Determination for multiple mycotoxins in agricultural products using HPLC-MS/MS via a multiple antibody immunoaffinity column.
Mycotoxins usually found in agricultural products such as peanut, corn, and wheat, are a serious threat to human health and their detection requires multiplexed and sensitive analysis methods. Herein, a simultaneous determination for aflatoxin B1, B2, G1, G2, ochratoxin A, zearalanone and T-2 toxin was investigated using high performance liquid chromatography coupled with tandem mass spectrometry in a single run via a home-made multiple immunoaffinity column. Four monoclonal antibodies were produced in our lab against aflatoxins, ochratoxin A, zearalanone and T-2 toxin, respectively, then combined as a pool and bound to Sepharose-4B for affinity chromatography. Seven mycotoxins were effectively extracted from the agricultural product samples by using acetonitrile/water/acetic acid (80:19:1, v/v/v) Then, the extraction was cleanup by multiple immunoaffinity column. This method demonstrated a considerable linear range of 0.30-25, 0.12-20, 0.30-20, 0.12-20, 0.60-30, 0.30-25, and 1.2-40μgkg(-1)and lower limits of detection at 0.1, 0.04, 0.1, 0.04, 0.2, 0.1 and 0.4μgkg(-1) for AFB1, AFB2, AFG1, AFG2, OTA, ZEN and T-2, respectively, in comparison with previously reported methods, as well as excellent recoveries. The mIAC capacity for AFB1, AFB2, AFG1, AFG2, OTA, ZEN, and T-2 were 187, 181, 153, 151, 105, 130, 88ng, respectively. It was found that all of the 7 mycotoxins were present in 90 agricultural product samples. The proposed method meets the requirements for rapid sample preparation and highly sensitive identification of multiple mycotoxins in agricultural product and food safety. This method provides a promising alternative with high throughput and high sensitivity for rapid analysis of seven mycotoxins in the monitoring of food safety.


First gender, then attractiveness: Indications of gender-specific attractiveness processing via ERP onsets.
We followed an ERP-based approach to gain knowledge on the dependence and temporal order of two essential processes of face perception: attractiveness and gender. By combining a dual-choice task with a go/nogo-paradigm focusing on the LRP and N200-effect, we could estimate the processing times and onsets of both types of face processing. The analyses of the LRP revealed that gender aspects were processed much earlier than attractiveness. Whereas gender was already analysed 243.9 ms post-stimulus onset, attractiveness came into play 58.6 ms later, i.e. after a post-stimulus onset delay of 302.5 ms. This resulting pattern was mirrored by the analyses of the N200-effect, an effect available mainly frontally which is supposed to correlate with the inhibition of inappropriate responses. Taking the onset of the N200 effect as an estimator for the moment at which information has been processed sufficiently for task decision, we could trace the N200 effect at 152.0 ms for go/nogo-decision on gender, while not as early as 206.7 ms on attractiveness. In sum, processing of facial attractiveness seems to be based on gender-specific aesthetic pre-processing, for instance via activating gender-specific attractiveness prototypes which show focused processing of certain facial aspects.


Gut microbiota modulation with long-chain corn bran arabinoxylan in adults with overweight and obesity is linked to an individualized temporal increase in fecal propionate.
Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota's ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework. Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman's test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes. This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies. Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.


A rare clinical presentation after COVID-19: Manic episode with psychotic features.
Neuropsychiatric manifestations of the COVID-19, caused by SARS-CoV-2, are under close scrutiny as the virus is shown likely to either directly or indirectly affects the central nervous system although it mainly targets the respiratory tract. Here, we describe a middle-aged male who developed acute psychiatric symptoms after a recent COVID-19 infection with no prior personal or family history of psychiatric disorder. Although there are reported cases of diagnosed psychosis or affective disorders following COVID-19 infection in the literature, to our knowledge, this is the first case where the development of autoimmune encephalitis after COVID-19 was considered and ruled out. This case report describes the comprehensive evaluation of all possible organic etiology. We also aimed to discuss possible biological underpinnings of such an exceptional comorbidity.


Histomorphometric analysis of newly formed bone after bilateral maxillary sinus augmentation using two different osteoconductive materials and internal collagen membrane.
Deproteinized bovine bone mineral (DBBM) and human freeze-dried bone allograft (FDBA) were compared in five patients undergoing bilateral maxillary sinus floor augmentation using DBBM on one side and FDBA on the contralateral side. After 9 months, core biopsy specimens were harvested. Mean newly formed bone values were 31.8% and 27.2% at FDBA and DBBM sites, respectively (P = .451); mean residual graft particle values were 21.5% and 24.2%, respectively (P = .619); and mean connective tissue values were 46.7% and 48.6%, respectively (P = .566). Within the limits of the present study, it is suggested that both graft materials are equally suitable for sinus augmentation.


Why Boron Nitride is such a Selective Catalyst for the Oxidative Dehydrogenation of Propane.
Boron-containing materials, and in particular boron nitride, have recently been identified as highly selective catalysts for the oxidative dehydrogenation of alkanes such as propane. To date, no mechanism exists that can explain both the unprecedented selectivity, the observed surface oxyfunctionalization, and the peculiar kinetic features of this reaction. We combine catalytic activity measurements with quantum chemical calculations to put forward a bold new hypothesis. We argue that the remarkable product distribution can be rationalized by a combination of surface-mediated formation of radicals over metastable sites, and their sequential propagation in the gas phase. Based on known radical propagation steps, we quantitatively describe the oxygen pressure-dependent relative formation of the main product propylene and by-product ethylene. Free radical intermediates most likely differentiate this catalytic system from less selective vanadium-based catalysts.


A 13-million turnover-number anionic Ir-catalyst for a selective industrial route to chiral nicotine.
Developing catalysts with both useful enantioselectivities and million turnover numbers (TONs) for asymmetric hydrogenation of ketones is attractive for industrial production of high-value bioactive chiral entities but remains a challenging. Herein, we report an ultra-efficient anionic Ir-catalyst integrated with the concept of multidentate ligation for asymmetric hydrogenation of ketones. Biocatalysis-like efficacy of up to 99% ee (enantiomeric excess), 13,425,000 TON (turnover number) and 224 s-1 TOF (turnover frequency) were documented for benchmark acetophenone. Up to 1,000,000 TON and 99% ee were achieved for challenging pyridyl alkyl ketone where at most 10,000 TONs are previously reported. The anionic Ir-catalyst showed a novel preferred ONa/MH instead of NNa/MH bifunctional mechanism. A selective industrial route to enantiopure nicotine has been established using this anionic Ir-catalyst for the key asymmetric hydrogenation step at 500 kg batch scale, providing 40 tons scale of product.


RSE prediction by EEG patterns in adult GCSE patients.
Electroencephalogram (EEG) can predict mortality in status epilepticus (SE) patients. However, we consider that the prediction for refractory status epilepticus (RSE) after SE initial treatment is more significant than long-term prognosis of SE. The objective of this study is to detect some predictive EEG patterns for RSE. Pooled data derived from two randomized controlled trials (RCTs) were prospectively analyzed in adult generalized convulsive status epilepticus (GCSE) patients. Etiology, GCSE duration and EEG patterns are three factors which were statistically different between non-RSE and RSE groups. However, when we introduced these factors into multivariable logistic regression model, only EEG pattern was an independent risk factor for RSE prediction. Comparing with rhythmic fast activities background (RFAB) pattern, there were positive correlations between interictal epileptiform discharges (IEDs), periodic epileptic discharges/subtle status epilepticus (PEDs/subtle SE) patterns and RSE incidence respectively. There was an increased risk of RSE incidence accompanied with IEDs and PEDs/subtle SE patterns appearance. Clinicians should adjust anti-epileptic strategies with the aid of these EEG patterns in order to reduce RSE incidence.


Ligand-Induced Coupling between Oligomers of the M2 Receptor and the Gi1 Protein in Live Cells.
Uncertainty over the mechanism of signaling via G protein-coupled receptors (GPCRs) relates in part to questions regarding their supramolecular structure. GPCRs and heterotrimeric G proteins are known to couple as monomers under various conditions. Many GPCRs form oligomers under many of the same conditions, however, and the biological role of those complexes is unclear. We have used dual-color fluorescence correlation spectroscopy to identify oligomers of the M2 muscarinic receptor and of Gi1 in purified preparations and live Chinese hamster ovary cells. Measurements on differently tagged receptors (i.e., eGFP-M2 and mCherry-M2) and G proteins (i.e., eGFP-Gαi1β1γ2 and mCherry-Gαi1β1γ2) detected significant cross-correlations between the two fluorophores in each case, both in detergent micelles and in live cells, indicating that both the receptor and Gi1 can exist as homo-oligomers. Oligomerization of differently tagged Gi1 decreased upon the activation of co-expressed wild-type M2 receptor by an agonist. Measurements on a tagged M2 receptor (M2-mCherry) and eGFP-Gαi1β1γ2 co-expressed in live cells detected cross-correlations only in the presence of an agonist, which therefore promoted coupling of the receptor and the G protein. The effect of the agonist was retained when a fluorophore-tagged receptor lacking the orthosteric site (i.e., M2(D103A)-mCherry) was co-expressed with the wild-type receptor and eGFP-Gαi1β1γ2, indicating that the ligand acted via an oligomeric receptor. Our results point to a model in which an agonist promotes transient coupling of otherwise independent oligomers of the M2 receptor on the one hand and of Gi1 on the other and that an activated complex leads to a reduction in the oligomeric size of the G protein. They suggest that GPCR-mediated signaling proceeds, at least in part, via oligomers.


