The effects of imagery perspective as a function of skill level on alpha activity.
A strategy being used by athletes to enhance their performance is imagery. In previous research studying imagery, Lang's (1977, 1979) Information-Processing Theory states two types of propositions: stimulus propositions (SP) and response propositions (RP). The beneficial use of imagery scripts emphasizing these propositions may depend on the skill level of the performer. The purpose of this study was to investigate differences in lower (8-10 Hz) and upper (11-13 Hz) alpha activities during imagery emphasizing SP and imagery emphasizing RP as related to the skill level of the subjects. Twenty-two right-handed male subjects were assigned to either an 'expert' (n=11) or a 'novice' (n=11) group. Lower and upper alpha activities from six active sites were recorded during imagery of a golf-putting task. After subsequent fast Fourier transform (FFT) analysis of results, mean lower and upper alpha power values were entered into separate repeated measures mixed model designs. Results revealed significant differences in skill level at the occipital sites in the lower alpha band. Moreover, a significant interaction between imagery perspective and skill level was found in the lower alpha band at the occipital site and in the upper alpha band at the parietal site. Significant differences were found in imagery perspective at the parietal, temporal, and occipital sites in the lower alpha band. In addition, a significant interaction effect, imagery perspective by hemisphere, was found in the upper alpha band at the parietal site. Conclusions are discussed based on the results and future research is suggested.


The HR-CS-GF-AAS determination and preconcentration of palladium in contaminated urban areas, especially in lichens.
The increasing content of platinum group metal particles emitted into the environment by car traffic is gradually attracting the attention of the scientific community. However, the methods for the determination of platinum group metals in environmental matrices are either costly or suffer from low sensitivity. To facilitate the use of less sensitive, but significantly cheaper, devices, the preconcentration of platinum group metals is employed. For platinum, a multitude of preconcentration approaches have been published. On the contrary, the preconcentration approaches for palladium are still rare. In this work, the development, optimization, and testing of a new approach is described; it is based on a preconcentration of palladium on octadecyl modified silica gel together with the complexing agent dimethylglyoxime, and it is then analyzed with the high-resolution continuum-source atomic absorption spectrometry. For comparison, a newly developed sorbent, QuadraSil™ TA, with a high affinity for platinum group metals was also tested. The preconcentraiton approach was tested on the lichen Hypogymnia physodes, which served as a bioindicator of palladium emissions. The case study site was a mid-sized city in central Europe: Brno, Czech Republic. The dry "bag" monitoring technique was used to collect the palladium near roads with a large span of traffic density. The developed analytical approach confirmed an increasing concentration of palladium with increasing exposure time and intensity of the traffic. Consequently, a simple relationship between the amount of bioaccumulated palladium and traffic density was established.


Cellulose acetate-zirconium (IV) phosphate nano-composite with enhanced photo-catalytic activity.
Cellulose acetate-zirconium (IV) phosphate nanocomposite (CA/ZPNC) was synthesized by sol-gel technique at pH 0-1 and was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, Fourier infrared spectroscopy (FTIR) and thermal analysis (TGA/DTA/DSC). Ion exchange capacity, pH titration, elution concentration, elution behaviour, thermal stability and distribution coefficient were investigated to explore ion exchange behaviour of CA/ZPNC. The nanocomposite showed an ion-exchange capacity of 1.4 mequiv. g(-1) for Na(+) and was highly selective for Pb(2+) and Zn(2+) over many other metal ions. The photocatalytic activity of the CA/ZPNC was explored for degradation of a model Congo red dye from aqueous phase. 90% of dye was removed in 60 min of irradiation. Simultaneous adsorption and photocatalysis had synergetic effect on dye degradation.


[Neonatal cleft lip repair: perioperative safety and surgical outcomes].
There is no international consensus on timing for surgical repair of cleft lip and palate. We argue that neonatal timing for repair of the lip deformity allows a better integration of the baby in his family and is of major support for the parents. Recent studies tend to challenge this neonatal practice. We want to study retrospectively the perioperative safety and the surgical outcomes of this procedure over the past 20 years in a series of 42 non-selected babies who had labial repair during the first four weeks of their life. All of them have been operated by the same senior surgeon. Median operative time is 45 minutes for unilateral cleft and 70 minutes in case of bilateral malformation. Oral feeding is initiated at the end of the operative day. Children's hospital stay is four days. The results show no anaesthetic complication. Four children had secondary lip correction. The risk of anaesthetic and surgical interventions limited to the lip before the age of 28 days is very low in a medical care environment specialized in neonatal surgery and postoperative care. The over all complication rate is very low.


The role of preoperative upper endoscopy in adolescents undergoing laparoscopic vertical sleeve gastrectomy.
Vertical sleeve gastrectomy (VSG) has been associated with gastroesophageal reflux symptoms and, in adults, with a development of Barrett's esophagus. Adults with Barrett's esophagus identified at baseline before bariatric operation are generally advised against VSG operations. The role of preoperative esophagogastroduodenoscopy (EGD) in adolescents preparing for bariatric surgery is not clearly defined. The goal of this study was to report the frequency of abnormalities identified on EGD performed at baseline in adolescents undergoing VSG for severe obesity. Free-standing academic children's hospital. United States. A retrospective chart review was conducted to describe findings of EGD performed just before VSG in a cohort of 40 adolescents and young adults (age range 14-25 yr) immediately before VSG. Review of findings from gross and histopathological evaluation of the esophagus, resected stomach, and duodenum was performed. Five individuals reported preoperative symptoms of gastroesophageal reflux. Anatomic findings at EGD were normal in 98% of individuals. Histopathology of the esophagus, stomach, and duodenum was normal in 88%, 70%, and 95%, respectively. Abnormal findings of gastritis (18%), esophagitis (13%), and/or Helicobacter pylori (10%) infection were most common. Those with evidence of H. pylori in gastric resection specimens were treated appropriately with eradication therapy postoperatively. With the exception of 2 patients with incidentally detected esophageal mucosal eosinophilia, EGD findings did not lead to additional changes in medical or surgical management. There were no complications of the EGD procedure. Routine EGD at the time of VSG was safe but resulted in low yield of abnormal findings requiring a change in clinical management.


The complete mitochondrial genomes of five Eimeria species infecting domestic rabbits.
Rabbit coccidiosis caused by members of the genus Eimeria can cause enormous economic impact worldwide, but the genetics, epidemiology and biology of these parasites remain poorly understood. In the present study, we sequenced and annotated the complete mitochondrial (mt) genomes of five Eimeria species that commonly infect the domestic rabbits. The complete mt genomes of Eimeria intestinalis, Eimeria flavescens, Eimeria media, Eimeria vejdovskyi and Eimeria irresidua were 6261bp, 6258bp, 6168bp, 6254bp, 6259bp in length, respectively. All of the mt genomes consist of 3 genes for proteins (cytb, cox1, and cox3), 14 gene fragments for the large subunit (LSU) rRNA and 11 gene fragments for the small subunit (SSU) rRNA, but no transfer RNA (tRNA) genes. The gene order of the mt genomes is similar to that of Plasmodium, but distinct from Haemosporida and Theileria. Phylogenetic analyses based on full nucleotide sequences using Bayesian analysis revealed that the monophyly of the Eimeria of rabbits was strongly statistically supported with a Bayesian posterior probabilities. These data provide novel mtDNA markers for studying the population genetics and molecular epidemiology of the Eimeria species, and should have implications for the molecular diagnosis, prevention and control of coccidiosis in rabbits.


A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage.
Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH. In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality. The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different. Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.


Comparative study of solvation parameter models accounting the effects of mobile phase composition in reversed-phase liquid chromatography.
Solvation parameter models relate linearly compound properties with five fundamental solute descriptors (excess molar refraction, dipolarity/polarizability, effective hydrogen-bond acidity and basicity, and McGowan volume). These models are widely used, due to the availability of protocols to obtain the descriptors, good performance, and general applicability. Several approaches to predict retention in reversed-phase liquid chromatography (RPLC) as a function of these descriptors and mobile phase composition are compared, assaying the performance with a set of 146 organic compounds of diverse nature, eluted with acetonitrile and methanol. The approaches are classified in two groups: those that only allow predictions of retention for the mobile phases used to build the models, and those valid at any other mobile phase composition. The first group includes the use of ratios between the regressed coefficients of the solvation models that are assumed to be characteristic for a column/solvent system, and the application of offsets to transfer the retention from a reference mobile phase to any other. Maximal accuracy in predictions corresponded, however, to the approaches in the second group, which were based on models that describe the retention as a function of mobile phase composition (expressed as the solvent volume fraction or a normalised polarity measurement), where the coefficients were made dependent on the solvent descriptors. The study revealed the properties that influence the retention and distinguish the particular behaviour of acetonitrile and methanol in RPLC.


Prediction of gastro-intestinal absorption using multivariate adaptive regression splines.
Multivariate adaptive regression splines (MARS) and a derived method two-step MARS (TMARS) were used for modelling the gastro-intestinal absorption of 140 drug-like molecules. The published absorption values for these molecules were used as response variable and calculated molecular descriptors as potential explanatory variables. Both methods were compared and their potential use in quantitative structure-activity relationship (QSAR) context evaluated. The predictive abilities of the models were studied using different sequences of Monte Carlo cross validation (MCCV). It was shown that both types of models had good predictive abilities and that for the data used, MARS gave better results than TMARS. It could be concluded that both methods could be valuable for QSAR modelling.


Childhood risk factors for lifetime bulimic or compulsive eating by age 30 years in a British national birth cohort.
To examine whether previously identified childhood risk factors for bulimia or compulsive eating (BCE) predict self-reported lifetime BCE by age 30 years in a prospective birth cohort. Using data from the 1970 British Cohort Study at birth, 5, and 10 years, associations between 22 putative childhood risk factors and self-reported lifetime BCE at 30 years were examined, adjusting for sex and socioeconomic status. Only female sex (odds ratio (OR): 9.2; 95% confidence interval (CI): 1.9-43.7; p = 0.005), low self-esteem (OR:2.9; 95%CI: 1.1-7.5; p = 0.03) and high maternal education (OR:5.4; 95%CI: 2.0-14.8; p = 0.001) were significantly associated with higher risk of BCE, whereas high SES at 10 years was significantly protective (OR:0.2; 95%CI: 0.1-0.8; p = 0.022) of BCE in fully adjusted multivariable logistic regression analysis. Our findings do not support a strong role for childhood weight status and eating behaviours in the development of bulimia and compulsive eating pathology, rather suggesting a focus on self esteem may have greater relative importance. Findings in relation to maternal education and SES need further exploration.


