B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort.
Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phosphate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0+/-1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.


[Comparative effectiveness of epsilon-aminocaproic acid and contrical in preventing complement activation on immune complexes].
Experiments on formation of circulatory immune complexes followed by activation of the complement components were made on sensitized guinea-pigs after intravenous injection of human gamma-globulin as specific antigen. epsilon-Aminocaproic acid did not affect the formation of circulatory immune complexes but significantly inhibited complement activation. Contrykal did not alter the formation of the immune complexes but slightly inhibited activation of the complement components.


Graph-Time Convolutional Neural Networks: Architecture and Theoretical Analysis.
Devising and analysing learning models for spatiotemporal network data is of importance for tasks including forecasting, anomaly detection, and multi-agent coordination, among others. Graph Convolutional Neural Networks (GCNNs) are an established approach to learn from time-invariant network data. The graph convolution operation offers a principled approach to aggregate information and offers mathematical analysis by exploring tools from graph signal processing. This analysis provides insights into the equivariance properties of GCNNs; spectral behaviour of the learned filters; and the stability to graph perturbations, which arise from support perturbations or uncertainties. However, extending the convolutional learning and respective analysis to the spatiotemporal domain is challenging because spatiotemporal data have more intrinsic dependencies. Hence, a higher flexibility to capture jointly the spatial and temporal dependencies is required to learn meaningful higher-order representations. Here, we leverage product graphs to represent the spatiotemporal dependencies in the data and introduce Graph-Time Convolutional Neural Networks (GTCNNs) as a principled architecture. We also introduce a parametric product graph to learn the spatiotemporal coupling. The convolution principle further allows a similar mathematical tractability as for GCNNs. In particular, the stability result shows GTCNNs are stable to spatial perturbations. owever, there is an implicit trade-off between discriminability and robustness; i.e., the more complex the model, the less stable. Extensive numerical results on benchmark datasets corroborate our findings and show the GTCNN compares favorably with state-of-the-art solutions. We anticipate the GTCNN to be a starting point for more sophisticated models that achieve good performance but are also fundamentally grounded.


Cell loss from human, canine and guinea-pig gastric mucosa measured by DNA radioimmunoassay.
A DNA radioimmunoassay, sensitive in the range 25-1000 ng, has been developed to measure gastric mucosal cell loss. Validity of the assay was based on antibody specificity, absence of interference from gastric contents, parallel tracer displacement by dilutions of gastric and standard DNA, and crossover with colorimetric assay. With this assay, gastric DNA shedding was examined in two animal species and man. In the guinea-pig stomach, DNA loss was 20-100 micrograms/h and in the canine Pavlov pouch, 260-580 micrograms/h. In the canine Pavlov pouch stimulation of acid secretion by histamine and exposure to exogenous acid increased DNA output. In the normal human stomach DNA loss was 544 +/- 175 micrograms/h and in duodenal ulcer patients, 649 +/- 225 micrograms/h. DNA radioimmunoassay provides a sensitive and reproducible measure of cell exfoliation from the stomach and may be a useful tool for studying aspects of gastric mucosal defence.


Simulation and theory of ions at atmospherically relevant aqueous liquid-air interfaces.
Chemistry occurring at or near the surface of aqueous droplets and thin films in the atmosphere influences air quality and climate. Molecular dynamics simulations are becoming increasingly useful for gaining atomic-scale insight into the structure and reactivity of aqueous interfaces in the atmosphere. Here we review simulation studies of atmospherically relevant aqueous liquid-air interfaces, with an emphasis on ions that play important roles in the chemistry of atmospheric aerosols. In addition to surveying results from simulation studies, we discuss challenges to the refinement and experimental validation of the methodology for simulating ion adsorption to the air-water interface and recent advances in elucidating the driving forces for adsorption. We also review the recent development of a dielectric continuum theory capable of reproducing simulation and experimental data on ion behavior at aqueous interfaces.


Peroxisomes in absorptive cells of mammalian small intestine.
Huge numbers of peroxisomes are present in guinea pig duodenum, jejunum, and ileum, and in rat duodenum. The peroxisomes have been studied by light and electron microscopy, including visualization by incubation in a newly-developed alkaline 3,3' diaminobenzidine (DAB) medium. Electron micrographs of more than 3700 guinea pig peroxisomes have been studied. The diameter of most peroxisomes ranges from 0.15 micro. to 0.25 micro. They often appear in clusters, surrounded by and continuous, in numerous places, with smooth endoplasmic reticulum (ER). The ER is extremely tortuous in these regions. Serial sectioning is valuable for studying the ER-peroxisome relationships but viewing sections at different angles, tilted with a goniometer stage, is more informative. The intimate relations of the two organelles appear the same in tissue fixed in four different fixatives. The peroxisomes may be interpreted as localized dilatations of smooth ER retaining multiple membranous continuities. This interpretation is discussed in light of the turnover data on peroxisomal proteins of rat hepatocytes reported by Poole and colleagues. The very large numbers of peroxisomes in intestinal epithelium lead to speculations concerning their functional significance. They resemble the small peroxisomes described in many other cell types. Although the distinctive relationship of these peroxisomes to the ER is probably more significant than their small size, for practical purposes we propose the term "microperoxisomes" to distinguish these peroxisomes from the better-known larger peroxisomes of liver and kidney.


New Antiretroviral Agents for the Treatment of HIV Infection.
Issues, such as complexity, tolerability, and drug resistance and cross-resistance, limit the effectiveness of current antiretroviral regimens and make the continued development of newer agents important, despite the availability of 20 approved drugs for the treatment of HIV infection. Many new compounds are in development in existing classes: nucleoside and nucleotide analogue reverse transcriptase inhibitors (eg, D-d4FC and SPD754), non-nucleoside analogue reverse transcriptase inhibitors (eg, capravirine and TMC125), and protease inhibitors (eg, tipranavir and TMC114). In addition, newer classes of antiretroviral drugs, such as HIV entry inhibitors (eg, TNX-355, SCH 417690, UK-427,857, AMD 11070), that target the first step in the HIV life cycle are under development. Continued improvement in the treatment of HIV infection will result from the availability of convenient, well-tolerated, and affordable drugs with potent and durable antiretroviral activity.


Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases.
The highly conserved RNAs, microRNAs (miRNAs), are a class of small single stranded noncoding RNAs that function through translational repression of specific target mRNAs. miRNAs exhibit a wide range of involvement regulating gene expressions. miRNA expression dysregulated in cancer cells and damaged tissues from different diseases implicates a functional role of miRNAs in the disease development. More recently miRNAs have been detected in cell-free serum, and these circulating miRNAs can distinguish diseased individuals from healthy controls. The noninvasive nature of circulating miRNA collection and their sensitivity and specificity in diseases has encouraged a pursuit of miRNA biomarker research. As a result, approximately 100 circulating miRNAs have been identified as biomarkers for different diseases, and the number is growing. Here we review recently reported circulating miRNA biomarkers and discuss their values and challenges for the disease biomarkers.


47XXY and 47XXX in Scleroderma and Myositis.
We undertook this study to examine the X chromosome complement in participants with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies. The participants met classification criteria for the diseases. All participants underwent single-nucleotide polymorphism typing. We examined X and Y single-nucleotide polymorphism heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used χ2 analyses with calculation of 95% confidence intervals. Three of seventy men with SSc had 47,XXY (P = 0.0001 compared with control men). Among the 435 women with SSc, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), seven had 47,XXY (P = 0.0016), whereas among the 1783 women with PM/DM, two had 47,XXX. Of 147 men with inclusion body myositis (IBM), six had 47,XXY, and 1 of the 114 women with IBM had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared with in controls as well as the known birth rate of Klinefelter syndrome or 47,XXX. Klinefelter syndrome (47,XXY) is associated with SSc and idiopathic inflammatory myopathies, similar to other autoimmune diseases with type 1 interferon pathogenesis, namely, systemic lupus erythematosus and Sjögren syndrome.


On the coupling of protein and water dynamics in confinement: Spatially resolved molecular dynamics simulation studies.
To ascertain protein-water couplings in confinement, we exploit that molecular dynamics simulations enable full control and systematic variation of the model system as well as componentwise and spatially resolved analyses. We use an elastin-like molecule and vary the thickness of the hydration shell by producing confinements of desired shape and size. Moreover, we tune the rigidity of the confinement. The approach reveals prominent dynamical couplings at the protein-water interface in combination with strong spatial variation of both protein and water dynamics. Explicitly, changes in the mobility of the hydration shell in response to altered confinement conditions are accompanied by changes in the mobility of the protein surface, leading to a relation of respective correlation times. Moreover, with increasing distance to the protein-water interface, water dynamics speeds up and protein dynamics slow down, where, however, internal and global protein motions show quantitative differences. These findings indicate that an understanding of biological functions requires consideration of mutual dependencies of protein and water dynamics, strong mobility gradients across the protein molecule and the hydration shell, and differences between internal and tumbling motions. In addition, we observe that the effect of the confining walls is very strong but short ranged. As a consequence, protein dynamics is significantly altered under severe confinement conditions, whereas bulk-like behavior is recovered for confinement sizes larger than ∼4.3 nm, corresponding to hydration levels above ∼1.5 g/g.


Feasibility study: in vivo neutron activation for regional measurement of calcium using californium 252.
The feasibility of using a collimated 252Cf neutron source to measure regional changes in skeletal calcium was tested because in vivo regional activation of diseased bone should offer advantages over the more widely reported total-body calcium measuring techniques. Regional activation allows examination of discrete regions where the greatest changes in calcium content occur. Additionally, a simpler radiation facility is required for regional studies. Using a 5.5-mug 252Cf source, thermal neutron flux and absorbed dose were measured in a tissue-equivalent phantom. Detection efficiency of 49Ca gamma rays for conditions simulating regional activation were measured using a 29-cm-diameter X 10-cm-thickness sodium iodide detector. These in vitro measurements indicate that a collimated 252Cf source can be used for regional neutron activation of the lower spine and legs. Preliminary calculations indicate that a 1-3-mg source provides adequate count rates for statistical accuracy with a bone marrow dosage acceptable for human patients and normal subjects.


