Glucocorticoid receptor-interacting protein 1 mediates ligand-independent nuclear translocation and activation of constitutive androstane receptor in vivo.
Phenobarbital (PB) induction of CYP2B genes is mediated by translocation of the constitutively active androstane receptor (CAR) to the nucleus. Interaction of CAR with p160 coactivators and enhancement of CAR transactivation by the coactivators have been shown in cultured cells. In the present studies, the interaction of CAR with the p160 coactivator glucocorticoid receptor-interacting protein 1 (GRIP1) was examined in vitro and in vivo. Binding of GRIP1 to CAR was shown by glutathione S-transferase (GST) pull-down and affinity DNA binding. N- or C-terminal fragments of GRIP1 that contained the central receptor-interacting domain bound to GST-CAR, but the presence of ligand increased the binding to GST-CAR of only the fragments containing the C-terminal region. In gel shift analysis, binding to CAR was observed only with GRIP1 fragments containing the C-terminal region, and the binding was increased by a CAR agonist and decreased by a CAR antagonist. Expression of GRIP1 enhanced CAR-mediated transactivation in cultured hepatic-derived cells 2-3-fold. In hepatocytes transfected in vivo, expression of exogenous GRIP1 alone induced transactivation of the CYP2B1 PB-dependent enhancer 15-fold, whereas CAR expression alone resulted in only a 3-fold enhancement in untreated mice. Remarkably, CAR and GRIP1 together synergistically transactivated the enhancer about 150-fold, which is approximately equal to activation by PB treatment. In PB-treated mice, expression of exogenous CAR alone had little effect, expression of GRIP1 increased transactivation about 2-fold, and with CAR and GRIP, a 4-fold activation was observed. In untreated mice, expression of GRIP resulted in nuclear translocation of green fluorescent protein-CAR. These results strongly suggest that a p160 coactivator functions in CAR-mediated transactivation in vivo in response to PB treatment and that the synergistic activation of CAR by GRIP in untreated animals results from both nuclear translocation and activation of CAR.


Bifrontal interhemispheric approach to aneurysms of the anterior communicating artery.
The authors review their experience with the bifrontal interhemispheric approach in 603 cases of single anterior communicating artery (ACoA) aneurysms and describe the operative technique. With this approach, the olfactory tracts are dissected, and both A1 segments of the anterior cerebral arteries are identified subfrontally. The interhemispheric fissure is then dissected and A2 segments are followed from the distal portion toward the ACoA complex. Following the administration of a combination of mannitol, vitamin E, and dexamethasone, a temporary clip is placed on at least the dominant A1 segment prior to dissection of the aneurysm itself. Once the aneurysm has been completely freed from the surrounding structures, the neck is ligated and clipped. If the aneurysm ruptures during surgery, temporary clips are placed on both A1 and A2 segments bilaterally and the operation proceeds in a completely dry field. With this method, it is possible to occlude any of the intracranial vessels for up to 40 minutes within 100 minutes of drug administration. To prevent the possibility of rerupture and the development of vasospasm in the period before aneurysm surgery, the authors have adopted a policy of performing ultra-early operations within 48 hours of the onset of symptoms. Among the 257 cases operated on during the 9 years since 1975, one-fifth have been operated on within 48 hours of rupture, and the in-hospital mortality rate has been only 4.3% (11 cases). Follow-up studies have shown that 87% of the 246 surviving patients have returned to useful lives.


Repeated stimulation of the HPA axis alters white blood cell count without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups.
The hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days. We collected blood at baseline, 2 h and 4 days after the beginning of treatment. ACTH and ACTH+RU486 elevated serum aldosterone and cortisol at 2 h, with effects diminishing at 4 days. RU486 alone induced a compensatory increase in aldosterone, but not cortisol, at 4 days. ACTH decreased neutrophils at 2 h, while decreasing lymphocytes and increasing the neutrophil:lymphocyte ratio at 4 days. These effects were abolished by RU486. Despite alterations in white blood cells, there was no effect of ACTH or RU486 on transforming growth factor-β or interleukin-6 levels; however, both cytokines decreased with the 4 day fasting progression. Similarly, ACTH did not impact protein oxidation, lipid peroxidation or antioxidant enzymes, but plasma isoprostanes and catalase activity decreased while glutathione peroxidase increased with fasting progression. These data demonstrate differential acute (2 h) and chronic (4 days) modulatory effects of HPA activation on white blood cells and that the chronic effect is mediated, at least in part, by GR. These results also underscore elephant seals' extraordinary resistance to oxidative stress derived from repeated HPA activation.


Non-Small Cell Lung Cancer Radiogenomics Map Identifies Relationships between Molecular and Imaging Phenotypes with Prognostic Implications.
Purpose To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Materials and Methods A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. For example, nodule attenuation and margins are associated with the late cell-cycle genes, and a metagene that represents the EGF pathway was significantly correlated with the presence of ground-glass opacity and irregular nodules or nodules with poorly defined margins. Conclusion Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways, and it can result in noninvasive identification of molecular properties of NSCLC. Online supplemental material is available for this article.


Early evolution of radial glial cells in Bilateria.
Bilaterians usually possess a central nervous system, composed of neurons and supportive cells called glial cells. Whereas neuronal cells are highly comparable in all these animals, glial cells apparently differ, and in deuterostomes, radial glial cells are found. These particular secretory glial cells may represent the archetype of all (macro) glial cells and have not been reported from protostomes so far. This has caused controversial discussions of whether glial cells represent a homologous bilaterian characteristic or whether they (and thus, centralized nervous systems) evolved convergently in the two main clades of bilaterians. By using histology, transmission electron microscopy, immunolabelling and whole-mount in situ hybridization, we show here that protostomes also possess radial glia-like cells, which are very likely to be homologous to those of deuterostomes. Moreover, our antibody staining indicates that the secretory character of radial glial cells is maintained throughout their various evolutionary adaptations. This implies an early evolution of radial glial cells in the last common ancestor of Protostomia and Deuterostomia. Furthermore, it suggests that an intraepidermal nervous system-composed of sensory cells, neurons and radial glial cells-was probably the plesiomorphic condition in the bilaterian ancestor.


Patient Involvement in RSV Research: Towards Patients Setting the Research Agenda.
Respiratory syncytial virus (RSV) causes a substantial disease burden among children, elderly and immunocompromised adults. Recognition of patient involvement in research is gradually increasing. Most research is being carried out without active patient involvement other than patients participating as study subjects, and most knowledge gained through research only partially reaches the general public. Since 2016, the RSV Patient Advisory Board has officially been involved as an advisory group in the Respiratory Syncytial Virus Consortium in Europe (RESCEU). What started as a small single-center initiative, is now growing towards an international organization providing patient perspectives as inputs to scientists, and improving awareness of RSV. This article summarizes the history, current role, and future aims of the RSV Patient Advisory Board as an advocate to improve patient involvement in research. RSV patients and their representatives are important stakeholders in setting the global research agenda, and educating patients, professionals, and the general public.


Favorable impact of Nigella sativa seeds on lipid profile in type 2 diabetic patients.
The atherogenic pattern of dyslipidemia associated with type 2 diabetes mellitus (DM) has been increasingly discussed. We have recently reported a hypoglycemic effect of Nigella sativa (NS) seeds in patients with type 2 DM. In this study we sought to assess the impact of NS seeds on lipid profile in type 2 diabetic patients. A total of 94 patients with type 2 DM were recruited and divided into 3 dose groups. Capsules containing NS were administered orally in a dose of 1, 2, and 3 g/day for 12 weeks. All patients were subjected to measurement of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) before treatment and 4, 8, and 12 weeks thereafter. Patients receiving 1 g/day NS seeds for 12 weeks (group 1) showed nonsignificant changes in all the parameters except for a significant increase in HDL-c after 4 weeks of treatment. However, patients ingested 2 g/day NS displayed a significant decline in TC, TG, and LDL-c, and a significant elevation in HDL-c/LDL-c, compared with their baseline data and to group 1 patients. Increasing NS dose to 3 g/day failed to show any increase in the hypolipdemic effect produced by the 2 g/day dose. NS supplementation at a dose of 2 g/day for 12 weeks may improve the dyslipidemia associated with type 2 diabetic patients. Therefore, NS is a potential protective natural agent against atherosclerosis and cardiovascular complications in these patients.


Emplacing reablement co-creating an outdoor recreation model in the rural Arctic.
Reablement aims to enable older persons with functional decline to re-engage in meaningful activities. The benefits of engagement in outdoor activities are significant; however, reablement services primarily target function in indoor environments whereas descriptions of outdoor activities are sparse. The aim of this study was to create a model that integrates outdoor recreation into reablement. We therefore elaborated on an experienced based co-design methodology to create a model that integrates outdoor recreation for older persons in reablement in an Arctic, rural context in northern Norway. Stakeholders (N = 35), including reablement participants, participated in workshops, focus groups, and individual interviews. Based on the results, we co-created a person-centred model for outdoor recreation in reablement, including an assessment tool that can guide reablement staff in goal-setting practices. Accordingly, we argue that cherished locations holds significant meaning in the lives of older people and warrant recognition in reablement programmes. There is a need to evaluate the effects and feasibility of the model and the possibility for its implementation in other health care settings.


