Field-dependent magneto-optical Kerr effect spectroscopy applied to the magnetic component diagnosis of a rubrene/Ni system.
Polar magneto-optical Kerr effect (MOKE) spectroscopy in the energy range from 1.75 eV to 5 eV at different magnetic field strength was applied to study Ni nanostructures formed on rubrene nanoislands. The magnetic hysteresis curves measured by MOKE change the shape depending on the photon energy and therefore deviate from those measured by superconducting quantum interference device (SQUID) magnetometry. Similar optical effects were previously observed in inorganic heterostructures. Our observations show that it correlates to the change in lineshape of the MOKE rotation and ellipticity spectra as a function of magnetic field strength. We show that this spectral dependence on magnetic field can be exploited to separate the contributions of two magnetic components to the magneto-optical spectra and hysteresis. The proposed model does not require the a priori knowledge of the (magneto-)optical constants of the heterostructure and its components.


Serum Osteocalcin Levels in Girls with Central Precocious Puberty: Relation to the Onset of Puberty.
Osteocalcin is the non-collagenous protein produced by osteoblasts in bone. When it is released into systemic circulation in its uncarboxylated form, it regulates fat and glucose metabolism. Recent studies have shown that osteocalcin is also involved in male fertility. Because the onset of puberty is determined by ethnic, genetic, environmental, and metabolic factors, we focused on determining the role of osteocalcin in the onset of puberty. Central precocious puberty (CPP) is defined as the activation of the hypothalamic-pituitary-gonadal axis before the age of 8 in girls and 9 in boys. CPP is diagnosed when peak luteinizing hormone (LH) reaches ≥ 5.0 IU/l after stimulation with gonadotropin-releasing hormone (GnRH). This retrospective study included 206 girls who showed breast budding before the age of 8 and whose bone age was more advanced than their chronological age. The CPP group included 100 girls who were diagnosed with CPP, and 106 girls were the non-CPP group whose peak LH did not reach ≥ 5.0 IU/l after GnRH stimulation test. Serum osteocalcin levels were measured to investigate the relationship between osteocalcin and the onset of puberty. Our data showed that serum osteocalcin levels were significantly higher in the CPP group (87.7 ± 24.4 ng/ml vs. 68.3 ± 19.5 ng/ml, P < 0.001). The multivariate analysis revealed that an increase in bone age and peak LH was significantly associated with the serum osteocalcin level. The results of this study suggest that serum osteocalcin is associated with the onset of puberty in girls.


Development and Validation of a Racial Discrimination Measure for Cambodian American Adolescents.
To date, the majority of studies examining experiences of racial discrimination among youth use measures initially developed for African American and Latino adults or college students. Few studies have attended to the ways in which discrimination experiences may be unique for Asian American youth, particularly subgroups such as Southeast Asians. The purpose of this study was twofold: (a) to describe the development of a racial discrimination measure using community-based participatory research with Cambodian American adolescents and (b) to psychometrically test the measure with respect to validity and reliability. This research used mixed-methods and comprised 3 phases. Phase 1 consisted of qualitative focus group research to assess community-identified needs. Phase 2 included quantitative survey development with community members and resulted in an 18-item measure assessing the frequency of ethnicity-based discrimination. Phase 3 involved psychometric testing of the measure's validity and reliability (n = 423). Exploratory factor analysis procedures yielded a 3-factor structure describing peer, school, and police discrimination from all items, capturing 96% of the combined variance. Using confirmatory factor analysis, the data demonstrated good fit with the 3-factor structure (CFI = .98; RMSEA = .054), with factor loadings ranging from .59 to .96 and all estimates statistically significant at the p < .05 level. Correlational analyses of racial discrimination subfactors and depression supported concurrent validity. In sum, this measure can be used to examine the degree and sources of racial discrimination reported by Cambodian American adolescents and potentially other adolescents of Southeast Asian descent living in diverse urban communities.


Intracellular transport of formaldehyde-treated serum albumin in liver endothelial cells after uptake via scavenger receptors.
Endocytosis of formaldehyde-treated serum albumin (FSA) mediated by the scavenger receptor was studied in rat liver endothelial cells. Suspended cells had about 8000 receptors/cell, whereas cultured cells had about 19,000 receptors/cell. Kd was 10(-8) M in both systems. Cell-surface scavenger receptors were found exclusively in coated pits by electron microscopy, by using ligand labelled with colloidal gold. Cell-surface-bound FSA could be released by decreasing the pH to 6.0; it was therefore possible to assess the rate of internalization of surface-bound ligand. This rate was very high: t1/2 for internalization of ligand prebound at 4 degrees C was 24 s. The endocytic rate constant at 37 degrees C, Ke, measured as described by Wiley & Cunningham [(1982) J. Biol. Chem. 257, 4222-4229], was 2.44 min-1, corresponding to t1/2 = 12 s. Uptake of FSA at 37 degrees C after destruction of one cell-surface pool of receptors by Pronase was decreased to 60%. This finding is compatible with a relatively large intracellular pool of receptors. The intracellular handling of 125I-tyramine-cellobiose-labelled FSA (125I-TC-FSA) was studied by subcellular fractionation in sucrose gradients, Nycodenz gradients or by differential centrifugation. The density distributions of degraded and undegraded 125I-TC-FSA after fractionation of isolated non-parenchymal cells and whole liver were similar, when studied in Nycodenz and sucrose gradients, suggesting that the subcellular distribution of the ligand was not influenced by the huge excess of non-endothelial material in a whole liver homogenate. Fractionation in sucrose gradients showed that the ligand was sequentially associated with organelles banding at 1.14, 1.17 and 1.21 g/ml. At 9-12 min after intravenous injection the ligand was in a degradative compartment, as indicated by the accumulation of acid-soluble radioactivity at 1.21 g/ml. A rapid transfer of ligand to the lysosomes was also indicated by the finding that a substantial proportion of the ligand could be degraded by incubating mitochondrial fractions prepared 12 min after intravenous injection of the ligand. The results indicate that FSA is very rapidly internalized and transferred through an endosomal compartment to the lysosomes. The endosomes are gradually converted into lysosomes between 9 and 12 min after injection of FSA. The rate-limiting step in the intracellular handling of 125I-TC-FSA is the degradation in the lysosomes.


A case-control study of cancer of the uterine cervix in Uganda.
As part of an epidemiological study of cancer in Uganda, we investigated social, sexual and reproductive factors in relation to the risk of cancer of the uterine cervix. Patients with all cancer types or with benign tumours were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against the human immunodeficiency virus-1 (HIV). The case-control study reported here involves 702 HIV-seronegative women, 343 of whom were diagnosed with cancer of the uterine cervix. Key findings were that the risk of cervical cancer increased linearly with the number of pregnancies [chi2(1)=44.7; P<0.0001]; a woman reporting having had 10 or more children had a roughly seven-fold increase in risk of the tumour as compared with women reporting fewer than four pregnancies (odds ratio=7.1; 95% confidence interval 3.8-13.2). The risk also varied inversely with age at first reported sexual intercourse [chi2(1)=8.4; P=0.004], perhaps reflecting an earlier age of infection with human papillomavirus, the main causal agent. These results are in line with those reported from studies in other countries.


Telemedicine in pre-hospital care: a review of telemedicine applications in the pre-hospital environment.
The right person in the right place and at the right time is not always possible; telemedicine offers the potential to give audio and visual access to the appropriate clinician for patients. Advances in information and communication technology (ICT) in the area of video-to-video communication have led to growth in telemedicine applications in recent years. For these advances to be properly integrated into healthcare delivery, a regulatory framework, supported by definitive high-quality research, should be developed. Telemedicine is well suited to extending the reach of specialist services particularly in the pre-hospital care of acute emergencies where treatment delays may affect clinical outcome. The exponential growth in research and development in telemedicine has led to improvements in clinical outcomes in emergency medical care. This review is part of the LiveCity project to examine the history and existing applications of telemedicine in the pre-hospital environment. A search of electronic databases including Medline, Excerpta Medica Database (EMBASE), Cochrane, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for relevant papers was performed. All studies addressing the use of telemedicine in emergency medical or pre-hospital care setting were included. Out of a total of 1,279 articles reviewed, 39 met the inclusion criteria and were critically analysed. A majority of the studies were on stroke management. The studies suggested that overall, telemedicine had a positive impact on emergency medical care. It improved the pre-hospital diagnosis of stroke and myocardial infarction and enhanced the supervision of delivery of tissue thromboplasminogen activator in acute ischaemic stroke. Telemedicine presents an opportunity to enhance patient management. There are as yet few definitive studies that have demonstrated whether it had an effect on clinical outcome.


