Microtubule regulation of cell surface receptor topography during granulosa cell differentiation.
A possible role for cytoplasmic microtubules in modulating lectin binding site topography has been examined during the hormone-directed differentiation of rat ovarian granulosa cells in vitro. Indirect immunofluorescence staining with anti-tubulin antibodies indicates that undifferentiated cultured granulosa cells contain a network of microtubules which radiate from the cell center to the cell periphery. Cultures induced to differentiate by a three day treatment with 1 microgram/ml prolactin exhibit a marginal distribution of microtubules and a centrally-located primary cilium. Prolactin enhances the incidence of granulosa cells containing a primary cilium from 9% in undifferentiated cultures to 53% in hormone-treated cultures. The pattern of lectin binding site redistribution induced by Concanavalin A (Con A) is also modified by prolactin treatment. In contrast to undifferentiated cells, which randomly endocytose fluorescein Con A, granulosa cells exposed to prolactin respond to fluorescein Con A by forming central surface caps to a greater extent (75%) than undifferentiated controls (25%). Double label fluorescence microscopy and transmission electron microscopy on Con A labeled cells show that caps form at central cell surface sites which contain the primary cilium. Disruption of cytoplasmic microtubules by colchicine, in undifferentiated granulosa cells, results in the formation of cell surface caps upon Con A addition. These data suggest that cytoplasmic microtubules modulate the topography of lectin bindings sites which is subject to hormonal control during the in vitro differentiation of ovarian granulosa cells.


Modeling intercellular interactions during carcinogenesis.
By modulating the microenvironment of malignant or premalignant cells, inhibitory or stimulatory signals from nearby cells can play a key role in carcinogenesis. However, current commonly used quantitative models for induction of cancers by ionizing radiation focus on single cells and their progeny. Intercellular interactions are neglected or assumed to be confined to unidirectional radiation bystander effect signals from cells of the same tissue type. We here formulate a parsimoniously parameterized two-stage logistic (TSL) carcinogenesis model that incorporates some effects of intercellular interactions during the growth of premalignant cells. We show that for baseline tumor rates, involving no radiation apart from background radiation, this TSL model gives acceptable fits to a number of data sets. Specifically, it gives the same baseline hazard function, using the same number of adjustable parameters, as does the commonly used two-stage clonal expansion (TSCE) model, so it is automatically applicable to the many data sets on baseline cancer that have been analyzed using the TSCE model. For perturbations of baseline rates due to radiation, the models differ. We argue from epidemiological and laboratory evidence, especially results for the atomic bomb survivors, that for radiation carcinogenesis the TSL model gives results at least as realistic as the TSCE or similar models, despite involving fewer adjustable parameters in many cases.


[Properties of free and bound glycolytic enzymes from scorpionfish brain. II. Lactate dehydrogenase].
It is known that a part of lactate dehydrogenase in animal tissues is bound to the structural elements. However, if in the tissues of higher animals this part is insignificant, in fish tissues it can make tens of percent. The work is the continuation of a series of experiments on the comparative characteristic of the free and bound glycolytic enzymes in fish tissues, in this case-brain of the sea teleost scorpion fish. It was found that the sensitivity of LDH activity to different pH values and to the inhibition by high pyruvate concentrations were different for the both forms. The enzyme affinity for pyruvate and NADH was 4-6 times lower in free enzyme. Possible physiological significance of bound LDH form existence in the energy supply of the brain is discussed.


Depressor responses to L-proline microinjected into the rat ventrolateral medulla are mediated by ionotropic excitatory amino acid receptors.
The essential amino acid L-proline produces a depressor response when microinjected into the caudal ventrolateral medulla (CVLM) of anesthetized rats. L-proline may activate some excitatory amino acid (EAA) receptors. The present study tested this hypothesis by investigating the effects of two ionotropic excitatory amino acid receptor antagonists on the depressor response to L-proline in the CVLM: the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the N-methyl-D-aspartate (NMDA) receptor-selective antagonist MK801. Urethane-anesthetized rats received arterial catheters and their ventrolateral medulla surface was exposed. Injections of the antagonists CNQX and MK801 (2 mM, 68 nl in each case) into the CVLM completely blocked depressor responses to subsequent administration of AMPA (2 pmol/34 nl) and NMDA (2 pmol/34 nl), respectively. The depressor response to L-proline (3.4 nmol/34 nl) was strongly inhibited by prior injection of CNQX (2 mM, 68 nl) and significantly attenuated by prior injection of a high dose (20 mM, 68 nl), but not a low dose (2 mM, 68 nl), of MK801. The results indicate that the depressor response to L-proline in the CVLM includes mechanisms of ionotropic excitatory amino acid receptors.


Activity of FoxP2-positive neurons correlate with tadpole begging behavior.
Motor function is a critical aspect of social signaling in a wide range of taxa. The transcription factor FoxP2 is well studied in the context of vocal communication in humans, mice, and songbirds, but its role in regulating social signaling in other vertebrate taxa is unclear. We examined the distribution and activity of FoxP2-positive neurons in tadpoles of the mimetic poison frog (Ranitomeya imitator). In this species, tadpoles are reared in isolated plant nurseries and are aggressive to other tadpoles. Mothers provide unfertilized egg meals to tadpoles that perform a begging display by vigorously vibrating back and forth. We found that FoxP2 is widely distributed in the tadpole brain and parallels the brain distribution in mammals, birds, and fishes. We then tested the hypothesis that FoxP2-positive neurons would have differential activity levels in begging or aggression contexts compared to non-social controls. We found that FoxP2-positive neurons showed increased activation in the striatum and cerebellum only during begging. Overall, this work suggests a generalizable role for FoxP2 in social signaling across terrestrial vertebrates.


A route to drastic increase of CO2 uptake in Zr metal organic framework UiO-66.
CO2 uptake in zirconium MOF UiO-66 almost doubles with post-synthetic exchange of Zr by Ti. This was due to smaller pore size and higher adsorption enthalpy, with good complementarity between experiment and simulation. Furthermore, the full effect is obtained with ~50% Ti loading, precluding the need to fully substitute frameworks for CO2 capture.


Evaluation of factors during OGTT to correlate insulin resistance in non-diabetic subjects.
The correlation between various factors obtained during oral glucose tolerance tests (OGTT) and insulin sensitivity tests (steady state plasma glucose, SSPG method) were analyzed in non-diabetic subjects by Pearson's simple correlation. Similar data were obtained for normal as well as normal and impaired glucose tolerance (IGT) subjects. Three factors (AUCI(120)0AUCG(120)0, AUCI(120)0 and AUCI(120)60, area of under curve (AUC), insulin (I), glucose (G)) were found to have significant correlation (r=0.47-0.54) with SSPG, thus indicating insulin resistance. Those with hyperinsulinemia were noted to have insulin resistance with high precision (98%), but insulin resistant subjects without hyperinsulinemia were all judged to have normal sensitivity. These three factors all had high specificity (98%), but low sensitivity (21-25%) with false negative results being obtained in 75-78%, and false positive results in less than 2%. It was difficult to distinguish positive and negative for the insulin resistance by receiver operating characteristic (ROC) curve of I0G0. The sensitivity of which was 12.8% and specificity 93.8%. By ROC curve, the specificities and sensitivities for the proposed factors, including homeostatic model assessment (HOMA) product (I0G0, I0-120, G0-120, insulin and glucose at 0-120' during OGTT) ranged from 60 to 70%, which is far from an acceptable level of 90% or more. Therefore, these factors were useful to correlate insulin sensitivity with OGTT results in hyperinsulinemic subjects or in general non-diabetic subjects, but less useful when it came to identifying individual cases with insulin resistance. These parameters should be used only in non-diabetic subjects and their significance is thought to be restricted to cases with hyperinsulinemia.


Cytotoxicity of the field lampricide 3-trifluoromethyl-4-nitrophenol (TFM) in tadpole cell lines from North American frogs.
The common field lampricide, 3-trifluoromethyl-4-nitrophenol (TFM), is used to treat streams and creeks infested with highly invasive and destructive sea lamprey (Petromyzon marinus) in the tributaries of the Great Lakes. Unfortunately, amphibian deaths have been reported following stream treatments with TFM. Larval amphibians (tadpoles) are more susceptible to TFM toxicity than adult amphibians. The aim of this study was to test the toxicity of TFM in eight new tadpole cell lines from the green frog (Lithobates clamitans), wood frog (Lithobates sylvaticus), and American toad (Anaxyrus americanus). A cell viability bioassay using two fluorescent dyes, Alamar Blue and CFDA-AM, was performed following 24-h and 72-h exposures to a range of TFM concentrations. In general, TFM exposure reduced Alamar Blue fluorescence more rapidly than CFDA-AM fluorescence in tadpole cells, suggesting that Alamar Blue is perhaps a better diagnostic indicator of cell health for acute TFM cytotoxicity. At present, the in vivo 96-h LC50s of TFM are only available for L. clamitans and they correlated well with the in vitro EC50 values for the green frog tadpole cell lines in this study. The eight tadpole cell lines with different relative sensitivities to TFM cytotoxicity could prove to be useful tools in assessing next-generation lampricides in high-throughput bioassays to ensure safety in frogs before their sea lamprey-targeted application in the field.