Intimate partner violence in the post-war context: Women's experiences and community leaders' perceptions in the Eastern Province of Sri Lanka.
Exposure to armed conflict and/or war have been linked to an increase in intimate partner violence (IPV) against women. A substantial body of work has focused on non-partner rape and sexual violence in war and post-war contexts, but research about IPV is limited, particularly in Asian settings. This paper presents the finding of a study conducted in the Eastern Province of Sri Lanka. The study explored women's experiences of and responses to IPV as well as how health and social service providers perceive the problem. It also explored the IPV-related services and supports available after the end of a 30-year civil war. We conducted in-depth, qualitative interviews with 15 women who had experienced IPV and 15 service providers who were knowledgeable about IPV in the Eastern Province of Sri Lanka. Interviews were translated into English, coded and organized using NVivo8, and analyzed using inductive thematic analysis. Participants described IPV as a widespread but hidden problem. Women had experienced various forms of abusive and controlling behaviours, some of which reflect the reality of living in the post-war context. The psychological effects of IPV were common, but were often attributed to war-related trauma. Some men used violence to control women and to reinstate power when their gender roles were reversed or challenged due to war and post-war changes in livelihoods. While some service providers perceived an increase in awareness about IPV and more services to address it, this was discordant with women's fears, feelings of oppression, and perception of a lack of redress from IPV within a highly militarized and ethnically-polarized society. Most women did not consider leaving an abusive relationship to be an option, due to realistic fears about their vulnerability to community violence, the widespread social norms that would cast them as outsiders, and the limited availability of related services and supports. These findings revealed the need for more research about IPV in post-war contexts. Women's experiences in such contexts are influenced and may be masked by a complex set of factors that intersect to produce IPV and entrap women in violence. A more nuanced understanding of the context-specific issues that shape women's experiences of IPV- and community responses to it-is needed to develop more comprehensive solutions that are relevant to the local context.


Importance of experimental as well as empirical qualitative studies in special education.
In the past few decades qualitative research has increasingly appeared in special education journals. However, much of this work falls within the parameters of producing useful technical information that can be applied to the contexts where children and adults with disabilities learn, work, and live. Experimental qualitative studies that rely on postmodern or poststructural analyses, critical theory, and narrative research with subjective personal stories seem to be considered too radical, ideological, and theoretical to make it into many special education scholarly outlets. We argue that experimental qualitative designs have much to contribute to the fields of special education and disability studies and, hence, should reach those who receive or provide services to people with disabilities.


COVID-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study.
The opportunistic fungus Aspergillus fumigatus infects the lungs of immunocompromised hosts, including patients undergoing chemotherapy or organ transplantation. More recently however, immunocompetent patients with severe SARS-CoV2 have been reported to be affected by COVID-19 Associated Pulmonary Aspergillosis (CAPA), in the absence of the conventional risk factors for invasive aspergillosis. This paper explores the hypothesis that contributing causes are the destruction of the lung epithelium permitting colonization by opportunistic pathogens. At the same time, the exhaustion of the immune system, characterized by cytokine storms, apoptosis, and depletion of leukocytes may hinder the response to A. fumigatus infection. The combination of these factors may explain the onset of invasive aspergillosis in immunocompetent patients. We used a previously published computational model of the innate immune response to infection with Aspergillus fumigatus. Variation of model parameters was used to create a virtual patient population. A simulation study of this virtual patient population to test potential causes for co-infection in immunocompetent patients. The two most important factors determining the likelihood of CAPA were the inherent virulence of the fungus and the effectiveness of the neutrophil population, as measured by granule half-life and ability to kill fungal cells. Varying these parameters across the virtual patient population generated a realistic distribution of CAPA phenotypes observed in the literature. Computational models are an effective tool for hypothesis generation. Varying model parameters can be used to create a virtual patient population for identifying candidate mechanisms for phenomena observed in actual patient populations.


Ojeok-san enhances platinum sensitivity in ovarian cancer by regulating adipocyte paracrine IGF1 secretion.
Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa. OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC50 values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC. Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance. In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.


Serious fighting-related injuries produce a significant reduction in intelligence.
Fighting-related injuries are common among adolescents within the United States, but how such injuries relate to subsequent cognitive functioning remains unclear. In particular, the long-term effect of fighting-related injuries suffered during important developmental periods, such as adolescence, on subsequent cognitive functioning has been overlooked by previous studies. The purpose of this study is to examine the association between sustaining serious fighting-related injuries and changes in verbal intelligence (IQ) over a 5- to 6-year time period. Longitudinal multivariate statistical models were used to analyze data from the National Longitudinal Study of Adolescent Health collected between 1994 and 2002 and analyzed in 2013. Even a single fighting-related injury resulted in a significant reduction in IQ over time even after controlling for age, race, sex, and changes in socioeconomic status (SES) over the study period. Additionally, females experienced a significantly greater reduction in IQ from each fighting-related injury than males. Fighting-related injuries have a significant impact on subsequent cognitive functioning and intelligence. The implications for future policies and research are discussed in more detail.


The urological evaluation and management of neurogenic bladder in children and adolescents-what every pediatric nephrologist needs to know.
Neurogenic bladder (NGB) is an encompassing term that includes multiple causes of bladder dysfunction linked to a congenital or acquired neurological condition that adversely impacts the innervation of the lower urinary tract. Multiple static or progressive conditions can be associated with NGB in pediatric and adolescent patients. Currently, spinal dysraphism (i.e., spina bifida) is one of the most common etiologies, which occurs in 3-4 per 10,000 live births in developed nations. Abnormal bladder dynamics can lead to kidney damage secondary to high pressures or recurrent infections, as well as urinary incontinence. The current management paradigm centers on a proactive approach to preserving kidney function and achieving continence through behavioral, pharmacological, and surgical means. This educational review highlights the key components of urological management to maximize collaboration with pediatric nephrologists.


Transmission of enteritis in the Syrian hamster.
Twenty-six of 39 Syrian hamsters obtained by this laboratory from a pet supplier had enteritis and showed signs of "wet tail." An enteritis was reproduced in healthy hamsters by oral inoculation of homogenized ilea and jejuna from the diseased hamsters. The most characteristic pathologicfeatures were a variably enlarged distal jejunum and ileum and granulomatous lesions in the ileal subserosal wall. Histologic findings included a greatly hyperplastic jejunal and ileal mucosa that frequently contained submucosal accumulations of inflammatory cells. Often mucosal glands extended into these areas. The gross and histologic lesions produced were identical to those described in proliferative ileitis. Bacterial cultures from infected tissues consistently grew a slow lactose-fermenting Escherichia coli. Although diarrhea could be produced by oral inoculation of the organism, the typical morphologic lesions were not produced.


Medial and lateral gastrocnemius H-reflex intersession reliability during standing and lying postures at varied foot positions in healthy participants.
Available H-reflex procedures do not allow a reliable or valid examination for the L5 radiculopathy. However, recording the gastrocnemius H-reflex may allow a reliable and valid method for examination of the L5 nerve root. Therefore, the purpose of this study was to examine the intersession reliability of the medial gastrocnemius (MG) and lateral gastrocnemius (LG) H-reflexes recordings during standing and lying postures at varied ankle positions in healthy participants. The MG and LG H-reflexes of eight healthy participants were elicited by stimulating the tibial nerve and recording the resultant muscle response using surface electrodes. The stimulation parameters were 1.0 ms, 0.2 PPS, with incremented stimulus intensity. Four traces of the maximum amplitude H-reflex and M-wave were recorded during lying and standing with the ankle in neutral, full dorsiflexion, and full plantarflexion over two consecutive days. The averaged traces were used to calculate the intersession intraclass correlation coefficients (ICC) among conditions. Intersession ICCs (2, 1) of MG and LG during standing and lying with varied ankle positions were moderate to high (ranging from 0.58 to 0.94). The MG was more stable than LG and the ICCs were greater during standing (ranging from 0.76 to 0.94) than during lying (ranging from 0.58 to 0.85), indicating higher sensitivity of the MG H-reflex when the limb is engaged in functional standing However, the LG H-reflex reliability was robust and, thus, could be recorded consistently in the examination of the L5 nerve root.


The Exeter-Trident THA with ceramic-on-ceramic-bearings: 10-year outcomes in 275 total hip arthroplasties.
This study reports on the Exeter-Trident total hip arthroplasty (THA) using an alumina ceramic-on-ceramic bearing with 10-year clinical and radiographic follow-up. Between January 2001 and January 2006, 275 THAs were performed. Mean age at surgery was 52.7 (17-86) years, with 84 patients (33.6%) aged <50 years. The primary outcome was all-cause construct survival at minimum 10 years. Secondary outcomes included functional and noise scores. Radiographs were compared between baseline and latest follow-up and assessed for component loosening, migration and lysis. No patient was lost to follow-up. Mean follow-up for surviving patients was 12.5 (9.5-15.6) years. Kaplan-Meier survival for all-cause revision was 94.0% (95% CI, 90.5-97.5) at 14.3 years. 2 patients had a femoral component fracture. All scores improved significantly at latest follow-up. HSS-NQ for 247 hips (90.2%) at mean 9.1 (7.0-14.4) years post implantation showed most hips (93.1%) reported no more than occasional noise. At minimum 5 years, radiolucency around the acetabular component was observed in 2 hips (0.8%), and lysis at the interface in 1 hip (0.4%). On the femoral side, endosteal lysis was observed in 7 hips. The Exeter-Trident THA with alumina ceramic-on-ceramic bearings performed well in this population. Patients are at low risk of revision in the first decade. However, there is a small risk of stem fracture as a late complication and some patients experience significant noise.


