Application of a green manure and green manure composted with beet vinasse on soil restoration: effects on soil properties.
Beet vinasse (BV), a green manure constituted by Trifolium pratense L. uncomposted (TP) and composted with beet vinasse (at 1:1 rate, (TP+BV)1, and 2:1 rate, (TP+BV)2) at 10t organic matter ha(-1) rate were applied during a period of four years for purpose of restoration of a Xelloric Calciorthid located near Seville (Guadalquivir Valley, Andalusia, Spain). The effect on the plant cover, soil physical (structural stability and bulk density), chemical (exchangeable sodium percentage), and biological properties (microbial biomass, soil respiration and enzymatic activities such as dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase) were determined. The application of BV had a detrimental impact on soil physical (structural stability decreased 16.5% and bulk density increased 18.7% respect to the control soil), chemical (exchangeable sodium percentage increased 87.3% respect to the control soil), and biological properties (microbial biomass, soil respiration, and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities decreased by 53.5%, 24.5%, 27.8%, 15%, 39.7%, 42.7%, and 65.6%, respectively with respect to the control soil), probably because high quantities of monovalent cations (Na principally) were introduced into the soil by the vinasse, thus destabilizing its structure. The application of TP had a positive impact on soil physical (structural stability increased 5.9% and bulk density decreased 6.1% respect to the control soil), and biological properties (microbial biomass, soil respiration, and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities increased by 66.3%, 45.6%, 97.7%, 98.9%, 97.7%, 87.2%, and 89.4%, respectively with respect to the control soil). However, when BV was co-composted with a green manure, principally at a 2:1 rate, the resulting compost had a positive effect on soil physical (structural stability increased 10.5% and bulk density decreased 13.5% respect to the control soil), and biological properties (microbial biomass, soil respiration, and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities increased by 68.9%, 46.2%, 97.5%, 98.4%, 99.1%, 90.5% and 91.6%, respectively with respect to the control soil). After four years, the percentage of plant cover decreased 64.3% in the BV-amended plots respect to the control soil, whereas increased 82.8%, 81.6% and 81% in the (TP+BV)2, (TP+BV)1 and TP treatments, respectively. While the application of BV deteriorates the soil and therefore does not contribute to its restoration, the application of TP, and BV composted with TP protects the soil and will contribute to its restoration.


The triple-isotope calibration approach: a universal and standard-free calibration approach for obtaining absolute isotope ratios of multi-isotopic elements.
The theory of a new calibration approach for obtaining absolute isotope ratios of multi-isotopic elements without the use of any standard has been developed. The calibration approach basically uses the difference in the instrumental isotope fractionation of two different types of mass spectrometers, leading to two different fractionation lines in a three-isotope diagram. When measuring the same sample with both mass spectrometers, the different fractionation lines have one point in common: this is the 'true' logarithmized isotope ratio pair of the sample. Thus, the intersection of both fractionation lines provides us with the absolute isotope ratios of the sample. This theory has been tested in practice by measuring Cd and of Pb isotope ratios in the certified reference materials BAM-I012 and NIST SRM 981 by thermal ionization mass spectrometry and by inductively coupled plasma mass spectrometry while varying the ionization conditions for both mass spectrometers. With this experiment, the theory could be verified, and absolute isotope ratios were obtained, which were metrologically compatible with the certified isotope ratios. The so-obtained absolute isotope ratios are biased by - 0.5 % in average, which should be improved with further developments of the method. This calibration approach is universal, as it can be applied to all elements with three or more isotopes and it is not limited to the type of mass spectrometers applied; it can be applied as well to secondary ion mass spectrometry or others. Additionally, this approach provides information on the fractionation process itself via the triple-isotope fractionation exponent θ. Graphical abstract The triple-isotope calibration approach: the intersection of the triple isotope fractionation lines of an element recorded by two individual mass spectometers yields the absolute isotope ratios of this element.


Prostacyclin--antiarrhythmic or arrhythmogenic? Comparison of the effects of intravenous and intracoronary prostacyclin and ZK36374 during coronary artery occlusion and reperfusion in anaesthetised greyhounds.
The effects of prostacyclin and ZK36374, a more stable analogue of prostacyclin, were examined in greyhounds anaesthetised with chloralose. Intravenous drug administration (100 ng kg-1 min-1) exacergbated the arrhythmias induced by occlusion of the left anterior descending coronary artery. The incidence of ventricular fibrillation (VF) was 50% in both drug groups compared with 10% in controls. An antiarrhythmic effect was observed when a lower dose (5 ng kg-1 min-1) was infused directly into the coronary circulation. The number of extrasystoles occurring during the first 30 min of occlusion was reduced from 720 +/- 136 in the controls to 327 +/- 167 in the prostacyclin group and 309 +/- 110 (p less than 0.05) in the dogs receiving ZK36374. The only haemodynamic change observed in the dogs receiving intracoronary drug infusions was a small decrease in systemic arterial blood pressure. In the intravenous groups systemic hypotension was accompanied by tachycardia, suggesting that there may have been a reflex increase in sympathetic drive. Increased catecholamine release could account for the higher incidence of VF in the dogs treated with intravenous prostacyclin or ZK36374. The intracoronary administration of both drugs markedly reduced the incidence of VF induced by the release of a 40-min coronary artery occlusion. This latter result suggests that the release of endogenous prostacyclin may have protective effects during reperfusion of the ischaemic myocardium.


Preeclampsia: Reflections on How to Counsel About Preventing Recurrence.
Preeclampsia is one of the most challenging diseases of pregnancy, with unclear etiology, no specific marker for prediction, and no precise treatment besides delivery of the placenta. Many risk factors have been identified, and diagnostic and management tools have improved in recent years. However, this disease remains one of the leading causes of maternal morbidity and mortality worldwide, especially in under-resourced settings. A history of previous preeclampsia is a known risk factor for a new event in a future pregnancy, with recurrence rates varying from less than 10% to 65%, depending on the population or methodology considered. A recent review that performed an individual participant data meta-analysis on the recurrence of hypertensive disorders of pregnancy in over 99 000 women showed an overall recurrence rate of 20.7%; when specifically considering preeclampsia, it was 13.8%, with milder disease upon recurrence. Prevention of recurrent preeclampsia has been attempted by changes in lifestyle, dietary supplementation, antihypertensive drugs, antithrombotic agents, and others, with much uncertainty about benefit. It is always challenging to treat and counsel a woman with a previous history of preeclampsia; this review will be based on hypothetical clinical cases, using common scenarios in obstetrical practice to consider the available evidence on how to counsel each woman during pre-conception and prenatal consultations.


[Pre-requisites, observations and benefits of the DGU trauma registry in Austria].
The trauma registry of the DGU was founded in 1992 with the objective of collecting data on severely injured patients. The purpose of this registry, in which Austrian trauma units have taken part since 1998, is to answer questions related to the field of trauma management. Using the example of the Linz Trauma Center (UKH Linz), which has actively participated since 2012, the authors would like to share their experiences of collecting data in order to motivate other departments to participate in the trauma registry. We would like to make suggestions regarding implementation methods for high-quality data acquisition.However, the availability of essential human resources must be guaranteed, since the recording of data from severely injured patients sometimes takes 60-90 min. Additionally, an automatic data acquisition method is currently unavailable for technical reasons.


Application of Predictive Modelling to Improve the Discharge Process in Hospitals.
To find out the factors influencing discharge process turnaround time (TAT) and to accurately predict the discharge process TAT. The discharge process of cardiology department inpatients in a tertiary care hospital was mapped over a month. The likely factors influencing discharge TAT were tested for significance by ANOVA. Multiple linear regression (MLR) was used to predict the TAT. The sample was divided into testing and training sets for regression. A model was generated using the training set and compared with the testing set for accuracy. After a process map was plotted, the significant factors influencing the TAT were identified to be the treating doctor, and pending evaluations on the day of discharge. The MLR model was developed with Python libraries based on the two factors identified. The model predicted the discharge TAT with a 69% R2 value and 32.4 minutes (standard error) on the testing set and a 77.3% R2 value and 26.7 minutes (standard error) on the overall sample. This study was an initiation to find out factors influencing discharge TAT and how those factors can be used to predict discharge in the hospital of interest. The study was validated and predicted the TAT with 77% accuracy after the significant factors that affect the discharge process were identified.


Some topological considerations of the optic pathway.
The contralateral projection of the vertebrate retinotopic map has a component of a mirror or uniaxial inversion in it. Here, a simple hypothesis is proposed which explains how this can come about. The emphasis is on topological considerations, in a global sense, of the overall map. An important feature of the hypothesis is that the optic nerve fibres follow pathways such that they retain their nearest neighbour relationships till they terminate in the optic tectum, i.e. no criss-crossing of the fibres is envisaged. Anatomical evidence for this is already available in the case of the optic tract of frog. Some speculations are also suggested concerning the role of this uniaxial inversion in information processing. The observations of optic tracts of other amphibian and some lower vertebrate systems are also considered.


Pragmatic Cluster Randomized Trials Using Covariate Constrained Randomization: A Method for Practice-based Research Networks (PBRNs).
Cluster randomized trials (CRTs) are useful in practice-based research network translational research. However, simple or stratified randomization often yields study groups that differ on key baseline variables when the number of clusters is small. Unbalanced study arms constitute a potentially serious methodological problem for CRTs. Covariate constrained randomization with data on relevant variables before randomization was used to achieve balanced study arms in 2 pragmatic CRTs. In study 1, 16 counties in Colorado were randomized to practice-based or population-based reminder recall for vaccinating children ages 19 to 35 months. In study 2, 18 primary care practices were randomized to computer decision support plus practice facilitation versus computer decision support alone to improve care for patients with stage 3 and 4 chronic kidney disease. For each study, a set of optimal randomizations, which minimized differences of key variables between study arms, was identified from the set of all possible randomizations. Differences between study arms were smaller in the optimal versus remaining randomizations. Even for the randomization in the optimal set with the largest difference between groups, study arms did not differ significantly on any variable for either study (P > .05). Covariate constrained randomization, which restricts the full randomization set to a subset in which differences between study arms are minimized, is a useful tool for achieving balanced study arms in CRTs. Because of the increasing recognition of the risk of imbalance in CRTs and implications for interpreting study findings, procedures of this type should be considered in designing practice-based or community-based trials.


