Authorisation within the European Union of vaccines against antigenically variable viruses responsible for major epizootic diseases.
Antigenically variable viruses are responsible for some of the most contagious and economically important diseases that affect domestic livestock. The serious consequences of such diseases in terms of economic loss, and human and animal health, were clearly demonstrated by recent epizootics of foot and mouth disease, and outbreaks of avian influenza and bluetongue in the European Union (EU). For such diseases, government authorities need to be able to respond, if appropriate, by making use of vaccines that are suited to the epidemiological situation. The current EU regulatory framework is not well adapted for approval and maintenance of vaccines where the antigens included have to be chosen to reflect the epidemiological need. An extensive revision of the technical requirements for authorisation of veterinary medicinal products within the EU is currently underway. Additionally, a major revision of the regulations that control how such authorisations are kept up-to-date is about to start. This provides an ideal opportunity to introduce into EU legislation the concept of the 'multistrain dossier' whereby a potentially large number of approved strains may be included within a marketing authorisation and the final vaccines may be blended to include strains according to need. In addition, new strains may be added onto the marketing authorisation by means of a rapid regulatory procedure should new antigenic variants actually or potentially threaten the EU.


Toxicological Effects of Aqueous Extract From African Walnut ( Tetracarpidium conophorum) Leaves in Rats.
Tetracarpidium conophorum leaves are used in traditional medicine for the treatment of male infertility, without considering its toxicity and side effects. In this study, we investigated the effects of T conophorum leaves on some biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, creatinine, and uric acid. Histology of the liver and kidney were also assessed. The result revealed that the alanine aminotransferase and aspartate aminotransferase levels of the control group were not significantly different from the experimental groups. There was no significant difference in the albumin and bilirubin levels of the control and experimental groups. Similarly, the uric acid and creatinine levels of the experimental rats were not significantly different from the control. The examination of liver and kidney sections did not show any morphological changes and inflammatory cell infiltrations. These findings suggest that the leaves did not induce any pathological changes at the doses tested.


Development, characterization, and transferability to other Solanaceae of microsatellite markers in pepper (Capsicum annuum L.).
A novel set of informative microsatellite markers for pepper (Capsicum annuum L.) is provided. Screening of approximately 168 000 genomic clones and 23 174 public database entries resulted in a total of 411 microsatellite-containing sequences that could be used for primer design and functional testing. A set of 154 microsatellite markers originated from short-insert genomic libraries and 257 markers originated from database sequences. Of those markers, 147 (61 from genomic libraries and 86 from database sequences) showed specific and scoreable amplification products and detected polymorphisms between at least 2 of the 33 lines of a test panel consisting of cultivated and wild Capsicum genotypes. These informative markers were subsequently surveyed for allelic variation and information content. The usefulness of the new markers for diversity and taxonomic studies was demonstrated by the construction of consistent phylogenetic trees based on the microsatellite polymorphisms. Conservation of a subset of microsatellite loci in pepper, tomato, and potato was proven by cross-species amplification and sequence comparisons. For several informative pepper microsatellite markers, homologous expressed sequence tag (EST) counterparts could be identified in these related species that also carry microsatellite motifs. Such orthologs can potentially be used as reference markers and common anchoring points on the genetic maps of different solanaceous species.


[Expression and activation of insulin receptor substrate-1 in endometrial carcinoma].
To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001). There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.


Hepatic encephalopathy with increased cerebral blood flow in SPECT and MRI abnormalities in the basal ganglia.
A case of hepatic encephalopathy with increased cerebral blood flow in single-photon emission computed tomography (SPECT) and abnormalities upon magnetic resonance imaging (MRI) is reported. SPECT showed increased blood flow exceeding 70 ml/100 g/min in the cerebellum, basal ganglia and cerebral cortex, with hyperammonemia and abnormal electroencephalographic signs showing severe generalized slowing. SPECT data and MRI might reflect abnormal metabolism and neuropathological changes in hepatic encephalopathy.


Bean Leaves Ameliorate Lipotoxicity in Fatty Liver Disease.
Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects in adipose and non-adipose tissues (lipotoxicity), leading to obesity and its comorbidities. Short-term supplementation of bean leaves exhibited anti-diabetic, anti-hyperlipidemic, and anti-obesity effects in high-fat/high-fructose diet animal models. This study aimed to evaluate the effect of bean leaves supplementation in the prevention of lipotoxicity in NAFLD and contribute to elucidating the possible mechanism involved for a longer period of time. During thirteen weeks, male Wistar rats (n = 9/group) were fed with: (1) S: Rodent Laboratory Chow 5001® (RLC); (2) SBL: 90% RLC+ 10% dry bean leaves; (3) H: high-fat/high-fructose diet; (4) HBL: H+ 10% of dry bean leaves. Overall, a HBL diet enhanced impaired glucose tolerance and ameliorated obesity, risk factors in NAFLD development. Additionally, bean leaves exerted antioxidant (↑serum GSH) and anti-inflammatory (↓mRNA TNFα in the liver) effects, prevented hepatic fat accumulation by enhanced ↑mRNA PPARα (β oxidation), and enhanced lipid peroxidation (↓liver MDA). These findings suggest that bean leaves ameliorated hepatic lipotoxicity derived from the consumption of a deleterious diet.


The Role of the Vascular and Structural Response to Activity in the Development of Achilles Tendinopathy: A Prospective Study.
Several risk factors have been suggested in the development of Achilles tendinopathy, but large-scale prospective studies are limited. To investigate the role of the vascular response to activity of the Achilles tendon, tendon thickness, ultrasound tissue characterization (UTC) of tendon structure, and foot posture as possible risk factors in the development of Achilles tendinopathy. Cohort study; Level of evidence, 2. The study began with 351 first-year students at Ghent University. After 51 students were excluded, 300 were tested in the academic years 2013-2014 and 2014-2015 and were followed prospectively for 2 consecutive years by use of a multilevel registration method. Of those, 250 students were included in the statistical analysis. At baseline, foot posture index and UTC were investigated bilaterally. Blood flow and tendon thickness were measured before and after a running activity. Cox regression analyses were performed to identify significant contributors to the development of Achilles tendinopathy. During the 2-year follow-up, 27 of the included 250 participants developed Achilles tendinopathy (11%). Significant predictive effects were found for female sex and blood flow response after running ( P = .022 and P = .019, respectively). The risk of developing Achilles tendinopathy increased if the blood flow increase after running was reduced, regardless of sex, foot pronation, and timing of flow measurements. The model had a predictive accuracy of 81.5% regarding the development of Achilles tendinopathy, with a specificity of 85.0% and a sensitivity of 50.0%. This prospective study identified both female sex and the diminished blood flow response after running as significant risk factors for the development of Achilles tendinopathy. UTC of tendon structure, Achilles tendon thickness, and foot posture did not significantly contribute to the prediction of Achilles tendinopathy. A general evaluation of tendon structure by UTC, measurement of tendon thickness, or determination of the foot posture index will not allow clinicians to identify patients at risk for developing Achilles tendinopathy. Furthermore, it may be possible to improve blood flow after activity by using noninvasive techniques (such as prostaglandins, compression stockings, heat, massage, and vibration techniques). These techniques may be useful in the prevention and management of Achilles tendinopathy, but further research is needed.


Mallory's ('alcoholic') hyaline in primary biliary cirrhosis.
Mallory's (;alcoholic') hyaline has been found in hepatocytes in 18 of 70 patients with primary biliary cirrhosis. These inclusions have previously been noted in only three cases of primary biliary cirrhosis. Current views on the nature of Mallory's hyaline are briefly discussed.


Therapeutic Effect of Murine Bone Marrow-Derived Mesenchymal Stromal/Stem Cells and Human Placental Extract on Testicular Toxicity Resulting from Doxorubicin in Rats.
Oncotherapeutics like doxorubicin can affect male gonads; as a result, it leads to infertility. This work was conducted to demonstrate the toxic effects of doxorubicin on testes of male albino rats. Fifty male albino rats aged 5-7 weeks were used in this study. The animals were randomly separated into 5 sets (each set containing ten rats). Group I received saline (i.p.) for 4 weeks. Group II was given doxorubicin (DOX), 5 mg/kg BW (i.p.) once/week for 4 weeks. Groups III and IV were treated in the same way as the DOX group, left for one week without medication, and then injected with mesenchymal stromal cells (MSCs) or human placental extract (HPE) therapy in a single dose of 5 × 106 in 200 ml PRP/week or 40 μl placental extract for 4 weeks via the caudal vein. Group V rats were treated in the same way as the DOX group also, left for one week without medication, and then injected with MSC+HPE. A significant decrease in serum testosterone, FSH, and LH levels was observed in rats treated with DOX compared to the control group. A significant elevation was recorded in rats treated with DOX+MSC or DOX+HPE when compared with the DOX group only. Rats that were given MSC+HPE after DOX intoxication showed a significant increase in hormone levels when compared to rats treated with either MSC or HPE. Light and electron microscopic examinations revealed that DOX intoxication initiated degenerative and necrotic changes in seminiferous tubules associated with partial or complete cessation of spermatogenesis. These effects were reversed by the effect of MSC or HPE. Coadministration of MSC and HPE even showed further improvement. Finally, we can say that doxorubicin has a deleterious impact on rat testes; however, therapeutic effects can be induced through MSC and/or HPE administration.


A comparison of the poverty impact of transfers, taxes and market income across five OECD countries.
This paper compares the poverty reduction impact of income sources, taxes and transfers across five OECD countries. Since the estimation of that impact can depend on the order in which the various income sources are introduced into the analysis, it is done by using the Shapley value. Estimates of the poverty reduction impact are presented in a normalized and unnormalized fashion, in order to take into account the total as well as the per dollar impacts. The methodology is applied to data from the Luxembourg Income Study database.


