Differentiation between mild and severe myocarditis using multiparametric cardiac magnetic resonance.
The pathophysiology of myocarditis is associated with mild inflammation and may progress silently, or in severe cases such as fulminant myocarditis, may lead to sudden hemodynamic compromise. An invasive myocardial biopsy is generally required for a definitive myocarditis diagnosis. Alternatively, cardiac magnetic resonance (CMR), which evaluates myocardial characteristics and cardiac function, can be used as a noninvasive tool for diagnosing myocarditis. We describe the cases of a 49-year-old woman with mild acute eosinophilic myocarditis and a 48-year-old man with severe acute lymphocytic myocarditis. CMR was performed during the acute and convalescent phases in both cases. Compared with mild myocarditis, CMR in severe myocarditis showed higher T2 values and decreased left ventricular and atrial volumes and strains; however, the right ventricular strain was preserved. Late gadolinium enhancement showed faint contrast enhancement in the whole and strong enhancement in the local myocardium. Follow-up CMR showed recovery from myocardial inflammation and cardiac function. Some late gadolinium enhancement persisted whereas acute inflammation-associated enhancement disappeared. This case report highlights the differences between the cardiac parameters of patients with mild and severe myocarditis. Severe myocardial inflammation can be caused by severe heart failure owing to the concurrent reduction of cardiac function and compliance. Additionally, preserved right ventricular strain may predict cardiac function recovery in acute myocarditis. Noninvasive and repeatable CMR provides information on myocardial characteristics, cardiac function, and hemodynamics in a single scan at that time, which is useful not only for diagnosis but also for severity assessment and patient management in acute myocarditis.


Studies on mycoflora of salt marshes in Egypt. IV. Osmophilic fungi.
Ninety-five species and seven varieties which belong to thirty-nine genera were isolated from 74 soil samples from salt marshes. At 28 degrees C, on 30% sucrose Czapek's agar, ninety species and four varieties which belong to thirty-six genera were encountered, from which A. niger, A. fumigatus A. terreus and P. notatum were the most frequent. On 60% sucrose Czapek's agar, sixty-three species and three varieties were recovered which belong to twenty-five genera, from which A. niger, A. fumigatus, Cladosporium herbarum and A. terreus were the most frequent. At 45 degrees C, on 30% sucrose, sixteen species and four varieties were identified but on 60% sucrose, fourteen species and three varieties were isolated. A fumigatus and A. niger were the most frequent on both sucrose concentrations. The results reveal that the soil samples poor in total osmophilic fungi (at 28 degrees C) were significantly higher in their content of total soluble salts, Na and K and significantly lower in the average number of species per soil samples than the rich ones; the difference was non-significant in case of organic matter.


Contractile, coronary, and metabolic effects of the acute and long-term treatment of cardiac failure with prenalterol.
Prenalterol was examined with regard to its acute intravenous effects on left ventricular function, coronary hemodynamics, and myocardial oxygen consumption, as well as for its long-term effects, by oral therapy, on left ventricular function and systemic hemodynamics. Intravenous prenalterol enhances myocardial contractility and left ventricular ejection function significantly. A decrease in total peripheral vascular resistance is effected. Myocardial oxygen consumption is only moderately increased, most probably because of the decrease in the systolic integrated wall stress of the left ventricle. The changes of coronary circulation (blood flow, resistance, arteriovenous, oxygen difference) indicate benign and metabolically induced coronary vasodilation. Long-term oral treatment of patients with severe cardiac failure by prenalterol effects significant enhancement in-left ventricular performance within the first 1-2 months of treatment; however, this effect is not present at longer therapy intervals (16-28 weeks). Tolerance development as well as the natural history of these patients may be responsible for this inotropic amelioration. There were no clinical side effects with either intravenous or oral application. It may be concluded that prenalterol is highly effective in acute cardiac failure (intravenous administration) and also in chronic heart disease (long-term oral application). However, the long-term effects are unpredictable, and tolerance development has to be considered.


Uptake, accumulation and metabolization of the antidepressant fluoxetine by Mytilus galloprovincialis.
Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI) antidepressant, is among the most prescribed pharmaceutical active substances worldwide. This study aimed to assess its accumulation and metabolization in the mussel Mytillus galloprovincialis, considered an excellent sentinel species for traditional and emerging pollutants. Mussels were collected from Ria Formosa Lagoon, Portugal, and exposed to a nominal concentration of fluoxetine (75 ng L(-1)) for 15 days. Approximately 1 g of whole mussel soft tissues was extracted with acetonitrile:formic acid, loaded into an Oasis MCX cartridge, and fluoxetine analysed by liquid chromatography with tandem mass spectrometry (LC-MSn). After 3 days of exposure, fluoxetine was accumulated in 70% of the samples, with a mean of 2.53 ng g(-1) dry weight (d.w.) and norfluoxetine was only detected in one sample (10%), at 3.06 ng g(-1) d.w. After 7 days of exposure, the accumulation of fluoxetine and norfluoxetine increased up to 80 and 50% respectively, and their mean accumulated levels in mussel tissues were up to 4.43 and 2.85 ng g(-1) d.w., respectively. By the end of the exposure period (15 days), both compounds were detected in 100% of the samples (mean of 9.31 and 11.65 ng g(-1) d.w., respectively). Statistical analysis revealed significant accumulation differences between the 3rd and 15th day of exposure for fluoxetine, and between the 3rd and 7th against the 15th day of exposure for norfluoxetine. These results suggest that the fluoxetine accumulated in mussel tissues is likely to be metabolised into norfluoxetine with the increase of the time of exposure, giving evidence that at these realistic environmental concentrations, toxic effects of fluoxetine in mussel tissues may occur.


Neuro-otologic surgery through minimally invasive retrosigmoid approach: endoscope assisted microvascular decompression, vestibular neurotomy, and tumor removal.
The objective of this study was to describe and evaluate the efficacy of the endoscope assisted minimally invasive retrosigmoid approach. Retrospective study and literature review. From December 1993 to December 2004, a total of 1,177 cases of endoscope assisted minimally invasive retrosigmoid approach were performed at the Otorhinolaryngology unit of Hôpital Nord in Marseille. By using this approach, we performed microvascular decompression for hemifacial spasm and trigeminal neuralgia, vestibular neurotomy for refractory Ménière's disease with repeated attacks of dizziness, and tumor removal of acoustic neurinoma. We examined the results and postoperative complications. All the results were positive, and we did not experience any mortal complications. The most common complication was cerebrospinal fluid leakage, encountered in 42 (3.6%) cases. We believe that the combination of an endoscope and microscope that provides accurate information with low invasion is becoming indispensable for these types of operations, which are in the category of functional surgery. We report the merits and significance of the approach of combining the endoscope and microscope and discuss the operational technique to perform a minimally invasive surgery as an oto-neurosurgeon.


Comparison of alternative flue gas dry treatment technologies in waste-to-energy processes.
Acid gases such as HCl and SO2 are harmful both for human health and ecosystem integrity, hence their removal is a key step of the flue gas treatment of Waste-to-Energy (WtE) plants. Methods based on the injection of dry sorbents are among the Best Available Techniques for acid gas removal. In particular, systems based on double reaction and filtration stages represent nowadays an effective technology for emission control. The aim of the present study is the simulation of a reference two-stage (2S) dry treatment system performance and its comparison to three benchmarking alternatives based on single stage sodium bicarbonate injection. A modelling procedure was applied in order to identify the optimal operating configuration of the 2S system for different reference waste compositions, and to determine the total annual cost of operation. Taking into account both operating and capital costs, the 2S system appears the most cost-effective solution for medium to high chlorine content wastes. A Monte Carlo sensitivity analysis was carried out to assess the robustness of the results.


Cyclic stretch stimulates nitric oxide synthase-1-dependent peroxynitrite formation by neonatal rat pulmonary artery smooth muscle.
Peroxynitrite, the reaction product of nitric oxide and superoxide, contributes to the pathogenesis of chronic pulmonary hypertension in immature animals by stimulating proliferation of pulmonary arterial smooth muscle cells (PASMCs). Pulmonary vasoconstriction, secondary to hypoxia and other stimuli, leads to enhanced pulsatile stretch of cells in the vascular wall, particularly in smooth muscle, which we hypothesized would cause increased peroxynitrite generation. Our objectives in this study were to determine whether cyclic mechanical stretch, at supraphysiologic levels, would cause increased production of reactive oxygen species (ROS), nitric oxide, and peroxynitrite in vitro. Early passage neonatal rat PASMCs were seeded and grown to subconfluence on collagen-coated elastomer-bottom plates and subjected to cyclic mechanical stretch (10% ("physiologic") or 20% ("supraphysiologic") at 0.5 Hz) for up to 24 h. Compared to nonstretched controls and to cells subjected to 10% stretch, 20% stretch increased H2O2 (stable marker of ROS) and nitrate/nitrite (stable marker of nitric oxide) in conditioned medium. These effects were accompanied by increased peroxynitrite, as evidenced by increased in situ dihydroethidium fluorescence and immunoreactive nitrotyrosine and by increased expression of nitric oxide synthase (NOS)-1 and NADPH oxidase 4 (NOX4), but not NOS-2. Stretch-induced H2O2 release and increased dihydroethidium fluorescence were prevented by pretreatment with a superoxide scavenger, nonspecific inhibitors of NADPH oxidase or NOS, or a peroxynitrite decomposition catalyst. Short-interfering RNA-mediated knockdown of NOS-1 or NOX4 attenuated increased nitric oxide and H2O2 content, respectively, in stretched-cell-conditioned medium. Knockdown of NOS-1 also attenuated increased immunoreactive nitrotyrosine content and stretch-induced proliferation, whereas knockdown of NOS-2 had no effect. We conclude that increased peroxynitrite generation by neonatal rat PASMCs subjected to supraphysiologic levels of cyclic stretch is NOS-1-dependent and that increased ROS production is predominantly mediated by NADPH oxidase, specifically NOX4.


