Enamelins in the newly formed bovine enamel.
The possibility of using the antisera raised in rabbits against the porcine 25 kDa amelogenin, 32 and 89 kDa enamelins, and the 13-17 kDa nonamelogenin for the differentiation and identification of the protein components in bovine immature enamel was examined. Although the immunoreactivities of these antisera against bovine enamel proteins were weaker than those against the porcine proteins, it was found that these antisera could differentiate and demonstrate immunohistochemically a characteristic distribution of three different kinds of enamel protein components in the bovine secretory stage enamel similar to those observed in the porcine immature enamel. Of the several high molecular weight proteins being reactive to the anti-porcine 32 and 89 kDa enamelin sera, the 130 kDa protein, having the highest molecular weight, was extracted and purified from the bovine enamel sample which was obtained by peeling approximately 30-microns thickness of the outermost layer of the secretory stage enamel. The amino acid composition of the 130 kDa protein was similar to the known bovine enamelins, and was rich in aspartic acid, glutamic acid, proline, and glycine. The results could suggest that the enamelins of lower molecular weight than this protein, which are found in the bovine secretory stage enamel, are derived from this precursor protein.


Sensory preconditioning in spatial learning using a touch screen task in pigeons.
The authors used a touch screen-based visual-search task to investigate spatial integration in pigeons. First, pigeons were presented with a consistent spatial relationship between compound visual landmarks (LMs) A-X and B-Y, separately. Next, pigeons learned to find a hidden goal on the monitor in the presence of LMs A and B. The goal bore a consistent spatial relationship to LM A, but not to LM B. On nonreinforced probe tests, the peak and distribution of responses to LM X suggest that pigeons computed a novel X-goal spatial relationship on the basis of X-A and A-goal spatial vectors. Responses to LM Y, however, revealed no evidence of spatial integration. These results replicate and extend those of A. P. Blaisdell and R. G. Cook (2005) using an open-field task.


Factor structure and internal reliability of breast cancer screening Champion's Health Belief Model Scale in Yemeni women in Malaysia: a cross-sectional study.
The reliability and validity of the Champion's Health Belief Model Scale (CHBMS) used in assessing the belief of women regarding breast cancer (BC) and breast cancer screening (BCS) have been examined on various populations. However, the use of this tool has not been adequately assessed for its validity in ethnic minorities. This study assessed the validity and reliability of CHBMS by analyzing the factor structure and internal reliability of the factors among Yemeni women in Malaysia. A survey was conducted among 103 female teachers from 10 schools. SPSS version 22.0 was utilized in analyzing the data. Descriptive statistics were computed for the socio-demographic characteristics. The Cronbach's alpha coefficients were used in assessing the internal reliability. The Exploratory Factor Analysis (EFA) was used to analyze the factor structure of the translated items. Parallel analysis was performed to determine the number of factors accurately. The alpha coefficients of the factors had acceptable values ranging between 0.76 and 0.87. The factor analysis yielded six and five factors for breast self-examination (BSE) and mammography (MMG), with a total explained variance of 47.69% and 52.63%, respectively. The Kaiser-Meyer-Olkin (KMO) index values of 0.64 and 0.72, and the Bartlett's Test of Sphericity (P = 0.0001) for BSE and MMG, respectively, verified the normality distribution and the adequacy of the sample size for EFA. All the items on each factor were from the same construct that were consistent with the number of factors obtained in the scale development study. The items achieved adequate factor loadings that ranged between 0.47 and 0.88. The translated version of the CHBMS is a validated scale used in assessing the beliefs related to BC and BCS among Yemeni women living in Malaysia. Healthcare workers could use the scales to assess women's beliefs on BC and BCS. This instrument could be used to test the effectiveness of the intervention programs.


Pituitary gland.
This review summarizes current knowledge on pathology of proliferative lesions of the human pituitary. The morphologic classification of pituitary adenomas--based on histology, immunohistochemistry and electron microscopy--has now been firmly established. It has been conclusively proven that all presently recognized adenohypophysial cell types give rise to adenoma and all known pituitary hormones may be secreted in excess. Evidence is accumulating that hyperplasia of various adenohypophysial cell types can lead to hypersecretory syndromes similar to those associated with the corresponding adenomas. Owing to the rarity of studies on pituitary hyperplasia, the condition is still incompletely defined. The difficulties regarding morphologic diagnosis of pituitary hyperplasia are discussed. Despite major advances in the field of pituitary pathology, several problems concerning structure-function relationship, as well as pathogenesis of proliferative lesions are still unresolved. There is strong circumstantial evidence suggesting that the cytological mapping of the pituitary is incomplete and there are still cell types waiting to be discovered.


Cross-reactivity between solid-phase immunoassay plates and intermediate filaments demonstrated by human monoclonal antibodies.
While screening supernatants of human-human hybridomas for rheumatoid factor and anti-cellular activity we found that a significant number of supernatants which react with the Falcon-polyvinyl chloride immunoassay plate used in an enzyme-linked immunosorbent rheumatoid factor assay also react with intracellular intermediate filaments.


Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: More efforts are necessary to address interdisciplinary research.
This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to-human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to-human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.


The relationship between psychological factors and disabling musculoskeletal pain in community-dwelling older persons.
To determine the relationship between two psychological factors (depressive symptoms and low functional self-efficacy) and the occurrence of disabling musculoskeletal pain in community-dwelling older persons. A 12-month prospective cohort study. Community-based. Two hundred twenty-six community-dwelling persons residing in the greater New Haven, Connecticut, region, aged 70 and older, who had a history of clinically evident musculoskeletal pain and were independent in bathing, walking, dressing, and transferring. Levels of depressive symptoms and functional self-efficacy were determined during a comprehensive baseline assessment along with information regarding participants' demographic, medical, and physical/cognitive status. The occurrence of disabling musculoskeletal pain, defined as staying in bed for at least one-half day or cutting down on one's usual activities due to joint or back pain, was ascertained during monthly interviews. The mean number of months of disabling musculoskeletal pain, adjusted for baseline covariates, increased from the lowest to the highest quartile of depressive symptoms: 1.2 (95% confidence intervals = 0.8-1.7), 1.4 (1.0-2.0), 2.0 (1.5-2.8), 2.3 (1.7-3.1), respectively, P for trend =.002. The corresponding results for functional self-efficacy were (from highest to lowest quartile) 1.4 (1.0-2.0), 1.6 (1.2-2.2), 1.6 (1.2-2.2), 2.2 (1.6-3.0), P for trend =.068. There was no interaction between depressive symptoms and functional self-efficacy. Depressive symptoms and, to a lesser extent, low functional self-efficacy were each associated with the occurrence of disabling musculoskeletal pain among community-dwelling older persons.


A Parallel-Plate Flow Chamber for Mechanical Characterization of Endothelial Cells Exposed to Laminar Shear Stress.
Shear stresses induced by laminar fluid flow are essential to properly recapitulate the physiological microenvironment experienced by endothelial cells (ECs). ECs respond to these stresses via mechanotransduction by modulating their phenotype and biomechanical characteristics, which can be characterized by Atomic Force Microscopy (AFM). Parallel Plate Flow Chambers (PPFCs) apply unidirectional laminar fluid flow to EC monolayers in vitro. Since ECs in sealed PPFCs are inaccessible to AFM probes, cone-and-plate viscometers (CPs) are commonly used to apply shear stress. This paper presents a comparison of the efficacies of both methods. Computational Fluid Dynamic simulation and validation testing using EC responses as a metric have indicated limitations in the use of CPs to apply laminar shear stress. Monolayers subjected to laminar fluid flow in a PPFC respond by increasing cortical stiffness, elongating, and aligning filamentous actin in the direction of fluid flow to a greater extent than CP devices. Limitations using CP devices to provide laminar flow across an EC monolayer suggest they are better suited when studying EC response for disturbed flow conditions. PPFC platforms allow for exposure of ECs to laminar fluid flow conditions, recapitulating cellular biomechanical behaviors, whereas CP platforms allow for mechanical characterization of ECs under secondary flow.


Differential effect of long-term oestrogen therapy on trabecular and cortical bone.
The effect of long-term oestrogen therapy has been assessed in 40 oophorectomised women. Twenty-one of the women had received mestranol (mean 26 micrograms/day) and 19 received placebo tablets for a mean duration of 14 yr. A newly developed gamma-ray computed tomography (CT) scanner was used to measure trabecular and cortical bone separately in the distal radius. Bone density in the lumbar spine was measured using dual photon absorptiometry (DPA). Prevention against bone loss was demonstrated at all sites for the mestranol treated group (P less than 0.01). The deficit of radial trabecular bone (27%) was greater than that for radical cortical bone (14%). The deficit for the spine was intermediate (20%). One-year follow-up radial measurements showed a significant 1.2% increase (P less than 0.01) in cortical bone for the treated group. The DPA measurement was found to be best correlated (r = 0.80) with a mixed trabecular and cortical bone parameter in the radius. We conclude that the degree of bone loss at any site is dependent on the proportion of trabecular bone present.


Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis.
Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs). Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I2 = 86.74%), 91% (95% CI, 72-98; I2 = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001). Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.


Buprenorphine treatment of patients with non-malignant musculoskeletal diseases.
Adequate pain control is vital in the treatment of patients with musculoskeletal disease. These diseases are characterised by a number of pain-induced vicious circles, and satisfactory control of pain acts to disrupt these self-perpetuating processes. Consequently, early mobilisation can be achieved in patients with painful osteoporotic vertebral fractures, low back pain and sciatica, for example. In other cases analgesics may act simply to maintain the mobility of patients and in this way preserve their quality of life. When simple analgesics are not sufficient, the use of opioid-type analgesics is justified. Buprenorphine transdermal therapeutic system (TDS) is a novel formulation of a well-tolerated and highly effective drug for satisfactory pain control that can also be used in patients with chronic non-malignant pain (CNMP) due to musculoskeletal diseases. Three case reports are presented to illustrate the effectiveness of buprenorphine TDS in such patients.


