A new governance model for the conservation and enhancement of Italian ancient transhumance routes.
Transhumance routes mark the natural path followed by herds during their seasonal movements. These routes are disappearing in many European countries. In Italy, a few fragments survive in Molise, in southern Italy, called Tratturi and run along grassy paths. The Tratturi are considered to be of archaeological, economic and landscape interest, sources of cultural and environmental attraction, protected by a national law. However, the landscapes connected to the Tratturi are disappearing both as a consequence of non-use and as a consequence of the advancement of wooded areas, and this poses a problem related to the governance system that involves many stakeholders, both at international, national and local level. The study, through the use of the combined approach of Stakeholder Basic Analysis and Social Network Analysis, identifies the role of the stakeholders involved, their power, their interest and their ability to support the decision-making system. Furthermore, the paper uses multivariate statistical analysis to detect the key stakeholders. A new model of governance, allowing to preserve the Tratturi and to enhance the services they can provide, is introduced, and it is named Authority for the Conservation and Enhancement of Tratturi (ACET). This study can help to identify appropriate management models for ancient routes based on all stakeholders involved, and more generally to implement shared and co-responsible planning choices in socio-ecological systems.


Cloning and characterization of two cDNAs encoding casein kinase II catalytic subunits in Arabidopsis thaliana.
Two cDNA clones, ATCKA1 and ATCKA2, encoding casein kinase II (CKII) catalytic subunits, were cloned from Arabidopsis thaliana and their nucleotide sequences were determined. Both cDNAs contain 999 bp open reading frames and are 94% identical on the amino acid sequence level. The deduced amino acid sequences of ATCKA1 and ATCKA2 are very similar to that of the human CKII catalytic alpha subunit (72% homology). Northern blot analysis indicates that the ATCKA1 and ATCKA2 mRNAs are present in all plant organs, but that ATCKA1 transcript levels are quite low compared to those of ATCKA2. Genomic Southern blot analysis suggests that there are at least three CKII genes in the A. thaliana genome. We expressed the ATCKA1 and ATCKA2 cDNAs in Escherichia coli using a pET vector derivative and analyzed the expressed protein in vitro. The expressed ATCKA1 protein phosphorylated casein using either ATP or GTP. This activity was inhibited by heparin, indicating that the expressed protein has activity similar to those reported for animal and yeast CKII.


Cyclic AMP stabilizes a class of developmentally regulated Dictyostelium discoideum mRNAs.
The stability of mRNA is an important facet of the regulation of protein synthesis. In mammalian cells most mRNAs have long half-lives (5-15 hours) but a substantial fraction are much less stable. There are few examples where the stability of a particular mRNA or class of mRNAs is specifically affected by environmental or developmental stimuli. Certain hormones cause specific stabilization of mRNAs species and preferential mRNA stability is important in the accumulation of globin and myosin mRNAs during the terminal stages of erythropoesis or myogenesis, respectively. Disaggregation of Dictyostelium discoideum aggregates induces the specific destabilization of a large class of developmentally regulated mRNAs; thus, this system is an excellent one in which to determine how such controls are effected. Here we show that addition of cyclic AMP to disaggregated cells specifically prevents the destabilization of these mRNAs.


Interconnection between biological abnormalities in borderline personality disorder: use of the Bayesian networks model.
There is agreement in that strengthening the sets of neurobiological data would reinforce the diagnostic objectivity of many psychiatric entities. This article attempts to use this approach in borderline personality disorder (BPD). Assuming that most of the biological findings in BPD reflect common underlying pathophysiological processes we hypothesized that most of the data involved in the findings would be statistically interconnected and interdependent, indicating biological consistency for this diagnosis. Prospectively obtained data on scalp and sleep electroencephalography (EEG), clinical neurologic soft signs, the dexamethasone suppression and thyrotropin-releasing hormone stimulation tests of 20 consecutive BPD patients were used to generate a Bayesian network model, an artificial intelligence paradigm that visually illustrates eventual associations (or inter-dependencies) between otherwise seemingly unrelated variables. The Bayesian network model identified relationships among most of the variables. EEG and TSH were the variables that influence most of the others, especially sleep parameters. Neurological soft signs were linked with EEG, TSH, and sleep parameters. The results suggest the possibility of using objective neurobiological variables to strengthen the validity of future diagnostic criteria and nosological characterization of BPD.


Enhanced local processing of dynamic visual information in autism: evidence from speed discrimination.
An important issue for understanding visual perception in autism concerns whether individuals with this neurodevelopmental disorder possess an advantage in processing local visual information, and if so, what is the nature of this advantage. Perception of movement speed is a visual process that relies on computation of local spatiotemporal signals but requires the comparison of information from more than a single spatial location or temporal point. This study examined speed discrimination in adolescents (ages 13-18 years old) with autism spectrum disorders (ASD). Compared to healthy controls (n=17), individuals with ASD (n=19) showed similarly precise speed discrimination when two comparison motion stimuli (random dot patterns) were presented closely in time (0.5s). With a longer temporal interval (3s) between the motion stimuli, individuals with ASD outperformed healthy controls on speed discrimination. On a second task--global motion perception--in which individuals were asked to detect coherent motion, individuals with ASD exhibited slightly degraded performance levels. The observed temporally selective enhancement in speed discrimination indicates that a local processing advantage in autism develops over a longer temporal range and is not limited to the spatial domain. These results suggest a dynamic perceptual mechanism for understanding, and therapeutically addressing, atypical visual processing in this neurodevelopmental disorder.


Expression and mechanisms of interferon-stimulated genes in viral infection of the central nervous system (CNS) and neurological diseases.
Interferons (IFNs) bind to cell surface receptors and activate the expression of interferon-stimulated genes (ISGs) through intracellular signaling cascades. ISGs and their expression products have various biological functions, such as antiviral and immunomodulatory effects, and are essential effector molecules for IFN function. ISGs limit the invasion and replication of the virus in a cell-specific and region-specific manner in the central nervous system (CNS). In addition to participating in natural immunity against viral infections, studies have shown that ISGs are essential in the pathogenesis of CNS disorders such as neuroinflammation and neurodegenerative diseases. The aim of this review is to present a macroscopic overview of the characteristics of ISGs that restrict viral neural invasion and the expression of the ISGs underlying viral infection of CNS cells. Furthermore, we elucidate the characteristics of ISGs expression in neurological inflammation, neuropsychiatric disorders such as depression as well as neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Finally, we summarize several ISGs (ISG15, IFIT2, IFITM3) that have been studied more in recent years for their antiviral infection in the CNS and their research progress in neurological diseases.


Identification and characterization of abundant repetitive sequences in Allium cepa.
Species of the genus Allium are well known for their large genomes. Allium cepa is of great economic significance. Among vegetables, it ranks second after tomato in terms of the global production value. However, there is limited genomics information available on A. cepa. In this study, we sequenced the A. cepa genome at low-coverage and annotated repetitive sequences by using a combination of next-generation sequencing (NGS) and bioinformatics tools. Nearly 92% of 16 Gb haploid onion genome were defined as repetitive sequences, organized in 162 clusters of at least 0.01 percent of the genome. Of these, a proportion representing 40.5% of the genome were further analyzed in detail to obtain an overview of representative repetitive elements present in the A. cepa genome. Few representative satellite repeats were studied by fluorescence in situ hybridization (FISH) and southern blotting. These results provided a basis for evolutionary cytogenomics within the Allium genus.


Multifunctional Nanostructures for Tumor-Targeted Molecular Imaging and Photodynamic Therapy.
A multifunctional ICG-FA-PPD nanostructure is constructed by a facile self-assembly method through the negatively charged indocyanine green (ICG)- and positively charged folic acid-modified PEI-PEG-gadoteric acid (FA-PPD). The resulting ICG-FA-PPD is not only able to be used for targeting tumors, magnetic resonance imaging (MRI), and near-infrared imaging, but, more importantly, it enables photodynamic therapy for tumor.


Basidiomycete Lentinula edodes CDC5 and a novel interacting protein CIPB bind to a newly isolated target gene in an unusual manner.
We isolated a target gene for the Lentinula edodes putative transcription factor Le.CDC5 that contains a c-Myb-type DNA-binding domain. The gene, termed ctg1, encodes a novel protein (159 amino acid residues) with a leucine zipper-like sequence and contains a 7-bp Le.CDC5-binding sequence, 5'GCAATCT3', in its transcribed region downstream of the start codon. Chromatin immunoprecipitation analysis strongly suggested that intracellular Le.CDC5 binds to this 7-bp sequence on L. edodes chromatin. Binding was most efficient on chromatin from the stipes of mature fruiting bodies. Two Le.CDC5-interaction partners were identified in L. edodes and named CIPA and CIPB. The CIPB protein (127 amino acid residues) binds to a 6-bp sequence with the consensus sequence 5'CAACAC/T/G3'. The ctg1 gene contains nine 6-bp consensus (or consensus-like) sequences, six are in the 5'-upstream region and three in the transcribed region downstream of the start codon. At least two each of the upstream and downstream sequences appear to bind CIPB in vitro. We suggest that Le.CDC5 and CIPB can cooperatively regulate the expression of ctg1.


Attenuation of experimental osteoarthritis with human adipose-derived mesenchymal stem cell therapy: inhibition of the pyroptosis in chondrocytes.
To explore the role and mechanism of human adipose-derived mesenchymal stem cells (hAD-MSCs) in the treatment of osteoarthritis (OA). OA hulth model of Sprague Dawley (SD) rats and 20 ng/ml TNF-α treated chondrocytes were used as models of OA in vivo and in vitro, respectively. hAD-MSCs were administrated in the articular cavity by injection in vivo and co-cultured with chondrocytes using transwell in vitro. Haematoxylin and eosin staining and Safranin-O/Fast green staining were performed to detect tissue destruction and histopathology. Scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructure of chondrocytes. The pyroptosis signaling pathway-related proteins were detected by immunohistochemistry, immunofluorescence, qRT-PCR and Western blot. And small interference technology was used to study the mechanism in depth. hAD-MSCs could delay the development of rat OA, improve the pathological changes of joints, inhibit the expression of NLRP3, Caspase1, GSDMD and TNFR1. In vitro, the expression of pyroptosis signal proteins in chondrocytes was significantly elevated when stimulated with TNF-α, the level of inflammatory factors such as IL-1β, IL-18 was increased, and the cell morphology was significantly destroyed. While co-cultured with hAD-MSCs, these syndromes were reversed. Knockout of TNFR1 also returned the upregulation of pyroptosis signals which caused by TNF-α. These results demonstrated that hAD-MSCs could inhibit pyroptosis signaling pathway of chondrocytes induced by TNF-α, which have raised our understanding of the role of hAD-MSCs as promising therapy for the management of OA.