Secretion by Toxoplasma gondii of an antigen that appears to become associated with the parasitophorous vacuole membrane upon invasion of the host cell.
Monoclonal antibodies against Toxoplasma gondii were prepared to characterize antigens of the parasite. Immunoperoxidase staining of parasites fixed with paraformaldehyde and glutaraldehyde (PFAGA) followed by Triton X-100 treatment showed that the antibody of clone I-63 recognized an antigen located in the anterior part of the parasite. When analysed by SDS-PAGE and immunoblotting, the antigen migrated in a 66 x 10(3) Mr region. The parasite antigen diminished greatly in parasites after invasion of host cells, but reappeared around a time when intracellular T. gondii multiplied. Immunodetection on PFAGA-fixed T. gondii-infected cells, whose membranes were permeabilized by freeze-thawing in the presence of 5% glycerol, demonstrated that, immediately after parasite invasion, the I-63 antibody-reactive antigen appeared to become associated with the parasitophorous vacuole (PV) membrane, that had been formed mainly by invagination of the host-cell plasma membrane so as to surround an invading parasite. The antigen remained associated with the PV membrane for some time, but disappeared later when the PV increased in size after the parasites had multiplied several times. These results were strengthened by immunoelectron microscopic observations: the antigen that had been localized at the anterior part of the parasite before invasion appeared in an area of the host cell cytoplasm around the tips of penetrating parasites and, thereafter, extended throughout the surface of the PV membrane when parasites completed invasion. Thus, it appears that the I-63-reactive antigen is secreted by T. gondii upon invasion of the host cell and becomes associated with the PV membrane shortly after invasion.


[Histology and prognosis of nephroblastoma--with special reference to special variants].
101 cases of Wilms' tumor (nephroblastoma) were investigated by light microscopy. In 80 cases a diagnosis of triphasic nephroblastoma was made. 21 cases were classified as special variants of Wilms' tumor. These included congenital mesoblastic nephroma (n = 5), fetal rhabdomyomatous nephroblastoma (n = 2), cystic partially differentiated nephroblastoma (n = 3), nephroblastoma with focal or diffuse anaplasia (n = 2), clear cell sarcoma or bone metastasizing renal tumor of childhood (n = 4), rhabdoid tumor (n = 2) and rhabdomyosarcomatous nephroblastoma (n = 3). Based on our own follow-up data and on information from the literature we propose to separate the group of nephroblastomas into three categories of different prognosis: 1. Nephroblastomas of low risk (congenital mesoblastic nephroma, fetal rhabdomyomatous nephroblastoma, cystic partially differentiated nephroblastoma) - in most of these cases simple nephrectomy sufficient as adequate therapy. 2. Nephroblastomas of standard risk (triphasic nephroblastomas) - therapy according to stage of disease. 3. Nephroblastomas of high risk (nephroblastomas with focal or diffuse anaplasia, clear cell sarcoma, rhabdoid tumor, rhabdomyosarcomatous nephroblastoma) - successful therapy has as yet to be developed.


Direct Meta-Analyses Reveal Unexpected Microbial Life in the Highly Radioactive Water of an Operating Nuclear Reactor Core.
The pools of nuclear reactor facilities constitute harsh environments for life, bathed with ionizing radiation, filled with demineralized water and containing toxic radioactive elements. The very few studies published to date have explored water pools used to store spent nuclear fuels. Due to access restrictions and strong handling constraints related to the high radioactivity level, nothing is presently known about life in water pools that directly cool nuclear cores. In this work, we investigated the microbial communities in the cooling pool of the French Osiris nuclear reactor using direct meta-omics approaches, namely, DNA metabarcoding and proteotyping based on 16S ribosomal RNA gene sequencing and on peptide analysis, respectively. We identified 25 genera in the highly radioactive core water supply during operation with radionuclide activity higher than 3 × 109 Bq/m3. The prevailing genera Variovorax and Sphingomonas at operation were supplanted by Methylobacterium, Asanoa, and Streptomyces during shutdown. Variovorax might use dihydrogen produced by water radiolysis as an energy source.


Saprochaete clavata Outbreak Infecting Cancer Center through Dishwasher.
Saprochaete clavata is a pathogenic yeast responsible for rare outbreaks involving immunocompromised patients, especially those with hematologic malignancies. During February 2016-December 2017, we diagnosed S. clavata infections in 9 patients (8 with fungemia), including 3 within 1 month, at a cancer center in Marseille, France. The patients (median age 58 years), 4 of 9 of whom had acute myeloid leukemia, were hospitalized in 3 different wards. Ten environmental samples, including from 2 dishwashers and 4 pitchers, grew S. clavata, but no contaminated food was discovered. The outbreak ended after contaminated utensils and appliances were discarded. Whole-genome sequencing analysis demonstrated that all clinical and environmental isolates belonged to the same phylogenetic clade, which was unrelated to clades from previous S. clavata outbreaks in France. We identified a dishwasher with a deficient heating system as the vector of contamination.


The genome sequence of the fungal pathogen Fusarium virguliforme that causes sudden death syndrome in soybean.
Fusarium virguliforme causes sudden death syndrome (SDS) of soybean, a disease of serious concern throughout most of the soybean producing regions of the world. Despite the global importance, little is known about the pathogenesis mechanisms of F. virguliforme. Thus, we applied Next-Generation DNA Sequencing to reveal the draft F. virguliforme genome sequence and identified putative pathogenicity genes to facilitate discovering the mechanisms used by the pathogen to cause this disease. We have generated the draft genome sequence of F. virguliforme by conducting whole-genome shotgun sequencing on a 454 GS-FLX Titanium sequencer. Initially, single-end reads of a 400-bp shotgun library were assembled using the PCAP program. Paired end sequences from 3 and 20 Kb DNA fragments and approximately 100 Kb inserts of 1,400 BAC clones were used to generate the assembled genome. The assembled genome sequence was 51 Mb. The N50 scaffold number was 11 with an N50 Scaffold length of 1,263 Kb. The AUGUSTUS gene prediction program predicted 14,845 putative genes, which were annotated with Pfam and GO databases. Gene distributions were uniform in all but one of the major scaffolds. Phylogenic analyses revealed that F. virguliforme was closely related to the pea pathogen, Nectria haematococca. Of the 14,845 F. virguliforme genes, 11,043 were conserved among five Fusarium species: F. virguliforme, F. graminearum, F. verticillioides, F. oxysporum and N. haematococca; and 1,332 F. virguliforme-specific genes, which may include pathogenicity genes. Additionally, searches for candidate F. virguliforme pathogenicity genes using gene sequences of the pathogen-host interaction database identified 358 genes. The F. virguliforme genome sequence and putative pathogenicity genes presented here will facilitate identification of pathogenicity mechanisms involved in SDS development. Together, these resources will expedite our efforts towards discovering pathogenicity mechanisms in F. virguliforme. This will ultimately lead to improvement of SDS resistance in soybean.


Ideal intensive care unit course following comprehensive stage II in hypoplastic left heart syndrome.
Comprehensive stage II is the advanced surgical part of the staged treatment of a newborn with hypoplastic left heart syndrome (HLHS) palliated initially by a Giessen-Hybrid approach. We report an almost ideal course following comprehensive stage II operation with focus on postoperative intensive care strategy. Following a short introduction of the postnatally performed Giessen-Hybrid approach, in which the surgical part is focused on bilateral pulmonary banding and duct stenting as well as manipulation of the atrial septum is postponed to transcatheter approach, it should be emphasized, that the quality of inter-stage I is eminently important for the success of the following comprehensive stage II. Furthermore, the interplay of the responsible surgeon, anesthesiologist, cardiologist and intensivist is mandatory for working as a team with a similar pathophysiological background. Presupposed a sophisticated surgical and anesthesiologic management, the immediate post-operative intensive care is crucial for the patient's final outcome, not only in terms of mortality but even morbidity (long-term neurological condition). Detailed treatment strategies are presented by pathophysiological reasonable hypotheses and the current pharmacological knowledge. Aiming to improve systemic and regional oxygen delivery and lowering oxygen consumption, as a sine qua none for a favorable patient's outcome.


Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells.
Detergent-soluble membrane vesicles are actively released by human pancreas (Colo-/Colo+) and colon (CX-/CX+) carcinoma sublines, differing in their capacity to present heat shock protein 70 (Hsp70)/Bag-4 on their plasma membranes. Floating properties, acetylcholine esterase activity, and protein composition characterized them as exosomes. An enrichment of Rab-4 documented their intracellular transport route from early endosomes to the plasma membrane. After solubilization, comparable amounts of cytosolic proteins, including tubulin, Hsp70, Hsc70, and Bag-4, but not ER-residing Grp94 and calnexin, were detectable in tumor-derived exosomes. However, with respect to the exosomal surface, only Colo+/CX+ but not Colo-/CX- derived exosomes were Hsp70 membrane positive. Therefore, concomitant with an up-regulated cell surface density of activation markers, migration and Hsp70 reactivity of natural killer (NK) cells was stimulated selectively by Hsp70/Bag-4 surface-positive exosomes, but not by their negative counterparts and tumor cell lysates. Moreover, the exosome-mediated lytic activity of NK cells was blockable by Hsp70-specific antibody. As already shown for TKD stimulation, NK cells preincubated with Hsp70 surface-positive exosomes initiated apoptosis in tumors through granzyme B release. In summary, our data provide an explanation how Hsp70 reactivity in NK cells is induced by tumor-derived exosomes.