Identification of synchronous esophageal tumors in patients with head and neck cancer.
Patients with a primary head and neck neoplasm are at risk for additional malignancies of the upper aerodigestive tract, which may be asymptomatic. This phenomenon may reflect the regional carcinogenic influence of alcohol and tobacco abuse. A review of the recent literature documents the value of performing laryngoscopy, bronchoscopy, and esophagoscopy on all patients being staged for head and neck tumors to identify second synchronous cancers, the presence of which may significantly alter the treatment plan.


Toxicity to bilirubin in neonates: infant development during first year in relation to maximum neonatal serum bilirubin concentration.
Neurologic and developmental performance during the first year of life was correlated with maximum neonatal serum bilirubin levels for 27,000 infants in the Collaborative Perinatal Project. The infants were grouped by race and by five birth weight/gestational age categories to control for the effect of these factors on hyperbilirubinemia and developmental outcome. Low mean eight-month motor scores and delayed one-year motor development were associated with serum bilirubin levels in the range of 10 to 14 mg/dl and above. This relationship was strongest for low-birth-weight/short-gestational-period infants. A persistent association of developmental outcome with hyperbilirubinemia was found over and above the variation of maturity within the birth weight/gestational age categories.


Src-mediated Tyr353 phosphorylation of IP3R1 promotes its stability and causes apoptosis in palmitic acid-treated hepatocytes.
Palmitic acid (PA)-induced hepatocyte apoptosis is critical for the progression of nonalcoholic fatty liver disease (NAFLD). Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) is an intracellular Ca2+-release channel and is involved in PA-induced hepatocyte apoptosis. While the expression of IP3R1 is elevated in patients with NAFLD and in hepatocytes treated with PA, it remains unclear how PA promotes the expression of IP3R1. In present study, our results showed that PA induced mitochondrial dysfunction and apoptosis, which is accompanied with the increase of the IP3R1 expression in hepatic cells. The inhibition of IP3R1 expression using siRNA ameliorated the PA-induced mitochondrial dysfunction. Furthermore, PA enhanced the stability of the IP3R1 protein instead of an increase in its mRNA levels. PA also promoted the phosphorylation of IP3R1 at the Tyr353 site and increased the phosphorylation of src in hepatic cells. Moreover, an inhibitor of src kinase (SU6656) significantly reduced the Tyr353 phosphorylation of IP3R1 and decreased its stability. In addition, SU6656 improved mitochondrial function and reduced apoptosis in hepatocytes. Conclusion: PA promotes the Tyr353 phosphorylation of IP3R1 by activating the src pathway and increasing the protein stability of IP3R1, which consequently results in mitochondrial Ca2+ overload and mitochondrial dysfunction in hepatic cells. Our results also suggested that inhibition of the src/IP3R1 pathway, such as by SU6656, may be a novel potential therapeutic approach for the treatment of NAFLD.


Simultaneously realizing enhancement of sensitivity for freshness monitoring and multinomial properties of carrageenan/konjac glucomannan/blueberry anthocyanin-based intelligent film by diatomite.
Here, highly sensitive blueberry anthocyanin (BBA)-induced intelligent indicating films were fabricated by incorporating a novel composite ingredient, diatomite (DA), into a matrix of konjac glucomannan (KGM), carrageenan (CAR) and BBA. We systematically investigated the effects of introducing DA and BBA on the structure, physical properties, colorimetric response, and practical application of the KGM/CAR film. Our findings revealed that the DA particles and BBA were well-distributed in the KGM/CAR matrix through hydrogen bonding interactions. This distribution significantly improved tensile strength, surface hydrophobicity, thermal stability, and barrier properties of the KGM/CAR film. Notably, the KGM/CAR-based intelligent film loaded with 6 % DA exhibited the most optimal properties. Furthermore, DA exhibited a hierarchical porous structure, enabling the KGM/CAR film to detect volatile amines with heightened sensitivity. When applied to monitor shrimp spoilage in transparent plastic packaging, the color of the composite film underwent remarkable changes from bright pink to bluish violet. These color changes correlated well with the total volatile basic nitrogen (TVB-N) and pH changes in the shrimp, as determined by standard laboratory procedures. Our work presents a promising approach to the development of high-performance and intelligent food packaging materials. These materials hold great potential for practical applications in the field of food packaging.


Pharmacokinetics and effects of i.m. alfentanil as premedication for day-case ophthalmic surgery in elderly patients.
We have studied the pharmacokinetics and effects of i.m. alfentanil as premedication for peribulbar block in 90 patients undergoing elective day-case cataract surgery. We compared alfentanil 12.5 micrograms kg-1 injected into the deltoid (n = 30) or gluteal muscle (n = 30) 15 min before the peribulbar block, and placebo (n = 30). The alfentanil concentrations were significantly greater in the deltoid group during the study and the mean peak concentration occurred more rapidly in this group. Only alfentanil injected into the deltoid muscle reduced pain (assessed with a visual analogue scale (VAS)) associated with the peribulbar block. A mild sedative effect (VAS) was found in both alfentanil groups. We conclude that i.m. alfentanil appears to be a suitable premedicant for short, painful procedures because it has a short duration of action and is not associated with any clinically significant side effects.


Facial axis angle as a risk factor for obstructive sleep apnea.
Many Japanese patients with obstructive sleep apnea (OSA) are less obese than Caucasian OSA patients despite their similar severity of OSA, suggesting that their etiology of OSA may differ. The purpose of this study was to identify bony factors associated with OSA in the Japanese population. The clinical records of study subjects were retrospectively reviewed, and cephalometric measurements based on Sella-Nasion references and the Ricketts method were statistically compared. Two hundred and six consecutive Japanese men complaining of habitual snoring and daytime sleepiness were enrolled in the study. All subsequently underwent an overnight polysomnographic examination. Multiple regression analysis showed that the body mass index (p<0.0001) and facial axis angle (p=0.007) were the dominant overall determinants for the apnea hypopnea index. The sella to nasion to subspinale angle (SNA) and sella to nasion to supramentale angle (SNB) were lower in the non-obese, severe group than for non-obese, mild and moderate patients with OSA (p=0.0047 and 0.0016, respectively). The risk factors for OSA in Japanese men may be obesity and the dolico facial pattern seen by the Ricketts method. In addition, a smaller SNA and SNB seem to be associated with the severity of OSA in non-obese patients.


ROLE OF INCISIONAL VACUUM THERAPY IN ENDOPROSTHETIC BONE RECONSTRUCTION SURGERY.
Reconstructive surgery with endoprostheses is the chosen method for treating bone malignancies. Postoperative infections are frequent complications, and their treatment involves prolonged hospital stays and antibiotic therapy. Among the advancements aimed at reducing the rate of postoperative infection, the use of incisional negative pressure therapy (iNPT) has shown promising results, with no reports in the literature regarding its use in patients with such conditions. To evaluate the effectiveness of iNPT in reducing postoperative complications in surgeries for resection of bone tumors associated with modular endoprosthesis reconstruction. Retrospective case series of 16 patients diagnosed with osteosarcoma, who underwent resection and reconstruction with endoprosthesis associated with iNPT during the postoperative period. Follow-up was performed for a period of six months, and the evaluated outcomes were the incidence of postoperative infection and complications of the surgical wound. The use of iNPT for a postoperative period of seven days resulted in only three (18.7%) cases of postoperative infection. No cases of wound dehiscence, seroma formation, or hematoma at the surgical site were observed. The rate of surgical wound complications in our case series is lower than that reported in most of the literature, and iNPT appears to be an efficient way to reduce the rate of local complications in reconstructive surgeries with endoprosthesis after resection of bone malignancies. Level of Evidence III, Retrospective Study.


Level of muscle regeneration in limb-girdle muscular dystrophy type 2I relates to genotype and clinical severity.
The balance between muscle regeneration and ongoing degeneration is a relationship that greatly influences the progression of muscular dystrophy. Numerous factors may influence the muscle regeneration, but more information about the relationship between genotype, clinical severity and the ability to regenerate is needed. Muscle biopsies were obtained from the tibialis anterior muscle, and frozen sections were stained for general histopathological and immunohistological evaluation. Differences between groups were considered statistical significant at P < 0.05 using Student's unpaired t-test. We found that all patients with limb-girdle muscular dystrophy type 2I (LGMD2I) had a large number of internally nucleated fibers, a sign of previous regeneration. The level of expression of muscle-specific developmental proteins, such as neonatal myosin heavy chain (nMHC) and myogenin, was related to the clinical severity. Additionally, we found that the majority of nMHC-positive fibers did not stain positively for utrophin in patients who were compound heterozygous for the L276I mutation, suggesting that the predominant form of regeneration in these patients is fiber repair rather than formation of new fibers. Double staining showed that many smaller nMHC-positive fibers were positive for antibodies against the glycosylation on α-dystroglycan, suggesting that such glycosylation may be a result of muscle regeneration. Severely affected patients with LGMD2I have a high level of muscle degeneration, which leads to a high rate of regeneration, but this is insufficient to change the imbalance between degeneration and regeneration, ultimately leading to progressive muscle wasting. Detailed information regarding the level and rate of muscle regeneration and potential obstructions of the regenerative pathway should be of use for future therapies involving satellite-cell activation.


