Caspase 3 activity is required for skeletal muscle differentiation.
The cellular alterations associated with skeletal muscle differentiation share a high degree of similarity with key phenotypic changes usually ascribed to apoptosis. For example, actin fiber disassembly/reorganization is a conserved feature of both apoptosis and differentiating myoblasts and the conserved muscle contractile protein, myosin light chain kinase, is required for the apoptotic feature of membrane blebbing. As such, these observations suggest that the induction of differentiation and apoptosis in the myogenic lineage may use overlapping cellular mechanisms. Here, we report that skeletal muscle differentiation depends on the activity of the key apoptotic protease, caspase 3. Peptide inhibition of caspase 3 activity or homologous deletion of caspase 3 leads to dramatic reduction in both myotube/myofiber formation and expression of muscle-specific proteins. Subsequently, we have identified Mammalian Sterile Twenty-like kinase as a crucial caspase 3 effector in this cellular process. Mammalian Sterile Twenty-like kinase is cleavage-activated by caspase 3, and restoration of this truncated kinase in caspase 3 null myoblasts restores the differentiation phenotype. Taken together, these results confirm a unique and unanticipated role for a caspase 3-mediated signal cascade in the promotion of myogenesis.


Radioimmunoassay of human prolactin (PRL).
A simple and rapid homologous radioimmunoassay of human prolactin (hPRL), by the use of 66% ethanol containing 6.6% ammonium acetate for the separation of free and bound hormones, has been established. PRL levels showed marked individual and daily variations as well as a circadian periodicity in both men and women. Levels of plasma PRL rose with puberty and decreased during post-menopause and in elderly men (ages 60-73 years). There was no marked change in plasma PRL levels at midcycle; however, in some subjects, luteal levels were slightly higher than follicular levels. Administration of oestradiol-17beta caused marked increase in plasma PRL levels during menstrual cycle. During pregnancy, the plasma PRL levels rose as high as 200 ng/ml and decreased within a week or two post-partum. During lactation, the levels were higher and increased with suckling. In a patient with habitual abortion, the plasma PRL level showed a sudden drop prior to abortion. Administration of LH-RH had no effect on the secretion of PRL in human subjects.


Proline Isomerization Regulates the Phase Behavior of Elastin-Like Polypeptides in Water.
Responsiveness of polypeptides and polymers in aqueous solution plays an important role in biomedical applications and in designing advanced functional materials. Elastin-like polypeptides (ELPs) are a well-known class of synthetic intrinsically disordered proteins (IDPs), which exhibit a lower critical solution temperature (LCST) in pure water and in aqueous solutions. Here, we compare the influence of cis/trans proline isomerization on the phase behavior of single ELPs in pure water. Our results reveal that proline isomerization tunes the conformational behavior of ELPs while keeping the transition temperature unchanged. We find that the presence of the cis isomers facilitates compact structures by preventing peptide-water hydrogen bonding while promoting intramolecular interactions. In other words, the LCST transition of ELPs with all proline residues in the cis state occurs with almost no noticeable conformational change.


Antioxidant Activities and Phenolic Compounds of Several Tissues of Pawpaw (Asimina triloba [L.] Dunal) Grown in Korea.
Pawpaw (Asimina triloba [L.] Dunal) possesses antioxidant compounds and strong inhibitors of cancer cells, and is widely cultivated in North America, Canada, and Korea. We analyzed the total phenolic and total flavonoid contents (TPC and TFC, respectively) of pawpaw plants grown in Korea and the antioxidant activities of their roots, twigs, leaves, and fruit with respect to 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity, 2,2'-azino-bis diammonium salt (ABTS) radical scavenging activity, ferrous (Fe2+ ) chelating ability, and nitrite scavenging activity. Pearson's correlation analyses revealed a linear correlation between TPC and antioxidant activities (r2 >0.69). Root methanol extracts had higher TPC and antioxidant activities than other extracts, which was also consistent with those from the phenolic compounds found in those extracts. Therefore, antioxidant activities seem to depend on the TPC of each pawpaw tissue and pawpaw roots might be useful as a natural source of natural antioxidants.


Improved estimation of DNA fragment length from gel electrophoresis data using a graphical method.
A computer program has been developed for computing DNA fragment size from its electrophoretic mobility using a graphical method. The program uses DNA marker data and selects the semilogarithmic linear range (sl-range), i.e., the linear portion of the semilogarithmic curve (mobility vs. log of DNA fragment length). Over this range a linear interpolation is derived for calculating the size of a DNA fragment whose mobility falls in the sl-range. The program also derives a hyperbolic interpolation formula that covers the entire range for determining the size of a DNA fragment whose mobility is beyond the semilogarithmic linear range. The method described in this paper is sensitive, accurate and reliable. This program can also be used to compute protein or polypeptide size from sodium dodecyl sulfate polyacrylamide gel electrophoresis data. The DOS version of the DNASIZE program is freely available from Netserver at EMBL or from BioTechNet by EMail.