Phase II open label pilot trial of aprepitant and palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic FOLFOX chemotherapy for the treatment of colorectal cancer.
Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients. Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3. Palonosetron 0.25 mg was given IV push on day 1 only. Dexamethasone 12 mg was administered orally on day 1 and 8 mg each morning on days 2 through 4. Assessments including emetic events, rescue doses, nutritional intake, and appetite were recorded in a patient diary which was returned to study personnel in the following cycle. Of the 53 patients screened, 50 were evaluable and had a complete dataset for cycle 1. For the first cycle, 74% of patients achieved a complete response (CR), 22% achieved a major response and 4% experienced treatment failure. The percentage of patients achieving a CR remained high throughout each cycle at 83, 83, and 86% for cycles 2, 3, and 4, respectively. Appetite and nutritional status remained largely unchanged throughout treatment. Adverse events occurring in more than 10% of patients included diarrhea (13.6%), fatigue (12.6%), and neutropenia (11%). Aprepitant added to standard antiemetic therapy appears to be an effective and safe regimen for prevention of CINV in patients receiving FOLFOX.


Effectiveness of Mirror Therapy for Subacute Stroke in Relation to Chosen Factors.
The aim of this study was to determine the effectiveness of mirror therapy (MT) combined with comprehensive treatment and to investigate the possible relationships of functional state. Prospective, controlled trial of 60 stroke inpatients. The Functional Index "Repty" (FIR) was an outcome measure to assess changes of independence in daily activities. The Frenchay Arm Test (FAT) and Motor Status Score were outcome measures to assess changes in hand function. The analysis of pre- and posttest data indicated a significant improvement in hand function ([INCREMENT]FAT in the Mirror group p = .035, N = 30). Age factor indicated a significant change in relation to FIR outcome ([INCREMENT]FIR in the Mirror group p = .005, N = 30 and [INCREMENT]FIR in the Mirror group [left hand paresis] p = .037, N = 15). Additional MT influenced improvement in hand function. The age is significant in terms of functional state. The older adults are likely to benefit from MT. A positive impact of combining MT with other treatment was indicated.


Bone marrow transplant patients with life-threatening organ failure: when should treatment stop?
To discuss issues surrounding life support in bone marrow transplant (BMT) patients, issues that may determine how far we go to keep a deteriorating BMT patient alive--and when we stop trying. How can we define survival chance in BMT patients, and when should prolongation of life be deemed inappropriate? Who should make the decision to terminate support? And how should life support be terminated? Prognostic factors that predict for almost certain nonsurvival have been identified in BMT patients with life-threatening organ failure. The concept of futility raises the question of how low the chance of survival must be before termination of life support is justified--but the concept is flawed, and the value judgments involved in decision making must also be considered. Then, once a decision is made, the manner of withholding or withdrawing life support is also open to discussion. Despite controversies, there are areas in which improvements to current practice might be considered. More data are required to determine survival chances of BMT patients with life-threatening organ failure. Greater attention might be devoted, in pretransplant counseling, to issues of intensive life support, with the patient's own views being ascertained before transplantation. And, because technologic possibilities are now imposing fewer boundaries, the problem of finite resources may need to be readdressed, with treatment limits being set down before transplantation.


Soil cadmium pollution facilitated the invasion of alligator weed through enhanced herbivore resistance and competitive ability over a congeneric species.
A number of invasive plant species, such as Alternanthera philoxeroides, have been documented to be able to accumulate trace metal elements in their tissues. Since metal accumulation in plants can serve as a defence against herbivores, we hypothesized that metal pollution will increase herbivore resistance of metal-accumulating invasive plant species and such a benefit will grant them a competitive advantage over local co-occurring plants. In this study, we compared the differences in plant growth and herbivore feeding preference between A. philoxeroides and its native congener Alternanthera sessilis in single and mixed cultures with and without soil cadmium (Cd) pollution. The results showed that A. philoxeroides plants were more tolerant to Cd stress and accumulated more Cd in the leaves than A. sessilis. Cd exposure increased the resistance of A. philoxeroides against a specialist and a generalist herbivore compared with A. sessilis. Competition experiments indicated that Cd stress largely increased the competitive advantage of A. philoxeroides over A. sessilis with or without herbivore pressures. The differences in herbivore resistance between the two plant species under soil Cd stress are most likely due to the deterring effect of Cd accumulation and Cd-enhanced mechanical defences rather than changes in leaf specialized metabolites.


Spectrally resolved white-light interferometry for measurement of ocular dispersion.
Spectrally resolved white-light interferometry was used to measure the wavelength dependence of refractive index (i.e., dispersion) for various ocular components. Verification of the technique's efficacy was substantiated by accurate measurement of the dispersive properties of water and fused silica, which have both been well-characterized in the past by single-wavelength measurement of the refractive index. The dispersion of bovine and rabbit aqueous and vitreous humors was measured from 400 to 1100 nm. In addition, the dispersion was measured from 400 to 700 nm for aqueous and vitreous humors extracted from goat and rhesus monkey eyes. An unsuccessful attempt was also made to use the technique for dispersion measurement of bovine cornea and lens. The principles of white-light interferometry, including image analysis, measurement accuracy, and limitations of the technique, are discussed. In addition, alternate techniques and previous measurements of ocular dispersion are reviewed.


[HbA1c: target value should remain 7%].
The treatment of diabetes mellitus is focused on the prevention of micro- and macrovascular complications. The target HbA(1c) should therefore be 7% or lower. However, a recent study advised a HbA(1c) of 7.5%, since it was found that mortality increased with an HbA(1c) below 7.5%. This was probably caused by hypoglycaemia. A higher mortality in patients with a low HbA(1c) has been described before, but the causes were never understood. It is true that a lower HbA(1c) leads to more hypoglycaemia, but there are no indications that this is the cause of the increased mortality. Changing the target HbA(1c) based on one epidemiological retrospective study is unwise. Taking into account historic prospective studies such as the United Kingdom Prospective Diabetes Study, we think the target HbA(1c) should remain 7% or lower in the treatment of diabetes mellitus.


Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria.
The notion that mitochondria cannot be lost was shattered with the report of an oxymonad Monocercomonoides exilis, the first eukaryote arguably without any mitochondrion. Yet, questions remain about whether this extends beyond the single species and how this transition took place. The Oxymonadida is a group of gut endobionts taxonomically housed in the Preaxostyla which also contains free-living flagellates of the genera Trimastix and Paratrimastix. The latter two taxa harbour conspicuous mitochondrion-related organelles (MROs). Here we report high-quality genome and transcriptome assemblies of two Preaxostyla representatives, the free-living Paratrimastix pyriformis and the oxymonad Blattamonas nauphoetae. We performed thorough comparisons among all available genomic and transcriptomic data of Preaxostyla to further decipher the evolutionary changes towards amitochondriality, endobiosis, and unstacked Golgi. Our results provide insights into the metabolic and endomembrane evolution, but most strikingly the data confirm the complete loss of mitochondria for all three oxymonad species investigated (M. exilis, B. nauphoetae, and Streblomastix strix), suggesting the amitochondriate status is common to a large part if not the whole group of Oxymonadida. This observation moves this unique loss to 100 MYA when oxymonad lineage diversified.


Congenital hyperinsulinism.
This clinical review will give doctors who work with children and neonates an introduction to the diagnosis and treatment of congenital hyperinsulinism, the most common cause of persistent neonatal hypoglycaemia. The condition is a rare monogenic disorder characterised by elevated insulin secretion and is a result of mutations in genes that regulate insulin secretion from pancreatic beta cells. The anabolic effect of insulin induces systemic glucose uptake and inhibits gluconeogenesis, glycogenolysis, ketogenesis and lipolysis. Low levels of glucose and ketone bodies in the blood are harmful to the central nervous system and can lead to brain damage or death. Early diagnosis and treatment of congenital hyperinsulinism are therefore crucial for a good prognosis.


Quantitative modeling of responses to chronic ionizing radiation exposure using targeted and non-targeted effects.
The biological effects of chronic ionizing radiation exposure can be difficult to study, but important to understand in order to protect the health of occupationally-exposed persons and victims of radiological accidents or malicious events. They include targeted effects (TE) caused by ionizations within/close to nuclear DNA, and non-targeted effects (NTE) caused by damage to other cell structures and/or activation of stress-signaling pathways in distant cells. Data on radiation damage in animal populations exposed over multiple generations to wide ranges of dose rates after the Chernobyl nuclear-power-plant accident are very useful for enhancing our understanding of these processes. We used a mechanistically-motivated mathematical model which includes TE and NTE to analyze a large published data set on chromosomal aberrations in pond snail (Lymnaea stagnalis) embryos collected over 16 years from water bodies contaminated by Chernobyl fallout, and from control locations. The fraction of embryo cells with aberrations increased dramatically (>10-fold) and non-linearly over a dose rate range of 0.03-420 μGy/h (0.00026-3.7 Gy/year). NTE were very important for describing the non-linearity of this radiation response: the TE-only model (without NTE) performed dramatically worse than the TE+NTE model. NTE were predicted to reach ½ of maximal intensity at 2.5 μGy/h (0.022 Gy/year) and to contribute >90% to the radiation response slope at dose rates <11 μGy/h (0.1 Gy/year). Internally-incorporated 90Sr was possibly more effective per unit dose than other radionuclides. The radiation response shape for chromosomal aberrations in snail embryos was consistent with data for a different endpoint: the fraction of young amoebocytes in adult snail haemolymph. Therefore, radiation may affect different snail life stages by similar mechanisms. The importance of NTE in our model-based analysis suggests that the search for modulators of NTE-related signaling pathways could be a promising strategy for mitigating the deleterious effects of chronic irradiation.