Imaging manifestations of congenital mesoblastic nephroma.
Congenital mesoblastic nephroma (CMN) is a rare renal tumor mainly observed in infants and young children. This study aims to analyze the imaging manifestations of CMN to improve the understanding of the disease. The imaging manifestations and clinical records of all pediatric patients with CMN admitted to our hospital over the last 7 years were retrospectively analyzed. The diagnosis of CMN was confirmed by postoperative pathology. All patients underwent computed tomography (CT) scans; 2 patients additionally underwent magnetic resonance imaging (MRI) scans (including one prenatal MRI scan). We evaluated 10 pediatric patients (6 males and 4 females) aged 7 days to 12 months (median age: 4 months) with CMN located on the left kidney in six cases and the right kidney in four cases. The CT imaging manifested as solid lesions (5 cases), solid-cystic lesions with solid predominance (4 cases), or solid-multicystic lesions with cystic predominance (1 case). Enhanced CT showed moderately and heterogeneously enhanced solid component and intracystic septations at the corticomedullary phase that were further enhanced at the nephrographic phase, although their CT values were still lower than those of the renal parenchyma. The "double-layer sign" were seen in 4 cases of classic type of CMN, and the "intratumor pelvis sign" were seen in 9 cases that include 5 classic, 3 cellular and 1 mixed type of CMN. In the 2 patients who underwent MRI, the scans showed solitary masses. The lesions had hypointense signals on the T1WI sequence and isointensity or slightly lower-intensity signals than the surrounding renal parenchyma on the fluid-sensitive sequences, whereas the lesions showed hyperintense signals on the diffusion-weighted imaging (DWI) sequence. The imaging manifestations of CMN are closely correlated with the pathological subtype and have certain characteristics. The "double-layer sign" was seen with most classic type CMN, and "intratumor pelvis sign" was seen in 90% cases.


Rituximab activates Syk and AKT in CD20-positive B cell lymphoma cells dependent on cell membrane cholesterol levels.
The introduction of rituximab, an anti-CD20 monoclonal antibody, has dramatically improved the treatment outcomes of patients with B cell lymphoma. Nevertheless, the clinical response to rituximab varies, and a subpopulation of patients does not respond well to this antibody. Although several molecular events have been shown to be involved in the mechanism of action of rituximab, recent studies have demonstrated that intracellular signaling pathways and the direct effects of rituximab on cell membrane components are responsible for the antilymphoma action of this drug. In the present study, we demonstrated that rituximab activated Syk and Akt, molecules with antiapoptotic functions, in several CD20-positive lymphoma cell lines. Notably, rituximab activated Syk and Akt in all the tested primary lymphoma samples from six patients. Our results show that the cholesterol levels in lymphoma cell membranes have a crucial role in the regulation of Syk and Akt. The depletion of cholesterol from the cell membrane completely blocked rituximab-induced Syk and Akt activation. Simvastatin, an inhibitor of cholesterol synthesis, also abrogated rituximab-mediated Syk and Akt activation. Finally, we report that rituximab inhibited the apoptosis induced by chemotherapeutic drugs, which was observed solely in Akt-activated cells. This work demonstrates for the first time that rituximab paradoxically works to suppress apoptosis under certain conditions in a manner that is dependent on the cell membrane cholesterol level. Our observations provide novel insights and suggest that the cell membrane cholesterol level represents a new biomarker for predicting patient response to rituximab. Furthermore, the modulation of lipid rafts could provide a new strategy for enhancing the antilymphoma action of rituximab.


Cytomegalovirus DNAemia detected with real-time polymerase chain reaction in hematopoietic stem cell transplant patients.
Cytomegalovirus (CMV) infections continue to cause significant morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Successful pre-emptive therapy in transplant patients depends on the availability of reliable diagnostic tests for CMV infections. The purpose of this retrospective study was to evaluate CMV DNA viral load, incidence of CMV disease and CMV seropositivity, risk factors and correlation between CMV DNA positivity and clinical course in HSCT patients. Two hundred and twenty-five patients who underwent peripheral blood stem cell or bone marrow transplantation between June 2003 and April 2010 were included. A real-time polymerase chain reaction (RT-PCR) assay was used for CMV monitoring. Recipient median age was 42.5 years. CMV seropositivity was 95.6%. CMV DNA positivity determined by RT-PCR was 24.9% among the entire patient group. CMV DNA positivity with RT-PCR was found to be significantly higher in allogeneic transplant recipients than autologous transplant recipients (46.7% vs 14.0%; P < 0.0001). Gender, age, conditioning regimen, stem cell source, underlying disease and recipient and donor seropositivity (alone or paired) were not significant risk factors for CMV DNAemia. We did not observe any CMV end-organ disease. CMV DNAemia was significantly higher in allogeneic transplant recipients than in autologous transplant patients. End-organ disease could be prevented with appropriate pre-emptive therapy.


Acylthiourea derivatives as colorimetric sensors for anions: Synthesis, characterization and spectral behaviors.
Several acylthioureas have been synthesized to develop colorimetric sensors for detection of biologically important anions. UV-vis titration experiments indicated that the absorbance values have a good linear relationship with concentration of anions when the anions were added in AR-1, AR-4 and AR-6 sensor molecules. The detection limit to AcO(-) and F(-) is 5×10(-6) mol/L when the concentration of receptors are 2×10(-5) mol/L. Especially, compounds AR-1 and AR-4, decorated with strong electron-withdrawing NO2 substituent, showed augmented anion sensing properties, being capable of naked-eye detecting of F(-) and AcO(-) when the water content is lower than 15%. The recognition details of anion sensing were also assessed using (1)H NMR technique and confirmed that the basic anions induced deprotonation of N-H.


UV/H2O2degradation of the antidepressants venlafaxine and O-desmethylvenlafaxine: Elucidation of their transformation pathway and environmental fate.
The aim of the present work is to investigate the removal and transformation of the antidepressants venlafaxine (VFX) and its main metabolite O-desmethylvenlafaxine (DVFX) upon advanced oxidation with UV/H2O2 under lab conditions. High-resolution mass spectrometry (HRMS) analyses were carried out by means of ultra-high pressure liquid chromatography (UHPLC)-linear ion trap high resolution Orbitrap instrument (LTQ-Orbitrap-MS) in order to elucidate the different transformation products (TPs) generated. The depletion of both VFX and DVFX was very significant, with the 99.9% of both compounds eliminated after 5 and 30 min of reaction, respectively. Eleven TPs for VFX and six for DVFX were detected and their molecular structures elucidated by means of MS(2) and MS(3) scans, and the corresponding degradation pathways were proposed. The combined ecotoxicity at different treatment times was evaluated by means of bioluminescence inhibition assays with the marine bacteria Vibrio fischeri. Results showed an increase in the ecotoxicity during the UV/H2O2 experiment, especially at those reaction times where the total abundance of TPs was higher.


Connectome: Graph theory application in functional brain network architecture.
Network science and graph theory applications have recently spread widely to help in understanding how human cognitive functions are linked to neuronal network structure, thus providing a conceptual frame that can help in reducing the analytical brain complexity and underlining how network topology can be used to characterize and model vulnerability and resilience to brain disease and dysfunction. The present review focuses on few pivotal recent studies of our research team regarding graph theory application in functional dynamic connectivity investigated by electroencephalographic (EEG) analysis. The article is divided into two parts. The first describes the methodological approach to EEG functional connectivity data analysis. In the second part, network studies of physiological aging and neurological disorders are explored, with a particular focus on epilepsy and neurodegenerative dementias, such as Alzheimer's disease.


Microsurgery in clinical urology.
Microsurgery is not a new tool to the urologist. Transurethral resection is probably the most challenging type of microsurgery, and we do it daily. The manipulations of microvascular dissections and anastomoses may be more intricate, but the basic concept of performing delicate procedures while looking down a tube is "old hat" to us. The new techniques discussed here may extend the range of operative solutions to difficult clinical problems in urology perhaps as transurethral resection did in the thirties and forties.


Commentary on "impact of body mass index on perioperative morbidity, oncological, and functional outcomes after extraperitoneal laparoscopic radical prostatectomy." Campeggi A, Xylinas E, Ploussard G, Ouzaid I, Fabre A, Allory Y, Vordos D, Abbou CC, Salomon L, de la Taille A, Institut National de la Sante et de la Recherche Medicale Unit 955 EQ7, Department of Urology, APHP, CHU Henri Mondor, Créteil, France: Urology 2012;80(3):576-84.
To evaluate the impact of obesity on the outcomes of laparoscopic radical prostatectomy. In a prospective urologic cancer database, 765 patients underwent extraperitoneal laparoscopic radical prostatectomy for localized prostate cancer. The patients were categorized into 3 groups of body mass index (kg/m(2)):<25.0 (n = 276, 30%, "normal weight", 25.0 to 30.0 (n = 365, 48%, "overweight") and>30.0 (n = 124, 16%, "obese"). We assessed the perioperative, oncological, and functional outcomes in this cohort of patients. Preoperative and postoperative evaluation of continence and erectile function were performed using validated questionnaires. Mean operative time was significantly longer in obese patients (P< 0.001) and blood loss was also more important (P< 0.01). The obese patients had the highest likelihood of having aggressive tumors: nonorgan confined prostate cancer (49%, P = 0.002) and Gleason score≥7 (80%, P = 0.005). The obese group had the higher positive surgical margins rate (overall: 27%, P = 0.012; pT2: 20%, P = 0.02). With a mean follow-up of 38 months, obesity was not an independent predictive factor of biochemical recurrence. At the 12-month follow-up, 85%, 74%, and 72% of normal, overweight, and obese men, respectively, were continent (no pad) (P = 0.04). At the 12-month follow-up, 57%, 58%, and 40% of normal, overweight, and obese men, respectively, reported an erection sufficient for intercourse (P = 0.01). Laparoscopic radical prostatectomy is a safe and effective procedure in obese men with midterm cancer control. However, obese patients are at higher risk of aggressive disease. Recovery of continence and potency in these patients are significantly lower compared to non-obese men.


