Exploring the individual patterns of spiritual well-being in people newly diagnosed with advanced cancer: a cluster analysis.
Research shows that spiritual well-being correlates positively with quality of life (QOL) for people with cancer, whereas contradictory findings are frequently reported with respect to the differentiated associations between dimensions of spiritual well-being, namely peace, meaning and faith, and QOL. This study aimed to examine individual patterns of spiritual well-being among patients newly diagnosed with advanced cancer. Cluster analysis was based on the twelve items of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale at Time 1. A combination of hierarchical and k-means (non-hierarchical) clustering methods was employed to jointly determine the number of clusters. Self-rated health, depressive symptoms, peace, meaning and faith, and overall QOL were compared at Time 1 and Time 2. Hierarchical and k-means clustering methods both suggested four clusters. Comparison of the four clusters supported statistically significant and clinically meaningful differences in QOL outcomes among clusters while revealing contrasting relations of faith with QOL. Cluster 1, Cluster 3, and Cluster 4 represented high, medium, and low levels of overall QOL, respectively, with correspondingly high, medium, and low levels of peace, meaning, and faith. Cluster 2 was distinguished from other clusters by its medium levels of overall QOL, peace, and meaning and low level of faith. This study provides empirical support for individual difference in response to a newly diagnosed cancer and brings into focus conceptual and methodological challenges associated with the measure of spiritual well-being, which may partly contribute to the attenuated relation between faith and QOL.


Phorbol ester induces tyrosine phosphorylation in normal and abnormal human B lymphocytes.
Tumor-promoting phorbol esters have been found to bind and activate phospholipid/Ca2+-dependent or C-kinase, and several of their effects, including proliferative responses in lymphocytes, have been assumed to be related to activity of this enzyme. However, phorbol esters have also recently been found to stimulate tyrosine phosphorylation in certain other cell types, and we therefore studied tyrosine kinase activity in normal and chronic lymphocytic leukemia (CLL) peripheral blood B lymphocytes stimulated with phorbol ester. High levels of tyrosine labeling were observed in unstimulated cells with major endogenous substrates of 75K, 66K, 43K, and 28K in Triton-soluble material, and of 56K to 61K in Triton-insoluble material; this profile was essentially similar in normal and CLL B cells. Treatment with phorbol ester for time periods varying from 20 min to 48 hr led to qualitative increases in tyrosine labeling of these phosphoproteins, as measured both in vitro and in intact cells "in vivo." Although the relative abundance of tyrosine phosphorylation as a percentage of total labeling was variable due to concomitant enhancement of serine and threonine phosphorylation, exogenous peptide substrate assays confirmed the increased tyrosine kinase activity quantitatively. Enhanced tyrosine phosphorylation was succeeded or accompanied in both normal and abnormal B cells by cellular activation, as judged by increased [3H]thymidine uptake, and terminal differentiation of CLL cells. These findings provide further evidence implicating tyrosine kinases in B lymphocyte activation.


Clonality and molecular pathogenesis of mastocytosis.
Mast cell is a hematopoietic lineage dependent on Kit signaling for growth, differentiation, and survival. Mast cells are found in excessive numbers in tissues in a heterogeneous group of disorders collectively known as mastocytosis. Last decade has witnessed important advancements in our understanding of the molecular pathology of mastocytosis. First, systemic mastocytosis has been found to be associated with activating codon 816 mutations of the c-kit gene. Second, this mutation was used as a tracking marker to elucidate the clonal nature of mastocytosis. These findings have resulted in consideration of systemic mastocytosis as a clonal neoplastic disorder of a hematopoietic progenitor cell. Improved knowledge of the mechanisms causing pathological mast cell growth will lead to the discovery of novel treatment options including drugs targeting the mutated Kit protein.


A wireless and artefact-free 128-channel neuromodulation device for closed-loop stimulation and recording in non-human primates.
Closed-loop neuromodulation systems aim to treat a variety of neurological conditions by delivering and adjusting therapeutic electrical stimulation in response to a patient's neural state, recorded in real time. Existing systems are limited by low channel counts, lack of algorithmic flexibility, and the distortion of recorded signals by large and persistent stimulation artefacts. Here, we describe an artefact-free wireless neuromodulation device that enables research applications requiring high-throughput data streaming, low-latency biosignal processing, and simultaneous sensing and stimulation. The device is a miniaturized neural interface capable of closed-loop recording and stimulation on 128 channels, with on-board processing to fully cancel stimulation artefacts. In addition, it can detect neural biomarkers and automatically adjust stimulation parameters in closed-loop mode. In a behaving non-human primate, the device enabled long-term recordings of local field potentials and the real-time cancellation of stimulation artefacts, as well as closed-loop stimulation to disrupt movement preparatory activity during a delayed-reach task. The neuromodulation device may help advance neuroscientific discovery and preclinical investigations of stimulation-based therapeutic interventions.


Association between blood concentration of polychlorinated biphenyls and manifestations of symptoms and signs in chronic "Yusho" patients from 1986 to 1997.
To examine the association between blood PCB level and manifestations of symptoms and signs by Yusho patients, a cross-sectional study was conducted using the results of nationwide health examination for Yusho. The subjects were the officially identified Yusho patients who admitted the health examination from 1986 to 1997. The number of examinees with known blood PCB level was 334 in 1986, and decreased to 214 in 1997. The numbers of male and female patients were similar. The geometric mean (95% confidence interval) of blood PCBs concentration was 4.05 ppb (3.75 to 4.37) in 1986 and 2.85 ppb (2.63 to 3.08) in 1997. Multiple logistic regression analysis was carried out for the data of each year with log-transformed blood PCB level as an explanatory variable and a manifestation of a sign or symptom as a response variable. Sex and age adjusted odds ratio and significance level (P) were computed. Positive association of blood PCB level with manifestations of comedones on the trunk and acneiform eruptions on the genital and gluteal regions was statistically significant for five, eight and six times, respectively. No other symptoms or signs showed such strong associations. Associations between manifestations of these signs and blood PCB level, however, did not seem to diminish in the twelve years of observation. It is suggested that the positive association of these signs with blood PCB level will still be maintained.


Two Dutch families with hereditary hyperferritinaemia-cataract syndrome and heterozygosity for an HFE-related haemochromatosis gene mutation.
Hereditary haemochromatosis is an autosomal recessive disorder, leading to progressive iron overload, which is very common among the Caucasian population. In the vast majority of the cases, the hereditary iron overload is caused by mutations in the HFE gene. Most prominently this is the homozygous Cys282Tyr mutation. We report two Dutch families in which both propositi were found to be heterozygous for Cys282Tyr in the work-up of hyperferritinaemia. Frequent phlebotomies had no effect on the ferritin level, but led to microcytic anaemia. Finally, the family history with bilateral cataracts was the clue for the correct diagnosis. Hereditary hyperferritinaemia-cataract syndrome (HHCS) is an autosomal dominant disease characterised by elevated serum ferritin levels and bilateral cataracts in the absence of iron overload. Several point mutations and deletions within the iron-responsive element (IRE) in the 5' noncoding region of the L-ferritin gene have been found in HHCS families. In the first Dutch family a G to C transition at position 32 was found and a G to A mutation at the same location was found in the second Dutch family. In individuals with an isolated hyperferritinaemia (normal transferrin saturation), the presence of early onset (familial) cataract should raise the possibility of HHCS, even when Cys282Tyr heterozygosity is found.


Generating hypotheses by discovering implicit associations in the literature: a case report of a search for new potential therapeutic uses for thalidomide.
The availability of scientific bibliographies through online databases provides a rich source of information for scientists to support their research. However, the risk of this pervasive availability is that an individual researcher may fail to find relevant information that is outside the direct scope of interest. Following Swanson's ABC model of disjoint but complementary structures in the biomedical literature, we have developed a discovery support tool to systematically analyze the scientific literature in order to generate novel and plausible hypotheses. In this case report, we employ the system to find potentially new target diseases for the drug thalidomide. We find solid bibliographic evidence suggesting that thalidomide might be useful for treating acute pancreatitis, chronic hepatitis C, Helicobacter pylori-induced gastritis, and myasthenia gravis. However, experimental and clinical evaluation is needed to validate these hypotheses and to assess the trade-off between therapeutic benefits and toxicities.


Correction factors for Farmer-type chambers for absorbed dose determination in 60Co and 192Ir brachytherapy dosimetry.
This paper presents experimentally determined correction factors for Farmer-type chambers for absorbed dose determination in 60Co and 192Ir brachytherapy dosimetry. The correction factors were determined from measurements made in a PMMA phantom and calculation of ratios of measured charges. The ratios were corrected for the different volumes of the ionization chambers, determined in external high-energy electron beams. The correction factors for the central electrode effect and the wall material dependency in 60Co brachytherapy dosimetry agree with those used in external 60Co beam dosimetry. In 192Ir dosimetry, the central aluminium electrode increases the response of an NE2571 chamber compared with that of a chamber with a central graphite electrode. The increase is 1.1 and 2.1% at 1.5 and 5.0 g cm(-2) distance, respectively. Similar values are obtained with an NE2577 chamber. The wall correction factor in 192Ir dosimetry for a chamber with an A-150 wall has been determined to be 1.018, independent of the measurement distance. For a graphite walled chamber, the correction factor is 0.996 and 1.001 at 1.5 and 5.0 g cm(-2) distance, respectively. The values of the wall correction factors are evaluated by a theory presented. If the chamber is used according to the 'large cavity' principle, the correction factor to account for the replacement of the phantom material by the ionization chamber was determined to be 0.982 for an NE2571 chamber when used with a Delrin cap, and 0.978 for an NE2581 when used with a polystyrene cap. The correction factors for the 'large cavity' principle are valid at both 60Co and 192Ir qualities.


Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma.
Nab-paclitaxel has radiosensitizing antitumor efficacy in pancreatic cancer. We aimed to establish maximum tolerated dose (MTD) of nab-paclitaxel with radiotherapy in unresectable locally advanced pancreatic cancer. In a phase I dose escalation trial patients received weekly nab-paclitaxel for 6 weeks with external beam radiotherapy (EBRT). 3 + 3 design was used with nab-paclitaxel doses: 25 mg/m 2 (cohort 1), 50 mg/m 2 (cohort 2), 75 mg/m 2 (cohort 3), and 100 mg/m 2 (cohort 4). Primary endpoint was MTD. Secondary objectives were progression-free survival and overall survival. Fourteen patients were recruited. Median age was 69 years (range, 40-86). Grade 1/2 toxicities were nausea (93%), vomiting (54%), diarrhea (57%), and fatigue (69%). There were no dose limiting toxicities (DLT) in cohorts 1 to 3. In cohort 4, DLTs of febrile neutropenia and enterocolitis were observed in patient 1. Subsequent DLT of febrile neutropenia and enterocolitis occurred in patient 5 in the expanded cohort. Following chemoradiotherapy median progression-free survival was 4.7 months (95% confidence interval, 2.5-27.5) and median overall survival was 10.8 months (95% confidence interval, 6.37-25.2). Nab-paclitaxel and EBRT was well-tolerated at doses below 100 mg/m 2 . The MTD and recommended phase II study dose for nab-paclitaxel with EBRT is 75 mg/m 2 in this disease.


A new preparation for microcirculatory studies of the hamster cheek pouch.
Existing methods of preparing the hamster cheek pouch for observation under an intravital microscope have several disadvantages. The everted method, described by Duling (Microvasc. Res. 5: 423-429, 1973), appears to restrict blood flow by placing unnatural tension on the retractor muscle and by requiring an incision in the tip of the pouch. The method of Yamaki et al. (Microvasc. Res. 21: 299-301, 1981) requires an incision in the tip of the pouch and complete disconnection of the retractor muscle. The chamber method of Greenblatt et al. (Microvasc. Res. 1: 420-432, 1969) has a limited optical resolution because the tissue cannot easily be transilluminated with properly condensed light. We have devised a less traumatic method of preparing the pouch, which eliminates these disadvantages. The hamster is anesthetized, and a thin, glass support plate is inserted into the left cheek pouch. The plate is constructed and positioned so that it does not restrict flow to any part of the pouch. The free end of the plate is secured to the animal stage. An incision is made in the skin to expose the cheek pouch, and the loose, avascular connective tissue investing the pouch and the retractor muscle is removed. The pouch is positioned at an angle of 20 degrees from the hamster's body in a temperature-controlled chamber over a standard microscope condensor system. Throughout both surgical and experimental procedures, the pouch is superfused with Ringer-bicarbonate solution at 37.5 degrees C. This preparation minimizes surgical trauma and allows the entire vascular supply to the cheek pouch to be studied.


The spleen-to-liver ratios in hepatic diseases.
We compared light pen (LPEN) and Region of Interest (ROI) computer methods in determining spleen-to-liver (S/L) ratios both in anterior and posterior images in various liver diseases. The S/L ratio was independent of age or type of colloid used (equal particle size provided). Results with corresponding LPEN and ROI programs did not differ significantly from each other. The sensitivity and specificity were tested and the anterior view yielded somewhat better results than the posterior view but the best results were obtained when both projections were used. The sensitivity for all liver diseases was 60% and the corresponding specificity 93%. In hepatocellular diseases the sensitivity was 80-100%, but the S/L ration had only 37% sensitivity for hepatic metastases. Hepatomegaly in the anterior view was found in 67% of fatty liver cases, in 25% of cirrhosis cases, in 20% of hepatitis and in 25% of metastatic livers. Splenomegaly was noted in 39-54% of patients with hepatocellular diseases but only in 4-10% of metastatic diseases.


Renal clearance of an ionic high-osmolar and a nonionic low-osmolar contrast medium.
One hundred patients with normal serum creatinine concentration underwent intravenous urography with either an ionic high-osmolar (diatrizoate) or a nonionic low-osmolar (iopamidol) contrast medium after randomization. Before injection of the contrast medium, a blood sample was drawn for determinating serum creatinine concentration, and a urine sample for measurement of urine osmolality. Using x-ray fluorescence, the plasma concentration of iodine (contrast medium) was determined on blood samples drawn approximately 3 and 4 hours after injection of the contrast medium. The glomerular filtration rate was calculated by two different formulas: one requiring only a single sample and one requiring at least two samples (standard). There were poor correlations between the standard contrast medium clearance and the serum creatinine concentration, the estimated creatinine clearance (calculated from a nomogram), as well as the urine osmolality. The 3-hour and the 4-hour single-sample values correlated well with the two-sample values for both contrast media. In patients with normal serum creatinine, the glomerular filtration rate determined by measuring the contrast medium concentration in a single plasma sample obtained at 3 hours, is almost identical to the value determined from two samples. Consequently, two samples are unnecessary.


Sequence of the immunodominant epitope for the surface protein on sporozoites of Plasmodium vivax.
Plasmodium vivax is one of the four malaria parasites that cause disease in humans. The structure of the immunodominant repeating peptide of the circumsporozoite (CS) protein of P. vivax was determined. A fragment of P. vivax DNA that encodes this tandemly repeating epitope was isolated by use of an oligonucleotide probe whose sequence is thought to be conserved in CS protein genes. DNA sequence analysis of the P. vivax clone indicates that the CS repeat is nine amino acids in length (Gly-Asp-Arg-Ala-Asp-Gly-Gln-Pro-Ala). The structure of the repeating region was confirmed with synthetic peptides and monoclonal antibodies directed against P. vivax sporozoites. This information should allow synthesis of a vaccine for P. vivax that is similar to the one being tested for P. falciparum.


Effects of Medicinal Plants and Flavonoids on Parkinson's Disease: A Review on Basic and Clinical Evidences.
Parkinson's disease (PD) is a neurodegenerative disorder which is characterized by typical symptoms including gradual progressive muscle rigidity, tremor and loss of motor skills. Although there is no definitive cure for PD, the extract of some medicinal plants and their ingredients have been suggested to relieve its symptoms and to prevent disability in patients. This review is focused on therapeutic effects of some medicinal plants and their ingredients on PD. The findings presented in this review were collected from experimental and clinical studies in databases including PubMed, Web of Science and Google Scholar until the end of May 2019. The keywords "neurotoxicity " or "Parkinson's disease" or "neuroprotective" and "Medicinal plants" and "Flavonoids" were searched. Based on the results of animal and clinical studies, the extract of medicinal plants and their components which are discussed in this review have neuro-protective effects against PD. These protective properties mainly are mediated through inhibition of dopamine metabolizing enzymes, reduction oxidant markers, increase of antioxidant agents and suppression of neuro-inflammation.


The Expression of Chemosensory Genes in Male Maxillary Palps of Anopheles coluzzii (Diptera: Culicidae) and An. quadriannulatus.
Because of its importance as a malaria vector, Anopheles coluzzii's Coetzee & Wilkerson olfactory system has been studied extensively. Among this work is a series of studies comparing the expression of chemosensory genes in olfactory organs in females and/or males of these species. These have identified species- and female-biased chemosensory gene expression patterns. However, many questions remain about the role of chemosensation in male anopheline biology. To pave the way for future work we used RNAseq to compare chemosensory gene expression in the male maxillary palps of An. coluzzii and its sibling species An. quadriannulatus Theobald. As expected, the chemosensory gene repertoire is small in the male maxillary palps. Both species express the tuning receptors Or8 and Or28 at relatively high levels. The CO2 receptor genes Gr22-Gr24 are present in both species as well, although at much lower level than in females. Additionally, several chemoreceptors are species-specific. Gr37 and Gr52 are exclusive to An. coluzzii, whereas Or9 and Gr60 were detected only in An. quadriannulatus. Furthermore, several chemosensory genes show differential expression between the two species. Finally, several Irs, Grs, and Obps that show strong differential expression in the female palps, are absent or lowly expressed in the male palps. While many questions remain about the role of chemosensation in anopheline male biology, these results suggest that the male maxillary palps could have both a sex- and species-specific role in the perception of chemical stimuli. This work may guide future studies on the role of the male maxillary palp in these species.


Cubic Rashba Effect in the Surface Spin Structure of Rare-Earth Ternary Materials.
Spin-orbit interaction and structure inversion asymmetry in combination with magnetic ordering is a promising route to novel materials with highly mobile spin-polarized carriers at the surface. Spin-resolved measurements of the photoemission current from the Si-terminated surface of the antiferromagnet TbRh_{2}Si_{2} and their analysis within an ab initio one-step theory unveil an unusual triple winding of the electron spin along the fourfold-symmetric constant energy contours of the surface states. A two-band k·p model is presented that yields the triple winding as a cubic Rashba effect. The curious in-plane spin-momentum locking is remarkably robust and remains intact across a paramagnetic-antiferromagnetic transition in spite of spin-orbit interaction on Rh atoms being considerably weaker than the out-of-plane exchange field due to the Tb 4f moments.