Evaluation of Clinical Reasoning Learning for students in SCMS2, pediatrics Module.
Learning clinical teaching is an alternative to traditional forms of teaching. Its objective is to lead the student to acquire a relevant diagnostic approach by developing a clinical reasoning. To evaluate these sessions in Pediatrics, with students in the second cycle of medical study. A session on the topic of "stunting" was scheduled as a CRL with second cycle of medical studies 2 (SCMS2) students during their Pediatrics internship, with a pre and post-test administered and a self-administered questionnaire. Two groups of students that included twenty-three students participated in the session. Pre-test scores ranged from 0/10 to 6.8 / 10 and post-test scores from 6.5 / 10 to 9/10. The average pre- and post-test scores, were respectively 4.26 ± 1.37/10 and 7.35 ± 0.7 / 10 (P <0.001). Twenty-two students reported their overall satisfaction with teaching. The overall rating score was 4.39 ± 0.49/ five points. The average of the ratings for new knowledge delivery, achievement of educational objectives, interaction and participation were greater than 4.3 / 5. This form of small group learning seems to have legitimacy in Pediatric education.


Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels.
The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.


Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2.
Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows. Associated eye findings include photophobia in childhood and corneal dystrophy. Due to the genetic and clinical heterogeneity of similar disorders, a definitive diagnosis of KFSD is often challenging. Toward identification of the causative gene we reanalyzed a large Dutch KFSD family. SNP arrays (1 M) redefined the locus to a 2.9-Mb region at Xp22.12-Xp22.11. Screening of all 14 genes in the candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation. The variant was also identified in two unrelated X-linked KFSD families and cosegregated with KFSD in all families. In symptomatic female carriers, skewed X-inactivation of the normal allele matched with increased severity of symptoms. MBTPS2 is required for cleavage of sterol regulatory element-binding proteins (SREBPs). In vitro functional expression studies of the c.1523A>G mutation showed that sterol responsiveness was reduced by half. Other missense mutations in MBTPS2 have recently been identified in patients with IFAP syndrome. We postulate that both phenotypes are in the spectrum of one genetic disorder with a partially overlapping phenotype.


It takes a (virtual) village: crowdsourcing measurement consensus to advance survivorship care planning.
We report results from the use of an innovative tool (the Grid-Enabled Measures (GEM) database) to drive consensus on the use of measures evaluating the efficacy and implementation of survivorship care plans. The goal of this initiative was to increase the use of publicly available shared measures to enable comparability across studies. Between February and August 2012, research and practice communities populated the GEM platform with constructs and measures relevant to survivorship care planning, rated the measures, and provided qualitative feedback on the quality of the measures. Fifty-one constructs and 124 measures were entered into the GEM-Care Planning workspace by participants. The greatest number of measures appeared in the domains of Health and Psychosocial Outcomes, Health Behaviors, and Coordination of Care/Transitional Care. Using technology-mediated social participation, GEM presents a novel approach to how we measure and improve the quality of survivorship care.


Proptosis secondary to subdural hematoma.
A subdural hematoma extending into the orbit through a fracture of the sphenoid bone appeared as unilateral proptosis with no neurologic abnormalities. Repeated percutaneous needle aspirations of the orbital portion of this mass provided only temporary relief of proptosis, but decompressed the intracranial portion of the hematoma adequately for prevention of neurologic manifestations. Ultrasonography correctly diagnosed the nature of the lesion and identified the bony dehiscence. Computed tomographic (CT) evaluation suggesting that a tumor might be present led to the performance of curative neurosurgery. Even when seemingly trivial, head trauma must be considered along with congenital, developmental, and neoplastic causes as a potential cause of intracranial cyst formation that can produce proptosis.


Survival of fetal rat otocyst cells grafted into the damaged inner ear.
Hair cell loss induced by aging, ototoxic drugs and noise leads to irreversible hearing loss and balance disorders in mammals due to the failure of hair cells to regenerate. To investigate the possibility of transplantation therapy to repair damaged inner ear, we have examined whether grafted fetal otocyst cells could survive and migrate into injured sensory organs. We obtained otocyst cells from green fluorescein protein (GFP)-transgenic rats on embryonic day 12.5, then transplanted these cells into the inner ears of young rats previously exposed to intense sound. One month after transplantation, the grafted inner ear sensory organs were examined immunohistochemically. Grafted otocyst cells had survived and demonstrated special morphological features in the host organs; cells that migrated into the organ of Corti were similar to supporting cells. These results indicate that injured sensory organs express some kind of scaffolding that plays important roles in the survival and differentiation of the grafted otocyst cells.


Differential regulation of CpG island methylation within divergent and unidirectional promoters in colorectal cancer.
The silencing of tumor suppressor genes by promoter CpG island (CGI) methylation is an important cause of oncogenesis. Silencing of MLH1 and BRCA1, two examples of oncogenic events, results from promoter CGI methylation. Interestingly, both MLH1 and BRCA1 have a divergent promoter, from which another gene on the opposite strand is also transcribed. Although studies have shown that divergent transcription is an important factor in transcriptional regulation, little is known about its implication in aberrant promoter methylation in cancer. In this study, we analyzed the methylation status of CGI in divergent promoters using a recently enriched transcriptome database. We measured the extent of CGI methylation in 119 colorectal cancer (CRC) clinical samples (65 microsatellite instability high [MSI-H] CRC with CGI methylator phenotype, 28 MSI-H CRC without CGI methylator phenotype and 26 microsatellite stable CRC) and 21 normal colorectal tissues using Infinium MethylationEPIC BeadChip. We found that CGI within divergent promoters are less frequently methylated than CGI within unidirectional promoters in normal cells. In the genome of CRC cells, CGI within unidirectional promoters are more vulnerable to aberrant methylation than CGI within divergent promoters. In addition, we identified three DNA sequence motifs that correlate with methylated CGI. We also showed that methylated CGI are associated with genes whose expression is low in normal cells. Thus, we here provide fundamental observations regarding the methylation of divergent promoters that are essential for the understanding of carcinogenesis and development of cancer prevention strategies.


Feasibility of the Figure-of-8-Suture as Venous Closure in Interventional Electrophysiology: One Strategy for All?
Background: Venous vascular access with higher sheath size is common in interventional electrophysiology. In contrast to arterial vascular access, no dedicated closure devices exist for closure after venous access with higher sheath sizes. The Figure-of-8-Suture, an easy to apply suture, may be as a feasible approach for closure venous puncture. Our aim was to evaluate the feasibility of closure of femoral venous access. Methods: From November 2016 to February 2018, patients undergoing electrophysiological procedures, closure of left atrial appendage or patent foramen ovale were included. Until May 2017, manual compression was performed to achieve haemostasis at venous access site (control group). From May 2017, patients were treated with a Figure-of-8-Suture (treatment group, Figure 1). Turnaround time and incidence of vascular complications were compared between the two groups. Results: In total, 290 patients were included, 132 in the control group and 158 in the Figure-of-8-Suture group. Hemostasis after sheath removal was achieved in 100% of the cases in the control group by manual compression and in 98.7% of the cases with the Figure-of-8-Suture (p=0.2). Vascular complications were more common in the control group (6.8 vs. 1.3 %, p=0.01). Turnaround time was significantly lower in the Figure-of-8-Suture group (58.6 ± 14 vs. 77 ± 33.9 min, p=0.004). In a sub-analysis in obese patients with body mass index (BMI) ≥30 kg/m2 (Figure-of-8 n=45, controls n=35), vascular complications were significantly more common in the control group (9.4 vs 0%, p=0.045). Conclusion: The Figure-of-8-Suture is an easy-to-apply, effective approach for venous closure after electrophysiological procedures.


Altered myoelectrical activity in noninflamed ileum of rats with colitis induced by trinitrobenzene sulphonic acid.
Changes in gastric emptying and orocaecal transit time in patients with ulcerative colitis suggest that disturbances in gut motility may not be restricted to inflamed sites. This study sought to characterize changes in the motility of noninflamed ileum in a rat colitis model and to explore the mechanism(s) potentially involved. The myoelectrical activity of the ileum was recorded in rats with trinitrobenzene sulphonic acid (TNBS)-induced colitis. The degree of ileal and colonic inflammation was assessed by quantification of macroscopic damage and myeloperoxidase activity (MPO). The effect on ileal motility of pretreatment with atropine, indomethacin and NG-nitro-L-arginine-methyl ester (L-NAME) was investigated. TNBS-induced inflammation was restricted to the distal colon, as evidenced by morphological scores and MPO. Colitis was associated with increased frequency of ileal migrating motor complexes, characterized mainly by a decrease in the duration of phases I and III. The occurrence of ileal giant migrating complexes remained unchanged. The myoelectrical changes observed in the ileum persisted after treatment with atropine, indomethacin and L-NAME. Distal colitis is associated with abnormal myoelectrical activity in the noninflamed ileum of rats. Neither acetylcholine nor prostaglandins and nitric oxide seem to be involved.