Genome-wide identification and characterization of SRO gene family in wheat: Molecular evolution and expression profiles during different stresses.
SRO (SIMILAR TO RCD ONE), a type of plant-specific small protein family, play important roles in plant growth and development, as well as in response to biotic/abiotic stresses. Although characterization of SROs have been performed in model plants, little is known about their function in wheat, especially under stress conditions. In this study, 30 SRO genes were identified from the wheat genome (TaSRO). They were phylogenetically separated into two groups with distinct structures. The cis-regulatory elements in the promoter region of TaSROs were analyzed and numerous elements functionally associated with stress responding and hormones were interpreted, implying the reason for induction expression patterns of TaSROs during abiotic and biotic stresses in wheat. Whole-genome replication events in the SRO gene family of wheat and seven other species (Arabidopsis thaliana, rice, maize, barley, soybean, upland cotton, and cucumber) were analyzed, resulting in 1, 12, 9, 23, 6, 5, and 3 of gene pairs, respectively. The tissue-specific expression pattern profiling revealed that most TaSROs are highly expressed in one or more tissues and may play an important role in wheat growth and development. In addition, qRT-PCR results further confirmed that these TaSRO genes are involved in wheat stress response. In summary, our study laid a theoretical basis for molecular function deciphering of TaSROs, especially in plant hormones and biotic/abiotic stress responses.


Shapes of krill swarms and fish schools emerge as aggregation members avoid predators and access oxygen.
Many types of animals exhibit aggregative behavior: birds flock, bees swarm, fish shoal, and ungulates herd. Terrestrial and aerial aggregations can be observed directly, and photographic techniques have provided insights into the behaviors of animals in these environments and data against which behavioral theory can be tested. Underwater, however, limited visibility can hamper direct observation, and understanding of shoaling remains incomplete. We used multibeam sonar to observe three-dimensional structure of Antarctic krill shoals acoustically. Shoal size and packing density varied greatly, but surface area:volume ratios (roughnesses) were distributed narrowly about ∼3.3 m(-1). Shoals of clupeid fish (e.g., sardine, anchovy) from geographically and oceanographically diverse locations have very similar roughnesses. This common emergent shape property suggests common driving forces across diverse ecosystems. Group behavior can be complex, but a simple tradeoff--that we model--in which individual fish and krill juggle only their access to oxygen-replete water and exposure to predation can explain the observed shoal shape. Decreasing oxygen availability in a warming world ocean may impact shoal structure: because structure affects catchability by predators and fishers, understanding the response will be necessary for ecological and commercial reasons.


Induced pluripotency in the context of stem cell expansion bioprocess development, optimization, and manufacturing: a roadmap to the clinic.
The translation of laboratory-scale bioprocess protocols and technologies to industrial scales and the application of human induced pluripotent stem cell (hiPSC) derivatives in clinical trials globally presents optimism for the future of stem-cell products to impact healthcare. However, while many promising therapeutic approaches are being tested in pre-clinical studies, hiPSC-derived products currently account for a small fraction of active clinical trials. The complexity and volatility of hiPSCs present several bioprocessing challenges, where the goal is to generate a sufficiently large, high-quality, homogeneous population for downstream differentiation-the derivatives of which must retain functional efficacy and meet regulatory safety criteria in application. It is argued herein that one of the major challenges currently faced in improving the robustness of routine stem-cell biomanufacturing is in utilizing continuous, meaningful assessments of molecular and cellular characteristics from process to application. This includes integrating process data with biological characteristic and functional assessment data to model the interplay between variables in the search for global optimization strategies. Coupling complete datasets with relevant computational methods will contribute significantly to model development and automation in achieving process robustness. This overarching approach is thus crucially important in realizing the potential of hiPSC biomanufacturing for transformation of regenerative medicine and the healthcare industry.


Identification of tmexC3-tmexD3-toprJ1b in an XDR Providencia rettgeri clinical isolate co-producing NDM-1 and OXA-10 carbapenemases.
Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes blaNDM-1, blaOXA-10 and the tmexCD3-toprJ1b gene cluster. The phenotype and genotype of P. rettgeri Pre20-95 were investigated by antimicrobial susceptibility testing, conjugation assay, stability testing and whole genome sequencing. Bioinformatics tools were used to uncover the genetic structures of its multidrug-resistant (MDR) plasmid pPre20-95-1 and SXT/R391 integrative and conjugative element ICEPreChn20-95. P. rettgeri strain Pre20-95 was isolated from a human clinical infection and displayed an extensively drug-resistant (XDR) phenotype. Whole genome sequencing (WGS) analysis identified a pPrY2001-like MDR plasmid, namely pPre20-95-1, co-harbouring blaNDM-1 and blaOXA-10 genes in Pre20-95. The multidrug resistance region of pPre20-95-1 was composed of a Tn6625-derived module and a ∆Tn1696 structure, and blaNDM-1 and blaOXA-10 were located in a composite Tn structure consisting of insertion sequences ISCR1 and ISAba125 and an In125-like class 1 integron, respectively. Furthermore, the novel RND efflux pump gene cluster tmexCD3-toprJ1b was identified on the SXT/R391 ICE ICEPreChn20-95 of its chromosome, and reverse PCR showed that it could form a circular intermediate for transmission. Our findings highlight further dissemination of the tmexCD3-toprJ1b gene cluster into a clinical isolate of P. rettgeri and convergence with multiple carbapenemase genes, which increases the risk of the emergence of XDR strains and threatens the treatment of Enterobacterales bacterial infections.


Tumor volume changes on serial imaging with megavoltage CT for non-small-cell lung cancer during intensity-modulated radiotherapy: how reliable, consistent, and meaningful is the effect?
Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intratreatment imaging capabilities on radiotherapy devices. This study assesses non-small-cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage computed tomography (MVCT) scans, with a specific emphasis on the frequency, reliability, and meaningfulness of these changes. Megavoltage CTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in five fractions) and 17 on a dose-per-fraction escalation protocol (57-80.5 Gy in 25 fractions). Four patients were treated palliatively (22-30 Gy in 8 to 10 fractions). Gross tumor volumes were contoured on serial MVCTs at weekly intervals. Each patient had 4 to 25 scans, including at least one at the beginning, midway, and one at the end of treatment. At completion of treatment, no patient demonstrated a complete response. Partial response occurred in 3 (12%) and marginal response was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease. The minimum "scorable threshold" for volume discrepancy between scans to account for interscan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, because there is no way to document histologic tumor clearance, and therefore field reductions during radiotherapy cannot be recommended.


An ultrasensitive fluorescent aptasensor based on truncated aptamer and AGET ATRP for the detection of bisphenol A.
Given the gigantic harmfulness of bisphenol A (BPA), a novel and ultrasensitive aptasensor, which employs the truncated BPA aptamer, click chemistry, and activators generated by electron transfer for atom transfer radical polymerization (AGET ATRP), was developed herein for the quantitative determination of BPA. Firstly, hairpin DNAs (hairpins) with a thiol at the 5' end and an azide group at the 3' end were conjugated with aminated magnetic beads (MBs) through heterobifunctional cross-linkers. BPA truncated aptamer (ssDNA-A) hybridizes with its complementary single-stranded DNA (ssDNA-B) to form double-stranded DNA. In the presence of BPA, ssDNA-A specifically captures BPA, and then ssDNA-B is released. Subsequently, the ssDNA-B hybridizes with hairpins to expose the azide group near the surface of the MBs. Then, propargyl-2-bromoisobutyrate (PBIB), the initiator of AGET ATRP containing alkynyl group, was conjugated with azide group of hairpins via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Consequently, a large number of fluorescein-o-acrylate (FA) were introduced to the MBs through AGET ATRP, resulting in that the fluorescence intensity was increased dramatically. Obviously, the fluorescence intensity was especially sensitive to the change of BPA concentration, and this method can be used in quantitative determination of BPA. Under optimal conditions, a broad liner range from 100 fM to 100 nM and a low limit of detection (LOD) of 6.6 fM were obtained. Moreover, the method exhibits not only excellent specificity for BPA detection over BPA analogues but high anti-interference ability in real water sample detection, indicating that it has huge application prospect in food safety and environment monitoring.


Cricoid split for acute subglottic injury in the older child.
To describe our experience of cricoid split in the older child for acquired subglottic stenosis secondary to chemical or thermal burns. A retrospective case series. We describe two patients, both two years old, who benefitted from the procedure and had a return to a normal-sized airway. Neither child required a tracheostomy or further airway intervention after the cricoid split. Laryngotracheal reconstruction (LTR) is the standard treatment for subglottic injuries with associated subglottic stenosis in children, infants and (where possible) neonates. We have found the cricoid split a useful technique in carefully selected older children with acute subglottic injury and associated early subglottic stenosis, where LTR or ballooning is not feasible, where there is limited experience of ballooning, and/or ballooning has failed in the early stages of treatment. Cricoid split is a technique that is part of the airway surgeon's open operative repertoire and therefore should be remembered as a management option.


Epicatechin Plus Treadmill Exercise are Neuroprotective Against Moderate-stage Amyloid Precursor Protein/Presenilin 1 Mice.
Epidemiological evidence suggests that exercise and dietary polyphenols are beneficial in reducing Alzheimer's disease (AD) risk. In the present study, 8 months old amyloid precursor protein/presenilin 1 (APP/PS1) mice (a moderate pathology phase) were given the green tea catechin (-)-epicatechin delivered orally in the drinking water (50 mg/kg daily), along with treadmill exercise for 4 months, in order to investigate whether the combination can ameliorate the cognitive loss and delay the progression of AD in APP/PS1 transgenic (Tg) mice. At termination, untreated-Tg mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermates. The combined intervention protected against cognitive deficits in the Morris water maze, lowered soluble Aβ1-40 and Aβ1-42 levels in the hippocampus as well as reducing brain oxidative stress. In addition, brain-derived neurotrophic factor proteins wee elevated and Akt/GSK-3/cAMP response element-binding protein signaling was activated in the combination group. Dietary polyphenol plus exercise may exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of AD. Amyloid precursor protein/presenilin 1 transgenic mice showed elevated soluble amyloid-β (Aβ1-40) and Aβ1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermatesOral administration of epicatechin, combined with treadmill exercise for 4 months, could protect against cognitive deficits, and lowered soluble Aβ1-40 and Aβ1-42 levels as well as reducing brain oxidative stressBrain-derived neurotrophic factor proteins were elevated, and Akt/GSK-3/cAMP response element binding protein signaling was activated in the combination groupDietary polyphenol plus exercise might exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of Alzheimer's disease. Abbreviations used: AD: Alzheimer's disease, Tg: APP/PS1 transgenic, BDNF: Brain-derived neurotrophic factor, Aβ: Amyloid-β, APP: Amyloid precursor protein, PS1: Presenilin 1, nTg: Wild-type littermates, IACUC: Institutional Animal Care and Use Committee, GSSG: Glutathione oxidized form, GSH: Glutathione reductase, SOD: Superoxide dismutase, CAT: Catalase, LPO: Lipoperoxidation, CREB: cAMP response element binding protein.