Synchrony--cyberknife respiratory compensation technology.
Studies of organs in the thorax and abdomen have shown that these organs can move as much as 40 mm due to respiratory motion. Without compensation for this motion during the course of external beam radiation therapy, the dose coverage to target may be compromised. On the other hand, if compensation of this motion is by expansion of the margin around the target, a significant volume of normal tissue may be unnecessarily irradiated. In hypofractionated regimens, the issue of respiratory compensation becomes an important factor and is critical in single-fraction extracranial radiosurgery applications. CyberKnife is an image-guided radiosurgery system that consists of a 6-MV LINAC mounted to a robotic arm coupled through a control loop to a digital diagnostic x-ray imaging system. The robotic arm can point the beam anywhere in space with 6 degrees of freedom, without being constrained to a conventional isocenter. The CyberKnife has been recently upgraded with a real-time respiratory tracking and compensation system called Synchrony. Using external markers in conjunction with diagnostic x-ray images, Synchrony helps guide the robotic arm to move the radiation beam in real time such that the beam always remains aligned with the target. With the aid of Synchrony, the tumor motion can be tracked in three-dimensional space, and the motion-induced dosimetric change to target can be minimized with a limited margin. The working principles, advantages, limitations, and our clinical experience with this new technology will be discussed.


Reproducibility and biases in high field brain diffusion MRI: An evaluation of acquisition and analysis variables.
Diffusion tensor imaging (DTI) of in-vivo human brain provides insights into white matter anatomical connectivity, but little is known about measurement difference biases and reliability of data obtained with last generation high field scanners (>3T) as function of MRI acquisition and analyses variables. Here we assess the impact of acquisition (voxel size: 1.8×1.8×1.8, 2×2×2 and 2.5×2.5×2.5mm(3), b-value: 700, 1000 and 1300s/mm(2)) and analysis variables (within-session averaging and co-registration methods) on biases and test-retest reproducibility of some common tensor derived quantities like fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity in a group of healthy subjects at 4T in three regions: arcuate fasciculus, corpus callosum and cingulum. Averaging effects are also evaluated on a full-brain voxel based approach. The main results are: i) group FA and MD reproducibility errors across scan sessions are on average double of those found in within-session repetitions (≈1.3 %), regardless of acquisition protocol and region; ii) within-session averaging of two DTI acquisitions does not improve reproducibility of any of the quantities across sessions at the group level, regardless of acquisition protocol; iii) increasing voxel size biased MD, axial and radial diffusivities to higher values and FA to lower values; iv) increasing b-value biased all quantities to lower values, axial diffusivity showing the strongest effects; v) the two co-registration methods evaluated gave similar bias and reproducibility results. Altogether these results show that reproducibility of FA and MD is comparable to that found at lower fields, not significantly dependent on pre-processing and acquisition protocol manipulations, but that the specific choice of acquisition parameters can significantly bias the group measures of FA, MD, axial and radial diffusivities.


Malignant histiocytosis and large cell anaplastic (Ki-1) lymphoma in childhood: guidelines for differential diagnosis--report of the Histiocyte Society.
A workshop of the Histiocyte Society was recently held, in order to discuss the problems and confusion of malignant histiocytosis (MH) and large cell anaplastic (Ki-1) lymphoma (LCAL). The aims of this workshop were to clarify the terminology for malignant histiocytic disorders and LCAL and to produce reliable criteria for diagnosis of both MH and LCAL. This article summarises the conclusions reached.


Early colour deprivation in the pigeon.
When cats and monkeys are deprived of specific stimuli during an early sensitive period the development of their visual system is known to be affected. In pigeons, pattern discrimination learning has been shown to be affected by monocular deprivation [2]. Our study was set up to examine whether colour discrimination learning could be affected by colour deprivation. Young pigeons were reared under restricted colour illumination for at least 3 months after hatching so as to obtain a group bred under red illumination, one bred under blue illumination and a control group. After this period several psychophysical tests were used to test the pigeons' sense of colour. No significant difference was found between the 'deprived' birds and the controls. The spectral sensitivity, determined with the help of the ERG, did not differ for the three groups. We conclude that early colour deprivation does not affect visual development in the pigeon.


Complete nitrification by a single microorganism.
Nitrification is a two-step process where ammonia is first oxidized to nitrite by ammonia-oxidizing bacteria and/or archaea, and subsequently to nitrate by nitrite-oxidizing bacteria. Already described by Winogradsky in 1890, this division of labour between the two functional groups is a generally accepted characteristic of the biogeochemical nitrogen cycle. Complete oxidation of ammonia to nitrate in one organism (complete ammonia oxidation; comammox) is energetically feasible, and it was postulated that this process could occur under conditions selecting for species with lower growth rates but higher growth yields than canonical ammonia-oxidizing microorganisms. Still, organisms catalysing this process have not yet been discovered. Here we report the enrichment and initial characterization of two Nitrospira species that encode all the enzymes necessary for ammonia oxidation via nitrite to nitrate in their genomes, and indeed completely oxidize ammonium to nitrate to conserve energy. Their ammonia monooxygenase (AMO) enzymes are phylogenetically distinct from currently identified AMOs, rendering recent acquisition by horizontal gene transfer from known ammonia-oxidizing microorganisms unlikely. We also found highly similar amoA sequences (encoding the AMO subunit A) in public sequence databases, which were apparently misclassified as methane monooxygenases. This recognition of a novel amoA sequence group will lead to an improved understanding of the environmental abundance and distribution of ammonia-oxidizing microorganisms. Furthermore, the discovery of the long-sought-after comammox process will change our perception of the nitrogen cycle.


The mPer2 clock gene modulates cocaine actions in the mouse circadian system.
Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present, however, the physiological basis of such an interaction is unclear. To address this question, we compared photic and non-photic phase-resetting responses between wild-type (WT) and Per2 mutant mice expressing nonfunctional PER2 protein to systemic and intra-SCN cocaine administrations. In the systemic trials, cocaine was administered i.p. (20 mg/kg) either at midday or prior to a light pulse in the early night to assess its non-photic and photic behavioral phase-resetting actions, respectively. In the intra-SCN trial, cocaine was administered by reverse microdialysis at midday to determine if the SCN is a direct target for its non-photic phase-resetting action. Non-photic phase-advancing responses to i.p. cocaine at midday were significantly (∼3.5-fold) greater in Per2 mutants than WTs. However, the phase-advancing action of intra-SCN cocaine perfusion at midday did not differ between genotypes. In the light pulse trial, Per2 mutants exhibited larger photic phase-delays than did WTs, and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine's actions in the circadian system. With regard to non-photic phase-resetting, the SCN is confirmed as a direct target of cocaine action; however, Per2 modulation of this effect likely occurs outside of the SCN.


Placental pathology varies in hypertensive conditions of pregnancy.
This study was a comprehensive analysis of placental phenotypes in hypertensive conditions of pregnancy, including recently described placental hypoxic lesions and lesions of shallow placentation. To this end, consecutive placentas from > 21 weeks pregnancies that were signed out by the author at 4 tertiary care centers on 3 continents were included. Twenty-four clinical and 50 placental phenotypes were studied in 6 groups and statistically compared: 91 cases of gestational hypertension, 187 cases of mild preeclampsia, 211 cases of severe preeclampsia, 84 cases of HELLP or eclampsia, 127 cases of chronic hypertension, and 55 cases of preeclampsia superimposed on chronic hypertension. Twenty percent of the placental and clinical phenotypes were statistically significantly different between the groups. Gestational hypertension and chronic hypertension distinguished themselves by having the highest perinatal mortality, lowest cesarean section rates, highest acute chorioamnionitis, and highest fetal vascular ectasia but conspicuously fewer differences in hypoxic and thrombotic lesions. The preeclamptic groups showed the highest rates of decidual arteriolopathy (both hypertrophic and atherosis), uterine pattern of chronic placental injury, villous infarctions, and clusters of maternal floor multinucleate trophoblasts. Based on placental pathology, severe preeclampsia may be more of a placental disease and mild preeclampsia more of a maternal disease; however, the significant overlap among the groups does not make the difference absolute, and the occurrence of decidual arteriolopathy in gestational hypertension and chronic hypertension may indicate that the conditions could be regarded as "occult preeclampsia."


Chronology of the push pull effect on nonhuman primates-shift of the arterial pressure threshold.
Fighter pilots are frequently exposed to high Gz acceleration which may induce in-flight loss of consciousness (G-LOC). One factor reducing tolerance to accelerations is a previous exposure to negative accelerations. This phenomenon, which happens during the first few seconds after the onset of the positive plateau, is called the push pull effect. Our goal was to validate a non human primate model in order to study push pull physiological mechanisms and possible changes in arterial pressure, which may occur after the first ten seconds of the positive acceleration plateau. Eight rhesus monkeys were centrifuged in profile runs, including positive Gz accelerations (+1.4, +2 and +3 Gz) with or without previous negative Gz acceleration (-2 and -3 Gz vs. +1.4 Gz). Heart rate, blood pressure and esophageal pressure were recorded during the entire centrifugation run. Results showed that the push pull effect was observed in the non human primate model. Moreover, the reduced tolerance to acceleration lingered longer than that during the first ten seconds after exposure to +Gz acceleration. It was found that, after the fourteenth second, mean blood arterial pressure stabilizes at a lower value, when the positive acceleration is preceded by a negative acceleration (15.8 kPa for -1 Gz and 15.5 for -2 Gz vs. 16.9 for 1.4 Gz). The chronology of the push pull effect seems to involve two periods. One has a short time span. The other one has a longer time span and could be induced by shift of pressure threshold, coming from exposure to previous negative acceleration.


