of Holliday junction (HJ) structures that need to be resolved to promote correct replication and chromosomal segregation. The molecular mechanisms of HJ branch migration and/or resolution are poorly characterized in Firmicutes. Genetic evidence suggested that the absence of the RuvAB branch migration translocase and the RecU HJ resolvase is synthetically lethal in Bacillus subtilis, whereas a recU recG mutant was viable. In vitro RecU, which is restricted to bacteria of the Firmicutes phylum, binds HJs with high affinity. In this work we found that RecU does not bind simultaneously with RecG to a HJ. RuvB by interacting with RecU bound to the central region of HJ DNA, loses its nonspecific association with DNA, and re-localizes with RecU to form a ternary complex. RecU cannot stimulate the ATPase or branch migration activity of RuvB. The presence of RuvB·ATPγS greatly stimulates RecU-mediated HJ resolution, but the addition of ATP or RuvA abolishes this stimulatory effect. A RecU·HJ·RuvAB complex might be formed. RecU does not increase the RuvAB activities but slightly inhibits them.


IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection.
B-1 cells play a critical role in early protection during influenza infections by producing natural IgM antibodies. However, the underlying mechanisms involved in regulating this process are largely unknown. Here we found that during influenza infection pleural cavity B-1a cells rapidly infiltrated lungs, where they underwent plasmacytic differentiation with enhanced IgM production. This process was promoted by IL-17A signaling via induction of Blimp-1 expression and NF-κB activation in B-1a cells. Deficiency of IL-17A led to severely impaired B-1a-derived antibody production in the respiratory tract, resulting in a deficiency in viral clearance. Transfer of B-1a-derived natural antibodies rescued Il17a-/- mice from otherwise lethal infections. Together, we identify a critical function of IL-17A in promoting the plasmacytic differentiation of B-1a cells. Our findings provide new insights into the mechanisms underlying the regulation of pulmonary B-1a cell response against influenza infection.


Dynamics in oxygen-induced changes in S-layer protein synthesis from Bacillus stearothermophilus PV72 and the S-layer-deficient variant T5 in continuous culture and studies of the cell wall composition.
Stable synthesis of the hexagonally ordered (p6) S-layer protein from the wild-type strain of Bacillus stearothermophilus PV72 could be achieved in continuous culture on complex medium only under oxygen-limited conditions when glucose was used as the sole carbon source. Depending on the adaptation of the wild-type strain to low oxygen supply, the dynamics in oxygen-induced changes in S-layer protein synthesis was different when the rate of aeration was increased to a level that allowed dissimilation of amino acids. If oxygen supply was increased at the beginning of continuous culture, synthesis of the p6 S-layer protein from the wild-type strain (encoded by the sbsA gene) was immediately stopped and replaced by that of a new type of S-layer protein (encoded by the sbsB gene) which assembled into an oblique (p2) lattice. In cells adapted to a prolonged low oxygen supply, first, low-level p2 S-layer protein synthesis and second, synchronous synthesis of comparable amounts of both types of S-layer proteins could be induced by stepwise increasing the rate of aeration. The time course of changes in S-layer protein synthesis was followed up by immunogold labelling of whole cells. Synthesis of the p2 S-layer protein could also be induced in the p6-deficient variant T5. Hybridization data obtained by applying the radiolabelled N-terminal and C-terminal sbsA fragments and the N-terminal sbsB fragment to the genomic DNA of all the three organisms indicated that changes in S-layer protein synthesis were accompanied by chromosomal rearrangement. Chemical analysis of peptidoglycan-containing sacculi and extraction and recrystallization experiments revealed that at least for the wild-type strain, a cell wall polymer consisting of N-acetylglucosamine and glucose is responsible for binding of the p6 S-layer protein to the rigid cell wall layer.


[Pathomorphology of extraplacental membranes in their premature rupture and undifferentiated connectivetissue dysplasia in women].
to investigate the morphological features of the extraplacental membranes (EPM) of the placentas obtained from women with undifferentiated connective tissue dystrophy (UCTD) and premature rupture of the fetal membranes (PROFM). EPMs of 65 placentas, including 55 from study group women and 10 from control women (having no manifestations of UCTD and PROFM), underwent morphological examination (visual examination, histological and immunohistochemical studies, and electron microscopy). There was subamniotic edema, disorientation and fragmentation of collagen structures in the compact layer, a structural change in the brush border of the amniotic epithelium, and a predominance of vacuolated cytotrophoblast forms in the structure of EPM of the placentas from of women with UCTD. Structural changes were accompanied by the altered function of EPM cells and identified by immunohistochemistry as higher MMP-9 expression by amniocytes and cytotrophoblast cells. PROFM was typified by the proliferation of amniotic epithelium; by the ordered arrangement of collagen fibers, and by large, longitudinally oriented fibroblasts. The structural changes in UCTD and PROFM were also accompanied by the altered function in the EPM cells as higher MMP-9 expression in amniocytes and cytotrophoblast cells. The latter was accompanied by the enhanced proteolysis of the extracellular matrix and can serve as one of the mechanisms, which triggers PROFM. Impaired histoarchitectonics and higher MMP-9 expression in the EPM cells should be considered as a manifestation of connective tissue disorganization and may be considered as one of the components in the pathogenesis of PROFM in the presence of UCTD.


Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial.
Plinabulin is a novel, non-granulocyte colony-stimulating factor (GCSF) small molecule with both anticancer and neutropenia-prevention effects. To assess the efficacy and safety of plinabulin compared with pegfilgrastim for the prevention of chemotherapy-induced neutropenia following docetaxel chemotherapy in patients with non-small lung cancer. This was a randomized, open-label, phase 2 clinical trial of 4 treatment arms that was conducted in 19 cancer treatment centers in the United States, China, Russia, and Ukraine. Participants were adult patients with non-small cell lung cancer whose cancer had progressed after platinum-based chemotherapy. Data were collected from April 2017 through March 2018 and analyzed from August 2019 through February 2020. All patients received docetaxel 75 mg/m2 on day 1 and were randomly assigned to 1 of 3 doses of plinabulin (5, 10, or 20 mg/m2) on day 1 or to pegfilgrastim 6 mg on day 2. Patients were treated every 21 days for 4 chemotherapy cycles. The primary end point was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Daily complete blood cell counts and absolute neutrophil counts were drawn during times of anticipated neutropenia during cycle 1. Of the 55 patients randomized and evaluated, the mean (SD) age was 61.3 (10.2) years, and 38 (69.1%) were men. With each escalation of the plinabulin dose, the incidence of any grade of neutropenia decreased. There were no significant differences in mean (SD) days of severe neutropenia among those treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 vs plinabulin 20 mg/m2 (0.36 [0.93] days; P = .76) when dosed at day 1, and no safety signals were detected. Single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim. Plinabulin 40 mg fixed dose, which is pharmacologically equivalent to 20 mg/m2, will be compared with pegfilgrastim 6 mg in the phase 3 portion of this trial. Noninferior days of severe neutropenia will be the primary end point, and bone pain reduction, thrombocytopenia reduction, and quality of life maintenance will be secondary end points. ClinicalTrials.gov Identifier: NCT03102606.


Combining enabling techniques in organic synthesis: continuous flow processes with heterogenized catalysts.
The concepts article describes enabling techniques (solid-phase assisted synthesis, new reactor design, microwave irradiation and new solvents) in organic chemistry and emphasizes the combination of several of them for creating new synthetic technology platforms. Particular focus is put on the combination of immobilized catalysts as well as biocatalysts with continuous flow processes. In this context, the PASSflow continuous flow technique fulfils both chemical as well as chemical engineering requirements. It combines reactor design with optimized, monolithic solid phases as well as reversible immobilization techniques for performing small as well as large scale synthesis with heterogenized catalysts under continuous flow conditions.


HIV-1 resistance to CCR5 antagonists associated with highly efficient use of CCR5 and altered tropism on primary CD4+ T cells.
We previously reported on a panel of HIV-1 clade B envelope (Env) proteins isolated from a patient treated with the CCR5 antagonist aplaviroc (APL) that were drug resistant. These Envs used the APL-bound conformation of CCR5, were cross resistant to other small-molecule CCR5 antagonists, and were isolated from the patient's pretreatment viral quasispecies as well as after therapy. We analyzed viral and host determinants of resistance and their effects on viral tropism on primary CD4(+) T cells. The V3 loop contained residues essential for viral resistance to APL, while additional mutations in gp120 and gp41 modulated the magnitude of drug resistance. However, these mutations were context dependent, being unable to confer resistance when introduced into a heterologous virus. The resistant virus displayed altered binding between gp120 and CCR5 such that the virus became critically dependent on the N' terminus of CCR5 in the presence of APL. In addition, the drug-resistant Envs studied here utilized CCR5 very efficiently: robust virus infection occurred even when very low levels of CCR5 were expressed. However, recognition of drug-bound CCR5 was less efficient, resulting in a tropism shift toward effector memory cells upon infection of primary CD4(+) T cells in the presence of APL, with relative sparing of the central memory CD4(+) T cell subset. If such a tropism shift proves to be a common feature of CCR5-antagonist-resistant viruses, then continued use of CCR5 antagonists even in the face of virologic failure could provide a relative degree of protection to the T(CM) subset of CD4(+) T cells and result in improved T cell homeostasis and immune function.


Differential modulation of plant immune responses by diverse members of the Pseudomonas savastanoi pv. savastanoi HopAF type III effector family.
The Pseudomonas savastanoi pv. savastanoi NCPPB 3335 type III secretion system (T3SS) effector repertoire includes 33 candidates, seven of which translocate into host cells and interfere with plant defences. The present study was performed to investigate the co-existence of both plasmid- and chromosomal-encoded members of the HopAF effector family, HopAF1-1 and HopAF1-2, respectively, in the genome of NCPPB 3335. Here, we show that the HopAF1 paralogues are widely distributed in the Pseudomonas syringae complex, where HopAF1-1 is most similar to the homologues encoded by other P. syringae pathovars infecting woody hosts that belong to phylogroups 1 and 3. We show that the expression of both HopAF1-1 and HopAF-2 is transcriptionally dependent on HrpL and demonstrate their delivery into Nicotiana tabacum leaves. Although the heterologous delivery of either HopAF1-1 or HopAF1-2 significantly suppressed the production of defence-associated reactive oxygen species levels, only HopAF1-2 reduced the levels of callose deposition. Moreover, the expression of HopAF1-2 by functionally effectorless P. syringae pv. tomato DC3000D28E completely inhibited the hypersensitive response in tobacco and significantly increased the competitiveness of the strain in Nicotiana benthamiana. Despite their functional differences, subcellular localization studies reveal that green fluorescent protein (GFP) fusions to either HopAF1-1 or HopAF1-2 are targeted to the plasma membrane when they are expressed in plant cells, a process that is completely dependent on the integrity of their N-myristoylation motif. Our results further support the notion that highly similar T3SS effectors might differentially interact with diverse plant targets, even when they co-localize in the same cell compartment.


AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition.
Inflammatory bowel disease (IBD) is driven by a seemingly aberrant immune response to the gut microbiota with disease development dictated by genetics and environmental factors. A model exemplifying this notion is our recent demonstration that colonisation of adherent-invasive Escherichia coli (AIEC) during microbiota acquisition drove chronic colitis in mice lacking the flagellin receptor TLR5 (T5KO). T5KO colitis persisted beyond AIEC clearance and requires TLR4 and the NLRC4 inflammasome. We hypothesised that AIEC instigates chronic inflammation by increasing microbial lipopolysaccharide (LPS) and flagellin levels. Examine if transient AIEC colonisation lastingly alters levels of LPS and flagellin and changes microbiota composition. Germ-free mice (wild type (WT) and T5KO) were inoculated with AIEC strain LF82 and placed in standard housing allowing a complex microbiota that eliminated AIEC in both mice strains. Faeces were assayed for the inflammatory marker, lipocalin-2, bacterial loads, and microbiota composition by pyrosequencing. Faecal LPS and flagellin bioactivity were measured via a cell-based reporter assay. Transient AIEC colonisation, in WT mice, did not alter inflammatory markers, bacterial loads, microbiota composition, nor its pro-inflammatory potential. By contrast, transient AIEC colonisation of T5KO mice drove chronic inflammation which correlated with microbiota components having higher levels of bioactive LPS and flagellin. Such AIEC-induced elevation of LPS and flagellin persisted well beyond AIEC clearance, required AIEC be flagellated, and was associated with alteration in microbiota species composition including a loss of species diversity. AIEC, and perhaps other pathobionts, may instigate chronic inflammation in susceptible hosts by altering the gut microbiota composition so as to give it an inherently greater ability to activate innate immunity/pro-inflammatory gene expression.


Relationships between maternal and child cardiovascular risk factors: ethnic differences and lack of influence of physical activity.
To obtain information about the relationship between cardiovascular and diabetic risk factors of mothers and their children and to determine whether these relationships differ by physical activity or ethnicity. Prospective study. The Texas site of the Studies of Child Activity and Nutrition Program. A 1986 to 1989 triethnic sample (European American, African American, and Hispanic) of 133 mothers and their 6- to 7-year-old children. Maternal and child fasting insulin levels; total, high-density lipoprotein, and low-density lipoprotein cholesterol levels; triglyceride levels; waist circumference; systolic and diastolic blood pressures; height; weight; and body mass index. Maternal physical activity was assessed by means of a 7-day recall. Child physical activity was assessed by heart rate monitoring. Correlational methods were used to describe the relationships among metabolic risk factors and physical activity; chi2 tests of independence were used to examine the relationships between ethnic groups. Body mass index and waist circumference were significantly (P<.05) associated among Hispanic mothers and their children, but not in other ethnic groups. Insulin, high-density lipoprotein, and low-density lipoprotein levels were significantly associated among African American mothers and their children, but not in other ethnic groups. Maternal and child physical activity were not significantly associated with any of the risk variables or each other. The relationships between the risk factors of mothers and children differed by ethnicity, but not by physical activity.


Integrated Patient Coordination System (IntPaCS): a bespoke tool for surgical patient management.
Efficient handover of patient information is fundamental for patient care and service efficiency. An audit exploring surgeons' views on written handover within a Trust's surgical specialties concluded that clear deficiencies existed. Such concerns have been echoed in the General Medical Council's guidance on safe surgical handover. To design and implement bespoke software for surgical handover using the audit results of surgeons' perceptions of existing processes. To gain feedback from the surgical department on this new software and implement a long-term sustainability strategy. Following an initial review, a proposal was presented for a new patient management tool. The software was designed and developed in-house to reflect the needs of our surgeons. The bespoke programme used open-source coding and was maintained on a secure server. A review of surgical handover occurred 12 and 134 weeks post-implementation of the new software. Integrated Patient Coordination System (IntPaCS) was successfully developed and delivered. The system is a centralised platform that enables the visualisation, handover and audit/research of surgical inpatient information in any part of the hospital. Feedback found that clinicians found it less stressful to create a post-take handover (60% vs 36%) than using a Word document. IntPaCS was found to be quicker to use too (15 min (SD 4) vs 24 min (SD 7.5)). Finally, the new system was considered safer with less reported missing/incorrect patient data (48% vs 9%). This study has shown that careful use of emerging technology and innovation over time has the potential to improve all aspects of clinical governance.


