Spontaneous rupture of hydronephrotic kidney during pregnancy: value of serial sonography.
Hydronephrosis during pregnancy is common but rarely results in renal rupture. We report an unusual case of spontaneous rupture of a hydronephrotic kidney during pregnancy. Although we could not predict the renal rupture on the basis of sonographic findings, serial sonography was useful in the early detection and management of the rupture.


Statistics of noisy growth with mechanical feedback in elastic tissues.
Tissue growth is a fundamental aspect of development and is intrinsically noisy. Stochasticity has important implications for morphogenesis, precise control of organ size, and regulation of tissue composition and heterogeneity. However, the basic statistical properties of growing tissues, particularly when growth induces mechanical stresses that can in turn affect growth rates, have received little attention. Here, we study the noisy growth of elastic sheets subject to mechanical feedback. Considering both isotropic and anisotropic growth, we find that the density-density correlation function shows power law scaling. We also consider the dynamics of marked, neutral clones of cells. We find that the areas (but not the shapes) of two clones are always statistically independent, even when they are adjacent. For anisotropic growth, we show that clone size variance scales like the average area squared and that the mode amplitudes characterizing clone shape show a slow [Formula: see text] decay, where n is the mode index. This is in stark contrast to the isotropic case, where relative variations in clone size and shape vanish at long times. The high variability in clone statistics observed in anisotropic growth is due to the presence of two soft modes-growth modes that generate no stress. Our results lay the groundwork for more in-depth explorations of the properties of noisy tissue growth in specific biological contexts.


Involuntary masturbation and hemiballismus after bilateral anterior cerebral artery infarction.
Ischemia of the areas supplied by the anterior cerebral artery is relatively uncommon. In addition, combined hemiballismus and masturbation have rarely been reported in patients with cerebrovascular disease. We describe herein a 62-year-old right-handed man simultaneously exhibiting right side hemiballismus and involuntary masturbation with the left hand after bilateral infarction of the anterior cerebral artery territory. Right side hemiballismus was related to the disruption of afferent fibers from the left frontal lobe to the left subthalamic nucleus. Involuntary masturbation using the left hand was exclusively linked to a callosal type of alien hand syndrome secondary to infarction of the right side of the anterior corpus callosum. After 2 weeks, these abnormal behaviours were completely extinguished. This report stresses the wide diversity of clinical manifestations observed after infarction of the anterior cerebral artery territory.


Chemically modified chiral monolithic silica column prepared by a sol-gel process for enantiomeric separation by micro high-performance liquid chromatography.
In this work a new type of chiral monolith silica column was developed for the chiral separation by micro high-performance liquid chromatography (micro-HPLC). The chiral monolith column with a continuous skeleton and a large through-pore structure was prepared inside a capillary of 100 microm I.D. by a sol-gel process, and chemically modified with chiral selectors, such as L-phenylalaninamide, L-alaninamide and L-prolinamide, on the surface of the monolithic silica column. Based on the principle of ligand exchange, these chiral monolithic columns were successfully used for the separation of dansyl amino acid enantiomers, as well as hydroxy acid enantiomers by micro-HPLC. The chromatographic conditions, the enantioselectivity and the performance of columns are discussed.


Opinions of practicing general surgeons on surgical education.
Collective opinions of practicing general surgeons on the current state of general surgical resident education are unknown. A 26-item survey was mailed to practicing general surgeons in Minnesota and Texas. Average scores on 17 Likert-formatted questions and opinions on multiple-choice questions were compared by geographic area and academic affiliation. Overall response was 954 of 1,745 (55%). All surgeons felt changes were needed in surgical education. There was agreement by geographic area and academic affiliation that the current system of resident education allows chief residents to graduate with significant gaps in their education, and that the responsibility for correcting these gaps lies with the residency program. Opinions of general surgeons in two geographic areas and of differing academic affiliation regarding surgical education showed marked similarity. These data suggest change in the process of surgical education is the responsibility of the residency program and should be a priority for the profession.


Junctional rhythm during cryoablation for typical atrioventricular nodal reentrant tachycardia.
Cryoablation is being used as an alternative to radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) owing to the lower risk of atrioventricular block (AVB) compared to RF ablation. Junctional rhythm often occurs during successful application of RF ablation for AVNRT. In contrast, junctional rhythm has rarely been reported to occur during cryoablation. This retrospective study evaluated the characteristics of junctional rhythm during cryoablation for typical AVNRT. This retrospective study included 127 patients in whom successful cryoablation of typical AVNRT was performed. Patients diagnosed with atypical AVNRT were excluded. Junctional rhythm appeared during cryofreezing in 22 patients (17.3%). These junctional rhythms appeared due to cryofreezing at the successful site in the early phase within 15 s of commencement of cooling. Transient complete AVB was observed in 10 of 127 patients (7.9%), and it was noted that atrioventricular conduction improved immediately after cooling was stopped in these 10 patients. No junctional rhythm was observed before the appearance of AVB. No recurrence of tachycardia was confirmed in patients in whom junctional rhythm occurred by cryofreezing at the successful site. Occurrence of junctional rhythms during cryoablation is not so rare and can be considered a criterion for successful cryofreezing. Furthermore, junctional rhythm may be associated with low risk of recurrent tachycardia.


Skin tumours in white South Africans. Part IV. Influence of occupation, sun sensitivity, colouring and associated skin tumours on the incidence of skin tumours.
Outdoor and industrial occupations in the southern Transvaal do not increase the incidence of any skin tumour excepting that of squamous cell carcinoma. However, they accelerate the onset of solar keratoses and squamous and basal cell carcinomas. A fair, sun-sensitive skin, red hair and blue eyes are more important factors predisposing towards the development of skin cancer. Unduly large numbers of seborrhoeic keratoses were found in association with polyps, and of intradermal naevi with both cavernous haemangiomas and lentigines. A high proportion of solar keratosis was found in both squamous cell carcinoma and Bowen's disease, and of basal cell carcinoma in superficial basal carcinoma, but the reverse associations were not significant.


Increased hepatic insulin clearance after Roux-en-Y gastric bypass.
Roux-en-Y gastric bypass (RYGB) improves glucose tolerance and ameliorates fasting hyperinsulinemia within days after surgery. Improvements in hepatic insulin sensitivity and insulin clearance could contribute importantly to these effects. The objective of the investigation was to study changes in insulin clearance after RYGB. This was a prospective study of fasting hepatic insulin clearance and, in a subgroup of patients, postprandial insulin clearance after a meal test before and 1 week, 3 months, and 1 year after RYGB. The study was conducted at Hvidovre Hospital (Hvidovre, Denmark). Patients included 2 groups of obese RYGB-patients: 1) type 2 diabetes (T2D) group: 32 patients with T2D (meal test, n = 13), 2) normal glucose tolerance (NGT) group: 32 patients with NGT (meal test, n = 12). The intervention was RYGB. Fasting hepatic insulin clearance (fasting C-peptide/fasting insulin). Postprandial insulin clearance (incremental areas under the curve of insulin secretion rates/incremental areas under the curve of insulin). Fasting hepatic insulin clearance increased after 1 week (P < .01) and further at 3 months (P < .01), remaining elevated 1 year postoperatively (P < .01) with no difference between the T2D and NGT groups. Postprandial insulin clearance changed only in the T2D group with an increase at 1 week (P < .01) that was maintained at 3 months (P = .06) and 1 year (P < .01). RYGB increases insulin clearance within 1 week after surgery, highlighting the liver as a key organ involved in the early beneficial effect on glucose metabolism. Postprandial insulin secretion may be underestimated postoperatively in patients with type 2 diabetes when evaluated by peripheral insulin concentrations instead of insulin secretion rates or C-peptide.


Effect of acceptor membrane phosphatidylcholine on the catalytic activity of bovine liver phosphatidylcholine transfer protein.
Protein-mediated transfer of phosphatidylcholine (PC) by bovine liver phosphatidylcholine transfer protein (PC-TP) was examined using a vesicle-vesicle assay system. Donor and acceptor membranes were prepared from Escherichia coli phospholipids and limiting amounts of egg yolk PC. PC transfer between vesicles of E. coli lipid/egg PC was markedly higher than transfer of PC from vesicles of E. coli lipid/egg PC to vesicles of E. coli lipid. Kinetic parameters of the interaction between PC-TP and E. coli lipid vesicles with or without PC was investigated. The apparent dissociation constants of the complex formed between PC-TP and these vesicles were determined kinetically and from double-reciprocal plots of intrinsic PC-TP fluorescence intensity increase versus vesicle concentration. The magnitude of the dissociation constant decreased as the PC content of the vesicles increased from 0 to 5 mol%. In addition, kinetic analysis revealed that the presence of PC in acceptor vesicles increased both the association and dissociation of PC-TP from vesicles. The effect of membrane PC molecules on transfer rates was examined using bis-phosphatidylcholine, a dimeric PC molecule which is not transferred by PC-TP. Rates of PC transfer to acceptor vesicles comprised of E. coli lipid/bis-PC were virtually identical to rates observed with acceptors vesicles prepared from E. coli lipid. The results suggest that transfer of PC by PC-TP is enhanced only when insertion of protein-bound PC occurs concurrently with the extraction of a molecule of membrane PC, i.e., a concerted, one-step catalytic mechanism for phospholipid exchange.


One hundred years ago: the dawning of the insulin era.
The dawn of the insulin era can be placed in 1921, when Banting and Best started their experiments which led, a year later, to the successful treatment of diabetes. They were preceded by the discoveries of the pancreatic cause of diabetes by Minkowski and von Mering in 1889 and of the islets by Paul Langerhans in 1869. The achievement of the first targeted treatment in medical history was a landmark of medical progress. However, it was accompanied by a mixture of human greatness and misery. Genius and recklessness, ambition and deception, camaraderie and rivalry, selflessness and pursuit of glory went along with superficial search of the existing literature, poor planning, faulty interpretation of results, failure to reproduce them, and misquoting of reports from other laboratories. Then as now, such faults surface whenever human nature aims to push forward the boundaries of knowledge and pose a real challenge in today's world, as the scientific method strives to keep healthy in the face of growing anti-scientific feelings.


