Microbial mechanism of biochar addition to reduce N2O emissions from soilless substrate systems.
The soilless peat-based substrate partially solves the global soil problem in greenhouse vegetable production. However, it still produces serious N2O emissions due to the application of nutrient solutions. The pyrolysis biochar is regarded as an effective measure to reduce soil N2O emissions. However, the effect and mechanism of biochar on N2O emissions from the soilless substrate remain unknown. Therefore, this study set up six treatments by adjusting the ratio of biochar addition of peat-based substrate: 0% (0BC), 2% (2BC), 4% (4BC), 6% (6BC), 8% (8BC) and 10% (10BC) (v/v). The results showed that compared to the control treatment, N2O emissions reduced by 81%, 71%, 51%, 61%, and 75% in the 2BC, 4BC, 6BC, 8BC and 10BC treatments, respectively. In addition, lettuce yield increased by 10% and 7% in the 2BC and 4BC treatments and decreased by 0.5%, 4% and 6% in the 6BC, 8BC and 10BC treatments, respectively. Combining stable isotope technology, qPCR analysis and high-throughput sequencing, five microbial pathways of N2O production, including bacterial and archaea nitrification (BN and AN), denitrification performed by fungi, denitrifier bacteria and nitrifier bacteria (FD, DD and ND), were roughly distinguished. In addition, the extent of N2O reduction was obtained by δ18O vs.δ15NSP map. For all treatments, overall, the DD process (over 50%) was the main process of N2O production and reduction, while ND and AN processes were almost negligible (less 5%). In detail, the decrease of N2O emissions was caused by decreasing the contribution of FD in the 6BC, 8BC and 10BC treatments and reducing the contribution of BN in the 0BC and 2BC treatments. In addition, biochar addition increased the extent of N2O reduction to N2. In summary, the 2% biochar addition presented the greatest extent of N2O reduction to N2 (83%) and the lowest N2O emissions as well as the highest lettuce yields and nitrogen utilization efficiency. Therefore, 2% biochar is deemed the most optimal addition to the peat-based substrate.


Transcriptomic Analysis of Soil Grown T. aestivum cv. Root to Reveal the Changes in Expression of Genes in Response to Multiple Nutrients Deficiency.
Deficiency of necessary macronutrients, i.e., Potassium (K), Magnesium (Mg), Nitrogen (N), Phosphorus (P), and Sulfate (S) in the soil leads to a reduction in plant growth and yield, which is a result of changes in expression level of various genes. This study was performed to identify the differentially expressed genes and its associated metabolic pathways occurred in soil grown wheat root samples excavated from the control and treated fields. To identify the difference in gene expression levels due to deficiency of the said nutrients, a transcriptomic, meta-analysis was performed on array expression profile data. A set of 435 statistically significant probes encoding 398 Nutrient Deficiency Response Genes (NRGs) responding at-least one nutrients deficiency (ND) were identified. Out of them 55 NRGs were found to response to minimum two ND. Singular Enrichment Analysis (SEA) predicts ontological based classifications and functional analysis of NRGs in different cellular/molecular pathways involved in root development and growth. Functional annotation and reaction mechanism of differentially expressed genes, proteins/enzymes in the different metabolic pathway through MapMan analysis were explored. Further the meta-analysis was performed to revels the active involvement each NRGs in distinct tissues and their comparative potential expression analysis in different stress conditions. The study results in exploring the role of major acting candidate genes such as Non-specific serine/threonine protein kinase, Xyloglucan endotransglucosylase/hydrolase, Peroxides, Glycerophosphoryl diester phosphodiesterase, S-adenosylmethionine decarboxylase proenzyme, Dehydrin family proteins, Transcription factors, Membrane Proteins, Metal binding proteins, Photosystem proteins, Transporter and Transferase associated in different metabolic pathways. Finally, the differences of transcriptional responses in the soil-grown root of T. aestivum cv. and in-vitro grown model plants under nutrients deficiency were summarized.


Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent Cushing's syndrome.
Mitotane is highly effective in the long-term management of Cushing's syndrome but has a slow onset of action. Mitotane combined with fast-acting steroidogenesis inhibitors might avoid the need for emergency bilateral adrenalectomy in patients with severe hypercortisolism. Our objective was to assess the efficacy and safety of combination therapy with mitotane, metyrapone, and ketoconazole in severe ACTH-dependent Cushing's syndrome. Eleven patients with severe Cushing's syndrome participated in this follow-up study in a tertiary referral hospital. High-dose therapy combining mitotane (3.0-5.0 g/24 h), metyrapone (3.0-4.5 g/24 h), and ketoconazole (400-1200 mg/24 h) was initiated concomitantly. Twenty-four-hour urinary free cortisol (UFC) excretion (normal values 10-65 μg/24 h) was monitored. Data are reported as medians (range). All 11 patients experienced a marked clinical improvement. UFC excretion fell rapidly from 2737 μg/24 h (range 853-22,605) at baseline to 50 μg/24 h (range 18-298) (P = 0.001) within 24-48 h of treatment initiation and remained low to normal on the combination therapy. In seven patients, metyrapone and ketoconazole were discontinued after 3.5 months (range 3.0-6.0) of combination therapy, and UFC excretion remained controlled by mitotane monotherapy (UFC 17 μg/24 h, range 5-85; P = 0.016). Five patients became able to undergo etiological surgery and are presently in remission. Four of them recovered normal adrenal function after mitotane discontinuation. Adverse effects were tolerable, consisting mainly of gastrointestinal discomfort and a significant rise in total cholesterol and γ-glutamyl transferase levels (P = 0.012 and P = 0.002, respectively). When surgical treatment for severe ACTH-dependent Cushing's syndrome is not feasible, combination therapy with mitotane, metyrapone, and ketoconazole is an effective alternative to bilateral adrenalectomy, a procedure associated with significant morbidity and permanent hypoadrenalism.


Understanding 30-day re-admission after hospitalisation of older patients for diabetes: identifying those at greatest risk.
To identify factors that contribute to older Australians admitted to hospital with diabetes being re-hospitalised within 30 days of discharge. A retrospective cohort study of Department of Veterans' Affairs administrative data for all patients hospitalised for diabetes and discharged alive during the period 1 January - 31 December 2012. Causes of re-hospitalisation and prevalence of clinical factors associated with re-hospitalisation within 30 days of discharge. Multivariate logistic regression analysis (backward stepwise) was used to identify characteristics predictive of 30-day re-hospitalisation. 848 people were hospitalised for diabetes; their median age was 87 years (interquartile range, 77-89 years) and 60% were men. 209 patients (24.6%) were re-hospitalised within 30 days of discharge, of whom 77.5% were re-admitted within 14 days of discharge. 51 re-hospitalisations (24%) were for diabetes-related conditions; 41% of those re-admitted within 14 days had not seen their general practitioner between discharge and re-admission. Factors predictive of re-hospitalisation included comorbid heart failure (adjusted odds ratio [aOR], 1.49; 95% confidence interval [CI], 1.03-2.17; P = 0.036), numbers of prescribers in previous year (aOR [for each additional prescriber], 1.06; 95% CI, 1.01-1.08; P = 0.031), and two or more hospitalisations in the 6 months before the index admission (aOR, 1.79; 95% CI 1.15-2.78; P = 0.009). Older people hospitalised for diabetes who have comorbid heart failure, multiple recent hospitalisations, and multiple prescribers involved in their care are at greatest risk of being re-admitted to hospital within 30 days. Targeted follow-up during the initial 14 days after discharge may facilitate appropriate interventions that avert re-admission of these at-risk patients.


Ethanol and brain ribosomes.
The effects of chronic ethanol intake by mice and rats have been determined on brain ribosomes. Under conditions of ethanol administration, when physical dependence on ethanol either does or does not develop in rats, significant inhibition of polypeptide synthesis was observed in comparison with animals not receiving ethanol. In both rats and mice drinking a 10% ethanol solution, in vitro protein synthesis was found to be diminished more in the free than membrane-bound polyribosomes (polysomes) when compared to similar fractions obtained from control animals. Addition of exogenous amino acids stimulated protein synthesis of free polysomes to a greater extent than that of bound polysomes obtained from both groups of micemin vivo incorporation of [5-3H]-orotic acid into RNA was more inhibited in polysomes than ribosomes of ethanol-drinking mice, suggesting that ethanol affects messenger RNA. In addition, chronic ethanol ingestion produced a decreased in vivo incorporation in ribosomal RNA of a mixed population of ribosomes and polysomes. Chronic ethanol ingestion by mice led also to a differential effect on the polysomal population of the brain. It decreased the amount and the incorporation of precursor label into RNA of free polysomes while exerting an opposite effect on bound polysomes. The significance of these findings relative to brain metabolism is discussed.


Does bariatric surgery improve adipose tissue function?
Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.


Inspiratory Muscle Training in Nemaline Myopathy.
Respiratory muscle weakness is a common feature in nemaline myopathy. Inspiratory muscle training (IMT) is an intervention that aims to improve inspiratory muscle strength. The aim of this controlled before-and-after pilot study was to investigate if IMT improves respiratory muscle strength in patients with nemaline myopathy. Nine patients (7 females; 2 males, age 36.6±20.5 years) with respiratory muscle weakness and different clinical phenotypes and genotypes were included. Patients performed eight weeks of sham IMT followed by eight weeks of active threshold IMT. The patients trained twice a day five days a week for 15 minutes at home. The intensity was constant during the training after a gradual increase to 30% of maximal inspiratory pressure (MIP). Active IMT significantly improved MIP from 43±15.9 to 47±16.6 cmH2O (p = 0.019). The effect size was 1.22. There was no significant effect of sham IMT. Sniff nasal inspiratory pressure, maximal expiratory pressure, spirometry, and diaphragm thickness and thickening showed no significant improvements. This pilot study shows that threshold IMT is feasible in patients with nemaline myopathy and improves inspiratory muscle strength. Our findings provide valuable preliminary data for the design of a larger, more comprehensive trial.


Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity.
Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and computational modelling shows that protein trafficking through the secretory machinery is often the rate-limiting step in single-cell production, and strategies to enhance the overall capacity of protein secretion within hosts for the production of heterologous proteins may improve productivity.


The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity.
Pseudoachalasia is an esophageal motor disorder usually associated with malignancy that has clinical, radiographic, and manometric findings that are often indistinguishable from primary achalasia. There are few reports examining the histologic features of the associated neoplasms and their relationship with the esophageal myenteric plexus. We studied the clinical and pathologic features of 13 cases of pseudoachalasia seen at our institution between 1979 and 1999. Detailed clinical and radiographic data were obtained from medical records. In all cases available histologic material was reviewed to confirm the presence and type of associated neoplasm. When possible, the relationship of the neoplasm to the esophageal myenteric plexus was examined. In selected cases immunohistochemical stains were performed to further evaluate this relationship. All patients had clinical, radiographic, and manometric features similar to primary achalasia. The cohort included seven men and six women, age range 24-79 years (median 61 years). Associated neoplasms included esophageal adenocarcinoma arising in Barrett's esophagus (n = 1), adenocarcinoma of the esophagogastric junction (n = 7), metastatic renal cell carcinoma to the esophagogastric junction (n = 1), breast adenocarcinoma (n = 1), pulmonary small cell carcinoma (n = 1), pleural malignant mesothelioma (n = 1), and mediastinal fibrosis (n = 1). The mechanism of pseudoachalasia was consistent with neoplastic infiltration of the esophageal myenteric plexus in 11 cases. Neoplastic cells surrounded myenteric ganglion cells, which appeared normal in number and morphology. In the patient with pulmonary small cell carcinoma, there was no evidence of neoplastic infiltration of the esophagogastric junction, and anti-ANNA-1 antibody was detected, suggesting a paraneoplastic syndrome. Tissue obtained at the time of esophagomyotomy revealed lymphocytic myenteric inflammation and marked depletion of ganglion cells identical to that seen in primary achalasia. The mechanism pseudoachalasia in the patient with breast adenocarcinoma is uncertain, as there was no evidence of direct involvement of the esophagogastric junction. In summary, we describe 13 cases of pseudoachalasia resulting in a clinical syndrome indistinguishable from primary achalasia. The most common mechanism is direct involvement of the esophageal myenteric plexus by neoplastic cells. Rarely, a distant neoplasm may cause this syndrome as a paraneoplastic process.


High Dielectric Transparent Film Tailored by Acceptor and Donor Codoping.
High dielectric constant materials are of particular current interests as indispensable components in transistors, capacitors, etc. In this context, there are emerging trends to exploit defect engineering in dielectric ceramics for enhancing the performance. However, demonstrations of similar high dielectric performance in integration-compatible crystalline films are rare. Herein, such a breakthrough via the functionalization of donor-acceptor dipoles by compositional tuning in GaCu codoped ZnO films is reported. The dielectric constant reaches ~200 at 1 kHz and the optical transmittance in visible light reaches ~80%. Importantly, by analyzing the impedance spectroscopy data, prominent relaxation mechanisms in correlation with the dipole properties, enabling consistent explanations of the dielectric constant as a function of frequency are discriminated. The atomistic nature of the dipoles is revealed by the systematic X-ray spectroscopy analysis. Spectacularly, similar trends for the dielectric properties are observed, while synthesizing samples by pulsed laser deposition and ion implantation, indicating the general character of the phenomena.


[Peri- and postoperative management in one staged operation of cardiac disease combined with pectus excavatum].
Patients with pectus excavatum occasionally have coexisting surgical heart disease. During a 10-year period up to the end of 1988, we surgically treated a total of 2015 cases of pectus excavatum, including 12 cases with one staged operation for pectus excavatum and heart disease. Proving the advantage of our one staged operation for the coexisting diseases we studied data resulting from the perioperative management in the group of one staged operations (n = 5), and in the other group of single valve replacement (n = 10). Operative time, amount of operative blood loss and total amount of transfused blood, were 433 +/- 66 min. (mean +/- SD), 3180 +/- 1867 ml and 4836 +/- 2247 ml, in the former group (n = 5), respectively. These data were almost similar to those in the latter group (n = 10). Postoperative ventilatory support time and ICU stay time also showed little difference between two groups. We conclude these data supports our previous report that one staged operation has no perioperative disadvantage in the surgical treatment of patients with both cardiac disease and pectus excavatum.


Female and male rats in late adolescence differ from adults in amphetamine-induced locomotor activity, but not in conditioned place preference for amphetamine.
Rodent models display differences in drug-induced behaviour between prepubertal/young adolescents and adults that parallel developmental differences in people; however, little is known as to when the transition to 'adultlike' behaviour occurs. We investigated the differences in locomotor and reward responses to amphetamines in male and female rats in late adolescence and compared them with corresponding adult responses. Long-Evans rats were tested for locomotor activity and conditioned place preference (CPP) for amphetamine (0.25, 0.5 or 1.0 mg/kg), beginning at 45 or 69 days of age. Adolescent female rats moved less to the first injection of amphetamine compared with adult female rats irrespective of dose, whereas adolescent male rats did not differ from adults. Adolescent female rats significantly increased locomotor activity in response to subsequent injections of amphetamine at all three doses, whereas such sensitization was only found at the highest dose for adult female and male rats. No effect of repeated injections at any dose was observed in adolescent male rats. No age differences were observed in CPP, but female rats showed greater CPP during the dioestrous than during the oestrous phase of the cycle. These data suggest that differences in neural systems underlying some behavioural responses to amphetamine continue to mature postpubertally into late adolescence in a sex-specific manner.


Computed tomography and magnetic resonance imaging features of ovarian fibrothecoma.
The aim of the present study was to investigate the imaging characteristics of ovarian fibrothecoma. The cases of 25 female patients with pathologically confirmed ovarian fibrothecomas were retrospectively reviewed. Tumor location, size, density, signal intensity, cystic degeneration, calcification, enhancement pattern and ascites were assessed by computed tomography (CT) (n=20) and magnetic resonance imaging (MRI) (n=5). Clinical and histological features were also evaluated. The results revealed that 23 (92.0%) patients were postmenopausal, with a mean age ± standard deviation (SD) of 60.7±10.8 years old. All 25 tumors were unilateral and a thickened endometrium was observed in 7 (28.0%) patients. In total, 24 (96.0%) tumors appeared to have well-defined boundaries, with 1 (4%) tumor exhibiting an obscure boundary. Tumors had a mean size of 9.8±5.3 cm. Solid and predominantly solid masses were found in 16 cases (64.0%), and cystic and predominantly cystic masses were found in 9 patients (36.0%). Solid regions of masses exhibited hypodensity or isodensity in 24 patients (96.0%), with 1 patient (4.0%) exhibiting hyperdensity. The mean CT value (± SD) was 44.2±12.8 HU (range, 31-79HU) in unenhanced images. All masses exhibited isointensity or slight hypointensity on T1-weighted imaging, and tumor parenchyma also exhibited slight hypointensity or isointensity on T2-weighted imaging compared with the myometrium, with or without areas of patchy hyperintensity. Contrast-enhanced CT or MRI scans were performed on 19 patients, and the solid components (94.7%) exhibited mild to moderate enhancement in 18 patients and 1 patient (5.3%) exhibited intense enhancement. Tumor size was positively correlated with the tumor cystic degeneration (r=0.77, P<0.001) and ascites (r=0.41, P<0.001). Therefore, ovarian fibrothecoma typically presents as solid or predominant solid masses with clear boundaries; the parenchyma of the tumor exhibits isodensity on CT scans, slight hypointensity or isointensity on MRI and mild enhancement following contrast-medium injection. The thickened endometrium observed in postmenopausal woman may also be a valuable imaging feature.


Room-temperature calorimeter for x-ray free-electron lasers.
We have developed a room-temperature calorimeter for absolute radiant power measurements of x-ray free-electron lasers. This room-temperature calorimeter is an electrical substitution device based on the equivalence of electrical and radiant heating. Consequently, the measured radiant powers are traceable to electrical standards, i.e., the International System Units (SI). We demonstrated the performance of the room-temperature calorimeter by electrical power measurements (offline tests). In the offline tests, the room-temperature calorimeter was proven to be able to measure external powers up to at least 6.9 mW, which exceeds the upper limit (∼4 mW) of a cryogenic radiometer (the primary standard detector in Japan). In addition, measurement uncertainties of the room-temperature calorimeter were evaluated to be less than 1.0%, which is adequate for the radiant power measurements of x-ray free-electron lasers. An indirect comparison with the cryogenic radiometer was performed using a synchrotron radiation source to confirm the validity of the absolute radiant powers measured with the room-temperature calorimeter. The absolute radiant powers measured by the calorimeter agreed with those measured by the cryogenic radiometer within 0.6%, which is less than the relative standard uncertainty of the comparison (1.0%).


Carcinogenic risk assessment in proper perspective.
The evidence that human cancers result in large measure from factors related to life style, working conditions, or other extrinsic variables--and are thus, in principle, preventable (Doll and Peto, 1981)--and the hypothesis that there is no threshold for the carcinogenic effects of many cancer-causing agents (Office of Science and Technology Policy, 1985) have spurred efforts to minimize human exposure to carcinogens. In pursuit of this goal, attempts have been made to identify airborne and other extrinsic carcinogens and to assess the extent to which they contribute to the occurrence of cancer. The status of such endeavors is summarized in the following, without any attempt at a comprehensive review, which would be beyond the scope of this report.


[Hypoinsulinemia and bioenergetic processes in the rat cerebral cortex].
Increase in activity of lactate dehydrogenase, of its isoenzymes LDH1, LDH2 and LDH3 as well as in content of lactic acid with simultaneous decrease in the pyruvic acid content were found in brain hemispheres of rats with alloxan diabetes. A decrease in the rate of energy reactions in rat brain hemispheres, caused by impairment of glucose oxidation in the Krebs cycle, proved to be the specific property of metabolic alterations in these cells under conditions of hypoinsulinemia.


Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project.
Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data. Clinical trials designed to assess efficacy are often insufficiently powered to generate reliable safety data. The West of Scotland Coronary Prevention Study (WOSCOPS), the Cholesterol and Recurrent Events (CARE), and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) studies collectively accumulated >112 000 person-years of exposure in double-blind randomized trials comparing placebo and pravastatin (40 mg once daily). During 5 years of exposure, the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups. No differences in noncardiovascular serious adverse events were detected. With >243 000 blood sample analyses, the percentage of patients with any abnormal liver function test after baseline sampling was similar (>3x the upper limit of normal for alanine aminotransferase: 128 [1.4%] versus 131 [1.4%] patients for pravastatin versus placebo, respectively). Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations; no cases of mild or severe myopathy were reported. A Cox regression model considering treatment group, age, diabetes, smoking, whether primary or secondary prevention study, and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo. This prospective analysis indicates that during prolonged exposure, 40 mg of pravastatin is well tolerated, with no excess of noncardiovascular serious adverse events, including liver function abnormalities and laboratory and clinical evidence for myositis. These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent.


A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads.
The development of a reliable biomarker for irritable bowel syndrome (IBS) remains one of the major aims of research in functional gastrointestinal disorders (FGIDs) and is complicated by the absence of a perfect reference standard. Previous efforts based on genetic and immune markers have showed promise, but have not been robust. To evaluate an extensive panel of gene expression and serology markers combined with psychological measures in differentiating IBS from health and between subtypes of IBS. Of subjects eligible for analysis (N = 244), 168 met criteria for IBS (60 IBS-C, 57 IBS-D and 51 mixed), while 76 were free of any FGID. A total of 34 markers were selected based on pathways implicated in pathophysiology of IBS or whole human genome screening. Psychological measures were recorded that covered anxiety, depression and somatisation. Models differentiating disease and health were based on unconditional logistic regression and performance assessed through area under the receiver-operator characteristic curve (AUC), sensitivity and specificity. The performance of a combination of 34 markers was good in differentiating IBS from health (AUC = 0.81) and was improved considerably with the addition of four psychological markers (combined AUC = 0.93). Of the 34 markers considered, discrimination was derived largely from a small subset. Good discrimination was also obtained between IBS subtypes with the best being observed for IBS-C vs. IBS-D (AUC = 0.92); however, psychological variables provided almost no incremental discrimination subtypes over biological markers (combined AUC = 0.94). A combination of gene expression and serological markers in combination with psychological measures shows exciting progress towards a diagnostic test for IBS compared with healthy subjects, and to discriminate IBS-C from IBS-D.


Dietary protein reduction on microbial protein, amino acid digestibility, and body retention in beef cattle: 2. Amino acid intestinal absorption and their efficiency for whole-body deposition.
The objective of this study was to determine the apparent and true intestinal digestibility of total and individual AA, and to estimate the efficiency of whole-body AA retention from individual and total absorbed AA. Four Nellore animals (241.3 kg initial BW) and four crossbred Angus × Nellore (263.4 kg initial BW) cannulated in rumen and ileum were randomly allocated in two 4 × 4 Latin squares. The experiment lasted four 17 d periods, with 10 d for adaptation to diets and another 7 d for data collection. The diets consisted of increasing CP levels: 100, 120, or 140 g/kg of DM offered ad libitum, and restricted intake diet with 120 g CP/kg DM (experiment 1). In experiment 2, forty-four bulls (22 Nellore and 22 crossbred F1 Angus × Nellore) with 8 months and initial shrunk BW 215.0 ± 15.0 kg (Nellore = 208.0 ± 12.78 kg; Angus × Nellore = 221.9 ± 14.16 kg) were used. Eight of those animals were slaughtered at the beginning of the experiment. The remaining 36 bulls were allocated in a completely randomized design with six replicates, in a 2 (genetic groups) × 3 (CP contents) factorial scheme. The amount of essential AA (EAA) and nonessential AA (NEAA) reaching the small intestine increased linearly (P < 0.05) in response to CP content. The apparent digestibility of EAA was not affected (P > 0.05) by CP content, with exception for histidine (P = 0.07, linear effect), leucine (P = 0.01, linear effect), and methionine (P = 0.05, linear effect). Differences existed among AA when compared the apparent digestibility of NEAA. The apparent digestibility of alanine (P = 0.05), aspartic acid (P = 0.07), glutamic acid (P = 0.02), glycine (P = 0.05), proline (P = 0.02), and serine (P = 0.04) responded quadratically to CP content increase. However, the apparent digestibility of cystine and tyrosine was not affected (P > 0.05) by increasing dietary CP. The true intestinal digestibilities of total, essential, nonessential AA, lysine, and methionine were 75.0%, 77.0%, 74.0%, 77.0%, and 86%, respectively. The true intestinal digestibility of total microbial AA was 80%. The efficiency of utilization of total AA for whole-body protein deposition was 40%. The efficiency of utilization of lysine and methionine was 37% and 58%, respectively. It was concluded that the AA flow to the omasum increases in response to dietary CP content. In addition, there are differences among AA in the efficiency that they are used by beef cattle.


[Low susceptibility of choriocarcinoma cell lines to lymphokine activated killer (LAK) cells].
We investigated the anti-tumor effect of lymphokine activated killer (LAK) cells on various carcinoma cell lines as it may play an important role in the immunotherapy of gynecologic cancers. Peripheral blood lymphocytes (PBL) were cultured in 10 U/ml of recombinant interleukin-2 (rIL-2). The cytotoxic action of LAK and natural killer (NK) on carcinoma cell lines was measured by a standard 4-hr 51Cr-releasing assay. Daudi and RPMI 1788, NK resistant B cell lines were lysed by rIL-2 activated PBL although they were not killed by human fresh PBL. LAK cells thus induced were markedly cytotoxic to sixteen carcinoma cell lines. However, five choriocarcinoma cell lines were resistant to LAK action because specific action was less than 30% at effector/target ratio of 20. The cold target competitive inhibition experiments showed that the choriocarcinoma cell line GCH-1 induced much lower inhibition than Daudi cells. These results indicate that the low susceptibility of the choriocarcinoma cell lines to LAK cells could be due to the lack of the effector molecules recognized by killer cells.


A Role of Corazonin Receptor in Larval-Pupal Transition and Pupariation in the Oriental Fruit Fly Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).
Corazonin (Crz) is a neuropeptide hormone, but also a neuropeptide modulator that is internally released within the CNS, and it has a widespread distribution in insects with diverse physiological functions. Here, we identified and cloned the cDNAs of Bactrocera dorsalis that encode Crz and its receptor CrzR. Mature BdCrz has 11 residues with a unique Ser11 substitution (instead of the typical Asn) and a His in the evolutionary variable position 7. The BdCrzR cDNA encodes a putative protein of 608 amino acids with 7 putative transmembrane domains, typical for the structure of G-protein-coupled receptors. When expressed in Chinese hamster ovary (CHO) cells, the BdCrzR exhibited a high sensitivity and selectivity for Crz (EC50 ≈ 52.5 nM). With qPCR, the developmental stage and tissue-specific expression profiles in B. dorsalis demonstrated that both BdCrz and BdCrzR were highly expressed in the larval stage, and BdCrzR peaked in 2-day-old 3rd-instar larvae, suggesting that the BdCrzR may play an important role in the larval-pupal transition behavior. Immunochemical localization confirmed the production of Crz in the central nervous system (CNS), specifically by a group of three neurons in the dorso-lateral protocerebrum and eight pairs of lateral neurons in the ventral nerve cord. qPCR analysis located the BdCrzR in both the CNS and epitracheal gland, containing the Inka cells. Importantly, dsRNA-BdCrzR-mediated gene-silencing caused a delay in larval-pupal transition and pupariation, and this phenomenon agreed with a delayed expression of tyrosine hydroxylase and dopa-decarboxylase genes. We speculate that CrzR-silencing blocked dopamine synthesis, resulting in the inhibition of pupariation and cuticular melanization. Finally, injection of Crz in head-ligated larvae could rescue the effects. These findings provide a new insight into the roles of Crz signaling pathway components in B. dorsalis and support an important role of CrzR in larval-pupal transition and pupariation behavior.


Detection of herpes simplex virus in the ependyma of experimentally infected mice.
Forty-five Swiss albino mice were inoculated with HSV-1 (strain McKrae) by the corneal route. The spread of HSV to the brain stem and the ventricular ependyma was investigated. The polymerase chain reaction (PCR) was used to detect HSV-DNA in the CSF during the course of infection. The ependyma of the third and fourth ventricle and the central canal contained viral antigen at a late stage of infection in up to 60% of mice. At this stage we found that many animals gave a positive PCR in the CSF although no antigen could be detected in the ependymal cells. The presence or absence of antigen containing cells could not be related to detection of HSV-DNA in the CSF. The results show that infection of the ventricular wall is not important for the spread of HSV to the CSF.


The Rho1p exchange factor Rgf1p signals upstream from the Pmk1 mitogen-activated protein kinase pathway in fission yeast.
The Schizosaccharomyces pombe exchange factor Rgf1p specifically regulates Rho1p during polarized growth. Rgf1p activates the beta-glucan synthase (GS) complex containing the catalytic subunit Bgs4p and is involved in the activation of growth at the second end, a transition that requires actin reorganization. In this work, we investigated Rgf1p signaling and observed that Rgf1p acted upstream from the Pck2p-Pmk1p MAPK signaling pathway. We noted that Rgf1p and calcineurin play antagonistic roles in Cl(-) homeostasis; rgf1Delta cells showed the vic phenotype (viable in the presence of immunosuppressant and chlorine ion) and were unable to grow in the presence of high salt concentrations, both phenotypes being characteristic of knockouts of the MAPK components. In addition, mutations that perturb signaling through the MAPK pathway resulted in defective cell integrity (hypersensitivity to caspofungin and beta-glucanase). Rgf1p acts by positively regulating a subset of stimuli toward the Pmk1p-cell integrity pathway. After osmotic shock and cell wall damage HA-tagged Pmk1p was phosphorylated in wild-type cells but not in rgf1Delta cells. Finally, we provide evidence to show that Rgf1p regulates Pmk1p activation in a process that involves the activation of Rho1p and Pck2p, and we demonstrate that Rgf1p is unique in this signaling process, because Pmk1p activation was largely independent of the other two Rho1p-specific GEFs, Rgf2p and Rgf3p.


