Potential anti-adhesion activity of novel carbosilane zwitterionic dendrimers against eukaryotic and prokaryotic pathogenic microorganisms.
The development of biofilms on different surfaces continues to be a major public health problem. The antimicrobial resistance and the difficulty of finding drugs capable of combating these established biofilms generates the urgent need to find compounds that prevent cells from settling and establishing of these complex communities of microorganisms. Zwitterionic modification of nanomaterials allows the formation of a hydration layer, and this highly hydrophilic surface provides antifouling properties as well as a good biocompatibility by preventing non-specific interactions. Thus, they are appropriate candidates to prevent microbial adhesion to different surfaces and, in consequence, avoid biofilm formation. For this reason, we have incorporated zwitterionic moieties in multivalent systems, as are carbosilane dendrimers. Characterization of these systems was performed using nuclear magnetic resonance and mass spectrometry. It has been analysed if the new molecules have capacity to inhibit the biofilm formation in Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that they were more effective against S. aureus, observing a biofilm reduction of 81.5% treating with 32 mg/L of G2SiZWsf dendrimer and by 72.5% using 32 mg/L of the G3SiZWsf dendrimer. Finally, the absence of cytotoxicity was verified by haemolysis and cytotoxicity studies in human cells lines.


Can a Neutrophil-Lymphocyte Ratio Derived from Preoperative Blood Tests Predict Arteriovenous Fistula Maturation?
To evaluate the association between inflammatory markers expressed as neutrophil-lymphocyte ratio (NLR) and process of arteriovenous fistula (AVF) maturation. A retrospective review of patients with end-stage renal disease referred for formation of a new AVF in one center. Patients referred to the vascular service in the University Hospital of Limerick for creation of vascular access between 2009 and 2013. The association between NLR, calculated from preoperative blood tests, and functional fistula maturation, as determined by successful use of the AVF for 6 consecutive hemodialysis sessions, was investigated using univariate and logistic regression analyses. A logistic regression analysis was carried out to assess potential influence from other factors related to AVF maturation. Stepwise regression test was performed including the NLR. Overall AVF functional maturation rate in our study was 53.7% (66/123). Patients with matured AVFs had an NLR of 4.850 (1.8-15.7) compared with 3.554 (1.7-15.0); this difference was found to be significant (P = 0.024). Female gender (P = 0.008) and a history of kidney transplant (P = 0.004) were the only independent factors of fistula maturation outcome in a logistic regression model. Increased level of NLR was found to be associated with fistula maturation; however, more studies are needed to validate this finding.


Development of portal vein thrombosis complicating idiopathic portal hypertension. A case report.
A 58-yr-old woman with biopsy-proven idiopathic portal hypertension presented with ascites and pretibial pitting edema. On admission, ultrasonic Doppler flowmetry demonstrated hepatopetal flow of a markedly reduced velocity in the portal vein, hepatofugal flow in the splenic vein, and a large spontaneous splenorenal shunt. The patient spontaneously developed hepatic encephalopathy 1 mo later. Percutaneous transhepatic portography demonstrated mural thrombi at the porta hepatis after the catheter had penetrated the mural thrombi without resistance; there was also a long retention of contrast medium in the portal vein. 99mTc-Macroaggregated albumin instilled into the superior mesenteric vein was caught in the lungs, and no activity entered the liver. Measurements of ammonia and immunoreactive insulin clearly indicated that superior mesenteric venous blood was shunted through the splenic vein and the splenorenal shunt. Subsequent ultrasonic examination with Doppler flowmetry suggested further growth of the thrombi and lack of blood flow in the portal vein. Although the procedure of percutaneous transhepatic catheterization could have contributed to the growth of thrombi, it is more likely that the thrombosis in the portal vein was a sequela to idiopathic portal hypertension, and was growing at the time of catheterization. This case may be of significance in the understanding of the relationship between idiopathic portal hypertension and extrahepatic portal obstruction.


Proven and nonproven facts in knee arthroplasty. Results with the semiconstrained GSB-prosthesis.
The great number of knee-replacement systems makes a comparative study difficult. Even more confusing are the different criteria used for the evaluation of the results. After a critical review of what can be taken as proven facts, our own experience with the semiconstrained GSB-III knee prosthesis is critically analyzed. The survivorship method is used, presenting the cumulative success rate and analyzing the reasons for the failure rates. We feel that all authors presenting results of knee arthroplasty should adopt this method, using the same or at least comparable evaluation sheets (for instance, that of ERASS). Moreover, more attention should be given to bone dynamics in a prospective study using modern technology (CT densitometry). This will help to detect possible factors responsible for the failure of knee arthroplasty and possibly to prevent failure with medication.


Forgetting is effortful: evidence from reaction time probes in an item-method directed forgetting task.
Reaction time (RT) was measured in response to visual detection probes embedded within an item-method directed forgetting paradigm. In Experiment 1, study words were presented individually followed by an instruction to remember (R) or forget (F). Probes were presented at stimulus onset asynchronies (SOAs) of 1,400, 1,800, or 2,600 msec in relation to the study word or memory instruction. After the study trials, a yes-no recognition task measured retention of R and F words. Experiment 2 added a no-word control condition and no-probe catch trials. In both experiments, post-F probe RTs were longer than post-R probe RTs at early SOAs. Confirming that participants attended to the memory instructions, there was a significant directed forgetting effect, with greater recognition of R than of F words. These findings contradict the view that directed forgetting in the item-method paradigm is due to the passive decay of nonrehearsed F items; instead, they are consistent with the view that intentional forgetting in an item-method paradigm occurs via the operation of an active, potentially inhibitory, cognitive process.


First phytochemical investigation of secondary metabolites of Euphorbia davidii Subils. and antiproliferative activity of its extracts.
The present work is the first phytochemical investigation of Euphorbia davidii Subils. After multistep separation process, three flavonoid glycosides were obtained from the ethyl acetate soluble fraction of the methanol extract of the whole plant. The structures of the isolated compounds were determined as kaempferol 3-O-rhamnoside, myricetin 3-O-rhamnoside, and quercetin 3-O-rhamnoside. Aqueous and organic extracts of the plant were screened in vitro for antiproliferative activity against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma) and MCF7 (breast epithelial adenocarcinoma) cells, using the MTT assay. n-Hexane and chloroform extracts demonstrated moderately dose-dependent cell growth inhibitory activity against all four cell lines.


Homogeneous static magnetic field of different orientation induces biological changes in subacutely exposed mice.
It has been shown that static magnetic field (SMF) of moderate intensity produces considerable impact on biological systems. SMF can be homogeneous or inhomogeneous. In many studies, inhomogeneous SMF was employed. Aware that inhomogeneous SMF could result in experimental variability, we investigated the influence of a vertical homogeneous SMF of different orientation. Male Swiss-Webster 9- to 10-week-old mice were subacutely exposed to upward- and downward-oriented SMF of 128 mT generated by a cyclotron for 1 h/day during a 5-day period. We found that SMF affected various organs and that these effects were, to some degree, dependent on SMF orientation. Both upward- and downward-oriented SMF caused a reduction in the amount of total white blood cells (WBC) and lymphocytes in serum, a decrease of granulocytes in the spleen, kidney inflammation, and an increase in the amount of high-density lipoprotein (HDL). In addition, upward-oriented SMF caused brain edema and increased spleen cellularity. In contrast, downward-oriented SMF induced liver inflammation and a decrease in the amount of serum granulocytes. These effects might represent a specific redistribution of pro-inflammatory cells in blood and among various organs. It appears that homogeneous SMF of 128 mT affected specific organs in the body, rather than simultaneously and equally influencing the entire body system.


Artificial intelligence: a solution to involution of design-build-test-learn cycle.
Iterative design-build-test-learn (DBTL) cycles are routinely performed during microbial strain development. This useful approach integrates computational strain design, genetic engineering, fermentation testing, and omics analysis to reveal and resolve production bottlenecks. However, the DBTL may enter involution, in which the numerous engineering cycles generate large amount of information and constructs without leading to breakthroughs. To avoid this problem, machine learning (ML) can be a promising yet not developed solution to multiscale modeling and process optimization. This review discusses the recent advances in ML applications, focusing on integrative metabolic models and knowledge engineering for guiding metabolic engineering and fermentation optimization. The ML-based strain development can eventually improve DBTL cycles to facilitate moving synthetic strains from laboratories to industries.


Synthesis and anti-inflammatory activity of chalcone derivatives.
Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.


The relationship between deinstitutionalization and quality of care in longer-term psychiatric and social care facilities in Europe: A cross-sectional study.
The process of deinstitutionalization (community-based care) has been shown to be associated with better quality of life for those with longer-term mental health problems compared to long stay hospitals. This project aimed to investigate the relationship between national progress towards deinstitutionalization and (1) quality of longer-term mental health care (2) service users' ratings of that care in nine European countries. Quality of care was assessed in 193 longer-term hospital- and community-based facilities in Bulgaria, Germany, Greece, Italy, the Netherlands, Poland, Portugal, Spain and the UK. Data on users' ratings of care were collected from 1579 users of these services. Country level variables were compiled from publicly available data. Multilevel models were fit to assess associations with quality of care and service user experiences of care. Significant positive associations were found between deinstitutionalization and (1) five of seven quality of care domains; and (2) service user autonomy. A 10% increase in expenditure was associated with projected clinically important improvements in quality of care. Greater deinstitutionalization of mental health mental health services is associated with higher quality of care and better service user autonomy.


