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Boron (specifically 10B) is the element of choice to shield thermal neutrons due to its large (n, α) cross‐section; however, very few polymer composites containing high boron concentrations are available. This study aimed to determine the maximum possible amount of boron that could be introduced into a polymer matrix. Diverse manufacturing techniques, ranging from additive manufacturing to compression molding, were employed to fabricate inks and filaments for 3D printing, foams, and flexible pads. Composites using siloxanes, poly(lactic acid), and acrylonitrile butadiene styrene containing up to 80 wt% boron were sucessufully fabricated. The addition of known plasticizers (polyethylene glycol) and reinforcing agents (carbon nanofibers and fumed silica) helped to overcome fabrication problems such as clogging of the printing nozzle or crumbling of compression molded parts. In addition, the thermal‐mechanical properties of these novel boron composites were determined and shown to vary according to boron concentration, presence of additives, and fabrication techniques utilized. [ABSTRACT FROM AUTHOR]

Von Hippel–Lindau disease (VHL) is a multineoplasm inherited disease manifesting with hemangioblastoma of the central nervous system and retina, adrenal pheochromocytoma, renal cell carcinoma, pancreatic neuroendocrine tumors and cysts, and neoplasms/cysts of the ear, broad ligament, and testicles. During 2018‐2020, the VHL Alliance gathered several committees of experts in the various clinical manifestations of VHL to review the literature, gather the available evidence on VHL, and develop recommendations for patient management. The current report details the results of the discussion of a group of experts in the pancreatic manifestations of VHL along with their proposed recommendations for the clinical surveillance and management of patients with VHL. The recommendations subcommittee performed a comprehensive systematic review of the literature and conducted panel discussions to reach the current recommendations. The level of evidence was defined according to the Shekelle variation of the Grading of Recommendations, Assessment, Development, and Evaluation grading system. The National Comprehensive Cancer Network Categories of Evidence and Consensus defined the committee members' interpretation of the evidence and degree of consensus. The recommendations encompass the main aspects of VHL‐related pancreatic manifestations and their clinical management. They are presented in a clinical orientation, including general planning of screening and surveillance for pancreatic neuroendocrine tumors, utility of biochemical biomarkers, the optimal choice for imaging modality, indirect risk stratification, indications for tissue sampling of VHL‐related pancreatic neuroendocrine tumors, and interventions. These recommendations are designed to serve as the reference for all aspects of the screening, surveillance, and management of VHL‐related pancreatic manifestations. Pancreatic neuroendocrine tumors that develop in the context of von Hippel–Lindau (VHL) disease have a distinct natural history. Other VHL manifestations complicate metastatic risk and their management. An international committee of experts in VHL‐related pancreatic neuroendocrine tumors has developed a set of recommendations for the management of these unique neoplasms to set a standard of care for expert centers worldwide. [ABSTRACT FROM AUTHOR]

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence. [ABSTRACT FROM AUTHOR]

Background: The only potential cure for neuroendocrine tumors (NETs) is operative resection, which may also offer a survival benefit for advanced disease. We aimed to assess the role of 68Ga-DOTATATE PET/CT in preoperative planning and compared its performance to CT with IV contrast and MRI with Eovist®, for abdominal NETs. Methods: Records of patients who underwent 68Ga-DOTATATE PET/CT in addition to MRI with Eovist® and/or CT with IV contrast were retrospectively evaluated. The effect of imaging findings on surgical management and characteristics of detected lesions were analyzed. Descriptive statistics were used. Results: Of 21 patients who underwent 68Ga-DOTATATE PET/CT prior to surgical resection, five (24%) had a change in surgical management due to findings. In three patients, 68Ga-DOTATATE PET/CT identified the primary tumor. In two patients, 68Ga-DOTATATE PET/CT helped clarify equivocal hepatic lesions seen on MRI with Eovist®. MRI with Eovist® had the highest number of lesions found (median 13, versus 9 on CT and 9.5 on 68Ga-DOTATATE PET/CT). DOTATATE-avid lesions were on average larger than lesions seen only on MRI with Eovist® (1.6 cm versus 0.6 cm, p = 0.0002). The optimal cutoff point for detection by 68Ga-DOTATATE PET/CT was a size of 0.95 cm, with a sensitivity of 56% and specificity of 98%. Conclusions: Preoperative 68Ga-DOTATATE PET/CT is useful only in a subset of patients undergoing surgical resection for NETs. MRI with Eovist® is superior at identifying liver metastases when compared to 68Ga-DOTATATE PET/CT and should therefore be used routinely before hepatic cytoreduction of NETs. [ABSTRACT FROM AUTHOR]

Malignant tumours show a marked degree of morphological, molecular and proteomic heterogeneity. This variability is closely related to microenvironmental factors and the location of the tumour. The activation of genetic alterations is very tissue‐dependent and only few tumours have distinct genetic alterations. Importantly, the activation state of proteins and signaling factors is heterogeneous in the primary tumour and in metastases and recurrences. The molecular diagnosis based only on genetic alterations can lead to treatments with unpredictable responses, depending on the tumour location, such as the tumour response in melanomas versus colon carcinomas with BRAF mutations. Therefore, we understand that the correct evaluation of tumours requires a system that integrates both morphological, molecular and protein information in a clinical and pathological context, where intratumoral heterogeneity can be assessed. Thus, we propose the term 'tissunomics', where the diagnosis will be contextualised in each tumour based on the complementation of the pathological, molecular, protein expression, environmental cells and clinical data. [ABSTRACT FROM AUTHOR]