Effects of GTP,GDP[beta S] and glucose on adenylate cyclase activity of E. coli B.
Adenylate cyclase activity was measured in suspensions of E.coli B, rendered permeable with toluene. The enzyme was activated in a dose-dependent manner by GTP and by its non-hydrolysable analogue, GTP[gamma S]. In contrast, incubation with GDP[beta S], a non-phosphorylatable analogue of GDP, caused a dose-related inhibition of adenylate cyclase; this was partially overcome by addition of GTP. GTP did not relieve, and GDP[beta S] augmented, the non-competitive and dose-related inhibition of E.coli adenylate cyclase by glucose.


Condition factor and organosomatic indices of parasitized Rattus rattus as indicators of host health.
This study describes the influence of parasitism (Trypanosoma lewisi and Cysticercus fasciolaris) on the condition factor, hepato and splenosomatic indices of the common house rat, Rattus rattus Linnaeus, 1758 from Rohilkhand, Uttar Pradesh, India. Examination of R. rattus (n = 389) revealed T. lewisi (prevalence 12.40 %; intensity14 parasites/1000 RBC) from the blood and C. fasciolaris (larval Taenia taeniaeformis) (prevalence 46.70 %; intensity 2-4 par/host) from the liver. Condition factor (K) and organosomatic indices [hepatosomatic index, spleenosomatic index (SSI)] were evaluated in two groups (Group I non pregnant, Group II pregnant) of female rats which were further subdivided into four subgroups each (a Uninfected, b T. lewisi infected, c C. fasciolaris infected, d T. lewisi and C. fasciolaris infected) belonging to three weight groups (A 50-100 g; B 100-150 g; C 150-200 g). The results indicated that reduction in K-factor was more apparent in young rats, Group Ic (weight category A) showing the maximum depletion (21.62 %), hepatomegaly and splenomegaly were frequent outcomes of parasitic infection and maximum change (50 %) was recorded in dual-infected pregnant rats (Group IId) expressed as SSI of the infected rat. The abnormal condition factor and organosomatic indices indicate perturbations in the biological systems at the organismal level. Thus, the information generated through this piece of work is a warning of an incipient or impending problem.


Extracellular matrix antigen of human muscle defined by a monoclonal antibody.
A monoclonal antibody (7.1B3) has been produced in mice previously immunised with a glycoprotein fraction prepared from human myotube cells grown in tissue culture. The antibody precipitates an antigen complex of four glycoprotein components from detergent extracted human muscle myotube cultures. These are two chains of about 205K MW and two chains of about 130-140K MW. The antigen complex is trypsin-sensitive collagenase insensitive and bands as a complex of 10S on sucrose gradients in NP40. Indirect immunofluorescence studies on cell cultures of myoblasts and myotubes showed that the antigen existed in a number of locations: as a granular stain on the cell surface of myotubes, and as short streaks of immunoreactivity in the extracellular matrix. Clonal populations of myoblasts and myotubes gave a similar result showing that 7.1B3 is specifically synthesized by cells of the myogenic lineage. Double indirect immunofluorescence staining with 7.1B3 antibody and fibronectin antibody showed no overlap of immunoreactivity indicating that these two antigens are different. 7.1B3 antigen was found during human fetal muscle development in vivo at all time points studied from 15 weeks onwards. Immunoreactivity was localised to the loose extracellular matrix and in the endomysium. Perymysium staining was very prominent at 25 weeks and in adult muscle. Double staining of 7.1B3 antibody and alpha-bungarotoxin was carried out to determine whether 7.1B3 was present in synaptic junctions. Although 7.1B3 was found in the endomysium it is excluded from synaptic areas. We conclude that 7.1B3 antibody defines a new and novel antigen in the extracellular matrix of human muscle in vivo and in vitro.


Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions.
Multiple sclerosis is considered to be an immune-mediated disease of the central nervous system, characterized by chronic inflammation, primary demyelination and axonal damage. The mechanisms of demyelination and axonal injury are heterogeneous and complex. One possible mechanism is direct damage of oligodendrocytes and neurons by Class I MHC restricted cytotoxic T-cells. In this study we analyzed the expression of functional MHC class I molecule complex, consisting of alpha-chain and beta2-microglobulin, in a large sample of human autopsy material, containing 10 cases of acute MS, 10 cases of chronic active MS, 10 cases of chronic inactive MS and 21 controls. To examine the expression of MHC class I and II molecules on the different cell-types in brain, we used quantitative immunohistochemical techniques, double staining and confocal laser microscopy scans on paraffin embedded sections. We found constitutive expression of MHC class I molecule on microglia and endothelial cells. A hierarchical up-regulation of MHC class I was present on astrocytes, oligodendrocytes, neurons and axons, depending upon the severity of the disease and the activity of the lesions. MHC class II molecules were expressed on microglia and macrophages, but not on astrocytes. These data indicate that in MS lesions all cells of the central nervous system are potential targets for Class I MHC restricted cytotoxic T-cells.


Bacteriophage-antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa: In vitro synergy testing.
Here, we investigate the impact of phage-antibiotic combinations (PAC) on bacterial killing, resistance development and outer membrane vesicle (OMV) production in multidrug-resistant (MDR) P. aeruginosa. After screening 10 well-characterized MDR P. aeruginosa strains against three P. aeruginosa phages, representative strains, R10266 and R9316, were selected for synergy testing based on high phage sensitivity and substantial antibiotic resistance patterns, while phage EM was chosen based on host range. To understand the impact of phage-antibiotic combinations (PAC) against MDR P. aeruginosa, time-kill analyses, OMV quantification and phage/antibiotic resistance testing were performed. Phage and meropenem demonstrated synergistic activity against both MDR strains. Triple combination regimens, phage-meropenem-colistin and phage-ciprofloxacin-colistin, resulted in the greatest CFU reduction for strains R9316 (3.50 log10 CFU ml-1 ) and R10266 (4.50 log10 CFU ml-1 ) respectively. PAC resulted in regained and improved antibiotic susceptibility to ciprofloxacin (MIC 2 to 0.0625) and meropenem (MIC 32 to 16), respectively, in R9316. Phage resistance was prevented or reduced in the presence of several classes of antibiotics and OMV production was reduced in the presence of phage for both strains, which was associated with significantly improved bacterial eradication. These findings support the potential of phage-antibiotic synergy (PAS) to augment killing of MDR P. aeruginosa. Systematic in vitro and in vivo studies are needed to better understand phage interactions with antipseudomonal antibiotics, to define the role of OMV production in P. aeruginosa PAC therapy and to outline pharmacokinetic and pharmacodynamic parameters conducive to PAS. This study identifies novel bactericidal phage-antibiotic combinations capable of thwarting resistance development in MDR and XDR P. aeruginosa strains. Furthermore, phage-mediated OMV reduction is identified as a potential mechanism through which PAC potentiates bacterial killing.


The induction of labour by the intravenous infusion of prostaglandin F2alpha.
Labour was induced by the intravenous infusion of prostaglandin F2alpha in 106 patients at 36-44 weeks of pregnancy. The induction was successful in 80% of the women. The total dose needed ranged from 0.1 to 14.2 mg of PGF2alpha. The uterine activity and fetal heart rate were recorded by cardiotocography. The contraction pattern and induction-delivery time were the same as reported for induction with oxytocin. In one case uterine hyperactivity occurred after rupture of the membranes. No serious adverse effects were seen, but in a few cases local irritation was noted at the site of infusion. The condition of the infants was generally good. It might be concluded that PGF2alpha seems valuable for the induction of labour, but due to the risk for over-stimulation careful supervision is needed.


Inducing dissociation and schizotypal experiences through "vision-deforming" glasses.
Derealization, depersonalization and schizotypal experiences are described as separate concepts but they can be hard to distinguish. One way to show the uniqueness of these concepts is by showing a dissociation between these experiences. The aim of this study was to experimentally induce derealization without inducing depersonalization or schizotypal experiences. Healthy participants watched a neutral video in one of four conditions: (1) with stroboscopic light, (2) while wearing deforming glasses, (3) with stroboscopic light and while wearing "vision deforming glasses" or (4) without any manipulation. The results show that the "vision deforming" glasses induced derealization without inducing depersonalization but not without inducing schizotypal experiences. The stroboscopic light showed no significant effect, nor was there a significant interaction between the stroboscopic light and the deforming glasses. The results indicate that using "vision deforming" glasses as a manipulation method can show a single dissociation between derealization and depersonalization but cannot dissociate derealization from state schizotypy. This association between derealization and schizotypal experiences might be helpful in understanding the high comorbidity rate between dissociative disorders and schizophrenia spectrum disorders.


Explaining nutritional habits and behaviors of low socioeconomic status women in Sanandaj: a qualitative content analysis.
Health and behavior are closely related subjects because disease is typically rooted in individuals' unhealthy behaviors and habits. This study aims to identify women's nutritional habits and behaviors in order to design interventions to promote nutritional literacy. This qualitative research is part of a mixed method (quantitative-qualitative) study, conducted based on content analysis. Data were collected using semistructured interviews, group discussions, and in-depth interviews with married women, aged 18-50 years, who were referred to four health care centers in Sanandaj in 2013-2014. Nutritional habits and behaviors of participants were classified into two categories: representation of nutritional behavior based on consumption pattern and representation of nutritional behavior based on consumption method. For the former, eight consumption pattern subcategories were formed: meat, dairy, fast food, local foods, fruits and vegetables, soft drinks, and oils. The latter (representation of nutritional behavior based on consumption method), included two subcategories: consumption method in line with health and consumption method inconsistent with health. Results of this qualitative study provide a solid foundation for development and designing interventions to nutritional literacy promotion based on needs. The designed intervention to healthy nutritional behavior should be based on empowering women and providing facilitator factors of a healthy diet. While designing this study, with a holistic perspective, individual and social aspects of a healthy diet should be taken into account.