Arginine as an eluent overcomes the hindrance of monoclonal antibody quantification by dextran sulfate in protein A affinity chromatography.
Analytical chromatography using protein A affinity columns was employed for the fast and simple quantitative analysis of monoclonal antibodies (mAb) from suspension cultures of recombinant Chinese hamster ovary (rCHO) cells. Reliable results could not be obtained from analysis of rCHO cell culture supernatants containing dextran sulfate using elution buffers such as phosphate, glycine, or MgCl2 . These problems increased as the number of analysis and the concentration of dextran sulfate in samples increased. Arginine was identified as an alternative eluent to overcome the hindrance by dextran sulfate. When the samples contain dextran sulfate up to 100 mg/L, the elution buffer containing 0.6-1.0 M arginine at pH 3.0-3.8 is useful for the effective analysis. Reproducible results in the mAb quantification could be obtained by this developed arginine elution buffer from rCHO cell culture supernatants containing dextran sulfate.


Oligomerization state-dependent elevations of adiponectin in chronic daily headache.
To evaluate serum adiponectin levels in female episodic migraineurs (EMs) and chronic daily headache (CDH) sufferers. Obesity is a risk factor for headache "chronification." Adiponectin (ADP) is an adipocytokine secreted primarily by adipose tissue. ADP and its oligomers (high-molecular-weight [HMW], middle-molecular-weight [MMW], and low-molecular-weight [LMW] ADP) have been shown to modulate several inflammatory pathways that have also been shown to be associated with migraine pathophysiology. Age- and body mass index (BMI)-matched women participants were enrolled. Anthropometric measures (including waist-to-hip ratio [WHR] and BMI) were measured in all participants. Serum total ADP (T-ADP) levels and its oligomers were measured in EMs during headache-free periods and CDH sufferers at baseline level of pain, as compared with healthy control subjects using ELISA. Although total body obesity as estimated by BMI showed no significant association between participants, visceral obesity as estimated by WHR was significantly associated with CDH as compared with EMs and controls. WHR was also inversely related to both T-ADP (p = 0.008) and HMW-ADP (p = 0.002). After adjusting for WHR, serum T-ADP levels were higher in CDH sufferers (10.1 +/- 4.0) than in both EMs (8.6 +/- 3.5) and controls (7.5 +/- 2.4) (p = 0.024). In addition, HMW-ADP was higher in CDH (6.1 +/- 2.8) as compared with EMs (4.2 +/- 1.7) and controls (3.9 +/- 1.5) (p = 0.003). MMW-ADP was also higher in CDH (2.0 +/- 1.2) as compared with EMs (1.5 +/- 0.7) and controls (1.1 +/- 0.4) (p = 0.009). Serum adiponectin levels are increased in women chronic daily headache (CDH) sufferers. In addition, visceral obesity, as measured by waist-to-hip ratio, is a risk factor for CDH in women.


Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas.
Stem cell research and the prospect of stem cell based therapies depend critically on the identification of specific markers that can be used for the identification and selection of stem and progenitor cells. Nestin is expressed in neuronal progenitor cells and has also been suggested to mark multipotent pancreatic stem cells. We show here that, throughout pancreatic development, markers of pancreatic progenitor cells and differentiated pancreatic cells are expressed in E-cadherin-positive epithelial cells that do not express nestin. The data presented demonstrate that nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas.


Heat shock proteins HSP70 and GP96: structural insights.
Several heat shock proteins (HSPs) act as potent adjuvants for eliciting anti-tumor immunity. HSP-based tumor vaccine strategies have been highly successful in animal models and are undergoing testing in clinical trials. It is generally accepted that HSPs, functioning as chaperones for tumor antigens, elicit tumor-specific adaptive immune responses. HSPs also appear to induce innate immune responses in an antigen-independent fashion. Innate responses generated by HSPs may contribute to anti-tumor immunity. Immunologically active chaperones with anti-tumor activity are referred to as "immunochaperones". Here, we review the studies that address the role of structural domains or regions of the immunochaperones HSP70 and GP96 that may be involved in the induction of adaptive or innate immune responses.


Parent's preferences for unscheduled paediatric healthcare: A discrete choice experiment.
Unscheduled healthcare is a key component of healthcare delivery and makes up a significant proportion of healthcare access, with children being particularly high users of unscheduled healthcare. Understanding the relative importance of factors that influence this behaviour and decision-making is fundamental to ensuring the system is best designed to meet the needs of users and foster appropriate cost-effective usage of health system resources. The aim of the study was to identify the parent's preferences for unscheduled healthcare for a common mild childhood illness. A discrete choice experiment (DCE) was developed to identify the preferences of parents accessing unscheduled healthcare for their children. Data were collected from parents in Ireland (N = 458) to elicit preferences across five attributes: timeliness, appointment type, healthcare professional attended, telephone guidance before attending and cost. Using a random parameters logit model, all attributes were statistically significant, cost (β = -5.064, 95% confidence interval, CI [-5.60, -4.53]), same-day (β = 1.386, 95% CI [1.19, 1.58]) or next-day access (β = 0.857, 95% CI [0.73, 0.98]), coupled with care by their own general practitioner (β = 0.748, 95% CI [0.61, 0.89]), identified as the strongest preferences of parents accessing unscheduled healthcare for their children. The results have implications for policy development and implementation initiatives that seek to improve unscheduled health services as understanding how parents use these services can maximise their effectiveness. The development of the DCE included a qualitative research component to ensure that the content accurately reflected parents experiences when seeking healthcare. Before data collection, a pilot test was carried out with the target population to gather their views on the survey.


The effects of resection of the peripheral branches of the posterior nasal nerves in the inferior turbinate, with special focus on olfactory dysfunction.
There are few detailed studies about peripheral branch resection of the posterior nasal nerves in the inferior turbinate; thus, this study aimed to investigate this. Patients who underwent submucosal turbinoplasty with or without resection of the peripheral branches of posterior nasal nerves in the inferior turbinate were included. The resection of the posterior nasal nerves with turbinoplasty significantly reduced detection and recognition thresholds on olfactory testing. The rhinorrhoea severity, detection threshold and recognition threshold were significantly lower after resection of the posterior nasal nerves with turbinoplasty than after turbinoplasty alone, although there were no significant differences between the two groups before surgery. This is the first study to show that the resection of the peripheral branches of the posterior nasal nerves in the inferior turbinate with turbinoplasty more effectively inhibits allergic symptoms compared with turbinoplasty alone. It also showed that the resection of the peripheral branches of the posterior nasal nerves can inhibit olfactory dysfunction.


The Brain Bench: virtual tools for stereotactic frame neurosurgery.
We present a suite of neurosurgery supporting tools developed around (i) the Virtual Workbench, a productive environment for the control of 3-D data, in which delicate work can be performed for hours on end without strain, and (ii) the Electronic Brain Atlas, integrating the major print brain atlases in day-to-day clinical use. We describe in detail the Brain Bench, a surgical planning system for stereotactic frame neurosurgery. Its objective is to prepare faster plans; have a better and more accurate choice of target points; improve the avoidance of sensitive structures; have fewer sub-optimal frame attachments and speedier, more effective planning and training. If validated by a clinical study now under way, this will improve medical efficacy and reduce costs.


Performance of noninvasive partial CO2 rebreathing cardiac output and continuous thermodilution cardiac output in patients undergoing aortic reconstruction surgery.
In the partial CO(2) rebreathing method, monitored changes in CO(2) elimination and end-tidal CO(2) in response to a brief rebreathing period are used to estimate cardiac output. However, dynamic changes in CO(2) production during ischemia and reperfusion may affect the accuracy of these estimates. This study was designed to compare measurements of cardiac output as produced by the partial CO(2) rebreathing (NICO), bolus (BCO), and continuous thermodilution (CCO) methods of monitoring cardiac output. Cardiac output was continuously monitored using both NICO and CCO in 28 patients undergoing aortic reconstruction. BCO measurements were taken at the following intervals when hemodynamic stability was achieved: (1) after anesthetic induction; (2) during aortic cross-clamp; (3) at reperfusion of the iliac artery; and, (4) during peritoneal closure. The bias and precision (1 SD) derived from all the measurements between NICO and BCO was -0.58 +/- 0.9 l/min, whereas for CCO and BCO it was 0.38 +/- 1.17 l/min. The bias between NICO and BCO was small after anesthetic induction and during cross-clamp, but increased following reperfusion. The bias between CCO and BCO was relatively small until reperfusion but increased significantly at peritoneal closure. Results indicate that in aortic reconstruction surgery the performance of NICO monitoring is comparable with that of CCO; however, the direction of bias in these continuous measurement devices is the opposite.


Cell proliferation in the Lichen planus infiltrate. Investigations by light- and electron-microscopic autoradiography.
In seven patients suffering from lichen planus (LP) light- and electron-microscopic 3H-thymidine (3HT) labeling studies were performed and the following results were obtained. 1. Using the light-microscope, a large number of 3HT labeled cells can be observed in the dermal infiltrate of LP. Most of the labeled nuclei belong to mononuclear, 'round cells' while isolated endothelial cells, fibroblasts, histiocytes and mast cells could be found labeled. 2. The mean labeling index of 'round cells' in our patients was 4.27 +/- 1.57%. 3. The evaluation of the electron microscopic autoradiographs showed that, as far as 'round' cells were concerned, exclusively nuclei of cells showing the morphological criteria of stimulated lymphocytes were labeled. These findings support the view that in LP, as in allergic contact dermatitis, a high proliferative activity of lymphocytes takes place.