Female's preference for oviposition site and larval performance in the water-lily beetle, Galerucella nymphaeae (Coleoptera: Chrysomelidae).
Water-lily beetles prefer younger rather than older water-lily leaves as oviposition sites. By the time of hatching, however, young leaves have aged consieerably. Larval performance of the water-lily beetle was measured on different types of leaves of the yellow water-lily and compared with oviposition preference of females. The leaf types used in the experiments were categorized as (i) young, (ii) natal (medium-aged) and (iii) old. The natal leaves were the ones on which larvae from a particular egg-batch had hatched. There were two sets of experiments. First, larvae were raised from eggs to pupae on young and on old leaves. Second, the growth of the 1st-instar larvae was measured on young, natal, and old leaves. The development time from egg to pupa did not differ between young and old leaves, but larvae growing on young leaves attained a higher pupal weight. In the second experiment the 1st-instar larvae grew fastest on their natal leaves, but there was also variation in the growth rate of progeny from different egg-batches. Larval growth on young and old leaves did not differ significantly. Larvae tried to emigrate much less from natal than other types of leaves. Females tended to lay eggs on leaves where larval growth was fastest. It seems that medium-aged leaves are best for larval growth, but the leaf characteristics responsible for this remain unresolved.


Optimised system configuration for stent manufacturing.
Optimising the major components of a laser stent machining platform will lead to improved part quality and machine throughput. Mechanical, control and software elements are reviewed here. Trends in stent design are also discussed together with their implications on these machine design elements.


Interaction between handling induced stress and anxiolytic effects of ethanol in zebrafish: A behavioral and neurochemical analysis.
Stress is often considered an important factor in the development of alcohol addiction. In rodents, various types of stressors have been shown to potentiate the effects of alcohol on behavioral responses, and to increase consumption of this substance. However, few have investigated the interaction between stress and alcohol in zebrafish. In the current study we present a repeated handling stress paradigm we developed for zebrafish, and examine whether stress alters alcohol induced behavioral and neurochemical responses. Our results show that repeated handling of zebrafish conducted for 2 consecutive days is sufficient to increase anxiety-like behavioral responses quantified 24h post-stressor. Repeatedly handled zebrafish also exhibited a reduction in the levels of serotonin's metabolite, 5-hydroxyindole acetic acid (quantified by high precision liquid chromatography) compared to unhandled controls. A 60-min acute exposure to 1% ethanol was found to significantly increase locomotor activity and decrease anxiety-like behavioral responses in stressed zebrafish but not in controls. Furthermore, unhandled control zebrafish exhibited a significant increase in whole-brain dopamine levels following exposure to ethanol but the increase was not observed in repeatedly handled fish. Our findings suggest that ethanol induced locomotor activity and anxiolysis is potentiated by handling stress and may be partially mediated by changes in dopaminergic and serotonergic activity. Overall, we demonstrate the validity of our repeated handling stressor paradigm for zebrafish, which can be used to investigate the interaction between stress and ethanol.


Instability of mitochondrial DNA and MRI and clinical correlations in malignant gliomas.
Mutations and instability of mitochondrial DNA (mtDNA) are frequent in tumors but their pathogenic relevance is not established. To assess their role in the clinical management of malignant gliomas we have studied the D loop of mtDNA in 42 such tumors. Alterations were found in 36% of the cases. The MRI and the clinical follow-up of these patients suggest that these mutations are not associated with increased aggressiveness. mtDNA could be amplified from post-surgical tumor cavities in patients undergoing a loco-regional treatment. These results imply that mtDNA mutations are unlikely to play a role in diagnostic or prognostic evaluations of gliomas: their detection, however, could be of use for the clinical follow-up of malignant gliomas.


Stress Myocardial Perfusion Imaging vs Coronary Computed Tomographic Angiography for Diagnosis of Invasive Vessel-Specific Coronary Physiology: Predictive Modeling Results From the Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) Trial.
Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement. To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR. Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018. Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and FFR by CT (FFR-CT), and semiquantitative scoring of rest/stress myocardial perfusion imaging (by magnetic resonance, positron emission tomography, or single photon emission CT). Multivariable generalized linear mixed models were derived and validated calculating the area under the receiver operating characteristics curve. The primary end point was invasive FFR of 0.80 or less. Of the 612 patients, the mean (SD) age was 64 (10) years, and 426 (69.9%) were men. An invasive FFR of 0.80 or less was measured in 26.5% of 1727 vessels. In the derivation cohort, CCTA vessel-specific factors associated with FFR 0.80 or less were stenosis severity, percentage of noncalcified atheroma volume, lumen volume, the number of lesions with high-risk plaque (≥2 of low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification), and the number of lesions with stenosis greater than 30%. Fractional flow reserve-CT was not additive to this model including stenosis and atherosclerotic plaque. Significant myocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001). A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion. ClinicalTrials.gov Identifier: NCT02173275.


Anticipatory guidance preferences of Latina migrant farmworker mothers.
The purpose of the study was to learn preferences of Latina migrant farmworker mothers regarding the presentation of health education materials by discussing the strengths and weaknesses of numerous mixed-media samples. This community-based participatory study was qualitative and descriptive in design. Focus groups were conducted in Spanish in four Midwest migrant camps with a convenience sample of mothers (N = 31). Adult learning and cultural care theories guided the study. Various modes of educational materials on various topics were presented. Mothers preferred comic book-style handouts, games, food replicas, text in English/Spanish, and digital video discs or digital versatile discs, but almost none of them had media-playing equipment. They did not like black-and-white photos or cartoon-like illustrations. Identified themes of importance were colored illustrations, sizes mothers could easily carry in purses, and limited verbiage on a page. The knowledge gained in this study will be used to customize health promotion interventions that are sensitive to migrant farmworker-preferred learning styles. The findings from this study can inform other interventions with Latino populations and serve as a prototype for other populations of immigrant non-English-speaking mothers.


Analysis of progression-free survival of first-line tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring leu858Arg or exon 19 deletions.
Gefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival. We conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals. Of the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib (n = 304, 67.6%), erlotinib (n = 63, 14.3%), or afatinib (n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5-16.5), 11.2 months in the erlotinib arm (IQR: 4.9-16.7), and 10.3 months in the afatinib arm (IQR: 7.0-14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group. Afatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.


Involvement of the proteasome in IL-1beta induced suppression of islets of Langerhans in the rat.
The cytokine IL-1beta suppresses rodent islets of Langerhans in vitro. Presently we used inhibitors of the proteasome to investigate if these compounds could counteract the suppressive effects of the cytokine. Thus, isolated rat islets were cultured and pre-treated with proteasome inhibitors and subsequently exposed for 48 h to 25 U/ml human IL-1beta. After this period functional tests were carried out. The rate of glucose oxidation (pmol/10 islets x 90 min) was suppressed by IL-1beta (115 +/- 17 vs. control 380 +/- 57). Pre-treatment with 10 microM of the proteasome inhibitor MG115 (N-carbobenzoxyl-leu-leu-norvalinal) and 100 microM of the calpain inhibitor norLEU (N-acetyl-leu-leu-norleucinal; known to affect proteasome activity) counteracted the suppressive effects (253 +/- 17 and 262 +/- 10 respectively). The calpain inhibitor alIMET (N-acetyl-leu-leu-methional) had no effect. MG115 (10 microM) and norLEU (100 microM) blocked nitric oxide formation induced by IL-1beta, while alIMET was without effect. We also investigated if IL-1beta could influence the expression of two inducible proteasome subunits, namely LMP2 and LMP7, and found that the cytokine increased the mRNA expression of the proteasome subunit LMP2 in islets, and that the proteasome inhibitor MG115 prevented this increase. In conclusion our study shows that IL-1beta increases the transcription of the proteasome subunit LMP2, and that the proteasome is involved in IL-1beta induced suppression of islet function. Moreover, the observation that inhibitors of the proteasome protect islets against IL-1beta induced inhibition of glucose metabolism, suggests that these compounds might be worthwile to explore in future therapies against the development of type 1 diabetes.


Endometrial progesterone receptor isoforms in women with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all reproductive-aged women and is often accompanied by endometrial progesterone (P4) resistance. Endometrial cells from PCOS patients display increased progesterone receptor (PGR) expression; however, in vivo knockout studies and in vitro experiments indicate the two PGR isoforms are not functionally equivalent. We aimed to compare endometrial PGR isoform expression between non-PCOS and PCOS patients during the proliferative phase. A case-control study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha (ERα), and markers of cell proliferation was determined by qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays. Patients were recruited and diagnosed with PCOS according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia (n = 11) and from PCOS patients with or without hyperplasia (n = 14). Although the alteration of PGRB mRNA and protein expression was different, we found that PGRA mRNA and protein expression was higher in PCOS patients than non-PCOS patients. PGRA/B and PGRB were localized in both epithelial and stromal cells, with notable changes in the nuclei of epithelial and stromal cells. A similar expression pattern of ERα, vimentin and Ki-67, in association with an increased PGR expression, was observed in PCOS patients. These results demonstrated that elevated both PGR isoform expression depends on the presence of PCOS, and our data suggest that abnormal regulation of PGR isoforms is a pathological outcome of defective endometrium in PCOS patients.