Effects of various combinations of cryoprotectants and cooling speed on the survival and further development of mouse oocytes after vitrification.
The objectives of this study were to analyze efficacy of immature and mature mouse oocytes after vitrification and warming by applying various combinations of cryoprotectants (CPAs) and/or super-rapid cooling using slush nitrogen (SN(2)). Four-week old ICR female mice were superovulated for GV- and MII-stage oocytes. Experimental groups were divided into two groups. Ethylene glycol (EG) only group: pre-equilibrated with 1.5 M EG for 2.5 minutes and then equilibrated with 5.5 M EG and 1.0 M sucrose for 20 seconds. EG+dimethylsulfoxide (DMSO) group: pre-equilibrated with 1.3 M EG+1.1 M DMSO for 2.5 minutes and equilibrated with 2.7 M EG+2.1 M DMSO+0.5 M sucrose for 20 seconds. The oocytes were loaded onto grids and plunged into SN(2) or liquid nitrogen (LN(2)). Stored oocytes were warmed by a five-step method, and then their survival, maturation, cleavage, and developmental rates were observed. The EG only and EG+DMSO groups showed no significant difference in survival of immature oocytes vitrified after warming. However, maturation and cleavage rates after conventional insemination were greater in the EG only group than in the EG+DMSO group. In mature oocytes, survival, cleavage, and blastocyst formation rates after warming showed no significant difference when EG only or EG+DMSO was applied. Furthermore, cleavage and blastocyst formation rates of MII oocytes vitrified using SN(2) were increased in both the EG only and EG+DMSO groups. A combination of CPAs in oocyte cryopreservation could be formulated according to the oocyte stage. In addition, SN(2) may improve the efficiency of vitrification by reducing cryoinjury.


Genetic variants of the autophagy pathway as prognostic indicators for prostate cancer.
Autophagy is a complex process of autodigestion in conditions of cellular stress, and it might play an important role in the pathophysiology during carcinogenesis. We hypothesize that genetic variants of the autophagy pathway may influence clinical outcomes in prostate cancer patients. We genotyped 40 tagging single-nucleotide polymorphisms (SNPs) from 7 core autophagy pathway genes in 458 localized prostate cancer patients. Multivariate Cox regression was performed to evaluate the independent association of each SNP with disease progression. Positive findings were then replicated in an independent cohort of 504 advanced prostate cancer patients. After adjusting for known clinicopathologic factors, the association between ATG16L1 rs78835907 and recurrence in localized disease [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.54-0.90, P = 0.006] was replicated in more advanced disease (HR 0.78, 95% CI 0.64-0.95, P = 0.014). Additional integrated in silico analysis suggests that rs78835907 tends to affect ATG16L1 expression, which in turn is correlated with tumor aggressiveness and patient prognosis. In conclusion, genetic variants of the autophagy pathway contribute to the variable outcomes in prostate cancer, and discovery of these novel biomarkers might help stratify patients according to their risk of disease progression.


The recycling of AMPA receptors/GABAa receptors is related to neuronal excitation/inhibition imbalance and may be regulated by KIF5A.
Excitation/inhibition imbalance (E/I imbalance), which involves an increase of alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptors (AMPARs) and decrease of gamma-aminobutyric acid type A (GABA) type A receptors (GABAaRs) on the neuron surface, has been documented in the pathogenesis of seizures. Notably, it has been established that both the glutamate receptor subunit 2 (GluR2) of AMPARs and beta 2/3 subunits of GABAaRs (Gabrb2+3) participate in the recycling mechanism mediated by the kinesin heavy chain isoform 5A (KIF5A), which determines the number of neuron surface receptors. However, it remains unclear whether receptor recycling is involved in the pathogenesis of seizures. Twelve adult male Sprague-Dawley rats were randomly allocated to the normal control (Ctl) group (n=6) and the pentylenetetrazol (PTZ)-induced seizure (Sez) group (n=6). The rats in the Ctl group were treated with saline. The rats in the Sez group received an intraperitoneal injection of PTZ at an initial dose of 40 mg/kg. Primary cultured neurons were obtained from newborn rats (24-hour-old). The neurons were exposed to magnesium-free (Mg2+-free) extracellular fluid for 3 hours to establish the seizure model in vitro. We detected the electrophysiology of the seizure model, the expression levels of KIF5A, GluR2, and Gabrb2+3, the recycling ratio of GluR2 and Gabrb2+3, the interaction between KIF5A and GluR2, and the interaction between KIF5A and Gabrb2+3. In the Sez group, the expression of GluR2 on the cell surface was increased and the expression of Gabrb2+3 on the cell surface was decreased. The amplitude and frequency of action potentials were significantly increased in the Mg2+-free group. The amplitude and decay time of AMPAR-mediated miniature excitatory postsynaptic currents were increased in the Mg2+-free group. The amplitude and decay time of miniature inhibitory postsynaptic currents were decreased in the Mg2+-free group. The recycling ratio of GluR2 was increased and the recycling ratio of Gabrb2+3 was decreased in the Mg2+-free group. The interaction between KIF5A and GluR2 was increased, and the interaction between KIF5A and Gabrb2+3 was decreased in the seizure model in vivo and in vitro. The recycling of AMPA receptors/GABAa receptors is related to E/I imbalance and may be regulated by KIF5A.


Dichotic-listening performance after complete callosotomy: No relief from left-ear extinction by selective attention.
The surgical section of the corpus callosum (callosotomy) has been frequently demonstrated to result in a left-ear extinction in dichotic listening. That is, callosotomy patients report the left-ear stimulus below chance level, resulting in substantially enhanced right-ear advantage (REA) compared with controls. A small number of previous studies also suggest that callosotomy patients can overcome left-ear extinction when the instruction encourages to attend selectively to the left-ear stimulus. In the present case study, we re-examine the role of selective attention in dichotic listening in two patients with complete callosotomy and 40 age- and sex-matched controls. We used the standardised Bergen dichotic-listening paradigm which uses stop-consonant-vowel syllables as stimulus material and includes both a free-report and selective-attention condition. As was predicted, both patients showed a clear left-ear extinction. However, contrasting the earlier reports, we did not find any evidence for a relief from this extinction by selectively attending to the left-ear stimulus. We conclude that previous demonstrations of an attention-improved left-ear recall in callosotomy patients may be attributed to the use of suboptimal dichotic paradigms or residual callosal connectivity, rather than representing a genuine effect of attention.


Association of Intravenous Drug Use and Length of Stay Following Infective Endocarditis.
Intravenous drug use (IVDU) and associated infective endocarditis (IE) has been on the rise in the US since the beginning of the opioid epidemic. IVDU-IE has high morbidity and mortality, and treatment can be lengthy. We aim to quantify the association between IVDU and length of stay (LOS) in IE patients. The National Inpatient Sample database was used to identify IE patients, which was then stratified into IVDU-IE and non-IVDU-IE groups. Weighted values of hospitalizations were used to generate national estimates. Multivariable linear and logistic regression analyses were applied to estimate the effects of IVDU on LOS. We identified 1,114,257 adult IE patients, among which 123,409 (11.1%) were IVDU-IE. Compared to non-IVDU-IE patients, IVDU-IE patients were younger, had fewer comorbidities, and had an overall longer LOS (median [interquartile range]: 10 [5-20] versus 7 [4-13] d, P < 0.001), with a greater percentage of patients with a LOS longer than 30 d (13.7% versus 5.7%, P < 0.001). After adjusting for multiple demographic and clinical factors, IVDU was independently associated with a 1.25-d increase in LOS (beta-coefficient = 1.25, 95% confidence interval [CI]: 0.95-1.54, P < 0.001) and 35% higher odds of being hospitalized for more than 30 d (odds ratio = 1.35, 95% CI: 1.27-1.44, P < 0.001). Among IE patients, being IVDU has associated with a longer LOS and a higher risk of prolonged hospital stay. Steps toward the prevention of IE in the IVDU population should be taken to avoid an undue burden on the healthcare system.


Nonsecretory multiple myeloma. Immunohistologic and ultrastructural observations on two patients.
Two well documented examples of nonsecretory multiple myeloma were studied by electron microscopic and immunohistologic methods. In one case, repeat studies revealed no intracytoplasmic immunoglobulins, and the cells displayed a "plasmacytoid" appearance with poor development of rough endoplasmic reticulum and Golgi regions. In the other case, most cells contained intracytoplasmic immmunoglobulins of a monoclonal type and the ultrastructural appearance was that of cells actively engaged in protein synthesis. These findings and others in the literature suggest that myelomas without an M component can be separated into nonproducers and true nonsecretors of immunoglobulins. In one case, immunofluorescence of bone marrow smears with double labels demonstrated three different plasma cell populations: those producing either monoclonal immunoglobulins M (IgM) or A (IgA) and those synthesizing simultaneously IgM and IgM. Dual immunoglobulin production, although known to occur in myelomas with paraproteinemia, has not been previously documented in the nonsecretory variety.


