A novel Fas ligand plays an important role in cell apoptosis of Crassostrea hongkongensis: molecular cloning, expression profiles and functional identification of ChFasL.
Apoptosis regulates normal development, homeostasis, immune tolerance and response to environmental stress by eliminating unwanted or diseased cells, and plays a key role in non-specific immunity of invertebrates. The exogenous pathway mediated by death receptors and death ligands is a very important pathway for cell apoptosis. Death ligands are mainly members of the tumour necrosis factor (TNF) family, of which FasL is an important member. The deep involvement of FasL in vertebrates cell apoptosis and immunity has been reported many times, but there is limited research on the FasL gene in shellfish, and its functional importance in oyster cell apoptosis and immunity remains unclear. The full length of ChFasL was identified and cloned based on the genome of Crassostrea hongkongensis. Quantitative PCR was used to detect the relative expression of ChFasL in different developmental stages and tissues, as well as the changes of relative expression in hemocytes after bacterial infection. The expression position of ChFasL in HEK293T cells was also located by subcellular localization, and the effect of increased recombinant protein content on the activity of reporter genes p53 and p21 was studied by dual-fluorescence reporter gene. Finally, the changes of apoptosis rate in hemocytes after ChFasL silencing was identified by RNA interference technology. We identified a novel FasL gene from C. hongkongensis and named it ChFasL. We found that ChFasL has potential N-linked glycosylation site, a transmembrane domain and a TNF region, which was a typical characteristics of TNF family. ChFasL was expressed in all developmental stages of larvae and in all tissues of oysters. After stimulation by V. alginolyticus or S. haemolyticus, its relative expression in hemocytes increased significantly, suggesting that ChFasL was deeply engaged in the immune response process of C. hongkongensis to external microbial stimulation. The results of subcellular localization showed that ChFasL was mainly distributed in the cytoplasm of HEK293T cells. With the overexpression of the recombinant protein pcDNA3 1- ChFasL, the activity of p53 and p21 significantly increased, showing a positive regulatory effect. Moreover, after dsRNA successfully reduced the relative expression of ChFasL, the apoptosis rate of hemocytes was significantly lower than that the dsGFP group. These results comprehensively confirmed the important role of ChFasL in the apoptosis process of C. hongkongensis, which provided the basis and premise for the in-depth understanding of the immune function of apoptosis in molluscs, and also contributed to the research on the pathogenic death mechanism and disease resistance breeding of marine bivalves.


Communication. Improving RNs' organizational and professional identification in managed care hospitals.
Nurse administrators are searching for an expanded repertoire of strategies to attract and retain qualified nursing staff in today's managed care environment. This study examined hospital registered nurses' interpretations of managed care and the effects of those views on nurses' identification with their employing organization and the nursing profession. Findings show that nurses held greater identification with their occupation than their organization. Significant factors influencing nurses' attachment to both of these reference groups included uncertainty about managed care changes, information received about managed care changes, and effects of managed care on the nursing role. Communication principles and strategies are presented to nurse leaders for use in fostering a stronger organizational affiliation among staff nurses while maintaining a strong identification with the nursing profession.


Effect of chronic central administration of glucagon-like peptide-1 (7-36) amide on food consumption and body weight in normal and obese rats.
Glucagon-like peptide (7-36) amide (GLP-1) acutely inhibits food and water consumption in rats after intracerebroventricular (icv) administration. To assess the potential for desensitization of these effects, we investigated the effects of chronic icv administration of GLP-1 on food consumption and body weight in Sprague-Dawley (SD) rats and Zucker (fa/fa) obese rats. In vitro functional densensitization of the GLP-1 receptor was not observed after overnight exposure of Rin m5F insulinoma cells to GLP-1 at concentrations up to 10 nM. Administration of GLP-1 to SD rats (30 microg icv twice a day for 6 days) resulted in significant reductions in 24-hour food consumption each day (25 +/- 1%). Continuous icv infusion of GLP-1 for 7 and 14 days significantly inhibited cumulative food consumption and reduced body weight in SD rats. In the genetically obese Zucker rat, chronic dosing with GLP-1 (30 microg icv) once a day for 6 days caused significant reductions in food consumption each day and a reduction in body weight. These results indicate that the GLP-1 pathways in the central nervous system controlling food consumption do not desensitize after chronic exposure to GLP-1 and suggest that agonists of the central GLP-1 receptor may be effective agents for the treatment of obesity.


Size and stability of a naturally occurring virus inhibitor.
We recently described a virus inhibitor (contact-blocking virus inhibitor) which was produced spontaneously by untransformed human and murine cells in tissue culture (S. Baron and L. McKerlie , Infect. Immun . 32:449-453, 1981). This contact-blocking virus inhibitor was characterized by broad antiviral activity, high potency, and reversible inhibition of viral attachment. Unlike interferon, the antiviral activity of the contact-blocking virus inhibitor is not species specific. An inhibitor with similar properties can also be demonstrated in many body fluids and surface secretions. We report here studies on the stability of the antiviral species which indicate that it is resistant to denaturation by heat (100 degrees C), acid (pH 2), and alkali (pH 12). The antiviral activity against all viruses tested resides in a low-molecular-weight molecule. The range of characteristics so far determined for the contact-blocking virus inhibitor distinguishes it from other virus inhibitors reported in the literature.


Cystoscopic-guided balloon dilation of a urethral stricture in a female dog.
A 9-year-old, spayed female, Labrador retriever was referred for evaluation of dysuria. Cystoscopic examination revealed a urethral stricture in the proximal urethra that was dilated by use of an angioplasty balloon (Gruntzig angioplasty balloon) under cystoscopic guidance. Following the procedure, the dysuria resolved.


[Ultrasound-guided Sciatic Nerve Block (Pulsed Radiofrequency) for Intractable Cancer Pain Caused by Sacral Bone Metastasis].
We report a case of successful pulsed radiofrequency stimulation of the sciatic nerve for intractable cancer pain caused by sacral bone metastasis of non-small cell lung cancer. A 57-year-old man who suffered from intractable left femoral pain was diagnosed with cancer metastasis to the sacral bone and lumbar spine. Oral oxycodone relieved the pain at rest but he could not walk or remain sitting due to the pain during exercise. Oxycodone rescue or increase did not relieve the pain, but induced drowsiness. Given that sciatic nerve block with mepivacaine was effective, we performed pulsed radiofrequency with ultrasound guidance twice. Pulsed radiofrequency relieved the left femoral pain and he could sit for hours and walk uneventfully. Our finding suggest that ultrasound-guided pulsed radiofrequency of the sciatic nerve effectively relieves intractable left femoral pain caused by sacral bone metastasis.


Microvascular remodeling of nasal mucosa in allergic rhinitis induced by an allergen in Sprague-Dawley rats.
This study aimed to observe microvascular changes in the nasal mucosa of Sprague-Dawley (SD) rats with allergic rhinitis (AR) after persistent exposure to an allergen with fluticasone propionate (FP) treatment. Ninety healthy SD rats were randomly distributed into the control group (A, N = 30), the group with continued exposure to an allergen (B, N = 30), and FP treatment group (C, N = 30). The animals of the persistence group were subjected to persistent exposure to an allergen after 7 weeks of modeling of ovalbumin (OVA) provocation in the nasal mucosa for 16 weeks. At the 8th, 12th, and 16th week after OVA provocation, each group was euthanized at each time point: the FP treatment after OVA provocation, and animals of the control group were not stimulated with OVA and were sacrificed at the same time point. The nasal mucosa of 5 animals from each group was analyzed for the expression of vascular endothelial growth factor (VEGF), and another 5 animals were used to make micro vascular corrosion casts for a scanning electron microscope. The results demonstrate that FP has a strong inhibitory effect on angiogenesis in AR. Inhalation of FP had an antiangiogenic effect through inhibition of VEGF expression but does not completely reverse the remodeling of the nasal mucosa in the short term nor does it have complete control over the expression of VEGF mRNA.


A variance component-based gene burden test.
We propose a novel variance component approach for the analysis of next-generation sequencing data. Our method is based on the detection of the proportion of the trait phenotypic variance that can be explained by the introduction of a new variance component that accounts for the local gene-specific departure of the empirical kinship relationship matrix, estimated from single-nucleotide polymorphism (SNP) genotypes, from their theoretical expectation based on the genealogical information in the pedigree. We tested our method with simulated phenotypes and imputed SNP genotypes from the Genetic Analysis Workshop 18 data set. We observed considerable variation in the differences between theoretical and gene-specific kinship estimates that proved to be informative for our test and allowed us to detect the MAP4 causal gene at a genome-wide significance level. The distribution of our test statistic show no inflation under the null hypothesis and results from a random set of genes suggest that the detection of MAP4 is both sensitive and specific. The use of 2 different strategies for the selection of the SNPs used to derive the gene-specific empirical kinship relationship matrices provides us with suggestive evidence that our method is performing as an empirical test of linkage.


[Tamsulosin in the treatment of patients with ureteroliths of the lower third of the ureter clinical and pharmacoeconomic grounds].
Alpha1-adrenoblocker tamsulosin reduces muscle spasm in the ureteric wall, decreases peristalsis below and raises pressure above the stone thus facilitating stone passage. Patients on tamsulosin had spontaneous stone passage in 73.8% cases while only 22.4% patients on routine therapy became stone free. Tamsulosin also shortens hospital stay. Use of tamsulosin 0.4 mg daily in patients with distal ureteric stones is pathogenetically validated, is highly clinically and cost effective.