Common scale valuations across different preference-based measures: estimation using rank data.
Different preference-based measures (PBMs) used to estimate quality-adjusted life years (QALYs) provide different utility values for the same patient. Differences are expected since values have been obtained using different samples, valuation techniques, and descriptive systems. Previous studies have estimated the relationship between pairs of PBMs using patient self-reported data. However, there is a need for an approach capable of generating values directly on a common scale for a range of PBMs using the same sample of general population respondents and valuation technique but keeping the advantages of the different descriptive systems. . General public survey data (n = 501) in which respondents ranked health states described using subsets of 6 PBMs were analyzed. We develop a new model based on the mixed logit to overcome 2 key limitations of the standard rank-ordered logit model-namely, the unrealistic choice pattern (independence of irrelevant alternatives) and the independence of repeated observations. . There are substantial differences in the estimated parameters between the 2 models (mean difference 0.07), leading to different orderings across the measures. Estimated values for the best states described by different PBMs are substantially and significantly different using the standard model, unlike our approach, which yields more consistent results. Limitations. Data come from an exploratory study that is relatively small both in sample size and coverage of health states. . This study develops a new, flexible econometric model specifically designed to reflect appropriately the features of rank data. Results support the view that the standard model is not appropriate in this setting and will yield very different and apparently inconsistent results. PBMs can be compared using a common scale by implementation of this new approach.


Effect on health-related quality of life of ongoing feedback during a 12-month maintenance walking programme in patients with COPD: a randomized controlled trial.
In patients with COPD, this study evaluated the effect on health-related quality of life (HRQoL) of adding ongoing feedback to a 12-month unsupervised maintenance walking programme. Participants were randomized to either an intervention group (IG) or control group (CG). Both groups completed the same 2-month supervised, walking training programme followed by a 12-month unsupervised maintenance walking programme. During the maintenance programme, the IG received ongoing feedback (telephone calls, biofeedback and progressive goal setting) and the CG received no feedback. A total of 75 participants completed the study (mean (SD): age 69 (8) years; forced expiratory volume in 1 s (FEV1 ) 43 (15) % predicted). There was no between-group differences in the magnitude of change in HRQoL when data collected on completion of the 12-month maintenance programme were compared with that collected either before the 2-month supervised programme (mean between-group difference (MD) in total St George's Respiratory Questionnaire change scores: 1 point, 95% CI: -9 to 7) or on completion of the 2-month supervised programme (MD: 4 points, 95% CI -2 to 10). Following a 2-month supervised walking training programme, ongoing feedback was no more effective than no feedback in maintaining HRQoL during a 12-month unsupervised walking programme.


Mechanobiology of Autophagy: The Unexplored Side of Cancer.
Proper execution of cellular function, maintenance of cellular homeostasis and cell survival depend on functional integration of cellular processes and correct orchestration of cellular responses to stresses. Cancer transformation is a common negative consequence of mismanagement of coordinated response by the cell. In this scenario, by maintaining the balance among synthesis, degradation, and recycling of cytosolic components including proteins, lipids, and organelles the process of autophagy plays a central role. Several environmental stresses activate autophagy, among those hypoxia, DNA damage, inflammation, and metabolic challenges such as starvation. In addition to these chemical challenges, there is a requirement for cells to cope with mechanical stresses stemming from their microenvironment. Cells accomplish this task by activating an intrinsic mechanical response mediated by cytoskeleton active processes and through mechanosensitive protein complexes which interface the cells with their mechano-environment. Despite autophagy and cell mechanics being known to play crucial transforming roles during oncogenesis and malignant progression their interplay is largely overlooked. In this review, we highlight the role of physical forces in autophagy regulation and their potential implications in both physiological as well as pathological conditions. By taking a mechanical perspective, we wish to stimulate novel questions to further the investigation of the mechanical requirements of autophagy and appreciate the extent to which mechanical signals affect this process.


Auxin transport promotes Arabidopsis lateral root initiation.
Lateral root development in Arabidopsis provides a model for the study of hormonal signals that regulate postembryonic organogenesis in higher plants. Lateral roots originate from pairs of pericycle cells, in several cell files positioned opposite the xylem pole, that initiate a series of asymmetric, transverse divisions. The auxin transport inhibitor N-1-naphthylphthalamic acid (NPA) arrests lateral root development by blocking the first transverse division(s). We investigated the basis of NPA action by using a cell-specific reporter to demonstrate that xylem pole pericycle cells retain their identity in the presence of the auxin transport inhibitor. However, NPA causes indoleacetic acid (IAA) to accumulate in the root apex while reducing levels in basal tissues critical for lateral root initiation. This pattern of IAA redistribution is consistent with NPA blocking basipetal IAA movement from the root tip. Characterization of lateral root development in the shoot meristemless1 mutant demonstrates that root basipetal and leaf acropetal auxin transport activities are required during the initiation and emergence phases, respectively, of lateral root development.