Clinical Characteristics, Associated Factors, and Predicting COVID-19 Mortality Risk: A Retrospective Study in Wuhan, China.
COVID-19 has become a serious global pandemic. This study investigates the clinical characteristics and the risk factors for COVID-19 mortality and establishes a novel scoring system to predict mortality risk in patients with COVID-19. A cohort of 1,663 hospitalized patients with COVID-19 in Wuhan, China, of whom 212 died and 1,252 recovered, were included in this study. Demographic, clinical, and laboratory data on admission were collected from electronic medical records between January 14, 2020 and February 28, 2020. Clinical outcomes were collected until March 26, 2020. Multivariable logistic regression was used to explore the association between potential risk factors and COVID-19 mortality. The receiver operating characteristic curve was used to predict COVID-19 mortality risk. All analyses were conducted in April 2020. Multivariable regression showed that increased odds of COVID-19 mortality was associated with older age (OR=2.15, 95% CI=1.35, 3.43), male sex (OR=1.97, 95% CI=1.29, 2.99), history of diabetes (OR=2.34, 95% CI=1.45, 3.76), lymphopenia (OR=1.59, 95% CI=1.03, 2.46), and increased procalcitonin (OR=3.91, 95% CI=2.22, 6.91, per SD increase) on admission. Spline regression analysis indicated that the correlation between procalcitonin levels and COVID-19 mortality was nonlinear (p=0.0004 for nonlinearity). The area under the receiver operating curve of the COVID-19 mortality risk was 0.765 (95% CI=0.725, 0.805). The independent risk factors for COVID-19 mortality included older age, male sex, history of diabetes, lymphopenia, and increased procalcitonin, which could help clinicians to identify patients with poor prognosis at an earlier stage. The COVID-19 mortality risk score model may assist clinicians in reducing COVID-19-related mortality by implementing better strategies for more effective use of limited medical resources.


Elevation of liver endoplasmic reticulum stress in a modified choline-deficient l-amino acid-defined diet-fed non-alcoholic steatohepatitis mouse model.
Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice. To establish the assay method for detection of ER stress in the liver, tunicamycin (TM) (0.3 mg/kg i. p.) was administered to ERAI-Luc mice, and the luciferase activity was measured in ex vivo and in vivo. To evaluate ER stress in the NASH model, ERAI-Luc mice were fed a modified choline-deficient l-amino acid-defined (mCDAA) diet for 14 weeks. After measurement of ER stress by luminescence imaging, levels of liver lipids and pro-fibrotic and pro-inflammatory gene expression were measured as NASH-related indexes. In non-invasive whole-body imaging, TM elevated luciferase activity in the liver, induced by activation of ER stress. The highest luminescence in the liver was confirmed by ex vivo imaging of isolated tissues. In parallel with progression of NASH, elevated luminescence induced by ER stress in liver was observed in mCDAA diet-fed ERAI-Luc mice. Luciferase activity was significantly and positively correlated to levels of triglyceride and free cholesterol in the liver, as well as to the mRNA expression of type 1 collagen α1 chain and tumor necrosis factor α. These data indicated that the use of ERAI-Luc mice was effective in the detection of ER stress in the liver. Moreover, the NASH model using ERAI-Luc mice can be a useful tool to clarify the role of ER stress in pathogenesis of NASH and to evaluate effects of drugs targeted against ER stress.


Dual-function of thiocyanate on nitrite-induced formation of reactive nitrogen oxide species in human oral cavity: inhibition under neutral and enhancement under acidic conditions.
Salivary nitrate is reduced to nitric oxide (NO) via nitrite in the human oral cavity. The nitrite and NO formed can be transformed to reactive nitrogen oxide species (RNOS). In this investigation, RNOS formed in mixed whole saliva and its fractions were detected by the oxidation of aminophenyl fluorescein (APF) and the transformation of 3-amino-4-monomethylamino-2',7'-difluorofluorecein (DAF-FM) to its triazol form (DAF-FMT). Nitrite-induced oxidation of APF and formation of DAF-FMT increased as pH was decreased from 7 to 5 and SCN- inhibited the oxidation of APF and the formation of DAF-FMT around neutral pH and enhanced at pH about 5. The SCN- -dependent inhibition was due to the suppression of salivary peroxidase and the enhancement was due to the formation of NOSCN from HNO2 and SCN-. It is deduced that the increase in the concentrations of nitrite and H+ in the oral cavity may result in the enhanced formation of


Driving in the elderly in health and disease.
Driving is a complex, multifaceted instrumental activity of daily living that has an independent influence on multiple health and well-being outcomes among older adults. Therefore, the benefits of driving to the individual must be balanced, through careful assessment and diagnosis, with the potential risk to self and others posed by a medically impaired driver. The influence of dementia changes substantially during the disease progression from very mild to mild, and driving is not advised for those who have progressed to the moderate stage of Alzheimer disease. Fortunately, validated high-quality screening instruments, including modern simulators and other technology aids, can help clinicians trichotomize risk (i.e., high, moderate, or low) and determine which patients need further evaluation by a driving specialist (e.g., those in the moderate range). Moreover, a body of evidence is building regarding the efficacy of certain intervention pathways to maintain current levels of driving performance among individuals with dementia, or at least slow its decline. Even with the progression of advanced driving technologies, understanding driving ability of patients with dementia will remain a critical challenge to clinicians for the foreseeable future.


Use of synthetic polymers for biomedical application.
Synthetic polymers have been used for numerous biomedical and pharmacologic purposes. These include prosthetic implants, suture material and drug carriers. Long-term results are often unpredictable despite the continuing exposure to an often hostile physiologic environment. Biocompatibility in general is influenced by physical, chemical and structural properties of these polymers. While surface phenomena are important, reactions related to the bulk itself are not negligible. Methods for analyzing surface and bulk interfaces are described. These tests are directly applicable to studies of polysiloxane (silicone) and polyurethane cardiac pacing leads.


A case of idiopathic normal pressure hydrocephalus with fragile X-associated tremor/ataxia syndrome.
Clinical management of patients with fragile X-associated tremor/ataxia syndrome (FXTAS) is a challenge, and there has been not an established treatment for FXTAS, which is now treated symptomatically. Diagnosis of coexistent idiopathic normal pressure hydrocephalus (iNPH) with FXTAS is also hard because clinical and imaging features can overlap between the FXTAS patients coexistent with and without iNPH. We present a 79-year-old male genetically diagnosed with FXTAS who was successfully treated by a shunt surgery and consequently diagnosed with iNPH, and suggest the management of coexistent iNPH with FXTAS when it is clinically suspicious.


Mycotic aneurysm and renal transplantation.
A case of mycotic aneurysm secondary to suppuration of a renal transplant is reported. This aneurysm was responsible for ischemia of the leg and was treated successfully by ligation and venous bypass grafting.


Continuing education: the British experience.
The methods used to assess proficiency in neurosurgical trainees and consultant staff are reviewed. Under the auspice of the Surgical Royal Colleges trainees undergo a formal assessment 6 monthly by their trainer, annually by a local training committee and in their 3rd year of training by the Specialist Advisory Committee (SAC) in Neurosurgery. This committee supervises all neurosurgical training in the UK and Ireland and recommends trainees for the Certificate of Completion of Training if their training assessments and operative experience are satisfactory and if they have passed the Intercollegiate Specialty Examination in Neurosurgery. Assessing proficiency of consultant staff in the UK poses greater difficulty. For several years neurosurgeons have registered Continuing Medical Education (CME) credits on a voluntary basis. Such action is insufficient to reassure the public of professional competence. The General Medical Council (GMC) have submitted proposals for revalidation based on- (i) the maintenance of a 'folder' including details of performance, CME and complaints, (ii) annual appraisals carried out internally, (iii) a 5 yearly external assessment which if satisfactory would lead to revalidation by the GMC. Team working will be encouraged and consultants made responsible for the quality of service of their professional colleagues. A national comparative audit of subarachnoid haemorrhage should permit comparison of outcomes between neurosurgical units.


[Occupational exposure to isocyanates and individual susceptibility].
Patients with organic diisocyanate-induced pulmonary disease may be specially susceptible to the toxic effects of agent. Among 11 cases diagnosed in one year, the majority (10/11) were slow acetylators. The same patients were different from the control population in terms of alpha-1-antitrypsin phenotypes. Heterozygous combinations were more frequent than among controls. It seems that the combination of low N-acetylation capacity and a heterozygous alpha-1-antitrypsin predisposes to the disease.


Establishment of HEp-2 cell preparation for automated analysis of ANA fluorescence pattern.
Identification of antinuclear antibodies (ANAs) has large clinical importance for the assessment of autoimmune diseases. HEp-2 cell preparations on microscopic slides are commonly used as antigenic substrate. Methods used for cell preparation are important for ANA pattern analysis; however, these methods differ widely and are mostly not specified. HEp-2 cells were fixed using acetic acid-ethanol, methanol-acetone, acetone, formaldehyde, paraformaldehyde, or glutaraldehyde. Morphological analysis was done after haematoxylin-eosin staining and DAPI-staining of cell nuclei. The results demonstrate a high variability of cell and nuclear morphology depending on the used fixatives. Aldehyde fixatives conserved the cell structures best, acetone fixatives revealed remarkable changes. After selecting appropriate fixation procedures to preserve nuclear structures further experiments are necessary to find out which fixation procedure preserves the disease-linked antigens the best way and are, therefore, suitable to be used in ANA-testing of AABs.


Toxicity evaluation of triphenyltin in zebrafish larvae by embryonic malformation, retinal development, and GH/IGF axis.
The adverse influences of triphenyltin (TPT) on the aquatic system have been of great concern due to their widespread use and ubiquity in water environment, although it has been prohibited as antifouling coatings. In the present study, we investigated the developmental toxicity of TPT on zebrafish embryos by exposure to different concentrations (0, 1, 10, and 100 ng/l) from 2-h post-fertilization (hpf). Some parameters of developmental abnormalities (hatching, survival, body length, and malformation) were recorded, as well as the expression of several genes involved in the retinal development and growth hormone/insulin-like growth factor (GH/IGF) axis. Our results showed that TPT exposure induced developmental toxicity, including growth inhibition, malformation, and the dysregulation of gene expression levels related to the retinal development and GH/IGF axis. Thus, our data indicated that environmental exposure of TPT could induce developmental toxicity in zebrafish embryos, and those parameters could extend our understanding of the adverse effects of TPT on aquatic organisms.