A new species of Euzonus (Polychaeta: Opheliidae) from subtidal zones in Japan.
A new opheliid polychaete, Euzonus japonicus sp. nov., is described. This species was collected from subtidal zones in Japanese coasts, while most Euzonus species inhabit intertidal sandy beaches. E. japonicus sp. nov. is morphologically most similar to another subtidal species, E. flabelliferus (Ziegelmeier, 1955) collected from northern Europe, but different from that in the form of branchiae. They share a unique characteristic on setiger 10, i. e., a pair of lateral transverse rows of conical cirri, instead of a pair of lateral smooth ridges that are common to all intertidal Euzonus species.


RFQAmodel: Random Forest Quality Assessment to identify a predicted protein structure in the correct fold.
While template-free protein structure prediction protocols now produce good quality models for many targets, modelling failure remains common. For these methods to be useful it is important that users can both choose the best model from the hundreds to thousands of models that are commonly generated for a target, and determine whether this model is likely to be correct. We have developed Random Forest Quality Assessment (RFQAmodel), which assesses whether models produced by a protein structure prediction pipeline have the correct fold. RFQAmodel uses a combination of existing quality assessment scores with two predicted contact map alignment scores. These alignment scores are able to identify correct models for targets that are not otherwise captured. Our classifier was trained on a large set of protein domains that are structurally diverse and evenly balanced in terms of protein features known to have an effect on modelling success, and then tested on a second set of 244 protein domains with a similar spread of properties. When models for each target in this second set were ranked according to the RFQAmodel score, the highest-ranking model had a high-confidence RFQAmodel score for 67 modelling targets, of which 52 had the correct fold. At the other end of the scale RFQAmodel correctly predicted that for 59 targets the highest-ranked model was incorrect. In comparisons to other methods we found that RFQAmodel is better able to identify correct models for targets where only a few of the models are correct. We found that RFQAmodel achieved a similar performance on the model sets for CASP12 and CASP13 free-modelling targets. Finally, by iteratively generating models and running RFQAmodel until a model is produced that is predicted to be correct with high confidence, we demonstrate how such a protocol can be used to focus computational efforts on difficult modelling targets. RFQAmodel and the accompanying data can be downloaded from http://opig.stats.ox.ac.uk/resources.


Translational Pharmacology of the Metabotropic Glutamate 2 Receptor-Preferring Agonist LY2812223 in the Animal and Human Brain.
LY2812223 [(1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid] was identified via structure-activity studies arising from the potent metabotropic glutamate mGlu2/3 receptor agonist LY354740 [(+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid] as an mGlu2-preferring agonist. This pharmacology was determined using stably transfected cells containing either the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human postmortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies. A guanosine 5'-O-(3-[35S]thio)triphosphate (GTPγS) functional binding assay, a method for measuring Gi-coupled signaling that is inherent to the group 2 mGlu receptors, was used to evaluate LY2812223 pharmacology of native mGlu receptors in mouse, rat, nonhuman primate, and human cortical brain tissue samples. In native tissue membranes, LY2812223 unexpectedly acted as a partial agonist across all species tested. Activity of LY2812223 was lost in cortical membranes collected from mGlu2 knockout mice, but not those from mGlu3 knockout mice, providing additional support for mGlu2-preferring activity. Other signal transduction assays were used for comparison with the GTP binding assay (cAMP, calcium mobilization, and dynamic mass redistribution). In ectopic cell line-based assays, LY2812223 displayed near maximal agonist responses at the mGlu2 receptor across all assay formats, while it showed no functional agonist activity at the mGlu3 receptor except in the cAMP assay. In native brain slices or membranes that express both mGlu2 and mGlu3 receptors, LY2812223 displayed unexpected partial agonist activity, which may suggest a functional interplay between these receptor subtypes in the brain.


Assessing post-abortion care in health facilities in Afghanistan: a cross-sectional study.
Complications of abortion are one of the leading causes of maternal mortality worldwide, along with hemorrhage, sepsis, and hypertensive diseases of pregnancy. In Afghanistan little data exist on the capacity of the health system to provide post-abortion care (PAC). This paper presents findings from a national emergency obstetric and neonatal care needs assessment related to PAC, with the aim of providing insight into the current situation and recommendations for improvement of PAC services. A national Emergency Obstetric and Neonatal Care Needs Assessment was conducted from December 2009 through February 2010 at 78 of the 127 facilities designated to provide emergency obstetric and neonatal care services in Afghanistan. Research tools were adapted from the Averting Maternal Death and Disability Program Needs Assessment Toolkit and national midwifery education assessment tools. Descriptive statistics were used to summarize facility characteristics, and linear regression models were used to assess the factors associated with providers' PAC knowledge and skills. The average number of women receiving PAC in the past year in each facility was 244, with no significant difference across facility types. All facilities had at least one staff member who provided PAC services. Overall, 70% of providers reported having been trained in PAC and 68% felt confident in their ability to perform these services. On average, providers were able to identify 66% of the most common complications of unsafe or incomplete abortion and 57% of the steps to take in examining and managing women with these complications. Providers correctly demonstrated an average of 31% of the tasks required for PAC during a simulated procedure. Training was significantly associated with PAC knowledge and skills in multivariate regression models, but other provider and facility characteristics were not. While designated emergency obstetric facilities in Afghanistan generally have most supplies and equipment for PAC, the capacity of healthcare providers to deliver PAC is limited. Therefore, we strongly recommend training all skilled birth attendants in PAC services. In addition, a PAC training package should be integrated into pre-service medical education.


The Enhancing Oncology Model: Leveraging improvement science to increase health equity in value-based care.
The Oncology Care Model (OCM), launched in 2016 by the Centers for Medicare and Medicaid Services, was the first demonstration of value-based payment in oncology. Although the OCM delivered mixed results in terms of quality of care and total episode costs, the model had no statistically significant impact on remediating racial, ethnic, and socioeconomic disparities among beneficiaries. These deficits have been prominent in other aspects of US healthcare, and as a result, the Institute for Healthcare Improvement has advocated for stakeholders to leverage improvement science, an applied science that focuses on implementing rapid cycles for change, to identify and overcome barriers to health equity. With the announcement of the new Enhancing Oncology Model, a continuation of the OCM's efforts in introducing value to cancer care for episodes surrounding chemotherapy administration, both policymakers and providers must apply tenets of improvement science and make eliminating disparities in alternative payment models a forefront objective. In this commentary, we discuss previous inequities in alternative payment models, the role that improvement science plays in addressing health-care disparities, and steps that stakeholders can take to maximize equitable outcomes in the Enhancing Oncology Model.


Laboratory evaluation of the antiphospholipid syndrome.
The antiphospholipid syndrome (APS) was first described in 1986. The original association of this hypercoagulable state with anticardiolipin antibodies (aCL) resulted from the synthesis of evidence stemming from laboratory findings in systemic lupus erythematosus (SLE), ie, the frequent occurrence of false-positive VDRL tests and the paradoxical observation of the so-called "lupus anticoagulant" (LA), an increase in phospholipid (PL)-dependent clotting times. By the early 1990s, it was clear that a co-factor was involved in the reaction of antibodies to PL (aPL) in SLE patients with secondary APS and that this was a hitherto-obscure protein, beta-2 glycoprotein I (beta2GPI). In the intervening years, it has been established that beta2GPI and other PL-binding proteins such as prothrombin (PT) are relevant antigens in APS and assays for these antigens have been developed, standardized, and applied to subjects with both primary and secondary APS. Measurement and confirmation of LA activity is based on a stepwise approach and should follow the recommendations of the International Society of Thrombosis and Haemostasis. Although antibodies to various PL-binding proteins have been suggested as diagnostic targets for APS, the current (2006) consensus guidelines recognize only LA, aCL, and anti-beta2GPI for the classification of APS.


Characterization of cyclophilin 40: highly conserved protein that directly associates with Hsp90.
Cyclophilin 40 (CyP4O) is a recently identified member of the cyclophilin family that may be a component of unactivated steroid receptor complexes. It consists of an N-half portion that is highly homologous to cyclophilin A and has peptidyl prolyl isomerase (PPIase) activity, and a C-half portion that resembles the C-terminal portion of FKBP52 (FK506 binding protein 52), another component of unactivated steroid receptor complexes. To better understand the structure and functional characteristics of this new class of cyclophilin, we have raised monoclonal antibodies against the C-half portion of human CyP4O. Immunostaining with the antibodies showed its preferential localization in cytoplasm. One antibody cross-reacted with a 45 kDa protein in yeast, suggesting high conservation throughout evolution. A CyP4O-associated protein was isolated from rabbit reticulocyte lysate by means of an affinity resin, and was identified as hsp90. The C-half portion of CyP4O was necessary and sufficient for the interaction.


