Monoclonal antibody production to a B16 melanoma associated antigen.
Eight different rat hybridoma cell lines have been produced which secrete MAbs identifying the melanoma-specific B700 antigen. This antigen has been previously shown to have significant sequence homology to the mammalian serum albumins, but antibodies specifically raised against B700 cross-react only with murine albumin. Each of these MAbs has been shown by Western immunoblotting to recognize an independent epitope on the B700 protein; it is concluded not only that the B700 protein is a highly immunogenic antigen, but also that the sequence homologies between the B700 antigen and murine albumin must occur extensively throughout the molecule.


Synthesis, Characterization, Antitubercular Activity, and Molecular Docking Studies of Pyrazolylpyrazoline-Clubbed Triazole and Tetrazole Hybrids.
To increase the antitubercular potency, we synthesized a series of novel pyrazolylpyrazoline derivatives (9a-p) using the one-pot multicomponent reaction of the substituted heteroaryl aldehyde (3a,b), 2-acetyl pyrrole/thiazole (4a,b), and substituted hydrazine hydrates (5-8) in the presence of base NaOH as a catalyst in ethanol as the solvent at room temperature. Substituted heteroaryl aldehyde (3a,b) was synthesized from 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-methyl-carbaldehyde on protection with ethylene glycol followed by treatment with 4-amino triazole/5-amino tetrazole and then deprotection using acid. The salient features of the green protocol are the one-pot reaction, shorter reaction time, and straightforward workup procedure. All of the compounds were tested against Mycobacterium tuberculosis H37Rv, wherein compounds 9i, 9k, 9l, 9o, and 9p were found to be most effective. The structures of newly synthesized compounds were determined using spectral methods. Furthermore, molecular docking investigations into the active site of mycobacterial InhA yielded well-clustered solutions for these compounds' binding modalities producing a binding affinity in the range from -8.884 to -7.113. Theoretical results were in good accord with the observed experimental values. The docking score of the most active compound 9o was found to be -8.884, and the Glide energy was -61.144 kcal/mol. and it was found to accommodate well into the active site of InhA, engaging in a network of bonded and nonbonded interactions.


SM22α inhibits vascular inflammation via stabilization of IκBα in vascular smooth muscle cells.
Smooth muscle (SM) 22α, an actin-binding protein, is down-regulated in atherosclerotic arteries. Disruption of SM22α promotes arterial inflammation through activation of reactive oxygen species (ROS)-mediated nuclear factor (NF)-κB pathways. This study aimed to investigate the mechanisms by which SM22α regulates vascular inflammatory response. The ligation injury model of SM22α(-/-) mice displayed up-regulation of inflammatory molecules MCP-1, VCAM-1, and ICAM-1 in the carotid arteries. Similar results were discovered in human atherosclerotic samples. In vitro studies, overexpression of SM22α attenuated TNF-α-induced IκBα phosphorylation and degradation, accompanied by decreased NF-κB activity and reduced inflammatory molecule expression. Using coimmunoprecipitation, we found that SM22α interacted with and stabilized IκBα in quiescent VSMCs. Upon TNF-α stimulation, SM22α was phosphorylated by casein kinase (CK) II at Thr139, leading to dissociation of SM22α from IκBα, followed by IκBα degradation and NF-κB activation. Our findings demonstrate that SM22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signaling cascades. SM22α may be a novel therapeutic target for human vascular diseases and other inflammatory conditions.


A mutant of Saccharomyces cerevisiae lacking catabolic NAD-specific glutamate dehydrogenase. Growth characteristics of the mutant and regulation of enzyme synthesis in the wild-type strain.
NAD-specific glutamate dehydrogenase (GDH-B) was induced in a wild-type strain derived of alpha-sigma 1278b by alpha-amino acids, the nitrogen of which according to known degradative pathways is transferred to 2-oxoglutarate. A recessive mutant (gdhB) devoid of GDH-B activity grew more slowly than the wild type if one of these amino acids was the sole source of nitrogen. Addition of ammonium chloride, glutamine, asparagine or serine to growth media with inducing alpha-amino acids as the main nitrogen source increased the growth rate of the gdhB mutant to the wild-type level and repressed GDH-B synthesis in the wild type. Arginine, urea and allantoin similarly increased the growth rate of the gdhB mutant and repressed GDH-B synthesis in the presence of glutamate, but not in the presence of aspartate, alanine or proline as the main nitrogen source. These observations are consistent with the view that GDH-B in vivo deaminates glutamate. Ammonium ions are required for the biosynthesis of glutamine, asparagine, arginine, histidine and purine and pyrimidine bases. Aspartate and alanine apparently are more potent inducers of GDH-B than glutamate. Anabolic NADP-specific glutamate dehydrogenase (GDH-A) can not fulfil the function of GDH-B in the gdhB mutant. This is concluded from the equal growth rates in glutamate, aspartate and proline media as observed with a gdhB mutant and with a gdhA, gdhB double mutant in which both glutamate dehydrogenases area lacking. The double mutant showed an anomalous growth behaviour, growth rates on several nitrogen sources being unexpectedly low.


Mutation in collagen gene induces cardiomyopathy in transgenic mice.
In many remodeling tissues, such as the heart, collagen degradation to provide new integrin-binding sites is required for survival. However, complete loss of integrin signaling due to disconnection from extracellular matrix (ECM) leads to apoptosis and dilatation. To test the hypothesis that a mutation in type I collagen gene induces cardiomyopathy, we employed a metalloproteinase-resistant collagen mutant homozygous transgenic male (B6,129-Colla-1) and compared with age-sex matched wildtype C57BL/J6 control mice. At the age of 38-42 weeks, aortic and left ventricle (LV) pressure were measured. The LV wall thickness and diameter were measured by a digital micrometer. The levels of matrix metalloproteinase-2 (MMP-2) activity and cardiospecific tissue inhibitor of metalloproteinase-4 (TIMP-4) were measured by zymography and Western blot analyses, respectively. The levels of collagenolysis were measured by Western blot using anti-collagen antibody. In transgenic and wildtype mice, end-diastolic pressure (EDP) was 8.3 +/- 1.7 and 6.5 +/- 1.1 mmHg; LV diameter was 3.43 +/- 0.07 and 2.94 +/- 0.05 mm; wall thickness was 1.18 +/- 0.03 and 1.28 +/- 0.04 mm; end-diastolic wall stress was 600 +/- 158 and 347 +/- 49 dynes/cm(2), respectively. The increase in LV wall stress was associated with increased MMP-2 activity, increased collagenolysis, and decreased levels of TIMP-4. This leads to reduced elastic compliance in collagen mutant transgenic mice. The occurrence of cardiomyopathy in adult Colla-1 mice may be a significant confounding factor as it may be indicative of increased basal levels of ECM disruption. This phenotype is what would be expected if collagen degradation normally supplies integrin ligands during cardiac muscle remodeling.


Infected donors in renal transplantation: expanding the donor pool.
The shortage of suitable organ donors is now the most important limiting factor in the field of transplantation and more expanded criteria have been accepted to overcome this problem. The objectives of this study were to evaluate the outcome of patients who received an organ from an infected donor and to compare them with patients who received organs from noninfected donors. Retrospective analysis of all patients who underwent transplantation in our unit between January 2008 and June 2011 was performed. The definition of infected donor included: (1) documented bacteremia at the time of transplantation; and (2) organ-related infection, either with or without isolation from biological products (urine, liquor, and bronchial secretions). Nineteen of 77 transplant recipients (24.7%) received organs from infected donors. There were 9 cases of pneumonia, 4 cases of meningitis with bacteremia, 5 cases of urinary tract infection, 1 case of bacteremia due to Staphylococcus aureus, and 1 case of ventriculo-peritoneal shunt infection. All these recipients were prescribed antibiotic prophylaxis for 10.9 ± 3.2 days, according to the antibiotic administered to the donor. Significant differences between both groups were not observed concerning demographics features, graft thrombosis, arterial disruption, delayed graft function, rejection episodes, and renal graft and patient survivals at 12 months. The recipients of infected donor kidneys were mostly treated with basiliximab for induction therapy. There was a trend toward fewer infectious complications among patients who received organs from infected donors (21.1% vs 44.8%; P = .065) and shorter hospital stay durations (median, 11 vs 17.5 days; P = .041). Kidney transplantation using organs from infected donors did not seem to be associated with a greater risk of complications. Antibiotic therapy initiated in the donor and continued in the recipient may explain these results, perhaps by reducing infectious complications that necessarily prolong the hospital stay.


Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study.
There is evidence that mast cells are involved in a number of pathophysiological processes. The significance of mast cells in hepatic fibrosis was examined in 28 patients with histologically normal livers, 34 with acute liver diseases, 51 with chronic liver diseases, and 59 with cholestatic biliary diseases, using immunostaining of the mast cell-specific proteinase, tryptase. Mast cells that were positive for tryptase and for chymase were significantly increased in frequency in fibrotic portal tracts and fibrous septa, particularly in cholestatic/biliary diseases. Mast cells were also increased in frequency around the fibrotic septal and intrahepatic large bile ducts and peribiliary glands of biliary diseases. However, they were less common or even rare in the sclerotic bile ducts and in scarred portal or septal fibrosis. More than half of these more numerous mast cells were positive for histamine, and some were also positive for basic fibroblast growth factor. These two substances were detectable by immunoelectron microscopic in the cytoplasmic granules of mast cells. In contrast, mast cell numbers were not significantly increased in acute viral or drug-induced hepatitis, or in zones 2 and 3 of the hepatic acinus with respect to pericellular and perivenular fibrosis in chronic liver diseases. These findings suggest that mast cells increase in number in cholestatic/biliary diseases, and to a lesser degree in chronic liver diseases, and are involved in the active fibrous enlargement of portal tract and fibrous septa formation and also in the fibrosis of the intrahepatic bile ducts as they display fibrosis-promoting factors such as tryptase, fibroblast growth factor and histamine.