Approach to the diagnosis and management of musculoskeletal disease.
Musculoskeletal disease is not an inevitable consequence of aging. Complaints of musculoskeletal disease indicate disease. Differential diagnosis relies on clinical skills. Management is directed toward maintaining function.


Selective adsorption of bilirubin against albumin to oxidized single-wall carbon nanohorns.
Bilirubin adsorption capacities of single-wall carbon nanohorns (SWNHs) are investigated to develop an efficient adsorbent in plasma apheresis. Pristine, thermally oxidized and H2O2-oxidized SWNHs are examined and it is demonstrated that higher oxidization levels of the SWNHs enhance bilirubin adsorption capacity owing to increase in their dispersibility and formation of nanoscaled holes on the SWNH walls. Under co-existance of albumin molecules, the bilirubin adsorption capacity of the SWNHs increases with the oxidation level whereas the albumin adsorption capacity is kept small. Bilirubin is selectively adsorbed to the SWNHs, especially to the SWNHs with high oxidation levels, against albumin. This selectivity is maintained under high-concentrations of albumin in the near-clinical environment.


Endothelin-1 as an aggravating factor of disseminated intravascular coagulation associated with malignant neoplasms.
Vascular endothelial damage may play an important role in the pathophysiology of disseminated intravascular coagulation (DIC), a frequent complication of malignant neoplasms. It may mediate a variety of triggering events to initiate DIC and platelet aggregation, which in turn leads to additional endothelial destruction. If so, endothelin-1 (ET-1), the most potent vasoconstrictor of naturally occurring pressor substances known, may leak from injured endothelial cells and aggravate the disease process. The study included 36 patients with various malignant neoplasms in whom DIC developed. The authors measured plasma levels of ET-1 and big ET-1, a precursor peptide of ET-1, in these patients and compared them with other laboratory abnormalities during the course of DIC. Plasma ET-1 and big ET-1 levels were elevated in most patients with DIC. When compared with the results of other diagnostic tests, elevated plasma big ET-1 was the most frequently found abnormality associated with DIC. Elevation of plasma ET-1 and big ET-1 levels was closely related to the initiation and progression of DIC and provided a higher degree of sensitivity and specificity than did other indicators in assessing patients with cancer and DIC. Vascular endothelial damage with the resultant increases in plasma ET-1 and big ET-1 levels is universally associated with DIC caused by malignancy. Excessive secretion or leakage of ET-1 and big ET-1 from injured endothelial cells may cause vasospasm and aggravate the DIC process by facilitating the formation of intravascular microthrombi, ultimately leading to ischemic end-organ dysfunction. Plasma ET-1 and big ET-1 are sensitive and specific markers for vascular endothelial injury in DIC.


Resection of more than 10 lung segments. A 30-year survey of 30 bronchiectatic patients.
A series of 30 bronchiectatic patients, treated by bilateral resection of 11, 12, or 13 lung segments, has been followed up for 30 years. The progress of the patients is analyzed and the results of treatment are evaluated. Ten patients required further resections for persisting collapse, kinking of the apical segment of a lower lobe, or because the previous resection had been too limited. The long-term results of these extensive bilateral resections in our group of patients are excellent. The quantitative function, more than 20 years after the last resection, lies markedly above the predicted value for the number of remaining segments. The qualitative function did not deteriorate over the years. It is clear that extensive bilateral bronchiectasis does not, per se, constitute a contraindication to resection, provided that at least six normal segments can be preserved.


Juvenile exposure to methamphetamine attenuates behavioral and neurochemical responses to methamphetamine in adult rats.
Previous research has shown that children living in clandestine methamphetamine (MA) labs are passively exposed to the drug [1]. The long-term effects of this early exposure on the dopaminergic systems are unknown, but may be important for adult behaviors mediated by dopamine, such as drug addiction. The current study sought to determine if juvenile exposure to low doses of MA would lead to altered responsiveness to the stimulant in adulthood. Young male and female rats (PD20-34) were injected daily with 0 or 2 mg/kg MA or left undisturbed and then tested at PD90. In the open field, adult rats exposed to MA during preadolescence had reduced locomotor activity compared to control non-exposed rats following an acute injection of MA (2 mg/kg). Likewise, methamphetamine-induced dopamine increases in the dorsal striatum were attenuated in male and female rats that had been exposed to MA as juveniles, although there were no changes in basal in vivo or ex vivo dopamine levels. These findings suggest that exposure of juveniles to MA leads to persistent changes in the behavioral and neurochemical responses to stimulants in adulthood.


Immunoscintigraphy using 111in-labelled F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody for staging of non-small cell lung carcinoma.
28 patients with primitive lung cancers were imaged by immunoscintigraphy (IS) with 111indium-labelled F(ab')2 anti-carcinoembryonic antigen (CEA), to assess this technique for mediastinal staging. IS revealed primitive tumours in 21 cases in whom mediastinal extension was assessed. There was concordance between clinical staging and IS confirmed by surgery in 17 cases, and discordance in 4. After surgery, discordance was in favour of IS in 2 cases (1 true positive and 1 true negative) and in favour of clinical staging in 2 (false positive of immunoscintigraphy). Anti-CEA IS could be useful for improving mediastinal staging of lung cancer.


Adolescence Predictors for Drug Crime Offending: A Follow-up Study of Former Adolescent Psychiatric Inpatients.
Our aim was to examine adolescent predictors (family- and school-related factors, substance use, and psychiatric disorders) for drug crime offending. The initial study population consisted of 508 former adolescent psychiatric inpatients aged between 13 and 17 years. Of them, 60 (12%) had committed a drug crime by young adulthood and they were matched with 120 (24%) non-criminal controls by sex, age and family type. During adolescent hospitalization, study participants were interviewed using valid semi-structured research instruments. Criminal records were obtained from the Finnish Legal Register Centre up to young adulthood. A distant relationship with a father, lying, and thieving, moderate/high nicotine dependence and weekly use of stimulants were shown to be the most prominent predictors for drug crime offending. Our findings encourage the use of modern child- and family-centered approaches in preventing youth involvement in illegal drug use and drug crimes.


Increased leptin expression selectively in the hypothalamus suppresses inflammatory markers CRP and IL-6 in leptin-deficient diabetic obese mice.
Low-grade systemic inflammation, as indicated by increased circulating levels of inflammatory markers CRP and IL-6, is linked to increased risks for cardiovascular diseases (CVD) and diabetes mellitus in obese subjects. Whereas hyperleptinemia in obesity are associated with increased CRP and IL-6 release, the hypothalamic versus peripheral site of leptin action has not been ascertained. The effects of increased leptin supply selectively in the hypothalamus by gene therapy on pro-inflammatory CRP and IL-6 levels and on markers of diabetes in the circulation of ob/ob mice displaying either age-related or dietary obesity were assessed. A recombinant adeno-associated viral vector encoding either green-fluorescent protein (control) or leptin gene was injected intracerebroventricularly. Five weeks later, one-half of each of the vector groups was switched to high-fat diet consumption and the other half continued to consume regular low-fat chow diet. Body weight and visceral white adipose tissue were drastically reduced and hyperinsulinemia and hyperglycemia were abrogated by leptin gene therapy, independent of the dietary fat content. The elevated plasma CRP and IL-6 levels seen in obese ob/ob mice receiving the control vector, regardless of the fat content of the diet, were markedly suppressed by increased hypothalamic leptin in both groups. The results show for the first time that leptin deficiency elevates and reinstatement of leptin selectively in the hypothalamus suppresses the release of pro-inflammatory biomarkers, a response likely to alleviate CVD associated with obesity.


Draft Genome Sequences of Four Bacterial Species as Part of an Experiential Microbiology Project at SUNY Geneseo.
We report four draft genome sequences related to the genera Bacillus and Escherichia, recovered from surfaces associated with human interaction, and Sediminibacterium, recovered from an aquatic environment. This study was part of an undergraduate microbial bioinformatics course at the State University of New York at Geneseo.


Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway.
Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure. We observed the Sjp40-induced decrease of α-SMA and the senescence of LX-2 cells, and Sjp40 could upregulate P27 and downregulate the protein level of SKP2. The senescence induced by Sjp40 might be reversed in LX-2 cells that treated with P27-specific siRNA or with SKP2-special over-expression plasmid. In addition, we also demonstrated that the decreased expression of P-Rb and α-SMA induced by Sjp40 were partly restored by SKP2-overexpression. These data suggest that Sjp40 might inhibit HSCs activation by promoting cellular senescence via SKP2/P27 signaling pathway, which put forward novel mechanism in the treatment of liver fibrosis.


Mandibular Osteosynthesis: A Comparative Evaluation of Two Different Fixation Systems Using 2.0 mm Titanium Miniplates and 3-D Locking Plates.
To compare and evaluate postoperative complications and treatment outcome in mandibular fracture fixation using 2.0 mm titanium miniplates and 3-D locking plates. Thirty patients were divided randomly into two groups of 15 each (including comminuted and malunited fractures). Group A was treated with open reduction internal fixation using 2.0 mm miniplates and group B with 3-D locking plates. A total of five complications were observed in four patients: implant exposure and infection in miniplate group and postoperative neurosensory deficit, implant failure and implant exposure in 3-D group. For fractures in symphysis and parasymphysis region, severely displaced angle fractures and for comminuted fractures 3-D locking plate could be a better option. In the angle and body region a single miniplate fixed according to Champy's technique is easy to place with less surgical time, less surgical trauma, is more economical and has similar clinical results.