MitoPho8Δ60 Assay as a Tool to Quantitatively Measure Mitophagy Activity.
Mitophagy, a selective type of macroautophagy (hereafter referred to as autophagy), specifically mediates the vacuole/lysosome-dependent degradation of damaged or surplus mitochondria. Because this process regulates the number and quality of mitochondria, it is vital for proper cellular homeostasis. Mitophagy also plays critical roles in the clearance of paternal mitochondria in C. elegans embryos, in erythroid cell maturation, and in the prevention of neurodegenerative disease and cancer. In order to study the molecular mechanism and regulation of mitophagy, sensitive assays are necessary to quantitatively measure mitophagy activity. In the budding yeast, Saccharomyces cerevisiae, a "mitoPho8Δ60" assay was developed to study mitophagy. In this assay, Pho8, a vacuolar phosphatase protein, is genetically engineered to be targeted to mitochondria. When mitophagy is induced, the phosphatase protein, along with mitochondria, is conveyed to the vacuole, where its C-terminal propeptide is removed and the phosphatase activity becomes activated; under growing conditions only a background level of delivery occurs. For this reason, the enzymatic activity of mitoPho8Δ60 is correlated with the amount of mitochondria delivered to the vacuole. Thus, this assay serves as a very convenient tool to quantitatively monitor mitophagy activity in yeast.


Inhibition of miR-21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM.
In type 1 and type 2 diabetes mellitus, increased cardiac fibrosis, stiffness and associated diastolic dysfunction may be the earliest pathological phenomena in diabetic cardiomyopathy. Endothelial-mesenchymal transition (EndMT) in endothelia cells (ECs) is a critical cellular phenomenon that increases cardiac fibroblasts (CFs) and cardiac fibrosis in diabetic hearts. The purpose of this paper is to explore the molecular mechanism of miR-21 regulating EndMT and cardiac perivascular fibrosis in diabetic cardiomyopathy. In vivo, hyperglycaemia up-regulated the mRNA level of miR-21, aggravated cardiac dysfunction and collagen deposition. The condition was recovered by inhibition of miR-21 following with improving cardiac function and decreasing collagen deposition. miR-21 inhibition decreased cardiac perivascular fibrosis by suppressing EndMT and up-regulating SMAD7 whereas activating p-SMAD2 and p-SMAD3. In vitro, high glucose (HG) up-regulated miR-21 and induced EndMT in ECs, which was decreased by inhibition of miR-21. A highly conserved binding site of NF-κB located in miR-21 5'-UTR was identified. In ECs, SMAD7 is directly regulated by miR-21. In conclusion, the pathway of NF-κB/miR-21/SMAD7 regulated the process of EndMT in T1DM, in diabetic cardiomyopathy, which may be regarded as a potential clinical therapeutic target for cardiac perivascular fibrosis.


Effective clinical applications of Monte Carlo-based independent secondary dose verification software for helical tomotherapy.
To investigate the scope of the effective clinical application of Monte Carlo (MC)-based independent dose verification software for helical tomotherapy. DoseCHECK was selected as the MC-based dose calculation software. First, the dose calculation accuracy of DoseCHECK was evaluated with film and chamber measurements in a water-equivalent phantom. Second, the dose calculation accuracy was examined in several heterogeneous materials. Finally, dosimetric comparisons between DoseCHECK and the treatment planning system (TPS) were performed for clinical patient plans. Prostate IMRT, head and neck IMRT (HN), total body irradiation (TBI), and brain stereotactic radiotherapy (SRT) were evaluated. The DoseCHECK calculations agreed with the chamber and film measurements in the homogenous phantom. For heterogeneous phantom cases, the dose differences between DoseCHECK and TPS were within 3 %, except in air, in which large dose differences of 20 % were observed. In clinical patient plans, the median dose differences between the lung Dmean in TBI cases and the normal brain Dmean in brain SRT cases were significantly >3 %. For HN and brain SRT cases, the median target dose differences were >3 %. Our results show that independent dose verification with the MC algorithm can detect systematic errors caused by the lack of heterogeneity correction in the TPS. In particular, MC-based independent dose verification is required for HN, TBI, and brain SRT cases in helical tomotherapy.


Transdermal delivery of corticosterone in terrestrial amphibians.
Stressors elicit allostatic responses that allow animals to cope with changing and challenging environments and also cause release of glucocorticoid hormones (GCs). Compared to other vertebrate classes, relatively little is known about amphibian behavioral and physiological responses to GCs. To understand the effects of elevated plasma GCs in amphibians, exogenous application of GCs is necessary, but traditional methods to elevate GCs require handling and/or anesthesia which themselves are stressors. A less invasive alternative successfully used in birds and reptiles utilizes transdermal delivery by applying GCs via a dermal patch. We asked whether dermal patches containing corticosterone (CORT, the main GC in amphibians) would elevate plasma CORT in terrestrial salamanders and frogs. We explored the use of the dermal patch to deliver CORT in an acute, sustained, and repeated manner. Patches adhered well to the amphibians' moist skin and were easily removed to regulate the time course of CORT delivery. Application of CORT treated patches elevated plasma CORT concentrations compared to vehicle patches in all species. Patches delivered physiological levels of plasma CORT in ecologically relevant time frames. Repeated application and removal of CORT patches were used to simulate exposure to repeated stressors. Application of patches did not represent a stressor because plasma CORT concentrations were similar between animals that received vehicle patches and untreated animals. Thus, transdermal delivery of GCs represents a potentially useful tool to better understand amphibian allostatic responses to stressors, and perhaps amphibian population declines.


Effectiveness and safety of sacubitril/valsartan for patients with hypertension and heart failure in the real-world setting: A retrospective study in China.
Hypertension (HP) is associated with heart failure (HF). Sacubitril/valsartan (sac/val) has been approved for primary HP by China Food and Drug Administration (CFDA) in June 2021. The present study aimed to provide evidence on the effectiveness and safety of sac/val in Chinese patients complicated with HP and HF. This retrospective study was conducted on adult patients diagnosed with HP and HF and treated with sac/val between July 2020 and December 2020. The potential risk factors for the discontinuation events caused by sac/val-related adverse events (AEs) were explored. The data, including blood pressure (BP), cardiac indicators, corresponding values on echocardiographic parameters, unplanned visits, and AEs throughout 3-12 months, were collected. A total of 446 eligible patients were included in this study. The discontinuation events of sac/val were mainly attributed to its AEs (hypotension, hyperkalemia, and deterioration in kidney function). Univariate analysis revealed that history of chronic kidney disease, atrial fibrillation, higher values of serum creatinine, serum uric acid, serum N-terminal pro B-type natriuretic peptide, and lower estimated glomerular filtration rate were potential risk factors for discontinuation. Patients who maintained sac/val therapy throughout 3-12 months showed significantly improved values of clinical BP, cardiac indicators, and echocardiographic parameters compared to those at baseline (p < 0.0001). Sac/val was effective on BP and improved cardiac function in patients complicated with HP and HF. The physicians should focus on patients with renal dysfunction to take timely precautions to improve tolerability for sac/val.


An assessment of tropical cyclones rainfall erosivity for Taiwan.
Rainfall erosivity (or water erosion) has severe implications on agriculture, water, and land use management. Though, there were Rainfall erosivity studies on regional and global scale, tropical cyclones' Rainfall erosivity is poorly assessed and have not been documented for one of the most cyclones affecting regions of the world like Taiwan. Here, using 15-years of raindrop size distributions (RSD) and 60-years of hourly rain gauges data, we estimated cyclones (also called typhoons) rainfall erosivity over Taiwan, and establish that typhoons' mean rainfall erosivity is higher than the global mean rainfall erosivity. Moreover, regional variability of typhoons rainfall erosivity showed an increasing pattern from north to south (Taipei to Pingtung), with relatively higher values over eastern and southern parts of Taiwan. The annual mean erosivity of typhoons rainfall showed raising trends over eastern and southern Taiwan during 1958-2017. Our results provide an insight in assessing the land use and agricultural management for Taiwan.


Electron microscopic study of purified polysaccharide components glucans and mannan of the cell walls in the yeast Saccharomyces cerevisiae.
In this study electron-microscopic characteristics of platinum shadowed or negatively stained preparations of purified beta-(1----3)-D-glucan, beta-(1----6)-D-glucan, and mannan were examined. These polysaccharides were isolated from cell walls of the yeast Saccharomyces cerevisiae. While purified samples of beta-(1----6)-D-glucan and mannan proved to be amorphous in structure and homogenous in appearance, the purified beta-(1----3)-D-glucan, isolated and presented to us as alkali-insoluble yeast glucan A2, was not homogenous. It consisted of (i) fibrillar component, (ii) amorphous matrix, and (iii) chitin bud scars. The ultrastructure of beta-(1----3)-D-glucan present in the glucan A2 sample did not change after treatment with 0.5 M acetic acid at 75 degrees C for 2 hours. After treatment with 1 M NaOH for 3 days at 4 degrees C scar material was removed by centrifugation and after a subsequent acidification of supernatant with acetic acid both the microfibrillar and the amorphous components were still present. It was concluded that beta-(1----3)-D-glucan component consists of molecules probably differing in their physico-chemical properties such as D. P., the degree of branching, conformation, and that cannot be separated by the methods currently used for their isolation.