Background: Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome-wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs.Methods: Thirty-three tissue samples were analyzed: they included samples from sporadic (n = 9), von Hippel-Lindau (VHL)-related (n = 10), and multiple endocrine neoplasia type 1 (MEN1)-related NFPanNETs (n = 10) as well as normal islet cells (n = 4) for comparison. Genome-wide CpG methylation profiling was performed with the Infinium MethylationEPIC BeadChip assay and was analyzed with R-based tools.Results: In unsupervised hierarchical clustering, sporadic and MEN1-related NFPanNETs clustered together, and the VHL group was in a separate cluster. MEN1-related NFPanNETs had a higher rate of hypermethylated CpG sites in comparison with sporadic and VHL-related tumor groups. Differentially methylated region analysis confirmed the higher rate of hypermethylation in MEN1-related tumors. Moreover, in an integrated analysis of gene expression data for the same tumor samples, downregulated gene expression was found in most genes that were hypermethylated. In a CpG island methylator phenotype analysis, 3 genes were identified and confirmed to have downregulated gene expression: secreted frizzle-related protein 5 (SFRP5) in sporadic NFPanNETs and cell division cycle-associated 7-like (CDCA7L) and RNA binding motif 47 (RBM47) in MEN1-related NFPanNETs.Conclusions: MEN1 NFPanNETs have a higher rate of geno me-wide hypermethylation than other NFPanNET subtypes. The similarity between the pathways enriched in a methylation analysis of known genes involved in NFPanNET tumorigenesis suggests a key role for aberrant methylation in the pathogenesis of NFPanNETs. [ABSTRACT FROM AUTHOR]

Summary: Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime®, yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post‐therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR‐2, FcγRII, HLA‐DR, CD86, IFN‐γR, TNF, IL‐12, NO, and an increase in FcγRIII and IL‐10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL‐10R and increasing IFN‐γR, IL‐12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL‐10 and TGF‐β modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re‐established the production of IL‐12, IL‐10, TGF‐β and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL‐10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL‐10 as robust predictive biomarkers for post‐therapeutic cicatrization during cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.Methods: Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed by real-time polymerase chain reaction analysis and immunohistochemistry. Gene expression profiles were analyzed by tumor genotype, and pathway analysis was curated.Results: Consensus clustering of mRNA expression revealed separate clustering of NICs, VHL-associated NFPanNETs, and MEN1-associated NFPanNETs; whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs. Among many genes, platelet-derived growth factor receptor β (PDGFRB), lymphoid enhancer-binding factor-1 (Lef-1), cyclin-dependent kinase 4 (CDK4), and CDK6 were upregulated in VHL or MEN1 NFPanNETs, providing potential subtype-specific treatment targets.Conclusions: Distinct mRNA expression patterns were identified in sporadic-associated, VHL-associated, and MEN1-associated NFPanNETs. The current results uncover new pathways involved in NFPanNETs that are subtype-specific and provide potential new diagnostic or therapeutic targets based on tumor subtype. Cancer 2018;124:636-47. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

During the last glaciation, most of the British Isles and the surrounding continental shelf were covered by the British-Irish Ice Sheet ( BIIS). An earlier compilation from the existing literature ( BRITICE version 1) assembled the relevant glacial geomorphological evidence into a freely available GIS geodatabase and map (Clark et al. 2004: Boreas 33, 359). New high-resolution digital elevation models, of the land and seabed, have become available casting the glacial landform record of the British Isles in a new light and highlighting the shortcomings of the V.1 BRITICE compilation. Here we present a wholesale revision of the evidence, onshore and offshore, to produce BRITICE version 2, which now also includes Ireland. All published geomorphological evidence pertinent to the behaviour of the ice sheet is included, up to the census date of December 2015. The revised GIS database contains over 170 000 geospatially referenced and attributed elements - an eightfold increase in information from the previous version. The compiled data include: drumlins, ribbed moraine, crag-and-tails, mega-scale glacial lineations, glacially streamlined bedrock (grooves, roches moutonnées, whalebacks), glacial erratics, eskers, meltwater channels (subglacial, lateral, proglacial and tunnel valleys), moraines, trimlines, cirques, trough-mouth fans and evidence defining ice-dammed lakes. The increased volume of features necessitates different map/database products with varying levels of data generalization, namely: (i) an unfiltered GIS database containing all mapping; (ii) a filtered GIS database, resolving data conflicts and with edits to improve geo-locational accuracy (available as GIS data and PDF maps); and (iii) a cartographically generalized map to provide an overview of the distribution and types of features at the ice-sheet scale that can be printed at A0 paper size at a 1:1 250 000 scale. All GIS data, the maps (as PDFs) and a bibliography of all published sources are available for download from: . [ABSTRACT FROM AUTHOR]