Misdiagnosis of primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type, a case report.
Extra-nodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue originating in the liver is less common. We described the clinical presentation, immunohistochemistry, and immunophenotypes of this lymphoma, which was misdiagnosed with tiny hepatic carcinoma in a 44-year-old woman with hepatitis C; the patient underwent left lateral sectionectomy. The immunophenotype identified the most of the lymphoid cells as positive CD20, CD34, Ki67, CD3, CD4, CD79a, CD45RO, MUM-1, and CD5 and negative CD10, CD15, CD30, ACT, CK, CRO, DES, and HMB45. The diagnosis of primary hepatic mucosa-associated lymphoid tissue (MALT) was made by histology after surgery; the patient went through the excellent recovery with no chemotherapy and is disease free for 27 months. Primary hepatic MALT is less common with incidental finding; local resection is beneficial due to its oncological indolence.


Electrokinetic remediation of a Cu-Zn contaminated red soil by controlling the voltage and conditioning catholyte pH.
Electrokinetics is an innovative technique for treating heavy metals contaminated soil, especially low pH soils such as the Chinese red soil (Udic Ferrisols). In this paper, a Cu-Zn contaminated red soil is treated by electrokinetics. When the Cu-Zn contaminated red soil was treated without control of catholyte pH during the electrokinetic treatment, the soil pH in the soil sections near cathode after the experiment was high above 6, which resulted in accumulation of large amounts of Cu and Zn in the soil sections with such high pH values. Compared to soil Cu, soil Zn was more efficiently removed from the soil by a controlled electrokinetic method. Application of lactic acid as catholyte pH conditioning solution caused an efficient removal of Cu and Zn from the soil. Increasing the electrolyte strength (salt concentration) of the conditioning solution further increased Cu removal, but did not cause a significant improvement for soil Zn. Soil Cu and Zn fractions after the electrokinetic treatments were analyzed using sequential extraction method, which indicated that Cu and Zn precipitation in the soil section closest to the cathode in the treatments without catholyte pH control limited their removal from the soil column. When the catholyte pH was controlled by lactic acid and CaCl(2), the soil Cu and Zn removal percentage after 554 h running reached 63% and 65%, respectively. Moreover, both the residual soil Cu and Zn concentrations were lower than 100 mg kg(-1), which is adequate and meets the requirement of the Chinese soil environmental quality standards.


A Torn or Reconstructed Anterior Cruciate Ligament Does Not Adversely Affect Clinical Outcome Scores and the Incidence of Reoperation After Unrestricted Kinematically Aligned Total Knee Arthroplasty.
There are no reports as to whether the condition of the anterior cruciate ligament (ACL) adversely affects the 2 to 3 year function and reoperation risk of a kinematically aligned (KA) total knee arthroplasty (TKA) performed with posterior cruciate ligament (PCL) retention and an intermediate medial conforming (MC) insert. A single surgeon's prospective database query identified 418 consecutive primary TKAs performed between January 2019 and December 2019. The surgeon recorded the ACL condition in the operative note. Patients filled out the Forgotten Joint Score (FJS), Oxford knee score (OKS), and Knee Injury and Osteoarthritis Outcome Scores for Joint Replacement at the final follow-up. There were 299 patients with an intact ACL, 99 with a torn ACL, and 20 with a reconstructed ACL. The mean follow-up was 31 months (range, 20 to 45). The median FJS, OKS, and Knee Injury and Osteoarthritis Outcome Score (KOOS) of the reconstructed/torn/intact KA TKAs were 90/79/67, 47/44/43, and 92/88/80 points, respectively. The median OKS and KOOS of the reconstructed ACL cohort were 4 and 11 points higher than in the intact ACL cohort (P = .003, .04). One patient who had a reconstructed ACL underwent manipulation under anesthesia (MUA) for stiffness. The 5 reoperations in the intact ACL cohort were for instability (n = 2), revision after failed MUA for stiffness (n = 2), and infection (n = 1). These results suggest that patients who have a torn and reconstructed ACL can expect high function and a low risk of reoperation comparable to patients who have an intact ACL when treated with unrestricted, caliper-verified KA, PCL retention, and an intermediate MC insert.


BDNF signaling in context: From synaptic regulation to psychiatric disorders.
Brain-derived neurotrophic factor (BDNF) is a neuropeptide that plays numerous important roles in synaptic development and plasticity. While its importance in fundamental physiology is well established, studies of BDNF often produce conflicting and unclear results, and the scope of existing research makes the prospect of setting future directions daunting. In this review, we examine the importance of spatial and temporal factors on BDNF activity, particularly in processes such as synaptogenesis, Hebbian plasticity, homeostatic plasticity, and the treatment of psychiatric disorders. Understanding the fundamental physiology of when, where, and how BDNF acts and new approaches to control BDNF signaling in time and space can contribute to improved therapeutics and patient outcomes.


Molecular dynamics in cells: A neutron view.
Experiments to characterize intracellular molecular dynamics in vivo are discussed following a description of the incoherent neutron scattering method. Work reviewed includes water diffusion in bacteria, archaea, red blood cells, brain cells and cancer cells, and the role of proteome molecular dynamics in adaptation to physiological temperature and pressure, and in response to low salt stress in an extremophile. A brief discussion of the potential links between neutron scattering results and MD simulations on in-cell dynamics concludes the review.


Proteolysis of smooth muscle myosin light chain kinase. Formation of inactive and calmodulin-independent fragments.
Proteolysis by trypsin of gizzard myosin light chain kinase in the absence of Ca2+-calmodulin causes a biphasic effect on kinase activity. During the initial phase of proteolysis, Ca2+-calmodulin-dependent kinase activity is reduced over a thousand-fold. Further proteolysis, in the second phase, causes an increase in activity that is independent of Ca2+-calmodulin. Loss of activity is associated with the formation of a 64,000-dalton fragment. Calmodulin-independent activity is associated with the formation of a 61,000-dalton fragment. Procedures for the isolation of each fragment are outlined. Tryptic hydrolysis of the isolated 64,000-dalton peptide generates the 61,000-dalton peptide and increases calmodulin-independent activity. Km values for ATP and light chains for the native kinase and two fragments are the same, i.e. approximately 100 and 5 microM, respectively. Neither fragment binds to F-actin. Amino acid analyses of both fragments are given. Synthetic peptides corresponding to the calmodulin-binding regions of the smooth and skeletal muscle kinases are potent inhibitors of the 61,000-dalton fragment. These data demonstrate the existence of an inhibitory region that is suggested to be located between the active site and the calmodulin-binding site. Whether it is distinct from or at the N-terminal end of the calmodulin-binding site cannot be determined from these data.


Evaluation of the mutagenic potential of ubidecarenone using three short-term assays.
Addition of ubidecarenone, coenzyme Q(10) (CoQ(10)), to foods has been proposed for its nutritive value. Ubidecarenone is present naturally in a number of foods, including meats (e.g., beef, chicken) and fish (e.g., herring, rainbow trout), and on average, people are estimated to consume 2-20 mg/day of this metabolically important substance. Currently, relatively little formal evidence regarding the safety of ubidecarenone has been identified in the toxicology literature, despite its consumption by humans for centuries without reported notable adverse effects. As such, a series of toxicological studies, including mouse bone marrow micronucleus, chromosomal aberration, and bacterial reverse mutation tests, were conducted to evaluate the in vivo and in vitro mutagenic potential of CoQ(10). The test article, ubidecarenone, was devoid of clastogenic activity when administered orally to mice at doses up to 2000 mg/kg/day. In addition, the test article did not induce chromosomal aberration in CHL/IU cells exposed to concentrations as great as 5.0 mg/ml, nor did it induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations as great as 5000 microg/plate.


Effectiveness of a medication-adherence tool: study protocol for a randomized controlled trial.
Research shows that more than half of the people taking medication for a chronic condition are non-adherent. Nonadherence hinders disease control with a burden on patient quality of life and healthcare systems. We developed a tool that provides insight into nonadherence risks and barriers for medication-adherence including an intervention strategy to overcome those barriers. This study aims to assess the effectiveness of using this adherence tool in starters with cardiovascular or oral blood glucose-lowering medication to improve medication-adherence. In a cluster-randomized controlled trial 25 pharmacies in the Netherlands will be randomized to the intervention or control arm. Patients registered in a general practice participating in a collaborative can be included when they start cardiovascular or oral blood glucose-lowering medication prescribed by their general practitioner. Participants complete an assessment consisting of measuring nonadherence risk and potential barriers to adherence. For patients with an increased nonadherence risk, a graphic barrier profile is created, showing to what extent eight cognitive, emotional, or practical barriers are present. All patients will fill in the medication-adherence assessment twice: between 1 and 2 weeks after the start of the medication and after 8 months. The intervention strategy consists of discussing this barrier profile to overcome barriers. Pharmacists and assistants of the intervention pharmacies are trained in discussing the profile and to offer a tailored intervention to overcome barriers. In the control arm, patients receive care as usual. The primary outcome is medication-adherence of patients with a high risk of nonadherence at 8 months follow-up. Secondary outcomes include the difference in the percentage of patients with an increased nonadherence risk between intervention and control group after 8 months, the predictive values of the baseline questionnaire in the control group in relation to medication-adherence after 8 months, medication-adherence after 1 year follow-up, and barriers and facilitators in the implementation of the tool. This manuscript presents the protocol for a cluster-randomized clinical trial on the use of an adherence tool to improve medication-adherence. This study will provide insight into the effectiveness of the tool in starters with cardiovascular or oral blood glucose-lowering medication in improvement of medication-adherence. The Netherlands National Trial Register, NTR5186 . Registered on 18 May 2015.


Enhancement of antibacterial properties and biocompatibility of Ti6Al4V by graphene oxide/strontium nanocomposite electrodepositing.
Ti6Al4V is a widely used orthopedic implant material in clinics. Due to its poor antibacterial properties, surface modification is required to prevent peri-implantation infection. However, chemical linkers used for surface modification have generally been reported to have detrimental effects on cell growth. In this work, by optimizing parameters related to electrodeposition, a composite structural coating with graphene oxide (GO) compact films in the inner layer and 35 nm diameter strontium (Sr) nanoparticles in the outer layer was constructed on the surface of Ti6Al4V without using substance harmful to bone marrow mesenchymal stem cells (BMSCs) growth. The antibacterial properties of Ti6Al4V are enhanced by the controlled release of Sr ions and incomplete masking of the GO surface, showing excellent antibacterial activity against Staphylococcus aureus in bacterial culture assays. The biomimetic GO/Sr coating has a reduced roughness of the implant surface and a water contact angle of 44.1°, improving the adhesion, proliferation and differentiation of BMSCs. Observations of synovial tissue and fluid in the joint in an implantation model of rabbit knee also point to the superior anti-infective properties of the novel GO/Sr coating. In summary, the novel GO/Sr nanocomposite coating on the surface of Ti6Al4V effectively prevents surface colonization of Staphylococcus aureus and eliminates local infections in vitro and in vivo.


