A live attenuated equine H3N8 influenza vaccine is highly immunogenic and efficacious in mice and ferrets.
Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81 ca vaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81 ca vaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81 ca vaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans. Equine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and protected mice and ferrets against homologous and heterologous EIV.


Donation After the Circulatory Determination of Death: Some Responses to Recent Criticisms.
This article defends the criterion of permanence as a valid criterion for declaring death against some well-known recent objections. We argue that it is reasonable to adopt the criterion of permanence for declaring death, given how difficult it is to know when the point of irreversibility is actually reached. We claim that this point applies in all contexts, including the donation after circulatory determination of death context. We also examine some of the potentially unpalatable ramifications, for current death declaration practices, of adopting the irreversibility criterion.


Well-Being During Recession in the UK.
This article explores the impact of the recent recession on the well-being of the UK working age population by comparing two measures of well-being. One is a measure of evaluative subjective well-being, a measure which previous research has shown to be stable in the UK throughout the economic crisis. The second is a different but complementary measure of positive psychological health. By comparing the trajectories of these two measures using the same sample and modelling techniques the analysis examines how different measures may lead to different interpretations. Six waves of longitudinal data from Understanding Society and the British Household Panel Survey (BHPS) are used. Latent curve models are used to analyse change over time. The results corroborate previous research showing that people's evaluative subjective well-being remained relatively stable, on average, throughout the economic crisis. In contrast, the positive psychological health measure was found to decline significantly during the recession period. The paper highlights that what we measure matters. Using single measures as summaries of well-being masks the complexity of the term, and given their appeal in the social policy arena, single measures of well-being can be seen as problematic in some scenarios.


Puromycin aminonucleoside-induced podocyte injury is ameliorated by the Smad3 inhibitor SIS3.
Smad3 signaling and transgelin expression are often activated during puromycin aminonucleoside (PAN)-induced podocyte injury. Here, we investigated whether the Smad3 inhibitor SIS3 can ameliorate damage to injured podocytes. A model of PAN-induced podocyte injury was constructed using the MPC5 cell line. The effects of SIS3 on the expression of the podocyte cytoskeletal proteins transgelin, p15INK4B , phosphor-smad3, phosphor-JAK/stat3, the apoptotic marker cleaved caspase 3, and c-myc were investigated using western blot. The distribution of F-actin in PAN-induced podocyte injury was observed under an immunofluorescence microscope. PAN-induced podocyte injury altered the distribution of F-actin and transgelin, and colocalization of these two proteins was observed. Transgelin expression and Smad3 phosphorylation were increased in the MPC5 cell line with prolonged PAN treatment. In addition, c-myc expression, p15INK4B , and JAK phosphorylation were all increased after treatment with PAN. Treatment with the Smad3 inhibitor SIS3 reversed these phenomena and protected against PAN-induced podocyte injury. Moreover, stimulating podocytes directly with TGFβ-1 also led to enhanced expression of transgelin or phosphor-JAK/stat3, and this could be inhibited by SIS3. In conclusion, transgelin expression was induced through the Smad3 signaling pathway during PAN-induced podocyte injury, and the resulting abnormal distribution of F-actin and the enhanced expression of transgelin could be reversed by blockade of this pathway.


Homocoupling of benzyl pyridyl ethers via visible light-mediated deoxygenation.
The photocatalytic coupling of ethers is uncommon because of the challenges in breaking C-O bonds and low selectivity. Herein, we report a visible light-mediated deoxygenation homocoupling of benzyl pyridyl ethers via their pyridium salts. This approach enables C(sp3)-O bond homolysis under mild conditions. Mechanistic experiments support the radical nature of the reaction. This method is highly compatible with electron-withdrawing groups and has potential applications for drug precursor synthesis.


Ecologic study of water hardness and cerebrovascular mortality in Japan.
Elevated levels of water hardness have been associated with reduced mortality from cardiovascular and cerebrovascular diseases. In this ecologic study, the authors examined the relationship between water hardness and cerebrovascular mortality in the 44 municipalities of Osaka Prefecture, Japan. Data on cerebrovascular death rates and water hardness in each municipality were obtained from public records; information on socioeconomic and health-care status in each municipality was incorporated with multiple logistic-regression analysis. The authors were unable to substantiate an inverse association of water hardness with cerebrovascular mortality--although the adjusted odds ratio in which the highest vs. lowest tertiles of water hardness were compared was 0.90 (95% confidence interval = 0.79, 1.02) in females. In addition, the difference between the sexes was not significant. In summary, the authors found no evidence that water hardness protected against cerebrovascular mortality.


Combating multidrug resistance in bacterial infection by targeting functional proteome with natural products.
Antibiotic resistance has become a major clinical and public health problem within the lifetime of most people living today. Development of new therapeutic approaches to prevent antimicrobial chemotherapy from bacterial multidrug resistance has thus been becoming a primary consideration in the medicinal community. In this study, we describe a protocol that is potential for combating multidrug resistance by rational screening of natural medicines to target the bacterial functional proteome. To achieve this, a pipeline of integrating virtual screening and susceptibility testing has been described to identify antibacterial agents from various natural products with diverse structures and high drug-likeness. A number of promising candidates with potent antibacterial activity were identified, from which six available compounds were assayed to determine their susceptibility to four multidrug-resistant strains. Consequently, while most tested candidates showed moderate (20 < MIC < 50 μg/mL) or low (MIC>50 μg/mL) antibacterial activities, two natural products, i.e. pseudopterosin A and ciprofloxacin, were measured to possess strong broad-spectrum potency combating different strains (MIC < 20 μg/mL).


Acute Hypoxia From Different Clinical Entities Can Potentially Break the Heart: Takotsubo Cardiomyopathy.
Takotsubo syndrome is characterized by transient regional left ventricular wall motion abnormalities and elevated troponin levels like those seen in classic myocardial infarction but without evidence of obstructive coronary artery disease. We present two uncommon cases of Takotsubo syndrome. In Case 1, a 64-year-old man presented with chronic obstructive pulmonary disease exacerbation who later developed chest pain and acute hypoxic respiratory failure. In Case 2, a 77-year-old woman with myasthenia gravis was admitted for acute hypoxic hypercapnic respiratory failure requiring mechanical ventilation following a myasthenic crisis. In both cases, serum high sensitivity troponin was elevated, electrocardiograph showed findings suggestive of infarction, and coronary angiogram did not show evidence of obstructive coronary artery disease. Echocardiogram in both patients revealed abnormal left ventricular wall motion, likely secondary to Takotsubo syndrome. Takotsubo syndrome is uncommon in the setting of chronic obstructive pulmonary disease exacerbation or myasthenic crisis, and proposed mechanisms for the disease include catecholamine surge, vasospasm of coronary arteries, and microvascular dysfunction. Takotsubo syndrome is reversible; thus, it is important to remove any trigger leading to catecholamine surge. Identification of such triggers and early diagnosis could help optimize pharmacotherapy.


Chromosomal Distribution of Ankylosing Spondylitis Susceptibility Loci.
Previous studies have been indicated that susceptible loci of several multifactorial diseases were non-randomly distributed on human genome. There is no published data on chromosomal distribution of genes associated with risk of ankylosing spondylitis. Therefore, the present study was carried out. Published meta-analyses indexed in the PubMed database were used in the present study. Non-randomness chromosomal distribution of these loci was evaluated by the statistical method of Tai et al. A total of 88 articles were obtained. There was 32 ankylosing spondylitis associated genes. The present study revealed that the human chromosome segments 6p11.2-p21.33, 19q13.2-q13.42, and 2q11.2-q14.1 were ankylosing spondylitis associated-rich regions by bearing 7, 6 and 4 susceptible loci, respectively. Ankylosing spondylitis associated-genes non-randomly have been distributed non-randomly on human chromosomes.


[Effects of water hardness and salt intake on the formation and disappearance of experimental atherosclerosis].
The present study examined the effects of water-hardness and salt-intake, both of which were higher in north China than in the south, on experimental atherosclerosis in quail. At the end of the experiment atherosclerotic lesions in the high-salt groups were found to be more marked than those in the low-salt groups. No significant difference in total cholesterol value was found between the two groups. There was a significant positive correlation between the degree of atherosclerosis and serum-sodium value (r = 0.501, P < 0.01). There was no difference in all values between hard-water or soft-water groups. Our study suggested that high salt-intake stimulated and enhanced the formation of atherosclerosis while it delayed and impeded its disappearance, but water-hardness did not.


Multi-Fresnel lenses pumping approach for improving high-power Nd:YAG solar laser beam quality.
To significantly improve the present-day high-power solar laser beam quality, a three-stage multi-Fresnel lenses approach is proposed for side-pumping either a Nd:YAG single-crystal or a core-doped Sm(3+)Nd:YAG ceramic rod. Optimum pumping and laser beam parameters are found through ZEMAX and LASCAD numerical analysis. The proposed scheme offers a uniform absorption profile along the rod. 167 W laser power can be achieved, corresponding to 29.3 W/m(2) collection efficiency. High brightness figure of merit of 8.34 W is expected for the core-doped rod within a convex-concave resonator, which is 1300 times higher than that of the most-recent high-power solar laser.


The Power of Massage in Children with Cancer-How Can We Do Effective Research?
Children with cancer experience multiple troubling symptoms. Massage offers a safe, non-pharmacological approach to address these symptoms. Numerous studies of massage in children and adults with cancer have been performed, yet most are unable to demonstrate significant benefit. This review aims to summarize what we know about the role of massage and sets goals and challenges for future massage research. This paper descriptively reviews the existing literature available in PubMed (both prior reviews and select papers) and the holes in prior research studies. Prior research on massage has been limited by small sample size/insufficient power, inappropriate outcome measures or timing, heterogeneous patient populations, inconsistent intervention techniques, and other design flaws. Based on the findings and limitations of previous work, numerous suggestions are made for future studies to increase the potency of findings, including thoughts about appropriate dosing, control groups, type of intervention, outcome measures, patient selection, feasibility, and statistics.


