Effect on liver and splanchnic circulation of graded flow rates through portal-systemic bypass during acute portal occlusion.
Using graded flow rates through a passive portal-systemic bypass during 2-hr portal occlusion in dogs, splanchnic, hemodynamic, and metabolic changes and liver insults were evaluated to determine critical bypass flow. To exclude effects caused by reduced circulating blood volume, constant preocclusion levels of cardiac output were maintained throughout the study by increasing intravenous infusion rates. With the decrease in bypass flow rates during portal occlusion, portal pressure increased, superior mesenteric arterial flow decreased, and hepatic arterial flow rapidly increased and these parameters maintained their individual levels during occlusion. These hemodynamic parameters recovered to nearly normal levels 3 hr after release of the portal clamp. Metabolic acidosis progressed with decreasing bypass flow, but portal potassium and inorganic phosphorus levels showed a significant rise only when there was no bypass. Portal levels of creatine phosphokinase BB, beta-glucuronidase, and endotoxin did not show significant changes corresponding to bypass flow. The amounts of infusion required were 3 to 6 times the basal level (10 ml/kg/hr) during occlusion and 1.7 to 3 times after release in 30% or less bypass groups. Upon ceasing infusion 3 hr after release, dogs in the 10% or less bypass groups underwent circulatory insufficiency. Changes in total adenine nucleotide and energy charge ratio of the liver, postoperative changes in transaminase levels, and animal survival indicated that a 2-hr interruption of the portal flow, either sufficiently or insufficiently bypassed, caused only minimal insults of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)


Making things difficult in lexical decision: the impact of pseudohomophones and transposed-letter nonwords on frequency and semantic priming effects.
Performance in a lexical decision task is crucially dependent on the difficulty of the word-nonword discrimination. More wordlike nonwords cause not only a latency increase for words but also, as reported by Stone and Van Orden (1993), larger word frequency effects. Several current models of lexical decision making can explain these types of results in terms of a single mechanism, a mechanism driven by the nature of the interactions within the lexicon. In 2 experiments, we replicated Stone and Van Orden's increased frequency effect using both pseudohomophones (e.g., BEEST) and transposed-letter nonwords (e.g., JUGDE) as the more wordlike nonwords. In a 3rd experiment, we demonstrated that simply increasing word latencies without changing the difficulty of the word-nonword discrimination does not produce larger frequency effects. These results are reasonably consistent with many current models. In contrast, neither pseudohomophones nor transposed-letter nonwords altered the size of semantic priming effects across 4 additional experiments, posing a challenge to models that would attempt to explain both nonword difficulty effects and semantic priming effects in lexical decision tasks in terms of a single, lexically driven mechanism.


The effect of chronic oral alcoholization upon late fetal development in mice.
The late fetal effect of chronic alcoholization in two strains of mice (RAP and RAP female x CBAT6 male) was controlled. Unilateral ocular anomalies (retinal folding, various degrees of ocular disorganization) were detected in 16% of the alcoholized RAP female x CBAT6 male group. The findings are discussed in connection with other experimental models of alcohol embryo and fetopathy.


Descriptors of alcohol consumption among noninstitutionalized nonalcoholic elderly.
This paper describes relationships between reported alcohol consumption and selected sociodemographic and health variables. Two hundred and four men and 367 women aged 60-95 years were examined as part of a nutritional status survey of elderly. Fifty-three percent of men and 44% of women reported drinking at least 2 g of alcohol per week. Men were more likely to drink than women, and the level of alcohol consumption decreased with age. Drinking was positively associated with education (p less than 0.01) and negatively associated with recent medical care (p less than 0.01), history of MI (p less than 0.05), and denture use (p less than 0.05). Among drinkers, reported alcohol intake was higher for subjects less than age 70 (p less than 0.01), males (p less than 0.01), the college educated (p less than 0.01), and smokers (p less than 0.05). Level of alcohol intake was lower for those who had received medical care in the year preceding study participation (p less than 0.05). Identical results were observed for alcohol intake expressed as percent of total calories. Intake ranged from 3.8% of total calories among subjects 80+ years old to 6.2% of total calories among 60-69-year-olds.


The reactive nitrogen species peroxynitrite is a potent inhibitor of renal Na-K-ATPase activity.
Peroxynitrite is a reactive nitrogen species produced when nitric oxide and superoxide react. In vivo studies suggest that reactive oxygen species and, perhaps, peroxynitrite can influence Na-K-ATPase function. However, the direct effects of peroxynitrite on Na-K-ATPase function remain unknown. We show that a single bolus addition of peroxynitrite inhibited purified renal Na-K-ATPase activity, with IC50 of 107+/-9 microM. To mimic cellular/physiological production of peroxynitrite, a syringe pump was used to slowly release (approximately 0.85 microM/s) peroxynitrite. The inhibition of Na-K-ATPase activity induced by this treatment was similar to that induced by a single bolus addition of equal cumulative concentration. Peroxynitrite produced 3-nitrotyrosine residues on the alpha, beta, and FXYD subunits of the Na pump. Interestingly, the flavonoid epicatechin, which prevented tyrosine nitration, was unable to blunt peroxynitrite-induced ATPase inhibition, suggesting that tyrosine nitration is not required for inhibition. Peroxynitrite led to a decrease in iodoacetamidofluorescein labeling, implying that cysteine modifications were induced. Glutathione was unable to reverse ATPase inhibition. The presence of Na+ and low MgATP during peroxynitrite treatment increased the IC50 to 145+/-10 microM, while the presence of K+ and low MgATP increased the IC50 to 255+/-13 microM. This result suggests that the EPNa conformation of the pump is slightly more sensitive to peroxynitrite than the E(K) conformation. Taken together, these results show that peroxynitrite is a potent inhibitor of Na-K-ATPase activity and that peroxynitrite can induce amino acid modifications to the pump.


Folding Dynamics of DNA G-Quadruplexes Probed by Millisecond Temperature Jump Circular Dichroism.
G-quadruplexes play important roles in cellular regulatory functions, but despite significant experimental and theoretical efforts, their folding mechanisms remain poorly understood. In this context, we developed a T-jump experiment to access the thermal denaturation and renaturation dynamics of short intramolecular G-quadruplexes in vitro, on the time scale of a few hundred milliseconds. With this new setup, we compared the thermal denaturation and renaturation kinetics of three antiparallel topologies made of the human telomeric sequences d[(5'-GGG(TTAGGG)3-3']/Na+ and d[5'-AGGG(TTAGGG)3-3']/Na+ and the thrombin-binding aptamer sequence d[5'-GGTTGGTGTGGTTGG-3']/K+, with those of the parallel topology made of the human CEB25 minisatellite d[5'-AAGGGTGGGTGTAAGTGTGGGTGGGT-3']/Na+. In all cases, exponential kinetics of the order of several hundred milliseconds were observed. Measurements performed for different initial temperatures revealed distinct denaturation and renaturation dynamics, ruling out a simple two-state mechanism. The parallel topology, in which all guanines adopt an anti conformation, displays much slower dynamics than antiparallel topologies associated with very low activation barriers. This behavior can be explained by the constrained conformational space due to the presence of the single-base propeller loops that likely hinders the movement of the coiled DNA strand and reduces the contribution of the entropy during the renaturation process at high temperatures.


Foveal thickness between stratus and spectralis optical coherence tomography in retinal diseases.
To compare the foveal thickness (FT) parameters measured by Stratus optical coherence tomography (OCT) and Spectralis OCT in various retinal diseases and to construct conversion formulas between the two types of OCT devices. We examined 366 consecutive patients (475 eyes) with retinal diseases and 13 normal controls (13 eyes). The patients were categorized into eight retinal disease groups. The mean amount and distribution of foveal thickness differences (FTD) measured by Stratus and Spectralis OCT were determined, and conversion formulas were constructed for Stratus OCT FT from Spectralis OCT FT for each retinal disease group. Among retinal diseases, the mean FTD was significantly larger in exudative age-related macular degeneration (AMD) patients (mean ± SD, 94.0 ± 55.0 µm) compared to normal subjects (66.2 ± 11.7 µm; p < 0.0001). The proportion of eyes with a mean FTD outside 1.96 standard deviations of normal subject FTD was greatest in the exudative AMD (50.0%) group and smallest in the macular hole (18.2%) group. The predicted FTs obtained through the conversion formulas showed lower variance than the actual FTD values, especially in the exudative AMD group. The prediction line for exudative AMD deviated most from that of normal subjects. FTD shows diverse values and variances among various retinal diseases, especially in exudative AMD, which indicates that Stratus OCT FT cannot be predicted from Spectralis OCT FT by FTD value alone. We constructed statistically significant conversion formulas, which provided more reliable methods to predict Stratus OCT-measured FT from Spectralis OCT measurements for different retinal disease groups.


Comparative bioavailability of two different diclofenac formulations in healthy volunteers.
The aim of the study was to assess the bioequivalence of two different diclofenac (CAS 15307-86-5) formulations (diclofenac free acid suspension as test formulation and diclofenac resinate suspension, Cataflam, as reference formulation) in 24 healthy volunteers. After an overnight fast, the volunteers received a single oral dose (50 mg) of each formulation, following an open, randomized, two-period crossover design, with a fourteen-day washout interval between doses. Serum samples were obtained over a 24-h interval post-dosing, and were analysed for their diclofenac content by HPLC-UV. No adverse effect was reported for any of the formulations administered. Geometric mean test/reference individual ratios were: 92.8% for AUC(0-24 h), 93.2% for AUC(0-infinity), 117.2% for Cmax, 131.0% for Ke and 76.2% for T1/2. The variability of Cmax parameter expressed as CV was greater than 25%. Since the 90% CI for AUC(0-24 h) mean ratio were within the 80-125% interval proposed by the Food and Drug Administration, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for the extent of absorption. Since the European Community Agency accepts a 90% CI for Cmax of 70-143%, it can be concluded that diclofenac free acid formulation is bioequivalent to diclofenac resinate formulation for both the rate and the extent of absorption after single dose administration.