Involvement of the sympathetic nervous system in the reversal of critical haemorrhagic hypotension by endogenous central histamine in rats.
An increase in endogenous central histamine concentration after inhibition of histamine N-methyltransferase (HNMT) activity reverses critical hypotension and improves the survival of rats in haemorrhagic shock. The purpose of the study was to examine the involvement of the sympathetic nervous system in this endogenous central histamine-induced resuscitation. Experiments were carried out in ethylurethane-anaesthetised male Wistar rats subjected to haemorrhagic hypotension (mean arterial pressure MAP 20-25 mmHg), which led to the death of all control animals within 30 min. The HNMT inhibitor metoprine (20 micro g; i.c.v.) administered 5 min after establishing the critical hypotension increased the endogenous histamine concentration, measured 20 min after treatment, in the hypothalamus (534.33+/-67.52 vs. 423.98+/-54.17 ng/g wet tissue; P<0.05) and medulla oblongata (53.12+/-9.78 vs. 39.58+/-11.16 ng/g wet tissue; P<0.05). These responses were accompanied by plasma levels of noradrenaline and adrenaline 2.7 and 1.7 times higher respectively than in the control group ( P<0.01). Metoprine evoked dose-dependent (5, 10, 20 micro g; i.c.v.) rises in MAP and heart rate (HR) that were significantly higher than those in normotensive animals, and resulted in a 100% survival rate at 2 h after treatment (20 micro g; i.c.v.). The resuscitative effect was associated with rises in renal, hindquarters and mesenteric blood flows. The nicotinic cholinoceptor antagonist hexamethonium (3 mg/kg; i.v.) attenuated the MAP and HR changes, whereas the muscarinic cholinoceptor blocker methylatropine (2 mg/kg; i.v.) attenuated only the pressor effect. Metoprine-induced MAP and regional haemodynamic effects were also reduced by alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin (0.5 mg/kg; i.v.) and yohimbine (1 mg/kg; i.v.), while the beta-adrenoceptor blocker propranolol (1 mg/kg; i.v.) diminished only HR changes. Ganglionic transmission inhibitors and adrenoceptor antagonists did not influence the survival rate at 2 h in the metoprine-treated groups. Bilateral adrenal demedullation diminished the pressor effect of metoprine, however, without influence on HR and survival at 2 h after treatment. In conclusion, the study demonstrates the activation of the sympathetic nervous system elicited by endogenous central histamine in haemorrhage-shocked rats and confirms its involvement in histamine-induced resuscitation.


[Human leucocyte antigen-DPA1 polymorphism distribution in Chengdu Chinese families with intrahepatic cholestasis of pregnancy].
To investigate the relationship between human leucocyte antigen (HLA)-DPA1 region gene polymorphism and intrahepatic cholestasis of pregnancy (ICP). The HLA-DPA1 alleles of 25 ICP families and 25 normal control group families were analysed by polymerase chain reaction-sequence specific primers(PCR-SSP) method. The analysis of the frequencies and feto-maternal or couples sharing of the DPA1 alleles showed that no statistically significant difference was observed between the two study groups. It is unlikely that an HLA-DPA1 allele is primarily associated with susceptibility or resistance to ICP.


In vitro oxime protection of human red blood cell acetylcholinesterase inhibited by diisopropyl-fluorophosphate.
Oximes are enzyme reactivators used in treating poisoning with organophosphorus cholinesterase (AChE) inhibitors. The oxime dose which can be safely administered is limited by the intrinsic toxicity of the substances such as their own AChE-inhibiting tendency. Clinical experience with the available oximes is disappointing. To meet this need, new AChE reactivators of potential clinical utility have been developed. The purpose of the study was to estimate in vitro both the intrinsic toxicity and the extent of possible protection conferred by established (pralidoxime, obidoxime, HI-6, methoxime, trimedoxime) and experimental (K-type) oximes, using diisopropyl-fluoro-phosphate (DFP) as an AChE inhibitor. The IC50 of DFP against human red blood cell AChE was determined ( approximately 120 nm). Measurements were then repeated in the presence of increasing oxime concentrations, leading to an apparent increase in DFP IC50. Calculated IC50 values were plotted against oxime concentrations to obtain an IC50 shift curve. The slope of this shift curve (tan alpha) was used to quantify the magnitude of the protective effect (nm IC50 increase per microm oxime). We show that, in the case of a linear relationship between oxime concentration and IC50, the binding constant K, determined using the Schild equation, equals IC50/DFP/tan alpha. Based on the values of tan alpha and of the binding constant K, some of the new K-oxime reactivators are far superior to pralidoxime (tan alpha = 0.8), obidoxime (1.5), HI-6 (0.8), trimedoxime (2.9) and methoxime (5.9), with K-107 (17), K-108 (20), and K-113 (16) being the outstanding compounds.


All carbon materials pn diode.
Semiconductor pn junctions are elementary building blocks of many electronic devices such as transistors, solar cells, photodetectors, and integrated circuits. Due to the absence of an energy bandgap and massless Dirac-like behaviour of charge carriers, graphene pn junction with electrical current rectification characteristics is hardly achieved. Here we show a graphene pn junction diode can be made exclusively from carbon materials by laminating two layers of positively and negatively charged graphene oxides. As the interdiffusion of oppositely charged mobile counterions, a built-in potential is created to rectify the current by changing the tunnelling probability of electrons across the junction. This graphene diode is semi-transparent, can perform simple logic operations, and since it has carbon nanotubes electrodes, we demonstrate an all carbon materials pn diode. We expect this graphene diode will expand material choices and provide functionalities (e.g. grafting recognition units on graphene oxides) beyond that of traditional semiconductor pn junctions.


Molecular moment similarity between clozapine and substituted [(4-phenylpiperazinyl)-methyl] benzamides: selective dopamine D4 agonists.
Moment descriptors of the molecular charge and mass distributions are investigated within the context of molecular similarity. Euclidean distances in the moment descriptor space are shown to yield molecular proximities in accord with chemical intuition for a substituted [(4-phenylpiperazinyl)-methyl] benzamide series of dopamine D4 agonists. The proximity of the dopamine D4 antagonist clozapine to the molecules of this series is also examined in the moment space.


Origin of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion and vagus nerve.
1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 X 10(-8)-3 X 10(-7) M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 X 10(-6) 1 X 10(-4) M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 X 10(-5) M), quipazine (1 X 10(-6) M) or MDL 72222 (1 X 10(-5) M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l-1. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 X 10(-3) M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 X 10(-7) - 3 X 10(-5)M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 X 10(-6)M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 X 10(-5)M) but were unaffected by spiperone (1 X 10(-7)M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not mediated through 5-HT3 receptors and is unlikely to be a consequence of depolarization. In contrast, on the rat vagus nerve, the post-5-HT hyperpolarization observed in the present study had the characteristics expected of depolarization-dependent activation of a sodium ion pump.


Exploring the Influence of Engineering the Linker between the Donor and Acceptor Fragments on Thermally Activated Delayed Fluorescence Characteristics.
We have expounded the unique molecular design architecture for efficient thermally activated delayed fluorescence (TADF) materials based on a donor-linker-acceptor-linker-donor (D-L-A-L-D) framework, which can be employed as predecessors of organic light-emitting diode (OLED) devices. Different from traditional donor-acceptor-type (D-A-type) TADF scaffolds, the D-L-A-L-D structural design avoids direct coupling amid the D and A fragments allowing the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs) to be spatially separated. It results in a reduced overlap between HOMOs and LUMOs, thus realizing fairly a slight singlet-triplet energy gap (ΔE ST) and higher photoluminescence quantum yield (Φ). We revealed that manipulating a linker between D and A fragments in intramolecular charge transfer compounds is an auspicious approach for realizing small ΔE ST. Herein, we report a group of organic electroluminescent D-L-A-L-D-type molecules with different electron-donating and electron-accepting moieties using density functional theory calculations and time-dependent density functional theory calculations. Two types of linkers, the π-conjugated phenylene (-C6H4-) and aliphatic alkyl chains or σ-spacer (-CH2- and -CH2-CH2-), were exploited between D and A fragments. In principle, the conjugation in D-π-A-π-D-type molecules and hyperconjugation in D-σ-A-σ-D type molecules encourage the spatial separation of the HOMO-LUMO causing a reduction in the ΔE ST. All the designed molecules show a blue-shift in the emission wavelengths (λem) over the directly linked parent molecules except DPA-DPS-C6H4 and BTPA-DPS-C6H4 which show a red-shift. Violet-blue to green-yellow (376-566 nm) λem was observed from all of the investigated molecules. Other important properties that affect the efficiency of emission quantum yields like frontier molecular orbital analysis, natural population analysis, electron excitation analysis, exciton binding energies, ionization potentials, electronic affinities, and reorganization energies of the designed molecules were also inspected. We are confident that our work will effectively give a straightforward and distinctive approach to building incredibly effective TADF-OLEDs and a new perspective on their structural design.


The neglected navigating web of the incomprehensibly emerging and re-emerging Sarcoptes mite.
Parasite presence in any ecosystem generates complex navigating webs (Parasite-NW) within the system, through which parasites move from one to another host. The appropriate assimilation of parasite navigating web is pivotal for a better understanding of pathogen flow in the ecosystem, with implications for disease control. Sarcoptes mite has been approached from medical, veterinary, entomological, physiological and, recently, molecular sides, to understand its epidemiological navigating web between isolates from different hosts and geographical regions. The obtained conclusions are still a matter of debate. Sarcoptes navigating web (Sarcoptes-NW) is intricate and uncertain, with unexplainable pathogenic flow. In this review we summarize by which routes, under what conditions and at what levels the Sarcoptes mite moves among its hosts.


V4O10: spectroscopic fingerprint of a well-defined, molecular metaloxo aggregate.
V4O10 can be considered as a molecular model for oxovanadium clusters deposited on the surfaces of corresponding heterogeneous catalysts, and here its generation, matrix isolation, and comprehensive characterization by IR, Raman, and UV/vis spectroscopy are described.


Influence of ester and amide-containing surfactant headgroups on selectivity in micellar electrokinetic chromatography.
The selectivity differences between six anionic surfactants in micellar electrokinetic chromatography (MEKC) are presented and the structural influence of the surfactant head-group is investigated. It was determined that the surfactant structure can have a significant impact on retention and selectivity. Linear solvation energy relationships (LSERs) are used to study the role of solute size, polarity/polarizability, and hydrogen bonding characteristics in determining retention and selectivity. While both the solute size and hydrogen bond accepting ability were found to be the most important factors in solute retention, the hydrogen bonding characteristic of the solutes have the largest influence on selectivity differences between surfactants.