Factors affecting response to proton pump inhibitor therapy in patients with gastroesophageal reflux disease: a multicenter prospective observational study.
Proton pump inhibitor (PPI) therapy, the first-line treatment for gastroesophageal reflux disease (GERD), is not always effective. This study aimed to examine the effect of pretreatment patient characteristics on response to PPI therapy. Japanese outpatients with symptomatic GERD scheduled to receive endoscopy and PPI therapy were enrolled in this multicenter prospective observational study. The patients' characteristics, including GERD and dyspeptic symptoms, anxiety, depression, and quality of life, were assessed using questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors affecting therapeutic response were examined by simple and multiple regression analyses using three patient-reported outcome measures as objective variables. Data from 182 patients were analyzed. In multiple regression analysis using the residual symptom rate as an objective variable, lower GERD symptom score (p < 0.05), absence of erosive esophagitis (p < 0.05), higher epigastric pain/burning symptom score (p < 0.05), and higher depression subscale score (p < 0.05) accompanied poorer therapeutic response. In analyses using the patient's impression of therapy, lower GERD symptom score (p < 0.05) and absence of erosive esophagitis (p < 0.05) accompanied poorer therapeutic response. In analyses using the relative GERD symptom intensity evaluated using a numeric rating scale, lower GERD symptom score (p < 0.05), higher epigastric pain/burning symptom score (p < 0.1), and lower body mass index (p < 0.05) accompanied poorer therapeutic response. Patients who complained of milder GERD symptoms before treatment were likely to have poorer response to PPI therapy. Association of absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower body mass index, and severer depression with poorer therapeutic response was also suggested.


Multicategory Large-Margin Unified Machines.
Hard and soft classifiers are two important groups of techniques for classification problems. Logistic regression and Support Vector Machines are typical examples of soft and hard classifiers respectively. The essential difference between these two groups is whether one needs to estimate the class conditional probability for the classification task or not. In particular, soft classifiers predict the label based on the obtained class conditional probabilities, while hard classifiers bypass the estimation of probabilities and focus on the decision boundary. In practice, for the goal of accurate classification, it is unclear which one to use in a given situation. To tackle this problem, the Large-margin Unified Machine (LUM) was recently proposed as a unified family to embrace both groups. The LUM family enables one to study the behavior change from soft to hard binary classifiers. For multicategory cases, however, the concept of soft and hard classification becomes less clear. In that case, class probability estimation becomes more involved as it requires estimation of a probability vector. In this paper, we propose a new Multicategory LUM (MLUM) framework to investigate the behavior of soft versus hard classification under multicategory settings. Our theoretical and numerical results help to shed some light on the nature of multicategory classification and its transition behavior from soft to hard classifiers. The numerical results suggest that the proposed tuned MLUM yields very competitive performance.


Climate and land-use change homogenise terrestrial biodiversity, with consequences for ecosystem functioning and human well-being.
Biodiversity continues to decline under the effect of multiple human pressures. We give a brief overview of the main pressures on biodiversity, before focusing on the two that have a predominant effect: land-use and climate change. We discuss how interactions between land-use and climate change in terrestrial systems are likely to have greater impacts than expected when only considering these pressures in isolation. Understanding biodiversity changes is complicated by the fact that such changes are likely to be uneven among different geographic regions and species. We review the evidence for variation in terrestrial biodiversity changes, relating differences among species to key ecological characteristics, and explaining how disproportionate impacts on certain species are leading to a spatial homogenisation of ecological communities. Finally, we explain how the overall losses and homogenisation of biodiversity, and the larger impacts upon certain types of species, are likely to lead to strong negative consequences for the functioning of ecosystems, and consequently for human well-being.


Helminth parasites of the lesser great cormorant Phalacrocorax carbo sinensis from two nesting regions in the Czech Republic.
Parasitological examinations of 102 specimens of the lesser great cormorant Phalacrocorax carbo sinensis (Blumenbach) from two nesting regions in the Czech Republic (South Bohemia and South Moravia) were carried out at the Institute of Parasitology, Czech Academy of Sciences (previously the Czechoslovak Academy of Sciences) in the years 1987-1992. In them, a total of 19 species of helminth parasites was found, including Trematoda (11 species), Cestoda (2), Nematoda (4) and Acanthocephala (2), which can be divided into three main groups regarding their host specificity: parasites specific for cormorants (Phalacrocorax spp.) (37%), those parasitic mainly in cormorants (16%) and non-specific parasites (47%). Of the 19 species recorded, 100% were found in South Moravia, but only 47% of these 19 species in South Bohemia. The higher number of helminth species in cormorants from South Moravia and a higher proportion of non-specific species may be associated with the presence of the large Nové Mlýny water reservoir, in addition to better ecological and environmental conditions in this warmer region. Scanning electron microscopical examination of three common nematode species parasitising cormorants, Contracaecum rudolphii Hartwich, 1964, Desmidocercella incognita Solonitsin, 1932 and Syncuaria squamata (von Linstow, 1883), revealed some taxonomically important, previously unreported morphological features, such as the cephalic structures, numbers and distribution of male caudal papillae or the shapes of spicules.


Evaluation of canal transportation and centering ability of K 3 (0.02%) and K 3 (0.04%) with hand K files in primary teeth using spiral computed tomography.
One of the objectives of root canal preparation is to clean and shape the root canal system while maintaining the original configuration. Therefore, it is important to keep the instruments centered to provide a correct enlargement, without excessive weakening of the root structure. The aim of the study was to compare canal transportation and centering ability of K 3 (0.02% taper) and K 3 (0.04% taper) with stainless steel hand K files in primary teeth using a spiral computed tomography (SCT) scan. A total of 75 extracted mandibular primary second molars was collected. Canals were divided randomly into three groups of 25 teeth each. Group I: K 3 files (0.02% taper), Group II: K 3 (0.04% taper), and Group III: Stainless steel hand K files. Three regions from apical, mid-root, and coronal levels of the canal were recorded. All the teeth were scanned before and after instrumentation by using SCT. K 3 (0.02% taper) showed less canal transportation and a better centering ratio than K 3 (0.04% taper) and stainless steel hand K files. The mean values were compared between different study groups and the P-value was calculated by using Kruskal-Wallis one-way ANOVA. The Mann-Whitney U-test followed by the Bonferroni correction method was employed to identify the significant groups at the 5% level. K 3 (0.02% taper) shaped root canals without significant shaping errors when compared to K 3 (0.04% taper) and stainless steel hand K files in primary teeth.


Palm tocotrienol supplementation enhanced bone formation in oestrogen-deficient rats.
Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.


Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.
Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.


Pharmacokinetics and plasma bactericidal activity of aztreonam in low-birth-weight infants.
Aztreonam (30 mg/kg) was administered intravenously every 12 h during week 1 and every 8 h during weeks 2 to 4 of life to 26 low-birth-weight (less than 2,000 g) infants, and plasma concentration-time curves were measured on two occasions. The pharmacokinetics were described equally well by one-compartment and noncompartment models, and the values on day 1 were similar to those measured during the steady state on days 3 to 6. The mean peak plasma concentrations at completion of the 10-min infusion were from 65 to 83 micrograms/ml, the higher concentrations being seen in the larger infants. The half-lives of aztreonam ranged from 5.4 to 8.6 h and did not change significantly with birth weight. The median peak and trough plasma bactericidal titer against a strain of Escherichia coli (MBC, 10 micrograms/ml) was 1:16. Against a strain of Pseudomonas aeruginosa (MBC, 16 micrograms/ml), the median peak and trough bactericidal titers were 1:8 to 1:16 and 1:4, respectively. The urinary concentrations of aztreonam on day 1 of therapy were from 24 to 460.7 micrograms/ml (mean +/- 1 standard deviation, 254 +/- 113 micrograms/ml).


Single Parameter Estimation Approach for Robust Estimation of SIR Model With Limited and Noisy Data: The Case for COVID-19.
The susceptible-infected-removed (SIR) model and its variants are widely used to predict the progress of coronavirus disease 2019 (COVID-19) worldwide, despite their rather simplistic nature. Nevertheless, robust estimation of the SIR model presents a significant challenge, particularly with limited and possibly noisy data in the initial phase of the pandemic. The K-means algorithm is used to perform a cluster analysis of the top 10 countries with the highest number of COVID-19 cases, to observe if there are any significant differences among countries in terms of robustness. As a result of model variation tests, the robustness of parameter estimates is found to be particularly problematic in developing countries. The incompatibility of parameter estimates with the observed characteristics of COVID-19 is another potential problem. Hence, a series of research questions are visited. We propose a Single Parameter Estimation (SPE) approach to circumvent these potential problems if the basic SIR is the model of choice, and we check the robustness of this new approach by model variation and structured permutation tests. Dissemination of quality predictions is critical for policy- and decision-makers in shedding light on the next phases of the pandemic.