Electronic components embedded in a single graphene nanoribbon.
The use of graphene in electronic devices requires a band gap, which can be achieved by creating nanostructures such as graphene nanoribbons. A wide variety of atomically precise graphene nanoribbons can be prepared through on-surface synthesis, bringing the concept of graphene nanoribbon electronics closer to reality. For future applications it is beneficial to integrate contacts and more functionality directly into single ribbons by using heterostructures. Here, we use the on-surface synthesis approach to fabricate a metal-semiconductor junction and a tunnel barrier in a single graphene nanoribbon consisting of 5- and 7-atom wide segments. We characterize the atomic scale geometry and electronic structure by combined atomic force microscopy, scanning tunneling microscopy, and conductance measurements complemented by density functional theory and transport calculations. These junctions are relevant for developing contacts in all-graphene nanoribbon devices and creating diodes and transistors, and act as a first step toward complete electronic devices built into a single graphene nanoribbon.Adding functional electronic components to graphene nanoribbons requires precise control over their atomic structure. Here, the authors use a bottom-up approach to build a metal-semiconductor junction and a tunnel barrier directly into a single graphene nanoribbon, an exciting development for graphene-based electronic devices.


[Evaluation of the filling ability of System-B continuous wave obturation technique to artificial lateral canals in vitro].
To evaluate the filling ability of System-B continuous wave obturation technique to artificial lateral canals of different diameters and at different levels. Forty extracted single-rooted human teeth were randomly divided into two groups. Standardized artificial lateral canals were created at 3, 6 and 9 mm from the apical foramen(AF) with K-file size 8 and 15. After preparation, the specimens were filled with System-B continuous wave vertical compaction or lateral compaction with cold gutta-percha. Transparent teeth were prepared. The filling situation of the lateral canals were measured with a stereoscope and statistically analyzed using SPSS 13.0 software package. The filling rate of the System-B continuous wave obturation technique group(85.00%) was significantly higher than CLC technique group(49.17%) (P<0.05). Significant difference in filling rate and filling length was found between 3 mm, 6 mm and 9 mm from the AF when using the System-B continuous wave obturation technique(P<0.05), but there was no significant difference between 6 mm and 9 mm from the AF(P>0.05). Lateral canals produced by K-file size 15 group were filled better than K-file size 8 group(P<0.05). The filling situation with the System-B continuous wave obturation technique is better than with CLC technique. The System-B continuous wave obturation technique fills differently to lateral canals with different diameters and at different levels.


Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis.
Establishing a system of procedures to qualitatively and quantitatively characterize in vivo and in vitro hepatic steatosis is important for metabolic study in the liver. Here, numerous assays are described to comprehensively measure the phenotype and parameters of hepatic steatosis in mouse and hepatocyte models. Combining the physiological, histological, and biochemical methods, this system can be used to assess the progress of hepatic steatosis. In vivo, the measurements of body weight and nuclear magnetic resonance (NMR) provide a general understanding of mice in a non-invasive manner. Hematoxylin and Eosin (H&E) and Oil Red O staining determine the histological morphology and lipid deposition of liver tissue under nutrient overload conditions, such as high-fat diet feeding. Next, the total lipid contents are isolated by chloroform/methanol extraction, which are followed by a biochemical analysis for triglyceride and cholesterol. Moreover, mouse primary hepatocytes are treated with high glucose plus insulin to stimulate lipid accumulation, an efficient in vitro model to mimic diet-induced hyperglycemia and hyperinsulinemia in vivo. Then, the lipid deposition is measured by Oil Red O staining and chloroform/methanol extraction. Oil Red O staining determines intuitive hepatic steatotic phenotypes, while the lipid extraction analysis determines the parameters that can be analyzed statistically. The present protocols are of interest to scientists in the fields of fatty liver diseases, insulin resistance, and type 2 diabetes.


[Gastric necrosis following gastroplasty].
Over the past ten years, laparoscopic surgery in the treatment of morbid obesity has expanded. However, there are few publications describing its side effects, notably the occurrence of gastric necrosis. Two years after laparoscopic-banding for morbid obesity, a case of acute gastroenteritis in a 45 Year-old woman proved to be a gastric necrosis. Relatively unknown, this complication is generally revealed by non-specific clinical signs. Only emergency oeso-gastro-duodenal opacification permits diagnosis. Early diagnosis permits conservative treatment before the onset of necrosis. Care must be taken when using this technique, which has not yet proved its innocuousness, and regular follow-up of the patient is crucial.


Emissions reduction and pricing of supply chain under cap-and-trade and subsidy mechanisms.
This paper explored how the government provides low-carbon subsidies for the manufacturers, retailers, and consumers in a secondary supply chain under cap-and-trade scheme. We calculated the best prices, emissions reductions, and the demands for common and low-carbon products when subsidizing each of the abovementioned market players. In particular, a comparative analysis of their equilibrium outcomes was made thereafter. The MATLAB simulation found that the optimal emissions reductions under the three subsidy modes were even and positively correlated to low-carbon subsidies, which, however, negatively correlated to the prices of both product types. Higher subsidies drove up demand for low-carbon products and dragged down that for common goods. But the prices of these products maintained the highest levels when consumers were subsidized; demand for common products was greater when subsidies went to retailers than to manufacturers or consumers, consequently generating the largest emissions and highest profits. When the subsidies were greater than [Formula: see text], all three subsidy modes saw a drop in total carbon emissions. That being so, the government should offer proper subsidies before seeing energy-saving progress.


Neonatal weight loss in rural Zaire.
It has been reported that some African babies lose less weight during the neonatal period than their Caucasian counterparts. A prospective study of 330 newborns in rural Zaire was done to evaluate the degree of newborn weight loss and to determine what factors might be causally associated with the weight loss. Overall, the mean weight loss was 7%. Factors correlated with weight loss were asphyxia, birthweight and age at the initiation of breast feeding. The weight loss in the population studied was similar to that reported in Caucasian babies. Early initiation of breast feeding might decrease the degree of weight loss. Further studies are needed to assess the significance of weight changes in the neonatal period.


Growth hormone-releasing factor-44 specificity for components of somatotroph and lactotroph immediate release pool substructures.
Rat somatotroph and lactotroph hormone storage is divisible into at least two functional compartments: an immediate release pool (IRP) and a pool that responds to prolonged stimulation. An IRP substructure has been defined by release in response to potassium ion (K+), prostaglandin E1 (PGE1), and Bu2cAMP. The somatotroph IRP is expandable; the lactotroph IRP is fixed in size. The present experiments examined which IRP components contribute to the rapid release of stored GH in response to GH-releasing factor-44 (GRF). Release of stored PRL was monitored for comparison. In vitro prelabeling defined stored rat (r) GH and rPRL. Release in response to 21 mM K+, 3 microM PGE1, 1 mM Bu2cAMP, and/or 3 nM GRF was monitored with a perifusion-immunoprecipitation system. After 120 min of basal perifusion, tissue was exposed to one of the four secretagogues for 90 min. During a second 90-min period a second secretagogue was added while exposure to the first secretagogue continued. We demonstrated that 21 mM K+ reduces peak rGH release in response to 3 nM GRF by 52%, whereas GRF does not reduce rGH release in response to K+; 3 microM PGE1 reduces rGH release in response to GRF by only 19% although GRF reduces rGH release in response to PGE1 by 88%; 1 mM Bu2cAMP reduces rGH release in response to GRF by 87%, and GRF eliminates rGH release in response to Bu2cAMP (1.2% of control value); combined K+ plus Bu2cAMP reduce rGH release in response to GRF to 2.5% of the control value, whereas after GRF pretreatment rGH release in response to combined K+ plus Bu2cAMP is 93% of the control value; and combined PGE1 and Bu2cAMP reduce the response to GRF to 17% of the control value. Effects on rPRL release are qualitatively similar. We conclude that immediate GRF-stimulated release of stored rGH originates in the somatotroph IRP components defined by responses to PGE1 and Bu2cAMP; it derives only slightly, if at all, from the IRP component defined by the response to K+. The smaller GRF-stimulated release of IRP rPRL is similarly derived.


The nurse's role in neuroleptic medications.
1. A questionnaire study of schizophrenia sufferers' (N = 132) views on medication, contrary to expectations, revealed generally favorable attitudes. Clients seemed to understand the fine balance between costs and benefits better than many health-care professionals imagine. 2. Because nurses spend more time communicating with clients than physicians, they are ideally placed to find out how patients perceive neuroleptic therapy, and to provide information, advice, and counseling support. 3. There is a strong case for asserting that mental health nurses should extend their role in monitoring the effects of medication on their clients.


Genetic Contributions to Health Literacy.
Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5783 English Longitudinal Study of Ageing (ELSA) participants (mean age = 65.49, SD = 9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004-2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE = 7.2%). Greater odds of having adequate health literacy were associated with a 1 standard deviation higher polygenic score for general cognitive ability [OR = 1.34, 95% CI (1.26, 1.42)], verbal-numerical reasoning [OR = 1.30, 95% CI (1.23, 1.39)], and years of schooling [OR = 1.29, 95% CI (1.21, 1.36)]. Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health [OR = 0.92, 95% CI (0.87, 0.98)] and schizophrenia [OR = 0.91, 95% CI (0.85, 0.96)). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic etiology. Larger studies are required to obtain accurate estimates of SNP-based heritability and to discover specific health literacy-associated genetic variants.