Increased efficacy of intermediate-dose cytarabine + G-CSF compared to DHAP + G-CSF for stem cell mobilization in patients with lymphoma: an analysis by the polish lymphoma research group.
Salvage regimens, like DHAP (dexamethasone, cytarabine, and cisplatin) are frequently used for stem cell mobilization in lymphoma. The aim of this study was to compare the efficacy of DHAP + G-CSF with intermediate-dose cytarabine (ID-AraC) + G-CSF, recently proposed as an alternative schedule. Consecutive patients with Hodgkin's or non-Hodgkin lymphoma who had received at least 2 lines of chemotherapy, mobilized with either DHAP (n = 51) or ID-AraC (n = 50) + G-CSF were included in the analysis. AraC was administered at the dose of 400 mg/m [1] bid intravenously for 2 days followed by filgrastim starting from day 5. In the AraC group, 96 % of patients collected at least 2 × 10 [2] CD34(+) cells/kg compared to 71 % in the DHAP group (p = 0.0006). The CD34(+) cell yield was 9.3 (0-30.3) × 10 [2]/kg vs. 5.6 (0-24.8) × 10 [2]/kg, respectively (p = 0.006). A single apheresis was sufficient to achieve the threshold number of CD34(+) cells in 82 % of the cases after AraC compared to 45 % after DHAP (p = 0.001). We conclude that stem cell mobilization using ID-AraC is associated with a significantly higher efficacy than DHAP, allowing for collection of the transplant material in almost all patients with lymphoma. Our observation suggests that ID-AraC + G-CSF may be a preferable mobilization regimen in this setting.


Emergency department visits vs. fatalities among substance-impaired underage youths involved in motor vehicle crashes.
Emergency department (ED) visits resulting from motor vehicle crashes (MVCs) among individuals younger than 21 impaired by alcohol and/or drugs have been less studied than MVC fatalities. Using data from 2004 to 2011, we compare the magnitude and pattern of national ED visit and mortality data for alcohol- and drug-impaired youths involved in MVCs. Temporal patterns of ED visits are similar to those of fatalities, but the two differ in magnitude. The ratio of ED visits to fatalities is 3.5:1; alcohol related events involvement dominates other drugs in both categories. The volume of injuries serious enough to warrant ED visits imposes significant health, social, and financial burdens. In ED visits, alcohol is the prime source of MVC morbidity burden; other drugs consistently contribute less. These incidents are persistent and require interventions aimed at multiple levels of prevention, including stricter corrective steps earlier in the impaired driving career to reduce subsequent incidents. ED visits for MVC injuries can be important "teachable moments." Limitations of the study indicate the need for improved surveillance of underage substance-involved crashes.


Health information exchange network under collaboration, cooperation, and competition: A game-theoretic approach.
Health Information Exchange (HIE) network allows securely accessing and sharing healthcare-related information among healthcare providers (HCPs) and payers. HIE services are provided by a non-profit/profit organizations under several subscription plans options. A few studies have addressed the sustainability of the HIE network such that HIE providers, HCPs, and payers remain profitable in the long term. However, none of these studies addressed the coexistence of multiple HIE providers in the network. Such coexistence may have a huge impact on the behavior of healthcare systems in terms of adoption rate and HIE pricing strategies. In addition, in spite of all the effort to maintain cooperation between HIE providers, there is still a chance of competition among them in the market. Possible competition among service providers leads to many concerns about the HIE network sustainability and behavior. In this study, a game-theoretic approach to model the HIE market is proposed. Game-theory is used to simulate the behavior of the three different HIE network agents in the HIE market: HIE providers, HCPs, and payers. Pricing strategies and adoption decisions are optimized using a Linear Programming (LP) mathematical model. Results show that the relation between HIEs in the market is crucial to HCP/Payer adoption decision specially to small HCPs. A small change in the discount rate proposed by a competitive HIE provider will highly affect the decision of HCP/payers to join the HIE network. Finally, competition opened the opportunity for more HCPs to join the network due to reduced pricing. Furthermore, collaborative HIEs provided better performance compared to cooperative in terms of profit and HCP adoption rate by sharing their overall costs and revenues.


Ultrastructural study of cholecystokinin-immunoreactive cells and processes in area CA1 of the rat hippocampus.
We used light and electron microscopic immunocytochemical methods to examine the structure of neuronal perikarya and processes containing cholecystokinin-like immunoreactivity (CCK-IR) in area CA1 of the rat hippocampus. The morphology of stained perikarya, their positions within all laminae, and the orientation of their dendrites indicate that CCK-IR is located in interneurons. These cells were seen in the electron microscope to have deeply folded nuclei and to receive both symmetric and asymmetric synaptic junctions on their cell somata and dendritic shafts. Their dendrites are essentially spine-free, but form bulges at the site of some asymmetric synaptic junctions. Axonal varicosities containing CCK-IR make symmetric synaptic junctions with cell somata and dendritic shafts of both pyramidal and non-pyramidal neurons. In addition, CCK-IR varicosities form symmetric junctions with unstained non-pyramidal neurons and with CCK-IR cells, suggesting either recurrent innervation of one cell on itself or interaction between interneurons. The presence of CCK-IR varicosities and synaptic junctions on pyramidal cells is in agreement with physiological data which indicate that CCK has a direct postsynaptic action. The observation of CCK-IR varicosities forming synaptic junctions on non-pyramidal cells suggests that CCK might also modify the response of interneurons.


[Off-label prescriptions in acute psychiatry: a practice-based evaluation].
In acute psychiatry the prescribed medication is frequently off-label. To investigate the indications for off-label prescriptions described in the literature and to evaluate the use of off-label medication in the emergency service of Altrecht, Utrecht, The Netherlands. We performed a systematic search of the PubMed database and we evaluated all the records of patients examined by the emergency service during two assessment periods (April 2009 and November 2010). The literature makes no mention of the prescribing of off-label medication in acute psychiatry. In general psychiatry, however, off-label medication is reported mainly for atypical antipsychotics. In the emergency service 41% of the medication prescribed during first contacts with patients was off-label. These prescriptions were most often for antipsychotics (54%) and benzodiazepines (38%) . The most important indications were aggression, agitation and sleep problems. If the term 'off-label' is interpreted in a broader sense with respect to antipsychotics for psychosis and hypomania, then 33% of the prescriptions appeared to be off-label. If benzodiazepines prescribed for aggression/agitation were not taken into account, then the proportion of off-label prescriptions decreased to 21%. We consider it advisable that the reason for prescribing off-label medication should be clearly documented. New medical guidelines could help by summarising current views on the use of off-label medication.


mRNP proteins, initiation factors and phosphorylation.
Information has been collected to stimulate interest regarding the nature and the possible role of mRNP protein phosphorylation in a cytoplasmic control mechanism for protein synthesis. It does not imply a direct relationship between mRNP protein and initiation factors. These proteins have some properties in common (e.g. molecular weight, phosphorylation, protein kinase, mRNA binding activity). We emphasize that some free mRNP may be translatable after modification of their protein by interference factors belonging to other cellular compartments. Thus, some mRNP proteins might possess initiation factor or protein synthetic activity if we accept Spirin's theory, i.e., "Eukaryotic messenger RNA and informosomes omnia mea mecum porto.


Isolation and characterization of Taka-amylase A apoprotein deglycosylated by digestion with almond glycopeptidase immobilized on Sepharose.
Taka-amylase A (1,4-alpha-D-glucan glucanohydrolase, EC 184.108.40.206), which contains a single asparagine-linked oligosaccharide unit, was digested with almond glycopeptidase immobilized on Sepharose 6B at 20 degrees C for 4 h. A maximum of 10% of the parent protein was isolated as apoprotein by column chromatography on Con-A Sepharose. The characteristics of the apoprotein were compared to those of the native Taka-amylase A. The removal of the sugar chain from Taka-amylase. A caused no change in the pH-activity profile or in kinetic parameters of the hydrolysis of soluble starch. The stability of the apoprotein toward changing pH and digestion by proteases did not show any appreciable difference from that of the native Taka-amylase. These results suggest that the carbohydrate moiety of Taka-amylase A is not an essential participant in the catalysis.


Posterior Malleolar Fracture Morphology in Tibial Shaft Versus Rotational Ankle Fractures: The Significance of the Computed Tomography Scan.
To compare posterior malleolar fracture morphology in ankle fractures compared with those with tibial shaft fractures. Level 1 trauma center. Retrospective cohort study. Fifty-four patients with tibial shaft fractures and 61 patients with ankle fractures. Posterior malleolar fractures in ankle fractures versus tibial shaft fractures were classified by type and pathomorphology analyzed. Posterior malleolar fractures were significantly larger when associated with tibial shaft fractures (32% cross-sectional area) as compared to ankle fractures (15% cross-sectional area) (P < 0.001). The distribution of posterior malleolar fracture type differed between tibial shaft fractures and ankle fractures. In addition, 47% of the type II posterior malleolar fractures in tibial shaft fractures had an additional fracture line oriented in the sagittal plane, a fracture pattern unique to these injuries that were not observed in the ankle fracture cohort. Posterior malleolar fracture morphology varied significantly between tibial shaft fractures and rotational ankle fractures. Posterior malleolar fractures in tibial shaft fractures were over twice the size of posterior malleolar fractures that occur with rotational ankle fractures and more likely to involved the medial malleolus. This information emphasizes the importance of recognizing that large posterior malleolar fractures are associated with tibial shaft fractures. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


The limits of public communication coordination in a nuclear emergency: lessons from media reporting on the Fukushima case.
Coordination of public communication has become a key issue in management of complex emergencies, and is a matter of debate between nuclear emergency management professionals. A particular problem is when inconsistent information is sent to the media and public by official sources from different levels, which has led to calls for a more coordinated approach. The IAEA created guidelines recommending a one-voice communication approach that provides clear, consistent and coordinated information by relevant stakeholders. The reviewed theory on the emergency communication coordination and the empirical results in this paper demonstrate some challenges regarding the feasibility of the above stated goal. This paper explores the communication process in the two-month period of the Fukushima nuclear emergency by using a quantitative comparative content and discourse analysis of 1340 printed media articles on the Fukushima nuclear disaster from two major newspapers in Spain ('El País' and 'El Mundo'), Italy ('Corriere della Sera' and 'La Repubblica'), Norway ('Aftenposten' and 'Dagsavisen'), Slovenia ('Delo' and 'Večer'), Belgium ('Le Soir' and 'De Standaard') and Russia ('Komsomolskaya Pravda' and 'Izvestiya'). The results show that it will be difficult to achieve a truly coordinated approach and one-voice communication in severe nuclear and radiological emergency due to the communication difficulties created by the dispersion of information sources, a broad and dispersed focus of the reported information, partially subjective and conflicting media reporting. The paper suggests ways to improve public communication coordination in nuclear and radiological disasters.


Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission.
We treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute non-lymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1,320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (+/- SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74 +/- 9%; acute nonlymphoblastic leukemia = 50 +/- 11%; and chronic myelogenous leukemia = 55 +/- 11%. Actuarial relapse rates for these three diagnoses were 19 +/- 9%, 17 +/- 11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59 +/- 7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.


Release and transportation of Hedgehog molecules.
Secretion of the Hedgehog morphogen induces different cell fates over the short and long ranges during developmental patterning. Mature Hedgehog carries hydrophobic palmitic acid and cholesterol modifications essential for its correct spread. The long-range activity of Hedgehog raises questions about how a dually lipidated protein can spread in the hydrophilic environment of the extracellular space. There is compelling experimental evidence in favour of the existence of several different carriers for Hedgehog transportation, via very different routes. This suggests that different accessory proteins and cellular machineries may be involved in the specific release of Hedgehog. I suggest that Hh carriers may work in parallel within a given cell and that developmental context may condition the choice of Hh carrier in secreting cells.


[The clinical results of combined periodontal-orthodontic treatment on patients with periodontitis and labial displacement of incisors].
To evaluate the clinical effects of combined periodontal and orthodontic method in treating labial displacement of anterior teeth caused by periodontitis. 21 cases with periodontitis and fly-out of anterior teeth were selected. After the inflammation was controlled by essential periodontal therapy, the anterior teeth were allied by edgewise appliances; meanwhile, periodontal care and occlusal adjustment were conducted to control inflammation and occlusal trauma, until normal occlusion was established. A total of 74 teeth were treated, the periodontal probing depth and the degree of alveolar ridge resorption was recorded before and after treatment, respectively. All the data were statistically analyzed by Ridit test and Chi-square test. After 1-2 years of follow-up, all cases under 40 years got satisfactory effects, with significantly decreased periodontal probing depth (P<0.01) and alveolar ridge (P<0.05). Combined periodontal and orthodontic treatment was effective in the management of periodontitis, occlusal trauma and teeth alignment, and the effects were stable for a relatively long period. But patients over 40 years was not suitable for the treatment.


Models for MAGDM with dual hesitant q-rung orthopair fuzzy 2-tuple linguistic MSM operators and their application to COVID-19 pandemic.
In this article, we introduce dual hesitant q -rung orthopair fuzzy 2-tuple linguistic set (DHq-ROFTLS), a new strategy for dealing with uncertainty that incorporates a 2-tuple linguistic term into dual hesitant q -rung orthopair fuzzy set (DHq-ROFS). DHq-ROFTLS is a better way to deal with uncertain and imprecise information in the decision-making environment. We elaborate the operational rules, based on which, the DHq-ROFTL weighted averaging (DHq-ROFTLWA) operator and the DHq-ROFTL weighted geometric (DHq-ROFTLWG) operator are presented to fuse the DHq-ROFTL numbers (DHq-ROFTLNs). As Maclaurin symmetric mean (MSM) aggregation operator is a useful tool to model the interrelationship between multi-input arguments, we generalize the traditional MSM to aggregate DHq-ROFTL information. Firstly, the DHq-ROFTL Maclaurin symmetric mean (DHq-ROFTLMSM) and the DHq-ROFTL weighted Maclaurin symmetric mean (DHq-ROFTLWMSM) operators are proposed along with some of their desirable properties and some special cases. Further, the DHq-ROFTL dual Maclaurin symmetric mean (DHq-ROFTLDMSM) and weighted dual Maclaurin symmetric mean (DHq-ROFTLWDMSM) operators with some properties and cases are presented. Moreover, the assessment and prioritizing of the most important aspects in multiple attribute group decision-making (MAGDM) problems is analysed by an extended novel approach based on the proposed aggregation operators under DHq-ROFTL framework. At long last, a numerical model is provided for the selection of adequate medication to control COVID-19 outbreaks to demonstrate the use of the generated technique and exhibit its adequacy. Finally, to analyse the advantages of the proposed method, a comparison analysis is conducted and the superiorities are illustrated.


The effect of induced hypertension on neurological outcome in forebrain ischaemia model in rats.
The present study investigated the effects of induced hypertension on hippocampal cell death after forebrain ischaemia in rats. In this study, forebrain ischaemia was induced in 20 Sprague-Dawley rats by clamping the bilateral common carotid arteries to induce systemic hypotension for 8min. All rats then underwent reperfusion during which the induced hypertension group (n=10) received intermittent intravenous injections of phenylephrine (5μg) to maintain their mean arterial blood pressure at 20mmHg above baseline for 10min and the control group (n=10) did not receive any treatment. In both groups, the numbers of viable and apoptotic neuronal cells in the cornu ammonis 1 (CA1) area of the hippocampus were evaluated 7 days after the induction of ischaemia. The mean percentage of viable neuronal cells was higher in the induced hypertension group than in the control group (35% vs. 26%, respectively; p=0.004), but there was no significant difference in the proportion of apoptotic neuronal cells between the groups (57% vs. 43%, respectively; p=0.165). Induced hypertension significantly attenuated necrotic cell death in the hippocampal CA1 area, but apoptotic cell death was not affected.


Efficacy evaluation and metabolomics analysis of Huanglian Jiedu decoction in combination with donepezil for Alzheimer's disease treatment.
Alzheimer's disease (AD) is a progressive disease with continuous brain changes and has caused a severe burden on families and society. Huanglian Jiedu Decoction (HLJD) is a classic traditional Chinese medicine formula that can improve AD animals' cognitive impairment. This study recruited 50 AD patients who were divided into two groups, one receiving donepezil (DON) treatment and the other receiving DON + HLJD treatment for 3 months. The curative effect, inflammatory and oxidative stress levels were analyzed. The PES-D/11, MMSE, and ADL scales were used to evaluate traditional Chinese medicine syndrome elements, cognitive function, mental state, and life ability. There were no significant differences between the two groups in baseline characteristics and vital sign indicators. After drug treatment, the results showed that AD patients with HLJD combined with DON treatment didn't increase the adverse effects and had good compliance. HLJD combined with DON could improve the disease syndrome, making the differences in PES-D/11, MMSE, and ADL scores before and after the intervention larger. Furthermore, both DON and DON+HLJD treatment inhibited the levels of IL-6, IL-1β, TNF-α, and MDA, raised SOD level, and HLJD enhances the inhibitory effect of DON on inflammation and oxidative stress. IL-6, IL-1β, TNF-α, and MDA levels were significantly correlated with curative effect. Moreover, this study found 107 (206) up-regulated metabolites and 1430 (145) down-regulated metabolites in urine (serum) and conducted differential metabolite screening and correlation analysis suggesting that HLJD may interfere with oxidative stress and inflammation in AD by regulating lipid metabolism and glutamic acid metabolism. Arachidonic acid, diaminopimelic acid, and 1-Aminocyclopropanecarboxylic acid may play an important role in HLJD to improve AD.


The effects of objectively-measured, free-living daily ambulatory movement on mortality in a national sample of adults with diabetes.
Previous research demonstrates that self-reported physical activity is protective against premature mortality among the general population, as well as those with diabetes. This confirmatory research study examines the relationship between physical activity and all-cause mortality risk among a national sample of diabetics while employing an objective measure of physical activity (ActiGraph 7164). Data from the 2003-2006 NHANES were employed, with follow-up through 2011.Among the 712 diabetics, 134 died during the median follow-up period of 79months. For every 60min increase in daily ambulatory movement, adults with diabetes had a 29% reduced risk of premature all-cause mortality (HRadjusted=0.71; 95% CI: 0.60-0.85). These confirmatory findings underscore the importance of physical activity promotion among adults with diabetes.


Haemophagocytic lymphohistiocytosis (HLH) secondary to miliary tuberculosis.
HLH is a rare, life-threatening, hematologic disorder resulting from prolonged and excessive activation of antigen presenting cells (macrophages, histiocytes) and CD8+ T cells. It is characterized by fever, pancytopenia,splenomegaly and haemophagocytosis in bone marrow,liver or lymph node. This hyperinflammatory condition is often triggered by a variety of agents or events, mostly genetic or infectious. HLH secondary to TB, have 100 % mortality in absence of anti-tubercular treatment .Since it mimics other disorders, its timely diagnosis remains a challenge. We report a case of hemophagocytic syndrome associated with disseminated tuberculosis in an immunocompetent man managed with anti-tubercular treatment and corticosteroid as immune modulator.


Pitfalls in the diagnosis of acute pulmonary embolism on spiral computer tomography.
Spiral computer tomography (CT) has become a widely accepted clinical tool in the diagnosis of acute pulmonary embolism. The accuracy of computed tomography in diagnosing pulmonary embolism has increased over the past 10 years, parallel to technological improvements. However, as with most imaging techniques, interpretative pitfalls may occur for a variety of reasons. These include technical problems caused by respiratory motion artifact, improper bolus timing, streak artifact, and patient body habitus. In addition, misinterpretation of normal bronchovascular anatomy may lead to an erroneous diagnosis. This article discusses the various diagnostic pitfalls and methods to minimize and overcome them.