Increasing Engagement of Imaging Professionals in Quality Improvement Using an Encounter-specific Quality-reporting Tool.
The involvement of pediatric imaging professionals in quality improvement (QI) in our department was low, with few available informatics tools to report issues or suggest improvement opportunities in a timely and efficient manner. We aimed to increase QI engagement in radiology by creating a real-time, encounter-specific reporting tool embedded into the clinical imaging workflow. A multidisciplinary team outlined requirements for a new electronic quality-reporting tool, including point-of-care access during imaging workflow and simultaneous automatic capture of encounter-specific clinical information from the hospital information system. Information system experts created a user-friendly interface for categories based on stages of imaging workflow (Planning, Acquisition, Processing, Interpretation, Communication, and Data Collection). Team members trained all department staff. Quality coordinators sorted entries and monitored personnel engagement for two 36-week periods: immediately after launch and 3 years later. Descriptive statistics were used to analyze proposed and completed QI projects during these periods. There were 1,498 entries during the first 36 weeks. Ninety-three percent of radiologists and 56% of technologists participated. Three years later, there were 1,251 entries in 36 weeks. Data collection entries for established QI projects increased from 380 (25%) to 487(39%). The engagement continued among radiologists but decreased among technologists over time. Submissions for QI projects increased from baseline. The project completion rate increased. We created a QI reporting tool embedded into the clinical imaging workflow, which improved the participation of our imaging professionals and increased the number of completed QI projects.


Arsenic and sulfur nanoparticle synthesis mimicking environmental conditions of submarine shallow-water hydrothermal vents.
Arsenic and sulfur mineralization is a natural phenomenon occurring in hydrothermal systems where parameters like temperature and organic matter (OM) can influence the mobilization of the toxic metalloid in marine environments. In the present study we analyze the influence of temperature and OM (particularly sulfur-containing additives) on As and S precipitation based on the recent discovery of As-rich nanoparticles in the hydrothermal system near the coast of the Greek island Milos. To this end, we experimentally recreate the formation of amorphous colloidal particles rich in As and S via acidification (pH 3-4) of aqueous precursors at various temperatures. At higher temperatures, we observe the formation of monodisperse particles within the first 24 h of the experiment, generating colloidal particles with diameters close to 160 nm. The S:As ratio and particle size of the synthetized particles closely correlates with values for AsxSy particles detected in the hydrothermal system off Milos. Furthermore, organic sulfur containing additives (cysteine and glutathione, GSH) are a key factor in the process of nucleation and growth of amorphous colloidal AsxSy particles and, together with the temperature gradient present in shallow hydrothermal vents, dictate the stabilization of As-bearing nanomaterials in the environment. Based on these findings, we present a simple model that summarizes our new insights into the formation and mobility of colloidal As in aquatic ecosystems. In this context, amorphous AsxSy particles can present harmful effects to micro- and macro-biota not foreseen in bulk As material.


Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus.
In addition to several infectious and neoplastic cutaneous entities, plasmacytoid dendritic cells (pDCs) have been shown to be involved in the pathogenesis of multiple cutaneous inflammatory and autoimmune disorders, including those characterized histologically by an "interface dermatitis" pattern such as lupus or lichen planus (LP), but their role in lichen striatus (LS), which is also known to have this histologic inflammatory pattern, has never been studied. The objective of the study was to investigate the role of pDCs in LS. Fifteen LS patients were found in our database and were immunohistochemically tested for pDC occurrence and activity using anti-blood-derived dendritic cell antigen-2 and anti-myxovirus resistance protein A (MxA) antibodies, respectively. These individuals were also compared with 15 individuals with LP. pDCs were present in all individuals with LS and LP, but they were less abundant in those with LS, although MxA (surrogate marker of local type I interferon production and thus an indirect assessment of pDC activity) was similarly intense and diffuse in all individuals with LS and LP. In addition to being part of the upper dermal inflammatory bandlike infiltrate as in LP, LS cases, unlike LP, also showed perieccrine pDCs. pDCs constitute a central component of the inflammatory infiltrate in LS, suggesting a significant role in its pathogenesis. pDC distribution (perieccrine distribution) could also help in microscopically differentiating LS from LP.


Detoxification of mycotoxins by probiotic preparation for broiler chickens.
Biological decontamination of mycotoxins using microorganisms is one of the well known strategies for the management of mycotoxins in foods and feeds. Among the different potential decontaminating microorganisms,Saccharomyces cerevisiae and lactic acid bacteria represent unique groups, which are widely used in food fermentation and preservation. The aim of this study was to determine the influence of spontaneous fermentation with the use of probiotic bacteria and yeast (Lactobacillus paracasei/casei ŁOCK 0920,L. brevis ŁOCK 0944,L. plantarum ŁOCK 0945,Saccharomyces cerevisiae ŁOCK 0142), on reduction of sum of aflatoxines (B1, B2, G1, G2) and ochratoxin A concentration during fermentation and the microflora pattern during fermentaton. The probiotic bacteria and yeast applied creates a starter culture for flour fermentation that has a stable feature of detoxication of aflatoxines and especially ochratoxin A.


Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex.
Assembly of the terminal complement proteins C5b-9 on human endothelial cells results in increased cytosolic calcium and nonlytic secretion of high molecular weight multimers of von Willebrand factor from intracellular storage granules. We now demonstrate that this C5b-9-induced secretory response is accompanied by vesiculation of membrane particles from the endothelial surface which express binding sites for factor Va and support prothrombinase activity. Exposure of factor Va binding sites after C5b-9 assembly was accompanied by greater than 2-fold increase in prothrombinase activity, which was not observed for cells exposed to C5b-8 (in the absence of C9). By contrast, only a 3-16% increase in prothrombinase activity was observed when these cells were maximally stimulated to secrete by either histamine, thrombin, or the Ca2+ ionophore A23187. Increased prothrombinase activity after C5b-9 was not accompanied by a change in thrombomodulin activity, and was unrelated to cell lysis, the complement-treated cells remaining greater than 99% viable. Endothelial prothrombinase activity was predominately associated with small membrane vesicles (less than 1 microns diameter) released from the cell monolayer. Analysis by fluorescence-gated flow cytometry revealed that these vesicles incorporate the C5b-9 proteins and express binding sites for factor Va. The capacity of the C5b-9 proteins to induce vesiculation of the endothelial plasma membrane and thereby expose catalytic surface for the prothrombinase enzyme complex may contribute to fibrin deposition associated with immune endothelial injury.


A clinical technique for virtual articulator mounting with natural head position by using calibrated stereophotogrammetry.
Accurate articulator-mounted casts are essential for occlusion analysis and for fabrication of dental prostheses. Although the axis orbital plane has been commonly used as the reference horizontal plane, some clinicians prefer to register the horizontal plane with a spirit level when the patient is in the natural head position (NHP) to avoid anatomic landmark variations. This article presents a digital workflow for registering the patient's horizontal plane in NHP on a virtual articulator. An orientation reference board is used to calibrate a stereophotogrammetry device and a 3-dimensional facial photograph with the patient in NHP. The horizontal plane can then be automatically registered to the patient's virtual model and aligned to the virtual articulator at the transverse horizontal axis level. This technique showed good repeatability with positional differences of less than 1 degree and 1 mm in 5 repeated measurements in 1 patient.


Expression of androgen-producing enzyme genes and testosterone concentration in Angus and Nellore heifers with high and low ovarian follicle count.
Follicle population is important when animals are used in assisted reproductive programs. Bos indicus animals have more follicles per follicular wave than Bos taurus animals. On the other hand, B taurus animals present better fertility when compared with B indicus animals. Androgens are positively related with the number of antral follicles; moreover, they increase growth factor expression in granulose cells and oocytes. Experimentation was designed to compare testosterone concentration in plasma, and follicular fluid and androgen enzymes mRNA expression (CYP11A1, CYP17A1, 3BHSD, and 17BHSD) in follicles from Angus and Nellore heifers. Heifers were assigned into two groups according to the number of follicles: low and high follicle count groups. Increased testosterone concentration was measured in both plasma and follicular fluid of Angus heifers. However, there was no difference within groups. Expression of CYP11A1 gene was higher in follicles from Angus heifers; however, there was no difference within groups. Expression of CYP17A1, 3BHSD, and 17BHSD genes was higher in follicles from Nellore heifers, and expression of CYP17A1 and 3BHSD genes was also higher in HFC groups from both breeds. It was found that Nellore heifers have more antral follicles than Angus heifers. Testosterone concentration was higher in Angus heifers; this increase could be associated with the increased mRNA expression of CYP11A1. Increased expression of androgen-producing enzyme genes (CYP17A1, 3BHSD, and 17BHSD) was detected in Nellore heifers. It can be suggested that testosterone is acting through different mechanisms to increase follicle development in Nellore and improve fertility in Angus heifers.