Molecular diagnosis of deafness: impact of gene identification.
Recent progress in identifying genes responsible for hearing loss enables the ENT clinician to apply molecular diagnosis by genetic testing. This article focuses on three genes, which are prevalent and therefore commonly encountered in the clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene responsible for congenital hearing loss in many countries. A series of reports revealed that different combinations of GJB2 mutations exist in different ethnic populations, indicating that ethnic background should be considered when performing genetic testing. GJB2 mutations will be of particular interest in combination with universal infant hearing screening programs, because it has been shown that early identification of hearing loss and early intervention are crucial for language development. Progress in genetic analysis has changed the concept of diseases. The present review introduces the example of two historically distinct categories of disease, Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, which are currently considered to be a continuum of diseases caused by the same gene, PDS. This review also emphasizes that some hearing impairment can be prevented. The 1555A-->G mitochondrial mutation, the most prevalent mitochondrial mutation found in the hearing-impaired population, was found in approximately 3% of the outpatients. The 1555A-->G mutation is known to be associated with a susceptibility to aminoglycoside antibiotics. There may be a considerably large high-risk population and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended.


Nanomedicine-Based Strategies Assisting Photodynamic Therapy for Hypoxic Tumors: State-of-the-Art Approaches and Emerging Trends.
Since the first clinical cancer treatment in 1978, photodynamic therapy (PDT) technologies have been largely improved and approved for clinical usage in various cancers. Due to the oxygen-dependent nature, the application of PDT is still limited by hypoxia in tumor tissues. Thus, the development of effective strategies for manipulating hypoxia and improving the effectiveness of PDT is one of the most important area in PDT field. Recently, emerging nanotechnology has benefitted progress in many areas, including PDT. In this review, after briefly introducing the mechanisms of PDT and hypoxia, as well as basic knowledge about nanomedicines, we will discuss the state of the art of nanomedicine-based approaches for assisting PDT for treating hypoxic tumors, mainly based on oxygen replenishing strategies and the oxygen dependency diminishing strategies. Among these strategies, we will emphasize emerging trends about the use of nanoscale metal-organic framework (nMOF) materials and the combination of PDT with immunotherapy. We further discuss future perspectives and challenges associated with these trends in both the aspects of mechanism and clinical translation.


Gamma Knife Radiosurgery With Mask Fixation Under General Anesthesia for Pediatric Patients.
Gamma knife radiosurgery (GKS) is performed on children by frame fixation of the skull under general anesthesia. With the introduction of the Gamma Knife Icon, treatment by fixing with a thermoplastic mask has become possible. In this study, we performed GKS by mask fixation under general anesthesia, measured the accuracy, and examined whether an accuracy equivalent to that of frame fixation could be guaranteed. We included three children who underwent mask fixation under general anesthesia between September and November 2020. After the induction of general anesthesia, a patient marker was attached to the nose, and the movement of the marker before mask fixation was measured using a real-time high-definition motion management (HDMM) system. The movement of the patient marker from the start to the end of treatment after mask fixation was monitored and measured. After the induction of general anesthesia, the movement of the patient marker was ≤0.3 mm in two cases and ≥1.0 mm in one case without mask fixation. When the mask was fixed, it was ≤0.2 mm in all three cases. It was confirmed that the marker could move even under general anesthesia without mask fixation, and it could be suppressed to a minimum after mask fixation. With the mask fixation method devised in this study, GKS under general anesthesia for children seems to be a safe and highly accurate method.


Microfluidic serial dilution cell-based assay for analyzing drug dose response over a wide concentration range.
In this paper we report a perfusion culture microchamber array chip with a serial dilution microfluidic network for analyzing drug dose response over a concentration range spanning 6 orders of magnitude, which is required for practical drug discovery applications. The microchamber array chip was equipped with a pressure-driven interface, in which medium and drug solution were added with a micropipet and delivered into the microfluidic network by pneumatic pressure. We demonstrated that the microchamber array chip could be used to estimate the 50% growth inhibitory concentration using the model anticancer drug paclitaxel and the model cancer cell line HeLa. The results obtained by using the microchamber array chip were consistent with those obtained by a conventional assay using microplates. The microchamber array chip, with its simple interface and well-designed microfluidic network, has potential as an efficient platform for high-throughput dose response assays in drug discovery applications.


Clinical decision support: progress and opportunities.
In 2005, the American Medical Informatics Association undertook a set of activities relating to clinical decision support (CDS), with support from the office of the national coordinator and the Agency for Healthcare Research and Quality. They culminated in the release of the roadmap for national action on CDS in 2006. This article assesses progress toward the short-term goals within the roadmap, and recommends activities to continue to improve CDS adoption throughout the United States. The report finds that considerable progress has been made in the past four years, although significant work remains. Healthcare quality organizations are increasingly recognizing the role of health information technology in improving care, multi-site CDS demonstration projects are under way, and there are growing incentives for adoption. Specific recommendations include: (1) designating a national entity to coordinate CDS work and collaboration; (2) developing approaches to monitor and track CDS adoption and use; (3) defining and funding a CDS research agenda; and (4) updating the CDS 'critical path'.


Association of FGD1 polymorphisms with early-onset breast cancer.
Recent cancer studies have suggested that the faciogenital dysplasia 1 (FGD1) gene may play a role in the development of tumor cells. Somatic alterations in the FGD1 gene and increased Fgd1 protein expression have been observed in many breast tumor cases. The present study sequenced the FGD1 gene in tumor DNA from 46 breast cancer patients using Ion Torrent sequencing. Three synonymous polymorphisms and one missense polymorphism were detected with next-generation sequencing; however, no somatic mutations were observed. The Thr697 variant was identified in 18 patients with an average age at diagnosis of 55 years, which was a lower average age than patients without the polymorphism. In addition, a higher frequency of Thr697 was observed in African-American patients. The Pro712 was observed in 15 breast cancer patients with an average age of 58 years, and was observed as a haplotype with the Thr697 variant in 28% of the breast cancer patients studied. The missense polymorphism (Ala226Thr) was identified in a 40-year-old female patient who had a recurrence of cancer. These polymorphisms (Ala226Thr, Thr697 and Pro712) may be associated with an earlier onset of breast cancer.


Two cases of pineal anlage tumor with molecular analysis.
Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.


Insulin resistance and risk for stroke.
Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance. The authors searched Medline (1977-2001) and reviewed bibliographies to identify pertinent English-language publications. Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke. Insulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.


Caenibacillus caldisaponilyticus gen. nov., sp. nov., a thermophilic, spore-forming and phospholipid-degrading bacterium isolated from acidulocompost.
A thermophilic and phospholipid-degrading bacterium, designated strain B157T, was isolated from acidulocompost, a garbage compost processed under acidic conditions at moderately high temperature. The organism was Gram-stain-positive, aerobic, spore-forming and rod-shaped. Growth was observed to occur at 40-65 °C and pH 4.8-8.1 (optimum growth: 50-60 °C, pH 6.2). The strain was catalase- and oxidase-positive. The cell wall contained meso-diaminopimelic acid, alanine, glutamic acid and galactose. The predominant respiratory quinone was menaquinone-7 (MK-7) and the major fatty acids were anteiso-C17 : 0 and iso-C17 : 0. Comparative 16S rRNA gene sequence analysis showed that strain B157T was related most closely to Tuberibacillus calidus 607T (94.8 % identity), and the phylogenetic analysis revealed that it belonged to the family Sporolactobacillaceae. The DNA G+C content was determined as 51.8 mol%. In spite of many similarities with the type strains of members of the family Sporolactobacillaceae, genotypic analyses suggest that strain B157T represents a novel species of a new genus, Caenibacilluscaldisaponilyticus gen. nov., sp. nov. The type strain of Caenibacilluscaldisaponilyticus is B157T (=NBRC 111400T=DSM 101100T).


The Role of Centrosome Distal Appendage Proteins (DAPs) in Nephronophthisis and Ciliogenesis.
The primary cilium is found in most mammalian cells and plays a functional role in tissue homeostasis and organ development by modulating key signaling pathways. Ciliopathies are a group of genetically heterogeneous disorders resulting from defects in cilia development and function. Patients with ciliopathic disorders exhibit a range of phenotypes that include nephronophthisis (NPHP), a progressive tubulointerstitial kidney disease that commonly results in end-stage renal disease (ESRD). In recent years, distal appendages (DAPs), which radially project from the distal end of the mother centriole, have been shown to play a vital role in primary ciliary vesicle docking and the initiation of ciliogenesis. Mutations in the genes encoding these proteins can result in either a complete loss of the primary cilium, abnormal ciliary formation, or defective ciliary signaling. DAPs deficiency in humans or mice commonly results in NPHP. In this review, we outline recent advances in our understanding of the molecular functions of DAPs and how they participate in nephronophthisis development.


Tetraplatinum cluster complexes bearing hydrophilic anchors as precursors for γ-Al2O3-supported platinum nanoparticles.
Tetraplatinum cluster complexes bearing hydrophilic anchors, [Pt4(μ-OCOCH3)4(μ-OCOC6H4OH-4)4] (2a), [Pt4(μ-OCOCH3)4(μ-OCOC6H4B(OH)2-4)4] (2b), and [Pt4(μ-OCOCH3)4(μ-OCOC6H4NH2-4)4] (2c), were successfully prepared by a selective substitution reaction of four in-plane acetates of [Pt4(μ-OCOCH3)8] (1) with the corresponding p-substituted benzoic acids. Solid-state structure determination of 2a revealed the 3D network structure through intermolecular hydrogen bonding between the hydroxy group of the p-hydroxybenzoate ligand and the oxygen atom of the carboxylate ligand of 2a. UV-vis analysis of 2a–c in CH3CN or CH3CN–H2O in the presence of γ-Al2O3 clearly indicated the adsorption efficiency of these platinum clusters on γ-Al2O3: 2a bearing a hydroxyl group and 2b bearing a B(OH)2 group were effectively deposited onto γ-Al2O3 from CH3CN solution, whereas less than 40% of 1 and 2c were chemically adsorbed onto γ-Al2O3. Highly dispersed and very small platinum nanoparticles (less than 1 nm) on γ-Al2O3 were obtained by thermal treatment of Pt4-deposited γ-Al2O3 at 500 °C.