The social disablement of men in hostels for homeless people. I. Reliability and prevalence.
Studies of mental health problems of homeless people have used diagnosis as the sole measure of these problems. In this study, the feasibility and reliability of measuring social disablement in the psychiatric assessment of homeless people was investigated. A random sample of 101 homeless men living in four long-stay hostels were assessed for their social disablement by the Social Behaviour Schedule (SBS). The prevalence of SBS problems in these men and the interobserver reliability were assessed. The results show that the SBS is a reliable screening instrument which is relatively easy to use. The most frequent SBS problems were 'Other problems', 'Hostility' and 'Depression". Less than 10% of the hostel sample had disablement items similar to those of patients in long-stay wards. The SBS is a useful and reliable tool in the psychiatric assessment of men in hostels for the homeless.


Therapeutic strategy and the role of apheresis therapy for ABO incompatible living donor liver transplantation.
Although in Japan, transplant organs obtained from brain-dead donors (BDD) has been allowed since October 1997, to date only 27 liver grafts from BDD have been obtained. The severe shortage of transplantable organs is a big problem, not only in liver transplantation but also other organ transplants. Liver transplantation is a fundamental treatment for end-stage liver disease. In order to perform living-donor liver transplantation (LDLT) in a safer manner, apheresis (plasmapheresis) plays a major role in Japan because of the prevalence of LDLT wherein later re-transplantation is difficult. Therefore, because of a limited donor supply and because the need of patients with end-stage liver disease is critical, use of grafts from ABO-incompatible donors may be the only available option. From June 1990 to November 2004, 1010 patients underwent 1060 LDLT cases at Kyoto University Hospital. Of these, 139 LDLT cases (13.1%) received ABO-incompatible living-donor liver grafts. The role of apheresis in ABO-incompatible LDLT is the reduction of antibody titers such as anti-A or anti-B antibody. We perform preoperative apheresis as a general rule for incompatible cases, and the recipient's antibody level against the donor's blood type is decreased to one eighth of the baseline value before LDLT. Up to the present, baseline antirejection regimens included steroids, tacrolimus and cyclophosphamide. At first, splenectomy was performed during operation to suppress antibody production, and intraportal infusion therapy was performed to control local disseminated intravascular coagulation (DIC) occurring in ABO-incompatible grafts. At that time, three agents--methylprednisolone, prostaglandin E1, and gabexate mesilate--were infused continuously for 3 weeks after LDLT. At present, instead of intraportal infusion therapy, hepatic artery infusion therapy without splenectomy is adopted because of portal thrombosis, and two agents--methylprednisolone and prostaglandin E1--are infused continuously for 3 weeks after LDLT. Recently, we introduced an anti-CD20 monoclonal antibody (Rituximab) instead of splenectomy for B cell deletion before ABO-incompatible LDLT. In this article, we describe our therapeutic strategy and the role of apheresis around ABO-incompatible LDLT.


Development of marine probiotics: prospects and approach.
The term probiotics stands for bacterial strain acting for the upliftment of beneficial gut microflora as well as restricting the growth of decay or disease causing bacteria and other agents. They protect us from disease causing microorganisms and are vital for the digestion of nutrients and food. Researchers are now trying to explore the possibilities of therapeutic applications of probiotics in inflammatory bowel disease, treating diarrhea, eczema prevention in children, and reducing bladder cancer recurrence and urinary tract infections. The best known probiotic strains are Bifidobacteria, Lactobacilli, and Streptococcus thermophilus and can be found in food products such as yoghurts, fermented and unfermented milk, miso, tempeh, and some juices and soy beverages. Thus, as a substitute to the use of antibiotics, the dietary supplementation with probiotic bacteria is being widely employed in the aquaculture industry. This chapter is an attempt to shift the paradigm of research in probiotic area to the marine environment and to find ways of expanding the research in marine probiotics development.


Structure of mannose-specific snowdrop (Galanthus nivalis) lectin is representative of a new plant lectin family.
Tetrameric Galanthus nivalis agglutinin (50,000 M(r)) belongs to a super-family of alpha-D-mannose-specific plant bulb lectins known to be potent inhibitors of retroviruses. The 2.3 A crystal structure of this lectin complexed with methyl alpha-D-mannose reveals a novel three-fold symmetric beta-sheet polypeptide fold. Three antiparallel four-stranded beta-sheets, each with a conserved mannose-binding site, are arranged as a 12-stranded beta-barrel. The tetramer displays 222 symmetry. Pairs of monomers form stable dimers through C-terminal strand exchange. The so formed hybrid beta-sheets are the sites for high affinity mannose binding in the dimer interface. Occupancy observed at corresponding sites in other beta-sheets suggests a potential for twelve sites per tetramer.


Framing stigma as an avoidable social harm that widens inequality.
This article discusses the social harms arising out of stigma experienced by people who use drugs (PWUD), and how stigmatisation compromises 'human flourishing' and constrains 'life choices'. Drawing on Wellcome Trust qualitative research using in-depth, semi-structured interview data (N = 24) with people who use heroin, crack cocaine, spice and amphetamine, this article firstly provides insight into how stigma is operationalised relationally between people via a lens of class talk and drug use predicated on normative ideas of 'valued personhood'. Secondly, it turns to how stigma is weaponised in social relations to keep people 'down', and thirdly, it shows how stigma is internalised as blame and shame and felt deeply 'under the skin' as 'ugly feelings'. Findings from the study show that stigma harms mental health, inhibits access to services, increases feelings of isolation, and corrodes a person's sense of self-worth as a valued human being. These relentless negotiations of stigma are painful, exhausting and damaging for PWUD, culminating in, as I argue, everyday acts of social harm that come to be normalised.


Expression of membrane progestin receptors in zebrafish (Danio rerio) oocytes, testis and pituitary.
A distinct family of membrane progestin receptors (mPRalpha, mPRbeta, and mPRgamma) that mediate rapid, nongenomic actions of progestins has been identified and characterized in several fish species as well as in frogs, rats, pigs, and humans. However, few studies to date have thoroughly examined tissue specific expression of mPR protein and transcripts in any model species. In the present study, the expression of both mPRalpha and mPRbeta in zebrafish was examined by RT-PCR, Western blotting and immunohistochemistry using mPR specific primers and antibodies. The proteins and mRNAs of mPRalpha and mPRbeta were co-localized in the major reproductive organs, including the ovary, testis, and pituitary. Both mPRalpha and mPRbeta were found in scattered cells in the pituitary for the first time. In the testis, immunostaining of mPRalpha was restricted to the sperm, while mPRbeta was found in spermatocytes and spermatogonia. In the ovary, both mPRalpha and mPRbeta were detected in denude oocytes and follicular layer cells. Furthermore, mPRalpha and mPRbeta proteins were localized at or near the oocyte membrane of maturationally competent stage IV oocytes in a probable location for mediating progestin-induced nongenomic signaling in oocytes.


Opioid-taking self-efficacy amongst Taiwanese outpatients with cancer.
The purpose of this study was to describe the level of opioid-taking self-efficacy amongst Taiwanese outpatients with cancer pain, and to examine the associations between various demographic and medical characteristics and opioid-taking self-efficacy. This was a cross-sectional study. Ninety-two outpatients who had taken prescribed opioid analgesics for cancer related pain in the past 1 week completed the Opioid-Taking Self-Efficacy Scale-CA (OTSES-CA). Details of the medical characteristics were obtained from the patients' medical record. Results show patients in this study were moderately confident of being able to perform many of the key tasks associated with effective opioid-taking. However, for many key behaviours relating to tailoring medication regimens, acquiring help and managing treatment-related concerns, only around one third to slightly more than two fifths reported high confidence. Individuals with lower levels of education and who were experiencing more side effects from opioids reported lower confidence in taking their analgesics. The results of this study suggest it is important to understand how patients perceive their ability to perform key tasks associated with effective opioid-taking, to effectively tailor educational and supportive interventions. Patients with lower levels of education and with side effects of opioids may be at risk of lower self-efficacy, requiring particular attention.


Causes and consequences of delayed diagnosis in breast cancer screening with a focus on mammographic features and tumour characteristics.
To study the prevalence, causes and consequences of delayed breast cancer diagnosis in the screening population. This retrospective study was performed in women who underwent biennial screening mammography between January 1, 2009 and June 30, 2019. Patients were divided into 3 groups; screen-detectedbreast cancer (SDC) without a diagnostic delay, a primary diagnostic delay(i.e. missed cancer at previous screening round)and a delay in diagnostic work-up after recall. Women with a true interval cancer (IC; i.e. not visible on prior examinations) were excluded. Outcome parameters included mammographic and tumour characteristics, lymph node status and surgical treatment. In our sample of 4491 women with breast cancer (4292 SDC and 199 'missed' IC), respectively, a total of 1112 women experienced a diagnostic delay of ≥ 4 months. Compared to women without a diagnostic delay (n = 2720), the 176 women with a delay in diagnostic work-up showed overall similar mammographic abnormalities (P = 0.052). These groups show similar distributions in invasive tumours, tumour stage and lymph node status (P = 0.25, P = 0.95 and P = 0.93, respectively). Women with a primary diagnostic delay (n = 936) showed less calcifications (P < 0.001), and more masses with calcifications and architectural distortions on mammography (P = 0.01 and P = 0.04, respectively). Moreover, this group comprised larger tumours (P < 0.001) and lymph node metastases (P < 0.001), and more often underwent mastectomy (P < 0.001). A primary diagnostic delay in breast cancer diagnosis results in less favourable tumour characteristics and relatively more mastectomies compared to no delay in breast cancer diagnosis and a delay in diagnostic work-up after recall.


Residual inferior glenohumeral instability after arthroscopic Bankart repair: radiological evaluation and functional results.
Treatment of anteroinferior shoulder instability by arthroscopy must restore stability while preserving joint motion. Inferior glenohumeral ligament (IGHL) laxity is an important parameter in the pathomechanism of this condition. The goals of this study is to use the Shoulder HyperAbduction Test (SHART) radiological test to quantify the tension in the IGHL following surgery and look for an eventual correlation between ligament tightening and joint motion. This was a single-center, retrospective study that included patients with unilateral anteroinferior instability who were treated with an arthroscopic Bankart repair between September 2004 and December 2005. These patients did not experience any recurrence within a follow-up period of at least 2 years. Twenty-three patients were followed-up. This series included 16 men and seven women with an average age of 29.7±12 years. The average Instability Severity Index Score (ISIS) was 1.7±1.3 (from 0 to 3). The main outcome measures were the bilateral SHART test at the last follow-up visit and bilateral joint range of motion, before surgery and at the last follow-up. The follow-up was 3.3 years on average. The average SHART on the operated side (116.9±11.7°) was lower than the healthy side (121.9±9.6°), P=0.01. A difference of less than 4° was statistically related to loss of external rotation, with an odds ratio of 16, P=0.03. At the last follow-up, the average Walch-Duplay functional score was 72.4±13.8/100 and the Rowe score 90.2±11.6/100. It is difficult to achieve a perfect compromise between shoulder stability and joint motion. Progress in arthroscopy technique has led to a greater demand for the tightening of capsulo-labral and ligament structures. An arthroscopic Bankart repair provides IGHL tightening that is quantifiable with the SHART. External rotation is reduced when excessive tightening is made.