Amphiphilic self-assemblies decorated by nucleobases.
Phosphatidyl-nucleosides are a class of functional amphiphiles, where a nucleic acid monomer is conjugated to a lipid skeleton. These derivatives self-organize in aqueous solution as assemblies of various size, shape, and interfacial curvature. This paper presents a comparison of the aggregation behavior of different 1-R,2-R-sn-glycero-3-phosphatidyl-nucleosides, where R = 8 (DiC8PN) or R = 12 (DLPN) and N is either adenosine (a purine) or uridine (a pyrimidine), a complementary pair in RNA. Surface tension, small angle neutron scattering, cryo-TEM, and circular dichroism are used to highlight and distinguish the impact of the hydrophobic assembler and of the base substitution on the solution phase behavior. Our main conclusion is that the nucleic functionalization provides an additional parameter to control self-assembly through specific interactions among the polar heads. Further nonideal effects are induced by mixing nucleolipids with complementary base substitution. We show that these contributions alter the aggregation thresholds and modulate properties of the aggregates on the mesoscale.


Dry versus conventional laser imagers: film properties and image quality.
The authors compared image quality and stability with a dry laser imager versus a conventional wet laser imager. Hard copies of 56 magnetic resonance imaging and computed tomographic studies were analyzed for gray-scale distribution and temperature stability. Results with the dry laser imager did not reach the quality of results with a wet laser imager, but the performance and ecologic criteria were sufficient to make use of this technique advantageous.


Targeted Mutation of Nuclear Bone Morphogenetic Protein 2 Impairs Secondary Immune Response in a Mouse Model.
We recently identified a nuclear variant of the BMP2 growth factor, called nBMP2. In an effort to understand the function of this variant protein, we generated a mouse line in which BMP2 is expressed and functions normally, but nBMP2 is excluded from the nucleus. This novel mutation allows the study of nBMP2 without compromising BMP2 function. To determine whether nBMP2 plays a role in immune function, we performed a series of experiments in which we compared mouse survival, organ weights, immune cells numbers, and bacterial load in wild type and nBmp2NLS(tm) mice following primary and secondary challenges with Staphylococcus aureus. Following primary challenge with S. aureus, wild type and nBmp2NLS(tm) mice showed no differences in survival or bacterial load and generated similar numbers and types of leukocytes, although mutant spleens were smaller than wild type. Secondary bacterial challenge with S. aureus, however, produced differences in survival, with increased mortality seen in nBmp2NLS(tm) mice. This increased mortality corresponded to higher levels of bacteremia in nBmp2NLS(tm) mice and to a reduced enlargement of mutant spleens in response to the secondary infection. Together, these results suggest that the recently described nuclear variant of BMP2 is necessary for efficient secondary immune responses.


Avascular necrosis of the intermediate cuneiform bone.
We present a case of avascular necrosis of the intermediate cuneiform bone in a skeletal immature patient with a spontaneous recovery following conservative treatment. We discuss the aetiology and options of treatment.


Microstructural characteristics and gastro-small intestinal digestion in vitro of potato starch: Effects of refrigerated storage and reheating in microwave.
The objective of our study was to evaluate paste clarity, retrogradation (syneresis %), thermal characteristics and kinetics of glucose release during in vitro gastro-small intestinal digestion of freshly cooked and refrigerated potato starch. Freshly cooked starch pastes had a paste clarity of 71%, which decreased to 35.4% whereas syneresis (%) increased after 7days of refrigerated storage. The X-ray and thermal characteristics of native, retrograded and microwave reheated starch samples differed significantly from each other. For the freshly cooked starch pastes, ∼88% starch hydrolysis was observed at the end (150min) of digestion under simulated gastro-small intestinal conditions that decreased to ∼70% for the 7day stored pastes. The hydrolysis (%) of refrigerated pastes increased to 86% and 92% after one and two cycles of microwave reheating, respectively. These results contribute to the understanding of starch retrogradation in relation to starch digestion.


Extravascular lung water and pulmonary vascular permeability index as markers predictive of postoperative acute respiratory distress syndrome: a prospective cohort investigation.
Robust markers of subclinical perioperative lung injury are lacking. Extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index are two promising early markers of lung edema. We aimed to evaluate whether extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index would identify patients at risk for clinically significant postoperative pulmonary edema, particularly resulting from the acute respiratory distress syndrome. Prospective cohort study. Tertiary care academic medical center. Adults undergoing high-risk cardiac or aortic vascular surgery (or both) with risk of acute respiratory distress syndrome. None. Extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index measurements were obtained intraoperatively and in the early postoperative period. We assessed the accuracy of peak extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index as predictive markers of clinically significant pulmonary edema (defined as acute respiratory distress syndrome or cardiogenic pulmonary edema) using area under the receiver-operating characteristic curves. Associations between extravascular lung water indexed to predicted body weight and pulmonary vascular permeability patient-important with important outcomes were assessed. Of 150 eligible patients, 132 patients (88%) had extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index measurements. Of these, 13 patients (9.8%) had postoperative acute respiratory distress syndrome and 15 patients (11.4%) had cardiogenic pulmonary edema. Extravascular lung water indexed to predicted body weight effectively predicted development of clinically significant pulmonary edema (area under the receiver-operating characteristic curve, 0.79; 95% CI, 0.70-0.89). Pulmonary vascular permeability index discriminated acute respiratory distress syndrome from cardiogenic pulmonary edema alone or no edema (area under the receiver-operating characteristic curve, 0.77; 95% CI, 0.62-0.93). Extravascular lung water indexed to predicted body weight was associated with the worst postoperative PaO2/FIO2, duration of mechanical ventilation, ICU stay, and hospital stay. Peak values for extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index were obtained within 2 hours of the primary intraoperative insult for the majority of patients (> 80%). Perioperative extravascular lung water indexed to predicted body weight is an early marker that predicts risk of clinically significant postoperative pulmonary edema in at-risk surgical patients. Pulmonary vascular permeability index effectively discriminated postoperative acute respiratory distress syndrome from cardiogenic pulmonary edema. These measures will aid in the early detection of subclinical lung injury in at-risk surgical populations.


Simple methods for determination of the release limits for drug products.
The potency of a batch of drug product needs to meet a release limits at the time of release so that the potency at the end of shelf life remains above the lower registration limit (LRL). This article discusses two methods which determine the release limits such that the chance to fail LRL at the end of shelf life of the product will be controlled under a desirable level. In additional to controlling failure rate, a method which determines the release limits such that the expected total cost due to rejecting a batch at time zero and at the end of shelf life is minimized. All the methods assume a very flexible sampling schedule, and are simple to implement. Each method is illustrated in an example.


Two- and live/real time three-dimensional transthoracic echocardiographic assessment of infective endocarditis of a valved pulmonary conduit.
We describe the use of a nonstandard left infraclavicular approach in making the diagnosis of an infected valved conduit with two-dimensional transthoracic echocardiography. The patient was an adult with tetralogy of Fallot and pulmonary atresia who had undergone multiple surgical repair procedures. The initial diagnosis of infective endocarditis was made by transesophageal echocardiography. Both techniques demonstrated a single, large vegetation in the conduit. Live/real time three-dimensional transthoracic echocardiography, on the other hand, provided further information by demonstrating several additional vegetations in the conduit and more comprehensively assessed their size by enabling measurement of their azimuthal dimensions and volumes. The patient was treated with antibiotics with complete resolution of the vegetations.


Peripheral blood versus bone marrow for hematopoietic cell transplantation.
Peripheral blood stem cell transplantation is being used more frequently in both the autologous and allogeneic setting. The use of cytokines either alone or in conjunction with chemotherapy priming has made peripheral procurement of the stem cells through apheresis possible. Differences exist both in the composition of the graft and in subsequent posttransplantation immune reconstitution between peripheral blood stem cells and bone marrow. Reliable estimates of the comparative incidence of acute and chronic graft-versus-host disease following blood or marrow allogeneic transplantation are not yet available.


Theoretical study on the relationship between Rp-phosphorothioation and base-step in S-DNA: based on energetic and structural analysis.
Phosphorothioation (PT), previously used in synthetic antisense drugs to arrest the transcription or translation process, is also a novel physiological modification in bacteria DNAs. In the previous study, we reported that Rp-phosphorothioation (Rp-PT) destabilizes B-type helix significantly, using a quantum-mechanics-based energy scoring function developed with a dinucleotide model ( Zhang et al. J. Phys. Chem. B , 2012 , 116 , 10639 - 10648 ). A consequent question surfaces in the field of the phosphorothioated DNA (S-DNA) research: does the endogenous chemical modification interact with the base sequence in the bacterial genomes, e.g., in terms of the most common structure of the B-type helix? In this work, we carried out further energetic analysis on the backbone relative energies calculated with the scoring function according to 16 groups of base-step classifications. Moreover, we conducted molecular dynamics simulations of the B-helical structure with the different base-pair steps, to investigate the detailed structural changes upon the O-/S-substitution. As a result, the Rp-PT modification definitively enhances the stiffness of the backbone and differentiates backbone stability as an interaction with base-steps. Furthermore, certain exceptional sequences such as GT and CC were highlighted in the structural analysis of the sulfur local contacts and relative orientation of double strands, indicating that Rp-PT can cross-talk with particular base-steps. The special effects between the phosphorothioation and base-step may be related to the conservative consensus observed highly frequently in bacterial genomes.