CircRTN4IP1 regulates the malignant progression of intrahepatic cholangiocarcinoma by sponging miR-541-5p to induce HIF1A production.
Recent studies indicate that circular RNA (circRNA) serves important roles in the development of intrahepatic cholangiocarcinoma (ICC). However, the role of circRNA reticulon 4 interacting protein 1 (circRTN4IP1) in ICC progression remains unknown. Expression of circRTN4IP1, microRNA-541-5p (miR-541-5p), hypoxia inducible factor 1 subunit alpha (HIF1A) and other indicated protein markers was detected by quantitative real-time polymerase chain reaction or Western blot. The functional effects of circRTN4IP1 knockdown in ICC cells were analyzed by cell counting kit-8, cell colony formation, flow cytometry analysis, Western blot, glucose and lactate kit assays. The positive expression rate of HIF1A was detected by immunohistochemistry assay. The interaction between miR-541-5p and circRTN4IP1 or HIF1A was identified by dual-luciferase reporter, RNA immunoprecipitation or RNA pull-down assays. Xenograft mouse model assay was performed to determine the effect of circRTN4IP1 depletion on tumor formation. In contrast, ICC tissues and cells showed high expression of circRTN4IP1 and HIF1A, but low expression of miR-541-5p. Knockdown of circRTN4IP1 led to repression of cell proliferation and glucose metabolism, but promotion of cell apoptosis; however, circRTN4IP1 overexpression had opposite effects. In mechanism, circRTN4IP1 acted as a sponge for miR-541-5p, which was found to target HIF1A. MiR-541-5p inhibitors could remit circRTN4IP1 knockdown-mediated action. Also, HIF1A participated in the regulation of miR-541-5p in ICC progression. In support, circRTN4IP1 depletion impeded tumor formation in vivo. CircRTN4IP1 knockdown inhibited ICC cell malignancy by miR-541-5p/HIF1A axis, providing us with a reliable target for the therapy of ICC.


Development of a novel progesterone analog in the treatment of traumatic brain injury.
Although systemic progesterone (PROG) treatment has been shown to be neuroprotective by many laboratories and in multiple animal models of brain injury including traumatic brain injury (TBI), PROG's poor aqueous solubility limits its potential for use as a therapeutic agent. The problem of solubility presents challenges for an acute intervention for neural injury, when getting a neuroprotectant to the brain quickly is crucial. Native PROG (nPROG) is hydrophobic and does not readily dissolve in an aqueous-based medium, so this makes it harder to give under emergency field conditions. An agent with properties similar to those of PROG but easier to store, transport, formulate, and administer early in emergency trauma situations could lead to better and more consistent clinical outcomes following TBI. At the same time, the engineering of a new molecule designed to treat a complex systemic injury must anticipate a range of translational issues including solubility and bioavailability. Here we describe the development of EIDD-1723, a novel, highly stable PROG analog with >104-fold higher aqueous solubility than that of nPROG. We think that, with further testing, EIDD-1723 could become an attractive candidate use as a field-ready treatment for TBI patients. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".


Opposite regulation of pro-opiomelanocortin gene transcription by glucocorticoids and CRH.
Pro-opiomelanocortin (POMC) is the pituitary precursor for adrenocorticotropin (ACTH), beta-endorphin, beta-lipotropin and the melanotropins. The level of ACTH secretion from the anterior pituitary is largely determined by the competing action of the stimulatory hypothalamic hormone, corticoliberin (corticotropin-releasing hormone, CRH), and the inhibitory effect of glucocorticoids. We now demonstrate that these two hormones, glucocorticoids and CRH, also inhibit and stimulate, respectively, the transcription rate of the POMC gene as measured by nuclear run-on transcription assays. Indeed, we show both by in vivo treatment and with rat anterior pituitary cells in primary culture that glucocorticoids inhibit within 30 min transcription of the POMC gene. Similarly, we find that CRH stimulates POMC gene transcription within 15 min. CRH and glucocorticoids can compete with each other to set the rate of POMC transcription. Our results indicate that CRH and glucocorticoids regulate anterior pituitary POMC gene transcription in addition to their well-documented role in the control of POMC peptide release.


Neuronal cell death and population dynamics in the developing rat geniculate ganglion.
In contrast to many neuronal systems, the pattern of developmental neuronal degeneration in the rat geniculate ganglion has remained undefined. To address this issue sectioned geniculate ganglia from embryonic day 13 to postnatal day 3 have been examined using standard histological techniques, TdT-mediated dUTP-digoxigenin nick end labeling to verify apoptotic activity, bromo-deoxyuridine incorporation to monitor neuronal precursor proliferation, and anti-beta-neurotubulin III to verify the neuronal identity of pycnotic cells. Results summed from alternate (embryonic day 13) or every third (embryonic day 14-postnatal day 3) section show that neuronal degeneration occurs as early as embryonic day 13 (6.8% of neurons counted), well before geniculate innervation of lingual taste buds at embryonic day 16. A degenerative peak occurs at embryonic day 17 (9.5%) followed by a decline (1.7% at embryonic day 18) and leveling off (0.1%-0.2% at embryonic day 22-postnatal day 3). Thus, geniculate neuronal degenerative pattern includes both innervation-associated histogenetic and morphogenetic cell death. Corresponding counts of mean neuronal numbers in the sections showed a continual rise from embryonic day 13 through embryonic day 18 (approx. 330-760) followed by a slight decline at embryonic day 19 (to approx. 630) and then a final leveling off at 800-825 by embryonic day 20. This pattern differs from many other developing neural systems which show a major population crash during initial target contact. It likely reflects different but slightly overlapping neuronal precursor proliferation and degeneration patterns in multiple geniculate neuronal subpopulations.


Primary marrow-derived stromal cells: isolation and manipulation.
Marrow stromal cells (MSCs) are relatively rare cells difficult to visualize in marrow biopsies or detect in aspirated marrow. Under specific conditions MSC can be expanded in vitro and the population can give rise to several mesenchymal lineages. "MSC" also refers to mesenchymal stem cells which implies that all cells in the population are multipotent. It is generally agreed that while there may be a few multipotent stem cells in an MSC population the majority are not stem cells. In either case MSCs do not produce hematopoietic cells. Although MSCs have been isolated and characterized from several tissues, bone marrow is their most common source for research and clinical use. Primary MSC populations can be derived from bone marrow mononuclear cells with relative ease, but it is important to recognize the cellular heterogeneity within a culture and how this may vary from donor to donor. In this chapter, we describe methodology to derive primary MSCs from bone marrow screens, an otherwise discarded by-product of bone marrow harvests used for clinical transplantation. We also describe some useful techniques to characterize and manipulate MSCs-both primary and immortalized cell lines.


Pharyngostomum cordatum (Trematoda: Alariidae) collected from a cat in Korea.
Ten adult worms of Pharynogostomum cordatum were recovered from a cat instesine purchased in August 1980 at the Namdaemun Market, Seoul, Korea. It is the first case report of cat pharyngostomiasis in Korea.


Sizing up stability: combination therapy with Apo-AI peptide mimetics and statins in systemic lupus erythematosus-mediated atherosclerosis.
In a study published recently in Arthritis Research & Therapy, Woo and colleagues investigated the effects of pravastatin in combination with an apolipoprotein-AI (Apo-AI) mimetic peptide in a mouse model of lupus-accelerated atherosclerosis. Combination treatment resulted in a significant decrease in systemic inflammation but increased aortic root lesion size. However, this treatment changed the phenotype of the lesion to a more stable plaque. Because plaque stability is also important for protection against the deadly manifestations of atherosclerosis, combination therapies using Apo-AI mimetics and statin might offer a good additional therapy to treat autoimmunity and cardiovascular disease in patients with lupus.


Interaction of mannose-6-phosphate with the hysteretic transition in glucose-6-phosphate hydrolysis in intact liver microsomes.
We showed previously that glucose-6-phosphatase activity was characterised in intact liver microsomes by a hysteretic transition between a rapid and a slower catalytic form of the enzyme. We have now further investigated the substrate specificity of these two kinetic forms. It was found that the pre-incubation of intact microsomes with mannose-6-phosphate or glucose-6-phosphate (50 microM for 30 s) suppressed the burst in glucose-6-phosphatase activity, that the hysteretic transition was reversible and that mannose-6-phosphate inhibited glucose-6-phosphate hydrolysis during the first seconds of incubation, but not anymore after the burst. Our results indicate (i) that mannose-6-phosphate is recognised by the enzyme and can promote the hysteretic transition and (ii) that the transient phase is part of the catalytic mechanism itself.


Does Green-Person-Organization Fit Predict Intrinsic Need Satisfaction and Workplace Engagement?
The current study assessed whether high green-person-organization fit (GPO; the extent to which an organization's commitment to pro-environmental outcomes is congruent with its employees' environmental values) predicts employees' intrinsic need satisfaction and engagement in the workplace. The sample consisted of 818 full-time Australian workers, which is sourced from an online panel. Consistent with the GPO model, pro-environmental work climate was a more potent predictor of intrinsic need satisfaction and engagement for employees with strong ecocentric values than those with weak ecocentric values. Mediation analyses revealed that the effect of work climate on employee engagement was fully mediated by intrinsic need satisfaction, and this effect was strongest when GPO fit was high. Overall, our findings suggest that organizations with pro-environmental work climates that match their employees' values have more satisfied and committed workforces.


[Donation protocol following controlled cardiac death (Maastricht type III donation). First experience].
To present our experience with the implementation of a donation protocol following controlled cardiac death (Maastricht type III donation). A retrospective descriptive and observational study was made. Intensive Care Unit of a third-level university hospital. Eight patients in an irreversible state, in which withdrawal of all life support had been agreed, were evaluated as potential donors. Application of the adopted protocol. Clinical data of donors, evaluation of a donation protocol following cardiac death, warm ischemia times, and short-term outcome of the recipients. Eight patients were evaluated. In one case donation was not possible because no cardiac arrest developed in the 120 minutes after extubation. The 7 remaining patients were effective kidney donors. Warm ischemia times were less than 23 minutes in all cases. Although 7 of the 14 recipients suffered delayed graft function, all of them achieved good renal function. Donation after cardiac death in patients in an overwhelming and irreversible state represents a potential source of donors not previously considered in this country. The prior development of a consensus-based protocol can help increase the number of organs in combination with those obtained after brain death. In our experience, the results of kidney transplants obtained from donors after cardiac death are good, and the success of these types of protocols could be extended to other organs such as the liver and lungs.