Methods for cDNA cloning and sequencing tobacco mosaic virus RNA.
DNA complementary to tobacco mosaic virus (TMV) RNA (cDNA) was prepared by priming reverse transcription with synthetic oligonucleotides. The cDNAs terminated prematurely at many specific sites and no transcripts longer than about 2000 nucleotides were obtained. However, the entire 6395 nucleotide long TMV RNA could be copied into cDNA by specific priming with a series of 13 to 17 residue long oligonucleotides or by non-specific priming with short, 4 to 7 residue, oligonucleotides. A number of different priming methods were used to convert the cDNA into double-stranded DNA (dsDNA). The double-stranded cDNA was recovered by shotgun cloning into M13 and analysed by sequencing. The frequency at which cDNA clones were recovered has been used to compare various cDNA cloning strategies.


Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and bla KPC-2 Coharboring Plasmids in Shandong, China.
Treatment strategies of infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight K. pneumoniae infections. However, reports on fosfomycin-resistant K. pneumoniae are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics of fosfomycin-resistant K. pneumoniae. Twenty-three isolates coharbored fosA kp and fosA3, with K. pneumoniae carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 (n = 13) and ST11-KL47-wzi209-OL101 (n = 8), the predominating clonal groups, while fosA3 was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for rmpA2, of which 12 carried fosA3. Four of the 23 fosA3-positive isolates could successfully transfer their fosfomycin-resistant determinants to Escherichia coli J53Azi R . All four strains belonged to ST11-KL47 with the same pulsed-field gel electrophoresis profile, and their transconjugants acquired fosfomycin, carbapenem, and aminoglycoside resistance. A 127-kb conjugative pCT-KPC-like hybrid plasmid (pJNKPN52_KPC_fosA) coharboring fosA3, bla KPC-2, bla CTX-M-65, bla SHV-12, rmtB, and bla TEM-1 was identified. ST11-KL64 and ST11-KL47 K. pneumoniae, with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.


Analysis of electromagnetic response of cells and lipid membranes using a model-free method.
Electromagnetic radiation (EMR) is omnipresent on earth and may interact with the biological systems in diverse manners. But the scope and nature of such interactions remain poorly understood. In this study, we have measured the permittivity of cells and lipid membranes over the EMR frequency range of 20 Hz to 4.35 × 1010 Hz. To identify EMR frequencies that display physically intuitive permittivity features, we have developed a model-free method that relies on a potassium chloride reference solution of direct-current (DC) conductivity equal to that of the target sample. The dielectric constant, which reflects the capacity to store energy, displays a characteristic peak at 105-106 Hz. The dielectric loss factor, which represents EMR absorption, is markedly enhanced at 107-109 Hz. The fine characteristic features are influenced by the size and composition of these membraned structures. Mechanical disruption results in abrogation of these characteristic features. Enhanced energy storage at 105-106 Hz and energy absorption at 107-109 Hz may affect certain membrane activity relevant to cellular function.


Polymorphism of blood plasma proteins in the Anser and Branta genera.
An electrophoretical analysis of blood plasma proteins of eight Anser and two Branta species was performed. Ten polymorphic proteins in blood plasma pattern were distinguished and described: four prealbumin proteins, albumin, three postalbumin proteins, transferrin, and a single posttransferrin protein. Genus-specific and species-specific variants of Pr-1, Al, Pa-3, Pa-X, and Tf proteins were found. The species of Branta differed in Pr-1, Pa-3, Pa-X, and Tf loci. The Anser species differed, apparently, in allele frequencies of described gene loci. A single species-specific protein marker was found in swan geese only. The electrophoretic mobilities of Pr-1, TfB, and PtfA, B, and C were similar for several species of Anser and Branta genera.


EFSA's scientific activities and achievements on the risk assessment of genetically modified organisms (GMOs) during its first decade of existence: looking back and ahead.
Genetically modified organisms (GMOs) and derived food and feed products are subject to a risk analysis and regulatory approval before they can enter the market in the European Union (EU). In this risk analysis process, the role of the European Food Safety Authority (EFSA), which was created in 2002 in response to multiple food crises, is to independently assess and provide scientific advice to risk managers on any possible risks that the use of GMOs may pose to human and animal health and the environment. EFSA's scientific advice is elaborated by its GMO Panel with the scientific support of several working groups and EFSA's GMO Unit. This review presents EFSA's scientific activities and highlights its achievements on the risk assessment of GMOs for the first 10 years of its existence. Since 2002, EFSA has issued 69 scientific opinions on genetically modified (GM) plant market registration applications, of which 62 for import and processing for food and feed uses, six for cultivation and one for the use of pollen (as or in food), and 19 scientific opinions on applications for marketing products made with GM microorganisms. Several guidelines for the risk assessment of GM plants, GM microorganisms and GM animals, as well as on specific issues such as post-market environmental monitoring (PMEM) were elaborated. EFSA also provided scientific advice upon request of the European Commission on safeguard clause and emergency measures invoked by EU Member States, annual PMEM reports, the potential risks of new biotechnology-based plant breeding techniques, evaluations of previously assessed GMOs in the light of new scientific publications, and the use of antibiotic resistance marker genes in GM plants. Future challenges relevant to the risk assessment of GMOs are discussed. EFSA's risk assessments of GMO applications ensure that data are analysed and presented in a way that facilitates scientifically sound decisions that protect human and animal health and the environment.


Identifying Advanced Illness Patients in the Emergency Department and Having Goals-of-Care Discussions to Assist with Early Hospice Referral.
The emergency department (ED) is often where patients with advanced illness (AI) present when faced with an acute deterioration in their disease. To investigate the effectiveness of our AI Management program in the ED on key outcomes. We conducted a pre-post study with a retrospective chart review with ED patients at an academic, tertiary care hospital in the New York metropolitan area. We assessed changes from baseline to intervention period on percent of patients identified in the ED with AI, percent who received an ED-led goals-of-care (GOC) discussion, and percent referred to hospice from the ED. We used the Fisher's exact test or the Mann-Whitney test to compare groups, as appropriate. Our sample consisted of 82 patients (21 baseline and 61 intervention). Patients in the baseline period had a median age of 75 years, with 61.9% being female, whereas those in the intervention period had a median age of 83 years, with 67.2% being female. Patients in the intervention, compared with baseline, were significantly more likely to be identified as having AI in the ED (90.2% vs. 0.0%; p < 0.0001), to receive an ED-led GOC conversation (83.6% vs. 0.0%; p < 0.0001), and to be discharged to home hospice (39.3% vs. 0.0%; p < 0.0001). The ED provides a critical opportunity to identify AI patients, have ED-led GOC discussions, and refer appropriate patients to hospice.


A rapid assay for the brevetoxin group of sodium channel activators based on fluorescence monitoring of synaptoneurosomal membrane potential.
A functional pharmacologically-based assay for the brevetoxin group of sodium channel activators was developed using synaptoneurosomes isolated from the brains of CD1 mice. The assay can detect the depolarizing effect of brevetoxin congeners PbTx-2 and PbTx-3 as enhancements of the veratridine-dependent increase in fluorescence of the voltage-sensitive fluorescent probe rhodamine 6G. The assay is relatively rapid and can detect brevetoxin activity in the nanomolar range. The synaptoneurosomal assay has been used to analyse mussel tissue extracts spiked with PbTx-2, and composite toxicity, expressed as PbTx-3 equivalents in extracts of oysters naturally exposed to brevetoxins. In this latter context, the synaptoneurosomal technique was shown to compare favorably with the cytotoxicity assay, the receptor binding assay and HPLC/MS. Our results support the concept that this membrane potential assay detects brevetoxins based on their interaction with sodium channels.


[Prevalence and antibiogram distribution of Salmonella isolated from broiler production and processing course in four provinces, China].
To determine the contamination condition of Salmonella in broiler breeding and slaughter processing in China and to investigate the distribution of antimicrobial resistance profiles. Five large-scale broiler holdings and fourteen slaughterhouses were chosen to detect Salmonella in Henan, Jiangsu, Sichuan and Shandong provinces in 2010. A total of 835 anal swabs and 744 chicken carcasses were sampled to compare the difference of Salmonella contamination rate.Salmonella isolates were identified by serotyping according to Kauffmann-White scheme.The antimicrobial susceptibilities of Salmonella isolates were determined by broth microdilution method and sixteen antimicrobial agents were chosen and examined. In total, Salmonella isolates were recovered in 56 (6.7%) specimens among 835 collected anal swabs and 122 (16.4%) specimens among 744 broiler carcasses. Positive rate of Salmonella in broiler carcasses was higher than anal swabs (χ(2) = 36.94, P < 0.05). The dominant Salmonella serovars isolated from broiler anal swabs were S.enterica serovar Indiana and S.enterica serovar Enteritidis, accounting for 58.9% (33/56) and 32.1% (18/56) respectively. The prevalent serovars in broiler carcasses were also the two serovars and occupied 29.8% (37/124), 32.2% (40/124) respectively. Nearly 95.0% (171/180) Salmonella isolates were resistant to at least one antimicrobial, 78.3% (141/180) Salmonella strains were multi-drug resistant isolates and 20 (11.1%) Salmonella isolates were resistant to 14 antimicrobials. Our findings indicated that Salmonella contamination was common and serious in commercial broiler production and processing course in China. Salmonella contamination rate in broiler slaughter processing performance was higher than broiler flocks. Additionally, antibiotic resistance of Salmonella was in serious situation.