Sequential anisotropic Wiener filtering applied to 3D MRI data.
We present three different sequential Wiener filters, namely, isotropic, orientation and anisotropic. The first one is similar to the classical Wiener filter in the sense that it uses an isotropic neighborhood to estimate its parameters. Here we present a sequential version of it. The orientation Wiener filter uses oriented neighborhoods to estimate the structure orientation present at each voxel, giving rise to a modified estimator of the parameters. Finally, the anisotropic Wiener filter combines both approaches adaptively so that the appropriate approach is locally selected. Several synthetic experiments are presented showing the performance of the filters with respect to their parameters. A mean square error analysis is performed using a publicly available magnetic resonance imaging (MRI) brain phantom and a comparison with other filtering approaches is carried out. In addition, results from filtering real MRI data are presented.


In vitro induction of nitric oxide by an extract of Plasmodium falciparum.
Malarial illness and pathology is generally accepted to be caused by material released when the infected red cells burst at schizogony. The released material has been partially purified and shown to stimulate macrophages to make TNF. We have extended this work to show that these same preparations, isolated from parasitized erythrocytes, induce the mouse macrophage cell line RAW 264.7 to produce inducible nitric oxide synthase and release nitric oxide. By using cytokine-specific antisera we have found that this induction is independent of TNF and IL-1 alpha and partly independent of IL-1 beta.


Infliximab but not methotrexate induces extra-high levels of VLDL-triglyceride in patients with rheumatoid arthritis.
Tumor necrosis factor (TNF-alpha), a pivotal inflammatory cytokine, is known to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA). We examined the effects of anti-TNF-alpha antibody (infliximab, IFX) compared with methotrexate (MTX) on lipid profiles in patients with RA. We selected retrospectively all patients with refractory RA (n = 32) who achieved a successful outcome (DAS-28 score < 2.6) in 6 months with IFX treatment, and control groups of age- and sex-matched patients with active RA treated with MTX and healthy participants. We traced fasting serum levels of total cholesterol (TCHO) and triglyceride (TG) for 6 months and used an online dual enzymatic method for simultaneous quantification of cholesterol (CHO) and TG by high performance liquid chromatography (HPLC). Mean C-reactive protein levels (baseline 4.5) fell to below 1 in 6 months. MTX treatment elevated and normalized TCHO and TG levels. IFX treatment, however, preferentially induced extra-high TG levels. HPLC analyses identified similar CHO profiles between patients treated with IFX or MTX, but IFX selectively induced a huge VLDL-TG peak. Statins successfully controlled these extra-high TG levels. In patients successfully treated with IFX or MTX, CHO levels were elevated and normalized, but IFX treatment preferentially induced extra-high levels of VLDL-TG. Thus, there is differential regulation of the lipid profile between IFX and MTX, necessitating careful attention to TG levels with IFX treatment.


Maternal genetic effects set the potential for evolution in a free-living vertebrate population.
Heritable maternal effects have important consequences for the evolutionary dynamics of phenotypic traits under selection, but have only rarely been tested for or quantified in evolutionary studies. Here we estimate maternal effects on early-life traits in a feral population of Soay sheep (Ovis aries) from St Kilda, Scotland. We then partition the maternal effects into genetic and environmental components to obtain the first direct estimates of maternal genetic effects in a free-living population, and furthermore test for covariance between direct and maternal genetic effects. Using an animal model approach, direct heritabilities (h2) were low but maternal genetic effects (m2) represented a relatively large proportion of the total phenotypic variance for each trait (birth weight m2=0.119, birth date m2=0.197, natal litter size m2=0.211). A negative correlation between direct and maternal genetic effects was estimated for each trait, but was only statistically significant for natal litter size (ram= -0.714). Total heritabilities (incorporating variance from heritable maternal effects and the direct-maternal genetic covariance) were significant for birth weight and birth date but not for natal litter size. Inadequately specified models greatly overestimated additive genetic variance and hence direct h2 (by a factor of up to 6.45 in the case of birth date). We conclude that failure to model heritable maternal variance can result in over- or under-estimation of the potential for traits to respond to selection, and advocate an increased effort to explicitly measure maternal genetic effects in evolutionary studies.


Ethanol vapor-induced fabrication of colloidal crystals with controllable layers and photonic properties.
A novel fabrication method for colloidal crystals has been proposed for the first time in this research. In this method, a suspension droplet containing colloidal particles was first spread onto a glass substrate placed in an ethanol vapor environment, and then the droplet was extracted from its center. In that case, the contact angle of the droplet reduced and the contact line receded toward the center, during which the colloidal particles self-assembled and immobilized forming a 2D colloidal crystal film on the substrate upon drying the liquid film. Alternately spreading and drying of suspension films could construct fine multi-layers of colloidal crystals, while the ethanol fraction in the suspension would be used to control roughly but rapidly the layer numbers of colloidal crystals. It was also found that the photonic properties of resultant colloidal crystal films were elevated by increasing their thickness.


Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
Folate metabolism pathway genes have been examined for association with neural tube defects (NTDs) because folic acid supplementation reduces the risk of this debilitating birth defect. Most studies addressed these genes individually, often with different populations providing conflicting results. Our study evaluates several folate pathway genes for association with human NTDs, incorporating an environmental cofactor: maternal folate supplementation. In 304 Caucasian American NTD families with myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase 1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and cystathionine-beta-synthase. Only single nucleotide polymorphisms (SNPs) in BHMT were significantly associated in the overall data set; this significance was strongest when mothers took folate-containing nutritional supplements before conception. The BHMT SNP rs3733890 was more significant when the data were stratified by preferential transmission of the MTHFR rs1801133 thermolabile T allele from parent to offspring. Other SNPs in folate pathway genes were marginally significant in some analyses when stratified by maternal supplementation, MTHFR, or BHMT allele transmission. BHMT rs3733890 is significantly associated in our data set, whereas MTHFR rs1801133 is not a major risk factor. Further investigation of folate and methionine cycle genes will require extensive SNP genotyping and/or resequencing to identify novel variants, inclusion of environmental factors, and investigation of gene-gene interactions in large data sets.


Organochlorine compounds and testicular dysgenesis syndrome: human data.
Cryptorchidism, hypospadias, subfertility and testicular germ-cell tumour have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during foetal life. Endocrine-disrupting chemicals have been hypothesized to be associated with these disorders, given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half-lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichloro-diphenyl-trichloroethane and its metabolites, polychlorinated biphenyls, and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p'-DDE, cis-nonachlor and trans-nonachlor with testicular germ-cell tumour. The sum of the evidence from human epidemiological studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias or fertility. Many other endocrine-disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.


The place of volition in addiction: differing approaches and their implications for policy and service provision.
'Addiction' is an ambiguous concept. Its meaning, and how it is used in drug policy and treatment, depends on how it is conceptualised. While the 'disease' model of addiction is prevalent in Australia, differing, sometimes contradictory, interpretations of this model are mobilised. Drawing on 20 semi-structured interviews conducted with professionals working in the area of drug use in Victoria, Australia, this paper develops a typology delineating different approaches to addiction. Five domains of meaning related to addiction were identified in the data. These were: (i) the sign of craving; (ii) susceptibility; (iii) social and psychological issues producing addiction; (iv) self-concept; and (v) social functions of addiction. These domains are further divided into two subtypes based on how the participants understood the role of a key notion in addiction: volition, that is, whether or not an 'addict' has control over drug use and other aspects of life. By systematically mapping different conceptualisations of addiction, this typology identifies the ambiguities and contradictions in the models currently in use, especially with respect to the notion of volition. While a homogeneous approach to these issues is neither practical nor desirable, there is a need to consider the implications of this lack of coherence. Service providers, medical practitioners and policy makers need to reflect on their assumptions, and consider the implications of their different approaches for clients, some of whom encounter more than one approach when undergoing treatment for drug use.


A comparison of knee extensor strength curves obtained theoretically and experimentally.
Strength curves relate a measure of maximal voluntary force of a group of synergistic muscles, typically a resultant knee joint moment, to a measure of muscular length, typically a joint angle. In this study, it was hypothesized that the shape of strength curves is primarily determined by the force-length properties of the individual muscles within a synergistic group. This hypothesis was tested for knee extensor strength curves by comparing theoretically determined strength curves based on the force-length relations of the individual muscles with those obtained experimentally. The agreement between theoretical and experimental curves was good, suggesting that the initial hypothesis was correct. Accepting this result, it is possible to determine the contribution of individual muscles to the total force of the synergistic group. This information, in turn, may be utilized for practical applications in sports or for evaluating strength curves of patients with injuries or diseases of the musculoskeletal system.


[Acceptance of assistive robots in the field of nursing and healthcare : Representative data show a clear picture for Germany].
In view of the ageing society and the high costs of support and care in private households, the question arises as to what role assistive robots can play. This article focuses on the extent to which robots in nursing are accepted by the adult population in Germany today, as well as the extent to which gender, age, and experience (professional and private) influence this level of acceptance. The analysis carried out for this purpose was based on three representative surveys conducted among a total of over 7000 respondents. Of these surveys two were conducted in the second half of 2017 on behalf of the German Academy of Science and Engineering (acatech) and the life insurance company ERGO, while the third was commissioned by the German Council of Economic Experts (SVRV) in the spring of 2018. An in-depth and cumulative analysis of these surveys and data sets, which the authors helped to design, with respect to assistive robotics has not yet been published. Despite the different application scenarios for assistive care robots, the results of all three surveys are surprisingly consistent: in Germany there is already a significant minority of people who are open to, and would accept nursing care robots as long as they do not replace but rather support traditional human nursing. Roughly one third of the sample differentiated according to age and gender, fundamentally rejected assistance by robots.


Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
PKD1 and PKD2 are two recently identified genes that are responsible for the vast majority of autosomal polycystic kidney disease, a common inherited disease that causes progressive renal failure. PKD1 encodes polycystin, a large glycoprotein that contains several extracellular motifs indicative of a role in cell-cell or cell-matrix interactions, and the PKD2 encodes a protein with homology to a voltage-activated calcium channel and to PKD1. It is currently unknown how mutations of either protein functionally cause autosomal polycystic kidney disease. We show that PKD1 and PKD2 interact through their C-terminal cytoplasmic tails. This interaction resulted in an up-regulation of PKD1 but not PKD2. Furthermore, the cytoplasmic tail of PKD2 but not PKD1 formed homodimers through a coiled-coil domain distinct from the region required for interaction with PKD1. These interactions suggest that PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis and that PKD1 may require the presence of PKD2 for stable expression.


An estimation of intrapartum-related perinatal mortality rates for booked home births in England and Wales between 1994 and 2003.
The objective of this study was to obtain the best estimate of intrapartum-related perinatal mortality (IPPM) rates for booked home births. A population-based cross-sectional study. England and Wales. All births in England and Wales, including home births (intended or unintended) occurring between 1994 and 2003. All IPPM data were derived from the Confidential Enquiry into Maternal and Child Health. Denominators were derived by using unintended home births and transfer rates from home to hospital, from previous studies, with sensitivity analyses. IPPM rates were calculated for the three following subgroups: (a) the completed home birth group, (b) the transferred group and (c) the unintended home birth group. IPPM rate. The overall IPPM rate for England and Wales improved between 1994 and 2003. However, data to obtain a precise estimate of IPPM rate for booked home birth were not available. The average IPPM rate for all births in the study period was 0.79 per 1000 births (95% CI 0.77-0.81), and the estimated IPPM rate for booked home births was 1.28 or 0.74 per 1000 births, depending on the method of calculation (range 0.49-1.47). The IPPM rates for the completed home birth group appeared to be lower throughout the study period compared with the unintended home birth groups. Those women who had booked for a home birth, but later needed to transfer their care for a hospital birth, appeared to have the highest risk of IPPM in the study period. The results of this study need to be interpreted with caution due to inconsistencies occurring in the recorded data. However, the data do highlight two important features. First, they suggest that IPPM rates for home births do not appear to have improved over the study period examined, even though rates did so overall. Second, although the women who booked for home births and had their babies at home seemed to have a generally low IPPM rate, those who required their care to be transferred to hospital did not. Women who book for home births should be offered comprehensive evidence-based information about the potential benefits, risks and uncertainties associated with their choice of birthplace by the healthcare professional responsible for supporting their decision. It is of considerable concern that the data recorded nationally in England and Wales do not provide accurate information about when and why a transfer from home to hospital booking occurs and about their outcomes.


Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis.
Expression of mRNAs coding for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) was examined in the hypothalamic paraventricular nucleus (PVN) of rats bearing hippocampal lesions. Either total hippocampectomy (HPX) or extirpation of the dorsal hippocampus (DHPX) precipitated a 4-fold increase in CRF mRNA expression relative to sham-operated controls (SHAM), as determined by semiquantitative in situ hybridization histochemistry. AVP mRNA was localized to individual parvocellular neurons of the medial parvocellular division of the PVN in only the HPX and DHPX groups, consistent with enhanced production of AVP message in this neuronal population subsequent to hippocampal damage. HPX did not affect AVP mRNA content in magnocellular divisions of PVN. Plasma beta-endorphin levels were significantly elevated in the HPX and DHPX groups relative to SHAM animals, indicating a chronic increase in release of proopiomelanocortin peptides from the anterior pituitary gland in response to hippocampal lesion. Circulating corticosterone levels were elevated in HPX rats as well. To control for effects of lesion size and location, additional animals received large ablations of cerebral cortex or cerebellum. In neither case was CRF or AVP mRNA significantly altered in the PVN. The results suggest that the hippocampus exercises a tonic inhibitory role on ACTH secretagogue production in neuroendocrine neurons promoting ACTH release.


Relaxation techniques for pain management in labour.
Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute to the popularity of complementary methods of pain management. This review examined currently available evidence on the use of relaxation therapies for pain management in labour. This is an update of a review first published in 2011. To examine the effects of mind-body relaxation techniques for pain management in labour on maternal and neonatal well-being during and after labour. We searched Cochrane Pregnancy and Childbirth's Trials Register (9 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 5 2017), MEDLINE (1966 to 24 May 2017), CINAHL (1980 to 24 May 2017), the Australian New Zealand Clinical Trials Registry (18 May 2017), ClinicalTrials.gov (18 May 2017), the ISRCTN Register (18 May 2017), the WHO International Clinical Trials Registry Platform (ICTRP) (18 May 2017), and reference lists of retrieved studies. Randomised controlled trials (including quasi randomised and cluster trials) comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We attempted to contact study authors for additional information. We assessed evidence quality with GRADE methodology. This review update includes 19 studies (2519 women), 15 of which (1731 women) contribute data. Interventions examined included relaxation, yoga, music and mindfulness. Approximately half of the studies had a low risk of bias for random sequence generation and attrition bias. The majority of studies had a high risk of bias for performance and detection bias, and unclear risk of bias for, allocation concealment, reporting bias and other bias. We assessed the evidence from these studies as ranging from low to very low quality, and therefore the effects below should be interpreted with caution.RelaxationWe found that relaxation compared to usual care provided lowered the intensity of pain (measured on a scale of 0 to 10 with low scores indicating less pain) during the latent phase of labour (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women). Four trials reported pain intensity in the active phase; there was high heterogeneity between trials and very low-quality evidence suggested that there was no strong evidence that the effects were any different between groups for this outcome (MD -1.08, 95% CI -2.57 to 0.41, four trials, 271 women, random-effects analysis). Very low-quality evidence showed that women receiving relaxation reported greater satisfaction with pain relief during labour (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women), and showed no clear benefit for satisfaction with childbirth experience (assessed using different scales) (standard mean difference (SMD) -0.03, 95% CI -0.37 to 0.31, three trials, 1176 women). For safety outcomes there was very low-quality evidence of no clear reduction in assisted vaginal birth (average RR 0.61, 95% CI 0.20 to 1.84, four trials, 1122 women) or in caesarean section rates (average RR 0.73, 95% CI 0.26 to 2.01, four trials, 1122 women). Sense of control in labour, and breastfeeding were not reported under this comparison.YogaWhen comparing yoga to control interventions there was low-quality evidence that yoga lowered pain intensity (measured on a scale of 0 to 10) with low scores indicating less pain) (MD -6.12, 95% CI -11.77 to -0.47, one trial, 66 women), greater satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women) and greater satisfaction with childbirth experience (MD 6.34, 95% CI 0.26 to 12.42 one trial, 66 women (assessed using the Maternal Comfort Scale with higher score indicating greater comfort). Sense of control in labour, breastfeeding, assisted vaginal birth, and caesarean section were not reported under this comparison.MusicWhen comparing music to control interventions there was evidence of lower pain intensity in the latent phase for women receiving music (measured on a scale of 0 to 10 with low scores indicating less pain) (MD -0.73, 95% CI -1.01 to -0.45, random-effects analysis, two trials, 192 women) and very low-quality evidence of no clear benefit in the active phase (MD -0.51, 95% CI -1.10 to 0.07, three trials, 217 women). Very low-quality evidence suggested no clear benefit in terms of reducing assisted vaginal birth (RR 0.41, 95% CI 0.08 to 2.05, one trial, 156 women) or caesarean section rate (RR 0.78, 95% CI 0.36 to 1.70, two trials, 216 women). Satisfaction with pain relief, sense of control in labour, satisfaction with childbirth experience, and breastfeeding were not reported under this comparison.Audio analgesiaOne trial evaluating audio analgesia versus control only reported one outcome and showed no evidence of benefit in satisfaction with pain relief.MindfulnessOne trial evaluating mindfulness versus usual care found an increase in sense of control for the mindfulness group (using the Childbirth Self-Efficacy Inventory) (MD 31.30, 95% CI 1.61 to 60.99, 26 women). There is no strong evidence that the effects were any different between groups for satisfaction in childbirth, or for caesarean section rate, need for assisted vaginal delivery or need for pharmacological pain relief. No other outcomes were reported in this trial. Relaxation, yoga and music may have a role with reducing pain, and increasing satisfaction with pain relief, although the quality of evidence varies between very low to low. There was insufficient evidence for the role of mindfulness and audio-analgesia. The majority of trials did not report on the safety of the interventions. Further randomised controlled trials of relaxation modalities for pain management in labour are needed. Trials should be adequately powered and include clinically relevant outcomes such as those described in this review.