BACE1 Translation: At the Crossroads Between Alzheimer's Disease Neurodegeneration and Memory Consolidation.
Human life unfolds not only in time and space, but also in the recollection and interweaving of memories. Therefore, individual human identity depends fully on a proper access to the autobiographical memory. Such access is hindered under pathological conditions such as Alzheimer's disease, which affects millions of people worldwide. Unfortunately, no effective cure exists to prevent this disorder, the impact of which will rise alarmingly within the next decades. While Alzheimer's disease is largely considered to be the outcome of amyloid-β (Aβ) peptide accumulation in the brain, conceiving this complex disorder strictly as the result of Aβ-neurotoxicity is perhaps a too straight-line simplification. Instead, complementary to this view, the tableau of molecular disarrangements in the Alzheimer's disease brain may be reflecting, at least in part, a loss of function phenotype in memory processing. Here we take BACE1 translation and degradation as a gateway to study molecular mechanisms putatively involved in the transition between memory and neurodegeneration. BACE1 participates in the excision of Aβ-peptide from its precursor holoprotein, but plays a role in synaptic plasticity too. Its translation is governed by eIF2α phosphorylation: a hub integrating cellular responses to stress, but also a critical switch in memory consolidation. Paralleling these dualities, the eIF2α-kinase HRI has been shown to be a nitric oxide-dependent physiological activator of hippocampal BACE1 translation. Finally, beholding BACE1 as a representative protease active in the CNS, we venture a new perspective on the cellular basis of memory, which may incorporate neurodegeneration in itself as a drift in memory consolidating systems.


Rab25 Small GTPase Mediates Secretion of Tumor Necrosis Factor Receptor Superfamily Member 11b (osteoprotegerin) Protecting Cancer Cells from Effects of TRAIL.
Expression of Rab25, which is located in the 1q amplicon present at high frequency in many cancer lineages, promotes cancer cell survival under multiple stress conditions. While Rab proteins play essential roles in all stages of vesicle trafficking, the functions and endogenous cargoes for Rab25 remain to be fully elucidated. Osteoprotegerin (OPG) is a secreted glycoprotein that binds the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) thus preventing it from activating the TNF-family death receptors. In the present study, we demonstrated that Rab25 regulates OPG at both the transcription and secretion level. The effect of Rab25 on OPG expression and its effect on TRAIL-induced cell were examined in both ovarian and breast cells. Signal transduction pathways regulation of OPG expression was examined in cells using pharmacogenetic approaches. Expression of Rab25 to levels similar to those in tumors with RAB25 amplification, increased OPG mRNA expression and secretion from ovarian and breast cancer cell lines, whereas down regulation with Rab25 specific siRNA decreased OPG secretion and sensitized cells to TRAIL-induced cell death. Critically, exogenous OPG mimicked the effects of Rab25 on cell death supporting the contention that Rab25-induced accumulation of OPG protects cancer cells from the effects of TRAIL. Rab25 cooperates with EGFR-mediated MAPK signaling to increase TRAIL production and release. Importantly, priming cells with EGFR inhibitors increased sensitivity to TRAIL-induced cells death regardless of the Rab25 background. Increased OPG expression induced by Rab25 may provide a mechanistic advantage for cancer development and progression.


Systemic Mastocytosis Complicated by Non-Cirrhotic Portal Hypertension and Variceal Bleeding.
Systemic mastocytosis is a myeloproliferative disorder characterized by extracutaneous involvement of at least one organ. Although rare, infiltration of inflammatory mast cells within the portal vein may lead to obstruction of the sinusoids resulting in non-cirrhotic portal hypertension. We present a patient with known history of systemic mastocytosis with bone marrow involvement presenting with new-onset esophageal variceal bleeding. Although systemic mastocytosis is uncommon, the subsequent development of hepatic involvement and non-cirrhotic portal hypertension are discussed. Further highlighted is a lack of organization guidelines and the potential for gastrointestinal and hepatic screening of mastocytosis patients with known extracutaneous involvement.


[Use of allogenic cartilage in reconstruction of the middle ear in patients with chronic otitis media].
We have analysed results treatment of 253 patients with chronic otitis media. Our tactic includes operation with application one-momental sanation and reconstruction of a middle ear. Sanational stage was performed in volume atticoantrotomia or radical operation. Reconstruction included reconstruction of a tympanic cavity and retrotympanic space. The shape of a plate was made so that to make a base for neotympanic membrane and to forma a lateral attic wall. Defect of a drum-type membrane restored free flap of a fascia temporal muscle. The mastoid process cavity was filled allogenic cartilage transplants the first variant of reconstruction formed artificial antrum cartilage by fragments and plates. At the second variant was acted similarly, however the artificial cavity wall of the antrum we made soft and mobile from the skin of external acoustical passage and neotympanic fascia flap. In postoperative period the position of a posterior wall of external acoustical passage was formed depending on intratympanic pressure, which depended on a acoustical tube function. Such technique allowed us to reduce formation retraction complications from 15% up to 6.7%.


Cost-effectiveness of Inpatient Tympanostomy Prophylaxis.
Tympanostomy is the most common pediatric ambulatory surgery. Post-tympanostomy otorrhea is a prevalent complication leading to high costs to patients for treatment. The cost-effectiveness of intraoperative prophylaxis for both patient and institution has not been examined. An analytical observational study of data collected from the literature and purchasing records. A break-even analysis was performed to determine the required absolute risk reduction (ARR) and final infection rate in post-tympanostomy otorrhea to make intraoperative prophylaxis using ofloxacin and ciprofloxacin dexamethasone otic version cost effective with the following outpatient treatments: ofloxacin, ciprofloxacin-dexamethasone ophthalmic version, and ciprofloxacin-dexamethasone otic version. Absolute risk reduction is a statistic used to express the difference in risk between a treatment and control. The conservative initial infection rate used was 10%. Ofloxacin intraoperative prophylaxis was not cost effective when prescribing ofloxacin outpatient treatment with an ARR of 0.20. Ofloxacin intraoperative prophylaxis was cost-effective with an ARR of 0.08 for ciprofloxacin-dexamethasone ophthalmic version outpatient treatment. Ofloxacin intraoperative prophylaxis was cost-effective for ciprofloxacin-dexamethasone otic version outpatient treatment with an ARR of 0.01.Ciprofloxacin-dexamethasone intraoperative prophylaxis was not cost-effective when prescribing ofloxacin outpatient treatment with an ARR of 1.52. Ciprofloxacin-dexamethasone intraoperative prophylaxis was not cost-effective when prescribing ciprofloxacin-dexamethasone ophthalmic version outpatient treatment with an ARR of 0.60. Ciprofloxacin-dexamethasone intraoperative prophylaxis was cost effective when prescribing ciprofloxacin-dexamethasone otic version outpatient treatment with an ARR of 0.09. Intraoperative prophylaxis can be cost effective for preventing post-tympanostomy otorrhea. Physicians can use this economic model to determine the cost-effectiveness of these interventions for their patients and institutions.


Use of ketorolac and fentanyl during outpatient gynecologic surgery.
In healthy outpatients undergoing minor gynecologic surgery, the analgesic efficacy of ketorolac was compared to fentanyl and to a combination of the two analgesics. One hundred and nine patients were randomly selected to receive fentanyl 50-100 micrograms, ketorolac 30-60 mg, or a combination of fentanyl 50-100 micrograms and ketorolac 30-60 mg, intravenously (IV). Anesthesia was induced with midazolam 2 mg IV and propofol 1 mg/kg, IV, and maintained with propofol, 50-160 micrograms.kg-1.min-1, IV, and nitrous oxide 67% in oxygen via a face mask. Intraoperative anesthetic conditions, recovery times, and postoperative pain and side effects were evaluated. In the ketorolac group, 75% of patients required supplemental fentanyl intraoperatively (mean dose +/- SD, 47 +/- 54 micrograms), compared to only 19% (13 +/- 30 micrograms) and 18% (6 +/- 15 micrograms) of patients in the fentanyl and combination groups, respectively. In the ketorolac group, 74% of patients moved in response to surgical stimulation compared to only 16% and 19% of patients in the fentanyl and combination groups, respectively. Although there were no significant differences in intraoperative mean arterial pressure, heart rate, and oxygen saturation of hemoglobin values among the three treatment groups, the ketorolac group manifested significantly more rapid respiratory rates throughout the procedure compared with the fentanyl and combination groups. Recovery times, postoperative side effects, and pain scores, as well as postoperative analgesic and antiemetic requirements, were similar in all three treatment groups. However, the ketorolac group reported significantly higher pain scores in the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnosis of intrauterine growth restriction: comparison of ultrasound parameters.
The objective of this study is an attempt to evaluate the best ultrasonic method of diagnosing intrauterine growth restriction (IUGR); a retrospective study of patients with singleton pregnancies who had been scanned at the author's institution within 2 weeks of their delivery was undertaken. Estimated fetal weight, abdominal circumference, head circumference/abdominal circumference ratio, abdominal circumference/femur length ratio, and umbilical artery S/D ratio were compared for accuracy in prediction IUGR in the neonate using both univariant and multivariant statistical analysis. Five hundred one (501) patients were analyzed. One hundred fourteen (114) neonates were classified as IUGR (22.8%). Doppler evaluation of the umbilical artery showed the best sensitivity while both abdominal circumference alone and estimated fetal weight showed similar specificity, positive and negative predictive value, and lowest false-positive and -negative results. Logistic regression analysis confirmed the univariant results and showed that, when used in combination, abdominal circumference and Doppler, or estimated fetal weight and Doppler resulted in the best predictive values. Either estimated fetal weight or abdominal circumference (alone) are accurate predictors of IUGR. Combined with Doppler studies of the umbilical artery either method will provide accurate evaluation of suspected IUGR.