Theoretical and experimental studies on the influence of ultrasound on immobilized enzymes.
Experimental investigations on alpha-amylase and glucoamylase bound to porous polystyrene show that the activity of immobilized enzymes can be raised in the presence of an ultrasonic field. The maximum activity increase in a flow cuvette at 7.6 MHz and a sound intensity of 5 kW/m(2) amounts to more than 200% under the given experimental conditions. A mathematical model based on the differential equation for the interior and exterior substrate transport is set up and solved numerically. From the theoretical considerations and the experiments it is evident that the mechanism of the ultrasonic effect can be explained in terms of a reduction of the unstirred diffusion layer around the matrix particles.


Perception is reality: How patients contribute to poor workplace safety perceptions.
Nurses and aides are among the occupational subgroups with the highest injury rates and workdays lost to illness and injury in North America. Many studies have shown that these incidents frequently happen during provision of patient care. Moreover, health care workplaces are a source of numerous safety risks that contribute to worker injuries. These findings identify health care as a high-risk occupation for employee injury or illness. The purpose of this study was to examine the relationships among patient care, employee safety perceptions, and employee stress. Using the National Institute for Occupational Safety and Health Model of Job Stress and Health as a foundation, we developed and tested a conceptual workplace safety climate-stress model that explicates how caring for high-risk patients is a safety stressor that has negative outcomes for health care providers, including poor workplace safety perceptions and increasing stress levels. We introduced the concept of "high-risk patients" and define them as those who put providers at greater risk for injury or illness. Using a nonexperimental survey design, we examined patient types and safety perceptions of health care providers (nurses, aides, and allied health) in an acute care hospital. Health care providers who care for high-risk patients more frequently have poor safety climate perceptions and higher stress levels. Safety climate was found to mediate the relationship between high-risk patients and stress. These findings bring insight into actions health care organizations can pursue to improve health care provider well-being. Recognizing that different patients present different risks and pursuing staffing, training, and equipment to minimize employee risk of injury will help reduce the staggering injury rates experienced by these employees. Moreover, minimizing employee stress over poor workplace safety is achievable through comprehensive workplace safety climate programs that include supervisor, management, and organizational commitment to safety enhancement.


Development of a Saudi Food Frequency Questionnaire and testing its reliability and validity.
To create a food frequency questionnaire specifically designed to capture the dietary habits of Saudis and test its validity and reliability. Methods: This investigation is a longitudinal, test-retest study conducted in King Saud University, Riyadh, Kingdom of Saudi Arabia between December 2015 and March 2016. A list of 140 food items was included in the questionnaire where a closed-ended and open-ended approach was used. Regarding past year food frequency consumption and 24 hours dietary recall, body weight and height were collected. Internal consistency, test-retest reliability, completeness of the food list, and criterion validity were assessed. Results: One-hundred and thirty eight participants were interviewed to complete the 24 hours dietary recall and the constructed questionnaire. Approximately 85% of the food items reported in the dietary recall were covered in the food frequency questionnaire. The association of body mass index with meats (regression coefficients: 2.28) and dairy products consumption frequency was statistically significant (regression coefficients: 2.31). A high overall reproducibility rate of the questionnaire was detected (Pearsons' correlation coefficient: 0.78 p less than 0.001). Conclusion: The developed questionnaire has a high reliability and reasonable validity, and suitable for use in nutritional epidemiological investigations in Saudi Arabia.


100Gb/s PolMux-NRZ-AOS-OFDM transmission system.
A novel high speed transmission system using all-optical sampling orthogonal frequency multiplexing (AOS-OFDM) technique is proposed and demonstrated. By utilizing polarization multiplexing (PolMUX) and non-return-to-zero (NRZ) format, the total bit rate is 100 Gb/s with high spectral efficiency of 1.6. In addition, optical cyclic postfixes are inserted to help improve the system performance. The 100 Gb/s PolMux-NRZ-AOS-OFDM signals can pass through 20 km single-mode fiber (SMF) transmission link without any compensation.


Synthesis of Thieno-Fused Five- and Six-Membered Nitrogen and Oxygen Heterocycles via Intramolecular Heteroannulation of 4,5-Substituted 3-Amino or 3-Hydroxy 2-Functionalized Thiophenes.
Diverse general high-yield routes for novel thieno-fused five- and six-membered nitrogen and oxygen heterocycles such as thieno[3,2-b]pyrroles, thieno[3,2-b]furans, thieno[3,2-b]indoles, thieno[3,2-b]benzofurans, thieno[3,2-b]pyridine-5-ones, thieno[3,2-b]pyran-5-ones, thieno[3,2-b]isoquinolin-5-ones, thieno[3,2-b]chromen-5-ones, thieno[3,2-b]quinolin-9-ones, and thieno[3,2-b]chromen-9-ones have been developed via in situ or stepwise intramolecular heteroannulation of newly synthesized 4,5-substituted 3-amino- or 3-hydroxy 2-functionalized thiophenes. These substituted 3-amino/hydroxythiophenes were readily obtained in high yields from easily accessible precursors, in a sequential one-pot process, by treatment of a range of (het)aryl/unsubstituted acetonitriles or acetates with (het)aryl dithioesters in the presence of LDA, followed by in situ alkylation-intramolecular condensation of the resulting enethiolate salts with functionalized activated methylene halides. The functionalized activated methylene halides employed in these reactions for the synthesis of various thieno-fused heterocycles were cinnamyl bromide, 2-bromobenzyl chloride, bromocrotonate, 2-(bromomethyl)benzoate, and 2-chlorophenacyl bromide. A few of the 4,5-substituted 3-amino/hydroxy-2-stryrylthiophenes (or 2-acrylates) displayed strong fluorescence, and their absorption/emission spectra have also been examined.


Out, out, damned blind spot! The problem of anxiety with dynamic psychotherapy.
This article discusses Lady Macbeth's famous sleepwalking scene from the Shakespearean tragedy, and how it became used as a template for the formulation of obsessive-compulsive disorder. Psychoanalysis maintained its role in understanding the condition, despite the lack of evidence base and the repeated finding from many therapists of a failure to control symptomatology. It is suggested that psychodynamic psychotherapy suffered from a failure to recognise what components of its practice were aesthetically attractive concepts rather than evidence-based medicine and outcome measures, and is an important issue in considering its future directions.


Long-term mechanical ventilation: management strategies.
This paper reviews management strategies for patients undergoing prolonged mechanical ventilation (PMV). Topics covered include how to identify and correct barriers to weaning, the systematic approach to weaning trials, when to cease weaning trials and proceed with life-long support, managing the tracheostomy tube during PMV, and, finally, how to select a suitable mechanical ventilator for PMV.


Deregulation of signaling pathways controlling cell survival and proliferation in cancer cells alters induction of cytochrome P450 family 1 enzymes.
Cytochrome P450 family 1 (CYP1) enzymes contribute both to metabolism of xenobiotics and to the control of endogenous levels of ligands of the aryl hydrocarbon receptor (AhR). Their activities, similar to other CYPs, can be altered in tumor tissues. Here, we examined a possible role of proliferative/survival pathways signaling, which is often deregulated in tumor cells, and possible links with p300 histone acetyltransferase (a transcriptional co-activator) in the control of CYP1 expression, focusing particularly on CYP1A1. Using cell models derived from human liver, we observed that the induction of CYP1A1 expression, as well as other CYP1 enzymes, was reduced in exponentially growing cells, as compared with their non-dividing counterparts. The siRNA-mediated inhibition of proliferation/pro-survival signaling pathway effectors (such as β-catenin and/or Hippo pathway effectors YAP/TAZ) increased the AhR ligand-induced CYP1A1 mRNA levels in liver HepaRG cells, and/or in colon carcinoma HCT-116 cells. The activation of proliferative Wnt/β-catenin signaling in HCT-116 cells reduced both the induction of CYP1 enzymes and the binding of p300 to the promoter of CYP1A1 or CYP1B1 genes. These results seem to indicate that aberrant proliferative signaling in tumor cells could suppress induction of CYP1A1 (or other CYP1 enzymes) via competition for p300 binding. This mechanism could be involved in modulation of the metabolism of both endogenous and exogenous substrates of CYP1A1 (and other CYP1 enzymes), with possible further consequences for alterations of the AhR signaling in tumor cells, or additional functional roles of CYP1 enzymes.


Processes that Inform Multicultural Supervision: A Qualitative Meta-Analysis.
As the fields of counseling and psychotherapy have become more cognizant that individuals, couples, and families bring with them a myriad of diversity factors into therapy, multicultural competency has also become a crucial component in the development of clinicians during clinical supervision and training. We employed a qualitative meta-analysis to provide a detailed and comprehensive description of similar themes identified in primary qualitative studies that have investigated supervisory practices with an emphasis on diversity. Findings revealed six meta-categories, namely: (a) Supervisor's Multicultural Stances; (b) Supervisee's Multicultural Encounters; (c) Competency-Based Content in Supervision; (d) Processes Surrounding Multicultural Supervision; (e) Culturally Attuned Interventions; and (f) Multicultural Supervisory Alliance. Implications for practice are discussed.


A novel water-soluble Hantzsch 1,4-dihydropyridine compound that functions in biological processes through NADH regeneration.
A novel Hantzsch 1,4-dihydropyridine derivative could function in an organic solvent-free solution, and thus it could function in biological systems. These functions can be accomplished through regeneration of the reduced form of nicotinamine adenine dinucleotide (NADH), an essential compound for living organisms. The results obtained here demonstrate the usefulness of a water-soluble Hantzsch 1,4-dihydropyridine derivative and its wide applicability as a chemical energy source, which drives various biological processes efficiently.