[Current developments in preventive health care].
On the occasion of the publication of the second revised edition of the Preventiegids (Prevention guide), some recent developments in preventive health care can be analysed and priorities for the near future can be formulated. Some controversies have been resolved (e.g. periconceptional use of folic acid, influenza vaccination of all elderly), a number of others still exist (e.g. postmenopausal oestrogen substitution, screening for hypertension and hypercholesterolaemia). Further health benefit can be obtained by preventive activities, albeit to a limited extent. The focus should be on correct implementation (standardisation) of existing prevention programmes plus evaluation, with improvements where possible. There will also be opportunities for new prevention programmes (e.g. use of the triple test in screening for Down syndrome). It will be possible to discontinue existing inefficient programmes (e.g. routine pregnancy ultrasonography, routine administration of iron to pregnant women.


[Evaluation of efficacy and tolerance of an antiasthmatic preparation--Ditec, consisting of low doses of disodium cromoglycate and fenoterol].
The efficacy, tolerance and, in addition, the effect of the antiasthmatic drug-Ditec, consisting of low doses disodium cromoglycate (DSCG) and fenoterol on bronchial hyperreactivity (BHR) were evaluated. The studies were carried out on a group of 22 mild asthma patients aged from 10 to 20 years. The patients took DSCG during the first four weeks and then were treated with Ditec, 4 x 2 puffs, for next four weeks. The following parameters were evaluated: symptom score, beta 2-agonist "taken on demand" consumption, spirometry, morning and evening PEF, and possible adverse effects. Decreases in the symptom score, beta 2-agonist consumption (mainly in Ditec period) and increase in PEF during the study were noted. The low doses of DSCG contained in Ditec were as effective as the 80 mg of this drug given previously. No statistically significant decrease in BHR after DSCG treatment was observed. At the end of the Ditec therapy, BHR to histamine markedly diminished. Because the last doses of Ditec were taken 2 hours before the bronchial provocation test with histamine, the increase in tolerance of histamine, mentioned above, was probably only due to the so-called acute effect of beta 2-agonist on BHR. Ditec seems to be a valuable antiasthmatic drug, especially for children and young persons. Unfortunately, our studies did not answer the additional question whether regular treatment with Ditec changes BHR.


Next generation sequencing of triple negative breast cancer to find predictors for chemotherapy response.
In triple negative breast cancers (TNBC) the initial response to chemotherapy is often favorable, but relapse and chemotherapy resistance frequently occur in advanced disease. Hence there is an urgent need for targeted treatments in this breast cancer subtype. In the current study we deep sequenced DNA of tumors prior to chemotherapy to search for predictors of response or resistance. Next generation sequencing (NGS) was performed for 1,977 genes involved in tumorigenesis. DNA from 56 pre-treatment TNBC-biopsies was sequenced, as well as matched normal DNA. Following their tumor biopsy, patients started neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. We studied associations between genetic alterations and three clinical variables: chemotherapy response, relapse-free survival and BRCA proficiency. The mutations observed were diverse and few recurrent mutations were detected. Most mutations were in TP53, TTN, and PIK3CA (55 %, 14 %, and 9 %, respectively). The mutation rates were similar between responders and non-responders (average mutation rate 9 vs 8 mutations). No recurrent mutations were associated with chemotherapy response or relapse. Interestingly, PIK3CA mutations were exclusively observed in patients proficient for BRCA1. Samples with a relapse had a higher copy number alteration rate, and amplifications of TTK and TP53BP2 were associated with a poor chemotherapy response. In this homogenous cohort of TNBCs few recurrent mutations were found. However, PIK3CA mutations were associated with BRCA proficiency, which can have clinical consequences in the near future.


Propofol Prevents the Progression of Malignant Pheochromocytoma In Vitro and In Vivo.
This study aimed to explore the efficacy of propofol to treat malignant pheochromocytoma (PCC) in vitro and in vivo. In vitro, PC12 cells were treated with different concentrations of propofol (0, 1, 5, and 10 μg/mL) for specific times followed by a MTT assay to detect cell proliferation. Transwell assays were performed to assess the function of propofol on the migration and invasion of PC12 cells, and flow cytometry to analyze cell apoptosis and cell cycle progression. Quantitative real-time polymerase chain reaction was carried out to analyze the expression level of mRNA (Bcl-2, Bax, and CyclinE). The levels of Bcl-2, Bax, CyclinE, FOXO1, FOXO3, Bim, procaspase-3, and active caspase-3 were determined by western blotting. In vivo, the effects of propofol on PCC tumor growth were detected by transplanted mouse model. Transferase dUTP nick-end labeling was performed to detect tissue cell apoptosis. The results indicated that propofol inhibited PC12 cell proliferation, prevented cell migration and invasion, and induced the apoptosis of PC12 cells in a dose- and time-dependent manner. Propofol treatment increased the expression of Bax and decreased that of Bcl-2. In addition, propofol significantly induced the G1/S phase arrest in PC12 cells, and the expression of Cyclin E was reduced. Moreover, the levels of FOXO1, FOXO3, Bim, procaspase-3, and active caspase-3 were enhanced by propofol treatment. In vivo, propofol treatment significantly reduced the PCC tumor growth and induced tissue cell apoptosis. In conclusion, propofol has potent anti-PCC activity in vitro and in vivo, and is a potential small-molecule drug for treating malignant PCC.


The Role of Individual and Small-Area Social and Environmental Factors on Heat Vulnerability to Mortality Within and Outside of the Home in Boston, MA.
Climate change is resulting in heatwaves that are more frequent, severe, and longer lasting, which is projected to double-to-triple the heat-related mortality in Boston, MA if adequate climate change mitigation and adaptation strategies are not implemented. A case-only analysis was used to examine subject and small-area neighborhood characteristics that modified the association between hot days and mortality. Deaths of Boston, Massachusetts residents that occurred from 2000-2015 were analyzed in relation to the daily temperature and heat index during the warm season as part of the case-only analysis. The modification by small-area (census tract, CT) social, and environmental (natural and built) factors was assessed. At-home mortality on hot days was driven by both social and environmental factors, differentially across the City of Boston census tracts, with a greater proportion of low-to-no income individuals or those with limited English proficiency being more highly represented among those who died during the study period; but small-area built environment features, like street trees and enhanced energy efficiency, were able to reduce the relative odds of death within and outside the home. At temperatures below current local thresholds used for heat warnings and advisories, there was increased relative odds of death from substance abuse and assault-related altercations. Geographic weighted regression analyses were used to examine these relationships spatially within a subset of at-home deaths with high-resolution temperature and humidity data. This revealed spatially heterogeneous associations between at-home mortality and social and environmental vulnerability factors.


Region-specific gene expression profiling along the human epididymis.
During their transit through the epididymis, spermatozoa undergo many biochemical modifications necessary to acquire flagellar motility and fertilizing ability. These modifications, collectively called sperm maturation, are well orchestrated along the epididymis and depend on highly regionalized gene expression patterns. Based on clinical observations, the role of the epididymis in human sperm maturation has been questioned. To further understand the function of the excurrent duct in humans, we analysed gene expression of three donors on 'Affymetrix human GeneChip U133 plus 2' representing 47,000 transcriptional variants. More than 50% of transcripts were detected in each epididymal region. The analysis of hierarchical clustering performed from 2274 modulated qualifers between the three regions revealed that 1184, 713 and 269 were highly expressed in the caput, corpus and cauda region, respectively, in a very specific manner. The expressed qualifers were grouped according their similarity by Gene Ontology to give an overview of the functional features of the encoded proteins and to elucidate their potential roles in the epididymis. Northern blot analysis of eight gene transcripts predicted by microarray data to be highly expressed in the human epididymis was performed. All the transcript expression patterns confirmed the microarrays results. The data generated in this study demonstrate a region-specific gene expression pattern along the human epididymis that seems to coincide with the morphologically distinctive features of the excurrent duct.


Visual place recognition with repetitive structures.
Repeated structures such as building facades, fences or road markings often represent a significant challenge for place recognition. Repeated structures are notoriously hard for establishing correspondences using multi-view geometry. They violate the feature independence assumed in the bag-of-visual-words representation which often leads to over-counting evidence and significant degradation of retrieval performance. In this work we show that repeated structures are not a nuisance but, when appropriately represented, they form an important distinguishing feature for many places. We describe a representation of repeated structures suitable for scalable retrieval and geometric verification. The retrieval is based on robust detection of repeated image structures and a suitable modification of weights in the bag-of-visual-word model. We also demonstrate that the explicit detection of repeated patterns is beneficial for robust visual word matching for geometric verification. Place recognition results are shown on datasets of street-level imagery from Pittsburgh and San Francisco demonstrating significant gains in recognition performance compared to the standard bag-of-visual-words baseline as well as the more recently proposed burstiness weighting and Fisher vector encoding.