Improved folding yields of a model protein using protein disulfide isomerase.
To study the effects of recombinant human protein disulfide isomerase (rhPDI) concentration, reduced glutathione:oxidized glutathione ratio (GSH:GSSG) and temperature on the efficiency of oxidative folding of a model protein, recombinant human interleukin 2 (C125A mutation) (C125A rhIL-2). C 125A rhIL-2 inclusion bodies were reduced and denatured by guanidium hydrochloride (Gdm.Cl) and 100 mM GSH. The solution was diluted 10 times into folding buffer, allowing C125A rhIL-2 to fold either in the absence or presence of rhPDI. The renatured and unfolded C125A rhIL-2 species were quantitated by reversed phase-HPLC. The initial folding rate of C125A rhIL-2 linearly increased with rhPDI:C125A rhIL-2 molar ratio in the first 2.5 minutes, and reached the highest rate when the rhPDI:C125A rhIL-2 ratio was 1:1. The oxidative folding of C125A rhIL-2 linearly increased as the GSH:GSSG molar ratio decreased from 10:0 to 10:3. The folding of C125A rhIL-2 was also dependent on temperature, and optimum folding was realized at 23 degrees C. These results demonstrate that under optimal redox potential and temperature, rhPDI enhances the oxidative folding of C125A rhIL-2. In the oxidative folding of C125A rhIL-2, rhPDI exerts its effect on folding by the acceleration of thiol/disulfide interchange.


Trace metals pollution in seawater and groundwater in the ship breaking area of Sitakund Upazilla, Chittagong, Bangladesh.
This study reveals potential accumulation of trace metals in the sea and groundwater due to ship breaking activities which take place along the Bay of Bengal in Sitakund Upazilla, Chittagong, Bangladesh. When compared with WHO and Bangladesh domestic standards for water quality, it is revealed that seawater was strongly polluted by Fe and Hg, moderately by Mn and Al, and slightly by Pb and Cd. Groundwater was strongly polluted by Fe, Pb and Hg, moderately by Mn and Al, and slightly by As. Trace element concentrations of all seawater samples exceeded the average concentration of elements in the Earth's seawater. The application of Principal Components Analysis identified two sources of pollution-marine and ship breaking. The mechanism of groundwater pollution inferred that if seawater is polluted, nearby groundwater is also polluted with trace metals due to the influence of seawater intrusion.


The toxicity of tri-substituted benzenes to the protozoan ciliate Spirostomum ambiguum.
The Spirotox test utilises a large ciliate protozoan Spirostomum ambiguum as a test organism. The goal of the present study was to evaluate the toxicity of tri-substituted benzenes in the Spirotox test. Twenty-six organic compounds were tested in this study and included: dimethylphenols (DMPs), dichlorophenols (DCMs), trichlorobenzenes (TCBs), dichloroanilines (DCAs), dinitrophenols (DNPs), dinitroaniline (DNA), dinitrochlorobenzene (DNCB) and dinitrofluorobenzene (DNFB). The toxicity of the compounds tested varied almost four orders of a magnitude. DMPs and DCAs were the least toxic, whereas dinitro derivatives were the most toxic to S. ambiguum. When chlorine or fluorine atoms were replaced by amino or hydroxy substituents, the toxicity increased dramatically. The results of the Spirotox test were compared with three other bioassays that are widely used around the world: Microtox, Tetrahymena pyriformis and Daphnia magna. The Spirotox was less sensitive than these other bioassays for the majority of these compounds, with an exception found for the dinitro derivatives.


A single-tube sample preparation method based on a dual-electrostatic interaction strategy for molecular diagnosis of gram-negative bacteria.
A single-tube method based on a dual-electrostatic interaction (EI) strategy for bacteria capture and DNA extraction was designed to enable the highly sensitive detection of nucleic acids. Specially designed magnetic nanoparticles were developed to meet the opposing requirements of a single-tube method, which exist between the strong EI required for efficient bacteria capture and the weak EI required for DNA extraction with minimal DNA adsorption. A dual-EI strategy for the single-tube (DESIGN) method was thus developed to integrate bacteria enrichment, bacteria cell lysis, and DNA recovery in a single tube, thereby minimizing precious sample loss and reducing handling time. Subsequently, we evaluated the performance with a variety of concentrations from 5 to 100 colony-forming units (CFU)/10 mL human urine and milk samples. The DESIGN method achieved the simple and sensitive detection of Salmonella enterica serovar Typhimurium in 10 mL of human urine and milk samples up to 5 CFU by quantitative PCR. Furthermore, the DESIGN method detected Brucella ovis and Escherichia coli from 10 mL of human urine with a detection limit up to 5 CFU/10 mL. Graphical abstract.


Structural features and water holding capacities of pressed potato fibre polysaccharides.
Pressed potato fibre (PPF) has a high water holding capacity (WHC) affecting its processing as an animal feed. The aim of this study was to characterize cell wall polysaccharides (CWPs) in PPF and investigate their WHC. This was done via sequential extractions. Half of all CWPs were recovered in the hot buffer soluble solids extract as pectins (uronic acid and rhamnose) and galactans wherein most pectins (76%) from PPF were water soluble. Most likely, the network of CWPs is loosened during processing of potatoes. PPF showed a WHC of 7.4 expressed as the amount of water held per g of dry matter (mL/g). Reconstituting hot buffer soluble solids with buffer insoluble solids in water gave a WHC comparable to that of PPF. Removal of alkali soluble solids, which mainly comprised xyloglucans, lowered the WHC of the final residue. The results indicated that interactions between CWPs could affect the WHC of PPF.


Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling.
Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.


Management of sedimentation in centrifugal counter-current distribution of sperm cells in an aqueous 2-phase system.
It is generally assumed that centrifugal counter-current distribution (CCCD) in aqueous two-phase systems cannot be employed for analyzing or fractioning cell populations, due to large particles of sediment in the system caused by enhanced gravity. The present work was undertaken to find out whether addition of Percoll to a two-phase system would be a useful method to avoid this cell sedimentation. The results obtained show that bull spermatozoa partition as a unique peak in a CCCD using a Dextran T500-poly(ethylene glycol) 6000 system, and that sedimentation takes place significantly in the upper phase during the process. Addition of increasing concentrations of Percoll made this unique peak wider and two different populations of bull spermatozoa were finally obtained when Percoll concentration rose to 13.6%. This management of cell sedimentation in CCCD could be of great interest for analyzing cell heterogeneity, since the shortening of the time required for counter-current distribution should prevent the loss of cell viability during the separation process. Finally, the results obtained suggest that an increase of viscosity rather than of density is the phase feature which has greater influence on managing cell sedimentation in CCCD.


Video-based coaching in surgical education: a systematic review and meta-analysis.
In the era of competency-based surgical education, VBC has gained increased attention and may enhance the efficacy of surgical education. The objective of this systematic review was to summarize the existing evidence of video-based coaching (VBC) and compare VBC to traditional master-apprentice-based surgical education. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) assessing VBC according to the PRISMA and Cochrane guidelines. The MEDLINE, EMBASE, and COCHRANE and Researchgate databases were searched for eligible manuscripts. Standard mean difference (SMD) of performance scoring scales was used to assess the effect of VBC versus traditional training without VBC (control). Of 627 studies identified, 24 RCTs were eligible and evaluated. The studies included 778 surgical trainees (n = 386 VBC vs. n = 392 control). 13 performance scoring scales were used to assess technical competence; OSATS-GRS was the most common (n = 15). VBC was provided preoperative (n = 11), intraoperative (n = 1), postoperative (n = 10), and perioperative (n = 2). The majority of studies were unstructured, where identified coaching frameworks were PRACTICE (n = 1), GROW (n = 2) and Wisconsin Coaching Framework (n = 1). There was an effect on performance scoring scales in favor of VBC coaching (SMD 0.87, p < 0.001). In subgroup analyses, the residents had a larger relative effect (SMD 1.13; 0.61-1.65, p < 0.001) of VBC compared to medical students (SMD 0.43, 0.06-0.81, p < 0.001). The greatest source of potential bias was absence of blinding of the participants and personnel (n = 20). Video-based coaching increases technical performance of medical students and surgical residents. There exist significant study and intervention heterogeneity that warrants further exploration, showing the need to structure and standardize video-based coaching tools.


Isolation of High-Molecular-Weight DNA from Mammalian Blood Using Proteinase K and Phenol.
This procedure is the method of choice for purification of genomic DNA from mammalian blood when large amounts of DNA are required, for example, for Southern blotting. The usual yield of DNA from buffy coat lymphocytes isolated from 20 mL of normal blood is ∼250 µg.


Investigating the basis of lineage decisions and developmental trajectories in the dorsal spinal cord through pseudotime analyses.
Dorsal interneurons (dIs) in the spinal cord encode the perception of touch, pain, heat, itch, and proprioception. While previous studies using genetic strategies in animal models have revealed important insights into dI development, the molecular details by which dIs arise as distinct populations of neurons remain incomplete. We have developed a resource to investigate dI fate specification, by combining a single-cell RNA-Seq atlas of mouse ESC-derived dIs with pseudotime analyses. To validate this in silico resource as a useful tool, we have used it to first identify novel genes that are candidates for directing the transition states that lead to distinct dI lineage trajectories, and then validated them using in situ hybridization analyses in the developing mouse spinal cord in vivo . We have also identified a novel endpoint of the dI5 lineage trajectory, and found that dIs become more transcriptionally homogenous during terminal differentiation. Together, this study introduces a valuable tool for further discovery about the timing of gene expression during dI differentiation and uses it to clarify dI lineage relationships. Pseudotime analyses of embryonic stem cell-derived dorsal spinal interneurons reveals both novel regulators and lineage relationships between different interneuron populations.