Transmembrane topology, genes, and biogenesis of the mitochondrial phosphate and oxoglutarate carriers.
Phosphate and oxoglutarate carriers transport phosphate and oxoglutarate across the inner membranes of mitochondria in exchange for OH- and malate, respectively. Both carriers belong to the mitochondrial carrier protein family, characterized by a tripartite structure made up of related sequences about 100 amino acids in length. The results obtained on the topology of the phosphate and oxoglutarate carriers are consistent with the six alpha-helix model proposed by Saraste and Walker. In both carriers the N- and C-terminal regions are exposed toward the cytosol. In addition, the oxoglutarate carrier has been shown to be a dimer by means of crosslinking studies. The bovine and human genes coding for the oxoglutarate carrier are split into eight and six exons, respectively, and five introns are found to the same position in both genes. The bovine and human phosphate carrier genes have the same organization with nine exons separated by eight introns at exactly the same positions. The phosphate carrier of mammalian mitochondria is synthesized with a cleavable presequence, in contrast to the oxoglutarate carrier and the other members of the mitochondrial carrier family. The precursor of the phosphate carrier is efficiently imported, proteolytically processed, and correctly assembled in isolated mitochondria. The presequence-deficient phosphate carrier is imported with an efficiency of about 50% as compared with the precursor of the phosphate carrier and is correctly assembled, demonstrating that the mature portion of the phosphate carrier contains sufficient information for import and assembly into mitochondria.


Transgenic rabbits with increased VEGF expression develop hemangiomas in the liver: a new model for Kasabach-Merritt syndrome.
Clinical studies have provided ample evidence that high (either systemic or local) levels of vascular endothelial growth factor (VEGF) are associated with several pathophysiological disorders, including hemangiomas. To investigate whether elevated VEGF expression could directly affect these disorders, we created a transgenic (Tg) rabbit model with increased hepatic expression of the human VEGF(165) transgene under the control of the human alpha-antitrypsin promoter. Tg rabbits exhibited marked hepatomegaly, with livers 2.5-fold heavier than those of control rabbits. Histological analysis revealed that the livers of Tg rabbits showed prominent dilation of the sinusoids and formed various-sized blood vessel networks, a feature of diffuse hemangiomas. Immunohistochemical staining revealed that the hepatocytes produced VEGF(165), whereas plasma VEGF(165) was not detected. Furthermore, Tg rabbits suffered from hemolytic anemia, thrombocytopenia and splenomegaly, which was associated with marked extramedullary hematopoiesis. The manifestations of Tg rabbits mimic many of the features of hemangiomatous disorders in humans such as the Kasabach-Merritt syndrome, and therefore this model may be potentially useful for the study of the pathogenesis and complications of hemangiomas as well as the investigation of angiogenesis inhibitors.


Comparison of anterior chamber flare among different glaucoma surgeries.
To compare postsurgical anterior chamber flare (ACF) among conventional (trabeculectomy, LEC) and novel (EX-PRESS Shunt, EXP) filtration surgeries and microhook ab interno trabeculotomy (μLOT), a novel minimally invasive glaucoma surgery (MIGS). This retrospective study included 125 primary open angle glaucoma eyes (89 consecutive subjects) treated with μLOT (n=38), LEC (n=12), or EXP (n=75). The intraocular pressure (IOP), numbers of antiglaucoma medication, and ACF at preoperatively and 2 weeks; 1, 3, and 6 months postoperatively were compared among the surgical groups using a mixed-effects regression model. The postoperative IOP (p<0.0001) and medication use were significantly (p<0.0001) lower in the LEC and EXP groups than with μLOT for up to 6 months postoperatively. The ACF differed significantly (p=0.0004) among groups; the ACF was significantly higher (p=0.0097, post-hoc Student's t-test) with μLOT (33.6±52.8 pc/msec) than the EXP (15.7±19.9 pc/msec) at 2 weeks and was significantly (p=0.0111, post-hoc t-test) lower with μLOT (7.9±2.0 pc/msec) than LEC (12.0±6.1 pc/msec) at 6 months. Considering our observation, although its clinical significance is unclear, not all MIGS are minimally invasive regarding early postsurgical inflammation.


Psychometric properties of the Chinese Breast Cancer Screening Beliefs questionnaire.
Breast cancer is the most common type of cancer in women. The Chinese Breast Cancer Screening Beliefs (CBCSB) questionnaire was developed to measure Chinese-Australian women's beliefs, knowledge and attitudes about breast cancer and breast cancer screening. To assess the psychometrics of the modified version CBCSB in a Chinese-speaking community. Two items in the original CBCSB were removed because they were not applicable to the Hong Kong setting, which resulted in an 11-item CBCSB. A total of 730 women aged at least 18 years old without a history of breast cancer self-completed the questionnaire. Based on 730 Chinese-speaking women with mean age of 43 years, the three hypothesized subscales of the CBCSB had Cronbach's alpha ranging between 0.69 and 0.75. Non-responses to the items were at most only 3.3%. The corrected item-total correlations for the hypothesized subscales ranged from 0.35 to 0.63 and were higher than those for the competing subscales. As hypothesized, the frequency of health practices was significantly associated with all subscales of the CBCSB. Confirmatory factor analysis showed an adequate fit for the hypothesized three-factor structure of the modified CBCSB questionnaire. The 11-item CBCSB questionnaire was culturally appropriate, reliable and valid in a Chinese-speaking community setting. It can be used to gain understanding of Chinese-speaking women's beliefs, knowledge and attitudes about breast cancer and breast cancer screening. It may also serve as an outcome for the development and assessment of public education programs for breast cancer screening.


Islet cell antibodies: variable immunostaining of pancreatic islet cells and carcinoid tissue.
Islet cell antibodies (ICA) in sera of patients with autoimmune diabetes mellitus generally stain not only the insulin-producing beta cells but also the non-beta cells of the islets of Langerhans. The antibodies have been reported to react also with the chromaffin cells of carcinoid tissue. In the present study, we examined in detail the reactivity of 10 ICA-positive sera of patients with new onset insulin-dependent diabetes mellitus (IDDM) and two sera of patients with stiff-man syndrome. The sera were analysed by immunofluorescence and by immunoperoxidase staining of human islets as well as by immunoprecipitations using 35S-methionine labelled rat islet lysates. In addition, immunofluorescence analyses of carcinoid tissues were carried out. Eight of the 10 IDDM-positive sera reacted with all islet endocrine cells, whereas two sera showed staining restricted to the beta cells, as did the two sera of the patients with stiff-man syndrome. All beta cell 'selective' sera, but only 6 of 8 'whole' islet positive sera, immunoprecipitated the 64.kDa glutamic acid decarboxylase (GAD) antigen. The staining of carcinoid tissue was variable and did not correlate with the 'whole' or 'selective' staining pattern of islets. The data underline a heterogeneity of ICA and indicate the presence of a separate, non-GAD antigen in islet cells. It is possible that in future studies, a resolution of ICA titres with respect to different types of islet cellular reactivity might provide insights into the pathogenesis of IDDM and improve the prognostic implications of antibody determinations.


Protective effect of N-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells.
Nicardipine hydrochloride (NIC) injection has been widely used for emergency treatment of abnormally high blood pressure. However, NIC injection often causes severe peripheral vascular injury. The purpose of the present study was to reduce the NIC-induced cell injury in human vascular endothelial cells by use of clinical agents. The mechanism of NIC-induced cell injury was evaluated by time-lapse microscopic imaging, autophagosome staining with monodansylcadaverine, immunostaining of light chain 3 isoform B (LC-3B) and assessment of cell viability after exposure to NIC with or without an inhibitor of autophagosome formation (3-methyladenine, 3-MA). Results from autophagosome labeling and immunostaining of LC-3B revealed an increase of autophagosomes and LC-3B in NIC-treated cells. NIC-mediated reduction of cell viability was inhibited by 3-methyladenine. Moreover, we found that N-acetylcysteine (NAC) reduced NIC-induced cell injury in human vascular endothelial cells. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy with NAC could contribute to the reduction of NIC-induced vascular injury.


Systems Genetics Analysis of Iron and Its Regulation in Brain and Periphery.
In this contribution, we demonstrate the utility of the systems genetics-systems biology approach to the study of iron regulation while employing a comprehensive database. We describe our work in iron regulation in the brain and periphery under normal iron and iron-restricted dietary conditions in the BXD family of recombinant inbred mouse strains. Using multiple measures, we showed wide variation among the strains in the effect of being fed an iron-restricted diet for 100 days in every measure from brain and from the periphery. All data were entered into GeneNetwork ( www.genenetwork.org ), a database that contains genotypic, phenotypic, and gene expression data (Rosen et al., Methods Mol Biol 401:287-303, 2007). Using this resource, we were able to ask the following four questions concerning possible candidate genes underlying our measures: (1) what is the range of response for each of the measures? (2) Does the pattern of variability show continuous (additive genetic) or discrete (Mendelian) distribution across strains? (3) Are there genetic markers that are associated with the variability in the measures? (4) Are there genes in near the markers that contain associated allelic differences, and whose expression is related to the variability in the measures? Other questions that we could address include: (5) what is the association among the measures between the sexes? (6) What is the association among the measures, e.g., is liver iron status under the diets related to brain iron? (7) What is the relationship between our measures and other phenotypic parameters-i.e., is there an association between our brain iron measures and neurochemical phenotypes extant in the database? And finally, (8) are there gene networks that underlie single or combined measures?


Maternal and paternal factors associated with congenital syphilis in Shenzhen, China: a prospective cohort study.
Maternal and paternal factors create considerable obstacles to the elimination of congenital syphilis (CS). A clear understanding of maternal and paternal factors is important in order to define interventions in every community. This study aimed to investigate the maternal and paternal factors associated with CS. A prospective cohort study was conducted from April 25, 2007 to October 31, 2012 at the Shenzhen Center for Chronic Disease Control and Prevention (SCCDC) in China. We screened 279,334 pregnant women and identified 838 women with syphilis. Finally, a total of 360 women with syphilis were included for analysis. At the end of follow-up, 34 infants [9.4 %, 95 % confidence interval (CI): 6.8-12.9 %] were diagnosed with CS. Following adjustment for confounders, maternal history of syphilis [adjusted risk ratio (aRR) = 0.21], prenatal care (aRR = 0.12), and complete treatment (aRR = 0.22) reduced the risk of infants being infected. Every two-fold increase of titer of non-treponemal antibodies (aRR = 1.88), early stage of syphilis (aRR = 9.59), a shorter length of time between the end of the first treatment to childbirth (aRR = 5.39), and every week of delay in treatment (aRR = 2.25) for maternal syphilis as well as paternal history of cocaine use (aRR = 6.28) and positive (aRR = 3.30) or unknown (aRR = 2.79) status of syphilis increased the risk of infants being infected. CS also increased the risk (aRR = 8.02) of neonatal death. Maternal and paternal factors constituted two separate profiles associated with CS. To become more effective, future strategies for the prevention of CS should be targeted to each profile.