Trends in Coded Indications for Percutaneous Coronary Interventions in Medicare and the Veterans Affairs After Implementation of Hospital-Level Reporting of Appropriate Use Criteria.
In 2009, the American College of Cardiology and American Heart Association published Appropriate Use Criteria for Coronary Revascularization (AUC) to aid patient selection for percutaneous coronary intervention (PCI). The subsequent decline in inappropriate PCIs was interpreted as a success of AUC. However, there are concerns clinicians reclassify nonacute PCIs to acute indications to fulfill AUC. A longitudinal, observational difference-in-differences analysis was performed using administrative claims from US Department of Veterans Affairs (VA) beneficiaries coenrolled in Medicare and from a national random sample of Medicare beneficiaries, undergoing PCI from September 30, 2009, to December 31, 2013. Non-VA hospitals participating in the American College of Cardiology CathPCI registry began receiving AUC reports in 2011, while VA hospitals did not receive reports, serving as quasiexperimental and control cohorts, respectively. We measured the proportion of PCIs coded for acute myocardial infarction, unstable angina, and nonacute coronary syndrome indications by quarter. There were 87 464 and 30 251 PCIs performed in the Medicare and VA cohorts, respectively. In Medicare, proportion of PCIs coded for acute myocardial infarction and unstable angina changed from 31.9% and 12.6% in quarter 4 2009 to 41.0% and 10.5% in quarter 4 2013, an associated 2.00% (95% CI, 1.56%-2.44%; P<0.001) increase per year in PCIs coded for acute coronary syndrome indications. In the VA, proportion of PCIs coded for acute myocardial infarction and unstable angina changed from 26.5% and 15.7% in quarter 4 2009 to 34.3% and 12.3% in quarter 4 2013, an associated 1.20% (95% CI, 0.56%-1.88%; P=0.001) increase per year in PCIs coded for acute coronary syndrome indications. Difference-in-differences modeling found no statistically significant change in PCI coded for acute indications between Medicare and VA, pre- and post-AUC reporting. After introduction of AUC assessments and reporting, we observed comparable increases in coding for acute myocardial infarction and corresponding decreases in coding for unstable angina and nonacute coronary syndrome indications among national cohorts of Medicare and VA enrollees. The provision of appropriate use reporting did not appear to have a substantial impact on the proportion of PCIs coded for acute indications during this study period.


Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases.
A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role. Adipose tissue was shown to synthesize and secrete adipokines that are pertinent to glucose and lipid homeostasis, as well as inflammation. Importantly, the obesity-induced adipose tissue expansion stimulates a plethora of signals capable of triggering an inflammatory response. These inflammatory manifestations of obese AT have been linked to insulin resistance, metabolic syndrome, and type 2 diabetes, and proposed to evoke obesity-induced comorbidities including cardiovascular diseases (CVDs). A growing body of evidence suggests that metabolic disorders, characterized by AT inflammation and accumulation around organs may eventually induce organ dysfunction through a direct local mechanism. Interestingly, perirenal adipose tissue (PRAT), surrounding the kidney, influences renal function and metabolism. In this regard, PRAT emerged as an independent risk factor for chronic kidney disease (CKD) and is even correlated with CVD. Here, we review the available evidence on the impact of PRAT alteration in different metabolic states on the renal and cardiovascular function. We present a broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT. We also argue that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.


Identification of a Lipid Metabolism-Associated Gene Signature Predicting Survival in Breast Cancer.
Cancer metabolism and specifically lipid metabolism play an important role in breast cancer (BC) progression and metastasis. However, the role of lipid metabolism-associated genes (LMGs) in the prognosis of breast cancer remains unknown. The expression profiles and clinical follow-up information of 1053 BC were downloaded from The Cancer Genome Atlas (TCGA), and metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. Finally, we analyzed the expression, interaction and correlation among the lipid metabolism-associated genes risk model. The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in TCGA, and single-sample gene set enrichment analysis (ssGSEA) shows it is plausible that lipid metabolism is highly correlated with tumor immunity. Lipid metabolism-associated genes may become a new prognostic indicator predicting the survival of BC patients. The prognostic genes (n = 16) may help provide new strategies for tumor therapy.


A novel technique to avoid perforation of the right ventricle by the temporary pacing lead during transcatheter aortic valve implantation.
Cardiac tamponade is a life-threatening complication during transcatheter aortic valve implantation (TAVI), often caused by perforation of the right ventricle (RV) by the temporary pacemaker used for rapid pacing during valve deployment. We aimed to assess the feasibility of performing rapid pacing while maintaining inflation of the pacing lead balloon in the RV during TAVI. Among 749 consecutive patients who underwent TAVI with SAPIEN XT valves between October 2013 and July 2015, 726 treated using rapid pacing with a transvenous balloon-tip lead were enrolled in our study, and were stratified into three groups according to the extent of balloon inflation in the RV as follows: full inflation (n = 100), partial inflation (n = 196), and deflation (n = 430). We compared the following clinical outcomes: pacing lead-related RV perforation, rapid pacing failure, valve malpositioning due to rapid pacing failure, device success, and 30-day mortality. Pacing lead-related RV perforation occurred only in patients in the deflation group (6 cases, 1.4%), but the differences among the groups were not statistically significant (p = 0.13). Rapid pacing failure, but no valve malpositioning, occurred most frequently in patients in the full inflation group (4.0% vs. 0.5% in the other groups, p = 0.004). The rate of device success (> 94%) and the 30-day mortality (2.0%) were similar among the three groups. Partial inflation of the balloon of the pacing lead may reduce the risk of RV perforation without increasing the risk of pacing failure or valve malpositioning.


p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features.
We screened 77 non-small-cell lung cancer (NSCLC) cell lines for mutations of the p53 gene using a single-strand conformation polymorphism (SSCP) assay. We found that 57 cell lines (74%) had mutations of the p53 gene. Three cell lines had a deletion of the p53 gene. Of the remaining 54 cell lines, 49 cell lines were sequenced and 52 mutations were confirmed. In contrast to previously published p53 mutations in other human tumors, the p53 gene mutations in NSCLC were diverse with regard to the location and nature of the mutations. The region corresponding to codons 144-166, which is outside the evolutionarily conserved regions, was a frequent site of p53 gene mutations in NSCLC. The presence of a p53 gene mutation was not associated with age, sex, histological types, culture site, treatment intent, presence of prior cytotoxic treatment, neuroendocrine differentiation, median culture time or patient survival. The prevalence of p53 mutations in cell lines with ras mutations did not differ from that in cell lines without ras mutations. However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene. We conclude that p53 and ras mutations are frequent and apparently independent genetic alterations which play different roles in the pathogenesis, progression and prognosis of NSCLC.


Effect of blocking Rac1 expression in cholangiocarcinoma QBC939 cells.
Cholangiocarcinomas (CCs) are malignant tumors that originate from epithelial cells lining the biliary tree and gallbladder. Ras correlative C3 creotoxin substrate 1 (Rac1), a small guanosine triphosphatase, is a critical mediator of various aspects of endothelial cell functions. The objective of the present investigation was to study the effect of blocking Rac1 expression in CCs. Seventy-four extrahepatic CC (ECC) specimens and matched adjacent normal mucosa were obtained from the Department of Pathology, Inner Mongolia Medicine Hospital, between 2007 and 2009. Our results showed that the expression of Rac1 was significantly higher (53.12%) in tumor tissues than in normal tissues. Western blotting data indicated a significant reduction in Rac1-miRNA cell protein levels. Rac1-miRNA cell growth rate was significantly different at 24, 48, and 72 h after transfection. Flow cytometry analysis showed that Rac1-miRNA cells undergo apoptosis more effectively than control QBC939 cells. Blocking Rac1 expression by RNAi effectively inhibits the growth of CCs. miRNA silencing of the Rac1 gene suppresses proliferation and induces apoptosis of QBC939 cells. These results suggest that Rac1 may be a new gene therapy target for CC. Blocking Rac1 expression in CC cells induces apoptosis of these tumor cells and may thus represent a new therapeutic approach.


Functional Characterization of a Dendrobium officinale Geraniol Synthase DoGES1 Involved in Floral Scent Formation.
Floral scent is a key ornamental trait that determines the quality and commercial value of orchids. Geraniol, an important volatile monoterpene in orchids that attracts pollinators, is also involved in responses to stresses but the geraniol synthase (GES) responsible for its synthesis in the medicinal orchid Dendrobium officinale has not yet been identified. In this study, three potential geraniol synthases were mined from the D. officinale genome. DoGES1, which was localized in chloroplasts, was characterized as a geraniol synthase. DoGES1 was highly expressed in flowers, especially in petals. DoGES1 transcript levels were high in the budding stage of D. officinale flowers at 11:00 a.m. DoGES1 catalyzed geraniol in vitro, and transient expression of DoGES1 in Nicotiana benthamiana leaves resulted in the accumulation of geraniol in vivo. These findings on DoGES1 advance our understanding of geraniol biosynthesis in orchids, and lay the basis for genetic modification of floral scent in D. officinale or in other ornamental orchids.


Interaction between fenbendazole and piperonyl butoxide: pharmacokinetic and pharmacodynamic implications.
The effect of the cytochrome P450 inhibitor, piperonyl butoxide on the pharmacokinetics and anthelmintic efficacy of the benzimidazole compound fenbendazole was studied in sheep and goats. Pretreatment of goats with the inhibitor caused a greater than three-fold increase in the relative bioavailability of fenbendazole and fenbendazole sulphoxide. A pharmacokinetic dose titration study was carried out in sheep with fenbendazole (5 mg kg-1) and piperonyl butoxide administered orally at 0, 15, 31, 63, 125 and 250 mg kg-1. The AUC of fenbendazole and the sulphoxide were significantly increased when fenbendazole was co-administered with piperonyl butoxide at dose rates equal to or higher than 31 mg kg-1. Peak plasma concentrations (Cmax) and mean residence time (MRT) were also significantly increased. The efficacy of the combination was assessed in sheep against two species of benzimidazole-resistant abomasal nematodes; Ostertagia circumcincta and Haemonchus contortus. The percentage reduction in the total number of O. circumcincta worms was 7.9% (fenbendazole) and 97.8% (fenbendazole-piperonyl butoxide). For H. contortus, the percentage reduction was 84.8% (fenbendazole) and 99.0% (fenbendazole-piperonyl butoxide). The in-vitro S-oxidation of fenbendazole and fenbendazole sulphoxide was studied using microsomal preparations from rat liver. Piperonyl butoxide inhibited significantly the sulphoxidation and sulphonation of fenbendazole. It was concluded that piperonyl butoxide inhibited the oxidative conversion of fenbendazole into inactive metabolites and this resulted in a potentiated anthelmintic action.