This work illustrates the practicality of investigating sinkholes integrating data gathered by ground penetrating radar (GPR), electrical resistivity imaging (ERI) and trenching or direct logging of the subsidence-affected sediments in combination with retrodeformation analysis. This mutidisciplinary approach has been tested in a large paleosinkhole developed during the deposition of a Quaternary terrace on salt-bearing evaporites. The subsidence structure, exposed in an artificial excavation, is located next to Puilatos, a village that was abandoned in the 1970s due to severe subsidence damage. Detailed logging of the exposure revealed that the subsidence structure corresponds to an asymmetric sagging and collapse paleosinkhole with no clear evidence of recent activity. The sedimentological and structural relationships together with the retrodeformation analysis indicate that synsedimentary subsidence controlled channel location, the development of a palustrine environment and local changes in the channel pattern. GPR profiles were acquired using an array of systems with different antenna frequencies, including some recently developed shielded antennas with improved vertical resolution and penetration depth. Although radargrams imaged the faulted sagging structure and provided valuable data on fault throw, they did not satisfactorily image the complex architecture of the fluvial deposit. ERI showed lower resolution but higher penetration depth when compared to GPR, roughly capturing the subsidence structure and yielding information on the thickness of the high-resistivity alluvium and the nature of the underlying low-resistivity karstic residue developed on top of the halite-bearing evaporitic bedrock. Data comparison allows the assessment of the advantages and limitations of these complementary techniques, highly useful for site-specific sinkhole risk management. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lakes developed in the inner depressions of tufa mounds are rare geomorphic features and still poorly understood. Sedimentation in this unusual type of endorheic lake with a very restricted catchment area is highly sensitive to environmental and hydrological changes. The Isona tufa mound complex, north-eastern Iberian Peninsula, is associated with the discharge zone of a confined artesian aquifer and comprises 11 tufa mounds consisting of an annular rimstone enclosing a central depression filled with lake deposits. Data gathered from trenches excavated in four palaeolakes located within three different morphostratigraphic units permitted a precise analysis of the geometrical characteristics and stratigraphic relationships of the deposits and provided a sedimentation model for the Late Quaternary infilling of the spring-fed lakes. The work illustrates that trenches allow a precise characterization of the stratigraphic arrangements, lateral facies changes and deformation structures, which are not apparent in studies relying solely on borehole records, and facilitate sampling for dating and geochemical analyses. The five sedimentary facies described represent different evolutionary stages of the lakes, including: (i) carbonate-rich palustrine deposits probably related to periods with strong hydrological seasonality; (ii) massive highly bioturbated organic ooze; (iii) banded organic carbonate-rich facies associated with an increase in the regional effective moisture; (iv) fine-grained quartz-rich aeolian/slope-wash sediments; and (v) colluvial facies deposited following the desiccation of the lakes located at higher altitudes. Geochemical and sedimentological analyses of the lacustrine sequences provided information on the palaeohydrological evolution of the Isona tufa mound complex and the palaeoenvironmental conditions of the area over the last 28 ka. Radiometric dating suggests that deposition occurred simultaneously at ca 22 ka in palaeolakes situated at different elevations. A drop in the piezometric level prompted by the opening of springs at lower altitudes probably caused the deactivation of the upper springs and the desiccation of the lakes. Arid conditions prevailed in the area during the Late Glacial and the early Holocene (28·0 to 8·5 ka bp). More humid conditions recorded from 8·5 to 4·2 ka and again since 1·7 ka are in accordance with palaeoenvironmental reconstructions available in the Western Mediterranean since the Last Glacial Maximum. [ABSTRACT FROM AUTHOR]

Objective No instrument has been developed and validated across cultures to measure the degree of support provided by informal carers to people with schizophrenia. We aimed to develop such a measure. Method The Maristán Scale of Informal Care was developed directly from the views of patients with schizophrenia in six countries. Face-to-face interviews were carried out with participants and 103 were repeated after 30 days. Principal Axis Factoring followed by Promax rotation evaluated the structure of the scale. Horn's parallel combined with bootstrapping determined the number of factors. Cronbach's alpha estimated the scale's internal consistency and intra-class correlation its test-retest reliability. Results A total of 164 interviews were undertaken, 103 with re-test. The Horn's Parallel Analysis and the analysis of the Promax rotation revealed one factor. Cronbach's alpha was 0.89. Intra-class correlation coefficient was 0.56 (95% CI 0.42-0.68) and this increased to 0.64 (95% CI 0.51-0.75) after removing two outlying values. Patients from Argentina recorded the lowest scores (poor informal support/care). Conclusion The Maristán Scale of Informal Care is a reliable instrument to assess the degree of support provided by informal carers to people with schizophrenia across cultures. A confirmatory factor analysis is needed to evaluate the stability of its factor structure. [ABSTRACT FROM AUTHOR]

ABSTRACT Talus flatirons are debris-covered relict slopes, disconnected from the source area, which are relatively common in arid and semi-arid areas. Talus flatiron sequences record the alternation of accumulation and incision phases. These chronosequences may be used for infer temporal changes in the morphogenetic processes acting on the slopes as well as information on the local paleoclimatic history. Talus flatiron sequences developed in the Tremp Depression, eastern Spanish Pyrenees, are analysed from the geomorphological, chronological and paleoenvironmental perspective. The two groups of relict slopes differentiated by means of detailed geomorphological mapping have been dated by optically stimulated luminescence (OSL) and radiocarbon dating at 25-20 kyr (S3) and 5·4-1·7 cal kyr (S2). The talus flatiron group S3 is correlated with a fluvial terrace of the Noguera Pallaresa River ( c. 23 kyr bp). The comparison of the ages obtained in the Tremp Depression with chronologies published for talus flatiron sequences in semi-arid areas and other paleoclimatic proxies suggests that the aggradation phases in the slopes occurred during periods with higher humidity and vegetation cover. The chronological differences observed between semi-arid Spain and the Tremp Depression may be partly related to the more humid climate of the latter mountain area. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article reports on the study that determines the molecular characterisation of canine calicivirus (CaCV) in faecal samples of puppies with enteritis in Brazil. The study identifies CaCV infection in specimes from dogs in South America. It suggests that CaAstVs may play a role as enteric pathogens in young dogs.