[Replantation of amputated ear with microtechnique].
To report replantation of amputated ear with microtechnique in 5 cases. From 2002 to 2005, 5 totally amputated ears were replanted and 4 obediently, 1 retrogressively. In every case, 1-2 arteries and 1-3 veins were anastomosed. Seven vessels were detective and 1-6 cm vessels were transplanted from forearm or dorsal side of hand. Amputated ears obtained blood supply again in about 6-10 hours after injury and exploration was enforced for venous crisis in 2 cases, and bloodletting in 1 case. All 5 cases survived. Auricles possess perfect shape, no pigmentation, slight atrophy and perfect sensation. Amputated ear should be replanted as long as no obvious contusion occurred, and the keys to prevent vascular crisis are cutting off unhealthy vessels, grafting superficial veins for bridging, and the high quality of vascular anastomosis.


Validity of the occupational sitting and physical activity questionnaire (OSPAQ) for home-based office workers during the COVID-19 global pandemic: A secondary analysis.
High levels of occupational sitting is an emerging health concern. As working from home has become a common practice as a result of COVID-19, it is imperative to validate an appropriate self-report measure to assess sitting in this setting. This secondary analysis study aimed to validate the occupational sitting and physical activity questionnaire (OSPAQ) against an activPAL4™ in full-time home-based 'office' workers (n = 148; mean age = 44.90). Participants completed a modified version of the OSPAQ and wore an activPAL4™ for a full work week. The findings suggest that the modified OSPAQ has fair levels of validity in terms of correlation for sitting and standing (ρ = 0.35-0.43, all p < 0.05) and agreement (bias = 2-12%) at the group level; however, estimates were poor at an individual level, as suggested by wide limits of agreement (±22-30%). Overall, the OSPAQ showed to be an easily administered and valid questionnaire to measure group level sitting and standing in this sample of adults.


Oral Candida colonization in xerostomic postradiotherapy head and neck cancer patients.
To evaluate (a) oral colonization of Candida species, especially for non-albicans Candida species (NACS), in xerostomic postradiotherapy head and neck cancer patients and (b) risk factors affecting their colonization. Subjective and objective dry mouth scores, stimulated salivary flow rates, pH and buffering capacity were measured in 72 xerostomic postradiotherapy head and neck cancer patients. Candida counts and species identification were performed using oral rinse samples cultured in Candida Chromagar, followed by polymerase chain reaction and API 20C AUX system. Candida colonization was observed in 87.5% of subjects, with 80.6% and 48.6% of study population colonized by C. albicans and NACS, respectively. NACS was associated with high objective dry mouth scores, denture use, and females (p = .006, .009, and .036, respectively). In addition, Candida glabrata was detected more in females (p = .018) and denture wearers (p = .026), while Candida tropicalis was associated with high objective dry mouth scores (p = .022) and females (p = .027). Quantity of Candida colonization correlated positively with objective dry mouth scores (r = 0.599, p < .001) and negatively with salivary flow rates (r = -0.258, p = .041) and pH (r = -0.290, p = .022). NACS colonization was common in xerostomic head and neck cancer patients. Increased signs of dry mouth, female and dental prostheses may promote NACS colonization.


Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis.
Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear. To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats. This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated. For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration. Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.


Screening mammography for young women treated with supradiaphragmatic radiation for Hodgkin's lymphoma.
Female survivors of Hodgkin's lymphoma (HL) treated with supradiaphragmatic radiation therapy (SRT) are at increased risk of breast cancer (BC), but there is little data on the optimal screening strategy. We report a prospective surveillance study of women treated for HL with SRT before age 30 participating in a high-risk screening clinic. Starting 8 years after treatment, women received annual mammography and clinical follow-up from 1997 to 2006. Method of detection and characteristics of BCs were identified. In all, 115 female HL survivors attended at least one clinic; 100 participated in annual surveillance. The majority had mammography alone; adjunctive magnetic resonance imaging (MRI) was used more frequently in women with high breast density (P = 0.025). Median age at first mammogram was 36 years and decreased with more recent year of diagnosis. Twelve of the 100 participating women (12%) were diagnosed with BC after a median of 5 years of surveillance (range, 1-9). Seven BCs presented as palpable masses [six invasive, one ductal carcinoma in situ (DCIS)], five were detected by mammography (one invasive, four DCIS). Despite earlier initiation of mammographic screening, most BCs were detected clinically and had unfavorable pathologic characteristics. Evaluation of more intensive screening and the contribution of MRI for earlier detection is warranted.


International Society for Stem Cell Research (ISSCR) Guidelines for the Conduct of Human Embryonic Stem Cell Research (December 2006).
The International Society for Stem Cell Research (ISSCR) Guidelines for the Conduct of Human Embryonic Stem Cell Research, prepared by an international group of leading stem cell scientists, bioethicists and lawyers, build on the proposals previously drafted by agencies active in the conduct and funding of stem cell science. They aim not to duplicate existing codes of ethics in research with humans or animals, but to address special sensitivities about human embryo research and acquisition of ova, sperm, embryos and somatic tissues from often vulnerable or dependent donors. Guidelines concern the procurement of research materials, the derivation of stem cells, and banking , distribution and use of cells and cell lines derived from pre-implantation stages of human development. They categorize research that on ethical grounds requires special stem cell research oversight (SCRO), and indicate how that should be undertaken. They emphasize international collaboration in these activities, to maximize benefits to humanity.


Effect of human periodontal ligament stem cell-derived exosomes on cementoblast activity.
Exosomes derived from stem cells are a potential cell-free tool for tissue regeneration with therapeutic potential. However, its application in cementum repair is unclear. This study aimed to investigate the effect of human periodontal ligament stem cell-derived exosomes on the biological activity of cementoblasts, the main effector cells in cementum synthesis. OCCM-30 cementoblasts were cultured with various human periodontal ligament stem cell-derived exosome concentrations. OCCM-30 cells proliferation, migration, and cementogenic mineralization were examined, along with the gene and protein expression of factors associated with cementoblastic mineralization. Exosomal promoted the migration, proliferation, and mineralization of OCCM-30 cells. The exosome-treated group significantly increased the expression of cementogenic-related genes and proteins. Furthermore, the expression of p-PI3K and p-AKT was enhanced by exosome administration. Treatment with a PI3K/AKT inhibitor markedly attenuated the gene and protein expression of cementoblastic factors, and this effect was partially reversed by exosome administration. Human periodontal ligament stem cell-derived exosomes can promote the activity of cementoblasts via the PI3K/AKT signaling pathway, providing a scientific basis for promoting the repair process in orthodontically induced inflammatory root resorption.


Pharmacogenomics of Old and New Immunosuppressive Drugs for Precision Medicine in Kidney Transplantation.
Kidney transplantation is the preferred therapeutic option for end-stage kidney disease, but, despite major therapeutic advancements, allograft rejection continues to endanger graft survival. Every patient is unique due to his or her clinical history, drug metabolism, genetic background, and epigenetics. For this reason, examples of "personalized medicine" and "precision medicine" have steadily increased in recent decades. The final target of precision medicine is to maximize drug efficacy and minimize toxicity for each individual patient. Immunosuppressive drugs, in the setting of kidney transplantation, require a precise dosage to avoid either adverse events (overdosage) or a lack of efficacy (underdosage). In this review, we will explore the knowledge regarding the pharmacogenomics of the main immunosuppressive medications currently utilized in kidney transplantation. We will focus on clinically relevant pharmacogenomic data, that is, the polymorphisms of the genes that metabolize immunosuppressive drugs.


[Rehabilitation of patients with cardiac pacemakers and implanted cardioverter-defibrillators: recommendations for training, physiotherapeutic procedures and re-employment].
Rehabilitation of patients with cardiac pacemakers (CP) or implantable cardioverter defibrillators (ICD) comprises secondary prevention of underlying cardiac disease, conditioning training activities and psychological education and includes furthermore the assessment of aggregate function, detection of any device malfunction as well as the return to work efforts. The extent to which the physical activities can be permitted is determined by both cardiopulmonary capacity and the primary arrhythmic indication. Under consideration of upper frequency limit, left ventricular dysfunction and the avoidance of mechanical exposure on device can and leads, an individually designed training programme is acceptable even on a high load level. Likewise, electrotherapeutic procedures due to musculoskeletal pain syndrome are not generally contraindicated, if differentiated limitations are respected. Beside the assessment of aggregate function and, if necessary, parameter optimization, psychologic intervention programs play an important role particularly in ICD-patients and can be utilized as an additive therapeutic module. Personalized recommendations for driving with an ICD are determined by the time interval since idex arrhythmia and the rhythmological risk profile as well as by the motor vehicle class. The return to work rate of CP and ICD patients is resumably influenced by the underlying cardiac disease and to a lesser extend by the implanted device. Except industrial jobs the risk of electromagnetic interference during the working process is low and can be objected by working place analysis including noise field measurement. Thus cardiac of CP and ICD patients should be used to a large extend for the recovery of individual physical and psychological integrity as well as for the organisation of reemployment.


Autoantibodies in HIV-infected patients that modulate the cholinergic activity of heart and gut tissue.
In human immune deficiency virus (HIV) disease, direct infection of heart tissue with HIV and repeated intestinal infections with opportunistic pathogens are thought to be the main cause of cardiac disease and diarrhoea respectively. A role for autoimmune phenomena may also be involved in the pathogeny of HIV disease. In this study, we demonstrate that immunoglobulins from the A and G classes from HIV positive patients are able to interfere with the function of the muscarinic cholinergic receptors from heart and gut. Both IgA and IgG HIV+ preparations decreased the tension of isolated atria and increased the tension of isolated ileum. The mechanical effect of carbachol was inhibited in both atria and ileum preparations, when they were preincubated with either IgA or IgG HIV+ fractions. An inhibitor of muscarinic cholinergic receptors (atropine) impaired the negative inotropic action of HIV+ immunoglobulins (Ig) on the heart and prevented the positive inotropic effect of HIV+ Igs on ileum. HIV+ IgA fraction was approximately ten fold more potent to interfere with the cholinergic function as compared to the IgG fraction. These results suggest that antibodies present in HIV+ serum may also modulate muscle's cholinergic activity in the heart and ileum from HIV+patients.


Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases.
The diagnosis of prosthetic infection remains a challenge, as no test is 100% sensitive and 100% specific. Recent advances in molecular biology have enabled the detection of infection in culture negative cases. We evaluated the effectiveness of polymerase chain reaction (PCR) in detecting infection in failed joint replacements prospectively in 91 consecutive patients (92 prosthetic joints) undergoing revision total hip or knee arthroplasty. Synovial fluid was collected intraoperatively and examined by broad-range PCR assay for detection of bacterial DNA. The clinical diagnosis of infection was based on the results of blood tests, preoperative joint aspiration, culture and histology of multiple intraoperative tissue samples, as well as the surgeon's assessment. 12 joints (13%) were infected, but the PCR was positive in 32 cases. The sensitivity of the technique was 92%, the specificity 74%, the accuracy 76%, the positive predictive value 34%, and the negative predictive value was 98%. The PCR technique cannot be recommended for the routine detection of prosthetic infection. The large number of false positive results may represent sample contamination, or bacterial presence related to low-virulence organisms, low bacterial load, or a strong host immune response.


How Narcissistic Leaders Impact on Subordinate's Followership During the COVID-19? The Moderating Role of Organizational Identification.
The COVID-19 pandemic gave rise to social and economic problems and pose a threat to most of enterprise. Faced with crisis and challenge, effective leaders and devoted employees are important factors for enterprises to overcome difficulties. We propose a moderated mediation model wherein narcissistic leader predicts subordinate's followership through leader self-interest behavior perceived by subordinates, with organizational identification of leader acting as the contextual condition. Two-wave data collected from 303 employees in the manufacturing and technology industry in China supported our hypothesized model. We found that narcissistic leader has negative impact on subordinates' followership due to their perception of leader's self-interest behavior. Further, organizational identification of leader plays a moderate role in the relationship between narcissistic leader and subordinates' followership. Theoretical and practical implications are discussed. We also offer several promising directions for future research.


[Hematological profile of the healthy elderly in the Amiata Grossetana region].
The haemochromocytometric reports and the main erythrocyte indices (VCM, HbCM , CHbCM ), as well as haematocrit and bilirubinemia levels were studied in 367 apparently healthy people over sixty, of whom a small group showed lower than normal results for their age and sex.


Photodynamic Diagnosis and Narrow-Band Imaging in the Management of Bladder Cancer: A Review.
Bladder cancer is the most common malignancy of the urinary tract. Its proper diagnosis and efficient treatment is still considered a challenge in urology today. White light cystoscopy is a gold standard for the diagnosis, follow-up, and endoscopic treatment of bladder cancer. To improve the efficacy of bladder cancer management, photodynamic diagnosis and narrow-band imaging have been introduced to the urological armamentarium. The article presents the current state of knowledge of technical solutions that are intended to improve the diagnosis and management of bladder cancer. A nonsystemic review of relevant PubMed literature was performed. Photodynamic diagnosis and narrow-band imaging improve the detection of bladder cancer and decrease recurrence rates of bladder tumors. Although the high cost of the equipment may limit its introduction to everyday use, it is a cost-effective method of bladder cancer management for long-term follow-up.


Naturally occurring oncogenic GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down syndrome.
Children with Down syndrome have an increased incidence of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia. The majority of these cases harbor somatic mutations in the GATA1 gene, which results in the loss of full-length GATA1. Only a truncated isoform of GATA1 that lacks the N-terminal 83 amino acids (GATA1-S) remains. We found through genetic studies of 106 patients with TAM that internally deleted GATA1 proteins (GATA1-IDs) lacking amino acid residues 77-119 or 74-88 (created by splicing mutations) contributed to the genesis of TAM in 6 patients. Analyses of GATA1-deficient embryonic megakaryocytic progenitors revealed that the GATA1 function in growth restriction was disrupted in GATA1-IDs. In contrast, GATA1-S promoted megakaryocyte proliferation more profoundly than that induced by GATA1 deficiency. These results indicate that the internally deleted regions play important roles in megakaryocyte proliferation and that perturbation of this mechanism is involved in the pathogenesis of TAM.


Bilateral total knee arthroplasty--staged or simultaneous? Ontario's orthopedic surgeons reply.
Total knee replacement is now the most common joint replacement procedure performed in Ontario, and many patients require bilateral replacement. However, whether bilateral total knee arthroplasty (TKA) should be staged or simultaneous is hotly debated. To determine the current common operative practices of orthopedic surgeons in Ontario, we carried out a province-wide survey. Orthopedic surgeons from Ontario listed in the 1999 Canadian Medical Directory or the membership list of the Canadian Orthopaedic Association were sent questionnaires, asking about their practice in the timing of bilateral TKA, tourniquet use, type of guide and use of techniques to minimize fat embolization. Of the 416 surveys mailed, 219 (53%) surgeons responded. The majority responded that they perform staged bilateral TKA (28% 3-mo interval and 37% 6-mo interval). Simultaneous TKA with 2 teams was the least performed procedure (2%). When performing bilateral TKA, 95% of surgeons use an intramedullary femoral alignment guide, 78% utilize an over-reamed entry hole and 53% suction the canal before inserting the guide rod. With respect to the tibia, 32% use an intramedullary guide, 60% over-ream the entry hole and 60% suction the entry hole; 22% of surgeons stated that they had never considered over-reaming or suctioning the canal to minimize fat embolization. There is no consensus regarding the timing of bilateral TKA in Ontario. Furthermore, many surgeons are not overdrilling or suctioning the femoral canal despite evidence in the literature that overdrilling may be beneficial in decreasing fat embolization. Further research is required to compare the risk of complications of bilateral TKA after staged versus simultaneous TKA.


Surgery for hand deformities due to electrical injury.
The study discusses the treatment of 56 patients with severe hand deformities due to electrical injury. This group of patients underwent clinical and laboratory examinations; the defect was excised and a plastic operation was performed using a pedicle flap, sporadically, Filatov's tubular flap. The defect was determined by angiography. As regards reconstruction and rehabilitation, good results were achieved only in patients with considerable trophic improvement of the hand at 8-10 months after surgery.


Practical office strategies for weight management of the obese diabetic individual.
Obesity is a key component of the insulin-resistance syndrome of type 2 diabetes, and intensifies comorbidities underlying the increased cardiovascular risk of individuals with type 2 diabetes. Weight loss leads to dramatic beneficial effects, with reductions in blood glucose levels and improvements in lipid profiles and blood pressure that often necessitate reductions in medications. Successful long-term weight loss is difficult to achieve in patients with diabetes, as standard dietary approaches often have minimal long-term impact, and intensive management strategies designed to improve glycemic control often contribute to further weight gain in these patients. This article offers a review of newer strategies for enhancing lifestyle change and weight loss in the obese diabetic individual. Use of meal replacements provides structure with portion control, and increased intake of fruits and vegetables promotes a healthier eating style for these patients. Encouraging physical activity such as walking, stair climbing, and gardening can significantly improve cardiorespiratory fitness and glycemic control, and helps patients maintain weight loss. Self-monitoring through lifestyle diaries can reinforce the healthy behaviors necessary for long-term management of obesity. Adjunctive antiobesity medication, medically-supervised intensive weight loss programs, and minimally invasive gastric bypass procedures are important options for patients unable to make significant progress with behavioral changes.


N-acetylcysteine attenuates the progression of chronic renal failure.
Lipid peroxidation impairs renal function. Aldosterone contributes to renal injury in the remnant kidney model. This study aimed to determine the effects of the antioxidant N-acetylcysteine (NAC) on renal function and aldosterone levels in chronic renal failure. Adult male Wistar rats were submitted to 5/6 nephrectomy or laparotomy (sham-operated) and received NAC (600 mg/L in drinking water, initiated on postoperative day 7 or 60), spironolactone (1.5 g/kg of diet initiated on postoperative day 7), the NAC-spironolactone combination or no treatment. Clearance studies were performed on postoperative days 21, 60, and 120. Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary potassium sodium [corrected] ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection. The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.


PAINT I: the effect of art therapy in preventing and managing delirium among hospitalized older adults in the PAINT I study-a proof-of-concept trial.
Delirium is common among older hospitalized patients and is regarded as a negative outcome parameter. Non-pharmacological strategies have been shown to be effective in the prevention and management of delirium. This study aimed to determine the effectiveness of art therapy as part of a multicomponent intervention in preventing and managing delirium in hospitalized older patients. 138 patients at risk of developing delirium were included and received art therapy twice daily for 25 min using a mobile atelier. 107 participants were included in the final analysis (N = 53 intervention, N = 54 control). The primary outcome was the effectiveness of art therapy in preventing delirium. The secondary outcome was to determine its impact on duration of delirium in patients with existing delirium. Delirium was assessed using the Nursing delirium Screening Scale (Nu-DESC). 8 patients (7.5%) developed new onset delirium after admission, equally distributed among control and intervention group. Therefore, no valid statistical analysis could be performed. There was a statistically non-significant decrease in the duration of delirium in the intervention group (4 days, IQR 2.25-8.75) compared to the control group (7 days, IQR 5-10), Mann-Whitney-U-Test p-value = 0.26. After stratifying by dementia diagnosis on admission, the non-significant decrease in duration of delirium in the intervention group was more apparent in patients without dementia. Findings from this study showed that the integration of art therapy as part of a multicomponent intervention in delirium management is feasible, and can reduce duration of delirium among hospitalized older adults.