Crystal Structure of Staphopain C from Staphylococcus aureus.
Staphylococcus aureus is a common opportunistic pathogen of humans and livestock that causes a wide variety of infections. The success of S. aureus as a pathogen depends on the production of an array of virulence factors including cysteine proteases (staphopains)-major secreted proteases of certain strains of the bacterium. Here, we report the three-dimensional structure of staphopain C (ScpA2) of S. aureus, which shows the typical papain-like fold and uncovers a detailed molecular description of the active site. Because the protein is involved in the pathogenesis of a chicken disease, our work provides the foundation for inhibitor design and potential antimicrobial strategies against this pathogen.


Catch Me If You Can: A Spatial Model for a Brake-Driven Gene Drive Reversal.
Population management using artificial gene drives (alleles biasing inheritance, increasing their own transmission to offspring) is becoming a realistic possibility with the development of CRISPR-Cas genetic engineering. A gene drive may, however, have to be stopped. "Antidotes" (brakes) have been suggested, but have been so far only studied in well-mixed populations. Here, we consider a reaction-diffusion system modeling the release of a gene drive (of fitness [Formula: see text]) and a brake (fitness [Formula: see text], [Formula: see text]) in a wild-type population (fitness 1). We prove that whenever the drive fitness is at most 1/2 while the brake fitness is close to 1, coextinction of the brake and the drive occurs in the long run. On the contrary, if the drive fitness is greater than 1/2, then coextinction is impossible: the drive and the brake keep spreading spatially, leaving in the invasion wake a complicated spatiotemporally heterogeneous genetic pattern. Based on numerical experiments, we argue in favor of a global coextinction conjecture provided the drive fitness is at most 1/2, irrespective of the brake fitness. The proof relies upon the study of a related predator-prey system with strong Allee effect on the prey. Our results indicate that some drives may be unstoppable and that if gene drives are ever deployed in nature, threshold drives, that only spread if introduced in high enough frequencies, should be preferred.


A retrospective journal-based case study of an infant with autism and his twin.
This report describes the development of an infant who was later diagnosed with autism, and a direct comparison of his development to that of his twin, from a prenatal period through the age of 4 years, through the examination of personal journals and medical records kept by the mother of the twins. Examination of these journals revealed several differences in development between the twins, some as early as 6 months of age. In the first year of life, the infants already differed in language development, social development, sleep patterns, and sensitivity to pain. This rare opportunity to view early autistic development gives direction to developmental theories of autism and clinically useful cues to early signs of autism.


Association Between Early Low-Dose Hydrocortisone Therapy in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years of Age.
Dexamethasone to prevent bronchopulmonary dysplasia in very preterm neonates was associated with adverse neurodevelopmental events. Early low-dose hydrocortisone treatment has been reported to improve survival without bronchopulmonary dysplasia but its safety with regard to neurodevelopment remains to be assessed. To assess whether early hydrocortisone therapy in extremely preterm infants is associated with neurodevelopmental impairment at 2 years of age. An exploratory secondary analysis of the PREMILOC (Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial conducted between 2008 and 2014 in 21 French neonatal intensive care units. Randomization was stratified by gestational age groups. Neurodevelopmental assessments were completed from 2010 to 2016. After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days). The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lézine scale (global developmental quotient score and subscores; mean norm, 100 [SD, 15]). The minimal clinically important difference on the global developmental quotient was 5 points. Of 1072 neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93%; 46% female) were evaluated (194 in the hydrocortisone group and 185 in the placebo group) at a median corrected age of 22 months (interquartile range, 21-23 months). The distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group) was not statistically significantly different between groups (P = .33). The mean global developmental quotient score was not statistically significantly different between groups (91.7 in the hydrocortisone group vs 91.4 in the placebo group; between-group difference, 0.3 [95% CI, -2.7 to 3.4]; P = .83). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups. In this exploratory analysis of secondary outcomes of a randomized clinical trial of extremely preterm infants, early low-dose hydrocortisone was not associated with a statistically significant difference in neurodevelopment at 2 years of age. Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants. clinicaltrials.gov Identifier: NCT00623740.


Tracer kinetic modeling of 11C-acetate applied in the liver with positron emission tomography.
It is well known that 40%-50% of hepatocellular carcinoma (HCC) do not show increased 18F-fluorodeoxyglucose (FDG) uptake. Recent research studies have demonstrated that 11C-acetate may be a complementary tracer to FDG in positron emission tomography (PET) imaging of HCC in the liver. Quantitative dynamic modeling is, therefore, conducted to evaluate the kinetic characteristics of this tracer in HCC and nontumor liver tissue. A three-compartment model consisting of four parameters with dual inputs is proposed and compared with that of five parameters. Twelve regions of dynamic datasets of the liver extracted from six patients are used to test the models. Estimation of the adequacy of these models is based on Akaike Information Criteria (AIC) and Schwarz Criteria (SC) by statistical study. The forward clearance K = K1 * k3/(k2 + k3) is estimated and defined as a new parameter called the local hepatic metabolic rate-constant of acetate (LHMRAct) using both the weighted nonlinear least squares (NLS) and the linear Patlak methods. Preliminary results show that the LHMRAct of the HCC is significantly higher than that of the nontumor liver tissue. These model parameters provide quantitative evidence and understanding on the kinetic basis of C-acetate for its potential role in the imaging of HCC using PET.