Interrogation of sphingosine-1-phosphate receptor 2 function in vivo reveals a prominent role in the recovery from IgE and IgG-mediated anaphylaxis with minimal effect on its onset.
Autocrine stimulation of S1PR2, a receptor for the lipid mediator sphingosine-1-phosphate (S1P), has been implicated in mast cell degranulation to IgE/antigen (Ag) although, paradoxically, its ligand cannot trigger substantial degranulation. Additionally, the in vivo role of S1PR2 in the overall allergic responses is unclear since S1PR2 was reported to be required for the onset of systemic anaphylaxis by IgE/Ag but, in apparent contradiction, also for the recovery from histamine-induced anaphylaxis in a mast cell independent manner. Here, we sought to clarify the role of S1PR2 in mast cell degranulation and in IgE and IgG-mediated anaphylaxis. Lack of S1PR2 reduced IgE/Ag-induced degranulation in in vitro experiments with mucosal mast cells, but had no effect on connective tissue type mast cells. This latter response correlated with a lack of involvement of S1PR2 in the onset of non-lethal IgE/Ag-mediated systemic and cutaneous anaphylaxis. However, S1pr2(-/-) mice were slow to recover (or did not recover) from FcɛRI-mediated anaphylaxis, an outcome that mirrored their known impairment in histamine clearance due to defective vascular tone. A minor role for S1PR2 in mast cell degranulation was uncovered upon engagement of low affinity receptors for IgG and in the onset of IgG-mediated anaphylaxis. Our findings show that S1PR2 is dispensable for initiating IgE/Ag-mediated connective tissue mast cell degranulation and anaphylaxis, but it is required for normal recovery from anaphylaxis.


Adrenal lesions with heterogeneous suppression on chemical shift imaging: clinical implications.
To investigate the frequency and significance of adrenal lesions that demonstrate heterogeneous suppression on chemical shift magnetic resonance imaging (MRI). A retrospective search of adrenal lesions identified on MR from November 1997-July 2001 was performed. The adrenal lesions were classified as having suppression typical for an adenoma, nonsuppression, or atypical heterogeneous suppression. Lesions with heterogeneous suppression were further reviewed. Follow-up for the heterogeneous lesions consisted of imaging studies or pathology from surgical excision. Adrenal lesions were identified in 242 patients. Heterogeneously suppressing lesions were seen in 34 (14%) patients. Several different patterns of heterogeneous suppression were identified. Imaging or pathologic follow-up was available for 18 of the heterogeneously suppressing lesions (one patient had both). Fifteen patients with follow-up imaging showed stability of the lesion over a significant interval, suggesting a benign lesion. Pathology was available for four patients revealing two patients with adenomas and two patients with nodular hyperplasia. Thus, all 18 patients with heterogeneous suppression had a benign lesion. Adrenal lesions that have a heterogeneous pattern of suppression on out-of-phase chemical shift MR images are a common finding. Our small series suggest that these lesions are probably benign.


Associations between anthropometric indices of adiposity and atherogenic risk factors in Japanese working women aged 21-40 years.
This study was conducted to explore whether anthropometric indices of obesity are associated with atherogenic risk factors in young adult working women in Japan. The subjects were 492 women in an occupational setting. Predictor variables were body mass index (BMI), the sum of triceps and subscapular skinfold thickness (SFT), and the waist to hip ratio (WHR). Outcome variables were serum total cholesterol, triglyceride and blood pressures. The average age of the subjects was 26.3 (SD 3.9) years. The upper quartiles of BMI and SFT were significantly associated with all atherogenic risk factors, while the upper quartiles of WHR were not. Multiple comparisons revealed the 4th quartiles of BMI (> 22.25) and SFT (> 39 mm) to have significantly higher values for all atherogenic risk factors. We found that BMI and skinfold thickness were more relevant to the prediction of atherogenic risk factors than WHR in young adult Japanese women.


Assessment of reclaimed municipal wastewater application on rice cultivation.
Field research was carried out to assess the effects of the application of reclaimed municipal wastewater on rice cultivation in Thessaloniki, Greece during a 2-year period (1999-2000). Effects on production cost, soil composition, and health risk were examined. A randomized complete block design was used for the paddy field with three treatments and four replicates. The treatments were (1) river irrigation water with N-P fertilization, (2) reclaimed wastewater irrigation with surface N fertilization, and (3) reclaimed wastewater irrigation without fertilization. The results showed that the total production cost decreased 8.8% and 11.9% by applying the second and third treatments, respectively, compared to the first treatment, without significant differences in the agronomic and rice quality traits. Soil composition showed discrepancies between the 2 years and the three treatments, whereas the pathogens of the reclaimed wastewater and rice tissues posed a low human risk when taking the needed precautions.


Self-assembly of highly ordered micro- and nanoparticle deposits.
The evaporation of particle-laden sessile droplets is associated with capillary-driven outward flow and leaves nonuniform coffee-ring-like particle patterns due to far-from-equilibrium effects. Traditionally, the surface energies of the drop and solid phases are tuned, or external forces are applied to suppress the coffee-ring; however, achieving a uniform and repeatable particle deposition is extremely challenging. Here, we report a simple, scalable, and noninvasive technique that yields uniform and exceptionally ordered particle deposits on a microscale surface area by placing the droplet on a near neutral-wet shadow mold attached to a hydrophilic substrate. The simplicity of the method, no external forces, and no tuning materials' physiochemical properties make the present generic approach an excellent candidate for a wide range of sensitive applications. We demonstrate the utility of this method for fabricating ordered mono- and multilayer patternable coatings, producing nanofilters with controlled pore size, and creating reproducible functionalized nanosensors.


Corrigendum: Accident injuries of children and adolescents in Germany. Results of the cross-sectional KiGGS Wave 2 study and trends.
[This corrects the article DOI: 10.17886/RKI-GBE-2018-086.2.].


Is hypertension a predictor for heart failure? A cross cultural comparison over a 10-year period.
This was a retrospective cohort study to assess the effect of hypertension (HTN) among Qatari and Asian patients admitted to the Hamad General Hospital in Qatar with heart failure (HF) and to identify risk factors that contribute to the development of HF in HTN patients in the State of Qatar. A total of 20,856 patients were treated during the 10-year period; 8446 were Qataris and 60% were male. Among the total Qatari patients admitted with HF (n=2342), 52.4% had HTN. The incidence of HTN was slightly higher in males than in females (50.4 vs. 49.6%; p<0.001). Significantly more HTN patients had diabetes mellitus (DM) (p<0.001) and hypercholesterolemia (p<0.001). There was also a significant difference between Qatari and Asian HTN patients in respect of their age (p<0.001) and gender (p<0.001). Qatari hypertensive patients were more likely to have DM (p<0.001). HTN and DM were the most common risk factors for HF.


Ruby Wax announces mental health cafes where people can share stories.
Comedian Ruby Wax is fronting a project that will introduce fortnightly mental health chat sessions at some Marks and Spencer store cafes.


Half or full core hole in density functional theory X-ray absorption spectrum calculations of water?
We analyze the performance of two different core-hole potentials in the theoretical modeling of XAS of ice, liquid and gas phase water; the use of a full core-hole (FCH) in the calculations, as suggested by Hetenyi et al. [B. Hetenyi, F. De Angelis, P. Giamozzi and R. Car, J. Chem. Phys., 2004, 120(18), 8632], gives poor agreement with experiment in terms of intensity distribution as well as transition energies, while the half core hole (HCH) potential, in the case of water, provides a better compromise between initial and final state effects, leading to good agreement with the experimental data.


Origin of symptoms in diverticular disease.
A significant number of patients with colonic diverticula experience unexplained, recurrent, short-lived but often debilitating abdominal pain and alteration in bowel habit. Such patients account for many medical consultations every year but, as our understanding of the cause of their symptoms remains imperfect, treatment options are limited. This article reviews the possible mechanisms that may be responsible for the symptoms of diverticular disease. Medline and Science Citation Index searches were performed to locate English language articles relating to colonic diverticula and symptoms published between January 1966 and July 2002. Manual cross-referencing was also performed and some historical articles were included. Several theories now exist about the mechanisms underlying the symptoms of diverticular disease. Initial studies suggested that they may be due to alterations in the intracolonic pressure, extrapolating earlier thoughts on the likely pathogenesis of diverticula. It seems more likely, however, that several inter-related processes, such as muscular dysfunction, visceral hypersensitivity and inflammation, are involved in symptom generation.


Gold nanoprism/Tollens' reagent complex as plasmonic sensor in headspace single-drop microextraction for colorimetric detection of formaldehyde in food samples using smartphone readout.
In this work, an assay with high sensitivity and selectivity for the detection of formaldehyde (FA) is presented. The assay applied a gold nanoprism/Tollens' reagent (Au-np/TR) complex as the sensor used in headspace single-drop microextraction (HS-SDME). A surface plasmon resonance signal enhancement as well as color change was caused by the formation of Au@Ag-np after a redox reaction between FA and TR during the HS-SDME process. With the utilization of smartphone nanocolorimetry (SNC), the FA could be detected and quantified. For HS-SDME-SNC, a linearity calibration curve ranging from 0.1 to 100 μM was obtained, and the limit of detection was determined to be 30 nM. Successful attempts to determine FA were demonstrated by analysis of the analyte in (adulterated) raw food samples (octopus and chicken flesh). Matrix effects from real samples were avoided by using HS-SDME, and only a 3-μL droplet of solvent was needed in the assay.