[The effect of diethylstilbestrol on inducing abdominal cryptorchidism and relevant genetic expression in rats].
To study the effect of diethylstilbestrol (DES) at different doses on transabdominal testicular descent in rats and the expression of INSL3 in the testis and HOXA10 in the gubernaculum. Fifty E13.5 (embryonic day 13.5) pregnant female SD rats were randomly divided into five groups that received a subcutaneous injection of DMSO, 2.5, 5.0, 10.0 and 20.0 mg/kg DES (group A, B, C, D and E), respectively. Male offspring were killed at E19.5, and then fetal mortality, the degree of transabdominal testicular ascent (DTA) was determined by a stereomicroscope. The mRNA expressions of INSL3 in the testis and HOXA10 in the gubernaculum were determined by RT-PCR. The expression of INSL3 protein was determined by Western blotting. Male fetal mortality in group A, B, C, D, and E were 3.57%, 6.90%, 12.00%, 19.23% and 36.36%, respectively, which showed a dose-effect relationship between DES and the male fatal mortality (r=0.999, P<0.01). DTA in group B, C, D and E were (23.7+/-1.7) U, (38.8+/-1.9) U, (49.3+/-1.8) U and (58.6+/-2.1) U that were significantly larger than that in group A [(8.5+/-1.3) U] (q=46.12, 88.53, 120.44 and 141.37, respectively, P<0.01). There was also a dose-effect relationship between DES and DTA. In group B, C, D, and E, the expression of INSL3 mRNA were 0.9570+/-0.1490, 0.6760+/-0.1380, 0.0170+/-0.0040 and 0.0013+/-0.0003, respectively; the expressions of INSL3 protein were 0.8360+/-0.1520, 0.5310+/-0.1070, 0.0140+/-0.0020 and 0.0011+/-0.0003, respectively, which were significantly larger than the expression of INSL3 mRNA (1.801+/-0.126) and INSL3 protein (1.612+/-0.134) in group A (qmRNA=40.4840, 52.4402, 83.1585 and 82.0582, respectively, and qprotein=38.6151, 52.2747, 77.2756 and 76.1983, respectively, P<0.01). The expression of HOXA10 mRNA in group A, B, C, D, and E were 0.945+/-0.125, 0.940+/-0.119, 0.656+/-0.115, 0.544+/-0.118 and 0.463+/-0.114, respectively. Compared with the expression of HOXA10 mRNA in group A, the expression of group B was not significantly different (q=0.2213, P>0.05), those in other groups were down-regulated significantly (q=12.4304, 17.2477 and 20.2789, respectively, P<0.01). DES inhibited transabdominal testicular descent dose-dependently via down-regulating the expression of INSL3. HOXA10 may play no role in low-dosage DES induced intra-abdominal cryptorchidism, but down-regulated HOXA10 mRNA was involved in high-dosage DES induced ones.


Assessment of current disease surveillance activities for pigs post-farmgate in New South Wales.
Evaluate current disease surveillance activities at saleyards and abattoirs in New South Wales (NSW) in order to establish the prevalence of clinical anomalies in pigs at different sites and to compare the sensitivity of detecting anomalies inside versus outside of pens. Routine inspections of pigs by staff and government inspectors were observed at two saleyards and two abattoirs in NSW during three visits over a 2-month period (January 2008-March 2008). All pigs presented for sale or slaughter were examined for 19 clinical anomalies from either the side of the pen or while animals were moving outside the pen, with data being combined to give an assumed 'gold standard'. We compared the prevalence of anomalies among animals at the four sites using logistic regression, as well as the sensitivity of detection of the two inspection methods. Frequency and methodology of routine inspection varied among sites. Of the 7747 pigs inspected, 822 (10.6%) showed at least one clinical anomaly. There was moderate agreement between detecting anomalies in penned pigs versus while being moved. Pigs at one abattoir exhibited significantly fewer anomalies than pigs at the other sites. The prevalence of anomalies among pigs at saleyards and abattoirs in NSW was relatively high ( approximately 10%). Weaknesses in current disease surveillance activities for pigs post-farmgate have been identified. Increased regulation, surveillance training and modification of standard operational procedures for inspection have the potential to improve the current system.


Use of dexmedetomidine in the adult intensive care unit.
Sedation and analgesia, which are universally used in intensive care units (ICUs), provide patients with comfort and safety. The current trends aim at light sedation; the objective is to ensure the minimal sedation level for improving patients' autonomy and enabling the professional staff to assess the patients' neurological status and cognitive functions. Reports in the literature have indicated that a sedative or an entire sedation procedure can affect cognitive processes, the duration of mechanical ventilation and treatment outcomes in critically ill patients. At present, special attention is given to post-sedation delirium. Although sedatives differ in their uptake points, which can influence the quality of sedation, their common characteristic is substantial impairment of cognitive functions, memory and respiration. Alpha 2-adrenergic receptor agonists, which comprise a novel group of agents, are used frequently for sedation. One of these medications is dexmedetomidine, which is designed to sedate adult ICU patients who exhibit a score ≥ -3 according to the Richmond Agitation-Sedation Scale. Recent studies comparing the use of dexmedetomidine and the other sedative agents that are most commonly administered in ICUs demonstrated that the former largely fulfils the expectations of intensivists.


Flexible ultrasound transceiver array for non-invasive surface-conformable imaging enabled by geometric phase correction.
Ultrasound imaging provides the means for non-invasive real-time diagnostics of the internal structure of soft tissue in living organisms. However, the majority of commercially available ultrasonic transducers have rigid interfaces which cannot conform to highly-curved surfaces. These geometric limitations can introduce a signal-quenching air gap for certain topographies, rendering accurate imaging difficult or impractical. Here, we demonstrate a 256-element flexible two-dimensional (2D) ultrasound piezoelectric transducer array with geometric phase correction. We show surface-conformable real-time B-mode imaging, down to an extreme radius of curvature of 1.5 cm, while maintaining desirable performance metrics such as high signal-to-noise ratio (SNR) and minimal elemental cross-talk at all stages of bending. We benchmark the array capabilities by resolving reflectors buried at known locations in a medical-grade tissue phantom, and demonstrate how phase correction can improve image reconstruction on curved surfaces. With the current array design, we achieve an axial resolution of ≈ 2 mm at clinically-relevant depths in tissue, while operating the array at 1.4 MHz with a bandwidth of ≈ 41%. We use our prototype to image the surface of the human humerus at different positions along the arm, demonstrating proof-of-concept applicability for real-time diagnostics using phase-corrected flexible ultrasound probes.


Research Strategy for the Development of a Quality-of-Life Decision-Making Model for Older Patients With Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is a deadly cancer, especially for patients over 60 years of age who face the dilemma of choosing the best treatment during a time of crisis. Current research in the older AML population is focused on survival without addressing quality of life (QOL). Survival and QOL data are essential for patients to decide which treatment best aligns with their goals, whether for survival or improved QOL. Research aims: The aims of this study are to: (1) Describe differences in QOL among newly diagnosed older AML patients receiving intensive chemotherapy compared with nonintensive chemotherapy (at baseline, and days 30, 60, 90, and 180 post treatment); (2) Identify the individual clinical disease characteristics and patient factors of newly diagnosed AML patients that predict QOL among those receiving two treatment intensities; and (3) Design a patient decision-making model that integrates the significant clinical disease and patient factor predictors of QOL for newly diagnosed older AML patients. Methods: An exploratory observational design will be used to address aims 1 and 2. Data will be collected from 200 patients ≥ 60 years of age with newly diagnosed AML. Subjects will complete the Functional Assessment of Cancer Therapy-Leukemia, Brief Fatigue Inventory, and Memorial Symptom Assessment Short Form within 7 days of beginning new treatment and at days 30, 60, 90 and 180. Clinical disease characteristics will be completed by the health-care team. A patient decision-making model will be developed to provide survival and quality-of-life data for intensive and nonintensive chemotherapy.


The radical revolution of radiology.
The radiologic segment of the health care industry has grown dramatically in size and functions. The focus on cancer and heart disease has made it a key core functional area for health systems and physician groups. Aggressive growth plans are based on key strategies, high demand services, and other critical success factors.


Narratives, memorable cases and metaphors of night nursing: findings from an interpretative phenomenological study.
The aim of the study was to explore the experiences of night nurses. An interpretative phenomenological study was undertaken, and 35 nurses working in Italian medical, surgical and intensive care units were purposely recruited. Data were gathered in 2010 by semi-structured interviews, collecting nurses' narratives, memorable cases and metaphors, aimed at summarising the essence of work as a nurse during the night. The experience of night nursing is based on four interconnected themes: (i) working in a state of alert, (ii) growing by expanding autonomy and responsibility, (iii) assuring sensitive surveillance and (iv) experiencing deep intimacy. Memorable episodes were polarised along (i) expected/unexpected events; (ii) positive/negative epilogues; and (iii) life/death issues. Many of the emergent metaphors described working during the night as being in the middle of a space where an apparent calm scene takes place, but unpredictable factors may suddenly change the order of events and the outcomes, creating chaos. Working during the night alerts nurses, who increase autonomy, expanding their role and assuming more responsibility with respect to that assumed during daily shifts. The nurses' clinical reasoning is based on data they carefully listen to, and on the meaning that nurses give time by time to different noises and silence. While in the past a sense of companionships was reported, a loneliness or a 'neutral' experience concerning the relationships with colleagues seems to prevail during night nursing. Working night shifts is a complex task, and specific training must be assured to students/novices.


In vitro and ex vivo activities of minocycline and EDTA against microorganisms embedded in biofilm on catheter surfaces.
Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin's device (MRD) was used whereby 25 catheter segments were flushed for 18 h with 10(6) CFU of biofilm-producing Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to catheter surfaces.