[A case of primary signet ring cell carcinoma of the urinary bladder presenting as nocturnal incontinence].
This is a report of our experience of a case of primary signet ring cell carcinoma of the urinary bladder. The patient was a 56-year-old man who was referred to our hospital presenting with incontinence and lumbago. A drip infusion pyelography study indicated bilateral hydronephrosis and a contracted bladder. Signet ring cell carcinoma was observed in the bladder submucosa after the second transurethral biopsy set. No other cancer lesions could be identified even after careful examination. Therefore, it was diagnosed as a primary signet ring cell carcinoma of the bladder. Total cystectomy with bilateral uretero-cutaneostomy reconstruction was performed. The pathological stage was T4bN0M0 and the surgical margin was positive at the site of the pubic bone. Adjuvant therapy was not given. There was no evidence of disease 20 months after the operation. In Japan, this is the third case of primary signet ring cell carcinoma of the bladder presenting as incontinence.


Calibration methods in respiratory calorimetry.
Methods for calibration of respiratory gas exchange measurement systems are evaluated. A new method is described in which O2 is removed from the subject chamber or gas stream and measured gravimetrically in a small combustion chamber containing steel wool. The "Fe-burner" method was tested by comparison with the N2-injection method and found to be of similar accuracy. The new method is easy to perform, quick, and readily applicable to both open- and closed-circuit respiratory systems. It has a rate of O2 uptake that can be adjusted to be similar to the rate by an experimental subject (10-600 kg). Complete calibration of open- and closed-circuit indirect calorimetric systems can be achieved when the Fe-burner method, involving measurement of O2 uptake, is combined with the gravimetric injection of specific gases (CO2, methane) produced by the subject.


Pleural mesothelioma: sensitivity and incidence of needle track seeding after image-guided biopsy versus surgical biopsy.
To retrospectively compare the sensitivity of image-guided core-needle biopsy, thoracoscopy, and thoracotomy in the diagnosis of malignant pleural mesothelioma and to retrospectively determine the incidence of needle track seeding after these procedures. Institutional review board approval was obtained, and informed consent was not required. The study included 100 consecutive patients (81 men, 19 women; average age, 65.8 years) with pathologically proved malignant pleural mesothelioma who were treated between 1994 and 2002. A total of 23 core-needle biopsies were performed in 22 patients, and 11 of these biopsies were coupled with fine-needle aspiration biopsy. A coaxial technique was used, and biopsy was performed with fluoroscopic (12 biopsies), computed tomographic (10 biopsies), or ultrasonographic (one biopsy) guidance. Sixty-nine patients underwent surgical biopsy in the form of thoracoscopy (n = 51) and/or thoracotomy (n = 21). Patients were followed up clinically for any evidence of needle track seeding after image-guided or surgical procedures. The sensitivity of diagnostic procedures and the incidence of needle track seeding as a result of intervention were calculated. Sensitivity was 86% for image-guided core-needle biopsy, 94% for thoracoscopy, and 100% for thoracotomy. The incidence of needle track seeding was 4% for image-guided core-needle biopsy and 22% for surgical biopsy. Image-guided core-needle biopsy in patients with malignant pleural mesothelioma has a lower incidence of needle track seeding than surgical biopsy and has a high sensitivity for diagnosis.


Rationale and design of the FreezeAF trial: a randomized controlled noninferiority trial comparing isolation of the pulmonary veins with the cryoballoon catheter versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation.
Atrial fibrillation is the most commonly encountered clinical arrhythmia, and there are an increasing number of patients with paroxysmal atrial fibrillation treated by catheter ablation. The criterion standard is the isolation of the pulmonary veins (PVs) using radiofrequency (RF) energy in combination with an open irrigated tip catheter. The procedure remains technically challenging with a significant number of complications. So far, no randomized comparisons between the outcome of cryoballoon versus RF ablation are available. The object of this randomized clinical trial is to compare the efficacy of isolating the PVs with either the cryoballoon or the open irrigated tip RF catheter. Two hundred forty-four patients with paroxysmal atrial fibrillation will be randomized for either RF or cryoballoon. With both techniques, PV isolation will be performed. Primary end point of the study is freedom from atrial fibrillation without antiarrhythmic drugs and without persistent complications at 6 and 12 months. Clinical success will be evaluated using Holter electrocardiogram and event recordings for at least 7 days. Within 6 months, no redo procedure is performed; and a redo after 6 months is performed with the previously used energy source. Secondary end points include the mid- and long-term clinical success, procedural data, and cost-effectiveness. The FreezeAF trial will examine for the first time in a randomized trial whether PV isolation with the cryoballoon is not relevantly inferior to open irrigated RF ablation in patients with paroxysmal atrial fibrillation during follow-up. It will additionally directly compare acute procedural success and safety of the procedures.


Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex.
The aim of this study was to assess the effects of prenatal exposures to cannabinoids or carbon monoxide (CO) in an animal experimental model reproducing the environmental conditions in which a fetus develops whose mother, during pregnancy, ingests by smoking low doses of cannabinoids or CO. Particular attention was devoted to analyses of the long-term effects of the exposures at the level of the cerebellar cortex, where already during prenatal development the GABAergic neuronal systems may be modulated by both cannabinoids and CO. Three groups of rats were subjected to the following experimental conditions: exposure to cannabinoids by maternal treatment during pregnancy with the cannabinoid CB-1 receptor agonist WIN 55212-2 (WIN) (0.5 mg/kg/day, s.c.); exposure to CO by maternal exposure during pregnancy to CO (75 parts per million, by inhalation); and exposure to WIN+CO at the above doses and means of administration; a fourth group was used as control. The body weight of dams, length of pregnancy, litter size at birth, body weight and postnatal mortality of pups were monitored in order to evaluate possible effects of the exposures on reproduction and on prenatal and postnatal development. In the different groups, the long-term effects of the exposures were studied in adult rats (120-150 days) by light microscopy analyses of the structure of the cerebellar cortex and of the distribution in the cortex of markers of GABAergic neurons, such as GAD and GABA itself. Results. Exposures to WIN or CO did not affect reproduction or prenatal/postnatal development. Moreover, the exposed rats showed no structural alterations of the cerebellar cortex and displayed qualitative distribution patterns of GAD and GABA immunoreactivities similar to those of the controls. However, quantitative analyses indicated significant changes of both of these immunoreactivities: in comparison with the controls, they were significantly increased in WIN-exposed rats and reduced in CO-exposed rats, but not significantly different in WIN+CO-exposed rats. The changes were detected in the molecular and Purkinje neuron layers, but not in the granular layer. Prenatal exposures of rats to WIN or CO, at doses that do not affect reproduction, general processes of development and histomorphogenesis of the cerebellar cortex, cause significant changes of GAD and GABA immunoreactivities in some GABAergic neuronal systems of the adult rat cerebellar cortex, indicating selective up-regulation of GABA-mediated neurotransmission as a long-term consequence of chronic prenatal exposures to cannabinoids or CO. Because the changes consist of overexpression or, vice versa, underexpression of these immunoreactivities, functional alterations of opposite types in the GABAergic systems of the cerebellum following exposure to WIN or CO can be postulated, in agreement with the results of behavioral and clinical studies. No changes in immunoreactivities were detected after prenatal exposure to WIN and CO in association.


Behavior of rate coefficients for ion-ion mutual neutralization, 300-550 K.
Rate coefficients k(MN) have been measured for a number of anion neutralization reactions with Ar(+) and Kr(+) over the temperature range 300-550 K. For the first time, the data set includes anions of radicals and other short-lived species. In the present paper, we review these results and make note of correlations with reduced mass, electron binding energy of the anion (equivalent to the electron affinity of the corresponding neutral), and temperature, and compare with expectations from absorbing sphere models. An intriguing result is that the data for diatomic anions neutralized by Ar(+) and Kr(+) have k(MN) values close to 3 × 10(-8) cm(3) s(-1) at 300 K, a figure which is lower than those for all of the polyatomic anions at 300 K except for SF(5)(-) + Kr(+). For the polyatomic anions studied here, neutralized by Ar(+) and Kr(+), the reduced mass dependence agrees with theory, on average, but we find a stronger temperature dependence of T(-0.9) than expected from the theoretical E(-0.5) energy dependence of the rate coefficient at thermal energies. The k(MN) show a weak dependence on the electron binding energy of the anion for the polyatomic species studied.


The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.
North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.


A novel generalized ridge regression method for quantitative genetics.
As the molecular marker density grows, there is a strong need in both genome-wide association studies and genomic selection to fit models with a large number of parameters. Here we present a computationally efficient generalized ridge regression (RR) algorithm for situations in which the number of parameters largely exceeds the number of observations. The computationally demanding parts of the method depend mainly on the number of observations and not the number of parameters. The algorithm was implemented in the R package bigRR based on the previously developed package hglm. Using such an approach, a heteroscedastic effects model (HEM) was also developed, implemented, and tested. The efficiency for different data sizes were evaluated via simulation. The method was tested for a bacteria-hypersensitive trait in a publicly available Arabidopsis data set including 84 inbred lines and 216,130 SNPs. The computation of all the SNP effects required <10 sec using a single 2.7-GHz core. The advantage in run time makes permutation test feasible for such a whole-genome model, so that a genome-wide significance threshold can be obtained. HEM was found to be more robust than ordinary RR (a.k.a. SNP-best linear unbiased prediction) in terms of QTL mapping, because SNP-specific shrinkage was applied instead of a common shrinkage. The proposed algorithm was also assessed for genomic evaluation and was shown to give better predictions than ordinary RR.