Treatment of diabetic microangiopathy and edema with HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides): a prospective, placebo-controlled, randomized study.
This study was planned to demonstrate in a prospective, placebo-controlled, randomized study, whether HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides), is effective in improving the microcirculation in subjects with diabetic microangiopathy and neuropathy. Patients with severe diabetic microangiopathy, neuropathy and edema, patients with microangiopathy, without neuropathy, and 20 healthy subjects were included. Microangiopathy was defined by laser Doppler flowmetry and capillary filtration (rate of ankle swelling (RAS)). Inclusion criteria were: increase in resting flux (RF) and RAS, a decrease in venoarteriolar response (VAR), and alterations in flux increase with temperature. The 2 groups of patients and the control group were randomized in a treatment sub-group which received HR (1 g, twice daily for 6 months); those in the placebo group received similar treatment. Groups were comparable; there were no drop-outs. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no adverse effects were reported. No variations were observed in healthy subjects at 6 months. In both groups of patients, significant decreases (P < 0.05) in RF and RAS were observed in the active treatment groups. The decrease in RAS was associated with a decrease in edema (P < 0.05) in both treatment groups. The decrease in RF and the increase in VAR were associated with a proportional decrease in RAS (P < 0.05). In patients without neuropathy, the variations in RF, VAR, and RAS were larger (P < 0.05) at 6 months. The variations in healthy subjects were limited and not significant. The decrease in capillary filtration and edema with HR is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of HR on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.


Etest and Sensititre YeastOne Susceptibility Testing of Echinocandins against Candida Species from a Single Center in Austria.
Candida species were tested for susceptibility to caspofungin, anidulafungin, and micafungin in order to evaluate the roles of Etest and Sensititre YeastOne in antifungal susceptibility testing for daily routines and to survey resistance. A total of 104 Candida species isolates detected from blood cultures were investigated. With EUCAST broth microdilution as the reference method, essential agreement (EA), categorical agreement (CA), very major errors (VME), major errors (ME), and minor (MIN) errors were assessed by reading MICs at 18, 24, and 48 h. By use of EUCAST broth microdilution and species-specific clinical breakpoints (CBPs), echinocandin resistance was not detected during the study period. Using EUCAST CBPs, MIC readings at 24 h for the Etest and Sensititre YeastOne resulted in CA levels of 99% and 93% for anidulafungin and 99% and 97% for micafungin. Using revised CLSI CBPs for caspofungin, CA levels were 92% and 99% for Etest and Sensititre YeastOne. The Etest proved an excellent, easy-to-handle alternative method for testing susceptibility to anidulafungin and micafungin. Due to misclassifications, the Etest is less suitable for testing susceptibility to caspofungin (8% of isolates falsely tested resistant). The CA levels of Sensititre YeastOne were 93% and 97% for anidulafungin and micafungin (24 h) by use of EUCAST CBPs and increased to 100% for both antifungals if CLSI CBPs were applied and to 100% and 99% if Sensititre YeastOne epidemiological cutoff values (ECOFFs) were applied. No one echinocandin could be demonstrated to be superior to another in vitro Since resistance was lacking among our Candida isolates, we cannot derive any recommendation from accurate resistance detection by the Etest and Sensititre YeastOne.


Face Perception and Test Reliabilities in Congenital Prosopagnosia in Seven Tests.
Congenital prosopagnosia, the innate impairment in recognizing faces, is a very heterogeneous disorder with different phenotypical manifestations. To investigate the nature of prosopagnosia in more detail, we tested 16 prosopagnosics and 21 controls with an extended test battery addressing various aspects of face recognition. Our results show that prosopagnosics exhibited significant impairments in several face recognition tasks: impaired holistic processing (they were tested amongst others with the Cambridge Face Memory Test (CFMT)) as well as reduced processing of configural information of faces. This test battery also revealed some new findings. While controls recognized moving faces better than static faces, prosopagnosics did not exhibit this effect. Furthermore, prosopagnosics had significantly impaired gender recognition-which is shown on a groupwise level for the first time in our study. There was no difference between groups in the automatic extraction of face identity information or in object recognition as tested with the Cambridge Car Memory Test. In addition, a methodological analysis of the tests revealed reduced reliability for holistic face processing tests in prosopagnosics. To our knowledge, this is the first study to show that prosopagnosics showed a significantly reduced reliability coefficient (Cronbach's alpha) in the CFMT compared to the controls. We suggest that compensatory strategies employed by the prosopagnosics might be the cause for the vast variety of response patterns revealed by the reduced test reliability. This finding raises the question whether classical face tests measure the same perceptual processes in controls and prosopagnosics.


CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.
Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be considered with caution.


Evidence-based (informed) macro practice paradigm: integration of practice expertise and research.
This article addresses some of the challenges and opportunities inherent in the empirical practice movement. In constructing an evidence-based macro practice paradigm, practitioners, educators, and their researcher colleagues will need to work together in critically examining the amount, type, and quality of the evidence that support major theories, policies, and interventions relevant to practice. Integrating relevant scientific information with professional judgment should be the guiding principle in supporting evidence-based practice. Even though the logic of EBP is appealing to funding sources, professionals, and the public, many issues need to be examined in transporting an evidence-based practice into a practice setting.


Diindolylquinoxalines: effective indole-based receptors for phosphate anion.
The synthesis of a new series of 2,3-diindol-3'yl quinoxalines (DIQ), as well as a comparison of their anion recognition properties to those of our previously reported pyrrole based sensors, 2,3-dipyrrol-2'yl quinoxalines, is reported. To the best of our knowledge, this new DIQ system represents the first example of a free-standing indole-based small molecule receptor for which evidence of anion binding is available both in solution and in the solid-state. It also provides one of the few structurally characterized neutral receptor-dihydrogen phosphate complexes. This work thus serves to demonstrate the utility of indoles as an anion recognition motif.


Factors associated with multimorbidity and its link with poor blood pressure control among 223,286 hypertensive patients.
Multimorbidity has become the norm worldwide as populations age. It remains, however, infrequently researched. This study evaluated factors associated with multimorbidity in a predominantly Chinese hypertensive population. We included all adult patients prescribed their first antihypertensive agents in the entire public sector in Hong Kong from a validated database. Multimorbidity was defined as having one or more medical conditions (cardiovascular diseases; respiratory diseases; diabetes or impaired fasting glucose; renal disease) in addition to hypertension. We studied the prevalence of multimorbidity and performed multinomial regression analyses to evaluate factors independently associated with multimorbidity. 223,286 hypertensive patients (average age of 59.9 years, SD 17.6) were included. The prevalence of having 0, 1 and ≥ 2 additional conditions was 59.6%, 32.8% and 7.5%, respectively. The most common conditions were cardiovascular disease (24.2%) and diabetes (23.0%), followed by respiratory disorders (14.6%) and renal disease (10.9%). Older age (>50 years), male sex, lower household income, receipt of social security allowance and suboptimal blood pressure control (>140 mmHg or >90 mmHg; >130 mmHg or >80 mmHg for diabetes patients; AOR = 3.38-4.49) were significantly associated with multimorbidity. There exists a synergistic effect among these variables as older (≥ 70 years), male patients receiving security allowance had substantially higher prevalence of multimorbidity (19.9% vs 7.5% among all patients). Multimorbidity is very common in hypertensive patients and its prevalence increased markedly with the presence of risk factors identified in this study. Hypertensive patients with multimorbidities should receive more meticulous clinical care as their blood pressure control tends to be poorer.


[A class of information integration models for the Oppel-Kundt illusion].
Oppel (1860/1861) first described the phenomenon that an equidistantly divided line usually looks longer than an undivided line of equal length (Oppel-Kundt illusion, OKI). The present paper begins with a discussion of the Hering-Kundt hypothesis (HKH) of the OKI. The HKH comprises two assumptions: (1) An assumption concerning the perceptual integration of the length of a single part of the divided line and the number of such parts; (2) an assumption about the psychophysical function of line length. There is no doubt that the HKH is empirically not tenable. However, nothing is known about the validity of the perceptual integration assumption when considered in isolation. It is shown that the HKH can be conceived as a special case of a more general information-integration model. According to this model, the subjective total length of a divided line is equal to the subjective length of one part of the line multiplied by the subjective number of parts. Two experiments with a total of 15 subjects are reported. The model is shown to be valid without any exception. On the background of these results published data on the OKI are re-analyzed, looking at whether they contain information about the psychophysical function for line length. It is shown that certain qualitative aspects of these data are inconsistent with a power function hypothesis while, at the same time, being compatible with a logarithmic (Fechner-) function.


Tubulin isotype substitution revealed that isotype combination modulates microtubule dynamics in C. elegans embryos.
Microtubules (MTs) are polymers composed of α- and β-tubulin heterodimers that are generally encoded by genes at multiple loci. Despite implications of distinct properties depending on the isotype, how these heterodimers contribute to the diverse MT dynamics in vivo remains unclear. Here, by using genome editing and depletion of tubulin isotypes following RNAi, we demonstrate that four tubulin isotypes (hereafter referred to as α1, α2, β1 and β2) cooperatively confer distinct MT properties in Caenorhabditis elegans early embryos. GFP insertion into each isotype locus reveals their distinct expression levels and MT incorporation rates. Substitution of isotype coding regions demonstrates that, under the same isotype concentration, MTs composed of β1 have higher switching frequency between growth and shrinkage compared with MTs composed of β2. Lower concentration of β-tubulins results in slower growth rates, and the two α-tubulins distinctively affect growth rates of MTs composed of β1. Alteration of ratio and concentration of isotypes distinctively modulates both growth rate and switching frequency, and affects the amplitude of mitotic spindle oscillation. Collectively, our findings demonstrate that MT dynamics are modulated by the combination (ratio and concentration) of tubulin isotypes with distinct properties, which contributes to create diverse MT behaviors in vivo.