Influence of glutamine on the growth of human glioma and medulloblastoma in culture.
Cellular supply of glutamine, an essential substrate for growth, is derived from extracellular fluid and de novo synthesis. We investigated the relative importance of these sources to the growth of six human anaplastic glioma- and one human medulloblastoma-derived permanent cell lines. Exogenous glutamine was limiting for the proliferation of glioma-derived lines D-54 MG, U-118 MG, and U-251 MG. In contrast, medulloblastoma-derived line TE-671 and glioma-derived lines U-373 MG, D-245 MG, and D-259 MG grew in the absence of supplemental glutamine. Two cell lines with contrasting glutamine requirements, D-54 MG and TE-671, were used to explore the pharmacological interference with glutamine metabolism. DL-alpha-Aminoadipic acid, a reported glutamic acid analogue with gliotoxic properties, significantly inhibited the growth of both lines. These effects were reversed by increasing glutamine, suggesting that the major action of DL-alpha-aminoadipic acid is as a glutamine antagonist. In contrast, the glutamine synthetase inhibitor delta-hydroxylysine demonstrated activity only against TE-671. Acivicin and 6-diazo-5-oxo-L-norleucine, glutamine analogues available for clinical use, reduced the proliferation of both cell lines at pharmacological concentrations. Methionine sulfoximine, a glutamine synthetase inhibitor previously used clinically, produced marked growth inhibition only against TE-671. These findings indicate that the synthesis and utilization of glutamine are potentially exploitable targets for the chemotherapy of some human gliomas and medulloblastomas.


Relationship between isotope half-life and prostatic edema for optimal prostate dose coverage in permanent seed implants.
The robustness of treatment planning to prostatic edema for three different isotopes (125I, 103Pd, and 131Cs) is explored using dynamical dose calculations on 25 different clinical prostate cases. The treatment plans were made using the inverse planning by simulated annealing (IPSA) algorithm. The prescription was 144, 127, and 125 Gy for 125I, 131Cs, and 103Pd, respectively. For each isotope, three dose distribution schemes were used to impose different protection levels to the urethra: V120 = 0%, V150 = 0%, and V150 = 30%. Eleven initial edema values were considered ranging from 1.0 (no edema) to 2.0 (100%). The edema was assumed to resolve exponentially with time. The prostate volume, seed positions, and seed activity were dynamically tracked to produce the final dose distribution. Edema decay half-lives of 10, 30, and 50 days were used. A total of 675 dynamical calculations were performed for each initial edema value. For the 125I isotope, limiting the urethra V120 to 0% leads to a prostate D90 under 140 Gy for initial edema values above 1.5. Planning with urethra V150 at 0% provides a good response to the edema; the prostate D90 remains higher than 140 Gy for edema values up to 1.8 and a half-life of 30 days or less. For 103Pd, the prostate D90 is under 97% of the prescription dose for approximately 66%, 40%, and 30% of edema values for urethra V120 = 0%, V150 = 0%, and V150 = 30%, respectively. Similar behavior is seen for 131Cs and the center of the prostate becomes "cold" for almost all edema scenarios. The magnitude of the edema following prostate brachytherapy, as well as the half-life of the isotope used and that of the edema resorption, all have important impacts on the dose distribution. The 125I isotope with its longer half-life is more robust to prostatic edema. Setting up good planning objectives can provide an adequate compromise between organ doses and robustness. This is even more important since seed misplacements will contribute to further degrade dose coverage.


The precision and comparative sensitivity of interferon assays.
Any interferon assay essentially measures the potency of unknown samples relative to each other or to a standard. The reliability of such measurements of relative potency, i.e. the precision of the assay, is a key feature of any method. In contrast, sensitivity is seldom a characteristic of great importance in an assay. Nevertheless, relatively high sensitivity can often be achieved quite readily by a suitable choice of cells and challenge virus.


Brain-dependent movements and cerebral-spinal connections: key targets of cellular and behavioral enrichment in CNS injury models.
One of the most difficult problems in experimental and clinical neurology is how to facilitate recovery of the ability to walk voluntarily. Local spinal mechanisms, descending input from the brain, and ascending sensory feedback to the brain are required for non-treadmill, self-initiated stepping. In evaluating the integrity of axons connecting the brain and spinal cord in neural injury models, the selection of behavioral tests may be at least as important as the histological procedures, if not more so. A comprehensive and clinically meaningful test battery should include assessments of brain-dependent movement capacity. Behavioral enrichment procedures that prominently encourage self-initiation of stepping have been used to facilitate plasticity and motor function after brain or spinal cord injury. Progressive degeneration characteristic of parkinsonian models can be slowed or halted altogether by forced exercise and limb use. Behavioral interventions may work partly because the animal adopts alternative behavioral strategies to compensate for impaired performance. However, mounting evidence suggests that motor rehabilitation can also promote restoration of function or prevent slow degeneration of tissue by engaging constitutively available mechanisms that protect, repair, rewire, or reactivate cells.


Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype.
Immune responses induced by currently licensed inactivated influenza vaccines are mainly directed against the hemagglutinin (HA) glycoprotein, the immunodominant antigen of influenza viruses. The resulting antigenic drift of HA requires frequent updating of the vaccine composition and annual revaccination. On the other hand, the levels of antibodies directed against the neuraminidase (NA) glycoprotein, the second major influenza virus antigen, vary greatly. To investigate the potential of the more conserved NA protein for the induction of subtype-specific protection, vesicular stomatitis virus-based replicons expressing a panel of N1 proteins from prototypic seasonal and pandemic H1N1 strains and human H5N1 and H7N9 isolates were generated. Immunization of mice and ferrets with the replicon carrying the matched N1 protein resulted in robust humoral and cellular immune responses and protected against challenge with the homologous influenza virus with an efficacy similar to that of the matched HA protein, illustrating the potential of the NA protein as a vaccine antigen. The extent of protection after immunization with mismatched N1 proteins correlated with the level of cross-reactive neuraminidase-inhibiting antibody titers. Passive serum transfer experiments in mice confirmed that these functional antibodies determine subtype-specific cross-protection. Our findings illustrate the potential of NA-specific immunity for achieving broader protection against antigenic drift variants or newly emerging viruses carrying the same NA but a different HA subtype.IMPORTANCE Despite the availability of vaccines, annual influenza virus epidemics cause 250,000 to 500,000 deaths worldwide. Currently licensed inactivated vaccines, which are standardized for the amount of the hemagglutinin (HA) antigen, primarily induce strain-specific antibodies, whereas the immune response to the neuraminidase (NA) antigen, which is also present on the viral surface, is usually low. Using NA-expressing single-cycle vesicular stomatitis virus replicons, we show that the NA antigen conferred protection of mice and ferrets against not only the matched influenza virus strains but also viruses carrying NA proteins from other strains of the same subtype. The extent of protection correlated with the level of cross-reactive NA-inhibiting antibodies. This highlights the potential of the NA antigen for the development of more broadly protective influenza vaccines. Such vaccines may also provide partial protection against newly emerging strains with the same NA but a different HA subtype.


Characterization of placental cholinesterases and activity induction associated to environmental organophosphate exposure.
Although non-innervated, the placenta contains both cholinesterases (ChEs), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). These enzymes are well-known for their multiple molecular forms. In a first approach, we used recognized specific inhibitors, substrate preferences and non-denaturating gel electrophoresis in order to characterize the ChE profile of term placenta from uncomplicated pregnancy. Results strongly suggest that the predominant cholinesterasic form present was tetrameric BChE. It is well established that both ChEs are targets of cholinesterase-inhibiting organophosphates (OP), one of the most important classes of chemicals actively applied to the environment. However, we have previously reported increased ChEs activity in placenta of rural residents exposed to OP. In the present work, we have studied: 1) whether this finding was reproducible and, 2) whether AChE or BChE up regulation is behind the increase of placental ChE activity. The population studied included forty healthy women who live in an agricultural area. Samples were collected during both the OP pulverization period (PP) and the recess period (RP). The placental ChEs activity increased in PP, evidencing reproducibility of previous results. The analysis of non-denaturating gels revealed that increased activity of total ChE activity in placenta from women exposed to OP may be attributable to tetrameric BChE up-regulation.


Expectations of recovery from revision knee replacement.
To evaluate outcome expectations of patients undergoing revision total knee replacement (TKR) and to examine personal factors, patient functioning, previous experiences with knee replacement surgery, concerns about surgery, and general health as predictors of expectations. Revision TKR patients (n = 184, 54% women; mean age 69 years) completed a questionnaire up to 2 weeks before surgery. This included demographics, experience with previous knee surgery, concerns about surgery, the Life Orientation Test (LOT), the Arthritis Helplessness Scale, the Western Ontario and McMaster Universities Osteoarthritis Index, and a rating of overall health. Outcome expectations were evaluated as 5 questions assessing global benefit; relief of pain; ease of disability; expectations of having complications; and whether the person expected to be fully recovered from surgery in <6 months, 6-12 months, >12 months, or did not expect to recover. Predictors of each of the 5 outcome expectations were evaluated using univariable and multivariable regression analyses. Expectations are a multidimensional construct (Cronbach's alpha = 0.63). Expectation of global benefit of surgery was high, but was lower for benefits related to ease of pain and improved function. Concerns about surgery were a consistent predictor of all expectation outcomes in multivariable modeling. When concerns about surgery and general health were entered into the model as an interaction with expectation of recovery time as the outcome, past experience (P = 0.05), pain (P = 0.03), LOT (P = 0.03), and interaction between concerns about surgery and general health were significant predictors. Clinicians need to understand and help patients shape appropriate expectations for recovery from revision TKR.