Linkage information content and efficiency of full-sib and half-sib designs for gene mapping.
The accuracy of a genetic map depends on the amount of linkage information contained in the data set used for construction of the map. The amount of linkage information is related to the designs employed for linkage analysis. The purpose of this study was to provide general formulations for various genotyping schemes and family structures in order to evaluate the amount of linkage information in a data set. Linkage information content (LIC) was defined as the frequency of fully informative gametes, which are gametes from doubly heterozygous parents with known linkage phases. Depending on the design, LIC is based on two generations if the parental phases are determined statistically, or three generations if the parental phases are determined genetically. Different schemes were considered in deriving LIC: (1) genotyping of one parent or two parents, and (2) genotyping of two or three generation families. The LIC for a full-sib design was found to be generally greater than for a half-sib design but requires typing a large number of individuals when at least one locus has only two alleles. The efficiency of the full-sib design is reduced significantly if a sex-specific linkage map is sought.


miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy.
Liver cancer is the sixth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. Adriamycin (ADR) resistance, which often leads to the progression of malignant tumors, is a major treatment obstacle for liver cancer. It has been confirmed that miR-155-5p could reverse drug resistance in human breast cancer. However, the biological function of miR-155-5p in ADR-resistant liver carcinoma (HepG2/ADR) cells remains unclear. miR-155-5p and ATG5 expression was determined by RT-qPCR and western blot. In addition, MTT, flow cytometry, immunofluorescence staining, and western blotting were performed to evaluate the proliferation, apoptosis, and autophagy of liver cancer cells. Finally, the effect of miR-155-5p on the expression of autophagy-related 5 (ATG5) was analyzed by luciferase activity assay, western blot, and RT-qPCR. Our results showed that miR-155-5p was downregulated in HepG2/ADR cells. Increasing the expression of miR-155-5p enhanced the sensitivity of liver carcinoma cells to ADR and promoted apoptosis through inhibition of autophagy in vitro. In addition, the binding site between miR-155-5p and ATG5 was identified, and miR-155-5p could directly regulate ATG5. Finally, ATG5 partially rescued the effect of miR-155-5p on autophagy and the apoptosis of HepG2/ADR cells. In conclusion, our findings showed that miR-155-5p could reverse ADR resistance in liver cancer by targeting ATG5, which may function as a potential target for liver cancer treatment.


Enantioselective Phosphine-Catalyzed Allylic Alkylations of mix-Indene with MBH Carbonates.
The first enantioenriched synthesis of 1,1,3-trisubstituted (trifluoromethyl)indene derivatives, bearing a quaternary stereogenic carbon center, is reported using a simple chiral sulfinamide phosphine-catalyzed asymmetric allylic alkylation of a mixture of indenes with Morita-Baylis-Hillman carbonates. The resulting derivatives can serve as a valuable synthetic building block for some drugs and natural products. Broad substrate scope and high regio- and enantioselectivity of this reaction were particularly remarkable.


Self-Injury in Adolescence Is Associated with Greater Behavioral Risk Avoidance, Not Risk-Taking.
Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have (n = 31) and who do not have (n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state.


[Epidemiology of tumour mortality from 2000 to 2005 in the province of Vercelli (Italy)].
The main aim of this study was to assess the burden of cancer disease in residents of Vercelli (northern Italy), by analysing mortality data and hospital discharge forms. This was done in order to verify whether, as widely suspected among the city's population, an increased risk of cancer exists in the area, due to the large number of existing agricultural and industrial activities. Tumour mortality rates were compared with mortality data from the tumour registries of the province of Biella and of the city of Turin to identify a possible excess number of cases in Vercelli.An increased mortality rate was observed with respect to reference values (mortality registry of the city of Turin) for several tumours; more specifically results revealed a significantly increased mortality rate due to colorectal tumours, leukemias and nervous system tumours in both genders. Excess mortality was detected in males but not in females for esophageal cancer, non melanoma skin cancers, pancreatic, laryngeal, prostatic, renal and bone cancers. Conversely, in females, the standard mortality ratios (SMR) were found to be statistically significant for renal and laryngeal cancers and for Hodgkin's lymphoma.


TLCoV- An automated Covid-19 screening model using Transfer Learning from chest X-ray images.
The Coronavirus disease (Covid-19) has been declared a pandemic by World Health Organisation (WHO) and till date caused 585,727 numbers of deaths all over the world. The only way to minimize the number of death is to quarantine the patients tested Corona positive. The quick spread of this disease can be reduced by automatic screening to cover the lack of radiologists. Though the researchers already have done extremely well to design pioneering deep learning models for the screening of Covid-19, most of them results in low accuracy rate. In addition, over-fitting problem increases difficulties for those models to learn on existing Covid-19 datasets. In this paper, an automated Covid-19 screening model is designed to identify the patients suffering from this disease by using their chest X-ray images. The model classifies the images in three categories - Covid-19 positive, other pneumonia infection and no infection. Three learning schemes such as CNN, VGG-16 and ResNet-50 are separately used to learn the model. A standard Covid-19 radiography dataset from the repository of Kaggle is used to get the chest X-ray images. The performance of the model with all the three learning schemes has been evaluated and it shows VGG-16 performed better as compared to CNN and ResNet-50. The model with VGG-16 gives the accuracy of 97.67%, precision of 96.65%, recall of 96.54% and F1 score of 96.59%. The performance evaluation also shows that our model outperforms two existing models to screen the Covid-19.


TOR Signaling Pathway in Cardiac Aging and Heart Failure.
Mechanistic Target of Rapamycin (mTOR) signaling is a key regulator of cellular metabolism, integrating nutrient sensing with cell growth. Over the past two decades, studies on the mTOR pathway have revealed that mTOR complex 1 controls life span, health span, and aging by modulating key cellular processes such as protein synthesis, autophagy, and mitochondrial function, mainly through its downstream substrates. Thus, the mTOR pathway regulates both physiological and pathological processes in the heart from embryonic cardiovascular development to maintenance of cardiac homeostasis in postnatal life. In this regard, the dysregulation of mTOR signaling has been linked to many age-related pathologies, including heart failure and age-related cardiac dysfunction. In this review, we highlight recent advances of the impact of mTOR complex 1 pathway and its regulators on aging and, more specifically, cardiac aging and heart failure.


Effects of the flexion-distraction technique and drop technique on straight leg raising angle and intervertebral disc height of patients with an intervertebral disc herniation.
[Purpose] The purpose of this study was to determine the effects of the flexion-distraction technique and drop technique on the straight leg raising angle and intervertebral disc height of patients with an intervertebral disc herniation. [Participants and Methods] Thirty patients with herniated intervertebral discs were divided into either an experimental group (n=15), who underwent flexion-distraction and drop techniques, or a control group (n=15), who obtained spinal decompression therapy. Both groups were treated three times per week for eight weeks. [Results] An intragroup comparison showed that the straight leg raising angle and the intervertebral disc height significantly increased in both groups. But it was not significantly difference in the intergroup comparison. [Conclusion] The flexion-distraction technique and the drop technique may serve as effective interventions for the straight leg raising angle and intervertebral disc height in patients with intervertebral disc herniations.


Magneto-Raman Study of Magnon-Phonon Coupling in Two-Dimensional Ising Antiferromagnetic FePS3.
Recently, the coupling between magnons (quanta of spin waves) and phonons (quanta of lattice vibrations) in two-dimensional (2D) antiferromagnet FePS3 offers a myriad of applications ranging from spintronic devices to quantum information technologies. However, the reported magnon-phonon coupling in the FePS3 flake using Raman measurements requires an ultrahigh magnetic field up to 30 T. Here, we investigate the magnon-phonon coupling in FePS3 by near-resonant magneto-Raman spectroscopy under a relatively small magnetic field (|H0| ≤ 9 T). Under near-resonant excitation, we find more pronounced coupling effects that are absent in non-resonant excitation: three optical phonons sensitive to the applied magnetic field are resolved, two of which show a frequency anti-crossing coupling with magnon, while the other coupled phonon exhibits only a polarization-coupled character without frequency anti-crossing. Besides, our polarized Raman results also show the polarization transferring between coupled magnon-phonon modes. On the basis of a modified theoretical model, we can well explain the measured Raman spectra.


Self-Awareness Deficits of Cognitive Impairment in Individuals With Schizophrenia. Really?
Misestimation of cognitive functioning has been largely described in individuals with schizophrenia. There is large evidence that correlations between subjectively assessed cognitive functioning and objectively determined cognitive functioning are weak in non clinical individuals and may be more closely related to other psychoaffective or clinical factors than to objective neuropsychological functioning. Surprisingly, no study to date has compared the associations between cognitive complaint and objective measures of cognitive functioning in individuals with schizophrenia and healthy controls. The main objective of this study was to 1) compare cognitive complaint between individuals with schizophrenia and non clinical controls, 2) explore the relationships between cognitive complaint and psychoaffective and clinical factors in the clinical group and 3) compare the relationships between subjective awareness of cognitive functioning and objective neuropsychological assessment in individuals with schizophrenia and non-clinical participants. In this study 30 individuals with schizophrenia and 20 non-clinical matched controls were included. In addition to objective cognitive measures and subjective cognition assessed by the Subjective Scale To Investigate Cognition In Schizophrenia, measures of psychotic symptoms, depression, and anxiety were included. Schizophrenia patients reported higher cognitive complaints in comparison with controls. In individuals with schizophrenia, cognitive complaint subscores were differently associated with depression, anxiety, and negative symptoms. When depression was controlled for, the same number of correlations between self-rated measures of cognition and objective measures of cognition were found in both groups, but accuracy of self-assessment of cognition was lower in the schizophrenia group.When the schizophrenia group was divided into a high cognitive complaint group (SZ High CC) and a low cognitive complaint group (SZ Low CC), findings indicated that self-assessment of cognition in the SZ high CC was highly accurate (correlations with large effect sizes). By contrast the SZ low CC group severely misjudge their cognition. A significant proportion of patients with schizophrenia can accurately estimate their cognitive skills. Self-awareness of cognitive deficits in individuals with schizophrenia is an heterogenous phenomenon and misestimation of cognitive functioning might have been overestimated, partly due to secondary psychoaffective factors. Caution is warranted before jumping to the conclusion that all individuals with schizophrenia misjudge their cognitive functioning.