Inadequacy of activity time as a niche difference: the case of diurnal and nocturnal raptors.
It has been assumed that differences in activity time of diurnal (Falconiform) and nocturnal (Strigiform) raptors reduce competition for food by giving them access to different prey resources. Consequently, dietary similarity should be greater between synchronously active raptors (either diurnal or nocturnal) than between asynchronous ones (diurnal versus nocturnal). Using five collective raptor assemblages I tested the hypothesis that the statistical distribution of food overlaps between synchronous raptors (Falconiform x Falconiform and Strigiform x Strigiform combined) should be composed of larger figures than that obtained from asynchronous pairs (Falconiform x Strigiform). Both a conservative (Kolmogorov-Smirnov test with Chisquare approximation) and a powerful (Mann-Whitney U-test) nonparametric procedure were used to deal with the problem of the degrees of freedom to be assigned to non-indepedent observations such as overlaps. The tests consistently failed to reject the null hypothesis, thus pointing to the inadequacy of temporal segregation as a means to partition prey resources between diurnal and nocturnal raptors. I propose that this can be accounted for by two factors, acting singly or in combination: a) that both Falconiforms and Strigiforms extend their hunting activities to crepuscular hours thus sharing prey of that activity period; b) that reputedly diurnal and nocturnal prey become vulnerable to predators of asynchronous hunting time by extending their activities in the field. Based on records of interspecific territoriality, prevation, and interference competition I propose that the evolution of nocturnality in Strigiforms might be more clearly related to interference interactions rather than exploitation competition with Falconiforms.


Emergence of National Nutrition Policy in the Lao People's Democratic Republic: an analysis of collaborations between governmental and external actors.
In most developing countries, addressing malnutrition involves a coalition of stakeholders that includes the government and international development partners. This study explores the evolution of the malnutrition actor coalition landscape before and after the emergence of the National Nutrition Policy in the Lao People's Democratic Republic (Lao PDR) in 2008. A qualitative study was conducted based on the theory of coalition structuring. Twenty semi-structured interviews were performed with representatives of national and international organisations involved in addressing malnutrition in Lao PDR. The information obtained from the interviews was complemented by an analysis of relevant documents dating back to 1990. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using NVivo 11 software and the diagrams of collaboration drawn by the participants were turned into a visual collaboration map using SocNetV software. We relied on various types of triangulation to increase the analysis's credibility, reliability, and confirmability. The results showed that before the emergence of the National Nutrition Policy, three coalitions representing the health, agriculture, and education sectors coexisted. These colalitions worked largely in silos, although with some interactions when deemed necessary mainly by United Nations agencies. The emergence of the National Nutrition Policy provided the government with an effective political tool for coalescing the three coalitions into a unique coalition involving all major stakeholders in the nutrition field. All three forces that incite actors to collaborate inside a coalition according to the theory of coalition structuring (transactions, control, intangible factors) were mobilised in the creation of the single coalition. Combating malnutrition is a government priority in the Lao PDR. The current study showed that the National Nutrition Policy in Lao PDR has led to a significant evolution in the malnutrition coalition landscape, resulting in improved collaboration among stakeholders. This finding highlights the effectiveness of public policies in facilitating intersectoral activities to tackle complex problems, such as malnutrition.


Antiplatelet and antithrombotic activity of indole-3-carbinol in vitro and in vivo.
Indole-3-carbinol, a natural compound found in cruciferous vegetables, is known to have anticancer activity. In the present study, the antiplatelet and antithrombotic activities of indole-3-carbinol were investigated in vitro and in vivo. Indole-3-carbinol significantly inhibited collagen-induced platelet aggregation in human platelet rich plasma (PRP) in a concentration-dependent manner. Indole-3-carbinol significantly inhibited fibrinogen binding to the platelet surface glycoprotein IIb/IIIa (GP IIb/IIIa) receptor by flow cytometric analysis. In addition, the levels of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) in collagen stimulated PRP were significantly inhibited in a concentration-dependent manner by indole-3-carbinol. Furthermore, indole-3-carbinol dose-dependently suppressed the death of mice with pulmonary thrombosis induced by intravenous injection of collagen and epinephrine. These results suggest that indole-3-carbinol can be a potent antithrombotic agent with antiplatelet activity through the inhibition of GP IIb/IIIa receptor and thromboxane B2 formation.


Psychometric properties of the Glaucoma Quality of Life-15 questionnaire: Use of explanatory factor analysis.
The purposes of this study were to validate the Persian translation of the Glaucoma Quality of Life-15 (GQL-15) questionnaire, evaluate its psychometric properties, and identify new composite items and item numbers. This cross-sectional study was conducted from August to November 2016, at the Glaucoma Clinic of the Ophthalmology Department at Shiraz University of Medical Sciences, Iran. One hundred ninety patients with glaucoma were enrolled. Habitual-corrected visual acuity (HCVA), intraocular pressure (IOP), slit-lamp biomicroscopy, fundus exam, and mean deviation (MD) of the visual field were recorded in the course of clinical examination by glaucoma professional. Psychometric properties, i.e. test-retest reliability, internal consistency, content validity, and construct validity were evaluated with factor analysis. Based on the Disc Damage Likelihood Scale (DDLS), patients were stratified to mild, moderate, and severe disc damage. The association between the GQL-15 scores and disease severity (mild, moderate and severe) were evaluated by the analysis of variance (ANOVA). Of 190 eligible glaucoma patients, reliable clinical data were available for 140 participants. Mean age [standard deviation (SD)] of the patients was 58.7 (13.3) years. Cronbach's α coefficient ranged from 0.74 to 0.91, and the correlation coefficient for total score was 0.53. The content validity ratio (CVR) was 0.91 based on evaluations in expert panel. Exploratory factor analysis (EFA) based on eigenvalue higher than one identified two factors after varimax rotation for the GQL-15 which explained 66.5% of the total variance. Discriminant validity analysis disclosed statistically significant differences in mean quality of life scores between levels of disease severity. The Persian version of the GQL-15 is a reliable and valid questionnaire for use in glaucoma clinics as a complementary tool for evidence-based decision-making.


DNA synthesis for true random number generation.
The volume of securely encrypted data transmission required by today's network complexity of people, transactions and interactions increases continuously. To guarantee security of encryption and decryption schemes for exchanging sensitive information, large volumes of true random numbers are required. Here we present a method to exploit the stochastic nature of chemistry by synthesizing DNA strands composed of random nucleotides. We compare three commercial random DNA syntheses giving a measure for robustness and synthesis distribution of nucleotides and show that using DNA for random number generation, we can obtain 7 million GB of randomness from one synthesis run, which can be read out using state-of-the-art sequencing technologies at rates of ca. 300 kB/s. Using the von Neumann algorithm for data compression, we remove bias introduced from human or technological sources and assess randomness using NIST's statistical test suite.


Neutralizing RGMa with Elezanumab Promotes Cerebroprotection and Recovery in Rabbit Middle Cerebral Artery Occlusion.
Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients. In this preclinical study, we evaluated whether elezanumab, a human anti-RGMa monoclonal antibody, could improve neuromotor function and modulate neuroinflammatory cell activation following AIS with delayed intervention times up to 24 h using a rabbit embolic permanent middle cerebral artery occlusion model (pMCAO). In two replicate 28-day pMCAO studies, weekly intravenous infusions of elezanumab, over a range of doses and TTIs of 6 and 24 h after stroke, significantly improved neuromotor function in both pMCAO studies when first administered 6 h after stroke. All elezanumab treatment groups, including the 24 h TTI group, had significantly less neuroinflammation as assessed by microglial and astrocyte activation. The novel mechanism of action and potential for expanding TTI in human AIS make elezanumab distinct from current acute reperfusion therapies, and support evaluation in clinical trials of acute CNS damage to determine optimal dose and TTI in humans. A: Ramified/resting astrocytes and microglia in a normal, uninjured rabbit brain. B: Rabbit pMCAO brain illustrating lesion on right side of brain (red), surrounded by penumbra (pink) during acute phase post stroke, with minimal injury to left brain hemisphere. Penumbra characterized by activated astrocytes and microglia (region in crosshair within circle), with upregulation of free and bound RGMa. C: Elezanumab binds to both free and bound RGMa, preventing full activation of astrocytes and microglia. D: Elezanumab is efficacious in rabbit pMCAO with a 4 × larger TTI window vs. tPA (6 vs. 1.5 h, respectively). In human AIS, tPA is approved for a TTI of 3-4.5 h. Elezanumab is currently being evaluated in a clinical Ph2 study of AIS to determine the optimal dose and TTI (NCT04309474).


Biomechanical foot therapy.
The podiatrist specializing in biomechanical therapy must begin with a solid foundation of standardized definitions in order to discuss theories of mechanical foot treatment as they have been presented and developed over the past century. Equally important, is the building of a working knowledge and familiarity with the wide variety of available materials and their diverse properties. In addition, in order to arrive at an accurate biomechanical diagnosis, the clinician must evaluate the patient from static, dynamic, and radiographic perspectives. One must also keep current in regard to various technological advances in casting and fabrication of orthotic devices, as well as in new developments in biomechanical theory and associated therapy. It also must be kept in mind that functional foot orthoses are not 100 per cent efficient, therefore, their shape, fabrication, and composition should all be devised and prescribed with specific goals for total body mechanics.


HipScreen mobile app for the measurement of hip migration percentage in children with cerebral palsy: Accuracy, reliability, and discriminatory ability.
To assess the accuracy, reliability, and discriminatory ability of a mobile app for measurement of migration percentage in hip surveillance radiographs of children with cerebral palsy (CP). The free mobile app HipScreen (www.hipscreen.org) was utilized by a diverse group of users to measure the migration percentage of 40 hips at two time points after completing an online tutorial and competency test. The mean absolute error (MAE) was calculated against the reference standard obtained on a radiology workstation. Statistical analyses included linear regression, intraclass correlation coefficient (ICC), and area under receiver-operating characteristic curve (AUC). Thirty-seven users completed the study, with 30 having a healthcare professional background, but only 15 with x-ray interpretation expertise. The overall MAE of migration percentage measurement using the HipScreen app was 5.72% (95% confidence interval [CI]: 5.38-6.06), with good reliability between time points (ICC = 0.83). With a migration percentage less than 30% considered as a positive case, the HipScreen app had a sensitivity of 94% (95% CI: 87-97), specificity of 66% (95% CI: 61-77), and an AUC of 0.92 (95% CI: 0.88-0.96). Users from a broad range of backgrounds can utilize the HipScreen app to measure hip surveillance radiographs with clinically acceptable accuracy, reliability, and discriminatory ability. The HipScreen app can accurately and reliably measure migration percentage. As a screening tool, HipScreen has excellent sensitivity and discriminatory ability. A broad range of HipScreen users achieve clinically acceptable performance.