Hemodilution and surgical hemostasis contribute significantly to transfusion requirements in patients undergoing coronary artery bypass.
We sought to determine the incidence of and risk factors for the development of low intraoperative hematocrit levels and of excessive postoperative bleeding in patients undergoing coronary artery bypass grafting, whether the risk factors are the same, and their effect on blood product transfusions. We performed a prospective cohort study of 613 adult patients who underwent coronary artery bypass grafting in 3 tertiary, university-affiliated hospitals during the period from October 1, 2000, to March 31, 2001. Low intraoperative hematocrit levels (<19%) were found in 131 (24%) patients who had operations performed with extracorporeal circulation compared with in 3 (4%) patients with operations performed off pump. In multivariate analysis this was associated with older age, female sex, lower preoperative hemoglobin levels, lower body surface area, longer duration on bypass, and use of higher total volumes with more hydroxyethyl starch in the circuit. Low intraoperative hematocrit levels did not predict excessive postoperative hemorrhage (>1 L of mediastinal drainage in the first 12 hours). This occurred in 26% (n = 140) of patients undergoing on-pump operations and in 25% of patients undergoing off-pump operations and in multivariate analysis was associated with male sex, longer pump times, not receiving aprotinin, and operations performed by certain surgeons but not with total circuit or hydroxyethyl starch volume. We observed that the risk factors for the development of a low intraoperative hematocrit level and excessive postoperative bleeding differed. Our results suggest that decreasing these outcomes in patients undergoing cardiac surgery requires a comprehensive approach, including limiting hemodilution, particularly in female subjects with lower preoperative hemoglobin levels, and careful attention to surgical hemostasis.


Changing testicular histology in AIDS: its implication for sexual transmission of HIV.
The understanding of testicular histology in acquired immunodeficiency syndrome (AIDS) is essential, because the sexual route is one of the main means of transmission of the human immunodeficiency virus, which is localized primarily in the germ cells of the testes. It is important to determine whether any changes have occurred in the testicular histologic patterns in the course of the AIDS epidemic. One hundred forty testicular specimens were available from AIDS autopsies during the AIDS epidemic (1981 to 1998). The epidemic was divided into pre-zidovudine (pre-AZT) therapy (1981 to 1987) and antiviral therapy (1988 to 1998) periods; the latter period was further subdivided on the basis of the particular treatment used. Testicular histology was evaluated and correlated with patient age, CD4 T-cell counts, and pathologic findings in other parts of the body. Testicular histologic findings were categorized into three groups: hypospermatogenesis (group S), spermatogenic arrest (group A), and Sertoli cell only (group O). The percentage of AIDS patients with group S histologic findings remained constant throughout the study period: 26% in the pre-AZT and 28% in the antiviral therapy periods. However, there was a reversal in the percentages of patients in groups A and O: group A decreased from 48% (pre-AZT) to 28% (antiviral) and group O increased from 26% (pre-AZT) to 44% (antiviral). There was no correlation between testicular histologic results and patient age or CD4 count. Opportunistic infections and testicular neoplasms were also identified. This study demonstrates that current therapy and prolongation of survival in AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. However, 28% of patients still show significant spermatogenesis at the time of death from AIDS and this subgroup cannot be identified by age or CD4 T-cell counts. The presence of large numbers of residual germ cells in these patients suggests that they may continue to be infectious throughout their disease course.


Association between age at menopause and fracture risk: a systematic review and meta-analysis.
Early menopause (EM, age at menopause < 45 years) and premature ovarian insufficiency (POI, age at menopause < 40 years) are associated with an increased risk of osteoporosis. However, their association with increased fracture risk has not been established, with studies yielding conflicting results. The primary aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and fracture risk. The secondary aim was to evaluate this effect concerning the site of fractures. A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 January 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). The I2 index was employed for quantifying heterogeneity. Eighteen studies were included in the qualitative and quantitative analysis (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36, 95% CI 1.11-1.66, p < 0.002, I² 81.5%). Women with POI did not display any difference in fracture risk compared either with women with age at menopause > 40 (OR 1.23, 95% CI 0.72-2.09, p = 0.436, I² 62.5%) or >45 years (OR 0.54, 95% CI 0.22-1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis was performed for vertebral, non-vertebral and hip fractures. This is the first meta-analysis showing that EM is associated with increased fracture risk compared with normal age at menopause, without any distinct effect on the site of the fracture.


Editorial Commentary: Racial and Economic Inequity Leads to Diminished Access to Rotator Cuff Repair: We Treat as One.
In a review of a U.S. State's health care data as it pertained to rotator cuff repair, there were key differences relating to the patients' race, ethnicity, and income status and eventuality for surgery. Black race, Hispanic ethnicity, and Medicaid insurance are associated with lower rates of rotator cuff repair, and Asian race, male gender, and workers' compensation insurance are associated with a greater rate. Consideration of these covariates can make us more aware of specific disparities that lead to differences in rotator cuff repair and to greater health care access in general. Patient, physician, and systemic factors are critical to reach a better level of understanding and potential treatment. There is a need for improved inclusivity and equity for all patients seeking rotator cuff repair.


Perceptions of pharmacists and physicians on generic substitution in a financial crisis context in Northwestern Spain: A qualitative study.
In Spain, the use of generics has considerably evolved in a short period of time through different anti-crisis legislation changes. Before the financial crisis the proposal of generics was an option for patients. Nowadays its use is actively enforced by Health authorities. To explore the perceptions of pharmacists and physicians regarding the generic substitution driven by new Spanish drugs policies as well as their adaptive strategies intended to lessen the impact of changes to their patients' treatment. Pharmacists (16) and physicians (13) from Ferrol and A Coruña participated in a qualitative study using semi-structured in-depth interviews. Qualitative analysis allowed identification of nine key components in the substitution process: Enabling factors: 'Adequate information to patients', 'Acute treatments', 'Bioappearance', 'Prescription by Estate Official Denomination followed by laboratory name', 'Personalized dosage systems'. Obstructing factors: 'Generics/Authorities distrust', 'Lack of time', 'Patient characteristics', 'Pharmacy financial management'. Pharmacists and physicians in our economic crisis context perceive different barriers resulting in difficulties in the generic substitution process. They have implemented strategies to capitalize on the enablers and overcome the additional budget-cut barriers imposed by the Administration that had prevented them from maintaining their patient's treatment preferences. Spanish health authorities could improve current legislation either by reducing the number of new laboratories of authorized generic manufacturers or by extending the pharmacist capability for equivalent drugs substitution.


Fourier transform-infrared microspectroscopy and microscopic imaging.
For age- and sex-matched subjects, osteoporotic bone is more fragile than healthy bone. Vibrational infrared spectroscopy and in particular infrared microspectroscopic imaging is a useful tool for investigating and characterizing changes associated with metabolic bone diseases including osteoporosis in biopsied tissues. Strength-related measures such as bone mineral content/composition as well as spectroscopically determined bone quality-related measures such as mineral crystallinity, carbonate substitution, and collagen cross-linking consequently differ between osteoporotic patients and normal subjects. Validated IR parameters specific to the mineral and matrix components of bone have been defined and can now be used to quantify anatomical/spatial variations and the effect of new therapies on osteoporotic bone.


Pharmacokinetic behavior of ciprofloxacin both in native cardiac and porcine valves treated in glutaraldehyde.
When judging a probable therapeutic success for antibiotic management of bioprosthetic endocarditis, sufficient drug levels in heterologous valve tissues play a very important role. The pharmacokinetic behavior of ciprofloxacin was investigated in native and porcine valvular tissues and compared with plasma levels during a 90- to 120-min period of surgery. Analysis was carried out by HPLC using excised valvular tissues (Hancock T 505). In all, 15-20 patients were investigated in each group. The antibiotics were administered intravenously or per os. Tissue concentrations after onset of the procedures showed ciprofloxacin plasma concentrations of 2.09-0.47 micrograms g in the native and 3.98-1.99 micrograms/g in the heterologous valvular tissues.


The modulation of membrane fluidity by hydrogenation processes. III. The hydrogenation of biomembranes of spinach chloroplasts and a study of the effect of this on photosynthetic electron transport.
A method is reported for the in situ modification of the lipids of isolated spinach chloroplast membranes. The technique is based on a direct hydrogenation of the lipid double bonds in the presence of the catalyst, chlorotris(triphenylphosphine)rhodium (I). The pattern of hydrogenation achieved suggests that the catalyst distributes amongst all of the membranes. The polyunsaturated lipids within the membranes are hydrogenated at a faster rate and at an earlier stage than are the monoenoic lipids. Whilst addition of the catalyst to the chloroplast causes an initial 10--20% decrease in Hill activity, saturation of up to 40% of the double bonds present can be accomplished without causing further significant alterations in photosynthetic electron transport processes or marked morphological changes of the chloroplast structure as observed in the electron microscope.