Sidedness of action of loop diuretics and ouabain on nonsensory cells of utricle: a micro-Ussing chamber for inner ear tissues.
It is known that nonsensory tissues of the utricle produce a lumen-positive transepithelial electrical potential difference (VT). This potential has been shown previously to be inhibited by ouabain and bumetanide applied to the bathing medium in vitro. In order to more fully characterize the origin of this potential we mounted the utricle as a flat sheet in a newly designed Ussing chamber and measured the VT and transepithelial resistance (RT) while perfusing the endolymphatic and perilymphatic surfaces independently with identical solutions. The aperture of the chamber was 1.5 X 10(-4) cm2. VT averaged 5.6 +/- 0.46 mV and RT was 24.0 +/- 2.43 omega X cm2 (n = 45). Ouabain and loop diuretics of the furosemide family were found to inhibit the VT only from the serosal side. The KI for ouabain was 7.63 X 10(-5) M. The loop diuretics tested inhibited the VT in the same order as in other tissues known to contain a Na/2 Cl/K cotransporter (KI: 2-benzylamino-4-cyclohexylsulfonyl-5-sulfamoylbenzolsulfonate++ + (BCSB), 1.72 X 10(-7) M; bumetanide, 1.10 X 10(-6) M; piretanide, 5.67 X 10(-6) M; furosemide, 4.14 X 10(-5) M). It is concluded that this tissue produces a lumen-positive VT (i) in the absence of a transepithelial chemical gradient; the generation of which is dependent upon the activity of (ii) Na,K-ATPase and (iii) a Na/2 Cl/K cotransporter; (iv) in the basolateral membranes of the nonsensory cells; (v) which is not depressed by luminal application of inhibitors of these transporters.


Effects of inspiratory flow on lung stress, pendelluft, and ventilation heterogeneity in ARDS: a physiological study.
High inspiratory flow might damage the lungs by mechanisms not fully understood yet. We hypothesized that increasing inspiratory flow would increase lung stress, ventilation heterogeneity, and pendelluft in ARDS patients undergoing volume-controlled ventilation with constant tidal volume and that higher PEEP levels would reduce this phenomenon. Ten ARDS patients were studied during protective volume-controlled ventilation. Three inspiratory flows (400, 800, and 1200 ml/s) and two PEEP levels (5 and 15 cmH2O) were applied in random order to each patient. Airway and esophageal pressures were recorded, end-inspiratory and end-expiratory holds were performed, and ventilation distribution was measured with electrical impedance tomography. Peak and plateau airway and transpulmonary pressures were recorded, together with the airway and transpulmonary pressure corresponding to the first point of zero end-inspiratory flow (P1). Ventilation heterogeneity was measured by the EIT-based global inhomogeneity (GI) index. Pendelluft was measured as the absolute difference between pixel-level inflation measured at plateau pressure minus P1. Plateau airway and transpulmonary pressure was not affected by inspiratory flow, while P1 increased at increasing inspiratory flow. The difference between P1 and plateau pressure was higher at higher flows at both PEEP levels (p < 0.001). While higher PEEP reduced heterogeneity of ventilation, higher inspiratory flow increased GI (p = 0.05), irrespective of the PEEP level. Finally, gas volume undergoing pendelluft was larger at higher inspiratory flow (p < 0.001), while PEEP had no effect. The present exploratory analysis suggests that higher inspiratory flow increases additional inspiratory pressure, heterogeneity of ventilation, and pendelluft while PEEP has negligible effects on these flow-dependent phenomena. The clinical significance of these findings needs to be further clarified.


Management of cardiac complications in neuromuscular disease.
Cardiovascular complications are common and varied in neuromuscular diseases. Knowledge of the complications specific to each disease is essential for appropriate screening for cardiovascular disease. Appropriate treatment of complications varies between neuromuscular diseases and draws primarily on experience from patients without neuromuscular disease. This article details the known cardiovascular complications and treatments for some of the major neuromuscular diseases.


CBCT Analysis of Edentulous Mandibular Symphysis in Iraqi Patients for Treatment with Implant-Supported Overdentures. Cross-Sectional Single-Center Study.
Overdentures supported by dental implants are a useful treatment strategy for patients with edentulous mandibles. The aim of this study was to evaluate certain characteristics of the mandibular symphyseal edentulous cases for dental implant treatment using CBCT; and if it is associated with gender differences. Ninety patients (45 females and 45 males) were included in this investigation. A section along the midline of each CBCT image was chosen for the edentulous symphyseal area. Symphysis height, width, and cortical thickness was measured for each patient. Bone density were calculated at four points A two-sample Student's t-test and Pearson correlation were used for statistical analysis. Males had a considerably greater symphysis height (26.66±6.21 mm) than females (24.07±5.00 mm) (p = 0.02). Similar results were found for bone width; males had greater means than females. In case of cortical bone thickness; males had thicker bone cortex in the buccal region than females (p = 0.01). While the difference in bone density between genders was small. However, a positive relationship was recorded between symphysis height and width. Height and width of the mandibular symphysis were influenced by gender in edentulous patients, with men showing higher measurements. The reduction of symphyseal height decreased concurrently with the width after teeth were lost, while bone density was maintained in both genders with no difference between them. The lingual cortical bone is significantly thicker than the buccal cortex at the lower part of the symphysis.


Captivity-Induced Changes in the Skin Microbial Communities of Hellbenders (Cryptobranchus alleganiensis).
Variation in environmental conditions can result in disparate associations between hosts and microbial symbionts. As such, it is imperative to evaluate how environmental variables (e.g., habitat quality) can influence host-associated microbiome composition. Within wildlife conservation programs, captive conditions can negatively influence the establishment and maintenance of "wild-type" microbiotas within a host. Alternative microbial communities can result in the proliferation of disease among captive stock or upon reintroduction. Hellbenders (Cryptobranchus alleganiensis) are a threatened salamander for which extensive captive management is currently employed. Using metabarcoding, we characterized the skin microbiota of wild and captive hellbenders from two subspecies in the state of Missouri, the eastern (C. a. alleganiensis) and the Ozark hellbender (C. a. bishopi). Both subspecies in our study included wild adults and captive juveniles that were collected from the wild as eggs. Our objectives were to investigate differences in the skin microbial communities' richness/diversity, composition, and functional profiles of microbes between wild and captive individuals. Captive eastern hellbenders possessed richer communities than wild cohorts, whereas the opposite pattern was observed within the Ozark subspecies. We found significant microbial community structure between wild and captive populations of both subspecies. Microbiota structure translated into differences in the predicted metagenome of wild and captive individuals as well. As such, we can expect captive hellbenders to experience alternative microbial structure and function upon reintroduction into the wild. Our study provides a baseline for the effect of captivity on the skin microbial communities of hellbenders, and highlights the need to incorporate microbiota management in current captive-rearing programs.


BWH emergency radiology-surgical correlation: omental hematoma with active extravasation: a rare diagnosis.
We describe the radiological and intraoperative correlation of a large omental hematoma with active intra-abdominal bleeding secondary to omental lacerations in a 75-year-old man following blunt trauma from a motor vehicle accident. The purpose of this article is to emphasize the importance of recognizing omental and mesenteric injuries in trauma patients, as these injuries are rare and can be overlooked on CT.


IgG4-related retroperitoneal fibrosis with acute kidney injury: a case report and literature review.
IgG4-related retroperitoneal fibrosis is a rare cause of renal dysfunction that usually manifests as obstructive nephropathy (sometimes with extrarenal manifestations). Due to the non-specific symptoms at the onset of the disease and often latent course, special laboratory and instrumental examination methods are usually needed to establish a diagnosis. The article describes a clinical case of a relapse of IgG4-related retroperitoneal fibrosis in a 53-year-old patient, who developed bilateral ureterohydronephrosis with postrenal acute kidney injury after the withdrawal of glucocorticoid therapy. The patient underwent bilateral percutaneous nephrostomy and resumed glucocorticoids at a dose of 30 mg/day. Postobstructive diuresis was 22 L. Treatment resulted in a complete normalization of the creatinine level and transient hypokalemia, which was eliminated with potassium medications. At the final stage of the treatment, bilateral stenting of both ureters was performed with a tapering of glucocorticoids to 5 mg per day with CT control of the retroperitoneal space after 5 months. A clinical case demonstrates that an interruption of glucocorticoid treatment in patients with IgG4-related retroperitoneal fibrosis can lead to ureterohydronephrosis with the development of acute kidney injury. In such cases, stenting of the ureters could be considered an optimal therapeutic option.


[Surgical surveillance and endoscopy. The problem of secondary complication and local recurrence].
Minimal access techniques in surgery are improving. At the same time, the significance of interventional flexible endoscopy is increasing. Postoperative complications can be treated endoscopically with low rates of morbidity and mortality. Anastomotic strictures after resection of the esophagus, colon or rectum are mostly treated with success by endoscopy. Reoperations are almost never necessary in these cases today. Although the efficient detection of locoregional recurrence of gastrointestinal carcinoma is still the subject of controversial discussion, in contrast, endoscopic therapy for palliation by ablation, dilatation or stenting leads to a clear benefit for many of these patients.


Endoscopic screening of the upper gastrointestinal tract for second primary tumors in patients with head and neck cancer in a Western country.
Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.


The sialoglycan-Siglec-E checkpoint axis in dexamethasone-induced immune subversion in glioma-microglia transwell co-culture system.
Dexamethasone (Dex) is considered as the main steroid routinely used in the standard therapy of brain tumor-induced edema. Strong immunosuppressive effects of Dex on effector systems of the immune system affect the patients' antitumor immunity and may thereby worsen the prognosis. Siglecs and their interacting sialoglycans have been described as a novel glyco-immune checkpoint axis that promotes cancer immune evasion. Despite the aberrant glycosylation in cancer is described, mechanisms involved in regulation of immune checkpoints in gliomas are not fully understood. The aim of this study was to investigate the effect of Dex on the Siglec-sialic acid interplay and determine its significance in immune inversion in monocultured and co-cultured microglia and glioma cells. Both monocultured and co-cultured in transwell system embryonic stem cell-derived microglia (ESdM) and glioma GL261 cells were exposed to Dex. Cell viability, immune inversion markers, and interaction between sialic acid and Siglec-E were detected by flow cytometry. Cell invasion was analyzed by scratch-wound migration assay using inverted phase-contrast microscopy. Exposure to Dex led to significant changes in IL-1β, IL-10, Iba-1, and Siglec-E in co-cultured microglia compared to naïve or monocultured cells. These alterations were accompanied by increased α2.8-sialylation and Siglec-E fusion protein binding to co-cultured glioma cell membranes. This study suggests that the interplay between sialic acids and Siglecs is a sensitive immune checkpoint axis and may be crucial for Dex-induced dampening of antitumor immunity. The targeting of sialic acid-Siglec glyco-immune checkpoint can be a novel therapeutic method in glioma therapy.