Exosome-Derived Mediators as Potential Biomarkers for Cardiovascular Diseases: A Network Approach.
Cardiovascular diseases (CVDs) are widely recognized as the leading cause of mortality worldwide. Despite the advances in clinical management over the past decades, the underlying pathological mechanisms remain largely unknown. Exosomes have drawn the attention of researchers for their relevance in intercellular communication under both physiological and pathological conditions. These vesicles are suggested as complementary prospective biomarkers of CVDs; however, the role of exosomes in CVDs is still not fully elucidated. Here, we performed a literature search on exosomal biogenesis, characteristics, and functions, as well as the different available exosomal isolation techniques. Moreover, aiming to give new insights into the interaction between exosomes and CVDs, network analysis on the role of exosome-derived mediators in coronary artery disease (CAD) and heart failure (HF) was also performed to incorporate the different sources of information. The upregulated exosomal miRNAs miR-133a, miR-208a, miR-1, miR-499-5p, and miR-30a were described for the early diagnosis of acute myocardial infarction, while the exosome-derived miR-192, miR-194, miR-146a, and miR-92b-5p were considered as potential biomarkers for HF development. In CAD patients, upregulated exosomal proteins, including fibrinogen beta/gamma chain, inter-alpha-trypsin inhibitor heavy chain, and alpha-1 antichymotrypsin, were assessed as putative protein biomarkers. From downregulated proteins in CAD patients, albumin, clusterin, and vitamin D-binding protein were considered relevant to assess prognosis. The Vesiclepedia database included miR-133a of exosomal origin upregulated in patients with CAD and the exosomal miR-192, miR-194, and miR-146a upregulated in patients with HF. Additionally, Vesiclepedia included 5 upregulated and 13 downregulated exosomal proteins in patients in CAD. The non-included miRNAs and proteins have not yet been identified in exosomes and can be proposed for further research. This report highlights the need for further studies focusing on the identification and validation of miRNAs and proteins of exosomal origin as biomarkers of CAD and HF, which will enable, using exosomal biomarkers, the guiding of diagnosis/prognosis in CVDs.


What is the normal heart rate of a term fetus?
There is controversy about the value of continuous versus intermittent auscultation of the fetal heart during labour, but there is no agreement on what constitutes normal heart rate of a term fetus. There are variations between the definitions adopted by different countries, and even within a single country. We propose 110-160 beats per minute for clinical use.


SUFE and the internet: are healthcare information websites accessible to parents?
Slipped upper femoral epiphysis is an adolescent hip disorder requiring rapid surgical intervention. Faced with the prospect of their child undergoing surgery, many fearful parents will turn to the internet to provide information and reassurance. Previous studies have shown the orthopaedic information can be difficult to comprehend. Assess the readability of healthcare websites regarding slipped upper femoral epiphysis. The term Slipped Upper Femoral Epiphysis was searched in Google, Bing and Yahoo. The websites were evaluated using readability software with seven specialised readability tests including the Flesch-Kincaid Reading Grade Level, the Flesch Reading Ease Score, the Simple Measure of Gobbledygook, Coleman-Liau Index, Automated Readability Index and the Gunning Fog Index. The reading grade level (RGL) was also calculated.A Flesich Read Ease Score (FRES) score above 65 and an RGL of sixth grade and under was considered acceptable. Websites were also assessed for translation services. 21 unique websites were assessed. The average FRES was 52.5±15.4. Only 3 websites scored 65 or higher (14%). There was a statistically significant difference between website scores based on affiliation, with physician websites having the overall highest mean(p=0.004).The average RGL was 8.67±1.8. Only two websites met the accepted RGL criteria (9.5%) while five websites were marked as extremely difficult to understand (23.8%). Only five websites offered translations (23.8%). There was no statistically significant difference in readability scores between websites which offered translation and those which did not.One-sample t-tests showed that both the RGL (p<0.001; CI 1.83 to 3.49) and the FRES (p<0.001, CI -19.4 to -5.4) scores were significantly different from the accepted standard. Most websites reviewed were above the recommended RGL, making content inaccessible. Improving readability and translation services would enhance the internet's usability as a healthcare tool for parents.


Turner syndrome in a mother and daughter: r(X) and fertility.
A patient with mosaic Turner syndrome and normal fertility had three documented pregnancies. She had a 45,X/46,X,r(X) karyotype and did not undergo spontaneous sexual maturation and menarche. Conception occurred while on hormone replacement therapy. Her first pregnancy ended with the birth of a normal 46,XY male, while the third pregnancy resulted in a healthy 45,X/46,X,r(X) female. A review of the literature reveals a myriad of theories to account for the variability of ovarian function in Turner syndrome, but, as yet, there are insufficient data to yield any conclusions. There appears to be an increased risk of trisomy 21 in the offspring of females with Turner syndrome.


Modulation of protein expression levels and DNA methylation status of breast cancer metastasis genes by anthracycline-based chemotherapy and the demethylating agent decitabine.
Epigenetic drugs are promising add-ons to cancer treatment; still, adverse effects concerning tumour promotion have been reported occasionally. In this in vitro study, we investigated the effect of combination treatment of decitabine with anthracycline-based chemotherapy [5-fluorouracil plus epirubicine plus cyclophosphamide (FEC)] on viability and metastatic activity of breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). The effect of decitabine and its combined treatment with FEC on viability of both cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and adenosine triphosphate (ATP) cell survival assays. DNA methylation specific real-time polymerase chain reaction (PCR) (Methylight®) was employed to document the methylation status of the metastasis-relevant urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-I (PAI-1) genes. Additionally, protein expression levels of uPA and PAI-1 were determined using enzyme-linked immunosorbent assays. Invasion capacity of cells was assayed using Matrigel® invasion assay. Decitabine lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not affected. Decitabine did not augment FEC-mediated cytotoxicity in both cell lines. In MCF-7 cells, methylation of the uPA and PAI-1 gene promoter was significantly reduced by decitabine or decitabine plus FEC. Protein levels of uPA and PAI-1 were induced by all treatments. Decitabine significantly induced the invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased invasion capacity of MDA-MB-231. Our results suggest differential effects of single-dose decitabine and its combination with FEC on the metastatic capacity and survival of breast cancer cell lines endowed with different metastatic behaviour.


Diagnostic Performance of Seven Commercial COVID-19 Serology Tests Available in South America.
Although RT-qPCR remains the gold-standard for COVID-19 diagnosis, anti-SARS-CoV-2 serology-based assays have been widely used during 2020 as an alternative for individual and mass testing, and are currently used for seroprevalence studies. To study the clinical performance of seven commercial serological tests for COVID-19 diagnosis available in South America. We conducted a blind evaluation of five lateral-flow immunoassays (LFIA) and two enzyme-linked immunosorbent assays (ELISAs) for detecting anti-SARS-CoV-2 antibodies. We found no statistically significant differences among ELISA kits and LFIAs for anti-SARS-CoV-2 IgG sensitivity (values ranging from 76.4% to 83.5%) and specificity (100% for the seven serological assays). For anti-SARS-CoV-2 IgM, the five LFIAs have a significantly higher sensitivity for samples collected 15 days after the first time RT-qPCR positive test, with values ranging from 47.1% to 88.2%; moreover, the specificity varied from 85% to 100%, but the only LFIA brand with a 100% specificity had the lowest sensitivity. The diagnostic performance of the seven serological tests was acceptable for the seven brands tested for anti-SARS-CoV-2 IgG detection for seroprevalence screening purposes. On the other hand, our results show the lack of accuracy of anti-SARS-CoV-2 IgM detection in LFIAs as a tool for SARS-CoV-2 acute-phase infection diagnosis.


Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus.
Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated. This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models. During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse. Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.


Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis.
The present study aimed to evaluate the protective effect of rosuvastatin treatment on the mechanism of oxidized low-density lipoprotein (Ox-LDL) in rats with liver fibrosis. In total, 72 male Sprague-Dawley rats were divided into 3 groups: 24 in the control group (A), 24 in the obstructive jaundice models group (B) and 24 in the rosuvastatin group (C). Each group was further divided into four subgroups for assessment at different time-points. The obstructive jaundice models were established and rosuvastatin was administered by gavage. Liver fibrosis indicators, Ox-LDL, malonaldehyde (MDA) and superoxide dismutase (SOD), were measured and liver pathological changes were observed at weeks 1, 2, 3 and 4 after model induction. In groups B and C, the rat models were successfully established, and there were significant changes in the expression of Ox-LDL and the three liver fibrosis indicators when compared to group A (P<0.01). However, the expression of Ox-LDL and the three liver fibrosis indicators in group C were decreased compared with group B (P<0.05), while SOD increased (P<0.05) and MDA decreased (P<0.05). The three liver fibrosis indicators were different in comparison to group B (P<0.05). Thus, there appeared to be an association between the expression of Ox-LDL and liver fibrosis. Treatment with rosuvastatin could regulate the expression of Ox-LDL and improve liver fibrosis in rat models with obstructive jaundice.