[Patterns of injuries of restrained car passengers (author's transl)].
A detailed analysis of actual traffic accidents involving car passengers wearing seat belts was carried out by an interdisciplinary team. The passengers were examined for the severity of their injuries, the combination of their injuries, and the practicality of their seat belt system. The type of injury to the car, the speed, and the line of impact were related to the injuries. Incorrect use of the belt system, malfunction due to external causes, and construction defects in the seat belt system were described and evaluated according to their specific importance.


Action of cholera toxin on dispersed acini from guinea pig pancreas.
In dispersed acini from guinea pig pancreas cholera toxin bound reversibly to specific membrane binding sites to increase cellular cyclic AMP and amylase secretion. Cholera toxin did not alter outflux of 45Ca or cellular cyclic AMP. Binding of 125I-labeled cholera toxin could be detected within 5 min; however, cholera toxin did not increase cyclic AMP or amylase release until after 40 min of incubation. There was a close correlation between the dose vs. response curve for inhibition of binding of 125I-labeled cholera toxin by native toxin and the action of native toxin on cellular cyclic AMP. With different concentrations of cholera toxin, maximal stimulation of amylase release occurred when the increase in cellular cyclic AMP was approximately 35% of maximal. Cholera toxin did not alter the increase in 45Ca outflux or cellular cyclic GMP caused by cholecystokinin or carbachol but significantly augmented the increase in cellular cyclic AMP caused by secretin or vasoactive intestinal peptide. The increase in amylase secretion caused by cholera toxin plus secretin or vasoactive intestinal peptide was the same as that with cholera toxin alone. On the other hand, the increase in amylase secretion caused by cholera toxin plus cholecystokinin or carbachol was significantly greater than the sum of the increases caused by each agent alone.


Collapsing the Metabolic PON2zi Scheme in Pancreatic Ductal Adenocarcinoma.
A hallmark of pancreatic ductal adenocarcinoma cancer (PDAC) cells is metabolic reprogramming that facilitates tumor progression. In a recent paper published in Molecular Cell, Nagarajan et al. discover that paraoxonase (PON)2 stimulates glucose transporter (GLUT)1-mediated glucose uptake, prevents AMP-activated protein kinase (AMPK)-mediated anoikis, and consequently promotes PDAC development and metastasis.


A Predictive Decision Analytics Approach for Primary Care Operations Management: A Case Study of Double-Booking Strategy Design and Evaluation.
Primary care plays a vital role for individuals and families in accessing care, keeping well, and improving quality of life. However, the complexities and uncertainties in the primary care delivery system (e.g., patient no-shows/walk-ins, staffing shortage, COVID-19 pandemic) have brought significant challenges in its operations management, which can potentially lead to poor patient outcomes and negative primary care operations (e.g., loss of productivity, inefficiency). This paper presents a decision analytics approach developed based on predictive analytics and hybrid simulation to better facilitate management of the underlying complexities and uncertainties in primary care operations. A case study was conducted in a local family medicine clinic to demonstrate the use of this approach for patient no-show management. In this case study, a patient no-show prediction model was used in conjunction with an integrated agent-based and discrete-event simulation model to design and evaluate double-booking strategies. Using the predicted patient no-show information, a prediction-based double-booking strategy was created and compared against two other strategies, namely random and designated time. Scenario-based experiments were then conducted to examine the impacts of different double-booking strategies on clinic's operational outcomes, focusing on the trade-offs between the clinic productivity (measured by daily patient throughput) and efficiency (measured by visit cycle and patient wait time for doctor). The results showed that the best productivity-efficiency balance was derived under the prediction-based double-booking strategy. The proposed hybrid decision analytics approach has the potential to better support decision-making in primary care operations management and improve the system's performance. Further, it can be generalized in the context of various healthcare settings for broader applications.


Future directions for bronchoalveolar lavage.
Bronchoalveolar lavage provides a means to sample the lung. The ability to describe material obtained from the lower respiratory tract has greatly facilitated pulmonary diagnosis, and it is likely that improvements in diagnostic techniques will continue to develop. The ability to accurately measure lower respiratory tract components has permitted staging of lung disease. Such staging will probably provide improved prognostic insight and permit the development of new therapeutic strategies in lung disease.


Diagnostic Test Characteristics of Ultrasound Based Hydronephrosis in Identifying Low Kidney Function in Young Patients with Spina Bifida: A Retrospective Cohort Study.
Kidney dysfunction in spina bifida is usually detected by low estimated glomerular filtration rate or ultrasound based hydronephrosis. We assessed the diagnostic test characteristics of hydronephrosis for detecting low estimated glomerular filtration rate, hypothesizing that hydronephrosis has low sensitivity compared to cystatin C based estimated glomerular filtration rate. We conducted a single center, retrospective cohort study, including patients with spina bifida from 2012-2017 with 2 kidneys and complete data needed to calculate estimated glomerular filtration rate via multiple pediatric (age 1-17.9 years) or adult (age ≥18 years) estimating equations. We evaluated the association of hydronephrosis status (high grade, low grade or none) with estimated glomerular filtration rate, adjusting for small kidney size and scarring, and calculated diagnostic test characteristics of hydronephrosis for low estimated glomerular filtration rate. We analyzed 247 patients (176 children and 71 adults). Mean±SD age was 13.7±6.6 years, and 81% of patients had myelomeningocele. Hydronephrosis (77% low grade) was found in 35/176 children and 18/71 adults. Hydronephrosis was associated with low estimated glomerular filtration rate in stepwise fashion, independent of kidney size and scarring. However, across cystatin C based pediatric equations, any hydronephrosis (compared to none) had 23%-48% sensitivity, and high grade hydronephrosis (compared to none or low grade) had 4%-15% sensitivity for estimated glomerular filtration rate <90 ml/min/1.73 m2, which remained unchanged after excluding small kidneys and scarring. Across cystatin C based adult equations, any and high grade hydronephrosis had 55%-75% and 40%-100% sensitivity, respectively, for estimated glomerular filtration rate <90 ml/min/1.73 m2, although with wide confidence intervals. Specificity was higher with high grade vs any hydronephrosis. Sensitivities were higher for estimated glomerular filtration rate <60 ml/min/1.73 m2. Hydronephrosis was associated with low estimated glomerular filtration rate but had poor sensitivity for cystatin C based estimated glomerular filtration rate <90 ml/min/1.73 m2, especially among children with spina bifida.


The phylogenetic position of the 'giant deer' Megaloceros giganteus.
The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers--the largest of any deer species, living or extinct--formed a focus of much past work. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer. Recent morphological studies, however, have challenged that view and placed the giant deer closer to the living red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach.


Are Israelis becoming healthier? Trends in self-rated health, 2002-2018.
Life expectancy at birth in Israel is steadily increasing. This raises the question whether Israelis are becoming healthier. The purpose of this study is to estimate trends in morbidity and to try to explain what causes morbidity levels to change. We used 17 years of repeated cross-sectional data from the Social Survey to estimate trends in self-rated health. We used regression models to explain the trends in self-rated health that were observed from 2002 to 2018. Four major findings emerged. First, morbidity as measured by self-rated health has declined. Second, gains in educational attainment do not explain the decline in morbidity. Third, the rise in national expenditure on health per capita is strongly correlated with the decline in morbidity. And fourth, the effect of the national expenditure on health per capita appears to be stronger among women and among those without an academic degree. Self-rated health has improved. However, it has not improved to the same extent for all Israelis. The results of this study show that the health of women has improved more than that of men and that the health of non-academics has improved more than that of academics. The latter suggests that the progressive effect of public financing has offset the regressive effect of out-of-pocket payments on self-rated health.


Cavity ring-down spectroscopy of the oxygen B-band with absolute frequency reference to the optical frequency comb.
Absolute positions of several oxygen B-band lines were measured with the Pound-Drever-Hall-locked frequency-stabilized cavity ring-down spectrometer. The frequency axis of spectra was linked to the optical frequency comb. Achieved uncertainties of line positions are between 0.9 and 2.9 MHz. Self-pressure shifts coefficients are also reported.


Identification of a novel copper-activated and halide-tolerant laccase in Geobacillus thermopakistaniensis.
Genome search of Geobacillus thermopakistaniensis, formerly Geobacillus sp. SBS-4S, revealed the presence of an open reading frame (ESU71923) annotated as laccase. However, the gene product did not display any laccase-like activity against the substrates examined. The laccase activity was, therefore, purified from G. thermopakistaniensis cells and N-terminal amino acid residues of the enzyme were determined. These residues matched the N-terminal sequence of an open reading frame annotated as a copper oxidase (ESU72270). In order to characterize the enzyme, recombinant ESU72270 was prepared in Escherichia coli. The recombinant protein was found to exhibit a negligible amount of laccase activity when produced in the absence of copper in the growth medium. However, the recombinant protein exhibited significantly high laccase activity when produced in the presence of copper. The recombinant enzyme showed highest activity at 60 °C and a pH of 7-7.5. The purified enzyme was highly tolerant to various halides and organic solvents, thus having a potential for various industrial applications. To the best of our knowledge, this is the first characterization of a laccase from genus Geobacillus which identifies a gene responsible for functional laccase in this genus.


Rat spatial memory and foraging on dual radial mazes.
Three experiments are reported that used a new test of spatial memory in rats. The apparatus used was dual eight-arm radial mazes that were connected at one arm of each maze, with a start arm and doors to each maze. Rats could be forced to go to one maze or the other or could make a free choice between mazes. In Experiment 1, rats formed reference memory for the arm containing food on one maze but had food randomly placed on different arms over trials on the other maze. In Experiment 2, rats formed working memory for the arm containing food on one maze but not the other. In Experiment 3, food location changed randomly among trials on both mazes, but one maze contained a cue for the location of food. Rats used reference and working memory to go directly to the food arm on one maze but found food only after searching several arms on the other maze. Most importantly, when given free-choice trials rats developed a significant preference for the maze where they knew the location of food reward or found the cue indicating the location of reward. We suggest these findings may be best interpreted by rats applying two successive rules: (1) choose the maze that leads to the most immediate reward, and (2) use extramaze or intramaze cues to find reward location on the maze.