Changes in quinone profiles of hot spring microbial mats with a thermal gradient
The respiratory and photosynthetic quinones of microbial mats which occurred in Japanese sulfide-containing neutral-pH hot springs at different temperatures were analyzed by spectrochromatography and mass spectrometry. All of the microbial mats that developed at high temperatures (temperatures above 68 degreesC) were so-called sulfur-turf bacterial mats and produced methionaquinones (MTKs) as the major quinones. A 78 degreesC hot spring sediment had a similar quinone profile. Chloroflexus-mixed mats occurred at temperatures of 61 to 65 degreesC and contained menaquinone 10 (MK-10) as the major component together with significant amounts of either MTKs or plastoquinone 9 (PQ-9). The sunlight-exposed biomats growing at temperatures of 45 to 56 degreesC were all cyanobacterial mats, in which the photosynthetic quinones (PQ-9 and phylloquinone) predominated and MK-10 was the next most abundant component in most cases. Ubiquinones (UQs) were not found or were detected in only small amounts in the biomats growing at temperatures of 50 degreesC and above, whereas the majority of the quinones of a purple photosynthetic mat growing at 34 degreesC were UQs. A numerical analysis of the quinone profiles was performed by using the following three parameters: dissimilarity index (D), microbial divergence index (MDq), and bioenergetic divergence index (BDq). A D matrix tree analysis showed that the hot spring mats consisting of the sulfur-turf bacteria, Chloroflexus spp., cyanobacteria, and purple phototrophic bacteria formed distinct clusters. Analyses of MDq and BDq values indicated that the microbial diversity of hot spring mats decreased as the temperature of the environment increased. The changes in quinone profiles and physiological types of microbial mats in hot springs with thermal gradients are discussed from evolutionary viewpoints.


3D Printing of Subclavian Artery: Utility for Preprocedural Planning and Correlation With Subclavian Artery Percutaneous Vascular Interventions.
Three-dimensional (3D) printing for subclavian artery (SA) percutaneous vascular interventions (PVI) may allow superior understanding of patient specific complex anatomy and aid with preprocedural planning. Five patients with computed tomography angiography (CTA) of the neck who underwent SA PVI were queried retrospectively. 3D printing of aortic arch and great vessels was accomplished with 3D slicer software and painted with acrylic paint to highlight anatomic features. The aortic arch type and implications for preprocedural planning for SA interventions including complex chronic total occlusion (CTO) lesions were determined. Comparisons were made with SA angiograms and 3D-CTA. Of the 5 patients, type I (n = 2), type II (n = 1), and type III (n = 2) aortic arches were identified. Proximal and distal reference vessel size and total lesion length were determined using a digital millimeter caliper and correlated with intraprocedural balloons and stents. In 3D-printed models (3D-PMs) of patients with SA-CTO (n = 2), cap morphology (tapered vs blunt) and distal vessel filling were visualized, permitting optimal arterial access site selection for successful cap crossing. The vertebral arteries (VAs) were also 3D printed which further allowed the ability to delineate optimal stent deployment site (proximal or distal to VA), a common dilemma that is faced intraprocedurally. The 3D-PMs also allowed preprocedural precision in stent and balloon size and length, potentially leading to procedural efficiency and cost-effectiveness. 3D printing of aortic arch and great vessel anatomy for SA-PVI allows multiple procedure-related factors to be predicted in advance, translating to decrease in contrast volume, radiation time, procedure and fluoroscopic time, thereby improving procedure and cost efficiency.


Urinary tract neoplasia.
This article is a review of reports on neoplasia of the equine urinary tract. Clinical signs associated with equine patients with urinary tract neoplasia are summarized along with a description of diagnostic methods used in such patients. The prognosis for treatment of urinary tract neoplasia is guarded. A review of the limited treatments that have been reported to date are also provided in this article.


The cobalt-albumin binding assay: insights into its mode of action.
We previously hypothesized that the N-terminus of human serum albumin (HSA) is altered during ischemic events, thus establishing the foundation for the cobalt-HSA binding assay phenomenon. In this investigation, we attempt to clarify the mode of action of the cobalt-HSA binding assay by direct observations of cobalt binding to HSA. High pressure liquid chromatography coupled to positive electrospray ionization mass spectrometry (HPLC/MS) was used to study cobalt binding to HSA in the plasma of patients with and without evidence of myocardial ischemia. Strong binding of cobalt to the N-terminus of HSA occurs at pH>7.0. No differences in cobalt binding to the N-terminus of HSA are observed in ischemic versus non-ischemic patients' plasma despite differences in the cobalt-HSA binding assay. Plasma free cysteine/cystine ratio appears to play a role in the quantitative response of the cobalt-HSA binding assay. The main determinants of the cobalt-HSA binding assay mechanism of action include but are not limited to: the proportion of intact N-terminus of HSA, HSA concentration, plasma cysteine/cystine ratio, plasma pH, and the state of oxidation of cys34 of HSA. Assay improvements that consider and take these factors into account could lead to an improved cobalt-HSA binding assay with greater clinical utility.


L5-S1 Pseudoarthrosis Rate with ALIF Versus TLIF in Adult Spinal Deformity Surgeries: A Retrospective Analysis of 100 Patients.
Lumbosacral pseudoarthrosis is a common complication following adult spine deformity (ASD) surgery. This study assessed the reoperation rate for L5-S1 pseudoarthrosis in the ASD population. Compared with transforaminal lumbar interbody fusions (TLIFs), we hypothesized that anterior lumbar interbody fusion (ALIF) would result in lower rates of L5-S1 pseudarthrosis. This is a single center study with patient data retrieved from a prospective ASD database. The patients had a long-segment fusion, ALIF or TLIF at the L5-S1 level with a 2-year follow-up and were divided into 2 groups (TLIF and ALIF). The study's primary outcome was to assess the difference in the reoperation rate for clinical pseudoarthrosis between the TLIF and the ALIF groups. The secondary outcomes measured the radiological pseudoarthrosis rate and identified risks for L5-S1 pseudoarthrosis development. A total of 100 patients were included; 49 patients (mean age, 62.9 years; 77.5% females) were in TLIF and 51 patients (mean age, 64.4 years; 70.6% females) were in the ALIF group. Baseline characteristics were similar in both groups. Thirteen (13%) patients with L5-S1 pseudoarthrosis required reoperation. Clinical pseudoarthrosis was higher in the TLIF group than in the ALIF group (12/49 vs. 1/51; P < 0.001). Univariate analysis demonstrated a higher risk of L5-S1 pseudoarthrosis with TLIF than ALIF (risk ratio, 12.4; 95% confidence interval: 1.68-92.4; P < 0.001). Multivariate analysis revealed 4.86 times the risk of L5-S1 clinical pseudoarthrosis with TLIF than with ALIF (risk ratio, 4.86; 95% confidence interval 0.57-47; P = 0.17), but this ratio did not reach statistical significance. No difference in reoperation risk for L5-S1 pseudarthrosis was observed based on the method of IF. rhBMP-2 was noted as a significant predictor.


Hospital study reveals strategies for improving media relations.
A nationwide study revealed that hospital administrators feel inadequate when dealing with the media, and also think the media does not understand the hospital business. Many strategies are available to counter these problems, including some that emphasize issues related to bed size.


Transforming growth factor beta and connective tissue growth factor are involved in the evolution of nevus of Nanta.
We report a 59-year-old Japanese male with nevus of Nanta on the face. Histological examination revealed a nest of nevus cells in the dermis and ossification beneath the nevus. Positive staining for transforming growth factor-beta and connective tissue growth factor suggested the involvement of these growth factors in the ossification of nevus of Nanta.


Juvenile hormone analog enhances Zika virus infection in Aedes aegypti.
In recent years, there has been a rise in the emergence of arboviruses of public health importance, including Zika, chikungunya, dengue, and yellow fever viruses. Insecticide-based mosquito control has been the primary method for mitigating transmission of arboviruses. The consequences for the application of insecticides include both lethal and sublethal effects, and associated development of insecticide resistance. However, little is known about the influence on arboviral transmission. Mosquitoes with phenotypes that exhibit insecticide resistance or experience sublethal effects may be associated with altered susceptibility to arbovirus infection and transmission. Juvenile hormone analogs (JHAs) are insecticides that prevent pupa to adult molting of mosquitoes by mimicking the action of their natural juvenile hormone. Here, we examined whether the JHA pyriproxyfen interacts with ambient temperature (20 °C and 30 °C) during juvenile stages to influence life-history traits, population growth (λ'), and Zika virus (ZIKV) infection in Aedes aegypti. Development time of females was lengthened at 20 °C and in the presence of JHA. Prevention of pupa to adult molting by JHA was differentially higher at elevated temperature than low temperature. Size of females was larger at 20 °C and smaller at 30 °C. Infection, disseminated infection, and transmission of ZIKV in females were enhanced by JHA at both 20 °C and 30 °C relative to the controls. These results demonstrate that mosquito life-history and vector competence parameters are strongly influenced by interactive effects of JHA and temperature. The JHA-induced enhancement of ZIKV infection in females should be a consideration when implementing JHA in vector control strategies.


The Relevance of Time in Biological Scaling.
Various phenotypic traits relate to the size of a living system in regular but often disproportionate (allometric) ways. These "biological scaling" relationships have been studied by biologists for over a century, but their causes remain hotly debated. Here, I focus on the patterns and possible causes of the body-mass scaling of the rates/durations of various biological processes and life-history events, i.e., the "pace of life". Many biologists have regarded the rate of metabolism or energy use as the master driver of the "pace of life" and its scaling with body size. Although this "energy perspective" has provided valuable insight, here I argue that a "time perspective" may be equally or even more important. I evaluate various major ways that time may be relevant in biological scaling, including as (1) an independent "fourth dimension" in biological dimensional analyses, (2) a universal "biological clock" that synchronizes various biological rates/durations, (3) a scaling method that uses various biological time periods (allochrony) as scaling metrics, rather than various measures of physical size (allometry), as traditionally performed, (4) an ultimate body-size-related constraint on the rates/timing of biological processes/events that is set by the inevitability of death, and (5) a geological "deep time" approach for viewing the evolution of biological scaling patterns. Although previously proposed universal four-dimensional space-time and "biological clock" views of biological scaling are problematic, novel approaches using allochronic analyses and time perspectives based on size-related rates of individual mortality and species origination/extinction may provide new valuable insights.


