A study on optimal share pledge rate based on bilateral risk-CVaR of pledgee.
This paper proposes the optimal pledge rate model based on the pledgee's bilateral risk-CVaR and dual-objective planning. First, a bilateral risk-CVaR model is constructed, for which a nonparametric kernel estimation method is presented, with a comparative analysis of the efficient frontier for "mean-variance", "mean-CVaR", and "mean-bilateral risk CVaR". Second, it establishes a dual-objective planning model by the objectives of bilateral risk-CVaR and expected return of the pledgee, and accordingly develops an optimal pledge rate model combined with objective deviation, priority factor, and entropy method. Finally, the relationships between the pledge rate, the number of pledged shares, and the expected return are explored through simulation. The results illustrate that: (i) There are sequential inclusion relationships between the "mean-bilateral risk CVaR", the "mean-CVaR" considering only the downside risk, and the "mean-variance" efficient sets of share pledge rate. (ii) As the number of shares increases, the pledgee's expected return also rises, and its sensitivity to the pledge rate grows. (iii) When the pledgee's expected return fixes, the number of pledged shares and the pledge rate have a U-shaped relationship. As it increases, the number of pledged shares rises, but the variation range of the pledge rate gradually decreases, and the pledgor's default risk declines.


Corticosterone metabolism and the incorporation of leucine, uridine, and thymidine into fetal mouse brain.
The change in the pattern of biotransformation of [14C]corticosterone in fetal mouse brain between gestational day 14 and 17 increased the proportion of unchanged hormone from 9-75%. A sharp decrease in the in vitro incorporation of [14C]leucine, [3H]uridine, and [3H]thymidine into incubated brain coincided with this change and continued until day 19, when the incorporation of the 3 substrates had fallen to 9, 54, and 16%, respectively, of that on day 14. Injection of dexamethasone reduced values on day 14 to those normally found on days 15-18. Enzymes which metabolize corticosteroids regulate their activity in specific tissues; these data suggest a hormonal influence on developing brain.


Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram.
Charting an organs' biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. Tangram can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.


The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates.
Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (TMEM97) and Progesterone Receptor Membrane Component 1 (PGRMC1) form a complex with the Low Density Lipoprotein Receptor (LDLR), and this intact complex is required for efficient uptake of lipoproteins such as LDL and apolipoprotein E (apoE). These receptors are expressed in the nervous system where they have implications in neurodegenerative diseases such as Alzheimer's disease (AD), where apoE is involved in neuronal uptake and accumulation of Aβ42, eventually cascading into neurodegeneration, synaptic dysfunction, and ultimately, dementia. We hypothesize that the intact Sigma-2 receptor complex-TMEM97, PGRMC1, and LDLR-is necessary for internalization of apoE and Aβ42 monomers (mAβ42) and oligomers (oAβ42), and the disruption of the receptor complex inhibits uptake. The results of this study suggest that the intact Sigma-2 receptor complex is a binding site for mAβ42 and oAβ42, in the presence or absence of apoE2, apoE3, and apoE4. The loss or pharmacological inhibition of one or both of these proteins results in the disruption of the complex leading to decreased uptake of mAβ42 and oAβ42 and apoE in primary neurons. The TMEM97, PGRMC1, and LDLR complex is a pathway for the cellular uptake of Aβ42 via apoE dependent and independent mechanisms. This study suggests that the complex may potentially be a novel pharmacological target to decrease neuronal Aβ42 internalization and accumulation, which may represent a new strategy for inhibiting the rate of neurotoxicity, neurodegeneration, and progression of AD.


Effects of heat and other inducers of the stress response on protein degradation in Chinese hamster and Drosophila cells.
Many recent studies have suggested that heat and other inducers of the heat shock (stress) response in eukaryotic cells might result in the generation of abnormal proteins which would result in the overloading of protein degradation systems and the stabilization of proteins involved in positively regulating heat shock (hs) gene expression. In this study we have examined the effects different heat treatments and other hs inducers have on protein degradation in Chinese hamster ovary (CHO) and Drosophila Kc and Schneider cells. We have found that intermediate temperatures which induced the hs response (42 degrees C in CHO and 34 degrees C in Kc cells) did increase protein degradation rates whereas, higher temperatures which also induced the hs response (45 degrees C in CHO and 37 degrees C in Kc cells) initially increased but then decreased protein degradation rates. While these results are consistent with a model in which the protein degradation system is being overloaded and/or components of it are being depleted, we have found several conditions which induce hs proteins which rule out this mechanism. Exposure of either cell type to amino acid analogs (5 mM canavanine or 5 mM S-aminoethyl cysteine) resulted in the rapid degradation of those proteins which had incorporated the analogs in both CHO and Drosophila cells. However, the addition of analogs had little or no effect on the degradation of preexisting proteins, indicating that the introduction of abnormal proteins probably didn't overload the protein degradation system(s). The addition of 100 microM cadmium sulfate or 100 microM sodium arsenite had little or no effect on protein degradation rates in CHO cells even though both were good inducers of the hs proteins. Thus, exposure to inducers of the hs response does not universally increase protein degradation rates nor does it stabilize preexisting proteins. Therefore, the degradation of abnormal proteins is probably not involved in inducing the hs genes.


Increased macroalgal abundance following mass mortalities of sea urchins (Strongylocentrotus droebachiensis) along the Atlantic coast of Nova Scotia.
Recurrent outbreaks of disease between 1980 and 1983 caused catastrophic mortality of sea urchins (>260,000 t fresh weight) along 280 km (straight line distance) of the Atlantic coast of Nova Scotia. The complete elimination of sea urchins and concomitant development of fleshy macroalgal communities have occurred along different parts of this coast in different years. Macroalgal communities in areas where sea urchins died off 1, 3 and 4 years previously are compared to existing sea urchin-dominated barren grounds and to a mature kelp bed without sea urchins. Changes in macroalgal cover and species composition, and increases in biomass, density and size of kelp (Laminaria) species, characterize the succession from barren grounds to 3- and 4-year-old kelp beds. The greatest change occurred between one and three years following sea urchin mass mortality. Within 3 years, kelp beds attained a level of biomass (7.6 kg m-2) comparable to that of mature beds. Recovery of sea urchin populations via recruitment of planktonic larvae has been slow and spatially variable. Large-scale reciprocal fluctuations in kelp and sea urchin biomass may characterize the trajectory of a dynamic system which cycles between two alternate community states: kelp beds and sea urchin-dominated barren grounds. Periodic decimation of sea urchin populations by disease may be an important mechanism underlying this cyclicity.


Effect of different stress factors on some physiological parameters of Nile tilapia (Oreochromis niloticus).
This study was conducted to determine the effect of different stress factors on some physiological measurements of Nile tilapia (Oreochromis niloticus). A total number of 160 Nile tilapia, the body weight ranging between 100 and 120 g, were exposed to three stress factors of hypoxia, overcrowding and starvation for different periods 24, 72 and 144 h. The results of cortisol level were 134.15, 144.27, 154.12 ng/ml and 140.18 ng/ml for control, hypoxia, overcrowding and starvation, respectively, while after 144 h did not show significant difference among treatments compared with control group. In contrast, the values of T3 and T4 observed reduction with significant difference that T3 ranged between the highest value 122.12 ng/ml for control group to lowest value of starvation group 94.35, 93.81 and 88.46 ng/ml after 24, 72 and 144 h. Also, similar trend of results observed in T4 and blood glucose among treatments. And the enzymatic activity of lactate dehydrogenise (LDH) increased in hypoxic group, while a significant reduction appeared in overcrowding and starved fish compared to control group. The pyruvate kinase (PK) activity decreased in hypoxic group but increased in other group.


Treatment of Orally Handicapped Edentulous Older Adults Using Dental Implants.
The oral handicap of complete edentulism is the terminal outcome of a multifactorial process involving biological factors and patient-related factors. Fully edentulous orally handicapped older adults have been neglected because removable acrylic dentures have been the classic therapy for complete edentulism but are only rehabilitative, not therapeutic. Not replacing missing teeth with stable dentures could prevent adequate food intake. Osseointegrated endosseous implants used as a therapeutic adjunct can reduce the problem of long-term bone resorption to less than 0.1 mm per year. Implant-borne prostheses substantially increase the overall health and quality of life of orally handicapped fully edentulous older adults.


Earliest changes in the left ventricular transcriptome postmyocardial infarction.
We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely, ischemic/infarcted tissue (IF), the surviving LV free wall (FW), and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis, and protein inhibitor of nitric oxide synthase (NOS) activity indicate that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L: -arginine. ARG1: was the single-most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported.


Differential gene expression of 36-kDa microfibril-associated glycoprotein (MAGP-36/MFAP4) in rat organs.
By using quantitative Western blot analysis and the real time polymerase chain reaction technique, we investigated the differential gene expression of microfibril-associated glycoprotein (MAGP-36) in rat organs. The gene was expressed highly in sites rich in elastic fibers, such as aorta, skin, and esophagus. However, MAGP-36 was also expressed highly in some other sites containing no elastic fibers. In lung and trachea, the expression levels of MAGP-36 mRNA were about seven times higher than those in other elastic tissues, although the protein abundances were almost at the same levels as other elastic tissues. MAGP-36 seemed to be secreted outside these organs. In brain, kidney, and spleen, although the expression levels of MAGP-36 mRNA were low, substantial amounts of MAGP-36 protein were detected. An immunohistochemical study revealed that MAGP-36 was present at the brush border of the S3 segment of proximal tubules in kidney. Since MAGP-36 is known to bind to mannan, MAGP-36 might be involved in mannose transport in the S3 segment. Thus, MAGP-36 might be multifunctional and present in a wide variety of sites in various organs.