State-to-state photodissociation dynamics of CO2 around 108 nm: the O(1S) atom channel.
State-to-state photodissociation of carbon dioxide (CO2) via the 3p1Πu Rydberg state was investigated by the time-sliced velocity map ion imaging technique (TSVMI) using a tunable vacuum ultraviolet free electron laser (VUV FEL) source. Raw images of the O(1S) products resulting from the O(1S) + CO(X1Σ+) channel were acquired at the photolysis wavelengths between 107.37 and 108.84 nm. From the vibrational resolved O(1S) images, the product total kinetic energy releases and the vibrational state distributions of the CO(X1Σ+) co-products were obtained, respectively. It is found that vibrationally excited CO co-products populate at as high as v = 6 or 7 while peaking at v = 1 and v = 4, and most of the individual vibrational peaks present a bimodal rotational structure. Furthermore, the angular distributions at all studied photolysis wavelengths have also been determined. The associated vibrational-state specific anisotropy parameters (β) exhibit a photolysis wavelength-dependent feature, in which the β-values observed at 108.01 nm and 108.27 nm are more positive than those at 107.37 nm and 107.52 nm, while the β-values have almost isotropic behaviour at 108.84 nm. These experimental results indicate that the initially prepared CO2 molecules around 108 nm should decay to the 41A' state via non-adiabatic coupling, and dissociate in the 41A' state to produce O(1S) + CO(X1Σ+) products with different dissociation time scales.


Accuracy of 3D acquisition mode for myocardial FDG PET studies using a BGO-based scanner.
The aim of the present study was to evaluate the quantitative and qualitative accuracy of 3D PET acquisitions for myocardial FDG studies. Phantom studies were performed with both a homogeneous and an inhomogeneous phantom. Activity profiles were generated along the phantoms using 2D and several 3D reconstructions, varying the 3D scaling value to adjust the scatter correction algorithm. Furthermore, ten patients underwent a dynamic myocardial FDG PET scan, using an interleaved protocol consisting of frames with alternating 2D and 3D acquisition. For each myocardial study, 13 volumes of interest were defined, representing 13 myocardial segments. First, the optimal scaling value for the scatter correction algorithm was determined using data from the phantom and four patient studies. This scaling value was then applied to all ten patients. 2D and 3D acquisitions were compared for both static (i.e. activity concentrations in the last 2D and 3D frames) and dynamic imaging (calculation of the metabolic rate of glucose). For both phantom and patient studies, suboptimal results were obtained when the default scaling value for the scatter correction algorithm was used. After adjusting the scaling value, for all ten myocardial FDG studies, a very good correlation (r2=0.99) was obtained between 2D and 3D data. With the present protocol no significant differences were observed in qualitative interpretation. The 3D FDG acquisition mode is accurate and has clear advantages over the 2D mode for myocardial FDG studies. A prerequisite is, however, optimisation of the 3D scatter correction algorithm.


Auditory Evoked Potentials with Different Speech Stimuli: a Comparison and Standardization of Values.
Introduction Long Latency Auditory Evoked Potentials (LLAEP) with speech sounds has been the subject of research, as these stimuli would be ideal to check individualś detection and discrimination. Objective The objective of this study is to compare and describe the values of latency and amplitude of cortical potentials for speech stimuli in adults with normal hearing. Methods The sample population included 30 normal hearing individuals aged between 18 and 32 years old with ontological disease and auditory processing. All participants underwent LLAEP search using pairs of speech stimuli (/ba/ x /ga/, /ba/ x /da/, and /ba/ x /di/. The authors studied the LLAEP using binaural stimuli at an intensity of 75dBNPS. In total, they used 300 stimuli were used (∼60 rare and 240 frequent) to obtain the LLAEP. Individuals received guidance to count the rare stimuli. The authors analyzed latencies of potential P1, N1, P2, N2, and P300, as well as the ampleness of P300. Results The mean age of the group was approximately 23 years. The averages of cortical potentials vary according to different speech stimuli. The N2 latency was greater for /ba/ x /di/ and P300 latency was greater for /ba/ x /ga/. Considering the overall average amplitude, it ranged from 5.35 and 7.35uV for different speech stimuli. Conclusion It was possible to obtain the values of latency and amplitude for different speech stimuli. Furthermore, the N2 component showed higher latency with the / ba / x / di / stimulus and P300 for /ba/ x / ga /.


Person-Centered Care in the Home Setting for Parkinson's Disease: Operation House Call Quality of Care Pilot Study.
Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson's disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson's disease was confirmed using standardized criteria, and the Unified Parkinson's Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program.


Suppressor of cytokine signaling 3 (SOCS3) is not an independent biomarker of colorectal adenoma risk.
Inflammation and its associated pathologies are increasingly suggested as risk factors for colorectal cancer (CRC) development. Previous research from our group has shown that increased levels of circulating, pro-inflammatory cytokines IL-6 and TNFalpha promote colorectal adenoma risk. Emerging data in mice and humans suggest that Suppressor of Cytokine Signaling 3 (SOCS3) may act as a tumor suppressor in the intestine, and decreased SOCS3 expression may promote CRC. As SOCS3 has been shown to inhibit the actions of IL-6 and TNFalpha in the intestine, we hypothesized that decreased SOCS3 expression in normal mucosa may predispose to adenomas and thus increase risk for CRC. We examined SOCS3 mRNA levels in normal mucosa biopsies of 322 screening colonoscopy patients (93 with adenoma and 229 without adenoma) using real-time qRT-PCR. Logistic regression analysis was used to generate odds ratios (OR) and 95% confidence intervals to determine if low SOCS3 expression was associated with adenoma status. Median SOCS3 values did not differ between patients with or without adenoma. Logistic regression analysis showed no association (unadjusted or adjusted for age and sex) between SOCS3 and colorectal adenomas. Low SOCS3 mRNA expression is not an independent biomarker of colorectal adenoma risk in the normal mucosa. SOCS3 silencing likely occurs later in CRC progression.


