Film from peroxidation of an amino phospholipid and its biocompatibility.
A new kind of phospholipid product with fluorescence was derived from autoxidation of an aminophospholipid, L-alpha-phosphatidylethanolamine dilinoleoyl in solid film state. Atomic force microscopy showed that the film product was composed of round and elliptical vesicles with diameters of about 20-45 nm. The product was difficult to dissolve in water and most organic solvents. Fourier transform infrared spectroscopy, solid-state (13)C NMR, and solid-state (31)P NMR indicated that the unsaturated double carbon bond decreased with the reaction, and polymerization within/between phospholipid molecules occurred. Endothelial cells from human vein seeded onto the film showed the highest proliferating activity compared with seeding onto Corning culture plate, glass plate, or phospholipid film with phosphorylcholine head group, as evaluated by 3-(4,5-timethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (p < 0.001). The hemocompatibility of the film was also assessed by platelet adhesion and protein adsorption. The results suggest that the product has potential applications as a new biomaterial coating.


Pretreatment with buflomedil enhances ventricular function by reducing the dysfunctional area after transient coronary artery occlusion.
The aim was to evaluate whether buflomedil (a drug used to treat peripheral vascular disease and which has a number of pharmacological actions potentially beneficial to dysfunctional myocardium) would preserve myocardial function after transient coronary artery occlusion followed by reperfusion. The physiological response to a 15 min balloon occlusion of the left anterior descending coronary artery followed by 1 h of reperfusion was monitored in 17 placebo treated dogs and compared with that of 15 dogs which received 10 mg.kg-1 of buflomedil. Buflomedil or its vehicle were given intravenously. Myocardial blood flow was assessed with radiolabelled microspheres and cardiac function was evaluated with quantitative contrast left ventriculography. Buflomedil did not affect baseline haemodynamic variables or contractile function. At the end of occlusion, there was no difference between dogs receiving vehicle compared with those receiving drug with respect to ejection fraction [33(SD 11)% v 34(11)%] or transmural blood flow [0.23(0.11) v 0.28(0.14) ml.g-1 x min-1]. However, at 30 min after reperfusion, ejection fraction was 89% of normal in the buflomedil group compared with 69% of normal in the placebo group (p < 0.03). This difference was sustained 60 min after reperfusion, and was due in part to slightly enhanced flow during reperfusion and a decrease in the dysfunctional area (16 compared with 28 chords lower than -2 SD from the mean, p < 0.04) in the hearts of dogs receiving buflomedil. Areas at risk were equivalent (15.9% and 15.8% of the left ventricle, respectively). The results suggest that buflomedil and agents with similar modes of action may be beneficial in preserving ventricular function after transient ischaemia followed by reperfusion.


ADMA and homoarginine independently predict mortality in critically ill patients.
Arginine metabolites are associated with cardiovascular and all-cause mortality in several patient groups. We investigated whether arginine metabolites are associated with mortality in patients with critical illness and whether associations are independent of other factors affecting prognosis in an Intensive Care Unit (ICU). 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU were studied. Arginine, asymmetric dimethyl-l-arginine (ADMA), monomethyl-l-arginine (MMA), symmetric dimethyl-l-arginine (SDMA) and l-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. In this cohort, 163 patients (14.1%) died. ADMA (odds ratio = 1.159 (1.033-1.300) per 0.1 μmol/L increment, p = 0.012), homoarginine (odds ratio = 0.963 (0.934-0.992), p = 0.013) and risk of death score (odds ratio = 1.045 (1.037-1.053) per 1% increment, p < 0.001) were independently associated with mortality in ICU patients. The area under the receiver operator characteristic curve for risk of death score, ADMA and homoarginine combined for mortality was greater than for risk of death score alone (0.815 (95% CI 0.790-0.837) vs 0.796 (95% CI 0.781-0.820), p = 0.019). Other arginine metabolites were not independently associated with mortality. ADMA is positively and homoarginine negatively associated with mortality in ICU patients, independent of other clinical factors. Measuring ADMA and homoarginine may refine models to predict ICU mortality. Reducing ADMA and increasing homoarginine are potential therapeutic targets to reduce mortality in critically ill patients.


Effect of aluminum on the renal handling of phosphate in the rat.
The effects of aluminum (Al) on the renal handling of phosphate (Pi) were studied by clearance techniques in the presence and absence of endogenous parathyroid hormone (PTH) and after Pi infusion. In all groups, a 1-h control period was followed by three 1-h experimental periods in which controls continued to receive saline and experimental animals received Al. Glomerular filtration rate, urine flow rate, and plasma sodium (Na) were not significantly changed between periods in any group. In the presence of endogenous PTH, the fractional excretion of phosphate (FEPi) increased significantly after 3 h of Al infusion (6.1 +/- 0.9 to 15.0 +/- 1.8%, P less than 0.05, n = 8), but not in controls (n = 7), while plasma calcium and Pi decreased, suggesting a PTH effect. However, in acutely thyroparathyroidectomized (TPTX) rats the FEPi also increased significantly after 3 h of Al infusion (4.3 +/- 3.0 to 10.6 +/- 4.2%, P less than 0.05, n = 7), but not in controls (n = 6). In TPTX rats infused with Pi where plasma Pi was increased to 10 mg/dl, FEPi increased significantly after 2 and 3 h of Al (7.0 +/- 1.4 to 15.5 +/- 2.1 to 16.9 +/- 2.2%, P less than 0.01, n = 15), but not in controls (n = 8). In this group, changes in FEPi were accompanied by a small but significant increase in FENa but not urinary cAMP. Blood pH was not significantly different between saline and Al-infused rats. These studies indicate that Al infusion inhibits renal Pi reabsorption by a mechanism independent of PTH, blood pH, or cAMP.


Experimental Satellite Quantum Communications.
Quantum communication (QC), namely, the faithful transmission of generic quantum states, is a key ingredient of quantum information science. Here we demonstrate QC with polarization encoding from space to ground by exploiting satellite corner cube retroreflectors as quantum transmitters in orbit and the Matera Laser Ranging Observatory of the Italian Space Agency in Matera, Italy, as a quantum receiver. The quantum bit error ratio (QBER) has been kept steadily low to a level suitable for several quantum information protocols, as the violation of Bell inequalities or quantum key distribution (QKD). Indeed, by taking data from different satellites, we demonstrate an average value of QBER=4.6% for a total link duration of 85 s. The mean photon number per pulse μ_{sat} leaving the satellites was estimated to be of the order of one. In addition, we propose a fully operational satellite QKD system by exploiting our communication scheme with orbiting retroreflectors equipped with a modulator, a very compact payload. Our scheme paves the way toward the implementation of a QC worldwide network leveraging existing receivers.


A Review of Associations between Externalizing Behaviors and Prenatal Cannabis Exposure: Limitations & Future Directions.
In utero cannabis exposure can disrupt fetal development and increase risk for various behavioral disruptions, including hyperactivity, inattention, delinquent behaviors, and later substance abuse, among others. This review summarizes the findings from contemporary investigations linking prenatal cannabis exposure to the development of psychopathology and identifies the limitations within the literature, which constrain our interpretations and generalizability. These limitations include a lack of genetic/familial control for confounding and limited data examining real world products, the full range of cannabinoids, and motives for use specifically in pregnant women. Taken together, our review reveals the need to continue to improve upon study designs in order to allow researchers to accurately draw conclusions about the development of behavioral consequences of prenatal cannabis exposure. Findings from such studies would inform policy and practices regarding cannabis use during pregnancy and move the field toward developing a comprehensive teratogenic profile of cannabis similar to what is characterized in the prenatal alcohol and tobacco literature.


Brines and interstitial brackish water in drill cores from the deep gulf of Mexico.
Marked increases in interstitial salinity occur in two drill holes located in the Gulf of Mexico at a water depth of more than 3500 meters. The increases probably arose through diffusion of salt from buried evaporites. In one hole, however, brackish water was encountered on penetrating the oil-permeated cap rock of a salt dome. The phenomenon is attributed to production of fresh water during oxidation of petroleum hydrocarbons and decomposition of gypsum to form native sulfur.


The current state of in-vivo pre-clinical animal models for heart valve evaluation.
For over 30 years, animal models have remained a central critical component in the pre-clinical safety evaluation of prosthetic heart valves developed for use in humans. Though many advances have been made in valve design, no ideal replacement prosthesis has yet been developed. As a result, valve manufacturers continue to address issues relating to thrombogenicity, structural integrity, fluid dynamics and calcification in their designs. Many animal models have been developed to examine these issues, including dog, pig, calf and sheep, yet no standard model has been accepted. Recently, the International Standard Organization has provided guidelines in document 5840 to address cardiovascular implants. The aim of this report is to provide a summary of the current state of pre-clinical valve evaluation in animals. Changes in ISO 5840 will be addressed that have occurred between 1998 and the present date, and the role of current available animal models. The aim also is to provide rational guidance in the selection of appropriate animal models to match the purpose of valve implantation studies.