Pulmonary Endometriosis which Probably Occurred through Hematogenous Metastasis after Artificial Abortion.
Pulmonary endometriosis (PEM) is a rare disease characterized by the proliferation of ectopic endometrial tissue in the lungs, which presents as catamenial hemoptysis. A 20-year-old-woman was admitted for repeated hemoptysis. Chest CT revealed a ground-glass opacity that appeared consistently with her menstrual cycle. Our detailed inquiry revealed a history of artificial abortion, which was followed by the use of oral contraceptives and catamenial hemoptysis after the discontinuation of these medications. Surgical removal was performed and histopathological examinations confirmed PEM. This clinical course suggested hematogenous metastasis. An inquiry regarding the patient's history of uterine procedures and use of oral contraceptives was suggestive for the diagnosis of this disease.


Single-molecule methods to study membrane receptor oligomerization.
Membrane receptors control fundamental cellular processes. Binding of a specific ligand to a receptor initiates communication through the membrane and activation of signaling cascades. This activation process often leads to a spatial rearrangement of receptors in the membrane at the molecular level. Single-molecule techniques contributed significantly to the understanding of receptor organization and rearrangement in membranes. Here, we review four prominent single-molecule techniques that have been applied to membrane receptors, namely, stepwise photobleaching, Förster resonance energy transfer, sub-diffraction localization microscopy and co-tracking. We discuss the requirements, benefits and limitations of each technique, discuss target labeling, present a selection of applications and results and compare the different methodologies.


Polyamine concentrations in the brain of vitamin B12-deficient rats.
To study the pathophysiology of the neuronal degeneration in vitamin B12 deficiency, we investigated the concentrations of the polyamines putrescine, spermidine, and spermine in brain regions and liver using high-performance liquid chromatography with fluorescence detection. Male Wistar rats were fed either a control or vitamin B12-deficient diet for 20 weeks. No remarkable behavioral changes were observed. Serum vitamin B12 and hepatic methionine concentrations were significantly lower and hepatic homocysteine was elevated in rats fed vitamin B12-deficient diet than in controls. Vitamin B12 deficiency was associated with decreased concentrations of spermidine, spermidine in liver and some regions of brain, although there were no observed abnormalities in behavior. These results suggest that vitamin B12 deficiency may play a role in neuronal degeneration through the disturbance of polyamine concentrations in rat brain.


Risk of recurrence when cutting into intramucosal (pT1a) cancer from the cutting-plane side during gastric endoscopic submucosal dissection.
During endoscopic submucosal dissection (ESD), procedural difficulty and poor visibility of the cutting plane sometimes cause the operator to cut into the lesion from the cutting-plane side, making the vertical margin positive (VM1) or unclear (VMX). In the present study, we evaluated the risk of recurrence of gastric cancer with VM1 /VMX after ESD. In total, 1723 consecutive gastric cancers treated by ESD at Osaka International Cancer Institute from July 2012 to December 2017 were included in this retrospective cohort study. Among them, 231 submucosal or more deeply invasive gastric cancers were excluded because nontechnical factors may contribute to VM1 /VMX in such lesions. To quantify the risk of cutting into cancer from the cutting-plane side during ESD, the proportion of lesions with VM1 /VMX among the pT1a gastric cancers treated by ESD was calculated. The proportion of recurrence among these cases was calculated after exclusion of lesions with positive lymphovascular invasion or a positive horizontal margin in order to eliminate the obvious risk factors for recurrence. Among 1492 pT1a gastric cancers treated by ESD, 28 lesions (1.9 %; 95 % confidence interval [CI] 1.3 % - 2.7 %) histologically showed VM1 /VMX. No local recurrence (0.0 %; 95 %CI 0.0 % - 12.2 %) occurred among 23 cases. The median follow-up period was 41 months (range 10 - 84 months). No local recurrence was detected in pT1a gastric cancers after VM1 /VMX resection by ESD. Surveillance endoscopy could be adopted for such cases without additional surgery.