Enhanced Visible Light Photocatalytic Degradation of Organic Pollutants over Flower-Like Bi₂O₂CO₃ Dotted with Ag@AgBr.
A facile and feasible oil-in-water self-assembly approach was developed to synthesize flower-like Ag@AgBr/Bi₂O₂CO₃ micro-composites. The photocatalytic activities of the samples were evaluated through methylene blue degradation under visible light irradiation. Compared to Bi₂O₂CO₃, flower-like Ag@AgBr/Bi₂O₂CO₃ micro-composites show enhanced photocatalytic activities. In addition, results indicate that both the physicochemical properties and associated photocatalytic activities of Ag@AgBr/Bi₂O₂CO₃ composites are shown to be dependent on the loading quantity of Ag@AgBr. The highest photocatalytic performance was achieved at 7 wt % Ag@AgBr, degrading 95.18% methylene blue (MB) after 20 min of irradiation, which is over 1.52 and 3.56 times more efficient than that of pure Ag@AgBr and pure Bi₂O₂CO₃, respectively. Bisphenol A (BPA) was also degraded to further demonstrate the degradation ability of Ag@AgBr/Bi₂O₂CO₃. A photocatalytic mechanism for the degradation of organic compounds over Ag@AgBr/Bi₂O₂CO₃ was proposed. Results from this study illustrate an entirely new approach to fabricate semiconductor composites containing Ag@AgX/bismuth (X = a halogen).


Occupational repetitive strain injuries and gender in Ontario, 1986 to 1991.
Repetitive strain injuries (RSIs) in Ontario were examined with respect to gender for the period 1986 to 1991, using data from Ontario Workers' Compensation Board systems. Technical issues surrounding analysis of workplace injuries and theoretical suggestions raised by the data are discussed. Analyses revealed that the risk of RSIs for women is greater than that for men. Furthermore, women receive compensation benefits because of RSIs for a longer period than do their male counterparts, which may indicate a longer-term effect of RSIs on women.


Healthcare for individuals without health insurance in Germany - a mixed methods approach to assess the situation and current challenges.
Health insurance is mandatory in Germany; nevertheless, many individuals there have no health insurance and depend on a parallel healthcare structure. Voluntary associations, such as MediNetz and healthcare vouchers ("Anonymer Krankenschein" - AKS), support uninsured citizens. This study aimed to provide insights into associations, such as MediNetz and AKS that provide healthcare for individuals without health insurance in North Rhine-Westphalia, the largest federal state in Germany. A mixed methods approach was chosen. A qualitative study using interviews with experts was performed to gain their knowledge and explore the various challenges that AKS and MediNetz associations faced and the possible improvements that could be made. A quantitative survey was conducted to analyse the demographic data of the patients who required AKS or MediNetz's assistance and the characteristics of each association through a separate questionnaire. Data was received from the association in Aachen, Bielefeld, Bonn, Düsseldorf, and Essen. More women than men sought medical care; most were between 25 and 49 years old. The proportion of individuals without residency status accounted for the largest share (53.6%). Common reasons for patients to make contact were acute illnesses (40.2%) and pregnancies (22.3%). Most patients were sent to gynaecologists and general practitioners. Asking the experts, it became apparent that the existing system could not reach the standard of the regular healthcare in Germany. Financial and human resources were insufficient. Therefore, prevention was limited, especially chronically ill patients or patients with a severe illness requiring hospitalisation could not be treated. AKS had advantages compared to MediNetz, as the care came closer to the expected German medical standards. The results showed a demand for associations providing healthcare for individuals without health insurance. However, the healthcare provided by MediNetz and AKS did not reach the standard of healthcare in Germany and mainly depended on the organisations' resources. Funded projects such as an AKS combined with clearing centres significantly improved healthcare. Until structural measures are implemented, they can be a transitional solution by spreading nationwide.


The Muller-Neel dispute and the fate of cancer risk assessment.
The National Academy of Sciences (NAS) Atomic Bomb Casualty Commission (ABCC) human genetic study (i.e., The Neel and Schull, 1956a report) showed an absence of genetic damage in offspring of atomic bomb survivors in support of a threshold model, but was not considered for evaluation by the NAS Biological Effects of Atomic Radiation (BEAR) I Genetics Panel. The study therefore could not impact the Panel's decision to recommend the linear non-threshold (LNT) dose-response model for risk assessment. Summaries and transcripts of the Panel meetings failed to reveal an evaluation of this study, despite its human relevance and ready availability, relying instead on data from Drosophila and mice. This paper explores correspondence among and between BEAR Genetics Panel members, including James Néel, the study director, and other contemporaries to assess why the Panel failed to use these data and how the decision to recommend the LNT model affected future cancer risk assessment policies and practices. This failure of the Genetics Panel was due to: (1) a strongly unified belief in the LNT model among panel members and their refusal to acknowledge that a low dose of radiation could exhibit a threshold, a conclusion that the Néel/Schull atomicbomb study could support, and (2) an excessive degree of self-interest among panel members who experimented with animal models, such as Hermann J. Muller, and feared that human genetic studies would expose the limitations of extrapolating from animal (especially Drosophila) to human responses and would strongly shift research investments/academic grants from animal to human studies. Thus, the failure to consider the Néel/Schull atomic bomb study served both the purposes of preserving the LNT policy goal and ensuring the continued dominance of Muller and his similarly research-oriented colleagues.


Differences in virulence within the species Bacteroides gingivalis.
In order to gain insight into the relative importance of several virulence factors of Bacteroides gingivalis, 8 strains with a varying virulence were studied. The virulence of B. gingivalis was determined in a mouse model. Strains HG 66, HG 76 and HG 184 were very virulent causing phlegmonous abscesses with lesions and necrosis. The strains HG 405 and HG 462 caused phlegomonous abscesses with pus. Strains HG 91, HG 94 and HG 185 were less virulent and induced gravity abscesses. In vitro strains HG 66, HG 76 and HG 184 induced low amounts of chemiluminescence by polymorphonuclear leucocytes. All other strains including HG 405 and HG 462 caused a relatively high chemiluminescence. Most strains displayed a high sensitivity to the bactericidal activity of fresh serum except for the highly virulent strains HG 66, HG 76 and HG 184. No differences in extracellular proteolytic activity on Azocoll, production of volatile fatty acids and ammonia were found between the B. gingivalis strains studied. In conclusion, differences in virulence were shown within the species B. gingivalis; the relative importance of several virulence factors was investigated.


Botulinum neurotoxin type E fragmented with endoproteinase Lys-C reveals the site trypsin nicks and homology with tetanus neurotoxin.
Botulinum neurotoxin type E, a 150 kDa single chain protein, cleaved with endoproteinase Lys-C yielded 113, 73, and 50 kDa fragments. The N-terminal sequence of the 113 kDa fragment, Gly-Ile-Arg-Lys-Ser-Ile-Cys-Ile, overlaps the N-terminal sequence, Lys-Ser-Ile-Cys-Ile, of the 103 kDa heavy chain produced by nicking the neurotoxin with trypsin. The -Arg-Lys- bond is therefore the site on the single chain type E NT where trypsin nicks generating the 50 kDa light and 103 kDa heavy chains of the dichain NT. The sequence of the first 50 N-terminal residues of the 73 kDa fragment were determined. This fragment is a segment of the heavy chain; 50% of the 50 residues are present in identical positions in a similar segment of the heavy chain of tetanus neurotoxin.


Tele-health services for the elderly: A novel southern Italy family needs-oriented model.
The world population is aging. By 2050, the global population aged over 65 years will have doubled, leading to big societal challenges for ensuring healthy, independent, and productive lives for older people. Thus, innovative local and national initiatives for e-health services are growing in an attempt to overcome such problems. We examined the effects of a telehealth system, i.e. tele-monitoring of vital parameters and neurological/psychological tele-counseling, within a family-centred service provided by a local day centre. We evaluated the clinical and neurobehavioral symptoms of 18 elderly patients (aged 65 years and over) and the care burden of their 20 caregivers, besides the usability of the tool. The one-way repeated analysis revealed a significant worsening in daily living activities (p < 0.01 and p = 0.02, respectively for Activities of Daily Living (ADL) and Independent IADL (IADL)) versus a significant improvement of the patients' psychiatric condition (p < 0.001), besides a significant gradual reduction of the caregivers burden (p < 0.001). Health status perception increased through time (from an average score of 5.67 ± 1.08 at baseline to 7.72 ± 1.32 at the end of the study). It appears that a telehealth system integrated in a local health care service may significantly improve elderly persons' behaviour, and also reduce the caregivers' burden.


Ultrastructural metabolic activity following quick-freezing and freeze-substitution in tetrahydrofuran in the superior cervical ganglion.
A method of quick-freezing and freeze-substitution has been developed for localizing diffusible substances such as 2-deoxyglucose-6-phosphate (2-DG-6-P) ultrastructurally in neural tissue. Quick-freezing under pressure provides well preserved tissue down to 30-35 microns from the surface. This allows blocks of neural tissue to be quick-frozen and analysed for diffusible substances in areas removed from the freezing face. Freeze-substitution in tetrahydrofuran following quick-freezing was found to dissolve and remove 2-deoxyglucose (2-DG) but not 2-DG-6-P. Consequently, this technique extends the ability to analyse localization of glucose utilization to postsynaptic as well as presynaptic sites. We have applied the technique to isolated superior cervical ganglion while provoking selective increases in energy metabolism. Exposure to an elevated extracellular potassium (12 mM) concentration produced a pattern of metabolic activity with enhanced neuropil labelling (neuronal and glial processes). With antidromic stimulation of the external carotid nerves, deoxyglucose uptake in neuronal and glial soma in the caudal portion of the ganglion was enhanced more than neuropil labelling. This caudal region corresponds to the region of origin of the cell bodies of the external carotid nerve. Results from this technique suggest that the contribution of glia to overall rate of energy metabolism may be significant and that this is a promising method for correlating the relationship between functional activity and cellular electrical activity.