Time to initiation of symptomatic treatment in untreated Parkinson disease in the Parkinson progression marker initiative cohort: A 10-year follow up.
Initiation of symptomatic therapy in Parkinson disease is a disease progression milestone, and its prediction is important. Previous studies were limited in duration and number of variables included in their predictive models. To identify predictors of time to initiation of symptomatic therapy in patients with PD not on treatment, using a large pool of candidate variables from the Parkinson's Progression Markers Initiative dataset, analyzed at ten years. Kaplan Meier survival curve was used to estimate time to initiation of symptomatic treatment. Potential predictors included 33 baseline clinical, imaging, biofluid, and genetic biomarkers. Univariate Cox regression was used for variable selection, significant predictors subsequently entering a multivariate Cox proportional hazard model, which was further reduced using the Akaike Information Criterion into a final reduced model. Of 425 participants with Parkinson's Disease, 406 initiated symptomatic therapy at last follow up. The outcome was censored for 4.5% of the sample. The risk of initiating symptomatic therapy was 65% (95%CI 60-70%) within the first year from enrollment. Predictors included dopamine transporter SPECT, the Movement Disorders Society Unified Parkinson Disease Rating Scale, and anxiety (State Trait Anxiety Inventory). Baseline dopamine transporter SPECT specific binding ratio was found to be the most impactful predictor for time to initiation of symptomatic therapy in this 10-year follow up analysis of the Progressive Parkinson Markers Initiative cohort, when treatment status was known for 95.5% of the sample.


On the use of the Positive and Negative Syndrome Scale in randomized clinical trials.
In the last 25 years, the Positive and Negative Syndrome Scale (PANSS) has been largely used to assess schizophrenia symptom intensity, but little information is available on how this scale was generally applied when evaluating the efficacy of schizophrenia therapies in randomized clinical trials. In the attempt to address this topic, a systematic PubMed Search was carried out using the keywords "PANSS" and "Randomized Clinical Trials". The analysis of retrieved articles highlighted that PANSS has constituted a suitable psychometric instrument to investigate the efficacy of pharmacological and non-pharmacological therapies. However, the information potentially provided by this scale was only partially reported in research articles, when characterizing the symptomatic features of patients at baseline. Furthermore, a consensus is needed to identify methodological strategies that may properly adapt PANSS-subscale structure with the symptomatic profiles of individuals enrolled in randomized controlled trials. The possibility that PANSS interview procedures and enrollment eligibility criteria may influence the symptomatic composition of patients involved in these studies is also discussed.


Incidence and spontaneous resolution of postpartum bacteriuria.
On the first postpartum day, 53 patients (17.2 per cent) had asymptomatic bacteriuria. Spontaneous resolution of bacteriuria occurred in 40 (75.5 per cent) of the 53 patients by the third postpartum day--the most appropriate time to identify patients with true asymptomatic bacteriuria.


The differential response to chemotherapy of ovarian metastases from colorectal carcinoma.
All patients with metastatic (ovarian and extraovarian) CRC who underwent resection of ovarian metastases in our institution from April 1988 to August 2006 were analyzed and the response to preoperative chemotherapy was evaluated according to the RECIST criteria, and analyzed with respect to the sites of metastases (ovarian and extraovarian). The studied population consisted of 23 women. At presentation, 20 patients had symptoms. Preoperative chemotherapy resulted in tumor control of measurable extraovarian metastases in 65% of cases. In contrast, no objective tumor response of ovarian metastases was observed, disease stabilization was obtained in only 3 patients (13%), and progression or occurrence of new ovarian metastases were observed in 20 patients (87%) (p=0.0005). With a median follow-up of 54 months [15-229], median overall survival was 30 months, and 3-year overall survival was 18%. Ovarian metastases are less responsive to chemotherapy compared to other sites. As these "metastatic sanctuaries" often cause symptoms, surgical resection should always be considered for ovarian metastases, even in the case of associated extraovarian metastases.


Recent advances in hyaluronic acid hydrogels for biomedical applications.
Hyaluronic acid (HA) is widely used in the design of engineered hydrogels, due to its biofunctionality, as well as numerous sites for modification with reactive groups. There are now widespread examples of modified HA macromers that form either covalent or physical hydrogels through crosslinking reactions such as with click chemistry or supramolecular assemblies of guest-host pairs. HA hydrogels range from relatively static matrices to those that exhibit spatiotemporally dynamic properties through external triggers like light. Such hydrogels are being explored for the culture of cells in vitro, as carriers for cells in vivo, or to deliver therapeutics, including in an environmentally responsive manner. The future will bring new examples of HA hydrogels due to the synthetic diversity of HA.


Myocardial revascularization with combined aortic and mitral valve replacements.
Although the results of coronary artery bypass grafting plus single aortic or mitral valve replacement have been documented, the risk of myocardial revascularization with combined aortic and mitral valve replacement is not well defined. We present a series of 33 consecutive patients undergoing myocardial revascularization with combined aortic and mitral valve replacement during a period of almost seven years. There were 21 men and 12 women with a mean age of 67 years. All patients had congestive heart failure, and 21 (64%) had angina pectoris. Mean New York Heart Association functional classification was 3.4; eight patients (24%) had ejection fractions less than 0.40, and 13 patients (41%) had cardiac indices less than 2.0 L/min/m2. All operations were performed with hypothermic crystalloid potassium cardioplegia. The number of coronary arteries grafted varied from one to four (mean, 1.7 grafts per patient). Four patients died while in the hospital (12.1%). There were no perioperative myocardial infarctions. At a follow-up of 2 to 80 months (mean 40.7 months), death had occurred in eight (27.6%) of the 29 hospital survivors. Actuarial survival rate at 72 months was 60.7%. Although no preoperative factors predicted late death, early deaths were related significantly to severe mitral regurgitation, low ejection fraction, high New York Heart Association classification and extensive coronary artery disease (p less than 0.05). Myocardial revascularization with combined aortic and mitral valve replacement can be performed with an acceptable early mortality rate but with an appreciable late mortality rate.


Determination of pancreatic carboxypeptidase A in human blood serum.
A method has been designed for the assay of pancreatic carboxypeptidase A in blood serum. It uses Z-Gly-Phe as the substrate and fluorimetric determination of the released phenylalanine in an amino acid analyser, which yields a measure of free carboxypeptidase A. In addition, the sum (free carboxypeptidase A + procarboxypeptidase A) can be determined on a second portion preincubated with trypsin, which converts the proenzyme to the active form. Determinations made in fifteen healthy individuals showed the presence of a measurable concentration of free carboxypeptidase A. In acute pancreatitis, total carboxypeptidase A is raised. An increase in circulating proenzyme is observed in some cases. Data from 46 patients show a good correlation between total carboxypeptidase A, lipase and immunoreactive trypsin. Differential determination of procarboxypeptidase A and free carboxypeptidase A provides an interesting new tool for the diagnosis of pancreatic disorders.


A new brain positron emission tomography scanner with semiconductor detectors for target volume delineation and radiotherapy treatment planning in patients with nasopharyngeal carcinoma.
We compared two treatment planning methods for stereotactic boost for treating nasopharyngeal carcinoma (NPC): the use of conventional whole-body bismuth germanate (BGO) scintillator positron emission tomography (PET(CONV)WB) versus the new brain (BR) PET system using semiconductor detectors (PET(NEW)BR). Twelve patients with NPC were enrolled in this study. [(18)F]Fluorodeoxyglucose-PET images were acquired using both the PET(NEW)BR and the PET(CONV)WB system on the same day. Computed tomography (CT) and two PET data sets were transferred to a treatment planning system, and the PET(CONV)WB and PET(NEW)BR images were coregistered with the same set of CT images. Window width and level values for all PET images were fixed at 3000 and 300, respectively. The gross tumor volume (GTV) was visually delineated on PET images by using either PET(CONV)WB (GTV(CONV)) images or PET(NEW)BR (GTV(NEW)) images. Assuming a stereotactic radiotherapy boost of 7 ports, the prescribed dose delivered to 95% of the planning target volume (PTV) was set to 2000 cGy in 4 fractions. The average absolute volume (±standard deviation [SD]) of GTV(NEW) was 15.7 ml (±9.9) ml, and that of GTV(CONV) was 34.0 (±20.5) ml. The average GTV(NEW) was significantly smaller than that of GTV(CONV) (p = 0.0006). There was no statistically significant difference between the maximum dose (p = 0.0585) and the mean dose (p = 0.2748) of PTV. The radiotherapy treatment plan based on the new gross tumor volume (PLAN(NEW)) significantly reduced maximum doses to the cerebrum and cerebellum (p = 0.0418) and to brain stem (p = 0.0041). Results of the present study suggest that the new brain PET system using semiconductor detectors can provide more accurate tumor delineation than the conventional whole-body BGO PET system and may be an important tool for functional and molecular radiotherapy treatment planning.