Passive geoacoustic inversion with a single hydrophone using broadband ship noise.
An inversion scheme is proposed, relying upon the inversion of the noise of a moving ship measured on a single distant hydrophone. The spectrogram of the measurements exhibits striations which depend on waveguide parameters. The periodic behavior of striations versus range are used to estimate the differences of radial wavenumber between couples of propagative modes at a given frequency. These wavenumber differences are stacked for several frequencies to form the relative dispersion curves. Such relative dispersion curves can be synthesized using a propagation model feeded with a bottom geoacoustic model. Inversion is performed by looking for the bottom properties that optimize the fit between measured and predicted relative dispersion curves. The inversion scheme is tested on simulated data. The conclusions are twofold: (1) a minimum 6 dB signal to noise ratio is required to obtained an unbiased estimate of compressional sound speed in the bottom with a 3 m s(-1) standard deviation; however, even with low signal to noise ratio, the estimation error remains bounded and (2) in the case of a multi-layer bottom, the scheme produces a single depth-average compressional sound speed. The inversion scheme is applied on experimental data. The results are fully consistent with a core sample measured around the receiving hydrophone.


Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population.
Diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined. Three groups of subjects were studied: normal subjects, suspected and proven Cushing's syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden's J index. We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing's syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing's syndrome group. The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing's syndrome (0.6798 ± 0.52 μg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity and specificity. Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism.


An exploration of angiotensin-converting enzyme (ACE) inhibitory peptides derived from gastrointestinal protease hydrolysate of milk using a modified bioassay-guided fractionation approach coupled with in silico analysis.
An improved bioassay-guided fractionation was performed to effectively screen angiotensin-I converting enzyme inhibitory (ACEI) peptides from milk protein hydrolysate. The aqueous normal phase liquid chromatography, namely hydrophilic interaction liquid chromatography (HILIC), was used as a format of solid-phase extraction (SPE) short column for the first fractionation, then the HILIC-SPE fraction with the best ACEI activity (IC50 = 61.75 ± 5.74 µg/mL; IC50 = half-maximal inhibitory concentration) was obtained when eluted by 95% acetonitrile + 0.1% formic acid (fraction F1). The best HILIC-SPE fraction was further fractionated using reversed-phase (RP)-SPE short column. The best RP-SPE fraction was obtained when eluted by 20% acetonitrile + 0.1% formic acid (fraction P3) with an ACEI activity of IC50 36.22 ± 1.18 µg/mL. After the 2-step fractionation, the IC50 value of fraction P3 significantly decreased by 8.92-fold when compared with the crude hydrolysate. Several peptides were identified from fraction P3 using liquid chromatography-tandem mass spectrometry. The in silico analysis of these identified sequences based on the BIOPEP database predicted that HLPLPLL (HL-7) was the most active peptide against angiotensin-converting enzyme (ACE). The HL-7 derived from β-casein showed a potent ACEI activity (IC50 value is 16.87 ± 0.3 µM). The contents of HL-7 in the gastrointestinal protease hydrolysate and RP-SPE fraction originated from 1 mg of milk proteins were quantified using a multiple reaction monitoring mode upon liquid chromatography-tandem mass spectrometry analysis to give 19.86 ± 1.14 pg and 14,545.8 ± 572.9 pg, respectively. Besides, the kinetic study indicated that HL-7 was a competitive inhibitor and the result was rationalized using the docking simulation. The study demonstrated an efficient screening of ACEI peptides from commercially available milk powders using a simple SPE process instead of a sophisticated instrument such as HPLC. Moreover, the potent ACEI peptide HL-7 uncovered by this method could be a natural ACE inhibitor.


Donor nephrectomy with and without preservation of gonadal vein while dissecting the ureter.
Preservation of the gonadal vein while dissecting the ureter for donor nephrectomy may decrease the distal ureteral ischemia and urological complications in kidney transplant recipients. In this study, we compared the outcome of kidney allografts harvested with preservation of the gonadal vein while dissecting the ureter with allografts harvested without preserving the gonadal vein. We reviewed 167 consecutive kidney transplantations between April 2003 and April 2004. During donor nephrectomy, we preserved the gonadal vein in 106 harvested kidneys (group 1), while we did not preserve this vein in 61 allografts (group 2). The recipients in each group were followed up for a 2-year follow-up on average, and the outcomes including ureteral complications, graft loss, and patient and graft survival were compared between the two groups. Urine leakage was noted in few patients (2 in group 1 and 3 in group 2) and its frequency was not significantly different between the two groups (P = .26). Ureteral stricture was not seen in any of the kidney allograft recipients. No differences were found in the frequencies of acute rejection episodes, graft loss, and death between the two groups. Preservation of the gonadal veins did not significantly decrease the frequency of ureteral complications in the kidney transplant recipients. We recommend meticulous handling of the ureter in donor nephrectomies to prevent further remote complications regardless of the approach to the gonadal veins while nephrectomy.


Anti-stokes fluorescence of phycobilisome and its complex with the orange carotenoid protein.
Phycobilisomes (PBSs) are giant water-soluble light-harvesting complexes of cyanobacteria and red algae, consisting of hundreds of phycobiliproteins precisely organized to deliver the energy of absorbed light to chlorophyll chromophores of the photosynthetic electron-transport chain. Quenching the excess of excitation energy is necessary for the photoprotection of photosynthetic apparatus. In cyanobacteria, quenching of PBS excitation is provided by the Orange Carotenoid Protein (OCP), which is activated under high light conditions. In this work, we describe parameters of anti-Stokes fluorescence of cyanobacterial PBSs in quenched and unquenched states. We compare the fluorescence readout from entire phycobilisomes and their fragments. The obtained results revealed the heterogeneity of conformations of chromophores in isolated phycobiliproteins, while such heterogeneity was not observed in the entire PBS. Under excitation by low-energy quanta, we did not detect a significant uphill energy transfer from the core to the peripheral rods of PBS, while the one from the terminal emitters to the bulk allophycocyanin chromophores is highly probable. We show that this direction of energy migration does not eliminate fluorescence quenching in the complex with OCP. Thus, long-wave excitation provides new insights into the pathways of energy conversion in the phycobilisome.


Chemokines, osteopontin, ICAM-1 gene expression in cultured rat mesangial cells.
To investigate whether MCP-1, CINC, RANTES, osteopontin and ICAM-1 mRNA could be induced in cultured rat mesangial cells by interleukin-1beta(IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), and whether MCP-1 and CINC gene expression could be modulated by dexamethasone, Northern blot assays were performed. IL-1beta induced MCP-1, CINC, RANTES and ICAM-1 gene expression in a time dependent manner. IL-1beta-induced MCP-1, CINC and ICAM-1 mRNA amount were maximal at 3 hours exposure around 14.5, 15.7, 2.2 folds increase and IL-1beta-induced RANTES mRNA at 24 hours around 2.0 folds. TNF-alpha and LPS also induced MCP-1 and ICAM-1 gene expression. TNF-alpha also induced RANTES gene expression but LPS did not. On the other hand, IL-1beta, TNF-alpha and LPS had little effect on osteopontin gene expression but fetal calf serum could increase osteopontin mRNA. Dexamethasone suppressed the IL-1beta-induced MCP-1 and CINC mRNA. These results suggest that, through these gene expressions, mesangial cells are able to communicate directly or indirectly with macrophages or neutrophils, which may lead to glomerulosclerosis.


[Principles of orientation safety body dialogue (O.S.B.D) for primary intervention for acute stress events].
Acute stress reaction (ASR) is related to a serious threat to the security or wellness of the individual physical being, or someone close to him/her. The incidence of ASR is predominant in the Israeli population, who in the last decade, are particularly exposed to terrorist or war-like events that often lead to many both physical and/or emotional casualties being referred to the Emergency Rooms or primary care clinics, necessitating expert professional intervention. These emotional victims are "anxiety casualties". In this article, the authors present basic principles and intervention procedures, which do not require extensive training for the professionals involved and can be implemented quickly and relatively simply in the treatment of these cases. The authors chose the acronym OSBD (in Hebrew these are the first ABCD letters) that reflect the four principles, O-orientation, S-security, B-body, D-dialogue. In this article, this concept is developed in the hope that these procedures will be both of practical value and available to those professionals in the Emergency Rooms, immediately after the patient is released into the primary care system.


Electron beam energy QA - a note on measurement tolerances.
Monthly QA is recommended to verify the constancy of high-energy electron beams generated for clinical use by linear accelerators. The tolerances are defined as 2%/2 mm in beam penetration according to AAPM task group report 142. The practical implementation is typically achieved by measuring the ratio of readings at two different depths, preferably near the depth of maximum dose and at the depth corresponding to half the dose maximum. Based on beam commissioning data, we show that the relationship between the ranges of energy ratios for different electron energies is highly nonlinear. We provide a formalism that translates measurement deviations in the reference ratios into change in beam penetration for electron energies for six Elekta (6-18 MeV) and eight Varian (6-22 MeV) electron beams. Experimental checks were conducted for each Elekta energy to compare calculated values with measurements, and it was shown that they are in agreement. For example, for a 6 MeV beam a deviation in the measured ionization ratio of ± 15% might still be acceptable (i.e., be within ± 2 mm), whereas for an 18 MeV beam the corresponding tolerance might be ± 6%. These values strongly depend on the initial ratio chosen. In summary, the relationship between differences of the ionization ratio and the corresponding beam energy are derived. The findings can be translated into acceptable tolerance values for monthly QA of electron beam energies.