Kinetics, tissue specificity and pathological changes in murine rotavirus infection of mice.
Mice that did not contain antibodies to rotavirus were orally infected with murine rotavirus (EDIM strain) and observed over 7 days. As judged by ELISA, only the small intestine was infected, not the colon. The infection was biphasic, viral antigen peaks being observed at 48 h and approximately 120 h post-infection. Clinically evident diarrhoea was maximal at 72 h. Virus in the upper, middle and lower regions of the small intestine was mainly tissue-associated; most virus was found in the middle small intestine. Two peaks (48 h and 120 h post-infection) of virus antigen were observed in the colon, but these corresponded to luminal, not tissue-associated viral antigen. Only enterocytes in the upper two-thirds of villus epithelia were infected as judged by fluorescent-antibody analysis and transmission electron microscopy. Scanning electron microscopy revealed morphological appearances not hitherto correlated with the progress of the infection: villus tips were convoluted, corresponding to the shedding of virus-infected cells but the lower regions of infected villi were shrunken and considerably narrowed compared to tips.


Experimental evidence of false-positive Comet test results due to TiO2 particle--assay interactions.
We have studied the genotoxicity of TiO2 particles with a Comet assay on a unicellular organism, Tetrahymena thermophila. Exposure to bulk- or nano-TiO2 of free cells, cells embedded in gel or nuclei embedded in gel, all resulted in a positive Comet assay result but this outcome could not be confirmed by cytotoxicity measures such as lipid peroxidation, elevated reactive oxygen species or cell membrane composition. Published reports state that in the absence of cytotoxicity, nano- and bulk-TiO2 genotoxicity do not occur directly, and a possible explanation of our Comet assay results is that they are false positives resulting from post festum exposure interactions between particles and DNA. We suggest that before Comet assay is used for nanoparticle genotoxicity testing, evidence for the possibility of post festum exposure interactions should be considered. The acellular Comet test described in this report can be used for this purpose.


Rectal self-sampling in non-clinical venues for detection of sexually transmissible infections among behaviourally bisexual men.
Rectal sexually transmissible infections are a common health concern for men who have sex with men but little is known about these infections among men who have sex with both men and women. Self-obtained rectal specimens were collected from a diverse sample of behaviourally bisexual men. From a total sample of 75 bisexual men, 58 collected specimens. A relatively high prevalence of rectal Chlamydia trachomatis infection was found. Participants who collected specimens reported overall acceptability and comfort with self-sampling. Future efforts are needed focusing on increasing awareness of and options for rectal sexually transmissible infection testing among bisexual men.


Slow Magnetic Relaxation in Dinuclear CoIIYIII Complexes.
Four new dinuclear complexes, [Co(μ-L)(μ-CCl3COO)Y(NO3)2]·2CHCl3·CH3CN·2H2O (1), [Co(μ-L)(μ-CH3COO)Y(NO3)2]·CH3CN (2), [Co(μ-L)(μ-PhCOO)Y(NO3)2]·3CH3CN·2H2O (3), and [Co(μ-L)(μ-tBuCOO)Y(NO3)2]·CHCl3·2H2O (4), having a CoIIYIII core, have been synthesized by employing a ferrocene based compartmental ligand which was synthesized by the reaction of diacetyl ferrocene with hydrazine hydrate followed by a condensation reaction with o-vanillin. A general synthetic protocol was employed to synthesize complexes 1-4, where the metallic core was kept the same with changing the bridging carboxylate groups. In all the complexes, the main structural motif is kept similar by only slightly varying the substitution on the bridging acetate groups. This variation has resulted in a small but subtle influence on the magnetic relaxation of all these four compounds. Ab initio CASSCF/NEVPT2 calculations were carried out to assess the effect of the different substitutions of the bridging ligands on the magnetic anisotropy parameters and on orbital arrangements. Ab initio calculations yield a very large positive D value, which is consistent with the geometry around the CoII ion and easy plane anisotropy (gxx, gyy > gzz), with the order of the calculated D in the range of 72.4 to 91.7 cm-1 being estimated in this set of complexes. To ascertain the sign of zero-field splitting in these complexes, EPR spectra were recorded, which support the sign of D values estimated from ab initio calculations.


Case Report: A Chinese Family of Woodhouse-Sakati Syndrome With Diabetes Mellitus, With a Novel Biallelic Deletion Mutation of the DCAF17 Gene.
Woodhouse-Sakati syndrome (WSS) (OMIM#241080) is a rare multi-system autosomal recessive disease with homozygous mutation of the DCAF17 gene. The main features of WSS include diabetes, hypogonadism, alopecia, deafness, intellectual disability and progressive extrapyramidal syndrome. We identified a WSS family with a novel DCAF17 gene mutation type in China. Two unconsanguineous siblings from the Chinese Han family exhibiting signs and symptoms of Woodhouse-Sakati syndrome were presented for evaluation. Whole-exome sequencing revealed a homozygous deletion NM_025000.4:c.1488_1489delAG in the DCAF17 gene, which resulted in a frameshift mutation that led to stop codon formation. We found that the two patients exhibited low insulin and C-peptide release after glucose stimulation by insulin and C-peptide release tests. These findings indicate that the DCAF17 gene mutation may cause pancreatic β cell functional impairment and contribute to the development of diabetes.


[Vascularization of the iris].
A part of the LEBER's scheme concerning vascularization of the iris may be discussed from iridian angiograms. Serial frontal sections permit to precise the following data: The great arterial circle, which is in a tight relation with the ciliary muscle gives rise to one artery by ciliary process, and veins are located more posteriorly. The iridian zone proper has one radiate artery for 3 or 4 veins. The small arterial circle located in the collarette zone is variable, most often discontinuous. The iridian sphincter zone has a high density vascularization, constituted of antero-posterior vessels, realizing a pre-sphincterian and retro-sphincterian networks. The marginal circle always exists; it seems mostly of an arteriovenous type. The density of this vascularization exceeds the nutritional needs of this organ, and suggests an other functional role.


Urinary tract infection in patients with acute coronary syndrome: a potential systemic inflammatory connection.
Inflammation has been linked with atherosclerotic disease development and instability. Contributors to systemic inflammation, such as subclinical infection, may trigger acute coronary syndromes (ACSs). Using a case-control study design, we evaluated the prevalence of urinary tract infection (UTI) among 100 consecutive ACS patients, compared with a contemporary control group undergoing elective coronary artery bypass graft (CABG) surgery. Cases were excluded if ACS was not confirmed by chart review or if a urinalysis was not obtained <or=6 hours of arrival. Patients excluded from the control group were those with myocardial infarction (MI) within 21 days before CABG or without a pre-CABG urinalysis. The case and control groups were well matched, with the only significant differences being less congestive heart failure (OR 7.3, 95% CI 3.3-15.9) and more prior MI (OR 0.5, 95% CI 0.3-0.9) in the CABG control group. UTI was present in 27 of the ACS cases and 11 of the controls. Among ACS case patients, those with UTI tended to be older and more often women, with more diabetes, hyperlipidemia, hypertension, and renal insufficiency, and more commonly had non-ST elevation MI. In unadjusted analysis, UTI was 3 times more common in the cases versus controls (OR 3.0, 95% CI 1.4-6.4); results were similar after multivariable adjustment (OR 3.0, 95% CI 1.3-6.8). Subclinical UTI is common among patients with ACS. Underlying infection may precipitate ACS via activation of systemic inflammation. This hypothesis should be explored in other data sets, and similar relationships with other bacterial and viral infections should be examined.


Role of Broca's area in implicit motor skill learning: evidence from continuous theta-burst magnetic stimulation.
Complex actions can be regarded as a concatenation of simple motor acts, arranged according to specific rules. Because the caudal part of the Broca's region (left Brodmann's area 44, BA 44) is involved in processing hierarchically organized behaviors, we aimed to test the hypothesis that this area may also play a role in learning structured motor sequences. To address this issue, we investigated the inhibitory effects of a continuous theta-burst TMS (cTBS) applied over left BA 44 in healthy subjects, just before they performed a serial RT task (SRTT). SRTT has been widely used to study motor skill learning and is also of interest because, for complex structured sequences, subjects spontaneously organize them into smaller subsequences, referred to as chunks. As a control, cTBS was applied over the vertex in another group, which underwent the same experiment. Control subjects showed both a general practice learning effect, evidenced by a progressive decrease in RT across blocks and a sequence-specific learning effect, demonstrated by a significant RT increase in a pseudorandom sequence. In contrast, when cTBS was applied over left BA 44, subjects lacked both the general practice and sequence-specific learning effects. However, surprisingly, their chunking pattern was preserved and remained indistinguishable from controls. The present study indicates that left BA 44 plays a role in motor sequence learning, but without being involved in elementary chunking. This dissociation between chunking and sequence learning could be explained if we postulate that left BA 44 intervenes in high hierarchical level processing, possibly to integrate elementary chunks together.


Illumination source optimization in optical lithography via derivative-free optimization.
Illumination source optimization (SO) in optical lithography is generally performed under a simulation model that does not consider critical effects such as the vectorial nature of light and mask topography. When a numerical aperture becomes large and the critical dimension reaches subwavelength, the prediction of this model generally fails; therefore, the previous works based on this model become inaccurate. In order to correctly compute SO, we first propose a new source pattern representation method that has moderate parameter variations but remains complete in solution space. Then we develop a derivative-free optimization (DFO) method to optimize these parameters under a rigorous simulation model. Unlike gradient-based techniques, DFO methods do not require a closed-form formulation of the model and are independent of the form of cost function.