Surgical management of constipation.
For the select small number of constipated patients who cannot be managed medically, surgical options should be considered. Increases in our knowledge of colorectal physiology and experience have fostered improvements in evaluation and surgical management of patients. Currently, patients with refractory colonic inertia are offered total abdominal colectomy and ileorectal anastomosis. With proper selection of patients, the results have been excellent for resolving the frequency and quality of bowel movements. However, symptoms such as bloating and abdominal pain, which may be related to irritable bowel syndrome rather than the colonic inertia, may persist.


Detection of Mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report.
We have searched for Mycobacterium leprae DNA for 36kDa protein in urine using a M. leprae specific PCR technique. A limited number of 16 patients (of which 11 belonged to lepromatous leprosy and five to tuberculoid leprosy) and eight healthy individuals were included for the present study. The number of urine samples positive by PCR were 36.4% (4/11) in lepromatous patients and 40% (2/5) in tuberculoid patients. None of the samples from healthy individuals was positive. To our knowledge, the results indicate, for the first time, the presence of M. leprae DNA in urine from leprosy patients. Another important finding obtained out of the study is that amongst treated patients 66.6% (4/6) were positive whereas amongst untreated only 20% (2/10) were positive. From the present indicative data it appears that treatment improves the PCR results with urine as a sample. Thus, the approach could prove to be useful for monitoring the treatment response of individual patients and needs to be further evaluated with a large number of patients.


Synthesis of Na(1.25)V(3)O(8) nanobelts with excellent long-term stability for rechargeable lithium-ion batteries.
Sodium vanadium oxide (Na1.25V3O8) nanobelts have been successfully prepared by a facile sol-gel route with subsequent calcination. The morphologies and the crystallinity of the as-prepared Na1.25V3O8 nanobelts can be easily controlled by the calcination temperatures. As cathode materials for lithium ion batteries, the Na1.25V3O8 nanobelts synthesized at 400 °C exhibit a relatively high specific discharge capacity of 225 mA h g(-1) and excellent stability at 100 mA g(-1). The nanobelt-structured electrode can retain 94% of the initial capacity even after 450 cycles at the current density of 200 mA g(-1). The good electrochemical performance is attributed to their nanosized thickness and good crystallinity. The superior electrochemical performance demonstrates the Na1.25V3O8 nanobelts are promising cathode materials for secondary lithium batteries.


[Regulation of progenitor cell function by hyaluronidase].
This study demonstrated the possibility of in vivo activation of progenitor cells by hyaluronidase. Specifically, treatment with hyaluronidase increased the number of mesenchymal and bone marrow precursor cells, their proliferative activity, and differentiation. Also, it promoted stem cell mobilization into blood under effect of granulocyte colony-stimulating factor (G-CSF) and enhanced progenitor cell adhesive properties. Therapeutic efficiency of transplantation of mononuclear cells isolated from peripheral blood after administration of G-CSF improved under effect of hyaluronidase. Hyaluronidase immobilized by electron beam synthesis nanotechnology exhibited high specific activity with respect to stem cells via both enteral and parenteral routes.


[Endobronchial pulmonary rhabdomyosarcoma. A case report].
We report a case of pleiomorphous pulmonary rhabdomyosarcoma observed in a 64-year-old patient with no history of soft tissue tumor. The tumor was found extending into the right lower and middle lobes. The intra-parenchymatous extension protruded into the middle lobular bronchus and was prolonged by a 4 cm polyp. The polyp extended up to the carina and reached the contralateral common bronchus. Outcome was fatal after surgery performed in an emergency setting due to asphyxia. Explorations could not be continued to determine the primary or secondary nature of the tumor. An intraparenchymatous endobronchial localization is uncommon. Primary rhabdomyosarcoma is generally a purely intra-parenchymatous tumor. The endobronchial localization has been described before but is very exceptional. This localization would also be exceptional for secondary rhabdomyosarcoma mimicking a primary malignant tumor. The histology study revealed an undifferentiated pleiomorphous tumor. Immunohistochemistry provided the final diagnosis.


The relationship of behavioral inhibition to executive functions in young adults.
Barkley's hybrid model of executive functions (EFs) predicts that individuals with deficient inhibitory control should show impairment of EFs. Thirty-eight nonreferred young adults were administered tests of EFs and four laboratory measures of inhibitory control: Stop Signal (SS), Go No-Go, Competing Motor Program (CMP), and Stroop Color-Word tests. Behavioral ratings of impulsivity were collected using the Barratt Impulsivity Scale-11 (BIS-11). CMP and SS accounted for a significant proportion of variance in measures of EFs beyond that accounted for by IQ. Additionally, increased impulsivity, as measured by the BIS-11, was associated with poorer performance on some tests of EFs. These findings provide partial support for Barkley's theory in that effective executive functioning is associated with sufficient inhibitory control.


Do we need new quality markers for chronic heart failure?
Guidelines are not cookbook medicine. Medical decisions for the treatment of chronic heart failure (CHF) are more determined by patient's characteristics than by knowledge of physicians or drug patterns. New quality markers are more favourable, because they have qualitative attributes (are more flexible and adaptable for each CHF patient due to considering objective reasons for deviation from guidelines) (Ref. 44).


Profound spinal tolerance after repeated exposure to a highly selective mu-opioid peptide agonist: role of delta-opioid receptors.
Recent studies suggest that delta-opioid receptors play a role in the development of opioid tolerance and led us to hypothesize that highly selective mu-opioid agonists may produce less tolerance. H-2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) has extraordinary selectivity for mu-receptors (K(i)(delta)/K(i)(mu) > 14,000). Daily administration of [Dmt(1)]DALDA (5 times ED(50); s.c.) for 7 days increased ED(50) 3.6-fold from 0.16 to 0.58 micromol/kg. A higher dose of [Dmt(1)]DALDA (10 times ED(50), every 12 h) for 2.5 days resulted in a 11.7 times increase in the ED(50) (1.9 micromol/kg). Complete cross-tolerance to morphine was observed, with a 3.4- and 15.1-fold shift in the morphine ED(50), respectively. We also compared the extent of spinal versus supraspinal tolerance after repeated s.c. [Dmt(1)]DALDA administration. Five doses of [Dmt(1)]DALDA (10 times ED(50), every 12 h) resulted in a 3.4 times shift in the i.c.v. ED(50) (15.4 versus 4.6 pmol/mouse) but a 44 times shift in the i.t. ED(50) (52.9 versus 1.2 pmol/mouse). Tolerance to [Dmt(1)]DALDA was associated with 30 to 35% reduction in [(3)H][Dmt(1)]DALDA binding in brain and spinal cord. Coadministration of [Dmt(1)]DALDA with delta-antagonist naltriben (NTB) reduced spinal tolerance by 50%. Even after spinal tolerance had been established, addition of a delta-antagonist (NTB or H-Tyr-TicPsi[CH(2)NH]Phe-Phe-OH) significantly enhanced the potency of i.t. [Dmt(1)]DALDA 2- to 4-fold. These results suggest that agonist activation of delta-receptors is not necessary for the development of opioid tolerance; however, delta-receptors play a modulatory role in the maintenance of the tolerant state.


Design of Chinese Grammar Recognition and Error Correction Model Based on the Deep Neural Network.
In order to further improve the performance of the automatic grammar error detection system, a new Chinese grammar recognition and correction model is proposed in this paper. Based on the transformer attention mechanism, the bias matrix of Gaussian distribution is added to improve the attention of the model to local text and strengthen the information extraction of wrong words and surrounding words in the wrong text. In addition, the ON_LSTM model is used to extract grammatical information from the special grammatical structure of error text. The experimental results show that the two methods can effectively improve the accuracy and recall rate, and the fused model achieves the highest F1 value. Finally, the Chinese text error correction system is designed to expand the application scope of the model, which helps to reduce the human cost in language learning.


[INTERNATIONAL AND LEGAL, REGIONAL AND SPECIALIZED MEDICAL STANDARDS IN THE HEALTH CARE SECTOR: EXPERIENCE OF UKRAINE].
The purpose of the article is to study specific features, problematic issues that arise during standardization in the health care sector, as well as the significance of this process for protecting the health of the population of Ukraine. The materials for identifying the essence of standardization in the health care sector were the legislation of the EU, Ukraine, as well as information from the WHO, the mass media, the caselaw of the European Court of Human Rights, political and legal publicism, analytical materials, reference editions and Internet resources. The methodological basis of the study is a set of general scientific and special legal methods of scientific cognition, the use of which is determined by the purpose, objectives and specific features of the subject matter of scientific inquiry. International, regional and specialized medical standards in the health care sector have been analyzed. The main requirements and standards enshrined in international acts have been highlighted. It has been established that the main objects of standardization in the health care sector are the rights and obligations of the population and medical workers, medical information and reporting, management and organization of health care, personnel, education, medicinal products, medical services, etc. The expediency of developing standards for medical workers practicing telehealth, cosmetology, as well as providing palliative care has been proved.


No clear winner in differing imaging modalities for cervical radiculopathy.
We review the literature pertaining to the strengths and limitation of myelography, computerized tomography (CT) and magnetic resonance imaging (MRI) relative to developing a diagnostic algorithm in the evaluation of cervical radiculopathy. To obtain the relevant literature, a Medline search was conducted using selected keywords and phrases. In addition, the bibliography of all retrieved articles was searched and pertinent articles were obtained and evaluated. The analysis revealed that developing a research based algorithm of imaging studies for the evaluation of cervical radiculopathy is not currently realistic. Furthermore, we found that most studies on the predictive value of imaging studies for cervical radiculopathy are outdated by more recent technology.