Models of thrombosis.
A critical review is presented on animal models of thrombosis. After a glance at the pathogenesis of clinical thrombosis and its multifactorial character, the classification, aims and a suggested rational design of thrombosis models are advanced and illustrated by some examples of an attempted solution of this complex problem.


Modified use of methylene blue in the tissue compression technique to detect sarcocysts in meat-producing animals.
Sarcocystosis in meat-producing animals is a major cause of reduced productivity in many countries, especially those that rely on agriculture. Although several diagnostic methods are available to detect sarcocystosis, many are too time-consuming for routine use in abattoirs and meat inspection centers, where large numbers of samples need to be tested. This study aimed to compare the sensitivity of the methylene blue tissue preparation, unstained tissue preparation and nested PCR in the detection of sarcocysts in tissue samples. Approximately three-fold more sarcocysts were detected in methylene blue-stained tissue compared to unstained controls (McNemar's test: P<0.01). Test sensitivity was comparable to that of the gold standard for sarcocyst detection, nested polymerase chain reaction. These results suggest that methylene blue can be used in tissue compression as a rapid, safe, and inexpensive technique for the detection of ruminant sarcocystosis in abattoirs.


The form of the human pupil.
The purpose of this study was to characterize the form of the pupil in normal human subjects. Using a modified slitlamp, photographs of pupils were taken in steady illumination and 10-20 sec after darkness. Transparencies were projected and digitized, and the pupil margin was represented as a circular Fourier series. Best-fit ellipses were also determined. The placement of the pupil relative to the limbus was determined in a number of subjects. Results from 23 subjects indicated that in both darkness and light, average pupil noncircularity was 0.0166. (A value of 0.0200 is easy to detect with the unaided eye from the photographs.) On average, the best-fit ellipse accounted for about half of the noncircularity (59.6% in darkness; 47.7% in light). Most of the contribution to shape was made by the first 4 or 5 harmonics. Shapes were usually stable within a session and could remain fairly stable for at least a year; however, shapes for different subjects were not very similar, especially in the light. (Average pairwise similarity: 0.106 in darkness; 0.034 in light; similarity can have values from -1 to 1.) For a given subject, shapes in light and dark were often fairly similar (average similarity 0.260), but there were systematic differences: in eyes where the ellipse contributed > 20% of noncircularity, ellipse major axes clustered around vertical in darkness, and horizontal in light, implying greater contraction near the vertical meridian. Even pupils with little elliptical contribution turned out to contract more near the vertical meridian. There was some tendency for left and right eyes of an individual to show mirror symmetry of shape. In the dark, pupils were located 0.27 +/- 0.09 mm nasal and 0.20 +/- 0.15 mm superior to the limbus center, and usually moved slightly further nasal or superior in the light. Noncircularity increased with age (0.0015/decade). It was concluded that pupils show individuality of shape, with significant regularities within and across subjects.


A spatiotemporal study on contamination and bioaccumulation of heavy metals in sediment and cyprinid fish (Capoeta razii) from Telar River, Iran.
The concentrations of heavy metals (Cr, Cd, Ni, and Pb) were investigated in sediment and cyprinid fish (Capoeta razii) from Telar River, Iran in spring, summer, and autumn. Mean concentration of metals in fish and sediment over the seasonal sampling was as follows: Cr > Ni > Pb > Cd. Metal deposition in sediment was higher than their bioaccumulation in fish tissue. Unlike sedimentary metals, the tissue-content of Pb and Cr varied seasonally. Enrichment Factor (EF) values of Cr and Ni showed partial enrichment, implicating the role of anthropogenic inputs, while Pb was derived from natural weathering. When considering Pollution Load Index (PLI), an uneven temporal and spatial distribution of contamination was observed in sediment with moderate contamination level in spring and summer and no pollution in autumn. Tissue-contents of Pb, Cr, and Cd were below permissible limits while a higher risk level of Ni was noted for human consumption.


Reduction of adhesion formation by intraperitoneal administration of Arg-Gly-Asp-containing peptides.
To evaluate the ability of a variety of peptides containing the Arg-Gly-Asp (RGD) sequence to reduce the formation of intraperitoneal adhesions in a rabbit model. Prospective, randomized, double-blinded study. University-based laboratory. New Zealand white rabbits. Administration of RGD-containing peptides. Reduction of adhesion information. In initial studies, two RGD-containing peptides (3 or a 10 amino acid peptides) were administered via Alzet miniosmotic pump to the site of injury. Administration of either of these peptides significantly reduced adhesion formation, but the larger peptide was more efficacious and reduced variability in the response. Further studies then were conducted with RGD-containing peptides five to six amino acids in length. Administration of these peptides also significantly reduced adhesion formation in a standard rabbit model. Administration of three of these peptides in a viscous vehicle at the end of surgery was also effective in reducing adhesion formation. The most effective combination tested was RGD-containing peptide Gly-dser-Arg-Gly-Asp-Ser-Pro in a viscous, cremophor-containing vehicle. These studies demonstrate that administration of an RGD-containing peptide was effective in reducing adhesion formation in this model.


Diagnosis and management of gastric carcinoid tumour with hepatic metastases.
The gastric carcinoid tumour is a rare variety of carcinoid characterized by atypical production of 5-hydroxytrytophane rather than serotonin. In our case it is likely that other polypeptides are the source of symptoms, though these are as yet unidentified. Since surgery was not feasible in the management of the hepatic metastases, we have used a non-operative technique of embolization to destroy the carcinoid secondaries and ameliorate symptoms. The patient tolerated this procedure well and improved dramatically, with remarkable diminution of liver size and the disappearance of all carcinoid symptoms. Destruction of hepatic secondaries without recourse to surgery has obvious advantages in severely ill patients. Careful attention should, however, be paid to the large quantities of pharmacologically active compounds released from the liver by the procedure.


Twenty-First Century Trends in Girls' Violence and the Gender Gap: Triangulated Findings from Official and Unofficial Longitudinal Sources.
Recent media and academic reports project rising levels of girls' violence and a narrowing gender gap. In response, the authors investigate 21st century trends in girls' violence as reported across multiple official and unofficial longitudinal sources: Uniform Crime Reports (UCR) arrest and juvenile court referral statistics; National Crime Victimization Survey (NCVS) victimization data; and three sources of self-reported violent offending-Monitoring the Future, Youth Risk Behavior Surveillance System, and National Survey on Drug Use and Health. Augmented Dickey-Fuller time-series tests and intuitive plot displays show much overlap in each source's portrayal of trends in girls' violence and the youth gender gap. Specifically, there is no systematic change in the gender gap for homicide, aggravated assault, nor the violent crime index. However, UCR police arrests and juvenile court referrals show a moderate female-to-male rise for simple assault during the early decades of the 21st century. This rise in official statistics is not borne out in NCVS counts based on victims' reports nor in self-reported violent-offending counts. Net-widening policy shifts and more gender-neutral enforcement have apparently elevated somewhat the arrest proneness of adolescent females for simple assault. Rather than girls having become more violent, triangulating data sources revealed a decline in both girls' and boys' violence levels, considerable similarity in their violent-offending trends, and little or no systematic change in the gender gap.


Internal hernia after laparoscopic-assisted proximal gastrectomy with jejunal interposition for gastric cancer: a case report.
Internal hernia after gastrectomy is a rare complication. It can progress rapidly to vascular disturbance, necrosis, and perforation, therefore early diagnosis and surgical treatment is essential. We present a case of internal hernia following laparoscopic-assisted proximal gastrectomy with jejunal interposition reconstruction in a 68-year-old man, who presented with acute abdominal pain and vomiting. Computed tomography showed a whirl sign, ascites, and a closed-loop formation of the small intestine. We diagnosed an internal hernia and performed emergency surgery. Laparotomy revealed chyle-like ascites and extensive small intestine with poor color. We recognized that about 20 cm of jejunum from the ligament of Treitz was strangulated behind the pedicle of the jejunum lifted during laparoscopic-assisted proximal gastrectomy. We relieved the strangulation, whereupon the color of the strangulated intestine was restored. Therefore, we did not perform intestinal resection and reconstruction. Finally, we fixed the jejunal pedicle and mesentery of the transverse colon. We report this case as there are few reported cases of internal hernia after laparoscopic-assisted proximal gastrectomy.


Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules.
Development of therapeutics for retinal disease with improved durability is hampered by inadequate understanding of pharmacokinetic (PK) drivers following intravitreal injection. Previous work shows that hydrodynamic radius is correlated with vitreal half-life over the range of 3 to 7 nm, and that charge and hydrophobicity influence systemic clearance. Better understanding the molecular attributes affecting vitreal elimination half-life enables improved design of therapeutics and enhances clinical translatability. Impacts of charge and hydrophobicity on vitreal PK in the rabbit were systematically assessed using antibody and antibody fragment (Fab) variant series, including ranibizumab, altered through amino acid changes in hypervariable regions of the light chain. The impact of molecule size on vitreal PK was assessed in the rabbit, nonhuman primate, and human for a range of molecules (1-45 nm, net charge -1324 to +22.9 in rabbit), including published and internal data. No correlation was observed between vitreal PK and charge or hydrophobicity. Equivalent rabbit vitreal PK was observed for ranibizumab and its variants with isoelectric points (pI) in the range of 6.8 to 10.2, and hydrophobicities of the variable domain unit (FvHI) between 1009 and 1296; additional variant series had vitreal PK similarly unaffected by pI (5.4-10.2) and FvHI (1004-1358). Strong correlations were observed between vitreal half-life and hydrodynamic radius for preclinical species (R 2 = 0.8794-0.9366). Diffusive properties of soluble large molecules, as quantified by hydrodynamic radius, make a key contribution to vitreal elimination, whereas differences in charge or hydrophobicity make minor or negligible contributions. These results support estimation of vitreal elimination rates based on molecular size in relevant preclinical species and humans.