Quantitative determination of 8-hydroxy-2'-deoxyguanosine in human urine by isotope dilution mass spectrometry: normal levels in hemochromatosis.
A previously developed method for quantitative determination of 8-hydroxyguanine by gas chromatography-mass spectrometry was modified to allow measurement of 8-hydroxy-2'-deoxyguanosine in human urine. [4,5,6,8-(13)C4]8-Hydroxy-2'-deoxyguanosine was prepared by enzymatic coupling of [4,5,6,8-(13)C4]8-hydroxyguanine to deoxyribose-1-phosphate. Samples of human urine (2 ml) were spiked with the labeled nucleoside (13 nmol) and subjected to solid phase extraction and reversed phase high performance liquid chromatography. The 8-hydroxy-2'-deoxyguanosine thus isolated was hydrolyzed by treatment with aqueous formic acid, and the resulting 8-hydroxyguanine was converted into its tetrakis-trimethylsilyl derivative and subjected to gas-liquid chromatographic-mass spectrometric analysis. Repeated determinations of 8-hydroxy-2'-deoxyguanosine in pools of urine showed coefficients of variation of 5 and 8% at concentrations of 8-hydroxy-2'-deoxyguanosine equal to 18 and 2 nM, respectively. Determination of 8-hydroxy-2'-deoxyguanosine in samples of urine spiked with different amounts of the unlabeled nucleoside showed a mean recovery of 102%. Application of the analytical method to a group of 11 apparently healthy subjects (mean age, 47 years) showed a mean level of endogenously produced 8-hydroxy-2'-deoxyguanosine equal to 1.33 +/- 0.29 micromol/mol creatinine. The level recorded for another group of 15 younger subjects (mean age, 28 years) was somewhat higher, that is, 1.58 +/- 0.84 micromol/mol creatinine, corresponding to a 24-h production rate of 8-hydroxy-2'-deoxyguanosine equal to 20.6 +/- 11.6 nmol (288 +/- 140 pmol/24 h x kg body weight). Hemochromatosis is a hereditary disease characterized by increased absorption of iron from the gastrointestinal tract and deposition of iron in organs. Application of the analytical method to a group of 12 patients with hereditary hemochromatosis who were under treatment with venesections showed a mean level of urinary 8-hydroxy-2'-deoxyguanosine equal to 1.39 +/- 0.40 micromol/mol creatinine. This value was not significantly different from those of healthy subjects. The fact that these patients had only slight or moderate iron overload at the time of urinary sample collection may have influenced the urinary levels of 8-hydroxy-2'-deoxyguanosine in the present study.


Long-lasting effects of distrust in government and science on mental health eight years after the Fukushima nuclear power plant disaster.
We aimed to explore the effects of erosion of trust in authorities on the long-term mental health of community residents after the 2011 Fukushima nuclear power plant accident in Japan. We investigated the effects of distrust in authorities on mental health in a cohort study following non-evacuee community residents after the 2011 Fukushima nuclear power plant accident. A baseline questionnaire survey was administered five years after the accident for a random sample of 4900 residents outside the evacuation zone in Fukushima. Distrust in the national government and in science were assessed using a four-point single-item scale. Psychological distress was measured using the K6. Posttraumatic stress symptoms were measured using an abbreviated version of the Posttraumatic Stress Disorder Checklist-Specific version. Longitudinal associations of distrust in the government and science at baseline and psychological distress and posttraumatic stress symptoms eight years after the accident were examined, controlling for the baseline level of distress or symptoms using multivariate logistic regression analyses. Valid responses were obtained from 927 (18.9%) residents. Distrust in the government at baseline was significantly associated with posttraumatic stress symptoms at follow-up, albeit controlling for baseline symptoms. While distrust in the government was also associated with psychological distress at follow-up, the association became non-significant after controlling for baseline distress. Distrust in science at baseline was not associated with posttraumatic stress symptoms or psychological distress at follow-up. Distrust in government after a nuclear power plant accident may have adverse effects on mental health in the long-term.


A Transistor-like pH Nanoprobe for Tumour Detection and Image-guided Surgery.
Because of profound genetic and histological differences in cancerous tissue, it is challenging to detect a broad range of malignant tumours at high resolution. Here, we report the design and performance of a fluorescent nanoprobe with transistor-like responses (transition pH = 6.9) for the detection of the deregulated pH that drives many of the invasive properties of cancer. The nanoprobe amplifies fluorescence signal in the tumour over that in the surrounding normal tissues, resulting in a discretized, binary output signal with spatial resolution smaller than 1 mm. The nanoprobe allowed us to image a broad range of tumours in mouse models using a variety of clinical cameras, and to perform real-time tumour-acidosis-guided detection and surgery of occult nodules (< 1 mm3) in mice bearing head-and-neck or breast tumours, significantly lengthening mice survivability. We also show that the pH nanoprobe can be used as a reporter in a fast, quantitative assay to screen for tumour-acidosis inhibitors. The binary delineation of pH achieved by the nanoprobe promises to improve the accuracy of cancer detection, surveillance and therapy.


Effects of childhood physical abuse on depression, problem drinking and perceived poor health status in adolescents living in rural Taiwan.
The aim of the present study was to investigate the magnitude and independence of the effects of childhood physical abuse on adolescent depression, problem drinking and perceived poor mental health in Taiwanese indigenous and non-indigenous adolescents living in rural areas controlling for individual and familial characteristics. A sample of adolescents was randomly selected from junior high schools in the rural areas of southern Taiwan. The associations between childhood physical abuse and adolescent depression, problem drinking and perceived poor health status were examined on univariate and multivariate logistic regression. Of the 1684 adolescents who completed the questionnaires, 374 (22.2%) reported that they had experienced physical abuse in childhood. Controlling for individual and familial factors, childhood physical abuse significantly increased the risk of depression, problem drinking and perceived poor health status in the present sample of adolescents on multivariate logistic regression. History of childhood physical abuse should be elicited from adolescents in treatment for depression, alcohol abuse or physical discomfort of unknown etiology. This finding may be of clinical benefit in terms of the design and implementation of intervention.


Methods for separating temporally overlapping sources of neuroelectric data.
The localization of intracranial sources of EEG or MEG signals can be misled by the combined effect of several sources, as illustrated by simulated MEG data in which two of the three dipolar sources have slightly out of phase activity and partly complementary scalp topographies. These data were analysed by three different source localization methods. Fitting a single source to each sequential topography worked perfectly when only one source was active; this could also account for as much as 95% of the spatial variance of topographies resulting from two overlapping sources, although the solution was then far from any source. A principal component analysis approach followed by an oblique rotation (fitting one source to the spatial aspect of each component) correctly localized two of the sources but severely mislocated the source that was never active alone. Spatio-temporal source modeling (simultaneously fitting a set of sources to all consecutive topographies) correctly localized all three sources, provided that the parameter optimization method could escape sub-optimal local minima of the error function. Temporally overlapping sources can thus be separated and correctly identified if the mathematical model is adequate and the optimization procedure is well adapted.


The influence of hepatitis C virus-human immunodeficiency virus co-infection on the appearance of liver enzyme elevation in people on high activity antiretroviral treatment.
Liver enzyme elevation (LEE) as a consequence of HAART is a problem among patients with HIV-HCV co-infection. In this retrospective study, 145 patients with HIV who were on HAART and who developed LEE grades 3 and 4 of the World Health Organization (WHO) were followed up. Basal ALT, alcohol consumption, and HCV and HBV co-infection were recorded. Comparisons were made between patients with and without HCV co-infection. Three patients without co-infection presented LEE grade 3 versus 38 with co-infection (104 episodes). An increase in basal ALT (RR: 1.01) and HCV co-infection (RR: 6.6) were the variables associated with LEE grade 3. The number of days that HAART had to be withdrawn due to LEE was 58.15 and 4.85 in subjects with and without co-infection, respectively (p=0.024). Patients with HCV-HIV co-infection have more episodes of LEE and must go longer without HAART than people without co-infection.


Fetal myocardial tissue Doppler indices before birth physiologically change in proportion to body size adjusted for gestational age in low-risk term pregnancies.
Few studies have investigated the relationship between myocardial tissue Doppler parameters and fetal size adjusted for gestational age and its trend has been controversial. To investigate fetal cardiac function before birth using tissue Doppler imaging (TDI: indicated by the prime symbol (')) in low-risk term pregnancies by comparing the TDI parameters with gestational age-specific birth weight percentiles and z scores. Interventricular septum, left and right ventricular myocardial peak early diastolic (E'), late diastolic (A') and systolic (S') velocities, E'/A' ratios, myocardial performance index (MPI') and umbilical artery pulsatility index were measured within three days before birth in 76 low-risk term pregnancies, including appropriate for gestational age (AGA, n=50), small for gestational age (SGA, n=10), and large for gestational age (LGA, n=16) subjects. Myocardial peak velocities showed higher in the LGA and lower in the SGA compared with the AGA group, and All S' positively correlated with birth weight (r=0.51-0.57). All z scores of S' demonstrated a positive correlation with birth weight z score (Spearman r=0.45-0.53). MPI' was significantly higher in the SGA and lower in the LGA compared with the AGA group. All MPI' negatively correlated with birth weight (r=-0.55 to -0.65). All z scores of MPI' showed a negative correlation with birth weight z score (Spearman r=-0.40 to -0.56). Fetal myocardial peak velocities and MPI' physiologically changed in proportion to body size adjusted for gestational age in low-risk term pregnancies.