Phase behavior of CO2 in room-temperature ionic liquid 1-ethyl-3-ethylimidazolium acetate.
Carbon dioxide solubility (vapor-liquid equilibria: VLE) in an ionic liquid, 1-ethyl-3-ethylimidazolium acetate ([eeim][Ac]) was measured using a gravimetric microbalance at four isotherms (about 283, 298, 323, and 348 K) up to about 2 MPa. An equation-of-state (EOS) model was used to analyze the VLE data and has predicted vapor-liquid-liquid equilibria (VLLE: or liquid-liquid separations) in CO(2)-rich solutions. The VLLE prediction was confirmed experimentally using a volumetric method and likely the liquid-liquid equilibria will intersect with the solid-liquid equilibria such that no lower critical solution temperature can exist and the binary system may be classified as Type III phase behavior. Carbon dioxide solubility in the ionic-liquid-rich solution show extremely unusual behavior. CO(2) dissolves in the ionic liquid at large concentrations (up to about 20 mole % of CO(2)) with almost no vapor pressure above the mixtures. This result is similar to our previous findings with 1-butyl-3-methylimidazolium acetate ([bmim][Ac]) and 1-ethyl-3-methylimidazolium acetate ([emim][Ac]). In all three cases the CO(2) forms a molecular complex (or chemical reaction) with the ionic liquid. (13)C NMR spectroscopy has identified the structure for CO(2) absorbed in [eeim][Ac] to be [eeim]-2-carboxylate. Addition of water to the carboxylate leads to the dissolution of CO(2). The thermodynamic excess properties (enthalpy, entropy, and Gibbs energy) for all three systems have been calculated using the EOS and support the complex formation of the type AB(2) (where A is CO(2) and B is ionic liquid). Isothermal differential scanning calorimetry has verified the heat of reaction calculations and found for CO(2) absorbing in [emim][Ac], [eeim][Ac] and [bmim][Ac] to be about -38 kJ mol(-1). Additional experiments have examined the effect of water on the density, viscosity and CO(2) solubility in [eeim][Ac] and the CO(2) solubility in mixtures of [eeim][Ac] with other acetate salts.


Electroencephalography abnormalities in generalized epilepsy and their predictors: A multicenter experience.
In spite of the overwhelming significance of knowledge of basic elements of electroencephalography (EEG) in its application to the diagnostic workup and the management of patients with suspected or already established generalized epilepsy (GE), there is a dearth of data on the pattern and utility of clinical variables that can independently determine EEG abnormalities in GE. The study was designed to evaluate the frequency and pattern of EEG abnormality as well as assess the utility of clinical variables in predicting the likelihood of an abnormal EEG in GE. It was a cross-sectional study involving the analysis of EEGs of consecutive patients with clinical diagnosis of idiopathic GE from three centers over a 7-year period. Information on sociodemographic and seizure variables was obtained. The International Federation of Societies for Electroencephalography and Clinical Neurophysiology definition of interictal epileptiform discharges (interictal epileptiform activity [IEA]) was adopted in the study. A total of 403 patients comprising 242 (60%) males and 161 (40%) females with clinical diagnosis of GE had EEG. Their age ranged between 2 weeks and 70 years, with a median age of 21 years and an interquartile age of 26 years. Two hundred and thirty-seven (58.8%) and 213 (52.9%) patients had abnormal EEG and IEA, respectively. Before adjustment for confounders, female gender (P = 0.0001), pediatric age group (P = 0.0388), duration of epilepsy of 1-4 years (P = 0.01387), uncontrolled seizure (P = 0.0060), and seizure frequency (P = 0.0001) were significantly associated with the presence of abnormal EEG. However, age, female gender, poor seizure control, and seizure frequencies were the independent predictors of EEG abnormality. The study showed that about 58% of patients with GE patients had abnormal EEG. Age, poor seizure control, and high frequency of seizure were independent predictors of the presence of EEG abnormality.


[Duplex ultrasound with echo contrast media].
Intravenous echo contrast agents transversing the lungs lead to improved detection of blood flow in arteries and veins due to enhancement of the Doppler signal by 20-25 dB. This echo enhancement improves the visualisation of vessel sections that are otherwise difficult to examine due to obesity, to deep vessel location, scarring or low flow state. The available contrast agents that pass through the lungs and are used in controlled studies, possess similar physico-chemical properties: mean bubble diameter 2-4 microns, viscosity and pH value close to that of the blood. The contrast agents enable the plotting of densitometric wash-in and wash-out curves from the heart and the vessels to aid in the investigation of tissue perfusion. Echo contrast agents induce some technical side effects that must be known to avoid annoying diagnostic pitfalls: spectral bubble noise, colour blooming, acoustic shadowing and changes in Doppler frequency shifts. Their origin and measures to avoid them are discussed. The contrast agents that pass through the lungs open up new fields of application in the investigation of blood flow.


Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol.
Background: The complex nature of stroke sequelae, the heterogeneity in rehabilitation pathways, and the lack of validated prediction models of rehabilitation outcomes challenge stroke rehabilitation quality assessment and clinical research. An integrated care pathway (ICP), defining a reproducible rehabilitation assessment and process, may provide a structured frame within investigated outcomes and individual predictors of response to treatment, including neurophysiological and neurogenetic biomarkers. Predictors may differ for different interventions, suggesting clues to personalize and optimize rehabilitation. To date, a large representative Italian cohort study focusing on individual variability of response to an evidence-based ICP is lacking, and predictors of individual response to rehabilitation are largely unexplored. This paper describes a multicenter study protocol to prospectively investigate outcomes and predictors of response to an evidence-based ICP in a large Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation. Methods: All patients with diagnosis of ischemic or hemorrhagic stroke confirmed both by clinical and brain imaging evaluation, admitted to four intensive rehabilitation units (adopting the same stroke rehabilitation ICP) within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled (expected sample: 270 patients). Measures will be taken at admission (T0), at discharge (T1), and at follow-up 6 months after a stroke (T2), including clinical data, nutritional, functional, neurological, and neuropsychological measures, electroencephalography and motor evoked potentials, and analysis of neurogenetic biomarkers. Statistics: In addition to classical multivariate logistic regression analysis, advanced machine learning algorithms will be cross-validated to achieve data-driven prognosis prediction models. Discussion: By identifying data-driven prognosis prediction models in stroke rehabilitation, this study might contribute to the development of patient-oriented therapy and to optimize rehabilitation outcomes. Clinical Trial Registration: ClinicalTrials.gov, NCT03968627. https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank=2.


Benchmarking the burden of 100 diseases: results of a nationwide representative survey within general practices.
Objective To assess the burden of diseases and quality of life (QOL) of patients for a large variety of diseases within general practice. Design In a representative nationwide cross-sectional study, a total of 825 general practitioners (GPs) were randomly selected from across France. Independent investigators recruited 8559 patients attending the GPs' practices. Data on QOL (12-Item Short Form questionnaire) and other individual characteristics were documented by the independent investigators for all participants in the waiting room. Medical information was recorded by GPs. Sampling was calibrated to national standards using the CALMAR (CALage sur MARges) weighting procedure. Associations of lower scores (ie, below vs above the first quartile) of physical and mental component scores (physical component summary score (PCS) and mental component summary score (MCS), respectively) with main diseases and patients characteristics were estimated using multivariate logistic regression. Weighted morbidity rates, PCS and MCS were computed for 100 diagnoses using the International Classification of Diseases (9th version). Results Overall mental impairment was observed among patients in primary care with an average MCS of 41.5 (SD 8.6), ranging from 33.0 for depressive disorders to 45.3 for patients exhibiting fractures or sprains. Musculoskeletal diseases were found to have the most pronounced effect on impaired physical health (OR=2.31; 95% CI 2.08 to 2.57) with the lowest PCS (45.6 (SD 8.8)) and ranked first (29.0%) among main diagnoses experienced by patients followed by cardiovascular diseases (26.7%) and psychological disorders (22.0%). When combining both prevalence and QOL, musculoskeletal diseases represented the heaviest burden in general practice. Conclusions Etude épidémiologique de l'Impact de santé public sur 3 groupes de pathologies (EPI3) is the first study to provide reference figures for burden of disease in general practice across a wide range of morbidities, particularly valuable for health-economics and healthcare-system evaluation.


Selective proximal renal tubular involvement and dyslipidemia in two cousins with oculocerebrorenal syndrome of Lowe.
Oculocerebrorenal syndrome of Lowe (OCRL) is a rare, X-linked disorder characterized by congenital cataracts, neonatal or infantile hypotonia, seizures, cognitive impairment, and renal tubular dysfunction. In this article, we report two maternal cousins with OCRL with a hemizygous p.Ala788Asp mutation in exon 22 of the OCRL gene. They presented with diverse features of selective proximal renal tubular defect and high serum levels of total cholesterol, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C).


Intramural Stomach Gas with Hepatic Portal Venous Gas Indicating Spontaneous Stomach Necrosis.
Intramural gas in the stomach associated with hepatic portal venous gas is a rare entity, which suggests ischemic or infectious pathology of the stomach. We report a case of a 73-year-old man who presented with epigastric pain and nausea of 6 hours duration followed by hematemesis. The patient had pale skin, anemia, and a diffusively tender and distended abdomen. Abdominal radiography and computed tomography (CT) revealed gas in thickened gastric wall and gas in intrahepatic portal vein branches. Surgery was indicated, which consisted of partial gastrectomy with Roux en esophago-jejunal anastomosis. Postoperative course was uneventful, and pathohistological analysis indicated stomach wall necrosis with emphysametous gastritis (EG). The patient was free of symptoms at 2 years follow-up. Intramural gas in the stomach should always be meticulously investigated to differentiate between emphysematous gastritis and gastric emphysema, as this would direct the therapeutic approach to be adopted.


A tolerability and patient acceptability pilot study of a novel antimicrobial urinary catheter for long-term use.
We have developed a novel antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin and demonstrated that it has long-term (∼84 days) protection against bacterial colonization in vitro. This study aimed to assess the safety and patient acceptability of this device in long-term catheter users. Adults who use long term (>28 days) indwelling urinary catheters with capacity to consent were invited to receive the AUC at their next catheter change. The primary outcome measure was adverse events (AE) attributable to antimicrobial impregnation of the catheter. Secondary outcome measures included severity of related AEs, patient acceptability, early removal of the trial catheter, and degree of microbial colonization of trial catheters. Except for the last, outcomes were assessed by telephone interviews. Original and trial catheters were collected, and the lumens and balloons were separated and analyzed for microbiological colonization. Thirty participants were recruited. Eighty four AEs were reported, and only one was rated as "probably" related to antimicrobial impregnation. The AE was mild and resolved within 48 h. A total of 82.14% of participants rated the catheter as no different or better than their usual catheter. Two participants chose to remove the AUC early due to it feeling shorter. There were significantly fewer bacterial isolates attached to the balloons of trial catheters compared to the matched original catheters. The AUC has an advantageous safety profile and was acceptable to the majority of participants. Information gained from this trial will support a larger randomized controlled study of efficacy.


Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis.
The impact of cerebral erythropoietin (Epo) in the regulation of the hypercapnic ventilatory response (HcVR) is controversial. While we reported that cerebral Epo does not affect the central chemosensitivity in C57Bl6 mice receiving an intracisternal injection of sEpoR (the endogenous antagonist of Epo), a recent study in transgenic mice with constitutive high levels of human Epo in brain and circulation (Tg6) and in brain only (Tg21), showed that Epo blunts the HcVR, maybe by interacting with central and peripheral chemoreceptors. High Epo serum levels in Tg6 mice lead to excessive erythrocytosis (hematocrit ~80-90%), the main symptom of chronic mountain sickness (CMS). These latter results support the hypothesis that reduced central chemosensitivity accounts for the hypoventilation observed in CMS patients. To solve this intriguing divergence, we reevaluate HcVR in Tg6 and Tg21 mouse lines, by assessing the metabolic rate [O consumption (V̇) and CO production (V̇)], a key factor modulating ventilation, the effect of which was not considered in the previous study. Our results showed that the decreased HcVR observed in Tg6 mice (~70% reduction; < 0.01) was due to a significant decrease in the metabolism (~40%; < 0.0001) rather than Epo's effect on CO chemosensitivity. Additional analysis in Tg21 mice did not reveal differences of HcVR or metabolism. We concluded that cerebral Epo does not modulate the central chemosensitivity system, and that a metabolic effect upon CO inhalation is responsible for decreased HcVR observed in Tg6 animals. As CMS patients also show decreased HcVR, our findings might help to better understand respiratory disorders at high altitude.


Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO.
The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous depolarization wave in the mouse embryo: origin and large-scale propagation over the CNS identified with voltage-sensitive dye imaging.
Spontaneous embryonic movements, called embryonic motility, are produced by correlated spontaneous activity in the cranial and spinal nerves, which is driven by brainstem and spinal networks. Using optical imaging with a voltage-sensitive dye, we have revealed previously that this correlated activity is a widely propagating wave of neural depolarization, which we termed the depolarization wave. We have observed in the chick and rat embryos that the activity spread over an extensive region of the CNS, including the spinal cord, hindbrain, cerebellum, midbrain and forebrain. One important consideration is whether a depolarization wave with similar characteristics occurs in other species, especially in different mammals. Here, we provide evidence for the existence of the depolarization wave in the mouse embryo by showing that the widely propagating wave appeared independently of the localized spontaneous activity detected previously with Ca(2+) imaging. Furthermore, we mapped the origin of the depolarization wave and revealed that the wave generator moved from the rostral spinal cord to the caudal cord as development proceeded, and was later replaced with mature rhythmogenerators. The present study, together with an accompanying paper that describes pharmacological properties of the mouse depolarization wave, shows that a synchronized wave with common characteristics is expressed in different species, suggesting fundamental roles in neural development.


The effect of radiation dose on mouse skeletal muscle remodeling.
The purpose of this study was to determine the effect of two clinically relevant radiation doses on the susceptibility of mouse skeletal muscle to remodeling. Alterations in muscle morphology and regulatory signaling were examined in tibialis anterior and gastrocnemius muscles after radiation doses that differed in total biological effective dose (BED). Female C57BL/6 (8-wk) mice were randomly assigned to non-irradiated control, four fractionated doses of 4 Gy (4x4 Gy; BED 37 Gy), or a single 16 Gy dose (16 Gy; BED 100 Gy). Mice were sacrificed 2 weeks after the initial radiation exposure. The 16 Gy, but not 4x4 Gy, decreased total muscle protein and RNA content. Related to muscle regeneration, both 16 Gy and 4x4 Gy increased the incidence of central nuclei containing myofibers, but only 16 Gy increased the extracellular matrix volume. However, only 4x4 Gy increased muscle 4-hydroxynonenal expression. While both 16 Gy and 4x4 Gy decreased IIB myofiber mean cross-sectional area (CSA), only 16 Gy decreased IIA myofiber CSA. 16 Gy increased the incidence of small diameter IIA and IIB myofibers, while 4x4 Gy only increased the incidence of small diameter IIB myofibers. Both treatments decreased the frequency and CSA of low succinate dehydrogenase activity (SDH) fibers. Only 16 Gy increased the incidence of small diameter myofibers having high SDH activity. Neither treatment altered muscle signaling related to protein turnover or oxidative metabolism. Collectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these effects appear to be related to fiber type and oxidative metabolism.


Protective Effects of Caffeic Acid and the Alzheimer's Brain: An Update.
Caffeic acid (CA) and related phenylpropanoic acids are ubiquitous natural products of the shikimic acid pathway origin. Due to the presence of diorthohydroxyl aromatic (catecholic) moiety, CA is not only one of the most potent antioxidant phenyl propanoids but also displays numerous other pharmacological effects ranging from antiinflammatory to anticancer effects. Recent studies also demonstrated that CA both in its free form or conjugated with other groups such as quinic acid and sugars displays profound effects in the brain including protection from toxicity induced by a variety of agents and/or experimental models of Alzheimer's disease (AD). In this communication, the anti-AD therapeutic potential of CA and its two most common conjugated natural bioactive derivatives, chlorogenic acid (CGA) and caffeic acid phenethyl ester (CAPE), is scrutinised by reviewing literature in the past ten years. Besides the common global antioxidant effects, specific antiinflammatory mechanisms in the brain along with the various processes of β-amyloid formation, aggregation and neurotoxicity targets are discussed. The mini-review also provides an insight into enhancing the therapeutic potential of existing anti-AD drugs by incorporating a CA structural moiety.


Psychologist suicide: Incidence, impact, and suggestions for prevention, intervention, and postvention.
Psychologist practitioners are not immune to some mental health problems, including suicidality, for which they provide services. In the aftermath of two recent psychologist suicides, the American Psychological Association's Advisory Committee on Colleague Assistance (ACCA) initiated the formation of a conjoint ad hoc committee consisting of members from ACCA, the American Psychological Association (APA) Practice Directorate, and the Section on Clinical Emergencies and Crises (Section VII of APA's Division 12) to investigate the incidence of psychologist suicide and its impact on colleagues, students or interns, patients or clients, and the profession. The committee reviewed the extant empirical literature on suicide rates for psychologists, evaluated unpublished data on psychologist suicide provided by the National Institute of Occupational Safety and Health (NIOSH), interviewed colleague survivors, reviewed published case reports of the impact of therapist suicides, and linked their findings to the literature on professional distress, impairment, and self-care. The committee concluded that there is evidence suggestive of an elevated risk of suicide for psychologists in past decades. It further concluded that there is a need for further research to confirm if there is a heightened risk of suicide for psychologists in the present day, and to determine factors that might contribute to such risk. Accounts from colleague-survivors suggest that the impact of a psychologist's suicide can affect many people including family, colleagues, students, and patients or clients. This article offers suggestions for possible preventive approaches, for intervention with potentially at-risk colleagues, and for postvention efforts in the wake of a colleague suicide.


Double lung transplantation.
In the past 3 years we and other centers have accumulated a small experience with double lung transplantation. We continue to believe that it offers potential benefit to patients with bilateral septic lung disease and possibly to those with obstructive lung disease as well. We have encountered significant airway complications that several other centers have avoided by improved preservation and the technical modification of bilateral bronchial anastomosis. Reliable resolution of the problem of airway viability will permit more widespread application of double lung transplantation in selected patients with end-stage pulmonary disease.


Au2Pt-PEG-Ce6 nanoformulation with dual nanozyme activities for synergistic chemodynamic therapy / phototherapy.
Although synergistic therapy for tumors has displayed significant promise for effective treatment of cancer, developing a simple and effective strategy to build a multi-functional nanoplatform is still a huge challenge. By virtue of the characteristics of tumor microenvironment, such as hypoxia, slight acidity and H2O2 overexpression, Au2Pt-PEG-Ce6 nanoformulation is constructed for collaborative chemodynamic/phototherapy of tumors. Specifically, the Au2Pt nanozymes with multiple functions are synthesized in one step at room temperature. The photosensitizer chlorin e6 (Ce6) is covalently linked to Au2Pt nanozymes for photodynamic therapy (PDT). Interestingly, the Au2Pt nanozymes possess catalase- and peroxidase-like activities simultaneously, which not only can generate O2 for relaxation of tumor hypoxia and enhancement of PDT efficiency but also can produce ∙OH for chemodynamic therapy (CDT). In addition, the high photothermal conversion efficiency (η = 31.5%) of Au2Pt-PEG-Ce6 nanoformulation provides the possibility for photoacoustic (PA) and photothermal (PT) imaging guided photothermal therapy (PTT). Moreover, the presence of high-Z elements (Au and Pt) in Au2Pt-PEG-Ce6 nanoformulation endows it with the ability to act as an X-ray computed tomography (CT) imaging contrast agent. All in all, the Au2Pt-PEG-Ce6 exhibits great potential in multimodal imaging-guided synergistic PTT/PDT/CDT with remarkably tumor specificity and enhanced therapy.


Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study.
More information is needed about the durability of weight loss and health improvements after bariatric surgical procedures. To examine long-term weight change and health status following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB). The Longitudinal Assessment of Bariatric Surgery (LABS) study is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Adults undergoing bariatric surgical procedures as part of clinical care between 2006 and 2009 were recruited and followed up until January 31, 2015. Participants completed presurgery, 6-month, and annual research assessments for up to 7 years. Percentage of weight change from baseline, diabetes, dyslipidemia, and hypertension, determined by physical measures, laboratory testing, and medication use. Of 2348 participants, 1738 underwent RYGB (74%) and 610 underwent LAGB (26%). For RYBG, the median age was 45 years (range, 19-75 years), the median body mass index (calculated as weight in kilograms divided by height in meters squared) was 47 (range, 34-81), 1389 participants (80%) were women, and 257 participants (15%) were nonwhite. For LAGB, the median age was 48 years (range, 18-78), the body mass index was 44 (range, 33-87), 465 participants (76%) were women, and 63 participants (10%) were nonwhite. Follow-up weights were obtained in 1300 of 1569 (83%) eligible for a year-7 visit. Seven years following RYGB, mean weight loss was 38.2 kg (95% CI, 36.9-39.5), or 28.4% (95% CI, 27.6-29.2) of baseline weight; between years 3 and 7 mean weight regain was 3.9% (95% CI, 3.4-4.4) of baseline weight. Seven years after LAGB, mean weight loss was 18.8 kg (95% CI, 16.3-21.3) or 14.9% (95% CI, 13.1-16.7), with 1.4% (95% CI, 0.4-2.4) regain. Six distinct weight change trajectory patterns for RYGB and 7 for LAGB were identified. Most participants followed trajectories in which weight regain from 3 to 7 years was small relative to year-3 weight loss, but patterns were variable. Compared with baseline, dyslipidemia prevalence was lower 7 years following both procedures; diabetes and hypertension prevalence were lower following RYGB only. Among those with diabetes at baseline (488 of 1723 with RYGB [28%]; 175 of 604 with LAGB [29%]), the proportion in remission at 1, 3, 5, and 7 years were 71.2% (95% CI, 67.0-75.4), 69.4% (95% CI, 65.0-73.8), 64.6% (95% CI, 60.0-69.2), and 60.2% (95% CI, 54.7-65.6), respectively, for RYGB and 30.7% (95% CI, 22.8-38.7), 29.3% (95% CI, 21.6-37.1), 29.2% (95% CI, 21.0-37.4), and 20.3% (95% CI, 9.7-30.9) for LAGB. The incidence of diabetes at all follow-up assessments was less than 1.5% for RYGB. Bariatric reoperations occurred in 14 RYGB and 160 LAGB participants. Following bariatric surgery, different weight loss patterns were observed, but most participants maintained much of their weight loss with variable fluctuations over the long term. There was some decline in diabetes remission over time, but the incidence of new cases is low following RYGB. clinicaltrials.gov Identifier: NCT00465829.


Pressor effects of brief and prolonged infusions of epinephrine in the conscious rat.
Plasma epinephrine may be increased in some patients with essential hypertension, and prolonged infusion of this catecholamine has been claimed to raise blood pressure. The objectives of our experiments were to determine whether continuous intravenous infusion of epinephrine raised blood pressure in a rat preparation known to respond in this way to angiotensin II in low dose and, if so, the plasma concentration of epinephrine required to raise pressure in comparison to the physiological range of plasma catecholamine concentration in the rat. Intravenous infusion of epinephrine at a rate of 400 ng X kg-1. min-1 or less for 30 min into Wistar rats did not increase mean arterial pressure (MAP); pressure did rise when the rate was increased to 800 ng X kg-1. min-1. However, when rats were given epinephrine at 400 ng X kg-1. min-1 for 4 days with continuous blood pressure recording, average MAP showed a progressive rise on successive days of infusion, reaching a maximum increase of 12 mmHg on the 4th and final day of infusion (P less than 0.02). Blood pressure did not change significantly during epinephrine infusion at 10 and 70 ng X kg-1. min-1. Plasma epinephrine was raised more than 13 times basal at the highest rate of infusion. In comparison, blood pressure and catecholamine concentrations increased only slightly although significantly during a period of restraint. We confirm the existence of a slowly developing pressor effect of epinephrine, but it is small and requires a large sustained increase of plasma epinephrine for its development.


Biofilm forming ability of Sphingomonas paucimobilis isolated from community drinking water systems on plumbing materials used in water distribution.
Sphingomonas paucimobilis, an oligotroph, is well recognized for its potential for biofilm formation. The present study explored the biofilm forming ability of a strain isolated from municipal drinking water on plumbing materials. The intensity of biofilm formation of this strain on different plumbing materials was examined by using 1 × 1 cm2 pieces of six different pipe materials, i.e. polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), aluminium (Al), copper (Cu) and rubber (R) and observing by staining with the chemical chromophore, Calcofluor. To understand whether biofilm formation occurs under flow through conditions, a laboratory-scale simulated distribution system, comprised of the above materials was fabricated. Biofilm samples were collected from the designed system at different biofilm ages (10, 40 and 90 hours old) and enumerated. The results indicated that the biofilm formation occurred on all plumbing materials with Cu and R as exceptions. The intensity of biofilm formation was found to be maximum on PVC followed by PP and PE. We also demonstrated the chemical chromophore (Calcofluor) successfully for rapid and easy visual detection of biofilms, validated by scanning electron microscope (SEM) analysis of the plumbing materials. Chlorination has little effect in preventing biofilm development.


Effectiveness of laser fluorescence-based device in detecting the extent of re-mineralisation in primary teeth compared to the conventional method: An In vitro study.
Laser fluorescence (LF)-based clinical device DIAGNOdent™ is at present being used to detect caries. Can the same be used to detect therapeutic remineralisation of early white spot lesions? To explore the feasibility of using LF-based device in monitoring the changes following remineralisation of demineralised primary teeth. The sample number for the present experimental in vitro study was 10. The LF based device readings were correlated with surface microhardness (SMH) test values to evaluate its efficiency. SMH analysis was performed using a microhardness tester (Tescol-HT1000AD). All the samples were demineralised, followed by remineralisation using fluoride varnish and pH cycling. The data was analysed using the Statistical Package for the Social Sciences (SPSS) version 17.0 (IBM SPSS®) software. Paired t-test was performed to compare laser fluorescence readings and SMH test result values at baseline, after demineralisation, and after remineralisation. Pearson's correlation was used to compare the relation between the laser fluorescence and SMH test. A good negative correlation was seen between the two methods at the baseline readings even though it was not statistically significant (P = 0.069). A positive correlation between the methods existed following demineralisation which was not significant (P = 0.074). The correlation between the parameters following remineralisation showed a moderate negative correlation but was not significant (P = 0.55). DIAGNOdent™ values at baseline, after demineralisation, and after remineralisation was consistent with SMH values. Thus, DIAGNOdent™ can be explored to provide chairside assistance in identifying remineralisation of white spot lesions.


Anastomotic leakage is associated with poor long-term outcome in patients after curative colorectal resection for malignancy.
The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented. This study aimed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer. Prospectively collected data of the 1,580 patients (904 men) of a median age of 70 years (range: 24-94), who underwent potentially curative resection for colorectal cancer between 1996 and 2004, were reviewed. Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method, and variables were compared with log rank test. Cox regression model was used in multivariate analysis. The cancer was situated in the colon and the rectum in 933 and 647 patients, respectively. Anastomotic leakage occurred in 60 patients (clinical leakage: n = 48; radiological leak: n = 12). The leakage rate was significantly higher in patients with surgery for rectal cancer (6.3 vs 2.0%, p < 0.001). The 5-year cancer-specific survivals were 56.9% in those with leakage and 75.9% in those without leakage (p = 0.012). The 5-year systemic recurrence rates were 48.4 and 22.6% in patients with and without anastomotic leak, respectively (p = 0.001), whereas the 5-year local recurrence rates were 12.9 and 5.7%, respectively (p = 0.009). Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival (p = 0.043, hazard ratio: 1.63, 95% CI: 1.02-2.60) and a higher systemic recurrence rate (hazard ratio: 1.94, 95% CI: 1.23-3.06, p = 0.004) on multivariate analysis. In rectal cancer, anastomotic leakage was an independent factor for a higher local recurrence rate (hazard ratio: 2.55, 95% CI: 1.07-6.06, p = 0.034). In conclusion, anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer. Efforts should be undertaken to avoid this complication to improve the long-term outcome.


Self-reported napping and nocturnal sleep in Taiwanese elderly insomniacs.
Abstract The aim of this study was to investigate the relationships between self-reported nocturnal sleep quality and napping patterns in elderly persons with insomnia and to compare the nocturnal sleep quality between napping and non-napping groups. Convenience sampling was used to recruit 60 community-dwelling elderly residents of Taichung City, Taiwan (age range 60-83 years, mean 67.1 years) who reported insomnia. All participants scored greater than 5 on the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Napping prevalence, frequency, and duration were assessed by participant interview. Self-reported sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction were measured with the PSQI. Sixty-four percentage of participants (n = 38) reported napping. There were no age, gender, and ethnicity differences on napping patterns. Global sleep quality, sleep efficiency, and sleep disturbance were significantly associated with prevalence of napping (r = 0.24-0.26, p < 0.05). A significant correlation was also found between global sleep quality and nap duration (r = 0.31, p < 0.05). Elders in the napping group reported better global sleep quality (t = 2.2, p < 0.05) and sleep efficiency (t = 2.1, p < 0.05) than those in the non-napping group. The findings suggest that there is no need for health care providers to restrict elderly insomniacs' daytime napping.


Cryptococcosis in Hodgkin's disease: description of two cases and review of the literature.
Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.