Medical patients' treatment decision making capacity: a report from a general hospital in Greece.
This study aimed to assess the decision-making capacity for treatment of patients hospitalized in an internal medicine ward of a General Hospital in Greece, and to examine the views of treating physicians regarding patients' capacity. All consecutive admissions to an internal medicine ward within a month were evaluated. A total of 134 patients were approached and 78 patients were interviewed with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the Mini Mental State Examination (MMSE) questionnaire. Sixty-eight out of 134 patients (50.7%) were incompetent to decide upon their treatment. The majority of them (n=56, 41.8%) were obviously incapable because they were unconscious, or had such marked impairment that they could not give their own names, and the rest (n=12, 8.9%) were rated as incompetent according to their performance in the MacCAT-T. Neurological disorders, old age and altered cognitive function according to MMSE were negatively correlated with decision making capacity. Physicians sometimes failed to recognize patients' incapacity. Rates of decision-making incapacity for treatment in medical inpatients are high, and incapacity may go unrecognized by treating physicians. Combined patient evaluation with the use of the MacCAT-T and MMSE, could be useful for the determination of incapable patients.


Effect of neoadjuvant chemotherapy on breast cancer phenotype, ER/PR and HER2 expression - Implications for the practising oncologist.
To assess the effect of neoadjuvant chemotherapy (NACT) on breast cancer characteristics, hormone receptors and human epidermal growth factor receptor 2 (HER2) expression and whether testing should be repeated on residual tumours. Patients with primary operable breast cancer who received NACT at a single United Kingdom tertiary referral centre were included. Tumour type, grade (including details of mitotic grade, tubule formation and pleomorphism), oestrogen receptor (ER), progesterone receptor (PR) and HER2 status were compared between pre-treatment and post-treatment residual samples using tissue microarrays. A control group of paired core and excision tumours from patients who did not receive NACT was also assessed. Two hundred forty-six cases and 113 controls were included. Pathological complete response (path CR) was achieved in 21.5% of patients. In those patients failing to achieve a path CR, a change in the histological type was noted in 29 out of 178 cases (16.3%, p<0.001) with increase in the lobular and metaplastic types. Downgrading occurred in 28.8%, due to significant reduction in mitotic rate and prominent tubule formation. A change in ER/PR/HER2 status occurred in 12%, 14.5% and 7.1% of cases, respectively, predominantly as a switch from negative to positive status for ER and from positive to negative status for HER2. Further alterations in expression levels were also noted. Minimal changes in the low ER/PR expressors and the HER2 2+ tumours were found in the control group. Significant changes in tumour morphology, grade, hormone receptors and HER2 status occur following NACT. We recommend testing on residual invasive carcinoma. A switch from negative to positive status warrants offering endocrine/trastuzumab-based therapy to this group of patients.


Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells.
Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Here, we further study the parthenolide mechanism of action using activity-based protein profiling-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 of focal adhesion kinase 1 (FAK1), leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a functional target exploited by members of a large family of anti-cancer natural products.


Resonance in a model of a mammalian neuron.
In this paper we show that for a small range of voltages the model described in the previous paper (Hindmarsh & Rose Phil. Trans. R. Soc. Lond. B 346, 129-150 (1994a)) will generate damped oscillations in response to a negative current pulse. As a consequence the cell has the property that it can be driven into bursting by periodic sinusoidal inputs close to the resonant frequency. The main objective of this paper is to analyse this resonant behaviour using the model of the model introduced in the previous paper. We derive analytical expressions which closely approximate the nonlinear resonance observed in the physiological model driven by a periodic sinusoidal input. This leads to the conclusion that resonance could play a role in synaptic transmission at relay nuclei in the mammalian brain.


Knowledge and data-driven prediction of organ failure in critical care patients.
The early detection of organ failure mitigates the risk of post-intensive care syndrome and long-term functional impairment. The aim of this study is to predict organ failure in real-time for critical care patients based on a data-driven and knowledge-driven machine learning method (DKM) and provide explanations for the prediction by incorporating a medical knowledge graph. The cohort of this study was a subset of the 4,386 adult Intensive Care Unit (ICU) patients from the MIMIC-III dataset collected between 2001 and 2012, and the primary outcome was the Delta Sequential Organ Failure Assessment (SOFA) score. A real-time Delta SOFA score prediction model was developed with two key components: an improved deep learning temporal convolutional network (S-TCN) and a graph-embedding feature extraction method based on a medical knowledge graph. Entities and relations related to organ failure were extracted from the Unified Medical Language System to build the medical knowledge graph, and patient data were mapped onto the graph to extract the embeddings. We measured the performance of our DKM approach with cross-validation to avoid the formation of biased assessments. An area under the receiver operating characteristic curve (AUC) of 0.973, a precision of 0.923, a NPV of 0.989, and an F1 score of 0.927 were achieved using the DKM approach, which significantly outperformed the baseline methods. Additionally, the performance remained stable following external validation on the eICU dataset, which consists of 2,816 admissions (AUC = 0.981, precision = 0.860, NPV = 0.984). Visualization of feature importance for the Delta SOFA score and their relationships on the basic clinical medical (BCM) knowledge graph provided a model explanation. The use of an improved TCN model and a medical knowledge graph led to substantial improvement in prediction accuracy, providing generalizability and an independent explanation for organ failure prediction in critical care patients. These findings show the potential of incorporating prior domain knowledge into machine learning models to inform care and service planning. The online version of this article contains supplementary material available 10.1007/s13755-023-00210-5.


Increasing Out-of-Pocket Costs for Neurologic Care for Privately Insured Patients.
To measure the out-of-pocket (OOP) costs of evaluation and management (E/M) services and common diagnostic testing for neurology patients. Using a large, privately insured health care claims database, we identified patients with a neurologic visit or diagnostic test from 2001 to 2016 and assessed inflation-adjusted OOP costs for E/M visits, neuroimaging, and neurophysiologic testing. For each diagnostic service each year, we estimated the proportion of patients with OOP costs, the mean OOP cost, and the proportion of the total service cost paid OOP. We modeled OOP cost as a function of patient and insurance factors. We identified 3,724,342 patients. The most frequent neurologic services were E/M visits (78.5%), EMG/nerve conduction studies (NCS) (7.7%), MRIs (5.3%), and EEGs (4.5%). Annually, 86.5%-95.2% of patients paid OOP costs for E/M visits and 23.1%-69.5% for diagnostic tests. For patients paying any OOP cost, the mean OOP cost increased over time, most substantially for EEG, MRI, and E/M. OOP costs varied considerably; for an MRI in 2016, the 50th percentile paid $103.10 and the 95th percentile paid $875.40. The proportion of total service cost paid OOP increased. High deductible health plan (HDHP) enrollment was associated with higher OOP costs for MRI, EMG/NCS, and EEG. An increasing number of patients pay OOP for neurologic diagnostic services. These costs are rising and vary greatly across patients and tests. The cost sharing burden is particularly high for the growing population with HDHPs. In this setting, neurologic evaluation might result in financial hardship for patients.


Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis.
To report the therapeutic effect and complications of amniotic membrane transplantation (AMT) in acute fungal keratitis. Diagnosis of fungal keratitis was confirmed by cultures in 23 eyes of 23 patients. The indications to perform AMT were to promote reepithelialization in non-healing ulcers or to prevent corneal perforation. Antifungal agents were administered throughout the whole course of hospitalization. Repeated cultures were performed immediately before AMT. The main outcome measurements were epithelial healing rate, necessity of therapeutic penetrating keratoplasty (TPK), and persistence of infection. During a mean follow-up time of 20.6 months +/- 23.22 (6-65 months) AMT was performed during the active phase of the keratitis (fungal culture was still positive) in 16 patients (69.6%), and during the inactive phase (fungal culture negative) in 7 patients (30.4%). Single-layer AMT was performed in 17 patients, and double-layer AMT was performed in 6 patients with corneal perforation and anterior chamber collapse. Complete epithelialization was observed in 12 patients (75%) in the active group and in 7 patients (100%) in the inactive group. Treatment failure requiring TPK was experienced in 4 patients (25%) in the active group. Persistent fungal keratitis was noted in 2 patients (8.7%) in that group. The final visual acuity improved in 17 cases, worsened in 2 cases, and remained unchanged in 4 cases. Twelve of the 23 eyes (52.2%) in this study preserved useful vision (20/400 and better) with or without subsequent surgeries. AMT is effective in promoting epithelialization and preventing corneal perforations in acute fungal keratitis, and there is no risk of rejection. However, the risk of persistent or recurrent infection necessitates continued antifungal treatment and patient monitoring.


The complete mitochondrial genome of the bag-shelter moth Ochrogaster lunifer (Lepidoptera, Notodontidae).
Knowledge of animal mitochondrial genomes is very important to understand their molecular evolution as well as for phylogenetic and population genetic studies. The Lepidoptera encompasses more than 160,000 described species and is one of the largest insect orders. To date only nine lepidopteran mitochondrial DNAs have been fully and two others partly sequenced. Furthermore the taxon sampling is very scant. Thus advance of lepidopteran mitogenomics deeply requires new genomes derived from a broad taxon sampling. In present work we describe the mitochondrial genome of the moth Ochrogaster lunifer. The mitochondrial genome of O. lunifer is a circular molecule 15593 bp long. It includes the entire set of 37 genes usually present in animal mitochondrial genomes. It contains also 7 intergenic spacers. The gene order of the newly sequenced genome is that typical for Lepidoptera and differs from the insect ancestral type for the placement of trnM. The 77.84% A+T content of its alpha strand is the lowest among known lepidopteran genomes. The mitochondrial genome of O. lunifer exhibits one of the most marked C-skew among available insect Pterygota genomes. The protein-coding genes have typical mitochondrial start codons except for cox1 that present an unusual CGA. The O. lunifer genome exhibits the less biased synonymous codon usage among lepidopterans. Comparative genomics analysis study identified atp6, cox1, cox2 as cox3, cob, nad1, nad2, nad4, and nad5 as potential markers for population genetics/phylogenetics studies. A peculiar feature of O. lunifer mitochondrial genome it that the intergenic spacers are mostly made by repetitive sequences. The mitochondrial genome of O. lunifer is the first representative of superfamily Noctuoidea that account for about 40% of all described Lepidoptera. New genome shares many features with other known lepidopteran genomes. It differs however for its low A+T content and marked C-skew. Compared to other lepidopteran genomes it is less biased in synonymous codon usage. Comparative evolutionary analysis of lepidopteran mitochondrial genomes allowed the identification of previously neglected coding genes as potential phylogenetic markers. Presence of repetitive elements in intergenic spacers of O. lunifer genome supports the role of DNA slippage as possible mechanism to produce spacers during replication.