Quantitative analysis of thiamylal and its metabolite secobarbital using liquid chromatography-tandem mass spectrometry in adipose tissue, serum, and liver.
Thiamylal is an ultrashort-acting barbiturate used for intravenous administration or general anesthesia induction. However, some cases of poisoning and suicide with thiamylal administration have been reported. Additionally, there are few reports on its analysis in the organs and adipose tissue, which requires purification by column chromatography and evaporation. A rapid and sensitive method was developed for quantifying thiamylal and its metabolite, secobarbital, in the adipose tissue, serum, and liver using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were prepared using modified QuEChERS extraction. For adipose tissue samples, an acetonitrile-hexane partitioning step was added to the extraction. This method was applied to investigate a suspected self-poisoning autopsy case. The quantitation accuracy for thiamylal added to porcine pericardial fat (0.18 µg/g), human serum (0.015 µg/mL), and porcine liver (0.18 µg/g) was 103%, 113%, and 95.3%, respectively. The quantitation limits calculated for porcine pericardial fat, human serum, and porcine liver at a signal-to-noise ratio of 10 were 0.06 µg/g, 0.005 µg/mL, and 0.06 µg/g, respectively. In addition, the thiamylal and secobarbital levels in the forensic autopsy case were 140 and 1.5 µg/g, respectively, in myocardial fat; 3.5-4.9 and 0.12-0.20 µg/mL, respectively, in serum; and 6.2-42 and 0.58-1.1 µg/g, respectively, in liver tissue. Thiamylal is especially distributed in the adipose tissue. The thiamylal-to-fat ratio may help estimate the time from administration to death. The developed modified QuEChERS extraction method with acetonitrile-hexane partitioning is suitable for analyzing hydrophobic compounds, such as thiamylal, in the adipose tissue.


Simultaneous determination of platinum group elements and rhenium in rock samples using isotope dilution inductively coupled plasma mass spectrometry after cation exchange separation followed by solvent extraction.
A simple and precise determination method for platinum group elements (PGEs) and Re in rock samples was developed using isotope dilution coupled with inductively coupled plasma mass spectrometry (ID-ICP-MS). Cation exchange separation was employed for simplicity, because it is applicable to group separation and simultaneous isotopic measurement in contrast with the widely used anion exchange separation which entails separate elution. However, its application to ID-ICP-MS has been limited due to spectral interferences from impurities retained in the PGE fraction even after ion chromatography. To overcome this limitation, solvent extraction using N-benzoyl-N-phenylhydroxylamine (BPHA) in chloroform was successfully applied for further purification. After the examination of optimum experimental parameters in cation exchange separation and solvent extraction using synthetic PGE solution, the established procedure was applied to the determination of PGEs and Re in some geochemical reference materials. The obtained results agreed well with the literature data determined using the different digestion methods (NiS fire assay and the use of a high-pressure asher) within the analytical uncertainties of each other. Significant difference in reproducibility between Ru, Ir, Pt and Os group, and Pd and Re group was observed in the results for BHVO-2 and JA-2. By considering the error factors affecting analytical reproducibility, we concluded that the difference is ascribed to the sample heterogeneity of minor minerals enriched in Ru, Ir, Pt and Os.


Attitudes of Lebanese community-dwelling older adults towards deprescribing using the rPATD tool.
To assess the attitude of community-dwelling Lebanese older adults towards deprescribing using the Revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire and to determine patient-related factors that impact their willingness for deprescribing. A cross-sectional face-to-face survey was conducted in Lebanon over the period extending between October 2021 and March 2022 using the validated Arabic version of the rPATD questionnaire. It included ambulatory older adults who were 65 years of age or older, presenting to the community pharmacy, taking at least one chronic medication, and having intact cognition. Of the 400 patients approached 300 (87%) agreed to participate. The mean age of participants was 65 (range 65-85 years) and 148 (56.3%) were females. The mean number of medications taken per patient was 5.8 ± 2.67 (range 1-18) and polypharmacy was reported among 188 patients (71.8%). Nearly all of study subjects 233 (89.0%) were willing to discontinue one or more of their regular medications if their physician said it was possible. The multivariate logistic regression analysis showed that the appropriateness of medications factor (OR= 3.9, 95% CI 1.308, 12.16, p=0.015) and patients' concern about stopping the medications factor (OR=0.116, 95% CI 0.033, 0.40, p = 0.001) were significantly associated with patients' willingness to deprescribe. A noteworthy percentage of the Lebanese older outpatients were willing to stop one or more of their regular medications if their doctor recommends so. Patients' belief in appropriateness of medications and concerns about stopping were noted to significantly influence their willingness to deprescribe in this sample population.


Comparative study of different fabric phase sorptive extraction sorbents to determine emerging contaminants from environmental water using liquid chromatography-tandem mass spectrometry.
A new sorptive extraction technique, fabric phase sorptive extraction (FPSE), using different coating chemistries: non-polar sol-gel poly(dimethyldiphenylsiloxane) (PDMDPS), medium polar sol-gel poly(tetrahydrofuran) (PTHF), and polar sol-gel poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG triblock) and sol-gel Carbowax 20 M were evaluated to extract a group of pharmaceuticals and personal care products (PPCPs) with wide range of polarity from environmental aqueous samples. Different parameters affecting FPSE such as sample pH, stirring speed, addition of salt, extraction time, sample volume, elution solvent and desorption time were optimized for each sorbent coated FPSE media. Under optimum conditions, FPSE media coated with sol-gel Carbowax 20 M provided the highest absolute recoveries (77-85%) for majority of the analytes with the exception of the most polar ones. Nevertheless, all four sorbents offered better recovery compared to the commercially available coating for stir-bar sorptive extraction based on Ethylene Glycol/Silicone (EG/Silicone). The method based on FPSE with sol-gel Carbowax 20 M media and liquid chromatography-(electrospray ionization) tandem mass spectrometry (LC-(ESI) MS/MS) was developed and validated for environmental water samples. Good apparent recoveries (41-80%), detection limits (1-50 ng L(-1)), repeatability (%RSD<15%, n=5) and reproducibility (%RSD<18%, n=5) were achieved.


Effects of the protein matrix on glycan processing in glycoproteins.
In the biosynthesis of glycoproteins containing asparagine-linked glycans, a number of regulatory factors must be involved in converting the single glycan precursor into the variety of different final structures observed in different eukaryotic species. Among these factors are the kind of glycan-processing enzymes available in the Golgi apparatus of different cells, the specificity and regulatory properties of these enzymes, and the unique properties of the protein matrix in which a given glycan resides during the biosynthetic processing. In examining the role of this latter regulatory factor, we have considered a simplified model in which a few key steps are common to all cells, regardless of the nature of the processing enzymes available. The protein-bound oligomannose precursor Man8GlcNAc2-, arriving in the Golgi after the initial trimming in the endoplasmic reticulum (ER), first undergoes a series of preprocessing steps to yield Man5GlcNAc2- in animals and plants or Man13-15GlcNAc2- in yeast. At this stage the key commitment step--to process or not to process--determines whether the above intermediates will remain as unprocessed oligomannose structures or be initiated into a new series of reactions to yield processed structures characteristic of the organisms involved (complex or hybrid for vertebrates, polymannose for yeast, xylosylated glycans for plants and some invertebrates, or Man3GlcNAc2- structures for other invertebrates). It is proposed that this commitment step, along with the obligatory preprocessing steps, is regulated primarily by each glycan's unique exposure on its protein matrix. Subsequent processing steps leading to complex or hybrid structures, fucosylation, extent of branching, and specific structures at the nonreducing terminals are most likely determined primarily by the enzyme makeup of the individual processing machineries, but with the protein matrix still playing a significant role.


Identification of ADPR-transferase activity in the rat tapeworm, Hymenolepis diminuta.
1. The nuclear fraction of the rat tapeworm Hymenolepis diminuta (Cestoda) contains the enzyme adenosine diphosphoribosyl transferase (ADPR-transferase). 2. The enzyme catalyzes the postsynthetic modification of some nuclear proteins by the covalent attachment of the (ADP-ribose) moiety of NAD to such proteins. 3. The reaction is dependent on DNA which contains strand-breaks, and chain lengths equivalent to (ADP-ribose) is estimated. 4. The formation of polynucleotide products was competitively inhibited by 3-acetamidobezamide, with a Km of 125 microM. 5. The catalytic properties of ADPR-transferase in Hymenolepis diminuta are similar to those in T. brucei.


Application of standardisation methods to correct the spectral differences induced by a fibre optic probe used for the near-infrared analysis of pharmaceutical tablets.
Near infrared spectroscopy has become very popular in the pharmaceutical industry because of many important practical advantages. With the help of powerful chemometric techniques, multivariate calibration models are developed, relating near-infrared spectra to the values to be modelled. However, because of small instrumental differences between near-infrared spectrometers, a calibration model can only be used with spectra collected on the same instrument, which represents a serious limitation for the use of near-infrared spectroscopy in the pharmaceutical industry. To deal with this important problem, a certain number of different standardisation approaches were proposed in the literature. In this article, an application of instrument standardisation methods is presented, where two different data measurement modules (internal measurement cell and external fibre optic module) of a near-infrared spectrometer must be standardised for the quantitative determination of an active compound in pharmaceutical tablets.


Immune effects of mesenchymal stromal cells in experimental stroke.
Preclinical trials confirmed the potential of mesenchymal stromal cells (MSCs) to improve functional recovery after experimental stroke. Beneficial effects of MSCs are often attributed to their immunosuppressive/immunomodulatory functions. Surprisingly, the influence of MSCs on the immune system after stroke is poorly understood, but requires special consideration because cerebral ischemia is associated with stroke-induced immunodepression that predisposes to bacterial infections with increased mortality. In this study, we intravenously transplanted syngeneic murine bone marrow-derived MSCs (mMSCs) into C57BL/6 mice at 6 hours after transient middle cerebral artery occlusion (MCAo; 60 minutes) to investigate the impact of MSCs on stroke-induced immunodepression. Transplantation of syngeneic splenocytes or phosphate-buffered saline (PBS) served as controls. An immune status was determined by flow cytometry on days 3 and 14 after MCAo, which did not reveal any negative effects of cell transplantation on stroke-induced immunodepression. Although our mMSCs were found to exert immunosuppressive effects in vitro, stroke-mediated immune cell dysfunction was not altered by mMSCs in ex-vivo stimulation assays with lipopolysaccharide or concanavalin A. Moreover, systemic inflammatory cytokine levels (interleukin-6, tumor necrosis factorα, interferonγ, monocyte chemoattractant protein-1) remained unchanged in the sera of mice after cerebral ischemia and cell transplantation. These results reduce safety concerns about MSC administration in ongoing clinical stroke trials.