Superior mesenteric artery syndrome following spinal deformity correction.
Superior mesenteric artery syndrome is a known complication associated with the correction of spinal deformity. Recent investigations of this disorder have focused on patient height and weight. We are not aware of any published study examining the degree of deformity, type of curve, or magnitude of correction, and to our knowledge all of the reported literature on this syndrome lacks control data. The purpose of this study was to examine the relationship between the correction of spinal deformity and the development of superior mesenteric artery syndrome in patients with scoliosis. Our hypothesis was that greater correction of spinal deformity would increase the risk of the development of superior mesenteric artery syndrome. A case-control study was performed over a five-year period. The primary outcome measure was the development of superior mesenteric artery syndrome. The predictor variables that were considered included demographic characteristics; preoperative height, weight, and body mass index; aspects of the deformity, including curve magnitude, Lenke curve classification, and correction; and operative factors, including surgical approach, estimated blood loss, and the presence of operative hypotension. A review of the records on 364 surgical procedures for scoliosis identified seventeen cases of superior mesenteric artery syndrome. Thirty-four subjects who had had surgery for scoliosis but no superior mesenteric artery syndrome were randomly selected as controls. Eight of the seventeen subjects with superior mesenteric artery syndrome had undergone a two-stage procedure (compared with one of the thirty-four controls, p < 0.001), nine of the seventeen had had combined anterior and posterior procedures (compared with two of the thirty-four controls, p < 0.001), and seven of the seventeen had had a thoracoplasty (compared with two of the thirty-four controls, p < 0.001). No significant differences were noted between the groups with regard to demographic factors. Compared with the controls, the patients in whom superior mesenteric artery syndrome developed were shorter (by a mean of 7.1 cm, p = 0.03), weighed less (by a mean of 11.5 kg, p = 0.001), had a lower body mass index (p = 0.003), had a greater minimal thoracic curve magnitude achieved by bending (a mean of 12 degrees greater [45 degrees for subjects with superior mesenteric artery syndrome and 33 degrees for controls], p = 0.015), had a lower percent correction of the thoracic curve on bending (a mean of 11% lower, p = 0.025), and had more lumbar lateralization (88%, compared with 61% in the control group, had a Lenke lumbar modifier of B or C instead of A, p = 0.008). Multivariate logistic regression analysis identified a staged procedure (odds ratio, 31.0), the lumbar modifier (odds ratio, 9.06), body mass index (odds ratio, 7.75), and thoracic stiffness (odds ratio, 6.67) as the most predictive of the development of superior mesenteric artery syndrome. Preoperative identification of the risk factors described above in conjunction with preoperative nutritional maximization should be considered in order to limit the prevalence of superior mesenteric artery syndrome in patients undergoing surgical correction of spinal deformity.


Vectorial near-field coupling.
The coherent exchange of optical near fields between two neighbouring dipoles plays an essential role in the optical properties, quantum dynamics and thus the function of many naturally occurring and artificial nanosystems. These interactions are challenging to quantify experimentally. They extend over only a few nanometres and depend sensitively on the detuning, dephasing and relative orientation (that is, the vectorial properties) of the coupled dipoles. Here, we introduce plasmonic nanofocusing spectroscopy to record coherent light scattering spectra with 5 nm spatial resolution from the apex of a conical gold nanotaper. The apex is excited solely by evanescent fields and coupled to plasmon resonances in a single gold nanorod. We resolve resonance energy shifts and line broadenings as a function of dipole distance and relative orientation. We demonstrate how these phenomena arise from mode couplings between different vectorial components of the interacting optical near fields, specifically from the coupling of the nanorod to both transverse and longitudinal polarizabilities of the taper apex.


Measurement of cytokine biomarkers using an aptamer-based affinity graphene nanosensor on a flexible substrate toward wearable applications.
We present an approach for the label-free detection of cytokine biomarkers using an aptamer-functionalized, graphene-based field effect transistor (GFET) nanosensor on a flexible, SiO2-coated substrate of the polymer polyethylene naphthalate (PEN). The nanosensor conforms to the underlying nonplanar surface and performs GFET-based rapid transduction of the aptamer-biomarker binding, thereby potentially allowing the detection of cytokine biomarkers that are sampled reliably from human bodily fluids (e.g., sweat) in wearable sensing applications. In characterizing the suitability of the nanosensor for wearable applications, we investigate the effects of substrate bending on the equilibrium dissociation constant between the aptamer and the biomarker as well as the graphene transconductance. The utility of the nanosensor is demonstrated by the detection of tumor necrosis factor-α (TNF-α), an inflammatory cytokine biomarker. Experimental results show that the flexible nanosensor can specifically respond to changes in the TNF-α concentration within 5 minutes with a limit of detection as low as 26 pM in a repeatable manner.


Spices to Control COVID-19 Symptoms: Yes, but Not Only….
There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.


Successful treatment of a stage IIIC small-cell carcinoma of the ovary hypercalcemic subtype using multi-modality therapeutic approach.
Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly undifferentiated, aggressive malignancy that primarily affects young women. Due to its early onset, unclear familial history and vague presenting symptoms, most SCCOHT patients present late with advanced disease. The prognosis is extremely poor, with <10% disease-free survival for advanced stages. Although several therapeutic regimens have been proposed, to date there is no consensus on the optimal strategy. Here, we describe a successful case of advanced-stage SCCOHT of the left ovary treated with cytoreductive surgery, semi-intense chemotherapy, high-dose consolidative chemotherapy, autologous hematopoietic stem cell transplantation and pelvic radiation with long-term survival. Given the almost universal mortality of advanced SCCOHT in long-term follow-up, we believe this case highlights the importance of prompt diagnosis when a young patient presents with abdominal swelling and hypercalcemia as well as early, aggressive, combined modality treatment. This case is also especially remarkable given the patient underwent fertility preservation surgery, which is not recommended by most of the current literature. However, as therapies improve and more young patients may survive SCCOHT, the question of fertility will increase in relevance. We believe the pros and cons of conservation should be discussed in detail with the patient.


De novo formation characteristics of dioxins in the dry zone of an iron ore sintering bed.
The objectives of this work are to understand the details of the mechanism of dioxin formation in the part of a sintering bed termed the dry zone, and to obtain ideas on how to prevent their formation. Sinter mixtures of various composition types were heated in a packed bed reactor, and dioxins in the outlet gas and in the sinter mixture residue were measured. The dioxin formation potential of a simple sinter mixture composed of iron ore, coke and limestone was markedly lower than that of fly ash from a municipal solid waste incinerator (MSWI). In consideration of this result, a series of experiments were conducted using a sinter mixture impregnated with CuCl2. Experimental results showed that dioxin formation was temperature-dependent in the range of 300-550 degrees C, with the maximum observed at around 300 degrees C, which was quite similar to that of fly ash from the MSWI. The homologue distribution of PCDD/Fs in gas and solid reflected the possible difference in carbonaceous materials in coke and activated coke. Gaseous hydrogen chloride acted as a chlorinating reagent for dioxin formation.


A public resource facilitating clinical use of genomes.
Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the Personal Genome Project choose to forgo privacy via our institutional review board- approved "open consent" process. The contribution of public data and samples facilitates both scientific discovery and standardization of methods. We present our findings after enrollment of more than 1,800 participants, including whole-genome sequencing of 10 pilot participant genomes (the PGP-10). We introduce the Genome-Environment-Trait Evidence (GET-Evidence) system. This tool automatically processes genomes and prioritizes both published and novel variants for interpretation. In the process of reviewing the presumed healthy PGP-10 genomes, we find numerous literature references implying serious disease. Although it is sometimes impossible to rule out a late-onset effect, stringent evidence requirements can address the high rate of incidental findings. To that end we develop a peer production system for recording and organizing variant evaluations according to standard evidence guidelines, creating a public forum for reaching consensus on interpretation of clinically relevant variants. Genome analysis becomes a two-step process: using a prioritized list to record variant evaluations, then automatically sorting reviewed variants using these annotations. Genome data, health and trait information, participant samples, and variant interpretations are all shared in the public domain-we invite others to review our results using our participant samples and contribute to our interpretations. We offer our public resource and methods to further personalized medical research.