Alternative, established models for the deglaciation of the midlands of Ireland are tested against an interpretation of a suite of deglacial sediments covering an area of 600 km2 in the east central midland area. Interpretation of the sediments is based on geomorphological mapping, lithostratigraphic characterization of exposures and geotechnical data supported by electrical resistivity tomography (ERT) and ground penetrating radar (GPR). GPR depicted small-scale sedimentological and deformational structures within low-conductivity soft sediments, such as cross-bedding, planar bedding, channel-like features and faulting planes, and revealed the internal architecture of eskers, glaciodeltas, subaqueous fans and raised bogs. ERT data permitted the detection of depth to bedrock and the lithological characterization of unconsolidated sediments. The ten sites presented were surveyed by traditional mapping methods and/or geophysical techniques. This allowed the construction of a local model of the deglaciation of the area which recognized five main stages. An ice sheet covering most of Ireland withdrew as a single body as far as the midlands. At this stage, two main directions of ice retreat are identified from the spatial distribution of meltwater/overflow channels, esker and morainic ridges, and ice-marginal glaciolacustrine deposits. A pattern of deglacial sedimentation into an expanding ice-marginal glacial lake is depicted. The glacial lake was dammed to the west by two ice dome fronts, one decaying to the north-west and another to the south-west, and by the Shannon Basin watershed to the east. Glacial lake outlets identified along the watershed and the altitude of the topset/foreset interface zone depicted in glaciodeltaic deposits allowed the identification of three lake water levels. The highest level is at 87-89 m Ordnance Datum (OD), the second lake level at 84 m OD and the third at 78 m OD. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Trindade SC, Olczak T, Gomes-Filho IS, Moura-Costa LF, Cerqueira EMM, Galdino-Neto M, Alves H, Carvalho-Filho PC, Xavier MT, Meyer R. Induction of interleukin (IL)-1β, IL-10, IL-8 and immunoglobulin G by Porphyromonas gingivalis HmuY in humans. J Periodont Res 2012; 47: 27-32. © 2011 John Wiley & Sons A/S Background and Objective: Porphyromonas gingivalis, an anaerobic gram-negative bacterium, is associated with chronic periodontitis. This study was undertaken to evaluate the production of interleukin (IL)-1β, IL-8 and IL-10 by human peripheral blood mononuclear cells (PBMC) stimulated with P. gingivalis antigens and to assess the levels of serum immunoglobulin (Ig)G, IgA and IgG subclasses raised against P. gingivalis HmuY protein. Material and Methods: PBMC from patients with chronic periodontitis (CP) and from nonperiodontitis (NP) control subjects were stimulated with P. gingivalis antigens, and the cytokine levels in the culture supernatants were determined by ELISA. The specificity of serum antibodies raised against HmuY was analyzed by Western blotting and by ELISA. Results: Compared with the NP controls, the CP patients produced higher levels of total serum IgG and IgG1 specific for P. gingivalis HmuY. No differences were found between CP and NP groups in the production of IL-1β and IL-8 by PBMC stimulated with total P. gingivalis antigens. Only P. gingivalis lipopolysaccharide (LPS) induced higher levels of IL-10 in the CP group. Higher levels of IL-1β and IL-10 were induced by HmuY than by other antigens derived from the wild-type P. gingivalis strains. In contrast, total antigens derived from the hmuY-deletion mutant strain induced the production of significantly higher levels of IL-8 and significantly lower levels of IL-1β. Conclusion: Our data suggest that P. gingivalis HmuY may be considered an immunogenic protein associated with host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L.) Plus-Hybrids are a blend of cytoplasmic male-sterile (CMS) hybrids and unrelated male-fertile hybrids ensuring pollination of the whole stand. Combining potential benefits of male sterility (CMS effect) and aDopollination (xenia effect), they often outperform the corresponding male-fertile sib-pollinated hybrids in terms of yield. The combining abilities of five CMS hybrids and eight pollinators were investigated in a factorial split-plot design in 12 environments in four countries and two years. The plant material from different breeders represented the three types of male-sterile cytoplasm. Plus-Hybrids increased grain yield, on average, by 10% or more and by up to 20% in specific environments. Three highly responsive CMS hybrids and four generally good p01tinators were identified. The Plus-Hybrid effect affected both yield components, CMS leading mainly to a higher number of kernels (KN) and the xenia effect mainly to an increase in the thousand kernel weight (TKW). Despite some differences in the response of the three types of CMS, the effect of the cytoplasm was not significant. While the CMS effect depended strongly on environment, the xenia was consistent in all environments but its extent varied. As well as increasing yield, we can expect that Plus-Hybrids can make a large contribution to the coexistence of transgenic and conventional maize by biocontainment, that is, eliminating or reducing the release of transgenic pollen in Bacillus thuringiensis (Bt) maize or herbicidetolerant (HT) maize. [ABSTRACT FROM AUTHOR]

It is estimated that at least one out of three children with recurrent wheezing is atopic. Reliable diagnostic tools are needed in primary care that allow for adequate identification of these children. The purpose of this study was to assess the value of ImmunoCAP® Rapid (ICR) Wheeze-Rhinitis Child in the identification of atopy with the use of 10 selected allergens in children with recurrent episodes of wheezing. A multicenter population study is based on primary care. It included children managed consecutively at the health center, who had three or more episodes of wheezing, at least one of them in the last 12 months. Each child completed a physical examination, an epidemiological survey, one capillary blood sampling (110 μl) for ICR, and one venous blood sampling for determination of Phadiatop Infant, total IgE and 10 specific IgE measurements. The children were identified as atopic, based on their clinical signs and symptoms and at least one positive specific IgE (0.35 kUA/l or higher), before knowing the results of ICR, Phadiatop Infant and total IgE. ICR was read by two independent observers. Six classes were evaluated, negative without any color and five positive degrees of pink-red color. Two hundred and fifteen children aged between 1 and 14 years were studied (138 boys); 50.7% were identified as atopic, 39.1% were sensitized only to inhalant allergens, 6.5% to food allergens and 5.1% to both. The predominant allergen was the dust mite (39.3%). For ICR, there were 2134 valid double observations. The Kappa index, comparing the negative results vs. any positive result, was 0.91 (95% CI: 0.88–0.94). The intraclass correlation coefficient was 0.98 (95% CI: 0.98–0.99). In the identification of a child as atopic, the positive post-test probability of ICR depended on the color degrees considered: 88.4% for any positive and 97.6% for the most intense tones. The positive post-test probability of Phadiatop Infant and total IgE was 95.6% and 68.2% respectively. ICR showed good reliability for the most prevalent allergen, the dust mite, with a sensitivity of 90.5% (95% CI: 82.1–95.8) and specificity of 88.5% (95% CI: 81.7–93.4). The analysis of the other allergens was limited by the small number of sensitized children. The analysis of receiver operating characteristic curves revealed an area under the curve of 0.84 (95% CI 0.80–0.88) for the cut-off point of specific IgE of 0.35 kUA/l and of 0.94(CI 0.91–0.97) for 2 kUA/l. A greater intensity of color of the lines of ICR was related to higher levels of specific IgE in blood. ICR is a reliable test for the identification of atopy in children, which identifies most children as atopic, and shows a good correlation in allergen-by-allergen identification. This suggests that it should be regarded as a first-rate tool, in the primary care clinic, for the evaluation of children with recurrent wheezing. [ABSTRACT FROM AUTHOR]