[Sporadical extraperitoneal desmoid tumors--review and report on 4 cases].
Desmoid tumors are very rare mesenchymal tumors with a partially aggressive growth pattern and high relapse rates. Without metastases, they are classified as semi-malignant tumours. The treatment of this neoplasia is discussed controversially. Up to now, there exists no broad consensus on the treatment regimes. Traditionally, the primary radical surgical resection is often preferred. This might be combined with an (neo-)adjuvant radiation therapy. Recently an increasing importance of radiotherapy has been described. Several studies favour radiotherapy as the single form of treatment. Furthermore several medication regimes have been described in the literature. We report the follow-up of 4 patients who were treated for desmoid tumours. In 2 cases surgery was the primary treatment. After R0-resection and adjuvant radiation therapy, one of the patients developed 7 relapses. In another patient, 5 relapses were observed after surgical therapy. Therapeutic guidelines with broad acceptance do not exist up to now due to missing data of prospective studies with sufficient case numbers. In our opinion wide surgical resection should be performed in primary occurring cases with resectable tumours. On account of the previous experiences, it can be concluded that therapy of primary non respectable or recurrent desmoid tumours is not only a domain of a surgical approach. At present an adequate treatment should be planned interdisciplinary by surgeons, radiation therapists and oncologists. For generally accepted guidelines for this rare disease, general therapeutic options based on prospectively randomised studies have to be elaborated.


[Spindle cell squamous carcinoma of the oral cavity: report of 2 cases].
Two cases with spindle cell squamous carcinoma were reported in this paper. The clinical, histopathologic features, therapy and prognosis were discussed. These tumors probably represented a heterogeneous group of squamous cell carcinoma whose components required either an identifiable squamous cell carcinoma or evidence of epithelial differentiation in the spindle cell. The clinical features were as follow: presents a male predominance among 60 to 70 years and site predilection for the low lip, tongue and gingiva, more aggressive and easy lymphatic metastases. Wide surgical excision, alone or with radical neck dissection was the most successful therapeutic modality. Local recurrence, lymphatic metastases and the depth of tumor invasion into underlying structures were found to be reliable prognostic indicators, the prognosis was dismal.


What does it mean when age is related to recidivism among sex offenders?
Age is a robust predictor of recidivism and an item on actuarial tools commonly used to predict sexual violent recidivism among sex offenders. However, little is known about whether or how much offenders' risk diminishes as a result of aging. In the first of two studies, we examined the sexual and violent recidivism of 533 sex offenders who were over age 50 on release. Age at index offense was at least as good at predicting both outcomes as was age at release, and age at index offense provided at least as much incremental validity in the prediction of violent recidivism to scores on a brief static actuarial tool. Neither age added incrementally to static score in the prediction of sexual recidivism. The second study examined how well age at first offense, age at index offense, and age at release predicted violent recidivism among 527 sex offenders aged 13 to 79 at release. Age at first offense predicted best. When age was removed from score on the Sex Offender Risk Appraisal Guide, all ages added incrementally but age at release least to SORAG score. When participants were divided into quartiles based on age at index offense, there was no evidence from any quartile that age at release predicted violent recidivism better than age at first offense. The authors concluded that age at release is a poor index of within-subject changes in risk of sexual or violent recidivism. No adjustment to a sex offender's score on a comprehensive actuarial tool that includes age at first or index offense should be made simply because the offender is older.


Second instance of co-occurring 22q11.2 deletion syndrome and Williams syndrome.
We present an 18-month-old male with Tetralogy of Fallot, retrognathia, short stature, global developmental delay, and dysmorphic features who was found to have dual diagnoses of both Williams syndrome and 22q11.2 deletion syndrome (22q11.2DS). To our knowledge, this is the second case of such a co-occurrence documented in the medical literature. Our patient presents with a blended physical phenotype of these two conditions and a behavioral phenotype that is distinct from what is typically observed in either disorder alone. We compare our patient's phenotype to the previously reported case and to the typical phenotypes for each individual condition. Additionally, we discuss why the occurrence of these two disorders together seems to be so rare, and the benefit of a genetics evaluation to an inpatient service team and the patient.


Enhanced larvicidal, antibacterial, and photocatalytic efficacy of TiO2 nanohybrids green synthesized using the aqueous leaf extract of Parthenium hysterophorus.
Titanium dioxide nanoparticles are emerging as a biocompatible nanomaterial with multipurpose bioactivities. In this study, titanium dioxide (TiO2) nanoparticles were effectively synthesized using the aqueous leaf extracts of Parthenium hysterophorus prepared by microwave irradiation. TiO2 nanoparticles were fabricated by treating the P. hysterophorus leaf extracts with the TiO4 solution. Biologically active compounds such as alcohols, phenols, alkanes, and fluoroalkanes were involved in bioreduction of TiO4 into TiO2. The formation of green-engineered TiO2 nanoparticles was confirmed by UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), and energy-dispersive X-ray (EDX) spectroscopy and further characterized by X-ray diffraction (XRD) studies. UV-vis spectroscopy analysis showed maximum absorbance at 420 nm due to surface plasmon resonance of synthesized TiO2 NPs. FTIR spectrum of the engineered TiO2 NPs showed the presence of bioactive compounds in the leaf extract, which acted as capping and reducing agents. FESEM exhibited an average size of 20-50 nm and a spherical shape of TiO2 NPs. EDX analysis indicated the presence of TiO2 NPs by observing the peaks of titanium ions. XRD results pointed out the crystalline nature of engineered TiO2 NPs. The larvicidal activity of TiO2 NPs was studied on fourth instar larvae of dengue, Zika virus, and filariasis mosquito vectors Aedes aegypti and Culex quinquefasciatus. Antimicrobial efficacy of TiO2 NPs was assessed on clinically isolated pathogens Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus vulgaris, and Staphylococcus epidermidis. Besides, we found that TiO2 NPs are able to quickly degrade the industrially harmful pigments methylene blue, methyl orange, crystal violet, and alizarin red dyes under sunlight illumination. Overall, this novel, simple, and eco-friendly approach can be of interest for the control of vector-borne diseases, as well as to formulate new bactericidal agents and to efficiently degrade dye solutions in the polluted areas.


p53 Gene Polymorphisms in the Turkish Population.
There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's were located on the exon 4 (CD 47), exon 6 (CD 213) and intron 6 (A-G). CD 47 (C-T) was not present. CD 213 (G) occurred very rarely with a frequency of 0.0114. The frequency of the Int 6 A/G a alteration was found to be 0.70 for "G". The heterozygosity rate was 32.72%.


SAHA Enhances Differentiation of CD34+CD45+ Hematopoietic Stem and Progenitor Cells from Pluripotent Stem Cells Concomitant with an Increase in Hemogenic Endothelium.
Epigenetic modification is an important process during hematopoietic cell differentiation. Histone deacetylase (HDAC) inhibitors have previously been shown to enhance expansion of umbilical cord blood-derived hematopoietic stem cells (HSCs). However, the effect of HDAC inhibitors on pluripotent stem cells (PSCs) in this context is less understood. For years, investigators have considered PSC-derived natural killer (NK) and T-cell therapies. These "off-the-shelf" cellular therapies are now entering the clinic. However, the in vitro commitment of PSCs to the hematopoietic lineage is inefficient and represents a major bottleneck. We investigated whether HDAC inhibitors (HDACi) influence human PSC differentiation into CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), focusing on hemogenic endothelium (HE). Pluripotent stem cells cultured in the presence of HDACi showed a 2-5 times increase in HSPCs. Concurrent with this, HDACi-treated PSCs increased expression of 7 transcription factors (HOXA5, HOXA9, HOXA10, RUNX1, ERG, SPI1, and LCOR) recently shown to convert HE to HSPCs. ChIP-qPCR showed that SAHA upregulated acetylated-H3 at the promoter region of the above key genes. SAHA-treated human PSC-derived CD34+CD45+ cells showed primary engraftment in immunodeficient mice, but not serial transplantation. We further demonstrate that SAHA-derived HSPCs could differentiate into functional NK cells in vitro. The addition of SAHA is an easy and effective approach to overcoming the bottleneck in the transition from PSC to HSPCs for "off-the-shelf" cellular immunotherapy.


Increased affective influence: situational complexity or deliberation time?
The affect infusion model (AIM) is a prominent theory of when current emotional state is expected to influence the interpretation of a social stimulus (situation). We discuss the assumptions in AIM and conclude that its current specification predicts that both deliberation time and situational complexity should lead to affect infusion. The aim of this research was to clarify the relative importance of these factors in determining affect infusion and hence promote the development of AIM. We present an experimental design in which situational complexity and deliberation time can be manipulated orthogonally as independent factors. Our results show that the latter factor, but not the former, can influence the degree of affect infusion.


Nursing Diagnosis Risk for Unstable Blood Glucose Level in Patients with Diabetes Mellitus.
To validate the nursing diagnosis risk for unstable blood glucose level in adult/elderly patients with type 1 and type 2 diabetes. Study Methodological was used in this article. The validation process was carried out using the model proposed by Hoskins (1989). The risk factors ineffective medication management and high carbohydrate and lipid food intake achieved a concordance index greater than 85%. This study contributed to the identification of new risk factors, at risk populations, and important associated conditions. It is believed that the findings reported in this paper can be used to improve clinical protocols for the prevention of unstable blood glucose, in addition to contributions to the advancement of nursing science.