[Use of radio-immuno-assay of gonadotropic hormones in farm animals (author's transl)].
The determination of the concentration of gonadotropic hormones in the peripheral plasma of farm animals by radio-immuno-assay is described. Particular attention was paid to the determination of ovine, bovine and porcine LH using an anti-ovine-LH serum. This serum was found to be specific for LH, and there was no cross-reaction with FSH. Cross-reactions with TSH cannot be ruled out. The usefulness of this antiserum was tested in studying the release of LH during oestrus (in sheep), after injection of LH-RH (in cattle and pigs) and after weaning (in pigs). The results are in accordance with those reported in the literature.


Obsessive-Compulsive Disorder.
This article reviews current knowledge regarding diagnosis, pathophysiology, and treatment trends in obsessive-compulsive disorder (OCD), a severe, underrecognized, and chronic condition frequently encountered in neurologic practice. With a lifetime prevalence estimated at 2.5%, OCD is a common condition that can also present comorbidly with neurologic disease. The core symptoms of OCD are obsessions and compulsions. Obsessions are intrusive repetitive thoughts, urges, images, or impulses that trigger anxiety and that the individual is not able to suppress. Compulsions are repetitive behaviors or mental acts occurring in response to an obsession with the intention of reducing the distress caused by obsessions. Neuroimaging, neuropsychological, and pharmacologic studies suggest that the expression of OCD symptoms is associated with dysfunction in a cortico-striato-thalamo-cortical circuit. Evidence-based treatments for OCD comprise pharmacotherapy and cognitive-behavioral therapy. Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs recommended for OCD, but significant differences exist in their use for OCD compared to their use for other mood and anxiety conditions, including the need for higher dosage, longer trials necessitated by a longer lag for therapeutic response, and typically lower response rates. Cognitive-behavioral therapy, based on the principles of exposure and response prevention, shows results superior to pharmacologic treatments with lower relapse rates on long-term follow-up and thus should be considered in the treatment plan of every patient with OCD. OCD and obsessive-compulsive symptoms are frequently encountered in the neurologic clinic setting and require a high index of suspicion to effectively screen for them and an illness-specific therapeutic approach.


Managing breastfeeding and work: a Foucauldian secondary analysis.
This paper is a report of a secondary analysis of the experiences of employed breastfeeding mothers. Health promotion policies exhort mothers to feed their infants breastmilk exclusively for the first 6 months and partially until the age of 2 years. More mothers are returning to paid employment less than a year after having a baby. Combining breastfeeding and paid work is an issue for nursing and midwifery as predominantly female professions caring for women and their children. Foucauldian discourse analysis was used for a secondary analysis of interviews performed in 2005 with 20 women who continued to breastfeed on their return to work. The discursive positions and disciplinary practices were identified and analysed. Combining breastfeeding and paid work required negotiating the positions of good mother and good worker. Being a good mother conferred health benefits on infants. Being a good worker required the mothers to constrain their breastfeeding practices. The practices performed by the mothers involved stockpiling breastmilk, maintaining milk supply, preparing the baby ready for absence, making sacrifices and remaining silent and invisible as a breastfeeding worker. Breastfeeding workers have the potential to threaten the focus of the workplace. They discipline themselves to minimize their disruptive potential. Such strategies serve to maintain the marginalization of breastfeeding in the workplace and to keep women's efforts to continue breastfeeding invisible. The work of breastfeeding workers needs to be better recognized and supported.


Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians' challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men.
The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians' everyday experiences and challenges in recommending HPV vaccination to older GBM patients. As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory. Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians' vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination. Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.


Utility of repeat head computed tomography after blunt head trauma: a systematic review.
Repeat head computed tomography (CT) is standard practice for head-injured patients at many trauma centers. Utilization of CT has increased over time, yet effects on outcome and associated risks are unknown. We systematically reviewed the literature to determine the incidence of progression of injury on repeat CT and resulting treatment changes. Studies were included from Medline, Embase, and a hand search of citations in reviewed articles. Main outcome measures were progression of injury on repeat CT and resulting intervention. Data were abstracted from 30 eligible studies and discrepancies were settled by consensus. Progression of injury on repeat CT was evident in 8 to 67% of patients in the included studies. Neurosurgical intervention resulting subsequent to a repeat CT occurred in 0 to 54% of patients. More severe traumatic brain injury, defined by Glasgow Coma Scale, was associated with a higher proportion of patients with progression of injury on CT and subsequent neurosurgical interventions. Risk factors associated with progression of injury on CT or resulting intervention were inconsistently reported, but coagulopathy and injury severity were most commonly reported. Few studies reported changes in nonsurgical management, in-hospital disposition, or adverse events associated with obtaining repeat CTs. Indications for repeat head CT after traumatic brain injury are unclear. The wide range of reported injury progression on CT and resulting surgical and medical treatment changes suggest there may be a subset of patients who benefit from repeat CT. Further research should stratify by severity of traumatic brain injury, clearly define inclusion and exclusion criteria, address selection bias, quantify progression of injury on CT, determine factors predictive of injury progression and intervention, and assess risks associated with repeat CT.


The role of Aspergillus fumigatus antigens in blood coagulation and platelet function.
The effects of Aspergillus fumigatus antigens on platelet function of rabbits was studied. A. fumigatus antigens produced spontaneous and irreversible aggregation of platelets. Aspirin, indomethacin or lidocaine did not block the antigen-induced aggregation. However, no aggregations occurred when complement depleted plasma was used. No differences were noted between the strains used. Our findings show that soluble Aspergillus antigens can cause platelet aggregation in vitro, possibly via a complement dependent pathway. The likely implications of these findings in clinical situations are discussed.


Resistant hypertension and renal sympathetic denervation--what does the future hold?
Hypertension is a major public health problem and despite adequate pharmacological treatment, blood pressure remains uncontrolled in a subset of patients with hypertension. Renal sympathetic denervation is a percutaneous catheter-based treatment for select patients with resistant hypertension. In this article, we discuss the development of this intervention, its role in patients with resistant hypertension and the need for guarded optimism in the future of device-directed renal sympathetic denervation.


Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury.
Neonatal hypoxic-ischemic brain injury remains a significant cause of morbidity and mortality and lacks effective therapies for prevention and treatment. Recently, interest in the biology of polyphenol compounds has led to the discovery that dietary supplementation with foods rich in polyphenols (e.g. blueberries, green tea extract) provides neuroprotection in adult animal models of ischemia and Alzheimer's disease. We sought to determine whether protection of the neonatal brain against a hypoxic-ischemic insult could be attained through supplementation of the maternal diet with pomegranate juice, notable for its high polyphenol content. Mouse dams were provided ad libitum access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water, and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling. At postnatal day 7, pups underwent unilateral carotid ligation followed by exposure to 8% oxygen for 45 min. Brain injury was assessed histologically after 1 wk (percentage of tissue area loss) and biochemically after 24 h (caspase-3 activity). Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60%) in all three brain regions assessed, with the highest pomegranate juice dose having greatest significance (p < or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84% in the hippocampus and 64% in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups. These results demonstrate that maternal dietary supplementation with pomegranate juice is neuroprotective for the neonatal brain.


Longitudinal associations among adolescents' internalizing problems, well-being, and the quality of their relationships with their mothers, fathers, and close friends.
Internalizing problems (i.e., depressive and anxiety symptoms) are known to decrease adolescents' well-being, but knowledge about potential underlying mechanisms is limited. The qualities of adolescents' most proximal relationships with their parents and close friends are expected to play a role in the association between adolescents' internalizing problems and well-being. The present study was conducted to 1) investigate the indirect longitudinal association between internalizing problems and adolescents' well-being via the quality of adolescents' relationships with both their mothers and fathers and their close friends, and 2) test whether our findings were gender invariant. Data were collected via online questionnaires in two waves at a 12-month interval from adolescents attending three secondary schools in the Netherlands (N = 1298; M age = 13.7 years, 53.2% girls). The data were analyzed using a two-wave cross-lagged panel model in R. Multigroup analyses were performed to examine the gender invariance of the findings. After controlling for baseline levels, results showed that (1) girls, but not boys, who reported more internalizing problems at T1 had lower well-being at T2; (2) girls and boys who reported more internalizing problems at T1 had lower-quality relationships with their mothers, fathers, and close friends at T2; and (3) boys, but not girls, who reported higher-quality friendships at T1 had higher well-being at T2. However, no significant indirect effects between internalizing problems and well-being via the quality of adolescents' relationships with their parents and close friends were detected. The current study contributes to understanding internalizing problems as an important risk factor to the quality of adolescents' proximal social relationships (parents, friends) and their well-being. The findings support the importance of building high-quality relationships, particularly friendships, and recommend future research to study adolescents' internalizing problems and well-being including gender-specific examinations.


Model parameters and outbreak control for SARS.
Control of the 2002-2003 severe acute respiratory syndrome (SARS) outbreak was based on rapid diagnosis coupled with effective patient isolation. We used uncertainty and sensitivity analysis of the basic reproductive number R0 to assess the role that model parameters play in outbreak control. The transmission rate and isolation effectiveness have the largest fractional effect on R0. We estimated the distribution of the reproductive number R0 under perfect isolation conditions. The distribution lies in the interquartile range 0.19-1.08, with a median of 0.49. Even though the median of R0 is <1, we found that 25% of our R0 distribution lies at R0 > 1, even with perfect isolation. This implies the need to simultaneously apply more than one method of control.