Feature issue of digital holography and 3D imaging (DH) introduction.
The OSA Topical Meeting "Digital Holography and 3D Imaging (DH)," was held in Seattle, Washington, July 13-17, 2014. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. This year Optics Express (OE) and AO jointly decided to have one such feature issue in each journal. The DH meeting will continue in the future, as expected, and the next meeting is scheduled to be held on 24 - 28 May 2015, in Shanghai Institute of Optics and Fine Mechanics, Shanghai, China.


Acute ischaemic ventricular inferoseptal defect in a pyretic patient: a diagnostic challenge.
A 78-year-old Caucasian male presented with a 5-day progressive history of fever, vomiting and dyspnoea. Initial clinical examination revealed fever, sinus tachycardia, hypotension, peripheral cyanosis and a systolic murmur. Investigations revealed a multiple organ dysfunction syndrome. A repeat trans-thoracic echocardiogram showed a basal inferoseptum aneurysm associated with an acquired ventricular septal defect not demonstrated on initial scan. An intra-aortic balloon pump was urgently inserted and he underwent surgical repair of the defect, 7 days after his initial presentation. He unfortunately died from postoperative complications.


Effect of sodium metabisulphite on germination, growth and yield of Vigna sinensis, Savi.
In the present study, the impact of sodium metabisulphite (Na2S2O5), a food preservative, on seed germination, growth and yield of Vigna sinensis, Savi has been evaluated. Observations clearly reveal the deleterious effect of Na2S2O5 on germination, stomatal development, stomatal index, chlorophyll content and yield. The shoot length exhibited a steady rise in length, while the biomass showed a gradual decrease with the increasing doses of Na2S2O5.


Patterns of telephone calls triaged by registered nurses in a urogynecology practice.
The volume and time required to manage a nurse telephone triage line in an urogynecology practice can be a concern for staffing, time management, and office patient flow. Therefore, telephone triage logs were retrospectively reviewed for a 12-month period to investigate whether call volume differed on days of the five-day office work week. Results showed Monday to be the busiest telephone triage day, with an average of 32.26 calls per day, and Friday as the second busiest day, with 28.52 calls per day. Based on this review, staffing patterns may need to be adjusted to accommodate the higher call volumes on Mondays and Fridays.


Biocontrol Agents Increase the Specific Rate of Patulin Production by Penicillium expansum but Decrease the Disease and Total Patulin Contamination of Apples.
Synthetic fungicides are commonly employed for the control of postharvest diseases of fruits. However, due to health concerns about the use of these chemicals, alternative control methods including biocontrol based on antagonistic yeasts are gaining in popularity. In this study, we investigated the effects of two biocontrol yeasts, Rhodotorula mucilaginosa strain 3617 and Rhodotorula kratochvilovae strain LS11, on blue mold and patulin (PAT) contamination caused by Penicillium expansum strains PY and FS7 in artificially inoculated Fuji apples stored at 20°C for 9 days. To correlate the development of the P. expansum strains in yeast-treated and untreated apples with PAT production, we quantified their biomass in the infected fruits using a recently published quantitative real-time polymerase chain reaction method based on specific primers for patF, a gene from P. expansum that is involved in PAT biosynthesis. Both yeasts significantly reduced the disease incidence caused by the two strains of P. expansum up to 5-7 days of incubation, and lowered their biomass and the progression of symptoms up to 9 days. Interestingly, both yeasts strains increased the rate of PAT production (expressed as ng patulin/μg fungal DNA) by the two pathogenic strains. Nevertheless, both biocontrol agents reduced the total PAT contamination, especially in the case of P. expansum strain FS7, the higher PAT producer of the two tested P. expansum strains. Comparing between the yeast strains, R. kratochvilovae LS11 was more effective than R. mucilaginosa 3617 for the control of P. expansum.


Sequential synthesis of type II colloidal CdTe/CdSe core-shell nanocrystals.
Colloidal type II CdTe/CdSe nanocrystals were synthesized by sequential addition of a tri-n-octylphosphine telluride (TOPTe)/TOP solution and several shell-precursor solutions to a CdO/TOP solution; the shell-precursor solutions consisted of CdO and TOPSe in TOP. For the growth of the CdTe core, the TOPTe/TOP solution was swiftly added to the CdO/TOP solution at a higher temperature (300 degrees C) than the growth temperature (250 degrees C). For the growth of the CdSe shell, in contrast, the CdO/TOPSe/TOP solution was slowly added to the CdTe/TOP solution at a lower temperature than the growth temperature (200-240 degrees C). The temporal evolution of the optical properties of the growing core-shell nanocrystals was monitored in detail. During the growth of the CdSe shell, the core-shell nanocrystals exhibited interesting changes in photoluminescence (PL) properties. The highest PL efficiency (approximately 38 %) was detected from core-shell nanocrystals with a CdSe shell thickness of 0.4-0.5 nm (indicated by TEM); the formation of the first monolayer is proposed. Our synthetic approach is well suited to a practical realization of engineering materials with bandgaps in the near-IR and IR spectral ranges.


Endobronchial metastasis from renal cell carcinoma: a case report.
A 46-year-old man had primary pulmonary symptoms of intermittent fever, cough and dyspnoea. Radiological investigations revealed a mass at right hilum with right upper lobe collapse. Bronchoscopy showed a luminal mass of which the biopsy showed a tumour with predominantly clear cell change. Subsequent investigations revealed primary renal adenocarcinoma. The differential diagnosis of clear cell lung tumour is discussed. This case of endobronchial metastasis from renal cell carcinoma is being presented because of its rarity.


Gene expression during camptothecin-induced apoptosis in human myeloid leukemia cell line ML-2.
Malignant cell proliferation and accumulation depends on the balance between the rates of cell production and cell death. Recent evidence indicates that apoptosis is important in the development of cancer. Apoptosis is strictly controlled by various regulators, which can take part in the apoptotic process, proliferation and differentiation alike. Apoptosis was induced in myeloid cell line ML-2 by camptothecin, an inhibitor of topoisomerase I. After 18 hours of induction by camptothecin 50% of cells were apoptotic. The apoptotic effect of CAM was reversible in the cells studied. The induction of apoptosis influenced the expression of apoptosis and cell cycle regulators as detected by cDNA arrays, RT-PCR or Western blotting. According to cDNA arrays e.g. bax, bfl1, bak, pRb2, c-jun, jun-B were upregulated, and cdk4, cyclin B1, wee1, CRAF1, DP1 were downregulated. A number of other regulators like p21 and cdc25A, as well as some other genes linked with apoptosis, as p53 and the bcl-2 family, were up- or down-regulated as determined by real-time PCR. Changes in gene expression were found not only in the group of regulators of apoptosis and the cell cycle, but also among regulators of differentiation.


The possible causes of the pandemic of peptic ulcer in the late 19th and early 20th century.
Helicobacter pylori is established as a cause of peptic ulcer (PU). Less well recognised is that an epidemic of PU began around the middle of the 19th century, reached a peak at the turn of the century, and is now on the wane. As the epidemic developed, the risk of PU increased in successive generations throughout life. Then the epidemic diminished in successive generations. The risk of gastric ulcer (GU) was highest in people born around 1885, while the risk of duodenal ulcer (DU) was highest in those born about 10-30 years later. H. pylori infection offers an inadequate explanation of the PU epidemic. Although the epidemic coincided with a major rise in cigarette smoking, PU then declined in spite of an increased incidence of smoking. None of the other possible causes of ulcer (non-steroidal anti-inflammatory drugs, stress or diet) satisfactorily explains the epidemics of GU and DU and their asynchronicity. The best, but inadequate, explanation for the epidemic is the coincidence of the acquisition of a new potent strain of H. pylori in childhood and the uptake of smoking in adult life.


Noise coefficients of backscattered electron detectors for low voltage scanning electron microscopy.
Noise coefficients of backscattered electron (BSE) detectors for low voltage scanning electron microscopy were studied theoretically and experimentally. The conversion method of BSE detection, the scintillation detector with an acceleration of BSE and detectors with electron multipliers were considered. Formulae for noise coefficients were derived and noise coefficients of detectors were computed for different values of gains of detectors' components. Theoretical predictions of noise coefficients were compared with experimental results.


Licorice Root Associated With Intracranial Hemorrhagic Stroke and Cerebral Microbleeds.
Chinese Licorice root "gan zao" (Glycyrrhiza uralensis) is an ancient, medicinal herb utilized in Traditional Chinese Medicine for its presumably antiulcer, anti-inflammatory, antiviral, antibacterial, and expectorant properties. One of the major biologically active components is glycyrrhizin, which when hydrolyzed to glycyrrhetinic acid in the human body, possesses significant hypertensive effects due to interaction with the enzyme 11-β-hydroxysteroid dehydrogenase-2.1 Glycyrrhizin and glycyrrhetinic acid also show antithrombotic properties, as orally active, direct inhibitors of blood coagulation factor Xa as well as of thrombin.2 To our knowledge, this is the first reported case of intracranial hemorrhagic stroke associated with Chinese Licorice Root, and first reported case of cerebral microbleeds (CMB) associated with it as well.