Building Trust and Partnership with Black Pediatric Patients and their Caregivers.
Systemic racism embedded within the US health care system results in disproportionately worse health outcomes for Black pediatric patients and their caregivers. One meaningful mechanism through which these health disparities persist is through discriminatory treatment and anti-Black bias from clinicians. Strengthening care provided to Black pediatric patients and their caregivers requires that clinicians adopt culturally tailored communication strategies that promote health equity and counter racism. We conducted a scoping review of evidence-based communication practices in the medical literature that improve care for Black pediatric patients. We mapped the specific practices to the Presence 5 for Racial Justice framework and identified cross-cutting themes to describe practices across the five domains. There are three cross-cutting themes that underlie the recommended practices: 1) promote unbiased implementation of clinician communication strategies (eg, providing equitable recommendations for preventive care), 2) tailor care to Black pediatric patients (eg, explore the importance of the family unit), and 3) address racism experienced by Black pediatric patients and their caregivers (eg, acknowledge any previous negative experiences with the health care system). This review highlights communication practices that clinicians can adopt to build trusting relationships, empower Black families, and promote racial justice in clinical care. Future opportunities include expanding to system level change and validating these practices with patients and clinicians.


Towards understanding the role of sialylation in melanoma progression.
Aberrant expression of sialic acids or altered linkage types is closely associated with malignant phenotype and metastatic potential, and can have prognostic significance in human cancer. The present study was undertaken to evaluate whether expression of sialylated derivatives on melanoma cell surface is associated with tumour progression. Four cell lines (WM1552C, WM115, IGR-39 and WM266-4) were used in the study. Cell surface expression of sialic acids was evaluated by flow cytometry with the use of Maackia amurensis and Sambucus nigra lectins. Moreover, adhesion and migration potential of melanoma cells and involvement of sialic acids in these processes were analysed. We have demonstrated that WM266-4 cells have a significantly higher level of α2,3-linked sialic acid residues than other cells, whereas IGR-39 cells had lower expression of α2,6-linked sialic acids. The adhesion efficiencies of WM1552C and WM115 cells were significantly lower than that of IGR-39 and WM266-4 cells. In contrast, WM266-4 cells repaired scratch wounds at least twice as fast as other cells. Melanoma cell adhesion to fibronectin in the presence of Sambucus nigra agglutinin (SNA) was reduced only in IGR-39 and WM266-4 cells, whereas the impact of Maackia amurensis agglutinin (MAA) on this process was much more important. Migration efficiency of melanoma cells was reduced more strongly in the presence of MAA than SNA. In conclusion, our results show that melanoma progression is associated with the increased expression of α2,3-linked sialic acids on the cell surface and these residues could promote melanoma cell interaction with fibronectin.


Stimulation of N-methyl-D-aspartate receptors, AMPA receptors or metabotropic glutamate receptors leads to rapid internalization of AMPA receptors in cultured nucleus accumbens neurons.
In hippocampus and other regions, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are inserted into synapses during long-term potentiation and removed during long-term depression. However, little is known about regulation of AMPA receptor trafficking in the nucleus accumbens (NAc), despite growing evidence that glutamate-dependent forms of plasticity in the NAc contribute to drug addiction. Using postnatal rat NAc cultures and an immunocytochemical method that selectively detects newly internalized GluR1, we studied the regulation of AMPA receptor internalization in NAc neurons by glutamate agonists. Newly internalized GluR1 was detected during 15 or 30 min of incubation at room temperature, indicating a basal rate of GluR1 turnover. The rate of GluR1 internalization was increased by glutamate (50 microM) within 5 min of its addition. Glutamate-induced GluR1 internalization was partially blocked by either an AMPA receptor antagonist (CNQX; 20 microM) or an N-methyl-D-aspartate (NMDA) receptor antagonist (APV; 50 microM). Both NMDA (50 microM) and AMPA (50 microM) increased GluR1 internalization in a Ca(2+)-dependent manner. The NMDA effect was blocked by APV while the AMPA effect was blocked by APV or CNQX. We interpret these findings to suggest that NMDA and AMPA ultimately trigger GluR1 internalization through the same NMDA receptor-dependent pathway. The effect of glutamate was also partially blocked by the group 1 metabotropic glutamate receptor antagonist N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC; 50 microM), while the group 1 agonist 3,5-dihydroxyphenylglycine (DHPG; 50 microM) stimulated GluR1 internalization. These data suggest that AMPA receptors on NAc neurons may be subject to rapid regulation of their surface expression in response to changes in the activity of glutamate inputs from cortical and limbic regions.


Earthquake insurance pricing: a risk-based approach.
Flat earthquake premiums are 'uniformly' set for a variety of buildings in many countries, neglecting the fact that the risk of damage to buildings by earthquakes is based on a wide range of factors. How these factors influence the insurance premiums is worth being studied further. Proposed herein is a risk-based approach to estimate the earthquake insurance rates of buildings. Examples of application of the approach to buildings located in Taipei city of Taiwan were examined. Then, the earthquake insurance rates for the buildings investigated were calculated and tabulated. To fulfil insurance rating, the buildings were classified into 15 model building types according to their construction materials and building height. Seismic design levels were also considered in insurance rating in response to the effect of seismic zone and construction years of buildings. This paper may be of interest to insurers, actuaries, and private and public sectors of insurance.


Cogan's Syndrome. High resolution MRI indicators of activity.
In the chronic-relapsing form of Cogan's syndrome, it can be difficult to evaluate the activity of the disease. In contrast to the initial stage, routine diagnostic techniques sometimes fail to indicate progression in the chronic stage. To determine whether high-resolution magnetic resonance imaging (HR-MRI) can be used to differentiate between active and inactive stages, we examined three patients with Cogan's syndrome (one during an acute relapse, two with chronic audiovestibular deficits), all of whom had antibodies to inner ear tissue (cochlea, vestibular labyrinth). Unenhanced T1-, T2, gadolinium-enhanced T1-weighted, and three-dimensional constructive interference in steady stage (CISS) images were used. Abnormal MRI signals of the inner ear were related to the activity of the disease. The patient studied during an acute exacerbation showed abnormal MRI signals in the vestibule, semicircular canals, vestibular nerve, and cochlea, which disappeared after the relapse. These abnormalities included high signal in the membranous labyrinth, the vestibule, and cochlea, with enhancement on T1-weighted images, indicating gadolinium leakage through the abnormal labyrinthine membrane into the perilymphatic spaces. In contrast, the other two patients with chronic audiovestibular deficits but no clinical signs of an acute relapse, had narrowing or occlusion of semicircular canals of the cochlea on the 3D-CISS images, but no high signal lesions (T1) and no enhancement. We conclude that sequential gadolinium-enhanced MRI can identify the active stage of Cogan's syndrome. The combination of HR-MRI and antibodies to inner ear antigens are helpful in the diagnosis of acute, sequential, bilateral audiovestibular impairment of autoimmune origin.


[Proposal for a practical diagnostic management of the etiology of acute childhood diarrhea].
Acute childhood diarrhea is highly common in our country and its treatment include rehydration, the early dietary management and in few cases the use of antibiotics. At the same time, watery diarrhea is much more common than bloody diarrhea. The ideal in the management of infectious diarrhea is to identify the microorganisms that are producing the disease, however, it is very important to mention that in the majority of etiological studies done in our country, two were the more common identified microorganisms: Rotavirus and E. coli (in its different types). Usually and due to the high price of Lab. tests, we don't search those microorganisms and the majority of Laboratories used to report as a result, Salmonella, Shigella or negative. Normally, we receive the results of these cultures after few days and as we can understand these results are not necessarily useful in the early management of the disease and as we mentioned, these results will not include the more common pathogens. In this article we propose to perform three simple fecal tests in patients affected with acute diarrhea: 1) Count and differentiation of leucocytes; 2) Occult blood; 3) Reducing substances. If we play with these three results, it is not too difficult to suspect in the probable pathogen that is affecting our patient. In that concern, we propose this very simple, cheap and highly practical method for the etiological management of our patients that, of course, is not infallible, but our experience for many years have shown us that it is of great help for pediatricians in their daily work.


Long-term Outcomes in Steroid-refractory Ulcerative Colitis Treated with Tacrolimus Alone or in Combination with Purine Analogues.
Tacrolimus is recommended for the treatment of steroid-refractory ulcerative colitis (UC). Concomitantly started purine analogues (PAs) are used for the maintenance of remission, though their therapeutic relevance remains uncertain. Here we studied the role of PAs in the long-term outcome of steroid-refractory UC after tacrolimus treatment. In five centres, charts of tacrolimus-treated UC patients with a steroid-refractory moderate to severe course were reviewed. Long-term efficacy was determined by colectomy rates and clinical remission in cases of colectomy-free survival for 3 months. We identified 156 patients (median age 34 years) with a median Lichtiger score of 12 (4-17) and pancolitis (E3) in 65% (101). The Kaplan-Meier curve for colectomy-free survival after month 3 showed a benefit in the PA group (p = 0.02). In patients treated with PA clinical remission was achieved in 82% (65/79) vs 67% (39/58) in those not treated with PA (p = 0.02). Time to colectomy was 2 years (median, 0.7-5.8) in the PA group and 0.8 years (0.3-4.7) in the group not treated with PAs (p = 0.02). Time to relapse was 1.2 years (median, 0.3-6.2) in patients with PA treatment and 0.5 years (0.3-3.9) in those without PA treatment (p = 0.05). Overall, clinical remission was achieved in 67% (104/156) of patients. Colectomy was performed in 29% (45/156) 0.5 years (median, 0.04-5.79) after initiation of tacrolimus. Ten (6%) patients had to stop tacrolimus due to adverse events and two (without PA treatment) died. Our study supports the efficacy of tacrolimus in steroid-refractory UC. Purine analogues appear to be beneficial for the long-term outcome of these patients.


Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis.
Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke. A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ≤2) at day 90. Ninety-five participants were randomized; 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence interval, 0.71-1.25 and odds ratio, 0.73; 95% CI, 0.31-1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74-5.16) but there was substantial heterogeneity among the trials. In this pilot study of a small sample of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline. http://www.anzctr.org.au. Unique identifier: ACTRN12612000237886.