Histopathological and biochemical assessments of Costus afer stem on alloxan-induced diabetic rats.
In continuation of our study of the biological activity of the aqueous extract of Costus afer stem used in tradomedicare in Nigeria, this work has investigated the biochemical, nephroprotective, hepatoprotective and protective effects of aqueous extract of C. afer stem on alloxan-induced hyperglycaemic albino Wistar rats. Thirty male albino Wistar rats (150-200 g) were weight-matched into six groups of five rats each. Groups 1 and 2 were the normal (non-induced) and toxic (alloxan-induced) controls, respectively. Groups 3-6 were induced and treated with 1, 2 and 3 g/kg of the aqueous extract of C. afer stem and glibenclamide (5 mg/kg), respectively. Food and fluid intake, body weight, absolute and relative weight of organs (liver, pancreas, and kidneys) and biochemical parameters were measured. There was a significant reduction in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin triglyceride, creatinine, urea and electrolyte when compared with toxic control group. The liver marker enzymes were restored in all the treated groups. The aqueous stem extract possessed hypoglycaemic effect and reversed the histopathological damage in alloxan-induced diabetic rats. This study suggests that aqueous stem extract of C. afer possesses both hypoglycaemic and organ protective properties.


Surgical dilemma - spare or replace regurgitant aortic valve: Late comparative outcomes of two strategies.
To evaluate different aortic root surgery techniques and their contemporary clinical outcomes in patients with regurgitant aortic valve and aortic root aneurysm. The study consisted of 141 adult patients who underwent aortic valve reimplantation (David group = 73) or aortic valve replacement surgery (Bentall group = 68) for aortic valve regurgitation (AR) and dilatation of the aortic root at our institution within the same period (April 2004-October 2016). Kaplan-Meier method was used to estimate survival and other clinically relevant outcomes between the groups. The completeness of clinical follow-up was 100%, with a mean time of 8.0 ± 3.8 years. Thirty-day (in-hospital) mortality rates were equivalent between groups (1.3 and 1.5%, p = 1.0). The overall survival rates at 10 years were significantly better for the David group patients comparing to Bentall group patients (95.3 ± 2.6% vs 79.7 ± 6.8%; p = 0.04) with similar freedom from AV related reoperation (94.4 ± 2.7% vs 98.5 ± 1.5%; p = 0.2). Freedom from bleeding events at 10 years was 90.7 ± 3.6% for Bentall group patients and none were observed among David group patients (p = 0.01). Aortic valve and root surgery can be performed with equivalent safety and efficacy using either valve-sparing (David procedure) or valve-replacing (Bentall procedure) techniques in selected patients. Furthermore, patients after the David procedure demonstrated significantly improved survival and low risk of bleeding in comparison to the Bentall procedure with an acceptable risk of reoperation at 10 years follow-up.


THE IMPACT OF A FLOWER-COLOR POLYMORPHISM ON MATING PATTERNS IN EXPERIMENTAL POPULATIONS OF WILD RADISH (RAPHANUS RAPHANISTRUM L.).
We conducted field experiments to determine how a naturally occurring petal-color polymorphism influences mating patterns in wild radish (Raphanus raphanistrum). The polymorphism is controlled at a single genetic locus, with white petal color being completely dominant to yellow. In experimental populations with equal numbers of yellow- and white-flowered homozygous individuals, insect visitors strongly discriminated against white flowers. Pieris rapae, the most frequent pollinator, was almost 50% more likely to visit yellow than white flowers. Maternal fecundity did not differ between the morphs and was not significantly influenced by a plant's compatibility with potential donors, suggesting that seed production was not limited by receipt of compatible pollen. In contrast, the yellow-flowered morph sired approximately 75% of all seeds produced during the study. This paternity proportion was consistently greater than that expected on the basis of postpollination compatibility measures and was indistinguishable from that expected on the basis of pollinator-visitation frequency. We conclude that the male-fitness advantage of the yellow morph resulted from enhanced pollen export due to the greater attractiveness of its flowers to insect pollinators. With color morphs evenly distributed in experimental arrays, insects did not move assortatively on the basis of petal color, and we found no evidence for assortative pollen flow due to the floral polymorphism. Once postpollination compatibility relationships within populations were taken into account, paternal success of yellow donors did not differ between yellow- and white-flowered maternal plants.


Variation in the fractional conversion of plasma estrone to estriol among women and men.
In the present investigation, we determined the transfer constant of conversion of plasma estrone to estriol (E3) ( [rho] E1- E3BU ) in men, postmenopausal women, and premenopausal parous and premenopausal nulliparous women. We found no significant difference in [rho] E1- E3BU among men, postmenopausal women, premenopausal parous or nulliparous women (whether the latter were studied during the midfollicular or midluteal phase of the ovarian cycle), or in women who were ingesting oral contraceptives. On the other hand, there was a striking variation in the [rho]E1- E3BU among individuals, viz. 0.02-0.27, whereas in a given individual, the variation in [rho] E1- E3BU , evaluated on separate occasions, was small. In addition, we found a negative correlation between age at first fullterm pregnancy and [rho] E1- E3BU .


Multiscale ATUM-FIB Microscopy Enables Targeted Ultrastructural Analysis at Isotropic Resolution.
Volume electron microscopy enables the ultrastructural analysis of biological tissue. Currently, the techniques involving ultramicrotomy (ATUM, ssTEM) allow large fields of view but afford only limited z-resolution, whereas ion beam-milling approaches (FIB-SEM) yield isotropic voxels but are restricted in volume size. Now we present a hybrid method, named ATUM-FIB, which combines the advantages of both approaches. ATUM-FIB is based on serial sectioning of tissue into "semithick" (2-10 μm) sections collected onto tape. Serial light and electron microscopy allows the identification of regions of interest that are then directly accessible for targeted FIB-SEM. The set of semithick sections thus represents a tissue "library" which provides three-dimensional context information that can be probed "on demand" by local high-resolution analysis. We demonstrate the potential of this technique to reveal the ultrastructure of rare but pathologically important events by identifying microglia contact sites with amyloid plaques in a mouse model of familial Alzheimer's disease.


Assessments of global drivers of vaccine hesitancy in 2014-Looking beyond safety concerns.
Vaccine hesitancy has become the focus of growing attention and concern globally despite overwhelming evidence of the value of vaccines in preventing disease and saving the lives of millions of individuals every year. Measuring vaccine hesitancy and its determinants worldwide is important in order to understand the scope of the problem and for the development of evidence-based targeted strategies to reduce hesitancy. Two indicators to assess vaccine hesitancy were developed to capture its nature and scope at the national and subnational level to collect data in 2014: 1) The top 3 reasons for not accepting vaccines according to the national schedule in the past year and whether the response was opinion- or assessment-based and 2) Whether an assessment (or measurement) of the level of confidence in vaccination had taken place at national or subnational level in the previous 5 years. The most frequently cited reasons for vaccine hesitancy globally related to (1) the risk-benefit of vaccines, (2) knowledge and awareness issues, (3) religious, cultural, gender or socio-economic factors. Major issues were fear of side effects, distrust in vaccination and lack of information on immunization or immunization services. The analysis revealed that 29% of all countries had done an assessment of the level of confidence in their country, suggesting that vaccine confidence was an issue of importance. Monitoring vaccine hesitancy is critical because of its influence on the success of immunization programs. To our knowledge, the proposed indicators provide the first global snapshot of reasons driving vaccine hesitancy and depicting its widespread nature, as well as the extent of assessments conducted by countries.


Individuals' knowledge and practices of the cold chain.
This study aims to identify the influence of education on the practices and knowledge of consumers to protect or maintain the cold chain in the Turkish capital of Ankara. Data were gathered by using a questionnaire. Participants were 700 randomly selected volunteering adults. The majority of the participants had a university degree (69.0%) and did not know the definition of cold chain but had some knowledge about it, and differences existed between primary school and university graduates. The scores of consumers' attitudes to maintain cold chain were determined to increase in parallel with education level. The rate of people knowing refrigerator temperature, the coldest part of refrigerator, and controlling whether shops correctly store the products was highest in university graduates. Adults were observed to believe that shop assistants were responsible for maintaining a cold chain. However, the actual importance of consumers in this process reveals the importance of education for individuals.


A case of rabies in man: some problems in diagnosis and management.
A patient who returned from India with a gastrointestinal disturbance subsequently developed the clinical features of rabies. The diagnosis was confirmed by isolation of rabies virus from saliva and the demonstration of rising titres of rabies antibody. He was treated in an intensive care unit, ventilated mechanically, and given rabies antiserum, but cerebral activity ceased and he died after 22 days. His course was marked by numerous bouts of cardiac arrhythmia including complete heart block. This case indicates the need for vaccination against rabies to be carried out immediately after exposure to a possibly rabid dog since encephalitis develops a fatal outcome may not be prevented even with intensive medical treatment.


Changing tastes: learning hunger and fullness after gastric bypass surgery.
Gastric bypass surgery is a specific medical technology that alters the body in ways that force patients to fundamentally change their eating habits. When patients enrol for surgery, they enter a learning process, encountering new and at times contested ways of sensing their bodies, tasting, and experiencing hunger and fullness. In this paper, we explore how patients begin to eat again after gastric bypass surgery. The empirical data used here are drawn from a Danish fieldwork study of individuals undergoing obesity surgery. The material presented shows how the patients used instructions on how to eat. We explore the ways in which diverse new experiences and practices of hunger and fullness are part of the process of undergoing surgery for severe obesity. New sensory experiences lead to uncertainty; as a result, patients practice what we term mimetic eating, which reflects a 'sensory displacement' and hence a rupture in the person's sense of self and social relations. We suggest that eating should be conceptualised as a practice that extends beyond the boundaries of our bodies and into diverse realms of relations and practices, and that changing the way we eat also changes the fundamentally embodied experience of who we are.


pH Gradient as a tool for the separation of ionizable analytes in reversed-phase high-performance chromatography.
The aim of this work was to propose a general scheme of optimizing separation of ionizable analytes and to determine conditions of maximal peak compression in pH-gradient reversed-phase high-performance liquid chromatography (RP HPLC). The approximated explicit equation of the linear pH gradient has been developed. It allows predicting retention times for a given organic modifier content, initial value of pH, and the start and steepness of the pH gradient. Also the formula for calculating maximal peak compression is provided. The developed theory was compared with experimental data on the example of a weak acid (ketoprofen) and a weak base (papaverine). Five parameters characterizing analyte retention (log k(w) and S of the ionized and nonionized forms along with pK(a,chrom)) were determined in a series of isocratic experiments carried out at different pH values and with different methanol contents in the eluent. Next, a series of pH gradients of different pH-gradient steepness and of different pH-gradient starting time has been obtained and used to test the validity of our theoretical approach. The conditions of maximal peak width compression have been found. The derived theory was proved to be in a good agreement with the experimental data. The pH-gradient method led to peak compression of up to 0.2, and minimized peak tailing was obtained for the tested analytes. Since the majority of analytical separations are done in an isocratic mode we proposed a means to transfer an isocratic method to a pH-gradient method.


MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia.
Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML); however, the regulation of DNA methyltransferase 1 (DNMT1), which is responsible for maintenance of DNA methylation patterns, has largely remained elusive. MUC1-C is a transmembrane oncoprotein that is aberrantly expressed in AML stem-like cells. The present studies demonstrate that targeting MUC1-C with silencing or a pharmacologic inhibitor GO-203 suppresses DNMT1 expression. In addition, MUC1 expression positively correlates with that of DNMT1 in primary AML cells, particularly the CD34+/CD38- population. The mechanistic basis for this relationship is supported by the demonstration that MUC1-C activates the NF-κB p65 pathway, promotes occupancy of the MUC1-C/NF-κB complex on the DNMT1 promoter and drives DNMT1 transcription. We also show that targeting MUC1-C substantially reduces gene promoter-specific DNA methylation, and derepresses expression of tumor suppressor genes, including CDH1, PTEN and BRCA1. In support of these results, we demonstrate that combining GO-203 with the DNMT1 inhibitor decitabine is highly effective in reducing DNMT1 levels and decreasing AML cell survival. These findings indicate that (i) MUC1-C is an attractive target for the epigentic reprogramming of AML cells, and (ii) targeting MUC1-C in combination with decitabine is a potentially effective clinical approach for the treatment of AML.


Diagnostic performance of CT-guided percutaneous transthoracic core needle biopsy using low tube voltage (100 kVp): comparison with conventional tube voltage (120 kVp).
Background Computed tomography (CT)-guided percutaneous transthoracic core needle biopsy (PTNB) is typically performed at 120 kVp tube voltage. However, there is no study that has demonstrated diagnostic performance including ground-glass nodules and radiation dose reduction at lower tube voltage in large population. Purpose To retrospectively compare the diagnostic performance and radiation dose between 100 kVp and 120 kVp during CT-guided PTNB. Material and Methods This study included 393 PTNBs performed in 385 patients (Group I; 120 kVp) from March 2011 to September 2011 and 1368 PTNBs performed in 1318 patients (Group II; 100 kVp) from October 2011 to December 2013. The patients underwent CT-guided PTNB with the coaxial technique. Diagnostic performance, complication rate, and radiation dose were compared between two groups. Results Technical success was achieved in 391 of 393 PTNBs (99.5%) in Group I and in 1344 of 1368 PTNBs (98.2%) in Group II ( P = 0.09). The diagnostic accuracies for pulmonary lesions were not significantly different between two groups (97.1% [362/373] versus 96.2% [1202/1249], P = 0.458). Complication rate showed no significant differences between two groups in terms of pneumothorax (19.7% [77/391] versus 19.4% [261/1344], P = 0.904) and hemoptysis (2.3% [9/391] versus 3.2% [43/1344], P = 0.360). Among patients who developed pneumothorax, three patients (3.9%, 3/77) in Group I and eight patients (3.1%, 8/261) in Group II required treatment with drainage catheter. Nobody needed further treatment for hemoptysis in the two groups. The mean radiation dose was 1.5 ± 1.9 mSv in Group I and 0.7 ± 0.3 mSv in Group II ( P < 0.001). Conclusion The 100-kVp protocol for CT-guided PTNB showed significant benefit of radiation dose reduction while maintaining high diagnostic accuracy and safety.


Infectious mononucleosis and corticosteroids: management practices and outcomes.
Although many studies have examined the effects of systemic corticosteroid therapy (SCT) on the clinical course of infectious mononucleosis (IM), few have evaluated the influence of these studies on treatment patterns and outcomes. The purpose of this study was to review current therapeutic strategies and outcomes in uncomplicated and complicated IM. Retrospective case series. Tertiary care center. We identified 206 immunocompetent patients with IM diagnosed during the previous 5 years. Patient information, including age, sex, history and physical findings at presentation, pertinent laboratory data, management practices, and treatment outcomes, were analyzed. Systemic corticosteroid therapy was used in 44.7% of patients. Evaluation of treatment indications for SCT revealed that 8.0% of the study population qualified by traditional criteria for the use of corticosteroids; 92.0% of patients received SCT for other indications. Factors associated with the observed increase in corticosteroid use included a history of repeat visits, inpatient admission, and otolaryngology consultation. Diagnosis was made on the basis of a positive heterophil antibody test (monospot test) with appropriate clinical findings (97.5% of patients) or by the presence of lymphocytosis with appropriate clinical findings (2.4% of patients). Systemic corticosteroid therapy was not positively associated with fever, decreased oral intake, tonsillar hypertrophy, or duration of symptoms. No significant differences in incidence of disease complications, rates of hospital admission, or length of hospital stay were noted between the steroid and nonsteroid treatment groups. Despite consistent and uniform acceptance in the medical literature that SCT in the setting of IM should be reserved for patients with impending airway obstruction, corticosteroids continue to be used on a much broader scale at this tertiary care institution. This observation suggests that clinicians see value in SCT for treatment of IM beyond the classically accepted reasons. Moreover, despite previous reports of possible adverse consequences of SCT in IM, our review failed to demonstrate any such trend.


[Discrepancies between human leukocyte antigen registry typing and confirmatory typing results of unrelated hematopoietic stem cell donors].
In unrelated hematopoietic stem cell transplantation, the accuracy of HLA registry typing (RT) of donors is important for timely search and coordination of HLA-matched donors. We analyzed discrepancies between HLA RT and confirmatory typing (CT) results of stem cell donors in Korean and foreign registries. We analyzed the HLA typing results of 834 donors for whom CT was performed at Seoul National University Hospital between April 1997 and March 2010. For CT, DNA typing was used in majority of the cases and HLA-A and HLA-B serological typing was used in some early cases. The discrepancies between the typing results were analyzed at the serological/generic level. The overall discrepancy rate (RT error rate) was 3.2%, and the rate was similar in the Korean and foreign registries. The discrepancy rates in the Korean and foreign registries were more than 10% in the 1997-2001 searches, but decreased to less than 3% in the 2002-2010 searches. Analysis of 19 cases of RT errors in the Korean registry revealed 3 cases of sample switchover errors and 16 cases of typing errors in one of the HLA-A, HLA-B, or HLA-DR loci. The RT error rate in Japan Marrow Donor Program was lower than those in other foreign registries. The error rate of HLA RT results of unrelated stem cell donors in the Korean registry was similar to those in the foreign registries, and has decreased in the recent searches following the change in the typing method from serological to DNA typing.


Combined treatment of endometriosis. GnRH agonists and laparoscopic surgery.
Use of preoperative gonadotropin-releasing hormone (GnRH) agonists may be beneficial in the case of laparoscopic surgery for large endometriomas. Further studies are necessary to confirm the claim that preoperative GnRH agonists facilitate laparoscopic surgery for endometriosis. Use of GnRH agonists after laparoscopic treatment of endometriosis has beneficial effects in preventing the recurrence of pelvic pain associated with endometriosis.


Identification and Expression Analysis of Zebrafish (Danio rerio) E-Selectin during Embryonic Development.
In this study, we cloned the full-length cDNA of E-selectin of zebrafish (Danio rerio), analyzed its expression pattern and preliminarily explored its biological function. Zebrafish E-selectin cDNA is 3146 bp and encodes a putative 871 amino acid protein. All structural domains involved in E-selectin function are conserved in the putative protein. Whole-mount in situ hybridization of zebrafish at 24 and 48 h post-fertilization (hpf) revealed E-selectin expression mainly in vascular/endothelial progenitor cells in the posterior trunk and blood cells in the intermediate cell mass and posterior cardinal vein regions. Real-time quantitative RT-PCR analysis detected E-selectin expression at 0.2, 24 and 48 hpf and significantly decreased from 48 to 72 hpf. The expression of E-selectin, tumor necrosis factor-α and interleukin-1β was significantly upregulated at 22 to 72 h after induction with bacterial lipopolysaccharide. Thus, the structure of E-selectin protein is highly conserved among species, and E-selectin may be involved in embryonic development and essential for hematopoiesis and angiogenesis during embryonic development in zebrafish. Furthermore, we provide the first evidence of inflammatory mediators inducing E-selectin expression in non-mammalian vertebrates, which suggests that zebrafish E-selectin may be involved in inflammation and probably has similar biological function to mammalian E-selectin.


Inhibition of phagocytes by cyclosporin in vitro.
Cyclosporin is an immunosuppressant that acts by selectively inhibiting the activation of T lymphocytes. Its effects on monocytes and neutrophils are not well explored. We investigated the in vitro effects of cyclosporin on these cells, harvested from venous blood from nine healthy, non-smoking volunteers. In vitro incubation of monocytes with increasing concentrations of cyclosporin (5, 25 and 625 micrograms) depressed their phagocytosis by 22%, 32% and 49%, respectively, compared to the control values. The intracellular killing capacity of monocytes decreased by 26%, 31% and 43% with these doses, and neutrophil phagocytosis was depressed in a similar manner (16%, 30% and 40%). Patients receiving cyclosporin are susceptible to infections, and inhibition of these phagocytic cells by cyclosporin may be partly responsible for this. Neutrophil chemotaxis is reduced in patients with impaired renal function. Treating these patients with cyclosporin may in addition suppress the phagocytic function of these cells.