Re-auditing a regional lithotripsy service.
To assess, in a repeat audit of a regional lithotripsy service, whether changes implemented after a regional audit in 1994 (which showed disappointing results from shock wave lithotripsy, attributable to both poor patient selection and an inadequate fixed-site lithotripter) have had any effect. A data-collection sheet was devised to gather information on the site, size and number of stones treated, together with information on the lithotripsy treatment and outcome. Patients selected for the audit were the first 50 new patients treated with lithotripsy at each centre in 1999. As only one hospital has a fixed-site lithotripsy machine, the results of mobile lithotripsy were grouped by machine for analysis. There was an overall improvement in patient selection from the previous audits. Few stones of > 16 mm or < 4 mm were treated. Two units treated more ureteric stones, thought to reflect first the influence of a fixed-site lithotripter, and second a willingness to insert a ureteric stent and await the next mobile lithotripter visit. The stone free rates were all disappointingly low (16.7-26.7%) but the results improved when fragments of < 4 mm were included as "successful" giving an "overall success rate" of 45.9-66.7%. The unit with a fixed-site lithotripter appeared to perform better (two-thirds successful) than the mobile machines (Modulith SLX, 51%; Modulith SLK, 46%). One centre visited by both mobile machines had a success rate of 65% but a high rate of auxiliary procedures (35% vs 16-19% vs the fixed-site). Although these results show some improvement in patient selection for our regional lithotripsy service, stone-free and success rates are poorer than those reported elsewhere. This may reflect the modern lithotripsy machines that allow day-case treatment with minimal analgesia, and confirms reports by other authors who encourage a re-examination of success rates of shock wave lithotripsy.


New Methodologies in the Molecular Monitoring of CML.
In chronic myeloid leukemia (CML), the BCR-ABL fusion gene is both the therapeutic target of tyrosine kinase inhibitors and the indisputable direct marker of disease burden. Thus, sensitive assays for BCR-ABL now drive therapeutic options and are good surrogates for short- and long-term outcomes. Because CML is such an ideal model, new methods are arising that should make testing in CML faster, more reliable, and reach a greater sensitivity. These methods should be able to be transferred to other hematological malignancies that have mutation markers.


Prucalopride: A Review in Chronic Idiopathic Constipation.
Prucalopride (Resolor®), a highly selective serotonin 5-HT4 receptor agonist, is indicated in the European Economic Area for the treatment of adults with chronic idiopathic constipation (CIC) in whom laxatives have failed to provide adequate relief. This article reviews the pharmacological properties of prucalopride and its clinical efficacy and tolerability in patients with CIC. In five well-designed, 12-week trials in patients with CIC, oral prucalopride 2 mg/day was significantly more effective than placebo at improving bowel function, including the number of bowel movements and a range of other constipation symptoms, as well as health-related quality of life and patient satisfaction; however, no significant differences in bowel function measures were observed between prucalopride and placebo in a 24-week trial. Oral PEG-3350 + electrolytes reconstituted powder was found to be noninferior but not superior to prucalopride according to primary endpoint data from a 4-week, controlled-environment trial. Prucalopride was generally well tolerated in clinical trials; the most common adverse events were headache, diarrhoea, nausea and abdominal pain. No cardiovascular safety issues have arisen with prucalopride treatment. Although further long-term and comparative data would be beneficial, prucalopride provides an additional treatment option for patients with CIC.


Overcoming challenges due to enhanced biomedical waste generation during COVID-19 pandemic.
Biomedical wastes (BMWs) are potentially infectious to the environment and health. They are co-dependent and accumulative during the ongoing coronavirus disease-2019(COVID-19) pandemic. In India the standard treatment processes of BMWs are incineration, autoclaving, shredding, and deep burial; however, incineration and autoclaving are the leading techniques applied by many treatment providers. These conventional treatment methods have several drawbacks in terms of energy, cost, and emission. But the actual problem for the treatment providers is the huge and non-uniform flow of the BMWs during the pandemic. The existing treatment methods are lacking flexibility for the non-uniform flow. The Government of India has provisionally approved some new techniques like plasma pyrolysis, sharp/needle blaster, and PIWS-3000 technologies on a trial basis. But they are all found to be inadequate in the pandemic. Therefore, there is an absolute requirement to micromanage the BMWs based on certain parameters for the possible COVID-19 like pandemic in the future. Segregation is a major step of the BMW management. Its guideline may be shuffled as segregation at the entry points followed by collection instead of the existing system of the collection followed by segregation. Other steps like transportation, location of treatment facilities, upgradation of the existing treatment facilities, and new technologies can solve the challenges up to a certain extent. Technologies like microwave treatment, alkaline hydrolysis, steam sterilization, biological treatment, catalytic solar disinfection, and nanotechnology have a lot of scopes for the treatment of BMWs. Hi-tech approaches in handling and transportation are found to be fruitful in the initial steps of BMW management. End products of the treated BMWs can be potentially fabricated for the application in the built environment. Some policies need to be re-evaluated by the health care facilities or government administrations for efficient BMW management.


Technology-mediated information sharing between patients and clinicians in primary care encounters.
The aim of this study was to identify and describe the use of electronic health records for information sharing between patients and clinicians in primary care encounters. This topic is particularly important as computers and other technologies are increasingly implemented in multi-user health care settings where interactions and communication between patients and clinicians are integral to interpersonal and organizational outcomes. An ethnographic approach was used to classify the encounters into distinct technology-use patterns based on clinicians` interactions with the technology and patients. Each technology-use pattern was quantitatively analysed to assist with comparison. Quantitative analysis was based on duration of patient and clinician gaze at EHR. Physicians employed three different styles to share information using EHRs: Active information-sharing, in which a clinician turns the monitor towards the patient and uses the computer to actively share information with the patient;Passive information-sharing, when a clinician does not move the monitor, but the patient might see the monitor by leaning in if they choose; andTechnology withdrawal, when a clinician does not share the monitor with the patient. A variety of technology-mediated information-sharing styles may be effective in providing patient-centred care. New EHR designs may be needed to facilitate information sharing between patients and clinicians.


Dynamics of diverse coherences in primary charge separation of bacterial reaction center at 77 K revealed by wavelet analysis.
To uncover the mechanism behind the high photo-electronic conversion efficiency in natural photosynthetic complexes it is essential to trace the dynamics of electronic and vibrational quantum coherences. Here we apply wavelet analysis to two-dimensional electronic spectroscopy data for three purple bacterial reaction centers with mutations that produce drastically different rates of primary charge separation. From the frequency distribution and dynamic evolution features of the quantum beating, electronic coherence with a dephasing lifetime of ~50 fs, vibronic coherence with a lifetime of ~150 fs and vibrational/vibronic coherences with a lifetime of 450 fs are distinguished. We find that they are responsible for, or couple to, different specific steps during the primary charge separation process, i.e., intradimer charge transfer inside the special bacteriochlorophyll pair followed by its relaxation and stabilization of the charge-transfer state. The results enlighten our understanding of how quantum coherences participate in, and contribute to, a biological electron transfer reaction.


[Involuntary psychiatric hospital admissions: a comparison between five hospitals in three German federal states].
There is considerable variance in involuntary psychiatric hospital admission rates both in Europe and Germany. In a prospective comparison between five hospitals in three German federal states we assessed and analyzed involuntary psychiatric hospital admissions, including the patient's perspective. All involuntarily admitted patients were assessed by an independent researcher. Clinical data, patient and psychiatrist views were documented with different instruments including the McArthur admission experience survey. In this study 104 out of 244 involuntarily admitted patients gave informed consent. We found considerable differences between study centres concerning involuntary admission quotas (3.2-25.8% of all hospital admissions) and involuntary admission rates (16.6-97.6 per year per 100,000 inhabitants). Hospitals in the state of Baden-Württemberg had the lowest involuntary admission rates while they were highest in Bavaria. In Baden-Württemberg involuntarily admitted patients were more likely to suffer from chronic schizophrenia, they were more severely ill and experienced the involuntary hospital admission as more strenuous. There were no differences between centres concerning frequency of dangerous behavior or self-harm. We found a high variance across regions concerning the reasons for, frequencies and legal basis of involuntary hospital admissions. Regional differences of legal frameworks and service organization can explain this only to a limited amount. Transparency, legal certainty and reflection of stakeholder roles are a future necessity. Furthermore, there is a need for stringent compliance with legal regulations and coherent documentation.