Axillary lymphadenopathy with IgG4 positive plasma cell infiltration as differential diagnosis of metastatic lung adenocarcinoma.
Immunoglobulin type G4 -related disease (IgG4-RD) is known as a chronic systemic inflammatory disease, which is sometimes associated with lung cancer. However, the detailed association between IgG4-RD and lung cancer in clinical settings is still poorly understood. An 80-year-old man was diagnosed with progressive lung adenocarcinoma carrying an EGFR point mutation at L858R, and osimertinib treatment was administered. Two months later, although osimertinib treatment showed good response to the primary tumor, fever and anorexia appeared, and multiple lymph nodes, in particular in the left axillary, became swollen. Ultrasonography-guided biopsy of the axillary lymph node revealed infiltration of lymphocytes with IgG4-positive plasma cells and fibrosis. Serum IgG4 levels were also increased. These results suggested that the multiple swollen lymph nodes were not metastasis, but IgG4-related disease. Based on these results, therapy using prednisolone was initiated. Multiple lymphadenopathy gradually decreased, and his symptoms improved. Currently, his good responses to osimertinib treatment have been maintained. Like in our case, multiple lymphadenopathy with IgG4-positive plasma cell infiltration during successful anti-cancer treatment is quite rare. In this case, it was hypothesized that anti-cancer treatment with osimertinib induced IgG4-positive plasma cell infiltration in multiple lymph nodes. When lymphadenopathy occurs during lung cancer treatment, IgG4-RD has to be considered other than lung cancer metastasis.


The BRCA2 missense mutation K2497R suppressed self-degradation and increased ATP production and cell proliferation.
Breast cancer susceptibility gene 2 (BRCA2) mediates genome maintenance during the S phase of the cell cycle, with important roles in replication stress, centrosome replication, and cytokinesis. In this study, we showed that a small heat shock protein, HSP27, interacted with and participated in the degradation of BRCA2 in estrogen-treated MCF-7 cells. BRCA2 degradation reportedly requires ubiquitination of the C-terminal region; thus, fragments of amino acid (aa) residues 2241-2940 were produced and assayed for their degradation following cycloheximide (CHX) treatment. The results showed that aa 2491-2580 affected the degradation of BRCA2, especially lysine (Lys) 2497. Furthermore, the K2497 A/R mutation increased ATP production and the proliferation of DLD-1 (BRCA2 knockout) cells compared to the cells expressing wild-type BRCA2-FLAG. Notably, a single residue, Lys2497, affected BRCA2 degradation, and K2497R is reportedly a missense mutation in hereditary breast cancer.


The implications of the Human Rights Act 1998 for the removal and detention of persons in need of care and attention.
The Human Rights Act 1998 ('HRA 1998') requires public authorities to act compatibly with the European Convention on Human Rights ('ECHR'). The ECHR contains rights, inter alia, to liberty and to respect for private life. Those rights--and, therefore, the HRA 1998--may be breached by provisions in the National Assistance Act 1948 and the National Assistance (Amendment) Act 1951 that enable persons in need of care and attention to be removed compulsorily to hospital. However, legal proceedings brought against a public authority that invoked its statuatory powers of removal may themselves be defensible under the HRA.


Use of Post-mortem Brain Tissue in Investigations of Obsessive- Compulsive Disorder: A Systematic Review.
Post-mortem examination of the brain is a key strategy to increase our understanding of the neurobiology of mental disorders. While extensive post-mortem research has been under taken on some mental disorders, others appear to have been relatively neglected. The objective of the study was to conduct a systematic review of post-mortem research on obsessive-compulsive disorder (OCD). A systematic review was performed in accordance with PRISMA guidelines to provide an overview of quantitative, qualitative, or mixed methods primary research studies on OCD. Search platforms included NCBI Pubmed, SCOPUS, and Web of Science. A total of 52 publications were found, and after the removal of works not meeting the inclusion criteria, six (6) peer-reviewed publications remained. These post-mortem studies have provided data on DNA methylation, cellular and molecular alterations, and gene expression profiling in brain areas associated with OCD. Included studies highlight the potential value of post-mortem brains from well-characterized individuals with OCD and suggest the need for additional work in this area.


Two-photon microscopy of aorta fibers shows proteolysis induced by LDL hydroperoxides.
Oxidatively modified LDL mimics several aspects of atherogenesis. In this disease, degradation of the matrix proteins' network also occurs. By a new morphological ex vivo approach, not requiring sample processing, we explored the relationship between the degradation of matrix protein and oxidatively modified LDL. Two-photon excitation fluorescence microscopy images of fresh cross-section rings of rat aorta, acquired while the sample was maintained in a glucose- and oxygen-supplemented buffer, showed straight, parallel, thick, long extracellular matrix proteins. Traditional microscopic examination, requiring sample fixation and staining, shows smaller and curved fibers. Instead, we observed curved and broken fibers after a 30-min incubation of aorta with either LDL containing lipid hydroperoxides, or tert-butyl-hydroperoxide. The adhesion of LDL to the endothelium and its internalization was directly visualized by using a lipid fluorophore. The damage to aorta matrix proteins induced by LDL and tert-butyl-hydroperoxide was fully prevented by antioxidants, such as ascorbate or Trolox C, or inhibitors of proteases. The image spectroscopy of the fibers' autofluorescence (polarization and lifetime) revealed an increased mobility of the fluorescent cross-link in fibers. Damaged matrix proteins were also imaged in aorta samples from apolipoprotein E knock-out mice. Our ex vivo images directly visualized the activation of a fast redox-sensitive proteolytic process in the arterial wall triggered by lipid hydroperoxides in LDL.


Bladder carcinoma with Werner syndrome.
Werner syndrome is a rapid premature aging disease and is considered chromosomal instability syndrome, occasionally associated with malignancy. Urologic malignancy associated with this syndrome is unusual. Herein we report a case of Werner syndrome with urinary bladder carcinoma.


Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model.
Our previous study using allergen-sensitized murine splenocyte cultures has shown that Lactobacillus casei strain Shirota (LcS), a lactic acid bacterium widely used as a starter for fermented milk products, suppresses IgE production through promoting a dominant Th1-type response mediated by IL-12 induction. We tried to evaluate the ability of LcS to suppress both IgE response and allergic reactions in vivo using a food allergy model with ovalbumin-specific T cell receptor transgenic (OVA-TCR-Tg) mice. The ability of heat-killed LcS to induce IL-12 in serum was tested. OVA-TCR-Tg mice were fed a diet containing OVA for 4 weeks and injected with LcS intraperitoneally three times in the first week of this period. Cytokine and antibody secretion by splenocytes, and serum IgE and IgG1 responses were examined. The inhibitory effect of LcS on systemic anaphylaxis induced by intravenous challenge of OVA-fed OVA-TCR-Tg mice with OVA was also tested. Intraperitoneal injection of LcS induced an IL-12 response in the serum of OVA-TCR-Tg mice. In the food allergy model, LcS administration skewed the pattern of cytokine production by splenocytes toward Th1 dominance, and suppressed IgE and IgG1 secretion by splenocytes. The ability of LcS to modulate cytokine production was blocked by anti-IL-12 antibody treatment. LcS also inhibited serum OVA-specific IgE and IgG1 responses and diminished systemic anaphylaxis. LcS administration suppresses IgE and IgG1 responses and systemic allergic reactions in a food allergy model, suggesting a possible use of this lactic acid bacterium in preventing food allergy.


Study on the use of toltrazuril to eliminate Neospora caninum in congenitally infected lambs born from experimentally infected ewes.
To determine if toltrazuril was effective in eliminating Neospora caninum infection from congenitally infected lambs. Twenty-eight ewes were allocated to 3 groups where animals in Groups A and B were inoculated with 1 × 10(7)N. caninum tachyzoites on Day 120 of gestation and Group C was maintained as a negative control group. Lambs born from ewes in Group A were treated with toltrazuril (20mg/kg) on Days 0, 7, 14 and 21 after birth. Lambs in Groups B and C were untreated. All lambs in Groups A and B were seropositive at 12 weeks of age. At 12 weeks of age, no differences between lambs in Group A and Group B were observed in serological results (ELISA and western blot), presence of N. caninum-related brain histopathological lesions or the number of organisms detected by qPCR. Group C remained negative for serology, detection of N. caninum DNA as well as histopathology throughout the study. Results indicate that N. caninum congenitally-infected lambs had a continuing infection with N. caninum despite being treated with toltrazuril.


Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection.
To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. This retrospective cross-sectional study included consecutive patients with HIV/HCV co-infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). One hundred and eleven patients were included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index < 0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co-infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.


Hybrid sliding mode position control for a piston air motor ball screw table.
Air motors have been generally applied in the automation industry. Since air motors operate without electricity, they will not produce sparks, explosions or short circuit phenomenon. The purpose of this paper is to analyze the behavior of a ball screw table actuated by a piston air motor and design a hybrid (backstepping and fuzzy) sliding mode controller for accomplishing accurate position performance. The experimental results validate the proposed position control strategy.


A Model-Based Insulin Dose Optimization Algorithm for People With Type 1 Diabetes on Multiple Daily Injections Therapy.
Multiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D) including basal insulin doses to keep glucose levels constant during fasting conditions and bolus insulin doses with meals. Optimal insulin dosing is critical to achieving satisfactory glycemia but is challenging due to inter- and intra-individual variability. Here, we present a novel model-based iterative algorithm that optimizes insulin doses using previous-day glucose, insulin, and meal data. Our algorithm employs a maximum-a-posteriori method to estimate parameters of a model describing the effects of changes in basal-bolus insulin doses. Then, parameter estimates, their confidence intervals, and the goodness of fit, are combined to generate new recommendations. We assessed our algorithm in three ways. First, a clinical data set of 150 days (15 participants) were used to evaluate the proposed model and the estimation method. Second, 60-day simulations were performed to demonstrate the efficacy of the algorithm. Third, a sample 6-day clinical experiment is presented and discussed. The model fitted the clinical data well with a root-mean-square-error of 1.75 mmol/L. Simulation results showed an improvement in the time in target (3.9-10 mmol/L) from 64% to 77% and a decrease in the time in hypoglycemia (< 3.9 mmol/L) from 8.1% to 3.8%. The clinical experiment demonstrated the feasibility of the algorithm. Our algorithm has the potential to improve glycemic control in people with T1D using MDI. This work is a step forward towards a decision support system that improves their quality of life.