Arteriovenous fistulas for hemodialysis and the diabetic. A report on eighteen patients.
Twenty-three subcutaneous arteriovenous fistulas were created for hemodialysis in 18 patients with terminal renal failure due to juvenile diabetes. Seventeen patients received well-functioning fistulas. Four patients needed reoperations due to late failure and the reoperations were successful in three. Venous hypertension syndrome developed in two patients because of thrombosis of the vein proximally to the anastomosis. In one patient extensive arteriosclerotic disease was the cause of late failure of two fistulas. Sepsis with low flow state was the cause of failure in one patient. None of the patients developed clinical signs of arterial insufficiency in the operated limb.


CD68 and CR3/43 immunohistochemical expression in secretory meningiomas.
Secretory meningiomas (SMs) are unusual benign meningiomas. SMs are highly vascularized lesions, with angiomatous features and a perivascular arrangement, and they are accompanied frequently by massive peritumoral edema. Microglia have been called the brain's immune system, although the specific role and prognostic significance of microglia remain uncertain. The objective of this study was to analyze the expression of CD68, a macrophage marker specific for resting microglia, and the expression of major histocompatibility complex Class II CR3/43 in SMs. From 1995 to 2002, six patients with SMs were treated surgically at our institution. Immunohistochemistry was used to analyze the expression of CD68 and CR3/43 in tumor specimens. The intensity of expression was graded semiquantitatively. A correlation between immunohistochemical expression and the occurrence of brain edema was studied. CD68-positive mononuclear cells were observed in neoplastic tissue or around pseudopsammoma bodies and in perivascular areas, with minimal expression in one patient and moderate expression in three patients. CR3/43-positive complexes were detected in mononuclear elongated elements with ameboid extensions, presumably referable to cells at different stages of immunological activation phenomena, with minimal expression in two patients, moderate expression in one patient, and marked expression in one patient. Edema was severe in all patients. Therefore, it may be indirectly hypothesized that edema may not be correlated with the CD68 and CR3/43 immunohistochemical expression. Macrophage infiltration and major histocompatibility complex Class II immunoreactivity in this subtype of meningioma suggest the occurrence of an immune response in the presence of SM.


[Quantitative analysis of landscape conditions of the desertified sandy grassland in Ordos Plateau].
The landscape condition of the sandy grassland in southeast of Ordos Plateau was analyzed based on the data from field investigation along two intercepting 5 km transects. Summary on frequency of the patches showed that small-scale patches were prominent in this area, with 95% of total patches smaller than 50 m and average dimension of patches 15 m, while there were also a couple of large-scale mobile sandy patches. Environmental heterogeneity dependent on spatial scales was revealed by semivarogram in the sampling area. The large fractal dimensions of percent coverage of bare ground, close to 2, indicated dominant small-scale spatial variance. This result implies a relative stabilized landscape and also a desertified area.


Permanent cell lines from erythrophoromas in goldfish (Carassius auratus).
Attempts to establish permanent cell lines from spontaneous erythrophoromas (tumors derived from red pigment cells or erythrophores) of goldfish were made with the use of biopsy specimens from 12 tumors in 10 fish. Three cell lines were established that grew in vitro in synthetic medium (L-15 or Dulbecco's modified Eagle's minimum essential medium) supplemented with 20% fetal bovine serum for more than 8 months. One of these lines (GEM-81) with high proliferative activity was cultured for over 200 generations without an obvious change in growth rate. From this cell line, clonal cultures were obtained that formed clones with relatively intense yellow pigmentation. Descendants of these cell lines and clones contained low but detectable amounts of pteridine pigments (such as 7-hydroxybiopterin, biopterin, xanthopterin, and isoxanthopterin) and numerous cytoplasmic organelles analogous to pterinosomes. Both these characteristics are phenotypic markers of normal erythrophores and their neoplastic counterparts. After numerous subcultivations, these long-term cultures differed from those of the initial explants in having much lower contents of total pteridines and relatively lowered contents of 7-hydroxybiopterin. As manifestations of their neoplastic origins, all cell lines examined showed disoriented growth with dense focal mounding in monolayer cultures. The population doubling time of the uncloned GEM-81 cell line was 31 hours at 35 degrees C over a feeder cell layer and 3 days at 25 degrees C without feeder cells. Injection of cultured cells (1.5 x 10(7) cells/fish) into normal goldfish that had not been immunosuppressed did not give rise to tumors within 5 months.


Pulmonary mucormycosis associated with medical marijuana use.
A 66-year-old man with diabetes presented to the hospital with a two-month history of dyspnea, cough, rust-colored sputum, night sweats and 20 pound weight loss. He had begun smoking medical marijuana 3 months earlier. CT of the chest showed multiple bilateral large ground glass opacities with surrounding consolidation. Infectious workup was negative. BAL was non-diagnostic. He was treated with broad spectrum antibiotics without improvement. VATS was performed and cultured lung tissue grew Rhizopus species. He was started on intravenous liposomal amphotericin B and micafungin and then transitioned to oral posaconazole after two weeks. Repeat CT two months later showed stable size of the cavities. One month later he died of massive pulmonary hemorrhage. Here we document what we believe is the first known case of pulmonary mucormycosis associated with medical marijuana use.


[Analysis on adverse event in acupotomy therapy based on literature research].
To explore the current domestic situation of the adverse event in acupotomy so as to promote the standardization of acupotomy and improve the clinical effect and safety of acupotomy therapy. The method of retrospective journal researching was used. The case report about the adverse event in acupotomy from CNKI, WANFANG and VIP databases was retrieved and the types, the features, the causes, the numbers of the papers and the cases were analyzed. Fifty-eight papers were included, with total 343 cases. It was indicated that the adverse events in acupotomy were mainly postoperative local pain, hematoma, swelling, nerve damage, tendon rupture, adhesion, injury, infection, syncope, anesthesia accident, undeserved hormone use, etc. The lower level of standardization of acupotomy in the clinical use may lead to adverse events. Safe acupotomy treatment for some complicated diseases and dangerous parts remains to be improved, and the standardization of the acupotomy is an important approach to improve its safety. The related work needs to be carried out.


Kallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) ranks among the top 8 causes of cancer death worldwide, with only a 60% 5-year survival rate, highlighting the need for discovery of novel biomarkers and therapeutic targets. We have previously reported that expression of a panel of serine proteinase kallikreins (KLK 5, 7, 8, and 10) is correlated with formation of more aggressive OSCC tumors in a murine orthotopic OSCC model and is elevated in human OSCC. Current studies focus on understanding the potential role of KLK5 in OSCC progression. In initial studies, KLK levels in malignant OSCC cells (SCC25) were compared with cells from normal oral mucosa (OKF/6) and pre-malignant oral keratinocytes (pp126) using qPCR. A marked elevation of all KLKs was observed in aggressive SCC25 cells relative to OKF/6 cells. In normal skin, KLKs are involved in desquamation during epidermal differentiation via proteolytic cleavage of the desmosomal cadherin component desmoglein 1 (Dsg1). As loss of cell-cell cohesion is prevalent in tumor metastasis, Dsg1 integrity was evaluated. Results show that SCC25 cells exhibit cleavage of Dsg1, which is blocked by proteinase inhibitor treatment as well as by siRNA silencing of KLK5 expression. Furthermore, cell-cell aggregation assays demonstrate that silencing of KLK5 enforces cell-cell adhesion; conversely, overexpression of KLK5 in normal oral mucosal cells (OKF/6) enhances cell dispersal. These data suggest that KLK5 may promote metastatic dissemination of OSCC by promoting loss of junctional integrity through cleavage of desmoglein 1.


Dental Malocclusion and Its Relation to the Podal System.
Background and Objective: This study analyzes the possibility that Stomatognathic and Postural systems are related by muscle chains. Malocclusion may influence the posture, contact between the foot and the ground, center of mass, footprint or vice-versa. This study aimed to verify whether there is a relationship between dental occlusion and podal system. Materials and Methods: A cross-cutting, descriptive study was carried out on 409 children (222 boys and 187 girls) between 8 and 14 years old. Dental occlusion was assessed on the sagittal plane (Angle's classification) the contact between the foot and the ground and the center of mass were evaluated using a stabilometric platform. Results: There was a statistically significant relationship between the plantigrade phase, the contact surface area and center of gravity. There was a prevalence of molar and canine Angle's class II malocclusion. In molar class II, an anterior center of gravity was predominant, in class I it was centered and in class III, it was posterior. There was significant correlation between malocclusions and the FPI (foot posture index) of the left foot and the height of the scaphoid in the right foot (P < 0.001). Conclusions: Some authors agree with our results. There is still much uncertainty in terms of showing a relationship between both systems. In addition, there is scarce scientific evidence on the topic. Some kind of relationship between the two systems has been proven. Studies that evaluate a group of subjects in a longitudinal manner are necessary to enable the changes taking place in both systems to be defined.


Effectiveness of preoperative pelvic floor muscle training for urinary incontinence after radical prostatectomy: a meta-analysis.
Radical prostatectomy (RP) is the most common treatment for patients with localized prostate cancer. Urinary incontinence (UI) is a significant bothersome sequela after radical prostatectomy that may dramatically worsen a patient's quality of life. Pelvic floor muscle training (PFMT) is the main conservation treatment for men experiencing urinary incontinence; however, whether additional preoperative PFMT can hasten the reestablishment of continence is still unclear. The objective of this meta-analysis is to determine whether the effectiveness of preoperative plus postoperative PFMT is better than postoperative PFMT only for the re-establishment of continence after RP. A meta-analysis was performed after a comprehensive search of available randomized controlled trials (RCTs). Quality of the included studies was assessed by the Cochrane Risk of Bias tool. Efficacy data were pooled and analyzed using Review Manager (RevMan) Version 5.0. Pooled analyses of continence rates 1, 3, 6, and 12 months postoperatively, using relative risk (RR) and 95% confidence intervals (CIs), were conducted. For data deemed not appropriate for synthesis, a narrative overview was conducted. Five eligible studies were ultimately included in this analysis. No significant differences in continence rates were detected at the early (1- and 3-month) time points: RR = 1.21, 95% CI = 0.71-2.08, P = 0.48; RR = 1.1, 95% CI = 0.09-1.34, P = 0.34, respectively), interim (6-month time point: RR = 0.98, 95% CI = 0.93-1.04, P = 0.59), or late recovery stage (RR = 0.93, 95% CI = 0.67-1.29, P = 0.66). Outcomes reported were time to continence in two trials and quality of life in three, but results were inconclusive because of insufficient data. According to this meta-analysis, additional preoperative PFMT did not improve the resolution of UI after RP at early (≤3-month), interim (6-month), or late (1-year) recovery stages. However, the results of time to continence and quality of life were inconclusive because of insufficient data. More high-quality RCTs are needed for better evaluation of the effectiveness of preoperative PFMT on post-prostatectomy UI.


Effect of accelerator in green synthesis of silver nanoparticles.
Silver nanoparticles (Ag-NPs) were successfully synthesized in the natural polymeric matrix. Silver nitrate, gelatin, glucose, and sodium hydroxide have been used as silver precursor, stabilizer, reducing agent, and accelerator reagent, respectively. This study investigated the role of NaOH as the accelerator. The resultant products have been confirmed to be Ag-NPs using powder X-ray diffraction (PXRD), UV-vis spectroscopy, and transmission electron microscopy (TEM). The colloidal sols of Ag-NPs obtained at different volumes of NaOH show strong and different surface plasmon resonance (SPR) peaks, which can be explained from the TEM images of Ag-NPs and their particle size distribution. Compared with other synthetic methods, this work is green, rapid, and simple to use. The newly prepared Ag-NPs may have many potential applications in chemical and biological industries.


The use of beta-thromboglobulin to detect platelet damage by therapeutic ultrasound in vivo.
Three sequential blood samples were drawn from arms of adult human volunteers by means of a cannula technique, and the plasma levels of beta-thromboglobulin (beta-TG an index of platelet damage) were measured. Ultrasound (0.75 MHz, continuous wave; spatially averaged intensity 0.34 to 0.5 W/cm-2) was applied to the blood vessels while the second sample of each series was being taken. No elevation of beta-TG was detected, indicating that under these conditions ultrasonic irradiation had not damaged an appreciable number of platelets. There was, however, an indication of decreased platelet sensitivity following insonation; and it is postulated that this may be the result of either increased production or secretion of the potent endothelial platelet inhibitor, prostacyclin, or both.


Results of postoperative radiotherapy of cervix carcinoma after radical versus non radical hysterectomy.
We studied the outcome of our 68 cervix carcinoma patients treated either with: 1) radical surgery and postoperative 192Ir high-dose rate afterloading brachytherapy or postoperative radiotherapy to the whole pelvis or with 2) standard hysterectomy and postoperative radiotherapy to the whole pelvis. Forty-eight women were treated by radical hysterectomy from 1988 to 1992 and--due to risk factors--by postoperative radiotherapy (Group 1), 20 other patients (Group 2) pretreated with standard hysterectomy were admitted to the university hospital for postoperative radiotherapy of the whole pelvis. Postoperative radiotherapy consisted of 39.6 Gy total dose using the box technique, plus two afterloading applications with a single dose of 7.5 Gy and 6 Gy external beam therapy to the pelvic lymph nodes sparing the midline. Comparing the Kaplan-Meier plots of both groups, the tumor related survival curve, the locoregional control and the rates of metastatic disease were nearly identical. But in the analysis of special subgroups, patients with positive lymph nodes after standard hysterectomy and postoperative radiotherapy had a worse prognosis (75% three years' survival rate) than patients after radical surgery (86% three years' survival rate). Lymphangiosis was a negative prognostic factor for the patients pretreated with standard hysterectomy (60% versus 80% three years' survival rate), but not for patients after radical surgery (80% three years' survival rate), despite the same radiotherapy in both groups. Standard hysterectomy fails to be an adequate treatment for early cervix carcinoma because moderately dosed postoperative radiotherapy cannot achieve complete locoregional control in all cases of positive lymph nodes or invasion of lymph vessels. However, based on the empirical results of many authors and our own results, postoperative radiotherapy is further indicated in high risk cases of cervix carcinoma after radical surgery.


[Impact of body mass index on men in their 20s and the effects of subsequent changes in body weight upon the rates of hypertension and diabetes and medical costs in their 40s].
To investigate the impact of body mass index (BMI) of men in their 20s and the effects of subsequent changes in body weight upon medication rates, prevalence of hypertension and diabetes, and medical costs in their 40s. A total of 10,125 men who were in their 20s in 1989 were recruited as subjects and grouped according to their BMI and a combination of BMI and increase in body weight over a 20-year period. A logistic regression analysis was performed to evaluate subsequent medication rates, prevalence of hypertension and diabetes, and consultation rate. Analysis of covariance was performed for mean medical costs on the basis of the BMI value in their 20s. All data were adjusted for age in 1989 and changes in body weight over the subsequent 20 yr. A mean increase of 7 kg in body weight was observed over the 20-year period. Medication rates and prevalence of hypertension and diabetes in the men in their 40s increased significantly in correlation with the BMI values in their 20s (men with higher BMI showed higher medication and symptom prevalence rates). The 25.0 or higher BMI group showed a 6.81-fold higher prevalence of hypertension and a 16.62-fold higher prevalence of diabetes than the 18.5-19.9 BMI group. Similarly, men with higher BMI values in their 20s incurred greater outpatient and total medical costs in their 40s. The mean total medical costs in 2009 of men in the 18.5 or lower BMI group in their 20s was 818.7 yen and that for men in the 25.0 or higher BMI group was 5,311.5 yen. Furthermore, men in their 40s showed increased risk of hypertension and diabetes, if their body weight increased by 10 kg or more in the subsequent 20 yr, even when they had BMI values between 20.0 and 24.9 in their 20s. Men with high BMI values in their 20s showed higher prevalence of hypertension and diabetes and incurred greater medical costs in their 40s. Even men with a BMI of less than 25.0 in their 20s, showed increases in the prevalence of hypertension and diabetes which were dependent on their weight gain in the subsequent years. Healthcare activities in Japanese corporations based on lifetime employment should promote anti-obesity strategies among young employees and help not only those employees who are obese but also those who are not controlling their weight.


St Elsewhere's or St Everywhere's: improving patient throughput in the private hospital sector.
Communication errors have been found to be most common root cause of medical errors by the US-based Agency for Healthcare Research and Quality [1]. Although elective admissions to hospital involves a high volume of important healthcare communications where incorrect, missing or illegible information could result in a serious medical error, there is little published research on the impact of improving pre-admission communication flow between admitting doctors and hospitals. The Sydney Adventist Hospital (the San) is a 341-bed private hospital in Sydney's northern suburbs that provides a comprehensive range of health services. A process improvement program began in early 2005 to streamline preadmission communications. The objectives of this ongoing program are broadly to improve patient safety and to increase operating efficiency. The first major initiative within this program was to implement a standardised method for inpatient booking/referral with over three hundred admitting doctors. Eighteen months on, the hospital has been able to demonstrate a significant shift in the timeliness of patient bookings from specialists' rooms, more comprehensive provision of clinical indicators that can facilitate resource planning in operating theatres and on the wards, and reduction in the ratio of bookings made in areas other than the hospital bookings department. The program continues with focus on improving accuracy of data entry, rationalising patient forms, making more effective use of information received and automation of pre-admission information flows.


Effects of neurogenic bladder dysfunction in utero seen in neonates with myelodysplasia.
Twenty neonates with myelodysplasia were prospectively evaluated during the first month of life with urodynamic studies, contrast voiding cystourethrograms (VCUG) and renal ultrasound scans. Ten of 20 infants had abnormal VCUGs--6 with vesicoureteric reflux (VUR) and 4 with bladder trabeculation alone. Only 2/20 neonates had abnormal ultrasounds--both with hydroureteronephrosis secondary to VUR. Elevated leak point pressure (LPP) and/or detrusor sphincter dyssynergia (DSD) were present in 10/20 infants--6 with elevated LPP and DSD, 3 with elevated LPP alone and 1 with DSD alone. Eight of 10 neonates with DSD or elevated LPP had abnormal VCUGs--4 with VUR and 4 with bladder trabeculation alone. Conversely, 8/10 neonates without DSD or elevated LPP had normal VCUGs. Contrast VCUG performed shortly after birth, therefore, is essential for the discovery of bladder trabeculation and reflux. There is a strong correlation between an abnormal VCUG and the presence of DSD and elevated LPP, suggesting that neurogenic bladder dysfunction in utero can lead to these structural abnormalities.