Adaptive tag switching reinforces the coevolution of contingent cooperation and tag diversity.
Most of the previous studies concerning the similarity-based interaction have assumed that the change of tags just happens in the imitation stage. Individuals actually can adjust their tags whenever the environments related to these tags grow nasty. We institute a spatial model to investigate the effect of the coevolution of tag and strategy on the evolution of cooperation in the context of the Prisoner's Dilemma game. Interactions just happen between tag-identical neighbors. Individuals exploited by defectors change their current tags at a certain cost. The time-scale ratio controls how fast interaction happens relatively to selection. Results show that whenever individuals have enough chance to adapt to the environment, cooperation is greatly improved even for quite large temptation to defect. Intensive exploration reveals that both little and large costs of tag switching can further favor the establishment of cooperation. Our work may add more into the literature concerning games on adaptive networks.


[Biomechanic and electromyography studies of gait in healthy subjects and patients with coxarthrosis].
This report deals with electromyographical-kinesiological examinations of 40 unimpaired subjects and 31 coxarthrosis patients before and 3 months after implantation of an artificial hip joint on a level gaitway 12 m in length with a newly developed computer-controlled measuring system. The accomplished gait analyses served the purpose of determining biomechanical and electromyographical norm values and tolerance levels of unimpaired test subjects and recognizing pathological aberrations as well as determining the success of therapeutical measures. The results showed that despite greater freedom of joint movements observable postoperatively, the muscle actions of the patients did not come to equal those of the unimpaired subject group.


Assessing knowledge of the patient bill of rights in central Saudi Arabia: a survey of primary health care providers and recipients.
Little is known about the implementation of the patient bill of rights (PBR) in Saudi Arabia. Therefore, this study was conducted to explore to what extent health care recipients and providers know about the bill and its implementation. A cross-sectional survey conducted on health care professionals and patients at Primary Health Care Centers in Riyadh, Saudi Arabia, during July 2010. The study employed a self-administered questionnaire to collect data from 500 patients (aged 18 years or older) and 500 health care providers (physicians and nurses) in primary health care (PHC) centers in Riyadh. Data was collected on the respondents' knowledge of the existence and contents of the bill, the extent to which the bill is implemented, and the obstacles that may hinder bill implementation. The data was analyzed and presented in a descriptive fashion. More than three quarters of patients and one third of PHC providers did not know about the existence of the bill. Among those who knew about its existence, about three quarters of patients and almost half of PHC providers had little (or very little) knowledge about the bill contents. In general, patients scored lower means of perception than PHC staff about the implementation of the bill's aspects. PHC staff reported several obstacles that may hinder the implementation of the PBR in Saudi Arabia. Patients and health care providers lack necessary knowledge about the PBR. More dissemination of information about the bill, taking into account the particularities of the Saudi population is needed. Future research is required to establish measures that are effective in ensuring that patients rights are ensured.


Okadaic acid induces apoptosis through the PKR, NF-κB and caspase pathway in human osteoblastic osteosarcoma MG63 cells.
Okadaic acid (OA) is the major component of diarrheic shellfish poisoning toxins and a potent inhibitor of protein phosphatase 1 and 2A. However, the underlying regulatory mechanisms involved in OA-induced cell death are not well understood. In the present study, we examined the effects of OA on apoptosis of MG63 cells by characterizing apoptotic morphological changes of the cells and DNA fragmentation. The roles of double-stranded RNA-dependent protein kinase (PKR), nuclear factor-κB (NF-κB) and caspase in OA-mediated apoptosis in MG63 cells were also examined. Results showed that OA induced cytotoxicity and apoptosis in MG63 cells at IC50 of 75 nM. A functional PKR pathway is required to induce apoptosis in response to OA treatment. Blockade of NF-κB by ammonium pyrrolidinedithiocarbamate (PDTC) resulted in down-regulation of apoptosis. The caspase-3 and caspase-8 inhibitors blocked apoptosis in MG63 cells. In conclusion, our results imply that OA can induce MG63 cell apoptosis through the PKR, NF-κB and caspase pathway.


More than two decades of Apc modeling in rodents.
Mutation of tumor suppressor gene adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/phenotype correlations.


Cartilage palisade tympanoplasty in children and adults: long term results.
To show long-term anatomic and functional results of full thickness cartilage palisade tympanoplasty in children and adults. In 51 patients (56 ears); 9 children (12 ears) and 42 adults (44 ears) full thickness cartilage palisade tympanoplasty and interposition with malleus head autograft was performed. On average 11 years after the tympanoplasty, an otomicroscopy and a tonal audiogram were done to assess anatomic and functional results. Anatomic results of 56 ears: 40 (71.43%) tympanic membranes have no anatomic irregularities; 14 (25.00%) have cartilage resorption (11 of them minor and 3 major resorptions), 2 (3.57%) have secondary perforation. In the group of children all ears tympanic membrane were with no or minor resorption and no perforations. Functional results (51 audiograms performed: in children 12 and in adults 39): pre- and post-operative average pure tone average air-bone gaps were 27.29 ± 10.26 and 10.73 ± 7.90 dB, respectively. In the group of children pre- and post-operative average pure tone average air-bone gaps were 29.44 ± 10.30 and 6.81 ± 3.47 dB, respectively. In the group of adults pre- and post-operative pure tone average air-bone gaps were 26.63 ± 10.30 and 11.93 ± 8.50 dB, respectively. The differences between the two groups preoperatively (z=0.733; p=0.463) and postoperatively are irrelevant (z=1.723; p=0.085). The hearing gain is bigger in children (F=4.788; p=0.033). The full thickness cartilage palisade tympanoplasty with malleus autograft interposition is also nowadays a successful method in solving of an advanced ear pathology also in children.


Iatrogenic hyperhomocysteinemia in patients with metabolic syndrome: a systematic review and metaanalysis.
Metabolic syndrome (MetS) is associated with increased cardiovascular mortality and its management incorporates hypolipidemic, antidiabetic and antihypertensive drugs. However, several classes of these drugs, such as biguanides, fibrates and hydrochlorothiazide have been reported to raise circulating total homocysteine (tHcy) levels. During the last decades, numerous large-scale epidemiological studies have identified Hcy as a moderate independent cardiovascular risk factor. Therefore, drug-induced hyperhomocysteinemia in MetS patients may add one cardiovascular risk factor in these high-risk patients. The present systematic review summarizes data from studies which investigated the effects of the above-mentioned drugs on tHcy, and calculates the treatment effect of each drug class on tHcy levels. We also discuss the underlying pathophysiology and the issues that should be addressed in the future.


Genome duplication effects on functional traits and fitness are genetic context and species dependent: studies of synthetic polyploid Fragaria.
Divergence in functional traits and adaptive responses to environmental change underlies the ecological advantage of polyploid plants in the wild. While established polyploids may benefit from combined outcomes of genome doubling, hybridization, and polyploidy-enabled adaptive evolution, whether genome doubling alone can drive ecological divergence or whether the outcome is genetically variable remains less clear. Using synthetic, colchicine-induced, autotetraploid (4x) plants derived from self-pollinated diploid (2x) seeds, and their colchicine-treated but unconverted diploid (2x.nc) full sibs from two diploid wild strawberry taxa (Fragaria vesca subsp. vesca and F. vesca subsp. bracteata), we examined the effects of genome doubling on functional traits, heat stress tolerance, and fitness components across taxa and maternal families (i.e., genetic families) within taxa. Comparisons between 2x and 2x.nc plants indicated a negligible effect of colchicine treatment on functional traits. Genome doubling increased stomatal length and decreased stomatal density, specific leaf area, and leaf vein density, recapitulating patterns observed in wild polyploid Fragaria. Trichome density, heat stress tolerance, and relative growth rate were not significantly affected by genome doubling. Although clonal reproduction was reduced in response to genome doubling, this effect was strongly genetic-family dependent. The results suggest that genome doubling during incipient speciation alone can generate ecological divergence and variation among genetic lineages. This response potentially allows for rapid short-term evolutionary adaptation and fuels genomic diversity and independent origins of polyploidy.


Risk and predictors of sudden death in cardiac sarcoidosis: A systematic review and meta-analysis.
To evaluate the risk for ventricular arrhythmia (VA) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and determine the prognostic factors. PUBMED, EMBASE and SCOPUS were searched up to 14th April 2020. Studies reporting the incidence of SCD, appropriate ICD therapy in CS patients, or relevant prognostic information in patients having undergone MRI, PET, or programmed electrical stimulation (PES) were included. Nineteen studies consisting of 1247 patients, reported the risk of ICD therapies or SCD over a follow-up period of 1.7-7 years. 22.7% (n = 9; 22.7, 95%CI [16.10-29.36]) of patients in primary and 58.4% (n = 9; 58.42, 95% CI [38.61-78.22]) in secondary prevention cohorts experienced appropriate device therapy or SCD events. 18% (n = 2; 18, 95%CI [14-23]) of patients received ≥5 appropriate therapies. 9 out of 664 patients with confirmed cardiac sarcoidosis but without implanted ICDs died suddenly. 17.9% of patients (n = 4; 17.9, 95%CI [10.80-25.03]) experienced inappropriate device therapy. Positive LGE-MRI and PES were associated with an 8.6-fold (n = 6; RR = 8.60, 95%CI [3.80-19.48]) and 9-fold (n = 5; RR = 9.07, 95%CI [4.65-17.68]) increased risk of VA respectively. Positive LGE-MRI and PET with associated with a 6.8-fold (n = 12; RR = 6.82, 95%CI [4.57-10.18]) and 3.4-fold (n = 7; RR = 3.41, 95%CI [2.03-5.74]) respectively for increased risk of major adverse cardiac events. The risk of appropriate ICD therapy or sudden cardiac death is high in patients with CS. The presence of LGE-MRI and positive electrophysiology study identify patients at increased risk of ventricular arrhythmias. [CRD42019124220].