The Effect of Judge Selection on Standard Setting Using the Mastery Angoff Method during Development of a Ventricular Assist Device Self-Care Curriculum.
Patients and caregivers need to perform ventricular assist device (VAD) self-care safely to help prevent complications (e.g., infection). We developed a VAD self-care simulation-based mastery learning (SBML) curriculum. We determined optimal minimum passing scores (MPSs) and evaluated effects of judge selection. A multidisciplinary team created a VAD self-care SBML curriculum including simulated skills and knowledge examinations. Patients, caregivers, VAD coordinators, and physicians were expert judges who determined MPSs using the Mastery Angoff method. MPSs for the skills and knowledge examinations were high (range = 94-99% and 97% correct), respectively. Judges closely agreed on MPSs. Stakeholders set stringent MPSs for high-stakes VAD self-care.


Leaf Litter Inhibits Growth of an Amphibian Fungal Pathogen.
Past studies have found a heterogeneous distribution of the amphibian chytrid fungal pathogen, Batrachochytrium dendrobatidis (Bd). Recent studies have accounted for some of this heterogeneity through a positive association between canopy cover and Bd abundance, which is attributed to the cooling effect of canopy cover. We questioned whether leaf litter inputs that are also associated with canopy cover might also alter Bd growth. Leaf litter inputs exhibit tremendous interspecific chemical variation, and we hypothesized that Bd growth varies with leachate chemistry. We also hypothesized that Bd uses leaf litter as a growth substrate. To test these hypotheses, we conducted laboratory trials in which we exposed cultures of Bd to leachate of 12 temperate leaf litter species at varying dilutions. Using a subset of those 12 litter species, we also exposed Bd to pre-leached litter substrate. We found that exposure to litter leachate and substrate reduced Bd spore and sporangia densities, although there was substantial variation among treatments. In particular, Bd densities were inversely correlated with concentrations of phenolic acids. We conducted a field survey of phenolic concentrations in natural wetlands which verified that the leachate concentrations in our lab study are ecologically relevant. Our study reinforces prior indications that positive associations between canopy cover and Bd abundance are likely mediated by water temperature effects, but this phenomenon might be counteracted by changes in aquatic chemistry from leaf litter inputs.


Postgraduate dental education and the 'new' graduate.
It is notoriously difficult to evaluate educational initiatives. Nevertheless, with the introduction of mandatory vocational training, it seems curious that there has been no formal, structured assessment of whether dental vocational training is perceived as having fulfilled its aims. Nor is there information on how participation in continuing dental education relates to feelings of competence or confidence in clinical practice. This paper reports on the experience of two cohorts of 'new' dental graduates from Scotland and provides evidence to inform the debate on vocational training, general professional training and recertification for the dental profession.


Carbon monoxide and ventricular fibrillation threshold in dogs with acute myocardial injury.
In a blind, randomized study, the effect of breathing 100 p.p.m. of CO versus compressed, purified air for 2 hours on ventricular fibrillation threshold (VFT) was investigated in 21 dogs with acute myocardial injury. The mean arterial carboxyhemoglobin was 1.16 per cent in the air control period, 1.07 per cent after air, 1.08 per cent in the CO control period, and 6.34 per cent after CO. In comparison to air, CO increased the mean arterial carboxyhemoglobin (P less than 0.001). One dog developed spontaneous ventricular fibrillation 100 minutes after CO. Mean VFTs in the other 20 dogs were 12.8 +/- 6.8 milliamperes after CO, 11.2 +/- 6.0 milliamperes in the air control period, and 15.0 +/- 5.1 milliamperes after air. In comparison to air, CO decreased the VFT (P less than 0.001). These data show that breathing 100 p.p.m. of CO for 2 hours reduces the VFT in dogs with acute myocardial injury.


Projections from the nucleus parafascicularis prerubralis to medullary raphe nuclei and inferior olive in the rat: a horseradish peroxidase and autoradiography study.
Horseradish peroxidase gel implants into either the nucleus raphe magnus (NRM) or inferior olive (IO) led to large numbers of retrogradely labeled cells in the prerubral subthalamic region in a cell group that surrounds the fasciculus retroflexus, which we suggest should be referred to as the nucleus parafascicularis prerubralis (nPfPr) to avoid the confusion of previous terminology. Autoradiographic studies, following injections of tritiated leucine into the nPfPr, confirmed projections to both medullary raphe nuclei (MRN) and IO. This common prerubral projection to IO, a well-established precerebellar nucleus, and MRN, again raises the question of whether the latter are involved in brainstem-mediated reflexes in addition to their well documented role in analgesic mechanisms.


Creating competition and accountability in a changing healthcare environment.
Many problems in the healthcare system mirror the structure of a competition in which the participants divide--and sometimes destroy--value instead of creating it, according to a recent study. Some healthcare leaders say that these problems can be dealt with by emphasizing accountability throughout a healthcare organization.


Retrospective Report of Academic Motivation Among College Students With Elevated ADHD Symptoms.
Children with ADHD exhibit deficits in academic motivation compared to their peers. Yet conceptualizations of motivation according to prominent motivation theories connected to achievement have not been studied in college-bound youth with ADHD symptoms. This study examined motivation according to these theories, differences in motivation by ADHD symptoms, and how the cross-sectional association between motivation and achievement varies by ADHD symptoms. The sample included 461 first-year college students retrospectively reporting their motivation and achievement in their last year of high school. Results indicated differences in motivation by ADHD symptoms. Mastery achievement goal orientation was uniquely associated with achievement and exerted beneficial effects on achievement at moderate to high ADHD symptom levels. Motivation may operate differently in association with achievement for college-bound youth with ADHD symptoms compared to youth with no to low symptoms.


Effects of artificial light at night on the feeding behaviour of three marine benthic grazers from the Adriatic Sea are species-specific and mostly short-lived.
Artificial light at night (ALAN) has the potential to change the day-night activity of marine benthic grazers, and can therefore alter the top-down control they exert on macroalgal communities. In laboratory experiments, we investigated the influence of three realistic ALAN regimes on food consumption and feeding rhythmicity in the sea urchins Arbacia lixula and Paracentrotus lividus as well as in the snail Cerithium spp. from the Adriatic Sea. Food consumption was assessed in assays with algal pellets, while feeding rhythms were documented with 24 h time-lapse photography. Both was done in ALAN-acclimated and in non-acclimated animals. We observed temporary and potential long-term changes in the feeding rhythms of Cerithium spp. and Paracentrotus lividus, respectively, but found no lasting influence of ALAN on consumption rates. Effects were weaker when ALAN was applied only part-night, which suggests a possible mitigation measure to reduce the impact of nighttime lighting on coastal ecosystems.


The bowel as substitute for the bladder.
The long-term results with 16 patients who underwent uretero-intestino-urethral urinary diversion are presented. We believe that with meticulous attention to the operative technique and the criteria for the operation this is a reasonable procedure for a patient undergoing cystectomy as an alternative to cutaneous or large bowel diversion of the urinary stream.


Pathogenesis and phylogenetic analyses of canine distemper virus strain 007Lm, a new isolate in dogs.
The pathogenesis of a new isolate of canine distemper virus (CDV), strain 007Lm, was investigated from lymph node tissue by using Vero cells that express canine signalling lymphocyte activation molecules with a tag (Vero-DST) in dogs. Two CDV sero-negative Beagle dogs were inoculated intranasally and intraconjunctively with a virus suspension. Both infected dogs showed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, lymphopenia, fever and weight loss. Titers of CDV-IgM and CDV-IgG in the blood were measured. CDV was detected by using reverse transcriptase-PCR and was recovered in swabs from one dog from 9 days and from the other dogs from 10 days after inoculation. Molecular and phylogenetic analyses of H and P genes showed that nucleotide and amino acid sequences of these genes of strain 007Lm after isolation in Vero-DST cells are identical to those of the original virus from fresh tissue and that strain 007Lm joins to the Asia 2 group cluster of CDV strains that is distinct from other clusters. These results indicate that (1) CDV strain 007Lm isolated in Vero-DST cells is virulent, (2) nucleotide and amino acid sequences of H and P genes of strain 007Lm do not change after isolation in Vero-DST cells compared with the original virus from fresh tissue and (3) strain 007Lm isolated from a vaccinated dog belongs to a cluster far from the vaccine strains in the phylogenetic trees of H and P genes.


Apoprotein B structure and receptor recognition of triglyceride-rich low density lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of normal size.
We compared the effect of lipid composition and particle size of triglyceride-rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vitro incubation with triglyceride emulsion and the neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic individuals made acutely hypertriglyceridemic by intravenous infusion of 10% Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced degradation at 37 degrees C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactivity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative content of neutral lipid in the core of LDL in the absence of changes in the size of the particle does not significantly affect apoprotein B conformation or its affinity for the LDL receptor.


Conformationally rigid N-acyl-5-alkyl-L-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors.
In the N-acyl-L-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-L-prolyl groups, resulting in a series of N-acyl-5-alkyl-L-prolyl-pyrrolidines. Since N-amides of 5-alkyl-L-prolines are conformationally more rigid than those of L-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain.