Application of a 4-h human patch test method for comparative and investigative assessment of skin irritation.
A human 4-h patch test has recently been developed for testing the irritation hazard potential of chemicals. The original method was developed for comparative irritation assessments relative to benchmark irritants using simple statistical tests. In this context, the method has been shown to be robust in intralaboratory testing over time. Recent interlaboratory testing has also established the consistency of the method in assessment of the relative irritation potential of selected chemicals. These data help to position the method as a suitable replacement for animal test methods in assessment of skin irritation hazard. In addition, the method has great utility for investigating different parameters of clinical skin irritation. Using kinetic response patterns and curve fitting analysis, we have compared the relative irritation potential of chemicals in greater detail, using as a basis the time required for test subjects to respond as well as the incidence of positive responses. Also, using the response to 20% sodium dodecyl sulfate (SDS) as a benchmark, we've been able to examine the intersubject variation in clinical skin irritation responses. In general, subjects most reactive to 20% SDS, in terms of the exposure time required to produce a positive response, were relatively more sensitive to a 2nd irritant chemical as well. However, this was not an absolute correlation in that some test subjects showed divergent patterns of response. The method was also used to compare directly the relative skin reactivity of different populations, based on race (Caucasian versus Asian) or on neurosensory skin sensitivity. Our results using this acute exposure test method indicate little difference in visually assessed skin irritation among these diverse human subpopulations.


Microscopic dissolution process of cellulose in alkaline aqueous solvents and its application in CNFs extraction - Investigating temperature as a variable.
The target of this study is to gain a deeper understanding of the micro-dissolution process of cellulose in alkaline aqueous solutions and to develop a novel method for extracting cellulose nanofibrils (CNFs). Herein, the dissolution process of cellulose in alkaline aqueous solutions will be controlled by varying the temperature, and the undissolved cellulose will be analyzed to reveal the microscopic dissolution process of cellulose, and a novel process for extracting cellulose nanofibrils (CNFs) will be developed based on the findings. The crystalline structure of cellulose was gradually disrupted as the dissolution progressed, and the crystal form of cellulose changed gradually from cellulose I to cellulose II during the dissolution process, while all undissolved cellulose crystals remained as cellulose I. Cellulose, after its structure is disrupted during the dissolution process, will inevitably decompose into CNFs, and the microscopic dissolution process of cellulose follows a "top-down" dissolution sequence. The CNFs extraction method developed in this study can extract CNFs with high yield (>60 %) in a stable manner, as well as narrow particle size distribution, high crystallinity (>77 %), and good thermal stability. This study enhances the comprehension of the dissolution process of cellulose and paves a possible way for industrialization of CNFs production.


Programmed Cell Death Protein 2-like Promotes Inflammation and Oxidative Stress in Vascular Endothelial Cells.
Programmed cell death protein 2-like (PDCD2L) is a shuttle protein of the nucleus and cytoplasm and is related to the ribosome biogenesis. However, there are few reports on the relationship between PDCD2L and inflammation, and the exact relationship between PDCD2L and inflammation has not been determined in vascular endothelial cells yet. Accordingly, we focus on exploring the relationship between PDCD2L and inflammation and its potential mechanisms. Our research findings suggested that PDCD2L is a proinflammatory target. The result showed that, by interfering with the expression of PDCD2L, LPS-induced inflammation of vascular endothelial cells can be reduced, such as IL-6 and IL-1β, as well as the adhesion factor ICAM1. Meanwhile, overexpression of PDCD2L can further increase LPS-induced inflammation levels, ICAM1, and ROS production, reduce CAT, GSH/GSSG levels, and increase SOD levels. Therefore, we determined that PDCD2L has a regulatory effect on inflammation and oxidative stress of vascular endothelial cells, and its regulatory mechanism may be related to inflammatory transcription factors STAT1, NF-κB regulation, transport of inflammatory messenger mRNA, and ribosome biogenesis. Then, we screened that andrographolide (Andro) can bind to PDCD2L, thus inhibiting inflammation and endothelial cell adhesion caused by the overexpression of PDCD2L. This study reveals that PDCD2L is a potential anti-inflammatory therapeutic target, providing new exploration for the development of anti-inflammatory drugs.


Flexural strength and microhardness of anterior composites after accelerated aging.
This study aimed to evaluate the flexural strength and microhardness of three different anterior composites after 10 000 thermocycles. The mechanical properties of a nano-fill composite (Filtek Ultimate Universal Restorative (FUR) (Enamel)), a nano-hybrid composite (Clearfil Majesty ES2 (ES2) (Enamel)), and a micro-hybrid composite (G Aenial Anterior (GAA)) were investigated in this study. For the microhardness test, 8-mm diameter and 2-mm thickness composite discs were used (n = 10), and for the flexural strength test, 25x2x2 mm bar-shaped specimens were prepared (n = 13). The specimens were tested at 24 h and after 10 000 thermocycles. Data were analyzed using two-way analysis of variance and the post-hoc Tukey test (p < .05). Correlations between hardness and flexural strength were calculated using Pearson's correlation analysis. There was a significant difference in the microhardness values of the materials (p < .05). FUR exhibited significantly higher microhardness than ES2 and GAA. However, the flexural strength of three composites was statistically similar at 24 h (p > .05). Pearson correlation analysis revealed that there was a negative relationship between the mean hardness and flexural strength values (correlation coefficient = -0.367, p = .043). After 10 000 thermocycles, microhardness values of each material and flexural strength of ES2 and GAA decreased significantly according to 24 h. The nano-fill composite FUR displayed significantly higher microhardness values. However, each resin composite was statistically similar for flexural strength values. Ten thousand thermocycles significantly affected microhardness and flexural strength. Key words:Flexural strength, microhardness, anterior composites.


Videoesophagography versus Endoscopy for Prediction of Intraoperative Hiatal Hernia Size.
Magnetic sphincter augmentation is a novel surgical procedure for gastroesophageal reflux disease. Limited dissection at the hiatus is one of the benefits of the procedure, but makes precise and accurate preoperative assessment of even small hiatal hernia critical. Retrospective cohort study of 136 patients having undergone both endoscopy (EGD) and videoesophagography followed by operative assessment for hiatal hernia during magnetic sphincter augmentation. The objective of the study is to determine which preoperative modality more accurately predicts operative hiatal hernia size. Videoesophagography underestimated operative measurement by 0.37 ± 1.41 cm (P = 0.003) and was less accurate in predicting intraoperative hiatal hernia size than EGD on linear regression analysis (β -0.729, SE 0.057, P < 0.001). EGD was less accurate at predicting hiatal hernia size as patient age increased (β -0.018, SE 0.007, P = 0.014) and with larger hernias (β -0.615, standard error (SE) 0.067, P < 0.001); however, endoscopic measurements did not differ significantly from intraoperative measurements (0.93 ± 1.23 cm vs 1.12 ± 1.43 cm, P = 0.12). EGD better predicts the size of small hiatal hernia measured during subsequent laparoscopic surgery.


Exposure to sperm competition risk improves survival of virgin males.
Sperm competition between the ejaculates of multiple males for the fertilization of a given set of ova is taxonomically widespread. Males have evolved remarkable adaptations to increase their reproductive success under postcopulatory sexual selection, which in many species includes the ability to modify behaviour and ejaculate characteristics plastically to match the perceived level of sperm competition. Males of the model species Drosophila melanogaster increase mating duration and modify seminal fluid composition in response to short-term changes in sperm competition risk. If these responses increase a male's total investment in reproduction, he must either trade-off this cost against other life-history traits or suffer reduced survival. We tested whether mounting a plastic sperm competition response bears an instantaneous survival cost, and instead found that male D. melanogaster exposed to a high risk of sperm competition survive 12 per cent longer than those at low risk, equating to a 49 per cent reduction in the hourly hazard of death. This striking effect was found only among virgins: the high cost of mating in this species eliminates any such benefit among non-virgin males. Our results suggest that the improvement in survival found among virgins may be a product of males' tactical responses to sperm competition.


Effect of Sulfur-Containing Primers for Noble Metals on the Bond Strength of Self-Cured Acrylic Resin.
This study investigated the effect of sulfur-containing primers for noble metals on the shear bond strength of self-cured acrylic resin after thermal cycling (TC). Four pure metals (Au, Ag, Cu, and Pd) and type IV Au alloy were either untreated, or treated with one of the five sulfur-containing metal primers (V-Primer, Metaltite, Alloy Primer, Metal Link Primer, and Metal Primer Z). Afterwards, a brass ring was placed on the metal surface and filled with self-cured acrylic resin (n = 10). The bond strengths were measured after 24 h (TC0) and after 2000 thermal cycles at 4-60 °C (TC2000). Three-way ANOVA and Tukey compromise post hoc tests were used to analyze the data (α = 0.05). All of the sulfur-containing primers significantly improved the resin bond strength as compared to that of the non-primed group at TC0 regardless of the metal type (p < 0.05). However, at TC2000, the bond strengths between the resin and the five metals significantly decreased with respect to the values obtained at TC0 regardless of the primer (p < 0.05). The sulfur-containing metal primers, except for Metal Link Primer, were found to be more effective for improving the bond strength between the self-cured acrylic resin and Ag as compared to the other three pure metals (p < 0.05). The bond strengths between the resin and Au and type IV Au alloy at TC2000 were the highest ones when Metal Primer Z was used.