Mutational signatures of DNA mismatch repair deficiency in C. elegans and human cancers.
Throughout their lifetime, cells are subject to extrinsic and intrinsic mutational processes leaving behind characteristic signatures in the genome. DNA mismatch repair (MMR) deficiency leads to hypermutation and is found in different cancer types. Although it is possible to associate mutational signatures extracted from human cancers with possible mutational processes, the exact causation is often unknown. Here, we use C. elegans genome sequencing of pms-2 and mlh-1 knockouts to reveal the mutational patterns linked to C. elegans MMR deficiency and their dependency on endogenous replication errors and errors caused by deletion of the polymerase ε subunit pole-4 Signature extraction from 215 human colorectal and 289 gastric adenocarcinomas revealed three MMR-associated signatures, one of which closely resembles the C. elegans MMR spectrum and strongly discriminates microsatellite stable and unstable tumors (AUC = 98%). A characteristic difference between human and C. elegans MMR deficiency is the lack of elevated levels of NCG > NTG mutations in C. elegans, likely caused by the absence of cytosine (CpG) methylation in worms. The other two human MMR signatures may reflect the interaction between MMR deficiency and other mutagenic processes, but their exact cause remains unknown. In summary, combining information from genetically defined models and cancer samples allows for better aligning mutational signatures to causal mutagenic processes.


(18)F-Fluorodeoxyglucose positron-emission tomography could have a prognostic role in patients with advanced hepatocellular carcinoma.
We set out to evaluate the prognostic value of (18)F-fluorodeoxyglucose positron-emission tomography (pet) in patients with advanced (non-transplant-eligible) hepatocellular carcinoma (hcc) and to evaluate the correlation between standardized uptake values (suvs) and survival outcomes. We identified patients with hcc who, from 2005 to 2013, underwent pet imaging before any treatment. This retrospective study from our hcc database obtained complete follow-up data for the 63 identified patients. Of the 63 patients, 10 underwent surgical resection, and 59 underwent locoregional therapy. In this cohort, 28 patients were pet-positive (defined as any lesion with a suv ≥ 4.0) before any therapy was given, and 35 patients were pet negative (all lesions with a suv < 4.0). On survival analysis, median survival was greater for the pet-negative than for the pet-positive patients: 29 months (range: 16.3-41.1 months) versus 12 months (range: 4.0-22.1 months) respectively, p = 0.0241. The pet-positive patients more often had large tumours (≥5 cm), poor differentiation, and extrahepatic disease, reflecting more aggressive tumours. On multivariate analysis, only pet positivity was associated with poor survival (p = 0.049). Compared with pet-positive patients, pet-negative patients with hcc experienced longer survival. Imaging by pet can be of value in early prognostication for patients with hcc, especially patients receiving locoregional therapy for whom pathologic tumour differentiation is rarely available. This potential role for pet requires further validation in a prospective study.


Implementation outcomes of policy and programme innovations to prevent obstetric haemorrhage in low- and middle-income countries: a systematic review.
Globally, obstetric haemorrhage (OH) remains the leading cause of maternal mortality. Much of the associated mortality is ascribed to challenges surrounding deployment of innovations rather than lack of availability. In low- and middle-income countries (LMICs), where the burden is highest, there is a growing interest in implementation research as a means to bridge the 'know-do' gap between proven interventions and their reliable implementation at scale. In this systematic review, we identified and synthesized qualitative and quantitative data across the implementation outcomes of OH prevention innovations in LMICs using a taxonomy developed by Proctor et al. We also identified service outcomes for the included innovations, as well as implementation strategies and implementation facilitators and barriers. Eligible studies were empirical, focused on the implementation of OH prevention programmes or policies and occurred in an LMIC. Eight databases were searched. Two authors independently assessed studies for selection and extracted data; the first author resolved discrepancies. Narrative synthesis was used to analyse and interpret the findings. Studies were predominantly focused in Africa and on primary prevention. Interventions included prophylactic use of uterotonics (n = 7), clinical provider skills training (n = 4) and provision of clinical guidelines (n = 1); some (n = 3) were also part of a multi-component quality improvement bundle. Various barriers were reported, including challenges among intervention beneficiaries, providers and within the health system; however, studies reported the development and testing of practical implementation solutions. These included training and monitoring of implementers, community and stakeholder engagement and guidance by external mentors. Some studies linked successful delivery to implementation outcomes, most commonly adoption and acceptability, but also feasibility, penetration and sustainability. Findings suggest that innovations to prevent OH can be acceptable, appropriate and feasible in LMIC settings; however, more research is needed to better evaluate these and other under-reported implementation outcomes.


Trends in acute myocardial infarction hospitalizations: Are we seeing the whole picture?
Payers and policy makers rely on studies of trends in acute myocardial infarction (AMI) hospitalizations and spending that count only hospitalizations where the AMI is the principal discharge diagnosis. Hospitalizations with AMI coded as a secondary diagnosis are ignored. The effects of excluding these hospitalizations on estimates of trends are unknown. Observational study of all AMI hospitalizations in Fee-for-Service Medicare beneficiaries 65 years and older, from 2002 through 2011. We studied 3,663,137 hospitalizations with any AMI discharge diagnosis over 288,873,509 beneficiary-years. Of these, 66% had AMI coded as principal (versus secondary). From 2002 to 2011, AMI hospitalization rates declined 24.5% (from 1,485 per 100,000 beneficiary-years in 2002 to 1,122 in 2011). Meanwhile, the proportion of these hospitalizations with a secondary AMI diagnosis increased from 28% to 40%; by 2011 these secondary AMI hospitalizations accounted for 43% of all expenditures for hospitalizations with AMI, or $2.8 billion. Major changes in comorbidities, principal diagnoses and mean costs for hospitalizations with a non-principal AMI diagnosis occurred in the 2006-2008 timeframe. Current estimates of the burden of AMI ignore an increasingly large proportion of overall AMI hospitalizations and spending. Changes in the characteristics of hospitalizations that coincided with major payment and policy changes suggest that non-clinical factors affect AMI coding. Failing to consider all AMIs could inflate estimates of population health improvements, overestimate the value of AMI prevention and treatment and underestimate current and future AMI burden and expenditures.


Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts.
In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 μM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 μM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 μM concentration to 150% and 0.5 μM concentration to 200% of normoxic activity.


Kinesio® Tape Barrier Does Not Inhibit Intramuscular Cooling During Cryotherapy.
Allied health care professionals commonly apply cryotherapy as treatment for acute musculoskeletal trauma and the associated symptoms. Understanding the impact of a tape barrier on intramuscular temperature can assist in determining treatment duration for effective cryotherapy. To determine whether Kinesio® Tape acts as a barrier that affects intramuscular temperature during cryotherapy application. A repeated-measures, counterbalanced design in which the independent variable was tape application and the dependent variable was muscle temperature as measured by thermocouples placed 1 cm beneath the adipose layer. Additional covariates for robustness were body mass index and adipose thickness. University research laboratory. Nineteen male college students with no contraindications to cryotherapy, no known sensitivity to Kinesio® Tape, and no reported quadriceps injury within the past 6 months. Topical cryotherapy: cubed ice bags of 1 kg and 0.5 kg. Intramuscular temperature. The tape barrier had no statistically significant effect on muscle temperature. The pattern of temperature change was indistinguishable between participants with and without tape application. Findings suggest that health care professionals can combine cryotherapy with a Kinesio® Tape application without any need for adjustments to cryotherapy duration.


The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex.
Sulfur metabolism has been implicated in the virulence, antibiotic resistance and anti-oxidant defence of Mycobacterium tuberculosis. Despite its human disease relevance, sulfur metabolism in mycobacteria has not yet been fully characterized. ATP sulfurylase catalyses the synthesis of activated sulfate (adenosine 5'-phosphosulfate, APS), the first step in the reductive assimilation of sulfate. Expression of the M. tuberculosis cysD gene, predicted to encode the adenylyl-transferase subunit of ATP sulfurylase, is upregulated by the bacilli inside its preferred host, the macrophage. This study demonstrates that cysD and cysNC orthologues exist in M. tuberculosis and constitute an operon whose expression is induced by sulfur limitation and repressed by the presence of cysteine, a major end-product of sulfur assimilation. The cysDNC genes are also induced upon exposure to oxidative stress, suggesting regulation of sulfur assimilation by M. tuberculosis in response to toxic oxidants. To ensure that the cysDNC operon encoded the activities predicted by its primary sequence, and to begin to characterize the products of the operon, they were expressed in Escherichia coli, purified to homogeneity, and tested for their catalytic activities. The CysD and CysNC proteins were shown to form a multifunctional enzyme complex that exhibits the three linked catalytic activities that constitute the sulfate activation pathway.


A multi-lingual web service for drug side-effect data.
In this paper, we describe a system that provides drug side-effect data for use as a component in service-oriented architectures. Our system uses "Web 2.0" techniques to collect data from a variety of public sources, and can provide its output in a variety of human languages (e.g. Spanish and Arabic). To demonstrate our tool's versatility and the ease with which it may be integrated into larger systems, we present several front-ends that use our system, including SMS ("text message"), "instant messenger", and iPhone interfaces. We enlisted a panel of Argentinean clinicians to review and rate the quality of our system's Spanish-language output in order to investigate whether freely-available general-purpose machine translation technology (Google's translation API) is adequate for consumer medical applications. Our raters found that Google's translation quality varied greatly among drugs, and we conclude that it is better used as a starting point than as a complete translation solution.