[Restorative surgery of the ligament apparatus of the metatarsal-phalangeal joint and metatarsus in hallux valgus].
The new operation method of 'hallux valgus' after Boriss Tserliuk is described. The innovation consists in creation of an artificial medial metatarsal ligament and bringing tarsal bones closely together. Thus the first finger is fixed in right position and tarsal sesamoid complex is recovered. The methods of metatarsal and intertarsal angles' measurements are described. The results of 40 operations in 30 cases (27 females and 3 males) are presented. The functional and cosmetic results are positive.


Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo.
Mast cells (MCs) are considered major players in IgE-mediated allergic responses, but have also recently been recognized as active participants in innate as well as specific immune responses. Recent work provided evidence that MCs are able to activate B and T lymphocytes through the release of vesicles called exosomes. Here we demonstrate that exosomes, which are located in the endocytic pathway, harbor exogenous Ags that associate with other molecules endowed with immunomodulatory functions, including 60- and 70-kDa heat shock proteins. Administration to naive mice of Ag-containing exosomes in the absence of conventional adjuvants elicits specific Ab responses across the MHC II haplotype barrier. We demonstrate that MC-exosomes induce immature dendritic cells (DCs) to up-regulate MHC class II, CD80, CD86, and CD40 molecules and to acquire potent Ag-presenting capacity to T cells. Uptake and processing of Ag-associated exosomes by endogenous DCs were also demonstrated. Finally, exosome-associated heat shock proteins are critical for the acquisition by DCs of the Ag-presenting function. This work demonstrates a heretofore unrecognized collaborative interaction between MCs and DCs leading to the elicitation of specific immune responses.


Optimized Flat-Detector CT in Stroke Imaging: Ready for First-Line Use?
Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated. Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed. FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (κ = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively). Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in acute stroke, but within a multimodal imaging approach primarily using the FD technology, native FD-CT seems capable to exclude reliably supratentorial hemorrhage. Currently, FD-CT imaging seems not yet ready for wide adoption, replacing regular CT, and should be reserved for selected patients. Furthermore, prospective evaluations are necessary to validate this approach in the clinical setting.


The floral transition is not the developmental switch that confers competence for the Arabidopsis age-related resistance response to Pseudomonas syringae pv. tomato.
Age-related resistance (ARR) is a plant defense response characterized by enhanced resistance to certain pathogens in mature plants relative to young plants. In Arabidopsis thaliana the transition to flowering is associated with ARR competence, suggesting that this developmental event is the switch that initiates ARR competence in mature plants (Rusterucci et al. in Physiol Mol Plant Pathol 66:222-231, 2005). The association of ARR and the floral transition was examined using flowering-time mutants and photoperiod-induced flowering to separate flowering from other developmental events that occur as plants age. Under short-day conditions, late-flowering plant lines ld-1 (luminidependens-1), soc1-2 (suppressor of overexpression of co 1-2), and FRI (+) (FRIGIDA) displayed ARR before the transition to flowering occurred. Early-flowering svp-31, svp-32 (short vegetative phase), and Ws-2 were ARR-defective, whereas early-flowering tfl1-14 (terminal flower 1-14) displayed ARR at the same time as Col-0. While svp-31, svp-32 and Ws-2 produced few rosette leaves, tfl1-14 produced a rosette leaf number similar to Col-0, suggesting that the development of a minimum number of rosette leaves is necessary to initiate ARR competence under short-day conditions. Photoperiod-induced transient expression of FT (FLOWERING LOCUS T) caused precocious flowering in short-day-grown Col-0 but this was not associated with ARR competence. Under long-day conditions co-9 (constans-9) mutants did not flower but displayed an ARR response at the same time as Col-0. This study suggests that SVP is required for the ARR response and that the floral transition is not the developmental event that regulates ARR competence.


The neural correlates of "mind blanking": When the mind goes away.
Mind blanking (MB) is the state where our minds are seemingly "nowhere," and attention calls no perceptual input into conscious awareness. It is little investigated, perhaps partly because it is difficult to detect the mysterious periods of blanking. In this study, we found that our participants could intentionally produce a state of MB whose neural correlates were deactivation of Broca's area and parts of the default mode network (namely, the hippocampus) which would be active during mind wandering (MW), in addition to activity in another region in the default mode network (namely, anterior cingulate cortex). Because the behavioral finding replicates a previous report of ours, we suggest that the simple instructions that we used to induce MB should be effective. From the neuroimaging data, we conclude that we cannot define the content of our thoughts during MB because our inner speech system does not work at that time. Another possibility is that we actually think of nothing in the MB state. Although more sophisticated studies would be needed to uncover the mechanism of such a phenomenon, the present study provides a methodology and clues for understanding MB and related concepts such as MW, awareness, and metacognitive ability.


Using computational and mechanical models to study animal locomotion.
Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms' performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: "Integrating living and physical systems."


A simple and soft chemical deaggregation method producing single-digit detonation nanodiamonds.
Detonation nanodiamonds (DNDs) are a class of very small and spherical diamond nanocrystals. They are used in polymer reinforcement materials or as drug delivery systems in the field of nanomedicine. Synthesized by detonation, only the final deaggregation step down to the single-digit nanometer size (<10 nm) unfolds their full potential. Existing deaggregation methods mainly rely on mechanical forces, such as high-power sonication or bead milling. These techniques entail drawbacks such as contamination of the sample and the need for a specialized apparatus. In this paper, we report a purely chemical deaggregation method by simply combining oxidation in air followed by a boiling acid treatment, to produce highly stable single-digit DNDs in a suspension. The resulting DNDs are surface functionalized with carboxyl groups, the final boiling acid treatment removes primary metal contaminants such as magnesium, iron or copper and the nanoparticles remain dispersed over a wide pH range. Our method can be easily carried out in a standard chemistry laboratory with commonly available laboratory apparatus. This is a key step for many DND-based applications, ranging from materials science to biological or medical applications.


Ethylene production from alpha-oxo-gamma-methylthiobutyric acid is a sensitive measure of ligninolytic activity by Phanerochaete chrysosporium.
Production of hydroxyl radical in ligninolytic cultures was determined by measuring the alpha-oxo-gamma-methylthiobutyric acid-dependent production of ethylene gas. The results showed that the pattern of ethylene production was very similar to that of ligninolytic activity [[14C]lignin leads to 14CO2). Furthermore, nutritional parameters, which are known to affect ligninolytic activity, affected OH.-radical-dependent ethylene production in a similar fashion. The results indicate that assay for ethylene production from alpha-oxo-gamma-methylthiobutyric acid is a simple and sensitive measure of ligninolytic activity by Phanerochaete chrysosporium.


Chitosan-based nanocapsules by emulsification containing PUFA concentrates from tuna oil.
Chitosan nanocapsules containing polyunsaturated fatty acid (PUFA) concentrates from tuna oil, with EPA + DHA contents around 57% (w w-1), were developed by emulsification process, using different chitosan concentration (1.0%, 1.5%, 2.0%, w v-1) and stirring speed (10,000, 15,000, 20,000 rpm). The effects of these parameters on particle size and zeta potential were evaluated. The physical and oxidative stabilities were used to measure the product quality during storage. Chitosan concentration, stirring speed and its interaction significantly affected (p < 0.05) the particle size. In addition, chitosan concentration significantly affected (p < 0.05) the zeta potential of nanocapsules emulsion. Based on the results of physical and oxidative stabilities, the nanocapsules were stable for 30 days under refrigeration temperature (7 °C), and with 1.5-2% chitosan resulted in improved protection against oil oxidation. The nanocapsules produced with 2% chitosan and 10,000 rpm showed the lowest variations of polydispersity index and nanocapsules size after 30 days of storage (221.8 ± 3.0 nm). These conditions can be considered the most suitable to produce nanocapsules of PUFA concentrates from tuna oil using chitosan as wall material. These nanocapsules showed physical characteristics and oxidative stability, which could enable their application in the food industry, representing an important source of EPA and DHA fatty acids.