Pancreas MRI Segmentation Into Head, Body, and Tail Enables Regional Quantitative Analysis of Heterogeneous Disease.
Quantitative imaging studies of the pancreas have often targeted the three main anatomical segments, head, body, and tail, using manual region of interest strategies to assess geographic heterogeneity. Existing automated analyses have implemented whole-organ segmentation, providing overall quantification but failing to address spatial heterogeneity. To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI. Retrospective. One hundred and fifty nominally healthy subjects from UK Biobank (100 subjects for method development and 50 subjects for validation). A separate 390 UK Biobank triples of subjects including type 2 diabetes mellitus (T2DM) subjects and matched nondiabetics. A 1.5 T, three-dimensional two-point Dixon sequence (for segmentation and volume assessment) and a two-dimensional axial multiecho gradient-recalled echo sequence. Pancreas segments were annotated by four raters on the validation cohort. Intrarater agreement and interrater agreement were reported using Dice overlap (Dice similarity coefficient [DSC]). A segmentation method based on template registration was developed and evaluated against annotations. Results on regional pancreatic fat assessment are also presented, by intersecting the three-dimensional parts segmentation with one available proton density fat fraction (PDFF) image. Wilcoxon signed rank test and Mann-Whitney U-test for comparisons. DSC and volume differences for evaluation. A P value < 0.05 was considered statistically significant. Good intrarater (DSC mean, head: 0.982, body: 0.940, tail: 0.961) agreement and interrater (DSC mean, head: 0.968, body: 0.905, tail: 0.943) agreement were observed. No differences (DSC, head: P = 0.4358, body: P = 0.0992, tail: P = 0.1080) were observed between the manual annotations and our method's segmentations (DSC mean, head: 0.965, body: 0.893, tail: 0.934). Pancreatic body PDFF was different between T2DM and nondiabetics matched by body mass index. The developed segmentation's performance was no different from manual annotations. Application on type 2 diabetes subjects showed potential for assessing pancreatic disease heterogeneity. 4 TECHNICAL EFFICACY STAGE: 3.


The fabrication of magnetic particle-based chemiluminescence immunoassay for human epididymis protein-4 detection in ovarian cancer.
The magnetic particles have a significant influence on the immunoassay detection and cancer therapy. Herein, the chemiluminescence immunoassay combined with the magnetic particles (MPCLIA) was presented for the clinical determination and analysis of human epididymis protein 4 (HE4) in the human serum. Under the optimized experiment conditions, the secure MPCLIA method can detect HE4 in the broader range of 0-1000 pmol/L, with a lower detection limit of 1.35 pmol/L. The satisfactory recovery rate of the method in the serum ranged from 83.62% to 105.10%, which was well within the requirement of clinical analysis. Moreover, the results showed the good correlation with enzyme-linked immunosorbent assay (ELISA), with the correlation coefficient of 0.9589. This proposed method has been successfully applied to the clinical determination of HE4 in the human serum.


Nitrification of industrial waste-waters with high nitrogen concentration in aerated packed-bed reactors.
The use of a two-step aerated packed-bed reactor yielded 99% nitrification of inorganic nitrogenous wastes carrying 800 to 1,300 mg N/l (COD of the wastes 55 mg O2/1). The beds were aerated with air enriched in CO2 pH values between the units were routinely adjusted. The efficiency of nitrification was 33 mg N/l/h. A change of the composition of the wastes to nitrogenous-organic (COD 1,200 mg O2/l) caused a drop in the efficiency of nitrification to 24 mg N/l/h and the subsequent introduction of a three-step system. Concomitant COD reduction was 85% with 73% reduction occurring in the first bed. The number of auto- and heterotropic bacteria in the nitrogenous-organic wastes and effluents from the separate beds were determined.


Relativistic and QED corrections for the beryllium atom.
Complete relativistic and quantum electrodynamics corrections of order alpha(2) Ry and alpha(3) Ry are calculated for the ground state of the beryllium atom and its positive ion. A basis set of correlated Gaussian functions is used, with exponents optimized against nonrelativistic binding energies. The results for Bethe logarithms ln(k(0)(Be)=5.750 34(3) and ln(k(0)(Be+)=5.751 67(3) demonstrate the availability of high precision theoretical predictions for energy levels of the beryllium atom and light ions. Our recommended value of the ionization potential 75 192.514(80) cm(-1) agrees with equally accurate available experimental values.


Stable and unstable angina: Identifying novel markers on circulating leukocytes.
There is currently no blood-based test that can rapidly and objectively distinguish between chest pain which is initiated by increased myocardial oxygen demand (stable angina pectoris (SAP)) and chest pain initiated due to decreased coronary blood flow (unstable angina pectoris (UAP)). Since leukocytes play an active role in the progression of coronary artery disease (CAD), we hypothesize these can provide novel markers of SAP and UAP. Here we use a microarray of 82 cluster of differentiation (CD) antibodies (plus controls) to selectively immobilize peripheral blood mononuclear cells. We find that the pattern of leukocyte immobilization from patients with CAD significantly differs from healthy donors. Within the CAD group, 15 SAP patients exhibited significant (p<0.05) changes in 8 of 82 CD antibody spots compared to 19 age-matched healthy blood donors. An additional ten CD antigens differed between healthy donors and patients with UAP (p<0.05). Furthermore, seven CD antibody spots are significantly different between SAP and UAP patients. These preliminary data suggest it is now appropriate to undertake a larger clinical trial to test the hypothesis that these antibody microarrays can monitor the progression from SAP to UAP.


A novel B-cell epitope of avian infectious bronchitis virus N protein.
This report describes the identification of a novel linear B-cell epitope at the N-terminus of the avian infectious bronchitis virus (IBV) nucleocapsid (N) protein. A monoclonal antibody designated 2D2 was prepared against the IBV N protein, and a series of 23 partially overlapping, tagged fragments of the IBV N gene were expressed. These peptides and five heterogeneous IBV strains were used to identify the epitope recognized by 2D2 using enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis. The linear motif (11)DSPAPIIKLGG(21), located at the N-terminus of the N protein, was identified as the epitope bound by 2D2. ELISA and Western blotting also showed that this epitope was recognized by IBV-positive chicken serum. We propose that this motif is a linear B-cell epitope of N protein, and is the core sequence for reactivity, as demonstrated by binding of 2D2 to the truncated peptides and different IBV strains. Alignment and comparison of the 2D2-defined epitope with other coronavirus sequences showed that the epitope is conserved among avian coronaviruses. The identified epitope might be useful for clinical applications and as a tool for further study of the structure and function of the IBV N protein.


Understanding the rates of nonpolar organic chemical accumulation into passive samplers deployed in the environment: Guidance for passive sampler deployments.
Polymeric passive samplers have become a common method for estimating freely dissolved concentrations in environmental media. However, this approach has not yet been adopted by investigators conducting remedial investigations of contaminated environmental sites. Successful adoption of this sampling methodology relies on an understanding of how passive samplers accumulate chemical mass as well as developing guidance for the design and deployment of passive samplers. Herein, we outline the development of a simple mathematical relationship of the environmental, polymer, and chemical properties that control the uptake rate. This relationship, called a timescale, is then used to illustrate how each property controls the rate of equilibration in samplers deployed in the water or in the sediment. Guidance is also given on how to use the timescales to select an appropriate polymer, deployment time, and suite of performance reference compounds. Integr Environ Assess Manag 2016;12:486-492. © 2015 SETAC.


Reverse the Resistance to PARP Inhibitors.
One of the DNA repair machineries is activated by Poly (ADP-ribose) Polymerase (PARP) enzyme. Particularly, this enzyme is involved in repair of damages to single-strand DNA, thus decreasing the chances of generating double-strand breaks in the genome. Therefore, the concept to block PARP enzymes by PARP inhibitor (PARPi) was appreciated in cancer treatment. PARPi has been designed and tested for many years and became a potential supplement for the conventional chemotherapy. However, increasing evidence indicates the appearance of the resistance to this treatment. Specifically, cancer cells may acquire new mutations or events that overcome the positive effect of these drugs. This paper describes several molecular mechanisms of PARPi resistance which were reported most recently, and summarizes some strategies to reverse this type of drug resistance.


Equilibrium theory revisited: factors influencing position of the teeth.
The major primary factors in the dental equilibrium appear to be resting pressures of tongue and lips, and forces created within the periodontal membrane, analogous to the forces of eruption. Forces from occlusion probably also play a role in the vertical position of teeth by affecting eruption. Respiratory needs influence head, jaw and tongue posture and thereby alter the equilibrium. "Deviate swallowing" is more likely to be an adaptation than a cause of tooth changes. Patients with failure of eruption have been recognized and alterations in the eruption mechanism may be more important clinically than has been recognized previously.


Unexpected Parabolic Temperature Dependency of CH4 Emissions from Rice Paddies.
Global warming is expected to affect methane (CH4) emissions from rice paddies, one of the largest human-induced sources of this potent greenhouse gas. However, the large variability in warming impacts on CH4 emissions makes it difficult to extrapolate the experimental results over large regions. Here, we show, through meta-analysis and multi-site warming experiments using the free air temperature increase facility, that warming stimulates CH4 emissions most strongly at background air temperatures during the flooded stage of ∼26 °C, with smaller responses of CH4 emissions to warming at lower and higher temperatures. This pattern can be explained by divergent warming responses of plant growth, methanogens, and methanotrophs. The effects of warming on rice biomass decreased with the background air temperature. Warming increased the abundance of methanogens more strongly at the medium air temperature site than the low and high air temperature sites. In contrast, the effects of warming on the abundance of methanotrophs were similar across the three temperature sites. We estimate that 1 °C warming will increase CH4 emissions from paddies in China by 12.6%─substantially higher than the estimates obtained from leading ecosystem models. Our findings challenge model assumptions and suggest that the estimates of future paddy CH4 emissions need to consider both plant and microbial responses to warming.


Cycle control and side effects of a new combiphasic oral contraceptive regimen.
In a multicentre study 882 women were treated during a total of 12,850 cycles with a new combiphasic contraceptive: CTR 24. The study period was 18 cycles. The combiphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinyl-estradiol daily for the subsequent 15 days. The bleeding patterns were analysed over pill cycles and a comparison was made between starters and switchers. The cycle control of the combination was very good. The side effect profile was favourable.