A case of Smith-Lemli-Opitz Syndrome, defect of cholesterol biosynthesis.
We report the case of a child with Smith-Lemli-Opitz Syndrome. The pregnancy was complicated by prenatal growth retardation. The baby was admitted to the Neonatal Intensive Care Unit of Chieti when she was five months old. She showed postnatal growth retardation, trouble sucking and swallowing, microcephaly and multiple major and minor malformations, including characteristic facial features and 2-3 syndactyly of the toes. We found correlations between multiple congenital malformations, failure to thrive and low plasmatic cholesterol measurement.


Multiple dimensions of biodiversity and ecosystem processes: Exploring the joint influence of intraspecific, specific and interspecific diversity.
The positive influence of biodiversity on ecosystem processes was the focus of intense debate in ecology throughout the recent decades, becoming accepted and treated as a new paradigm in contemporary ecology. However, the available literature in this research field extensively explores species richness as an unidimensional measure for biodiversity. The present study explores how different components of biological diversity (number of genotypes, species, and functional groups) can influence an ecosystem process (biomass fixation). A mathematical model was employed and the simulation results showed that species richness per se does not affect the ecosystem productivity. Genotypic richness affected positively the ecosystem, but only if the genotypes are functionally complementary. The functional groups richness always affected positively the simulated ecosystem process. When together, richness at the different components of biological diversity showed stronger effect on ecosystem, and the scenarios with high species, genotypes and functional groups richness were the most productive ones. The results also allowed to observe that the ecosystems which are diverse in terms of functional groups and genotypes can be less susceptible to species loss. Finally, it is argued that a multiple dimension approach to biodiversity is relevant to advance the current knowledge on the relation between biodiversity and ecosystem functioning.


Genomic evidence of repeat-induced point mutation (RIP) in filamentous ascomycetes.
The genomes of 49 filamentous ascomycetes (subphylum Pezizomycotina) were examined by two independent methods for evidence of multiple C→T transitions typical of RIP. At least one transposable element or other repeat family was identified in each genome, and members were assessed for transition and transversion mutations relative to a model of their intact progenitor. Occurrence of RIP was indicated where family members differed by excess of directional transitions over transversions. Transition mutations were quantified by an algorithm taking double mutations in CpG and CpC dinucleotides into account. A second method assessed dinucleotide frequency distribution anomalies in whole genomes, a procedure that allowed quantification of fractions of the non-coding genome that had been subject to extensive directional mutation. The results of both methods revealed that RIP-like activity varied greatly, both in extent of mutation and in dinucleotide context for C→T transitions. In the most extreme case, 75% of a Blastomyces dermatitidis genome had suffered conspicuous GC-depletion, all of it in the non-coding fraction. Many genomes carried both intact repeats as well as others that had suffered heavily from transitions. Only one species, Chaetomium globosum, showed no evidence of directional mutation.


The prostacyclin analogue taprostene and recombinant human superoxide dismutase increase the permanent survival rate of endotoxemic rats.
The permanent survival rate of endotoxemic rats was studied. In 40 untreated control rats the survival rate 7 days after the endotoxin administration was 33%. The survival rate was increased to 40% with recombinant human superoxide dismutase (r-HSOD), to 55% (p less than 0.05) with the prostacyclin analogue Taprostene and to 70% (p less than 0.01) with the combination of r-HSOD and Taprostene (20 rats for each treatment group). r-HSOD and Taprostene provide significant and permanent protection in rat endotoxic shock.


Effect of catheter tip length and position on lesion volume in temperature controlled RF ablation in canine tricuspid valve annulus.
Radiofrequency (RF) energy has been delivered to the tricuspid valve annulus (TVA) in humans with both 4 mm and 8 mm long catheter tip electrodes to treat atrial flutter. However, lesion volume with temperature controlled RF delivery systems has not been previously characterized. In 10 anesthetized canines, a single pulse of temperature controlled RF energy at a 70 degrees C set point, 30 second duration was delivered with either a 7 Fr/4 mm tip or a 7 Fr/8 mm tip electrode in a position both anterolateral and posteroseptal to the tricuspid valve annulus (TVA). Surface echocardiogram was obtained prior and after ablation. The animals were sacrificed after ablation and the lesions underwent gross and histological examination. Lesion size, tip temperature and power were related to tip electrode surface area (SA). Eight mm tips (SA = 59 mm2) tended to create significantly larger lesions than 4 mm tips (SA = 29 mm2). Median lesion volume was 22 vs. 1.5 mm3, respectively. Eight mm tips were also associated with higher power requirements and lower temperatures than 4 mm tips. Posteroseptal TVA lesions tended to be larger than anterolateral lesions. No significant complications were noted. Using temperature controlled RF ablation, large lesions may be safely created on the canine TVA using 7 Fr catheters with 8 mm long tips.


Analysis of the expression of PHTF1 and related genes in acute lymphoblastic leukemia.
Previous study showed that downregulated BCL11B expression in T cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4 inhibited cell proliferation and induce apoptosis, which may be related to PHTF1 gene overexpression. The objective of this study was to investigate the expression of PHTF1 and related genes in ALL and further explore its function in T-ALL cell lines. Real-time PCR was used to determine the gene expression level of PHTF1 in hematologic malignancies. The PHTF1, BCL11B, FEM1B and Apaf-1 gene expression levels and correlations were analyzed in patients with primary ALL (including T-ALL and B-ALL) and healthy individuals (HIs). Inhibition and overexpression of PHTF1 by lentiviral transduction were performed using the Molt-4 and Jurkat cell lines. Cell growth and apoptosis were measured by the Cell Counting Kit-8 assay and flow cytometry, respectively. Upon PHTF1 overexpression, the BCL11B, FEM1B and Apaf-1 gene expression levels were determined by real-time PCR. PHTF1 overexpression was found in both T-ALL (p = 0.004) and B-ALL (p < 0.001) groups compared with HIs group. A trend toward a negative correlation between the PHTF1 and BCL11B genes was detected for the T-ALL group, while positively correlated expression was found for the PHTF1 and BCL11B genes in HIs (P = 0.001). FEM1b and Apaf-1 overexpression was found in recently diagnosed ALL patients compared with HIs (p < 0.05). Positively correlated expression was found for the PHTF1, FEM1b and Apaf-1 genes in patients with ALL (p < 0.05) and HIs (p < 0.05). Direct up-regulation of PHTF1 expression inhibited the proliferation of Jurkat and Molt-4 cells and effectively induced apoptosis in Molt-4 cells. Direct inhibition of PHTF1 expression had no significant effect on the proliferation or apoptosis of Jurkat and Molt-4 cells. FEM1b and Apaf-1 overexpression, which did not obviously alter the BCL11B expression level, was detected in PHTF1-transduced T-ALL cell lines. PHTF1 overexpression is responsible for regulating cell proliferation and apoptosis in T-ALL cell lines. PHTF1 may be a tumor-suppressor like gene and a therapeutic target for triggering the PHTF1-FEM1b-Apaf-1 apoptosis pathway.


Early stage nanocrystallization as a method of enhancement of electrical properties of lead/barium titanate doped vanadium borate glasses.
Glass-ceramic nanocomposites (GCNs) of (10 - x) BaTiO3 (BT)-xPbTiO3 (PT)-60V2O5-30B2O3 with x = 0, 2.5, 5, 7.5 and 10 mol% were formed during heat treatment of conventional melt quenching glasses. X-ray diffraction was used to ensure glass and GCNs formation. Glasses and GCNs densities were measured by Archimedes principle. Fine polar clusters of lead titanate and/or barium titanate incorporation into vanadium borate glass matrix strongly depend on the composition. It was found out that the electrical conductivity of the initial glasses can be considerably improved by proper early stage of nanocrystallization at temperatures approaching the crystallization temperatures determined by DSC method. GCNs show massive increase in electrical conductivity (up to 6 orders of magnitude) as a function of BaTiO3 content. By increasing BaTiO3 content, the activation energy values have been found to increase. The enhancement in electrical conductivity of GCNs can be attributed to the increase in the crystalline phases in the glassy matrix which increases the concentrations of the V ion pairs.


Stimulation of the retina with a multielectrode extraocular visual prosthesis.
An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.


Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations.
Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study. We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed. Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence.


A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy.
Perampanel is a once-daily oral anti-seizure medication for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures (FBTCS), and generalized tonic-clonic seizures. Study 402 (NCT02033902) collected safety information on clinically important treatment-emergent adverse events (TEAEs) from real-world clinical practice in patients aged ≥12 years with refractory epilepsy who were receiving perampanel as an add-on therapy. Study 402 was a multicenter, observational, 52-week cohort study conducted in Austria, Belgium, Czech Republic, Denmark, France, Israel, Sweden, and the United Kingdom. Safety data were gathered prospectively from patients at clinic visits. The primary endpoint was the incidence of clinically important TEAEs defined as dizziness; blurred vision; somnolence; aggression; balance disorders (including ataxia and falls); weight gain; suicidality; drug abuse, misuse, dependence, and withdrawal; skin photosensitivity; and unintended pregnancy while taking levonorgestrel-containing contraceptives. Off-label use of perampanel and outcomes associated with any suspected drug-drug interaction were also monitored and recorded. Secondary endpoints included the Hospital Anxiety and Depression Scale (HADS) and Clinical Global Impression of Change. Of 483 patients in the Safety Analysis Set, mean (standard deviation [SD]) age was 38.3 (15.1) years, 48.4% were female, mean (SD) time since diagnosis was 23 (14.8) years, 56.5% had focal impaired awareness seizures, and 48.7% had FBTCS. Overall, 243 (49.3%) patients treated with perampanel completed the study and 227 (46.0%) patients discontinued. The most common primary reason for discontinuation was adverse events (n = 130 [26.4%]). A total of 301 (62.3%) patients reported at least one TEAE, of which 45 (15.0%) patients had severe TEAEs and 256 (85.0%) patients had TEAEs judged as mild to moderate in severity. Overall, 51 (10.6%) patients had serious TEAEs, including two deaths that were judged as not related to perampanel, and 136 (28.2%) patients experienced a TEAE that led to treatment discontinuation. Clinically important TEAEs were reported by 153 (31.7%) patients, with the most common being dizziness (13.9%), balance disorders (5.6%), aggression (5.4%), and weight gain (5.4%). In general, the frequencies of clinically important TEAEs were lower in this study compared with previous interventional clinical studies, except for the incidence of suicidality (2.1% vs 1.0%) and aggression (5.4% vs 5.1%). Mean total HADS scores were similar at the end of the study compared with baseline; at the end of treatment, most (>60%) patients had no shift in HADS score category; ∼15% of patients moved to a worse category vs baseline and ∼20% of patients moved to an improved category vs baseline for both anxiety and depression. Based on investigator assessment, disease severity was improved in 185/415 (44.6%) patients. A subanalysis in elderly patients aged ≥65 years showed similar results to the overall population. The data from this observational study are consistent with the known safety profile of perampanel derived from previous interventional phase II and III clinical studies. No unusual or unexpected TEAEs were observed in this real-world clinical practice setting.