Duration of protection from clinical hepatitis A disease after vaccination with VAQTA.
Recent papers examining the expected persistence of anti-hepatitis A virus antibody following vaccination with inactivated hepatitis A vaccine have estimated that geometric mean antibody levels will remain above cut-off levels for 10-30 years. However, the methodology used in these papers did not take into account any estimates of variability between subjects. In this paper data from the persistence of antibody after the administration of another vaccine, VAQTA (hepatitis A vaccine, inactivated; MSD), were used to develop further models of antibody decay. Using individual subject estimates instead of group means allowed the estimation of time to negativity for various percentiles of the population (including the median), and the construction of confidence intervals on estimates of time to negativity. Data from studies of subjects who seroreverted to negativity, and subsequently received a booster dose, were also considered to show that subjects who lose detectable antibody are likely to remain protected from hepatitis A disease by persistent immune memory and rapid anamnestic response soon after exposure to hepatitis A virus. The estimates of duration of protection suggest that VAQTA will provide protection for many years, first through presence of antibody and further through an anamnestic response based on persistent immune memory.


Is there a role for the apex in shoot geotropism?
Experiments with horizontal etiolated sunflower (Helianthus annuus L.) seedlings supported centrally such that both apical and basal ends are free to react to geostimulus, revealed that the apical end commences curvature 1 to 2 hours earlier than the basal end. The later curvature in the basal region is a consequence of the absence of growth in the initial period rather than merely slower growth. A comparison of zonal growth rates in a vertical and a horizontal seedling confirmed that geostimulus induces a renewal of growth in a region where growth had ceased. Removing the apical half of the hypocotyl showed that the curvature resulting from this growth initiation in the basal region is dependent on attachment to the apical region. Evidence that this dependence is unlikely to be due to energy deficiency is adduced. The prior response of the apical end to geostimulus and the apically dependent later initiation of new growth in the basal region are compatible with the delay inherent in message transport from apex to base and are considered as evidence for apical involvement in the totality of the seedling's georesponse.


Orosomucoid influences the response to antidepressants in major depressive disorder.
Orosomucoid, an acute phase protein, carries basic drugs including antidepressants in plasma. Elevated levels have been reported in patients with depression. It has yet to be established whether orosomucoid concentration influences antidepressant response. The orosomucoid gene (ORM1) is polymorphic and the protein isoforms have differing pharmacokinetic properties which could alter plasma profile and blood brain barrier transport of antidepressants. Outpatients (n = 157) in a randomised control trial of fluoxetine versus nortriptyline were genotyped for the ORM1 variants. Plasma concentrations of acute phase proteins were also measured. Outcomes were the completion of an adequate six week trial of antidepressant and response. Response was defined as an improvement >/=60% on the Montgomery-Asperg Depression Rating Scale (MADRS) over six weeks. The first notable finding was that individuals with an ORM1*S/*S genotype were less likely to complete an adequate six week trial of an antidepressant (OR = 4.707, 95% CI 1.769-12.527, P = 0.002). The second was that higher orosomucoid concentrations were found in antidepressant non-responders (91.4%) than responders (79.1%) (F1, 106 = 5.669, P = 0.019). These findings highlight the potential importance of variables such as orosomucoid which impact on drug availability on the therapeutic efficacy of antidepressant drugs.


Novel probiotic lactic acid bacteria isolated from indigenous fermented foods from West Sumatera, Indonesia.
Probiotics play an important role in maintaining a healthy gut and consequently promote good health. This study aimed to find novel probiotic lactic acid bacteria (LAB) from indigenous fermented foods of West Sumatera, Indonesia. This study utilized 10 LAB previously isolated from fermented buffalo milk (dadih), fermented fish (budu), and fermented cassava (tape) which have the ability to produce gamma-aminobutyric acid. The study commenced with the screening of LAB for certain properties, such as resistance to acid and bile salts, adhesion to mucosal surface, and antagonism against enteric pathogens (Escherichia coli, Salmonella Enteritidis, and Staphylococcus aureus). The promising isolates were identified through biochemical and gram staining methods. All isolates in this study were potential novel probiotics. They survived at a pH level of 2.5 for 3 h (55.27-98.18%) and 6 h (50.98-84.91%). Survival in bile at a concentration of 0.3% was 39.90-58.61% and the survival rate was 28.38-52.11% at a concentration of 0.5%. The inhibitory diameter ranged from 8.75 to 11.54 mm for E. coli, 7.02 to 13.42 mm for S. aureus, and 12.49 to 19.00 mm for S. Enteritidis. All the isolates (84.5-92%) exhibited the ability to adhere to mucosal surfaces. This study revealed that all the isolates were potential probiotics but N16 proved to be superior because it was viable at a pH level of 2 (84.91%) and it had a good survival rate in bile salts assay (55.07%). This isolate was identified as Lactobacillus spp., Gram-positive bacilli bacteria, and tested negative in both the catalase and oxidase tests. All the isolates in this study may be used as probiotics, with isolate N16 (Lactobacillus spp.) as the most promising novel probiotic for poultry applications based on its ability to inhibit pathogenic bacteria.


Nonuniversal size dependence of the free energy of confined systems near criticality.
The singular part of the finite-size free-energy density f(s) of the O(n) symmetric phi(4) field theory is calculated for confined geometries of linear size L with periodic boundary conditions in the large-n limit and with Dirichlet boundary conditions in one-loop order. We find that both a sharp cutoff and a subleading long-range interaction cause a leading nonuniversal L dependence of f(s) near T(c). This implies a significant restriction for the validity of universal finite-size scaling for model systems and real systems. For film geometry we predict a leading nonuniversal contribution to the critical Casimir force above the superfluid transition of (4)He.


Highly selective tripeptide thrombin inhibitors.
Tripeptide aldehydes such as Boc-D-Phe-Pro-Arg-H (51) exhibit potent direct inhibition of thrombin. This distinction offers important insight for the design of more potent and selective serine protease inhibitors which may be useful pharmacological tools and hold promise for development of clinically useful agents. The structure-activity relationships (SAR) on a series of anticoagulant peptides with high selectivity for the enzyme thrombin are discussed. The SAR is centered on a series of di- and tripeptide arginine aldehydes based on the structure of 51. The structural and conformational role of the amino acid residue in position 1 was investigated by substitution with conformationally restricted aromatic amino acids, aromatic acids, and a dipeptide isostere containing the psi[CH2N] amide bond replacement. Many of these peptides demonstrate potent antithrombotic activity along with selectivity toward thrombin, determined by comparison of in vitro inhibitory effects on trypsin, plasmin, factor Xa, and tissue plasminogen activator. Compound 5f, D-1-Tiq-Pro-Arg-H.sulfate is highly active and the most selective tripeptide aldehyde inhibitor of thrombin reported to date.


Needlescopic versus laparoscopic appendectomy: a systematic review.
Needlescopic appendectomies (NA) have been performed since the 1990s. We sought to systematically analyze trials comparing NA with laparoscopic appendectomies (LA) in the management of appendicitis. We performed a systematic review of the literature. We compared and analyzed clinical trials on NA and LA to generate summative data expressed as standardized mean differences (SMD). Of 5 retrieved trials from the electronic database 2 trials involving 412 patients met our inclusion criteria. In the fixed-effects models, NA took longer than LA, and this time difference was statistically significant: SMD 0.20 min, 95% confidence interval 0.01-0.40, p = 0.030, z(1) = 2.09. In both fixed-and random-effects models, the difference in total hospital stay and in perioperative complications between the NA and LA groups were nonsignificant. Furthermore, in both fixed-and random-effects models, NA was associated with a higher conversion rate to open appendectomy than LA. There was no heterogeneity between the trials (Q = 0.34, p = 0.55). Needlescopic appendectomy can be a safe and effective procedure for the management of appendicitis. It is comparable to LA in terms of hospital stay and perioperative complications. However, NA is associated with a longer duration of surgery and a higher conversion rate, indicating technical challenges of the procedure. Before recommending routine use of the needlescopic technique for appendectomy, a major multicentre randomized controlled trial is necessary.


Normative data for PID-5 domains, facets, and personality disorder composites from a representative sample and comparison to community and clinical samples.
The introduction of the alternative model of personality disorders in the fifth edition of the Diagnostic and Statistical Model of Mental Disorders (American Psychiatric Association, 2013) represented a substantive change in how personality disorders (PDs) are diagnosed. One barrier to its adoption (among several) in clinical practice, however, is a lack of information as to what constitutes an elevated score on the 25 domains and facets that comprise Criterion B. Unique sets of facets can be configured to assess any 1 of 6 PDs retained in the alternative model of personality disorders; each of these facets can in turn be added to create a PD sum score. In the current study, using the Personality Inventory for Diagnostic and Statistical Model of Mental Disorders, Fifth Edition (Krueger et al., 2012), we report mean scores using this instrument that align with 1.0, 1.5, and 2.0 SD elevations for the 25 facets, five domains, and six PD composites on the basis of Krueger and colleagues' (2012) representative sample and compare these with those obtained from a community and a clinical sample. These normative data may be useful to clinicians in determining whether a client has elevated scores on pathological personality domains, facets, or PDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Trianthema portulacastrum restores the antioxidant defense enzyme levels and hepatic biotransformation patterns in experimental rat hepatocarcinogenesis.
The chloroform fraction of Trianthema portulacastrum L. has been found to be very effective in restoring glutathione levels and the levels of Phase I (cytochrome P-450 monooxygenase) and Phase II (UDPGT) enzymes, which undergo substantial changes during chemical rat hepatocarcinogenesis. Experimental heptocarcinogenesis was initiated by a single i.p. injection of Diethylnitrosoamine (DENA) at a dose of 200 mg/kg body weight in 0.9% normal saline. A single administration of the carcinogen is adequate to evoke the appearance of a neoplasm after 22 weeks. Various fractions of T. portulacastrum (crude aqueous, [ethanolEtOH] fraction, chloroform-fractions) in the form of plant extracts were administered to the control as well as to the experimental animals at a dose of 100 mg/kg body weight to the basal medium. After 22 weeks on this regimen, animals were sacrificed, and the different biomarkers were assayed from the hepatic tissues. The results obtained after treatment with the chloroform extract of T. portulacastrum were remarkable. The ethanol and crude aqueous extracts were less effective. Ethanol control, chloroform controls and Trianthema controls displayed similar values as that of normal untreated animals with regard to the different parameters tested. Our findings reflect strong anticarcinogenic potential of the chloroform extract of T. portulacastrum as far as these important biomakers are concerned.