Effectiveness of atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: study protocol for a randomised controlled trial.
Uterine contractions may interfere with embryo implantation in assisted reproductive technology. To reduce these contractions and improve success rates, the oxytocin antagonist atosiban has been suggested for administration during embryo transfer. The aim of this study is to evaluate the effectiveness of atosiban in increasing live birth rates among women who have previously experienced a single implantation failure and are scheduled for single blastocyst transfer. We conduct a single-centre randomised controlled study comparing atosiban and placebo in women undergoing a single blastocyst transfer with a previous failed blastocyst transfer. Women with endocrine or systemic illnesses, recurrent miscarriages, uterine malformations or fibroids, untreated hydrosalpinx, endometriosis (stage III or IV) or uterine fibroids, as well as women undergoing preimplantation genetic testing, are ineligible. The primary outcome is live birth resulting from the frozen-thawed embryo transfer. Secondary outcomes include biochemical/clinical pregnancy, miscarriage, ectopic pregnancy, multiple pregnancies as well as maternal and perinatal outcomes. We plan to recruit 1100 women (550 women per group). This will allow us to demonstrate or refute an increase in live birth rate from 40% to 50%. Data analysis will follow the intention-to-treat principle. We will measure patterns of uterine peristalsis which will allow subgroup analysis for women with or without uterine peristalsis. This study has been approved by the Institutional Review Board of Northwest Women's and Children's Hospital (No. SZ2019001). Written informed consent will be obtained from each participant before randomisation. The results of the trial will be presented at scientific meetings and reported in publications. ChiCTR1900022333.


Molecular approaches to nerve regeneration.
Current research into regeneration of the nervous system has focused on defining the molecular events that occur during regeneration. One well-characterized system for studying nerve regeneration is the sciatic nerve of rat. Numerous studies have characterized the sequence of events that occur after a crush injury to the sciatic nerve (Cajal 1928; Hall 1989). These events include axon and myelin breakdown, changes in the permeability of the blood vessels, proliferation of Schwann cells, invasion of macrophages, and the phagocytosis of myelin fragments by Schwann cells and macrophages. The distal segment of the injured sciatic nerve provides a supportive environment for the regeneration of the nerve fibres (Cajal 1928; David & Aguayo 1981). Within a period of weeks, the injured sciatic nerve is able to regrow and successfully reinnervate the appropriate targets. Some of the molecules that provide trophic support for the regrowing nerve fibres have been identified, including nerve growth factor (NGF) (Heumann et al. 1987) and glial maturation factor beta (Bosch et al. 1989). Another class of molecules show changes in their rates of synthesis during regeneration, including both proteins (Skene & Shooter 1983; Muller et al. 1986) and mRNA species (Trapp et al. 1988; Meier et al. 1989). To better understand nerve regeneration, we have taken two, parallel molecular approaches to study the events associated with regeneration. The first of these is to study in detail the mechanism of action of a molecule that has been implicated in the regeneration process, nerve growth factor. The second approach is to identify novel gene sequences which are regulated during regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)


New Members of SHG Active Dugganite Family, A3BC3D2O14 (A = Ba, Pb; B = Te, Sb; C = Al, Ga, Fe, Zn; D = Si, Ge, P, V): Synthesis, Structure, and Materials Properties.
A family of compounds, A3BC3D2O14 (A = Ba, Pb; B = Te, Sb; C = Al, Ga, Fe, Zn; D = Si, Ge, P, V), with the Dugganite structure was prepared employing traditional solid-state chemistry methods. PXRD and Rietveld refinement studies indicate that the compounds are stabilized in P321 space group (no. 150). The compounds are found to be SHG active with values ranging from 1.9 to 15.0 × KDP. The compounds exhibit high dielectric constants and low loss in our studies. The noncentrosymmetry related properties of the new Dugganites were understood by band structure calculations. We also explored the present Dugganite-structured oxides for the development of new inorganic colored materials by substituting Co2+, Ni2+, Cu2+, and Fe3+ in place of Zn2+. Thus, substitution of Co2+ and Fe3+ together tunes the blue color of the cobalt compound to blue-green color arising from metal-to-metal charge transfer (MMCT) of Fe3+ and Co2+ ions. The tetrahedrally coordinated Ni2+ in the Dugganite imparts a magenta color.


Fabrication of DNA-Templated Pt Nanostructures by Area-Selective Atomic Layer Deposition.
We report the fabrication of DNA-templated Pt nanostructures by area-selective atomic layer deposition. A DNA-templated self-assembled monolayer was used to mediate the area-selective deposition of Pt. Using this approach, we demonstrated the fabrication of both single- and two-component nanostructure patterns, including Pt, TiO2/Pt, and Al2O3/Pt. These nanoscale patterns were used as hard masks for plasma deep etching of Si to fabricate anti-reflection surfaces. This work demonstrated a gas-phase, DNA-templated fabrication of metal nanostructures, which complements earlier work of solution-based DNA metallization. The nanostructures obtained here are useful for applications in nanoelectronics, nanophotonics, and surface engineering.


Neurologic manifestations in 18q- syndrome.
We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q- syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.


Superfund research program--accomplishments and future opportunities.
This special issue of the International Journal of Hygiene and Environmental Health provides extensive background on the Superfund programs, findings of specific research studies and future directions. Three federal agencies are leading the effort in this program. They are the National Institute of Environmental Health Sciences, U.S. Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry. As a result of their collaboration, a comprehensive program has been developed that ranges from basic to applied research with the aim of improving public health services and protection. This paper highlights the research within areas of toxicological investigation, exposure assessment, risk evaluation and engaging communities. Each of the agencies has developed strategies and initiatives to enhance the effectiveness of the Superfund research program. The continuation of research will contribute significantly towards achieving the Healthy People 2010 goals that have been set for the United States.


Semelil as Adjunctive Therapy in Chronic Periodontitis: A Preliminary Randomized Controlled Clinical Study.
Host modulation therapy is recently employed to improve periodontal treatments outcome. This randomized controlled clinical trial aimed to evaluate the effects of Semelil (ANGIPARS) as an adjunct to non-surgical treatment in patients with chronic periodontitis. Forty-four healthy subjects with moderate to severe chronic periodontitis were enrolled in the study. After completion of phase I periodontal therapy, including oral hygiene instruction, scaling, and root planing, the patients were randomly divided into two groups to receive capsules of Semelil (test) or placebo (control), consuming two capsules a day for three months. Clinical parameters (probing depth [PD], clinical attachment level [CAL], modified sulcular bleeding index [MSBI], modified gingival index [MGI], and plaque index [PI]) and biochemical parameters (interleukin-1β [IL-1β], 8-hydroxy-2-deoxyguanosine [8-OHdG]), and lipid peroxidation [LPO]) were measured at baseline and after completion of treatment. Twenty-five patients completed the study: 15 in the test group and 10 in the control group. All clinical and biochemical parameters were significantly improved from baseline to the final measurements in both groups (p < 0.001). The changes were more pronounced in the test group in comparison to the control group. However, the differences between the groups were significant only for MGI, MSBI, PD, and CAL (p < 0.05). Semelil may reveal promising results as an adjunctive treatment for chronic periodontitis.


Aberrant promoter methylation of the TPEF gene in esophageal squamous cell carcinoma.
Aberrant methylation of tumor suppressor genes plays an important role in the development of esophageal squamous cell carcinoma (ESCC). The purpose of the present study was to identify the epigenetic changes in ESCC. Methylation-sensitive arbitrarily primed polymerase chain reaction (MS AP-PCR) analysis was used on 22 matched ESCC tumors and adjacent normal tissues. Through this screen we identified a frequently methylated fragment that showed a high homology to the 5'-CpG island of the gene encoding a transmembrane protein containing epidermal growth factor and follistatin domains (TPEF). The methylation status of the TPEF gene was then detected by bisulfite sequencing and the levels of TPEF mRNA were detected by RT-PCR. In addition, the effects of a methylation inhibitor 5-aza-2'-deoxycytidine on TPEF mRNA expression was determined in cells of ESCC cell lines. Hypermethylation of the 5'-CpG island of TPEF was found in 12 of 22 (54.5%) primary tumors. Reverse transcription PCR analysis demonstrated that TPEF mRNA expression was significantly lower in tumors than in adjacent normal tissues, which is associated with promoter hypermethylation. In addition, treatment of ESCC cell lines with 5-aza-2'-deoxycytidine led to re-expression of the TPEF transcript. In conclusion, we observed promoter of TPEF gene is frequently hpermethylated, and is associated with the loss of TPEF mRNA expression in ESCC samples. Promoter hypermethylation of TPEF gene may play a role in the development of ESCC.


Staff Efficiency Trends Among Pediatric Hospices, 2002-2011.
This study provided the first examination of staff efficiency trends among pediatric hospices. Although pediatric staff efficiency demonstrated large variability from 2002 to 2011, the general trend in efficiency from 2003 to 2010. The decline in efficiency means, on average, pediatric hospices had higher operating expenses and used more capacity, but greater amounts of these greater outputs as measured by visits per patient. The study also highlights the crucial role pediatric hospice nurse managers play in developing effective workforce strategies that allow for responsive changes to workload fluctuations. Due to the associations between efficiency, regulation, and growth, nurse leaders' abilities to develop effective strategies are more imperative than ever to ensure quality end-of-life care for children and their families.