Agouti-related peptide-expressing neurons are mandatory for feeding.
Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.


Laparoscopic surgery for omental pregnancy.
A 16-year-old girl underwent emergency laparoscopic surgery for what was thought to be hematoperitoneum secondary to extrauterine pregnancy. During the operation, omental pregnancy was diagnosed and treated by laparoscopy. According to Studiford's criterion, this case can be classified as a primary omental pregnancy. When performing laparoscopy for suspected tubal pregnancy with no visible pathologic changes on either tube, careful evaluation of the whole abdominal cavity is necessary so as not to overlook an abdominal pregnancy.


Classification of central retinal vein occlusion.
Our prospective clinical study of 360 eyes with central retinal vein occlusion (CRVO) and our experimental studies on CRVO in 54 eyes of rhesus monkeys have shown that CRVO consists of the following two distinct entities: (1) Nonischemic CRVO in which there is essentially a stasis of retinal venous circulation; we call it venous stasis retinopathy (VSR). (2) Ischemic CRVO: We call this hemorrhagic retinopathy (HR). Our prospective clinical studies have revealed that it is absolutely essential to differentiate CRVO into VSR and HR because of their very different prognoses and management. VSR is a benign and self-limited condition, while HR is a severe, potentially blinding disorder. Lumping the two types of CRVO together as one disease has caused much confusion concerning the prognosis and management of CRVO. The basis of such a classification and differential diagnosis of VSR and HR is discussed at length.


Structural basis for reversible and irreversible inhibition of human cathepsin L by their respective dipeptidyl glyoxal and diazomethylketone inhibitors.
Cathepsin L plays a key role in many pathophysiological conditions including rheumatoid arthritis, tumor invasion and metastasis, bone resorption and remodeling. Here we report the crystal structures of two analogous dipeptidyl inhibitor complexes which inhibit human cathepsin L in reversible and irreversible modes, respectively. To-date, there are no crystal structure reports of complexes of proteases with their glyoxal inhibitors or complexes of cathepsin L and their diazomethylketone inhibitors. These two inhibitors - inhibitor 1, an α-keto-β-aldehyde and inhibitor 2, a diazomethylketone, have different groups in the S1 subsite. Inhibitor 1 [Z-Phe-Tyr (OBut)-COCHO], with a K(i) of 0.6nM, is the most potent, reversible, synthetic peptidyl inhibitor of cathepsin L reported to-date. The structure of the inhibitor 1 complex was refined up to 2.2Å resolution. The structure of the complex of the inhibitor 2 [Z-Phe-Tyr (t-Bu)-diazomethylketone], an irreversible inhibitor that can inactivate cathepsin L at μM concentrations, was refined up to 1.76Å resolution. These two inhibitors have substrate-like interactions with the active site cysteine (Cys25). Inhibitor 1 forms a tetrahedral hemithioacetal adduct, whereas the inhibitor 2 forms a thioester with Cys25. The inhibitor 1 β-aldehyde group is shown to make a hydrogen bond with catalytic His163, whereas the ketone carbonyl oxygen of the inhibitor 2 interacts with the oxyanion hole. tert-Butyl groups of both inhibitors are found to make several non-polar contacts with S' subsite residues of cathepsin L. These studies, combined with other complex structures of cathepsin L, reveal the structural basis for their potency and selectivity.


Long-term Outcome of Hirschsprung Disease: Impact on Quality of Life and Social Condition at Adult Age.
Hirschsprung disease is a rare congenital disease typically requiring surgical treatment during childhood. Quality of life and social condition at adult age can be impaired by disease-specific sequelae. This study aimed to assess the quality of life and social outcome of adult patients operated on for Hirschsprung disease during childhood. Patients operated on for Hirschsprung disease during childhood were identified and specific questionnaires were sent to them. Data from 2 referral centers were used. Patients who completed the questionnaires regarding quality of life and social condition were included. The Hirschsprung's Disease and Anorectal Malformations Quality of Life disease-specific questionnaire (8 dimensions explored; each scored from 0 to 100 maximum score) and a sociodemographic questionnaire were sent to identified patients. Sociodemographic data were compared with those of the French general population. Thirty-four patients had Hirschsprung disease (men, 76%; mean age, 32 years) were included in the study. Mean total Hirschsprung's Disease and Anorectal Malformations Quality of Life score was 611 of 800 (maximum score 800). The 2 most impaired dimensions were "physical symptoms" and "diarrhea" (62.9/100 and 73.6/100). Fecal continence was only marginally affected (mean score, 89/100). Patients with Hirschsprung disease achieved better educational levels than the French general population. Parental and marital status did not differ between the 2 groups. This study had the limitations inherent to a retrospective study. The quality of life of adult patients with Hirschsprung disease sequelae is marginally impaired in this study. Despite the consequences of this congenital abnormality, the condition eventually achieved can be considered as satisfactory. See Video Abstract at http://links.lww.com/DCR/A917.


Rates of Molecular Evolution Suggest Natural History of Life History Traits and a Post-K-Pg Nocturnal Bottleneck of Placentals.
Life history and behavioral traits are often difficult to discern from the fossil record, but evolutionary rates of genes and their changes over time can be inferred from extant genomic data. Under the neutral theory, molecular evolutionary rate is a product of mutation rate and the proportion of neutral mutations [1, 2]. Mutation rates may be shared across the genome, whereas proportions of neutral mutations vary among genes because functional constraints vary. By analyzing evolutionary rates of 1,185 genes in a phylogeny of 89 mammals, we extracted historical profiles of functional constraints on these rates in the form of gene-branch interactions. By applying a novel statistical approach to these profiles, we reconstructed the history of ten discrete traits related to activity, diet, and social behaviors. Our results indicate that the ancestor of placental mammals was solitary, seasonally breeding, insectivorous, and likely nocturnal. The results suggest placental diversification began 10-20 million years before the K-Pg boundary (66 million years ago), with some ancestors of extant placental mammals becoming diurnal and adapted to different diets. However, from the Paleocene to the Eocene-Oligocene transition (EOT, 33.9 mya), we detect a post-K-Pg nocturnal bottleneck where all ancestral lineages of extant placentals were nocturnal. Although diurnal placentals may have existed during the elevated global temperatures of the Paleocene-Eocene thermal maximum [3], we hypothesize that diurnal placentals were selectively extirpated during or after the global cooling of the EOT, whereas some nocturnal lineages survived due to preadaptations to cold environments [4].


Longitudinal course and risk factors associated with psychosis in bipolar youths.
To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.


Comparison of three PCR-based methods to detect Loa loa and Mansonella perstans in long-term frozen storage dried blood spots.
Loa loa and Mansonella perstans are two very common filarial species in Africa. Although microscopy is the traditional diagnostic method for human filariasis, several polymerase chain reaction (PCR) methods have emerged as an alternative approach for identifying filarial parasites. The aim of this study is to compare three molecular methods and decide which is the most suitable for diagnosing human loiasis and mansonellosis in non-endemic regions using dried blood spot (DBS) as a medium for sample collection and storage. A total of 100 DBS samples, with their corresponding thin and thick blood smears, were selected for this study. Microscopy was used as the reference method to diagnose and calculate the microfilaraemia. Filarial DNA was extracted using the saponin/Chelex method and the DNA isolated was assayed by Filaria-real time-PCR, filaria-nested PCR, and cytochrome oxidase I PCR. All PCR products were subsequently purified and sequenced. The statistical values for each molecular test were calculated and compared. Overall, 64 samples were identified as negative by all tests and a further 36 samples were positive by at least one of the methods used. The sensitivity and specificity were similar for the different molecular methods, all of which demonstrated good agreement with microscopy. Based on this study, and from a practical point of view (single and short amplification round), the optimal technique for diagnosing filarial infection in non-endemic regions is filaria-real time-PCR, which presents high sensitivity and specificity and is also able to detect a wide range of human filariae.


Immunologic alterations and efficacy of subcutaneous immunotherapy with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients.
There is a continuing debate about whether monoallergen subcutaneous immunotherapy (SCIT) is able to modulate immune and clinical responses toward main causal allergen in polysensitized patients. To investigate short-term immunologic changes and clinical effectiveness of SCIT with Dermatophagoides pteronyssinus in monosensitized and polysensitized patients who have rhinitis with or without asthma. Nineteen monosensitized and 24 polysensitized patients participated in this prospective, self-placebo-controlled, interventional study. Cluster immunotherapy with D pteronyssinus was administered after 2 months of placebo in both groups. Immunologic parameters, including CD203c expression on basophils after allergen stimulation, total IgE, specific IgE, and specific IgG4, were evaluated at baseline, after placebo, and after immunotherapy. Clinical effectiveness was assessed using monthly symptom-medication scores, visual analog scale, quality-of-life questionnaire, and nasal allergen provocation test. At baseline, polysensitized patients had higher CD203c expression on basophils than monosensitized patients (P = .007). Activated basophils expressing CD203c, total IgE, and specific IgG4 were significantly increased after immunotherapy compared with baseline and placebo in the polysensitized group (P < .025). After immunotherapy, specific IgE and D pteronyssinus-induced CD203c expression were significantly higher in polysensitized than monosensitized patients (P < .05). The total symptom scores and the Mini Rhinoconjunctivitis Quality of Life Questionnaire scores in polysensitized patients and the visual analog scale scores in both groups were lower after immunotherapy compared with baseline and placebo (P < .025). Titrated nasal allergen provocation test with D pteronyssinus increased after immunotherapy in the monosensitized group (P < .05). This study indicates that monosensitized and polysensitized patients have distinct humoral response and basophil behavior to SCIT. However, a single-allergen immunotherapy corresponding to the most clinically troublesome allergy in polysensitized patients can lead to early clinical efficacy comparable to that seen in monosensitized patients. clinicaltrials.gov Identifier: NCT01795846.