Because of the risk of vein collapse, the benefits of using a centrifugal pump to assist venous drainage for cardiopulmonary bypass are limited when the tips of peripheral cannulas are maintained within the vena cava. Using a mock circuit including 20 mm diameter latex tubing to mimic a vena cava, we compared the performance of 6 commercially available peripheral venous cannulas and attempted to determine potential factors influencing maximal flow drainage before vein collapse. A close correlation was observed with the total hole area of the cannula. Best performance (5.10 ± 0.08 L/min) was obtained with an 8 mm internal diameter (ID) cannula and 343 mm[sup 2] total hole area. A larger cannula (ID 9.2 mm) with only 209 mm[sup 2] total hole area drained 5.03 ± 0.05 L/min whereas a smaller cannula (ID 6.7 mm) with a total hole area of 586 mm[sup 2] also allowed a similar flow of 5.03 ± 0.12 L/min. Therefore, the total hole area appears to be a critical factor in designing peripheral cannulas used in restricted chambers such as vena cavae. [ABSTRACT FROM AUTHOR]

Investigations of mitochondrial oxidative phosphorylation have been mainly carried out in isolated mitochondria, where the experimental conditions can be precisely set. However, in intact living systems oxidative phosphorylation takes place in a complex environment, whose experimental dissection is a major challenge. It has long been recognized that the efficiency of oxidative phosphorylation depends on the nature of the respiratory substrates, which feed electrons to the respiratory chain at different levels. Yet, the role of substrates in determining mitochondrial function and their response to energetic stress has been largely overlooked. Here we review recent work showing that the nature of the energetic substrates profoundly affects the mitochondrial responses to manipulations of pathophysiological relevance, such as uncoupling and opening of the permeability transition pore (PTP). Uncoupling of intact hepatocytes caused very different metabolic effects depending on whether carbohydrates or lipids were the energy source. With dihydroxyacetone as the substrate dinitrophenol caused a collapse of the mitochondrial membrane potential and of the ATP/ADP ratio, while the respiratory rate was increased only transiently. With octanoate as the substrate, on the other hand, dinitrophenol caused a dramatic stimulation of the respiratory rate, while the mitochondrial membrane potential and ATP/ADP ratio were affected only marginally. We then review results indicating that the activity of complex I directly regulates the PTP, a finding that emphasizes the importance of the respiratory substrates in PTP regulation. [ABSTRACT FROM AUTHOR]

Abstract: The thrombogenicity of membrane oxygenators as well as clotting parameters profiles, using standard human clotting tests, was analyzed in calves and pigs during 6 h perfusion. Three calves and 3 pigs were connected to extracorporeal circulation with standard heparinization. Blood samples were taken for coagulation variables throughout perfusion, and oxygenators were examined for clot deposits at the end of the experiment. Two out of 3 oxygenators of the calf group presented clot deposits while none in the pig group did. Baseline coagulation variables of pigs showed values similar to those of humans while neither extrinsic nor intrinsic pathways could be activated in calves with standard human coagulation tests. The calf model, in conclusion, was confirmed to be a difficult model for the testing of extracorporeal circulation device resistance to thrombus formation, which is, however, not reflected by standard human coagulation tests. The pig model is a better model in which both coagulation pathways could be activated with standard human coagulation tests. [ABSTRACT FROM AUTHOR]

Abstract: The AB-180 is a new implantable centrifugal pump with a low volume dome (10 ml) and a local heparin delivery system which avoids systemic heparinization. This study focuses on its hemodynamic performance. We analyzed 3 anesthetized calves (71.0 ± 2.5 kg), equipped with arterial pressure (AP), and Swan-Ganz and left atrial pressure (LAP) catheters. The AB-180 pump was installed through a left thoracotomy, with a transmitral left ventricular (LV) inflow cannula inserted via the left appendage and an outflow tract sutured to the descending aorta. LAP, AP, and blood flow across the pump were recorded for various pump speed and in different preload conditions (right atrial pressure = 4, 7, and 10 mm Hg, respectively). The pump significantly unloaded the left heart cavities and was able to increase the mean AP. For an RAP of 10 mm Hg, running the pump at 4,500 rpm decreased the LAP from 11.0 ± 0.8 mm Hg to 3.0 ± 0.8 mm Hg (p < 0.001) and augmented the mean AP from 48.2 ± 6.4 mm Hg to 80.8 ± 12.1 mm Hg (p < 0.001). A maximal pump flow of 5.6 ± 0.2 L/min was obtained under these conditions. In addition to the advantage of its particular design, the AB-180 can be considered as an efficient left ventricular assist device (LVAD). It significantly unloads the left heart cavities and ensures efficient systemic AP and blood flow. [ABSTRACT FROM AUTHOR]