Actin cytoskeletal architecture regulates nitric oxide-induced apoptosis, dedifferentiation, and cyclooxygenase-2 expression in articular chondrocytes via mitogen-activated protein kinase and protein kinase C pathways.
Nitric oxide (NO) in articular chondrocytes regulates differentiation, survival, and inflammatory responses by modulating ERK-1 and -2, p38 kinase, and protein kinase C (PKC) alpha and zeta. In this study, we investigated the effects of the actin cytoskeletal architecture on NO-induced dedifferentiation, apoptosis, cyclooxygenase (COX)-2 expression, and prostaglandin E2 production in articular chondrocytes, with a focus on ERK-1/-2, p38 kinase, and PKC signaling. Disruption of the actin cytoskeleton by cytochalasin D (CD) inhibited NO-induced apoptosis, dedifferentiation, COX-2 expression, and prostaglandin E2 production in chondrocytes cultured on plastic or during cartilage explants culture. CD treatment did not affect ERK-1/-2 activation but blocked the signaling events necessary for NO-induced dedifferentiation, apoptosis, and COX-2 expression such as activation of p38 kinase and inhibition of PKCalpha and -zeta. CD also suppressed activation of downstream signaling of p38 kinase and PKC, such as NF-kappaB activation, p53 accumulation, and caspase-3 activation, which are necessary for NO-induced apoptosis. NO production in articular chondrocytes caused down-regulation of phosphatidylinositol (PI) 3-kinase and Akt activities. The down-regulation of PI 3-kinase and Akt was blocked by CD treatment, and the CD effects on apoptosis, p38 kinase, and PKCalpha and -zeta were abolished by the inhibition of PI 3-kinase with LY294002. Our results collectively indicate that the actin cytoskeleton mediates NO-induced regulatory effects in chondrocytes by modulating down-regulation of PI 3-kinase and Akt, activation of p38 kinase, and inhibition of PKCalpha and -zeta


Research and development trend of green mining: a bibliometric analysis.
As green development has become a mainstream feature of modern development, green technology has become an inevitable trend in the development of mining technology, and related research on the subject continues to accumulate. Based on the bibliometric analysis of the green mining (GM) research from 2001 to 2020, we try to capture GM research and development trends from the perspective of global green development. The results show that the growth rate of GM research is much higher than that of conventional mining research, and the research results are growing rapidly. A visual collaborative network was created to identify the main research countries and author distribution and explore the most contributed journals. The research themes in GM show an evolution from sustainability theory to the application of green technologies in mines to the establishment of long-term mechanisms and policy regulation. The keyword co-occurrence results show that the current GM research covers the whole life cycle of mines. Soil, waste disposal, and recycling are long-standing research hotspots, and the most relevant articles are about resource recycling. Based on the keyword co-occurrence results, the proportion of restoration and management research has rapidly increased from 7.3 to 28.9%. Ecological restoration, reclamation and monitoring, remote sensing, and other technologies are more closely integrated usually accompanied by research related to evaluation and management. With the evolution of the theme, the research on GM is becoming more and more comprehensive. It reflects an extremely strong interdisciplinary and cross-disciplinary character.


Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma.
We examined the effects of troglitazone, one of thiazolidinedione derivatives on human basophilic leukemia cell line KU812. Troglitazone caused the suppression of cell growth, which was suggested to result from the decrease in cyclin E and the hyperphosphorylated form of retinoblastoma tumor suppressor gene product (pRb). In addition, troglitazone caused a decrease in histamine secretion due to the reduced expression of histidine decarboxylase mRNA. Peroxisome proliferator-activated receptor (PPAR)-gamma mRNA was undetectable by reverse transcription-polymerase chain reaction (RT-PCR) in KU812 cells. These findings suggested that troglitazone suppressed cell growth and histamine synthesis independently of PPARgamma.


Non-alcoholic fatty liver disease is a potential risk factor for liver injury caused by immune checkpoint inhibitor.
Because of their survival benefits, immune checkpoint inhibitors (ICIs) are widely administered to patients with various advanced-stage malignancies. During ICI treatment, drug-induced liver injury (DILI) occasionally occurs. In particular, hepatic immune-related adverse events (irAEs) are rare but serious and fatal. In patients with hepatic irAEs, immediate steroid treatment is generally recommended; however, the risk factors for ICI-associated DILI remain unknown. In the present study, we identified a risk factor for ICI-associated DILI. We retrospectively analyzed 135 patients treated with anti-programmed cell death-1 (PD-1) antibodies, such as nivolumab and pembrolizumab, at Asahikawa Medical University Hospital. We investigated grade ≥ 2 hepatotoxic AEs during anti-PD-1 therapy, and PD-1 inhibitor-associated DILI was then diagnosed according to the Digestive Disease Week Japan (DDW-J) 2004 scale. The risk factors for PD-1 inhibitor-associated DILI were identified by Cox hazard analysis. Thirty-six patients developed grade ≥ 2 hepatic AEs during anti-PD-1 therapy. Among them, eight patients were diagnosed with PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. Cox hazard analysis revealed that non-alcoholic fatty liver disease (NAFLD) was a risk factor for PD-1 inhibitor-associated DILI. In addition, we revealed that the outcomes of patients with the DDW-J 2004 score = 3 were improved without steroid treatment. NAFLD is a potential risk factor for PD-1 inhibitor-associated DILI based on the DDW-J 2004 scale. The DDW-J 2004 scale might be useful for determining whether steroid treatment is required in patients with PD-1 inhibitor-associated DILI.


Depth of consciousness and deep sedation attained in children as administered by nonanaesthesiologists in a children's hospital.
Sedation of children is administered by nonanaesthesiologists in a variety of locations within our children's hospital. The purpose of this study was to assess the depth of sedation administered to children in four locations using the Bispectral Index (BIS) and the University of Michigan Sedation Scale (UMSS). Eighty-six children under the age of 12 years undergoing procedures with conscious or deep sedation were enrolled. The study included patients undergoing cardiac catheterization, computerized tomography imaging, gastrointestinal endoscopy, and dental procedures. Sedation for each procedure was based on departmental protocols and preferences; the study did not dictate choice or dose of drugs. An independent observer applied the UMSS sedation scale at 10 min intervals for 1 h. The observer and the personnel administering sedation were blinded to the BIS score, which was recorded continuously. The goal of either conscious or deep sedation was attained in 53% (BIS) and 72% (UMSS) of patients. Depth consistent with general anaesthesia was observed in 35% (BIS) and 0% (UMSS), and an awake state was observed in 12% (BIS) and 28% (UMSS). About 8% of patients experienced desaturation and airway events associated with deeper levels of sedation. Our data demonstrate wide variations in depth of sedation attained in the hospital. The goal of either conscious or deep sedation was not achieved in a significant number of children. This is a therapeutic failure that requires reassessment of sedation protocols and investigation of new approaches.


Electrophysiological relationship between claustrum and contralateral area 4 and 6 pyramidal tract neurons.
The connections between the claustrum and the contralateral motor areas were electrophysiologically investigated in cats under chloralose anesthesia. The extracellular unitary activity of 81 pyramidal tract neurons (PTNs) was recorded; 22 PTNs were inhibited by activation of the contralateral claustrum; inhibition was preceded by an early activation of 4 out of the 22 inhibited PTNs. Section of the corpus callosum abolished the contralateral claustrum effect, while the action of the ipsilateral homologous structure persisted.


Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).
The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels.


Expression of the alpha and beta tubulin genes of the African trypanosome in Escherichia coli.
The African trypanosome, Trypanosoma brucei, contains multiple genes for both alpha- and beta-tubulins, which code for similar if not identical proteins. Studies of the structure and function of trypanosome microtubules have been limited due to the difficulties in obtaining sufficient amounts of purified tubulin. To produce large amounts of purified tubulin for studies of structure and function and to begin developing a system for producing systematic alterations of tubulin structure we have cloned and expressed the alpha- and beta-tubulin genes of T. brucei in Escherichia coli to produce the unfused proteins. Controlled high-level expression of both alpha- and beta-tubulin was achieved using a plasmid vector, pOTS, in which expression is controlled by phage lambda promoter/operator and a temperature-sensitive lambda repressor. The tubulins produced are insoluble, as has been found for many other proteins expressed to high levels in E. coli; they are readily purified to near homogeneity by chromatography on DEAE-cellulose in 7 M urea. N-terminal analysis of the purified proteins indicates that they are initiated correctly and that the N-formyl group is removed from the initiating methionine. This factor will probably prove important in the reconstitution of biologically active tubulin.


Cartilage formation from perichondrium in a weight-bearing joint. An experimental study.
In 30 young and 20 adult rabbits a standard defect was made in the cartilage of both lateral tibial plateaus. Spontaneous healing on the left side was compared with healing after transplantation of an auricular perichondrial graft on the other. The latter was fixed in two different ways. Autologous perichondrial grafts result in repair of the articular cartilage, in young as well as in adult animals, provided that the chondral side of the graft is directed to the joint cavity. The different findings in both age groups are discussed.


Do multiple community-based interventions on health promotion tackle health inequalities?
Previous systematic reviews of the impact of multi-component community-based health promotion interventions on reducing health inequalities by socio-economic status (SES) were restricted to physical activity and smoking behavior, and revealed limited and rather disillusioning evidence. Therefore, we conducted a comprehensive review worldwide to close this gap, including a wide range of health outcomes. The Pubmed and PsycINFO databases were screened for relevant articles published between January 1999 and August 2019, revealing 87 potentially eligible publications out of 2876 hits. In addition, three studies out of a prior review on the effectiveness of community-based interventions were reanalyzed under the new research question. After a systematic review process, 23 papers met the inclusion criteria and were included in the synthesis. More than half (56.5%) of the studies reported improvements of socially disadvantaged communities overall (i.e. reduced inequalities at the area level) in at least one health behavior and/or health status outcome. Amongst the remaining studies we found some beneficial effects in the most deprived sub-groups of residents (8.2%) and studies with no differences between intervention and control areas (34.8%). There was no evidence that any program under review resulted in an increase in health disparity. Our results confirm that community-based interventions may be reducing absolute health inequalities of deprived and disadvantaged populations, but their potential so far is not fully realized. For the future, greater attention should be paid to inequalities between sub-groups within communities when analyzing changes in health inequality over time.