[The glycemic effect of glutinous rice dumplings in non-insulin-dependent diabetes mellitus].
Postprandial hyperglycemia is a known physiological effect in diabetics. The glycemic index classifies starchy carbohydrate foods into predictable postprandial glycemic responses and was thought to be a useful tool for the planning of diabetic diets. Recently, There has been some debates over the applicability of the glycemic index to mixed meals. The purpose of this study was to study the glycemic effect of glutinous rice dumplings, a mixed food, on non-insulin-dependent diabetics and discuss the applicability of rice dumplings in diet planning. A total of 31 patients with non-insulin-dependent diabetes mellitus participated in this study. The ingredients of the glutinous rice dumplings included 60 grams glutinous rice, 30 grams lean meat, 1/3 of a salted egg yolk, and 1/3 of a mushroom. After a preprandial blood sample, each subject ate one rice dumplings. Postprandial blood samples were taken at 30, 60, 90 and 120 minutes respectively. The glucose hexokinase method was used to determine the plasma glucose value. Subjects were divided into two groups (poor control group and fair control group) by preprandial blood glucose, the cutoff point was 140 mg/dL. For the poor control group, the preprandial value was 226.0 +/- 62.2 mg/dL compared to 102.8 +/- 19.0 mg/dL in the fair control group. The values for the poor and fair control groups postprandially were: 30 minutes, 212.7 +/- 47.6 mg/dL vs 138.3 +/- 30.3 mg/dL; 60 minutes, 259.5 +/- 51.8 mg/dL vs 189.9 +/- 34.6 mg/dL; 90 minutes, 291.5 +/- 69.5 mg/dL vs 210.6 +/- 46.4 mg/dL; and 120 minutes, 297.1 +/- 80.0 mg/dL vs 196.6 +/- 54.0 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)


Multicenter analyses demonstrate significant clinical effects of minor histocompatibility antigens on GvHD and GvL after HLA-matched related and unrelated hematopoietic stem cell transplantation.
The effect of minor H antigen mismatching on the occurrence of graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) after HLA-matched hematopoietic stem cell transplantation (HSCT) has mainly been demonstrated in single-center studies. Yet, the International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 20 laboratories of the IHIW, the roles of 10 autosomal and 10 Y chromosome-encoded minor H antigens were investigated on GvHD and relapse incidence in 639 HLA-identical related donor (IRD) and 210 HLA-matched unrelated donor (MUD) HSCT recipients. Donor and recipient DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, and HY. The correlations with the primary outcomes GvHD (acute or chronic GvHD), survival, and relapse were statistically analyzed. The results of these multicenter analyses show that none of the HLA class I-restricted HY antigens were found to be associated with any of the primary outcomes. Interestingly, of the HLA class II-restricted HY antigens analyzed, HLA-DQ5 positive recipients showed a significantly increased GvHD-free survival in female-to-male HSCT compared with male-to-female HSCT (P = .013). Yet, analysis of the overall gender effect, thus independent of the known HY antigens, between the gender groups demonstrated an increased GvHD incidence in the female-to-male transplantations (P < .005) and a decreased GvHD-free survival in the female-to-male transplantations (P < .001). Of all autosomally encoded minor H antigens, only mismatching for the broadly expressed minor H antigen HA-8 increased the GvHD incidence in IRD HSCT (Hazard ratio [HR] = 5.28, P < .005), but not in MUD HSCT. Most striking was the influence of hematopoietic restricted minor H antigens on GvL as mismatching for hematopoietic minor H antigens correlated with lower relapse rates (P = .078), higher relapse-free survival (P = .029), and higher overall survival (P = .032) in recipients with GvHD, but not in those without GvHD. In conclusion, the significant GvHD effect of the broadly expressed minor H antigen HA-8 favors matching for HA-8 in IRD, but not in MUD, patient/donor pairs. The GvHD-GvL association demonstrating a significant lower relapse in hematopoietic minor H antigen mismatched patient/donor pairs underlines their clinical applicability for adoptive immunotherapy, enhancing the GvL effect in a GvHD controllable manner.


Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine.
1. Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea-pig small intestine in vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH- and S-type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S-type and increased in AH-type neurones. 2. The selective B(2) BK receptor antagonist HOE-140, but not the selective B(1) receptor antagonist des-arg(10)-HOE-140, suppressed the BK-evoked responses. RT-PCR confirmed the expression of B(2) receptor mRNA, but not B(1) receptor mRNA. 3. Binding of fluorescently- labeled HOE-140 (HOE741) was localized to ganglion cells in whole-mount preparations. BK B(2) receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase. 4. Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE-140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK. 5. The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E(2), D(2), F(2alpha) or I(2) mimicked the BK-evoked responses. 6. The results suggest that BK acts at B(2) BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.


A benchmark too far: findings from a national survey of surgical site infection surveillance.
The national surgical site infection (SSI) surveillance service in England collates and publishes SSI rates that are used for benchmarking and to identify the prevalence of SSIs. However, research studies using high-quality SSI surveillance report rates that are much higher than those published by the national surveillance service. This variance questions the validity of data collected through the national service. To audit SSI definitions and data collection methods used by hospital trusts in England. All 156 hospital trusts in England were sent questionnaires that focused on aspects of SSI definitions and data collection methods. Completed questionnaires were received from 106 hospital trusts. There were considerable differences in data collection methods and data quality that caused wide variation in reported SSI rates. For example, the SSI rate for knee replacement surgery was 4.1% for trusts that used high-quality postdischarge surveillance (PDS) and 1.5% for trusts that used low-quality PDS. Contrary to national protocols and definitions, 10% of trusts did not provide data on superficial infections, 15% of trusts did not use the recommended SSI definition, and 8% of trusts used inpatient data alone. Thirty trusts did not submit a complete set of their data to the national surveillance service. Unsubmitted data included non-mandatory data, PDS data and continuous data. The national surveillance service underestimates the prevalence of SSIs and is not appropriate for benchmarking. Hospitals that conduct high-quality SSI surveillance will be penalized within the current surveillance service.


A critique of MSHA procedures for determination of permissible respirable coal mine dust containing free silica.
The literature in selected technical subject areas related to the Mine Safety and Health Administration's (MSHA) respirable mine dust control policy was critically reviewed. Specific topics included: (1) the technical aspects of respirable dust sampling, (2) the development of a sampling strategy and (3) currently used analytical techniques for free silica content of respirable coal mine dust. The 2.0 Lpm MSHA respirable dust sampling flow rate does not conform with published results which indicate that to simulate existing pulmonary particle deposition models, the sampling flow rate should range from 1.4 to 1.7 Lpm. MSHA's sampling strategy focuses on controlling respirable coal mine dust with both area and personal samples of workers in selected occupations or activities. Many uncertainties are encountered as area samples are used to estimate personal exposures. Although all of the analytical methods for crystalline free silica are sufficiently sensitive to be able to detect and quantitate free silica at environmentally significant concentrations, they are all plagued with similar difficulties. Analytical standards representing the various forms of silica are not available. Available analytical methods do not differentiate among polymorphs of silica. Recommendations are presented to resolve identified problem areas.


Hand-assisted retroperitoneoscopic live donor nephrectomy: experience from the first 75 consecutive cases.
The two major life-threatening complications associated with laparoscopic live donor nephrectomy are sudden severe bleeding and intestinal injury. A combined technique-hand-assisted and retroperitoneoscopic (HARS)-reduces the risk of these life-threatening complications. In this study, we report on our experience from the first 75 consecutive HARS operations. The data has been collected prospectively according to intention to treat and includes all consecutive donors operated with the HARS technique. Warm ischemia time, operating time, and blood loss were recorded. Complications, convalescence, and allograft outcome were followed postoperatively with a mean follow-up of 701 (range 60-1438) days. The mean operating time was 138 (range 85-260) minutes and the mean warm ischemia time 175 (85-510) seconds. The operative time was significantly longer in male donors. The mean bleeding was 176 (50-700) ml. There were no conversions to open surgery. Major complications comprised one pulmonary embolus and one donor required 2 units of blood transfusion. One donor was reoperated due to suspicion of trocar hernia. Nine patients experienced minor complications (fever, n=4; urinary tract infection, n=2; chylous ascites, n=1; orchialgia, n=1; subcostal pain, n=1). All except two kidneys had immediate onset of function. Neither of these could, however, be attributed to the donor operation. One recipient experienced urinary leakage and one a stenosis. Recipient and graft survival were 99% and 96%, respectively. We conclude that HARS facilitates the procedure by enabling short operating times and at the same time significantly reducing the risks associated with endoscopic live donor nephrectomy.


Similar cellular responses after treatment with either praziquantel or oxamniquine in Schistosoma mansoni infection.
The effect of treatment with either oxamniquine or praziquantel on S.mansoni specific IFN-gamma, IL-4, IL-5 and IL-10 was compared on PBMC which were collected pretreatment, 6 and 18 weeks post treatment. Using sandwich ELISA on the supernatants harvested from the PBMC stimulation by crude S. mansoni SEA and SWAP antigens after 5 days the levels of PBMC proliferation and cytokine production were similar according to treatment with either praziquantel or oxamniquine. Before treatment, infected groups showed low ratios, of IL-4:IFN-gamma, IL-5:IFNgamma and IL-10:IFN-gamma, indicating that IFN-gamma was high in the infected individuals. The general increase in immuno-modulation was observed post-treatment with elevated immune reactivity and cytokine production in both treatment groups. Treatment induced significant increases in levels of IL-4 (p < 0.05), IL-5 (p < 0.0001) and IL-10 (p < 0.05) cytokines 6 and 18 weeks after treatment. There were no significant differences in the increase in IL-4, IL-5 and IL-10 between children treated with praziquantel or oxamniquine. Pre-treatment IFN-gamma and IL-5 levels were positively correlated with infection (p < 0.001), while post treatment IL-4 cytokine levels were negatively correlated with baseline infection status (p < 0.001). The results suggest that treatment-induced immune responses are similar for both common anti-schistosome drugs praziquantel or oxamniquine having similar and immunizing effect.


Characterization of bacteria by gas chromatography: comparison of trimethylsilyl derivatives of whole-cell hydrolysates.
A method for the formation of the trimethylsilyl (TMS) derivatives of the whole-cell hydrolysate of bacteria was developed. The TMS derivatives were examined by gas-liquid chromatography. TMS profiles of various bacteria at the genus and species level were compared. Differences in TMS profiles of Listeria, Neisseria, and Clostridium were significant as were differences between the TMS profiles of C. perfringens and C. sporogenes. Two types of C. perfringens, two serotypes of L. monocytogenes, and one culture of C. sporogenes and N. meningitidis were studied. The possible application of TMS profiles as an aid in differentiating closely related organisms which are troublesome to separate by conventional means is discussed.