Post-medication Stevens-Johnson syndrome in a girl hospitalized for a norovirus and rotavirus infection.
Stevens-Johnson syndrome (SJS) is a cutaneous mucosal disorder characterized by extended necrosis and detachment of the epidermis affecting <10% of the body surface, caused by drugs or infections. The authors report a case of a girl with Depakine resistant epilepsy, who develops a SJS in the third week of introducing lamotrigine. The girl also presents an acute diarrheal disease with double viral etiology - rotavirus and norovirus. The clinical image comprises polymorphic erythematous maculopapular exanthema with vesicular and bullous elements, with ulcerations and desquamations at the level of the eyelids, mouth, anogenital area and tegument denuding at the level of the abdomen and limbs. The SCORTEN score (SCORe of Toxic Epidermal Necrosis) for establishing the seriousness is 1. The evolution of the disease is slowly favorable under conservative treatment, which does not involve the use of corticotherapy or intravenous immunoglobulins. Although there is a low incidence of this syndrome in pediatrics, it may occur as complication of using some drugs - mostly anti-epileptics or antibiotics, corroborated or not with an infectious process.


The Effect of Platelet-Rich Fibrin, Calcium Sulfate Hemihydrate, Platelet-Rich Plasma and Resorbable Collagen on Soft Tissue Closure of Extraction Sites.
Rapid and complete soft tissue healing after tooth extraction minimizes surgical complications and facilitates subsequent implant placement. We used four treatment methods and assessed changes in soft tissue socket closure following tooth extraction in humans. The effects of platelet-rich fibrin-calcium sulfate hemihydrate (PRF-CSH), platelet-rich plasma-calcium sulfate hemihydrate (PRP-CSH), a resorbable collagen dressing (RCD), and no grafting material were compared in a randomized, controlled pilot study with a blinded parallel design (N = 23). Patients with a hopeless tooth scheduled for extraction were randomly assigned to one of the four treatment groups. Socket measurements were obtained immediately after extraction and treatment, as well as after 21 days. There was a significant decrease in the total epithelialized external surface area of the extraction sockets in each group at all time points. However, there were no significant differences in soft tissue closure (p > 0.05) at any time point and PRF-CSH or PRP-CSH did not provide any additional benefit to enhance the soft tissue closure of extraction sockets compared with either RCD or sites without graft.


[Proctological emergencies in pregnant women].
Hemorrhoids affect up to 85 % of pregnant women during the last two trimesters. The maximum incidence for anal fissure is 20 %. One of the common risk factors is constipation promoted during pregnancy. The history of anal pathology, the length of delivery and the baby's birth weight also promote these two entities. The treatment includes above all hygiene and dietary measures to prevent constipation and conservative measures (local anesthetics, sitz baths). Surgical procedures should be avoided and indicated only in case of failure of conservative treatment. Rectal prolapse is more rare and must be reduced manually before surgery. Measures to prevent constipation also apply.


Preparation of porcine pancreatic lipase free of co-lipase activity.
Porcine pancreatic lipase LB was purified and released from co-lipase activity by reduction with beta-mercaptoethanol in the presence of guanidine chloride. The amino acid and carbohydrate composition of the enzyme is presented. The following physical constants were measured or calculated: Molecular weight 52 000, sedimentation coefficient (s degrees 20, w) 4.0 S, diffusion coefficient (D degrees 20, w) 6.7 X 10(-7) cm2 s-1. Stokes' radius (r) 30.3 A, partial specific volume (v) 0.72 cm3 g-1, frictional ratio (f/f0) 1.23 and isoelectric point (pI) 5.18.


Let's Talk about Children Evaluation (LTCE) study in northern Finland: a multiple group ecological study of children's health promotion activities with a municipal and time-trend design.
Making change towards child and family-based and coordinated services is critical to improve quality, outcomes and value. The Let's Talk about Children (LTC) approach, which consists of brief psychoeducational discussions with parents of kindergarten-aged and school-aged children, has been launched as a municipality-specific programme in the Council of Oulu Region. The aim of this paper is to present a protocol of an ecological study evaluating the group-specific effects of an intervention about LTC activities in a geographically defined population. The programme is designed to promote children's socioemotional well-being. A quasi-experimental ecological study protocol is implemented to evaluate whether systematic LTC practices improve children's well-being. A multi-informant setting covers 30 municipalities in northern Finland and involves all the municipal teachers, social and healthcare workers. In each municipality, a Local Management Team is responsible for implementing the LTC programme and collecting the annual data of LTC discussions and network meetings. The outcome data are retrieved from child welfare statistics and hospital registers. The population data, child welfare statistics and referrals to hospitals was retrieved at baseline (2014), and will be retrieved annually. Furthermore, the annual data of LTC discussions and network meetings will be collected of the years 2015-2018. The study design has been approved by the management of the Oulu University Hospital in accordance with the guidelines given by The Regional Ethics Committee of the Northern Ostrobothnia Hospital District in Oulu, Finland. All data are treated and implemented according to national data security laws. Study findings will be disseminated to provincial and municipal partners, collaborative community groups and the research and development community. The Let's Talk about Children Evaluation study databases will guide future regional development action and policies.


Molecular basis of late-flowering phenotype caused by dominant epi-alleles of the FWA locus in Arabidopsis.
The late-flowering phenotype of dominant fwa mutants is caused by hypomethylation in the FWA locus leading to ectopic expression of a homeodomain leucine zipper (HD-ZIP) protein. However, little is known about whether FWA has any role in regulation of flowering and how ectopically expressed FWA delays flowering. Through analysis of FWA expression in wild-type seedlings, it was shown that FWA is not expressed during the vegetative phase. This suggests that FWA has no role in flowering. The previous reports that fwa suppressed the precocious-flowering phenotype of plants overexpressing FLOWERING LOCUS T (FT) suggest that the flowering pathway(s) either at and/or downstream of FT is blocked by FWA. Comparison of gene expression profiles in three genetic backgrounds ectopically expressing FWA and their respective wild types failed to detect common changes, ruling out the possibility that FWA acts through transcriptional misregulation. Yeast two-hybrid analysis and in vitro pull-down assay showed that FWA protein can specifically interact with FT protein. The importance of protein interaction with FT in delaying flowering was supported by studies involving N-terminal and C-terminal truncations of FWA. The C-terminal truncation with abolished interaction did not delay flowering when overexpressed, while the N-terminal truncation, which retains interaction, did. Specific interaction of FWA with FT enabled us to use FWA protein as a specific inhibitor of FT protein function. Through tissue-specific ectopic expression of FWA, further support for the shoot apex being the site of action of FT protein was provided.


Melanoma cells interfere with the interaction of dendritic cells with NK/LAK cells.
Dendritic cells (DCs) and natural killer (NK) cells are key players at the interface between innate resistance and acquired immunity. NK cells can induce DC maturation, a differentiation process whereby DCs respond to a environmental stimulus and acquire the ability of eliciting adaptive immunity. Conversely, maturing DCs promote NK functions in vivo and in vitro. This interplay has important consequences on the immune response to pathogens and possibly to neoplastic cells. Here, we show that B16 melanoma cells actively modulate the interaction between DCs derived from bone marrow precursors and NK/LAK cells propagated from the spleen of C57BL/6 mice. DCs increased in a dose-dependent manner the ability of NK/LAK cells to kill melanoma cells and to produce cytokines. This activatory cross-talk entailed the production of IL-18 by DCs and of IFN-gamma by NK/LAK cells. Melanoma cells were not a passive target of NK activity; they regulated the outcome of the interaction between DCs and NK/LAK cells, inhibiting the in vitro production of cytokines as effectively as the genetic deletion of IL-18 or IFN-gamma. Interference with the NK/DC interaction possibly represents a mechanism used by growing tumors to evade the immune response.


Universality and Intermittency of Pair Dispersion in Turbulence.
Turbulence can disperse a concentrated parcel of pollutants at a rate over nine orders of magnitude higher than its purely diffusive counterpart. One intriguing signature of turbulent dispersion is its superdiffusive scaling. However, the universality of this scaling law is still in question. By leveraging a new laboratory facility, particle pairs with small initial separations can be tracked over four decades of separation in time and five decades of separation in squared displacement, thereby observing the full range of dispersion scaling laws. The results show that the classical Richardson cubic scaling will be reached not for an initial separation asymptotically close to zero but at a critical value, and this value does not appear to depend on the Reynolds number, providing an effective way to study universal dispersion dynamics. Additionally, the results agree well with the prediction based on the multifractal model and may help reconcile different reported scaling laws from laboratory experiments and field studies.


Moving Toward a Unified Platform for Insulin Delivery and Sensing of Inputs Relevant to an Artificial Pancreas.
Advances in insulin pump and continuous glucose monitoring technology have primarily focused on optimizing glycemic control for people with type 1 diabetes. There remains a need to identify ways to minimize the physical burden of this technology. A unified platform with closely positioned or colocalized interstitial fluid glucose sensing and hormone delivery components is a potential solution. Present challenges to combining these components are interference of glucose sensing from proximate insulin delivery and the large discrepancy between the life span of current insulin infusion sets and glucose sensors. Addressing these concerns is of importance given that the future physical burden of this technology is likely to be even greater with the ongoing development of the artificial pancreas, potentially incorporating multiple hormone delivery, glucose sensing redundancy, and sensing of other clinically relevant nonglucose biochemical inputs.