An investigation of luminescence properties of CaF2: Dy nanophosphor irradiated with gamma rays and low energy proton beams.
This paper reports the luminescence properties of nanocrystalline calcium fluoride doped with dysprosium (CaF2: Dy). The nanophosphor has been synthesized by the chemical co-precipitation technique and the dopant concentration has been optimized at 0.3 mol% using thermoluminescence (TL) intensity emitted post 50Gy gamma dose irradiation of samples doped with different dopant concentrations. X-ray diffraction shows the formation of crystalline particles with an average size of 49.233 nm. Photoluminescence (PL) emission spectrum shows the characteristic peaks at 455 nm, 482 nm, 573 nm corresponding to 4I15/2 to 6H15/2, 4F9/2 to 6H15/2 and 4F9/2 to 6H13/2 Dy3+ transitions respectively. PL excitation spectrum shows a peak at 327 nm which corresponds to the Dy3+ transition of 6H15/2 to 4L19/2. Gamma (of 1.25 MeV) and low energy proton beam (of 30 keV) irradiated nanophosphor shows a variation in TL glow curve structure and peak position with an increase in radiation dose/fluence. However, the nanophosphor shows a wide linear dose response for 60Co gamma radiation in the range 10 Gy - 1.5 kGy and for low energy proton beam in the fluence range of 1012-1014 ions/cm2. Srim 2013 has been used to calculate the ion beam parameters including the range of protons in CaF2: Dy 0.3 mol%. The nanophosphor CaF2: Dy could be further investigated as a potential dosimeter for gamma rays and proton beam by studying its TL properties for different energies of these radiations.


Orthognathic Surgery and Orthodontics: Inadequate Planning Leading to Complications or Unfavorable Results.
Complications in orthognathic surgery are commonly a result of inadequate preoperative planning and communication between the surgeon and orthodontist. Unfavorable outcomes can often be avoided when overall treatment goals along with a surgical and orthodontic plan are developed and agreed upon by the orthodontist, surgeon, and patient before the start of active tooth movement or any surgical procedures. Continuous evaluation of the patient's progress throughout treatment and subsequent communication between the surgeon and orthodontist are recommended to prevent frequent errors, such as inadequate dental decompensation, poor appliance selection or management, and occasional contraindicated orthodontic elastic traction or tooth movements.


Bombyxin-stimulated ecdysteroidogenesis in relation to sugar transporter/trehalase expressions in Bombyx prothoracic glands.
Our previous studies showed that bombyxin stimulated ecdysteroidogenesis in Bombyx mori prothoracic glands (PGs) during a long-term incubation period in a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent manner. In the present study, we further investigated the downstream signaling cascade in bombyxin-stimulated PGs. Our results showed that upon treatment with bombyxin, expression levels of the sugar transport 1 (St1) and St4 genes and trehalase 1 (Treh1) gene, but not ecdysteroid biosynthesis genes were greatly enhanced compared to the controls. Treatment with LY294002 (an inhibitor of PI3K) reduced the enhanced St1 and Treh1 expression levels, clearly indicating the involvement of PI3K. Treatment with 1 mM of mpV(pic) (a potent inhibitor of protein phosphotyrosine phosphatase and activator of insulin receptor (InR) kinase) also stimulated expression levels of the St1 and Treh1 genes, thus further confirming the involvement of the InR. Determining Treh enzyme activity showed that bombyxin treatment stimulated Treh enzyme activity in time- and PI3K-dependent manners. Validamycin A (a Treh inhibitor) blocked bombyxin-stimulated Treh enzyme activity and partly decreased bombyxin-stimulated ecdysteroidogenesis. A specific sugar transport inhibitor (cytochalasin B) and a glycolysis inhibitor (2-deoxy-D-glucose (2-DG)) also reduced bombyxin-stimulated ecdysteroidogenesis. Taken together, these results indicated that increased expressions of Sts and Treh1 and enhanced Treh enzyme activity downstream of InR/PI3K are involved in bombyxin-stimulated ecdysteroidogenesis in B. mori PGs.


Making a NeST for a persistent virus.
In a recent issue of Cell, Gomez et al. (2013) describe a long intergenic noncoding RNA, called NeST, that regulates the ability of mice to respond to viral and bacterial infections. NeST recruits histone H3 lysine 4 methyltransferases to the IFN-γ gene locus, enhancing IFN-γ expression in key T cell subsets.


Insights into needs of business travelers to China from calls to a medical assistance provider.
Although 17.5% of German travelers were business travelers in the years 2011-2013, little is known about their pathologies. Recent publications indicate that infections are the primary health issue in general travelers. Our aim was to investigate whether business travelers from Germany to China also primarily suffer from infections. From 2011 to 2013, 587 calls for service of German business travelers to China were collected by a medical assistance provider. 482 of these calls were evaluated regarding demographics, reported diseases and conditions and the type of service provided by the medical assistance company. The most common reasons for calls for service were "factors influencing health status and contact with health service" (18.8%), "injury and poisoning" (16.0%) as well as "symptoms, signs, and ill-defined conditions" (13.7%). Most patients asked for "medical advice" (37.8%), referral to "outpatient care" (25.1%) or "inpatient care" (16.6%). "Evacuation and/or repatriation" was required mainly due to "injury and poisoning" (n = 12), "diseases of the circulatory system" (n = 5) or "mental disorders" (n = 3). German business travelers to China are seeking primarily administrative support from a medical assistance provider and are mostly affected by non-infectious diseases. Pre-travel preparation of such travelers need to place more emphasis on non-communicable health risks and prevention.


Bradykinin preconditioning modulates aquaporin-4 expression after spinal cord ischemic injury in rats.
The study investigated whether bradykinin (BK) preconditioning could regulate the expression of aquaporin-4 (AQP4) using an in vivo transient spinal cord ischemia model in rats. BK was infused continuously via the left femoral artery with infusion pump for 15 min (10 microg/kg/min) then we induced ischemia for 20 min and reperfusion for 24 and 72 h respectively. The results demonstrated that the central part of the white matter exhibited loss of perivascular AQP4 and showed a partial recovery toward 72 h of reperfusion. The border zone of white matter was different from the central part of the white matter by showing no loss of perivascular AQP4 at 24 h of reperfusion but rather a slight increase. BK significantly reduced the expression level of AQP4 protein in the white matter, but it had none of this effect in the gray matter region at 72 h post-reperfusion. There was no difference in AQP4 protein levels between BK group and control group at the two above-mentioned spinal cord regions at 24 h after reperfusion. In addition, the changes in AQP4 protein induced by BK preconditioning were obvious at 72 h after reperfusion, which were accompanied by a reduction of spinal cord edema. Our results demonstrated that the expression of AQP4 protein after spinal cord ischemia/reperfusion was region-specific, time-dependent and also indicated that the attenuation of AQP4 expression induced by BK could be one of the important molecular mechanisms in physiopathology of spinal cord ischemic edema.


Stroke preparedness in children: translating knowledge into behavioral intent: a systematic review and meta-analysis.
If translated into behavioral intent, improving stroke knowledge may potentially impact on better outcomes. Children are an attractive target population since they can drive familial behavioral changes. However, the impact of interventions on stroke knowledge among children is unclear. We performed a systematic review and meta-analysis to investigate whether educational interventions targeting children improve stroke knowledge and lead to behavioral changes. We searched Ovid, PubMed, and Embase between January 2000 and December 2014. We included studies written in English reporting the number of children aged 6-15 years undergoing educational interventions on stroke and providing the results for baseline and early and late postintervention tests. We compared the proportion of correct answers between baseline, early, and late responses for two endpoints: knowledge and behavioral intent. Of the initial 58 articles found, we included nine that met the inclusion criteria. Compared with baseline tests (51·7%, 95% confidence interval 40·9-62·4), there was improvement in stroke knowledge in early (74·0%, 95% confidence interval 64·4-82·5, P = 0·002) and late (67·3%, 95% confidence interval 55·4-78·2, P = 0·027) responses. There was improvement in the early (92·1%, 95% confidence interval 86·0-96·6, P < 0·001) and late (83·9%, 95% confidence interval 73·5-92·1, P = 0·001) responses for behavioral intent compared with the baseline assessment (63·8%, 95% confidence interval 53·5-73·4). Children are a potentially attractive target population for improvement in stroke knowledge and behavioral intent, both in the short and long term. Our findings may support the implementation of large-scale stroke educational initiatives targeting children.


Meniscus Allograft Transplantation Augmented With Autologous Bone Marrow Aspirate Concentrate.
Meniscus allograft transplantation (MAT) has been shown to be a feasible surgical option for younger patients, below 50 years of age who have meniscal insufficiency and have failed conservative treatment measures. In this technical note, we describe a procedure of harvesting and injecting bone marrow aspirate concentrate in a meniscus allograft during a MAT procedure, which may allow for longer lasting transplants and improve patient outcomes. In this technical note, bone marrow aspirate concentrate is harvested arthroscopically from the intercondylar notch at the surgical site, which prevents additional donor site morbidity, as seen with harvesting from other locations, such as the iliac crest. This also reduces operating time, since harvesting from the iliac crest requires different patient positioning and usually additional anesthesia. The authors of this surgical technique believe that biological augmentation during MATs will assist surgeons in maximizing graft survivorship and, ultimately, lead to better patient outcomes.