Optimization of Hg(II) adsorption on bio-apatite based materials using CCD-RSM design: characterization and mechanism studies.
Bio-apatite based materials were prepared from bovine bone wastes (BBW) by thermal treatments using a direct flame (BBS) and annealing at 500-1,100 °C (BB500-BB1100). These low-crystalline materials were characterized by means of SEM, XRD, FTIR, TG, and pHPZC and were used for the adsorption of Hg(II) ions. A CCD-RSM design was used to optimize and analyze independent variables consisting of initial mercury concentration (10-100 mg L-1), pH (2-9), adsorbent mass (0.1-0.5 g), temperature (20-60 °C), and contact time (15-120 min). The results indicated that the order of the mercury uptakes for bio-apatite based adsorbents was BB500 > BB600 > BB800 > BB1100 > BBS > BBW. The dissolution-precipitation and ion-exchange reaction are the two dominant mechanisms for the removal of Hg(II) ions at low and high pH values, respectively. The CCD-RSM predicted maximum mercury adsorption of 99.99% under the optimal conditions of 51.31 mg L-1, 0.44 g, 6.5, 67.5 min, and 50 °C for initial mercury concentration, adsorbent mass, pH, contact time, and temperature, respectively. The findings of the present study revealed that the bio-apatite based materials, particularly BB500, are suitable and versatile adsorbents for the treatment of mercury-containing wastewater.


Technical note: evaluation of new Ilizarov rings.
New Ilizarov rings composed of aluminum (Al) or carbon composite (C) are lower in weight and more radiolucent than the stainless steel (SS) rings currently in use. The new rings were subjected to a variety of mechanical tests. The aluminum rings performed as well as the stainless steel rings in all tests; in some tests the carbon rings proved to be less rigid.


Inherited thrombophilia in childhood arterial stroke: data from Lebanon.
Pediatric ischemic stroke still represents a burden, and more than half of the survivors will experience cognitive or motor disabilities. The objective of this study was to investigate the role of thrombophilia in a cohort of children with arterial ischemic stroke. The records of infants and children with clinically and radiologically confirmed stroke were reviewed. Patients with venous or perinatal stroke were not included. Thirty-three patients were diagnosed with arterial ischemic stroke. The male/female ratio was 1.75:1. The median age was 4 years. The most frequent clinical manifestations were hemiparesis (54.5%) and seizures (33.3%). Genetic thrombophilia testing was available on 24 patients. Nine of the 24 patients (37.5%) were heterozygous for factor V Leiden. None of the patients carried the factor II G20210A variant. Ten patients (41.7%) were heterozygous and 3 (12.5%) were homozygous for methylenetetrahydrofolate reductase (MTHFR) C677T variant. Fifteen patients (62.5%) had one or more genetic polymorphism. Factor V Leiden was significantly associated with arterial ischemic stroke (P < 0.001). Stroke recurred in 2 children with multiple risk factors and MTHFR C677T mutation. Factor V Leiden is one of the major genetic risk factors for pediatric arterial ischemic stroke in Lebanon. MTHFR C677T was prevalent among patients with recurrent stroke.


The usefulness and prognostic value of Memorial Symptom Assessment-Short Form and Condensed Memorial Symptom Assessment Scale in assessment of lung cancer patients.
Lung cancer is associated with high level of symptoms and patient-reported symptoms have been rarely used as a prognostic score to predict patients survival. Frequency and burden of symptoms in lung cancer patients were evaluated before the diagnosis with the Memorial Symptom Assessment-Short Form (MSAS-SF) and Condensed Memorial Symptom Assessment Scale (CMSAS) questionnaires. Performance status, stage of disease, serum albumin, and C-reactive protein (CRP) levels were recorded. Patients were staged according to 8th TNM classification. A survival analysis was applied. The mean age of 116 patients (adenocarcinoma 51, squamous cell 43, non-small cell 5, small cell 17) was 65.2 ± 10.1 (28-87) years. The most common seen physical and psychological symptoms were cough (86.3%), lack of energy (74.3%), dyspnea (70.1%), and feeling sad (61.5%), feeling nervous (61.5%), and worrying (53.8%). Total and subscores of MSAS and CMSAS are significantly higher in M1 disease than M0 disease. All MSAS-SF and CMSAS scores, but not MSAS-PSYCH and CMSAS-PSYCH, positively correlated with age, high serum CRP, white blood cells/neutrophils counts, and TNM stage, and negatively correlated with albumin levels, performance status, and overall survival (OS). Median survival was 77, 195, 370, and 579 days for the four prognostic interquartile groups according to CMSAS-SUM score (p < 0.0001). MSAS-SF and CMSAS questionnaires can be useful tool for discriminating metastatic from non-metastatic disease in treatment-naïve patients with lung cancer. Since both questionnaires well correlated with OS and important prognostic factors, they can use to plan palliative care and to help for predicting survival of lung cancer patients.


Understanding diversity in impact and responses among HIV/AIDS-affected households: the case of Msinga, South Africa.
To gain a more comprehensive understanding of the impact of HIV and AIDS on rural households in Msinga, South Africa, the sustainable livelihoods framework was adapted. An ethnographic perspective was employed to examine: 1) the impact of HIV/AIDS-related illnesses on people's mind and spirit (the internal environment), and 2) the influence of institutional structures and processes (the external environment), in order to better understand 3) the actions taken by individuals and households in response to HIV and AIDS. Members of three support groups at a local drop-in centre were consulted about the impact of HIV and AIDS on their lives through focus groups, a questionnaire and in-depth interviews. The study shows that the psychosocial impact and associated coping strategies, as well as prevailing gender-based power relations and exclusion from social-exchange networks - which are not (readily) available factors in the sustainable livelihoods framework - affect people's lives in different ways and depend on the specific situation of the individual or household concerned. The study confirms the need to restore a household's resource base and to address psychosocial issues. However, the variation in impact to different households requires a diversified and holistic programme of development interventions.


[Defects of adrenal steroidogenesis in patients with hirsutism].
To determine the frequency and the type of adrenal steroidogenic abnormalities in hirsute women. ACTH test was performed during follicular phase in 127 hirsute and 40 normal (control) women. Before ACTH injection we measured in serum by RIA: 17-OH-pregnenolone (17-OH-P5), 17-OH-progesterone (17-OH-P4), androstenedione (AN), cortisol (CT), 11-deoxycortisol (DCT), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), total (TT) and free (FT) testosterone, oestradiol (E2), progesterone (PR), androstenediol glucuronide (AG), LH, FSH and prolactin. After 60 min of ACTH injection 17-OH-P5, 17-OH-P4, AN, DHEA, CT and DCT were measured. Net increment of stimulated steroids and the ratios 17-OH-P5/17-OH-P4, DHEA/AN, 17-OH-P4/CT, 17-OH-P5/CT and DCT/CT were calculated. Pelvic ultrasonographic exploration was done when irregular menses were reported. Up to 31% of the patients presented enzymatic defects in adrenal steroidogenesis. Diagnostic criteria for enzyme defects were established. Late-onset 21-hydroxylase deficiency was diagnosed in 6 (4.5%) patients, HLA typing of these patients demonstrated that 4 out of 6 had B14-DR1. Sixteen women (12.6%) displayed a 17-OH-P4 response and the net increment 2 SD above the normal mean concentration, which are diagnostic criteria for late-onset 21-hydroxylase deficiency carriers. We diagnosed a 3 beta-hydroxysteroid dehydrogenase defect when 17-OH-P5 and DHEA responses, their net increment and the 17-OH-P5/17-OH-P4 and 17-OH-P5/CT ratios were 2 SD above the normal mean after ACTH: 14 women were diagnosed. 11 beta-hydroxylase deficiency diagnosis was made when DCT response, its net increment and the DCT/CT ratio after ACTH were 2 SD above the normal mean: 7 women were detected. Associated biosynthetic defects were described. One third of our patients with hirsutism presented anomalous response to ACTH, consistent with enzymatic abnormalities in adrenal steroidogenesis.


The synthetic heat shock protein 90 (Hsp90) inhibitor EC141 induces degradation of Bcr-Abl p190 protein and apoptosis of Ph-positive acute lymphoblastic leukemia cells.
The prognosis of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is poor. Chemotherapy is rarely curative and tyrosine kinase inhibitors (TKIs) induce only transient responses. Heat shock protein 90 (Hsp90) is a chaperone protein that is important in signal transduction, cell cycle control, and transcription regulation in both normal and leukemia cells. In the current study, we tested the growth inhibitory and apoptotic effects of a novel Hsp90 inhibitor, EC141 on the Ph+ ALL lines Z-119, Z-181, and Z-33, as well as primary bone marrow-derived blasts from patients with newly diagnosed Ph+ ALL. We found that EC141 inhibited the growth of Ph+ ALL cells in a concentration-dependent manner with IC(50) ranged from 1 to 10 nM. EC141 also inhibited the proliferation of primary bone marrow-derived blasts using the ALL blast colony assay. EC141 down-regulated Hsp90 and up-regulated Hsp70 protein levels, inhibited CrkL phosphorylation, and induced degradation of Bcr-Abl p190 protein through ubiquitin-dependent proteasomal pathway. Furthermore, exposure of Ph+ ALL cells to EC141 resulted in activation of caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and induction of apoptosis. In conclusion, our data suggest that EC141 is a potent Hsp90 inhibitor with activity against Ph+ ALL. Further studies to investigate the anticancer effect of EC141 either as a single agent, or in combination in Ph+ ALL and other hematological malignancies are warranted.


Young People Under Youth Justice Supervision With Varying Child Protection Histories: An Analysis of Group Differences.
There is now convincing evidence that childhood maltreatment is associated with youth offending; however, relatively little is known about the characteristics and needs of those who are involved in both the child protection and youth justice systems, and the extent to which these might differ according to level of child protection involvement. This study reports the characteristics and needs of 2,045 young people who were under supervision in secure custody or detention in South Australia between 1995 and 2012 according to the level of exposure to the child protection system in an Australian jurisdiction. Five groups of young offenders were compared: (a) no known child protection notifications or substantiated experience of abuse and/or neglect, (b) notifications only, (c) substantiated notifications, (d) notifications or substantiations and subsequent placement in out-of-home care (OHC), and (e) placement in OHC only. The results indicate that young people who have a history of child protection system involvement have significantly greater and more complex needs than those who have no child protection experience. It is concluded that different service responses may be required to meet the diverse needs of these groups of young people under youth justice supervision.