Validity of Toluidine Blue test as a diagnostic tool for high risk oral potentially malignant disorders- a multicentre study in Sri Lanka.
- Early detection plays a major role to reduce the mortality of oral squamous cell carcinoma (OSCC). Many adjunctive techniques have emerged with claims of differentiating high risk oral potentially malignant disorders (OPMDs) from benign lesions. Toluidine blue (TB) test has been established as a diagnostic adjunct in detecting high risk OPMDs and early asymptomatic OSCCs. As majority of OSCC are preceded by OPMDs, recognition of them at an early stage is important in the management of this devastating disease. -This study was conducted as a multi-center study prospectively for a period of 2 years. Sixty five patients presented with OPMDs were selected and TB test was performed followed by a biopsy for histopathological confirmation. Criterion validity was assessed with histological diagnosis of the incisional biopsy of the OPMD as a gold standard test verses TB test results. The sensitivity of the TB test was 68.3% and the specificity 63.1% with a false positive rate of 36.8% and false negative rate of 31.7%. However, the predictive value of the positive test was 80%. - TB testing might be a potential adjunct diagnostic aid in identifying high risk OPMDs. Further studies with extensive sample size and different demographics are needed to validate our findings.


A novel ionic-bonded cellulose stationary phase for saccharide separation.
A hydrophilic interaction liquid chromatography (HILIC) stationary phase of cellulose-coated silica was synthesized as a novel saccharide separation material. The material, prepared with a method based on ionic interaction, was demonstrated to be efficient for immobilization of saccharides on silica supports. The method is more efficient than traditional immobilized saccharide stationary phase synthesis methods. It was evolved from a method using anion exchanger microparticles agglomerated onto macroparticles of cation exchangers to produce anion exchangers. Cationic cellulose, which has a large number of hydroxyl groups, was immobilized on sulfonated silica. The cellulose-coated stationary phase we designed used strong hydrogen bonding between cellulose hydroxyl and carbohydrate compounds for HILIC retention and separation. The stationary phase was successfully used to separate the samples of polar compounds and the complex samples of oligosaccharides, and demonstrated good reproducibility and stability. The material exhibited good separation selectivity for carbohydrates and ability to enrich glycosylated peptides. The method described here is easy to achieve, environmentally safe and innovative than other methods. It also has extensive application possibilities to separate other categories polar compounds.


Alleviation of the Adverse Effect of Dietary Carbohydrate by Supplementation of Myo-Inositol to the Diet of Nile Tilapia (Oreochromis niloticus).
This study investigated the effect of dietary myo-inositol (MI) on alleviating the adverse effect of the high carbohydrate diet in Nile tilapia (Oreochromis niloticus). Six diets contained either low carbohydrate (LC 30%) or high carbohydrate (HC 45%) with three levels of MI supplementation (0, 400 and 1200 mg/kg diet) to each level of the carbohydrate diet. After an 8-week trial, the fish fed 400 mg/kg MI under HC levels had the highest weight gain and fatness, but the fish fed 1200 mg/kg MI had the lowest hepatosomatic index, visceral index and crude lipid in the HC group. The diet of 1200 mg/kg MI significantly decreased triglyceride content in the serum and liver compared with those fed the MI supplemented diets regardless of carbohydrate levels. Dietary MI decreased triglyceride accumulation in the liver irrespective of carbohydrate levels. The content of malondialdehyde decreased with increasing dietary MI at both carbohydrate levels. Fish fed 1200 mg/kg MI had the highest glutathione peroxidase, superoxide dismutase, aspartate aminotransferase and glutamic-pyruvic transaminase activities. The HC diet increased the mRNA expression of key genes involved in lipid synthesis (DGAT, SREBP, FAS) in the fish fed the diet without MI supplementation. Dietary MI significantly under expressed fatty acid synthetase in fish fed the HC diets. Moreover, the mRNA expression of genes related to lipid catabolism (CPT, ATGL, PPAR-α) was significantly up-regulated with the increase of dietary MI levels despite dietary carbohydrate levels. The gene expressions of gluconeogenesis, glycolysis and MI biosynthesis were significantly down-regulated, while the expression of the pentose phosphate pathway was up-regulated with the increase of MI levels. This study indicates that HC diets can interrupt normal lipid metabolism and tend to form a fatty liver in fish. Dietary MI supplement can alleviate lipid accumulation in the liver by diverging some glucose metabolism into the pentose phosphate pathway and enhance the antioxidant capacity in O. niloticus.


Quercetin Ameliorates Neuropathic Pain after Brachial Plexus Avulsion via Suppressing Oxidative Damage through Inhibition of PKC/MAPK/ NOX Pathway.
Brachial plexus avulsion (BPA) animally involves the separation of spinal nerve roots themselves and the correlative spinal cord segment, leading to formidable neuropathic pain of the upper limb. The right seventh cervical (C7) ventral and dorsal roots were avulsed to establish a neuropathic pain model in rats. After operation, rats were treated with quercetin (QCN) by intragastric administration for 1 week. The effects of QCN were evaluated using mechanical allodynia tests and biochemical assay kits. QCN treatment significantly attenuated the avulsion-provoked mechanical allodynia, elevated the levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and total antioxidant capacity (TAC) in the C7 spinal dorsal horn. In addition, QCN administration inhibited the activations of macrophages, microglia and astrocytes in the C6 dorsal root ganglion (DRG) and C6-8 spinal dorsal horn, as well as attenuated the release of purinergic 2X (P2X) receptors in C6 DRG. The molecular mechanism underlying the above alterations was found to be related to the suppression of the PKC/MAPK/NOX signal pathway. To further study the anti-oxidative effects of QCN, we applied QCN on the H2O2-induced BV-2 cells in vitro, and the results attested that QCN significantly ameliorated the H2O2-induced ROS production in BV-2 cells, inhibited the H2O2-induced activation of PKC/MAPK/NOX pathway. Our study for the first time provided evidence that QCN was able to attenuate pain hypersensitivity following the C7 spinal root avulsion in rats, and the molecular mechanisms involve the reduction of both neuro-inflammatory infiltration and oxidative stress via suppression of P2X receptors and inhibition of the activation of PKC/MAPK/NOX pathway. The results indicate that QCN is a natural compound with great promise worthy of further development into a novel therapeutic method for the treatment of BPA-induced neuropathic pain.


Determining the complex modulus of alginate irreversible hydrocolloid dental material.
The aim of the study is to investigate the visco-elastic response of an alginate irreversible hydrocolloid dental impression material during setting. A novel squeeze film Micro-Fourier Rheometer (MFR, GBC Scientific Equipment, Australia) was used to determine the complex modulus of an alginate irreversible hydrocolloid dental impression material (Algident, ISO 1563 Class A Type 1, Dentalfarm Australia Pty. Ltd.) during setting after mixing. Data was collected every 30s for 10 min in one study and every 10 min for a total of 60 min in another study. A high level of repeatability was observed. The results indicate that the MFR is capable of recording the complex shear modulus of alginate irreversible hydrocolloid for 60 min from the start of mixing and to simultaneously report the changing visco-elastic parameters at all frequencies between 1 Hz and 100 Hz. The storage modulus shows a dramatic increase to 370% of its starting value after 6 min and then reduces to 55% after 60 min. The loss modulus increases to a maximum of 175% of its starting value after 10 min and then reduces to 94% after 60 min. The MFR enables the changes in the complex modulus through the complete setting process to be followed. It is anticipated this approach may provide a better method to compare the visco-elastic properties of impression materials and assist with identification of optimum types for different clinical requirements. The high stiffness of the instrument and the use of band-limited pseudo-random noise as the input signal are the main advantages of this technique over conventional rheometers for determining the changes in alginate visco-elasticity.


Cetuximab enhances radiosensitivity of esophageal squamous cell carcinoma cells by G2/M cycle arrest and DNA repair delay through inhibiting p-EGFR and p-ERK.
Although radiotherapy has improved local control in esophageal squamous cell carcinoma (ESCC), a considerable number of patients still experience relapse due to resistance. In this study, we aimed to evaluate the effects of cetuximab on radiosensitivity in two ESCC cell lines (ECA109 and TE-13) and to investigate their underlying mechanisms. Cells were pretreated with or without cetuximab before irradiation. The MTT assay and clonogenic survival assay were performed to evaluate cell viability and radiosensitivity. Flow cytometry was performed to analyze cell cycle distribution and apoptosis. The γH2AX foci were counted to determine cellular DNA-repairing capacity via immunofluorescence assay. The phosphorylation of key molecules involved in the epidermal growth factor receptor (EGFR) signaling pathway and DNA double-strand break (DSB) repair were measured by western blot. Cetuximab alone was not sufficient to suppress cell viability, but significantly enhanced radiation-induced inhibition of clonogenic survival in ECA109 and TE-13. The radiation sensitivity enhancement ratio (SER) was 1.341 and 1.237 for ECA109 and TE-13, respectively. ESCC cells treated with cetuximab were arrested at the G2/M phase in response to radiation. No significant increase in apoptotic rate was observed in irradiated cells that were treated with cetuximab. The average number of γH2AX foci increased in the combination group (cetuximab and radiation). Cetuximab suppressed phosphorylation of EGFR and downstream ERK, but had no significant effect on AKT. These results indicate the potential for use of cetuximab as an effective radiosensitizer in ESCC. Cetuximab promotes G2/M cycle arrest and reduces DSB repair, as well as inhibiting EGFR and downstream ERK pathways in ESCC.


Paliperidone Long-Acting Injections in Huntington's Disease for Motor and Behavioural Disturbances.
Oral antipsychotics are used to treat motor and behavioural disturbances in Huntington's disease (HD). However, patients with behavioural disturbances are often non-compliant, thus the oral route is inappropriate. The effects of antipsychotic long-acting injections (LAI) in HD are significantly underrepresented in literature. Paliperidone LAI (P-LAI), an atypical antipsychotic, has benefits over other antipsychotics LAI with its long dosing interval and no initial oral overlap, but has no documented cases for this indication. This case of a 45-year-old female highlights the use of P-LAI for severe aggression and chorea secondary to HD causing failed placement in assisted-care accommodation and mobility via an electronic-wheelchair. Three weeks after commencing treatment, she could walk unassisted, and displayed no aggression. After 10 months, she still had significant improvements and resided in the same accommodation for 6 months without any concern. Thus, this case suggests that P-LAI may be a treatment option for non-compliant HD patients.