Dual responsive PMEEECL-PAE block copolymers: a computational self-assembly and doxorubicin uptake study.
The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens-Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20-AE M compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (T cg) of these copolymers and finding appropriate CG mapping for both PMEEECL-PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75-80%) at different concentrations inside the PMEEECL-PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL-PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.


Immunogenetic studies of chronic lymphocytic leukemia: revelations and speculations about ontogeny and clinical evolution.
Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes associated with a different clinical course that drew attention. As the years ensued, this not only continued to hold strong, but also revealed an unprecedented BcR restriction (aptly coined as "stereotypy"), thus cementing the idea that antigenic elements select the leukemic clones. With all this in mind, in the present review, we focus on the CLL BcR IG, a molecule that clearly lies at the heart of disease pathogenesis, and attempt to distil from past and emerging biologic knowledge the most relevant aspects in the context of the immunogenetics of CLL, while at the same time provoking questions that remain unanswered. We juxtapose CLL with mutated BcR IGs against CLL with unmutated BcR IGs due to their striking clinicobiologic differences; however, when considering ontogeny, common derivation of the two mutational subtypes cannot be excluded. The issue of stereotypy is intertwined throughout and we also raise the subject of isotype-switched CLL, which, despite its rarity, contributes intriguing ontogenetic hints.


Impact of Noise Exposure on Risk of Developing Stress-Related Health Effects Related to the Cardiovascular System: A Systematic Review and Meta-Analysis.
: Exposure to acute noise can cause an increase in biological stress reactions, which provides biological plausibility for a potential association between sustained noise exposure and stress-related health effects. However, the certainty in the evidence for an association between exposures to noise on short- and long-term biomarkers of stress has not been widely explored. The objective of this review was to evaluate the strength of evidence between noise exposure and changes in the biological parameters known to contribute to the development of stress-related adverse cardiovascular responses. This systematic review comprises English language comparative studies available in PubMed, Cochrane Central, EMBASE, and CINAHL databases from January 1, 1980 to December 29, 2021. Where possible, random-effects meta-analyses were used to examine the effect of noise exposure from various sources on stress-related cardiovascular biomarkers. The risk of bias of individual studies was assessed using the risk of bias of nonrandomized studies of exposures instrument. The certainty of the body of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. : The search identified 133 primary studies reporting on blood pressure, hypertension, heart rate, cardiac arrhythmia, vascular resistance, and cardiac output. Meta-analyses of blood pressure, hypertension, and heart rate suggested there may be signals of increased risk in response to a higher noise threshold or incrementally higher levels of noise. Across all outcomes, the certainty of the evidence was very low due to concerns with the risk of bias, inconsistency across exposure sources, populations, and studies and imprecision in the estimates of effects. : This review identifies that exposure to higher levels of noise may increase the risk of some short- and long-term cardiovascular events; however, the certainty of the evidence was very low. This likely represents the inability to compare across the totality of the evidence for each outcome, underscoring the value of continued research in this area. Findings from this review may be used to inform policies of noise reduction or mitigation interventions.


[Psychosocial aspects regarding pregnant university students].
Determining the subjective construction of psychosocial factors affecting pregnancy in adolescents in a sample of students. 68 students who had become pregnant during their adolescence were selected after reviewing their files and sampling by logical criteria. The implications of pregnancy on personal, family and academic conditions were analysed by means of life stories and in-depth interviews. Crises and adjustments appeared in family and affective structure during the first trimester of pregnancy which culminated in them accepting motherhood as part of their life project, thereby reproducing the single-mother stereotype. Accompaniment of the pair occurred mainly during the first months, followed by abandonment. Although prejudiced, the university community's support had a bearing on interest in personal and academic development and in the baby. Specialised referents were consulted which scared the girls due to their pathological emphasis, thereby leading to them consulting family sources. The pregnant girls' mothers provided ongoing support for their daughters; this was not true of the fathers with whom constant conflict was presented. The services offered by the university were little used even though their importance was recognised. Forming integral students require programmes preparing students to be responsible for motherhood and fatherhood. Prevention was conveyed as promoting healthy affective links and strengthening family and social communication.


Grass bud responses to fire in a semiarid savanna system.
Increasingly, land managers have attempted to use extreme prescribed fire as a method to address woody plant encroachment in savanna ecosystems. The effect that these fires have on herbaceous vegetation is poorly understood. We experimentally examined immediate (<24 hr) bud response of two dominant graminoids, a C3 caespitose grass, Nassella leucotricha, and a C4 stoloniferous grass, Hilaria belangeri, following fires of varying energy (J/m2) in a semiarid savanna in the Edwards Plateau ecoregion of Texas. Treatments included high- and low-energy fires determined by contrasting fuel loading and a no burn (control) treatment. Belowground axillary buds were counted and their activities classified to determine immediate effects of fire energy on bud activity, dormancy, and mortality. High-energy burns resulted in immediate mortality of N. leucotricha and H. belangeri buds (p < .05). Active buds decreased following high-energy and low-energy burns for both species (p < .05). In contrast, bud activity, dormancy, and mortality remained constant in the control. In the high-energy treatment, 100% (n = 24) of N. leucotricha individuals resprouted while only 25% (n = 24) of H. belangeri individuals resprouted (p < .0001) 3 weeks following treatment application. Bud depths differed between species and may account for this divergence, with average bud depths for N. leucotricha 1.3 cm deeper than H. belangeri (p < .0001). Synthesis and applications: Our results suggest that fire energy directly affects bud activity and mortality through soil heating for these two species. It is imperative to understand how fire energy impacts the bud banks of grasses to better predict grass response to increased use of extreme prescribed fire in land management.


The interaction between respiratory viruses and pathogenic bacteria in the upper respiratory tract of asymptomatic Aboriginal and non-Aboriginal children.
Associations between respiratory viruses and the bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis may be important in the pathogenesis of otitis media (OM). However, data on asymptomatic identification rates of respiratory viruses are limited, particularly in Indigenous populations, who suffer a high burden of OM. We describe the identification of respiratory viruses alone and in combination with pathogenic OM bacteria in 1006 nasopharyngeal aspirates collected from asymptomatic Aboriginal and non-Aboriginal children in a longitudinal community-based cohort study in rural Western Australia. Viruses were identified in 42% of samples from Aboriginal and 32% from non-Aboriginal children. Rhinoviruses were the most frequently identified virus with higher identification rates in Aboriginal (23.6%) than non-Aboriginal children (16.5%; P = 0.003). Rhinoviruses were associated with H. influenzae (odds ratio [OR], 2.24; 95% CI, 1.24-4.07 for Aboriginal children) and M. catarrhalis (OR, 1.94; 95% CI, 1.05-3.57 for Aboriginal children). Adenoviruses were positively associated with H. influenzae in Aboriginal children (OR, 3.30; 95% CI, 1.19-9.09) and M. catarrhalis in non-Aboriginal children (OR, 5.75; 95% CI, 1.74-19.23), but negatively associated with S. pneumoniae in Aboriginal children (OR, 0.39; 95% CI, 0.18-0.84). We found a high identification rate of rhinoviruses and adenoviruses in asymptomatic children. The associations between these viruses and OM bacteria have implications for preventive strategies targeted at specific pathogens.


Intercalated duct cell is starting point in development of pancreatic ductal carcinoma?
Although it is well known that the pancreatic ductal carcinoma may develop having a relationship to the mucous gland hyperplasia (MGH) with atypia (PanIN-1B by PanIN system), the starting point of this atypical MGH is unclear. To know it, we examined the pancreas tissue using many methods described below. 1. Twenty-seven surgically resected pancreas tissue specimens, including pancreatic ductal carcinomas (PDC), chronic pancreatitis and normal pancreas, were investigated using immunohistochemical stainings for MUC1, MUC6, 45M1, Ki67 and p53. 2. DNA extraction and analysis of K-ras mutation at codon 12 using microdissection method: The paraffin blocks with 16 regions including the intercalated duct cell (IC) adjacent to the atypical MGH were prepared for DNA extraction. Mutation of K-ras codon 12 was analyzed and compared in enriched polymerase chain reaction-enzyme-linked mini sequence assay (PCR-ELMA). 1. In the normal pancreas, although no positive cell was seen in 45M1, p53, Ki67, the cytoplasm of IC were always positive for MUC1 and sometimes positive for MUC6. In the pancreas with fibrosis or inflammation, MGH was positive for MUC6 and 45M1. And atypical MGH was positive for MUC1, MUC6 and 45M1. Some IC adjacent to the atypical MGH was positive for Ki67 as well as atypical MGH. The carcinoma cells in all cases of PDC were diffusely positive for MUC1, 45M1, p53 and Ki67, and focally positive for MUC6. 2. In K-ras mutation, we examined the regions including IC adjacent to the atypical MGH, because the immunohistochemical apomucin stainings of these regions resembled those of PDC as described above. And K-ras mutation was confirmed in 12 of 16 regions (75%). All mutations were a single mutation, in 6 regions GTT was detected, in 4 regions GAT was detected and in 2 region AGT was detected. Some intercalated duct cell may be the starting point of the pancreatic ductal carcinoma, because the exhibitions of mucin expressions, Ki67, p53 and K-ras mutation in some intercalated duct cell resembled those of mucous gland hyperplasia or pancreatic ductal carcinoma.