Calcification of the linea aspera: A systematic narrative review.
This review aims to consolidate the published demographics, clinical and radiological features of calcific tendonitis affecting the linea aspera. Using the PRISMA protocol, 55 clinical cases were extracted from 19 shortlisted papers. In a patient presenting with thigh and/or hip pain, radiologic evaluation should commence with plain radiographs; subsequent cross-sectional imaging, if necessary. Our review of the literature indicates that calcific tendonitis can be safely diagnosed when intratendinous calcification is observed in the region of the linea aspera with cortical erosion but no discrete soft tissue mass.


Fetal hemoglobin quantitations using the Hemocue system are rapid and accurate.
To determine whether hemoglobin quantitations using the Hemocue system, a rapid and portable hemoglobin photometer, on fetal blood obtained via funipuncture were accurate compared to the Coulter S-Plus IV. We also examined whether gestational age or extremes in hemoglobin levels significantly affected the accuracy of the Hemocue system. We performed fetal hemoglobin quantitations using both systems on 58 specimens obtained between 18-38 weeks' gestation. Correlation between values by both systems was determined by linear regression analysis. The effects of gestational age and hemoglobin extremes on the accuracy of the Hemocue system were evaluated by stepwise regression. The mean Hemocue value was 12.0 +/- 2.4 g/dL (range 3.3-16.4); the mean Coulter value was 11.7 +/- 2.3 g/dL (range 3.6-16.2). The regression equation for Hemocue (y) versus Coulter (x) values was y = 0.72 + 0.97x; r = 0.94 (P < .0001). Neither gestational age nor hemoglobin extremes significantly affected the accuracy of the Hemocue system. The Hemocue system is rapid and accurate for fetal hemoglobin quantitation between 18-38 weeks' gestation regardless of extremes in gestational age or hemoglobin levels.


Effects of interferential current stimulation in women with pelvic organ prolapse: a prospective randomized sham-controlled study.
The objective was to investigate the effects of interferential (IF) current stimulation on pelvic floor symptoms, prolapse stages, pelvic floor muscle (PFM) strength/endurance, quality of life (QoL), sexual function, perception of subjective improvement (PSI), and satisfaction in women with pelvic organ prolapse (POP). The patients were randomly divided into the IF (n=13) and sham groups (n=12). Lifestyle advice was given in both groups. Active IF current was applied in the IF group and sham IF was applied in the sham group 3 days a week for 8 weeks. The following tools were used for data evaluation: pelvic floor symptom severity with the Pelvic Floor Distress Inventory-20 (PFDI-20), POP with the simplified POP-quantification system, PFM strength/endurance with a perineometer, QoL with the Prolapse Quality of Life Scale (P-QoL), and sexual function with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Scale (PISQ-12). Evaluations were made before treatment (BT), mid-term (MT, 4th week), and after treatment (AT). PSI and satisfaction were evaluated AT with Likert-type scales. In the intergroup comparison AT, a greater increase in PFM strength/endurance, P-QoL-role limitations, P-QoL-sleep/energy scores, PSI, and satisfaction level, and a decrease in cystocele stages were observed in the IF group than in the sham group (p<0.05). Further, there was a greater increase in PFM endurance in the IF group in MT (p<0.05). Interferential current stimulation was effective in improving POP stage, PFM strength/endurance, and QoL in women with POP. IF current stimulation can be used as a complementary treatment method in women with POP.


Adolescent epidemic hysteria presenting as a mass casualty, toxic exposure incident.
Discussed is a case of explosive epidemic hysteria presenting as a mass casualty, toxic inhalation incident. Fifteen adolescent female students were triaged from a school of 700 persons exposed to sewer gas and arrived simultaneously at the emergency department complaining of a variety of nonspecific symptoms without physical findings. These symptoms quickly remitted with reassurance and dispersion of the group. Factors important in the recognition and treatment of epidemic hysteria are presented.


Soluble P-selectin levels, P-selectin polymorphisms and cardiovascular disease.
P-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells and platelets. A number of polymorphisms in the gene encoding P-selectin have been identified. Objectives were to investigate the relationship of soluble P (sP)-selectin with P-selectin gene polymorphisms and coronary artery disease (CAD). Two hundred and forty-nine patients, with extent of CAD characterized by >or=50% stenosis in one or more coronary arteries, and 252 healthy controls were studied. Soluble P-selectin was significantly higher in the patients than controls after adjustment for age, sex and smoking [patients 49.8 (47.5-52.1) ng mL-1; controls 46.7 (44.5-49.1) ng mL-1, P = 0.03). There was no association of sP-selectin with myocardial infarction (MI) or presence of >or=50% stenosis. The -1817 T/C, -1969 G/A and -2123 C/G (but not the Thr715Pro) polymorphisms were in strong linkage disequilibrium. The Thr715Pro polymorphism was significantly associated with sP-selectin even after adjustment for covariates [TT 48.9 (46.9-50.0) ng mL-1; TP + PP 40.7 (38.1-43.6) ng mL-1, P < 0.0001]. A significant interaction of Thr715Pro and smoking status was identified in the determination of sP-selectin levels. There was no significant association of genotype at any of the polymorphism in relation to MI or stenosis. The Thr715Pro polymorphisms is associated with plasma sP-selectin. This association is modulated by smoking, although the underlying mechanism remains unclear.


Valsartan decreases type I collagen synthesis in patients with hypertrophic cardiomyopathy.
Fibrosis, as well as myocyte hypertrophy, is the major determinant of prognosis in hypertrophic cardiomyopathy (HCM). Valsartan, an angiotensin II type 1 receptor blocker, may improve myocardial fibrosis in patients with HCM. Twenty-three patients with HCM were randomly divided into 2 groups: 11 patients had valsartan added to conventional treatment (V group) and 12 patients received the conventional therapy (C group). Plasma concentrations of brain natriuretic peptide (BNP), troponin T (TnT), aldosterone (ALDO), procollagen type I (PIP) and procollagen type III aminoterminal peptide (PIIINP) were measured before and 12 months after this study. Left ventricular wall thickness (LVWT) and ejection fraction (LVEF) were measured by echocardiography. PIP was decreased in the V group (123.2+/-63.1 ng/ml to 102.8+/-37.6, p<0.05), but unchanged in C group (110+/-40.5 ng/ml to 119.9+/-47.4, p=0.22). ALDO concentration was unchanged in the V group (88.5+/-26.2 pg/ml to 91.2+/-26.8, p=0.27), and increased in C group (92.6+/-36.6 ng/ml to 116.0+/-33.3, p<0.05). BNP, PIIINP, and TnT were unchanged by the treatment. There was no significant difference between the 2 groups in either LVWT or LVEF. Valsartan suppresses the synthesis of type I collagen in patients with HCM and this was associated with suppression of the increase in ALDO.


Nomenclatural changes in two families of asellote isopods (Acanthaspidiidae and Ischnomesidae).
Iolanthe Beddard, 1886a is shown to be a senior synonyn of Acanthaspidia Stebbing, 1893, the replacement name for the preoccupied Acanthoniscus Sars, 1879 (Isopoda: Asellota: Acanthaspidiidae). Ischnomesus kussakini nom. nov. is erected as a replacement name for Ischnomesus antarcticus (Kussakin, 1982), preoccupied in this combination (Isopoda: Asellota: Ischnomesidae).


What is the impact of vasospasm on traumatic subarachnoid hemorrhage: Two cases of report.
It is difficult to predict that vasospasm would occur in traumatic subarachnoid hemorrhage (SAH) patients. Younger age, a lower score of Glasgow coma scale (GCS≦8) on admission, and greater cisternal blood volume are considered to correlate with post-traumatic vasospasm. We present two cases of traumatic SAH with post-traumatic vasospasm; one was a 74-year-old man and the other was a 72-year-old woman. They were alert without any neurological deficits on admission, although the SAH was focally thick as if caused by an aneurysmal rupture. The thick SAH was still identified on follow-up CT performed in a few days. The patients demonstrated cognitive dysfunction at the 4th and 5th day of admission, respectively, and imaging studies revealed vasospasm at the artery in the thick SAH. After treatments, the vasospasm resolved and both patients recovered from the disorientation completely in three weeks. The authors considered that focally thick traumatic SAH with poor clearance is the most influential factor to post-traumatic vasospasm independent of age or a GCS score. A low GCS score in head trauma patients might be mainly associated with existence of brain contusion, intracerebral hemorrhage, epidural, or subdural hemorrhages, which are frequently associated with traumatic SAH. If the traumatic SAH is focally thick with poor clearance, it might be better to initiate prompt treatments for vasospasm within 3 days after trauma. The delay in treatments for vasospasm contributes to poor outcomes.


Ketogenic diet containing medium-chain triglyceride ameliorates transcriptome disruption in skeletal muscles of rat models of duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a myopathy characterized by progressive muscle weakness caused by a mutation in the dystrophin gene on the X chromosome. We recently showed that a medium-chain triglyceride-containing ketogenic diet (MCTKD) improves skeletal muscle myopathy in a CRISPR/Cas9 gene-edited rat model of DMD. We examined the effects of the MCTKD on transcription profiles in skeletal muscles of the model rats to assess the underlying mechanism of the MCTKD-induced improvement in DMD. DMD rats were fed MCTKD or normal diet (ND) from weaning to 9 months, and wild-type rats were fed with the ND, then tibialis anterior muscles were sampled for mRNA-seq analysis. Pearson correlation heatmaps revealed a one-node transition in the expression profile between DMD and wild-type rats. A total of 10,440, 11,555 and 11,348 genes were expressed in the skeletal muscles of wild-type and ND-fed DMD rats the MCTKD-fed DMD rats, respectively. The MCTKD reduced the number of DMD-specific mRNAs from 1624 to 1350 and increased the number of mRNAs in common with wild-type rats from 9931 to 9998. Among 2660 genes were differentially expressed in response to MCTKD intake, the mRNA expression of 1411 and 1249 of them was respectively increased and decreased. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that the MCTKD significantly suppressed the mRNA expression of genes associated with extracellular matrix organization and inflammation. This suggestion was consistent with our previous findings that the MCTKD significantly suppressed fibrosis and inflammation in DMD rats. In contrast, the MCTKD significantly increased the mRNA expression of genes associated with oxidative phosphorylation and ATP production pathways, suggesting altered energy metabolism. The decreased and increased mRNA expression of Sln and Atp2a1 respectively suggested that Sarco/endoplasmic reticulum Ca2+-ATPase activation is involved in the MCTKD-induced improvement of skeletal muscle myopathy in DMD rats. This is the first report to examine transcription profiles in the skeletal muscle of CRISPR/Cas9 gene-edited DMD model rats and the effect of MCTKD feeding on it.