Salivary cortisol and cortisone in the clinical setting.
A resurgence of interest in salivary biomarkers has generated evidence for their value in assessing adrenal function. The advantages of salivary measurements include only free hormone is detected, samples can be collected during normal daily routines and stress-induced cortisol release is less likely to occur than during venepuncture. We review the use of salivary biomarkers to diagnose and monitor patients for conditions of cortisol excess and deficiency and discuss the value of measuring salivary cortisone versus salivary cortisol. Developments in laboratory techniques have enabled the measurement of salivary hormones with a high level of sensitivity and specificity. In states of altered cortisol binding, salivary biomarkers are more accurate measures of adrenal reserve than serum cortisol. Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations. Salivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.


Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis.
Overdiagnosis and underdiagnosis of attention-deficit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence. Medline, PsycINFO, CINAHL, Embase, and Web of Science were searched for studies with point prevalence estimates of ADHD. We included studies of children that used the diagnostic criteria from DSM-III, DSM-III-R and DSM-IV in any language. Data were extracted on sampling procedure, sample characteristics, assessors, measures, and whether full or partial criteria were met. The 175 eligible studies included 179 ADHD prevalence estimates with an overall pooled estimate of 7.2% (95% confidence interval: 6.7 to 7.8), and no statistically significant difference between DSM editions. In multivariable analyses, prevalence estimates for ADHD were lower when using the revised third edition of the DSM compared with the fourth edition (P = .03) and when studies were conducted in Europe compared with North America (P = .04). Few studies used population sampling with random selection. Most were from single towns or regions, thus limiting generalizability. Our review provides a benchmark prevalence estimate for ADHD. If population estimates of ADHD diagnoses exceed our estimate, then overdiagnosis may have occurred for some children. If fewer, then underdiagnosis may have occurred.


Obliteration of pulp canal space after concussion and subluxation: endodontic considerations.
Concussion and subluxation injuries to permanent teeth lead to obliteration of the pulp canal space in 3% to 11% of cases, depending on the severity of the injury and the developmental stage of the tooth. Obliteration of the pulp canal space may make root canal treatment necessary because of the development of apical periodontitis or for cosmetic reasons. If carefully executed, root canal treatment in teeth with an obliterated pulp canal space is highly successful and may act as a basis for internal bleaching.


[Control of diabetes in the perioperative period].
Surgical procedure and anaesthesia commonly induce severe diabetes maladjustment. In these circumstances, optimal insulin administration is crucial and has been shown to prevent hyperglycaemia which is mostly due to insulin-counteracting hormones. We report the results obtained in 12 diabetic patients treated with a new method during various surgical procedures. The method consists of constant rate intravenous administration of a 5% glucose solution associated with intravenous insulin infusion delivered by an electric syringe at the rate of 1/2 U of insulin per hour for each glycaemic variation of 50 mg/dl. With this simple method, blood glucose concentrations remain close to physiological levels, and no hypoglycaemia occurs.


Building a vertical provider system.
There is probably no geographic area in the United States in which the health care environment is more turbulent than that of Southern California. Long before President Clinton's proposals began serious national debate on health care reform, a massive provider-driven realignment of the system was occurring in that region of the country. Multispecialty medical groups have generally led the way and have acquired ever larger managed care populations through merger and acquisition of other groups and practices. Hospitals, hampered by large fixed capital bases, have struggled to reinvent themselves as cost-effective and primary care-friendly environments in order to be attractive to managed care physicians. Almost ignored in this reconfiguration has been the university teaching hospital. This article discusses one attempt to reconcile contractually an integrated, capitated, and managed care-oriented health care system with an academic medical center in a strategic alliance.


Involvement of the Motor System in Comprehension of Non-Literal Action Language: A Meta-Analysis Study.
Although numerous studies have shown that the sensory-motor system is involved in semantic processing of language stimuli, it is still unclear whether comprehension of abstract concepts is embodied, and whether the involvement of the sensory-motor system is context-dependent. Investigation of how the motor system is activated during comprehension of non-literal action languages can help address these issues. So far several studies have reported brain activations during non-literal action language comprehension, but the findings are highly inconsistent because of different types of non-literal action language stimuli. To clarify how the motor system is involved in comprehension of different types of non-literal languages, the current study conducted quantitative meta-analyses on fMRI findings about comprehension of sentences describing fictive motions, metaphoric actions, and idiomatic actions. Results showed that fictive motion sentences elicited activation in the right parahippocampal gyrus, an area important for spatial processing. For metaphoric actions, the left precentral gyrus (BA 6) was strongly activated, suggesting a link between metaphoric and literal meanings. For idiomatic actions, activity was found in the left inferior frontal gyrus (BA 44/45), highlighting semantic selection and inhibition. No premotor or motor activity was found in idiom condition. These results together suggest that the involvement of the sensory-motor system in abstract concepts processing is flexible, depending on semantic features of the language stimuli and links between abstract and literal meanings.