Modulation of lipid metabolism with the overexpression of NPC1L1 in mouse liver.
Niemann-Pick C1-like 1 protein (NPC1L1), a transporter crucial in intestinal cholesterol absorption, is expressed in human liver but not in murine liver. To elucidate the role of hepatic NPC1L1 on lipid metabolism, we overexpressed NPC1L1 in murine liver utilizing adenovirus-mediated gene transfer. C57BL/6 mice, fed on normal chow with or without ezetimibe, were injected with NPC1L1 adenovirus (L1-mice) or control virus (Null-mice), and lipid analyses were performed five days after the injection. The plasma cholesterol levels increased in L1-mice, and FPLC analyses revealed increased cholesterol contents in large HDL lipoprotein fractions. These fractions, which showed α-mobility on agarose electrophoresis, were rich in apoE and free cholesterol. These lipoprotein changes were partially inhibited by ezetimibe treatment and were not observed in apoE-deficient mice. In addition, plasma and VLDL triglyceride (TG) levels decreased in L1-mice. The expression of microsomal triglyceride transfer protein (MTP) was markedly decreased in L1-mice, accompanied by the reduced protein levels of forkhead box protein O1 (FoxO1). These changes were not observed in mice with increased hepatic de novo cholesterol synthesis. These data demonstrate that cholesterol absorbed through NPC1L1 plays a distinct role in cellular and plasma lipid metabolism, such as the appearance of apoE-rich lipoproteins and the diminished VLDL-TG secretion.


Balance Improvement Effects of Biofeedback Systems with State-of-the-Art Wearable Sensors: A Systematic Review.
Falls and fall-induced injuries are major global public health problems. Balance and gait disorders have been the second leading cause of falls. Inertial motion sensors and force sensors have been widely used to monitor both static and dynamic balance performance. Based on the detected performance, instant visual, auditory, electrotactile and vibrotactile biofeedback could be provided to augment the somatosensory input and enhance balance control. This review aims to synthesize the research examining the effect of biofeedback systems, with wearable inertial motion sensors and force sensors, on balance performance. Randomized and non-randomized clinical trials were included in this review. All studies were evaluated based on the methodological quality. Sample characteristics, device design and study characteristics were summarized. Most previous studies suggested that biofeedback devices were effective in enhancing static and dynamic balance in healthy young and older adults, and patients with balance and gait disorders. Attention should be paid to the choice of appropriate types of sensors and biofeedback for different intended purposes. Maximizing the computing capacity of the micro-processer, while minimizing the size of the electronic components, appears to be the future direction of optimizing the devices. Wearable balance-improving devices have their potential of serving as balance aids in daily life, which can be used indoors and outdoors.


Chronic ethanol downregulates Gal-beta-1,4GlcNAc alpha 2,6-sialyltransferase and Gal-beta-1,3GlcNAc alpha 2,3-sialyltransferase mRNAs in rat liver.
We have previously demonstrated that chronic ethanol specifically decreases the hepatic level and rate of synthesis of 2,6-sialyltransferase (2,6-ST). To understand its mechanism of action, effects of 8 weeks of chronic ethanol feeding on the expression of sialyltransferase (ST) genes in rat liver and kidneys were determined by Northern-blot analysis of ST mRNAs. It was found that, compared with the pair-fed control rats, the percentage decreases in ST mRNAs in the ethanol-fed group were as follows: liver-Gal-beta-1,4GlcNAc alpha 2,6-ST (2,6-ST): 59% (p < 0.001); liver-Gal-beta-1,3GlcNAc alpha 2,3-ST (2,3-ST): 32% (p < 0.01); and kidneys-2,6-ST: 5% (NS). In contrast, glyceral-dehyde-3-phosphate dehydrogenase mRNA in both liver and kidneys was unaffected by the same ethanol treatment. Taken together, these results demonstrate that chronic ethanol downregulates the expression of 2,6-ST and 2,3-ST genes in rat liver.


The genetic contribution to longitudinal changes in knee structure and muscle strength: a sibpair study.
To estimate the heritability of longitudinal changes in knee cartilage volume, chondral defects, subchondral bone size, and lower limb muscle strength. A sibpair design was used. Longitudinal changes in lateral and medial tibial cartilage volume and bone size, as well as progression of chondral defects, were determined on serial magnetic resonance images. Radiographs were obtained and scored for individual features of radiographic osteoarthritis (OA) at baseline. Lower limb muscle strength was measured by dynamometry. Heritability was estimated using the SOLAR software package. A total of 115 subjects (55 men and 60 women, mean age 45 years) from 48 families representing 95 sibling pairs were successfully followed up for a mean of 2.4 years. The adjusted heritability estimates for changes in cartilage volume were 73% for the medial compartment (P < 0.01) and 40% for the lateral compartment (P = 0.10). The adjusted heritability estimates for changes in bone size were 62% for the lateral compartment (P = 0.03) and 20% for the medial compartment (P = 0.22). The adjusted heritability estimate for changes in muscle strength was 64% (P = 0.01). The adjusted heritability estimates for progression of chondral defects were 80% for the lateral compartment (P = 0.06) and 98% for the medial compartment (P = 0.03). These estimates changed little after adjusting for each other and for the predominantly mild radiographic OA, with the exception of progression of chondral defects in the lateral compartment. Early longitudinal changes in knee structures of relevance to later OA, such as changes in medial tibial cartilage volume, lateral tibial bone size, progression of chondral defects, and muscle strength, have high heritability, most likely reflecting a strong genetic component and suggesting their potential to be studied in quantitative trait linkage and association analysis.


Early pathways to bullying: A prospective longitudinal study examining the influences of theory of mind and social preference on bullying behaviour during the first 3 years of school.
Research has focused on the role of theory of mind (ToM) for positive social behaviour, while the association between ToM and negative social behaviours is less well understood. This longitudinal study compares two mediation models examining the role of ToM and peer-rated social preference at ages 5 and 6 for bullying at age 7. Participants were 114 children (58 boys, Mage = 67 months) at entry to primary school (T1). At Time 2 (T2), 106 children and, at Time 3 (T3), 96 children remained. Teacher-rated externalizing problems and children's language ability were controlled at T1. Poor ToM was found to indirectly predict later bullying via poor social preference, while for boys only, greater earlier ToM directly predicted greater bullying 2 years later. These results suggest that there are different pathways to bullying via ToM and social preference, which has implications for interventions to prevent the development of bullying behaviour.


Progress and challenges in understanding the regulation and function of p53 dynamics.
The dynamics of p53 expression provide a mechanism to increase differentiation between cellular stresses and specificity in appropriate responses. Here, we review recent advances in our understanding of the molecular mechanisms regulating p53 dynamics and the functions of the dynamics in the regulation of p53-dependent cell stress responses. We also compare dynamic encoding in the p53 system with that found in other important cell signaling systems, many of which can interact with the p53 network. Finally, we highlight some of the current challenges in understanding dynamic cell signaling within a larger cellular network context.


ERK crosstalks with 4EBP1 to activate cyclin D1 translation during quinol-thioether-induced tuberous sclerosis renal cell carcinoma.
The mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase signaling cascades have been implicated in a number of human cancers. The tumor suppressor gene tuberous sclerosis-2 (Tsc-2) functions as a negative regulator of mTOR. Critical proteins in both pathways are activated following treatment of Eker rats (Tsc-2(EK/+)) with the nephrocarcinogen 2,3,5-tris-(glutathion-S-yl)hydroquinone (TGHQ), which also results in loss of the wild-type allele of Tsc-2 in renal preneoplastic lesions and tumors. Western blot analysis of kidney tumors formed following treatment of Tsc-2(EK/+) rats with TGHQ for 8 months revealed increases in B-Raf, Raf-1, pERK, cyclin D1, 4EBP1, and p-4EBP1-Ser65, -Thr70, and -Thr37/46 expression. Similar changes are observed following TGHQ-mediated transformation of primary renal epithelial cells derived from Tsc-2(EK/+) rats (quinol-thioether rat renal epithelial [QTRRE] cells) that are also null for tuberin. These cells exhibit high ERK, B-Raf, and Raf-1 kinase activity and increased expression of all p-4EBP1s and cyclin D1. Treatment of the QTRRE cells with the Raf kinase inhibitor, sorafenib, or the MEK1/2 kinase inhibitor, PD 98059, produced a significant decrease in the protein expression of all p-4EBP1s and cyclin D1. Following siRNA knockdown of Raf-1, Western blot analysis revealed a significant decrease in Raf-1, cyclin D1, and all p-4EBP1 forms noted above. In contrast, siRNA knockdown of B-Raf resulted in a nominal change in these proteins. The data indicate that Raf-1/MEK/ERK participates in crosstalk with 4EBP1, which represents a novel pathway interaction leading to increased protein synthesis, cell growth, and kidney tumor formation.


Core Competencies in Cancer Genomics for Healthcare Professionals: Results From a Systematic Literature Review and a Delphi Process.
The continuous development and use of genomic sequencing requires healthcare professionals to constantly integrate these advancements into their clinical practice. There is a documented lack of cancer genomics contents in the teaching and learning programs. We aimed to identify the core competencies in cancer genomics for non-genetic healthcare professionals. We performed a literature review in PubMed, SCOPUS, and Web of Science databases to retrieve articles published from 2000 to 2018, in English or Italian language. We included articles that reported the competencies for non-genetic healthcare professionals in cancer genomics. A web-based modified Delphi survey was conducted, aiming to define, through consensus, a set of core competencies that should be covered in the curricula. The international expert panel included specialists in genetics, genomics, oncology, and medical specialists. In the literature review, we retrieved nine articles, from which we identified core competencies for general physicians and nurses. The competencies were organized in three main domains: knowledge, attitudes, and practical abilities. In the second round of Delphi survey, consensus of 83.3% was reached for the definition of the core competencies. Thirty-seven items were defined as the competencies required for physicians and forty-two items for nurses. Through a consensus-based approach, a set of core competencies in cancer genomics for non-genetic healthcare professionals has been identified. Our findings could benchmark standards for curriculum development and future educational strategies.