Hydration status measured by BCM: A potential modifiable risk factor for peritonitis in patients on peritoneal dialysis.
Peritoneal dialysis peritonitis and fluid overhydration (OH) are frequent problems in peritoneal dialysis. The latter can cause gut wall oedema or be associated with malnutrition. Both may lead to increased peritonitis risk. We wished to determine if OH is an independent risk factor for peritonitis (caused by enteric organisms). Retrospectively study of patients with >2 bioimpedance assessments (Body Composition Monitor). We compared peritonitis rates of patients with above or below the median time-averaged hydration parameter (OH/extracellular water, OH/ECW). Multivariate analysis was performed to determine independent risk factors for peritonitis by enteric organism. We studied 580 patients. Peritonitis was experienced by 28% patients (followed up for an average of 17 months). The overall peritonitis rate was 1:34 patient months. Patients with low OH/ECW values had significantly lower rates of peritonitis from enteric organisms than overhydrated patients (incident rate ratio 1.53, 95% confidence interval 1.38-1.70, P < 0.001). Hydration remained an independent predictor of peritonitis from enteric organisms when multivariate model included demographic parameters (odds ratio for a 1% increment of OH/ECW was 1.05; 95% confidence interval 1.01-1.10, P < 0.02). However, including biochemical parameters of malnutrition reduced the predictive power of overhydration. We found an association between overhydration and increased rates of peritonitis. While this may partly be due to the high co-morbidity of patients (advanced age and diabetes), on multivariate analysis, only inclusion of nutritional parameters reduced this association. It remains to be determined if overhydration will prove to be a modifiable risk factor for peritonitis or whether malnutrition will prove to be more important.


Improving staff safety through an aggression management program.
This article provides information regarding the relationship of a formal inpatient Aggression Management Program and subsequent aggression-related staff injuries at one university medical center. Data related to staff injuries, collected before and after the program, were compared as a means of measuring the program's effectiveness. Although the frequency of injury changed only slightly, the results indicate that there was a decrease in the severity of aggression-related staff injuries after institution of the formal program, as well as a reduction in time missed from work and cost to the system. Improvements of other aspects of care such as resource management and staff satisfaction as outcomes of this program are also discussed.


Candesartan treatment enhances liposome penetration and anti-tumor effect via depletion of tumor stroma and normalization of tumor vessel.
The poor penetration of nanoparticles in solid tumors has been a critical factor limiting the clinical benefits of nanomedicine. Therefore, we depleted the dense extracellular matrix (ECM) and normalized tumor vessels to enhance drug delivery and therapeutic efficacy. We used candesartan as an angiotensin system inhibitor, which reduced ECM content and facilitated "vascular normalization" by targeting the angiotensin-signaling axis, resulting in improved anti-cancer therapeutic effects. We also combined candesartan with PEGylated liposome-encapsulated zoledronic acid (ZOL) (PEG-ZOL-LPs) to assess how this affected anti-tumor therapy. Our findings indicated that the migration of 4T1 mouse breast cancer cells was inhibited by candesartan. Moreover, the ECM depletion (including collagen I and hyaluronan) by candesartan was achieved through the downregulation of TGF-β1 in vitro, consistent with in vivo results. Furthermore, treatment groups that received candesartan also had significantly decreased tumor vessel permeability and proportions of circulating endothelial progenitor cells (CEPCs) in the serum, which resulted in normalization of tumor vasculature and improved delivery of PEG-ZOL-LPs. Finally, the positive effect candesartan in terms of tumor growth was found not to have an impact of the efficacy of the PEG-ZOL-LPs treatment. This unexpected lack of effect of candesartan on the performance of PEG-ZOL-LPs would be due to dynamics of the effect of both treatments. It might be possible that a different protocol of administration could lead to a synergistic effect. Graphical abstract The schematic illustration showed that candesartan favored depletion of tumor stroma and tumor vascular normalization to improve the anti-cancer efficacy of PEG-ZOL-LPs.


Study of cell surface antigens induced by herpes simplex virus. Note I. Identification of the antigens by means of protein A-containing staphylococci.
A rapid, easy-to-perform and specific technique for the visualization of herpes simplex virus (HSV)-induced cell surface antigens is described. The technique consists in the incubation of HSV-infected cells with hyperimmune HSV antiserum and formation of rosettes with FITC-labelled Cowan strain staphylococci containing protein A. The "nonspecific background" of the reaction can be estimated by comparison with the rate of bacteria binding by control cells not incubated with HSV antiserum.


Safety of Distal His Bundle Pacing Via the Right Ventricle Backed Up by Adjacent Ventricular Capture.
This study investigated the differences between distal His bundle pacing (HBP) via the right ventricle and proximal HBP via the right atrium with regard to pacing and sensing parameters. HBP preserves physiological ventricular activation. The capture threshold of the adjacent ventricle accompanying HBP has not been evaluated after implantation. Fifty patients with bradycardia (58% with atrioventricular block) underwent successful HBP and were followed for 1 year. Precise locations of the lead tips were confirmed using follow-up echocardiography. HBP leads were fixed via the right atrium or right ventricle (25 patients each). Overall, the local ventricle and HBP thresholds were elevated during follow-up. The distal HBP thresholds did not significantly differ from the proximal HBP thresholds, although local ventricular thresholds of distal HBP were markedly lower than those of proximal HBP. At 6 months, the accepted ventricular threshold (≤2.5 V) was maintained in 39 patients (78%). An amplitude of ventricular electrogram post-fixation of ≥2.0 mV and a capture threshold of ≤1.1 V at implantation were determined to be optimal values for predicting the accepted threshold at 6 months, with areas under the curve of 0.86 and 0.84, respectively. Atrial oversensing was often detected in proximal HBP but not distal HBP. Distal HBP via the right ventricle captured the His bundle, similar to proximal HBP via the right atrium, with a superior local ventricular threshold during follow-up. Anatomy and electrophysiological ventricular properties at implantation may be critical for maintaining adjacent ventricle capture to prevent lead revision (Evaluation of Electrophysiological Parameters related to His Bundle Pacing in Patients With Bradyarrhythmias; UMIN000031364).


Auditory noise associated with MR procedures: a review.
This review article discusses the various types of acoustic noise produced during the operation of MR systems, describes the characteristics of the acoustic noise, and presents information regarding noise control techniques. In addition, the problems related to acoustic noise for patients and healthcare workers are discussed.


Practice guidelines: a more rational approach to diagnosis and treatment and a more effective use of health care resources.
Practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The implementation of practice guidelines is justified by factors such as variations in clinical practice, malpractice and its associated costs, and the need to contain health care expenditures. In this context, practice guidelines promote a more rational approach to clinical decision making and better quality of care. Although there are several limitations to the use of guidelines in current practice, different organizations (professional societies, government agencies, licensing authorities, educational institutions) have a potential interest in their development. A working group on the development of practice guidelines endorsed by the Italian Society of Neurology has been active since 1995. The aims of this group include the development of guidelines to be accepted by the medical community and to be placed within the framework of initiatives of the Italian Ministry of Health.


Effects of in vitro addition of exogenous vitamins C and E on gilthead seabream (Sparus aurata L.) phagocytes.
The phagocytic cell function is an important factor of resistance to infection in fish. Although it is known that several nutritional factors affect phagocyte function and that vitamins C and E modulate the vertebrate immune system, there are no data on the direct effect of these vitamins or on their possible synergistic effects on the fish phagocyte functions. We report the in vitro effect of vitamin C and/or E on the functions and ultrastructure of gilthead seabream (Sparus aurata L.) head-kidney phagocytic leukocytes. Head-kidney leukocytes were incubated with different concentrations of vitamins C and/or E for 48 h and then their migration, respiratory burst, phagocytosis and ultrastructure were studied. Leukocyte migration and phagocytosis increased when vitamin C or E were added, while the respiratory burst was synergistically enhanced when both vitamins were used together. Noticeable ultrastructural changes not previously reported were induced by these vitamins in gilthead seabream phagocytes (acidophilic granulocytes and macrophages). These results indicated that vitamins C and E added in vitro modulate the main functions of gilthead seabream phagocytes and induced ultrastructural changes characteristic of cell activation on such cells.


Analysis of multiyear studies in horses in Kentucky to ascertain whether counts of eggs and larvae per gram of feces are reliable indicators of numbers of strongyles and ascarids present.
Increasing levels of anthelmintic resistance in equine nematodes have led to recommendations of more sustainable anthelmintic treatment protocols with emphasis on parasite surveillance and diagnosis, rather than prophylactic calendar-based treatments. This requires knowledge of the diagnostic test performance of techniques for counts of eggs per gram of feces (EPG) as well as methods for culturing, counting and identifying third stage (L(3)) strongyle larvae per gram of feces (LPG). For horses, such information does not exist in the published literature. The aim of this study was to examine the relationship between worm count and fecal egg count (FEC) data for strongyle and Parascaris equorum infections as well as larval culture counts for diagnosing Strongylus spp. infections. Necropsy data from 693 horses used for critical or controlled tests, including information on total worm counts, fecal egg counts (FEC) and larval culture results collected at the University of Kentucky over a period of 50 years were analyzed. Sensitivity, specificity, positive and negative predictive values, and receiver operator characteristic (ROC) curves were generated for the larval cultures and ascarid egg counts. For the strongyle egg counts, potential FEC cutoff values for treatment were evaluated statistically by comparing the total strongyle worm counts below and above chosen cutoff values. All tests had high positive predictive values (>0.95), but moderate negative predictive values (<0.70). The negative predictive values of the larval counts were negatively affected by increasing egg count levels. Strongyle FEC cutoff values up to the level of 500 EPG yielded significantly higher strongyle worm counts in the treatment group, whereas no differences were found at higher cutoffs. This supports usage of cutoffs for treatment in the 0-500 EPG range. Altogether, the present study yields unique and useful information of widely used methods for parasite surveillance and diagnosis in equine establishments.