COHABITATION AND UNION DISSOLUTION IN CENTRAL UGANDA: DIFFERENCES BETWEEN COHABITORS AND NON-COHABITORS.
The aim of this paper was to establish whether the differences in the risks of union dissolution between cohabitors and non-cohabitors in Uganda have converged over time using event history data. Data were collected in 2013 from 1200 women in central Uganda using retrospective methods. Of these, 839 provided information on three types of first union: women who married directly (without first cohabiting), those who married following cohabitation and those who were still cohabiting. The data were analysed using decrement lifetable analysis. Though the analysis indicated a small difference in the timing of first union dissolution for women who married directly, no evidence was found that the difference in the risk of union dissolution between cohabitors and non-cohabitors had converged over the 9-year period following first union. Women's union/marriage status, number of living children in a union, parental union status and birth cohort were found to significantly influence the timing of union dissolution. Overall, the rate of union dissolution was fairly high, regardless of type of union.


A highly infective plant-associated bacterium influences reproductive rates in pea aphids.
Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction.


Profiles of eHealth Adoption in Persons with Multiple Sclerosis and Their Caregivers.
(1) Background: Persons with multiple sclerosis (pwMS) are often characterized as ideal adopters of new digital healthcare trends, but it is worth thinking about whether and which pwMS will be targeted and served by a particular eHealth service like a patient portal. With our study, we wanted to explore needs and barriers for subgroups of pwMS and their caregivers when interacting with eHealth services in care and daily living. (2) Methods: This study comprises results from two surveys: one collecting data from pwMS and their relatives (as informal caregivers) and another one providing information on the opinions and attitudes of healthcare professionals (HCPs). Data were analyzed descriptively and via generalized linear models. (3) Results: 185 pwMS, 25 informal caregivers, and 24 HCPs in the field of MS participated. Nine out of ten pwMS used information technology on a daily base. Individual impairments like in vision and cognition resulted in individual needs like the desire to actively monitor their disease course or communicate with their physician in person. HCPs reported that a complete medication overview, additional medication information, overview of future visits and a reminder of medication intake would be very helpful eHealth features for pwMS, while they themselves preferred features organizing and enriching future visits. (4) Conclusions: A closer look at the various profiles of eHealth adoption in pwMS and their caregivers indicated that there is a broad and robust enthusiasm across several subgroups that does not exclude anyone in general, but constitutes specific areas of interest. For pwMS, the focus was on eHealth services that connect previously collected information and make them easily accessible and understandable.


Exercise-induced asthma: comparison of cromoglycate powder and aerosol four hours before exercise.
To establish whether sodium cromoglycate delivered by pressurised aerosol was more effective than sodium cromoglycate powder in preventing exercise-induced asthma four hours after drug administration, eight subjects known to be protected by sodium cromoglycate taken immediately pre-exercise, underwent delayed exercise challenge following double-blind premedication with sodium cromoglycate powder, sodium cromoglycate aerosol and placebo. The maximum fall in FEV1 induced by exercise four hours after inhaling sodium cromoglycate was modified slightly by sodium cromoglycate powder and by a smaller amount, sodium cromoglycate aerosol, compared with the unpremedicated run, but the calculated protection provided by sodium cromoglycate was not significantly different from that given by placebo. It was concluded that asthmatics should not expect significant suppression of exercise-induced bronchoconstriction four hours after the last dose of either cromoglycate powder or aerosol.


[NSAID demonstrate convincing effect on postoperative pain].
Non-steroidal antiinflammatory drugs (NSAID) are increasingly being included in the management of postoperative pain as part of a multimodal therapeutic approach. However, there is an ongoing debate among clinicians as to the perioperative use of NSAID's as many authors have cautioned against their use in this setting. Concerns about their impact on coagulation and renal function as well as a risk for gastrointestinal bleeding have been raised. However, many of the adverse effects reported have occurred during long term treatment and might not be directly applicable to the perioperative period. Still the clinician must be aware of the potential risks and benefits of these drugs. This review focuses on the pro's and con's of perioperative NSAID usage. We address the background for a multimodal approach to postoperative pain relief as well as potential alternatives to NSAID's and the recently introduced COX2-selective inhibitors.


Mthfd1 is a modifier of chemically induced intestinal carcinogenesis.
The causal metabolic pathways underlying associations between folate and risk for colorectal cancer (CRC) have yet to be established. Folate-mediated one-carbon metabolism is required for the de novo synthesis of purines, thymidylate and methionine. Methionine is converted to S-adenosylmethionine (AdoMet), the major one-carbon donor for cellular methylation reactions. Impairments in folate metabolism can modify DNA synthesis, genomic stability and gene expression, characteristics associated with tumorigenesis. The Mthfd1 gene product, C1-tetrahydrofolate synthase, is a trifunctional enzyme that generates one-carbon substituted tetrahydrofolate cofactors for one-carbon metabolism. In this study, we use Mthfd1(gt/+) mice, which demonstrate a 50% reduction in C1-tetrahydrofolate synthase, to determine its influence on tumor development in two mouse models of intestinal cancer, crosses between Mthfd1(gt/+) and Apc(min)(/+) mice and azoxymethane (AOM)-induced colon cancer in Mthfd1(gt/+) mice. Mthfd1 hemizygosity did not affect colon tumor incidence, number or load in Apc(min/+) mice. However, Mthfd1 deficiency increased tumor incidence 2.5-fold, tumor number 3.5-fold and tumor load 2-fold in AOM-treated mice. DNA uracil content in the colon was lower in Mthfd1(gt/+) mice, indicating that thymidylate biosynthesis capacity does not play a significant role in AOM-induced colon tumorigenesis. Mthfd1 deficiency-modified cellular methylation potential, as indicated by the AdoMet: S-adenosylhomocysteine ratio and gene expression profiles, suggesting that changes in the transcriptome and/or decreased de novo purine biosynthesis and associated mutability cause cellular transformation in the AOM CRC model. This study emphasizes the impact and complexity of gene-nutrient interactions with respect to the relationships among folate metabolism and colon cancer initiation and progression.


Multi-platform segmentation for joint detection of copy number variants.
With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels. Currently, there is still a relative lack of procedures for combining information from different platforms. We develop a method, called MPSS, based on a correlated random-effect model for the unobserved patterns and extend the robust smooth segmentation approach to the multiple-platform scenario. We also propose an objective criterion for discrete segmentation required for downstream analyses. For each identified segment, the software reports a P-value to indicate the likelihood of the segment being a true CNV. From the analyses of real and simulated data, we show that MPSS has better operating characteristics when compared to single-platform methods, and have substantially higher sensitivity compared to an existing multiplatform method. The methods are implemented in an R package MPSS, and the source is available from http://www.meb.ki.se/~yudpaw.


Public health nurses' responses to domestic violence: a report from the Enhanced Domestic Abuse Intervention Project.
Public health nurses (PHNs) can play an important role in the detection of domestic violence. This study examines whether the introduction of a domestic violence assessment protocol by public health nurses in a maternal and child health visiting program increases the identification and referral rates of women experiencing domestic violence. Data collected from case files during the baseline year prior to the initiation of the protocol were compared to case file information after the protocol had been implemented. When the protocol was used, there was a higher rate of identification, although the difference was not statistically significant. Significantly more women, however, were provided with information about domestic violence resources after the protocol was in place, and significantly more women were referred to services in the second year after the protocol had been implemented. This study provides support for the use of a domestic violence protocol to improve the public health nursing response to domestic violence.


Age-Appropriate Formulations Including Pharmaceutical Excipients in Neonatal Medicines.
The development of appropriate pharmaceutical formulations for routine neonatal practice is challenging because of the developmental characteristics and the need for it to be specifically ageappropriate. This has led to wide use of extemporaneous formulations, which lack standardized procedures that can result in medication errors in clinical practice resulting in suboptimal efficacy and safety concerns. We have reviewed the most recent literature on formulations and pharmaceutical excipients. We present the issues related with the lack of age-appropriate formulations, discuss the importance and extent of exposure to pharmaceutical excipients known to be harmful to neonates, indicate ways that can reduce exposure to excipients of concern, and review challenges of the design of age-appropriate drug formulations and dosage forms/drug delivery systems for neonates. Finally, we summarize novel approaches regarding drug delivery for neonates. Novel approaches in age-appropriate drug delivery should overcome the present obstacles and improve the quality of medicines, thus avoiding errors in treatment and improving the management of neonates. Further basic researches on discovering new technologies and modern formulations, using in vitro testing systems as well as preclinical and clinical trials, are needed to improve the feasibility, practicality and safety of new formulations, including research on pharmaceutical excipients.