Effects of pentoxifylline on human sperm parameters in vitro.
Pentoxifylline was tested in three raising concentrations (0.7 mM/l, 1.5 mM/l, 3.6 mM/l) on human sperm cells in vitro. On 143 samples, we examined drug effect on motile sperm concentration, grade of their motility, acrosome reaction and membrane status. Obtained results show improvement in motile sperm concentration, as well as in the grade of progression in the majority of samples. Spermatozoa membranes as well as occurrence of the acrosomal reaction were not affected by pentoxifylline.


Comparative sialotranscriptome analysis of the rare Chinese cicada Subpsaltria yangi, with identification of candidate genes related to host-plant adaptation.
Little is known about the mechanisms underlying the relationship between changes in salivary proteins and the adaptation of insects to different host-plants. To address this knowledge gap, the transcriptional profiles of salivary glands were compared among three populations of the rare cicada Subpsaltria yangi, in which two populations specialize on Zizyphus jujuba var. spinosa, but the population occurring in the Helan (HL) Mountains is locally specialized on the endemic plant Ephedra lepidosperma. The comparisons indicate that genes related to digestion and detoxification are differentially regulated in populations feeding on different plants, possibly reflecting adaptative changes in salivary proteins of S. yangi in response to different host chemistries. In detail, 38 differentially expressed genes and 21 up-regulated genes related to digestion and detoxification were identified respectively in two pairwise comparisons among the populations using different hosts, with some genes exclusively expressed in the HL population. Our results are consistent with the hypothesis that the host plant shift in the HL population was facilitated by differential regulation of genes related to digestion and detoxification. This study provides new information for elucidating the molecular mechanisms underlying the relationship between changed salivary proteins and the adaptability of plant-feeding insects to novel host plants.


Mapping of atrial fibrillation: strategies to understand an enigmatic arrhythmia.
The three-dimensional (3D) mapping of cardiac arrhythmias has evolved in recent years to an important and extremely useful tool, providing important insights into arrhythmia mechanisms and thus improving ablation success rates, especially in complex arrhythmias. In atrial fibrillation (AF), the most common but also one of the most complex cardiac arrhythmias, progress in mapping technology has been focusing on several aspects according to the type of AF.In paroxysmal AF, important progress in the exact anatomic reconstruction of the main ablation target, i.e., the pulmonary veins (PV), has been achieved. Perhaps even more importantly, new insights into conduction patterns, such as deceleration at the PV ostia, spiral conduction more distally into the PV, and PV cross-talk have been detected and enable faster and more sustainable PV isolation.In persistent AF, the basic understanding of ongoing AF is perhaps the electrophysiological challenge of the 21st century. Since AF is instable in its course, mapping tools that assess statistically returning patterns or deal with so-called AF "rotors" or "drivers" have been developed, offering unique insights into possible AF mechanisms. Refined high-density bi-atrial voltage maps make it possible to further characterize the arrhythmogenic substrate and scar zones, while new and innovative mapping algorithms enable automated, fast, and reliable annotation of up to thousands of electrograms.This improved understanding of AF mechanisms has led to the development of promising new ablation strategies, some of which are already in use in clinical routine.


Allium stipitatum Extract Exhibits In Vivo Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus and Accelerates Burn Wound Healing in a Full-Thickness Murine Burn Model.
The in vivo antibacterial and burn wound healing potency of Persian shallot bulbs (Allium stipitatum) were explored in a mice burn model infected with methicillin-resistant Staphylococcus aureus (MRSA). Hexane (ASHE) and dichloromethane (ASDE) extracts were tested. Female BALB/c mice were inflicted with third-degree thermal injury followed by infection with MRSA. ASHE and ASDE formulated with simple ointment base (SOB) at concentrations of 1%, 2%, and 5% (w/w) were topically applied to burn wounds twice a day for 20 days. Silver sulfadiazine (1%) served as drug positive control. Microbiological analysis was carried out on 1, 2, 3, 4, and 5 days postwounding (dpw) and histopathological analysis at the end of the experiment (20 dpw). Both ointments demonstrated strong antibacterial activity with complete elimination of MRSA at 48-72 h after infection. The rate of wound contraction was higher (95-100%) in mice groups treated with ASHE and ASDE ointments after 15 dpw. Histological analysis revealed significant increase (p < 0.05) in epithelialization and collagenation in treated groups. The ASHE and ASDE were found to be relatively noncytotoxic and safe to Vero cell line (383.4 μg mL-1; 390.6 μg mL-1), suggesting the extracts as safe topical antibacterial as well as promising alternatives in managing thermal injuries.


Temporal changes in endocardial energy metabolism following propranolol and the metabolic basis for protection against isoprenaline cardiotoxicity.
Propranolol infusions in open-chested, anesthetised dogs increased endocardial levels of ATP and phosphocreatine. It reduced ADP, AMP, glucose-6-phosphate and lactate in this region. Endocardial glycogen was transiently increased. Metabolic perturbations in the endocardium produced by cardiotoxic doses of isoprenaline were prevented or reduced by propranolol pretreatment. Thus, propranolol appears to have a more selective action on endocardial versus midmyocardial or epicardial metabolism.


The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection.
The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency. On the other hand, the diphtheria toxin T domain fuses with endosome membrane by pH decrease, then enhances the endosomal escape of the diphtheria toxin C fragment. In this study, we constructed diphtheria toxin T domain-conjugated poly(ethylenimine)s (PEI) polyplex for enhancing the endosomal escape of exogenous gene. The conjugation of diphtheria toxin T domain with PEI/pDNA polyplex leads to the significant enhancement of transfection efficiency when compared with plain PEI/pDNA polyplex. The pH-responsive increase in hydrophobicity of the diphtheria toxin T domain might not only trigger the perturbation of the endocytic vesicle membrane but might also increase the membrane permeability.


Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section.
In a previous study, lactic acid bacteria were isolated from meconium obtained from healthy neonates born by cesarean section. Such a finding suggested that term fetuses are not completely sterile, and that a mother-to-child efflux of commensal bacteria may exist. Therefore, presence of such bacteria in umbilical cord blood of healthy neonates born by elective cesarean section was investigated. The blood samples were submitted to an enrichment step and then inoculated onto agar plates. All the identified isolates belonged to the genus Enterococcus, Streptococcus, Staphylococcus, or Propionibacterium. Later, a group of pregnant mice were orally inoculated with a genetically labeled E. faecium strain previously isolated from breast milk of a healthy woman. The labeled strain could be isolated and polymerase chain reaction detected from the amniotic fluid of the inoculated animals. In contrast, it could not be detected in the samples obtained from a noninoculated control group.


Assessment of in vitro percutaneous absorption of glycolic acid through human skin sections using a flow-through diffusion cell system.
The percutaneous absorption studies were performed using a flow-through diffusion cell system with skin specimens from 24 healthy women to assess the penetration of glycolic acid (GA). Percentages of GA, based on 14C-labelled activity, found in the skin after application of 4% GA at pH 2.0 or pH 3.8, after 24 h were as follows: stratum corneum (SC)= 2.65+/-1.80 versus 1.13+/-1.14 (P<0.05); viable skin (VS)= 13.46+/-7.44 versus 2.23+/-1.51 (P< 0.05) and effluent fraction (EF) = 12.22+/-9.03 versus 1.42+/-0.77 (P < 0.05), respectively. The applications of 4-60%, GA at their native pH resulted in an increased penetration of GA through the skin. For example, application of 20% GA, pH 1.9, resulted in the following values: SC = 2.69+/-2.26 (P > 0.05); VS = 4.88+/-4.05 (P > 0.05) and EF = 30.69+/-13.25 (P < 0.05). Duration of application also affected the extent of penetration of drug. For example, application of 20% GA, pH 1.9, for 6 h resulted in the following levels: SC = 1.16+/-0.80 (P < 0.05); VS = 4.07+/-1.78 (P > 0.05) and EF = 6.12+/-4.95 (P < 0.05). (i) absorption of GA in human skin are pH-, strength- and time-dependent; and (ii) the in vitro method appears to provide an appropriate model to reflect in vivo absorption of GA through human skin.


Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: II. Effects of triflusal.
Clinical data suggest that Alzheimer disease (AD) and stroke together potentiate cognitive impairment. Our rat model demonstrates that this interaction may be mediated through inflammatory cells and pathways. Thus, anti-inflammatory agents such as Triflusal, a nonsteroidal anti-inflammatory agent (NSAID), may provide neuroprotection for susceptible neurons in AD and cerebral ischemia. AD was modeled by cerebroventricular injections of beta-amyloid (Abeta25-35) and subcortical lacunar infarcts by striatal endothelin injections. Inflammatory mechanisms were examined by immunohistochemical analysis. Behavioral tasks were assessed with the Montoya staircase test. Triflusal reduced pathologic and inflammatory markers and functional deficits in rats receiving Abeta or endothelin alone but was less effective in the more severe pathology of the combined Abeta/endothelin model. Higher doses or more prolonged treatment with NSAIDs may be required for more effective neuroprotection in combined AD and stroke conditions.


Production and characterization of cellulolytic enzymes from the thermoacidophilic fungal Aspergillus terreus M11 under solid-state cultivation of corn stover.
The production of extracellular cellulases by a newly isolated thermoacidophilic fungus, Aspergillus terreus M11, on the lignocellulosic materials was studied in solid-state fermentation (SSF). The results showed that the high-level cellulase activity was produced at 45 degrees C pH 3 and moisture 80% with corn stover and 0.8% yeast extract as carbon and nitrogen sources. 581 U endoglucanase activity, 243 U filter paper activity and 128 U beta-glucosidase activity per gram of carbon source were obtained in the optimal condition. Endoglucanase and beta-glucosidase exhibited their maximum activity at pH 2 and pH 3, respectively, and both of them showed remarkable stability in the range of pH 2-5. The activities of endoglucanase and beta-glucosidase were up to the maximum at 70 degrees C and maintained about 65% and 53% of their original activities after incubation at 70 degrees C for 6h. The enzyme preparations from this strain were used to hydrolyze Avicel. Higher hydrolysis yields of Avicel were up to 63% on 5% Avicel (w/v) for 72 h with 20 U FPase/g substrate.