[Gene delivery system based on low molecular weight polyethylenimine and its transfection activity in the skin tissue].
Low molecular weight polyethylenimine (LMW-PEI) was linked to an expressing plasmid contains a green fluorescence protein (GFP) reporter gene and effective gene transfer was observed in CM7221 cell line tested. We examined the relationship among the molecular weight, structure of PEI and their transfection activity and cytotoxicity on CM7221 cell line. We also examined the position and continuance time of the GFP reporter gene expressed in the skin tissue of mouse. Results showed that LMW-PEI/DNA complexes led to high levels of expression in the CM7221 cell line (about 55%). However, with the increasing of PEI molecular weight, the transfection activity of PEI was decreasing. There was an increasing cytotoxicity with the larger PEI molecules. Further research showed that LMW-PEI induced a significant and long-lasting (7 days) expression of the GFP reporter gene in the hair vesicle, sweat, gland, sebaceous gland in the mouse skin tissues. The LMW-PEI described here is a new, highly efficient and non-cytotoxic vector. It would be a useful non-viral vector for gene delivery technology, particular useful as simple skin-specific vehicles of therapeutic genes.


What EEG criteria for diving fitness?
The authors have tried to consider EEG criteria applicable to fitness for diving. In a study of 90 professional divers, 37 (41%) displayed patterns susceptible of being interpreted as falling outside of strict normalcy. These patterns have sometimes been considered incompatible with diving, or even pathological by some authors. Considering the fact that these subjects were in good health, the value of these EEG signs is discussed in comparison with the literature. A general guideline is proposed placing subjects in three groups: fit, unfit, and questionable. In the last case, a final decision is taken in each individual case in agreement with the other medical examinations and based on the type of diving considered. Some explicit EEG criteria of definitive or temporary fitness and unfitness are proposed.


Sex Hormones and Healthy Psychological Aging in Women.
Besides their key role in reproduction, estrogens have effects in several organs in the body, as confirmed by the identification of estrogen receptors (ER) in multiple tissues. Experimental evidence has shown that estrogens have significant impacts on the central nervous system (CNS), and a key question is to what extent the fall in estrogen levels in the blood that occurs with increasing age, particularly around and following the menopause, has an impact on the cognitive function and psychological health of women, specifically regarding mood. This review will consider direct effects of menopausal changes in estrogens on the brain, including cognitive function and mood. Secondary pathways whereby health factors affected by changes in estrogens may interact with CNS functions, such as cardiovascular factors, will be reviewed as well insofar as they also have an impact on cognitive function. Finally, because decline in estrogens may induce changes in the CNS, there is interest in clarifying whether hormone therapy may offer a beneficial balance and the impact of hormone therapy on cognition will also be considered.


The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans.
The tetrachloroethene (PCE)-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B12, which, in comparison to other cobamides, e.g., cobalamin and pseudo-B12, lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the SMUL_1544 gene successfully complemented a Salmonella enterica ΔcobD mutant. The cobD gene encodes an l-threonine-O-3-phosphate (l-Thr-P) decarboxylase responsible for the synthesis of (R)-1-aminopropan-2-ol O-2-phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B12 was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with l-Thr-P supported cobamide biosynthesis in S. enterica producing SMUL_1544 or S. multivorans Under these conditions, both microorganisms synthesized pseudo-B12 This observation indicated a flexibility in the SMUL_1544 substrate spectrum. From the formation of catalytically active PCE reductive dehalogenase (PceA) in S. multivorans cells producing pseudo-B12, a compatibility of the respiratory enzyme with the cofactor was deduced. This result might indicate a structural flexibility of PceA in cobamide binding. Feeding of l-[3-(13)C]serine to cultures of S. multivorans resulted in isotope labeling of the norpseudo-B12 linker moiety, which strongly supports the hypothesis of EA-P formation from l-serine-O-phosphate (l-Ser-P) in this organism. The identification of the gene product SMUL_1544 as a putative l-Ser-P decarboxylase involved in norcobamide biosynthesis in S. multivorans adds a novel module to the assembly line of cobamides (complete corrinoids) in prokaryotes. Selected cobamide-containing enzymes (e.g., reductive dehalogenases) showed specificity for their cobamide cofactors. It has recently been proposed that the structure of the linker moiety of norpseudo-B12 and the mode of binding of the EA-P linker to the PceA enzyme reflect the high specificity of the enzyme for its cofactor. Data reported herein do not support this idea. In fact, norpseudo-B12 was functional in the cobamide-dependent methionine biosynthesis of S. enterica, raising questions about the role of norcobamides in nature.


Dental problems in diabetes - add a dentist to the diabetes team.
A healthy tooth in a healthy gum and healthy mouth is fairly secure. The roots are firmly embedded in bone and the gum firmly encases the tooth, leaving only the resistant enamel exposed to any debris and bacteria that saliva has not flushed away.


CD38 deficiency in the tumor microenvironment attenuates glioma progression and modulates features of tumor-associated microglia/macrophages.
Gliomas are the most frequent primary tumors of the brain, and for highly malignant gliomas there is no successful treatment. The tumor microenvironment contains large numbers of infiltrating microglia and macrophages (MM). There is increasing evidence that the tumor-associated MM support glioma expansion. CD38 is a multifunctional ectoenzyme that uses nicotinamide adenine dinucleotide as a substrate to generate second messengers. Previously we showed that CD38 deficiency modulates microglial "activation" and impaired recovery from head trauma by a microglia-associated mechanism. In view of the supportive role of MM in glioma progression and the role of CD38 in microglia activation, we hypothesize that deficiency of CD38 in the tumor microenvironment would inhibit glioma progression. Using the syngeneic GL261 model of glioma progression in wild-type and CD38 null mice, we show here that CD38 deficiency significantly attenuates glioma expansion and prolongs the life span of the glioma-bearing mice. The CD38 deficiency effect was associated with increased cell death and decreased metalloproteinase-12 expression in the tumor mass, as well as modulation of the tumor-induced MM properties, as indicated by a reduction in the expression of the MM marker F4/80 and matrix metalloproteinases. Our results thus suggest that CD38 participates in the tumor-supporting action of MM and that targeting CD38 might be a potential therapeutic approach for glioma treatment.


Pathophysiology of cutaneous lupus erythematosus--novel aspects.
The pathophysiology of cutaneous lupus erythematosus (CLE) has been investigated in numerous studies demonstrating that the combination of specific cellular and molecular events is leading to inflammation and tissue damage in this disease. However, a complete understanding of the diverse pathophysiological mechanisms and interactions does not exist. Various environmental factors influence the clinical expression of CLE and a striking relationship has emerged between sunlight exposure and the various subtypes of this disease. In the past years, photoprovocation tests with different ultraviolet (UV) wavelengths have been approved to be an optimal way to evaluate photosensitivity in patients with CLE. Furthermore, research on the pathogenetic mechanisms of UV-induced skin lesions has become an increasingly dynamic field and several new aspects of this disease could be identified. In this review, the impact of UV exposure that contributes to the manifestations of CLE is discussed and recently reported mechanisms in the pathophysiology of this disease are considered including the clearance of apoptotic cells, expression of inducible nitric oxide synthase, function of CD4(+)CD25(+) regulatory T cells, and the role of chemokines for lymphocyte recruitment. Elucidation of the relevant factors might lead to future development of effective strategies to prevent abnormal reactivity in patients with CLE.


Influence of plasma exchange on serum levels of cytokines and adhesion molecules in ANCA-positive renal vasculitis.
Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. Serum levels of IL-1beta, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener's granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1beta and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.


A 750 K Photocharge Linear Full Well in a 3.2 μm HDR Pixel with Complementary Carrier Collection.
Mainly driven by automotive applications, there is an increasing interest in image sensors combining a high dynamic range (HDR) and immunity to the flicker issue. The native HDR pixel concept based on a parallel electron and hole collection for, respectively, a low signal level and a high signal level is particularly well-suited for this performance challenge. The theoretical performance of this pixel is modeled and compared to alternative HDR pixel architectures. This concept is proven with the fabrication of a 3.2 μm pixel in a back-side illuminated (BSI) process including capacitive deep trench isolation (CDTI). The electron-based image uses a standard 4T architecture with a pinned diode and provides state-of-the-art low-light performance, which is not altered by the pixel modifications introduced for the hole collection. The hole-based image reaches 750 kh+ linear storage capability thanks to a 73 fF CDTI capacitor. Both images are taken from the same integration window, so the HDR reconstruction is not only immune to the flicker issue but also to motion artifacts.


Rapid Isolation of BMPR-IB+ Adipose-Derived Stromal Cells for Use in a Calvarial Defect Healing Model.
Invasive cancers, major injuries, and infection can cause bone defects that are too large to be reconstructed with preexisting bone from the patient's own body. The ability to grow bone de novo using a patient's own cells would allow bony defects to be filled with adequate tissue without the morbidity of harvesting native bone. There is interest in the use of adipose-derived stromal cells (ASCs) as a source for tissue engineering because these are obtained from an abundant source: the patient's own adipose tissue. However, ASCs are a heterogeneous population and some subpopulations may be more effective in this application than others. Isolation of the most osteogenic population of ASCs could improve the efficiency and effectiveness of a bone engineering process. In this protocol, ASCs are obtained from subcutaneous fat tissue from a human donor. The subpopulation of ASCs expressing the marker BMPR-IB is isolated using FACS. These cells are then applied to an in vivo calvarial defect healing assay and are found to have improved osteogenic regenerative potential compared with unsorted cells.