Herbst appliance anchored to miniscrews in the upper and lower arches vs standard Herbst: A pilot study.
The aim of this pilot study was to present the preliminary results of Class II malocclusion treatment using a skeletally anchored Herbst appliance with miniscrews inserted in the maxillary and mandibular arches to improve anchorage control and skeletal effects. The treatment group (TG) consisted of 13 patients (10 males [M], 3 females [F]; mean age of 12.8 years) with Class II Division 1 malocclusion who were treated with the Herbst appliance and miniscrews inserted in the maxillary and mandibular arches. They were compared with a control group (CG) of 13 patients (10 F, 3 M, mean age of 12.2 years) with Class II Division 1 malocclusion treated with the standard Herbst appliance without miniscrews. Lateral cephalograms were taken before and after Herbst treatment, and cephalometric analysis was performed. In the TG group SNB (°) increased by 2.9°, whereas in CG group SNB (°) increased by 1.1° (P = 0.017). ANB (°) decreased in both groups: -3.3° in the TG group vs -1.3° in the CG group (P = 0.014). Pg-OLp distance increased in both groups: 5.70 mm in the TG group and 0.8 mm in the CG group (P = 0.022). Mandibular incisors proclined 1.6° in the TG group and 3.7° in the CG group. Herbst treatment reinforced with 4 miniscrews (2 in each arch) increased the orthopedic effect of treatment in growing patients with Class II malocclusion.


Resistance training in breast cancer patients undergoing primary treatment: a systematic review and meta-regression of exercise dosage.
Exercise is recognised as an adjunct therapy for breast cancer patients; however, little is known about the resistance training dose-response. We conducted a systematic review and meta-regression to examine the resistance training dose-response (i.e., volume and intensity) in breast cancer patients undergoing primary treatment. Searches in MEDLINE, CINAHL, and SPORTDiscus were conducted for studies published up to November 2019. Experimental studies that evaluated resistance-based exercise interventions in women with breast cancer undergoing primary treatment were included. Information about resistance training components, average change and change per week, as well as standardised mean difference were extracted, and used for meta-regression analysis. Outcome measures were upper and lower body muscle strength and body composition. 10 trials were included in the systematic review and 4 trials in the dose-response analysis. Resistance training weekly prescribed volume was inversely associated with increases in upper and lower body muscle strength (r2 = 98.1-100%; p = 0.009), although there was no relationship between resistance training intensity and strength gains. There was insufficient data for the dose-response analysis of body mass index, percent body fat, and lean mass. Low volume resistance training might be a suitable exercise recommendation for breast cancer patients undergoing primary treatment producing superior benefits for muscle strength compared to higher volume training, regardless of the training intensity. Low volume resistance training may provide a conservative and appropriate approach for breast cancer patients, allowing gradual progression and modification throughout the exercise program.


The wheezy infant -- immunological and molecular considerations.
Most of the data on the pathogenesis of asthma is based on information obtained through bronchial biopsies and bronchoalveolar lavage in adults and young adults. Ethical considerations linked to the invasive nature of airway endoscopy have limited the studies on the pathophysiology of asthma in infancy and early childhood. Although there is evidence that an asthma-like inflammation, with increased inflammatory cells and thickening of the lung basement membrane, may be present also at a very early age, clinical and epidemiologic studies suggest that asthma manifestations in preschool children may significantly differ from those observed in older subjects. In western countries, the vast majority of infants and young children has episodic (or intermittent) asthma, and the exacerbations generally defined "wheezing episodes" occur more frequently with a seasonal pattern being usually related to acute viral infections. There is strong epidemiological evidence that approximately 2/3 of all children who wheeze because of viral infections in early life (and are not atopic) have a transient condition that tends to disappear during early school years. All respiratory viruses may be implicated in the wheezing episodes, the principal being respiratory syncytial virus (RSV) and, with a lower frequency, adenovirus and parainfluenza viruses during the first 3 years of life, and rhinoviruses after that age. Infants and preschool children have on average 6-8 "colds" per year, but the illness tends to be limited to the upper respiratory tract alone in a considerable proportion of individuals, without causing symptomatic involvement of the lower respiratory tract. The variety of factors determining the different outcomes are only partially known, but complex interactions between the intrinsic pathogenicity of the virus and host factors, including the socio-economic conditions of the family, are central to define the type of manifestations and the severity of the process.


Studies on the use of plant extracts in assessing the effects of plant metabolism on the mutagenicity and toxicity of pesticides.
We have carried out studies on the effects of plant metabolism on the mutagenicity of agricultural chemicals. Our approach is to use a cell-free plant extract, as a source of metabolic enzymes, in a standard Ames test. Using a number of test compounds, we observe that plant metabolism can alter the mutagenicity of several pesticides, and can in some instances give rise to metabolites apparently unique from those which are formed in animal cells. A number of parameters of the assay have been examined, and we find that the assay temperature and preincubation of the pesticide with the extract can significantly alter the outcome of the test. We also have devised a method of controlling for the effects that natural extracts can have on the spontaneous reversion rate of the Salmonella tester strains, in an effort to distinguish slight mutagenic responses from the effects of nutrients (e.g. histidine for his- bacteria) in the assay.


[Situation of Mycobacterium tuberculosis drug resistances in Spain].
The Mycobacteriology Spanish Working Group (MSWG) has conducted an epidemiological, descriptive and retrospective study to try to know the level of first line drug resistances in Mycobacterium tuberculosis strains in Spain. Data were obtained from a total of 1083 strains isolated between October and November 2006 in 120 microbiology laboratories from 16 autonomous communities and Melilla. A primary resistance rate of 8.3% and 4.9% was obtained for isoniazid (INH). The probability of suffering resistant tuberculosis was major in the immigrant population with a resistance rate of 12%. Repeating these surveillance studies in later years is recommended.


Effects of amount of contact between mother and child on the mother's nursing behavior.
Short-term effects of different amounts of body contact between mother and newborn on human nursing behavior were studied. Extended contact immediately after parturition was related to an increase in affective components of maternal nursing behavior observed on postpartum Days 2 and 4.


Preparation of chitosan nanoparticles for simultaneous drug delivery of dacarbazine and enoxaparin in melanoma.
The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 ± 1.84 nm, zeta potential of -7.12 ± 0.25 mV, efficiency of drug loading (DL%) of 73.90 ± 3.84 %, and attached enoxaparin percentage of 98.53 ± 0.96 %. Both drugs had extended-release profiles and approximately 96 % of enoxaparin and 67 % dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 ± 1.25 μg/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant difference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 ± 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.


Analgesia after tonsillectomy with controlled intravenous morphine - overdue or exaggerated?
To assess the value of a morphine Patient Controlled Intravenous Analgesia (PCIA) after Tonsillectomies (TE). 30 adult patients were treated with oral analgesics (protocol group) and compared to 30 patients treated with a morphine PCIA for the first 3 Postoperative Days (PODs) after TE. Average and maximum pain severities (Numeric Rating Scale - NRS: 0-10) on PODs 1-3, analgesic score, quality of life, patient satisfaction and side effects were defined as outcome measures. Average pain severities of the protocol and the PCIA group were of similar magnitude (NRS) (POD1: 4.48 vs. 4.71 [p = 0.68], POD2: 4.75 vs. 4.22 [p = 0.32] and POD3: 4.44 vs. 4.25 [p = 0.71]). Maximum pain intensities on POD1 (p = 0.92), POD2 (p = 0.51) and POD3 (p = 0.36) were also comparable between both groups. Patients with a PCIA consumed significantly more opioids (p = 0.001) without significant more side-effects. The PCIA did not provide a superior pain control compared to oral analgesics. In view of the considerable effort and the high opioid consumption, it cannot be recommended as a standardized application for pain control after TE.


Zinc oxide nanoparticles (ZnONPs) influenced seed development, grain quality, and remobilization by affecting the transcription of microRNA 171 (miR171), miR156, NAM, and SUT genes in wheat (Triticum aestivum): a biological advantage and risk assessment study.
Limited studies have been conducted on the role of microRNAs (miRs) and transcription factors in regulating plant cell responses to nanoparticles. This study attempted to address whether the foliar application of zinc oxide nanoparticles (ZnONPs; 0, 10, 25, and 50 mgL-1) can affect miRs, gene expression, and wheat grain quality. The seedlings were sprayed with ZnONPs (0, 10, 25, and 50 mgL-1) or bulk counterpart (BZnO) five times at 72 h intervals. The application of ZnONPs at 10 mgL-1 increased the number of spikelets and seed weight, while the nano-supplement at 50 mgL-1 was accompanied by severe restriction on developing spikes and grains. ZnONPs, in a dose-dependent manner, transcriptionally influenced miR156 and miR171. The expression of miR171 showed a similar trend to that of miR156. The ZnONPs at optimum concentration upregulated the NAM transcription factor and sucrose transporter (SUT) at transcriptional levels. However, the transcription of both NAM and SUT genes displayed a downward trend in response to the toxic dose of ZnONPs (50 mgL-1). Utilization of ZnONPs increased proline and total soluble phenolic content. Monitoring the accumulation of carbohydrates, including fructan, glucose, fructose, and sucrose, revealed that ZnONPs at 10 mgL-1 modified the source/sink communication and nutrient remobilization. The molecular and physiological data revealed that the expression of miR156 and miR171 is tightly linked to seed grain development, remobilization of carbohydrates, and genes involved in nutrient transportation. This study establishes a novel strategy for obtaining higher yields in crops. This biological risk assessment investigation also displays the potential hazard of applying ZnONPs at the flowering developmental phase.