Contribution of monoaminergic nervous system in potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by malathion in male mice.
Malathion-induced marked potentiation of BPMC toxicity (about fivefold) was analyzed by measuring LD50 as an index of acute toxicity. The acute lethality of BPMC was decreased by muscarinic blockers (atropine, methylatropine, or trihexyphenidyl) or a monoamine oxidase inhibior (pargyline) and increased by a monoamine depleter (reserpine) or a dopaminergic blocker (haloperidol). The potentiation observed with BPMC and malathion was decreased by the muscarinic blockers, monoamine depleters (reserpine, alpha-methyl-p-tyrosine), an alpha-noradrenergic blocker (phentolamine), or haloperidol. The acute toxicities of other N-methylcarbamates MPMC (3,4-dimethylphenyl N-methylcarbamate), MTMC (3-methylphenyl N-methylcarbamate), NAC (1-naphthyl N-methylcarbamate), and XMC (3,5-dimethylphenyl N-methylcarbamate) were potentiated by malathion to a lesser degree than that of BPMC. Atropine protected against the lethalities of all N-methylcarbamates. Reserpine or haloperidol potentiated the lethalities of N-methylcarbamates with a similar tendency toward malathion. When the inhibitory effect of each N-methylcarbamate on brain acetylcholinesterase (AChE) was compared with its LD50, among five N-methylcarbamates BPMC had particularly strong anti-AChE activity. This characteristic of BPMC was not observed after the treatment with reserpine. These results suggest that BPMC may act not only on cholinergic nerves as an anti-AChE, but also on monoaminergic nerves which antagonize the lethal cholinergic effect. Malathion might inhibit the effect of BPMC on the monoaminergic nerves, thereby markedly potentiating the lethal effect of BPMC.


The Supera Interwoven Nitinol Stent as a Flow Diverting Device in Popliteal Aneurysms.
The feasibility of using a compressed interwoven Supera stent as a flow diverting device for popliteal aneurysms was recently demonstrated in patients. It is unclear, however, what the optimal flow diverting strategy is, because of the fusiform shape of popliteal aneurysms and their exposure to triphasic flow. To assess this flow diverting strategy for popliteal aneurysms, flow profiles and thrombus formation likelihood were investigated in popliteal aneurysm models. Six popliteal aneurysm models were created and integrated into a pulsatile flow set-up. These models covered a bent and a straight anatomy in three configurations: control, single-lined and dual-lined Supera stents. Two-dimensional flow velocities were visualized by laser particle image velocimetry. In addition, the efficacy of the stent configurations for promoting aneurysm thrombosis was assessed by simulations of residence time and platelet activation. On average for the two anatomies, the Supera stent led to a twofold reduction of velocities in the aneurysm for single-lined stents, and a fourfold reduction for dual-lined stents. Forward flow was optimally diverted, whereas backward flow was generally deflected into the aneurysm. The dual-lined configuration led to residence times of 15-20 s, compared to 5-15 s for the single stent configurations. Platelet activation potential was not increased by the flow diverting stents. A compressed Supera stent was successfully able to divert flow in a popliteal aneurysm phantom. A dual-lined configuration demonstrated superior hemodynamic characteristics compared to its single-lined counterpart.


Can surgeons rely on growth-related changes to achieve lip height and width symmetry in unilateral complete cleft lip repair?
Surgeons face difficulties achieving simultaneous lip height and width symmetry while repairing unilateral complete cleft lip, so one is often sacrificed at the expense of the other. The aim of this study was to evaluate the effect of growth on lip height and width symmetry, to guide the surgeon to the best decision. The study patients (N = 105) were divided into two groups based on the treatment method: 42 were treated with the modified rotational advancement technique (MRA group) and 63 with the Millard rotation-advancement technique (RA group). Furthermore, based on lip height and width symmetry at 6 months postoperative, the patients were divided into three groups: 38 with symmetrical lip height and width (SL), 41 with horizontal lip width more symmetrical than lip height (RAW), and 26 with vertical lip height more symmetrical than lip width (RAH). Measurements were taken preoperatively (T0), 6 months (T1) and 5 years (T2) postoperatively. The MRA group had significantly more symmetrical lip height than the RA group at T1 (P = 0.003) and T2 (P = 0.002); however no statistically significant difference in lip width symmetry was observed between the two groups. In relation to the effects of growth, only lip width symmetry in the RAH group improved significantly between T1 and T2 (P = 0.023). In conclusion the improvement in lip width symmetry following 5 years of postoperative growth did not achieve the same symmetry as when lip width symmetry was achieved intraoperatively. Thus, the MRA technique could be used to obtain intraoperative symmetry of lip height and width.


Nasal cytology as a reliable non-invasive procedure to phenotype patients with type 2 chronic rhinosinusitis with nasal polyps.
The identification of type-2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) acquires a crucial role in the endotypization needed for selecting patients for biological drugs targeting type-2 inflammation: to date, the parameters used include systemic and histological biomarkers. The aim of this study was to investigate whether nasal cytology could identify type-2 inflammation in patients with CRSwNP. Thirty-three consecutive patients with CRSwNP underwent nasal cytology sampling at the level of the lower nasal turbinate, and of the polypoid tissue, and surgical polyp tissue sample was collected. The cellularity of the 3 collected samples were compared. Mean nasal polyp tissue, nasal polyps cytology and inferior turbinate cytology eosinophils counts were 43.7 ± 39.6 cells/HPF, 32.8 ± 44.7 cells/HPF and 27.6 ± 58.0 cells/HPF respectively with inferior turbinate cytology eosinophils significantly lower than nasal polyp tissue count (p = 0.007). Both mean nasal polyps cytology eosinophils and mean inferior turbinate cytology eosinophils were significantly higher in patients with type-2 CRSwNP (52.5 ± 67.0 cells/HPF vs 12.2 ± 17.3 cells/HPF, p = 0.012, and 32.0 ± 62.1 cells/HPF vs 2.9 ± 2.9 cells/HPF, p = 0.020 respectively). Nasal cytology is suitable tool for assessing local biomarkers of type-2 inflammation in CRSwNP.


Efficacy of the autogenous dentin graft for implant placement: a systematic review and meta-analysis of randomized controlled trials.
The aim of this study was to determine whether the autogenous dentin graft (ADG) shows comparable results and similar clinical performance to other graft materials when utilized for implant placement. Four databases were searched, and controlled human studies that applied autogenous dentin for implant surgery, comparing it with other bone grafts, were included. Nine articles met the inclusion criteria, five of which were randomized controlled trials and were included in the meta-analysis. ADG showed equivalent primary and secondary implant stability when compared to Bio-Oss (primary: mean difference -0.74, 95% confidence interval (CI) - 3.36 to 1.88, P = 0.58; secondary: mean difference - 1.29, 95% CI - 5.69 to 3.11, P = 0.57). The standardized mean difference (SMD) of marginal bone loss at 6 months and at the final follow-up (18 months) showed the two grafts to be similar (6 months: SMD -0.26, 95% CI -0.64 to 0.12, P = 0.18; final follow-up: SMD -0.12, 95% CI -0.50 to 0.26, P = 0.53), and survival after immediate implant placement was the same in the two groups: 97.37% and 97.30%, respectively. Incidences of complications with the autogenous dentin particles or blocks were in line with those of Bio-Oss or autogenous bone blocks, respectively. This meta-analysis indicates that the autogenous dentin graft is an effective option for bone augmentation around dental implants, with acceptable implant stability, marginal bone loss, and incidences of complications and failure.


Hospital-based register of stroke in the Molise Region: focus on main subtypes of stroke. Years 2009-2013.
We determined incidence and intra-hospital mortality rate of stroke in Molise, Italy, to provide information for planning regional healthcare facilities and to ameliorate stroke management in this region. This study is part of the "Rete Molisana dell'Ictus Cerebrale (REMOLIC)" study, a population-based Cerebrovascular Registry in Molise, from 2009 to 2013, with a cold pursuit approach. The crude annual incidence rates for total stroke per 100,000 inhabitants, notified by hospital discharge records, were 198 for 2009, 185 for 2010, 169 for 2011, and 176 for both 2012 and 2013. There was a significant decrease in risk in the years 2011-2013 [RR2011 vs. 2009: 0.85 (0.76-0.98), RR2012 vs. 2009: 0.89 (0.79-0.99), RR2013 vs. 2009: 0.89 (0.79-0.99)] as compared with 2009. For the year 2010, after adjustment to the Italian, European, and world populations, the overall incidence rates were 165, 134, and 67 per 100,000/year, respectively. Similar trends were found when men and women were analyzed separately. In the average, 20.8 % of subjects admitted for a cerebrovascular accident died during the hospitalization, among these 93.5 % in the first 28 days. The duration of hospital stay was constant in the years (2009-2012), except during 2013, where there was a significant decrease in the average (p < 0.001). Our study shows incidence rates decreasing from 2009 to 2013, while mortality rates were stable during the same years. This study underlines the need to plan better stroke management in Italy, in order to obtain outcomes more similar to those of the best performing countries.


Phenomenological study of the North Dakota flood experience and its impact on survivors' health.
Grand Forks, North Dakota, was devastated by an unprecedented flood, forcing the evacuation of an entire community of 50,000 residents in 72 hours. A qualitative descriptive study with use of phenomenological methods was conducted 6 months after the flooding. Its purpose was to gain a deeper understanding of the meaning of a traumatic flood experience and its influence on the health of the residents of Grand Forks. Data were generated through interviews, observations, and media reports. The sample included 3 female and 3 male residents of the city of Grand Forks, North Dakota, who ranged in age from 26 to 77 years. Five essential themes were identified: (1) shock and disbelief, (2) uncertainty, (3) grief and loss, (4) emotional exhaustion, and (5) hope and meaning. The participants' descriptions of emotional exhaustion were similar to those found with survivors of posttraumatic stress disorder. Older adults appeared to be especially vulnerable. Nurses who are aware of the effects of natural disasters, particularly flooding, may be better able to identify vulnerable populations and understand the health needs of other survivors.