[Expression of p75 neurotrophin receptor during the mineralization of ectomesenchymal stem cells in vitro].
To investigate the mineralized capacities of ectomesenchymal stem cells (EMSC) from facial process of Sprague Dawley(SD) rat embryo of different age in vitro and the expression of p75 neurotrophin receptor(p75NTR) in this process. The stem cell surface antigens of EMSC from 12.5 d, 15.5 d and 18.5 d SD rat embryonic facial process were tested by flow cytometry technology. E12.5 d EMSC, E15.5 d EMSC and E18.5 d EMSC were incubated under mineralization induction and analysed by alkaline phosphatase(ALP) staining on day 7(d7) and alizarin red staining on day 21(d21). Expression changes of Runt-related transcription factor-2(RUNX2), collagen Ⅰ (Col Ⅰ) and p75NTR in each group were measured using Western blotting and real time(RT)-PCR on day 0(d0), day 7(d7), day 14(d14) and day 21(d21). The expression of the special substances CD29, CD146 and p75NTR in E12.5 d EMSC, E15.5 d EMSC and E18.5 d EMSC were positive, and the expression of CD45 was negative. The expression level of p75NTR in E18.5 d EMSC(84.04%) was much higher than that of E12.5 d EMSC (22.53%) and E15.5 d EMSC(81.43%). The mineralized capacities of E18.5 d EMSC was stronger than that of E12.5 d EMSC and E15.5 d EMSC. The higher expression of RUNX2, Col Ⅰ in E18.5 d EMSC(RUNX2: 1.92±0.20, Col Ⅰ: 1.85±0.66) was found compared with E12.5 d EMSC(RUNX2: 0.38±0.02, Col Ⅰ: 0.33± 0.94) and E15.5 d EMSC(RUNX2: 0.72±0.22, Col Ⅰ: 0.64±0.07) (P<0.05), and p75NTR in the E18.5 d EMSC experimental group(E12.5 d: 0.79±0.23, E15.5 d: 0.84±0.29, E18.5 d: 1.35±0.22) was significantly higher than the in control group(E12.5 d: 0.42±0.12, E15.5 d: 0.43±0.13, E18.5 d: 0.48±0.15)(P<0.05). RT-PCR further proved the results of the Western blotting. p75NTR participated in the mineralization differentiation of EMSC. E18.5 d EMSC had a higher expression of p75NTR and stronger mineralization capacity and was the ideal engineering seed cells.


Direct magnitude estimation and interval scaling of stuttering severity.
The appropriateness of direct magnitude estimation and interval scaling for assessing stuttering severity was investigated by determining whether the continuum of the stutterers' judged severity was prothetic or metathetic. As operationally defined by Stevens, prothetic continua show a curvilinear relation between magnitude estimates and interval scale values of the same set of stimuli, whereas metathetic continua show a linear relation between these scale values. The stuttering severity of 20 stutterers was scaled by three groups of 15 listeners who used interval scaling, direct magnitude estimation with standard/modulus, and direct magnitude estimation without standard/modulus. The results indicated that the two sets of direct magnitude estimation scale values were related to the interval scale values in the curvilinear fashion that is typical of prothetic continua. These findings suggest that direct magnitude estimation is preferable to interval scaling for measuring stuttering severity.


Participation in the Healthy Rewards Program Predicts Staying Employed, Medical Costs, and Utilization.
To identify who is participating in the healthy rewards program (HRP), how participation corresponds with employment, and to compare health care costs and utilization between partial and full participants with non-participants. A retrospective analysis of employees in a large US company during 2016 to 2019, with statistically significant results reported, adjusted for sex, age, and year. Women, ages 30 to 59, and those employed in more recent years correspond with higher HRP participation. Participants were 15.7% more likely to remain employed from year to year. Compared with non-participants, partial and full participants experienced $740.43 and $884.07 lower annual costs. If all employees experienced the same health care costs as non-participants, partial participants, and full participants, there would be an 8% increase, 13% decrease, and 17% decrease in costs, respectively. HRP participation is a marker of interest in healthier living.


Cosmogenic Radionuclides in the Bondoc Meteorite.
Long-lived cosmogenic radionuclides were measured in the stone phase and in a mechanically separated metallic nodule from a fragment of the Bondoc mesosiderite. Activity levels of the various radionuclides in both phases, along with results of mass-spectrometric measurements of rare-gas isotopes in the stone phase, indicate that heavy shielding was the chief cause of the low specific activities observed.


TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune diabetes in the biobreeding diabetes-resistant rat.
Viral infections are associated epidemiologically with the expression of type 1 diabetes in humans, but the mechanisms underlying this putative association are unknown. To investigate the role of viruses in diabetes, we used a model of viral induction of autoimmune diabetes in genetically susceptible biobreeding diabetes-resistant (BBDR) rats. BBDR rats do not develop diabetes in viral-Ab-free environments, but approximately 25% of animals infected with the parvovirus Kilham rat virus (KRV) develop autoimmune diabetes via a mechanism that does not involve beta cell infection. Using this model, we recently documented that TLR agonists synergize with KRV infection and increase disease penetrance. We now report that KRV itself activates innate immunity through TLR ligation. We show that KRV infection strongly stimulates BBDR splenocytes to produce the proinflammatory cytokines IL-6 and IL-12p40 but not TNF-alpha. KRV infection induces high levels of IL-12p40 by splenic B cells and Flt-3-ligand-induced bone marrow-derived dendritic cells (DCs) but only low levels of IL-12p40 production by thioglycolate-elicited peritoneal macrophages or GM-CSF plus IL-4-induced bone marrow-derived DCs. KRV-induced cytokine production is blocked by pharmacological inhibitors of protein kinase R and NF-kappaB. Genomic KRV DNA also induces BBDR splenocytes and Flt-3L-induced DCs from wild-type but not TLR9-deficient mice to produce IL-12p40; KRV-induced up-regulation of B lymphocytes can be blocked by TLR9 antagonists including inhibitory CpG and chloroquine. Administration of chloroquine to virus-infected BBDR rats decreases the incidence of diabetes and decreases blood levels of IL-12p40. Our data implicate the TLR9-signaling pathway in KRV-induced innate immune activation and autoimmune diabetes in the BBDR rat.


[Radiotherapy in HIV positive patients].
HIV-positive Patients often suffer from the symptoms of accompanying diseases. Palliative radiation therapy of associated tumors leads to an improvement of the patient's condition. Particularly skin tumors, which give rise to pronounced itching and ulcerating, are eliminated fast and safe by radiation therapy. Between 1984 and 1988, 6 HIV patients with Kaposi's sarcoma at different sites, and one HIV-patient with non-Hodgkin's lymphoma were treated by radiation therapy. Depending on tumor site, photons or fast electrons were used. Cosmetic results were satisfying or even excellent in all patients. With one exception complete local tumor control was obtained. Side effects leading to a peace of treatment did not occur.


Investigation of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae outbreaks in Hungary between 2005 and 2008.
Fourteen outbreaks in Hungary between 2005 and 2008 caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) were epidemiologically investigated and the isolated pathogens were characterized by molecular techniques. Ten of the fourteen outbreaks occurred in adult wards and four in neonatal units affecting a total number of 73 patients. The 54% [40] of the patients developed bloodstream infections and 21.9%-21.9% [16] pneumonia and surgical site infections, respectively. The overall rate of mortality proved high: 36.9% [27]. Outbreaks in adults affected more patients, had higher attack rates, were more prolonged in duration and had a 6.9-fold higher mortality rate than outbreaks observed in neonates. The outbreaks in neonates were caused by SHV-type ESBL-producing klebsiellae, while in the "adult outbreaks" exclusively CTX-M-type ESBL-KP strains were involved. While the outbreak strains isolated from neonatal units could be assigned to a variety of pulsotypes, the previously described K. pneumoniae epidemic clones, ST15 and ST147, could be identified among the pathogens causing outbreaks in adult units.


Environmental stress affects the expression of a carotenoid-based sexual trait in male zebra finches.
Abiotic factors including thermal stress are suggested to exert constrains on sexual ornaments through trade-offs between sexual displays and physiological functions related to self-maintenance. Given the health properties of carotenoid pigments, carotenoid-based ornaments offer a relevant context in which to investigate the effect of environmental stress, such as ambient temperature, on the production and maintenance of secondary sexual traits and, also, to explore the proximate mechanisms shaping their expression. In this study, we exposed male zebra finches (Taeniopygia guttata) to environmental stress by exposing them to two temperature regimes (6 and 26 degrees C) over a 4 week period. Simultaneously, half of the males in each temperature group were supplemented with carotenoids, whereas the other half were not. The expression of a carotenoid-based sexual trait (bill colour) and the amount of circulating carotenoids were assessed before and at the end of the experiment. Carotenoid-supplemented males developed a redder bill, but the effect of supplementation was reduced under cold exposure. However, we found evidence that birds facing a cold stress were carotenoid limited, since supplemented males developed redder bills than the non-supplemented ones. Interestingly, while cold-exposed and non-supplemented males developed duller bills, they circulated a higher amount of carotenoids at the end of the experiment compared to the pre-experimental values. Together, these results suggest that ambient temperature might contribute to the modulation of the expression of carotenoid-based ornaments. Our findings suggest that carotenoids are a limiting resource under cold exposure and that they might be prioritized for self-maintenance at the expense of the ornament. The physiological functions related to self-maintenance that might have benefited from carotenoid saving are discussed.


Enhanced treatment of secondary municipal wastewater effluent: comparing (biological) filtration and ozonation in view of micropollutant removal, unselective effluent toxicity, and the potential for real-time control.
Ozonation and three (biological) filtration techniques (trickling filtration (TF), slow sand filtration (SSF) and biological activated carbon (BAC) filtration) have been evaluated in different combinations as tertiary treatment for municipal wastewater effluent. The removal of 18 multi-class pharmaceuticals, as model trace organic contaminants (TrOCs), has been studied. (Biological) activated carbon filtration could reduce the amount of TrOCs significantly (>99%) but is cost-intensive for full-scale applications. Filtration techniques mainly depending on biodegradation mechanisms (TF and SSF) are found to be inefficient for TrOCs removal as a stand alone technique. Ozonation resulted in 90% removal of the total amount of quantified TrOCs, but a post-ozonation step is needed to cope with an increased unselective toxicity. SSF following ozonation showed to be the only technique able to reduce the unselective toxicity to the same level as before ozonation. In view of process control, innovative correlation models developed for the monitoring and control of TrOC removal during ozonation, are verified for their applicability during ozonation in combination with TF, SSF or BAC. Particularly for the poorly ozone reactive TrOCs, statistically significant models were obtained that correlate TrOC removal and reduction in UVA254 as an online measured surrogate parameter.


Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia.
This review compared the clinical results of transepithelial corneal crosslinking (CXL) to epithelium-off (epi-off) CXL in progressive corneal ectasia using a metaanalysis. The Cochrane databases and Medline were searched for randomized controlled trials (RCTs). Seven RCTs involving 505 eyes that met the eligibility criteria were identified. The epi-off CXL group showed significantly better outcomes in postoperative changes in maximum keratometry (K) during 1-year observation periods. Transepithelial CXL resulted in significantly greater post-treatment central corneal thickness and best spectacle-corrected visual acuity (BSCVA). The presence of a postoperative demarcation line was significantly more frequent after epi-off CXL than that after transepithelial CXL. No statistically significant difference was found between other parameters. Although patients in the transepithelial CXL group demonstrated a greater improvement in BSCVA compared with patients in the epi-off CXL group at the 1 year follow-up, transepithelial CXL had less impact on halting progressive corneal ectasia in terms of maximum K than epi-off CXL.


Degeneracy and long-range correlations.
Degeneracy is a ubiquitous property of complex adaptive systems, which refers to the ability of structurally different components to perform the same function in some conditions and different functions in other conditions. Here, we suppose a causal link between the level of degeneracy in the system and the strength of long-range correlations in its behavior. In a numerical experiment, we manipulated degeneracy through the number of networks available in a model composed of a chain of correlated networks over which a series of random jumps are performed. Results showed that correlations in the outcome series increased with the number of available networks, and that a minimal threshold of degeneracy was required to generate long-range correlations. We conclude that degeneracy could underlie the presence of long-range correlations in the outcome series produced by complex systems. In turn, we suggest that quantifying long-range correlations could allow to assess the level of degeneracy of the system. Degeneracy affords a maybe more intuitive way than former hypotheses for understanding the effects of complexity on essential properties such as robustness and adaptability.


Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.
The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.


Patient Safety Subcultures among Nursing Home Staff in Italy: A Cross-Sectional Study.
Nursing home (NH) residents are vulnerable subjects and highly susceptible to adverse events. Knowledge of patient safety culture (PSC) is essential for an organization to ensure patient safety. However, research on PSC in NHs, and its variability among staff, is still scarce. This study aimed to explore whether and how PSC differed among NH staff (Managers, Nurses, Direct Care Staff, Support Staff, Administrative Staff and Other Providers) in the Autonomous Province of Trento, Italy. This study employed a cross-sectional design and collected data from 1145 NH providers using the Nursing Home Survey on Patient Safety Culture (NHSPSC). Data were analyzed using linear mixed models, with each of the 12 NHSPSC domains as a response variable. The majority of the respondents (61.6%) were Direct Care Staff members. 'Feedback and Communication about Incidents' and 'Overall Perceptions of Resident Safety' were the domains with the highest proportions of positive answers (PPAs). For most staff categories, 'Staffing' was the domain with the lowest PPA. Support Staff showed significantly lower scores in the majority of domains (8/12). Shorter job tenure, fewer weekly working hours, working mostly during the day and working in highly specialized areas were associated with higher scores in several domains. Interventions to improve PSC must consider the differences between professional groups. Further research is needed to explore the relationship between job-related features and perceptions of patient safety among NH workers.


Expanded Criteria for Hepatocellular Carcinoma in Liver Transplant.
Hepatocellular carcinoma is the sixth most common cancer worldwide and is the third highest cause of malignancy-related death. Because of its typically late diagnosis, median survival is approximately 6 to 20 months, with 5-year survival of < 12%. Hepatocellular carcinoma typically arises in the background of cirrhosis, with liver transplant regarded as the optimal therapy for selected patients. Initially, orthotopic liver transplant was limited to patients with extensive unresectable tumors, resulting in uniformly dismal outcomes due to high tumor recurrence rates. Here, we evaluated our long-term results with expanded-criteria liver transplant. From December 1988 to January 2017, we performed 552 liver transplants at Baskent University. In candidates with hepatocellular carcinoma, our expanded criteria for liver transplant is applied regardless of tumor size and number, includes those without major vascular invasion and without distant metastasis, and those with negative cytology (if the patient has ascites). Since 1994, of 61 liver transplants for hepatocellular carcinoma, 36 patients received transplants according to our expanded criteria. Of 36 expanded-criteria patients, 11 were children and 25 were adults. Sixteen patients (4 pediatric, 12 adult) were within our expanded criteria both radiologically and pathologically before transplant. The other 20 patients (7 pediatric, 13 adult) were within Milan criteria radiologically before transplant; however, after liver transplant, when pathologic specimens were evaluated, patients were found to be within our center's expanded criteria. During follow-up, 9/36 patients (25%) had hepatocellular carcinoma recurrence. In pediatric patients, 5-year and 10-year survival rates were 90%; in adults, 5-year survival was 58.7% and 10-year survival was 49.7%. Overall 5-year and 10-year survival rates were 71.7% and 62.7%. Liver transplant is safe and effective in patients with hepatocellular carcinoma in combination with interventional radiology procedures, regardless of tumor size and number, without major vascular invasion and distant metastasis.


Changes of serum IGF-1 and ET-1 levels in patients with osteoporosis and its clinical significance.
To investigate the correlations of levels of serum insulin-like growth factor-1 (IGF-1) and endothelin-1 (ET-1) with cytokines including interleukin (IL)-18, IL-6 and high-sensitivity C-reactive protein (hs-CRP) and bone material density in patients with osteoporosis d. Eighty patients with osteoporosis who were treated in our hospital from April 2016 to October 2017 were selected as observation group, and 60 healthy elderly people who received physical examination in our hospital in the same period were selected as control group. The serum levels of IGF-1 and ET-1 were detected using enzyme-linked immunosorbent assay. The bone material density of the lumbar vertebra, tibial neck and Ward's triangle of every research subject was measured using dual-energy x-rays absorptiometry. The correlations between variables were analyzed using Pearson correlation analysis. The level of IGF-1 in the observation group was lower than that in the control group, and the level of ET-1 in the observation group was higher than that in the control group (P<0.05). The levels of interleukin (IL)-18, IL-6 and high-sensitivity C-reactive protein (hs-CRP) in the observation group were significantly higher than those in the control group (P<0.05). Bone mineral density of lumbar vertebra, tibial neck and Ward triangle in the observation group was significantly lower than that in the control group (P<0.05); the IGF-1 level of osteoporosis patients was negatively correlated with IL-18, IL-6, hs-CRP levels and positively correlated with bone mineral density; the ET-1 level was positively correlated with IL-18, IL-6, hs-CRP levels and negatively correlated with bone mineral density. Patients with osteoporosis have decreased level of IGF-1 but increased level of ET-1, and they are closely related to cytokines and bone mineral density and may participate in the pathogenesis of osteoporosis.


Alcohol drinking and risk of hemorrhagic stroke.
In view of conflicting prior reports, we prospectively studied associations between alcohol consumption and subsequent hospitalization for hemorrhagic stroke (HS) in 431 persons. Alcohol use was determined at examinations in 1978-1984 among 128,934 members of a prepaid health plan. Cox proportional hazards models, with 6 covariates, yielded the following multivariate relative risks (95% CI's) for HS: lifelong abstainers (ref) = 1.0, exdrinkers = 0.9 (0.5-1.5), persons drinking <1/month = 1.1 (0.8-1.4), >1/month; <1 drink/day = 0.7 (0.5-0.9), 1-2/day = 0.8 (0.6-1.1), 3-5/day = 1.0 (0.6-1.5), 6+/day = 1.9 (1.0-3.5). Relationships to alcohol were similar for subarachnoid (31% of HS) or intracerebral hemorrhage (69% of HS) and in men or women. Beverage choice (wine, beer, and liquor) was not independently related. We conclude that only heavy drinking is weakly related to increased HS risk and that light drinking need not be proscribed with respect to HS risk.


Determination of H2O2 Generation by pHPA Assay.
The production of reactive oxygen species, including H2O2, is a process that can be used in signaling, cell death, or immune response. To quantify oxidative stress in cells, a fluorescence technique has been modified from a previously described method to measure H2O2 release from cells (1-5). This assay takes advantage of H2O2-mediated oxidation of horseradish peroxidase (HRP) to Complex I, which, in turn, oxidizes p-hydroxyphenylacetic acid (pHPA) to a stable, fluorescent pHPA dimer (2,2'-dihydroxy-biphenyl-5,5' diacetate [(pHPA)2]). The H2O2-dependent HRP-mediated oxidation of pHPA is a sensitive and specific assay for quantifying H2O2 release from cells. This assay can measure H2O2 release from whole cells, mitochondria, or the NADPH oxidase.


COVID-19 Testing in African American Churches Using a Faith-Health- Academic Partnership.
Increasing access to COVID-19 testing in influential, accessible community settings is needed to address COVID-19 disparities among African Americans. We describe COVID-19 testing intervention approaches conducted in Kansas City, Missouri, African American churches via a faith-health-academic partnership. Trained faith leaders promoted COVID-19 testing with church and community members by implementing multilevel interventions using a tailored toolkit and standard education information. The local health department conducted more than 300 COVID-19 tests during or after Sunday church services and outreach ministry activities. (Am J Public Health. 2022;112(S9):S887-S891. https://doi.org/10.2105/AJPH.2022.306981).