Effects of interaction of ration and temperature on growth and bioenergetics of Achaea janata Linnaeus (Lepidoptera: Noctuidae).
Growth and bioenergetics of the last instar larvae of Achaea janata fed on a wide range of rations of leaves of Ricinus communis (ad libitum to 50 or 100 mg leaf per larva per day) at 22, 27, 32 and 35° C were studied. Increase in larval mortality, extension of larval duration and decrease in final body weight were some of the adverse effects of restricted rations. Whereas larval duration was influenced by ration level, pupal period was dependent on temperature. The larvae partially compensated for restricted rations by enhancing feeding rate over the limit expected in proportion to the ration offered. The level of compensation was higher at 27° C. Influence of temperature or its interaction with ration on assimilation efficiency was more significant than the independent influence of ration; the efficiency ranged from 57 to 67%. Restriction of ration below a critical level (300 mg/larva/day at 35° C and 200 mg/larva/day at other temperatures) significantly influenced the net conversion efficiency; the lowest efficiency of 1.3% was recorded for the larvae fed 100 mg leaf/day. Energy content of the terminal larva determined the percentage of energy transferred to the imago, which ranged from 37 to 55% of the terminal larval energy.


Osteochondral lesion of the talus: prognostic factors affecting the clinical outcome after arthroscopic marrow stimulation technique.
The treatment of symptomatic osteochondral lesions of the talus (OLT) has difficulties and limitations caused by the poor regeneration of articular cartilage and the limited access to the ankle joint. It is important that the surgeon understand the causes of failure as well as the factors influencing the results of arthroscopic treatment of OLTs. The presence of such a risk factor may encourage surgeons to find new treatment strategies as well as counsel patients differently.


Knowledgeability and Identification: Explaining Military Interprofessional Healthcare Teams' Excellence and Readiness.
The importance of successful interprofessional collaboration for effective patient care is generally acknowledged. Research into interprofessional collaboration has thus far been mainly situated in the civilian context and has mostly indicated barriers that prevent successful interprofessional collaboration. However, military interprofessional healthcare teams (MIHTs) seem to be exceptionally successful. Building on the overarching finding of the studies within this special edition-i.e., that MIHTs' readiness and excellence are in part due to healthcare professionals' "shared understanding" of what is needed to effectively serve on an MIHT-this commentary uses the theory of Landscape of Practice as a lens to further explain the processes through which healthcare professionals attain this shared understanding. Used within the fields of Health Professions Education and workplace learning, Landscapes of Practice (LoP) helps to explain how learning occurs within practice. It highlights how, by engaging within the various working environments belonging to a profession, social interactions between the various professionals within that environment form the conduit for learning. LoP highlights that the outcome of this learning process is "knowledgeability," i.e., understanding of how to engage within the field and with its players, resulting in being an acknowledged member of the field. Fostered through a process called "identification," professionals learn to see how their professional practice aligns with that of others and how to effectively collaborate with others. The commentary explains how the findings of the separate studies within this special edition strongly resonate with knowledgeability and identification. It is concluded that civilian interprofessional healthcare teams may benefit from incorporating characteristics of MIHTs in their training programs.


Differences in Clinical Characteristics between Patients with Transient Ischemic Attack Whose Symptoms Do and Do Not Persist on Arrival.
Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. Two hundred sixty-six patients (158 men, 68.0 ± 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long-duration TIA (≥60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00-3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival.


Some unusual cases of apexification subsequent to trauma.
Three cases are reported in which apexification occurred without the benefit of endodontic treatment. These reports illustrate that immature teeth which are avulsed and replanted, dislocated and repositioned, or traumatized with pulp necrosis supervening, may progress to form complete apices without intracanal therapy. The value of using calcium hydroxide is not in question, but may not be as essential an aid to apical closure as was previously thought. In one case, the appearance of isolated apixes forming, deep in the bone after loss of very immature lateral incisors poses the question of whether this event does not occur more frequently after extraction of newly erupted or young impacted teeth.


Histological and biochemical changes of experimental meniscus tear in the dog knee.
When degeneration is noted in the meniscus, sutures should not be applied even for a tear of the vascularized region of the meniscus because the meniscus may rerupture after suturing. In this study, the degeneration process of bucket-handle tear of the meniscus was investigated using histological and biochemical markers. A bucket-handle tear in the intercondylar notch was prepared in the dog knee. Eight animals each were killed at 2, 4, 12, 24, and 48 weeks; and changes in the articular cartilage were observed. The cell count and morphology in the meniscus were investigated by hematoxylin and eosin staining, and glycosaminoglycans in the matrix were investigated by toluidine blue staining. Glycosaminoglycans were also measured by high-performance liquid chromatography. Erosion was noted in the weight-bearing region of the articular cartilage after 12 weeks. The cell count in the meniscus was markedly decreased at 48 weeks. Regarding cell morphology, fibrochondrocytes remained in the meniscus until 12 weeks. The cell morphology varied at 24 weeks, but the number of cells was maintained. Cell proliferation, mainly fibroblasts, was noted from 2 weeks and 4 weeks after surgery in the periphery and body of the meniscus, respectively. Fibrochondrocyte-like cells proliferated from 12 weeks in the meniscal body, and metachromasia was detected by toluidine blue staining, indicating meniscal repair. A marked decrease in glycosaminoglycans was noted at 48 weeks, which was consistent with the decrease in the cell count in the meniscus. Early application of sutures is desirable for bucket-handle tear of the meniscus because lesions appear in the cartilage within 12 weeks, but suturing may be performed until 24 weeks because of the absence of obvious meniscal degeneration. However, disorder of the meniscus progresses after 48 weeks and may affect the outcome of the meniscal suture.


Growth hormone, insulin and aging: the benefits of endocrine defects.
Longevity of mice can be increased by spontaneous or experimentally induced mutations that interfere with the biosynthesis or actions of growth hormone (GH), insulin-like growth factor 1 (IGF-1), or insulin in the adipose tissue. The effects of GH resistance and deficiency of GH (along with thyrotropin and prolactin) on aging and lifespan are the most pronounced and best established of these mutations. Potential mechanisms linking these endocrine deficits with delayed aging and extended longevity include increased stress resistance, alterations in insulin and mammalian target of rapamycin (mTOR) signaling and metabolic adjustments. Physiological relationships deduced from the extreme phenotypes of long-lived mouse mutants appear to apply broadly, encompassing genetically normal ("wild-type") mice and other mammalian species. The role of GH in the control of human aging continues to be hotly debated, but recent data indicate that reduced somatotropic signaling provides protection from cancer and other age-related diseases and may promote old age survival.


Biosynthesis from gluconate of a random copolyester consisting of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates by Pseudomonas sp. 61-3.
Pseudomonas sp. 61-3 isolated from soil was found to produce a polyester consisting of 3-hydroxyalkanoic acids of even carbon numbers C4, C6, C8, C10 and C12 when sodium gluconate was fed as the sole carbon source. The polyester produced was fractionated with boiling acetone. The acetone-insoluble fraction (28 wt%) of the polyester was a poly(3-hydroxybutyrate) homopolymer, while the acetone-soluble fraction (72 wt%) was composed of seven different 3-hydroxyalkanoate (3HA) units ranging from C4 to C12: 40 mol% 3-hydroxybutyrate (3HB), 5 mol% 3-hydroxyhexanoate (3HH), 20 mol% 3-hydroxyoctanoate (3HO), 24 mol% 3-hydroxydecanoate (3HD), 1 mol% 3-hydroxy-5-cis-decenoate (3H5D), 4 mol% 3-hydroxydodecanoate (3HDD) and 6 mol% 3-hydroxy-5-cis- dodecenoate (3H5DD). The copolymer was characterized by nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography and differential scanning calorimetry. The acetone-soluble fraction of this amorphous copolymer was shown to have a random sequence distribution of the seven 3HA units of C4 to C12 by analysis of the 150 MHz 13C-NMR spectrum. This is the first example of microbial synthesis of a random copolyester consisting of 3HB and medium-chain-length 3HA units.


Testing a "content meets process" model of depression vulnerability and rumination: Exploring the moderating role of set-shifting deficits.
MacCoon and Newman's (2006) "content meets process" model posits that deficits in cognitive control make it difficult to disengage from negative cognitions caused by a negative cognitive style (NCS). The present study examined if the interactive effect of cognitive set-shifting abilities and NCS predicts rumination and past history of depression. Participants were 90 previously depressed individuals and 95 never depressed individuals. We administered three laboratory tasks that assess set-shifting: the Wisconsin Card-Sorting Task, the Emotional Card-Sorting Task, and the Internal Switch Task, and self-report measures of NCS and rumination. Shifting ability in the context of emotional distractors moderated the association between NCS and depressive rumination. Although previously depressed individuals had more NCS and higher trait rumination relative to never depressed individuals, shifting ability did not moderate the association between NCS and depression history. The cross-sectional correlational design cannot address the causal direction of effects. It is also not clear whether findings will generalize beyond college students. NCS was elevated in previously depressed individuals consistent with its theoretical role as trait vulnerability to the disorder. Furthermore, NCS may be particularly likely to trigger rumination among individuals with poor capacity for cognitive control in the context of emotional distraction.


Human factor-designed multimodal intervention reduces the rate of unused peripheral intravenous cannula insertion.
Our objective was to examine the impact of a human factor-designed multimodal intervention on the proportion of unused peripheral i.v. cannula (PIVC) insertion in our ED. A pre- and post-multimodal intervention retrospective cohort study was conducted using a structured electronic medical record review within a single adult tertiary ED in Australia. Pre-intervention data was collected 30 days prior to the multimodal intervention, with 30 day post-intervention data collected 3 months after the intervention commenced. The rates of PIVC inserted, the unused rate and the unused but appropriately inserted cannulas were the main outcome measures. Intravenous cannula insertion rates decreased by 12.9% (95% confidence interval [CI] 12.19-13.61) between the pre-intervention (1413/4167 [33.9%]; 95% CI 32.5-35.4) and post-intervention cohort (928/4421 [21.0%]; 95% CI 19.8-22.2). An analysis of 754 cases (376 pre-intervention and 378 post-intervention) showed that 139 of 376 (37.0%; 95% CI 32.1-42.1) i.v. cannulas were unused pre-intervention, while 73 of 378 (19.3%; 95% CI 15.4-23.7) was unused post-intervention; an absolute reduction of 17.7% (95% CI 14.98-20.42). The relative risk of an unused i.v. cannula was 0.52 (95% CI 0.41-0.67). The proportion of unused but appropriately inserted i.v. cannulas remained unchanged in both cohorts, with a relative risk of 0.91 (95% CI 0.58-1.42). Our multimodal intervention successfully reduced the number of unused PIVCs inserted in the ED, with a reduction in overall and unused PIVC insertions without any change in appropriate insertions.


[Effect of an analog of vasopressin on the fixation of temporary connections in the intact rat and after destruction of the locus coeruleus].
Subcutaneous injection to intact rats and rats with destroyed locus coeruleus of 10 mcg of triglycide-glycinamide-lysinevasopressin (TGDGA-LVP) immediately after elaboration of labyrinth defensive conditioned reflex improves consolidation of temporary connections and raises its resistance to extinction. Improved consolidation of temporary connection is retained in animals with destroyed locus coeruleus for a shorter time than in intact animals. At the same time according to some characteristics, TGDGA-LVP has a more expressed influence of positive character on animals with destroyed locus coeruleus than on intact rats.


Improved fish lymphocyte culture for chromosome preparation.
Cytogenetic methodology is still underdeveloped in fishes compared with mammals. Culture condition for fish lymphocytes was optimized to improve chromosome preparation using the rainbow trout (Oncorhynchus mykiss) as a model after changing the combination of parameters such as mitogens, incubation periods, media, cell components, and freshness of blood. The optimized culture condition included isolation of lymphocytes from fresh blood by a stirring method, their culture in medium 199 supplemented with 10% FBS, 18 microg/ml of phytohemagglutinin (PHA-W) and 100 microg/ml of lipopolysaccharide (LPS) as mitogens, and harvested at 6 days after culture. This condition provided a notably increased mitotic index (MI) of 4.3-10.0% in rainbow trout lymphocytes. In addition, the condition was highly reproducible as shown by the similar level of MI in cultured lymphocytes from 181 individuals without failure. Applicability of this method in a wide range of fish groups was also proven with Ml of 1.1-13.3% in cultured lymphocytes from other 16 freshwater species of Acipenseridae, Anguillidae, Solmonidae, Cyprinidae, and Centrarchidae, and five marine species of Sparidae, Kyphosidae, Paralichthyidae, and Scorpaenidae. Chromosome preparations of improved quality by the present method were successfully applied for the replication R-banding with incorporation of 5-bromo-2'-deoxyuridine and direct R-banding fluorescence in situ hybridization.


DNA Methylation Analysis of Imprinted Genes in the Cortex and Hippocampus of Cross-Fostered Mice Selectively Bred for Increased Voluntary Wheel-Running.
We have previously shown that high runner (HR) mice (from a line genetically selected for increased wheel-running behavior) have distinct, genetically based, neurobiological phenotypes as compared with non-selected control (C) mice. However, developmental programming effects during early life, including maternal care and parent-of-origin-dependent expression of imprinted genes, can also contribute to variation in physical activity. Here, we used cross-fostering to address two questions. First, do HR mice have altered DNA methylation profiles of imprinted genes in the brain compared to C mice? Second, does maternal upbringing further modify the DNA methylation status of these imprinted genes? To address these questions, we cross-fostered all offspring at birth to create four experimental groups: C pups to other C dams, HR pups to other HR dams, C pups to HR dams, and HR pups to C dams. Bisulfite sequencing of 16 imprinted genes in the cortex and hippocampus revealed that the HR line had altered DNA methylation patterns of the paternally imprinted genes, Rasgrf1 and Zdbf2, as compared with the C line. Both fostering between the HR and C lines and sex modified the DNA methylation profiles for the paternally expressed genes Mest, Peg3, Igf2, Snrpn, and Impact. Ig-DMR, a gene with multiple paternal and maternal imprinted clusters, was also affected by maternal upbringing and sex. Our results suggest that differential methylation patterns of imprinted genes in the brain could contribute to evolutionary increases in wheel-running behavior and are also dependent on maternal upbringing and sex.


Hexagonal mesoporous silica modified with copper phthalocyanine as a photocatalyst for pesticide 2,4-dichlorophenoxiacetic acid degradation.
A new mesoporous catalyst was prepared by the reaction between 3-aminopropyltrimethoxisylane and Cu(II)-hexadecafluorophthalocyanine, followed by co-condensation of tetraethylorthosilicate around a micelle formed by n-dodecylamine. The surfactant was removed from the pores by continuous extraction with ethanol, giving the Si-CuF16Pc catalyst. This catalyst was characterized by SEM, FTIR, TGA, 29Si NMR, N2 adsorption and X-ray diffraction. SEM images confirmed that the catalyst material is formed by nanoaggregates with a diameter of 100 nm. N2 adsorption isotherms showed that Si-CuF16Pc has a surface area of approximately 200 m2 g(-1) and a porous diameter of 7.7 nm, characterizing the mesoporosity of this product. This novel material shows an excellent photocatalytic activity, degrading almost 90% of 2,4-dichlorophenoxyacetic acid (2,4-D) up to 30 min, while only approximately 40% of photodegradation was obtained in its absence.


Cell-selective inhibition of NF-κB signaling improves therapeutic index in a melanoma chemotherapy model.
The transcription factor NF-κB promotes survival of cancer cells exposed to doxorubicin and other chemotherapeutic agents. IκB kinase is essential for chemotherapy-induced NF-κB activation and considered a prime target for anticancer treatment. An IκB kinase inhibitor sensitized human melanoma xenografts in mice to killing by doxorubicin, yet also exacerbated treatment toxicity in the host animals. Using mouse models that simulate cell-selective targeting, we found that impaired NF-κB activation in melanoma and host myeloid cells accounts for the therapeutic and the adverse effects, respectively. Ablation of tumor-intrinsic NF-κB activity resulted in apoptosis-driven tumor regression following doxorubicin treatment. By contrast, chemotherapy in mice with myeloid-specific loss of NF-κB activation led to a massive intratumoral recruitment of interleukin-1β-producing neutrophils and necrotic tumor lesions, a condition associated with increased host mortality but not accompanied by tumor regression. Therefore, a molecular target-based therapy may be steered toward different clinical outcomes depending on the drug's cell-specific effects. Our findings show that the IκB kinase–NF-κB signaling pathway is important for both promoting treatment resistance and preventing host toxicity in cancer chemotherapy; however, the two functions are exerted by distinct cell type–specific mechanisms and can therefore be selectively targeted to achieve an improved therapeutic outcome.


The spontaneous mouse mutant low set ears (Lse) is caused by tandem duplication of Fgf3 and Fgf4.
The external ear develops from an organized convergence of ventrally migrating neural crest cells into the first and second branchial arches. Defects in external ear position are often symptomatic of complex syndromes such as Apert, Treacher-Collins, and Crouzon Syndrome. The low set ears (Lse) spontaneous mouse mutant is characterized by the dominant inheritance of a ventrally shifted external ear position and an abnormal external auditory meatus (EAM). We identified the causative mutation as a 148 Kb tandem duplication on Chromosome 7, which includes the entire coding sequences of Fgf3 and Fgf4. Duplications of FGF3 and FGF4 occur in 11q duplication syndrome in humans and are associated with craniofacial anomalies, among other features. Intercrosses of Lse-affected mice revealed perinatal lethality in homozygotes, and Lse/Lse embryos display additional phenotypes including polydactyly, abnormal eye morphology, and cleft secondary palate. The duplication results in increased Fgf3 and Fgf4 expression in the branchial arches and additional discrete domains in the developing embryo. This ectopic overexpression resulted in functional FGF signaling, demonstrated by increased Spry2 and Etv5 expression in overlapping domains of the developing arches. Finally, a genetic interaction between Fgf3/4 overexpression and Twist1, a regulator of skull suture development, resulted in perinatal lethality, cleft palate, and polydactyly in compound heterozygotes. These data indicate a role for Fgf3 and Fgf4 in external ear and palate development and provide a novel mouse model for further interrogation of the biological consequences of human FGF3/4 duplication.


Prevalence of some virulence factors and genotyping of hospital-acquired uropathogenic Escherichia coli isolates recovered from cancer patients.
This study aimed to determine the prevalence of virulence factors among uropathogenic Escherichia coli (UPEC) isolates from cancer patients and to investigate their genetic diversity using ERIC-PCR. A total of 42 E. coli were recovered from urine samples from cancer patients admitted to Assiut University Hospital. PCR was used to detect the presence of three virulence genes (papC, iutA and cnf1). Genetic diversity of the isolates was determined using the ERIC-PCR fingerprinting method, and amplified products were separated by agarose gel electrophoresis. Gel electrophoresis banding patterns were used for dendrogram generation using NTSYSpc software. Among the 42 UPEC isolates, papC was the most common virulence gene (55% of isolates), followed by iutA (38%) and cnf1 (2%). ERIC-PCR successfully produced multiple amplicons (range 2-11 bands) in each strain, with molecular weights ranging from 285 to 3000 bp. Some UPEC isolates had identical ERIC-PCR profiles (identical banding patterns), whilst 22 UPEC isolates had different ERIC-PCR profiles. The phylogenetic dendrogram of ERIC-PCR showed that the 42 isolates can be differentiated into three major clusters (I, II and III), with cluster I representing 76% of isolates, cluster II representing 19% and cluster III representing 5%. The results of this study suggest that both papC and iutA genes may have an important role in the pathogenesis of overt urinary tract infection. Dendrogram analysis of the ERIC-PCR profiles revealed that all UPEC isolates were assigned into three main clusters, indicating the spread of distinct clonal groups that are responsible for hospital-acquired infections.