Metabolism and production of angiotensin I in different vascular beds in subjects with hypertension.
To study the metabolism and production of angiotensin I, highly purified monoiodinated [125I] angiotensin I was given by constant systemic intravenous infusion, either alone (n = 7) or combined with unlabeled angiotensin I (n = 5), to subjects with essential hypertension who were treated with the angiotensin converting enzyme inhibitor captopril (50 mg b.i.d.). Blood samples were taken from the aorta and the renal, antecubital, femoral, and hepatic veins. [125I]Angiotensin I and angiotensin I were extracted from plasma, separated by high-performance liquid chromatography, and quantitated by gamma counting and radioimmunoassay. Plasma renin activity was measured at pH 7.4. The plasma decay curves after discontinuation of the infusions of [125I]angiotensin I and unlabeled angiotensin I were similar for the two peptides. The regional extraction ratio of [125I]angiotensin I was 47 +/- 4% (mean +/- SEM) across the forearm, 59 +/- 3% across the leg, 81 +/- 1% across the kidneys, and 96 +/- 1% across the hepatomesenteric vascular bed. These results were not different from those obtained for infused unlabeled angiotensin I. Despite the rapid removal of arterially delivered angiotensin I, no difference was found between the venous and arterial levels of endogenous angiotensin I across the various vascular beds, with the exception of the liver where angiotensin I in the vein was 50% lower than in the aorta. Thus, 50-90% of endogenous angiotensin I in the veins appeared to be derived from regional de novo production. The blood transit time is 0.1-0.2 minute in the limbs and in the kidneys and 0.3-0.5 minute in the hepatomesenteric vascular bed. This is too short for plasma renin activity to account for the measured de novo angiotensin I production. It was calculated that less than 20-30% in the limbs and in the kidneys and approximately 60% in the hepatomesenteric region of de novo-produced angiotensin I could be accounted for by circulating renin. These results indicate that a high percentage of plasma angiotensin I may be produced locally (i.e., not in circulating plasma).


Parent-Infant Closeness, Parents' Participation, and Nursing Support in Single-Family Room and Open Bay NICUs.
This was a prospective survey study, comparing parent-infant closeness, parents' perceptions of nursing support, and participation in medical rounds in single-family room (SFR) and an open bay (OB) neonatal intensive care units. Nurses' assessments of provided support were also measured. In total, 115 parents of 64 preterm infants less than 35 weeks' gestational age and 129 nurses participated. Parents recorded the presence and skin-to-skin care. Parents were sent 9 text message questions in random order. Nurses answered corresponding Internet-based questions. SFR mothers were more present, 20 hours daily (median) versus 7 hours (P < .001), initiated skin-to-skin contact (SSC) at 4 versus 12 hours (P = .03), and preformed SSC 180 min/24 h versus 120 min/24 h for mothers in the OB unit (P = .02). SFR fathers were also more present, 8 versus 4 hours (P < .001), initiated SSC at 3 versus 40 hours (P = .004), and performed SSC 67 min/24 h versus 31 min/24 h (P = .05). SFR parents rated participation in medical rounds and emotional support higher than OB parents. Parental trust was rated higher by nurses in the OB unit (P = .02). SFR facilitated parent-infant closeness, parents' participation in medical rounds, and increased support from nurses.


Health and Healthcare: Assessing the Real World Data Policy Landscape in Europe.
Real-world data (RWD) is an umbrella term for different types of data that are not collected in conventional randomised controlled trials. RWD in the healthcare sector comes from various sources and includes patient data, data from clinicians, hospital data, data from payers and social data. There are already examples of ways in which research has contributed to the provision, construction and capture of RWD to improve health outcomes. However, to maximise the potential of these new pools of data in the healthcare sector, stakeholders need to identify pathways and processes which will allow them to efficiently access and use RWD in order to achieve better research outcomes and improved healthcare delivery. Current efforts to improve access to RWD and facilitate its use take place in a context of resource scarcity. Based on a literature review, case studies, a small set of interviews of experts from public and private organisations and a scenario based workshop, the study outlined possible strategies to illustrate how RWD standards development could facilitate RWD-based research. By investigating the current forms and uses of RWD in Europe, this study has highlighted their significant potential for assessing the (short- or long-term) impact of different drugs or medical treatments and for informing and improving healthcare service delivery. Although the potential of RWD use seems quite clear, this research reveals barriers that restrict further development towards its full exploitation: the absence of common standards for defining the content and quality of RWD, methodological barriers that may limit the potential benefits of RWD analysis, governance issues underlying the absence of standards for collaboration between stakeholders, and privacy concerns and binding data protection legislation which can be seen to restrict access and use of data.


Biomechanical comparison of anterior, posterior, and circumferential fixation after one-level anterior cervical corpectomy in the human cadaveric spine.
In vitro biomechanical study of cadaveric cervical spine. To compare the rigidity of the cervical spine after anterior, posterior, and circumferential fixation after 1-level corpectomy, and evaluate the effects of the integrity of the facet capsules and posterior ligaments (PL). Anterior cervical corpectomy is commonly used for decompression of the spinal canal in the treatment of different pathologic conditions. The effect of the integrity of the facet capsules and PLs on the biomechanical stability provided by anterior, posterior, or circumferential fixation following 1-level corpectomy has not been investigated. Nine cadaveric cervical spines were potted rostrally at C2, and caudally at T1-T2, and were tested in 6 directions with pure moment application, in 5 conditions: In the intact spine, after a C5 corpectomy and anterior fixation, after anterior fixation and disruption of the C4-C5 and C5-C6 facet capsules and PL, after circumferential fixation, and after posterior fixation alone without anterior cage. Angular motion of C4 relative to C6 was measured. Despite C5 corpectomy, anterior grafting and plate fixation was more rigid than the intact spine with all loads in flexion, at loads of 0.5 Nm and 1.0 Nm in right axial rotation and right lateral bending, and at all loads in left lateral bending. Posterior ligamentous disruption increased motion in the coronal and axial planes, but not in the sagittal plane. Circumferential instrumentation resulted in a significant reduction in motion of the spine compared with anterior instrumentation in both the coronal and axial planes but not in the sagittal plane. Posterior fixation without anterior cage failed to limit cervical spine motion in the sagittal plane, but was restrictive in axial rotation and lateral bending when compared with circumferential fixation. After C5 corpectomy, with intact PLs and facet capsules, anterior instrumentation is sufficient for spinal stabilization as the resultant construct is more rigid than the intact state. In the presence of C5 corpectomy with PL and bilateral facet capsule disruption, anterior plus posterior instrumentation is more rigid than anterior instrumentation alone in the axial and coronal planes and more rigid than posterior instrumentation without anterior cage in the sagittal plane.


Scale dependency of biocapacity and the fallacy of unsustainable development.
Area-based information obtained from remote sensing and aerial photography is often used in studies on ecological footprint and sustainability, especially in calculating biocapacity. Given the importance of the modifiable areal unit problem (MAUP; i.e. the scale dependency of area-based information), a comprehensive understanding of how the changes of biocapacity across scales (i.e. the resolution of data) is pivotal for regional sustainable development. Here, we present case studies on the effect of spatial scales on the biocapacity estimated for two typical river basin and watershed in Northwest China. The analysis demonstrated that the area sizes of major land covers and subsequently biocapacity showed strong signals of scale dependency, with minor land covers in the region shrinking while major land covers expanding when using large-grain (low resolution) data. The relationship between land cover sizes and their change ratio across scales was shown to follow a logarithm function. The biocapacity estimated at 10 × 10 km resolution is 10% lower than the one estimated at 1 × 1 km resolution, casting doubts on many regional and global studies which often rely on coarse scale datasets. Our results not only suggest that fine-scale biocapacity estimates can be extrapolated from coarse-scale ones according to the specific scale-dependent patterns of land covers, but also serve as a reminder that conclusions of regional and global un-sustainability derived from low-resolution datasets could be a fallacy due to the MAUP.


Dimethyl fumarate for multiple sclerosis.
Multiple sclerosis (MS) often leads to severe neurological disability and a serious decline in quality of life. The ideal target of disease-modifying therapy for MS is to prevent disability worsening and improve quality of life. Dimethyl fumarate is considered to have an immunomodulatory activity and neuroprotective effect. It has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency as a first-line therapy for adult patients with relapsing-remitting MS (RMSS). To assess the benefit and safety of dimethyl fumarate as monotherapy or combination therapy versus placebo or other approved disease-modifying drugs (interferon beta, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, alemtuzumab) for patients with MS. The Trials Search Co-ordinator searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (4 June 2014). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to June 2014) from the MS societies in Europe and America. We also communicated with investigators participating in trials of dimethyl fumarate and the Biogen Idec Medical Information. We included randomised, controlled, parallel-group clinical trials (RCTs) with a length of follow-up equal to or greater than one year evaluating dimethyl fumarate, as monotherapy or combination therapy, versus placebo or other approved disease-modifying drugs for patients with MS without restrictions regarding dosage, administration frequency and duration of treatment. We used the standard methodological procedures of The Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. We contacted the principal investigators of included studies for additional data or confirmation of data. Two RCTs were included, involving 2667 adult patients with RRMS to evaluate the efficacy and safety of two dosages of dimethyl fumarate (240 mg orally three times daily or twice daily) by direct comparison with placebo for two years. Among them, a subsample of 1221 (45.8%) patients were selected to participate in MRI evaluations by each study site with MRI capabilities itself. No powered head-to-head study with an active treatment comparator has been found. Meta-analyses showed that dimethyl fumarate both three times daily and twice daily reduced the number of patients with a relapse (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.50 to 0.66, P < 0.00001 and 0.64, 95% CI 0.54 to 0.77, P < 0.00001, respectively) or disability worsening (RR 0.70, 95% CI 0.57 to 0.87, P = 0.0009 and 0.65, 95% CI 0.53 to 0.81, P = 0.0001, respectively) over two years, compared to placebo. The treatment effects were decreased in the likely-case scenario analyses taking the effect of dropouts into consideration. Both dosages also reduced the annualised relapse rate. Data of active lesions on MRI scans were not combined because there was a high risk of selection bias for MRI outcomes and imprecision of MRI data in both studies, as well as an obvious heterogeneity between the studies. In terms of safety profile, both dosages increased the risk for adverse events and the risk for drug discontinuation due to adverse events. The most common adverse events included flushing and gastrointestinal events (upper abdominal pain, nausea and diarrhoea). Uncommon adverse events included lymphopenia and leukopenia, but they were more likely to happen with dimethyl fumarate than with placebo (high dosage: RR 5.25, 95% CI 2.20 to 12.51, P = 0.0002 and 5.23, 95% CI 2.47 to 11.07, P < 0.0001, respectively; low dosage: RR 5.69, 95% CI 2.40 to 13.46, P < 0.0001 and 6.53, 95% CI 3.13 to 13.64, P < 0.00001, respectively). Both studies had a high attrition bias resulting from the unbalanced reasons for dropouts among groups. Quality of evidence for relapse outcome was moderate, but for disability worsening was low. There is moderate-quality evidence to support that dimethyl fumarate at a dose of 240 mg orally three times daily or twice daily reduces both the number of patients with a relapse and the annualised relapse rate over two years of treatment in comparison with placebo. However, the quality of the evidence to support the benefit in reducing the number of patients with disability worsening is low. There is no high-quality data available to evaluate the benefit on MRI outcomes. The common adverse effects such as flushing and gastrointestinal events are mild-to-moderate for most patients. Lymphopenia and leukopenia are uncommon adverse events but significantly associated with dimethyl fumarate. Both dosages of dimethyl fumarate have similar benefit and safety profile, which supports the option of low-dose administration. New studies of high quality and long-term follow-up are needed to evaluate the benefit of dimethyl fumarate on prevention of disability worsening and to observe the long-term adverse effects including progressive multifocal leukoencephalopathy.