Marked variation in free radical injury between bovine and porcine endothelial cells cultured in different media.
Previous studies produced models of oxygen-derived free radical (OFR) injury, using H(2)O(2) or xanthine/xanthine oxidase (X/XO), in cultured porcine aortic endothelium (PAE) and rat coronary endothelium. H(2)O(2) at 0.1 mM resulted in 50% viability in both cell types. To determine if comparable H(2)O(2) or X/XO concentrations have the same injurious effect on endothelium from other sources, models of OFR injury were developed for bovine aortic endothelium (BAE) and bovine brain microvessel endothelium (BBME). Varying concentrations of H(2)O(2) (0.01 to 6 mM) or X/XO (10 microM/0.1 to 0.3 U/mL) were added to medium 24 h prior to evaluating cell damage. Injury was assessed using the Trypan blue exclusion test (% viability) and by measuring the release of lactate dehydrogenase into medium. H(2)O(2) concentrations required to produce 50% viability were >6 mM in BAE and BBME versus 1 mM in PAE when cells were grown in Dulbecco's modified Eagle's medium (DMEM). Similarly, BAE and BBME were less sensitive than PAE to damage by X/XO. Cells from both species were more sensitive to H(2)O(2) or X/XO injury when grown in Medium 199 (M199) versus DMEM. The most profound difference was observed with PAE where 50% viability was obtained with 0.12 versus 1.05 mM H(2)O(2) in M199 versus DMEM. These results indicate that bovine endothelial cells from aorta and brain are more resistant to free radical injury than PAE. The presence or absence of key media components (iron, pyruvate, cysteine, histidine) likely influences the extent of OFR injury.


The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.
The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.


PROVE-IT proved it: lower is better--pro.
Data from prospective epidemiological studies and randomized controlled trials have clearly demonstrated that lower low density lipoprotein cholesterol (LDL-C) concentrations are associated with the greatest reduction in cardiovascular events. Coronary artery disease mortality is lowest in epidemiological studies in those individuals with the lowest cholesterol concentrations. In angiographic studies, patients who had their cholesterol lowered had less angiographic worsening of their atherosclerosis, with those trials that had the lowest on-treatment LDL-C, and especially those that had the greatest percentage of LDL-C lowering, showed the least progression of atherosclerosis. Clinical trials have also highlighted the fact that lower LDL-C concentrations are associated with reduced risk for both a first and a subsequent coronary event with analyses showing that event rates in both primary and secondary prevention trials are directly proportional to on-treatment LDL-C concentrations. An aggressive approach to LDL-C lowering, especially in the high-risk patient, seems warranted.


A Case of Urethrocutaneous Fistula: A Forgotten Segment of a Broken Urethral Catheter.
A retained urethral catheter is a rare iatrogenic complication of which few cases have been reported in the literature. In this study, we describe a case of a forgotten urethral Foley catheter causing urethracutaneous fistula on scrotum. An 80-year-old man was referred for a small pus-draining cutaneous opening on the lower part of the scrotum. The distal segment of a broken Foley catheter was found, and it was located from urinary bladder to bulbous urethra with its tip penetrating the urethral mucosa. This catheter was removed using flexible cystoscopic forceps, and urethracutaneous fistula was well resolved with conservative therapy.


HIV Prevention Tools Across the Pregnancy Continuum: What Works, What Does Not, and What Can We Do Differently?
Multiple tools exist to support the primary prevention of HIV in pregnant and postpartum women; however, there are opportunities to enhance their use and impact. This review summarizes the current status of HIV prevention tools and existing gaps and opportunities to improve their use along the pregnancy care continuum. HIV screening efforts have steadily improved with close to universal screening of pregnant women in several East and Southern African countries. Strategies to implement partner testing through the distribution of HIV self-test kits are promising though linkage to care remains challenging. Syphilis screening rates are increasing though detection of other sexually transmitted infections could benefit from improved diagnostic capacity. Male and female condoms are rarely used and are often not the optimal tool of choice during pregnancy. Oral pre-exposure prophylaxis (PrEP) is a promising tool, although barriers such as the need for daily adherence, side effects, and stigma may limit its use. There is a growing pipeline of PrEP agents with alternative delivery platforms that might suit women's preferences better and supports the notion that choice is vital to improving HIV prevention coverage during the pregnancy-postpartum continuum. Clear guidance on which tools to use and how to use them, safety data supporting their use, and surveillance data documenting the scale and effectiveness of the tools will be imperative in establishing a path to more impactful prevention efforts among pregnant and postpartum women.


High-performance liquid chromatographic separation of enantiomers and diastereomers of 2-methylcyclohexanone thiosemicarbazone, and determination of absolute configuration and configurational stability.
Simultaneous HPLC diastereo- and enantioseparations of 2-methylcyclohexanone thiosemicarbazone (2-MCET) were accomplished on coated- and immobilized type polysaccharide-based chiral stationary phases (CSPs). The identification of all stereoisomeric forms and their stereochemistry were achieved by combining theoretical, HPLC and chiroptical data. The stereochemical stability of the target compound was studied by classical off-column and dynamic HPLC kinetic procedures and the influence of different parameters such solvent, TFA concentration and temperature on stereoisomerization process was evaluated. The findings obtained by chromatographic and kinetic experiments were used to develop a simple method to convert the racemic form of 2-MCET into a single enantiomer.


Merging the Interfaces of Different Shape-Shifting Polymers Using Hybrid Exchange Reactions.
Sophisticated shape-shifting structures and integration of advanced functions often call for different-chemistry-based polymers (such as epoxy and polyurethane) in a unified system. However, permanent cross-links pose crucial obstacles to be seamless. Here, merging interfaces via hybrid exchange reactions among different dynamic covalent bonds (including ester, urethane, thiourethane, boronic-ester, and oxime-ester linkages) is proposed, breaking the long-lasting restriction that these widely used bonds only undergo self-exchange reactions. Model compound studies are conducted to verify that hybrid exchange reactions occur. As demonstrations, different liquid crystal elastomers are tenaciously joined into coherent assemblies, with the desired biomimetic structures (e.g., flying fish containing stiff and flexible parts) and rare deformation modes (e.g., flower blooming upon both heating and cooling). Besides connecting polymers, hybrid exchange reactions also facilitate the creation of new materials through cross-fusion of different polymers. In addition to the polymers used in this work, hybrid exchange reactions can be adapted to other polymers based on similar mechanisms and beyond. Besides shape-shifting-related areas (e.g., soft robots, flexible electronics, and biomedical devices), it may also foster innovation in other fields involving general polymers, as well as promote deeper understanding of dynamic covalent chemistry.


DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)](2+) and [Pt(bpy)(miip)](2.).
Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)2 (1) and [Pt(bpy)(miip)](PF6)2·2H2O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, (1)H NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K b = 3.55 ± 0.6 × 10(4) M(-1) and 7.01 ± 0.9 × 10(4) M(-1) for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.


On metabolic shift to lactate consumption in fed-batch culture of mammalian cells.
Fedbatch culture is the prevalent cell cultivation method in producing protein therapeutics. A metabolic shift to lactate consumption in late stage of cultivation has been shown to extend the culture viability and increase product concentrations. To better understand the factors, which trigger metabolic shift we performed transcriptome and metabolic flux analysis on a fedbatch culture of mouse myeloma cell line (NS0) and developed a mechanistic kinetic model for energy metabolism. Experimental observation indicates that the shift to lactate consumption occurs upon the cessation of rapid growth and under conditions of low glycolysis flux and high extracellular lactate concentrations. Although the transition is accompanied by a general down regulation of enzymes in energy metabolism, that alone was insufficient to elicit a metabolic shift. High lactate level has been reported to exert an inhibitory effect on glycolysis enzyme phosphofructokinase; model simulation suggests that a high lactate level can contribute to reduced glycolytic flux as well as providing a driving force for its conversion to pyruvate. The transcriptome data indicate that moderate alteration in the transcript levels of AKT1 and P53 signaling pathways genes occurs in the late stage of culture. These signaling pathways are known to regulate glycolytic activity. Model simulations further suggest that AKT1 signaling plays a key role in facilitating lactate consumption. Collectively, our results strongly suggest that lactate consumption in fedbatch culture is an outcome of reduced glycolysis flux, which is a product of lactate inhibition and regulatory action of signaling pathway caused by reduced growth rate.


Expression of HAb18G/CD147 and its localization correlate with the progression and poor prognosis of non-small cell lung cancer.
This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p<0.05) in squamous cell carcinoma. In adenocarcinomas, HAb18G/CD147 expression was associated with male gender, tumor diameter, differentiation, lymph node status, distant metastasis status, and clinical stage (p<0.05). HAb18G/CD147 expression with higher PU was predominantly localized in the tumor cell membranes rather than in cytoplasms. In squamous cell carcinomas, membranous localization of HAb18G/CD147 was linked to distant metastasis status and TNM stage (p<0.05). Cytoplasmic localization of HAb18G/CD147 was associated with male gender and smoking history. In adenocarcinomas, membranous localization of HAb18G/CD147 correlated with tumor diameter, differentiation and distant metastasis (p<0.05). Univariate analysis indicated that patients with high HAb18G/CD147 expression and membranous localization predicted poor prognosis in both squamous cell carcinomas and adenocarcinomas. Multivariate analysis showed that lymph node status (HR=1.762, 95%CI 1.105-2.811, p=0.017), distant metastasis status (HR=3.789, 95%CI 2.196-6.539, p=0.000), expression (HR=6.632, 95%CI 2.457-17.904, p=0.000), and localization (HR=0.520, 95%CI 0.341-0.794, p=0.002) were good or excellent independent predictors of patient survival. HAb18G/CD147 is a biomarker characterizing progression and survival of NSCLC. More importantly, its cellular localizations should be considered in the analysis of clinicopathological characteristics and prognostic factors in NSCLC.