Sex differences in the densities of alpha 2-adrenergic receptors in the song control system, but not the medial preoptic nucleus in zebra finches.
In songbirds, song is regulated by a specialized group of brain nuclei known as the song system. Other aspects of courtship, such as male sexual interest in a female, are likely regulated by the medial preoptic nucleus (POM). The song control system and the POM are rich in norepinephrine, which appears to regulate courtship behaviors, including song. Zebra finches (Taeniopygia guttata) exhibit an extreme sexual dimorphism in song behavior; males sing, primarily to attract or maintain mates, and females do not. We explored possible sex differences in the distribution and density of the alpha(2)-adrenergic receptors in the song system and POM of zebra finches. Receptors were labeled with the selective ligand, [(3)H] RX821002, via autoradiographic procedures. In males, dense alpha(2)-receptors were observed in the song system (Area X, the high vocal center (HVc), the lateral portion of the magnocellular nucleus of the anterior neostriatum, and the robust nucleus of the archistriatum). In contrast, in females neither the lateral portion of the magnocellular nucleus of the anterior neostriatum nor the HVc could be identified based on alpha(2)-receptor binding. Females lack Area X and indeed differential alpha(2)-binding was not observed within the female lobus parolfactorius. The robust nucleus of the archistriatum contained less dense alpha(2)-binding in females compared to males. Alpha(2)-binding in the POM was similar in males and females. The dimorphism in alpha(2)-binding in nuclei of the song system likely relates to the dimorphism in song behavior observed in male and female zebra finches.


Glutamate Synthetase in Developing Cotyledons of Pisum sativum.
Glutamate synthetase (glutamine[amide]:alpha ketoglutarate amino transferase oxidoreductase) activity has been demonstrated in the developing cotyledons of Pisum sativum L. cv. Burpeeana. The enzyme appears to be soluble and is specific for glutamine as amide donor. The enzyme activity is greater with NADH than with NADPH as electron donor.It is suggested that glutamate synthetase in the developing cotyledon provides a mechanism by which the amide nitrogen of glutamine, from the translocatory stream, is converted into the amino nitrogen of glutamate; transamination reactions involving this synthesized glutamate could provide the amino groups for the biosynthesis of the seed protein amino acids.


Dynamic principles of gait and their clinical implications.
A healthy gait pattern depends on an array of biomechanical features, orchestrated by the central nervous system for economy and stability. Injuries and other pathologies can alter these features and result in substantial gait deficits, often with detrimental consequences for energy expenditure and balance. An understanding of the role of biomechanics in the generation of healthy gait, therefore, can provide insight into these deficits. This article examines the basic principles of gait from the standpoint of dynamic walking, an approach that combines an inverted pendulum model of the stance leg with a pendulum model of the swing leg and its impact with the ground. The heel-strike at the end of each step has dynamic effects that can contribute to a periodic gait and its passive stability. Biomechanics, therefore, can account for much of the gait pattern, with additional motor inputs that are important for improving economy and stability. The dynamic walking approach can predict the consequences of disruptions to normal biomechanics, and the associated observations can help explain some aspects of impaired gait. This article reviews the basic principles of dynamic walking and the associated experimental evidence for healthy gait and then considers how the principles may be applied to clinical gait pathologies.


Comparison of the thiamine level in blood and erythrocyte transketolase activity in hemodialyzed and nondialyzed patients during recombinant human erythropoietin therapy.
Thiamine and erythrocyte transketolase activity (ETKA) disturbances in end-stage renal disease are caused mainly by uremia and dialysis treatment. We examined whether recombinant human erythropoietin (rhEPO) can correct these abnormalities in uremic patients. Thirteen hemodialysis (HD) and 12 nondialyzed (ND) anemic patients showed decreased free and total thiamine levels in plasma and in erythrocytes and decreased ETKA when compared to 20 healthy subjects. Thiamine blood levels (mumol/l) were determined using a fluorimetric technique, and ETKA (mumol/l per minute) was assessed with a photocolorimetric method. Over 20 weeks of study, rhEPO was given intravenously for 8 weeks at 50 Ul/kg body weight (BW) three times a week, and subcutaneously for 4 weeks at 25 Ul/kg BW, twice a week, and for the last 8 weeks at 25 Ul/kg BW once a week. The correction of anemia was associated with an increase in plasma thiamine and erythrocyte total thiamine as well as ETKA in HD patients and with an increase in erythrocyte total thiamine in ND patients only during the period of intravenous infusions.


Functional role of extranucleosomal DNA and the entry site of the nucleosome in chromatin remodeling by ISW2.
A minimal amount of extranucleosomal DNA was required for nucleosome mobilization by ISW2 as shown by using a photochemical histone mapping approach to analyze nucleosome movement on a set of nucleosomes with varied lengths of extranucleosomal DNA. ISW2 was ineffective in repositioning or mobilizing nucleosomes with <or=20 bp of extranucleosomal DNA. In addition, ISW2 was able to slide nucleosomes to within only 10 to 13 bp of the edge of DNA fragments. The nucleosome mobilization was promoted by extranucleosomal single-stranded DNA with modest strand preference. Gaps (10 bp) just inside the nucleosome and in the extranucleosomal DNA showed that the transfer of torsional strain (twist) into the nucleosomal DNA region was not required for mobilizing nucleosomes. However, indications are that the extranucleosomal DNA immediately adjacent to the nucleosome has an important role in the initial stage of nucleosome movement by ISW2.


Effects of additives on the stability of Humicola lanuginosa lipase during freeze-drying and storage in the dried solid.
The effects of various classes of additives on the stability of a protein with a relatively hydrophobic surface, Humicola lanuginosa lipase (HLL), during lyophilization and storage in the dried solid, were investigated. Prior to lyophilization, it was found that 1 M trehalose or 1% (wt/vol) Tween 20 caused the protein to precipitate. Infrared spectroscopy indicated that trehalose "salted-out" native HLL, whereas Tween 20 induced non-native aggregates. Optimal recovery of native protein in the initial dried solid was obtained in the presence of additives which formed an amorphous phase and which had the capacity to hydrogen bond to the dried protein (e.g., trehalose and sucrose). Additives which crystallized during lyophilization (e.g., mannitol) or which remained amorphous, but were unable to hydrogen bond to the dried protein (e.g., dextran), afforded less stabilization relative to that seen in the absence of additives. Optimal storage stability in the dried solid required that both protein unfolding during lyophilization was minimized and that the formulation was stored at a temperature below its Tg value. Crystallization of sucrose during storage greatly reduced the storage stability of HLL. This was attributed to the increased moisture content and the reduced Tg value in the remaining amorphous phase containing the protein. Sucrose crystallization and the resulting damage to the protein were inhibited by decreasing the mass ratio of sucrose:protein.


State newborn screening in the tandem mass spectrometry era: more tests, more false-positive results.
The advent of tandem mass spectrometry has made it possible to test newborns for multiple conditions efficiently. It is not known how state newborn screening programs have changed screening practices in response to this technology and how it affects the number of false-positive test results. We obtained data from the National Newborn Screening and Genetics Resource Center regarding the screening practices for each of the 50 states, to determine the number of mandated disorders added to state newborn screening panels between 1995 and 2005. Combining these data with reported specificities from the literature and the number of births in each state, we estimated the number of infants who would have received false-positive results through screening with tandem mass spectrometry in 2005. The average state mandated screening for 5 disorders in 1995 (range: 0-8 disorders). Wyoming was the only state that decreased its panel size over the next decade. Kansas and Texas were the only states that did not add disorders to their panels between 1995 and 2005; the average state added 19. Iowa, Minnesota, Mississippi, South Dakota, and Tennessee each added > or = 40 disorders. Assuming that an individual test for a disorder had a specificity of 99.995%, we estimated that approximately 2575 infants would have received false-positive results through screening with tandem mass spectrometry in 2005. If specificity was assumed to be 99.9%, then the number increased to > 51000. State newborn screening programs have expanded dramatically in the past decade. Because the benefit of such testing may be unclear in some cases and because the number of infants who may receive false-positive results and may be labeled falsely as having disease is potentially sizeable, a more cautious approach is needed.


Update on the evaluation and diagnosis of celiac disease.
Our understanding of the pathophysiology of celiac disease has advanced with associated improvement in diagnostic modalities. Recent studies have placed the prevalence of celiac disease in Western populations at between 1:250 and 1:67. Celiac disease is common throughout the world and most cases go undiagnosed. Understanding the risk factors, clinical presentations and diagnostic modalities is necessary to identify and treat patients with this commonly misdiagnosed disorder. Increased prevalence of celiac disease in individuals with autoimmune diseases, reduced bone mineral density and undiagnosed liver disease have been confirmed. However, celiac disease may not be associated with Down's syndrome or epilepsy. Evidence supports high sensitivity and specificity of endomysial- and tissue transglutaminase-based tests in most settings. In children, high or low tissue transglutaminase levels may preclude the need for duodenal biopsy. Cost-effectiveness studies suggest using tissue transglutaminase or endomysial initially, while distal duodenal or jejunal biopsy may confirm celiac disease in the absence of proximal changes. There is insufficient evidence to support mass screening for celiac disease. However, case finding in individuals with risk factors for celiac disease is recommended. Further study is necessary to define diagnostic algorithms and target populations likely to benefit from testing.