Experimental cryopreservation and autotransplantation of parathyroid glands: technique and demonstration of function.
A canine model for cryopreservation and autotransplantation of parathyroid glands was developed as a prototype for cryopreservation of human parathyroid glands; Each of 18 dogs had two parathyroids removed, sectioned, and cooled at a controlled rate to -80 degrees in media containing 10% dimethylsulfoxide and 10% autologous serum. After storage for two months at -196 degrees the tissue was thawed and implanted in muscle; the remaining two parathyroid glands were removed from the neck. Function was assessed by monitoring serum calcium levels and measuring parathyroid hormone levels in venous effluent from the graft beds. Autograft function was demonstrated in ten of 18 dogs; graft failure occurred in four dogs. In the remaining four dogs, function could not be evaluated because of accessory parathyroid tissue. Parathyroid tissue cryopreserved for nine months was documented to function in six of seven dogs. Histologic study of the cryopreserved, autografted tissue showed normal parathyroid architecture.


Comparing cancer mortality and GDP health expenditure in England and Wales with other major developed countries from 1979 to 2006.
Cancer and gross-domestic-product on health expenditure (GDPHE) are critical issues for major developed countries (MDC). Each country's economic input, GDPHE 1980-2005 is contrasted with clinical outputs, cancer mortality rates (CMRs), to compare their efficiency and effectiveness in reducing CMR. World Health Organization's CMR data for baseline years (1979-1981) are compared with 2004-2006 by sex and age. The χ(2)-tests are used to determine differences between MDC. Efficiency is analysed by calculating a ratio of average GDPHE to reduced CMR over the period. Inputs: All the countries GDPHE grew substantially. For the United Kingdom this reached 9.3%, which is below the MDC average (10%). Outputs: CMR fell substantially (>20%) in six of the ten countries. The male average (15-74 years) CMR in England and Wales had been third highest but by 2004-2006 was sixth, a 31% reduction, which was significantly greater than seven other countries. Initially England and Wales female average CMR was the highest of all countries and is now the second highest. There were significantly greater reductions for the 55-64 and 65-74 years old than in seven and four countries, respectively. GDPHE reduced CMR ratios--the average GDPHE:reduced CMR ratio of England and Wales was 1:120, greater than all MDC and double that in four countries. Comparing GDPHE input with CMR output showed that relatively the NHS achieved more with proportionately less than other MDC.


Rapid, efficient and activation-neutral gene editing of polyclonal primary human resting CD4+ T cells allows complex functional analyses.
CD4+ T cells are central mediators of adaptive and innate immune responses and constitute a major reservoir for human immunodeficiency virus (HIV) in vivo. Detailed investigations of resting human CD4+ T cells have been precluded by the absence of efficient approaches for genetic manipulation limiting our understanding of HIV replication and restricting efforts to find a cure. Here we report a method for rapid, efficient, activation-neutral gene editing of resting, polyclonal human CD4+ T cells using optimized cell cultivation and nucleofection conditions of Cas9-guide RNA ribonucleoprotein complexes. Up to six genes, including HIV dependency and restriction factors, were knocked out individually or simultaneously and functionally characterized. Moreover, we demonstrate the knock in of double-stranded DNA donor templates into different endogenous loci, enabling the study of the physiological interplay of cellular and viral components at single-cell resolution. Together, this technique allows improved molecular and functional characterizations of HIV biology and general immune functions in resting CD4+ T cells.


Factors associated with success and failure of patient-controlled oral analgesia after total hip and knee arthroplasty: a historical comparative cohort study.
Patient-controlled oral analgesia (PCOA) is a novel method of oral opioid administration using set doses of short-acting oral opioids self-administered by patients with a "lockout" period as part of a multimodal regimen. Failure of PCOA can result in severe postoperative pain necessitating use of intravenous patient-controlled analgesia (IV-PCA) with its potential complications. This study evaluated factors related to success or failure of PCOA following total hip arthroplasty (THA) and total knee arthroplasty (TKA). We conducted a retrospective cohort study of all adults who underwent THA and TKA at our institution by extracting data from the proprietary database of our acute pain service. Patient, anesthetic, and surgical variables associated with PCOA failure defined as inadequate analgesia requiring conversion to IV-PCA within 24 hr following THA and TKA were evaluated. Univariable and multivariable logistic regression analyses were performed to identify predictors of PCOA failure. Of the 926 patients who underwent THA or TKA (n = 411 and 515, respectively), 147 (15.9%) patients (67 THA and 80 TKA patients) had PCOA failure with moderate-to-severe pain. Multivariable regression analysis showed that PCOA failure occurred in those with younger age (adjusted odds ratio [aOR] per year of age, 0.97; 99% CI, 0.95 to 0.99; P < 0.001), preoperative chronic use of controlled-release opioids (aOR, 3.45; 99% CI, 1.60 to 7.35; P < 0.001), and with the use of general anesthesia vs spinal anesthesia (aOR, 2.86; 99% CI, 1.20 to 6.84; P = 0.002). The use of PCOA provides adequate analgesia to a majority of patients undergoing THA and TKA. Factors predictive for PCOA failure should be considered when choosing the primary breakthrough analgesic modality following THA/TKA.


Green light phototherapy in newborn infants with ABO hemolytic disease.
The efficacy of fluorescent green light phototherapy was compared with that of blue light phototherapy in the treatment of full-term infants with hemolytic disease and jaundice caused by ABO incompatibility. The efficacy of the treatment was expressed as actual (milligrams per hour) and quantum (milligrams per hour per square centimeter per megawatt) efficiency, taking into account the differential emission of energy from the green versus the blue fluorescent tubes. No statistically significant difference in the rate of serum bilirubin photodegradation was found between the two groups after treatment for 84.6 +/- 14.1 hours versus 81.5 +/- 14.2 hours with the green and the blue phototherapy, respectively. These results, coupled with the known effects of the blue light on the genetic apparatus of mammalian cells, support the application of the green light phototherapy for the treatment of neonatal hyperbilirubinemia caused by ABO incompatibility.


Texas Star-SR: attenuated "Vibrio cholerae" oral vaccine candidate.
Texas Star-SR, a laboratory-derived mutant of Vibrio cholerae El Tor Ogawa 3083, which produces B but not A subunit of cholera toxin was given to 68 healthy adult volunteers in doses of 10(5) to 5 X 10(10) organisms. 16 of 68 exhibited loose stools but in only one individual was stool volume notable. Vomiting occurred in 1 and abdominal cramps in 3 vaccines; malaise and fever were not seen. Texas star was recovered from stools of 22% who received low doses (10(5) or 10(6) organisms) and from 63% who received high doses (10(8), 10(10), 2 X 10(10) or 5 X 10(10)). The attenuated strain was also recovered from jejunal fluid of 76% in the high dose group; cultures revealed 10(2)-10(5) organisms/ml. Seroconversions of vibriocidal antibody occurred in 93% and peak organisms/ml. Seroconversions of vibriocidal antibody occurred in 93% and peak titers were resembling those seen following clinical cholera. In contrast, serum IgG ELISA antitoxin rose significantly in only 29% and levels were below those encountered after clinical cholera. Only 5 of 18 vaccinees tested so far had significant rises in intestinal SIgA antitoxin; these also manifested rises in serum antitoxin. The occurrence of loose stools did not correlate with dose ingested, excretion of vibrios or rise in serum antitoxin. 503 clones recovered from coprocultures and jejunal fluids were negative when tested for enterotoxin. One month following a single 5 X 10(10) organism dose of Texas Star, 7 vaccinees and 6 controls were challenged with 10(6) pathogenic El Tor Ogawa vibrios. Diarrhea occurred in 7 of 10 controls but in only 1 of 7 vaccinees (p = 0.05). Despite clinical protection, excretion of pathogenic V. cholerae was similar in vaccinated and control groups. Twelve vaccinees who received two 10(9) or two 2 X 10(10) organisms doses of Texas Star 1 week apart were challenged with 10(6) pathogenic V. cholerae El Tor of the heterologous serotype. Diarrhea occurred in 11 of 15 controls but in only 3 of 12 vaccinees (p. 0.01). The 3 vaccinees with diarrhea all had mild illness. Texas Star-SR is a prototype that commonly causes mild diarrheal responses but is genetically stable in vivo and stimulates protective immunity against challenge with either the homologous or heterologous serotype.


Biotransformation of rice bran to ferulic acid by pediococcal isolates.
Ferulic acid (FA) is widely used in foods, in beverages, and in various pharmaceutical industries as a precursor of vanillin. FA biotransformation can occur during the growth of lactic acid bacteria (LAB), and its conversion to other phenolic derivatives is observed by many scientists, where ferulic acid esterase (FAE) and ferulic acid decarboxylase (FDC) play significant roles. The present study aimed at screening a panel of LAB for their ability to release FA from rice bran, an agro waste material. FAE and FDC activities were analyzed for the preliminary screening of various dairy isolates. Two Pediococcus acidilactici isolates were selected for studying further the hydrolysis of FA from rice bran and its bioconversion into phenolic derivatives like 4-ethylphenol, vanillin, vanillic acid, and vanillyl alcohol. P. acidilactici M16, a probiotic isolate, has great potential for the production of FA from rice bran and could be exploited as starter culture in the food industry for the production of biovanillin.


Peripheral neuropathy caused by antiepileptic drugs. Neurophysiological study of the A delta and C fibers.
The risk that antiepileptic drugs may cause damage to the peripheral nervous system led us to investigate 12 patients on carbamazepine and 12 patients on phenobarbital with the thermal threshold test. The heat and cold thresholds were measured at the ankle and wrist and, compared with those in 30 healthy subjects, they proved to be significantly higher. When the two groups of epileptics were compared separately with the controls, their thresholds were always higher. These findings are consistent with a toxic effect of both drugs on fine peripheral nerve fibers.