Saved by focused echo evaluation in resuscitation.
A 74-year-old woman received thrombolysis for pericarditis. She subsequently developed shock and cardiac arrest. The case report describes the events of how a simple immediate bedside focused echo proved to be a life saving assessment. Current availability and training issues in focused transthoracic echo are discussed.


Hybrid metamaterial design and fabrication for terahertz resonance response enhancement.
Planar hybrid metamaterial with different split ring resonators (SRR) structure dimensions are fabricated on silicon substrates by femtosecond (fs) laser micro-lens array (MLA) lithography and lift-off process. The fabricated metamaterial structures consist of: (a) uniform metamaterial with 4 SRRs at same design and dimension as a unit cell and (b) hybrid metamaterial with 4 SRRs at same design but different dimensions as a unit cell. The electromagnetic field responses of these hybrid and single dimension metamaterial structures are characterized using a terahertz (THz) time-domain spectroscopy. Transmission spectra of these metamaterial show that a broader resonance peak is formed when 2 SRRs are close to each other. FDTD simulation proves that there is a strong mutual coupling between 2 SRRs besides a strong localized electric field at the split gap, which can enhance the electric field up to 364 times for tunable, broad band and high sensitivity THz sensing. Meanwhile, the strong coupling effect could lead to the formation of an additional resonance peak at approximately 0.2 THz in the THz spectra regime.


Insulin resistance in Cushing's disease. Evaluation by studies of insulin binding to erythrocytes.
Studies of 125I -insulin binding to erythrocytes (RBC) from 5 patients with Cushing's disease were performed in an attempt to evaluate the insulin resistance in this disease. Five obese, nondiabetic patients and six normal subjects served as controls. Insulin resistance was present in both the obese, nondiabetic subjects and in the patients with Cushing's disease. Patients with Cushing's disease showed insulin resistance out of proportion to obesity, and of greater severity than in the obese subjects. As in previous studies, the insulin resistance of the obese subjects could be at least partially ascribed to a reduced number of receptors. In contrast, in our patients with Cushing's disease, no physiologically significant changes in the parameters of insulin-receptor interaction could be demonstrated. This suggests that the RBC insulin receptor is not involved in this type of insulin resistance.


Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.
RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.


The Addict in Us all.
In this paper, we contend that the psychology of addiction is similar to the psychology of ordinary, non-addictive temptation in important respects, and explore the ways in which these parallels can illuminate both addiction and ordinary action. The incentive salience account of addiction proposed by Robinson and Berridge (1-3) entails that addictive desires are not in their nature different from many of the desires had by non-addicts; what is different is rather the way that addictive desires are acquired, which in turn affects their strength. We examine these "incentive salience" desires, both in addicts and non-addicts, contrasting them with more cognitive desires. On this account, the self-control challenge faced by addicted agents is not different in kind from that faced by non-addicted agents - though the two may, of course, differ greatly in degree of difficulty. We explore a general model of self-control for both the addict and the non-addict, stressing that self-control may be employed at three different stages, and examining the ways in which it might be strengthened. This helps elucidate a general model of intentional action.


Microglia function in Alzheimer's disease.
Contrary to early views, we now know that systemic inflammatory/immune responses transmit to the brain. The microglia, the resident "macrophages" of the brain's innate immune system, are most responsive, and increasing evidence suggests that they enter a hyper-reactive state in neurodegenerative conditions and aging. As sustained over-production of microglial pro-inflammatory mediators is neurotoxic, this raises great concern that systemic inflammation (that also escalates with aging) exacerbates or possibly triggers, neurological diseases (Alzheimer's, prion, motoneuron disease). It is known that inflammation has an essential role in the progression of Alzheimer's disease (AD), since amyloid-β (Aβ) is able to activate microglia, initiating an inflammatory response, which could have different consequences for neuronal survival. On one hand, microglia may delay the progression of AD by contributing to the clearance of Aβ, since they phagocyte Aβ and release enzymes responsible for Aβ degradation. Microglia also secrete growth factors and anti-inflammatory cytokines, which are neuroprotective. In addition, microglia removal of damaged cells is a very important step in the restoration of the normal brain environment, as if left such cells can become potent inflammatory stimuli, resulting in yet further tissue damage. On the other hand, as we age microglia become steadily less efficient at these processes, tending to become over-activated in response to stimulation and instigating too potent a reaction, which may cause neuronal damage in its own right. Therefore, it is critical to understand the state of activation of microglia in different AD stages to be able to determine the effect of potential anti-inflammatory therapies. We discuss here recent evidence supporting both the beneficial or detrimental performance of microglia in AD, and the attempt to find molecules/biomarkers for early diagnosis or therapeutic interventions.


Kinetic mechanism of acetyl-CoA synthase: steady-state synthesis at variable Co/Co2 pressures.
Steady-state initial rates of acetyl-CoA synthesis (upsilon/[E(tot)]) catalyzed by acetyl-CoA synthase from Clostridium thermoaceticum (ACS) were determined at various partial pressures of CO and CO2. When [CO] was varied from 0 to 100 microM in a balance of Ar, rates increased sharply from 0.3 to 100 min(-1). At [CO] > 100 microM, rates declined sharply and eventually stabilized at 10 min(-1) at 980 microM CO. Equivalent experiments carried out in CO2 revealed similar inhibitory behavior and residual activity under saturating [CO]. Plots of upsilon/[E(tot)] vs [CO2] at different fixed inhibitory [CO] revealed that Vmax/[E(tot)] (kcat) decreased with increasing [CO]. Plots of upsilon/[E(tot)] vs [CO2] at different fixed noninhibitory [CO] showed that Vmax/[E(tot)] was insensitive to changes in [CO]. Of eleven candidate mechanisms, the simplest one that fit the data best had the following key features: (a) either CO or CO2 (at a designated reductant level and pH) activate the enzyme (E' + CO right arrow over left arrow E, E' + CO2/2e-/2H+ right arrow over left arrow E); (b) CO and CO2 are both substrates that compete for the same enzyme form (E + CO right arrow over left arrow ECO, E + CO2/2e-/2H+ right arrow over left arrow ECO, and ECO --> E + P); (c) between 3 and 5 molecules of CO bind cooperatively to an enzyme form different from that to which CO2 and substrate CO bind (nCO + ECO right arrow over left arrow (CO)nECO), and this inhibits catalysis; and (d) the residual activity arises from either the (CO)nECO state or a heterogeneous form of the enzyme. Implications of these results, focusing on the roles of CO and CO2 in catalysis, are discussed.


Long-lasting consequences of neonatal maternal separation on social behaviors in ovariectomized female mice.
Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty.


Plasma lipoproteins, antihypertensive drugs and coronary heart disease.
There is now a large body of evidence that susceptibility to coronary atherosclerosis is inversely related to the plasma high-density lipoprotein (HDL) cholesterol concentration, in addition to being directly related to blood pressure and the plasma low-density lipoprotein (LDL) level. Studies of the effects of drugs on coronary disease in humans and on experimental atherosclerosis in animals have provided evidence that the associations with HDL and LDL are causal, reflecting an atherogenic effect of one lipoprotein and a protective effect of the other. Interest in the effects of antihypertensive drugs on plasma lipoproteins was stimulated by the failure of these drugs in several clinical trials to reduce the incidence of coronary heart disease in hypertensive subjects, even though the incidence of other complications of high blood pressure were reduced. Many beta-blocking drugs and thiazides have now been shown to have a theoretically adverse effect on the plasma lipoprotein profile, measured in the terms of the ratio of HDL cholesterol to LDL. Although the consequences of these changes and their mechanisms remain to be established, they may explain the negative outcome of the prevention trials, the protection against coronary disease offered by the reduction of blood pressure being offset by the associated changes in lipoprotein metabolism.