A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation.
Short- and long-term effects of hyperlipidemia with elevated FFA on insulin secretion were investigated. Male Sprague-Dawley rats were fed ad libitum and additionally infused with Intralipid 10%, 1.0 ml/h. After 3 h of Intralipid the response to 27 mM glucose in isolated perfused pancreas was enhanced by 86%, P less than 0.02. After 6 h of Intralipid enhancement had subsided. After 48 h of Intralipid glucose-induced insulin release was inhibited by 49%, from 1950 +/- 177 microU/min after saline to 1003 +/- 232 microU/min after Intralipid, P less than 0.02. Inhibition was glucose-selective since responses to other secretagogues (1 mM 3-isobutyl-1 methylxanthine, 10 mM octanoate, or 5 mM alpha-ketoisocaproic acid) were unaffected as were pancreatic contents of insulin (2284 +/- 111 mU/pancreas after saline, 2566 +/- 131 mU/pancreas after Intralipid). In isolated islets from 48 h lipid infused rats production of [14-C]CO2 from D[U-14-C]glucose was decreased (P less than 0.02) in parallel with the insulin response to 27 mM glucose. Glucose-induced secretion was partially normalized by in vitro exposure to a carnitine palmitoyl-transferase I inhibitor (Etomoxir). Effects of a 48 h lipid infusion were also tested during hyperglycemia. Rats were infused with glucose, and hyperglycemia was enhanced by dexamethasone (25 micrograms/24 h). Hyperglycemia depressed glucose-induced secretion from perfused pancreas from 2072 +/- 22 microU/min after saline + dexamethasone to 1185 +/- 155 microU/min after glucose + dexamethasone, P less than 0.01). Intralipid, added to the latter protocol, further inhibited glucose-induced secretion to 437 +/- 87 microU/min, P less than 0.005. Hyperlipidemia is concluded to be associated with short term stimulation but long term inhibition of glucose-induced insulin secretion. Evidence indicates that inhibition depends on fatty acid oxidation, is coupled to decreased glucose oxidation and operates both during normo- and hyperglycemia.


T7 RNA polymerase: use of limited proteolysis for the study of enzyme's interaction with substrates and inhibitors.
The specific limited trypsinolysis of bacteriophage T7 RNA polymerase (T7RP) was performed in the presence of various components of the polymerase reaction and some GTP-analogs--irreversible inhibitors of the enzyme. The differences in the rate and sites of proteolysis were observed. Basing on the data obtained the role of the N-terminal domain of the T7RP in the interaction with promoter-containing template is proposed.


Restless legs syndrome and pregnancy: prevalence, possible pathophysiological mechanisms and treatment.
Restless legs syndrome (RLS) is a common sleep disorder that may be associated with pregnancy. Studies have found that the prevalence of RLS among pregnant women ranged from 10 to 34%. Typically, there is complete remission of symptoms soon after parturition; however, in some patients, they may continue postpartum. RLS has been shown to be associated with a number of complications in pregnancy including preeclampsia and increased incidence of Cesarean sections. Although multiple hypotheses have been proposed to explain this association, each individual hypothesis cannot completely explain the whole pathogenesis. Present understanding suggests that a strong family history, low serum iron and ferritin level, and high estrogen level during pregnancy might play important roles. Vitamin D deficiency and calcium metabolism may also play a role. Medical treatment of RLS during pregnancy is difficult and challenging considering the risks to mother and fetus. However, in some cases, the disease may be severe enough to require treatment.


Can Fundus Fluorescein Angiography be Performed for Diabetic Patients on Oral Metformin?.
Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.


Development and application of recombinase polymerase amplification assay for rapid detection of Blastocystis sp.
Blastocystis sp. is a common parasite in the intestinal tract of humans and animals. The clinical diagnosis of Blastocystis sp. mainly depends on the microscopic observation of parasite, which can lead to false-negative results. An accurate and convenient diagnostic approach for Blastocystis sp. infection is crucial for effectively preventing and controlling blastocystosis. Herein, we developed a recombinase polymerase amplification (RPA) method for detecting Blastocystis sp. The results showed that the DNA amplification by RPA established in this study could be performed within 5 min at 37°C, with maximum band intensity observed at 30 min. The minimum detection limit of RPA was 100 fg μL−1, consistent with conventional polymerase chain reaction (cPCR). Furthermore, the RPA method exhibited no cross-reactivity with 7 other non-target pathogens in the intestinal tract. Next, the newly established RPA method was used to analyse 40 fecal samples collected clinically, and the detection results were consistent with cPCR. These results corroborate that the newly developed RPA method has good sensitivity and specificity and offers the advantage of short detection times, which can be harnessed for differential diagnosis and rapid detection of Blastocystis sp.


[Human lymphocyte immunophenotype after interaction with mesenchymal stromal cells].
Human multipotent mesenchymalstromal cells were cocultured for 72h with allogeneic blood-borne mononuclear cells (MNCs) of different maturity (lymphocytes from adult peripheral blood and umbilical cord blood) and functional state (intact and PHA-activated human peripheral blood lymphocytes): After coculture with MMSCs the share ofB-cells among MNCs and cbMNCs decreased. The proportion ofT- and NK cells declined only among cbMNCs (p < 0.05). Only T-NK subpopulation reduced among MNC and cbMNC T-cells. The drop of CD8+ cells was detected in coculture of MMSCs and PHA-MNCs. Activated HLA-DR+ cells declined, CD25+ cells increased compared to monoculture of PHA-MNCs. MMSCs supported MNC, PHA-MNC and cbMNC viability. These results are important for understanding the physiology of the allogeneic cell-to-cell interaction in connection of potential clinical application of allogeneic cell products of blood-borne and stroinal origin.


Inhibitors in hemophilia patients: current status and management.
The development of inhibitor antibodies is a long-standing, well-documented complication of coagulation factor replacement therapy and is difficult to treat. Previous estimates of 5-15% of patients developing inhibitors may be low, since newer data suggest a wider range of occurrence. Factors that appear to affect inhibitor development include the severity of hemophilia, age, genetics, and, possibly, the type of replacement therapy administered. Recent studies raise the concern that recombinant factor therapies may be associated with more rapid development and higher levels of inhibitors in previously untreated patients. However, results of different studies are often difficult to compare owing to differences in methodology and populations studied. Further studies standardized in design and methods are clearly needed. Management of patients with inhibitors involves control of acute bleeding episodes and, over the long term, induction of immune tolerance for the coagulation replacement therapy. Many with low or moderate levels of inhibitors may be treated simply by administering higher doses of clotting factor. Other therapies appropriate for those with high levels of inhibitors include porcine F VIII and factor VIII "bypassing" agents, such as recombinant factor VIIa. Long-term immune tolerance has been achieved through the high-dose "Bonn" regimen and immunosuppressive regimens such as the "Malmö" method. Although management of inhibitor patients has improved, it still represents a major challenge. Further research is needed to identify which patients will develop inhibitors and tolerance, as well as to develop better methods to manage, reduce, or eliminate inhibitors from these patients.


Sensory feedback control of upper- and lower-extremity motor prostheses.
The topic is introduced with a conceptual definition of sensory feedback control applied to prosthetic systems. An overview of sensory physiology is then provided. Tactile sensation and audition are specifically discussed. Next, the artificial sensory systems are evaluated. This is done with respect to sensory (input) transducers, signal encoding/decoding, and sensing output transducers. Specific prosthetic systems are then reviewed. First, upper-extremity prostheses are reviewed with respect to artificial arm/hand systems as well as neuroprostheses. Next, lower-extremity prostheses are reviewed, and include both artificial leg and foot systems as well as neuroprostheses. Finally, conclusions are drawn regarding effective state-of-the-art sensory feedback control used with orthotic and prosthetic systems.


Specificity in the familial aggregation of overt and covert conduct disorder symptoms in a referred attention-deficit hyperactivity disorder sample.
To examine the familial associations of overt and covert antisocial behavior within the diagnosis of conduct disorder (CD) in families ascertained by referred children with attention-deficit hyperactivity disorder (ADHD), and to test if these familial associations differed between male and female probands. Subjects were clinically-referred male and female ADHD children (n = 273) and their first-degree biological relatives (n = 807). Scores for overt and covert conduct problems were calculated by summing the DSM-III-R conduct disorder symptoms, as derived from structured diagnostic interviews. Familial aggregation analyses were conducted with multivariate regression modeling methodology. Proband overt scores significantly predicted the overt scores of their relatives, and proband covert scores significantly predicted the covert scores of their relatives. There was no evidence of covert symptom scores predicting overt scores or vice versa. There was some evidence that the aggregation of covert symptoms was stronger in the families of female probands. These results provide preliminary evidence that overt and covert conduct disorder symptoms are independently transmitted through families and may represent distinct familial syndromes.


[In vitro development of rifampicin resistance in the epithelial cells].
It has been first in vitro demonstrated on a model of epithelial cells that rifampicin may develop not only at the level of Mycobacterium tuberculosis, but also at the level of somatic cells. The mechanism of this phenomenon, its specificity (whether cross resistance to other antituberculous agents will occur), the way it puts into effect under the conditions of a microorganism, and how promptly it may be gone after discontinuation of the drug remain unknown. The effect of rifampicin on the functional activity of Pgp is an important factor that influences as a result not only the absorbability of drugs, but also normal transport processes in the body. These aspects seem to be topical and are the subject for further studies. The authors have obtained an epithelial cell line that resides in the presence of 100 microg/ml of rifampicin and that is 2-2.5 times more resistant to the drug as compared with the parental line. The cells of this line are 2-2.5 times more active in discharging the substrate rhodamine-123 for P-glycoprotein than those of the parental line, which suggests the enhanced functional activity of P-glycoprotein. The presence of P-glycoprotein in this line is confirmed by the action of this protein-specific blocker verapamil. At the same time rifampicin is not a substract for P-glycoprotein. Therefore, the mechanism of rifampicin resistance is unassociated with the functional activity of P-glycoprotein. The mechanism of the resistance remains open. At the same concentration (100 microg/ml), rifampicin can block the functional activity of P-glycoprotein. These results suggest the double mechanism of rifampicin in its long presence in the culture medium: as an inductor and a blocker of P-glycoprotein functional activity. The findings point to the fact that the pharmacokinetics of rifampicin and co-administered dtugs may change during their long use.