Synchronized coronary revascularization and multiple cardiac cysthydatid operation.
Cardiac cysthydatid is rare pathology and is seen in 0.5 to 2% of echinococcal infections. It is found in the left ventricle most frequently and then in the right ventricle. We present a case with a ruptured cysthydatid at the right atrium's interatrial septum and multiple cysthydatids localized at the outer surface of the left ventricle's apex, which necessitated a synchronized coronary revascularization with our diagnosis and surgical procedure modalities. Our patient was a 61-year-old man with complaints of fever, dyspnea, tachycardia and chest pain, which began 2 months before admittance. An echocardiography in our clinic revealed a 4.7 x 1.7 centimeter, pediculled, going in and out to tricuspidal inflow, cystic mass adherent to the interatiral septum in the right atrium, which prompted immediate hospitalization. He was in New York Heart Association Class II. His electrocardiography (EKG) showed ischemia at inferior and lateral surfaces, so we performed a coronary angiography and determined a severe stenosis at the proximal part of the left anterior descending artery. His EKG showed ischemia at the inferior and lateral surfaces, so we performed a coronary angiography and determined a severe stenosis at the proximal part of the left anterior descending artery. His preoperative biochemical parameters were normal, and cysthydatid serology tests were negative. With these results,l we planned a synchronized surgical procedure for coronary artery disease with multiple cardiac cysthydatids. During operation, after the right atriotomy, a fragile cystic mass with a ruptured image and dimensions of 5 x 2 x 2 centimeters, originating from the interatrial septum and in a conglomerate form, was resected and extirpated. The left atrium was not involved. Then, 3 masses with dimensions of 2 x 2 centimeters, which were not diagnosed with the echocardiogram, at the epicardial surface of the left ventricle apex were excised. The defected part of the left ventricle was repaired with teflon felt supports for rupture prophylaxis. Then, a left internal mammary artery graft, which was prepared at the beginning of the operation, was anastomosed to LAD. The patient didn't have any additional problem during the postoperative period, and he was discharged at 1 week after surgery. To avoid recurrence, the patient was prescribed albendazole as a prophylaxis for the duration of 2 months. Histopathology confirmed the diagnosis of cysthydatid. Patients with cardiac cysthydatid can be asymptomatic or can cause minimal nonspecific symptoms for years. The condition can be lethal if not diagnosed and treated. The primary treatment for cysthydatid is surgery. Echocardiography is an important diagnostic method for cysthydatid. Serological tests can produce negative results if the immune responses of the patient is not sufficient, so it must be remembered in the endemic places for echinococcus.


Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells.
A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of a homologous series of drugs (beta-blocking agents) of different lipophilicity across intestinal epithelium. The permeability of the Caco-2 monolayers was modulated by the use of a calcium switch assay. The transmembrane resistance could be reversibly decreased from approximately 280 ohms.cm2 (a resistance similar to that of colon epithelium) to approximately 60 ohms.cm2 (a resistance similar to that of small intestine epithelium). Transmission electron microscopy showed that the increased electrical permeability was caused by a reversible separation of the components of the junctional complex and not by cell detachment. In general, the increased paracellular permeability resulted in a 2- to 9-fold increase in the apparent permeability coefficients for the more hydrophilic drugs (e.g., from 0.20 +/- 0.010 x 10(-6) to 1.43 +/- 0.185 x 10(-6) cm/s for atenolol), while the transport parameters for the more lipophilic drugs remained unchanged (e.g., 43.03 +/- 3.64 x 10(-6) and 46.10 +/- 3.25 x 10(-6) cm/s for propranolol). These findings indicate that it is possible to study the contribution of the paracellular pathway to the transport of drugs in the Caco-2 model.


The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers.
Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.


[Determination of the inequality of ventilation by the helium mixing time in a spirograph--lung system].
The dependence of the time of He mixing in the lung-spyrograph system upon the factors influencing its value was taken into consideration. Cases of equal lung ventilation of the lungs were graphically illustrated; the "ideal" mixing time was determined with the aid of these diagrams. It is suggested that the inequality of the lung ventilation can be judged by the value by which the mixing time obtained in the examination of the patient's respiration exceeded the "ideal" one found by the diagram in the same patient.


Densitometric studies on the shadows of paranasal sinuses in sagittal projection.
In taking a X-ray photography of the head in sagittal projection, it is most important that the center of the X-ray beam passes exactly through the median-sagittal line. If the subject turns his head either to the right or to the left, the paranasal sinuses become denser on one side, leading to erroneous interpretation of the radiographic findings. In order to eliminate such a misinterpretations, studies were carried out on the following: 1) Application of a standard of what degree of head turning to either side would start to influence judgment of the shadow of the paranasal sinuses. 2. Application of a standard to judge whether they are projected to an exact center position or not in actually diagnosing the X-ray films.


Normalization of cancer antigen 125 after mitral valve replacement in a patient with congestive heart failure due to mitral valve endocarditis.
A 63-year-old woman with a history of uterine cancer was admitted to our hospital with dyspnea and stroke. Echocardiography showed a huge vegetation attached to the posterior mitral leaflet with severe mitral regurgitation. Blood culture identified Streptococcus galactiae. The serum level of cancer antigen 125 (CA125) was elevated at 199.4 U/ml. Resection of infected tissue including mobile vegetation and replacement of mitral valve were performed. The postoperative course was uneventful and the patient was discharged after 4 weeks of antibiotic therapy. The values of CA125 returned to normal (less than 15 U/ml) on the 90th postoperative day. These findings have suggested that a high serum value of CA125 is a possible indicator of infection-related congestive heart failure.


Modulation of kappa-opioidergic systems on mecamylamine-precipitated nicotine-withdrawal aversion in rats.
The present study was designed to examine the modulation of the kappa-opioidergic system on mecamylamine-precipitated nicotine-withdrawal aversion. The nicotinic receptor antagonist mecamylamine, which is known to pass the blood-brain barrier, produced a place aversion in rats chronically treated with nicotine using an osmotic mini-pump. This effect was significantly attenuated by pretreatment with -opioid receptor agonists U50,488H (1.0 mg/kg, s.c.) and TRK-820 (0.03 mg/kg, s.c.). The attenuation of mecamylamine-precipitated nicotine-withdrawal aversion by U50,488H was completely reversed by the combination with a selective -opioid receptor antagonist nor-binaltorphimine (10.0 mg/kg, i.p.). These results suggest that the activation of endogenous -opioidergic systems can suppress the mecamylamine-precipitated nicotine-withdrawal aversion.


AV universal (DDD) pacemaker-mediated reentrant endless loop tachycardia initiated by a reciprocal beat of atrial origin.
An AV universal (DDD) pacemaker-mediated, reentrant, endless loop tachycardia initiated by a reciprocal beat is described. Pacemaker-mediated tachycardias are discussed and addressed in the light of their growing frequency and importance in patients with physiological pacemakers.


An acidic and thermostable carboxymethyl cellulase from the yeast Cryptococcus sp. S-2: purification, characterization and improvement of its recombinant enzyme production by high cell-density fermentation of Pichia pastoris.
The extracellular carboxymethyl cellulase (CSCMCase) from the yeast, Cryptococcus sp. S-2, was produced when grown on cellobiose. It was purified to homogeneity from the supernatant by ultrafiltration, DEAE-5PW anion exchange column and TSK-Gel G3000SW gel filtration. The purified enzyme was monomeric protein with molecular mass of approximately 34kDa. The optimum temperature and pH for the action of the enzyme were at 40-50 degrees C and 3.5, respectively. It was stable at pH range of 5.5-7.5 and retained approximately 50% of its maximum activity after incubating at 90 degrees C for 1h. Moreover, it could able to hydrolyze carboxymethyl cellulose sodium salt higher than insoluble cellulose substrate such as Avicel, SIGMACELL and CM cellulose. Due to its action at acidic pH and moderately stable at high temperature, the gene encoding carboxymethyl cellulase (CSCMCase) was isolated and improved the enzyme yield by high cell-density fermentation of Pichia pastoris. The CSCMCase cDNA contains 1023 nucleotides and encodes a 341-amino acid. It was successfully expressed under the control of alcohol oxidase I promoter using methanol induction of P. pastoris fermentation in a 2L ABLE bioreactor. The production of the recombinant carboxymethyl cellulases was higher than that from Cryptococcus sp. S-2 of 657-fold (2.75 and 4.2 x 10(-3) mg protein L(-1), respectively) indicating that the leader sequence of CSCMCase has been recognized and processed as efficiently by P. pastoris. Furthermore, the recombinant enzyme was purified in two-step of ultrafiltration and hydrophobic interaction chromatography which would be much more convenient for large-scale purification for successful industrial application.


Antimicrobial prophylaxis in immunocompromised patients.
The results of a randomised, prospective trial to investigate the efficacy of prophylactic treatment with ofloxacin during granulocytopenia after cytostatic treatment are presented. 42 patients with metastasised testicular germ-cell tumours entered the study. Cytostatic treatment consisted of at least 4 courses, 2 of which were succeeded by prophylactic treatment with ofloxacin. Three patients undergoing prophylactic treatment developed fever. Fever occurred in 16 patients during control phases (no ofloxacin prophylaxis) of cytostatic treatment. Seven of the 19 infections could be documented microbiologically. No side effects that related to ofloxacin were noted. In conclusion, ofloxacin was highly effective in the prevention of infection and, therefore, should be given prophylactically to patients with granulocytopenia.