A new colorimetric peptide nucleic acid-based assay for the specific detection of bacteria.
Developments on synthetic molecules, such as peptide nucleic acid (PNA), make FISH procedures more robust for microbial identification. Fluorochromes use might hinder a broader implementation of PNA-FISH, but colorimetric applications are inexistent so far. A biotin-labeled eubacteria probe was used to develop a colorimetric PNA-in situ hybridization (ISH) assay. An enzymatic-conjugate, targeting biotin, was introduced. The procedure was optimized and evaluated regarding sensitivity, specificity and detection limit. RESULTS have shown strong ISH signals. The method was specific, but permeabilization problems were observed for Gram-positive bacteria. Detection limit was 5 × 10(7) CFU/ml, limiting current applications to pre-enriched samples. The PNA-ISH procedure described here is a simple alternative to other detection methods, and is also the base for the development of other PNA colorimetric systems.


Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an immunohistochemical study.
Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone macrophages (MOMA-1). All macrophages were negative for the scavenger receptor MARCO and 50% were positive for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for more than 70% CD4-positive. ICAM-1 was positive both in atherosclerotic and control mice. In early plaques, fibrosis was observed on the luminal and medial site of the foam cells while smooth muscle cells were only observed in the fibrous cap. To study regression, we used a high fat, high cholesterol diet to rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow. Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels dropped in 4 weeks to control levels. The animals did not show a significantly decrease in plaque size over time. but the percentage macrophages was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leiden mouse is a useful model to study the progression and regression of atherosclerosis.


Sorry to ask but … how is apology effectiveness dependent on apology content and gender?
While it is well understood that the content included in an apology matters, what constitutes an effective apology may differ depending on the gender of the person delivering it. In this article, we test competing theoretical perspectives (i.e., role congruity theory and expectancy violation theory [EVT]) about the relative effectiveness of apologies that include language that conforms (or not) with the gender stereotypes ascribed to the apologizer. Results of four studies supported an EVT perspective and showed that apologies were perceived to be relatively more effective when they contradicted gender stereotypes (i.e., communal [agentic] apologies by men [women]). Specifically, Study 1 provided an initial test of the competing hypotheses using celebrity apologies on Twitter. Then, results of three experiments (Studies 2, 3a, and 3b) built upon these initial findings and tested the psychological mechanisms proposed by EVT to explain why counterstereotypical apologies are beneficial (i.e., attributions of interpersonal sensitivity [assertiveness] and enhanced perceptions of benevolence [competence] for men [women]). Our contributions to theory and practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Effect of Hydraulic Retention Time on Anaerobic Digestion of Wheat Straw in the Semicontinuous Continuous Stirred-Tank Reactors.
Three semicontinuous continuous stirred-tank reactors (CSTR) operating at mesophilic conditions (35°C) were used to investigate the effect of hydraulic retention time (HRT) on anaerobic digestion of wheat straw. The results showed that the average biogas production with HRT of 20, 40, and 60 days was 46.8, 79.9, and 89.1 mL/g total solid as well as 55.2, 94.3, and 105.2 mL/g volatile solids, respectively. The methane content with HRT of 20 days, from 14.2% to 28.5%, was the lowest among the three reactors. The pH values with HRT of 40 and 60 days were in the acceptable range compared to that with HRT of 20 days. The propionate was dominant in the reactor with HRT of 20 days, inhibiting the activities of methanogens and causing the lower methane content in biogas. The degradation of cellulose, hemicellulose, and crystalline cellulose based on XRD was also strongly influenced by HRTs.


Women, families and the Provincial Hospital for the Insane, British Columbia, 1905-1915.
The article examines the role of the family in the lives of women in a turn-of-the-century psychiatric institution in British Columbia, Canada. The continued connection between institutionalized women and their families is highlighted. Evidence drawn from the psychiatric case files of 774 women patients at British Columbia's Provincial Hospital for the Insane show that families significantly influenced such factors of institutional life as the conditions of care, the timing of discharge and the possibility of readmission. Conclusions presented here underscore the negotiated and conflictual nature of asylum practice.


DNA-dependent RNA polymerase activities in hepatopancreas nuclei from Mytilus galloprovincialis Lamarck.
It has been shown that RNA synthesis in isolated hepatopancreas nuclei from Mytilus galloprovincialis is catalyzed by three DNA-dependent RNA polymerases (I, II and III) which resemble those identified in nuclei from mammalian cells. RNA polymerase I is active at 50 mM (NH4)2SO4, catalyzes the synthesis of GMP-rich ribosomal-like RNA and is completely resistant to the toadstool toxin alpha-amanitin. RNA polymerase II and III are active at higher (NH4)2SO4 concentrations, catalyze the synthesis of DNA-like RNA and are inhibited by very low (0.5-1 microgram/ml) and high (200 microgram/ml) concentrations of alpha-amanitin, respectively. Hepatopancreas nuclei retain considerable RNAase activity. Nuclear RNA polymerase activity may be underestimated since a part of the synthetized RNA is degraded.


A Wireless, Mechanically Flexible, 25μm-Thick, 65,536-Channel Subdural Surface Recording and Stimulating Microelectrode Array with Integrated Antennas.
This paper presents a fully wireless microelectrode array (MEA) system-on-chip (SoC) with 65,536 electrodes for non-penetrative cortical recording and stimulation, featuring a total sensing area of 6.8mm×7.4mm with a 26.5μm×29μm electrode pitch. Sensing, data telemetry, and powering are monolithically integrated on a single chip, which is made mechanically flexible to conform to the surface of the brain by substrate removal to a total thickness of 25μm allowing it to be contained entirely in the subdural space under the skull.


Bile acids regulate the ontogenic expression of ileal bile acid binding protein in the rat via the farnesoid X receptor.
In the rat, an increase in ileal bile acid binding protein (IBABP) expression occurs during the third postnatal week. In vitro studies suggest that bile acids (BAs) increase IBABP transcription by activating the BA receptor, farnesoid X receptor (FXR). Thus, we investigated the role of BAs on the ontogenic expression of IBABP and whether FXR may mediate these effects. Suckling rats were gavage-fed taurocholate for 3 days or were allowed to develop normally. Ileums were collected for Northern and Western blot analyses. Electrophoretic mobility shift assays for functional FXR were performed using nuclear extracts from ileums of both adult and developing rats. Taurocholate gavage significantly elevated IBABP messenger RNA and protein levels in suckling animals. Gelshift assays using adult ileal nuclear extracts incubated with a radiolabeled consensus inverted repeat-1 oligonucleotide (response element for FXR) revealed a high-molecular weight DNA/protein complex. Cold competition and supershift assays showed that this complex is sequence specific and confirmed that FXR is a component of the complex. Gelshift assays with nuclear extracts from rat ileum at different ages revealed absence of the DNA/protein complex in the second postnatal week when there is lack of IBABP expression and presence of these complexes at later ages when there is normally high expression. Western blot analyses showed FXR and its heterodimer partner, retinoid X receptor alpha, protein levels are low in the ileum during the suckling period and increase during the third postnatal week. BAs play a role in the normal developmental expression of IBABP through FXR activation, and decreased functional FXR in ileal nuclei during the suckling period may account, in part, for the lack of IBABP expression at this time.


Continuous nucleation of metallic nanoparticles via photocatalytic reduction.
Whether in organic synthesis or solar energy conversion, light can be a powerful reagent in chemical reactions and introduce new opportunities for synthetic control including duration, intensity, interval, and energy of irradiation. Here, we report the use of a molecular photosensitizer as a reducing agent in metallic nanoparticle syntheses. Using this approach, we report three key findings. (1) Nanoparticles produced by photocatalytic reduction form via a continuous nucleation mechanism, as opposed to burst and burst-like nucleation processes typically observed in metal nanoparticle syntheses. (2) Because nucleation is continuous, as long as the solution is irradiated (and there remains excess reagents in solution), nanoparticle nucleation can be turned on and off by controlling the timing and duration of irradiation, with no observable particle growth. (3) This synthetic method extends to the formation of bimetallic nanoparticles, which we show also form via a continuous nucleation pathway, and follow predicted patterns of metal incorporation as a function of the magnitude of the difference between the reduction potentials of the two metals. Taken together, these results establish a versatile synthetic method for the formation of multimetallic nanoparticles using visible light.


An EPR and optical absorption study of Cu(2+) doped in disodium malonate trihydrate single crystal.
Single crystals and powder electron paramagnetic resonance (EPR) studies of Cu(2+)-doped disodium malonate trihydrate [C(3)H(2)O(4)Na(2).3H(2)O] have been carried out at room temperature. The angular variation of the disodium malonate trihydrate single crystal have shown that two different Cu(2+) complexes are located in different chemical environments, and each environment contains one magnetically inequivalent Cu(2+) sites in distinct orientations occupying substitutional positions in the lattice and show very high angular dependence. The principal values of the g and the hyperfine tensors were determined and were found to be in agreement with the literature values. Crystal field around the Cu(2+) ion is nearly rhombic. The optical absorption studies show two bands at 603nm (16584cm(-1)) and 890nm (11236cm(-1)) which confirm the rhombic symmetry. The crystals field parameters and than the wave function are determined.


Identification of Jmjd1a as a STAT3 downstream gene in mES cells.
Mouse embryonic stem (mES) cells can be maintained in undifferentiated state in the presence of a cytokine, leukemia inhibitory factor (LIF). Many investigators found that STAT3 activation is important for the maintenance of pluripotency by LIF. However, the downstream pathways of STAT3 activation are still unknown. To look for STAT3-downstream target genes, we performed DD-RT PCR in the presence or absence of LIF. Through further confirmation, we finally selected 8 genes whose expressions were significantly dependent upon the presence of LIF. Among them, Jmjd1a was down-regulated after LIF withdrawal, and it was selected for further investigation. Its expression started to decrease 1 day after the removal of LIF, and disappeared on day 3. It was also shown that STAT3 could bind to the promoter region of Jmjd1a gene. These data demonstrate that Jmjd1a might be a critical signaling molecule underlying the maintenance of pluripotency in mES cells.


Cd/Se/Te-based quantum dot 705 modulated redox homeostasis with hepatotoxicity in mice.
The objective of this study was to investigate whether quantum dot 705 (QD705) disrupts the cellular antioxidant systems leading to hepatotoxicity in mice. Mice were intravenously injected with QD705 and then sacrificed at week 12 or 16. Homeostasis of antioxidant-related metals, antioxidant activities, induction of oxidative stress, and toxicity in the liver were investigated. Although no histopathological change was observed, a time- and dose-dependent increase in metallothionein expression and reduction in liver function was noticed. Increased copper, zinc, and selenium levels and enhancements of the trace metal-corresponding transporters were noted at week 12. At week 16, a decline of selenium from its elevated level at week 12 was observed, which was accompanied by changes in glutathione peroxidase activity as well as in redox status. A significant reduction in superoxide dismutase activity was observed at 16 weeks. Furthermore, a corresponding elevation of heme oxygenase-1 expression, 8-oxo-7,8-dihydro-2'-deoxyguanosine, interleukin-6 and tumor necrosis factor-alpha suggested the presence of oxidative stress, oxidative DNA damage and inflammation.


Overexpression of the transmembrane protein BST-2 induces Akt and Erk phosphorylation in bladder cancer.
Bladder cancer, the majority of which is urothelial carcinoma (UC), is a common malignancy worldwide. Genes encoding transmembrane/secretory proteins expressed specifically in certain cancers may be ideal biomarkers for cancer diagnosis and may represent therapeutic targets. In the present study, the expression and function of the bone marrow stromal cell antigen 2 (BST2) gene was analyzed in UC. Reverse transcription-quantitative polymerase chain reaction demonstrated that expression of BST2 in normal tissue samples was the highest in liver tissue. However, expression of BST2 in UC tissue samples was higher than in normal liver. Immunohistochemical analysis revealed weak or no staining of BST-2 in non-neoplastic mucosa, whereas UC tissue exhibited stronger and more extensive staining compared with non-neoplastic mucosa. BST-2 staining was observed mainly on UC cell membranes. In total, 28 (41%) of 69 UC cases were positive for BST-2. UC cases positive for BST-2 were more frequently T2/3/4 cases [so-called muscle-invasive bladder cancer (MIBC)] than Ta/is/1 cases (P=0.0001). However, Kaplan-Meier analysis demonstrated no association between BST-2 expression and survival. BST2 small interfering RNA (siRNA)-transfected T24 cells exhibited significantly reduced cell growth relative to negative control siRNA-transfected T24 cells. The levels of phosphorylated Akt and extracellular signal-regulated kinase were lower in BST2 siRNA-transfected T24 cells than in control cells. These results suggest the involvement of BST-2 in the pathogenesis of UC. Since BST-2 is expressed on the cell membrane, BST-2 may be a good therapeutic target for MIBC.


Mediterranean diet and depression: reanalysis of a meta-analysis.
On the basis of comments we received from readers, we made some changes in the original version of our article about our study and re-analyzed the data. In this corrected version, we found an inverse significant association between adherence to the Mediterranean diet and risk of depression in cohort studies (overall hazard ratio, 0.81; 95% confidence interval, 0.70-0.94). In addition, combining 8 cross-sectional studies that examined the association between adherence to the Mediterranean diet and depression, we found a significant inverse association (overall odds ratio, 0.81; 95% confidence interval, 0.71-0.92).


Simply solvable model capturing the approach to statistical self-similarity for the diffusive coarsening of bubbles, droplets, and grains.
Aqueous foams and a wide range of related systems are believed to coarsen by diffusion between neighboring domains into a statistically self-similar scaling state, after the decay of initial transients, such that dimensionless domain size and shape distributions become time independent and the average grows as a power law. Partial integrodifferential equations for the time evolution of the size distribution for such phase separating systems can be formulated for arbitrary initial conditions, but these are cumbersome for analyzing data on nonscaling state preparations. Here we show that essential features of the approach to the scaling state are captured by an exactly-solvable ordinary differential equation for the evolution of the average bubble size. The key ingredient is to characterize the bubble size distribution approximately, using the average size of all bubbles and the average size of the critical bubbles, which instantaneously neither grow nor shrink. The difference between these two averages serves as a proxy for the width of the size distribution. Solution of our model shows that behavior is controlled by a signed length δ that is proportional to the width of the initial distribution relative to that in the scaling state. In particular, δ is negative if the initial preparation is too monodisperse, and is positive if it is too polydisperse. To test our approach, we compare with data for quasi-two dimensional dry foams created with three different initial amounts of polydispersity. This allows us to readily identify the critical radius from the average area of six-sided bubbles, whose growth rate is zero by the von Neumann law. The growth of the average and critical radii agree quite well with exact solution, though the most monodisperse sample crosses over to the scaling state faster than expected. A simpler approximate solution of our model performs equally well. Our approach is applicable to 3d foams, which we demonstrate by re-analyzing prior data, as well as to froths of dilute droplets and to phase separation kinetics for more general systems such as emulsions, binary mixtures, and alloys.


The welfare significance of the castration of cattle: a review.
Castration is an ancient husbandry procedure used to produce docile cattle for draught work, to reduce unwanted breeding, and to modify carcass quality. All the physical methods used to castrate cattle have side-effects and cause pain. The plasma cortisol response to castration using Burdizzo clamps and, by inference, the acute pain experienced, is less than that caused by surgical, rubber-ring or latex-band castration. The cortisol response may be influenced by the age of the animal castrated, but this has not been well defined. Local anaesthesia virtually eliminates the cortisol response, and thus the acute pain, caused by rubber-ring or latex-band castration, but needs to be combined with a systemic analgesic such as the non-steroidal anti-inflammatory drug ketoprofen to eliminate the cortisol response to Burdizzo or surgical castration. When used alone, ketoprofen sometimes reduces the cortisol response to Burdizzo or surgical castration but may need to be accompanied by local anaesthesia to eliminate the pain-induced behaviour seen during the castration process itself. Thus, pharmacological methods are available to virtually eliminate the acute pain experienced by calves during the 12 h following castration. The use of these methods is an additional cost for farmers and may be limited by the availability of drugs for farmers to use and the scarcity of veterinarians in farm animal practice.


Physical and Chemical Stability of Budesonide Mucoadhesive Oral Suspensions (MucoLox).
Budesonide is a corticosteroid that has been shown effective in the treatment of eosinophilic esophagitis, but there are currently no commercial medicines to treat this chronic allergic/immune condition, despite its prevalence in the U.S. Therefore, pharmaceutical compounding is the alternative choice to meet the therapeutic need of eosinophilic esophagitis patients. Two budesonide mucoadhesive oral suspensions (1 mg/10 mL and 2 mg/10 mL) were developed using the compounding vehicle MucoLox, a proprietary mucoadhesive polymer blend that promotes mucosal adhesion. The physical and chemical stability of the oral suspensions was tested over a period of 182 days, at room temperature and refrigerated conditions, in order to determine the corresponding beyond-use date. The physical characterization consisted in observing all samples for color/appearance and odor, and testing for pH and density, whereas the chemical characterization consisted in ultra-performance liquid chromatography assay testing. Both oral suspensions were proven physically and chemically stable, and the ultra-performance liquid chromatography method was proven stability indicating. As a result, the beyond-use date of the budesonide 1-mg/10-mL and 2-mg/10-mL mucoadhesive oral suspensions (MucoLox), in amber plastic bottles, is six months at both room temperature and refrigerated conditions.


Vascular Dementia, Depression, and Financial Capacity Assessment.
We still know little about financial capacity, which consists of multiple cognitive domains as well as specific skills, and the influence of depression in patients with vascular dementia (VaD). Participants were divided into 4 groups: (1) VaD with and (2) without depressive symptoms, (3) nondemented elders with and (4) without depression. The participants were examined with the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). The findings extend earlier work in other groups of older patients and indicate that VaD patients' performance in cognitive functioning and financial capacity is severely impaired, while there is a statistically significant difference between depressed and nondepressed VaD patients. Thus, depression negatively influences financial capacity. Depression and mood disorders should be considered in future capacity research with older adults and with larger VaD populations.


Proflavin binding within the fibrinopeptide groove adjacent to the catalytic site of human alpha-thrombin.
Human alpha-thrombin with high fibrinogen-clotting activity binds proflavin at a single specific site (n = 0.996 site/alpha-thrombin, Kd = 22.0 microM) with the same affinity as the bovine enzyme (Kd = 22 +/- 3 vs. 24 +/- 3 microM, respectively, at pH 7.4, approximately 23 degrees C). This human enzyme form further displayed no significant difference in its ability to bind the dye over a broad NaCl concentration range (0.15-3 microM), and its hydrolysis of Bz-Arg-OEt was inhibited by the dye in a simple competitive manner (Ki = 30 +/- 3 microM). Conversion of the human alpha- to gamma-thrombin by controlled tryptic digestion essentially destroyed clotting activity without appreciably altering synthetic substrate activities and caused only approximately 2-fold reduction in proflavin binding. Chemical modification of approximately four tryptophans or approximately four tyrosines per enzyme also caused analogous differential losses of clotting vs. synthetic substrate activities and reduced proflavin binding approximately 5- and approximately 10-fold, respectively. Inactivation of the enzyme by conjugation at the catalytic serine (Ser-195, chymotrypsin numbering) with MeSO2 -F, PhMeSO2 -F, or i- Pr2P -F decreased binding approximately 4-, 26-, and 55-fold, respectively, following the increasing size and steric hindrance properties of the conjugated group. Conjugation of the catalytic histidine (His-57) with Tos-Lys-CH2-Cl decreased binding only approximately 10-fold, suggesting partial displacement by the dye. Such partial displacement appeared to occur to a slightly greater extent with the conjugate of a large exo site affinity-labeling reagent, which covalently attaches to the enzyme within the fibrino-peptide groove distal to the catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS)


Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium.
Modeling Salmonella-epithelial cell interaction in vitro has led to the realization that epithelial cells are crucial in orchestrating neutrophil (PMN) responses, in part by stimulating basolateral release of epithelial chemokines, including IL-8. However, such basolaterally released chemokines, while likely important in orchestration of PMN movement across the subepithelial matrix, are unlikely to be responsible for the final step of transepithelial migration of PMN and entry into the apical compartment. We now show that S. typhimurium attachment to T84 cell apical epithelial membranes induces polarized apical secretion of a pathogen-elicited epithelial chemoattractant (PEEC) bioactivity. Experiments employing semipurified PEEC indicate that it is released in a polarized apical fashion and is sufficient to explain the observed final step of transepithelial migration of PMN induced by Salmonella-apical membrane interaction. By preliminary physical characterization and profiles of PMN activation, PEEC appears to be a novel PMN chemotactic bioactivity. This 1- to 3-kDa nominal molecular mass chemokine-like bioactivity directly stimulates PMN via a pertussis toxin-sensitive receptor and elicits a Ca2+ signal. While these latter features are shared by most other chemokines, analysis of PEEC-elicited PMN activation reveals that, unlike these other agonists, PEEC, even at saturating concentrations, elicits chemotactic activity in the absence of stimulation of superoxide production and/or release of primary and/or secondary granules. These data suggest that the apically released PEEC activity appears to represent a novel epithelial-derived chemoattractant that directs PMN movement across epithelial monolayers.


Folliculotropic Cutaneous Metastases and Lymphangitis Carcinomatosa: When Cutaneous Metastases of Breast Carcinoma Are Mistaken for Cutaneous Infections.
Dear Editor, Cutaneous metastases (CM) are detected in about 0.6-10.4% of patients with an internal malignancy (1-3). Excluding melanoma, breast and lung carcinomas are the main source of CM in women and men, respectively (1,4,5). CM can have different clinical features, and a diagnosis of CM is usually suspected before performing a biopsy. However, this can be a pitfall for clinicians when the clinical presentation is not the typical inflammatory nodule or mass. Herein we report 2 cases of cutaneous metastases of breast carcinoma, initially treated as a common skin infection. Case 1 A 51-year-old Caucasian woman presented to our Institute with a four-month history of diffuse and erythematous pustular, lesions on the right arm that were painless and non pruritic (Figure 1). The patient had undergone excision for a breast adenocarcinoma (stage IIIA) 5 years earlier. An initial diagnosis of folliculitis was established, and the patient started systemic and topical antibiotics without any improvement. Based on the clinical features and the patient medical history, we performed a skin biopsy. Pathologically dermal nests of tumor cells, arranged in a glandular-like pattern and involving the perifollicular and follicular areas (Figure 2, Figure 3), were highlighted. The tumor cells were positive to cytokeratin (CK) 7, CK19, and carcinoembryonic antigen (CEA) and negative for CK20, CK5/6, CD10, and thyroid transcription factor-1 (TTF-1) (Figure 4). According to the clinical history and pathology, a final diagnosis of folliculotropic metastatic breast carcinoma was established. Unfortunately, the patient died after 10 months. Case 2 A 61-year old Caucasian woman presented to our Department with a two-month history of pink/violet macular lesions with diffuse telangiectasia on the left breast and arm (Figure 5, Figure 6). Five years earlier she had undergone excision for a breast adenocarcinoma (stage II A). A previous diagnosis of cellulitis had been made, and systemic antibiotic therapy had been started without any improvement. Based on the clinical features and the patient medical history, a punch biopsy was performed. Examination of skin biopsy showed a diffuse, sclerotic, and mixoid stroma with several dense ectatic lymphatic vessels (Figure 7, Figure 8). The dermal and hypodermal lymphatic lumens were filled with neoplastic cells. Thus, a diagnosis of cutaneous lymphangitis carcinomatosa (CLC) was established. Unfortunately, the patient died after 8 months. Discussion CM are present after breast carcinoma in about 23.9% of patients, often involving the chest and abdomen and manifesting on average 5 years after surgical removal of the first malignancy (1,6). CM of breast cancer are usually solitary or multiple nodular pinkish lesions (ranging between 1 and 3 cm) (1). However, several clinical features have been reported in the literature, including telangiectatic carcinoma, erythema-like, erythema annulare centrifugum-like, morphea-like, erysipelas-like, dermatofibroma-like, herpes-zoster-like, and alopecia-like lesions (1,7-10). Clinical and pathological images of folliculitis-like metastases are rarely reported in the literature, especially after breast cancer (11,13) Clinically, folliculitis-like metastases could resemble a zosteriform-like metastatic lesion (7,14,15) although they do not follow a dermatome and are pustular lesions rather than violaceous indurate papules and/or nodules (13,14) Pathologically, our cases showed an infiltration of the dermis and pilosebaceous units growing through the pilosebaceous unit in a "pseudo-eruptive way". In this regard, folliculitis-like CM could be similar to alopecia neoplastica, where the metastatic process involves and destroys the pilosebaceous units completely, leading to scarring alopecia (9,10). However, in our case, the pilosebaceous unit was still slightly recognizable, and clinically there were no scar-like features. The mechanism of folliculitis-like metastasis formation is currently unknown. As reported in zosteriform-like metastases, the lymphatic and hematogenous spread of malignant cells or the koebnerization at the site of a previous viral and/or bacterial infection could lead to metastasis (7,14-16). However, unlike zosteriform-like metastases, the spread of neoplastic cells from the dorsal root ganglia was not a plausible mechanism of metastasization in our cases because of the absence of dermatome involvement. Furthermore, there were no signs of possible koebnerization in a previous bacterial and/or viral infection site (7,13) In our opinion, folliculitis-like metastasis may be a result of the skin extruding malignant cells through the pilosebaceous unit to limit the neopalstic proliferation. This could explain the clinical and pathological features of folliculitis-like metastasis. Alternatively, the adnexotropic behavior of malignant cells may be explained by homing mechanisms, involving the up-regulation of the intercellular adhesion molecule 1 (ICAM-1) on the follicular epithelium, such as folliculotropic mycosis fungoides (17). In our patient, the folliculitis-like eruption was the first sign of recurrence after 5 years of disease-free survival. It is evident that the unusual folliculitis-like eruption of CM led to a delay in the diagnosis. CLC is a rare presentation of skin metastasis, characterized by an occlusion of dermic lymphatic vessels by neoplastic cells (18). CLC has been reported in the literature in association with several malignancies, including lung, breast, and ovarian cancer (19). CLC shows pink/violet macular lesions with diffuse telangiectasias, often associated with itching and burning sensation. The main differential diagnoses are erysipelas and cellulitis. However, CLC is not associated with fever, chills, and leukocytosis. Furthermore, CLC shows no response to antibiotic therapies. Several clinicopathological types of cutaneous metastasis have been reported in the literature, including telangiectatic metastatic breast carcinoma (TMBC) and carcinoma erysipelatous (CE). TMBC is characterized by yellowish/reddish or violaceous papulo-vesicular lesions. CE usually shows blistering erythematous eruptions resembling erysipelas. However, CLC, TMBC, and CE are different clinical expressions of the same metastatic process, pathologically characterized by edema of the dermis and ectatic lymphatic vessels. Positivity to CD31 and podoplanin in the endothelial cells shows that the tumor metastatises predominantly via lymphatic vessels (20). In conclusion, we stress that every cutaneous lesion should be studied and examined carefully in patients with a personal history of cancer. Indeed, a correct diagnosis remains the pivotal point for a better management of these patients.


Subjective experience of difficulty depends on multiple cues.
Human cognition is characterized by subjective experiences that go along with our actions, but the nature and stability of these experiences remain largely unclear. In the current report, the subjective experience of difficulty is studied and it is proposed that this experience is constructed by integrating information from multiple cues. Such an account can explain the tight relationship between primary task performance and subjective difficulty, while allowing for dissociations between both to occur. Confirming this hypothesis, response conflict, reaction time and response repetition were identified as variables that contribute to the experience of difficulty. Trials that were congruent, fast or required the same response as the previous trial were more frequently rated as easy than trials that were incongruent, slow or required a different response as the previous trial. Furthermore, in line with theoretical accounts that relate metacognition to learning, a three day training procedure showed that the influence of these variables on subjective difficulty judgments can be changed. Results of the current study are discussed in relation to work on meta-memory and to recent theoretical advancements in the understanding of subjective confidence.


Atlas-guided quantification of white matter signal abnormalities on term-equivalent age MRI in very preterm infants: findings predict language and cognitive development at two years of age.
The developmental significance of the frequently encountered white matter signal abnormality (WMSA) findings on MRI around term-equivalent age (TEA) in very preterm infants, remains in question. The use of conventional qualitative analysis methods is subjective, lacks sufficient reliability for producing accurate and reproducible WMSA diagnosis, and possibly contributes to suboptimal neurodevelopmental outcome prediction. The advantages of quantitative over qualitative diagnostic approaches have been widely acknowledged and demonstrated. The purpose of this study is to objectively and accurately quantify WMSA on TEA T2-weighted MRI in very preterm infants and to assess whether such quantifications predict 2-year language and cognitive developmental outcomes. To this end, we constructed a probabilistic brain atlas, exclusively for very preterm infants to embed tissue distributions (i.e. to encode shapes, locations and geometrical proportion of anatomical structures). Guided with this atlas, we then developed a fully automated method for WMSA detection and quantification using T2-weighted images. Computer simulations and experiments using in vivo very preterm data showed very high detection accuracy. WMSA volume, particularly in the centrum semiovale, on TEA MRI was a significant predictor of standardized language and cognitive scores at 2 years of age. Independent validation of our automated WMSA detection algorithm and school age follow-up are important next steps.