Incidental findings of therapeutic misconception in biobank-based research.
This article explores expressions of therapeutic misconception (TM) in a deliberative-engagement project focused on the return of aggregate and individual genetic results from biobank-based research. We enrolled 45 self-described African Americans in a deliberative-engagement project to explore their attitudes regarding the return of results from biobank-based research. Four groups of individuals participated in four sessions over 2 days that included both educational and focus-group components. TM was expressed by individuals from both clinics on each day that they met. Three main typological categories of TM were noted: (i) the reasons for consenting to participate in a biobank, (ii) the conflation of research with clinical care, and (iii) mistrust about the meaning of biomedical research findings. Although trust may explain why some research participants express TM, it was also fueled by mistrust (e.g., a disbelief that a condition described as untreatable was truly untreatable). We also found that TM is not due solely to research participants' misunderstandings but is a bidirectional phenomenon that can be exacerbated by researchers. This finding raises questions about how to engage prospective research participants in the long-term goals of biobank-based research without unintentionally overstating possible short-term clinical benefits.


Quantitative determination of dopamine in human plasma by a highly sensitive LC-MS/MS assay: Application in preterm neonates.
The determination of dopamine facilitates better understanding of the complex brain disorders in the central nervous system and the regulation of endocrine system, cardiovascular functions and renal functions in the periphery. The purpose of this study was to develop a highly sensitive and reliable assay for the quantification of dopamine in human neonate plasma. Dopamine was extracted from human plasma by strong cation exchange (SCX) solid phase extraction (SPE), and subsequently derivatized with propionic anhydride. The derivatized analyte was separated by a Waters Acquity UPLC BEH C18 column using gradient elution at 0.4 ml/min with mobile phases A (0.2% formic acid in water [v/v]) and B (MeOH-ACN [v/v, 30:70]). Analysis was performed under positive electrospray ionization tandem mass spectrometer (ESI-MS/MS) in the multiple reaction monitoring (MRM) mode. The stable and relatively non-polar nature of the derivatized analyte enables reliable quantification of dopamine in the range of 10-1000 pg/ml using 200 μl of plasma sample. The method was validated with intra-day and inter-day precision less than 7%, and the intra-day and inter-day accuracy of 91.9-101.9% and 92.3-102.6%, respectively. The validated assay was applied to quantify dopamine levels in two preterm neonate plasma samples. In conclusion, a sensitive and selective LC-MS/MS method has been developed and validated, and successfully used for the determination of plasma dopamine levels in preterm neonates.


[Effect of acetylcholine on the structuro-functional characteristics of bush-like interoceptors of the urinary bladder of the frog].
In the preparation of the frog (Rana temporaria) isolated urinary bladder, it has been stated by morphological and physiological experiments that under an exogenic acetilcholine influence certain structural-functional changes take place in the bushy interoceptor. They are manifested as a sharp deterioration in coloration the receptor with methylene blue, the receptory plates decrease in their size, character of granuloformation changes in them. Simultaneously, an increased electrical activity is observed and, on the contrary, under the influence of atropine the impulse activity drops. It should be suggested that acetilcholine acts as an activator of metabolic and as a modulator of physiological processes in the receptor.


Expression of Ki-67 and P16 INK4a in chemically-induced perioral squamous cell carcinomas in mice.
to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins. The correlation between variables was determined by application of the Spearman correlation test. the mean time to onset of perioral lesions was 21.1 ± 2.13 weeks; mean tumor volume was 555.91 ± 205.52 mm3. Of the induced tumors, 80% were classified as low score and 20% high score. There was diffuse positivity for Ki-67 in 100% of lesions - Proliferation Index (PI) of 50.1 ± 18.0. There was a strong direct correlation between Ki-67 immunoreactivity and tumor volume (R = 0.702) and a low correlation with the malignancy score (R = 0.486). The P16INK4a protein expression was heterogeneous, showing a weak correlation with tumor volume (R = 0.334). There was no correlation between the immunohistochemical expression of the two proteins studied. in an experimental model of DMBA-induced perioral carcinogenesis, tumor progression was associated with the tumor proliferative fraction (Ki-67 positive cells) and with tumor histological grading, but not with P16INK4a expression. avaliar a influência da expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a sobre parâmetros clínico-morfológicos em carcinomas espinocelulares periorais quimicamente induzidos com 9,10-dimetil-1,2-benzantraceno (DMBA) em modelo murino. as lesões foram induzidas topicamente na comissura labial de dez camundongos Swiss durante 20 semanas, sendo determinado o momento de surgimento dos tumores e volume tumoral médio até 26 semanas. Na análise histopatológica, as variáveis estudadas foram gradação histológica de malignidade tumoral e expressão imuno-histoquímica das proteínas Ki-67 e p16INK4a. A correlação entre as variáveis estudadas foi determinada pela aplicação do teste de correlação de Spearman. o tempo médio de surgimento das lesões periorais foi 21,1±2,13 semanas. Volume tumoral médio foi de 555,91±205,52mm3. Dos tumores produzidos, 80% foram classificados como de baixo escore e 20%, alto escore. Evidenciou-se positividade difusa para Ki-67 em 100% das lesões - índice de marcação (PI) de 50,1±18,0. Verificou-se correlação direta forte entre a imunoexpressão do Ki-67 e o volume tumoral (R=0,702) e fraca correlação com o escore de malignidade (R=0,486). A expressão da proteína p16INK4a foi heterogênea, mostrando fraca correlação com o volume tumoral (R=0,334). Não houve correlação entre a expressão imuno-histoquímica das duas proteínas estudadas. Em modelo experimental de carcinogênese perioral DMBA-induzida, a progressão tumoral está associada à fração proliferativa do tumor (células ki-67 positivas) e com a gradação histológica tumoral, porém não com a expressão da p16INK4a.


The sorption behavior of a nickel-insolubilized humic acid system in a column arrangement.
The sorption characteristics of insolubilized humic acid (IHA) were investigated for Ni (II) in a column arrangement. The sodium form of the IHA (INaA) was used as a solid phase. Column operations were performed with five steps and all of them were monitored continuously by a flowthrough cell-adapted UV-Vis spectrophotometer. Thus, all solid-phase extraction (SPE) steps were visualized by breakthrough curves and analyses progress were evaluated. However, all calculations and evaluations were focused on the atomic absorption spectrophotometric (AAS) analyses of the solutions collected during the stripping steps. There was a high correlation (r(2), 0.972) between peak area and AAS data of stripping steps. The effect of concentration and pH of the loading solution onto sorption of Ni (II) by INaA was investigated. Sorption characteristics were evaluated by using Freundlich, Langmuir, and Dubinin-Radushkevich (D-R) adsorption isotherms, as well as by Scatchard plot analysis. Multilayer sorption was found to be agreeable for Ni (II). From the D-R isotherm the mean free energy of sorption (E) was calculated (6.65 kJ mol(-1)) and attributed to the multilayer sorption. Finally, the sorption characteristic of the INaA-Ni (II) system was compared with that of the INaA-Cu (II) system, and possible separation of two ions in a binary mixture system is discussed.


Sustained decreases in sedentary time and increases in physical activity are associated with preservation of estimated β-cell function in individuals with type 2 diabetes.
In the Italian Diabetes and Exercise Study_2, a counselling intervention produced modest but sustained increments in moderate-to vigorous-intensity physical activity (MVPA), with reallocation of sedentary-time (SED-time) to light-intensity physical activity (LPA). This post hoc analysis evaluated the impact of intervention on estimated β-cell function and insulin sensitivity. Patients with type 2 diabetes were randomized to one-month counselling once-a-year or standard care for 3 years. The HOmeostatic Model Assessment-2 (HOMA-2) method was used for estimating indices of β-cell function (HOMA-B%), insulin sensitivity (HOMA-S%), and insulin resistance (HOMA-IR); the disposition index (DI) was estimated as HOMA-β%/HOMA-IR; MVPA, LPA, and SED-time were objectively measured by accelerometer. HOMA-B% and DI decreased in control group, whereas HOMA-B% remained stable and DI increased in intervention group. Between-group differences were significant for almost all insulin secretion and sensitivity indices. Changes in HOMA-B% and DI correlated with SED-time, MVPA and LPA. Changes in HOMA-B%, DI, and all indices were independently predicted by changes in SED-time (or LPA), MVPA, and BMI (or waist circumference), respectively. In individuals with type 2 diabetes, increasing MVPA, even without achieving the recommended target, is effective in maintaining estimated β-cell function if sufficient amounts of SED-time are reallocated to LPA.


Association between toe pressure strength in the standing position and postural control capability in healthy adults.
A method has been developed to assess toe pressure strength in the standing position, taking into account concerns about toe grip strength. Which is more associated to postural control capability, the conventional toe grip strength or the newly devised toe pressure strength in the standing position, which is close to the actual movement? This study is a cross-sectional study. This study included 67 healthy adults (mean age, 19 ± 1 years; 64% male). The postural control capability was measured using the center-of-pressure shift distance in the anterior-posterior axis. Toe pressure strength in the standing position was assessed using a toe pressure measuring device to evaluate the force of pressure on the floor surface by all toes. During measurement, care is taken to ensure that the toes do not flex. However, toe grip strength in the sitting position was measured using muscle strength for toe flexion in a conventional manner. Statistical analysis was conducted by performing a correlation analysis between each of the measured items. Additionally, multiple regression analysis was used to examine the functions associated with postural control capability. Pearson's correlation analysis revealed that the postural control capability was correlated with toe pressure strength in the standing position (r = 0.36, p = 0.003). Multiple regression analysis demonstrated that only toe pressure strength in the standing position was significantly associated with the postural control capability, even after adjusting for covariates (standard regression coefficient: 0.42, p = 0.005). The results of this study indicated that toe pressure strength in the standing position was more strongly associated with the postural control capability in healthy adults than toe grip strength in the sitting position. It has been suggested that a rehabilitation program for toe pressure strength in the standing position would help improve postural control capability.