Bax345/BLyS: a novel, completely human fusion protein targeting malignant B cells and delivering a unique mitochondrial toxin.
We generated a fusion protein Bax(345)/BLyS containing the truncated form of Bax (Bax(345)) at the N-terminus followed by a 218 linker to the B lymphocyte stimulator (BLyS). Bax(345)/BLyS was cytotoxic to a panel of diffuse large B cell lymphoma and mantle cell lymphoma lines expressing the BLyS receptors. Specific delivery of Bax(345)/BLyS to malignant B cells drove cells into apoptosis by mitochondrial dysfunction and treatment of cells with Bax(345)/BLyS induced down-regulation of Mcl-1, X-IAP, and survivin. Bax(345)/BLyS represents a new class of targeted therapeutic agents with a unique mechanism of action and may have therapeutic potential for malignant B cells.


Drug switching patterns among patients taking non-steroidal anti-inflammatory drugs: a retrospective cohort study of a general practitioners database in the United Kingdom.
To examine the frequency and determinants of switching between different non-steroidal anti-inflammatory drugs (NSAIDs) and the relationship with co-prescription of gastro-protective drugs (GPDs). This was an analysis of 30,654 patients receiving a total of 209,140 NSAID prescriptions in the UK from 1 January 1997 to 31 December 1998 identified through the MediPlus database. Analyses examined switching, repeat, termination and GPD co-prescription rates in new and continuing takers according to age and sex. Each patient received an average of 6.8 prescriptions in the year of study. Of the prescriptions 72.2% were for one of three NSAIDs, ibuprofen, diclofenac, or naproxen, and 7.2% of prescriptions were for fixed combination products of an NSAID plus a gastroprotective drug. At least 16.0% of continuing takers, and 28.5% of new takers switched to another NSAID in the review period. On average, new patients switched more frequently than continuing patients (0.39 switches/patient/year versus 0.23 switches/patient/year, p < 0.001). Switching between NSAIDs decreased with age and was less common in women (p < 0.05). Switching was associated with a 24% and 33% increased probability of GPD prescription in new and continuing takers, respectively. The frequency of switching, and of GPD co-prescription at switching, suggest that dissatisfaction with NSAIDs is frequent, and that gastrointestinal intolerance is a common feature of this dissatisfaction.


Characterization of tissue-specific biomarkers with the expression of circRNAs in forensically relevant body fluids.
Messenger RNA (mRNA) markers have been extensively investigated for the identification of forensically relevant body fluids and tissues based on their expression profiles among cell types. As products of the backsplicing of pre-mRNAs, circular RNAs (circRNAs) share exonic sequences with their linear counterparts. The inclusion of circRNAs in mRNA profiling is shown to facilitate the detection of biomarkers in the identification of body fluids. In this study, we identified the expression of circRNAs of 14 out of 45 biomarkers from five body fluid types using outward-facing primer sets and revealed the ratio of circular to total transcripts of biomarkers by RNase R treatment. Furthermore, our results of qPCR analysis show that the inclusion of circRNAs in the detection of biomarkers, including HBA and ALAS2 for blood; MMP7 and MMP10 for menstrual blood; HTN3 for saliva; SPINK5, SERPINB3, ESR1, and CYP2B7P1 for vaginal secretions; TGM4, KLK3, and PRM2 for semen; and SLC22A6 and MIOX for urine, does not impair the specificity of these biomarkers. Additionally, a high copy number of targets from linear transcripts could be employed to increase the detection sensitivity of TGM4 and KLK3 with a low expression level of circRNAs in urine samples. Altogether, these results will help with the development of robust multiplex assays for body fluid identification.


Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy.
Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.


COMPARATIVE EFFECT OF FUCOIDAN FROM ALGA FUCUS VESICULOSUS AND ITS FRACTIONS, OBTAINED BY ANION-EXCHANGE CHROMATOGRAPHY, ON CELL LINES HeLa G-63, Hep G2 AND CHANG LIVER.
The aim of the present study was to compare the effect of sulfated fucopolysaccharides isolated from Fucus vesiculosus on cell lines HeLa G-63, Hep G2 and Chang liver. Native fucoidan F3 and two fractions (F3-0.5 and F3-1), obtained by anion-exchange chromatography, were analyzed using chemical methods and IR-spectroscopy. Their action on cells demonstrates that F3 and F3-1, characterized by higher content of sulfates, preferable location of sulfo-groups at C4 atom of fucose residue and low content of uronic acids, inhibit cell proliferation more efficiently. Human liver tumor cells Hep G2 appeared to be the most sensitive to fucoidan treatment whereas nonmalignant human cells Chang liver were the least sensitive.


Application of physical and genetic map of Rhizobium leguminosarum bv. trifolii TA1 to comparison of three closely related rhizobial genomes.
A combined physical and genetic map of Rhizobium leguminosarum biovar trifolii TA1 (RtTA1) genome was constructed and used in comparison of chromosomal organization with the closely related R. leguminosarum bv. viciae 3841 (Rlv) and Rhizobium etli CNF42 (Rhe). This approach allowed evaluation of chromosome and genome plasticity and provided important insights into R. leguminosarum lineage diversity. MssI, SmiI, PacI, and I-CeuI restriction endonucleases were chosen for the analysis, generating fragments with suitable size distributions for RtTA1 genome mapping. The fragments were assembled into a physical map using a combination of complementary methods, including multiple and partial digests of genomic DNA, hybridization with homologous gene probes, and cross-Southern hybridization. About 100 genetic markers were located on the RtTA1 restriction map. Comparison of genetic maps of RtTA1, Rlv, and Rhe revealed extensive chromosomal colinearity despite differences in the physical maps. The comparison provides bases for comprehensive analysis of the evolution of R. leguminosarum genome, indicating that, at least on the chromosomal level, no major rearrangements had occurred after the evolutionary divergence of R. leguminosarum biovars.


Cell type specificity of lung cancer associated with air pollution.
The aim of this study is to explore whether lung cancer associated with air pollution has cell type specificity. The air quality data (SO(2), CO, O(3), NOx) from the Taiwan EPA's air quality monitoring stations were collected between 1995 and 1998. Patients with lung cancer were identified through the National Cancer Registration Program operated by the Taiwanese government. Two major pathological types (adenocarcinoma (AC) and squamous cell carcinoma (SCC)) were considered. The Pearson correlation coefficients between the air quality index and age-standardized incidence rate per 100,000 person years (ASR) of AC and SCC were calculated for both genders for three township categories characterized by different levels of air pollution. The traffic-related NOx and CO showed significant correlations with female lung cancer incidence rate, with Pearson's correlation 0.33 (P=0.03) and 0.40 (P=0.01) respectively. However, the correlation between air pollution and lung cancer was not significant for males. Significant correlation coefficients were also found between the ratio of AC/SCC and the mean concentrations of NOx (r=0.41, P=0.04) and CO (r=0.47, P=0.02) in females. Our results show that the worse the air pollution was in the area, the higher the AC rate, regardless of gender. On the other hand, SCC incidence rates did not increase with increasing air pollution. Our results show that a correlation exists between air pollution and lung adenocarcinoma incidence.


Efficacy of Montelukast in Allergic Rhinitis Treatment: A Systematic Review and Meta-Analysis.
In treating allergic rhinitis, montelukast has the potential to be used as an alternative or addition to an oral antihistamine or intranasal corticosteroid. The objective of this systematic review was to assess the effectiveness of montelukast in treating allergic rhinitis. An electronic literature search was performed using the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE from 1966 to 21 January 2019. The eligibility criteria were randomized controlled trials comparing montelukast with placebo or other standard treatments. The primary outcomes assessed were daytime nasal symptom score (DNS) and night-time nasal symptom score (NNS). The secondary outcomes assessed were composite nasal symptom score (CSS), daytime eyes symptom score (DES), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). The meta-analysis was conducted using Review Manager 5.3 software based on the random-effects model. Fifteen studies of 10387 participants met the inclusion criteria. Montelukast was more effective than placebo in improving DNS (mean difference [MD] - 0.12, 95% confidence interval [CI] - 0.15 to - 0.08; p < 0.001), NNS (MD - 0.09, 95% CI - 0.13 to - 0.05; p < 0.001), CSS (MD - 0.08, 95% CI - 0.11 to - 0.06; p < 0.001), DES (MD - 0.17, 95% CI - 0.33 to - 0.02; p < 0.030), and RQLQ (MD - 0.34, 95% CI - 0.49 to - 0.20; p < 0.001). Oral antihistamine was superior to montelukast in improving DNS (MD 0.08, 95% CI 0.03-0.13; p = 0.002), CSS (MD 0.03, 95% CI - 0.02 to 0.07; p = 0.27), DES (MD 0.06, 95% CI 0-0.12; p = 0.040), and RQLQ (MD 0.03, 95% CI - 0.05 to 0.12; p = 0.430). Montelukast was superior to oral antihistamine in improving NNS (MD -0.03, 95% CI - 0.08 to 0.03; p = 0.330). Intranasal fluticasone spray was superior to montelukast in improving DNS (MD 0.71, 95% CI 0.44-0.99; p < 0.001) and NNS (MD 0.63, 95% CI 0.29-0.97; p < 0.001). Combined montelukast and oral antihistamine was superior to oral antihistamine in improving DNS (MD - 0.15, 95% CI - 0.27 to - 0.03; p = 0.010), NNS (MD - 0.16, 95% CI - 0.28 to - 0.05; p = 0.006), CSS (MD - 0.12, 95% CI - 0.25 to - 0.01; p = 0.070), DES (MD - 0.12, 95% CI - 0.30 to 0.06; p = 0.180), and RQLQ (MD - 0.10, 95% CI - 0.28 to 0.08; p = 0.290). Combined montelukast and OAH was superior to montelukast in improving DNS (MD 0.15, 95% CI 0.08-0.21; p < 0.001), NNS (MD 0.05, 95% CI - 0.09 to 0.19; p = 0.510), CSS (MD 0.1, 95% CI 0.03-0.17; p = 0.007), DES (MD 0.18, 95% CI 0-0.36; p = 0.050), and RQLQ (MD 0.07 95% CI - 0.15 to 0.29; p = 0.530). Montelukast is more effective than placebo in treating the overall symptoms of allergic rhinitis while the combined therapy of montelukast and an oral antihistamine is superior to either montelukast or an oral antihistamine alone.