Isolation and Characterization of Lactic Acid Bacteria from Fermented Goat Milk in Tajikistan.
The lactobacilli associated with a fermented goat milk product from Tajikistan were isolated to characterize their technological properties and antibiotic resistances in order to assess their suitability for development as starter cultures. In this study, twenty three strains were identified by 16S rRNA sequencing as typical dairy-associated lactic acid bacterial strains, i.e. L. plantarum, L. pentosus, L. delbrueckii, L. helveticus and L. paracasei. These strains were generally susceptible to most antibiotics tested in this study and this allowed a selection of strains as safe starters. The draft genomes of four representative strains were sequenced and the number of contigs of the four assembled genomes ranged from 51 to 245 and the genome sizes ranged from 1.75 to 3.24 Mbp. These representative strains showed differences in their growth behavior and pH-reducing abilities in in vitro studies. The co-inoculation of these Lactobacillus spp. strains together with a yeast Kluyveromyces marxianus MBT-5698, or together with the yeast and an additional Streptococcus thermophilus MBT-2, led to a pH reduction to 3.4 after 48 h. Only in the case of fermentation inoculated with the co-culture, the viscosity of the milk increased noticeably. In contrast, fermentations with single strains did not lead to gelation of the milk or to a decrease in the pH after 24h. The results of this study provide a comprehensive understanding of the predominant lactobacilli related to Tajikistani fermented milk products.


Isoform-specific monoclonal antibodies against 3β-hydroxysteroid dehydrogenase/isomerase family provide markers for subclassification of human primary aldosteronism.
Therapeutic management of primary aldosteronism requires accurate differentiation between aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). However, little is known about the molecular features that delineate the difference between APA and IHA. Two different isoforms of 3β-hydroxysteroid dehydrogenase (HSD3B1 and HSD3B2) are thought to be expressed in the human adrenal gland, but the lack of isoform-specific antibody has so far hampered mapping of these isoforms in APA and IHA. The aim of our study is to develop and characterize isoform-specific monoclonal antibodies against HSD3B1 and HSD3B2. Using these antibodies, we determined for the first time the immunolocalization of HSD3B1 and HSD3B2 in normal human adrenal cortex as well as in adrenal specimens from APA and IHA. Immunohistochemical analysis with isoform-specific antibodies revealed zone-specific expression of HSD3B1 and HSD3B2 in the adrenal cortex. HSD3B1 immunoreactivities were essentially confined to the zona glomerulosa (ZG), in which aldosterone is produced. In contrast, HSD3B2 was not confined to the ZG but was found across the zona fasciculata, which is where cortisol is produced. Moreover, immunohistopathological analysis of primary aldosteronism revealed a previously uncharacterized difference between APA and IHA. Notably, hyperplasia of ZG seen for IHA was accompanied by a robust expression of ZG isoform HSD3B1. In contrast, tumor cells in APA were not immunopositive to HSD3B1. Rather, a strong and dominant expression of HSD3B2 characterized APA. Moreover, perhaps due to compensatory responses to excess aldosterone, APA had an adjacent ZG whose immunoreactivities to HSD3B1 and HSD3B2 were profoundly reduced. Isoform-specific monoclonal antibodies against HSD3B1 and HSD3B2 may be of great value for immunohistochemical differentiation between APA and IHA.


Observation of the structural consequences of a reversible S = 3/2 and S = 1/2 spin crossover in the single crystal.
Highly saddle shaped iron(III) porphyrin complex 1 showing a novel spin crossover process between the S = 3/2 and S = 1/2 has been crystallographically analyzed at 298, 180, and 80 K. As the temperature is lowered, the lattice contraction has occurred specifically along the b-axis. Correspondingly, the iron-pyridine bonds, which tilt slightly from the b-axis, have decreased by 7.3%. In contrast, the lattice contractions along the a- and c-axes are much smaller and the iron-porphyrin bonds, which almost coincide with the a- and c-axes, have shown much smaller contraction, ca. 2.2%. The large contraction of the specific bonds caused by packing force raises the energy level of the d(z)2 orbital and induces the spin transition. The detailed structural and lattice changes in the single crystal, which may be regarded as a superstructure parallel to a protein matrix, have been clarified.


Nanostructured antireflective in-plane solar harvester.
In this work, we demonstrate a two-dimensional nano-hole array that can reduce reflection losses while passively trapping and harvesting incident light. The surface structure is designed to scavenge a small portion of incident light that would typically be lost due to Fresnel reflection, while the majority of light transmits unobstructed like a regular window. The trapping mechanism is dependent on angle and wavelength, and can be designed to selectively trap narrow wavelength bands using the constructed theoretical models. We demonstrate that structures with periods of 275 nm and 325 nm can trap different wavelength range within the visible spectrum, while simultaneously suppressing reflection losses. The trapping effect can be observed visually, and can be converted to a current output using a photovoltaic (PV) cell on the glass edge. The fabrication of such materials employs a simple replication process, and can be readily scaled up for large-scale manufacturing. The demonstrated solar harvester can be potentially be widely deployed in residential and commercial buildings as multifunctional windows for solar energy harvesting, scavenging, spectra splitting, and anti-glare properties.


Development and persistence of local and systemic antibody responses in adults given live attenuated or inactivated influenza A virus vaccine.
An enzyme-linked immunosorbent assay was used to measure nasal-wash and serum isotype-specific hemagglutinin antibody responses in 109 seronegative (hemagglutination-inhibiting titer less than or equal to 1:8) adults vaccinated intranasally with live attenuated A/Washington/897/80 (H3N2) or A/California/10/78 (H1N1) cold-adapted (ca) virus or with licensed subvirion vaccine subcutaneously. Live and inactivated virus elicited serum immunoglobulin A (IgA) responses in 83 and 96% of vaccinees, respectively, and elicited serum IgG responses in 72 and 100% of vaccinees. Inactivated virus induced higher titers of serum antibodies than did live virus and stimulated a nasal-wash IgG response more often than did live virus (94 versus 59%, P less than 0.01). In contrast, only 38% of inactivated virus vaccinees had local IgA responses compared with 83% of live virus vaccinees. Serum IgA and IgG and nasal IgG antibody titers remained elevated above prevaccination levels for at least 6 months in most of the live and inactivated vaccine responders, but the mean level of local IgA antibody induced by infection with live virus vaccine, in particular, decreased substantially. Considered in the context of previous work, the finding that live virus vaccine induced relatively long-lasting antibody in both local and serum compartments suggested that this vaccine may be a suitable alternative to inactivated vaccine for use in healthy persons.


STAT3 Establishes an Immunosuppressive Microenvironment during the Early Stages of Breast Carcinogenesis to Promote Tumor Growth and Metastasis.
Immunosurveillance constitutes the first step of cancer immunoediting in which developing malignant lesions are eliminated by antitumorigenic immune cells. However, the mechanisms by which neoplastic cells induce an immunosuppressive state to evade the immune response are still unclear. The transcription factor STAT3 has been implicated in breast carcinogenesis and tumor immunosuppression in advanced disease, but its involvement in early disease development has not been established. Here, we genetically ablated Stat3 in the tumor epithelia of the inducible PyVmT mammary tumor model and found that Stat3-deficient mice recapitulated the three phases of immunoediting: elimination, equilibrium, and escape. Pathologic analyses revealed that Stat3-deficient mice initially formed hyperplastic and early adenoma-like lesions that later completely regressed, thereby preventing the emergence of mammary tumors in the majority of animals. Furthermore, tumor regression was correlated with massive immune infiltration into the Stat3-deficient lesions, leading to their elimination. In a minority of animals, focal, nonmetastatic Stat3-deficient mammary tumors escaped immune surveillance after a long latency or equilibrium period. Taken together, our findings suggest that tumor epithelial expression of Stat3 plays a critical role in promoting an immunosuppressive tumor microenvironment during breast tumor initiation and progression, and prompt further investigation of Stat3-inhibitory strategies that may reactivate the immunosurveillance program.


The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis.
The membrane present at the bone-cement interface was retrieved from twenty patients with a loose, non-septic failed total hip replacement at a site clearly remote from the pseudocapsule that reformed postoperatively. The orientation of the membrane was carefully marked to identify the surface in contact with cement. The membrane was studied histologically, histochemically, by cell culture, by organ culture, and by assessment of its ability to synthesize prostaglandin E2 and collagenase. This membrane, rather than being a nondescript so-called fibrous membrane, has the histological and histochemical characteristics of a synovial-like lining. The synovial-like cells are adjacent to the cement layer. Deep to them macrophages predominate. Inflammatory cells are absent. Cell cultures of this membrane contain stellate cells similar to those found in cell cultures of normal and rheumatoid synovial tissue. This membrane has the capacity to produce large amounts of prostaglandin E2 and collagenase. This transformation of tissue at the bone-cement interface in patients with a non-septic, loose total hip component to a synovial-like tissue with the capacity to generate prostaglandin E2 and collagenase may explain the progressive lysis of bone that is seen in some patients with loose cemented total joint implants. Loosening of the component may be a stimulus to the synthetic activity of this tissue, which leads to further resorption of bone. Understanding and the possibility of pharmacological control of this membrane may contribute to improved duration of total joint implants.


Targeted down-regulation of caveolin-3 is sufficient to inhibit myotube formation in differentiating C2C12 myoblasts. Transient activation of p38 mitogen-activated protein kinase is required for induction of caveolin-3 expression and subsequent myotube formation.
Caveolin-3 is the principal structural protein of caveolae membrane domains in striated muscle cells. Caveolin-3 mRNA and protein expression are dramatically induced during the differentiation of C2C12 skeletal myoblasts, coincident with myoblast fusion. In these myotubes, caveolin-3 localizes to the sarcolemma (muscle cell plasma membrane), where it associates with the dystrophin-glycoprotein complex. However, it remains unknown what role caveolin-3 plays in myoblast differentiation and myotube formation. Here, we employ an antisense approach to derive stable C2C12 myoblasts that fail to express the caveolin-3 protein. We show that C2C12 cells harboring caveolin-3 antisense undergo differentiation and express normal amounts of four muscle-specific marker proteins. However, C2C12 cells harboring caveolin-3 antisense fail to undergo myoblast fusion and, therefore, do not form myotubes. Interestingly, treatment with specific p38 mitogen-activated protein kinase inhibitors blocks both myotube formation and caveolin-3 expression, but does not affect the expression of other muscle-specific proteins. In addition, we find that three human rhabdomyosarcoma cell lines do not express caveolin-3 and fail to undergo myoblast fusion. Taken together, these results support the idea that caveolin-3 expression is required for myoblast fusion and myotube formation, and suggest that p38 is an upstream regulator of caveolin-3 expression.