In a calf model, 3 standard and 3 heparin coated intraaortic balloons (IAB) were inserted and left deflated in the descending aorta during 20 min to simulate balloon rupture. At the end of the experiment, the IAB were examined, and 3 samples of each were collected for scanning electron microscopy (SEM) analysis. None of the heparin coated IAB showed any sign of clot or deposit whereas all 3 standard IAB exhibited clots. SEM revealed no deposit on the heparin coated samples while 8 of the 9 standard samples disclosed deposits (p < 0.001). Morphometrically, 16.1 ± 21.4% of the surfaces of the standard samples were covered with deposits whereas all the heparin coated samples were free (p = 0.004). The presence of clots on every standard IAB supports the hypothesis that other than local factors of the insertion site can play a role in the vascular complications of IAB. The absence of clots and deposits on the heparin coated IAB suggests a promising role of such devices in circumventing the tendency of clot formation on deflated balloons while avoiding the drawback of systemic anticoagulation. [ABSTRACT FROM AUTHOR]

With advances in heart transplantation, a growing number of recipients are at risk of developing gastrointestinal disease. We reviewed our experience with gastrointestinal disease in 92 patients undergoing 93 heart transplants. All had follow-up, with the median time 4.8 years (range 0.5–9.6 years). During the period of the study we progressively adopted a policy of low immunosuppression aiming toward monotherapy with cyclosporine. Nineteen patients (20.6%) developed 28 diseases related to the gastrointestinal tract. Thirteen patients required 18 surgical interventions, five as emergencies: closure of a duodenal ulcer, five cholecystectomies (one with biliary tract drainage), a sigmoid resection for a diverticulitis with a colovesical fistula, a colostomy followed by a colostomy takedown for an iatrogenic colon perforation, appendectomy, two anorectal procedures, and six abdominal wall herniorrhaphies. At the onset of gastrointestinal disease, 8 patients were on standard triple-drug immunosuppression, all of them within 6 months of transplantation; 13 were on double-drug immunosuppression; and 7 were on cyclosporine alone. All the patients with perforations/fistulas were on steroids. Among the 11 infectious or potentially infectious diseases, 10 were on triple- or double-drug immunosuppression. One death, a patient who was on triple-drug immunosuppression, had a postmortem diagnosis of necrotic and hemorrhagic pancreatitis. Except for an incisional hernia following a laparoscopic cholecystectomy, there was no morbidity and, importantly, no septic complications. We concluded that a low immunosuppression policy is likely to be responsible for the low morbidity and mortality of posttransplant gastrointestinal disease, with a lower incidence of viscous perforation/fistula and infectious gastrointestinal disease. [ABSTRACT FROM AUTHOR]

Previously, we have shown in experiments with isolated mitochondria that almitrine, a drug used for patients with chronic lung disease, affects the H/ATP stoichiometry of the F0F1-ATPase (Rigoulet, M., Fraisse, L., Ouhabi, R., Guérin, B., Fontaine, E. & Leverve, X. M. (1990) Biochim. Biophys. Acta 1018, 91-97]. In the present study, we have investigated the effect of almitrine on gluconeogenesis and oxygen consumption in isolated hepatocytes. Almitrine decreased both the cytosolic and mitochondrial ATP/ADP ratios but had no effect on oxygen consumption in cells incubated with and without octanoate. This must have been due to a double effect. On the one hand, a decrease in the ATP/ADP ratio decreases ATP utilization: on the other hand, in the presence of almitrine more oxygen is required to synthesize ATP. Almitrine did affect gluconeogenesis from various substrates (lactate + pyruvate, glycerone or fructose), but had no effect on glycerol or glutamine metabolism. The effect on gluconeogenesis from glycerone was due to an increase in glycolytic flux. The rate of lactate + pyruvate production increased whereas there was no effect on glycerone utilization. This effect was caused by an activation of pyruvate kinase. Our data indicate that this enzyme is an extremely sensitive sensor of the cytosolic ATP/ADP ratio decrease affects only the balance between glucose and lactate + pyruvate productions and not the phosphorylation of glycerone, the first and controlling step of this pathway. [ABSTRACT FROM AUTHOR]

The mechanisms responsible for the stimulation by phenylephrine of gluconeogenesis from dihydroxyacetone and glycerol were studied in perifused rat hepatocytes. 1. The stimulation by phenylephrine of glucose formation from dihydroxyacetone was biphasic. Transient stimulation of about 25% after 3 min was followed by a stable stimulation of about 15% 7 min later. Concomitantly there was a transient inhibition by phenylephrine of pyruvate kinase flux during the first few minutes followed by a more stable inhibition after about 10 min. The stable inhibition could quantitatively account for the stable stimulation of gluconeogenesis by the hormone when dihydroxyacetone was the gluconeogenic substrate. The effects of phenylephrine were independent of cAMP. 2. With the reduced gluconeogenic substrate, glycerol, a transient aminooxyacetate-sensitive stimulation of gluconeogenesis occurs, followed by a stable stimulation of smaller magnitude [Leverve, X. M., Groen, A. K., Verhoeven, A. J. and Tager, J. M. (1985) FEBS Lett. 181, 43-46]. This transient phase of stimulation was abolished by addition of low concentrations of pyruvate, in accordance with our previous proposal that phenylephrine transiently accelerates the mitochondrial oxidation of cytosolic NADH via the malate/aspartate shuttle. The transient stimulation of gluconeogenesis from glycerol was accompanied by a transient increase in the cytosolic/mitochondrial aspartate concentration gradient. 3. Phenylephrine caused a transient stimulation of mitochondrial aspartate efflux in two other systems dependent on the operation of the malate/aspartate shuttle, i.e. gluconeogenesis from lactate and the oxidation of ethanol. 4. It is proposed that addition of phenylephrine to hepatocytes brings about a transient increase in the mitochondrial membrane potential and hence an increased rate of transport of aspartate from the mitochondria to the cytosol. [ABSTRACT FROM AUTHOR]