Treatment of invasive fungal infections in high-risk haematological patients: what have we learnt in the past 10 years?
Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.


Treatment of Cr(VI) and phenol by illuminated TiO2.
Industrial wastewater from organic chemical manufacturing and metal plating industries may contain significant amounts of refractory organic matter and heavy metals. Heavy metals such as Cr(VI) and refractory organic matter like phenol were simultaneously removed by reduction and mineralization, respectively, during photocatalytic process. Therefore, this study was carried out to evaluate the effects of phenol on the removal of Cr(VI) in several environmental conditions. Cr(VI) and phenol were more effectively eliminated in UV/TiO2 condition than either by UV or TiO2-alone. The removal efficiencies of Cr(VI) increased as the pH of the TiO2 slurry decreased, the concentration of phenol increased up to 10 mg L(-1), and nitrogen gas was used. Otherwise, the removal efficiencies of phenol were higher at O2-purged system and neutral pH. Without regard to purging gases, complete Cr(VI) removal was observed at pH 4 after 80 min while 90% phenol destruction and 60% mineralization were found after 120 min. It wasfound that application of photocatalytic reaction by using illuminated TiO2 to treat wastewater containing both Cr(VI) and phenol was possible.


Learning free energy landscapes using artificial neural networks.
Existing adaptive bias techniques, which seek to estimate free energies and physical properties from molecular simulations, are limited by their reliance on fixed kernels or basis sets which hinder their ability to efficiently conform to varied free energy landscapes. Further, user-specified parameters are in general non-intuitive yet significantly affect the convergence rate and accuracy of the free energy estimate. Here we propose a novel method, wherein artificial neural networks (ANNs) are used to develop an adaptive biasing potential which learns free energy landscapes. We demonstrate that this method is capable of rapidly adapting to complex free energy landscapes and is not prone to boundary or oscillation problems. The method is made robust to hyperparameters and overfitting through Bayesian regularization which penalizes network weights and auto-regulates the number of effective parameters in the network. ANN sampling represents a promising innovative approach which can resolve complex free energy landscapes in less time than conventional approaches while requiring minimal user input.


Moving forward together: the practice doctorate in nursing.
Societal drivers, as well as trends in education and health care, are advancing the practice doctorate in nursing. For nurse practitioner preparation, the current resurgence of interest in the practice doctorate could precipitate change that mimics the evolution from post-basic certificate to Master's level education. The National Organization of Nurse Practitioner Faculties (NONPF) is a resource for the study of the practice doctorate relative to quality nurse practitioner education. This article will offer some insights into the movement toward the practice doctorate by describing, from the NP perspective, the societal impetus for change, the historical perspective of NP and doctoral education, the 4 Ws (why, what, where, and when) of the movement, and some of the myths and realities about the practice doctorate.


Assessment of clotting factor concentrates--pivotal studies and long-term requirements.
Assessment of quality in terms of safety and efficacy of clotting factor concentrates (CFCs) is very important for all new therapeutic products. In rare diseases this is often complicated due to small number of trial participants. In hemophilia, an extra complication is the large impact previous treatments have on both the risk on inhibitors and the overall response to bleedings. For new CFCs, safety needs to be evaluated against inhibitor risk whereas efficacy is primarily judged against the most common clinical manifestations of the disease, namely, bleeding into joints and muscles. In this article the challenges are described for hemophilia that recruits patients globally. Recommendations of ISTH are discussed; these propose to substitute the single-arm prelicensure study with a two-stage approach, which considers epidemic and endemic incidence rate, and might increase the feasibility of studying multiple new products in populations with rare disease without compromising the assessment of product safety and efficacy. We also suggest that the annual bleeding rate (ABR) is an unreliable predictor of efficacy. The response to treatment highly depends on the current disease status of every patient participating in a clinical trial. The phenotype of patients with hemophilia is highly influenced by previous treatment history. Patients with severe hemophilia of the same age can demonstrate a different response to treatment.


Routes to lenition: an acoustic study.
Vowel lenition and its link with coarticulation have been the subject of extensive debate in the literature. The aims of the present paper are to demonstrate how vowel lenition and coarticulation are linked in Cypriot Greek (henceforth CG), to determine the nature of vowel lenition, and to illustrate how vowel lenition and coarticulation result from aerodynamic phenomena. Eight speakers were recorded producing utterances ending in either /i/ or /u/. Acoustic measures such as V(1)F2 and stop duration were employed to determine whether lenition of the vowels results in coarticulation with the preceding consonant. Results show that there is extensive stop-vowel coarticulation in CG and that stop production is as variable as vowel production, with full vowels never co-occurring with canonical consonants, indicating the existence of two routes to lenition in CG. These findings suggest that lenition in the final syllable is a consequence of the supralaryngeal articulation coupled with a marginal glottal setting.


Sedimentation, viscosity and partial specific volumes of membrane proteins and lipoproteins.
1. Lipoproteins or defatted proteins from the membrane of Halobacterium halobium were dissolved in 0.02m-phosphate buffer, pH7.4, with or without urea (8m). Physicochemical measurements were made on these solutions with and without addition of sodium chloride. 2. In the presence of 8m-urea the lipoproteins could be resolved into two sedimenting groups. The faster group had an average apparent molecular weight of 390 000; sedimentation coefficients of the slower group could not be determined. 3. Proteins that had been defatted by extraction with a chloroform-methanol mixture could also be resolved into two groups distinguished by their sedimentation velocities. Sedimentation coefficients of both groups were readily determined. The average apparent molecular weight of the faster group of defatted proteins in 8m-urea was 340 000 and that of the slower group was 97 000. It is concluded that attachment of lipid does not affect the state of aggregation of the proteins in 8m-urea. 4. Intrinsic viscosities of lipoproteins and defatted proteins were higher than is customary for globular proteins and suggest expanded highly-solvated molecules, consistent with the ;denaturing' action on the proteins of solutions of low ionic strength.


Growing season temperatures in Europe and climate forcings over the past 1400 years.
The lack of instrumental data before the mid-19th-century limits our understanding of present warming trends. In the absence of direct measurements, we used proxies that are natural or historical archives recording past climatic changes. A gridded reconstruction of spring-summer temperature was produced for Europe based on tree-rings, documentaries, pollen assemblages and ice cores. The majority of proxy series have an annual resolution. For a better inference of long-term climate variation, they were completed by low-resolution data (decadal or more), mostly on pollen and ice-core data. An original spectral analog method was devised to deal with this heterogeneous dataset, and to preserve long-term variations and the variability of temperature series. So we can replace the recent climate changes in a broader context of the past 1400 years. This preservation is possible because the method is not based on a calibration (regression) but on similarities between assemblages of proxies. The reconstruction of the April-September temperatures was validated with a Jack-knife technique. It was also compared to other spatially gridded temperature reconstructions, literature data, and glacier advance and retreat curves. We also attempted to relate the spatial distribution of European temperature anomalies to known solar and volcanic forcings. We found that our results were accurate back to 750. Cold periods prior to the 20(th) century can be explained partly by low solar activity and/or high volcanic activity. The Medieval Warm Period (MWP) could be correlated to higher solar activity. During the 20(th) century, however only anthropogenic forcing can explain the exceptionally high temperature rise. Warm periods of the Middle Age were spatially more heterogeneous than last decades, and then locally it could have been warmer. However, at the continental scale, the last decades were clearly warmer than any period of the last 1400 years. The heterogeneity of MWP versus the homogeneity of the last decades is likely an argument that different forcings could have operated. These results support the fact that we are living a climate change in Europe never seen in the past 1400 years.


Building motion models of lung tumours from cone-beam CT for radiotherapy applications.
A method is presented to build a surrogate-driven motion model of a lung tumour from a cone-beam CT scan, which does not require markers. By monitoring an external surrogate in real time, it is envisaged that the motion model be used to drive gated or tracked treatments. The motion model would be built immediately before each fraction of treatment and can account for inter-fraction variation. The method could also provide a better assessment of tumour shape and motion prior to delivery of each fraction of stereotactic ablative radiotherapy. The two-step method involves enhancing the tumour region in the projections, and then fitting the surrogate-driven motion model. On simulated data, the mean absolute error was reduced to 1 mm. For patient data, errors were determined by comparing estimated and clinically identified tumour positions in the projections, scaled to mm at the isocentre. Averaged over all used scans, the mean absolute error was under 2.5 mm in superior-inferior and transverse directions.


Benefit incidence analysis in public health facilities in India: utilization and benefits at the national and state levels.
Benefit Incidence Analysis (BIA) is used to understand the distribution of health care utilization and spending in comparison to income distribution. The results can illustrate how effectively governments allocate limited resources towards meeting the needs of the poor. In analyzing the distribution of public spending on inpatient, outpatient, and deliveries, this paper represents the most recent BIA completed in India. In order to conduct the BIA statistical analysis for this project, 2014 utilization data from the most recently completed Indian National Sample Survey (NSS) was used. Unit costs were estimated for primary care, hospital inpatient, hospital outpatient, and deliveries. Concentration curves and concentration indices were estimated both at the national and state levels. Analyses were reported for overall utilization, as well as for the gross and net benefits for inpatient, outpatient, and deliveries. According to the results, utilization of government inpatient and delivery services is pro-poor. When gross and net benefits are included in the analysis, services become more equal and less pro-poor. Gross benefits, which are measured with state-level unit costs, are virtually equal for all services. Although there are some pro-poor gross benefits trends for national outpatient services, the results also show that the equality of national gross benefits trends hides a significant disparity across Indian States. While a number of Indian States have outpatient gross benefits that are pro-poor, few show pro-poor benefits for inpatient and delivery services. Net benefits, which considers both unit costs for each respective service, and out-of-pocket (OOP) expenditures, trend similarly to gross benefits. In addition, those who use public facilities spend considerable OOP to supplement government services. This BIA reveals that government spending on public health care has not resulted in significantly pro-poor services. While some progress has been made relative to deliveries and outpatient services, inpatient stays are not pro-poor. In addition, national results mask significant disparities across Indian states.