Empathy and the Public Perception of Stillbirth and Memory Sharing: An Australian Case.
Objective: Stillbirth devastates families and leaves them struggling to grieve the death of their baby in a society that expects grief symptoms to decrease over time. Previous research has suggested that increased memory sharing opportunities can lead to positive mental health outcomes. The aim of the current study was to examine people's perceptions of stillbirth as well as the perceived appropriateness of affected parents sharing memories of their child. In addition, we examined whether manipulating empathy would have an effect on people's perceptions of stillbirth. Method: Participants included 200 Australian men and women 18 to 74 years of age (M = 36.76, SD = 12.59) randomly allocated to one of three experimental conditions (i.e., low empathy, high empathy, and control). The high empathy group watched a video about stillbirth and was instructed to imagine how the people portrayed felt; the low empathy group watched the same video but was instructed to remain detached; and the control group watched an unrelated video. Participants were then asked how much money they would be willing to donate to a fictional stillbirth organization, followed by the completion of questionnaires measuring (a) perceptions of stillbirth, (b) empathy, and (c) the appropriateness of parents sharing memories of a stillborn child with different groups of people over time. Results: The empathy manipulation had an effect on empathy and the willingness to help effected parents (high empathy vs. control). However, empathy did not have an effect on participants' perceptions toward stillbirth nor appropriateness of sharing memories. The appropriateness of sharing memories decreased as time passed and social distance increased. Discussion: Individuals who have experienced stillbirth need to be aware that societal expectations and their own expectations in relation to sharing memories may not correspond to each other and that they may need to educate their social group about their need to share memories. Removing the taboo surrounding stillbirth is vital for both parents and those to whom they would wish to communicate.


Ivermectin for the control of swine scabies: relative values of prefarrowing treatment of sows and weaning treatment of pigs.
Ivermectin given in a single subcutaneous dose (300 micrograms/kg of body weight) was tested for activity against swine scabies (Sarcoptes scabiei). Efficacy was determined by recoveries of mites from ear scrapings and by observations of clinical signs. Treatment of infected sows 8 to 37 days before farrowing eliminated scabies from the sows and prevented its transmission to their offspring. Pigs farrowed by ivermectin-treated sows remained noninfected throughout the study regardless of whether they were treated with ivermectin at weaning. Placebo-treated sows remained infected and transmitted scabies to their offspring. Ivermectin treatment of pigs at weaning eliminated the infection, whereas placebo treatment did not. The placebo-treated pigs remained infected while in the nursery, but ivermectin treatment eliminated the infection when they were moved to the growing and finishing floor at 12 weeks of age. It appears that an effective control program for swine scabies using ivermectin could be based on a single treatment of the sows before farrowing. Any infection (epizootic) appearing in growing pigs could be controlled by a single treatment of all in-contact pigs.


Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives.
Tumours are complex systems with dynamic interactions between tumour cells, non-tumour cells, and extracellular components that comprise the tumour microenvironment (TME). The majority of TME's cells are cancer-associated fibroblasts (CAFs), which are crucial in extracellular matrix (ECM) construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour cell motility. CAF subtypes have been identified based on the expression of protein markers. CAFs may act as promoters or suppressors in tumour cells depending on a variety of factors, including cancer stage. Indeed, CAFs have been shown to promote tumour growth, survival and spread, and secretome changes, but they can also slow tumourigenesis at an early stage through mechanisms that are still poorly understood. Stromal-cancer interactions are governed by a variety of soluble factors that determine the outcome of the tumourigenic process. Cancer cells release factors that enhance the ability of fibroblasts to secrete multiple tumour-promoting chemokines, acting on malignant cells to promote proliferation, migration, and invasion. This crosstalk between CAFs and tumour cells has given new prominence to the stromal cells, from being considered as mere physical support to becoming key players in the tumour process. Here, we focus on the concept of cancer as a non-healing wound and the relevance of chronic inflammation to tumour initiation. In addition, we review CAFs heterogeneous origins and markers together with the potential therapeutic implications of CAFs "re-education" and/or targeting tumour progression inhibition.


Azathioprine and penicillamine in treatment of rheumatoid arthritis: a controlled trial.
Sixty-five patients, 33 receiving azathioprine and 32 receiving penicillamine, took part in a one-year, single-blind external-observer trial designed to compare the efficacy and toxicity of these two drugs in the treatment of rheumatoid arthritis. By six months there was a significantly greater rise in haemoglobin and fall in erythrocyte sedimentation rate among those receiving penicillamine, and by one year this difference remained only in the increase in haemoglobin levels. Fifteen patients, 10 on azathioprine and 5 on penicillamine, had to stop treatment because of side effects; 90 single side effects occurred, 48 in those on penicillamine and 42 in those on azathioprine. After one year both drugs were similar in efficacy and toxicity, but longer-term trials are needed. Both drugs were effective.