Chronic treatment of rats with phenobarbital has been reported to decrease gluconeogenesis in rat hepatocytes by a 50% inhibition of phosphoenolpyruvate (P-pyruvate) carboxykinase activity [Argaud, D., Halimi, S., Catelloni, F. & Leverve, X. (1991) Biochem. J. 280, 663 -- 669]. Contrary to the current knowledge of P-pyruvate carboxykinase regulation, we failed to find a diminution of either P-pyruvate carboxykinase protein (by using a polyclonal antibody) or P-pyruvate carboxykinase mRNA, in the liver of rats treated with phenobarvital for 2 weeks. Kinetic studies of P-pyruvate carboxykinase activity, measured by either carboxylation of P-pyruvate carboxykinase specificity was confirmed by the full inhibition of the enzyme with its specific inhibitor 3-mercaptopicolinate in the micromolar range, P-Pyruvate carboxkinase, purified either by ammonium sulfate fractionation or by immunoprecipitation, exhibited a similar decrease in affinity after phenobarbital treatment. Although the molecular mass does not appear to be altered, the pH sensitivity to 3-mercaptopicolinate inhibition and the enzyme recovery after immunoprecipitation both seemed to be affected. This leads us to propose that the effect of chronic phenobarbital treatment on P-pyruvate carboxykinase activity is not the result of transcriptional regulation but is exerted at the post-translation level. [ABSTRACT FROM AUTHOR]

Examines the effect of 2,4-dinitrophenol with or without fatty acid addition on the malate-aspertate shuttle. Inhibition of the malate-aspertate shuttle by the transaminase inhibitor; Translocation of reducing equivalents into the mitochondrial matrix.

Metformin (dimethylbiguanide) has been used for more than 30 years as an antihyperglycemic agent in the treatment of diabetes mellitus, but its effect on gluconeogenesis is still controversial. In isolated hepatocytes from fasted rats, a significant inhibition of glucose production from lactate/pyruvate (10:1, mol/mol), fructose, alanine or glutamine, following metformin addition, is observed. Moreover, in hepatocytes perifused with dihydroxyacetone as the gluconeogenic substrate and treated with 0.5 mM metformin, an inhibition of the glucose flux and a simultaneous stimulation of the lactate/pyruvate flux were observed. This enhancement of lactate/pyruvate formation appears to be due to an effect on the pyruvate-kinase enzyme. A direct effect of metformin on pyruvate kinase cannot explain this result, since pyruvate-kinase activity was not affected by metformin at this concentration. In contrast, the addition of metformin caused a significant decrease in the cellular ATP concentration, a known allosteric inhibitor of this enzyme. This could explain the stimulation of pyruvate-kinase activity following metformin addition and thus the inhibition of gluconeogenesis. [ABSTRACT FROM AUTHOR]

It has been shown previously that the inhibition of autophagic proteolysis in liver by a physiological mixture of amino acids can be mimicked completely by addition of leucine in combination with alanine [Leverve, X. M., Caro, L. H. P., Plomp, P. J. A. M. and Meijer, A. J. (1987) FEBS Lett. 219, 455-458]. We have now further defined conditions which lead to this inhibition. Isolated rat hepatocytes were incubated in the perifusion system in which the cells can be maintained at a steady state in the presence of low amino acid concentrations. Combinations of leucine (0.5 mM) with either alanine, glutamine, asparagine or proline (2 mM) inhibited proteolysis by 40-50%. Under these conditions, both in the absence and presence of the transaminase inhibitor, aminooxyacetate, a correlation was found between the extent of inhibition of proteolysis and the sum of the total intracellular amounts of aspartate and glutamate. Inhibition of proteolysis by leucine and leucine analogues did not correlate with their ability to activate glutamate dehydrogenase. [ABSTRACT FROM AUTHOR]