Gastric stromal tumors: a clinicopathologic study of 77 cases with correlation of features with nonaggressive and aggressive clinical behaviors.
Gastrointestinal stromal tumors are a heterogeneous group of neoplasms that have clinical and histologic features that vary depending on their location within the gastrointestinal tract. Prediction of clinical behavior in this group of tumors is notoriously difficult, and the same criteria for malignancy do not necessarily apply to stromal tumors from different sites within the gastrointestinal tract. Using known clinical behavior with long-term follow-up, we attempted to determine which features, if any, are associated with clinical behavior in stromal tumors arising in the stomach, the most common site for such tumors. Seventy-seven gastric stromal tumors were studied and classified as "adverse outcome (AO) tumors" (malignant) or "nonadverse outcome tumors" (benign) based on their known clinical outcome. AO was defined as metastasis and/or death due to tumor. Patients with a non-AO had at least 5 years of tumor/metastasis-free follow-up. Thirty-seven patients had an AO (follow-up [metastasis at presentation] 0-73 months; median 6 months), and 40 patients had a non-AO (follow-up 60-264 months; median 84 months). All cases were reviewed by two authors (J.R.G., H.D.A.), who were blinded to clinical outcome and gross features, and classified as histologically benign or not benign using preset, defined histologic criteria based upon the authors' prior experience with a large number of these tumors. If the tumor did not fit with either the characteristic cellular spindle cell or benign epithelioid cell patterns, the tumor was classified as not benign. Clinical outcome was then correlated with the histologic designation to determine if these preset criteria were valid. The authors were able to accurately classify the tumors as benign or not benign with a sensitivity of 100% and a specificity of 92%. In addition, for all cases individual morphologic and clinical features were examined. Features associated with an AO included tumor size >/=7 cm, high cellularity, mucosal invasion, high nuclear grade, mitotic counts >/=5/50 high power fields, mixed cell type, and the presence of a myxoid background and/or absence of stromal hyalinization. By recognizing several well-defined patterns of benign gastric stromal tumors and the myriad of individual features shown to correlate with an AO, one can better predict the clinical behavior of gastric stromal tumors.


An analysis of responses to levosimendan in the pulmonary vascular bed of the cat.
Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart failure. We investigated the hypothesis that levosimendan is a pulmonary vasodepressor mediated through inhibition of phosphodiesterase, adenosine triphosphate (ATP)-dependent potassium channels, or both. We investigated responses to the calcium sensitizer levosimendan in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was increased to a high steady level with the thromboxane A(2) analog U-46619. Under increased-tone conditions, levosimendan caused dose-related decreases in lobar arterial pressure without altering systemic arterial and left atrial pressure. Responses to levosimendan were significantly attenuated, although not completely, after the administration of U-37883A, a vascular selective nonsulfonylurea ATP-sensitive K(+)-channel-blocking drug. Responses to levosimendan were not significantly different after the administration of the nitric oxide synthase inhibitor L-N(5)-(1-iminoethyl)-ornithine or the cyclooxygenase inhibitor sodium meclofenamate or when lung ventilation was interrupted. These data show that levosimendan has significant vasodilator activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to levosimendan are partially dependent on activation of ATP-sensitive K(+) channels and independent of the synthesis of nitric oxide, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the cat. Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart-failure treatment. The lung circulation affects both right- and left-sided heart failure. Levosimendan decreased lobar arterial pressure via a partial K(+)(ATP) (potassium channel sensitive to intracellular adenosine triphosphate levels)-dependent mechanism. These data suggest that, in addition to calcium-sensitizing activity, levosimendan decreases pulmonary resistance, which may also aid in the treatment of heart failure.


Nonoperative management of blunt hepatic injuries: safe at any grade?
Nonoperative management of blunt hepatic injury (BHI) has become more widely accepted. A prospective trial was undertaken to test the belief that clinical state could identify the patients with BHI confirmed by computed tomography (CT) who could be safely managed without a surgical operation. Patients were excluded from nonoperative management only if they manifested hemodynamic instability, the presence or suspicion of any other injury requiring laparotomy, or would be unavailable for controlled monitoring. Of 60 patients treated for BHI, 30 were managed nonoperatively. The 30 who had laparotomies served as a comparative group. The groups were statistically similar in age, sex, and Injury Severity Score (ISS). The group managed nonoperatively had significantly more severe BHI. There were no deaths or delayed laparotomies in the nonoperative management group. The groups had similar ICU and total hospital stays when analyzed as independent variables or with control for BHI grade and ISS. Transfusion requirements were significantly lower for the nonoperative management group when analyzed independently or when controlled for BHI grade, ISS, and the number of non-abdominal injuries. Nineteen (63%) patients managed nonoperatively were followed until their CT scans showed complete resolution. None had complications. We conclude that nonoperative management of BHI is a safe and effective technique applicable to hemodynamically stable patients who lack other indications for laparotomy and who can be adequately monitored.


The 5-HT(4) receptor-induced depolarization in rat hippocampal neurons is mediated by cAMP but is independent of I(h).
Intracellular recordings were used to examine the mechanisms underlying the 5-hydroxytryptamine (5-HT)4 receptor-mediated depolarization seen in CA1 region pyramidal cells in in vitro hippocampal brain slices. This depolarization was mimicked and occluded by administration of the membrane permeable cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP but was unaffected by blockade of protein kinase A (PKA). These results suggest that 5-HT4 receptors signal this depolarization through a cAMP-dependent but PKA-independent mechanism. In many cell types, 5-HT elicits a depolarization via cAMP by facilitating Ih, a hyperpolarization-activated cation current. In contrast, we find no evidence for the involvement of Ih in this response. Rather, this depolarization may involve a cyclic nucleotide gated channel.


Correct names for some of the closest relatives of Carica papaya: A review of the Mexican/Guatemalan genera Jarilla and Horovitzia.
Using molecular data, we recently showed that Carica papaya L. is sister to a Mexican/Guatemalan clade of two genera, Jarilla Rusby with three species and Horovitzia V.M. Badillo with one. These species are herbs or thin-stemmed trees and may be of interest for future genomics-enabled papaya breeding. Here we clarify the correct names of Jarilla heterophylla (Cerv. ex La Llave) Rusby and Jarilla caudata (Brandegee) Standl., which were confused in a recent systematic treatment of Jarilla (McVaugh 2001). We designate epitypes for both, provide weblinks to type specimens, a key to the species of Jarilla and Horovitzia, and notes on their habitats and distribution.


Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy.
Bacterial superantigens (SAgs) are effective T-cell stimulatory molecules that lead to massive cytokine production. Superantigens crosslink between MHC class II molecules on the Antigen Presenting Cells (APC) and TCR on T-cells. This enables them to activate up to 20% of resting T cells, whilst conventional antigen presentation results in the activation of 0.001-0.0001% of the T cell population. These biological properties of superantigens make them attractive for use in immunotherapy. Previous studies have established the effectiveness of superantigens as therapeutic agents. This, however, was achieved with severe side effects due to the high lethality of the native toxins. Our study aims to produce superantigen-based peptides with minimum or no lethality for safer cancer treatment. In previous work, we designed and synthesized twenty overlapping SPEA-based peptides and successfully mapped regions in SPEA superantigen, causing a vasodilatory response. We screened 20 overlapping SPEA-based peptides designed and synthesized to cover the whole SPEA molecule for T-cell activation and tumor-killing ability. In addition, we designed and synthesized tumor-targeted superantigen-based peptides by fusion of TGFαL3 either from the N' or C' terminal of selected SPEA-based peptides with an eight-amino acid flexible linker in between. Our study identified parts of SPEA capable of stimulating human T-cells and producing different cytokines. We also demonstrated that the SPEA-based peptide conjugate binds specifically to cancer cells and can kill this cancer. Peptides induce T-cell activation, and tumor killing might pave the way for safer tumor-targeted superantigens (TTS). We proposed the combination of our new superantigen-based peptide conjugates with other immunotherapy techniques for effective and safer cancer treatment.


Diffusion-prepared segmented steady-state free precession: Application to 3D black-blood cardiovascular magnetic resonance of the thoracic aorta and carotid artery walls.
This work developed a three-dimensional (3D) diffusion-prepared segmented steady-steady free precession (DP-SSFP) cardiovascular magnetic resonance (CMR) sequence for black-blood (BB) thoracic aortic and carotid wall visualization. In 14 healthy volunteers, BB CMR of the thoracic aorta (n = 7) and carotid arteries (n = 7) was performed over 12 cm and 3 cm of transversal coverage, respectively, with a single 3D DP-SSFP acquisition and multiple two-dimensional (2D) slices using a T2-weighted (T2W) double inversion-recovery fast spin-echo (DIR-FSE) sequence. Arterial wall area (WA), lumen area (LA), and wall-lumen contrast-to-noise ratio (CNR) measured from the 3D DP-SSFP images were compared to those measured from the 2D T2W DIR-FSE images. Strong agreement in WA and LA between the two techniques was observed in the thoracic aorta (WA: intraclass correlation coefficient (ICC) = 0.866, LA: ICC = 0.993; p < 0.001 for both) and carotid arteries (WA: ICC = 0.939, LA: ICC = 0.991; p < 0.001 for both). Adjusted for slice thickness and number of slices, higher effective CNR per unit time (i.e., CNR efficiency) was attained with 3D DP-SSFP than 2D T2W DIR-FSE during thoracic aortic wall imaging (11.6 +/- 1.4 vs. 2.9 +/- 0.5; p < 0.001) and carotid artery wall imaging (10.1 +/- 1.9 vs. 3.1 +/- 0.5; p < 0.001). Diffusion-prepared segmented SSFP is a promising vessel wall CMR sequence that allows for 3D acquisition of thin and contiguous slices with BB image contrast.