[Normoglycemia as a therapy goal in diabetes treatment--concept and realization].
In diabetic patients (near-)normoglycemic control of blood glucose can only rarely be achieved by conventional insulin treatment. Novel strategies for this goal include transplantation of pancreatic tissue (whole organ, segment or isolated islets), the artificial pancreas with continuous blood glucose monitoring, insulin pump treatment and the intensified conventional treatment both of the latter including self-measurement of blood glucose and self-adaptation of the insulin dosis. The results of pancreas transplantation in recent years have shown a marked improvement, the one-year survival rate of a functioning organ is in the range of 50-70%. Due to the lifelong immunosuppression pancreas transplantation should be considered in diabetic patients who need a kidney transplantation and for this reason already require immunosuppression. In spite of encouraging results in animals islet transplantation in humans has been disappointing to date. The artificial pancreas at present cannot be used for long-term treatment mainly due to the problems of the glucose sensor. The application of insulin pump treatment without continuous monitoring of blood glucose (open loop) and intensified conventional treatment both can lead to improved glycemic control in spite of a more flexible life style. Only this way of treatment made it possible to perform randomized prospective studies in diabetic patients on the effect of (near-)normoglycemic control on secondary complications. The first results show a tendency towards a positive effect on mild to moderate diabetic retinopathy over 2 years. Thus, every juvenile diabetic patient should be informed about these possibilities of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis.
Diagnostic testing for primary ciliary dyskinesia (PCD) usually includes transmission electron microscopy (TEM), nasal nitric oxide, high-speed video microscopy, and genetics. Diagnostic performance of each test should be assessed toward the development of PCD diagnostic algorithms. We systematically reviewed the literature and quantified PCD prevalence among referrals and TEM detection rate in confirmed PCD patients. Major electronic databases were searched until December 2015 using appropriate terms. Included studies described cohorts of consecutive PCD referrals in which PCD was confirmed by at least TEM and one additional test, in order to compare the index test performance with other test(s). Meta-analyses of pooled PCD prevalence and TEM detection rate across studies were performed. PCD prevalence among referrals was 32% (95% CI: 25-39%, I2 = 92%). TEM detection rate among PCD patients was 83% (95% CI: 75-90%, I2 = 90%). Exclusion of studies reporting isolated inner dynein arm defects as PCD, reduced TEM detection rate and explained an important fraction of observed heterogeneity (74%, 95% CI: 66-83%, I2 = 66%). Approximately, one third of referrals, are diagnosed with PCD. Among PCD patients, a significant percentage, at least as high as 26%, is missed by TEM, a limitation that should be accounted toward the development of an efficacious PCD diagnostic algorithm.


Prevalence of Bovine Genital Campylobacteriosis, Associated Risk Factors and Spatial Distribution in Spanish Beef Cattle Based on Veterinary Laboratory Database Records.
Bovine genital campylobacteriosis (BGC) is a sexually transmitted disease that causes early reproductive failure in natural breeding cattle that are managed extensively. The aim of this study was to assess the BGC prevalence in Spain from 2011 to 2019 using data collected cross-sectionally from the diagnostic reports issued by the SALUVET veterinary diagnostic laboratory from a total of 5,182 breeding bulls from 1,950 herds managed under "dehesa" systems (large herds within fenced pastures and all-year breeding season) or mountain systems (smaller herds with seasonal breeding management and grazing in communal mountain pastures). Infection was detected by PCR in 7.7 and 12.2% of the bulls and herds tested, respectively. The "dehesa" herd management system (OR = 2.078, P = < 0.001, 95% CI = 1.55-1.77), bovine trichomonosis status of the herd (OR = 1.606, P = 0.004, 95% CI = 1.15-2.22), and bulls ≥3 years old (OR = 1.392, P = 0.04, 95% CI = 1.01-1.92) were identified as risk factors associated with Campylobacter fetus venerealis infection. We also studied the high-risk areas for circulation of the infection in extensive beef cattle herds in Spain, showing four significant clusters in "dehesa" areas in the south-western provinces of the country and a fifth cluster located in a mountain area in northern Spain. The results obtained in the present study indicate that BGC is endemic and widely distributed in Spanish beef herds. Specifically, "dehesa" herds are at greater risk for introduction of Cfv based on relatively high local prevalence of the infection and the use of specific management practices.


Analysis of the contribution of nasopharyngeal epithelial cancer cells to the induction of a local inflammatory response.
We investigated the local contribution of nasopharyngeal epithelial cancer cells to the inflammatory process. THP-1 monocytes were treated with phorbol 12-myristate 13-acetate to induce the production of differentiated macrophages (D-THP-1), which were subsequently activated by lipopolysaccharide (LPS) (10 ng/ml). The production of pro-inflammatory cytokines in D-THP-1 cells was detected by ELISA and qRT-PCR. The effects of conditioned media harvested from LPS-treated D-THP-1 cells were investigated with regard to cell proliferation (MTT), production of pro-inflammatory cytokines (ELISA) and activation of NF-κB and STAT3 (western blot) in the nasopharyngeal epithelial cancer cell line 5-8F. LPS induced the production of the pro-inflammatory cytokines TNF-α (875.1 ± 68.31 pg/ml), IL-6 (42.2 ± 5.32 pg/ml), IL-1β (9.6 ± 1.34 pg/ml) and IL-8 (19.3 ± 3.47 pg/ml) in D-THP-1 cells significantly (P < 0.001) with similar results detected at the mRNA level. Exposure of 5-8F cells to conditioned medium from LPS-treated D-THP-1 cells significantly induced production of TNF-α (632.3 ± 71.32 pg/ml), IL-6 (51.3 ± 3.57 pg/ml), IL-1β (7.3 ± 1.31 pg/ml) and IL-8 (20.1 ± 2.36 pg/ml) (P < 0.01) and triggered significant activation of NF-κB and STAT3, which correlated with a concomitant degradation of IκBα and an increase in JAK2 phosphorylation (P < 0.05). Moreover, the LPS-treated D-THP-1 conditioned media promoted the proliferation of 5-8F cells (P < 0.05). Nasopharyngeal epithelial cancer cells may play a significant role in maintaining and amplifying the inflammation process via activation of NF-κB and STAT3 pathway and through the local production of pro-inflammatory cytokines, which recruit and activate additional immune cells in the nasopharyngeal path and promote tumour progression.


Using multielectrode arrays to investigate neurodegenerative effects of the amyloid-beta peptide.
Multielectrode arrays are widely used to analyze the effects of potentially toxic compounds, as well as to evaluate neuroprotective agents upon the activity of neural networks in short- and long-term cultures. Multielectrode arrays provide a way of non-destructive analysis of spontaneous and evoked neuronal activity, allowing to model neurodegenerative diseases in vitro. Here, we provide an overview on how these devices are currently used in research on the amyloid-β peptide and its role in Alzheimer's disease, the most common neurodegenerative disorder. Most of the studies analysed here indicate fast responses of neuronal cultures towards aggregated forms of amyloid-β, leading to increases of spike frequency and impairments of long-term potentiation. This in turn suggests that this peptide might play a crucial role in causing the typical neuronal dysfunction observed in patients with Alzheimer's disease. Although the number of studies using multielectrode arrays to examine the effect of the amyloid-β peptide onto neural cultures or whole compartments is currently limited, they still show how this technique can be used to not only investigate the interneuronal communication in neural networks, but also making it possible to examine the effects onto synaptic currents. This makes multielectrode arrays a powerful tool in future research on neurodegenerative diseases.


Investigations on Acinetophage, QAB 3.4, Targeting Extensively Drug-Resistant Acinetobacter baumannii Isolates.
Drug resistance against antimicrobials is on the rise at alarmingly high rates. Acinetobacter baumannii is one of the six ESKAPE pathogens which are a significant "one health" issue. Clinical isolates of A. baumannii exhibit MDR phenotype mostly and infrequently the XDR and PDR phenotype. As a result, these infections have one of the highest mortality rates in hospitals. Alternative therapies are urgently needed. Various phages were enriched against XDR clinical strain of A. baumannii. A potent phage, QAB 3.4, was further tested against 100 clinical strains. Because of its broad lytic activity, it was further tested for stability, resistance development and as an infection control agent. Phage QAB 3.4 showed broad lytic activity against 100 MDR and XDR clinical isolates representing a wide diversity of infection sites. Assays conducted to document the phage's stability, and ability of clinical isolates to develop resistance against it, showed promising outcomes for its potential use in clinical applications. Phage QAB 3.4 was able to eradicate A. baumannii from pre-inoculated solid surfaces. It provides a proof of concept that phages can be used as environmentally friendly infection control agents. We propose the phage QAB 3.4 is a promising candidate for further pre-clinical and clinical studies to test its biosafety and efficacy.


Effect of sewage sludge composition on the susceptibility to spontaneous combustion.
The different technologies applied to the sewage sludge management have in common a first step devoted to the storage. In the case of dried sludges, this storage leads to important safety concerns because of the explosive character of the resulting dusts. In order to ensure safety in the storage step, it is necessary to evaluate the spontaneous combustion trends on terms of measurable chemical and physical properties of the dried sludges. In order to accomplish this scope, twelve samples from different wastewater treatment plants were characterized, correlating the susceptibility to spontaneous combustion with both the sludge composition and the heating value. Equations traditionally used for coals were used to determine the higher heating value from the chemical composition, finding as main source of error the high oxygen content of the sludge samples. Concerning the thermal susceptibility, different parameters were obtained (Maciejasz Index, induction temperature, maximum weight loss temperature, characteristic temperature and activation energy), being in all cases the spontaneous combustions favored by high H/C and low O/C ratios. Likewise, the presence of sulphur in the dried sludge was found to increase the thermal susceptibility of the material. This effect is tentatively explained with the formation of pyrophoric iron sulfides.


Combined use of multiplex ligation-dependent probe amplification and automatic sequencing for identification of KAL1 defects in patients with Kallmann syndrome.
To investigate the role of KAL1 abnormalities in Brazilian patients with Kallmann syndrome. In vitro experiments. Academic medical center. One hundred fifteen Brazilian patients (98 men) with Kallmann syndrome. Peripheral blood leukocytes were used to obtain DNA. Direct sequencing and multiplex ligation-dependent probe amplification were used to identify KAL1 abnormalities. We identified four KAL1 mutations (p.Met1?, p.Ala33Glyfs, p.Arg257*, and p.Trp462*) and two multiple exon deletions (exons 1-2 and 3-14) in six new male patients. Overall, 17 KAL1 defects (14.8%) were identified in the entire cohort of patients with Kallmann syndrome, including previously studied cases. KAL1-mutated patients presented with a more severe reproductive and nonreproductive phenotype (synkinesia, renal malformations, cryptorchidism, and anatomic olfactory abnormalities) in comparison with patients without KAL1 mutations. Intragenic deletions were one of the most often encountered defects (29.4%). These deletions can be missed by polymerase chain reaction (PCR) due to Yq11.2 KAL1 pseudogene (KALP) spurious amplification. These results indicate that intragenic multiexon deletions are one of the most frequent KAL1 abnormalities, which can be more accurately detected by multiplex ligation-dependent probe amplification. In addition, KAL1 sequencing results should be interpreted with caution, and stringency conditions of the PCR reaction should be adjusted to avoid pseudogene amplification.


Evidence for a serotonin-mediated slow excitatory potential in the guinea-pig coeliac ganglia.
The nature of the putative transmitter(s) mediating the non-cholinergic excitatory post-synaptic potential (e.p.s.p.) described in the preceding paper was investigated by means of electrophysiological, pharmacological and immunohistochemical methods. Serotonin (1-10 microM) when applied by superfusion caused a slow depolarization that closely mimicked the synaptic response in about 60% of the coeliac neurones that exhibited a non-cholinergic e.p.s.p. The serotonin depolarization evoked in low-Ca2+, high-Mg2+ solution or in a Krebs solution containing cholinergic antagonists was quantitatively similar to that elicited in normal Krebs solution. When compared in the same neurones the membrane resistance change during the course of the serotonin depolarization and of the non-cholinergic e.p.s.p., as well as their respective responses to conditioning polarization, were similar. The non-cholinergic e.p.s.p. was reversibly abolished during serotonin-induced depolarization; the blockade persisted when the membrane potential was restored to the resting level by hyperpolarizing current. The serotonin depolarization as well as the non-cholinergic e.p.s.p. were reversibly suppressed by cyproheptadine (20-50 microM), a serotonin antagonist, and enhanced by fluoxetine (30-50 microM), a serotonin reuptake inhibitor. On the other hand, pre-treating the ganglia with L-tryptophan (50 microM), a precursor of serotonin, preferentially augmented the synaptically induced response. A portion of the neurones (15%) were depolarized by substance P (1 microM) which also reversibly desensitized the non-cholinergic e.p.s.p. elicited in these neurones. The remaining neurones (25%) were insensitive to either serotonin or substance P, and the non-cholinergic e.p.s.p.s elicited in these cells were likewise not appreciably affected by these two agents. Furthermore, cyproheptadine, fluoxetine and L-tryptophan had no significant effect on the non-cholinergic e.p.s.p.s elicited in serotonin-insensitive neurones. Using the immunohistofluorescent techniques, dense but unevenly distributed serotonin immunoreactive nerve fibres could be observed surrounding many coeliac neurones. Immunoreactivity was not observed in the ganglia incubated with antisera pre-absorbed with excess serotonin. Collectively our results suggest that serotonin is the mediator of non-cholinergic e.p.s.p.s. elicited in about 60% of coeliac neurones sampled in this study, and that in the remaining neurones the slow depolarization may be generated by substance P and/or some unknown transmitter(s).


Insights into Delivering Cross-Cultural Medical Education in the UK and Malaysia.
Newcastle University UK operates an international campus, NUMed, in Malaysia. NUMed delivers the same medical degree programme as in the UK, within a different cultural context. In this paper, medical education faculty and NUMed graduates with experience working in both the UK and Malaysia provide insights into cross-cultural diversity in approaches to learning. Observations from small and large group teaching and approaches to assessment are discussed in relation to students' cultural backgrounds including previous learning experiences and English language abilities. We provide practice points for educators preparing a diverse range of students to work in global healthcare settings.


Solar Radiation Flux Provides a Method of Quantifying Weed-Crop Balance in Present and Future Climates.
A systematic approach to quantifying the weed-crop balance through the flux of solar radiation was developed and tested on commercial fields in a long-established Atlantic zone cropland. Measuring and modelling solar energy flux in crop stands has become standard practice in analysis and comparison of crop growth and yield across regions, species and years. In a similar manner, the partitioning of incoming radiation between crops and the in-field plant community may provide 'common currencies' through which to quantify positive and negative effects of weeds in relation to global change. Here, possibilities were explored for converting simple ground-cover measures in commercial fields of winter and spring oilseed rape in eastern Scotland, UK to metrics of solar flux. Solar radiation intercepted by the crops ranged with season and sowing delay from 129 to 1975 MJ m-2 (15-fold). Radiation transmitted through the crop, together with local weed management, resulted in a 70-fold range of weed intercepted radiation (14.2 to 963 MJ m-2), which in turn explained 93% of the corresponding between-site variation in weed dry mass (6.36 to 459 g m-2). Transmitted radiation explained almost 90% of the variation in number of weed species per field (12 to 40). The conversion of intercepted radiation to weed dry matter was far less variable at a mean of 0.74 g MJ-1 at both winter and spring sites. The primary cause of variation was an interaction between the temperature at sowing and the annual wave of incoming solar radiation. The high degree of explanatory power in solar flux indicates its potential use as an initial predictor and subsequent monitoring tool in the face of future change in climate and cropping intensity.


Genotoxic effects of the ochratoxin A (OTA), its main metabolite (OTα) per se and in combination with fumonisin B1 in HepG2 cells and human lymphocytes.
Ochratoxin A (OTA) and fumonisin B1 (FB1) are mycotoxins distributed in a wide variety of foods for human or animal consumption and are classified as possible carcinogens for humans. This study aimed to evaluate the cytotoxic, cytostatic and genotoxic effects of OTA and its main metabolite, ochratoxin α (OTα), FB1 and three combinations of OTA and FB1 at moderate and environmental doses. Cell viability was evaluated through MTT assay and the trypan blue exclusion method. The cytostatic and genotoxic effects were evaluated through the cytokinesis-block micronucleus assay. The results showed synergistic time- and concentration-dependent cytotoxic effects of one of the combinations of OTA and FB1. In contrast, significant differences were observed in the micronuclei (MN) frequency from OTA, OTα and coexposure of OTA + FB1. Some of these combinations increased the frequency of nuclear buds, nucleoplasmic bridges, donut-shaped nuclei, necrotic and apoptotic cells and MN in mononucleated cells. In conclusion, OTA and its main metabolite OTα, as well as the co-exposure of OTA and FB1, cause stable DNA damage at environmentally relevant concentrations, which was greater in metabolically competent cells. More studies are needed to understand the chemical interactions that occur due to the joint presence of mycotoxins, which occurs commonly.


Studies on chemotherapy of parasitic helminths (XVII). Effects of pyrantel on the motility of various parasitic helminths and isolated host tissues.
Pyrantel tartrate caused spastic paralysis in various parasitic nematodes, but not in cestodes and trematodes.


Insulin-induced phosphorylation of the beta-4 integrin subunit expressed on murine metastatic carcinoma cells.
A tumor surface protein (TSP-180) that is highly expressed on highly malignant metastatic cells has been identified on murine lung carcinomas. On SDS-PAGE under reducing conditions, TSP-180 shows a complex banding pattern corresponding to 204, 183, 150, 135, and 116 kDa. All bands of the TSP-180 complex are glycosylated and are labeled by lactoperoxidase-catalyzed radioiodination of viable cells. The mouse TSP-180 complex described here is homologous to the human integrin alpha 6 beta 4 complex, and in particular it has been demonstrated that protein corresponding to 204 kDa is homologous to the beta 4 subunit of the integrin complex. It has been shown recently that monoclonal antibody to TSP-180 (MoAb 135-13C) stimulates cell growth in vitro and induces phosphorylation of the 204-kDa protein. We now report that insulin increases the phosphorylation of the 204-kDa protein 30-fold in intact carcinoma cells and epidermal growth factor (EGF) causes a threefold increase. Insulin-like growth factor (IGF-I) and platelet-derived growth factor have no effect. The effect of insulin and of IGF-I on phosphorylation of their own receptors was studied using solubilized cell membranes. Insulin and IGF-I each induced a fivefold increase in the phosphorylation of their respective receptor beta subunits. In order to test if phosphorylation of the 204-kDa protein was induced by direct binding of growth factors to TSP-180 and to identify growth factor receptors on line 1 cells, affinity cross-linking studies were performed. Affinity labeling of receptors demonstrated that insulin and IGF-I both bind to a 135-kDa protein that corresponds to the insulin and IGF-I receptor alpha subunits. Affinity labeling of EGF receptors failed to demonstrate EGF receptor molecules (175-kDa protein) on line 1 cells. Further investigations by using a different approach confirmed the very low amount of EGF receptors on line 1 cells. Direct phosphoamino acid analysis of the 204-kDa protein purified from insulin-stimulated cells demonstrated that this beta 4 integrin subunit is phosphorylated on serine and tyrosine. We conclude that beta 4 integrin molecule is a target for phosphorylation through an indirect receptor-mediated mechanism.


Ligustilide alleviates podocyte injury via suppressing the SIRT1/NF-κB signaling pathways in rats with diabetic nephropathy.
Diabetic nephropathy (DN) is one of the common chronic microvascular complications of diabetes, and podocyte injury and dysfunction are strictly related to the pathogenesis of DN. Studies have shown that ligustilide (LIG) has anti-inflammatory, antioxidant, and anti-apoptotic activities. This study was designed to investigate the therapeutic effect of LIG in DN rats and their mechanisms. DN rat models (n=10) were induced by streptozotocin (STZ) combined with a high-fat diet. Rats in the LIG group were intragastrically administered with LIG daily for eight weeks, and animals in the positive control group were treated with Losartan potassium. The body weight and blood glucose were checked weekly during the treatment. The pathological changes of kidney tissue were observed with hematoxylin and eosin (HE) staining. Blood lipid profiles and renal function-related markers, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen (BUN), and serum creatinine (Scr) were monitored using a biochemical analyzer. The protein expression of nephrin was determined by immunohistochemistry and Western blotting. Finally, Western blot was used to determine the protein expression of Sirtuin 1 (SIRT1) and nuclear factor-kappa B (NF-κB). Compared with the healthy control group, rats in the DN group have slower weight gain, increased blood sugar level, renal lesions, and impaired renal function, along with decreased nephrin expression, abnormally activated NF-κB, and inhibited SIRT1 protein expression. All the above conditions were improved after intervention with either losartan potassium or LIG. LIG attenuates podocyte injury by regulating the SIRT1/NF-κB signaling pathway and thereby exerts its protective effect on renal function in DN rats.


Exacerbation of group B streptococcal sepsis and arthritis in diabetic mice.
Group B streptococci (GBS) have been recognised as an ever-growing cause of serious invasive infections in non-pregnant adults, in particular in association with severe underlying diseases such as diabetes mellitus. In the present study we used mice rendered diabetic to gain further insights into host-pathogen interaction during induced GBS sepsis and septic arthritis. Type I diabetes was induced in adult CD-1 mice by low-dose streptozotocin treatment. Mice were then infected with different doses of GBS, and mortality, appearance of arthritis, growth of microorganisms in the organs and cytokine and chemokine profile were assessed in diabetic and control animals. The LD50 was significantly lower in diabetics than in controls, while both incidence and severity of arthritis were higher. A significantly higher number of microorganisms were recovered from the organs of diabetic mice than in controls. The worsening of sepsis and arthritis was associated with a significant increase in systemic and local production of IL-6, IL-1 beta, TNF-alpha, IL-10, macrophage inflammatory protein 1 alpha (MIP-1alpha), and MIP-2 and with a decrease in IFN-gamma production. Taken together, our results indicate an impaired host resistance to GBS infection in diabetics, likely due to a dysregulation of the cytokine network and prolonged local inflammatory response.


Patient tolerability during office cystoscopy and bladder tumor cauterization: a multivariate analysis of risk factors.
Cystoscopy and cauterization performed in the operating room is expensive and exposes patients to anesthesia risks. Patient tolerability during office cystoscopy and cauterization is critical to the office management of bladder cancer (BC) and other urologic diseases. We evaluated the risk factors for pain of flexible cystoscopy in the office-setting with emphasis on a sub-group of BC patients who underwent cauterization. Retrospective analyses of 110 anonymous patient surveys completed after cystoscopy and/or cauterization. Survey information included age, gender, indication for cystoscopy, number of prior cystoscopies, number of prior office-based cauterizations, anxiety prior/during cystoscopy, and pain during cystoscopy and/or cauterization. Univariate/multivariate and linear-regression analyses were performed to evaluate the association of pain with clinical parameters. Average pain during cystoscopy (1.75 ± 1.331) was not significantly different when cauterization was also performed (2.37 ± 2.214) (p < 0.001) (p = 0.2840). Patients in the lower age group (<66 years) indicated higher anxiety levels (p = 0.0005), more pain at cystoscopy (P = 0.004) and cauterization (p < 0.001). Although the patients' overall anxiety level was low (1-3/10), it was associated with some pain during cystoscopy (p = 0.0005) and cauterization (p < 0.000). In multivariate analysis, anxiety was the only independent predictor of pain during cystoscopy (p = 0.03, OR: 6.52,95% CI: 1.2-35.6) and cauterization (p = 0.0012, OR: 3.4, 95%CI: 1.6-7.0). In BC patients, pain scores during cystoscopy and cauterization were not significantly different (p = 0.4772) but associated with anxiety. Office-based cystoscopy and cauterization are tolerable with minimal pain. Higher pain levels during cystoscopy were associated with procedure anxiety, and pain during cauterization was associated with procedure anxiety and younger age. Younger and more anxious patients may need more counseling before cystoscopy.


A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth.
Chromosome translocations involving mixed lineage leukemia 1 (MLL1) cause acute leukemia in most infants and 5-10% children/adults with dismal clinical outcomes. Most frequent MLL1-fusion partners AF4/AFF4, AF9/ENL and ELL, together with CDK9/cyclin-T1, constitute super elongation complexes (SEC), which promote aberrant gene transcription, oncogenesis and maintenance of MLL1-rearranged (MLL1-r) leukemia. Notably, ENL, but not its paralog AF9, is essential for MLL1-r leukemia (and several other cancers) and therefore a drug target. Moreover, recurrent ENL mutations are found in Wilms tumor, the most common pediatric kidney cancer, and play critical roles in oncogenesis. Proteolysis-Targeting Chimera (PROTAC) molecules were designed and synthesized to degrade ENL. Biological activities of these compounds were characterized in cell and mouse models of MLL1-r leukemia and other cancers. Compound 1 efficiently degraded ENL with DC50 of 37 nM and almost depleted it at ~ 500 nM in blood and solid tumor cells. AF9 (as well as other proteins in SEC) was not significantly decreased. Compound 1-mediated ENL reduction significantly suppressed malignant gene signatures, selectively inhibited cell proliferation of MLL1-r leukemia and Myc-driven cancer cells with EC50s as low as 320 nM, and induced cell differentiation and apoptosis. It exhibited significant antitumor activity in a mouse model of MLL1-r leukemia. Compound 1 can also degrade a mutant ENL in Wilms tumor and suppress its mediated gene transcription. Compound 1 is a novel chemical probe for cellular and in vivo studies of ENL (including its oncogenic mutants) and a lead compound for further anticancer drug development.


Complications of neonatal extracorporeal membrane oxygenation.
From 1973-1985 to 1988 the average patient complications per case were 1.44 per case and significantly increased during 1990 to 1992 to 2.10 per case (Figure 3). During the same periods patient survival significantly decreased from 84% (1973-1985 to 1988, n = 2463) to 80% (1990 to 1992, n = 4005) (Figure 4). The association between total complication rates and survival rate was examined by regression analysis (Table 5). The correlation of patient complication rate and total complication rate with survival is highly significant; however, causality cannot be established. When comparing different entry criteria (Table 2) for incidence of mechanical and patient complications, no significant differences are apparent. This is not surprising since each of the entry criteria were designed to identify the same patient population. When premature neonates (> 35 weeks) were placed on ECMO, 36% of them had intracranial haemorrhage (ICH) with 62% mortality while only 12% of the neonates < 35 weeks had ICH and a 49% mortality. Similar findings were noted with low birthweight neonates (< 2.2 kg), 28% had ICH with 64% mortality while only 12% of the neonates > 2.2 kg had ICH with a 50% mortality. Selection criteria remain problematic for a variety of reasons. They cannot be viewed as absolute because of variability between centres. What represents likely 80% mortality in one centre may not apply to another. Historical controls are misleading because changing respiratory therapy strategies make historical populations difficult to compare. Also, once an ECMO centre becomes established, a more challenging group of patients will be attracted than previously was the case. Further, a single entry criterion cannot be generalized for all entry diagnoses. Criteria for an 80% predicted mortality is probably not the same for MAS, CHN, PPHN, and sepsis. Subsequent patients registered in the Neonatal ECMO Registry of the Extracorporeal Life Support Organization will address these issues more thoroughly, as specific details of the pre-ECMO condition and therapeutic strategies are collected. This collective review should help to identify trends which require reassessment of technique or patient management.


Epigenetic modulators promote mesenchymal stem cell phenotype switches.
Discoveries in recent years have suggested that some tissue specific adult stem cells in mammals might have the ability to differentiate into cell types from different germ layers. This phenomenon has been referred to as stem cell transdifferentiation or plasticity. Despite controversy, the current consensus holds that transdifferentiation does occur in mammals, but only within a limited range. Understanding the mechanisms that underlie the switches in phenotype and development of the methods that will promote such type of conversions can open up endless possibilities for regenerative medicine. Epigenetic control contributes to various processes that lead to cellular plasticity and DNA and histone covalent modifications play a key role in these processes. Recently, we have been able to convert human mesenchymal stem cells (hMSCs) into neural-like cells by exposing cells to epigenetic modifiers and neural inducing factors. The goal of this study was to investigate the stability and plasticity of these transdifferentiated cells. To this end, neurally induced MSCs (NI-hMSCs) were exposed to adipocyte inducing factors. Grown for 24-48 h in fat induction media NI-hMSCs reversed their morphology into fibroblast-like cells and regained their proliferative properties. After 3 weeks approximately 6% of hMSCs differentiated into multilocular or plurivacuolar adipocyte cells that demonstrated by Oil Red O staining. Re-exposure of these cultures or the purified adipocytes to neural induction medium induced the cells to re-differentiate into neuronal-like cells. These data suggest that cell plasticity can be manipulated by the combination of small molecule modulators of chromatin modifying enzymes and specific cell signaling pathways.


Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies.
An effective HIV-1 vaccine probably will need to be able to induce broadly neutralizing HIV-1 antibodies (bNAbs) in order to be efficacious. The many bNAbs that have been isolated from HIV-1 infected patients illustrate that the human immune system is able to elicit this type of antibodies. The elucidation of the structure of the HIV-1 envelope glycoprotein (Env) trimer has further fueled the search for Env immunogens that induce bNAbs, but while native Env trimer mimetics are often capable of inducing strain-specific neutralizing antibodies (NAbs) against the parental virus, they have not yet induced potent bNAb responses. To improve the performance of Env trimer immunogens, researchers have studied the immune responses that Env trimers have induced in animals; they have evaluated how to best use Env trimers in various immunization regimens; and they have engineered increasingly stabilized Env trimer variants. Here, we review the different approaches that have been used to increase the stability of HIV-1 Env trimer immunogens with the aim of improving the induction of NAbs. In particular, we draw parallels between the various approaches to stabilize Env trimers and ones that have been used by nature in extremophile microorganisms in order to survive in extreme environmental conditions.


Rescue of thymocytes from cell death by vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP) has previously been shown to increase survival of cultured neurons and to prevent the neurotoxic effect of the envelope glycoprotein 120 of human immune deficiency virus (HIV). The present report shows that VIP also protects mouse and human thymocytes exposed to a cytolytic dose of prednisolone in vitro. The activity of VIP is dose-dependent, and specific, since the structurally related secretin has no effect. The effective concentration of VIP is within the physiological range, suggesting that VIP released from nerve terminals may modulate cell death in the thymic cortex. Results with an N-terminal and a C-terminal fragment of VIP implied that the complete VIP molecule is required for optimal protection against cytolysis.