Speed up of dynamic observables in coarse-grained molecular-dynamics simulations of unentangled polymers.
Coarse-grained models that preserve atomistic detail display faster dynamics than atomistic systems alone. We show that this " indirect speed up" is robust: coarse-grained dynamic observables computed with time scaled by a constant factor are in excellent agreement with their underlying atomistic counterparts. Borrowing from accelerated dynamics methods used in the field of rare events, we predict the scaling factor within 7%, based on reduced intermolecular attraction yielding faster neighbor cage escapes.


Significant increase of activated partial thromboplastin time by heparinization of the radial artery catheter flush solution with a closed arterial catheter system.
Evaluate whether the use of a heparinized flush for an arterial catheter with a closed-loop blood sampling system leads to erroneous coagulation studies. Prospective study. Twenty-two-bed surgical adult intensive care unit in a university hospital. Sixty patients, 30 in each phase of the study. Phase 1: coagulation studies on a blood sample from a venous puncture and an arterial blood sample from an arterial catheter with heparinized flush. Phase 2: the same protocol but the arterial catheter was flushed with saline. Activated partial thromboplastin time, fibrinogen, percentage of prothrombin time, and international normalized ratio of prothrombin time on the venous and arterial samples. Activated partial thromboplastin time in the arterial blood samples taken from an arterial catheter with heparinized flush was significantly prolonged compared with the venous controls. This was not the case in blood samples from an arterial catheter with saline flush. The magnitude of this difference found by the Bland and Altman analysis was clinically significant. In 23.3% of the patients in phase 1, there was a difference of >50% between the arterial and venous sampled activated partial thromboplastin time, compared with 0% of the patients in phase 2 (p =.018). There was no difference between the venous and the arterial blood samples for the non-heparin-sensitive coagulation studies in both phases of the study. An explanation for these findings could be that there was release of heparin bound to the arterial catheter into the blood sample. A heparinized flush solution for the arterial catheter, when used together with a closed-loop blood sampling system, leads to erroneous results of heparin-sensitive coagulation studies. Heparin-sensitive coagulation studies, therefore, should not be analyzed on blood samples from such a system if a heparinized flush solution is used.


Case report: High chromium and cobalt levels in a pregnant patient with bilateral metal-on-metal hip arthroplasties.
Metal-on-metal bearings frequently are used in young patients leading to the concern that disseminated metals such as chromium (Cr) and cobalt (Co) as the main constituents could affect pregnancies. We describe a 41-year-old patient with bilateral metal-on-metal hip arthroplasties, a recurrent pseudotumor, and extremely high blood levels (Cr 39 μg/L, Co 138 μg/L) at 12 gestational weeks. At different gestational weeks, maternal blood, aspirate of the pseudotumor, and amniotic fluid were analyzed for Cr and Co. Therapy with chelating agents was not recommended because the mother showed no symptoms of toxicity and the safety of chelating therapy during pregnancy is not established. At 38 weeks of gestation, a healthy male infant was delivered with elevated Cr and Co cord blood levels. At the age of 8 weeks, the infant's Cr was comparable to the cord blood level, whereas the Co decreased considerably without treatment. At the age of 14 weeks, the infant's development was seemingly uneventful and no signs of toxicity were obvious. Carcinogenic, mutagenic, and teratogenic potentials of these metals have been suggested. However, we found no published clinical observations in context with pregnancies of women with hip arthroplasties using metal-on-metal implants. To our knowledge, this is the first report of such high levels of Cr and Co in a human pregnancy. Although we cannot generalize from one case, the seemingly uneventful outcome of this pregnancy may reassure colleagues when counseling patients with high ion levels whether to carry a pregnancy to term.


Synthesis and PKC binding of a new class of a-ring diversifiable bryostatin analogues utilizing a double asymmetric hydrogenation and cross-coupling strategy.
The design, asymmetric synthesis, and biological evaluation of a new class of bryostatin analogues based on a pseudosymmetric spacer domain are described. An aryl bromide diversification site is incorporated allowing access to systematically varied analogues. The new analogues all exhibit potent, nanomolar affinity to PKC.


Anti-emetics in development.
Despite important advances in pharmacotherapeutic options for the prevention and treatment of nausea and vomiting during the 1990s, a significant proportion of patients still suffer debilitating nausea and vomiting symptoms. The most problematic areas are chemotherapy-induced nausea and vomiting particularly delayed emesis, postoperative nausea and vomiting, opioid-induced nausea and vomiting and motion sickness. The most vigorous research into new anti-emetics has focused on the neurokinin-1 (substance P) antagonists. Clinical trials conducted to date indicate that these agents have similar efficacy to 5-HT(3) antagonists in acute chemotherapy-induced nausea and vomiting, superior efficacy to available agents in delayed emesis, possibly superior efficacy against emesis in postoperative nausea and vomiting and no evidence of efficacy versus opioid or motion-induced nausea and vomiting. Other pharmacological strategies in development include agonising CB1 (cannabinoid) receptors, "broad spectrum" receptor antagonists and 5-HT(1A) receptor agonists, although clinical trials of these types of agents are not yet available. The neurokinin-1 antagonists appear to be promising agents for some nausea and vomiting states, although further clarification of their role is required.


Oligothiophene-linked bisnaphthopyrans: sequential and temperature-dependent photochromism.
Photochromic bisnaphthopyrans linked with oligothiophenes were synthesized and their photochromic behavior studied. Sequential and temperature-dependent photochromism was observed in the oligothiophene linked bisnaphthopyrans. The kinetics of photo and thermal processes in bisnaphthopyrans in comparison with naphthopyrans were studied. Substituent and linking effects on the photochromic properties are discussed. We demonstrate that the cross-talk between the two photochromophores is dependent on the length of the oligothiophene linker. The presence of the bithiophene linker led to high colorability and high quantum yield of coloration.


Granulomatous mastitis caused by sparganum. A case report.
Sparganosis is not a common disease, and its rarity makes it difficult to distinguish from others. Close examination of fine needle aspiration biopsy (FNAB) samples, however, can aid in histologic examination of the lesion. A 64-year-old female, born and raised in a rural area in the state of Goiás, Brazil, presented with a relatively mobile and hard lump in the lower inner quadrant of the right breast. It was initially diagnosed as granulomatous mastitis, but cytologic examination of the surgical specimen revealed a sparganum larva, also revealed by anterior FNAB. Sparganum should be considered in the differential diagnosis of granulomatous mastitis, especially among Asians living in other countries.


Granular chaos and mixing: Whirled in a grain of sand.
In this paper, we overview examples of chaos in granular flows. We begin by reviewing several remarkable behaviors that have intrigued researchers over the past few decades, and we then focus on three areas in which chaos plays an intrinsic role in granular behavior. First, we discuss pattern formation in vibrated beds, which we show is a direct result of chaotic scattering combined with dynamical dissipation. Next, we consider stick-slip motion, which involves chaotic scattering on the micro-scale, and which results in complex and as yet unexplained peculiarities on the macro-scale. Finally, we examine granular mixing, which we show combines micro-scale chaotic scattering and macro-scale stick-slip motion into behaviors that are well described by dynamical systems tools, such as iterative mappings.


Squamous carcinoma arising in a parotid Warthin's tumour.
Warthin's tumour is the second most common benign neoplasm to affect the salivary glands. It virtually affects the sole parotid gland. A sudden increase in a tumour's size is usually due to a malignant transformation of the tumour. The transformation of the lymphoid stroma into malignant lymphoma is relatively common, while an epithelial malignancy is extremely rare. In this paper, the authors present a case of squamous cell carcinoma arising in Warthin's tumour. The patient underwent enucleoresection of the tumour. Intraoperative frozen section revealed the presence of a cystic component associated with the squamous cell carcinoma areas. In consideration of the result of the intraoperative consultation, the surgeons decided to enlarge the previous resection by removal of a 30×25 mm cuff from the surrounding parotid tissue. Close follow-up was carried out and 12 months after surgery there was no evidence of recurrence or metastatic neoplasm.


Ultra-low-dose interleukin-2 in unresectable hepatocellular carcinoma.
At present, no effective therapy is available for hepatocellular carcinoma, when local treatments have failed. We reported the results obtained with prolonged, ultra-low-dose (1 MIU/d until progression), subcutaneous interleukin-2 (IL-2) in a series of 18 consecutive patients (14 men and 4 women, median age 66 years, range 49-82 years) with advanced, histologically proven HCC on liver cirrhosis. During a median follow-up time of 19.5 months, two complete responses (11.1%), lasting 35 and 46 months, respectively, and one partial response (5.5%) were recorded (overall response rate: 16.6%; 95% CI: 0-33.8%). Thirteen patients (72.3%; 95% CI: 61.6-82.7) had stable disease lasting at least 4 months; 1 of these patients obtained a complete response on lung metastases. Median time to progression was 15.3 months (95% CI: 10-33). Median overall survival was 24.5 months (95% CI: 12-43). Two patients (11.1%) progressed during therapy. Toxicity was only local (usually pain and pomphus in the site of injection). Low-dose IL-2 can be considered an active and well-tolerated treatment for unresectable hepatocellular carcinoma. Future studies on large numbers of patients are necessary to confirm these results.


C-values of seven marine mammal species determined by flow cytometry.
C-values, which estimate genome size, have puzzled geneticists for years because they bear no relationship to organismal complexity. Though C-values have been estimated for thousands of species, considerably more data are required in order to better understanding genome evolution. This is particularly true for mammals, in which C-values are known for less than 8% of the total number of mammalian species. Among marine mammals, a C-value has been estimated only for the bottlenose dolphin (Tursiops truncatus). Thus examination of additional species of marine mammals is necessary for comparative purposes. It will enable a better understanding of marine mammal genome evolution, and it is also relevant to conservation, because larger genome size has been linked to increased likelihood of extinction in some plant and animal groups. Our study presents C-values of seven marine mammal species, including five cetacean species that are endangered to varying degrees. Similarly to the results for other groups, our results suggest that larger genome size in cetaceans is related to an increased likelihood of extinction.