Aims: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD., Design: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance., Setting and Participants: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys., Measurements: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview., Findings: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders., Conclusions: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Context: In university programmes preparing students to work with patients with mental illness, clerkship is proposed as a component that may contribute to the battle against stigma, through bringing students into contact with the patients' reality. Yet, the precise contribution of clerkship remains unclear, perhaps because of the variety of university programmes, clerkship characteristics or types of stigma explored. This is the first systematic meta-analysis of available evidence determining the precise effect size of the influence of clerkship on stigma and the potential moderators., Methods: We carried out a systematic literature review in Eric, PsycINFO, Pubmed, Scopus, UMI and Proquest dissertations, aiming to identify all the studies exploring health care students' stigma of mental illness (measured as overall stigma or as attitudes, affect and behavioural intentions) before and after a clerkship from 2000 to 2017. Twenty-two studies were included in the meta-analysis, providing data from 22 independent samples. The total sample consisted of 3161 students. The effects of programme (medicine, nursing, occupational therapy, and their combination), study design (paired-unpaired samples), publication year, sex, age and clerkship context, and inclusion of theoretical training and duration, were examined as potential moderators., Results: Our analyses yielded a highly significant medium effect size for overall stigma (Hedge's g = 0.35; p < 0.001; 95% confidence interval [CI], 0.20, 0.42), attitudes (Hedge's g = 0.308; p = 0.003; 95% CI, 0.10, 0.51) and behavioural intentions (Hedge's g = 0.247; p < 0.001; 95% CI, 0.17, 0.33), indicating a considerable change, whereas there was no significant change in the students' affect. Moderator analyses provided evidence for the distinct nature of each stigma outcome, as they were influenced by different clerkship and student characteristics such as clerkship context, theoretical training, age and sex., Conclusions: The robust effect of clerkship on students' stigma of mental illness established by the present meta-analysis highlights its role as a crucial curriculum component for experiential learning and as a necessary agent for the battle against stigma., (© 2018 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Objective: While psychotic experiences (PEs) are known to be associated with a range of mental and general medical disorders, little is known about the association between PEs and measures of disability. We aimed to investigate this question using the World Mental Health surveys., Method: Lifetime occurrences of six types of PEs were assessed along with 21 mental disorders and 14 general medical conditions. Disability was assessed with a modified version of the WHO Disability Assessment Schedule. Descriptive statistics and logistic regression models were used to investigate the association between PEs and high disability scores (top quartile) with various adjustments., Results: Respondents with PEs were more likely to have top quartile scores on global disability than respondents without PEs (19.1% vs. 7.5%; χ 2  = 190.1, P < 0.001) as well as greater likelihood of cognitive, social, and role impairment. Relationships persisted in each adjusted model. A significant dose-response relationship was also found for the PE type measures with most of these outcomes., Conclusions: Psychotic experiences are associated with disability measures with a dose-response relationship. These results are consistent with the view that PEs are associated with disability regardless of the presence of comorbid mental or general medical disorders., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The current study sought to examine the diagnostic overlap in DSM-IV and DSM-5 alcohol use disorder (AUD) and determine the clinical correlates of changing diagnostic status across the 2 classification systems., Methods: DSM-IV and DSM-5 definitions of AUD were compared using cross-national community survey data in 9 low-, middle-, and high-income countries. Participants were 31,367 respondents to surveys in the World Health Organization's World Mental Health Survey Initiative. The Composite International Diagnostic Interview, version 3.0, was used to derive DSM-IV and DSM-5 lifetime diagnoses of AUD. Clinical characteristics, also assessed in the surveys, included lifetime DSM-IV anxiety; mood and drug use disorders; lifetime suicidal ideation, plan, and attempt; general functional impairment; and psychological distress., Results: Compared with DSM-IV AUD (12.3%, SE = 0.3%), the DSM-5 definition yielded slightly lower prevalence estimates (10.8%, SE = 0.2%). Almost one-third (n = 802) of all DSM-IV abuse cases switched to subthreshold according to DSM-5 and one-quarter (n = 467) of all DSM-IV diagnostic orphans switched to mild AUD according to DSM-5. New cases of DSM-5 AUD were largely similar to those who maintained their AUD across both classifications. Similarly, new DSM-5 noncases were similar to those who were subthreshold across both classifications. The exception to this was with regard to the prevalence of any lifetime drug use disorder., Conclusions: In this large cross-national community sample, the prevalence of DSM-5 lifetime AUD was only slightly lower than the prevalence of DSM-IV lifetime AUD. Nonetheless, there was considerable diagnostic switching, with a large number of people inconsistently identified across the 2 DSM classifications., Competing Interests: Declaration of interest: The views and opinions expressed in this paper are those of the authors only and do not necessarily represent the views, official policy or position of the US. Department of Health and Human Services or any of its affiliated institutions or agencies. Dr. Glantz’s role on this paper is through his involvement as a Science Officer on U01-MH60220. He had no involvement in the other cited grants. In the past three years, Dr. Kessler has been a consultant for Hoffman-La Roche, Inc., Johnson & Johnson Wellness and Prevention, and Sonofi-Aventis Groupe. Dr. Kessler has served on advisory boards for Mensante Corporation, Johnson & Johnson Services Inc. Lake Nona Life Project, and U.S. Preventive Medicine. Dr. Kessler is a co-owner of DataStat, Inc. The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUS-Murcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia., (Copyright © 2016 by the Research Society on Alcoholism.)

Background: The feasibility and the results of the introduction of an off-pump coronary artery bypass (OPCAB) program aimed at total arterial revascularization in a multidisciplinary institution were analyzed. Uniform surgical and anesthetic protocols were established and applied throughout the study period., Methods: From March 2003--when the first OPCAB procedure of the program was performed--to July 2004, the data related to all the coronary artery bypass grafting procedures (N = 408) were prospectively recorded. The program was divided into two stages: the purpose of the first stage was to perform OPCAB in more than 90% of the patients, and that of the second stage was to proceed toward total arterial revascularization. The patients were grouped into four periods (102 patients for each period). Comparisons were performed with analysis of variance test and chi-square test where appropriate., Results: For periods 1 to 4, the number of OPCAB procedures was 65/102 (64%), 82/102 (80%), 97/102 (95%), and 99/102 (97%), respectively (p < 0.001). The number of conversions did not vary significantly throughout the study (overall: 7/408, 1.7%), neither did the number of bypass/patient (overall: 3.05 +/- 0.86). The number of arterial graft/patient was 1.03 +/- 0.64, 1.01 +/- 0.4, 1.29 +/- 0.64, and 2.56 +/- 1, respectively (p < 0.001). During the last period, 81% (253/312) of the grafts were arterial. Overall mortality was 4.6% (19/408). For the OPCAB group, mortality was 2.9% (10/343) and perioperative myocardial infarction rate was 1.5% (5/343) with no statistically significant difference between the periods., Conclusions: With predefined standardized and coordinated protocols, an OPCAB program aimed at total arterial revascularization can be implemented rapidly and safely in a multidisciplinary setting.