Somatosensory cortex: acetylcholinesterase staining of barrel neuropil in the rat.
Acetylcholinesterase (AchE) staining of layer IV of rat somatosensory (SmI) cortex was studied. In the barrel field of SmI, there are periodic, intensely AchE staining foci in the pattern and with the dimensions of barrels. The onset of this staining, at age 3 days, corresponds with the arrival of thalamocortical input to the barrels. Undercutting of SmI prevents staining in layer IV. We conclude that there are AchE-rich zones in layer IV that coincide with the specific thalamocortical projection to SmI.


Synthesis and properties of high performance thermoplastic polycarbonate polyurethane elastomers through a non-isocyanate route.
Thermoplastic polycarbonate polyurethane elastomers (TPCUEs) are synthesized through a solvent-free non-isocyanate melt polycondensation route. The route starts with the synthesis of 1,6-bis(hydroxyethyloxycarbonylamino)hexane (BHCH) from ethylene carbonate and 1,6-hexanediamine, and then the TPCUEs are prepared by the melt polycondensation of BHCH and polycarbonate diols (PCDLs). The TPCUEs are characterized by GPC, FT-IR, 1H NMR, XRD, AFM, DSC, TGA and tensile testing. The TPCUEs prepared have linear structures and high molecular weights, with Mn over 3.0 × 104 g mol-1. And these TPCUEs exhibit excellent thermal and mechanical properties, with T g ranging from -18 to -1 °C, T m ranging from 93 to 122 °C, T d,5% over 240 °C, tensile strength between 28.1-47.3 Mpa, elongation at break above 1000%, Young's modulus between 13.8-32.7 Mpa and resilience at 200% fixed-length between 70-90%, which makes them a promising alternative to products synthesized through the isocyanate route. In addition, the effects of the hard segment contents and the molecular weights of soft segment on the properties of TPCUEs are researched.


HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo.
Progress in the understanding of the molecular mechanism for acute myeloid leukaemia is of great significance to generate new potential targets for treatment. Recent studies showed that HOXA9, a homeodomain-containing transcription factor, is commonly deregulated in acute leukaemia. In this study, we elucidated the direct correlation between HoxA9 expression and progression of leukaemia using 2 different types of leukaemia cells HL-60 and MOLT-3. The HoxA9 expression level was decreased in leukaemia cells with the treatment of all-trans retinoic acid or arsenic trioxide (As2 O3 ). Downregulation of HoxA9 could impair the proliferation and promote the leukaemia cell death. HoxA9 silencing also potentiated the differentiation of leukaemia cells, and in vivo studies demonstrated that HoxA9 downregulation could interfere the tumour growth. Interestingly, HoxA9 silencing also led to the alteration in miRNA expression, mediating the promoting effect on the leukaemia cell differentiation. Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia. In this study, we elucidated the critical role of HoxA9 in the proliferation and differentiation of leukaemia cells both in vitro and in vivo. The effect of HoxA9 modulation was correlated with the clinical effect of all-trans retinoic acid and As2 O3 . Furthermore, HoxA9 also regulated the miRNA expression, controlling the leukaemia cell differentiation. Therefore, this work provided new insights into molecular mechanism underlying the leukaemia treatment, potentially putting forward a brand new target to the gene therapy against leukaemia.


Were there long-term economic effects of exposure to polio vaccination? An analysis of migrants to Sweden 1946-2003.
Recent research showed that exposure to the vaccine against polio in early life had no long-term economic benefits among native Swedes. However, whether this result holds for individuals from other countries remains unexplored. This study explores the relationship between exposure to the vaccine and later-life outcomes, but focuses on individuals who migrated to Sweden (birth cohorts 1946-1971), and constitute a diverse sample in terms of national origin. Using a differences-in-differences approach and register data from the Swedish Longitudinal Immigrant Database, this study explores if being exposed to the vaccine against polio in the year of birth in the country of origin has any impact on adult income, educational achievement, or days or number of hospitalizations. The results are in line with the previous research in showing that there are no statistically significant effects on adult income, education, or health from exposure to the vaccine against polio, regardless of national origin. Furthermore, no scarring effects of exposure to polio epidemics were found on any of the outcomes, reinforcing the hypothesis that polio did not scar individuals in the same way as other contemporary epidemic diseases did, and that the lack of scarring could explain the absence of long-term impact from vaccine exposure.


Extracranial and intracranial vertebral artery dissections: A comparison of clinical findings.
The diagnostic criteria for extracranial vertebral artery dissection (VAD) have not been standardized among stroke centers. Recent studies have shown that extracranial (EVAD) and intracranial (IVAD) VAD may be different clinical entities. In this study, we reviewed clinical findings, including image findings of VAD cases, and compared these findings to EVAD and IVAD cases to highlight the clinical characteristics of EVAD. We searched our database to identify VAD cases registered between April 2008 and October 2014. We performed retrospective chart reviews to obtain detailed clinical information and compared clinical characteristics and radiological findings between EVAD and IVAD cases. We identified 10 patients with EVAD and 113 patients with IVAD. Clinically, patients with EVAD had initial symptoms that included significantly higher frequencies of neck pain, nausea, and vertigo, whereas medical hypertension and alcohol consumption were more commonly associated with IVAD cases. EVAD cases were also more likely to manifest as ischemic stroke. Radiologically, intramural hematomas were more commonly observed by magnetic resonance imaging (MRI) in patients with EVAD, whereas MRI and computed tomography more frequently revealed aneurysm formation in IVAD cases. Our data identified the clinical differences between patients with EVAD and IVAD. When relatively young patients complain of sudden-onset neck pain and/or other neurological symptoms, MRI studies may be useful to diagnose EVAD, especially when associated with mechanical stress.


Is there a special psychoanalytic love?
Although the analyst's role mandates a degree of detachment, analysts have often said that they offer patients a special kind of love. They have tended to equate that love with understanding, thus neutralizing the paradox but also diluting the love. When something more resembling a loving affect is sought, the suggestions include the love a scholar feels for his subject, the love that accompanies immersion in great literature, and love that is self-generated by deliberate efforts to move toward the patient or to generate empathy in oneself. But a form of love may also arise from the analyst's unique and relatively pure acquaintance with a person's "appeal," by which is meant the patient's effort to elicit responses from the analyst. Although the awareness of transference most obviously tends to immunize him, it also gives him a poignant "insider's" feel of the patient's appeal, since he is the target of that appeal while being unencumbered by the myriad considerations that would color his perception were he to regard himself as a proper object.


Two base pair deletion in IL2 receptor γ gene in NOD/SCID mice induces a highly severe immunodeficiency.
Genome editing has recently emerged as a powerful tool for generating mutant mice. Small deletions of nucleotides in the target genes are frequently found in CRISPR/Cas9 mediated mutant mice. However, there are very few reports analyzing the phenotypes in small deleted mutant mice generated by CRISPR/Cas9. In this study, we generated a mutant by microinjecting sgRNAs targeting the IL2 receptor γ gene and Cas9 protein, into the cytoplasm of IVF-derived NOD.CB17/Prkdcscid/JKrb (NOD/SCID) mice embryos, and further investigated whether a 2 bp deletion of the IL2 receptor γ gene affects severe deficiency of immune cells as seen in NOD/LtSz-scid IL2 receptor γ-/- (NSG) mice. Our results show that the thymus weight of mutant mice is significantly less than that of NOD/SCID mice, whereas the spleen weight was marginally less. T and B cells in the mutant mice were severely deficient, and NK cells were almost absent. In addition, tumor growth was exceedingly increased in the mutant mice transplanted with HepG2, Raji and A549 cells, but not in nude and NOD/SCID mice. These results suggest that the NOD/SCID mice with deletion of 2 bp in the IL2 receptor γ gene shows same phenotype as NSG mice. Taken together, our data indicates that small deletions by genome editing is sufficient to generate null mutant mice.


Duchenne muscular dystrophy newborn screening: the first 50,000 newborns screened in Taiwan.
Duchenne muscular dystrophy (DMD/Duchenne) is a progressive X-linked muscular disease with an overall incidence of 1:5,000 live male births. Recent availability in treatment for DMD raised the need of early diagnosis, and DMD became as a selective item of newborn screening (NBS) since Feb. 2021 in our center. Dried blood spots (DBS) muscle-type creatine kinase (CK) isoform was measured with a commercialized kit with age-adjusted cutoffs. Subjects with an elevation of CK in the first screen were requested for a re-screen 2 weeks later. A DBS whole-exome sequencing (WES) panel for dystrophin and other neuromuscular-related genes was applied to confirm the diagnosis for subjects with persistent hyperCKemia. During a 1-year period, 50,572 newborns (male 26,130) received DMD screening at a mean age of 2 days (SD 1 day). Among them, 632 (1.2%) had an elevated CK value. A re-screen at a mean age of 14 days (SD 8 days) revealed 14 subjects with persistent hyperCKemia, and DMD was confirmed in 3 of them. The incidence of DMD in Taiwan was 1:8,710 (95% CI 1 in 2,963 to 1 in 25,610) live birth males. Results of DMD DBS also assisted in Pompe newborn screening. NBS for DMD enables earlier management of the disease. The high re-screening rate could potentially be waived by moving the DBS WES assay to a second-tier test. The long-term benefit and the impact of newborn screening on the prognosis of DMD, however, remain further elucidated.


Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for generalized anxiety disorder and comorbid disorders: A randomized controlled trial.
Generalized anxiety disorder (GAD) can be treated effectively with either disorder-specific cognitive behavior therapy (DS-CBT) or transdiagnostic CBT (TD-CBT). The relative benefits of DS-CBT and TD-CBT for GAD and the relative benefits of delivering treatment in clinician guided (CG-CBT) and self-guided (SG-CBT) formats have not been examined. Participants with GAD (n=338) were randomly allocated to receive an internet-delivered TD-CBT or DS-CBT intervention delivered in either CG-CBT or SG-CBT formats. Large reductions in symptoms of GAD (Cohen's d ≥ 1.48; avg. reduction ≥ 50%) and comorbid major depressive disorder (Cohen's d ≥ 1.64; avg. reduction ≥ 45%), social anxiety disorder (Cohen's d ≥ 0.80; avg. reduction ≥ 29%) and panic disorder (Cohen's d ≥ 0.55; avg. reduction ≥ 33%) were found across the conditions. No substantive differences were observed between DS-CBT and TD-CBT or CG-CBT and SG-CBT, highlighting the public health potential of carefully developed TD-CBT and SG-CBT.


Acute effects of low-dose cranial irradiation on regional capillary permeability in experimental brain tumors.
To determine the acute effects of low-dose cranial irradiation (CRT) on regional capillary permeability (RCP) of normal brain, brain tumor and damaged brain surrounding the tumor, we used quantitative autoradiography (QAR) to measure regional blood-to-tissue transport (K) of [14C]aminoisobutyric acid (AIB) in experimental C6 brain tumors 3-4 h after a single dose of 3 Gy CRT. K increased 63% in cortex, 30% in basal ganglia and 31% in brain surrounding the tumor (BST) vs. controls (P less than 0.005). K did not change in the tumor or in the brain adjacent to the tumor (BAT), suggesting that capillaries of normal parenchyma are more sensitive to the acute effects of CRT than capillaries of damaged parenchyma or tumor.


Bilayer lipid membrane permeation and rupture due to hole formation.
A theory is developed for the permeation and rupture of bilayer lipid membranes due to fluctuation formation of holes (or pores) in them. The two monolayers of the bilayer lipid membrane are considered as mutually adsorbed on each other and the bilayer lipid membrane equilibrium is described by an adsorption isotherm in mean field approximation. The theory of nucleation is used for determination of the work for hole formation and the hole equilibrium size distribution as functions of the concentration C of monomer lipid in the solution. The bilayer lipid membrane permeation and rupture are analyzed from a unified point of view and expressions are derived for the dependence of the bilayer lipid membrane diffusion permeability coefficient and lifetime on C. The effect of foreign bodies (e.g., proteins) on the bilayer lipid membrane permeation and rupture is considered and a possible experimental application of the theory is discussed. The results obtained are directly applicable to dense monolayer films on liquid surfaces.


Do sufficient vitamin D levels at the end of summer in children and adolescents provide an assurance of vitamin D sufficiency at the end of winter? A cohort study.
The changes in serum 25-hydroxyvitamin D (25(OH)D) in adolescents from summer to winter and optimal serum vitamin D levels in the summer to ensure adequate vitamin D levels at the end of winter are currently unknown. This study was conducted to address this knowledge gap. The study was conducted as a cohort study. Sixty-eight participants aged 7-18 years and who had sufficient vitamin D levels at the end of the summer in 2011 were selected using stratified random sampling. Subsequently, the participants' vitamin D levels were measured at the end of the winter in 2012. A receiver operating characteristic (ROC) curve was used to determine optimal cutoff points for vitamin D at the end of the summer to predict sufficient vitamin D levels at the end of the winter. The results indicated that 89.7% of all the participants had a decrease in vitamin D levels from summer to winter: 14.7% of them were vitamin D-deficient, 36.8% had insufficient vitamin D concentrations and only 48.5% where able to maintain sufficient vitamin D. The optimal cutoff point to provide assurance of sufficient serum vitamin D at the end of the winter was 40 ng/mL at the end of the summer. Sex, age and vitamin D levels at the end of the summer were significant predictors of non-sufficient vitamin D at the end of the winter. In this age group, a dramatic reduction in vitamin D was observed over the follow-up period. Sufficient vitamin D at the end of the summer did not guarantee vitamin D sufficiency at the end of the winter. We found 40 ng/mL as an optimal cutoff point.


Diagnostic performance of non-contrast magnetic resonance angiography in patients with lower extremity arterial disease
Hungary. Knowing the consequences of burnout syndrome, it is important to prevent and recognize symptoms as early as possible.


Identification of N-acetylcysteine as a new substrate for rat liver microsomal glutathione transferase. A study of thiol ligands.
N-Acetyl-L-cysteine serves as an efficient substrate for the rat liver microsomal glutathione transferase with 1-chloro-2,4-dinitrobenzene as second substrate (8.8 +/- 0.37 mumol/min mg). The activity is actually higher than that obtained with glutathione (2-4 mumol/min mg). In examining the activity of liver subcellular fractions, no activity with N-acetyl-L-Cys could be detected in dialyzed or N-ethylmaleimide-treated (in order to remove endogenous glutathione) cytosol. The activity in rat liver microsomes was 0.11 +/- 0.007 mumol/min mg, which is accounted for by the content of microsomal glutathione transferase. Thus, N-acetyl-L-Cys can be used as a specific substrate for determining the conjugating activity of microsomal glutathione transferase. N-Acetyl-L-Cys was also shown to function as a substrate for the enzyme when other second substrates than 1-chloro-2,4-dinitrobenzene (with varying electrophilicity) are used. The pH dependence of microsomal glutathione transferase was studied. The kcat/Km(1-chloro-2,4-dinitrobenzene) was dependent on pH with an apparent pKa of 6, > or = 9, and > or = 8 with saturating glutathione, gamma-L-Glu-L-Cys, and N-acetyl-L- cysteine, respectively. Apparently the enzyme has the ability to lower the pKa of glutathione by 3 orders of magnitude. The kcat/Km(thiol) did not vary appreciably with pH (except for N-acetyl-L-cysteine), indicating that no rate-determining deprotonation occurs on the enzyme itself between pH 5.5 and 9. The abilities of histidine-, lysine-, and arginine-selective reagents to inactivate the enzyme when N-acetyl-L-cysteine and gamma-L-Glu-L-Cys were used as substrates were investigated. The activity toward N-acetyl-L-cysteine was decreased considerably less after treatment with the arginine-selective reagent phenylglyoxal, as compared to the activity toward GSH and gamma-L-Glu-L-Cys. This indicates that an arginine makes contact with gamma-L-Glu residue in GSH. With the other reagent/substrate combinations tested the enzyme was inactivated almost completely. The ability of microsomal glutathione transferase to stabilize the Meisenheimer complex formation between 1,3,5-trinitrobenzene and various glutathione analogues, including non-substrate thiols, has been examined. It is shown that, in general, substrates exhibited higher formation constants (approaching 50 mM-1) than non-substrates (4.5 +/- 1.7 mM-1, n = 7), whereas simpler thiols did not yield enzyme-bound complexes. The fact that the enzyme can stabilize Meisenheimer complexes from non-substrate thiol analogues of glutathione offers new possibilities for examining the substrate interactions of glutathione transferases.


Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract.
Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2',6'-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μ g/mL (7.4 μ M) and could be a lead for anti-malarial drug discovery.


Achievement of clinical remission in patients with juvenile idiopathic arthritis under a 2-10-year Etanercept exposure.
The objective of this retrospective study was to record the achievement of clinical remission (CR) in juvenile idiopathic arthritis patients under a 2-10 years' administration of Etanercept (ETN) and to detect any variables associated with CR. Patients previously resistant to conventional regimens were enrolled. The annual impact of ETN was assessed by: (a) the American College of Rheumatology pediatric criteria (ACRpedi), (b) the pre- and posttreatment disease activity score (juvenile arthritis disease activity score [JADAS71]), and (c) Wallace's criteria for CR. A total of 41 patients (F: 31) were registered. The median age and disease duration at baseline were 10.6 and 4.17 years, respectively, and their disease course was mainly polyarthritis (32/41). In respect to baseline, there was an impressive JADAS71 reduction posttreatment, most prominent after the first year. From year 1 to 5, more than 50 % of the patients achieved and retained CR and 66 % reached an ACRpedi 70, whereas after the 5th year, no patient was withdrawn due to an ACRpedi <30. JADAS71 at baseline was not associated with the subsequent CR achievement. However, JADAS71 1-year posttreatment had a significant association with the CR of the second posttreatment year, (p = 0.028, OR 0.79; 95 % CI 0.63-0.98) and a similar trend was observed for the following years. These findings emphasize the sustained impact of ETN in the achievement of CR. A low JADAS71 score 1-year posttreatment, may be associated with the maintenance of CR over the next treatment year.


Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma: Prophylaxis and Treatment of Thromboembolic Events.
Does routine screening for deep venous thrombosis prevent pulmonary embolism (or venous thromboembolism (VTE)-associated morbidity and mortality) in patients with thoracic and lumbar fractures? There is insufficient evidence to recommend for or against routine screening for deep venous thrombosis in preventing pulmonary embolism (or VTE-associated morbidity and mortality) in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. For patients with thoracic and lumbar fractures, is one regimen of VTE prophylaxis superior to others with respect to prevention of pulmonary embolism (or VTE-associated morbidity and mortality)? There is insufficient evidence to recommend a specific regimen of VTE prophylaxis to prevent pulmonary embolism (or VTE-associated morbidity and mortality) in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. Is there a specific treatment regimen for documented VTE that provides fewer complications than other treatments in patients with thoracic and lumbar fractures? There is insufficient evidence to recommend for or against a specific treatment regimen for documented VTE that would provide fewer complications than other treatments in patients with thoracic and lumbar fractures. Strength of Recommendation: Grade Insufficient. Based on published data from pooled (cervical and thoracolumbar) spinal cord injury populations, the use of thromboprophylaxis is recommended to reduce the risk of VTE events in patients with thoracic and lumbar fractures. Consensus Statement by the Workgroup The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_7.