Chronic inflammation and extracellular matrix-specific autoimmunity following inadvertent periarticular influenza vaccination.
Viral infections may trigger autoimmunity in genetically predisposed individuals. Immunizations mimic viral infections immunologically, but only in rare instances vaccinations coincide with the onset of autoimmunity. Inadvertent vaccine injection into periarticular shoulder tissue can cause inflammatory tissue damage ('shoulder injury related to vaccine administration, SIRVA). Thus, this accident provides a model to study if vaccine-induced pathogen-specific immunity accompanied by a robust inflammatory insult may trigger autoimmunity in specific genetic backgrounds. We studied 16 otherwise healthy adults with suspected SIRVA occurring following a single work-related influenza immunization campaign in 2017. We performed ultrasound, immunophenotypic analyses, HLA typing, and influenza- and self-reactivity functional immunoassays. Vaccine-related bone toxicity and T cell/osteoclast interactions were assessed in vitro. Twelve of the 16 subjects had evidence of inflammatory tissue damage on imaging, including bone erosions in six. Tissue damage was associated with a robust peripheral blood T and B cell activation signature and extracellular matrix-reactive autoantibodies. All subjects with erosions were HLA-DRB1*04 positive and showed extracellular matrix-reactive HLA-DRB1*04 restricted T cell responses targeting heparan sulfate proteoglycan (HSPG). Antigen-specific T cells potently activated osteoclasts via RANK/RANK-L, and the osteoclast activation marker Trap5b was high in sera of patients with an erosive shoulder injury. In vitro, the vaccine component alpha-tocopheryl succinate recapitulated bone toxicity and stimulated osteoclasts. Auto-reactivity was transient, with no evidence of progression to rheumatoid arthritis or overt autoimmune disease. Vaccine misapplication, potentially a genetic predisposition, and vaccine components contribute to SIRVA. The association with autoimmunity risk allele HLA-DRB1*04 needs to be further investigated. Despite transient autoimmunity, SIRVA was not associated with progression to autoimmune disease during two years of follow-up.


Tepidisphaera mucosa gen. nov., sp. nov., a moderately thermophilic member of the class Phycisphaerae in the phylum Planctomycetes, and proposal of a new family, Tepidisphaeraceae fam. nov., and a new order, Tepidisphaerales ord. nov.
Three strains of facultatively aerobic, moderately thermophilic bacteria were isolated from terrestrial hot springs in Baikal Lake region and Kamchatka (Russia). Cells of the new isolates were cocci reproducing by binary fission. The temperature range for growth was between 20 and 56 °C and the pH range for growth from pH 4.5 to 8.5, with optimal growth at 47-50 °C and pH 7.0-7.5. The organisms were chemoheterotrophs preferring sugars and polysaccharides as growth substrates. 16S rRNA gene sequences of strains 2842, 2813 and 2918Kr were nearly identical (99.7-100 % similarity) and indicated that the strains belonged to the phylum Planctomycetes. The phylogenetically closest cultivated relatives were Algisphaera agarilytica 06SJR6-2(T) and Phycisphaera mikurensis FYK2301M01(T) with 16S rRNA gene sequence similarity values of 82.4 and 80.3 %, respectively. The novel strains differed from them by higher growth temperature, sensitivity to NaCl concentration above 3.0 % and by their cellular fatty acids profile. On the basis of phylogenetic and physiological data, strains 2842(T), 2813 and 2918Kr represent a novel genus and species for which we propose the name Tepidisphaera mucosa sp. nov. The type strain is 2842(T) ( = VKM B-2832(T) = JCM 19875(T)). We also propose that Tepidisphaera gen. nov. is the type genus of a novel family, Tepidisphaeraceae fam. nov. and a novel order, Tepidisphaerales ord. nov.


CeFra-seq: Systematic mapping of RNA subcellular distribution properties through cell fractionation coupled to deep-sequencing.
The subcellular trafficking of RNA molecules is a conserved feature of eukaryotic cells and plays key functions in diverse processes implicating polarised cellular activities. Large-scale imaging and subcellular transcriptomic studies suggest that regulated RNA localization is a highly prevalent process that appears to be disrupted in several neuromuscular disorders. These features underline the importance and usefulness of implementing procedures to assess global transcriptome subcellular distribution properties. Here, we present a method combining biochemical fractionation of cells and high-throughput RNA sequencing (CeFra-seq) that enables rapid and efficient systematic mapping of RNA cytotopic distributions in cells. The described procedure involves biochemical fractionation to derive extracts of nuclear, cytosolic, endomembrane, cytoplasmic insoluble and extracellular material from cell culture lines. The RNA content of each fraction can then be profiled by deep-sequencing, revealing global subcellular signatures. We provide a detailed protocol for the CeFra-seq procedure along with relevant validation steps and data analysis guidelines to graphically represent RNA spatial distribution features. As a complement to imaging approaches, CeFra-seq represents a powerful and scalable tool to investigate global alterations in RNA trafficking.


Advertising and Risk Selection in Health Insurance Markets.
This paper studies the impact of advertising as a channel for risk selection in Medicare Advantage. We provide evidence that insurer advertising is responsive to the gains from risk selection. Then we develop and estimate an equilibrium model of Medicare Advantage with advertising, allowing rich individual heterogeneity. Our estimates show that advertising is effective in attracting healthy individuals who are newly eligible for Medicare, contributing to advantageous selection into Medicare Advantage. Moreover, risk selection through advertising substantially lowers premiums by improving insurers' risk pools. The distributional implication is that unhealthy consumers may be better off through cross-subsidization from healthy individuals.


Auditory filter width affects response magnitude but not frequency specificity in auditory cortex.
Spectral analysis of acoustic stimuli occurs in the auditory periphery (termed frequency selectivity) as well as at the level of auditory cortex (termed frequency specificity). Frequency selectivity is commonly investigated using an auditory filter model, while frequency specificity is often investigated as neural adaptation of the N1 response in electroencephalography (EEG). However, the effects of aging on frequency-specific adaptation, and the link between peripheral frequency selectivity and neural frequency specificity have not received much attention. Here, normal hearing younger (20-31 years) and older participants (49-63 years) underwent a psychophysical notched noise experiment to estimate individual auditory filters, and an EEG experiment to investigate frequency-specific adaptation in auditory cortex. The shape of auditory filters was comparable between age groups, and thus shows intact frequency selectivity in normal aging. In auditory cortex, both groups showed N1 frequency-specific neural adaptation effects that similarly varied with the spectral variance in the stimulation, while N1 responses were overall larger for older than younger participants. Importantly, the overall N1 amplitude, but not frequency-specific neural adaptation was correlated with the pass-band of the auditory filter. Thus, the current findings show a dissociation of peripheral frequency selectivity and neural frequency specificity, but suggest that widened auditory filters are compensated for by a response gain in frequency-specific areas of auditory cortex.


Being more than "just a bog-standard knee": the role of person-centred practice in physiotherapy: a narrative inquiry.
The aim of this study was to understand how physiotherapeutic encounters were experienced over time by one service user and the extent to which the encounters were person-centred. This narrative inquiry study had one participant purposively sampled due to their extensive experience of physiotherapy in healthcare systems in the United Kingdom. Data were collected through interviews and analysed using Clandinin and Connelly's three-dimensional framework. Time-related aspects of physiotherapeutic encounters were noted in the evolutionary journey of physiotherapy practice. Personal and social aspects were evident in the words and attitude of the physiotherapists. The influence of place was noted in the role that external forces and the environment played in shaping how physiotherapy was experienced. These narratives remind physiotherapists and healthcare providers to reflect on the role they play in shaping the experience of service users and whether those experiences are considered to be person, therapist, or institution centred. Those training pre-registration physiotherapy students need to consider giving students the opportunity to develop and reflect on their philosophy of practice early in the curriculum to enhance the experience of service users in the long-term.IMPLICATIONS FOR REHABILITATIONIt is important for therapists to consider preconceived ideas of what a service user may want, and to listen to them as unique people, with a future journey ahead of them to understand what is truly important to them.Physiotherapists need to reflect on the role they play and the words they use in shaping the experience of care for service users, and whether this is perceived as being person or therapist centred.Physiotherapists who are more person-centred in practice were better placed to promote self-management of long-term conditions.Providing pre-registration physiotherapists with the opportunity to develop their own value-based philosophy of practice during training may enhance the experiences of their service users in the future.


High symmetric anisometropia in monozygotic twins.
The first case in the literature of anisometropia of more than 20 dioptres in both left eyes of a pair of monozygotic 64-year-old twins is presented. The refractive parameters are given together with a short overview of the literature on anisometropia.


Role of Oct4 in maintaining and regaining stem cell pluripotency.
Pluripotency, a characteristic of cells in the inner cell mass of the mammalian preimplantation blastocyst as well as of embryonic stem cells, is defined as the ability of a cell to generate all of the cell types of an organism. A group of transcription factors is essential for the establishment and maintenance of the pluripotent state. Recent studies have demonstrated that differentiated somatic cells could be reverted to a pluripotent state by the overexpression of a set of transcription factors, further highlighting the significance of transcription factors in the control of pluripotency. Among these factors, a member of the POU transcription factor family, Oct4, is central to the machinery governing pluripotency. Oct4 is highly expressed in pluripotent cells and becomes silenced upon differentiation. Interestingly, the precise expression level of Oct4 determines the fate of embryonic stem cells. Therefore, to control the expression of Oct4 precisely, a variety of regulators function at multiple levels, including transcription, translation of mRNA and post-translational modification. Additionally, in cooperation with Sox2, Nanog and other members of the core transcriptional regulatory circuitry, Oct4 activates both protein-coding genes and noncoding RNAs necessary for pluripotency. Simultaneously, in association with transcriptional repressive complexes, Oct4 represses another set of targets involved in developmental processes. Importantly, Oct4 can re-establish pluripotency in somatic cells, and proper reprogramming of Oct4 expression is indispensable for deriving genuine induced pluripotent stem cell lines. In the past several years, genome-wide identification of Oct4 target genes and Oct4-centered protein interactomes has been reported, indicating that Oct4 exerts tight control over pluripotency regulator expression and protects embryonic stem cells in an undifferentiated state. Nevertheless, further investigation is required to fully elucidate the underlying molecular mechanisms through which Oct4 maintains and reinitiates pluripotency. Systemic and dynamic exploration of the protein complexes and target genes associated with Oct4 will help to elucidate the role of Oct4 more comprehensively.