Protease inhibitors decrease rabbit cartilage degradation after meniscectomy.
In vitro proteoglycan (PG) synthesis and release were measured on cartilage removed from rabbit knees within 1 week of meniscectomy. Three days following partial lateral meniscectomy, 72% of the femurs and 82% of the tibias had visible ulcers. Cartilage from the weight-bearing areas incorporated 2.0-2.9 times more 35S-sulfate in vitro than cartilage from the opposite, unoperated knees. 3H-thymidine incorporation was 2.5-3.4 times higher for surgical than control groups. 35S-sulfate incorporation by the surgical group was inhibited by 22% in the presence of 10(-4) M U24522, an inhibitor of rabbit chondrocyte metalloprotease (CMP). 3H-thymidine incorporation by the surgical group was inhibited by 28% by 10(-4) M U24522. In vitro PG release from cartilage removed 2 days after surgery was 1.6-3.7 times higher for the surgical than the control group. PG release by the surgical group after 22 h of incubation was reduced to the control level by three CMP inhibitors, U24278, U24279, and U24522. PG release by cartilage from the nonsurgical group was also reduced by these compounds at 22 h. These results suggest that both the anabolic and catabolic processes that are stimulated by surgery can be isolated in vitro and that CMP may be involved in the catabolic process.


Melatonin protects female rats against steatosis and liver oxidative stress induced by oestrogen deficiency.
Melatonin has been shown to protect cells against oxidative and inflammatory damage via endocrine, paracrine and autocrine actions. Postmenopausal condition is associated with a high incidence of many features of metabolic syndrome including obesity, steatosis and liver oxidative injuries. The aim of this work was to investigate whether treatment with melatonin improves metabolic disturbances associated with oestrogen deficiency in ovariectomised (OVX) rats. OVX and control (CON) female rats were treated with melatonin (10mg/kg×day for 3weeks, p.o.). Body weight gain, adiposity index, plasma biochemical parameters, liver lipid content, hepatic mitochondrial respiration, fatty acid oxidation and mitochondrial H2O2 generation and the activity of the most important enzymatic and non-enzymatic reactive oxygen species (ROS) scavenger systems were measured. In OVX rats, melatonin suppressed lipid accumulation and cellular oxidative stress in the liver. There was a reduction in the levels of carbonylated proteins in the mitochondria and cytosol, reduction in the malondialdehyde contents in the liver homogenates, stimulation of cytosolic glutathione peroxidase and glutathione reductase activities and restoration of reduced glutathione contents to normal levels. Exogenous melatonin protects the liver of OVX rats against steatosis and cellular oxidative stress, possibly via activation of antioxidant enzymes related to glutathione metabolism and by a direct radical scavenging activity.


Proximal aortic stent-graft displacement with type I endoleak due to Heimlich maneuver.
The Heimlich maneuver has saved countless lives by relieving foreign body obstruction from the respiratory tract. Complications related to this life-saving technique, particularly involving the abdominal aorta, are extremely rare. We report the case of a patient who underwent successful endovascular abdominal aortic aneurysm (AAA) repair, with AAA reduction at postoperative surveillance. Endograft displacement after performance of the Heimlich maneuver resulted in a proximal type I endoleak. This case underscores both the potential for aortic trauma from the Heimlich maneuver and the risk for clinical failure as a result of abdominal compression after successful endovascular AAA repair.


Association between MTHFR microRNA binding site polymorphisms and methotrexate concentrations in Chinese pediatric patients with acute lymphoblastic leukemia.
The pharmacokinetics and therapeutic response to methotrexate (MTX) display large variability in the treatment of acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the association of two microRNA (miRNA) binding site polymorphisms (rs3737966 G > A and rs35134728 DEL/TTC) in the 3'-untranslated region of MTHFR with serum MTX concentrations, in a Chinese pediatric population with ALL. Genotyping for MTHFR rs3737966 and rs35134728 in 144 children with ALL was performed using the Sequenom MassArray system (Sequenom, San Diego, CA, USA). Serum MTX concentrations were measured by a fluorescence polarization immunoassay 24 h (C24h ) and 42 h (C42h ) after administration. The effects of the polymorphisms on concentration-to-dose (C/D) ratios of MTX were assessed. Complete linkage disequilibrium between rs3737966 and rs35134728 polymorphisms (r2 = 1) was found in the study population. The minor allele frequency observed in the present study (17.4%) was significantly lower than those in European and African samples reported in the 1000 Genomes Project (42.9% and 63.9%, respectively; p < 0.01). The C/D ratios of MTX at 24 and 42 h for the TTC/TTC-A/A haplotype carriers (11.74 and 0.07 μmol/l per g/m2 , respectively) were significantly lower than those in DEL/DEL-G/G or DEL/TTC-G/G haplotype carriers (12.49 and 0.09 μmol/l per g/m2 , respectively; p < 0.05). Computational predictions suggested that the two polymorphisms overlapped with putative binding sites of several miRNAs. The rs3737966 and rs35134728 polymorphisms in MTHFR were associated with serum MTX concentrations. The findings of the present study indicate that miRNAs might be involved in the post-transcriptional regulation of MTHFR.


Health care reform: what history doesn't teach.
The paper begins by tracing the historical development of American medicine as practice, profession, and industry from the eighteenth century to the present. This historical outline emphasizes shifting conceptions of physicians and physician ethics. It lays the basis for showing, in the second section, how contemporary controversies about the physician's role in managed care take root in medicine's past. In the final two sections, I revisit both the historical analysis and its application to contemporary debates. I argue that historical narratives can function as "master narratives" that suppress or leave out historical facts. I bring to the surface what is covered up by the master narrative approach, and show its relevance to contemporary ethical debates. I conclude by proposing that preserving the integrity of medicine will require modifying the master narratives we tell about physicians. The integrity of medicine also offers new perspectives for thinking about managed care and the broader topic of health care reform.


Modification of nutritional values and flavor qualities of muscle of swimming crab (Portunus trituberculatus): Application of a dietary lipid nutrition strategy.
Lipid sources as alternatives to fish oil could alter the nutritional value and flavor quality of crab meat affecting consumer preferences. Herein, an 8-week nutritional trial was designed to investigate the effects of dietary lipid sources including fish oil (FO), krill oil (KO), palm oil, rapeseed oil, soybean oil and linseed oil on profiles of amino acids, fatty acids and volatiles in muscle of swimming crab (Portunus trituberculatus). Volatiles of crab muscle were characterized by headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. Results revealed that crabs fed FO and KO had significantly higher levels of protein, indispensable amino acids, eicosapentaenoic acid and docosahexaenoic acid in muscle. Principal component analysis and hierarchical cluster analysis demonstrated that muscle volatiles of crabs fed different dietary oils exhibited significant variations. Dietary FO and KO significantly increased the relative levels of 3-methylbutanal, heptanal, benzaldehyde and nonanal in muscle, which may produce more pleasant flavors.


Blunt Thoracic Aortic Injury and Acute Trauma: The Effect on Aortic Diameter and the Consequences for Stent-graft Sizing.
Blunt thoracic aortic injury (BTAI) is associated with a high mortality and large trauma burden. Trauma and resuscitation after injury affect cardiovascular status, which may in turn affect aortic diameter. Measurement of aortic diameter is necessary to guide stent-graft sizing as part of BTAI management. Inaccurate measurement may lead to stent-graft complications. This pilot study aimed to assess the effect of acute major trauma on stent-graft sizing and stent-graft complications, in the context of BTAI and to assess whether any effect could be predicted. Patients who were admitted to a UK major trauma center between January 2007 and December 2017, and were diagnosed with BTAI, were identified. The thoracic aortic diameter was measured at six points on initial and surveillance computed tomography imaging. Data on patient demographics, admission heart rate, mean arterial pressure (MAP), and serum lactate were gathered. Thirty-two patients were identified. Twenty met inclusion criteria. Of these, 12 were managed operatively and eight nonoperatively. The mean age was 40, the mean injury severity score was 43, and 85% were male. A mean increase in diameter between initial trauma scan and surveillance scan was noted throughout the thoracic aorta (P < 0.05). Stent-graft oversizing relative to aortic diameter changed significantly from initial trauma imaging to surveillance imaging (P < 0.05). Admission heart rate, MAP, and serum lactate were not predictive of the percentage change in aortic diameter. There were no complications at surveillance imaging (mean 45 days) or during medium term follow-up (mean 532 days). Aortic diameter is affected by BTAI, acute major trauma, and resuscitation in a significant and variable manner. Measurements of the aorta in a patient with BTAI in the acute trauma setting should be viewed with uncertainty. A lack of complications in the short term is suggestive of a wide tolerance range regarding stent-graft sizing, but long-term results are unknown.


Decolorization and degradation potential of enhanced lignocellulolytic enzymes production by Pleurotus eryngii using cherry waste from industry.
Lignocellulosic wastes accumulate in large quantities and thus cause environmental issues. Cherry waste (CW) of them collected from industry was used as the substrate to increase production of lignocellulolytic enzymes, laccase (Lac), manganese peroxidase (MnP), lignin peroxidase (LiP), carboxymethyl cellulase (CmCase), xylanase, exoglucanase, β-glucosidase (BGLA), by Pleurotus eryngii. Then, the decolorizations of some azo dyes were examined. The effects of different concentrations of some compounds, such as copper, iron, Tween 80, ammonium nitrate, and manganese, on the productions of lignocellulolytic enzymes were studied depending on incubation period. The maximum productions of lignocellulolytic enzymes were achieved by performing 5.0 g CW and 1,000 µM Cu2+ , 1,000 µM Fe2+ , 2.0 g L-1 ammonium nitrate, 180 µM Mn2+ as the inducers. To the results determined under optimized conditions, 3.61, 4.79, 1.86, 1.15, 2.24, and 2.91-fold increases were respectively obtained for Lac, MnP, LiP, CMCase, xylanase, and BGLA activities. The chemical changes of dye structure during decolorization by lignocellulolytic enzymes extract containing Lac with decolorization performance as 12.6 ± 0.8% were partially characterized using Fourier transform infrared spectroscopy. This study is important in terms of dye decolorization and degradation by achieving the enhancement of the activities of seven lignocellulolytic enzymes using various inductors.