Artificial intelligence for ocular oncology.
The aim of this article is to provide an update on the latest applications of deep learning (DL) and classical machine learning (ML) techniques to the detection and prognostication of intraocular and ocular surface malignancies. Most recent studies focused on using DL and classical ML techniques for prognostication purposes in patients with uveal melanoma (UM). DL has emerged as the leading ML technique for prognostication in ocular oncological conditions, particularly in UM. However, the application of DL may be limited by the relatively rarity of these conditions.


Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments.
Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments. The data are consistent with the hypothesis that the skeletal effects of lithium are not mediated via inhibition of the parathyroid hormone-adenyl cyclase-cyclic AMP system.


A study of mechanisms responsible for incorporation of cesium and radiocesium into fruitbodies of king oyster mushroom (Pleurotus eryngii).
Ex vitro cultures of Pleurotus eryngii were carried out under controlled conditions using sterile medium composed of barley seeds. The influence of alkali and alkaline earth element salts (CsCl, KCl, NaCl, RbCl, and CaCl(2)) and tetraethylammonium chloride on incorporation of cesium, potassium, sodium, rubidium and calcium, and their distribution within fruitbodies, was examined. The results show that incorporation of cesium into fruitbodies was not suppressed by Na(+) and Rb(+) or tetraethylammonium chloride. However, it was inhibited by Ca(2+) and stimulated by high concentrations of K(+). The inhibition of cesium incorporation by Ca(2+), lack of influence of tetraethylammonium chloride and stimulation by high K(+) concentrations suggest that there may exist two pathways of passive transport of cesium in mycelium: (i) uptake mediated by a non-specific potassium channel localised in plasmalemma (similar to voltage-insensitive cation channel, VICC) followed by diffusive transport inside hyphae and (ii) extracellular transport from the medium through inter-hyphal cavities into fruitbodies. The results highlight distinctiveness of mechanisms responsible for the uptake and incorporation of cesium in mushrooms and plants.


Distinct kinetic properties of cardiac myosin isoforms revealed by in vitro studies.
To clarify the physiological significance of myosin isoform redistribution in cardiac adaptation process, we compared the kinetic property of the two cardiac myosin isoforms using in vitro motility assay techniques. Cardiac myosin isoforms V1 and V3 were obtained from ventricular muscle of young rats and hypothyroid rats respectively. On each of these myosin isoforms fixed on a glass coverslip, fluorescently labeled actin filaments were made to slide in the presence of ATP. To measure the force generated by actomyosin interaction, a small latex bead was attached to the barbed end of an actin filament and the bead was captured by the laser optical trap installed in a microscope. The force was determined from the distance between the bead and the trap positions under either auxotonic or isometric conditions. The time-averaged force generated by multiple cross-bridges did not differ significantly between the two isoforms. On the other hand, the unitary force measurement revealed the same level of amplitude but a longer duration for V3 isoform. The same level of time-averaged force is in agreement with not only our previous finding but the results of maximum force measurement in muscle preparations. The difference in kinetic characteristics of the two isoforms could account for the difference in economy of force development and the basis for cardiac adaptation mechanism.


Thickness influence of veneering composites on fiber-reinforced systems.
Short fiber reinforced composites (SFRC) require a veneering layer of conventional composite when used as restorations in the oral environment. The current study investigates the toughening effects during the path of a preexisting crack propagating through the bilayer system as it confronts the interface, through the attempted alignment of fibers and matrix-fiber interactions in the SFRC, and the distance it travels in the SFRC. Bilayer systems of SFRC and conventional composite were produced with aligned fibers perpendicular to load direction. Single-edge-notched bend (SENB) specimens (25 × 5 × 2.5 mm3) with pre-crack length (a) to width (W) ratios (a/W = 0.2-0.8) were produced and tested in 3-point bending configuration until complete fracture. The specific work of fracture (we) was deduced from calculating the area under the load-displacement curves. Fiber alignment was digitally evaluated from images taken from the top and side planes of the specimen. The toughness of the bilayer system is optimal when maximum SFRC thickness is used. EWF methods showed toughness and increasing nonessential work of fracture scaling with ligament length. A longer distance is accompanied by a higher distribution of aligned fibers bridging behind the crack wake, reducing crack driving forces at the crack tip. SFRC materials provide increasing toughening potential with increasing thickness, and have the ability to be more anisotropic than other composite materials. Clinically, the layer must have a conventional composite cover layer, but which thickness does not affect toughness potential. Therefore the thickness of the conventional composite can be dictated by wear behavior.


In vivo assessment of the Combat Ready Clamp to control junctional hemorrhage in swine.
Junctional wounds and associated hemorrhage have become more common and more lethal in the current war. The Combat Ready Clamp (CRoC) has been developed and deployed for treating junctional hemorrhage on the battlefield. This study examined the efficacy of CRoC and its acute effects in an animal model. Anesthetized pigs (n = 6) were subjected to laparotomy, splenectomy, and abdominal closure. Next, coagulopathy was induced in animals by hemodilution and hypothermia. The left femoral artery was isolated, punctured (6-mm hole), and allowed to bleed for 15 seconds. The groin wound was packed with gauze, and a CRoC applied and tightened until hemorrhage stopped. It was kept in place for 1 hour (treatment period) and then released for another hour or less (control-period) if animal exsanguinated. Fluid resuscitation was administered, and vascular blood flow was examined by Doppler and CT scans. After death, local tissues were collected for histology. CRoC generated 800 to 900 mm Hg pressure on the wounds, which stopped the hemorrhage and prevented rebleeding during the first hour in all animals. Blood loss was minimal (≤137 mL), and mean arterial pressure remained at or higher than the target level (65 mm Hg) during this period. Removal of the clamp promptly led to rebleeding and exsanguination of five of six pigs during the second hour despite fluid resuscitation. Blood loss, survival, shock indices, and other measures were significantly (p < 0.01) different between the two periods. Doppler tests and CT scans showed no blood flow in the proximal, distal, and collateral arteries of the clamped leg. Minor inflammation was seen on blood vessels (endothelium) and nerves. CRoC functioned as an effective hemostatic adjunct for compression and control of groin hemorrhage. Although no acute histological damages were seen in compressed tissues, the short- and long-term effects of CRoC application (e.g., total ischemia) on limb function remain unknown and warrant investigation.


The nature content and interpractice variation of general practice: a regional study in Italy.
The activity of 34 general practitioners (GP) working in solo practices in six Local Health Units were assessed, as a preliminary step of a main study, to evaluate and possibly improve the quality of GP professional performance using peer review and feed-back information. A wide interpractice variation was observed in patient visit and patient visiting rates, drug and test prescribing, in- and out-patient referrals, as well as in the composition of the practice case-mix. The extent of interpractice variation for relevant actions in the process of care was unchanged after adjusting for case-mix, suggesting that case-mix differences have little effect in explaining differences among physicians' overall pattern of care and health care resource consumptions.


Excess mortality of acute and transient psychotic disorders: comparison with bipolar affective disorder and schizophrenia.
To investigate mortality and causes of death of short-lived psychotic disorders, by carrying out a comparison with bipolar disorder and schizophrenia. Record linkage study to the official register of causes of death of all cases aged 15-64 years who were listed for the first time in the Danish Psychiatric Register between 1995 and 2008 with an ICD-10 diagnosis of 'acute and transient psychotic disorders' (ATPDs; n = 4157), bipolar disorder (n = 3200) and schizophrenia (n = 4576). A total of 232 patients (5.6%) with ATPDs, 172 (5.4%) with bipolar disorder and 233 (5.1%) with schizophrenia had died over a mean follow-up period of 6.6 years. The standardized mortality ratio for all causes, natural causes and unnatural causes was significantly high for the three conditions. Mortality of ATPDs was greater in men, with about two-thirds of all deaths resulting from natural causes mainly cardiovascular, digestive, neoplastic and respiratory diseases. Suicide was the major cause of premature death in patients with ATPDs. These findings suggest that ATPDs are associated with an increased mortality from both natural causes and suicide.