The development of laying hen locomotion in 3D space is affected by early environmental complexity and genetic strain.
Adult laying hens are increasingly housed in spatially complex systems, e.g., non-cage aviaries, where locomotion between elevated structures can be challenging for these gallinaceous birds. This study assessed the effect of early environmental complexity on spatial skills in two genetic strains. Brown (B) and white (W) feathered birds were raised in: Conventional cages with minimal complexity (Conv) or rearing aviaries with low (Low), intermediate (Mid), or high complexity (High). Birds from each housing treatment were challenged at three different time points in three different, age-appropriate vertical spatial tasks. Whites performed better than brown birds in all tests regardless of rearing environment. In chicks, test performance was predominantly explained by variation between replicates and differences in motivation for test participation. Treatment effects were seen in pubertal birds (pullets), with pullets from aviaries performing better than those from Conv. White High pullets performed better than white Mid or Low, an effect that was not found in browns. Pullets preferred to use a ramp to move downwards, but only when ramps had previously been experienced and when the ramp was not too steep. Overall, early environmental complexity affected spatial skills of laying hen pullets with stronger effects in white than brown feathered birds.


A new approach to an old problem: how to categorize the habit of ferns and lycophytes.
Substrate preferences are often treated as species traits and are used to distinguish different habits, i.e. an epiphytic, lithophytic or terrestrial habit. Such a categorization, however, ignores substantial intraspecific variation. An approach that takes biological variability within a species into account is needed. We focused on four large genera of ferns and lycophytes and found relevant information in >500 sources, such as online databases, checklists, floras and species descriptions. Translating textual information into a quantitative index, we quantified the propensity to grow on either substrate as a continuous trait for 1475 species. Only a minority of species exhibited strict substrate fidelity, but a majority of them showed clear habitat preferences. The relative frequencies of intermediates between strict lithophytes, epiphytes and terrestrials does not support the frequent notion of ecological similarity of the lithophytic and epiphytic habitat. The compiled data are useful immediately for ecological and evolutionary studies with the focal taxa. More importantly, we propose the replacement of the concept of distinct habits with one of gradual differences. This should have a profound impact on any such study with plants in general.


Resection extent and BRAF V600E mutation status determine postoperative tumor growth velocity in pediatric low-grade glioma: results from a single-center cohort analysis.
Despite excellent long-term overall survival rates, pediatric low-grade gliomas (pLGG) show high variety of clinical behavior regarding progress or senescence post incomplete resection (IR). This study retrospectively analyzes tumor growth velocity (TGV) of pLGG before surgery and after IR to investigate the impact of surgical extent, tumor location and molecular BRAF status on postoperative residual tumor growth behavior. Of a total of 172 patients with pLGG receiving surgical treatment, 107 underwent IR (66%). Fifty-three vs 94 patients could be included in the pre- and post-operative cohort, respectively, and were observed over a mean follow-up time of 40.2 vs 60.1 months. Sequential three-dimensional MRI-based tumor volumetry of a total of 407 MRI scans was performed to calculate pre- and postoperative TGV. Mean preoperative TGV of 0.264 cm3/month showed significant deceleration of tumor growth to 0.085 cm3/month, 0.024 cm3/month and -0.016 cm3/month after 1st, 2nd, and 3rd IR, respectively (p < 0.001). Results remained significant after excluding patients undergoing (neo)adjuvant treatment. Resection extent showed correlation with postoperative reduction of TGV (R = 0.97, p < 0.001). ROC analysis identified a residual cut-off tumor volume > 2.03 cm3 associated with a higher risk of progress post IR (sensitivity 78,6%, specificity 76.3%, AUC 0.88). Postoperative TGV of BRAF V600E-mutant LGG was significantly higher than of BRAF wild-type LGG (0.123 cm3/month vs. 0.016 cm3/month, p = 0.047). This data suggests that extensive surgical resection may impact pediatric LGG growth kinetics post incomplete resection by inducing a significant deceleration of tumor growth. BRAF-V600E mutation may be a risk factor for higher postoperative TGV.


Interprofessional Collaboration: A Model for Nurse Executives to Follow to Support Magnet® Designation.
This case study reveals how 1 organization moved beyond traditional professional boundaries to achieve Magnet recognition.


Posterior cranial fossa tumors: Results and prognostic factors in a consecutive series of 14 operated patients by occipital transtentorial approach.
The objective of our study was to determine the safety and usefulness of performing surgery via occipital transtentorial approach to treat posterior cranial fossa tumors, which is well known as an approach to the pineal region (Poppen's approach). Fourteen patients with posterior cranial fossa tumors were successfully treated using occipital transtentorial approach between 2007 and 2012. The lesions included five meningiomas, three astrocytomas, two metastases, two hemangioblastomas, one cavernoma, and one dysgerminoma. Lesions were <3 cm in 12 cases and ≥3 cm in two cases. Average Karnofsky Performance Status (KPS) scoring at admission was 88.5. Eleven patients scored ≥70 and seven patients <70. Average age was 43.1 years. All patients underwent surgical treatment by the same surgical team. All tumors were completely removed surgically without any injury to the venous complex and the adjoining structures. There was no incidence of mortality or morbidity in all patients, and all functional outcomes were good to excellent postoperatively. Postoperative computed tomography (CT) imaging revealed that none of the patients had suffered brain damage or infarction around the cerebellum, brainstem, or occipital lobe. We found that the use of occipital transtentorial approach is strongly supported by the successful removal of posterior cranial fossa tumors without serious complications. Open microneurosurgery is probably still the most effective therapy in improving survival and KPS in patients with posterior cranial fossa tumors, given that the proper surgical technique is used and complications do not occur. This case study has strongly suggested that this approach is very useful, safe, and accurate for removing the tumors of posterior fossa and evaluating the surrounding anatomy, as well as for determining operative strategy.


Chain length affects pancreatic lipase activity and the extent and pH-time profile of triglyceride lipolysis.
Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of porcine pancreatic lipase was studied by means of an in vitro lipolysis model under bio-relevant conditions at pH 6.80. In order to determine the total extent of lipolysis, back-titration experiments at pH 11.50 were performed. Results suggest that there is a specific chain length range (C2-C8) for which pancreatic lipase shows higher activity. This specificity could result from a combination of physicochemical properties of TGs, 2-monoglycerides (2-MGs) and FAs, namely the droplet size of the TGs, the solubility of 2-MGs within mixed micelles, and the relative stability of the FAs as leaving groups in the hydrolysis reaction. During experimentation, it was evident that an optimisation of lipolysis conditions was needed for tighter control over pH levels so as to better mimic in vivo conditions. 1M NaOH, 3.5 mL/min maximum dosing rate, and 3 μL/min minimum dosing rate were the optimised set of conditions that allowed better pH control, as well as the differentiation of the lipolysis of different lipid loads.


[Evaluation of the work environment in a local healthcare organisation in Italy: practical aspects and public health relevance].
The aim of this study was to evaluate a model of analysis of the work environment in a healthcare setting in Italy and its potential utility as tool for improving the quality of care and safeguarding the health of users. The experimental model was generated in a publicly funded hospital and in a healthcare district of a local healthcare organisation. A questionnaire was used to evaluate the work environment and its constituents. Sixty-eight percent of those interviewed were aware of the objectives of the organisation, and 74% of the organisational structure. Only 34% however admitted feeling satisfied with the organisation's communication strategies and integration processes. Overall, most workers (84%) reported being highly satisfied with their work even though only half (52%) reported feeling part of the organisation, 34% of being satisfied with the organisation's current career advancement opportunities and 29% of being satisfied with the professional training opportunities offered. Nurses reported the lowest level of satisfaction, especially those working in healthcare districts. The results of this study show that healthcare workers' perception of the work environment are varied in both hospitals and healthcare districts. They also show that the proposed model is useful for evaluating the work environment in a healthcare setting.


Primary squamous cell carcinoma of the ampulla of Vater: a case report.
Primary squamous cell carcinoma of the ampulla of Vater is a very rare type of tumor, and the prognosis is not well known mainly due to a limited number of cases reported. Here, we aimed to report a case with primary squamous cell carcinoma of the ampulla of Vater. A 54-year-old woman presented with weight loss, jaundice, and pain in the epigastric and right upper quadrant of the abdomen. With extensive radiological imaging, the patient was diagnosed with periampullary tumor and Whipple's procedure was performed. The immunohistochemical analyses supported the diagnosis of primary squamous cell carcinoma. The postoperative course was uneventful. The patient was discharged, and adjuvant chemotherapy was recommended. Primary squamous cell carcinoma of the ampulla of Vater is a very rare histological type with an unclear pathogenesis. A better understanding of pathogenesis might be helpful in optimizing the treatment for this specific rare type of tumor.


Predator attack rate evolution in space: the role of ecology mediated by complex emergent spatial structure and self-shading.
Predation interactions are an important element of ecological communities. Population spatial structure has been shown to influence predator evolution, resulting in the evolution of a reduced predator attack rate; however, the evolutionary role of traits governing predator and prey ecology is unknown. The evolutionary effect of spatial structure on a predator's attack rate has primarily been explored assuming a fixed metapopulation spatial structure, and understood in terms of group selection. But endogenously generated, emergent spatial structure is common in nature. Furthermore, the evolutionary influence of ecological traits may be mediated through the spatial self-structuring process. Drawing from theory on pathogens, the evolutionary effect of emergent spatial structure can be understood in terms of self-shading, where a voracious predator limits its long-term invasion potential by reducing local prey availability. Here we formalize the effects of self-shading for predators using spatial moment equations. Then, through simulations, we show that in a spatial context self-shading leads to relationships between predator-prey ecology and the predator's attack rate that are not expected in a non-spatial context. Some relationships are analogous to relationships already shown for host-pathogen interactions, but others represent new trait dimensions. Finally, since understanding the effects of ecology using existing self-shading theory requires simplifications of the emergent spatial structure that do not apply well here, we also develop metrics describing the complex spatial structure of the predator and prey populations to help us explain the evolutionary effect of predator and prey ecology in the context of self-shading. The identification of these metrics may provide a step towards expansion of the predictive domain of self-shading theory to more complex spatial dynamics.


Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection.
Understanding the mechanism of protective antibody recognition against highly pathogenic avian influenza A virus H5N1 in humans is critical for the development of effective therapies and vaccines. Here we report the crystal structure of three H5-specific human monoclonal antibodies bound to the globular head of hemagglutinin (HA) with distinct epitope specificities, neutralization potencies and breadth. A structural and functional analysis of these epitopes combined with those reported elsewhere identifies four major vulnerable sites on the globular head of H5N1 HA. Chimeric and vulnerable site-specific mutant pseudoviruses are generated to delineate broad neutralization specificities of convalescent sera from two individuals who recovered from the infection with H5N1 virus. Our results show that the four vulnerable sites on the globular head rather than the stem region are the major neutralizing targets, suggesting that during natural H5N1 infection neutralizing antibodies against the globular head work in concert to provide protective antibody-mediated immunity.


Tardive Dyskinesia Development, Superoxide Dismutase Levels, and Relevant Genetic Polymorphisms.
Tardive dyskinesia (TD) is a prevalent movement disorder that significantly impacts patients with schizophrenia (SCZ) due to extended exposure to antipsychotics (AP). Several genetic polymorphisms, including superoxide dismutase (SOD) and DRD3 9ser, have been suggested as explanations why some patients suffer from TD. Methods. A PubMed search was used to search relevant articles using the following keywords: "Tardive Dyskinesia and Superoxide Dismutase". Fifty-eight articles were retrieved. Among them, 16 were included in this review. Results. Overall, 58 studies were retrieved from PubMed. Most studies investigated the association between TD and the SOD-related polymorphisms. In addition, previous studies reported an association between TD occurrence and other genetic polymorphisms. Conclusion. This study found that the risk of TD is associated with altered SOD levels and several genetic polymorphisms, including VAL 66 Met and DRD3 9ser.


Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome.
Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.


Can the lumpy distribution of galaxies be reconciled with the smooth X-ray background?
The fluctuations in X-ray background intensity that would be generated by clusters or superclusters of galaxies exceed those observed. It may be that the X-ray background arises from low-luminosity objects which are distributed much more smoothly and are more numerous than bright optical galaxies. Hierarchical universe models in which the distribution of X-ray sources follows the cosmological mass distribution are ruled out.


Plant response to water stress of native and non-native Oenothera drummondii populations.
Invasive plants can spread over climatically diverse areas. We explore the effects of drought on gas exchange and water relations on the invasive dune species Oenothera drummondii, using plants from four populations with different rainfall and temperatures regimes. Plant material was obtained germinating plants from one native and three non-native populations in a greenhouse. Drought stress was induced by withholding water. Responses to drought stressed plants were then compared to well-watered controls. Measurements of gas exchange, chlorophyll fluorescence and leaf traits were taken initially and every 10 days after water was withheld, until day 36 when plants were re-watered and recover capacity was measured. The effect of water stress was more evident in Fv/Fm and gas exchange variables. The results suggest that this species possess a mechanism of thermal dissipation of energy. Leaf relative water content was significant lower in drought stressed than control plants. At the end of withholding water period, stressed plants are separated from control plants along the axis I of the ordination analysis evidencing differences in functional traits. All plants recovered well after re-watering. Our results provide evidence for permanent differences in morphological traits and functional responses to drought stress among native and invasive populations of O. drummondii. Although we have only studied four populations, these results may provide evidence for the role of plasticity in contributing to the invasion success of this species.


Cryptocarya chinensis from the Upper Pleistocene of South China and its biogeographic and paleoecological implications.
Anatomical structure of mummified wood of Cryptocarya (Lauraceae) from the Upper Pleistocene of Maoming, South China and the woods of 15 extant species of Cryptocarya from China and Malaysia were examined. The fossil wood has been convincingly attributed to extant species Cryptocarya chinensis (Hance) Hemsl. This is the first reliable fossil record of Cryptocarya in Asia. The finding combined with the results of Biomod2 species distribution modeling suggest that the range of C. chinensis in the Late Pleistocene in South China and North Vietnam was very restricted due to increased continental aridity and enhanced temperature seasonality in this region. Thus, modern populations of C. chinensis in Maoming can be considered as glacial relicts. The mines (larval tunnels) produced by the larvae of flies from the genus Phytobia Lioy (Agromyzidae, Diptera) were observed in fossil wood under study. These cambial miners have never been reported in Cryptocarya.


The effect of social trust on citizens' health risk perception in the context of a petrochemical industrial complex.
Perceived risk of environmental threats often translates into psychological stress with a wide range of effects on health and well-being. Petrochemical industrial complexes constitute one of the sites that can cause considerable pollution and health problems. The uncertainty around emissions results in a perception of risk for citizens residing in neighboring areas, which translates into anxiety and physiological stress. In this context, social trust is a key factor in managing the perceived risk. In the case of industrial risks, it is essential to distinguish between trust in the companies that make up the industry, and trust in public institutions. In the context of a petrochemical industrial complex located in the port of Castellón (Spain), this paper primarily discusses how trust - both in the companies located in the petrochemical complex and in the public institutions - affects citizens' health risk perception. The research findings confirm that while the trust in companies negatively affects citizens' health risk perception, trust in public institutions does not exert a direct and significant effect. Analysis also revealed that trust in public institutions and health risk perception are essentially linked indirectly (through trust in companies).


Protein C: comparison of different assays in normal and abnormal plasma samples.
Two assay methods for Protein C (PC) are described. Both tests are based on the activation of PC by a fraction of the venom of the Copperhead snake. Activated PC can be measured either by cleaving of a chromogenic substrate or by an APTT test. Both tests were compared with ELISA tests for PC. In 27 healthy persons the results were around 100% by all test systems when compared with normal pooled plasma. In 13 patients under stable anticoagulant therapy the average results were 54% for the ELISA and 52% for the chromogenic substrate test whilst the corresponding figures were 22% for the APTT test and 25% for the Quick test. In 4 cases of liver cirrhosis PC was diminished and there was no difference between the three tests. In two patients with congenital PC deficiency all results were close to 50% and in three patients the ELISA and the substrate tests were normal but the APTT test showed results of 44, 28 and 54% respectively. These results give rise to the conclusion that the snake venom activator is also capable of activation of decarboxylated PC molecules which can thereby split a chromogenic substrate but remain inactive in an APTT test.


Ambient outdoor air pollutants and sex ratio of singletons born after in vitro fertilization: the effect of single blastocyst transfer.
To evaluate the impact of air pollution on the sex ratio in singletons after IVF treatment and to evaluate the influence of the number of and the developmental stage of transferred embryos on the sex ratio. Retrospective cohort study. University-affiliated IVF unit. A total of 7,004 singletons born after fresh transfer or frozen-thawed embryo transfer (FET) between January 2013 and December 2017. None. Male-to-female ratio in live-born singletons. The estimated medians (interquartile range) of particle matter (PM)10, PM2.5, CO, NO2, O3, and SO2 at the IVF site were 51.4 (39.5-64.6), 27.7 (20.7-37.4), 0.62 (0.5-0.72), 32.5 (25.4-40.1), 79.6 (63.3-96.6), and 11.9 (9.3-15.9) μg/m3, respectively. Multivariate analysis indicated that SO2 was the only pollutant clearly associated with sex ratio. In singletons from single blastocyst transfer (SBT), as indicated by the generalized additive model, the SO2 concentration and sex ratio showed an inverted-U-shape association. In singletons after non-SBT, a monotonic decreasing in the sex ratio was observed with increased SO2 concentration. Compared with the referent category (SO2 < 7.57 μg/m3), the sex ratio at the 5th decile of SO2 (10.81-11.94 μg/m3) was increased by 2.1-fold (95% confidence interval [CI], 1.3-3.14) after adjusting covariates. In singletons born from non-SBT, the sex ratio significantly decreased only in the 9th (odds ratio = 0.69; 95% CI, 0.53-0.90) and 10th (OR = 0.74, 95% CI, 0.56-0.98) deciles. Low concentrations of SO2 showed an association with increased sex ratio in singletons of SBT, while in singletons born from another ET system the sex ratios did not show an association at low concentrations of SO2.


Significance of suspected "chronic aggressive hepatitis" in acute hepatitis.
Transition from acute to chronic hepatitis has important prognostic and therapeutic implications. In 17 patients with acute viral hepatitis, observed during a period of 7 years, a liver biopsy showed changes compatible with chronic aggressive hepatitis and superimposed acute hepatitis. Follow-up biopsies showed normal liver in 14 cases, chronic persistent hepatitis in 1, and cirrhosis in 2. In 12 cases the initial biopsy which showed changes suggestive of chronicity was taken 1 month after onset of symptoms of acute hepatitis, or later. Cases developing chronic liver disease showed no characteristic clinical, laboratory, or histological features at the time of the first biopsy. If the diagnosis of chronic active hepatitis is based on histological findings alone in patients with prolonged acute hepatitis, the incidence of this condition will be grossly overestimated. The transition from acute to chronic hepatitis cannot be recognized with any degree of certainty by presently available methods.


Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell.
Genomic imprinting is an epigenetic gene-marking phenomenon that occurs in the germline, whereby genes are expressed from only one of the two parental copies in embryos and adults. Imprinting is essential for normal mammalian development and its disruption can cause various developmental defects and diseases. The process of imprinting in the germline involves DNA methylation of the imprint control regions (ICRs), and resulting parental-specific methylation imprints are maintained in the zygote and act as the marks controlling imprinted gene expression. Recent studies in mice have revealed new factors involved in imprint establishment during gametogenesis and maintenance during early development. Clinical studies have identified cases of imprinting disorders where involvement of factors shared by multiple ICRs for establishment or maintenance is suspected. These include Beckwith-Wiedemann syndrome, transient neonatal diabetes, Silver-Russell syndrome and others. More severe disruptions can lead to recurrent molar pregnancy, miscarriage or infertility. Imprinting defects may also occur during assisted reproductive technology or cell reprogramming. In this review, we summarize our current knowledge on the mechanisms of imprint establishment and maintenance, and discuss the relationship with various human disorders.


Asthma-COPD Overlap and Chronic Airflow Obstruction: Definitions, Management, and Unanswered Questions.
Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a common clinical presentation of chronic airways disease in which patients show some features usually associated with asthma, and some usually associated with COPD. There is ongoing debate over whether ACO is a discrete clinical entity, or if it is part of a continuum of airways disease. Furthermore, there is considerable variation among current definitions of ACO, which makes diagnosis potentially challenging for clinicians. Treating ACO may be equally challenging because ACO is an understudied population, and the evidence base for its management comes largely from asthma and COPD studies, the relevance of which deserves careful consideration. In this review, we synthesize the various approaches to ACO diagnosis and evaluate the role of currently available diagnostic tests. We describe the potential benefits of existing asthma and COPD therapies in treating patients with ACO, and the value of a "treatable traits" approach to ACO management. Throughout the review, we highlight some of the pressing, unanswered questions surrounding ACO that are relevant to the clinical community. Ultimately, addressing these questions is necessary if we are to improve clinical outcomes for this complex and heterogeneous patient population.


Association between out-of-bed mobilization and complications of immobility in acute phase of severe stroke: A retrospective observational study.
Medical complications often occur, particularly in the acute phase of severe stroke, and lead to poor outcomes. However, it is unclear whether out-of-bed mobilization (OM) reduces such complications or not in the acute phase of severe stroke. Thus, we investigated the association between OM and complications of immobility in the acute phase of severe stroke. We enrolled 407 patients diagnosed with ischemic stroke or intracerebral hemorrhage and patients with modified Rankin Scale 5 at discharge in this study. Patients were divided into two groups: OM (303 patients) and bed rest (BR; 104 patients) at discharge based on their medical records. Complications of immobility (such as pneumonia, urinary tract infection, pressure sore, and falls) during hospitalization in each group were recorded. The total complication rate of immobility, incidence of pneumonia, and the incidence of pressure sores were significantly lower in the OM group than in the BR group [60.7% vs. 88.5%, 45.5% vs. 62.5%, and 3.6% vs. 12.5%; odds ratio, 0.20, 0.50, and 0.26; and 95% confidence intervals, 0.11-0.39, 0.32-0.79, and 0.11-0.61, respectively]. Urinary tract infection and falls did not differ significantly between the two groups. In the acute phase of severe stroke, OM was significantly associated with a lower risk of total complication rate of immobility, incidence of pneumonia, and incidence of pressure sore without increasing falls.


The implementation of an aminoglycoside induced ototoxicity algorithm for people with cystic fibrosis.
Aminoglycoside antibiotics treat respiratory infections in cystic fibrosis (CF). An aminoglycoside induced ototoxicity algorithm (AIOA) was implemented to assess ototoxicity among people with CF treated with intravenous and/or inhaled aminoglycosides. Prior to AIOA implementation, 14 of 52 patients (27%) treated with intravenous aminoglycosides had an audiogram. In the 24 months post AIOA implementation, 43 of 44 patients (98%) treated with intravenous aminoglycosides had an audiogram, with 27 (63%) demonstrating abnormalities. Prior to AIOA development, 18 of 70 patients (26%) who received at least two courses of inhaled aminoglycosides had an audiogram. Post AIOA implementation, 33 patients qualified for an audiogram after receiving inhaled aminoglycosides. Of these, 19 (58%) had an audiogram and 10 (53%) had abnormalities. Overall, we identified 46 (61%) people with CF with hearing abnormalities compared to 2.4% in the CF Foundation Patient Registry. This suggests an urgent need for CF programs to implement AIOAs.


A case series study on the effect of Ebola on facility-based deliveries in rural Liberia.
As communities' fears of Ebola virus disease (EVD) in West Africa exacerbate and their trust in healthcare providers diminishes, EVD has the potential to reverse the recent progress made in promoting facility-based delivery. Using retrospective data from a study focused on maternal and newborn health, this analysis examined the influence of EVD on the use of facility-based maternity care in Bong Country, Liberia, which shares a boarder with Sierra Leone - near the epicenter of the outbreak. Using a case series design, retrospective data from logbooks were collected at 12 study sites in one county. These data were then analyzed to determine women's use of facility-based maternity care between January 2012 and October 2014. The primary outcome was the number of facility-based deliveries over time. The first suspected case of EVD in Bong County was reported on June 30, 2014. Heat maps were generated and the number of deliveries was normalized to the average number of deliveries during the full 12 months before the EVD outbreak (March 2013 - February 2014). Prior to the EVD outbreak, facility-based deliveries steadily increased in Bong County reaching an all-time high of over 500 per month at study sites in the first half of 2014 - indicating Liberia was making inroads in normalizing institutional maternal healthcare. However, as reports of EVD escalated, facility-based deliveries decreased to a low of 113 in August 2014. Ebola virus disease has negatively impacted the use of facility-based maternity services, placing childbearing women at increased risk for morbidity and death.


BRAF mutations in Iranian patients with papillary thyroid carcinoma.
Papillary thyroid cancer or papillary thyroid carcinoma (PTC) is the most common thyroid cancer. The fact that it occasionally occurs in women aged 30-40 years old suggests that genetic alterations are involved its genesis. Recently, activator mutations in BRAF gene have been relatively frequently discovered. In this study, we tested 63 DNA samples from PTC patients to identify the V600E mutation frequency in the Ahvaz population. DNA was isolated from formalin fixed paraffin-embedded (FFPE) PTC tumor tissues. Genotyping was performed by PCR-RFLP and confirmed by direct DNA sequencing of a subset of PCR products. PCR-RFLP data were reported as genotype frequencies and percentages. Forty nine out of 63 patients (77.8%) had a mutated heterozygote form while 14 (22.2%) showed normal genotype but none demonstrated a mutant homozygote genotype. The frequency of V600E mutation was significantly high in PTC patients. These findings support involvement of V600E mutations in PTC occurrence in Iran. Assessment of correlations between BRAF V600E mutations and papillary thyroid cancer progression needs to be performed.


Tryptamine, a substrate for the serotonin transporter in human platelets, modifies the dissociation kinetics of [3H]imipramine binding: possible allosteric interaction.
Tricyclic antidepressants and nontricyclic serotonin (5-hydroxytryptamine) uptake blockers monophasically inhibit [3H]imipramine binding in human platelets. Similarly, serotonin and tryptamine inhibit the binding of [3H]imipramine in the low micromolar range and with a pseudo-Hill coefficient near unity. Dissociation of the [3H]imipramine receptor complex in the presence of uptake inhibitors follows first-order kinetics with a half-life of approximately 60 min. Although serotonin and tryptamine do not decrease [3H]imipramine binding when added under equilibrium conditions, simultaneous addition of serotonin or tryptamine with serotonin uptake inhibitors decreases the rate of ligand-receptor dissociation in a concentration-dependent manner. These data suggest a common site of action for serotonin, which is the substrate of the transporter system, and of tryptamine, its nonhydroxylated analog. This hypothesis is supported by the identification of a high-affinity (Km = 0.55 microM), saturable, and temperature-dependent uptake of [3H]tryptamine in human platelets. Uptake of [3H]tryptamine was inhibited potently by imipramine and nontricyclic serotonin uptake inhibitors with a potency similar to that observed for [3H]serotonin uptake. These data support the hypothesis that in platelets, [3H]imipramine, tricyclic, and nontricyclic serotonin uptake inhibitors bind to a common recognition site that is associated with the serotonin transporter but that differs from the substrate recognition site of the carrier through which serotonin and tryptamine exert a heterotropic allosteric modulation on [3H]imipramine binding.


Correction osteotomy for malunion of the talar head: a case report.
Talar head fractures are rare injuries. We present a 26-year-old man with malunion of the talar head. The displaced fracture was initially neglected. The patient was treated with osteotomy and bone grafting to improve the congruity and movement of the talonavicular joint. Three months after surgery, he returned to his pre-injury activity level with no disability.


Simultaneous early ovarian and endometrial cancer treated conservatively with spontaneous pregnancy.
Young cancer patients increasingly request fertility sparing alternatives to their cancer treatments, which they should be offered when allowed so by the risk-benefit balance and after obtaining informed consent. Here, we report the case of a 25 year-old nulliparous patient who presented with a synchronous endometrioid ovarian and endometrial carcinoma. She was able to conduct a full-term spontaneous pregnancy after conservative surgical treatment followed by adjuvant chemotherapy and hormonal treatment. Fertility sparing treatment is feasible in selected cases of synchronous ovarian and endometrial cancers. Thorough follow-up remains mandatory. This case demonstrates some interesting and unique features of synchronous ovarian and endometrial cancers since it resulted in a spontaneous pregnancy and normal delivery.