Burst-suppression is reactive to photic stimulation in comatose children with acquired brain injury.
Burst-suppression is an electroencephalographic pattern observed during coma. In individuals without known brain pathologies undergoing deep general anesthesia, somatosensory stimulation transiently increases the occurrence of bursts. We investigated the reactivity of burst-suppression in children with acquired brain injury. Intensive care unit electroencephalographic monitoring recordings containing burst-suppression were obtained from 5 comatose children with acquired brain injury of various etiologies. Intermittent photic stimulation was performed at 1Hz for 1min to assess reactivity. We quantified reactivity by measuring the change in the burst ratio (fraction of time in burst) following photic stimulation. Photic stimulation evoked bursts in all patients, resulting in a transient increase in the burst ratio, while the mean heart rate remained unchanged. The regression slope of the change in burst ratio, referred to as the standardized burst ratio reactivity, correlated with subjects' Glasgow Coma Scale scores. Reactivity of the burst-suppression pattern to photic stimulation occurs across diverse coma etiologies. Standardized burst ratio reactivity appears to reflect coma severity. Measurement of burst ratio reactivity could represent a simple method to monitor coma severity in critically ill children.


Functional lengths of the lower limb arterial tree measured by CT angiography centreline analysis: implications for catheter lengths in peripheral angioplasty.
Lower limb angioplasty is a common procedure. However, arterial lengths have not been well studied and there is no evidence base for the optimum catheter lengths required for the various applications of femoral or distal below-the-knee angioplasty. The industry standard catheter measures 80 cm. Fifty CT angiograms were post-processed using vessel tracking and centreline analysis tools and lengths were measured from the ipsilateral first segment of the femoral artery (FSFA) (common femoral artery) to the contralateral FSFA and on to the second segment of the femoral artery (superficial femoral artery) and popliteal arteries down to the posterior tibial (PT) artery at the ankle. This allowed clinically meaningful lengths for 'cross-over' and 'antegrade' angioplasty to be calculated. Mean cross-over length to the second segment of the femoral artery as it crossed the femoral cortex was 72.3 cm, and the mean cross-over length to the popliteal artery at the knee joint was 83.8 cm, and the length from the FSFA to the PT was 85.1 cm. Selection of a standard length catheter can result in a situation where the catheter is too short. Optimum catheter length for a particular task will reduce the need for catheter exchanges and use of multiple balloons and therefore reduce complications, procedure time, radiation dose and cost.


Mouse "protective protein". cDNA cloning, sequence comparison, and expression.
The "protective protein" is the glycoprotein that forms a complex with the lysosomal enzymes beta-galactosidase and neuraminidase. Its deficiency in man leads to the metabolic storage disorder galactosialidosis. The primary structure of human protective protein, deduced from its cloned cDNA, shows homology to yeast serine carboxypeptidases. We have isolated a full-length cDNA encoding murine protective protein. The nucleotide sequences as well as the predicted amino acid sequences are highly conserved between man and mouse. Domains important for the protease function are completely identical in the two proteins. Both human and mouse mature protective proteins covalently bind radiolabeled diisopropyl fluorophosphate. Transient expression of the murine cDNA in COS-1 cells yields a protective protein precursor of 54 kDa, a size characteristic of the glycosylated form. This cDNA-encoded precursor, endocytosed by human galactosialidosis fibroblasts, is processed into a 32- and a 20-kDa heterodimer and corrects beta-galactosidase and neuraminidase activities. A tissue-specific expression of protective protein mRNA is observed when total RNA from different mouse organs is analyzed on Northern blots.


Radiation-induced cerebral lesions in childhood.
Post-irradiation cerebral pathologies may appear in various forms from localized radiation necrosis to a plurifocal type or from local to diffuse vasculopathies. Contrary to the current prevalent opinion, these lesions are not rare in children since young nerve tissue is particularly sensitive to ionizing radiation. Given the seriousness of some of these lesions, the authors recommend careful evaluation of the risk involved in relation to the real necessity of administering irradiation therapy in childhood.


Kampo medicine "Dai-kenchu-to" prevents bacterial translocation in rats.
Kampo medicine "Dai-kenchu-to" (DKT) has been used for treatment of ileus. The aim of this study was to evaluate the role of DKT on the bacterial translocation (BT) model in rats. Rats were divided into the following four groups: group 1, receiving only water, and groups 2, 3, and 4, receiving 100, 300, and 1,000 mg/kg/day of DKT. Rats were sacrificed 6 days after the beginning of the fast, and then the mesenteric lymph node was cultured. Inflammatory cytokines, intestinal integrity, and apoptosis were assessed. Incidence of BT in groups 3 (33%) and 4 (16%) was lower than in group 1 (66%). Interferon-gamma expression in groups 2, 3, and 4 was significantly lower than in group 1. Villous height and number of villus in groups 2, 3, and 4 were significantly taller and greater than in group 1. Apoptotic index in groups 2, 3, and 4 was significantly lower than in group 1. This is the first evidence that DKT prevents BT by reducing inflammatory reaction and maintaining intestinal integrity.


The formation of a covalent complex between a dipeptide ligand and the src SH2 domain.
The X-ray crystal structure of the src SH2 domain revealed the presence of a thiol residue (Cys 188) located proximal to the phosphotyrosine portion of a dipeptide ligand. An aldehyde bearing ligand (1) was designed to position an electrophilic carbonyl group in the vicinity of the thiol. X-ray crystallographic and NMR examination of the complex formed between (1) and the src SH2 domain revealed a hemithioacetal formed by addition of the thiol to the aldehyde group with an additional stabilizing hydrogen bond between the acetal hydroxyl and a backbone carbonyl.


99mTc-HIDA cholescintigraphy in children with Dubin-Johnson syndrome.
Tc-HIDA cholescintigraphy in Dubin-Johnson syndrome (DJS) demonstrates intense prolonged homogeneous visualization of the liver, together with delayed visualization of the gall bladder and extrahepatic ducts. Such a cholescintigram has not been described for any other hyperbilirubinemic state. Because it is a noninvasive and easy technique, it is recommended for the evaluation of children suspected of having DJS.


A hematoma detector-a practical application of instrumental motion as signal in near infra-red imaging.
In this paper we discuss results based on using instrumental motion as a signal rather than treating it as noise in Near Infra-Red (NIR) imaging. As a practical application to demonstrate this approach we show the design of a novel NIR hematoma detection device. The proposed device is based on a simplified single source configuration with a dual separation detector array and uses motion as a signal for detecting changes in blood volume in the dural regions of the head. The rapid triage of hematomas in the emergency room will lead to improved use of more sophisticated/expensive imaging facilities such as CT/MRI units. We present simulation results demonstrating the viability of such a device and initial phantom results from a proof of principle device. The results demonstrate excellent localization of inclusions as well as good quantitative comparisons.


Temperature influence on Penicillium citrinum thom growth and citrinin accumulation kinetics.
To study the temperature influence on both Penicillium citrinum growth and citrinin accumulation, a 20, 25 and 30 degrees C. Radial and 30 degrees C. Radial growth rate and lag phase were determined from the increase in colony diameter with time. The optimal temperature for P. citrinum growth was 30 degrees C. Citrinin extracted from the agar medium was determined by thin layer chromatography. Citrinin accumulation kinetics were analyzed by fitting the data to curves generated by using a logistic function. The parameters obtained from this equation demonstrated, for all temperatures studied, that the maximum citrinin accumulation by P. citrinum on Czapek agar with maize extract was at about 30 degrees C. At 37 degrees C a rapid decrease in the citrinin concentration was observed after a maximal value was reached.


Antibody against globular domain of H10 histone.
Antibodies against the globular domain of histones H10 and H5 were developed in rabbit. The antibody against the globular domain of H5 cross-reacted with H10 but not with H1; the antibody against the globular domain of H10 did not cross-react with H5, H1 or with HMG proteins. The globular domain of H10 therefore appears to have an immunological determinant(s) which does not exist in H1 and H5. By use of these antibodies, we show that nucleated erythrocytes of bullfrog contain an H10-like protein (not an H5-like protein). This observation coincided with the report of Shimada, T. et al. [J. Biol. Chem. 256 (1981) 10577-10582]. These antibodies have application in detecting H10-like proteins in eukaryotic cells.


Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1 fibroblasts. Evidence that phosphorylation of map kinase is mediated by the Gi-p21ras pathway.
Lysophosphatidic acid (LPA) is a platelet-derived phospholipid that serves as a mitogen for fibroblasts. LPA activates its own G protein-coupled receptor(s) leading to stimulation of phospholipase C and inhibition of adenylate cyclase. Furthermore, LPA rapidly activates p21ras through a pertussis toxin-sensitive pathway. In this study, we have examined LPA-induced protein tyrosine phosphorylation in Rat-1 fibroblasts. LPA action was compared with that of endothelin, which is a stronger activator of phospholipase C than LPA but fails to activate p21ras and to stimulate DNA synthesis in these cells. LPA and, more effectively, endothelin rapidly stimulate tyrosine phosphorylation of proteins of 110-130, 95, and 65-75 kDa. The effect of LPA is dose- and time-dependent, being half-maximal at 3-30 nM and peaking after 2-5 min. Among the 110-130-kDa group of phosphotyrosyl proteins is the 125-kDa "focal adhesion kinase" (p125FAK) but not the 120-kDa p21ras GTPase-activating protein. Furthermore, LPA, like epidermal growth factor, causes tyrosine phosphorylation and activation of the p42/p44 mitogen-activated protein (MAP) kinases, paralleling p21ras activation. In contrast, endothelin fails to phosphorylate MAP kinase. Treatment of the cells with pertussis toxin blocks LPA-induced MAP kinase phosphorylation without affecting the other tyrosine phosphorylations. The kinase inhibitor staurosporine (1 microM) blocks LPA-induced, but not epidermal growth factor-induced, activation of p21ras and MAP kinase, consistent with an intermediate protein kinase linking the LPA receptor to p21ras activation. The results support a model in which LPA-induced phosphorylation of MAP kinase is mediated by p21ras, and tyrosine phosphorylation of the other substrates, including p125FAK, is associated with phospholipase C activation.


Nephrogenic adenoma in urethral diverticulum: an unusual finding.
The 3rd case of nephrogenic adenoma in the urethral diverticulum of a female is reported herein. A short review of the literature is presented.


Proposed changes to the nomenclature of Ichthyophonus sp. life stages and structures.
Much of the terminology describing Ichthyophonus sp. life stages and structures can be traced to the mistaken classification of this organism as a fungus. This misidentification led early investigators to use mycological terms for the structures they observed; while some terminology is not so easily explained, it appears to have been co-opted from the fields of botany and bacteriology. The purpose of this exercise is to attempt to standardize the terminology associated with Ichthyophonus and to bring it into agreement with terminology currently used to define similar life stages of other protists. The proposed changes are (1) spore/macrospore/mother spore to "schizont," (2) microspore/endospore to "merozoite," and (3) pseudohyphae to "hyphae" or "germ tube."