Investigation of the awareness of and demand for hospice care and attitudes towards life-sustaining treatment at the end of life among community residents in Hangzhou.
To understand the status of residents' awareness of and demand for hospice care services in Hangzhou and to provide a reference for promoting the formulation of hospice care-related policies in China. A small cross-sectional survey of 519 adults aged over 40 years old living in the rural-urban fringe and urban area of Xihu District, Hangzhou City, was conducted using convenience sampling and a self-designed questionnaire. The measures assessed awareness of hospice care (13-item scale), attitudes towards life support therapy (3-item scale), and demand for hospice care services (9-item scale). The rate of awareness of hospice care among community residents was 50.30%. A total of 51.0% of residents wanted only comfortable life-sustaining treatment at the end of their lives. The acceptance of hospice care was positively correlated with the degree of understanding (x2 = 18.382, P = 0.001), and residents in the urban area were more likely to prefer hospice care than residents in the urban-rural fringe (x2 = 7.186, P = 0.028). Elderly residents showed a stronger tendency to prefer comfortable life support therapy (x2 = 12.988, P < 0.001). A total of 83.04% of the residents accepted the current necessity for hospice care to be provided in medical institutions. The preferred locations were professional hospice care institutions or general hospitals. A total of 93.64% of the residents agreed that the number of beds in hospice care wards should not exceed 2. In addition, the residents could afford part of the out-of-pocket expenses for hospice care services, with the ability to pay under 200 yuan per day, and the improvement of facilities was expected. To improve public awareness and acceptance of hospice care and promote healthy development in China, it is necessary to promote hospice care education for everyone.


[Assessment of a software application tool for managing nursing care processes in the period 2005-2010].
To identify problems and critical points in the software application. Assessment of the implementation of the software tool "Azahar" used to manage nursing care processes. The monitored population consisted of nurses who were users of the tool, at the Hospital and those who benefited from it in Primary Care. Each group was selected randomly and the number was determined by data saturation. A qualitative approach was employed using in-depth interviews and group discussion as data collection techniques. The nurses considered that the most beneficial and useful application of the tool was the initial assessment and the continuity of care release forms, as well as the recording of all data on the nursing process to ensure quality. The disadvantages and weaknesses identified were associated with the continuous variability in their daily care. The nurses related an increase in workload with the impossibility of entering the records into the computer, making paper records, thus duplicating the recording process. Likewise, they consider that the operating system of the software should be improved in terms of simplicity and functionality. The simplicity of the tool and the adjustment of workloads would favour its use and as a result, continuity of care.


Multiple fluorescence polymer dots-based differential array sensors for highly efficient heavy metal ions detection.
Water pollution caused by harmful heavy metal ions (HMIs) can significantly impact aquatic ecosystems and pose a high risk to human health. In this work, equipped with ultra-high fluorescence brightness, efficient energy transfer, and environmentally friendly performance, polymer dots (Pdots) were employed to construct a pattern recognition fluorescent HMIs detection platform. A single-channel unary Pdots differential sensing array was first developed to identify multiple HMIs with 100% classification accuracy. Then an "all-in-one" multiple Förster resonance energy transfer (FRET) Pdots differential sensing platform was constructed to discriminate HMIs in the artificial polluted water samples and actual water samples, exhibiting high classification accuracy in distinguishing HMIs. The proposed strategy leverages the compounded cumulative differential variation of diverse sensing channels for analytes, which is anticipated to find extensive applications in other fields for detection purposes.


Streptolytic activities of a lytic enzyme from Staphylococcus hyicus.
The LE IIIb fraction of the bacteriolytic enzyme from Staphylococcus hyicus could be isolated by ionic exchange chromatography and subsequent gel filtration. Isoelectric focusing of the highly purified enzyme preparation revealed an isoelectric point at pH 10.3. The lytic activity of LE IIIb on streptococci of various serogroups could be effectively analyzed with the help of an aggregometer and expressed as increase of transmittance at 546 nm. The streptococci differed in their LE IIIb lysis pattern, which was more pronounced with those of serological groups C and D and Streptococcus uberis. The lytic effect of the LE IIIb fraction was optimal at low molarity (0.01 mol/l) of the lysis buffer and reduced in the presence of HgCl2 and EDTA.


Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery.
We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be. ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric oxide-sensitive fluorescent dye diaminofluorescein-2) within the endothelial cells of rabbit mesenteric resistance arteries. This effect was significantly smaller in arteries isolated from NTG-treated rabbits than in those from control rabbits. The reduction in endothelial [NO]i in NTG-treated rabbits was prevented when olmesartan (blocker of type 1 angiotensin II receptors (AT1Rs)) was coadministered in vivo with NTG and also when the superoxide scavenger manganese (III) tetrakis-(4-benzoic acid) porphyrin (Mn-TBAP), the protein kinase C (PKC) inhibitor GF109203X or L-arginine (with or without the active form of folate (5-methyltetrahydrofolate)) was incubated with the arteries in vitro. Endothelial cell superoxide production (estimated by ethidium fluorescence) was greatly increased in arteries from NTG-treated rabbits. This was normalized by in vivo coadministration of olmesartan with NTG and also by in vitro application of Mn-TBAP or GF109203X (but not of 5-methyltetrahydrofolate+L-arginine). ACh increased the intracellular Ca2+ concentration (estimated using the Ca2+-sensitive dye Fura 2) within endothelial cells, the increase being not significantly different between NTG-treated rabbits and control rabbits. We conclude that in NTG-treated rabbits, endothelial nitric oxide production in mesenteric resistance arteries is reduced, possibly through a reduction in the bioavailability of L-arginine via an action mediated by superoxide. Activation of the AT1R-PKC pathway may be involved in increasing superoxide production.


Stereospecific radioimmunoassays for l-ephedrine and d-ephedrine in human plasma.
Haptens were prepared by the reaction of d-ephedrine or l-ephedrine with methyl acrylate and subsequent alkaline hydrolysis of the methyl ester groups. The haptens were coupled to bovine serum albumin by a mixed anhydride method, and the resulting drug-protein conjugates were used to immunize rabbits. Antisera raised to these conjugates were highly stereospecific. Neither antiserum cross-reacted with the optical antipode of its substrate nor with racemic pseudoephedrine. Separate radioimmunoassays (RIAs), developed for d-ephedrine and l-ephedrine, were used to measure the concentrations of the enantiomers of ephedrine in the blood of two volunteers dosed with racemic ephedrine. The RIAs were validated by comparing the sum of the concentrations of the enantiomers, determined by RIA, with total ephedrine concentrations determined by a nonstereoselective GLC-ECD method.


False positive findings on liver scans in carcinoma of kidney.
In most urologic centers, liver scan is a routine investigation for evaluation of carcinoma of the kidney. Herein are described 3 patients with carcinoma of the right kidney, who had abnormal liver scans and did not show any metastases on exploration and open liver biopsy. These false positive findings were found to be due to the extrinsic compression of the liver by the tumor. When interpreting the liver sacn in a patient with renal tumor on the right side, the possibility of this false positive finding due to extrinsic compression to be considered and an abnormal hepatic scan alone should not be a contraindication for possible radical surgery.


Diagnosis and management of acute movement disorders.
Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders.Drug-induced movement disorders are mainly caused by dopamine-receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief. Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased. Neuroleptic Malignant Syndrome is a rare, but life-threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial. Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non-Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer. Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied by dysarthria and dystonia and usually respond to phenytoin. In Type 2 they can last for several hours, may be accompanied by vertigo, headache and malaise and usually respond to acetazolamide. Symptomatic episodic ataxias can occur in a number of metabolic disorders, but also in multiple sclerosis and Behcet's disease.


DLG1/SAP97 modulates transforming growth factor alpha bioavailability.
TGFalpha and its receptor EGFR participate in the development of a wide range of tumors including gliomas, the main adult primary brain tumors. TGFalpha soluble form results from the cleavage by the metalloprotease TACE/ADAM17 of the extracellular part of its transmembrane precursor, pro-TGFalpha. To gain insights into the mechanisms underlying TGFalpha bioavailability, a yeast two-hybrid screen was performed to identify proteins interacting with pro-TGFalpha intracellular domain (ICD). DLG1/SAP97 (Discs Large Gene 1 or Synapse Associated Protein 97) was found to interact with both pro-TGFalpha and TACE ICDs through distinct PDZ domains. An in vivo pro-TGFalpha-DLG1-TACE complex was detected in U251 glioma cells and in gliomas-derived tumor initiating cells. Interaction between DLG1 and TACE diminished in response to stimulations promoting pro-TGFalpha shedding. Manipulation of DLG1 levels revealed dual actions of DLG1 on pro-TGFalpha shedding, favoring approximation of pro-TGFalpha and TACE, while limiting TACE full shedding activity. These results show that DLG1 participates in the control of TGFalpha bioavailability through its dynamic interaction with the growth factor precursor and TACE.


Diallelic multilocus model of neutral genes.
The evolution of a completely linked diallelic multilocus system of neutral genes in a finite population is studied. A diffusion model incorporating random genetic drift and mutation is used. We neglect the recombination. To begin with, the spectral analysis of the Kolmogorov backward equation for this model is investigated. We apply this to two extreme situations when the number of sites approaches to infinity. One is a DeMoivre-Laplace type approximation and the other is a Poisson type approximation. The former is applied to the study of the simultaneous distribution and evolution of a large number of neutral genes. It is applicable to the distribution of a polygenic character controlled by clustered loci on a chromosome, and we show that it differs from the normal distribution on account of random genetic drift and linkage disequilibrium. The latter is applied to the distribution of the number of segregating sites in DNA nucleotide sequences, and the rate of evolution is obtained.


Current Pathology Model of Pancreatic Cancer.
Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated "cross-talk" that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients' outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis.