A potentiometric study of the adsorption of a cationic surfactant onto laponite in water-methanol and water-dimethylsulfoxide mixtures.
We studied the adsorption of a cationic surfactant, dodecyltrimethylammonium bromide (DTABr), onto laponite in water-methanol and water-DMSO mixtures at 298 K. Adsorption isotherms were determined by potentiometric methods using DTA(+) and Br(-)-selective electrodes. All of the isotherm shapes in the mixture were classical. Activity coefficients were determined for the transfer between water and hydroorganic mixtures. Comparison of the adsorption isotherms obtained for different surfactant chemical potentials showed that at higher concentrations of free surfactant, the aggregation state does not depend on the nature of the surrounding media. A study of the influence of the ionic strength showed that there is a common intersection point in each hydroorganic mixture. This point corresponds to the charge compensation point and depends on the nature of the surrounding medium.


Assessing the impact of climate change and human activity on streamflow in a semiarid basin using precipitation and baseflow analysis.
Assessment of streamflow variations under the influence of climate change and human activity is crucial for sustainable water resource management, especially in semiarid areas. In this study, we first used the Hydrograph Separation Program to separate and analyze the base flow index (BFI) that was impacted directly by human activity and precipitation as an important climate factor from 1967 to 2016 in the Dez River Basin. Second, the Mann-Kendall trend test was used to identify trends and change points. Then, the elasticity coefficient method was applied to calculate the impacts of natural factors and anthropogenic activities. The results of the separation methods showed that the sliding interval method produced a better performance. Furthermore; the analyzed trend test at the annual scale showed a significant decreasing trend for runoff as well as increasing trends for the baseflow index in the four of five sub-basins of the Dez River at confidence levels of 95% and 99%, while the average precipitation in these sub-basins was not significant. Additionally, at the seasonal scale in these sub-basins, the average precipitation in winter showed a significant downward trend, while runoff showed a decreasing trend and the BFI index showed increasing trends in winter, spring and summer. The abrupt change point was determined after the change in the BFI index; the runoff was reduced. The maximum change occurred in the sub-basin tireh which after change point from 1977 to 1993,runoff reduced - 1.49% comparison with the base period( from 1967 to 1976) also elasticity estimation was - 0.46,but after change point in Baseflow index from 1994 to 2016 runoff reduced - 55.02% and elasticity estimation was - 0.65. The baseflow index trend and elasticity estimation also indicated that intensive human activities had more significant effects on the Dez Basin's hydrological processes and streamflow variation.


Effect of positive end-expiratory pressure on right ventricular performance. Importance of baseline right ventricular function.
Thirty-six patients with diverse baseline right ventricular function were evaluated during incremental positive end-expiratory pressure (PEEP) application. Right heart pressures, cardiac output, right ventricular ejection fractions, and ventricular volumes were obtained at each PEEP level. Right ventricular peak systolic pressure-end-systolic volume relations were analyzed as an index of contractile function. Patients with severely depressed baseline right ventricular ejection fractions (30 percent or less) had an increase in end-diastolic (270 +/- 74 to 391 +/- 76 ml, 0 to 20 cm water (H2O) PEEP, p less than 0.05) and end-systolic volumes (210 +/- 70 to 321 +/- 70 ml, 0 to 20 cm H2O PEEP, p less than 0.05). These patients also had a decline in estimated right ventricular contractile function at 20 cm H2O PEEP as estimated by the slope of systolic pressure-volume relations (0.12 to 0.04 mm Hg/ml, 0 to 15 and 15 to 20 cm H2O PEEP, respectively, p less than 0.05). Patients with normal (40 percent or more) or moderately depressed (31 to 40 percent) baseline right ventricular ejection fractions had no change in right ventricular volumes or estimated contractile function. Therefore, the effect of PEEP on right ventricular function differs depending on the baseline right ventricular ejection fraction.


Synthesis, characterization and antimicrobial activity of biguanidinylated chitosan-g-poly[(R)-3-hydroxybutyrate].
Chitosan biguanidine hydrochloride (ChG) and low molecular weight poly[(R)-3-hydroxybutyrate] (PHB) were successfully prepared to overcome the solubility problem of chitosan and PHB and also to enhance antimicrobial activity of chitosan. The graft copolymers based on ChG and PHB (ChG-grafted PHB) were then prepared via condensation reaction of the carboxylic groups of PHB with the amino groups of ChG. These graft copolymers swell in water. The prepared graft copolymers were characterized by FTIR, 1H NMR, X-ray diffraction (XRD) and thermal analyses (TGA and DSC). TGA and DSC results revealed that the thermal stability and crystallinity of the graft copolymers were found to increase as the content of PHB increased. The antimicrobial activity of both ChG and ChG-grafted PHB, against Streptococcus pneumoniae, Bacillus subtilis, Escherichia coli (as examples of bacteria) and Aspergillus fumigatus, Geotricum candidum and Syncephalastrum recemosum (as examples of fungi), were tested. Among them, ChG and ChG-grafted PHB with the highest grafting percent investigated showed to possess relatively higher antimicrobial activity with low MIC values in the range of 0.49-3.90μgmL-1.


Transitioning issues in adolescent to young adult hemophilia patients with inhibitors: an approach for a growing population.
The major adverse effect of factor replacement therapy in patients with hemophilia is the development of neutralizing antibodies termed inhibitors. This complication renders standard factor replacement therapy ineffective resulting in increased morbidity and mortality. Until recently, the population of adults with inhibitors was relatively small due to the death of many of the patients from HIV that they contracted from contaminated factor in the early 1980s. With the advent of factor products with reduced risks for deadly infections in the mid-1980s to early 1990s, a cohort of inhibitor patients is now beginning to enter adulthood thus raising the issues regarding the transition of these patients into adulthood. It is, therefore, expected that adult hematologists will be seeing more inhibitor patients and that pediatric hematologists will be faced with managing this transition process, which may not necessarily include transition to an adult facility or adult hematologist. This review will discuss the various issues ranging from choice of medical provider to a discussion of psychosocial and financial issues facing this specific patient population.


Tumorous phosphaturic osteomalacia. Report of a case associated with multiple hemangiomas of bone.
A case of osteomalacia associated with hypophosphatemia, decreased tubular reabsorption of phosphorus, hyperphosphaturia and renal glycosuria with associated bone pain and myopathy is presented. The patient was found to have multiple osteolytic lesions of bone which, on biopsy, proved to be sclerosing hemangiomas of bone. Treatment with oral phosphate and vitamin D effected a diminution in his symptoms of bone pain and muscular weakness. The literature on hypophosphatemic phosphaturic osteomalacia associated with mesenchymal tumors is reviewed. It has been suggested that certain mesenchymal tumors elaborate a yet to be identified humoral substance which decreased synthesis of 1 alpha, 25-dihydroxycholecalciferol causing decreased tubular reabsorption of phosphorus, hyperphosphaturia, hypophosphatemic osteomalacia and hypophosphatemic myopathy.


Factors associated with mortality risk in critical care patients treated with veno-arterial extracorporeal membrane oxygenation.
To identify factors associated with mortality in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and to validate the discrimination of the risk assessment tools to predict mortality. VA-ECMO is a rescue therapy for patients with life-threatening cardiac failure, but mortality remains high. In this retrospective study, we reviewed the medical records of adult patients who underwent VA-ECMO in an intensive care unit of a university hospital, between 2009 and 2013. VA-ECMO was performed in 89 patients, with a median duration of 116 h. The survival rate until hospital discharge was 27%. The pre-ECMO simplified acute physiology score (SAPS) II and diabetes mellitus were significant predictors of hospital mortality. The optimal prognostic SAPS II score was 81 overall, 80 in patients with diabetes, and 84 in those without diabetes. Our findings indicate that high pre-ECMO SAPS II score and diabetes are risk factors for mortality in patients who undergo VA-ECMO.


Practices of infectious control management during neutropenia: A survey from 149 French hospitals.
Neutropenic patients represent a growing and fragile population in our hospitals. Numerous treatments induce neutropenia in haematology wards and elsewhere. Although strict isolation is recommended during post-haematopoietic stem cell transplantation neutropenia, this may not be the current practice in other situations. In this study, our objective was to analyse what protective measures are applied in neutropenic patients in a French survey. A questionnaire was sent out to infection control teams of 400 public and private French hospitals to enquire about their local recommendations regarding infection prevention in neutropenic patients. Among the 166 (41%) responders, 134 (81%) managed neutropenic patients. All of the centres recommended protective isolation for neutropenic patients. However, only 46 (34%) had clearly defined patients warranting specific isolation measures in terms of the level of neutropenia. All of the centres recommended several barrier measures, but these were highly variable according to the type of air treatment in the wards (note that only 72% of haematology wards are equipped with air treatment). Gowns, gloves, masks, hats and shoe covers were respectively recommended in 128 (95%), 79 (59%), 132 (98%), 87 (65%), and 34 (25%) of the establishments. Surprisingly, the recommendations vary both among hospitals and within the same hospital among different clinical wards. In conclusion, protective measures for neutropenic patients are applied variably and urgently require a consensus to homogenize practices.


The axillopectoral muscle (of Langer): report of three cases.
The axillopectoral muscle, usually called Langer's axillary arch instead of Langer's arm arch, is a supernumerary muscle and is the principal anatomic variation of the axilla. Three cases of the muscle were observed originating from latissimus dorsi crossing over the axillary neurovascular bundle and inserting deep to the insertion of pectoralis major or into the coracoid process. Clinicians should be aware of its existence as it can give rise to different pathologies. It should be recognised and excised to expose the axillary artery and vein in patients with trauma and to perform axillary lymphadenectomy or axillary bypass. It should be considered in the differential diagnosis of axillary masses or in a history of intermittent axillary vein obstruction. If the muscle causes problems its excision should be curative.


Bacterial community associated with gingivitis and periodontitis in dogs.
Periodontal disease is a chronic condition characterized by bacterial adhesion, followed by biofilm formation, and subsequently by an inflammatory process that progresses to gingivitis and later to periodontitis. The variations in the oral microbiota have been associated with the progression of this disease. This study evaluated the alteration of the cultivable oral microbiota in dogs with different oral health status. Thirty dogs were selected and divided into three groups: healthy, gingivitis, and periodontitis. The collected oral samples were seeded, and colonies with distinct phenotypic characteristics were isolated and classified using sequencing of the 16S rRNA gene. The DNA sequences were aligned, and a phylogenetic tree was constructed. Simpson's diversity index was calculated, and a dissimilarity matrix based on the Jaccard similarity index was used to plot a principal coordinate analysis. A total of 119 bacteria with different colony morphologies were isolated and classified into 4 phyla, 29 genera, and 45 species based on phylogenetic analysis. The results indicated an increase in bacteria belonging to the Proteobacteria phylum and a less extended decrease in Actinobacteria, Firmicutes, and Bacteroidetes phyla in dogs with periodontal disease (gingivitis and periodontitis) compared to healthy dogs. Representatives of the genera Neisseria sp., Corynebacterium sp., Pasteurella sp., and Moraxella sp. increased through the worsening of the periodontal disease, while Staphylococcus sp. decreased. All groups exhibited moderate to high levels of biodiversity index, and the plotted PCoA show a clear separation in the oral microbiome of dogs with periodontitis compared to dogs with gingivitis and the healthy group.


Transport and killing mechanism of a novel camptothecin-deoxycholic acid derivate on hepatocellular carcinoma cells.
Abstract Camptothecin-20(s)-O-glycine ester-[N-(3'α, 12'α-dihydroxy-24'-carbonyl-5'β-cholan)] (A2), 10-(3'α,12'α-dihydroxy-5'β-cholan-24'-carboxyl)-(20 s)-camptothecin (C2), and 10-O-(3-O-(3'α, 12'α-dihydroxy-24'-carbonyl-5'β-cholan)-propyl)-(20S)-camptothecin (D2) are novel camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the anticancer activity of these compounds against hepatocellular carcinoma SMMC-7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells. A2 had a high killing ability on SMMC-7721 cells selectively, but C2 and D2 did not exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were performed in an effort to elucidate the transport mechanisms of A2 into SMMC-7721 cells. A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting polypeptide) and uptake of A2 was inhibited by rifampin (inhibitor of OATP1B3), which indicated that the transporter-mediated transport of A2 was mediated by OATP1B3. In addition, according to the western blot and apoptosis assays, we found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria apoptosis pathway.


Diethyl pyrocarbonate inactivation of human placental aldehyde reductase II.
Diethyl pyrocarbonate inactivated aldehyde reductase II (L-gulonate:NADP+ 6-oxidoreductase, EC 188.8.131.52) from human placenta. A concentration of 0.5-1.0 mM diethyl pyrocarbonate caused 40-65% loss of activity. The inactivation of the enzyme by diethyl pyrocarbonate was reversed by hydroxylamine and was accompanied by a large change in the absorbance of the protein at 242 nm, but not at 278 nm, indicating that only the histidine residues were modified. NADPH, but not glucuronate afforded significant protection to the enzyme from inactivation by diethyl pyrocarbonate. With 0.2-1.0 mM diethyl pyrocarbonate, 4-5 histidine residues were modified with a pseudo-first-order rate process. A double log plot of the fraction of the unmodified residues indicates that only one functional histidine residue is essential for the catalytic activity of aldehyde reductase II.


Interactions among heart rate, autonomic activity, and arterial pressure upon the multiple repetitive extrasystole threshold in the dog.
The effects of heart rate, autonomic stimulation, and arterial blood pressure upon the multiple repetitive extrasystole threshold (MRET) were studied after coronary occlusion in anesthetized dogs. The MRET was unaffected by changes in heart rate. Sympathetic stimulation alone reduced the MRET from 52.4 +/- 3.7 (mean +/- SEM) to 41.3 +/- 2.7 mA. Vagal stimulation alone was without effect. During simultaneous sympathetic and vagal stimulation the threshold was 48.7 +/- 3.0 mA. This supports the contention that vagal activity serves mainly to oppose the tendency for sympathetic activity to lower the MRET. Reduction of blood pressure significantly decreased the average MRET from 38.6 +/- 2.5 to 34.4 +/- 1.8 mA. The presence of a post junctional site for the observed sympathetic-vagal interaction was investigated using isoproterenol infusion and vagal stimulation. Infusion of isoproterenol lowered the MRET. Vagal stimulation in this situation raised the MRET; the effect varied directly with the rate of isoproterenol infusion. This suggests that part of the vagal effect is exerted postjunctionally; that is, directly upon the myocardial cell and not merely by inhibition of adrenergic transmitter release at sympathetic nerve endings.


The Impact of Family Presence in Surgical Settings.
After major surgery at a facility where her wife was prohibited from being in the surgical setting, a nurse practitioner encourages others to advocate for family presence and respectful care.


Tolerance and effect of sodium thiosulfate in calcific tendinitis of the rotator cuff.
Calcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. Ultrasound-guided percutaneous lavage of calcific tendinopathy is performed when conservative treatments have failed. Sodium thiosulfate (STS) has recently been used with success in the treatment of tumoral calcinosis. The goal of this phase II study was to assess the tolerance and the feasibility of STS lavage of calcific tendinopathy. We included patient with type hard calcifications. Patients were treated with puncture and lavage followed by injection of STS in the calcification. VAS pain at rest and during activities, ultrasound, and X-ray were evaluated at 1 week and 1 and 3 months. Seventeen patients were included. Baseline VAS at rest and during daily activities was a mean 40.2 ± 25.9 and 65.5 ± 21.6 respectively. All patients underwent the entire procedure with no adverse event. Calcium backflow could be obtained in 15 patients (88.2%). Five patients (30%) had more than 50% decrease of their calcific deposit size at 1 month and 8 (47%) patients at 3 months. VAS pain during activities and at rest decreased significantly at 3 months (p = 0.0004; p = 0.001). Efficacy would be demonstrated if 60% of the patients had more than 50% decrease size of their calcification CONCLUSION: Overall, STS was well tolerated with no side effect occurring during the procedure and the follow-up. However, no significant effect on calcium disappearance could be demonstrated compared with what is expected without STS. New studies using larger volume and repeated injections of STS are now needed. NCT02538939Key Points• Lavage of calcific tendinopathy of the rotator cuff with sodium thiosulfate is feasible• No adverse events have been observed after or in the 3 months after the procedure• We could not demonstrate that sodium thiosulfate increases the chance of calcium disappearance• New studies using larger volume and repeated injections of STS are needed to further explore the interest of sodium thiosulfate in the treatment of calcific tendinopathy.


Weight bearing or non-weight bearing after surgically fixed ankle fractures, the WOW! Study: study protocol for a randomized controlled trial.
The optimal post-operative care regimen after surgically fixed Lauge Hansen supination exorotation injuries remains to be established. This study compares whether unprotected weight bearing as tolerated is superior to protected weight bearing and unprotected non-weight bearing in terms of functional outcome and safety. The WOW! Study is a prospective multicenter clinical trial. Patients between 18 and 65 years of age with a Lauge Hansen supination exorotation type 2, 3 or 4 ankle fractures requiring surgical treatment are eligible for inclusion. An expert panel validates the classification and inclusion eligibility. After surgery, patients are randomized to either the 1) unprotected non-weight-bearing, 2) protected weight-bearing, or 3) unprotected weight-bearing group. The primary outcome measure is ankle-specific disability measured by the Olerud-Molander ankle score. Secondary outcomes are 1) quality of life (e.g., return to work and resumption of sport), 2) complications, 3) range of motion, 4) calf wasting, and 5) maximum pressure load after 3 months and 1 year. This trial is designed to compare the effectiveness and safety of unprotected weight bearing with two commonly used post-operative treatment regimens after internal fixation of specified, intrinsically stable but displaced ankle fractures. An expert panel has been established to evaluate every potential subject, which ensures that every patient is strictly screened according to the inclusion and exclusion criteria and that there is a clear indication for surgical fixation. The WOW! Study is registered in the Dutch Trial Register ( NTR3727 ). Date of registration: 28-11-2012.


Current practice in the measurement and interpretation of intervention adherence in randomised controlled trials: A systematic review.
Ideally all participants in a randomised controlled trial (RCT) should fully receive their allocated intervention; however, this rarely occurs in practice. Intervention adherence affects Type II error so influences the interpretation of trial results and subsequent implementation. We aimed to describe current practice in the definition, measurement, and reporting of intervention adherence in non-pharmacological RCTs, and how this data is incorporated into a trial's interpretation and conclusions. We conducted a systematic review of phase III RCTs published between January 2018 and June 2020 in the National Institute for Health Research Journals Library for the Health Technology Assessment, Programme Grants for Applied Research, and Public Health Research funding streams. Of 237 reports published, 76 met the eligibility criteria and were included. Most RCTs (n = 68, 89.5%) reported adherence, though use of terminology varied widely; nearly three quarters of these (n = 49, 72.1%) conducted a sensitivity analysis. Adherence measures varied between intervention types: behavioural change (n = 10, 43.5%), psychological therapy (n = 5, 83.3%) and physiotherapy/rehabilitation (n = 8, 66.7%) interventions predominately measured adherence based on session attendance. Whereas medical device and surgical interventions (n = 17, 73.9%) primarily record the number of participants receiving the allocated intervention, a third (n = 33, 67.3%) of studies reported a difference in findings between primary and sensitivity analyses. Although most trials report elements of adherence, terminology was inconsistent, and there was no systematic approach to its measurement, analyses, interpretation, or reporting. Given the importance of adherence within clinical trials, there is a pressing need for a standardised approach or framework.


Target gene delivery from targeting ligand conjugated chitosan-PEI copolymer for cancer therapy.
In this study, we designed a novel carrier which was having low cytotoxicity, site-specific target function, and high transfection efficiency using low molecular weight water soluble O-carboxymethyl chitosan (OCMCh), branched low molecular weight poly(ethyleneimine) (bPEI), and targeting ligand (epitope type, HER-2/neu). OCMCh/bPEI/targeting ligand, HPOCP copolymer, and targeting ligand-modified polyamphoteric polymer, and were prepared by chemical reaction and characterized by (1)H NMR and FT-IR. The binding affinity, protecting efficiency, and releasing ability of gene/HPOCP polyplex were confirmed by gel retardation assay. The pDNA(pEGFP)/HPOCP polyplexes showed high gene transfection efficiency in HCT 119 cell. In addition, siRNA/HPOCP polyplexes formed spherical shape and have particle sizes from 100 to 300nm. The siRNA/HPOCP polyplexes have lower cytotoxicity than PEI in the all of siRNA concentrations ranging from 0 to 2μg/μL in HEK 293 cells. The cell viability of siRNA/HPOCP polyplexes was performed in SK-Br3 cells with VEGF siRNA or BCL2 siRNA. In addition, confocal laser-scanning microscopy and flow cytometry assay were performed for cellular localization and cellular uptake efficiency of siRNA/HPOCP polyplexes. The results of the present study demonstrate that HPOCP copolymer is a good candidate as gene delivery carriers for gene delivery system or gene therapy.


A chemiluminescence method to detect malondialdehyde in plasma and urine.
A highly sensitive and convenient method to detect malondialdehyde (MDA) in specimens of plasma and urine was developed using high-performance liquid chromatography combining chemiluminescence detection. MDA was separated through a reverse-phase C18 column at a flow rate of 0.8 ml min(-1). It was then detected by a chemiluminescence detector. Variables that affected chemiluminescence reaction, including mobile phase, flow rate, chemiluminescence reagent, parameters of the photomultiplier tube, and temperature, were studied. This assay was linear from 0.50 to 50 μmol L(-1), with limits of detection and quantification of 0.08 and 0.30 μmol L(-1), respectively. The recoveries were in the range of 92.2 to 98.5%, and the intra- and interday reproducibilities were obtained with relative standard deviations of less than 4% and less than 6%, respectively. MDA in plasma and urine was stable for 12 h at 4°C. MDA levels were 2.74, 3.19, and 3.20 μmol L(-1) for plasma and 1.25, 2.04, and 1.58 μmol L(-1) for urine, respectively. The proposed method is simple, rapid, and sensitive with low cost. Taken together, this method can be suitable for detecting MDA in tissue and feed specimens.


Comparison of capsaicin and substance P induced cyclic AMP accumulation in spinal cord tissue slices.
Capsaicin (CAP) caused a time, concentration and Ca++ dependent increase in cyclic AMP accumulation in tissue slices from rat and guinea pig spinal cord. The CAP-induced increase occurred uniquely in slices from dorsal cord of both rat and guinea pig and the increase was significantly greater in dorsal cord slices from guinea pig vs rat spinal cord. CAP mediated release of substance P does not appear to mediate the CAP-induced increase in cyclic AMP accumulation since the increase in cyclic AMP is significantly less with substance P and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P does not antagonize the CAP-induced increase. The CAP-induced increase in cyclic AMP accumulation appears to be a direct effect. Structural requirements for this effect are both the substituted aromatic and alkyl side chain portion of the CAP molecule. The present results suggest that CAP has the ability to interact with sites in dorsal spinal cord which are linked to the synthesis of cyclic AMP, which could modulate spinal processing of nociceptive information.


Adenosine-mediated synaptic inhibition: partial blockade by barium does not prevent anti-epileptiform activity.
Adenosine-induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 microM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine-induced inhibition of the PSPs was still evident, although the magnitude of the effect was significantly reduced. Adenosine also reduced Ba(2+)-induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium-sensitive increase in gK and a presynaptic effect independent of this adenosine-evoked outward potassium conductance.


Difference in microbes contaminating pancreatic necrosis in biliary and alcoholic pancreatitis.
There are differences in the microbiology of infected pancreatic necrosis in alcoholic and biliary pancreatitis. One possible explanation may be different routes of contamination. Infection is a severe complication in acute pancreatitis. Bacteria are found in 40-70% of all patients suffering from necrotizing pancreatitis. We investigated whether there were any differences in microbes isolated from pancreatic necrosis in biliary and alcoholic pancreatitis. Microbiological tests were conducted on necrosis taken at the operation for pancreatitis with the etiology of (group A) alcoholic pancreatitis (n = 47) and (group B) biliary pancreatitis (n = 23). Patients with simultaneous cholecystitis were excluded. The time from the first symptoms to the operation or the extent of necrosis did not differ between the groups. Microbes were isolated more often in the cultures from group B than group A (17/23 = 74% vs 15/47 = 32%, p = 0.001). The most common were Gram-positive bacteria in group A and Gram-negative bacteria in group B. From the first week, from the onset of symptoms to the operation. Gram-negative bacteria were isolated significantly more often in the cultures from group B patients than from group A patients (8/10 = 80% vs 1/5 = 20%, p = 0.04). In multivariate analysis, we found that biliary pancreatitis was an independent risk factor (adds ratio 5.5, 95% confidence interval [CI] 0.59-52.10) of contamination of necrosis with Gram-negative bacteria.


When are metal ion-dependent hydroxyl and alkoxyl radical adducts of 5,5-dimethyl-1-pyrroline N-oxide artifacts?
The formation of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/.OH adduct of the spin trap DMPO has been reported to occur through nucleophilic addition of water in the presence of aqueous ferric chloride (K. Makino, T. Hagiwara, A. Hagi, M. Nishi, and A. Murakami, 1990, Biochem. Biophys. Res. Commun. 172, 1073-1080). Due to the serious implications of these findings with respect to many spin trapping studies, the suitability of DMPO as a hydroxyl radical spin trap was studied in typical Fenton systems. Using 17O-enriched water, we show conclusively that nucleophilic addition of water occurs at the nitrone carbon (or C-2 position) of DMPO in the presence of either Fe or Cu ions. Furthermore, our results demonstrate that this nucleophilic reaction is a major pathway to the DMPO/.OH adduct, even during the reaction of Fe(II) or Cu(I) with hydrogen peroxide. Primary alkoxyl adducts of DMPO also form in aqueous solution through nucleophilic addition in the presence of both Fe(III) and Cu(II). Attempts to obtain secondary and tertiary alkoxyl adducts by this mechanism were unsuccessful, possibly due to steric effects. When the reaction is carried out in various buffers, however, or in the presence of metal ion chelators, nucleophilic addition to DMPO from Fe(III) is effectively suppressed. Chelators also suppress the reaction with Cu(II). Hence, under most common experimental conditions in biochemical free radical research, nucleophilic addition to DMPO should not be of major concern.


Normal gestation after 5 years on home parenteral nutrition.
A case of normal gestation after 5 years on HPN is reported. The patient had her entire jejunum and ileum and right colon resected because of gangrene and has subsisted normally on HPN ever since. From the second trimester on, her HPN formula was supplemented to meet the requirement for growth and development of the foetus. Anaemia, hypoalbuminaemia, low plasma zinc levels and jaundice became manifest in the final trimester. These responded readily to readjustment of her HPN formula. A normal baby weighing 2020 g was delivered by Caesarean section at 36 weeks. Long-term HPN, final trimester abnormalities and HPN formula adjustments are discussed.


Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones.
1. Rats were pretreated with 50 mg/kg s.c. capsaicin or solvent on the second day of life; 5 months later 3H-diprenorphine binding to homogenates of the whole spinal cord or of the upper dorsal horn of the spinal cord was investigated. 2. Capsaicin pretreatment resulted in a 17% decrease of opiate binding sites in the whole spinal cord and a 37% decrease in the upper dorsal horn with no change in their affinity. 3. Since neonatal capsaicin pretreatment causes degeneration of chemosensitive primary sensory neurones it is concluded that some opiate receptors are located presynaptically on the central terminals of these neurones.


Spatial control of cell transfection using soluble or solid-phase redox agents and a redox-active ferrocenyl lipid.
We report principles for active, user-defined control over the locations and timing with which DNA is expressed in cells. Our approach exploits unique properties of a ferrocenyl cationic lipid that is inactive when oxidized, but active when chemically reduced. We show that methods that exert spatial control over the administration of reducing agents can lead to local activation of lipoplexes and spatial control over gene expression. The versatility of this approach is demonstrated using both soluble and solid-phase reducing agents. These methods provide control over cell transfection, including methods for remote activation and the patterning of expression using solid-phase redox agents, that are difficult to achieve using conventional lipoplexes.


Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved in inhibition of both Akt1 translocation and pAkt1 expression.
Oleanolic acid (OA) derivatives exhibit numerous pleiotropic effects in many cancers. The present study aimed to investigate the molecular mechanisms of 5'-amino-oleana-2,12-dieno[3,2-d]pyrimidin-28-oic acid (compound 4) and oleana-2,12-dieno[2,3-d]isoxazol-28-oic acid (compound 5) inducing apoptosis in human leukemia K562 cell. We investigated the effects of the compounds on K562 cell growth, apoptosis and cell cycle. The compounds showed strong inhibitory effects on K562 cell viability in a dose-dependent manner determined by the 3-(4,5-dimethylthiazoyl)-2,5-diphenyltetrazolium bromide assay and significantly increased chromatin condensation and apoptotic bodies in K562 cells. Flow cytometry assay suggested that the compounds induced inhibition of K562 cell proliferation associated with G1 phase arrest. In addition, the compounds inhibited Akt1 recruiting to membrane in CHO cells which express Akt1-EGFP constitutively and down-regulated the expression of pAkt1 in K562 cell. These results suggested that the compounds can efficiently inhibit proliferation and induce apoptosis perhaps involved in inactivation of Akt1. The OA derivatives may be potential chemotherapeutic agents for the treatment of human cancer.


High-pressure Sterilization of Ice Nucleation-active Xanthomonas campestris and Its Application to Egg Processing.
Xanthomonas campestris INXC-1 is able to freeze water at a subzero temperature higher than -5°C. High-pressure treatment at 300 MPa and 5°C for 5 min killed the cells without affecting their ice-nucleation activity. Egg white containing the pressurized cells began to freeze with a slight degree of supercooling. Ice crystals with a dendritic structure were formed when the egg white froze in the presence of the killed bacterial cells. The frozen egg white thawed more quickly than egg white frozen without the cells.


Optimized Proteomics Workflow for the Detection of Small Proteins.
Small open reading frame encoded proteins (SEPs) gained increasing interest during the last few years because of their broad range of important functions in both prokaryotes and eukaryotes. In bacteria, signaling, virulence, and regulation of enzyme activities have been associated with SEPs. Nonetheless, the number of SEPs detected in large-scale proteome studies is often low as classical methods are biased toward the identification of larger proteins. Here, we present a workflow that allows enhanced identification of small proteins compared to traditional protocols. For this aim, the steps of small protein enrichment, proteolytic digest, and database search were reviewed and adjusted to the special requirement of SEPs. Enrichment by the use of small-pore-sized solid-phase material increased the number of identified SEPs by a factor of 2, and utilization of alternative proteases to trypsin reduced the spectral counts for larger proteins. The application of the optimized protocol allowed the detection of 210 already annotated proteins up to 100 amino acids (aa) length, including 16 proteins below 51 aa in the Gram-positive model organism Bacillus subtilis. Moreover, 12% of all identified proteins were up to 100 aa, which is a significantly larger fraction than that reported in studies involving traditional proteomics workflows. Finally, the application of an integrated proteogenomics search database and extensive subsequent validation resulted in the confident identification of three novel, not yet annotated, SEPs, which are 21, 26, and 42 aa long.


Quantitative assessment of intra- and inter-modality deformable image registration of the heart, left ventricle, and thoracic aorta on longitudinal 4D-CT and MR images.
Magnetic resonance imaging (MRI)-based investigations into radiotherapy (RT)-induced cardiotoxicity require reliable registrations of magnetic resonance (MR) imaging to planning computed tomography (CT) for correlation to regional dose. In this study, the accuracy of intra- and inter-modality deformable image registration (DIR) of longitudinal four-dimensional CT (4D-CT) and MR images were evaluated for heart, left ventricle (LV), and thoracic aorta (TA). Non-cardiac-gated 4D-CT and T1 volumetric interpolated breath-hold examination (T1-VIBE) MRI datasets from five lung cancer patients were obtained at two breathing phases (inspiration/expiration) and two time points (before treatment and 5 weeks after initiating RT). Heart, LV, and TA were manually contoured. Each organ underwent three intramodal DIRs ((A) CT modality over time, (B) MR modality over time, and (C) MR contrast effect at the same time) and two intermodal DIRs ((D) CT/MR multimodality at same time and (E) CT/MR multimodality over time). Hausdorff distance (HD), mean distance to agreement (MDA), and Dice were evaluated and assessed for compliance with American Association of Physicists in Medicine (AAPM) Task Group (TG)-132 recommendations. Mean values of HD, MDA, and Dice under all registration scenarios for each region of interest ranged between 8.7 and 16.8 mm, 1.0 and 2.6 mm, and 0.85 and 0.95, respectively, and were within the TG-132 recommended range (MDA < 3 mm, Dice > 0.8). Intramodal DIR showed slightly better results compared to intermodal DIR. Heart and TA demonstrated higher registration accuracy compared to LV for all scenarios except for HD and Dice values in Group A. Significant differences for each metric and tissue of interest were noted between Groups B and D and between Groups B and E. MDA and Dice significantly differed between LV and heart in all registrations except for MDA in Group E. DIR of the heart, LV, and TA between non-cardiac-gated longitudinal 4D-CT and MRI across two modalities, breathing phases, and pre/post-contrast is acceptably accurate per AAPM TG-132 guidelines. This study paves the way for future evaluation of RT-induced cardiotoxicity and its related factors using multimodality DIR.


Stent grafting for aneurysmal degeneration of chronic descending thoracic aortic dissections.
The objective of this study was to examine the results of thoracic endovascular aneurysm repair (TEVAR) for chronic descending thoracic aortic (DTA) dissections with aneurysmal degeneration. Over 70 months at a single institution, 27 patients underwent TEVAR for aneurysms related to chronic (>6 weeks) DTA dissections. Mean patient age was 67.5 ± 9.6 years; 18 were men. Primary indications for repair were aneurysm size (n = 20), rapid aneurysmal growth (n = 5), saccular aneurysm (n = 1), and rupture (n = 1). Preoperative false lumen status was patent in 18 patients, partially thrombosed in 8 patients, and unknown in the patient whose aneurysm ruptured. The proximal entry tear was covered in all 27 patients. Fourteen patients required coverage of the left subclavian artery, of which 9 patients underwent prophylactic revascularization. On completion angiogram, no patient had antegrade perfusion of the aneurysmal false lumen. There were three procedural complications: 2 patients sustained paraparesis (one resolved and one improved), and 1 patient had an access injury requiring stent graft placement. Thirty-day mortality was 3.7% (1 of 27); the one death was in the patient whose aneurysm ruptured. Of the 26 surviving patients, 23 (88.5%) had thrombosis of the aneurysmal false lumen. Twenty-two patients (84.6%) had stability or decrease in maximal aneurysm diameter on last radiographic follow-up at 18 ± 20 months. Three-year Kaplan-Meier survival was 90.3% ± 6.5% in the 26 patients who survived to hospital discharge, with a mean follow-up of 27.3 ± 22.1 months. In patients with preoperatively partially thrombosed false lumens (n = 8), 3-year survival was 100%. TEVAR for aneurysms due to chronic dissections of the DTA can be performed safely and effectively at midterm follow-up according to this single-institution study. Stent graft therapy may be of particular benefit in patients presenting with partially thrombosed false lumens.


Metabolic engineering of Escherichia coli for efficient degradation of 4-fluorophenol.
As a kind of refractory organic pollutant, 4-fluorophenol (4-FP) can be degraded by only a few microorganisms with low efficiency because of the great electron-withdrawing ability of fluorine atoms. So it is necessary to artificially construct engineered strain to improve the degradation efficiency and meet the requirements of pollutant degradation. In this study, four genes (fpdA2, fpdB, fpdC, and fpdD) for 4-FP degradation from Arthrobacter sp. strain IF1 were optimized and synthesized and then reconstructed into Escherichia coli by a multi-monocistronic vector to obtain recombinant BL-fpd that could degrade 4-FP efficiently. Under optimized induction conditions (inducing the strain by 2 g/L L-arabinose and 1 mM IPTG at 37 ℃), BL-fpd could completely degrade 2 mM 4-FP, 4-chlorophenol, 4-bromophenol, and 4-nitrophenol into β-ketoadipate, which could be further metabolized by the bacteria. FpdA2 showed the highest activity towards 4-bromophenol. The strain could completely degrade 1 mM 4-FP in industrial wastewater within 3 h. This study provided a promising strain for the degradation of 4-FP and some other 4-substituted phenols. The construction technologies of multi-monocistronic expression vector may also be used to construct other organic pollutants degrading bacteria.


Development and Suggestion of a Cardiac CTA Scoring System for the Prediction of Revascularization Success in Chronic Total Occlusions (CTO) of the Coronary Arteries.
Analyzing occluded segments with computed tomography angiography (CTA) prior to percutaneous coronary intervention (PCI) increased revascularization success in chronic total occlusions (CTO). The aim of our study was to develop a scoring system for the prediction of PCI success in CTO. 41 consecutive CTO patients (30 male; 63.1 years +/- 8.3 standard deviation) underwent CTA prior to PCI. All CTOs were categorized by two radiologists in consensus regarding the presence of special features and without knowledge of PCI outcome. All outcome criteria were evaluated. Afterwards one point was assigned for each unequally distributed outcome criteria per CTO and all points were added up to a single score. Severe calcifications (failure group 68.8 % vs. success group 28.0 %; p < 0.02) and intraluminal calcifications (68.8 %; 40.0 %), tortuosity (25.0 %; 0 %; p < 0.02), linear intrathrombus enhancement (37.5 %; 60.0 %) and distal vessel disease (68.8 %; 44.0 %) were unequally distributed. By adopting a threshold of 4 points or higher (maximum 5 points), the results were: sensitivity 31.3 %, specificity 100 %, negative predictive value (NPV) 69.4 % and positive predictive value (PPV) 100 %. The PCI complication rate was 9.8 % and the mean contrast media amount was 234.4 ml. With the suggested scoring system, based on five CTA criteria, PCI failure could be predicted with high PPV and specificity in our group of patients, but the NPV and sensitivity are low. However, 5 unsuccessful PCIs (13.2 %) could have been avoided and none would have been wrongly omitted. Regarding the complication rate during PCI and the high amounts of contrast media needed, a prediction system appears to be desirable and should be the object of large-scale trials. Single predictors of revascularization success in CTO have been identified. Success rates are improved by analyzing CTA data sets prior to revascularization approaches. Prediction of revascularization success via a scoring system based on five CTA criteria seems promising. Patient selection for the right treatment options might be improved in the future due to application of the scoring system. Also risks, complications, contrast media amounts and radiation doses might be reduced.


Clinicopathologic study and outcome analysis of thyroid lymphomas: experience from a tertiary cancer center.
The aim of this study was to review clinicopathologic presentations of patients diagnosed with thyroid lymphomas at a tertiary cancer center. Thyroid lymphomas represent less than 2% of all lymphomas. The lymphoma clinic database was retrospectively reviewed to collect information on patients diagnosed with thyroid lymphomas. Tissue microarrays were constructed in 37 patients for evaluation of germinal center (CD10/bcl-6) and activated B-cell immunophenotype markers (FoxP1, Mum1). During 2000 to 2010, 64 of 5668 patients registered at our lymphoma clinic were diagnosed with thyroid lymphoma (1.7%). Complete response (CR) to treatment was seen in 80.7%. The germinal center immunophenotype and activated B-cell immune phenotype did not influence the prognosis. FoxP1, however, was associated with poor treatment response and decreased survival. Advanced International Prognostic Index (IPI) score and combined-modality treatment emerged as significant prognostic factors for treatment response and overall survival. Immunophenotype expression of FoxP1 carries a poor prognosis in diffuse large B-cell lymphoma as elsewhere.


A prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy.
The results of a prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy conducted over a 38-month period are presented. One-hundred twenty patients were randomized following variceal bleeding, 63 to esophageal variceal sclerotherapy and 57 to control. Mean follow-up was similar in both groups (esophageal variceal sclerotherapy, 12.5 +/- 8.8 months; control, 14.9 +/- 6.6 months). Twenty-one percent of the patients in each group were lost to follow-up. Esophageal variceal sclerotherapy decreased rebleeding as evidenced by a decrease in the mean bleeding risk factor, transfusion requirement and by an increase in bleeding free interval; differences between the treated and control groups in these parameters were especially significant after variceal obliteration. A high incidence of asymptomatic ulceration and low frequency of strictures were notable effects of esophageal variceal sclerotherapy. Cumulative life table analysis revealed no differences in survival between esophageal variceal sclerotherapy and control groups. However, when patients who received portal-systemic shunt surgery (esophageal variceal sclerotherapy, 6%; control, 28%) were removed from the analysis at the time the shunt surgery was performed (defining the shunt as an endpoint, a significant difference in survival (p less than 0.05, F ratios) in favor of esophageal variceal sclerotherapy was observed.


Gastroinvasive Helicobacter infection in an Ocelot (Leopardus pardalis).
Highly invasive Helicobacter-like organisms were found in a 19-year-old female ocelot (Leopardus pardalis) with multiple ulcers in the fundic region of the stomach. The bacteria, resembling Helicobacter heilmannii, were located largely within canaliculi or in the cytosol of parietal cells. Except in the ulcerative lesions, parietal cells were hyperplastic, while chief cells and neck mucous cells were reduced in number. The term "gastroinvasive Helicobacter-like organism" was applied. It seems probable that this organism differs from other Helicobacter organisms in pathogenicity, and possible that its behaviour in vitro would help it to evade antibacterial treatment.


In-situ generation of fluorescent silica nano-aggregates of silatranyl appended furfural Schiff base and its application to the spectrofluorimetric analysis of phenolic brominated flame retardants in aqueous medium.
A silatranyl appended furfural Schiff base (Silt-FUR) has been synthesized and characterized by spectroscopic techniques, elemental analysis and mass spectrometry. The dissolution of Silt-FUR in methanol-water (90:10 v/v) results in the formation of fluorescent nano-aggregates due to the hydrolysis of the silatranyl ring. The formation of nano-aggregates has been confirmed by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. The nano-aggregates exhibit quenching of fluorescence in the presence of phenolic brominated flame retardants such as 3,3',5,5'-tetrabromobisphenol A, 2,4-dibromophenol, 2,4,6-tribromophenol, and pentabromophenol. Density-Functional Theory and NMR titration suggest that acid-base pair formation between azomethinic functionality and flame retardants is the main cause of quenching of fluorescent signal as it causes photoinduced electron transfer. Due to the excellent spectrofluorimetric response of Silt-FUR nano-aggregates to detect brominated phenols, a spectrofluorimetric method has been standardized for the quantification of brominated flame retardants. The detection limit for pentabromophenol obtained is 0.432 µM under optimal experimental conditions, and the linear range of the determination is 0.0495-1.35 µM. Thus, the in-situ generation of nano-aggregates offers a user-friendly method for the detection, quantification and extraction of the brominated phenols with exceptionally high sensitivity and selectivity for pentabromophenol.


A realist evaluation approach to explaining the role of context in the impact of a complex eHealth intervention for improving prevention of cardiovascular disease.
Reduction of cardiovascular disease (CVD) is a worldwide health priority and innovative uses of technology-based interventions may assist patients with improving prevention behaviours. Targeting these interventions to recipients most likely to benefit requires understanding how contexts of use influence responsiveness to the intervention, and how this interaction favours or discourages health behaviour. Using a realist evaluation approach, the aim of this study was to examine the contextual factors influencing behaviour change within a multi-feature eHealth intervention with personalised data integration from the primary care electronic health record (EHR). Realist evaluation of qualitative data from the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) randomised trial (N = 934). Thirty-six participants from the intervention group (N = 486) who had completed 12 months of study follow-up were interviewed. Coding of transcripts was structured around configurations of contexts, mechanisms, and outcomes of intervention use. Contextual narratives were derived from thematic analysis of the interviews. Mechanisms favouring positive health behaviour occurred when participants responded to four interactive features of the intervention. Facilitating mechanisms included greater cognitive engagement whereby participants perceived value and benefit, and felt motivated, confident and incentivised. Participants moved from being unconcerned (or unaware) to more task-oriented engagement with personal CVD risk profile and prevention. Increased personalisation occurred when modifiable CVD risk factors became relatable to lifestyle behaviour; and experiences of feeling greater agency/self-efficacy emerged. Use and non-use of the intervention were influenced by four overarching narratives within the individual's micro-level and meso-level environments: illness experiences; receptiveness to risk and prevention information; history of the doctor-patient relationship; and relationship with technology. Intervention-context interactions are central to understanding how change mechanisms activate within complex interventions to exert their impact on recipients. Intervention use and non-use were context-dependent, underscoring the need for further research to target eHealth innovations to those most likely to benefit.


Rhinocerebral mucormycosis due to Rhizopus oryzae in a diabetic patient: a case report.
Mucormycosis is an opportunistic fulminant fungal infection, which affects nose and paranasal sinuses by direct invasion or through the blood vessels mainly in diabetic and immunocompromised patients. In the present study, a rhino-orbito-cerebral mucormycosis in a 24-year-old female with diabetes mellitus as underlying disease was reported. Computed tomography (CT scan) demonstrated an increase in the soft tissue densities in the left nasal cavity, maxillary and ethmoid sinuses and destruction of the antral wall with soft tissue densities in the pterygopalatine fossa and retromaxillary fissure. In histopathology, wide ribbon-shape non-septate hyphae were seen in tissue sections stained with hematoxylin-eosin (H&E). The etiologic fungus isolated from tissue biopsy on mycological media was identified by the amplification and sequencing of the 5.8S RNA gene and of the adjacent internal transcriber spacer domains, ITS1/ITS4, as Rhizopous oryzae. Recognition of the unique patterns of this high mortality rhinocerebral fungal infection in patients with diabetes is a key to early diagnosis and successful treatment.


Erratum: The role and therapeutic value of syndecan-1 in cancer metastasis and drug resistance.
[This corrects the article DOI: 10.3389/fcell.2021.784983.].


Rescue of dopamine transporter function in hypoinsulinemic rats by a D2 receptor-ERK-dependent mechanism.
The dopamine (DA) transporter (DAT) is a major target for abused drugs and a key regulator of extracellular DA. A rapidly growing literature implicates insulin as an important regulator of DAT function. We showed previously that amphetamine (AMPH)-evoked DA release is markedly impaired in rats depleted of insulin with the diabetogenic agent streptozotocin (STZ). Similarly, functional magnetic resonance imaging experiments revealed that the blood oxygenation level-dependent signal following acute AMPH administration in STZ-treated rats is reduced. Here, we report that these deficits are restored by repeated, systemic administration of AMPH (1.78 mg/kg, every other day for 8 d). AMPH stimulates DA D(2) receptors indirectly by increasing extracellular DA. Supporting a role for D(2) receptors in mediating this "rescue," the effect was completely blocked by pre-treatment of STZ-treated rats with the D(2) receptor antagonist raclopride before systemic AMPH. D(2) receptors regulate DAT cell surface expression through ERK1/2 signaling. In ex vivo striatal preparations, repeated AMPH injections increased immunoreactivity of phosphorylated ERK1/2 (p-ERK1/2) in STZ-treated but not control rats. These data suggest that repeated exposure to AMPH can rescue, by activating D(2) receptors and p-ERK signaling, deficits in DAT function that result from hypoinsulinemia. Our data confirm the idea that disorders influencing insulin levels and/or signaling, such as diabetes and anorexia, can degrade DAT function and that insulin-independent pathways are present that may be exploited as potential therapeutic targets to restore normal DAT function.


[Analytic study of juices obtained by pressure, by cold extraction and warm extraction (the DDS system) of marc from apples of the Golden Delicious variety].
The cold water extraction of apple press residues to increase the juice yield has found much interest in recent years. Such a process has been developed by a Swiss company, but the food legislation does not permit it yet. Juice yield is increased up to 91 p. 100 (w.). Therefore we investigated the chemical and sensorical properties of pressed juice, cold water extract of press residues and warm water extract (System DDS) of identical raw material. The water extract differs from the pressed juice mainly by an increased amount of non-sugar extract and changes of the pigment and polyphenole content. The cold water extract had more and the better aroma than the warm extract.


Effects of supplements on intake, rumen function and nutrient supply and growth in cattle eating alkali-treated oat straw.
1. Expt 1. Six 200 kg Hereford heifers fitted with rumen and abomasal cannulas were fed ad lib. on alkali-treated oat straw sprayed with urea and minerals, with no supplement (O), or 700 g rolled barley (B) or cottonseed meal (C)/d, in a 3 x 3 Latin square with two replicates. 2. Intakes of the basal diet were not significantly affected by the supplements. Intakes of digestible organic matter (OM) were 3135, 3325 and 3515 g/d on diets O, B and C respectively. Abomasal OM flow on diet C was 13 and 12% higher than on diets O and B respectively (P less than 0.05) which was associated with a decrease in the proportion of OM intake apparently digested in the rumen (P less than 0.05) and an increase in the proportion of abomasal OM digested in the lower gut (P less than 0.05). 3. Total nitrogen and bacterial N flows at the abomasum were significantly higher (P less than 0.01 and P less than 0.05 respectively) on diet C than on diets O and B. Efficiency of bacterial N synthesis on diet C was 19 and 28% higher than on diets O and B respectively (P less than 0.05). 4. Dry matter (DM) pool size in the rumen was greater on diet C than on diets O and B (P less than 0.05). 5. Expt 2. Thirty-three 210 kg Friesian heifers were allocated to the same treatments as in Expt 1. Intakes of the basal straw diet were not significantly affected by the supplements.(ABSTRACT TRUNCATED AT 250 WORDS)


Congenital dyserythropoiesis with intererythroblastic chromatin bridges and ultrastructurally-normal erythroblast heterochromatin: a new disorder.
Two non-anaemic subjects, a father and daughter, with a new form of congenital dyserythropoiesis are reported. The features of their disorder are: (1) an abnormal blood film with basophilic stippling of red cells and oval macrocytes, (2) various dysplastic changes in the erythroblasts, including internuclear chromatin bridges, (3) ultrastructurally-normal erythroblast heterochromatin, (4) normal serum thymidine kinase activity, and (5) a probable autosomal dominant inheritance. The last three features distinguish this disorder from CDA type I.


Preparation of nucleotide advanced glycation endproducts--imidazopurinone adducts formed by glycation of deoxyguanosine with glyoxal and methylglyoxal.
An analytical procedure was developed for nucleotide advanced glycation endproducts formed by the reaction of glyoxal and methylglyoxal with deoxyguanosine under physiological conditions. For this, the imidazopurinone derivatives, 3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one (dG-G) and 3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one (dG-MG), were prepared. Authentic standard and stable isotope-substituted standard adducts were prepared and an isotopic dilution analysis assay methodology was developed using liquid chromatography with tandem mass spectrometry and optimized DNA extraction and nuclease digestion procedures. Analysis of dG-G, dG-MG, and the oxidative marker 8-hydroxydeoxyguanosine in the DNA of cultured human cells and mononuclear leukocytes showed that nucleotide advanced glycation endproducts are major markers of DNA damage in human cells.


Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects.
To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.


[Clinical retrospective evaluation of the arthroscopic treatments of the triangular fibrocartilage complex of the wrist].
The aim of this study is the retrospective clinical evaluation of the arthroscopic treatments for triangular fibrocartilage complex tears. Between 2003 and 2010, 76 patients with a traumatic lesion (Palmer type 1) and 25 patients with a degenerative lesion (Palmer type 2) of the triangular fibrocartilage complex underwent wrist arthroscopy. Clinical evaluations were based on the Mayo Modified Wrist Score (MMWS), on a compared measurement of the grip force and on a measurement of the different ranges of motion. We also made a subjective evaluation of the benefit brought by arthroscopy and a retrospective evaluation of the pre and postoperative pain. Mean MMWS was 86.3 for traumatic lesions and 83 for degenerative lesions. Mean grip force was 84.8 (Palmer type 1) and 84.2 (Palmer type 2) compared to the controlateral side. Mean ranges of flexion-extension, prosupination and radioulnar motions were 135°, 164° and 56° respectively for traumatic lesions and 130°, 156° and 54° respectively for degenerative lesions. Ninety-four percent of the operated patients reported an improvement of the symptomatology with better results for type 1 (98.7%) compared to type 2 (80%). We noted a clear diminution of the postoperative pain compared to the preoperative's one with frequently some mild persistent pain however. Arthroscopic treatments of the triangular fibrocartilage complex seem to be effective with an improvement of the symptomatology.


The effects of an innovative pulping technique of synchronously pulping and gelatinizing treatment on raw materials properties, oenological parameters, fermentation process, and flavor characteristics of glutinous rice wine.
Liquid-state fermentation has been increasingly applied in the industrial glutinous rice wine (GRW) production. However, products brewed by this emerging technique possess some deficiencies in flavor quality. Therefore, this study firstly developed and optimized an innovative pulping technique by the synchronously pulping and gelatinizing treatment (Process I) to improve GRW flavor quality, and then revealed the influences of Process I on raw materials properties, oenological parameters, fermentation process, and flavor characteristics of GRW. Results show that Process I significantly (p < 0.05) enriched the soluble solid and crude protein content of glutinous rice milk by improving gelatinization degree and pulping efficiency, which consequently enhanced the microbial growth, glycolysis, and protein decomposition during the GRW fermentation process. GC-MS analysis shows that Process I sequentially significantly (p < 0.05) enhanced the esterification and Ehrlich or Harrison pathway during the fermentation process. This contributed to a higher content of key ester and alcohol compounds. The online version contains supplementary material available at 10.1007/s10068-022-01119-7.


Endogenous methionine enkephalin may play an anticonvulsant role in the seizure-susceptible El mouse.
After the intracisternal injection of three protease inhibitors which prevent the degradation of methionine enkephalin (amastatin, Des-Pro2-bradykinin, and phosphoramidon) and a mixture of these protease inhibitors, we investigated the effect on convulsive seizures in the seizure-susceptible El mouse. We also measured the cerebral methionine enkephalin content by high-performance liquid chromatography coupled with radioimmunoassay. Protease inhibitors significantly decreased both the incidence of seizures and the seizure score in El mice in a dose-dependent manner. This anticonvulsant effect was reversed by naloxone (2 mg/kg, sc). The cerebral methionine enkephalin content increased significantly after the administration of protease inhibitors in comparison with saline injection. These findings suggest that it was not protease inhibitors but instead increase of endogenous methionine enkephalin that reduced the incidence of seizures and the seizure score in El mice. Together with our previous data, the present findings support our hypothesis that a deficit in anticonvulsant endogenous methionine enkephalin is involved in the pathogenesis of seizures in the El mouse.


Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis.
Although it is well established that equine laminitis can be triggered by extreme hyperinsulinemia, the mechanism of insulin action is not known. High concentrations of insulin lead to separation of the weight-bearing apparatus from the hoof wall and are associated with an increased cycle of cell death and proliferation in the lamellae. Gene expression and immunohistochemistry studies have indicated that the lamellae are sparsely populated with insulin receptors, whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of insulin may be mediated by insulin binding to the IGF-1R. To investigate this possibility, cell membrane fragments containing IGF-1R were extracted from the livers of 6 horses and the lamellae of >50 horses euthanized for nonresearch purposes at an abattoir. Radioligand-binding studies using 125I-IGF-1 and 125I-insulin confirmed an abundance of high-affinity IGF-1R in the liver (KD 0.11 nM, Bmax 223 fmol/mg protein) and lamellae (KD 0.16 nM, Bmax 243 fmol/mg protein). However, the affinity of insulin for binding to the lamellar IGF-1R (Ki 934 nM) was >5,800 fold less than that of IGF-1, suggesting that insulin is unlikely to bind to equine IGF-1R at physiological concentrations. Although insulin receptors could be detected in the liver (KD 0.48 nM, Bmax 123 fmol/mg protein), they were barely detectable in lamellae (estimated Bmax 14 fmol/mg protein). There was no evidence to support the presence of insulin/IGF-1 hybrid receptors in either tissue. These findings suggest that insulin does not act directly through IGF-1 receptors and that an alternative theory is required to explain the mechanism of insulin action in laminitis.


Differential cognitive impairment in subjects with geriatric depression who will develop Alzheimer's disease and other dementias: a retrospective study.
The aim of this study was to retrospectively differentiate the cognitive profile of subjects with geriatric depression who will later be diagnosed with Alzheimer's disease (AD) from those who will be diagnosed with other dementias, and subjects who will remain with no dementia. Forty-four depressed patients admitted to a day hospital program for depression who participated in a historical cohort study were assessed after 7.5 years of follow-up. Fourteen of these subjects subsequently developed dementia: seven met the criteria for probable AD and seven met the criteria for dementias other than AD (Dementia-No-AD; D-NAD, such as dementia with Lewy bodies (DLB), vascular and mixed dementia). Thirty subjects remained without dementia (No Dementia, ND) at follow-up. The three groups were thus compared on their baseline cognitive performances on the six sections of the Mini-mental State Examination (MMSE) and on the five subscales of the Dementia Rating Scale (DRS). An analysis of variance (ANOVA) and post-hoc Student-Newman-Keuls analyses with an alpha of p < 0.05 revealed that the subjects who received a diagnosis of dementia at follow-up had previously had more impairment on tasks measuring attention and memory (DRS-MMSE) than those who did not develop dementia (AD = D-NAD < ND). Moreover, the future AD subjects could be differentiated on the basis of their difficulties on the MMSE-orientation subtest (AD < ND = D-NAD), whereas the future D-NAD subjects initially had more problems with executive functions (DRS) and MMSE-visuospatial abilities (D-NAD < AD = ND). The identification of early neuropsychological markers in elderly depressed patients highlights the need to evaluate this population broadly as soon as possible in the depression/dementia process in order to improve the prognosis.


Blood transfusion in liver transplantation.
Liver transplantation is a relatively new procedure in which unusually large quantities of blood are used. Blood use in 68 adult and 49 pediatric liver transplants was reviewed. The median (range) intraoperative red cell use for adults and children was 28.5 (3-251) and 11 (2-55), respectively. Blood use closely correlated with the patient's primary diagnosis. Adult patients with primary biliary cirrhosis and carcinoma used about one-half as much blood as those with a diagnosis of sclerosing cholangitis, hepatitis, or cirrhosis. Patients in the former diagnostic groups also had better survival rates. Total red cell use for the patient's entire hospitalization was about twice that used during surgery. Fresh-frozen plasma use paralleled red cell transfusions, but platelet use was modest. These data can serve as a baseline in helping other hospital transfusion services prepare for the advent of liver transplantation in their institutions.


ERP correlates of anticipatory attention: spatial and non-spatial specificity and relation to subsequent selective attention.
Brain-based models of visual attention hypothesize that attention-related benefits afforded to imperative stimuli occur via enhancement of neural activity associated with relevant spatial and non-spatial features. When relevant information is available in advance of a stimulus, anticipatory deployment processes are likely to facilitate allocation of attention to stimulus properties prior to its arrival. The current study recorded EEG from humans during a centrally-cued covert attention task. Cues indicated relevance of left or right visual field locations for an upcoming motion or orientation discrimination. During a 1 s delay between cue and S2, multiple attention-related events occurred at frontal, parietal and occipital electrode sites. Differences in anticipatory activity associated with the non-spatial task properties were found late in the delay, while spatially-specific modulation of activity occurred during both early and late periods and continued during S2 processing. The magnitude of anticipatory activity preceding the S2 at frontal scalp sites (and not occipital) was predictive of the magnitude of subsequent selective attention effects on the S2 event-related potentials observed at occipital electrodes. Results support the existence of multiple anticipatory attention-related processes, some with differing specificity for spatial and non-spatial task properties, and the hypothesis that levels of activity in anterior areas are important for effective control of subsequent S2 selective attention.


Creatine phosphate inhibition of adenylate deaminase is mainly due to pyrophosphate.
Inhibition of rat skeletal muscle adenylate deaminase by creatine phosphate reported previously is due to inorganic pyrophosphate present as a contaminant in commercial preparations of creatine phosphate. This conclusion is based on the following evidence: a compound that inhibits adenylate deaminase can be separated from commercially prepared creatine phosphate by ion exchange chromatography; the inhibition by "creatine phosphate" and by the separated inhibitory compound is relieved by treatment with inorganic pyrophosphatase; inhibition by inorganic pyrophosphate is similar to that produced by unpurified creatine phosphate; and pyrophosphate is present in commercially available creatine phosphate in amounts sufficient to account for the inhibition. Some commercial preparations of creatine phosphate contain much less pyrophosphate than others; these preparations are only weakly inhibitory. Inorganic triphosphate is a more powerful inhibitor of the enzyme than pyrophosphate; it may also be present as a contaminant in creatine phosphate.


Comparison of the effects of flavone acetic acid, fostriecin, homoharringtonine and tumour necrosis factor alpha on colon 38 tumours in mice.
Advanced subcutaneous Colon 38 tumours in mice were used for the assessment of activity of a number of anticancer drugs. Activity was measured by histological examination of tumours 24 h after a single dose of the drug and in some cases by tumour growth delay. Agents thought to exert their cytotoxic effect by damaging DNA, including Adriamycin, amsacrine and its analogue CI-921, cyclophosphamide, 5-fluorouracil and methotrexate produced no gross histological changes after 24 h, even though some delayed the growth of subcutaneous tumours. In contrast, flavone acetic acid, fostriecin and homoharringtonine caused extensive necrosis of tumours after 24 h, and each delayed the growth of advanced subcutaneous tumours by at least 10 days when administered as a single dose. The histological effects of flavone acetic acid and fostriecin were indistinguishable from those of recombinant human tumour necrosis factor alpha. It is proposed that histological assay of advanced tumours may provide a useful adjunct to existing methods in screening for antitumour agents with novel mechanisms of action.


[Perception of kidney donation in Senegal and potential donors].
The objective of this study was to explore the potential for kidney donation in the Senegalese population, as a prelude to a proposed kidney transplant from living donors. A survey of cross type, and descriptive analysis was conducted from June 15 to September 15, 2010 in Dakar (Senegal). A two-stage sampling was done. The data, collected on the basis of a questionnaire, were captured and analyzed with Epi Info software version 3.3.2 and R version 2.9.2. The study population comprised 400 people with 56.75% of men, a sex ratio of 1.3. The average age was 33.58±11 years. It consisted of people between 18 and 30 (48.5%), married (44.25%). The subjects surveyed were mostly Senegalese (91%), students and pupils (24%) and educated (86.75%). The questioned subjects heard of kidney failure (65%). They knew at least one person who died of renal failure or dialyzed respectively in 19% and 24% of cases. The respondents have heard of the graft (47.3%). They knew at least one grafted patient in 5%. The public has expressed a desire to donate a kidney to a relative or friend in treatment of chronic renal failure in 71.5% of cases. The subjects taught at secondary level, higher level and those informed of renal failure were more prone to kidney donation than others. This study shows a large pool of potential kidney donors, hence the need to conduct outreach activities to turn them into actual donors.


Lymphedema: patient and provider education: current status and future trends.
The majority of patients schedules for breast surgery or radiation therapy for breast carcinoma do not receive basic information about the risk of lymphedema or its treatment. A review of the literature documenting patient and provider education on the risk, prevention and treatment of lymphedema was undertaken. Formal education about lymphedema is not a part of the training of most medical and allied health professionals. Thus, patients do not receive information about the risk, prevention, or treatment of lymphedema. Educational strategies for patients and providers need to be developed and implemented.


[Vogt Koyanagi Harada syndrome. Report of a case with hearing loss, tinnitus, vertigo associated to uveitis].
Vogt-Koyanagi-Harada sindrome is an autoimmune sistemic disease characterized by granulomatous bilateral uveitis with involvement of the central nervous system which can compromise the VIII craneal pair function producing tinnitus and neurosensorial hypoacusia. We report a case diagnosed in a young woman who also suffered episodes of vertigo. We review the literature of that pathology.


Classification schemes of small-for-gestational age and type of intrauterine growth retardation and its implications to early neonatal mortality.
Classification of small-for-gestational age (SGA) and pattern of intrauterine growth retardation (IUGR) and their relationship to early neonatal mortality (first 3 days) were studied in a population of 9201 full-term infants in a maternal and child center in Mexico City. SGA infants were classified on the basis of two methods: one, using the tenth percentile of a birth weight (BW) by gestational age reference growth distribution, and the other, using a cut-off point of birth weight of 2900 g. Crown-heel length (CHL) and Rohrer's ponderal index (PI = BW/CHL3) were used to classify patterns of proportionate and disproportionate IUGR. Overall, infants classified as SGA and type of IUGR had an increased risk of death in comparison to full-term appropriate-weight infants. IUGR proportionate infants with short CHL had a significantly greater mortality than disproportionate IUGR infants with normal CHL. A slightly but not significantly greater mortality was observed for IUGR disproportionate versus proportionate using PI regardless of the method of SGA used. The combination of misclassification for SGA and for type of IUGR were examined relative to the availability of gestational age and the uses of data for clinical management versus research. It is concluded that hospitals may tolerate misclassification of SGA but should pay close attention in assessing the pattern of IUGR when evaluating the mortality of newborn term infants.


Suitability of DNN-based vessel segmentation for SIRT planning.
The segmentation of the hepatic arteries (HA) is essential for state-of-the-art pre-interventional planning of selective internal radiation therapy (SIRT), a treatment option for malignant tumors in the liver. In SIRT a catheter is placed through the aorta into the tumor-feeding hepatic arteries, injecting small beads filled with radiation emitting material for local radioembolization. In this study, we evaluate the suitability of a deep neural network (DNN) based vessel segmentation for SIRT planning. We applied our DNN-based HA segmentation on 36 contrast-enhanced computed tomography (CT) scans from the arterial contrast agent phase and rated its segmentation quality as well as the overall image quality. Additionally, we applied a traditional machine learning algorithm for HA segmentation as comparison to our deep learning (DL) approach. Moreover, we assessed by expert ratings whether the produced HA segmentations can be used for SIRT planning. The DL approach outperformed the traditional machine learning algorithm. The DL segmentation can be used for SIRT planning in [Formula: see text] of the cases, while the reference segmentations, which were manually created by experienced radiographers, are sufficient in [Formula: see text]. Seven DL cases cannot be used for SIRT planning while the corresponding reference segmentations are sufficient. However, there are two DL segmentations usable for SIRT, where the reference segmentations for the same cases were rated as insufficient. HA segmentation is a difficult and time-consuming task. DL-based methods have the potential to support and accelerate the pre-interventional planning of SIRT therapy.


Endovascular Treatment of Small Ruptured Intracranial Aneurysms (<5 mm) : Long-term Clinical and Angiographic Outcomes and Related Predictors.
To investigate the long-term clinical and angiographic outcomes and their related predictors in endovascular treatment (EVT) of small (<5 mm) ruptured intracranial aneurysms (SRA). The study retrospectively reviewed patients with SRAs who underwent EVT between September 2011 and December 2016 in two Chinese stroke centers. Medical charts and telephone call follow-up were used to identify the overall unfavorable clinical outcomes (OUCO, modified Rankin score ≤2) and any recanalization or retreatment. The independent predictors of OUCO and recanalization were studied using univariate and multivariate analyses. Multivariate Cox proportional hazards models were used to identify the predictors of retreatment. In this study 272 SRAs were included with a median follow-up period of 5.0 years (interquartile range 3.5-6.5 years) and 231 patients with over 1171 aneurysm-years were contacted. Among these, OUCO, recanalization, and retreatment occurred in 20 (7.4%), 24 (12.8%), and 11 (7.1%) patients, respectively. Aneurysms accompanied by parent vessel stenosis (AAPVS), high Hunt-Hess grade, high Fisher grade, and intraoperative thrombogenesis in the parent artery (ITPA) were the independent predictors of OUCO. A wide neck was found to be a predictor of recanalization. The 11 retreatments included 1 case of surgical clipping, 6 cases of coiling, and 4 cases of stent-assisted coiling. A wide neck and AAPVS were the related predictors. The present study demonstrated relatively favorable clinical and angiographic outcomes in EVT of SRAs in long-term follow-up of up to 5 years. THE AAPVS, as a morphological indicator of the parent artery for both OUCO and retreatment, needs further validation.


Delayed hypersensitivity. A critical evaluation of five recall antigens in a large reference population.
The reactivity to five recall antigens, candida, mumps, PPD, varidase and trichophyton and the corresponding diluents was tested in 840 healthy persons aged between 17 and 101 years. Candida antigen was tested in a lower (l) and a higher (h) dose. The size of reactions did not follow a Gaussian distribution and we therefore used the 10th and 5th percentiles instead of standard deviation to define the limits between positive, weak and negative reactions. The number of positive reactions to each of candida-h, mumps, PPD and varidase was between 80 and 95 per cent in patients less than 60 years of age and above this age it varied between 0 and 85 per cent. The number of positive reactions to candida-l and trichophytin was low in all ages. The reactivity was regarded as normal if there was a positive reaction i.e.sum of right angle diameters >10 mm to atl east one antigen, relatively anergic if there was only a weak reaction (7-9 mm) and anergic if there was a negative reaction (0-6 mm) to all antigens. A normal reaction was found in 100 per cent of subjects up to 60 years of age, and in 95 per cent up to 30 years. Among those with normal reactivity, positive results were found with candida-h alone in between 67-93 per cent, candida-h + mumps between 92-100 per cent and candida + mumps + PPD in 100 per cent irrespective of age.


Femoroacetabular impingement: role of imaging.
The femoroacetabular impingement (FAI) is an impingement characterized by repetitive abutment between the femur and the acetabular rim during hip motion due to loss of joint clearance (Imam and Khanduja in Int Orthop 35(10):1427-1435, 2011; James et al. in AJR Am J Roentgenol 187(6):1412-1419, 2006). Femoroacetabular impingement (FAI) can be classified as either cam or pincer type, and it can be differentiated on the basis of a predominance of either a femoral or an acetabular abnormality (Pfirrmann et al. in Radiology 244(2):626, 2007; Ganz et al. in Clin Orthop Relat Res 466(2):264-272, 2008). In cases of cam FAI, the nonspherical shape of the femoral head at the femoral head-neck junction and reduced depth of the femoral waist lead to abutment of the femoral head-neck junction against the acetabular rim. In cases of pincer FAI, acetabular overcoverage limits the range of motion and leads to a conflict between the acetabulum and the femur. The most important role of preoperative MR evaluation in patients affected by FAI is the accurate assessment of the damage's extension.


Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor.
Bisphenol A (BPA) is a well-known endocrine disruptor (ED) which represents a major toxicological and public health concern due to its widespread exposure to humans. BPA has been reported to induce DNA adduct and aneuploidy in rodents. Recent studies in humans depicted its association with recurrent miscarriages and male infertility due to sperm DNA damage indicating that BPA might have genotoxic activity. Hence, the present study was designed to determine genotoxic and mutagenic effects of BPA using in-vivo and in-vitro assays. The adult male and female rats were orally administered with various doses of BPA (2.4 μg, 10 μg, 5mg and 50mg/kgbw) once a day for six consecutive days. Animals were sacrificed, bone marrow and blood samples were collected and subjected to series of genotoxicity assay such as micronucleus, chromosome aberration and single cell gel electrophoresis (SCGE) assay respectively. Mutagenicity was determined using tester strains of Salmonella typhimurium (TA 98, TA 100 and TA 102) in the presence and absence of metabolically active microsomal fractions (S9). Further, we estimated the levels of 8-hydroxydeoxyguanosine, lipid per-oxidation and glutathione activity to decipher the potential genotoxic mechanism of BPA. We observed that BPA exposure caused a significant increase in the frequency of micronucleus (MN) in polychromatic erythrocytes (PCEs), structural chromosome aberrations in bone marrow cells and DNA damage in blood lymphocytes. These effects were observed at various doses tested except 2.4 μg compared to vehicle control. We did not observe the mutagenic response in any of the tester strains tested at different concentrations of BPA. We found an increase in the level of 8-hydroxydeoxyguanosine in the plasma and increase in lipid per-oxidation and decrease in glutathione activity in liver of rats respectively which were exposed to BPA. In conclusion, the data obtained clearly documents that BPA is not mutagenic but exhibit genotoxic activity and oxidative stress could be one of the mechanisms leading to genetic toxicity.


Stabilization of mRNA following serum-induction of quiescent 3T3 cells.
The stability of mRNA has been measured in 3T3 cells in the resting and the growing states, and also during the transition from the resting to the growing state. Pulse labled poly (A)+ mRNA chased with uridine and cytidine supplemented growth medium decayed with a half-life of 6.5 hr in the resting state, 26 hr during the transition from the resting to the growing condition, and 18 hr during serum-stimulated growth. The half-life of poly(A)+ mRNA determined by steady state labeling yielded similar results in resting and serum-stimulated 3T3 cells. Thus during the transition from resting to serum-stimulated growth in 3T3 cells poly(A)+ mRNA becomes more stable.


Inhalation of swine-house dust increases the concentrations of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1ra) in peripheral blood.
Inhalation of dust in swine confinement buildings causes airway inflammation and systemic symptoms. The proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) increase in bronchoalveolar and nasal lavage fluid, and in serum. The aim of this investigation was to study changes in the IL-1 family of cytokines in peripheral blood in 36 healthy volunteers exposed to swine house dust for 3 h. Interleukin (IL-1 beta) was measured in platelet poor plasma and in a mononuclear cell fraction (PBMC) and interleukin-1 receptor antagonist (IL-Ira), IL-6 and TNF-alpha were measured in serum 4 and 7 h after the start of 3 h exposure. Lung function and a methacholine bronchial provocation test were performed before and 7 h after the start of exposure. The leukocyte count in whole blood and the mononuclear cell count in PBMC were examined before, and 4 and 7 h after the start of exposure. The concentration of airborne inhalable dust and endotoxin were measured using personal samples. The concentration of inhalable dust was 23 (20-30) mg m-3 (median 25th-75th percentile) endotoxin was 1.1 (0.8-1.4) micrograms m-3 and respirable dust (n = 8) was 1.0 (0.7-1.2) mg m-3. IL-1 beta increased from < 0.125 to 0.9 (0.5-1.3) ng l-1 in plasma and from 1.6 to 2.7 (1.1-4.4) ng l-1 in PBMC (P < 0.01). IL-1 ra, IL-6 and TNF-alpha increased 2-, 12- and 2-fold in serum after exposure, respectively. Changes in IL-1 ra correlated with changes in FEV1, bronchial responsiveness, oral temperature (P < 0.01) and blood white cell count (P < 0.05). IL-1 beta correlated significantly with temperature (P < 0.05). These results indicate that IL-1 beta and IL-1 ra increase in peripheral blood following inhalation of swine house dust and may participate in and modulate the inflammatory response together with IL-6 and TNF-alpha.


An integrated approach to the toxicity assessment of Irish marine sediments: validation of established marine bioassays for the monitoring of Irish marine sediments.
This paper describes the ecotoxicological evaluation of marine sediments from three sites around Ireland representative of a range of contaminant burdens. A comprehensive assessment of potential sediment toxicity requires the consideration of multiple exposure phases. In addition to the evaluation of multi-exposure phases the use of a battery of multi-trophic test species has been advocated by a number of researchers as testing of single or few organisms may not detect toxicants with a specific mode of action. The Microtox solid phase test (SPT) and the 10-d acute amphipod test with Corophium volutator were used to assess whole sediment toxicity. Porewater and elutriates were assessed with the Microtox acute test, the marine prasinophyte Tetraselmis suecica, and the marine copepod Tisbe battagliai. Solvent extracts were assayed with the Microtox and T. battagliai acute tests. Alexandra Basin was identified as the most toxic site according to all tests, except the Microtox SPT which identified the Dunmore East site as being more toxic. However, it was not possible to correlate the observed ecotoxicological effects with a specific and/or class of contaminants based on sediment chemistry alone. Therefore porewaters found to elicit significant toxicity (Dunmore East and Alexandra Basin) with the test battery were selected for further TIE assessment with T. battalgiai and the Microtox system. The results of this study have important implications for risk assessment in estuarine and coastal waters in Ireland, where, at present the monitoring of sediment and water quality is predominantly reliant on chemical analysis alone.


Functional linkage of Na(+)-Ca2+ exchange and sarcoplasmic reticulum Ca2+ release mediates Ca2+ cycling in vascular smooth muscle.
Ca2+ loss from the sarcoplasmic reticulum (SR) of rabbit inferior vena cava smooth muscle was monitored by measuring the decay of caffeine-induced fura-2 fluorescence transients. Removal of Ca2+ from the extracellular space caused a rapid loss of SR Ca2+ and a decline of cytoplasmic Ca2+ concentration ([Ca2+]i). Simultaneous removal of extracellular Na+ greatly inhibited the rate of this (SR) Ca2+ loss. A rapid loss of SR Ca2+ was induced by 20 microns CPA, regardless of the presence or absence of extracellular Na+ or Ca2+. These effects were not influenced by alterations in membrane potential owing to activity of Ca2(+)-activated K+ channels since 3 mM TEA had no effect on the rate of Ca2+ loss from the SR. These results indicate that when Ca2+ is removed from the extracellular space, it induces Ca2+ release from the SR towards the plasma membrane Na(+)-Ca2+ exchanger which subsequently translocates it from the junctional cytoplasmic space to the extracellular space. When the Na(+)-Ca2+ exchanger is arrested by removal of extracellular Na+ and Ca2+, Ca2+ released from the SR is re-sequestered by the sarco-endo-plasmic reticulum Ca2(+)-ATPase (SERCA). However, when both the Na(+)-Ca2+ exchanger, and, the SERCA are blocked, Ca2+ released from the SR is extruded from the cells by the plasma membrane Ca2(+)-ATPase. These results reveal a hierarchy of interaction between the different Ca2+ transporters in the SR, and cell membranes.


Early molecular events during the interaction of enveloped riboviruses with cells. II. A kinetic study.
A kinetic model was constructed and partly solved to describe the migration of the fluorescence label 1,6-diphenylhexatriene (DPH) in both directions when enveloped viruses, labelled with DPH in their envelopes are in contact with unlabelled cells or cell labelled in their membranes are in contact with unlabelled enveloped viruses. The central assumption is that two types of receptor sites exist on the cell surface, i.e., physical adsorption sites (P-sites), available to all the viruses studied in these papers and binding sites (B-sites) available only to the viruses which penetrate into the specific cells. The differential equations for the label migration, for different values of the ratio number of viruses number of sites were numerically solved, assuming different fractions of P- and B-sites. The equations also describe, appropriately the mechanism of rapid label migration in the system and substantiate the magnitude "time of residence" of the nonpenetrating viruses adsorbed on the cell surface. The resulting curves match satisfactorily those for the label release by the viruses and account well for the steady state values of the kinetics of label migration in the virus-cell system.


The International Mouse Strain Resource (IMSR): cataloging worldwide mouse and ES cell line resources.
The availability of and access to quality genetically defined, health-status known mouse resources is critical for biomedical research. By ensuring that mice used in research experiments are biologically, genetically, and health-status equivalent, we enable knowledge transfer, hypothesis building based on multiple data streams, and experimental reproducibility based on common mouse resources (reagents). Major repositories for mouse resources have developed over time and each has significant unique resources to offer. Here we (a) describe The International Mouse Strain Resource that offers users a combined catalog of worldwide mouse resources (live, cryopreserved, embryonic stem cells), with direct access to repository sites holding resources of interest and (b) discuss the commitment to nomenclature standards among resources that remain a challenge in unifying mouse resource catalogs.


Dissipation by tetraethylammonium of verapamil-stimulated p-aminohippurate accumulation in rat kidney cortical slices.
The stimulatory effect of verapamil on p-aminohippurate (PAH) accumulation was studied in rat kidney cortical slices. PAH accumulation was stimulated by the presence of 0.3 mM verapamil in the incubation medium, but this stimulatory action of verapamil was dissipated by adding tetraethylammonium (TEA) to the medium. TEA accumulation by the kidney cortical slices was inhibited by verapamil in a concentration-dependent fashion. In addition, kinetic studies revealed that verapamil resulted in an increase in the Michaelis constant (Km) of TEA transport, with the Vmax remaining constant, suggesting that verapamil competitively inhibited TEA transport. These results suggest that the transport system for verapamil is the same as that for TEA and that verapamil taken up within the cells may stimulate PAH transport.