A Demographic Profile of Mothers and Their Children Who Are Victims of Family and Domestic Violence: Using Linked Police and Hospital Admissions Data.
The aim of this study was to examine the key sociodemographic characteristics of Australian mothers and their children who were victims of family and domestic violence (FDV) that resulted in the male perpetrator being criminally charged for the offense or the mother being hospitalized. A population-based retrospective cohort study using de-identified linked health and police data of mothers with children born 1987-2010 who were victims of FDV 2004-2008 was utilized. Results indicate that mothers who were identified in police data are different demographically from those identified in health data and differed again from mothers identified in both health and police data. Within Western Australia, 3% of the population identify as Aboriginal; however, 44% of mothers identified as victims in police data and 73% within the health data were Aboriginal. Of the mothers identified in police data, 30% were under 25 years of age at their first assault recorded in police data compared with 21% in those identified in both police and hospital data. Most mothers identified as victims of FDV in police data had children present at their assault (60.6%). Prevalence of FDV exposure, identified in police data, was significantly different in Aboriginal children compared with non-Aboriginal children. Aboriginal children had a 19-fold (p < .0001) increased difference in prevalence of exposure compared with their non-Aboriginal counterparts. The study reveals the challenges in identifying victims of FDV when relying on a single data source for research and highlights the need for multiple datasets when investigating FDV. The overrepresentation of Aboriginal mothers and children should be taken in the context of the long-lasting impact of colonization. As such, prevention and early intervention strategies need to be underpinned by Aboriginal communities' cultural authority.


Thyroidal changes associated with endurance training in women.
The associations between endurance training, body composition, and the pituitary-thyroid axis were studied in 17 healthy, young women. Body composition and plasma concentrations of T4, T3, rT3, resin T3 uptake, TSH, and TRH-stimulated TSH were examined at baseline and after each subject's weekly distance had increased 48 km (delta 48) and 80 km (delta 80) above baseline. Total body weight did not change at delta 48 or delta 80. Mean (+/- SE) lean weight in kg increased from 42.9 +/- 1.2 at baseline to 44.8 +/- 1.2 at delta 80 (P = 0.002). We have reported previously that at delta 48 the subjects had evidence of mild thyroidal impairment, which consisted of decreased T3 and rT3, and an exaggerated TSH response to TRH. With more prolonged training (delta 48 to delta 80) there were significant increases in T4, rT3, and unstimulated TSH, while the ratios of T4/rT3 and T3/rT3 and the TSH response to TRH decreased significantly. Some of the thyroidal changes that occurred between delta 48 and delta 80 are similar to those seen in other stressful non-thyroidal conditions.


Differentiation of chronic total occlusion and subtotal occlusion of the femoropopliteal artery-role of retrograde flow sign and collateral circulation on CT angiography images.
To study the value of a retrograde flow sign and the collateral circulation on CT angiography (CTA) for the differential diagnosis of chronic total occlusion from subtotal occlusion of the femoropopliteal artery (FPA). 50 patients with obstruction of the FPA underwent CTA and digital subtraction angiography examinations of the lower limbs. The frequency of a retrograde flow sign and collateral circulation on CTA in chronic total and subtotal occlusion was noted and analyzed, with the results of digital subtraction angiography as a standard to judge total or subtotal occlusion. The decreasing CT value from the distal to proximal direction on CTA suggests the existence of retrograde flow. There were significant differences in the occurrence rates of a retrograde flow sign on CTA in the chronic total and subtotal obstruction groups (X2 = 13.1, p < 0.05), as well as a collateral circulation sign (X2 = 13.5, p < 0.05). Employing both the retrograde flow sign and the collateral circulation sign to diagnose chronic total obstruction of the FPA had a sensitivity of 92.3% and specificity of 89.8%. The retrograde flow sign combined with a collateral circulation sign is of great clinical value for differentiation of chronic total stenosis from severe stenosis (subtotal occlusion) of the FPA. Advances in knowledge: A retrograde flow sign combined with a collateral circulation sign is of great clinical value to differentiate between chronic total stenosis and severe stenosis (subtotal occlusion) of the FPA.


Progress on the regulation of neural crest and the genetics in craniofacial development.
The craniofacial features endow vertebrates with unparalleled evolutionary advantages. The craniofacial is composed of bone, cartilage, nerves, and connective tissues mainly developed from cranial neural crest cells (cNCCs). These tissues form complex organs which enable vertebrates to have powerful neural and sensory systems. NCCs are groups of migratory and pluripotent cells that are specific to vertebrates. The specification, premigration and migration, proliferation, and fate determination of the NCCs are precisely and sequentially controlled by gene regulatory networks, to ensure the ordered and accurate development of the craniofacial region. The craniofacial region represents a combined set of highly heritable phenotypes, which could be illustrated by the inherited facial features between relatives but perceptible differences among non-relatives. Such phenomena are termed heredity and variation, which are in accordance with the precision and plasticity of cNCCs gene regulatory network, respectively. Evidence has shown that genetic variations within the regulatory network alter the proliferation and differentiation of NCCs within a tolerable range, while deleterious mutations will lead to craniofacial malformations. In this review, we first summarize the development procedure of NCCs and their gene regulatory networks and then provide an overview on the genetic basis of the facial morphology and malformations. This review will benefit the understanding of craniofacial development and the prevention of craniofacial diseases.


Assessment of acquired immune response to Rhipicephalus appendiculatus tick infestation in different goat breeds.
Changes in serum gamma globulin levels, numbers of replete female ticks and engorged tick mass were used as parameters to monitor the acquired immune response (antibody mediated immune response) elicited by Rhipicephalus appendiculatus adult tick infestations. Three consecutive Rhipicephalus appendiculatus adult tick infestations were applied to South African Indigenous goats (Nguni), Saanen goats and cross-bred goats (Saanen goats crossed with South African Indigenous goats [Nguni]) under laboratory conditions. During the three consecutive Rhipicephalus appendiculatus adult tick infestations the serum gamma globulin levels increased in all three breeds, whilst the mean replete female tick numbers and engorged tick mass decreased. Even though all three goat breeds exhibited an acquired immune response, the South African Indigenous goats (Nguni) response was significantly higher than that of the Saanen and cross-bred goats. However, the acquired immune response elicited by Saanen goats was significantly lower when compared with cross-bred goats.


Approximal caries increment in relation to baseline approximal caries prevalence among adolescents in Sweden with and without a school-based fluoride varnish programme.
Approximal surfaces are a focal point for caries prevention among adolescents in Sweden and the aims of this study were therefore to evaluate approximal caries incidence and caries progression among adolescents with and without a three-year school-based fluoride varnish programme in relation to approximal caries prevalence at baseline. In all, 758 (89%) 13-year-olds completed the three-year randomised controlled trial. They all used fluoride toothpaste at home and had regular dental check-ups at the public dental clinics. The mean approximal caries incidence for the adolescents who were caries free on these surfaces at baseline was 0.13 (SD 0.54) in the fluoride varnish group and 0.79 (1.93) in the control group. The corresponding values for those who had caries at baseline in these groups were 1.29 (2.21) and 2.62 (3.22) respectively. The latter two groups also had 0.34 (1.00) and 0.70 (1.13) approximal enamel lesions that progressed. All differences were statistically significant (p⟨0.001). Among those individuals who had approximal caries at baseline, double the number of early approximal enamel lesions in the control group progressed compared with the fluoride varnish group. The school-based fluoride varnish programme inhibited new approximal lesions to a great extent and effectively kept approximal enamel lesions within the enamel among 13-16-year-olds. It is therefore recommended that such a programme is warranted when the approximal surfaces are still caries free in order to keep these surfaces free from caries and keep upcoming approximal enamel lesions within the enamel.


SAPHO syndrome: pathogenesis, clinical presentation, imaging, comorbidities and treatment: a review.
Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a constellation of dermatological and osteoarticular symptoms. The pathogenesis of SAPHO is unknown, but infectious, genetic, immunological and environmental factors may play a role. SAPHO is classified along two different spectrums: pustulo-psoriatic hyperostotic spondyloarthritis and chronic recurrent multifocal osteomyelitis. The typical skin lesions are palmoplantar pustulosis and acne. The sign of arthritis is involvement of the anterior chest wall, most often the sternoclavicular joints. There are no standard treatment recommendations, but nonsteroidal anti-inflammatory drugs, sulfasalazine, methotrexate, antibiotics and biological drugs can be considered.


Effect of high 131I doses to the thyroid gland on tumorigenicity of 90Sr and 90Y in mice.
The incidence of tumors was studied in mice injected with 90Sr only or with 90Sr in combination with high amounts of 131I. The high 131I-dose to the thyroid gland was necrotizing to the glandular tissue and the main aim of the investigation was the possible effects of the thyroidal destruction on the formation of bone tumors. After correction for competing mortality, no significant difference in the frequency of bone tumors could be found between 90Sr-treated and (90Sr + 131I)-treated mice. The incidence rate of bone tumors, however, was higher in mice with radiogenically destroyed glands than in those with intact glands. The limitations of using the concept of 'actuarial tumor incidence' in correction for competing mortality in animal experiments are discussed. Large numbers of lymphatic tumors were found in all animal groups. The frequencies of such tumors were independent of the radiation doses but their incidence rates were shortened in a dose dependent manner. Other, directly or indirectly radiation induced tumors were observed.