Prelacteal feeding and its relationship with exclusive breastfeeding and formula consumption among infants in low- and middle-income countries.
Early feeding practices are important determinants of optimal feeding patterns later in life. We aimed to investigate if giving any fluids or foods other than breast milk during the first three days after birth (prelacteal feeds) affects exclusive breastfeeding and consumption of formula among children under six months of age in low and middle-income countries (LMICs). We conducted a retrospective cohort study using data from 85 nationally representative Demographic Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) in LMICs (2010-2019). We considered three exposures: any prelacteal feeding (PLF), milk-based only prelacteal feeding (MLK), and water-based only prelacteal feeding (WTR), according to the DHS/MICS definition. The outcomes were exclusive breastfeeding, based on the World Health Organization definition, and consumption of formula among infants under six months of age. We used Poisson models adjusting for sociodemographic indicators, antenatal care, birth assistance, and early initiation of breastfeeding to estimate the effects of the exposures on the outcomes. Findings were grouped by each country, as well as by regions of the world and national income classification. We included data from 91 282 children. PLF, MLK, and WTR had a prevalence of 33.9% (95% confidence interval (CI) = 33.6-34.2), 22.2% (95% CI = 21.9-22.4), and 9.4% (95% CI = 9.2-9.6), respectively. Exclusive breastfeeding and consumption of formula had a prevalence of 35.2% (95% CI = 34.9-35.5) and 27.7% (95% CI = 27.4-28.0), respectively. In the crude analysis, children who were given PLF were 40% less likely to be exclusively breastfed (prevalence ratio (PR) = 0.60; 95% CI = 0.56-0.64) and nearly twice more likely to receive formula (PR = 1.89; 95% CI = 1.72-2.08); the direction of the associations was the same across income groups and regions of the world. In the adjusted analysis, the observed crude effects were only slightly reduced (exclusive breastfeeding - PR = 0.62; 95% CI = 0.59-0.66, consumption of formula - PR = 1.72; 95% CI = 1.59-1.85). MLK showed a stronger impact on the outcomes than PLF, especially for formula consumption (adjusted PR = 1.81; 95% CI = 1.67-1.97) and in low-income countries. WTR was only negatively associated with exclusive breastfeeding (adjusted PR = 0.69; 95% CI = 0.63-0.75), but not with formula consumption (adjusted PR = 1.09; 95% CI = 0.99-1.20). Feeding babies prelacteal foods shortens exclusive breastfeeding duration and increases the likelihood of formula consumption in children under six months of age in LMICs. Pro-breastfeeding interventions must be prioritized during antenatal care and throughout the stay in the maternity facility to properly protect, support, and promote exclusive breastfeeding since birth.


[Superior vena cava replacement with autologous pericardial conduit in redo cardiac surgery].
Iatrogenic lesions needing repair can occur during redo cardiac surgery. Lacerations of the superior vena cava in redo cardiac surgery have been underreported. There is still debate around what prosthesis is best to replace the superior vena cava. A case of superior vena cava replacement for iatrogenic injury in a case of redo mitral valve surgery is reported. Use of fresh autologous pericardium to create a total conduit restoring the continuity of the superior vena cava is described. 54-year-old female with previous cardiac surgery undergoing prosthetic mitral valve replacement. During the course of the procedure, a major laceration in the superior vena cava was detected and successfully repaired by interposing a total conduit of fresh autologous pericardium. Use of autologous pericardium in order to make a total conduit for the superior vena cava reconstruction can be recommended because no long-term anticoagulation is required, and there is no additional economical cost and virtually no risk of infection.


Measuring Dirac Cones in a Subwavelength Metamaterial.
The exciting discovery of bidimensional systems in condensed matter physics has triggered the search of their photonic analogues. In this Letter, we describe a general scheme to reproduce some of the systems ruled by a tight-binding Hamiltonian in a locally resonant metamaterial; by specifically controlling the structure and the composition it is possible to engineer the band structure at will. We numerically and experimentally demonstrate this assertion in the microwave domain by reproducing the band structure of graphene, the most famous example of those 2D systems, and by accurately extracting the Dirac cones. This is direct evidence that opting for a crystalline description of those subwavelength scaled systems, as opposed to the usual description in terms of effective parameters, makes them a really convenient tabletop platform to investigate the tantalizing challenges that solid-state physics offer.


Organic solar cells using a ZnO/Cu/ZnO anode deposited by ion beam sputtering at room temperature for flexible devices.
The development of indium-free transparent conductive oxides (TCOs) on polymer substrates for flexible devices requires deposition at low temperatures and a limited thermal treatment. In this paper, we investigated the optical and electrical properties of ZnO/Cu/ZnO multi-layer electrodes obtained by ion beam sputtering at room temperature for flexible optoelectronic devices. This multilayer structure has the advantage of adjusting the layer thickness to favor antireflection and surface plasmon resonance of the metallic layer. We found that the optimal electrode is made up of a 10 nm-thick Cu layer between two 40 nm-thick ZnO layers, which results in a sheet resistance of 12 omega/(see symbol), a high transmittance of 85% in the visible range, and the highest figure of merit of 5.4 x 10(-3) (see symbol)/omega. A P3HT:PCBM-based solar cell showed a power conversion efficiency (PCE) of 2.26% using the optimized ZnO (40 nm)/Cu (10 nm)/ZnO (40 nm) anode.


Nonstationary Phase of the Plio-Pleistocene Asian Monsoon
Paleoclimate records indicate that the strength of the Asian summer monsoon is sensitive to orbital forcing at the obliquity and precession periods (41,000 and 23,000 years, respectively) and the extent of Northern Hemisphere glaciation. Over the past 2.6 million years, the timing (phase) of strong monsoons has changed by approximately 83 degrees in the precession and approximately 124 degrees in the obliquity bands relative to the phase of maximum global ice volume (inferred from the marine oxygen isotope record). These results suggest that one or both of these systems is nonstationary relative to orbital forcing.


In vitro maturation of Mammalian oocytes: outcomes and consequences.
The application of in vitro maturation (IVM) of oocytes as a technology to assist animal production and clinical infertility treatment remains poor because of the reduced developmental competence of oocytes after IVM, despite several decades of research. Reduced meiotic maturation rates, fertilization rates, and blastocyst production reveal short-term developmental insufficiency of oocytes when compared with in vivo-matured counterparts. However, there is an increasing body of evidence that demonstrates the capacity of IVM efficiency to be improved, some of which is reviewed here. Of more concern is the role that IVM of oocytes may play in causing or accentuating long-term development and health of fetuses and neonates after in vitro production of embryos and embryo transfer. This is a largely unexplored area, yet the application of such techniques, especially the safety of clinical IVM, is significant and requires monitoring before acceptance as a routine procedure.


Biochar amendment before or after composting affects compost quality and N losses, but not P plant uptake.
We investigated the use of biochar (10% on a dry weight basis) to improve the composting process and/or the compost quality by adding it to either the feedstock mixture or the mature compost. The addition of biochar to the feedstocks was essayed in a full scale trial using a mixture of green waste and the organic fraction of municipal solid waste. Addition of biochar to mature compost was performed in a medium scale experiment. The use of biochar, even in small amounts, changed the composting process and the properties of the end products. However these effects depended on the time of application. We observed a faster decomposition in the bio-oxidative phase and lower greenhouse gas emissions when biochar was added at the beginning of the composting process, and a reduction in readily available P when biochar was applied during compost storage. Biochar as a means to increase the C content of the compost was only effective during compost storage. The P fertilizer replacement value of the compost with and without biochar was tested in a plant trial with annual ryegrass. While there was a clear effect on readily available P concentrations in the compost, adding biochar to the feedstock or the compost did not affect the P fertilizer replacement value.


Textile-Friendly Interconnection between Wearable Measurement Instrumentation and Sensorized Garments-Initial Performance Evaluation for Electrocardiogram Recordings.
The interconnection between hard electronics and soft textiles remains a noteworthy challenge in regard to the mass production of textile-electronic integrated products such as sensorized garments. The current solutions for this challenge usually have problems with size, flexibility, cost, or complexity of assembly. In this paper, we present a solution with a stretchable and conductive carbon nanotube (CNT)-based paste for screen printing on a textile substrate to produce interconnectors between electronic instrumentation and a sensorized garment. The prototype connectors were evaluated via electrocardiogram (ECG) recordings using a sensorized textile with integrated textile electrodes. The ECG recordings obtained using the connectors were evaluated for signal quality and heart rate detection performance in comparison to ECG recordings obtained with standard pre-gelled Ag/AgCl electrodes and direct cable connection to the ECG amplifier. The results suggest that the ECG recordings obtained with the CNT paste connector are of equivalent quality to those recorded using a silver paste connector or a direct cable and are suitable for the purpose of heart rate detection.