The impact of global budgets on pharmaceutical spending and utilization: early experience from the alternative quality contract.
In 2009, Blue Cross Blue Shield of Massachusetts implemented a global budget-based payment system, the Alternative Quality Contract (AQC), in which provider groups assumed accountability for spending. We investigate the impact of global budgets on the utilization of prescription drugs and related expenditures. Our analyses indicate no statistically significant evidence that the AQC reduced the use of drugs. Although the impact may change over time, early evidence suggests that it is premature to conclude that global budget systems may reduce access to medications.


Modification of atrioventricular conduction by selective AV nodal artery catheterization.
The effects of selective AV nodal artery embolization on AV nodal function was investigated in six closed-chest adult dogs. Programmed atrial stimulation was performed to determine control values for AV nodal effective refractory period (AVN-ERP) and the paced cycle length at which AV nodal Wenckebach conduction occurred (WCL). Using standard percutaneous femoral techniques of coronary artery catheterization, a flexible infusion catheter was positioned selectively in the AV nodal artery. Proper positioning of the catheter was confirmed angiographically and by selective acetylcholine (ACH) infusion into the AV nodal artery, which caused transient complete AV nodal block in three dogs, and for the group, caused lengthening of both AVN-ERP and WCL. Following cessation of ACH infusion and autonomic blockade with atropine 0.04 mg/kg and propranolol 0.2 mg/kg, denervated recontrol values for AVN-ERP and WCL were 192 msec and 243 msec, respectively. The AV nodal artery was then embolized with a suspension of cross-linked collagen fibrils in either normal saline or absolute ethanol. Successful embolization of the AV nodal artery, confirmed angiographically, caused an acute increase in AVN-ERP (243 msec, P less than 0.05 compared to denervated control) and WCL (287 msec, P = 0.058 compared to denervated control). However, at a mean follow-up of 37 days, only one animal exhibited a chronic increase in AVN-ERP and WCL. Selective AV nodal artery catheterization can be performed using standard percutaneous catheterization techniques. Selective administration of agents with direct cidal effects on the AV node using this technique may provide an alternative to conventional methods of catheter ablation of AV conduction in patients with drug-resistant supraventricular arrhythmias.


Caffeinated Alcoholic Beverages and Intimate Partner Violence Victimization.
Background: Caffeinated alcoholic beverage (CAB) use is associated with general victimization beyond the use of alcohol alone. Materials and Methods: No prior research has evaluated the association between CAB use and intimate partner violence (IPV) victimization. This study evaluated the CAB-IPV victimization relationship using the responses of 100 (40 female) respondents to an online survey. Results: Results of logistic regression analyses indicated that CAB use was associated with IPV physical and sexual victimization after adjusting for demographics and heavy alcohol use. Exploratory analyses detected little evidence of sex differences in the strength of the relationship between CAB use and IPV victimization. Conclusions: The current results provide initial evidence that CAB use may place males and females at greater risk of IPV victimization.


Memory failures in everyday life following severe head injury.
Questionnaires concerning the incidence of memory failures in everyday life were used in a postal survey of the aftereffects of severe head injury. Several years after a severe injury, 50 patients were compared to 33 patients a similar period after a very mild injury. A questionnaire completed on behalf of each patient by someone living in daily contact with him appeared to have some validity as a memory measure. The pattern of memory failures reported was similar to that found in a previous study and this may primarily reflect the ease with which certain forms of memory failure can be observed. A questionnaire completed by the patients themselves had little validity, possibly because severely injured patients could not recall their own memory failures. Only a minority of severely injured patients were reported to be significantly handicapped by memory failures at this stage in their recovery.


A numerically stable T-matrix method for acoustic scattering by nonspherical particles with large aspect ratios and size parameters.
We consider a two-part method for computing the acoustic scattering T-matrix of a three dimensional particle. The first part involves accurately computing the far fields by solving a number of particular scattering problems. The second part calculates the T-matrix from these far fields using the Fourier transform over the sphere. The two-part method was first introduced in Ganesh and Hawkins [J. Comput. Appl. Math. 234, 1702-1709]. The focus of this work is to demonstrate the numerical stability and physical correctness of the two-part method for scattering by nonspherical particles with large aspect ratios and size parameters that are at the upper limit of numerical stability for the current state-of-the-art algorithm. The numerical stability of the method is attributed to elimination of the Hankel functions by working with the far field. The numerical experiments use our recently developed open-source software package (TMATROM3) that implements the two-part method.


Evaluation of focus and deep learning methods for automated image grading and factors influencing image quality in adaptive optics ophthalmoscopy.
Adaptive optics flood illumination ophthalmoscopy (AO-FIO) is an established imaging tool in the investigation of retinal diseases. However, the clinical interpretation of AO-FIO images can be challenging due to varied image quality. Therefore, image quality assessment is essential before interpretation. An image assessment tool will also assist further work on improving the image quality, either during acquisition or post processing. In this paper, we describe, validate and compare two automated image quality assessment methods; the energy of Laplacian focus operator (LAPE; not commonly used but easily implemented) and convolutional neural network (CNN; effective but more complex approach). We also evaluate the effects of subject age, axial length, refractive error, fixation stability, disease status and retinal location on AO-FIO image quality. Based on analysis of 10,250 images of 50 × 50 μm size, at 41 retinal locations, from 50 subjects we demonstrate that CNN slightly outperforms LAPE in image quality assessment. CNN achieves accuracy of 89%, whereas LAPE metric achieves 73% and 80% (for a linear regression and random forest multiclass classifier methods, respectively) compared to ground truth. Furthermore, the retinal location, age and disease are factors that can influence the likelihood of poor image quality.


Synthesis, characterization and cytocompatibility of polyurethaneurea elastomers with designed elastase sensitivity.
In designing a synthetic scaffold for engineering soft, mechanically active tissues, desirable properties include elasticity, support of cell adhesion and growth, ease of processability, and responsiveness to in vivo remodeling. To achieve these properties, we have developed a family of thermoplastic elastomers, polyurethaneureas (PUs), that possess enzymatic remodeling capabilities in addition to simple hydrolytic lability. PUs were synthesized using either polycaprolactone or triblock copolymer polycaprolactone-b-poly(ethylene glycol)-b-polycaprolactone as the soft segment, 1,4-butanediisocyanate as the hard segment, and the peptide Ala-Ala-Lys as a chain extender. The synthesized PUs had high molecular weights, low glass transition temperatures (< -54 degrees C), and were flexible with breaking strains of 670-890% and tensile strengths of 15-28 MPa. Incubation in buffered saline without elastase for 8 weeks resulted in mass loss from 12% to 18% depending on soft segment composition. The degradation significantly increased (p < 0.05) in the presence of elastase, ranging from 19% to 34% with degradation products showing no cytotoxicity. To encourage cell adhesion, PUs were surface-modified with radio frequency glow discharge followed by coupling of Arg-Gly-Asp-Ser (RGDS). Endothelial cell adhesion was >140% of tissue culture polystyrene on PU surfaces and >200% on RGDS-modified surfaces. The synthesized PUs thus combine mechanical, chemical, and bioresponsive properties that might be employed in soft-tissue engineering applications.


Nature and properties of hexitol transport systems in Escherichia coli.
In Escherichia coli K-12 the naturally occurring hexitols D-mannitol, D-glucitol, and galactitol are taken up and phosphorylated via three distinct transport systems by a mechanism called either group translocation or vectorial phosphorylation. For every system, a membrane-bound enzyme II-complex of the phosphoenolpyruvate-dependent phosphotransferase system has been found, each requiring phosphoenolpyruvate, enzyme I, and HPr or alternatively P-HPr as the phosphate donor. Cells with a constitutive synthesis of all hexitol transport systems but with low P-HPr levels have very low transport and phosphorylating activities in vivo, although 40 to 90% of the enzyme II-complex activities are detected in cell extracts of such mutants. No indications for additional hexitol transport systems, especially for systems able to transport and accumulate free hexitols as in Klebsiella aerogenes, have been found. Substrate Km, and Vmax of the three transport systems for several hexitols and hexitol analogues have been determined by growth rates, transport activities, and in vitro phosphorylating activities. Each system was found to take up several hexitols, but only one hexitol serves as the inducer. This inducer invariably is the substrate with the highest affinity. Since bacterial transport systems, as a general rule, seem to have a relatively broad substrate specificity, in contrast to a more restricted inducer specificity, we propose to name the system inducible by D-mannitol and coded by the gene mtlA the D-mannitol transport system, the system inducible by D-glucitol and coded by gutA the D-glucitol transport system, and the system inducible by galactitol and coded by gatA the galactitol transport system.


IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma.
Isocitrate dehydrogenase (IDH) enzymes have recently become a focal point for research aimed at understanding the biology of glioma. IDH1 and IDH2 are mutated in 50%-80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas but are seldom mutated in primary glioblastomas. Gliomas with IDH1/2 mutations always harbor other molecular aberrations, such as TP53 mutation or 1p/19q loss. IDH1 and IDH2 mutations may serve as prognostic factors because patients with an IDH-mutated glioma survive significantly longer than those with an IDH-wild-type tumor. However, the molecular pathogenic role of IDH1/2 mutations in the development of gliomas is unclear. The production of 2-hydroxyglutarate and enhanced NADP+ levels in tumor cells with mutant IDH1/2 suggest mechanisms through which these mutations contribute to tumorigenesis. Elucidating the pathogenesis of IDH mutations will improve understanding of the molecular mechanisms of gliomagenesis and may lead to development of a new molecular classification system and novel therapies.