Analysis of the Errors in the Electrostatically Embedded Many-Body Expansion of the Energy and the Correlation Energy for Zn and Cd Coordination Complexes with Five and Six Ligands and Use of the Analysis to Develop a Generally Successful Fragmentation Strategy.
In the present paper, we apply the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE) to the calculation of zinc-ligand and cadmium-ligand bond dissociation energies, and we analyze the errors due to various fragmentation schemes in a variety of neutral, positively charged, and negatively charged Zn2+ and Cd2+ coordination complexes. As a result of the analysis, we are able to present a new, simple, and unambiguous fragmentation strategy. Following this strategy, we show that both methods perform well for zinc-ligand and cadmium-ligand bond dissociation energies for all systems studied in the paper, including a model of the catalytic site of the zinc-bearing anthrax toxin lethal factor (LF), which has garnered substantial attention as a target for drug development. To draw general conclusions we consider ten pentacoordinate and hexacoordinate zinc and cadmium containing coordination complexes, each with 10 or 15 different fragmentation schemes. By analyzing errors, we developed a prescription for the optimal fragmentation strategy. With this scheme, and using MP2 correlation energies as a test, we find that the electrostatically embedded three-body expansion of the correlation energy (EE-3B-CE) method is able to reproduce all 53 conventionally calculated bond energies with an average absolute error of only 0.59 kcal/mol. The paper also presents EE-MB-CE calculations using the CCSD(T) level of theory on an LF model system. With CCSD(T), EE-3B-CE has an average error of 0.30 kcal/mol.


Face value: testing the utility of contextual face cues for face recognition.
The presence of multiple faces during a crime may provide a naturally-occurring contextual cue to support eyewitness recognition for those faces later. Across two experiments, we sought to investigate mechanisms underlying previously-reported cued recognition effects, and to determine whether such effects extended to encoding conditions involving more than two faces. Participants studied sets of individual faces, pairs of faces, or groups of four faces. At test, participants in the single-face condition were tested only on those individual faces without cues. Participants in the two and four-face conditions were tested using no cues, correct cues (a face previously studied with the target test face), or incorrect cues (a never-before-seen face). In Experiment 2, associative encoding was promoted by a rating task. Neither hit rates nor false-alarm rates were significantly affected by cue type or face encoding condition in Experiment 1, but cuing of any kind (correct or incorrect) in Experiment 2 appeared to provide a protective buffer to reduce false-alarm rates through a less liberal response bias. Results provide some evidence that cued recognition techniques could be useful to reduce false recognition, but only when associative encoding is strong.


Rentran. An on-line computer-based regional kidney transplant matching system.
An interactive on-line computerized renal transplant matching system called RENTRAN which serves the Southwest Kidney Transplant Region is described. The region consists of one transplant center in Arkansas, two in Oklahoma, and six in Texas. The computer used is the DECsystem-10 located in the Medical Computing Resources Center at Dallas. RENTRAN participants have remotely located standard interactive computer terminals and gain access to the computer by dialing over normal telephone lines. Functions provided by RENTRAN include obtaining instructions, performing a donor-recipient match, obtaining a list of potential recipients, making a user comment or adding, updating or deleting a potential recipient record. Either long or short formats for dialog with the computer system are available for inexperienced and experienced and users, respectively. In the time period from August 1,1973, when the system went into production on February 1, 1976, there have been in excess of 232 matches attempted and approximately 142 kidneys have been transplanted according to RENTRAN results. There are about 361 recipients currently on the data base. The system was developed with funds provided by the Texas Regional Medical Program. Expenses of maintaining the system as well as occasional programmed improvements as deemed appropriate by the Southwest Kidney Transplant Region Registry Committee on the basis of user comments are provided through a $25 per year charge to patients for being listed on the data base.


Bioactive Cellulose Nanocrystal-Poly(ε-Caprolactone) Nanocomposites for Bone Tissue Engineering Applications.
3D-printed bone scaffolds hold great promise for the individualized treatment of critical-size bone defects. Among the resorbable polymers available for use as 3D-printable scaffold materials, poly(ε-caprolactone) (PCL) has many benefits. However, its relatively low stiffness and lack of bioactivity limit its use in load-bearing bone scaffolds. This study tests the hypothesis that surface-oxidized cellulose nanocrystals (SO-CNCs), decorated with carboxyl groups, can act as multi-functional scaffold additives that (1) improve the mechanical properties of PCL and (2) induce biomineral formation upon PCL resorption. To this end, an in vitro biomineralization study was performed to assess the ability of SO-CNCs to induce the formation of calcium phosphate minerals. In addition, PCL nanocomposites containing different amounts of SO-CNCs (1, 2, 3, 5, and 10 wt%) were prepared using melt compounding extrusion and characterized in terms of Young's modulus, ultimate tensile strength, crystallinity, thermal transitions, and water contact angle. Neither sulfuric acid-hydrolyzed CNCs (SH-CNCs) nor SO-CNCs were toxic to MC3T3 preosteoblasts during a 24 h exposure at concentrations ranging from 0.25 to 3.0 mg/mL. SO-CNCs were more effective at inducing mineral formation than SH-CNCs in simulated body fluid (1x). An SO-CNC content of 10 wt% in the PCL matrix caused a more than 2-fold increase in Young's modulus (stiffness) and a more than 60% increase in ultimate tensile strength. The matrix glass transition and melting temperatures were not affected by the SO-CNCs but the crystallization temperature increased by about 5.5°C upon addition of 10 wt% SO-CNCs, the matrix crystallinity decreased from about 43 to about 40%, and the water contact angle decreased from 87 to 82.6°. The abilities of SO-CNCs to induce calcium phosphate mineral formation and increase the Young's modulus of PCL render them attractive for applications as multi-functional nanoscale additives in PCL-based bone scaffolds.


A Ubiquitin-Based Module Directing Protein-Protein Interactions in Chloroplasts.
A promising approach for the genetic engineering of multiprotein complexes in living cells involves designing and reconstructing the interaction between two proteins that lack native affinity. Thylakoid-embedded multiprotein complexes execute the light reaction of plant photosynthesis, but their engineering remains challenging, likely due to difficulties in accurately targeting heterologous membrane-bound proteins to various sub-compartments of thylakoids. In this study, we developed a ubiquitin-based module (Nub-Cub) capable of directing interactions in vivo between two chloroplast proteins lacking native affinities. We applied this module to genetically modify thylakoid multiprotein complexes. We demonstrated the functionality of the Nub-Cub module in the model organism Arabidopsis thaliana. Employing this system, we successfully modified the Photosystem II (PSII) complex by ectopically attaching an extrinsic subunit of PSII, PsbTn1, to CP26-a component of the antenna system of PSII. Surprisingly, this mandatory interaction between CP26 and PsbTn1 in plants impairs the efficiency of electron transport in PSII and unexpectedly results in noticeable defects in leaf development. Our study not only offers a general strategy to modify multiprotein complexes embedded in thylakoid membranes but it also sheds light on the possible interplay between two proteins without native interaction.


Identification of trans-dominant modifiers of Prat expression in Drosophila melanogaster.
The first committed step in the purine de novo synthesis pathway is performed by amidophosphoribosyltransferase (EC 188.8.131.52) or Prat. Drosophila melanogaster Prat is an essential gene with a promoter that lacks a TATA-box and initiator element and has multiple transcription start sites with a predominant start site. To study the regulation of Prat expression in the adult eye, we used the Prat:bw reporter gene, in which the Prat coding region was replaced with the brown (bw) coding region. The pale-orange eye color of a single copy of Prat:bw prompted us to use a multicopy array of Prat:bw that was derived using P transposase mutagenesis and produces a darker-orange eye color in a bw(D); st genetic background. We used a 13-copy array of Prat:bw as a tool to recover dominant EMS-induced mutations that affect the expression of the transgene. After screening 21,000 F(1)s for deviation from the orange eye color, we isolated 23 dominant modifiers: 21 suppressors (1 Y-linked, 5 X-linked, 4 2-linked, and 11 3-linked) and 2 enhancers (1 2-linked and 1 3-linked). Quantification of their effect on endogenous Prat gene expression, using RT-PCR in young adult fly heads, identifies a subset of modifiers that are candidates for genes involved in regulating Prat expression.


Influence of work-related factors and individual characteristics on work ability among Dutch construction workers.
The objective of this study was to evaluate the association of individual characteristics, health problems, lifestyle factors, and work-related factors with work ability among Dutch construction workers. In this cross-sectional survey, the study population consisted of 19 507 Dutch construction workers who had participated in a voluntary periodic medical examination in 2005 and for whom complete information on laboratory tests and spirometry was available. The main outcome of the study was work ability, measured by the work ability index. Independent variables consisted of physical and psychosocial work-related factors, individual characteristics, lifestyle factors, and some objective health indicators. Multiple linear and logistic regression models were used to determine the influence of different factors on work ability. Physical workload and, to a less extent, psychosocial factors at work together explained 22% of the variability in work ability. Age, leisure-time physical activity, lung obstruction, and cardiovascular risk profile explained about 10% of the workers' ability to work, but, when adjusted for work-related risk factors, their effects became very small. Awkward back posture, static work postures, repetitive movements, and lack of support at work had the highest influence on work ability. In the construction industry, work-related risk factors were the most important in association with work ability. This finding suggests that interventions aimed at preventing construction workers from dropping out of the workforce should primarily focus on reducing physical and psychosocial load at work.