Fast versus slow onset of depressive episodes: a clinical criterion for subtyping patients with major depression.
The speed of onset of depressive episodes is a clinical aspect of affective disorders that has not been sufficiently investigated. Thus, we aimed to explore whether patients with fast onset of the full-blown depressive symptomatology (≤7 days) differ from those with slow onset (>7 days) with regard to demographic and clinical aspects. Data were obtained within an observational study conducted in outpatients with major depression who were treated with duloxetine (30-120 mg/day). Onset of depression (without any preceding critical life event) was fast in 416 (less than one week) and slower in 2220 patients. Compared to patients with slow onset, those with fast onset of depression had more suicide attempts in the previous 12 months (2.7% versus 1.3%, P=0.046) and less somatic comorbidity (61.7% versus 74.1%, P<0.0001). In addition, they were slightly younger at onset of depression (mean±SD 40.2±14.6 versus 42.8±14.2 years, P<0.001) and used analgesics at baseline significantly less frequently (22.8% versus 33.4%, P<0.0001). The speed of onset of depression has to be regarded as a relevant clinical characteristic in patients with unipolar depression.


Efficient Simulation of 3D Reaction-Diffusion in Models of Neurons and Networks.
Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well-represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma. We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON's 1D mechanisms for ion channels, synapses, pumps, and so forth. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.


"U" route transforaminal percutaneous endoscopic thoracic discectomy as a new treatment for thoracic spinal stenosis.
To describe the rationale, surgical technique, and short-term follow-up results of a new minimally invasive treatment for thoracic spinal stenosis (TSS) caused by herniation, ossification of the ligamentum flavum (OLF), and/or ossification of the posterior longitudinal ligament (OPLL) with a "U" route transforaminal percutaneous endoscopic thoracic discectomy (PETD). Fourteen patients, including seven males and seven females, underwent "U" route PETD. Myelopathy was caused by OLF in 14 patients, OPLL in one, combined OLF-OPLL in ten, and intervertebral disc herniation (IDH) in five. Decompression was performed in one segment in 12 patients, and in two segments in two patients. The Japanese Orthopedic Association (JOA) scores, visual analog scale (VAS) scores, and complications were documented. The JOA scores improved from 4.64 ± 2.31 pre-operatively to 7.07 ± 1.59 one day post-operatively and 11.79 ± 1.85 at final follow-up. The difference between pre-operation and post-operation was statistically significant (P < 0.05). Moreover, the VAS score was 6.07 ± 2.06 points pre-operatively, decreasing to 3.00 ± 1.24 points at one day post-operatively, and 1.14 ± 0.86 points at last follow-up (P < 0.05). Dural tear was observed in two cases during the intervention. No patient had transient worsening of pre-operative paralysis. This retrospective analysis shows that "U" route PETD for decompression may be a feasible alternative to treat thoracic spinal stenosis.


Electrophysiology of T-wave alternans: mechanisms and pharmacologic influences.
Extensive experimental evidence indicates a fundamental link between T-wave alternans (TWA) and arrhythmogenesis. Diverse physiologic and pathophysiologic influences alter TWA magnitude in parallel with their effects on vulnerability to ventricular tachyarrhythmias. Specifically, interventions that impede intracellular calcium handling, such as elevated heart rate, heightened adrenergic activity, myocardial ischemia, and heart failure, predispose to greater levels of TWA, reflecting heightened risk for arrhythmias. Conversely, vagus nerve stimulation, blockade of beta-adrenergic receptors and late sodium and L-type calcium channels, and sympathetic denervation decrease TWA magnitude, reflecting the potential of these interventions to reduce risk for ventricular tachycardia and fibrillation. TWA thus appears able to detect the influence of pathophysiologically relevant triggers as well as the efficacy of antiarrhythmic drugs without reducing the predictive capacity of the phenomenon.


Intraventricular infusions of anti-NCAM PSA impair the process of consolidation of both avoidance conditioning and spatial learning paradigms in Wistar rats.
Processing of information for long-term storage requires specific patterns of activity that lead to modification of synapse structure and eventual change in neural connectivity pattern. Morphological change associated with memory consolidation is reliant on neural cell adhesion molecule (NCAM) function and that of its polysialylated variant (NCAM PSA). Across species and paradigms, a transient frequency increase of polysialylated neurons in the hippocampal dentate has been found necessary for memory consolidation, however, recent studies suggest that NCAM PSA may serve to suppress memory formation in certain paradigms. As intraventricular infusions of NCAM blocking antibodies have been used successfully to demonstrate its time-dependent role at the 6 h post-training period of memory consolidation, we employed the same procedure to demonstrate a functional requirement for NCAM PSA in the consolidation of two commonly used behavioral paradigms: avoidance conditioning and spatial learning in Wistar rats. Anti-PSA was found to significantly induce amnesia of the passive avoidance response when infused at the 10 h post-training time, a period coincident with the learning-associated increase in dentate polysialylated cell frequency. Moreover, the amnesia became apparent at the 48 h recall time and was not apparent at the 24 h post-training time, suggesting a possible role in memory reconsolidation. A similar anti-PSA action was observed following water maze training in aged animals but was not apparent in young animals, an effect suggested to be due to inadequate antibody saturation of the polysialylated cell population. These studies confirm the requirement for NCAM PSA in memory consolidation and separate it from that of NCAM.


Local antitumor effects of intratumoral delivery of rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres.
In this study, we formulated a rIL-2 loaded sustained-release dextran/PLGA-PLA core/shell microsphere, mimicking the paracrine mechanisms of cytokine action, to investigate its local antitumor efficacy. The presented microspheres were formed in two steps: rIL-2 was firstly loaded into dextran particles to keep its bioactivity by a unique method of stabilizing aqueous-aqueous "emulsion"; subsequently, the particles were encapsulated into poly(dl-lactide-co-glycolide)/polylactic acid (PLGA/PLA). A stable sustained release behavior in vitro was achieved for a period of about 25 days. In the subcutaneous colon carcinoma BALB/c mice models, a single dose of microspheres was introtumorally administrated and compared with multiple doses of rIL-2 solution to investigate the long acting effect of microspheres on tumor. The animal experiments showed the local efficacy at tumor site mediated by rIL-2 from a single dose of microspheres was better than that of multiple rIL-2 solution injections. Based on the experimental results, we conclude that rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres represent a promising approach for local cancer treatment in animals.


Estimating the burden of seasonal influenza in Spain from surveillance of mild and severe influenza disease, 2010-2016.
Estimating the national burden of influenza disease is challenging. We aimed to estimate the disease burden of seasonal influenza in Spain, at the primary care and hospital level, over the 6 influenza seasons after 2009 pandemic. We used data from the Spanish Influenza Sentinel Surveillance System to estimate weekly influenza rates and the number of influenza-like illness (ILI) and mild confirmed influenza cases (MCIC). From the surveillance of severe hospitalized confirmed influenza cases (SHCIC), we obtained hospitalization rates and total number of SHCIC, intensive care unit (ICU) admissions and deaths in influenza hospitalized patients. We estimated both mild and severe influenza cases, overall, and by age-group (<5, 5-14, 15-64, and ≥65 years). The highest cumulative rates of MCIC were observed in <15 years (1395-3155 cases/100 000 population in 5-14 years) and the lowest in ≥65 years (141-608 cases/100 000 population). SHCIC rates revealed a characteristic U-shaped distribution, with annual average hospitalization rates of 16.5 and 18.9 SHCIC/100, 000 p in 0-4 years, and ≥65 years, respectively. We estimated an annual average of 866 868 cases of ILI attended in primary care (55% were MCIC), 3616 SHCIC, 1232 ICU admissions, and 437 deaths in SHCIC. The percentage of ICU admission among SHCIC was highest at 15-64 years (42%), while the hospitalization fatality rate ranged from 1% in 0-4 years to 18% in ≥65 years. The ongoing Spanish Influenza Surveillance System allowed obtaining crucial information regarding the impact of mild and severe influenza in Spain.


Review of hot flash diaries.
Currently, there is only 1 published hot flash diary. This diary rates hot flash severity according to 4 categories: mild, moderate, severe, and very severe. The descriptions of these 4 severity categories are located on a separate form from the main data form. For each 24-h period, subjects record the number of hot flashes experienced for each of the 4 severity categories either by recollection or from a separate data source on which hot flashes have been tallied. This diary has been validated but does not conform to the FDA and EMEA guidance for industry. After we observed a high percentage of subjects reporting confusion when using this 4-category diary, we constructed and used a hot flash diary containing 3 severity categories that offered real-time recording of hot flashes, contained all severity definitions on the principle data form and also conformed to the FDA and EMEA guidance for industry. We compare these 2 diaries here and provide a sample of the 3-category diary, which has not been formally validated but is considered valid by the FDA and EMEA in support of drug approval. Either diary is acceptable for use in clinical trials.


A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis.
The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.


Facile one-pot synthesis of gold nanoparticles and their sensing protocol.
This communication reports facile one pot synthesis of amoxicillin and sodium salt of amoxicillin stabilized gold nanoparticles (Au-NPs). Primarily the cyclic thioether linkage i.e. the thiozolidine ring of amoxicillin is utilized for sequestering Au(III). Fluorescence quenching of these clusters makes it an efficient protocol for sensing Cu(2+) at nano scale levels.


Cephalic tetanus: a case report and review of the literature.
Cephalic tetanus is a rare form of tetanus defined as trismus plus paralysis of one or more cranial nerves. The most frequently involved cranial nerve is the seventh. It accounts for 1 to 3% of the total number of reported cases of tetanus and has a mortality of 15 to 30%. The incubation period is 1 to 14 days, and approximately two thirds of cases progress to generalized tetanus. The mechanism of the paralysis is not completely understood. Treatment involves debridement of wounds, administration of penicillin and tetanus immune-globulin, aggressive supportive care, and initiation of active immunization.


Trisomy 9 mosaicism with punctate mineralization in developing cartilages.
A case of mosaic trisomy 9 (46,XX/47,XX,+9) is described. The main clinical findings included intrauterine growth retardation, failure to thrive, hydrocephalus, deeply set eyes, prominent antihelix, highly arched palate, subluxation of the interphalangeal joints of some fingers, hip dislocation, excessive sweating, and punctate mineralization in developing cartilages.