Mesolimbic novelty processing in older adults.
Normal aging is associated with neuronal loss in the dopaminergic midbrain (substantia nigra/ventral tegmental area, SN/VTA), a region that has recently been implicated in processing novel stimuli as part of a mesolimbic network including the hippocampus. Here, we quantified age-related structural degeneration of the mesolimbic system using magnetization transfer ratio (MTR) and correlated it with mesolimbic hemodynamic responses (HRs) to stimulus novelty. Twenty-one healthy older adults between 55 and 77 years performed a visual oddball paradigm allowing to distinguish mesolimbic HRs to novelty from rareness, negative emotional valence, and targetness using functional magnetic resonance imaging. The HRs in the right SN/VTA and the right hippocampus to novelty were positively correlated both with the SN/VTA MTR and hippocampus MTR but not amygdala MTR. However, the HR of the amygdala to negative emotional valence correlated with the amygdala MTR but not with the MTR in SN/VTA or the hippocampus. The results establish a structure-function relationship in support of a hippocampal-SN/VTA loop of mesolimbic novelty processing by showing that the hemodynamic activation in SN/VTA and hippocampus for novelty is selectively affected by age-related degeneration of these structures.


Specific amino acids of Olive mild mosaic virus coat protein are involved in transmission by Olpidium brassicae.
Transmission of Olive mild mosaic virus (OMMV) is facilitated by Olpidium brassicae (Wor.) Dang. An OMMV mutant (OMMVL11) containing two changes in the coat protein (CP), asparagine to tyrosine at position 189 and alanine to threonine at position 216, has been shown not to be Olpidium brassicae-transmissible owing to inefficient attachment of virions to zoospores. In this study, these amino acid changes were separately introduced into the OMMV genome through site-directed mutagenesis, and the asparagine-to-tyrosine change was shown to be largely responsible for the loss of transmission. Analysis of the structure of OMMV CP by comparative modelling approaches showed that this change is located in the interior of the virus particle and the alanine-to-threonine change is exposed on the surface. The asparagine-to-tyrosine change may indirectly affect attachment via changes in the conformation of viral CP subunits, altering the receptor binding site and thus preventing binding to the fungal zoospore.


Food acquisition habits in a group of African refugees recently settled in Australia.
This study investigated how recently arrived refugees acquired food in their local food neighbourhood. Ten African humanitarian migrants belonging to separate households were asked to keep a travel and food diary for one week. Participants' food neighbourhoods were mapped using online satellite pictures and direct observation. On average 78 food outlets were available within a 2km radius of participants' homes. Vegetable consumption was higher in participants who resided <1km from a major grocery retailer (p<0.05). Foods provided during migrant orientation events were the major opportunities where subjects were introduced to foods more typical of reported usual intake in the general sedentee Australian population. The initial 12 months of resettlement is a critical period for acculturation as participants stabilise food habits. While participants seemed not to live in food deserts, intakes of all food groups remained inferior to recommended levels suggesting physical proximity and implied in-store choice alone do not guarantee a healthy diet. Migrant orientation events may represent an important setting for education about suitable options for adopting new foods into diets.


Hyaluronan in cervical epithelia protects against infection-mediated preterm birth.
Increased synthesis of cervical hyaluronan (HA) from early to late pregnancy has long been proposed to play an essential role in disorganization of the collagen-rich extracellular matrix to allow for maximal compliance and dilation of the cervix during the birth process. Here, we show that HA is not essential for increased cervical distensibility during late pregnancy. Rather, cervicovaginal HA plays an unanticipated important role in epithelial barrier protection of the lower reproductive tract. Specifically, HA depletion in the cervix and vagina resulted in inappropriate differentiation of epithelial cells, increased epithelial and mucosal permeability, and strikingly increased preterm birth rates in a mouse model of ascending vaginal infection. Collectively, these findings revealed that although HA is not obligatory for cervical compliance, it is crucial for maintaining an epithelial and mucosal barrier to limit pathogen infiltration of the lower reproductive tract during pregnancy and thereby is protective against infection-mediated preterm birth.


Mindfulness for teachers: A pilot study to assess effects on stress, burnout and teaching efficacy.
Despite the crucial role of teachers in fostering children's academic learning and social-emotional well-being, addressing teacher stress in the classroom remains a significant challenge in education. The present study reports results from a randomized controlled pilot trial of a modified Mindfulness-Based Stress Reduction course (mMBSR) adapted specifically for teachers. Results suggest the course may be a promising intervention, with participants showing significant reductions in psychological symptoms and burnout, improvements in observer-rated classroom organization and performance on a computer task of affective attentional bias, and increases in self-compassion. In contrast, control group participants showed declines in cortisol functioning over time and marginally significant increases in burnout. Furthermore, changes in mindfulness were correlated in the expected direction with changes across several outcomes (psychological symptoms, burnout, sustained attention) in the intervention group. Implications of these findings for the training and support of teachers are discussed.


Objectifying specific and nonspecific effects of acupuncture: a double-blinded randomised trial in osteoarthritis of the knee.
Introduction. Acupuncture was recently shown to be effective in the treatment of knee osteoarthritis. However, controversy persists whether the observed effects are specific to acupuncture or merely nonspecific consequences of needling. Therefore, the objective of this study is to determine the efficacy of different acupuncture treatment modalities. Materials and Methods. We compared between three different forms of acupuncture in a prospective randomised trial with a novel double-blinded study design. One-hundred and sixteen patients aged from 35 to 82 with osteoarthritis of the knee were enrolled in three study centres. Interventions were individualised classical/ modern semistandardised acupuncture and non-specific needling. Blinded outcome assessment comprised knee flexibility and changes in pain according to the WOMAC score. Results and Discussion. Improvement in knee flexibility was significantly higher after classical Chinese acupuncture (10.3 degrees; 95% CI 8.9 to 11.7) as compared to modern acupuncture (4.7 degrees; 3.6 to 5.8). All methods achieved pain relief, with a patient response rate of 48 percent for non-specific needling, 64 percent for modern acupuncture, and 73 percent for classical acupuncture. Conclusion. This trial establishes a novel study design enabling double blinding in acupuncture studies. The data suggest a specific effect of acupuncture in knee mobility and both non-specific and specific effects of needling in pain relief.


Evidence for the presence of oligophosphoglyceroyl-ATP in rat offney.
The inability to account for large systematic variations in total purine nucleotide content of perfused rat hearts led to the demonstration that the soluble adenine nucleotides are in rapid equilibrium with a highly phosphorylated hetero-oligomeric derivative whose structure appears to be 3-phospho[glyceroyl-gamma-triphospho-5'-adenosine-3'-3-phosp ho]4glyceroyl- gamma-triphospho-5'-adenosine [Hutchinson, Morris & Mowbray (1986) Biochem. J. 234, 623-627]. Analogous techniques to those used with hearts for specifically labelling tissue purine nucleotides followed by extration and purification of nucleotides from the trichloroacetic acid-precipitable fraction show the existence of a corresponding rapid equilibrium between ATP and an oligomeric tetraphosphoadenosine derivative in perfused kidneys.


The use of natural media amendments to produce kale enhanced with functional lipids in controlled environment production system.
Diets high in vegetable consumption is highly correlated with reduced risk of developing common lifestyle related diseases. We investigated the effects of three natural growth media amendments [potassium humate, dry vermicast, volcanic minerals or Promix alone (Control)] in enhancing the accumulation of functional lipids in greenhouse grown kale. Functional lipids (n9, n6, n3 fatty acids, diglycerides, galactolipids and phytosterols) were assessed using either gas chromatography/mass spectrometry (GC/MS) or ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HRMS/MS). The results showed volcanic minerals and dry vermicast were the most successful in enhancing the accumulation of functional lipids in kale. For example, dry vermicast enhanced the accumulation of total C18:1n9 and C16:3n3 fatty acids, while total C18:2n6 fatty acid accumulation was enhanced by volcanic minerals. In conclusion, natural growing medium amendments are remarkably effective in modulating the accumulation of functional lipids in kale grown under controlled-environment conditions. This could be a useful strategy for functional foods production in control environment production systems. Increase access to kale with enhanced functional lipids could aid in increase consumption of these health promotive compounds in the diet with potential implications in population health.


Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism.
This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30 degrees N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency's being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy. Further investigation of this hypothesis is warranted.