A novel two-stage MBR denitrification process for the treatment of high strength pet food wastewater.
A novel paradigm using pre-denitrification process is presented to optimize an existing system of two-stage MBRs treating high strength pet food wastewater. Successive reduction of organics in the 1st stage and almost complete nitrification in the 2nd stage generated effluent meeting stringent surface discharge criteria i.e. BOD5, TSS and NH4+ -N of < 10 mg/L at an overall HRT of 6.3 days. Pre-anoxic zone was created by a submerged coil in the path of influent to the 1st stage. Final effluent and the 1st stage mixed liquor were recirculated to the coil. With prevailing high denitrification rates, more than 94% of the recirculated nitrates were denitrified in less than 15 min of effective anoxic residence time. At a recycle ratio of 3:1, total nitrogen was reduced by 84%, aeration energy by 25% and the external alkalinity requirement by 65%, enhancing economical viability of the system.


Comparison of opportunities to respond and generation effect as potential causal mechanisms for incremental rehearsal with multiplication combinations.
Incremental rehearsal (IR) is an intervention with demonstrated effectiveness in increasing retention of information, yet little is known about how specific intervention components contribute to the intervention's effectiveness. The purpose of this study was to further the theoretical understanding of the intervention by comparing the effects of opportunities to respond (OTR) and generation demand on retention of multiplication combinations. Using a between subject 2 × 2 factorial design, 103 4th and 5th grade students were taught seven multiplication combinations using one of four versions of IR that orthogonally varied OTR (high versus low) and generation demands (high versus low). A two-way ANOVA revealed main effects for OTR, generation demands, and an interaction of the two factors. The effect of generation demands was large (d=1.31), whereas the overall effect of OTR was moderate (d=0.66). Critically, the two factors interacted, with the largest learning gains observed when OTR and generation demands were both high. The results of this study suggest that generation demand is an important factor in the effectiveness of rehearsal interventions.


An improved procedure for separation/purification of boron from complex matrices and high-precision measurement of boron isotopes by positive thermal ionization and multicollector inductively coupled plasma mass spectrometry.
In order to eliminate boron loss and potential isotopic fractionation during chemical pretreatment of natural samples with complex matrices, a three-column ion-exchange separation/purification procedure has been modified, which ensures more than 98% recovery of boron from each step for a wide range of sample matrices, and is applicable for boron isotope analysis by both TIMS and MC-ICP-MS. The PTIMS-Cs2BO2(+)-static double collection method was developed, ensuring simultaneous collection of (133)Cs2(11)B(16)O2(+)(m/z 309) and (133)Cs2(10)B(16)O2(+) (m/z 308) ions in adjacent H3-H4 Faraday cups with typical zoom optics parameters (Focus Quad: 15 V, Dispersion Quad: -85 V). The external reproducibilities of the measured (11)B/(10)B ratios of the NIST 951 boron standard solutions of 1000 ng, 100 ng and 10 ng of boron by PTIMS method are ±0.06‰, ±0.16‰ and ±0.25‰, respectively, which indicates excellent precision can be achieved for boron isotope measurement at nanogram level boron in natural samples. An on-peak zero blank correction procedure was employed to correct the residual boron signals effect in MC-ICP-MS, which gives consistent δ(11)B values with a mean of 39.66±0.35‰ for seawater in the whole range of boron content from 5 ppb to 200 ppb, ensuring accurate boron isotope analysis in few ppb boron. With the improved protocol, consistent results between TIMS and MC-ICP-MS data were obtained in typical geological materials within a wide span of δ(11)B values ranging from -25‰ to +40‰.


Investigations on purine and pyrimidine bases stacking associations in aqueous solutions by the fluorescence quenching method. II. Heteroassociation between 2-aminopurine and thymidine.
Heteroassociation between A and B compounds in liquid solution was considered. Provided that concentration of A molecules is low, a general equation describing fluorescence quantum yield and lifetime of compound A as a function of B molecules concentration was derived. The heteroassociation between 2-aminopurine and thymidine in aqueous solutions was examined within the range of temperatures 0 to 90 degrees C. The equilibrium constants of the first step of association, namely heterodimer formation, were determined and its thermodynamic parameters (deltaH equals - 2.76 kcal/mol, deltaS equals - 5.9 e.u.) were calculated. The observed changes of the stacking rate constants with temperature confirm the two-step mechanism of the reaction. The activation energy (approximately 10.7 angstroms) are only slightly larger than in the case of 2-aminopurine autoassociation, most probably because of a stronger solvation of thymidine molecules.


Consensus on Integrated Care for Older People Among Dutch Experts: A Delphi Study.
In a previous rapid realist review (RRR), an initial programme theory (PT) was established giving insight into the interrelatedness of context items, mechanisms, programme-activities, and outcomes that influence integrated care programmes (ICPs) for community-dwelling frail older people. As ICPs need to be tailored to their local setting, the objective of this study is to assess consensus on the relevance of the items identified in the RRR for the Dutch setting, and refine the PT, where appropriate. A two-round e-Delphi study was carried out among Dutch experts to determine the relevance of 71 items. Consensus on relevance was reached on 57 out of 71 items (80%). Items added to refine the PT included: increasing number of older people, decreasing access to hospital beds, well-designed ICP implementation processes, case management, having a clear portfolio of patients, the role of the government, aligning existing health and social care systems, management and monitoring of care activities, strong relationship between older person and healthcare providers (HCP), and providing continuous feedback to HCPs. The initial PT was refined for the Dutch setting. Items on which no consensus was found, need to be further investigated on the reason behind it.


Neck Circumference as a Predictor of Adiposity among Healthy and Obese Children.
Obesity, particularly in the upper part of body, is a major health problem. Because body mass index (BMI) does not adequately describe regional adiposity, other indices of body fatness are being explored. To determine if neck circumference is a valid measure of adiposity (fat distribution) among group of Egyptian children. This is a cross sectional study, included 50 obese subjects, aged 7 - 12 years recruited from Endocrine, obesity and Metabolism Pediatric Unit at Children Hospital, Cairo University and 50 healthy children, age and sex matched. All children were subjected to blood pressure assessment (systolic SBP and diastolic DBP), and anthropometric assessment (body weight, height, neck circumference (NC), waist (WC) and hip (HC) circumferences, and skin fold thicknesses at three sites: biceps, triceps and sub scapular. BMI [weight (kg)/height (m2)] was calculated. In healthy females, significant associations were detected between NC and SBP, DBP and all anthropometric measurements. However, in healthy males NC was not significantly associated with BMI, SBP and DBP. In the obese group; both sexes; insignificant association was found between NC and SBP, DBP, BMI and skinfold thickness. NC is related to fat distribution among normal healthy female children. However, this relation disappears with increasing adiposity. The results do not support the use of NC as a useful screening tool for childhood obesity.


Antibodies against AT1-receptor in transplantation (diagnostics, treatment, clinical relevance).
The influence of ATR-1-autoantibodies on antibody mediated rejection (AMR) is still discussed controversially. Here we demonstrate some aspects as to diagnostics, treatment, clinical relevance and graft outcome. A total of 27 transplant recipients (6 heart, 16 kidney, 3 lung and 2 multi-organ) suffering from AMR and a control group without transplant (8 pre-Tx, 1 pregnancy and 16 autoimmune and haematological diseases) were studied. In total, 290 IA eluates and the corresponding patient serum samples before and after immunoadsorption (IA) were analysed. ATR-1-and ETR-auto-antibodies (aAB) were found only in 4.5% of sera previous to IA treatment by using ELISA, but could be detected in 42% of IA eluates. AB with very high titres (>1:8 to 1:256) in the eluate were found more frequently in heart than in kidney recipients. These strong aAB are clinically relevant and cause dysfunction or loss of the grafts. A quick and reliable diagnosis of the aAB is essential for successful application of the therapeutic possibilities, like removal of the pathogenic autoantibodies or the blockage of their actions. The use of eluates for antibody detection was more sensitive and more reliable than patient serum. Yet, the test results are only meaningful when AB titres are measured, as this allows for a quick statement about the actual antibody elimination. The removal of pathogenic aAB via IA is better than medication-based treatment.


Prediction of Oxygen Evolution Activity for NiCoFe Oxide Catalysts via Machine Learning.
Transition metal (such as Fe, Co, and Ni) oxides are excellent systems in the oxygen evolution reaction (OER) for the development of non-noble-metal-based catalysts. However, direct experimental evidence and the physical mechanism of a quantitative relationship between physical factors and oxygen evolution activity are still lacking, which makes it difficult to theoretically and accurately predict the oxygen evolution activity. In this work, a data-driven method for the prediction of overpotential (OP) for (Ni-Fe-Co)O x catalysts is proposed via machine learning. The physical features that are more related to the OP for the OER have been constructed and analyzed. The random forest regression model works exceedingly well on OP prediction with a mean relative error of 1.20%. The features based on first ionization energies (FIEs) and outermost d-orbital electron numbers (DEs) are the principal factors and their variances (δFIE and δDE) exhibit a linearly decreasing correlation with OP, which gives direct guidance for an OP-oriented component design. This method provides novel and promising insights for the prediction of oxygen evolution activity and physical factor analysis in (Ni-Fe-Co)O x catalysts.