Influence of hydroxyapatite crystallization temperature and concentration on stress transfer in wet-spun nanohydroxyapatite-chitosan composite fibres.
Hydroxyapatite possesses appropriate osteoconductivity and biocompatibility for hard-tissue replacement implants but suffers from brittleness. One approach to overcome this problem is to incorporate nanometre hydroxyapatite (nHA) into a polymer matrix, such as chitosan, to yield a hydroxyapatite-chitosan (HC) composite. Here, a novel HC composite was synthesized and its elastic properties were investigated by varying (1) nHA concentration and (2) crystallization temperature (T), where T is a parameter which influences the morphology of the crystals. Crystals of nHA were precipitated at T = 40 degrees C and 100 degrees C, blended in a chitosan matrix, and wet-spun to yield fibres of HC composites at 5, 15, 20 and 40% concentrations (mass fraction of nHA). Scanning electron microscopy and energy-dispersive x-ray spectroscopy revealed a uniform distribution of nanocrystallites within the fibre. Tensile testing revealed that HC fibres, which comprised nHA treated at T = 100 degrees C, possessed low tensile strength, sigma(0), and stiffness, E, at low nHA concentrations but high sigma(0) and E at higher concentrations, i.e. beyond a 15% mass fraction of nHA. However, with nHA treated at T = 40 degrees C, the fibres yielded high sigma(0) and E at low nHA concentrations but low sigma(0) and E at high concentrations. The results strongly implicate the underlying effect of crystallite morphology on stress transfer at different concentrations.


Is fluoride a mutagen?
Recent studies suggest that fluoride may be genotoxic. While the concentration of fluoride in artificially fluoridated water (1 mg Fl-1) is generally considered to be "safe", levels of fluoride present in a number of widely used dental health products, such as fluoride-containing toothpaste, appear to be potentially mutagenic. Since fluoride is increasingly being used as a drug, and contamination of the total environment by fluoride emissions and solid wastes from industry is a growing problem, a review of the evidence regarding the potential mutagenicity of fluoride may be in order.


Covalent interaction of 3,3'-dichlorobenzidine with hepatic lipids. Enzymic basis and stability of the adducts.
Administration of a single oral dose (20 mg/kg) of [U-14C]3,3'-dichlorobenzidine to rats resulted in the in vivo covalent binding of the compound to hepatic lipids. More than 70% of the lipid-3,3'-dichlorobenzidine adducts were accounted for in microsomes. Loss of the lipid-bound 3,3'-dichlorobenzidine residues from either total liver or endoplasmic reticulum occurred in at least two phases--an initial fast phase and a terminal slow phase. In vitro studies with hepatic microsomes in the presence of antibodies to specific P450 isozymes and chemical inhibitors to determine the enzymes that activate 3,3'-dichlorobenzidine to the lipid-binding derivative(s) implicated cytochrome P450d. The 3,3'-dichlorobenzidine-bound microsomal lipids were not mutagenic to Salmonella TA98 in the Ames test. The results suggest that adduct formation between 3,3'-dichlorobenzidine and membrane lipids may provide a measure of 3,3'-dichlorobenzidine activation. It is speculated that covalent interaction of the compound with membrane lipids may modify cellular processes, leading to either enhancement or attenuation of carcinogenesis by the chemical.


Cavitation sounds during spinal manipulative treatments.
The purpose of this study was to confirm a practitioner's perception of cavitation during spinal manipulative therapy in a clinically relevant situation using accelerometer recordings. Experimental study. Human Performance Laboratory and Sports Medicine Center, University of Calgary. Twenty-eight patients from a single practitioner's patient pool who had pain in the area of the thoracic spine. Spinal manipulative treatment (SMT) on the transverse process of T4 using a reinforced unilateral contact and delivering a thrust in the posterior to anterior direction. Instantaneous acceleration signals obtained from the spinous process of T3 during SMT and the practitioner's perception if cavitation had occurred or not at the end of each treatment. It appears that cavitation may be measured during SMT using accelerometry and that a practitioner's perception of the occurrence of cavitation during SMT is very accurate.


Development of a system model to predict flows and performance of regional waste management planning: A case study of England.
Significant loss of valuable resources and increasing burdens on landfills are often associated with a lack of proper planning in waste management and resource recovery strategy. A sustainable waste management model is thus urgently needed to improve resource efficiency and divert more waste from landfills. This paper proposes a comprehensive system model using stock-and-flow diagram to examine the current waste management performance and project the future waste generation, treatment and disposal scenarios, using England as a case study. The model comprises three integrated modules to represent household waste generation and collection; waste treatment and disposal; and energy recovery. A detailed mass and energy balance has been established and waste management performance has been evaluated using six upstream and downstream indicators. The base case scenario that assumes constant waste composition shows that waste to landfills can be reduced to less than 10% of the total amount, by 2035. However, it entails greater diversion of waste to energy-from-waste facilities, which is not sustainable and would incur higher capital investment and gate fees. Alternative case scenarios that promote recycling instead of energy recovery result in lower capital investment and gate fees. Complete elimination of the food and organic fraction from the residual waste stream will help meet the 65% recycling target by 2035. In light of the need for achieving a more circular economy in England, enhancing material recovery through reuse and recycling, reducing reliance on energy-from-waste and deploying more advanced waste valorisation technologies should be considered in future policy and planning for waste management.


Optimization of L-glutaminase production by Monascus ruber URM 8542 isolated from ice cream industrial effluent.
L-glutaminase is a hydrolytic enzyme with wide biotechnological applications. Mostly, these enzymes are employed in the feed industry for flavor enhancement and acrylamide mitigation. Also, L-glutaminase may have antiviral and antineoplastic effects making it a good choice for pharmaceutical applications. In this study, the strain Monascus ruber URM 8542 was identified through classical and molecular taxonomy using partial sequencing of β-tubulin and calmodulin genes. Subsequently, the optimal culture conditions were evaluated by submerged fermentation (L-glutamine 10 g.L- 1) for L-glutaminase excretion. The isolate was identified as M. ruber URM 8542 which showed significant extracellular enzyme production with a yield of 11.4 times in relation to the specific activity of intracellular L-glutaminase. Regarding the optimization experiments, several factors such as L-glutamine concentration, temperature, and pH were compared using a full factorial design (23). The concentrations greater than 1% proved to be significantly better for glutaminase production (R2 = 0.9077). Additionally, the L-glutaminase was optimally active at pH 7.0 and 30 ºC. The L-glutaminase was remarkably stable across an alkaline pH range (7.0-8.0) and had a thermal stability ranging from 30 ºC to 60 ºC for 1 h. Taken together, these findings suggest that the L-glutaminase produced by M. ruber is a promising candidate for pharmacological application, although further studies need to be performed. To the best of our knowledge, this is the first report of L-glutaminase production by Monascus ruber.


Very long-term clinical outcomes after radiofrequency catheter ablation for atrial fibrillation: A large single-center experience.
Radiofrequency catheter ablation (RFCA) has become widely used for drug-refractory atrial fibrillation (AF). However, there is a paucity of data on the long-term clinical outcomes after RFCA for AF. The aim of the present study was to investigate the very long-term outcomes after RFCA for AF in a large number of consecutive patients. In this retrospective single-center study, we evaluated very long-term follow-up results in 1206 consecutive patients undergoing first RFCA for AF. The primary outcomes were adverse outcomes at 30-day as a safety outcome measure and event-free rates from recurrent atrial tachyarrhythmias as efficacy outcome measures. Final follow-up rate reached 99.3% with a mean follow-up duration of 5.0±2.5years. The incidence of overall 30-day adverse outcomes was 3.6% without death. The 10-year event-free rates from recurrent atrial tachyarrhythmias after the initial and last procedures were 46.9% and 76.4%, respectively. Arrhythmia recurrence occurred most commonly during the first year and decreased beyond 3-year, although it continued to occur at an annual rate of 2.0% and 1.3%, respectively, throughout the 10-year follow-up period. The cumulative 10-year incidences of stroke and major bleeding were 4.2% and 3.5%, respectively, with annual rates of 0.3%. Discontinuation rate of oral anticoagulation at 1-, 3-, and 10-year was 34.6%, 53.4%, 58.0% and 61.9%. RFCA for AF provided favorable very long-term arrhythmia-free survival without much safety concerns. The 10-year rates of stroke and major bleeding were low even with discontinuation of oral anticoagulation in a large proportion of patients.


Assessment of specific drug disorders in a sample of substance abuse patients: a comparison of the DIS and the SADS-L procedures.
Both the DIS and the SADS-L interviews offer researchers a procedure for assessing the presence of drug disorders categorized by drug class, as defined by psychiatric nomenclatures. In this study, the performance of the drug section of each interview was compared in a sample of hospitalized substance abuse patients. The classes of drug disorders assessed by both instruments and reported here include narcotics, amphetamines, sedatives and tranquilizers, cannabis, cocaine, and hallucinogens. On a group level, the DIS and SADS-L agreed fairly well for all drug classes except hallucinogens. A within-DIS comparison of DSM-III and Research Diagnostic Criteria (RDC) diagnoses followed the same pattern, except with higher agreement. Distinctions between drug abuse and dependence within a drug class were not as reliable as overall assessments. On only a small proportion of patients did the instruments agree completely for all drug classes within an individual. Implications of the findings for research on drug problems are discussed.


Time, carbimazole and the outcome of Graves' disease.
A detailed comparison was made over 18 months of the serial mean 20 min 132I uptake behavior between 15 Graves' disease patients whose hyperthyroidism ultimately remitted (Group E) and 20 in whom it persisted (Group R). All were treated with carbimazole and T3. There were not qualitative differences in uptake between the 2 groups. In both, the uptake fell with time, and the slopes were parallel. The fact that the mean uptake started lower in Group E patients was sufficient to explain why it became normal much earlier than that of Group R, which had not normalized by 18 months. In both groups, over half the overall fall in uptake occurred during the first month of treatment with carbimazole. We conclude that, while time remains the most important determinant of outcome in Graves' disease, some possible immunosuppressive action of carbimazole can shorten the cycle length to a major degree.