Combined radiofrequency ablation-cooling catheter for reversible cryothermal mapping and ablation.
Reversible cryothermal mapping of cardiac arrhythmias has been performed intraoperatively. However, a steerable cooling catheter for reversible mapping has not yet been developed. We therefore developed and tested a cooling system consisting of a -15 degrees C hypertonic saline reservoir and a 7F steerable catheter also capable of radiofrequency (RF) ablation. Using excised ovine hearts placed in a 37 degrees C circulating saline bath, we measured the temperatures at depths of 0 mm, 1 mm, and 2 mm. The temperature after 90 seconds of cooling was 16.5 +/- 2.1 degrees C at 0 mm compared to 23.9 +/- 4.1 degrees C at 1 mm and 31.1 +/- 3.9 degrees C at 2 mm depth (p < 0.01). These data suggest that a 7F steerable combined RF ablation-cooling catheter may achieve temperatures suitable for mapping arrhythmias such as atrial tachycardias and right ventricular outflow tract tachycardias. Further enhancements to achieve lower temperatures at depth may be needed to reversibly map other arrhythmias such as left ventricular tachycardias.


ExpGCN: Review-aware Graph Convolution Network for explainable recommendation.
Existing works in recommender system have widely explored extracting reviews as explanations beyond user-item interactions, and formulated the explanation generation as a ranking task to enhance item recommendation performance. To associate explanations with users and items, graph neural networks (GNN) are usually employed to learn node representations on the heterogeneous user-item-explanation interaction graph. However, modeling heterogeneous graph convolution poses limitations in both message passing styles and computational efficiency, resulting in sub-optimal recommendation performance. To address the limitations, we propose an Explanation-aware Graph Convolution Network (ExpGCN). In particular, the heterogeneous interaction graph is divided to subgraphs regard to the edge types in ExpGCN. By aggregating information from distinct subgraphs, ExpGCN is capable of generating node representations for explanation ranking task and item recommendation task respectively. Task-oriented graph convolution can not only reduce the complexity of heterogeneous node aggregation, but also alleviate the performance degeneration caused by the conflicts between task learning objectives, which has been neglected in current studies. Extensive experiments on four public datasets show that ExpGCN significantly outperforms state-of-the-art baselines with high efficiency, demonstrating the effectiveness of ExpGCN in explainable recommendations.


Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.
Monogenic forms of obesity are caused by single-gene variants which affect the energy homeostasis by increasing food intake and decreasing energy expenditure. Most of these variants result from disruption of the leptin-melanocortin signaling, which can cause severe early-onset obesity and hyperphagia. These mutation have been identified in genes encoding essential proteins to this pathway, including leptin (LEP), melanocortin 2 receptor accessory proteins 2 (MRAP2) and proopiomelanocortin (POMC). We aimed to investigate the prevalence of LEP, MRAP2 and POMC rare variants in severely obese adults, who developed obesity during childhood. To the best of our knowledge, this is the first study screening rare variants of these genes in patients from Brazil. A total of 122 Brazilian severely obese patients (BMI ≥ 35 kg/m2) were screened for the coding regions of LEP, MRAP2 and POMC by Sanger sequencing. All patients are candidates to the bariatric surgery. Clinical characteristics were described in patients with novel and/or potentially pathogenic variants. Sixteen different variants were identified in these genes, of which two were novel. Among them, one previous variant with potentially deleterious effect in MRAP2 (p.Arg125Cys) was found. In addition, two heterozygous mutations in POMC (p.Phe87Leu and p.Arg90Leu) were predicted to impair protein function. We also observed a POMC homozygous 9 bp insertion (p.Gly99_Ala100insSerSerGly) in three patients. No pathogenic variant was observed in LEP. Our study described for the first time the prevalence of rare potentially pathogenic MRAP2 and POMC variants in a cohort of Brazilian severely obese adults. Level V, cross-sectional descriptive study.


One way to rule them all: G2/M gene regulation by oncogenic YAP1 and B-MYB.
The Hippo pathway plays a major role in regulating organ size during embryogenesis. Loss of Hippo signaling can cause cancer due to unrestricted cell proliferation. Recently we found that Yes-associated protein 1 (YAP1), the major downstream effector of Hippo, promotes mitotic gene expression and proliferation through binding and activating the Myb-MuvB (MMB) complex subunit MYB proto-oncogene like 2 (B-MYB).


Early diagnosis and exclusion of acute myocardial infarction using biochemical monitoring. The BIOMACS Study Group. Biochemicals Markers of Acute Coronary Syndromes.
The aim was to evaluate whether frequent analysis of creatine kinase MB (CK-MB), myoglobin and troponin T alone or in combination could either confirm or exclude acute myocardial infraction (AMI) within the first few hours after patients were admitted to hospital with chest pain and a non-diagnostic ECG. One hundred and forty-two patients with chest pain (< or = 12 h) and a non-diagnostic ECG were included in the study. Blood samples were obtained every 30 min during the first 3 h and thereafter at longer intervals. Different discriminatory levels and combinations of markers were tested for their ability to detect (n = 59) or exclude (n = 83) AMI during the first 6 h after admission. No single marker adequately combined high early sensitivity and specificity. However, a combination of myoglobin and CK-MB analyses had a sensitivity at entry of 59%, which increased by 5-10% every 30 min and reached 92% after 2 h and 98% after 6 h with a specificity of 93%. A combination of myoglobin and troponin T analyses showed identical sensitivity but a slightly inferior specificity. In the patients with no AMI it was possible to exclude AMI in 64% within 3 h by using myoglobin and within 6 h in approximately 70% by using CK-MB or troponin T. Monitoring of a combination of myoglobin and CK-MB or troponin T will allow confirmation or exclusion of AMI within 3-6 h in almost all patients. This method will have a large impact on the handling of patients with suspected AMI without a diagnostic ECG.


Protein kinase C activity as a potential marker for colorectal neoplasia.
Protein kinase C (PKC) is a mediator of transmembrane signal transduction, important in cell growth and differentiation. Cell activation by extracellular signals is associated with a translocation of PKC from the cytosol to the membrane. We measured and compared PKC activity in cytosol and membrane fractions of normal and neoplastic colorectal tissue. Total and membrane-associated PKC activity in normal colorectal tissue was greater in patients (N = 16) with colorectal cancer compared to that from patients with a normal colonoscopy (N = 16), P < 0.01. A similar trend was noted in PKC activity of normal colorectal tissue from patients with adenomas compared to patients with a normal colonoscopy. PKC activity (total, membrane-associated, percent membrane) was not different in neoplastic colorectal tissue compared to that of adjacent normal tissue. However, there was a considerable range of PKC activity noted in all groups, which would limit the utility of PKC activity as a marker for colorectal neoplasia.


Overcoming tolerance in hepatitis B virus transgenic mice: a possible involvement of regulatory T cells.
The hepatitis B virus (HBV) transgenic mouse (Tg) 50-4 strain is immunologically tolerant to HBV antigens. Various vaccination strategies have been attempted but failed to break the tolerance in the mouse. Although the tolerance to HBV antigen is maintained, this mouse strain develops spontaneous liver disease beginning at the age of about 3 months. We attempted to induce immune responses to HBV surface antigen (HBsAg) in the Tg by immunization with recombinant vaccinia virus expressing HBsAg (vvHBV), and observed different immunological responsiveness between 2-month-old and 5-month-old Tg. In contrast to the unbreakable tolerance reported previously, we could induce both the cytotoxic T lymphocyte (CTL) and the antibody response against HBsAg by the vvHBV immunization. The cytokine expression pattern indicated that T helper 1 type immune response was induced. However, interestingly, these immune responses were observed only in the 5-month-old Tg, but not in the 2-month-old Tg. Furthermore, CD4+ T cells from 2-month-old mice, but not those from 5-month-old mice, inhibited CTL response to HBV antigen when adoptively transferred to C57BL/6. These results suggest the possible involvement of regulatory T cell function in the HBV Tg for maintaining tolerance. This study would contribute to a better understanding of immune status of the HBV Tg as a model of human chronic hepatitis and to the search for new therapeutic targets for chronic viral infections.


Accuracy of F-18 FDG PET/CT with optimal cut-offs of maximum standardized uptake value according to size for diagnosis of regional lymph node metastasis in patients with rectal cancer.
The low sensitivity of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of metastatic lymph nodes (LNs) is mainly due to the partial volume effect in patients with rectal cancer. This retrospective study evaluated the diagnostic accuracy of F-18 FDG PET/CT with optimal cut-off values of the maximum standardized uptake value (SUVmax), according to LN size, for the evaluation of regional LN in rectal cancer patients. This study included 176 patients with rectal cancer who underwent F-18 FDG PET/CT for initial staging. Patients were classified based on the long-axis diameter of the regional LN on CT images as small (≤ 7 mm; n = 118) and large (> 7 mm; n = 58) LN groups. The optimal cut-off value of SUVmax was determined for each group, using receiver operating characteristic curve analysis. Areas under the curve (AUC) were compared by C-statistics using two methods: the cut-off value of SUVmax optimized according to LN size, and a fixed SUVmax cut-off value of 2.5. The optimal cut-off values of SUVmax for the small and large LN groups were 1.1, and 2.1, respectively. The sensitivity, specificity, and accuracy of F-18 FDG PET/CT using the optimal cut-off values were 90.6, 70.9, and 76.3% in the small LN group, and 68.6, 78.3, and 72.4% in the large LN group. The sensitivity, specificity, and accuracy of F-18 FDG PET/CT using the fixed cut-off value were 18.8, 100, and 78.0% in the small LN group, and 51.4, 87.0, and 65.5% in the large LN group. The AUC was significantly higher using the optimal cut-off values than the fixed cut-off value (0.808 vs. 0.594, p = 0.005) in the small LN group, but not in the large LN group (0.734 vs. 0.692, p = 0.429). Application of the lower cut-off value of SUVmax improves the diagnostic performance of F-18 FDG PET/CT for the evaluation of small regional LNs in patients with rectal cancer.


Incorporation of L-[1-14C]leucine into protein by liver postmitochondrial supernatant: opposing effects of preincubated nicotinamide-adenine dinucleotide phosphate and 4-dimethylamino-3'-methylazobenzene.
Combination of preincubated drug-metabolizing medium containing NADP+ with a cell-free protein-synthesizing system resulted in marked stimulation of incorporation of L-[1-14C]leucine into protein. Addition of 4-dimethylamino-3'-methylazobenzene, present and previously preincubated in the drug-metabolizing medium, decreased this effect.