On the "general acceptance" of handwriting identification principles.
Informed by the admissibility requirements of the broad and narrow Frye tests as well as Daubert's general acceptance factor, the present study elicited the views of a homogeneous group of forensic document examiners and a heterogeneous group of handwriting scientists regarding the degree to which a set of principles relating to the nature of handwriting and its identification were generally accepted within the respondents' fields. Among forensic document examiners, the greatest agreement was found concerning the process of examination, and somewhat less agreement on other matters. Forensic document examiners and handwriting scientists appear not to agree on the acceptability of most of the propositions.


A prospective study of the effect of childbearing on weight gain in African-American women.
To prospectively assess the influence of bearing a first, second, or later child on weight gain among African-American women in the context of other risk factors. Data were obtained in a prospective follow-up study of African-American women from across the U.S. who are participants in the Black Women's Health Study. Postal questionnaires were used to collect baseline data in 1995 and follow-up data in 1997 and 1999. Parous and nulliparous women (11,196) (21 to 39 years old at baseline), of whom 1230 had a singleton birth during follow-up, are the subjects of the present analyses. We assessed change in BMI (kilograms per meter squared) in relation to childbearing during 4 years of follow-up, with use of multivariable linear regression to control for important risk factors. During 4 years of follow-up, the BMI of participants increased by an average of 1.6 kg/m2, equivalent to a weight gain of approximately 4.4 kg. Women who had a child during follow-up gained more weight than women who remained nulliparous, and those who had a first child gained more than those who had a second or later child. The weight gain associated with childbearing increased with increasing baseline BMI and was appreciable among heavier women. For example, among women with a baseline index of 36, the increase in BMI for women who bore a first child was 1.1 kg/m2 more than that of nulliparous women, equivalent to a difference in weight gain of approximately 3.0 kg. Childbearing is an important contributor to weight gain among African-American women.


Nonmedical use of opioid analgesics among Ontario students.
To explore the prevalence and the demographic predictors of nonmedical use of opioid analgesics in the Canadian adolescent population. Data are based on self-reports derived from the 2007 Ontario Student Drug Use and Health Survey, which is an anonymous, in-school, cross-sectional survey. Schools in Ontario. A total of 2914 students in grades 7 to 12. Demographic predictors of nonmedical use of opioid analgesics during the past year and the sources of opioid analgesics. Students ranged in age from 12 to 19 years (mean 15.0, SD 1.9) and 52% were male. Of the students surveyed, 20.6% (95% confidence interval [CI] 18.9% to 22.3%) reported using opioid analgesics at least once nonmedically during the past year, with 6.2% using exclusively nonmedically and 14.4% using nonmedically and medically. Female students (16.6%, CI 14.1% to 19.6%) were more likely than male students (12.0%, CI 10.0% to 14.2%) to have used opioid analgesics both nonmedically and medically in the past year, although exclusive nonmedical use was similar between female (6.7%, CI 5.3% to 8.5%) and male (5.8%, CI 4.5% to 7.3%) students. Among students who reported using opioid analgesics nonmedically, 72% reported obtaining them from home and only 6% reported obtaining them from friends. Nonmedical opioid analgesic users had higher past-year prevalences for alcohol use, daily smoking, and other illicit drug use compared with nonusers. Nonmedical use of opioids is common among Ontario students. The motivation for using these medications without prescriptions or without medical supervision is not known. Students might have used these medications recreationally or for pain relief. Regardless of motivation, these medications are being used without medical supervision. It is important to note that the home is the main source for opioid analgesics in the absence of a prescription. Parents should be vigilant and educate themselves and their children about these medications, ensuring that prescription opioids are stored properly and avoiding casual sharing of these medications among family members.


Dietary supplement laboratory quality assurance program: the first five exercises.
The National Institute of Standards and Technology (NIST) has established a Dietary Supplement Laboratory Quality Assurance Program (DSQAP) in collaboration with the National Institutes of Health Office of Dietary Supplements. Program participants measure concentrations of active and/or marker compounds as well as nutritional and toxic elements in food and dietary supplements distributed by NIST. Data are compiled at NIST, where they are analyzed for accuracy relative to reference values and concordance among the participants. Performance reports and certificates of completion are provided to participants, which can be used to demonstrate compliance with current Good Manufacturing Practices as promulgated by the U.S. Food and Drug Administration. The DSQAP has conducted five exercises to date, with total participation including more than 75 different laboratories and many more individual analysts.


Alteration in Expression of Primordial Germ Cell (PGC) Markers During Induction of Human Amniotic Mesenchymal Stem Cells (hAMSCs).
Currently, scientists are looking for a solution to the problem of the couples who have a lack of germ cells by through cell therapy. It is found that human amniotic membrane mesenchymal stem cells (hAMSCs) could be a good candidate for solving this problem. In the present study, an attempt was made to show that hUMSCs can express the PGC markers in the presence of retinoic acid (RA). Placenta was obtained from healthy mothers and amniotic stem cells were isolated by enzymatic method from amniotic membrane. The cells were treated by retinoic acid for 14 days. Mesenchymal properties of hAMSCs were assessed by flow-cytometry and expression of PGC markers was established by Q-PCR. Mesenchymal stem cell properties were confirmed by antibodies against mesenchymal stem cell markers (CD73, CD90, and CD105). After that, the expression of the C-kit, Oct4, SSEA4, VASA genes were determined as primordial germ cell markers using quantitative PCR. It was found that the use of retinoic acid led to the highest expression of C-kit, SSEA4, VASA genes and lower expression of Oct4. Our study indicates that retinoic acid can be used as a suitable factor for induction of hAMSCs into primordial germ cells (PGCs) and hAMSCs have enough potential to do that.


Statistical learning and probabilistic prediction in music cognition: mechanisms of stylistic enculturation.
Music perception depends on internal psychological models derived through exposure to a musical culture. It is hypothesized that this musical enculturation depends on two cognitive processes: (1) statistical learning, in which listeners acquire internal cognitive models of statistical regularities present in the music to which they are exposed; and (2) probabilistic prediction based on these learned models that enables listeners to organize and process their mental representations of music. To corroborate these hypotheses, I review research that uses a computational model of probabilistic prediction based on statistical learning (the information dynamics of music (IDyOM) model) to simulate data from empirical studies of human listeners. The results show that a broad range of psychological processes involved in music perception-expectation, emotion, memory, similarity, segmentation, and meter-can be understood in terms of a single, underlying process of probabilistic prediction using learned statistical models. Furthermore, IDyOM simulations of listeners from different musical cultures demonstrate that statistical learning can plausibly predict causal effects of differential cultural exposure to musical styles, providing a quantitative model of cultural distance. Understanding the neural basis of musical enculturation will benefit from close coordination between empirical neuroimaging and computational modeling of underlying mechanisms, as outlined here.


Metabolic changes in undifferentiated and differentiated human colon adenocarcinoma cells studied by multinuclear magnetic resonance spectroscopy.
Aspects of energetic and intermediary metabolism were studied in a colon adenocarcinoma cell line (HT29) by multinuclear magnetic resonance spectroscopy. Experiments were carried out on the HT29-D4 clone, which was isolated by limit dilution techniques. This clone, usually undifferentiated (D4-UD), can be maintained in a differentiated state (D4-D) in a glucose-free medium. Metabolic data were obtained by NMR analysis of perchloric acid extracts from D4-UD and D4-D cells. Phosphorus-31 and proton NMR spectra showed the presence of a large amount of choline and phosphorylcholine in the differentiated state (400% and 200%, respectively, of the levels found in D4-UD cells). Other differences appeared in the content of phosphocreatine (absent in D4-D cells) and myoinositol (absent in D4-UD cells). Carbon-13 spectra were recorded from perchloric acid extracts of cells incubated with [1-13C]-labeled glucose or [2-13C]-labeled acetate. The data indicated that both types of cells metabolize glucose through the glycolytic pathway to give lactate, but only D4-D cells were able to store glucose as glycogen at a very high level. A mathematical analysis of fluxes through the tricarboxylic acid (TCA) cycle was developed on the basis of models derived from previous 14C tracer studies. The model was based on the steady-state labeling of glutamate carbons by the 13C isotope and gave the fraction of labeled acetyl-Coa entering the TCA cycle, and the activity y of anaplerotic reactions relative to the flux through the citrate synthetase reaction. The data indicated that y greater than 0.3 in all cases. Only 15% and 30% of labeled acetyl CoA entered the TCA cycle in D4-UD and D4-D cells, respectively, under labeled glucose incubation: these values were significantly different upon labeled acetate feeding, reaching 55% for D4-UD cells and 85% for D4-D cells. The main result of this study is that the process of differentiation of HT29 cells is correlated with a large increase in the activity of oxidative metabolism.


Codeveloping an effective EMPA to maturity in an acute NHS Trust: an implementer report.
University Hospitals Leicester has codeveloped, with Nervecentre, an Electronic Prescribing and Medicines Administration System that meets specific clinical and interoperability demands of the National Health Service (NHS). The system was developed through a frontline-led and agile approach with a project team consisting of clinicians, Information Technology (IT) specialists and the vendor's representatives over an 18-month period. The system was deployed successfully with more than a thousand transcriptions during roll-out. Despite the high caseload and novelty of the system, there was no increase in error rates within the first 3 months of roll-out. Healthcare professionals perceived the new system as efficient with improved clinical workflow, and safe through an integrated medication alert system. This case study demonstrates how NHS trusts can successfully co-develop, with vendors, new IT systems which meet interoperability standards such as Fast Healthcare Interoperability Resources, while improving front line clinical experience. Alternative methods to the 'big bang' deployment of IT projects, such as 'gradual implementation', must be demonstrated and evaluated for their ability to deliver digital transformation projects in the NHS successfully.