Reperfusion injury and its pharmacologic modification.
Reperfusion injury includes a spectrum of events, such as reperfusion arrhythmias, vascular damage and no-reflow, and myocardial functional stunning. The concept of reperfusion injury remains controversial with many proposed mechanisms when applied to humans, whereas in animal models, there are two main proposed mechanisms: calcium over-load and formation of oxygen free radicals. To prove that reperfusion injury is specifically caused by reperfusion would require evidence that an intervention given at the time of reperfusion can diminish or abolish the injury as in the case of arrhythmias, which are thought to be mediated by excess recycling of cytosolic calcium with delayed afterdepolarizations and ventricular automaticity. In the case of myocardial stunning, the phenomenon may be mediated, at least in part, by a burst of free radicals formed within the first minute of reperfusion and improved by free radical scavengers given at the time of reperfusion. The alternate hypothesis is that cytosolic calcium overload damages mechanisms for normal intracellular calcium regulation so that the stunned myocardium responds to agents that are thought to increase intracellular cytosolic calcium, such as beta-receptor agonists. A further component of reperfusion injury, under active investigation, is microvascular damage with alterations at the level of platelets, leukocytes, and endothelial integrity. From the therapeutic point of view, the divergent results of experimental interventions and the possibility that the abrupt onset of reperfusion in animals differs from the situation in humans with thrombolysis means that the best way currently available to limit reperfusion injury is by minimizing the ischemic period by early reperfusion and by optimizing the metabolic status of the ischemic myocardium at the end of the ischemic period.


The diagnosis and management of 689 chronic leg ulcers in a single-visit assessment clinic.
accurate diagnosis is essential if patients with chronic leg ulceration are to receive optimal treatment. This prospective study describes the findings of a standardised assessment protocol and the initial management of a consecutive series of patients with chronic leg ulceration presenting to a single-visit leg ulcer assessment clinic. between January 1993 and January 1999, a total of 555 patients (220 men and 335 women of median age 73, range 28-95 years) with 689 chronic leg ulcers were assessed. Full clinical assessment, ankle:brachial pressure index and lower limb venous duplex scan were performed according to a standardised protocol and diagnostic and management data were recorded prospectively on a computerised database. venous disease alone was responsible for 496 of 689 (72%) ulcers. Isolated superficial venous reflux (SVR) was identified in 52% of limbs and two-thirds of these had superficial venous surgery. Combined SVR and segmental deep venous reflux (DVR) was present in 13%, and full-length DVR was present in 33% of limbs. Nineteen (4%) limbs had deep venous stenosis or obstruction. Overall, superficial venous surgery was performed in 43% and compression bandages or hosiery alone were applied in 52% of limbs. Mixed arterio-venous ulceration was present in 100 (14.5%) limbs of which 56 had arterial revascularisation, 38 had superficial venous surgery and 23 had compression alone. Fifteen limbs with pure arterial ulceration had angioplasty (n=13) or simple dressings alone (n=2). Ulceration due to lymphoedema (n=17), mixed lymphoedema and venous reflux (n=11) and other causes (n=50) were managed by compression, dressings or skin grafting. a standardised protocol of clinical and duplex assessment can lead to a diagnosis in 97% of chronic leg ulcers. Duplex is essential to confirm or exclude potentially correctable venous disease and allow tailored surgical intervention for those patients who many benefit.


Effect of thyroid state on cyclic AMP-mediated induction of hepatic phosphoenolpyruvate carboxykinase.
Hepatic phosphoenolpyruvate carboxykinase (PEPCK) is significantly increased in the hyperthyroid starved rat, and moderately decreased in the hypothyroid starved rat. As tri-iodothyronine by itself has only a small and sustained effect on the induction of this enzyme, as was previously shown in the isolated perfused organ, the effect of hypo- and hyper-thyroidism on the increase in cytosolic PEPCK provoked by dibutyryl cyclic AMP (Bt2cAMP) was investigated in vivo and in the isolated perfused liver. Compared with euthyroid fed controls, in hypothyroid fed rats Bt2cAMP provoked in 2 h only a small increase in translatable mRNA coding for PEPCK. In contrast, in hyperthyroid animals PEPCK mRNA as measured by translation in vitro was already increased in the fed state, and further enhanced by Bt2cAMP injection to values as in euthyroid controls. Under all thyroid states a close correlation between PEPCK mRNA activity and PEPCK synthesis was observed. In the isolated perfused liver from the hyperthyroid fed rat, the increase in PEPCK provoked by Bt2cAMP or Bt2cAMP + isobutylmethylxanthine was considerably enhanced compared with those obtained in livers of hypothyroid rats. Also, adrenaline provoked a stimulated induction of PEPCK in hyperthyroid rats compared with hypothyroid rats. To summarize, our data indicate that the primary action of thyroid hormones on the synthesis of hepatic cytosolic PEPCK is to accelerate the cyclic AMP- or adrenaline-induction of the enzyme, acting primarily at a pretranslational level.


Identification of fungi of the genus Aspergillus section nigri using polyphasic taxonomy.
In spite of the taxonomy of the Aspergillus species of the Nigri Section being regarded as troublesome, a number of methods have been proposed to aid in the classification of this Section. This work aimed to distinguish Aspergillus species of the Nigri Section from foods, grains and caves on the basis in Polyphasic Taxonomy by utilizing morphologic and physiologic characters, and sequencing of ß-tubulin and calmodulin genes. The morphologic identification proved useful for some species, such as A. carbonarius and Aspergillus sp UFLA DCA 01, despite not having been totally effective in elucidating species related to A. niger. The isolation of the species of the Nigri Section on Creatine Sucrose Agar (CREA) enabled to distinguish the Aspergillus sp species, which was characterized by the lack of sporulation and by the production of sclerotia. Scanning Electron microscopy (SEM) allowed distinguishing the species into two distinct groups. The production of Ochratoxin A (OTA) was only found in the A. carbonarius and A. niger species. The sequencing of β-tubulin gene was efficient in differing most of the Aspergillus species from the Nigri Section with the exception of Aspergillus UFLA DCA 01, which could not be distinguished from A. costaricaensis. This species is morphologically similar to A. costaricaencis for its low sporulation capacity and high sclerotia production, but it differs morphologically from A. costaricaensis for its conidial ornamentation and size of vesicles. Equally, based on partial calmodulin gene sequence data Aspergillus UFLA DCA 01 differs from A. costaricaensis.


The quality and cost of medical care. The potential for information technology to meet the challenge.
The rising cost of health care has precipitated a variety of cost containment initiatives. With the accelerated transition to managed care, the question of quality has emerged. The feeling of many is that cost reduction alone can have only one effect, a reduction in quality. In response, many have focused on the need to reassess and reengineer the processes involved in the delivery of care and to integrate these processes to ensure better management of the patient through the monitoring of the continuum of care. In this paper, we describe the potential for the application of an information technology, known as workflow management technology, in the design and control of health care delivery processes.


Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity.
The aim of this study was to identify and compare factors associated with Plasmodium falciparum gametocyte carriage in three regions of differing malaria endemicity. Retrospective data from Thailand, The Gambia and Tanzania were used. The data came from large prospective field-based clinical trials, which investigated gametocyte carriage after different anti-malarial drug treatments. Gametocytaemia was detected during the observation period in 12% of patients (931 out of 7548) in Thailand, 34% (683 out of 2020) in The Gambia, and 31% (430 out of 1400) in Tanzania (p < 0.001). Approximately one third (33%, 680/2044) of the patients with gametocytaemia during the observation period, already had patent gametocytaemia at enrolment (day 0 or day 1): 35% (318/931) in Thailand, 37% (250/683) in The Gambia, 26% (112/430) in Tanzania. Maximum gametocytaemia was usually observed on or before the seventh day after starting treatment (93% in Thailand, 70% in Tanzania and 78% in The Gambia). Lowest gametocyte carriage rates were observed following treatment with artemisinin derivatives, while sulphadoxine-pyrimethamine (SP) was associated with significantly greater development of gametocytaemia than other drug treatments (p < 0.001). The duration of gametocyte carriage was shorter in Thailand by 86% and Tanzania by 65% than in The Gambia. Gametocyte carriage was 27% longer among people presenting with anaemia, and was shorter in duration among patients who received artemisinin derivatives, by 27% in Thailand and by 71% in Tanzania and The Gambia. This study confirms the independent association of gametocytaemia with anaemia, and the significantly lower prevalence and duration of gametocyte carriage following treatment with an artemisinin derivative. The large differences in gametocyte carriage rates between regions with different levels of malaria transmission suggest that drug interventions to prevent transmission will have different effects in different places.


Nitric acid-induced injury in the hamster lung.
Severe airway lesions can result following exposure to various pathogens or toxic gases and can show a variety of pathologic lesions including necrotizing bronchitis, bronchiolitis and bronchiectasis. The purpose of this study was to develop a chronic airway lesion in the hamster, a species recognized for its lack of endogenous pulmonary disease. We have successfully adapted a technique of inducing rabbit airway lesions with nitric acid to the hamster lung and have characterized the morphologic, morphometric and biochemical features of the model. Following a transorotracheal instillation of 0.5% HNO3 in saline, Syrian golden hamsters showed during a 60-day study period a spectrum of airway changes including acute bronchitis, acute bronchiolitis, obliterative bronchiolitis, bronchiolectasia and bronchiectasis. Morphometric changes in the HNO3-treated hamsters included decreased lung volumes and decreased internal surface areas. Biochemical changes showed increases in lung weight and in total collagen and elastin. The model is useful because a prolonged insult to the airways develops rapidly and persists over a long period of time, important features for investigations designed to study the effects of superimposed insults upon pre-existent airway lesions.