Correlation between thermoluminescence and optically stimulated luminescence responses of natural alexandrite.
Luminescent properties of alexandrite crystals (BeAl2O4:Cr3+) are studied. Partial readouts of thermoluminescence (TL) and optically stimulated luminescence (OSL) signals were obtained to infer the relations of OSL and TL trapping centers. Four TL peaks were studied; their intensities decrease at different rates by illumination with blue OSL light. The OSL curve shows two-time components (exponential decay constants 3.15 and 28.4 s). The short time component is preferentially diminished when the sample is heated to temperatures from 363 to 513 K. About 50% of the whole TL intensity remains after a complete 300s OSL readout.


A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing.
The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore "temoporfin", which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection.


RORγt-Expressing Pathogenic CD4+ T Cells Cause Brain Inflammation during Chronic Colitis.
Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's disease and ulcerative colitis patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease patients remains unknown. Studies have linked the Th17 subset of CD4+ T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis, ischemic brain injury, and Alzheimer's disease. To better understand how CD4+ T lymphocytes contribute to brain pathology in chronic intestinal inflammation, we investigated the development of brain inflammation in the T cell transfer model of chronic colitis. Our findings demonstrate that CD4+ T cells infiltrate the brain of colitic Rag1 -/- mice in proportional levels to colitis severity. Colitic mice developed hypothalamic astrogliosis that correlated with neurobehavioral disorders. Moreover, the brain-infiltrating CD4+ T cells expressed Th17 cell transcription factor retinoic acid-related orphan receptor γt (RORγt) and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of RORγt-deficient naive CD4+ T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1 -/- recipients, with significantly less brain infiltration of CD4+ T cells. The finding is mirrored in chronic dextran sulfate sodium-induced colitis in Rorcfl/fl Cd4-Cre mice that showed lower frequency of brain-infiltrating CD4+ T cells and astrogliosis despite onset of significantly more severe colitis compared with wild-type mice. These findings suggest that pathogenic RORγt+CD4+ T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation.


The first step to integrating the child's voice in adverse event reporting in oncology trials: a content validation study among pediatric oncology clinicians.
Children with cancer experience significant toxicities while undergoing treatment. Documentation of adverse events (AEs) in clinical trials is mandated by federal agencies. Although many AEs are subjective, the current standard is clinician reporting. Our long-term goal is to create and validate a self-report measure of subjective AEs for children aged 7 years and older that will inform AE reporting for the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). This content validation study aimed to identify which of the AEs in the current CTCAE should be included in a pediatric self-report measure. We sought expert panel review and consensus among 187 pediatric clinicians from seven Children's Oncology Group institutions to determine which of the 790 AEs are amenable to child self-report. Two survey iterations were used to identify suitable AEs, and clinician agreement estimated by the content-validity ratio (CVR) was assessed. Response rates for surveys 1 and 2 were 72% and 67%, respectively. After the surveys, 64 CTCAE terms met the criteria of being subjective, relevant for use in pediatric cancer trials, and amenable to self-report by a child. The most frequent reasons for removal of CTCAE terms were that they relied on laboratory or clinical measures or were not applicable to children. The 64 CTCAE terms will be translated into child-friendly terms as the basis of the child-report toxicity measure. Ultimately, systematic collection of these data will improve care by enhancing the accuracy and completeness of treatment toxicity reports for childhood cancer.


The effect of delmopinol on glucosyltransferase adsorbed on to saliva-coated hydroxyapatite.
The aim was to explore the effects of delmopinol, a substituted amino-alcohol compound recently reported as a potential antiplaque agent, on GTF activity in solution and when adsorbed on to sHA. Delmopinol was without a significant effect on GTF activity in solution. In contrast, a reduction in the bound glucans synthesized by the adsorbed GTF was found in the presence of delmopinol. Delmopinol did not displace the adsorbed GTF from the sHA, nor was there significant desorption of glucans from sHA. The total glucan synthesis (bound and unbound) was reduced in the presence of delmopinol. Inhibition of GTF was not reversed by sucrose. Inhibition of GTF activity by delmopinol apparently results from drug-enzyme interaction on the surface of sHA beads. These observations provide further support for the important differences in the properties of adsorbed GTF and GTF in solution, illustrating that GTF-drug interaction differs between enzyme adsorbed to surfaces and enzyme in solution.


Anti-idiotype stimulation of antigen-specific antigen-independent antibody responses in vitro. II. Triggering of B lymphocytes by idiotype plus anti-idiotype in the absence of T lymphocytes.
Antibodies specific for the idiotypes of B10 anti-(T,G)-A--L antibodies (anti-id) induced B lymphocytes to secrete anti-(T,G)-A--L antibodies in vitro in the absence of both antigen and T lymphocytes, provided either that the B lymphocytes were previously primed in vivo with (T,G)-A--L or that id specific for (T,G)-A--L was added to the cultures. These antigen- and T lymphocyte-independent responses were antigen specific and appeared not to require accessory cells. The results suggested that B lymphocyte activation occurred via the formation of id-anti-id complexes, and evidence was obtained that this activation involved two separate interactions between the B lymphocytes and the id-anti-id complexes. These studies document a previously undescribed regulatory function of anti-idiotype antibodies.


The defendant in a medical malpractice suit: an integral part of the defense team.
This article explains the litigation process of a medical malpractice suit and offers suggestions to help pediatric radiologists cope with the stress of being sued. It provides tangible ways in which the pediatric radiologist can become an important part of the defense team. Our goal is to enable the pediatric radiologist to place the lawsuit in a proper perspective and demonstrate the importance of providing medical insight to aid in forming legal strategy.


Concept for an off-line gain stabilisation method.
Conceptual ideas are presented for an off-line gain stabilisation method for spectrometry, in particular for alpha-particle spectrometry at low count rate. The method involves list mode storage of individual energy and time stamp data pairs. The 'Stieltjes integral' of measured spectra with respect to a reference spectrum is proposed as an indicator for gain instability. 'Exponentially moving averages' of the latter show the gain shift as a function of time. With this information, the data are relocated stochastically on a point-by-point basis.


Efficacy and safety of So-Cheong-Ryong-Tang in treatment of perennial allergic rhinitis: study protocol for a double-blind, randomised, parallel-group, multicentre trial.
So-Cheong-Ryong-Tang (SCRT) is a herbal medicine widely used in traditional medicine for treating allergic rhinitis (AR). In animal studies, SCRT has suppressed the progression of AR. The main purpose of this study is to assess the efficacy and safety of the SCRT for the treatment of perennial allergic rhinitis (PAR) and discover the underlying mechanisms resulting in anti-inflammatory effects in humans. We will conduct a double-blind, randomised, placebo-controlled, parallel-group, multicentre trial of Korean adults with PAR. For the study, 156 subjects with PAR will be recruited. The trial will consist of a 4-week oral administration of SCRT or placebo with two visits at 2-week intervals and an 8-week follow-up period with two visits at 4-week intervals. The primary outcome is a change in the total nasal symptoms score. The secondary outcomes include changes in the Rhinoconjunctivitis Quality of Life Questionnaire score, total serum IgE and cytokines levels. This study was approved by the Institutional Review Board at each research centre (name of each centres and approval numbers): Kyung Hee University Hospital at Gangdong (KHNMC-OH-IRB 2015-04-009), Kyung Hee University Medical Centre (KOMCIRB-160321-HRBR-011), Pusan National University Hospital (2016-004), Dongguk University Medical Centre (2016-03) and Semyung University hospital (2016-01). This result will be published in a peer-reviewed journal. NCT03009136; Pre-results.


VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process.
Retromer is a complex of proteins that functions in the endosome-to-Golgi retrieval cargo transport pathway. VPS35 works as the central subunit of retromer to recognize the cargos and binds with VPS29 and VPS26 via distinct domains. We show that deficiency of VPS35 or VPS29 accompanies degradation of other subunits, whereas VPS26 deficiency had no effect on VPS29 and VPS35 levels. Although VPS35 forms VPS26-VPS35 and VPS29-VPS35 sub-complexes with similar efficiency in vitro, VPS26-VPS35 was more easily degradable by the ubiquitin-proteasome-system than VPS29-VPS35. These results indicate that VPS29 and VPS35 form a biologically stable sub-complex in vivo.


Prognostic Value of Computed Tomography in Empyema: A Multicenter Retrospective Cohort Study.
Rationale: Chest computed tomography is performed in patients with empyema for various reasons. However, its predictive ability for patient outcomes in empyema has not been evaluated. Objectives: To evaluate the predictive ability of computed tomography findings (pleural thickness, loculation, interlobar pleural effusion, lung abscess, and bronchopleural fistula) for 90-day mortality in empyema. Methods: This multicenter retrospective cohort study was conducted across six acute care hospitals in Japan. We included patients with confirmed empyema diagnoses who underwent chest computed tomography within 7 days of diagnosis. Imaging findings were defined as pleural thickness, loculation, interlobar pleural effusion, lung abscess, or bronchopleural fistula. One radiologist interpreted the computed tomography scans without patient information. The primary outcome was 90-day mortality. We calculated the differences in 90-day mortality between the presence and absence of each computed tomography finding using logistic regression with or without adjustment for early thoracic surgery. Results: A total of 711 patients were included in our study. Thoracic surgery was performed in 27% of patients, and the 90-day mortality rate was 10%. The differences (95% confidence intervals) in 90-day mortality without and with adjustment for early thoracic surgery were as follows: pleural thickness, 3.09% (-1.35% to 7.54%) and 2.70% (-1.80% to 7.20%); loculation, -4.01% (-8.61% to 0.60%) and -3.80% (-8.41% to 0.81%); interlobar pleural effusion, -9.15% (-14.58% to -3.72%) and -8.96% (-14.39% to -3.53%); lung abscess, 7.04% (-1.16% to 15.2%) and 6.86% (-1.34% to 15.05%); and bronchopleural fistula, 13.80% (7.66% to 19.94%) and 13.63% (7.50% to 19.77%), respectively. Conclusions: Although interlobar pleural effusion predicted lower 90-day mortality regardless of early thoracic surgery, the presence of bronchopleural fistula predicted higher 90-day mortality with empyema. Our results warrant further validation.