Tolerability of the Intravenously Administered Tolvaptan Prodrug, OPC-61815, in Patients With Congestive Heart Failure Who Have Difficulty With, or Are Incapable of, Oral Intake (TRITON-HF) - A Phase III, Multicenter, Open-Label Trial.
OPC-61815, a prodrug of tolvaptan, is an injectable aquaretic drug. This study evaluated the tolerability of OPC-61815 in patients with congestive heart failure (CHF) who had difficulty with, or were incapable of, oral intake in a multicenter, uncontrolled, open-label Phase III study.Methods and Results: Forty-five patients were enrolled at 30 Japanese sites. OPC-61815 infusion was administered once daily; the 8 mg initial dose could be increased to 16 mg if the dose escalation criteria were met. Patients were treated for up to 5 days. Thirty-eight patients maintained the 8-mg dose and 7 had a dose increase to 16 mg; 41 completed the trial (34 completed early). One patient had mild hypernatremia. No significant safety concerns were observed with OPC-61815 administration at a starting dose of 8 mg and with dose escalation in accordance with the protocol-specified criteria. Treatment resulted in weight decrease (-3.01 kg); improvement or disappearance rates for other CHF symptoms (including edema, dyspnea, orthopnea, pulmonary congestion, and rales) indicated that treatment was effective. Urine excretion was increased 0-1 h after OPC-61815 administration and reached a maximum level at 1-2 h. The tolerability of once daily (up to 5 days) intravenous OPC-61815 (8 mg or 16 mg) was confirmed in patients with CHF who had difficulty with, or were incapable of, oral intake.


Hyperoxic increases in lung ICAM-1 mRNA are independent of TNF-alpha and IL-1 beta mRNA.
Hyperoxia-exposure results in neutrophil accumulation and edema in the exposed lung. Intercellular adhesion molecule-1 (ICAM-1), a ligand for neutrophil beta 2 integrins, is upregulated in hyperoxia-exposed lungs and enhances neutrophil-mediated injury. Because tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are potent inducers of ICAM-1, we investigated whether TNF-alpha and IL-1 beta mRNA increase prior to the increase in ICAM-1 mRNA in hyperoxia-exposed mouse lungs. We exposed mice to > 95% oxygen for up to 96 h, isolated lung RNA, and assessed ICAM-1, TNF-alpha, and IL-1 beta mRNA by Northern blotting. We found that neither, TNF-alpha nor IL-1 beta mRNA was detectable prior to 96 h, while ICAM-1 mRNA increased by 48 h. To further assess TNF-alpha and IL-1 beta mRNA, we employed quantitative reverse-transcriptase polymerase chain reaction (RTPCR) using a mimic DNA (mimic) species as an internal control for PCR. Mimic DNA was identical to reverse-transcribed cDNA (wild type), except for 147 bp of irrelevant DNA ligated into the original cDNA. For each lung RNA sample we reverse transcribed total lung RNA and coamplified the resulting wild-type cDNA with serial dilutions of mimic DNA in a PCR containing [32P] dCTP. After PCR, we electrophoresed the samples and determined the concentration of TNF-alpha and IL-1 beta wild-type cDNAs by the ratios of wild type to mimic counts. We found no increase in TNF-alpha or IL-1 beta mRNA through 72 h of hyperoxia exposure, while there was an approximately 10-fold increase in TNF-alpha mRNA and a 35-fold increase in IL-1 beta mRNA within 2 h in the lungs of animals exposed to endotoxin. In conclusion, our data suggest that TNF-alpha and IL-1 beta are not responsible for the upregulation of ICAM-1 in hyperoxia-exposed mouse lungs.


Exogenous glutamate is metabolized to glutamine and exported by rat primary astrocyte cultures.
Rat cortical astrocytes in primary culture were examined for their capacity to transport and metabolize exogenous L-[U-14C]glutamate. After incubation for time periods up to 120 min, cells and incubation media were analyzed for labelled and endogenous glutamate and its metabolic products by HPLC coupled with fluorescence detection and liquid scintillation counting. Glutamine was the major labelled metabolite after 120 min, accounted for 38% of the original glutamate label, and was found primarily in the incubation medium. A further 13.5% of the label was recovered in deaminated metabolites of glutamate, 1.2% was associated with aspartate, 23% remained in glutamate, and 10.2% was found in an acid-precipitated cell fraction. More than 84% of the label was recovered in these fraction. suggesting that the maximum possible formation and loss of 14CO2 was 16%. The rate of total glutamine synthesis was 1.1 nmol X mg protein-1 X min-1 when 9 microM exogenous glutamate was present. The total amount of glutamine synthesized greatly exceeded the consumption of glutamate, indicating that a substantial proportion of glutamine was synthesized from other carbon sources. Almost all of the newly formed glutamine was exported into the medium. These results indicate that astrocytes in primary culture, by accumulating glutamate, producing glutamine, and exporting it, are capable of carrying out the glial component of the glutamine cycle.


[Weaning from respirators via biphasic positive airway pressure].
Weaning procedures during the course of intermittent positive pressure ventilation are often difficult. A case is presented in which biphasic positive airway pressure (BiPAP) seemed to be superior to other well known ventilator weaning regimens. The course of the weaning procedure is described.


Multiphasic perfusion CT in acute middle cerebral artery ischemic stroke: prediction of final infarct volume and correlation with clinical outcome.
To assess the utility of multiphasic perfusion CT in the prediction of final infarct volume, and the relationship between lesion volume revealed by CT imaging and clinical outcome in acute ischemic stroke patients who have not undergone thrombolytic therapy. Thirty-five patients underwent multiphasic perfusion CT within six hours of stroke onset. After baseline unenhanced helical CT scanning, contrast-enhanced CT scans were obtained 20, 34, 48, and 62 secs after the injection of 90 mL contrast medium at a rate of 3 mL/sec. CT peak and total perfusion maps were obtained from serial CT images, and the initial lesion volumes revealed by CT were compared with final infarct volumes and clinical scores. Overall, the lesion volumes seen on CT peak perfusion maps correlated most strongly with final infarct volumes (R(2)=0.819, p<0.001, slope of regression line=1.016), but individual data showed that they were less than final infarct volume in 31.4% of patients. In those who showed early clinical improvement (n=6), final infarct volume tended to be overestimated by CT peak perfusion mapping and only on total perfusion maps was there significant correlation between lesion volume and final infarct volume (R(2)=0.854, p=0.008). The lesion volumes depicted by CT maps showed moderate correlation with baseline clinical scores and clinical outcomes (R=0.445-0.706, p< or = 0.007). CT peak perfusion maps demonstrate strong correlation between lesion volume and final infarct volume, and accurately predict final infarct volume in about two-thirds of the 35 patients. The lesion volume seen on CT maps shows moderate correlation with clinical outcome.


Dip coating of charged colloidal suspensions onto substrates with patterned wettability: Coating regime maps.
Aqueous dispersions of silica nanoparticles were dip coated onto Si substrates that contained patterned wettability. The patterns were prepared by photolithography and consisted of groups of hydrophilic lines (5-100μm wide) separated by hydrophobic areas (5-100μm wide). Coating were made from two aqueous silica dispersions: a cationic dispersion in which particles have positive surface charge, and an anionic dispersion in which particles have negative surface charge. Coating morphology, thickness, and pattern quality were characterized. For a pattern containing 25μm wide hydrophilic stripes separated by equally wide hydrophobic spaces, coating regime maps were created to show the effect of process variables on pattern features and morphology. Within the map there is a critical concentration for both dispersions, above which uniform stripes are formed and below which a segregated non-uniform structure results. Coatings prepared at withdrawal rates of 0.1mm/s or lower resulted in a monolayer of coatings in the case of cationic silica and no deposition in the case of anionic silica. A maximum withdrawal rate was also found; above a critical speed, excess liquid is entrained and results in nonuniformity in the bottom of the pattern. The physical origin of the regimes and differences between the two types of particles are discussed.


Identification and characterization of radiation damaged products of monophosphate nucleosides by on-line capillary isotachophoresis-electrospray ionization mass spectrometry.
Analysis of trace levels of DNA damage as a biomarker of human exposure to radiation levels represents a significant challenge. Capillary isotachophoresis (CITP) is well suited for this application due to its high separation efficiency, large sample loading capacity, and relative ease of interfacing with highly specific and sensitive mass spectrometric detectors. This study describes the use of reversed anionic CITP coupled on-line with electrospray ionization-mass spectrometry (ESI-MS) for the identification and characterization of small quantities of radiation induced damage to deoxynucleotide monophosphates. CITP with ESI-tandem MS also provides structural information on the nature of the damage in addition to the molecular weight. This approach has the attraction of allowing the direct on-line determination of damaged nucleotides, as well as the free bases and nucleosides, and avoids the need for sample hydrolysis and/or derivatization.


Usefulness of liver biopsy in anti-hepatitis C virus antibody-positive and hepatitis C virus RNA-negative kidney transplant recipients.
Some guidelines recommend a liver biopsy to all anti-hepatitis C virus (HCV) antibody-positive kidney transplant (KT) recipients. However, in the case of HCV RNA-negative KT recipients, the benefit of a liver biopsy is unclear. We examined the usefulness of a liver biopsy for anti-HCV antibody-positive and HCV RNA-negative patients by analyzing the hepatic histologic findings and clinical outcomes. A total of 30 anti-HCV antibody-positive patients who underwent liver biopsy before KT at Asan Medical Center were retrospectively recruited. The patients were divided into two groups based on HCV RNA positivity: 17 patients were positive and 13 patients were negative. Histologic evidence of hepatic inflammation and fibrosis was assessed using the METAVIR score, and clinical outcomes, including mortality, graft loss, and progression of liver disease, were compared. The mean histologic activity scores for inflammation and fibrosis for the HCV RNA-positive and HCV RNA-negative groups were significantly different (inflammation score 1.11 ± 0.85 vs. 0.46 ± 0.51; P=0.01 and fibrosis score 1.05 ± 1.24 vs. 0.15 ± 0.37; P=0.01, respectively). The overall rates of mortality and graft loss were not significantly different between the two groups. Progression of liver disease was noted in the HCV RNA-positive group only. The HCV RNA-negative group showed no evidence of liver disease progression. Neither did they show any histologic evidence of liver inflammation and fibrosis before KT. Therefore, it appears that liver biopsy is not necessary in anti-HCV antibody-positive and HCV RNA-negative KT recipients.