Spectroscopic observation of atomic hydrogen radicals entrapped in icy hydrogen hydrate.
A hydrogen molecule entrapped in the cages of icy hydrogen hydrate is confined in host water framework and thus behaves unlike pure solid or liquid hydrogen. The gamma-irradiated hydrogen radicals are for the first time observed from ESR and solid-state MAS 1H NMR spectra to stably exist in the icy hydrate channels without any collapse of the host framework, confirming the chemical shift consistency of ionized hydrogen derivatives. We discuss the confined icy hydrate channels, which can act as potential storage sites for simultaneously imprisoning both molecular and ionized hydrogen and further as icy nanoreactors.


Knockdown of Long Non-Coding RNA-ZFAS1 Protects Cardiomyocytes Against Acute Myocardial Infarction Via Anti-Apoptosis by Regulating miR-150/CRP.
ZFAS1 is one of cardiac-specific or cardiac-related lncRNAs. This study was to explore the functional involvement of ZFAS1 and its regulatory role in AMI. In this study, the models of AMI rat and myocardial cell cultured under hypoxia were made. The expression of ZFAS1 and miR-150 of myocardial infarction tissue or cardiac myocytes was determined by quantitative real time PCR. The regulatory role of ZFAS1 on miR-150 was examined by RNA pull down assay. The effect of miR-150 or ZFAS1 expression on cell viability was analyzed by MTT assay. The relative expression of ZFAS1 in the myocardium infracted zone and border zone was significantly upregulated at 1-48 h of AMI rats, but it downregulated at 1 week and 2 weeks; miR-150 was significantly downregulated at AMI-1-48 h and upregulated at 1 and 2 weeks after model establishment. The result of RNA pull down assay indicated that ZFAS1 could interact directly with miR-150. C-reactive protein (CRP) was regulated by ZFAS1/miR-150 axis and negatively targeted by miR-150. Hypoxia caused the decrease of cell viability and the upregulation of CRP at mRNA and protein levels; whereas this upregulation could be attenuated by miR-150 mimic or si-ZFAS1 in H9C2 cells and cardiomyocytes. Knockdown of ZFAS1 or miR-150 overexpression effectively relieved AMI-induced myocardial infarction in AMI-1 week rats. The ZFAS1/miR-150 axis was involved in the molecular mechanism of AMI induced cardiomyocytes apoptosis via regulating CRP. J. Cell. Biochem. 118: 3281-3289, 2017. © 2017 Wiley Periodicals, Inc.


Lentiviral transgenesis in mice via a simple method of viral concentration.
Transgenic animals are important in vivo models for biological research. However, low transgenic rates are commonly reported in the literature. Lentiviral transgenesis is a promising method that has greater efficiency with regard to generating transgenic animals, although the transgenic rate of this approach is highly dependent on different transgenes and concentrated lentiviruses. In this study, we modified a method to concentrate lentiviruses using a table centrifuge, commonly available in most laboratories, and carried out analysis of the transgenic efficiency in mice. Based on 26 individual constructs and 627 live pups, we found that the overall transgenic rate was more than 30%, which is higher than obtained with pronuclear microinjection. In addition, we did not find any significant differences in transgenic efficiency when the size of inserts was less than 5000 bp. These results not only show that our modified method can successfully generate transgenic mice but also suggest that this approach could be generally applied to different constructs when the size of inserts is less than 5000 bp. It is anticipated that the results of this study can help encourage the wider laboratory use of lentiviral transgenesis in mice.


Knowledge and Attitude of Human Monkeypox Viral Infection Among Healthcare Practitioners and Students in Saudi Arabia: A Cross-Sectional Study.
Human monkeypox (Mpox) is a viral zoonotic infectious disease occurs mostly in central and western Africa that can be transmitted to humans and animal. On July 2022, the World Health Organization declared the global Mpox outbreak, which considered as a huge health issue. The prevalence of Mpox in Saudi Arabia has been very low until now. This research aims to assess knowledge and attitudes of healthcare practitioners and students toward human Mpox in Saudi Arabia. A cross-sectional study conducted among healthcare practitioners and students in Saudi Arabia assessing knowledge, practice and attitudes towards Mpox infection. We conducted descriptive statistics for all variables. A total of 212 participants were included in the study. The majority of participants provided correct responses about the type of microorganisms that cause human Mpox infection and were aware about the low prevalence of the Mpox in Saudi Arabia, but they were not able to identify the correct number of cases in Saudi Arabia. About the symptoms of Mpox, participants showed good knowledge about the common symptoms like skin rash but poor knowledge about less common symptoms like lymph-node swelling. About 70% of participants were aware of the effectiveness of antiviral drugs to treat Mpox. Gaps in knowledge were detected among participants. Therefore, increasing knowledge of Mpox by providing educational courses for healthcare practitioners and healthcare students is crucial.


Maximal tachycardia and high cardiac strain during night shifts of emergency physicians.
To compare tachycardia and cardiac strain between 24-hour shifts (24hS) and 14-hour night shifts (14hS) in emergency physicians (EPs), and to investigate key factors influencing tachycardia and cardiac strain. We monitored heart rate (HR) with Holter-ECG in a shift-randomized trial comparing a 24hS, a 14hS, and a control day, within a potential for 19 EPs. We also measured 24-h HR the third day (D3) after both shifts. We measured perceived stress by visual analog scale and the number of life-and-death emergencies. The 17 EPs completing the whole protocol reached maximal HR (180.9 ± 6.9 bpm) during both shifts. Minutes of tachycardia >100 bpm were higher in 24hS (208.3 ± 63.8) than in any other days (14hS: 142.3 ± 36.9; D3/14hS: 64.8 ± 31.4; D3/24hS: 57.6 ± 19.1; control day: 39.2 ± 11.6 min, p < .05). Shifts induced a cardiac strain twice higher than in days not involving patients contact. Each life-and-death emergency enhanced 26 min of tachycardia ≥100 bpm (p < .001), 7 min ≥ 110 bpm (p < .001), 2 min ≥ 120 bpm (p < .001) and 19 min of cardiac strain ≥30% (p = .014). Stress was associated with greater duration of tachycardia ≥100, 110 and 120 bpm, and of cardiac strain ≥30% (p < .001). We demonstrated several incidences of maximal HR during shifts combined with a high cardiac strain. Duration of tachycardia were the highest in 24hS and lasted several hours. Such values are comparable to those of workers exposed to high physical demanding tasks or heat. Therefore, we suggest that EPs limit their exposure to 24hS. We, furthermore, demonstrated benefits of HR monitoring for identifying stressful events. ClinicalTrials.gov identifier: NCT01874704.


Physicochemical Properties and Bioactivity of a New Guar Gum-Based Film Incorporated with Citral to Brown Planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).
The brown planthopper (BPH), Nilaparvata lugens (Stål), is the most notorious rice insect pest. In order to repel BPH effectively while being environmentally friendly, a new film based on guar gum incorporated with citral (GC film) was formulated. A toxicity bioassay of citral and guar gum at different proportions (ratios of 3:1, 2:1, 1:1, 1:2, and 1:3 in w/w) of GC film-forming emulsion to BPH was performed with the rice stem dipping method. Results showed that the most effective ratio of citral to guar gum was 1:1 with the median lethal concentration (LC50) of 4.30 mg/mL, far below the LC50 of guar gum (GG)/citral individual (141.51 and 44.38 mg/mL, respectively). The mortality of BPH adults and nymphs in the third instar treated with different dilution multiples of GC film-forming emulsion ranged from 46.67% to 82.22% and from 37.78% to 71.11%, respectively. These indicated that GC film-forming emulsion had a direct toxicity on BPH, and the mixture of citral and GG had synergistic interactions. Subsequently, Fourier-transform infrared spectroscopy showed that the incorporation of guar gum with citral was successful and did not result in the formation of new chemical bonds. The GC film exhibited a darker color and rougher surface topography with larger apertures and deeper gullies (Ra = 1.42 nm, Rq = 2.05 nm, and Rmax = 25.40 nm) compared to the guar gum film (GG film) (Ra = 1.00 nm, Rq = 1.33 nm, and Rmax = 16.40 nm), as determined by transmission electron microscopy and atomic force microscopy. The GC film exhibited a 50.4% lower solubility in water (30.30% vs. 15.00%) and 71.3% oxygen permeability (8.26 × 10-9 vs. 2.37 × 10-9 cm3/m2·d·Pa) (p < 0.05) but did not demonstrate any significant difference in mechanical properties, such as thickness (39.10 vs. 41.70 mm), tensile strength (41.89 vs. 38.30 N/mm2), and elongation at break (1.82% vs. 2.03%) (p < 0.05) compared to the GG film. Our findings established a link between physicochemical properties and bioactivity, which can provide useful information on developing and improving GC films and may offer an alternative approach for the control of BPH in the near future.


Effect of organophosphorus compounds on acetylcholine synthesis in brain.
Effects of parathion and di-isopropyl fluorophosphate (DFP) on acetylcholine (ACh) synthesis in the mouse brain were investigated. In addition to well known cholinesterase (ChE) inhibition, parathion showed inhibitory effects on the activity of synaptosomal choline acetyltransferase (ChAc), and on the uptake of [14C-methyl]-choline and ACHh synthesis in subcellular fractions of the brain. DFP inhibited ChE activity, but had no significant effects on the choline uptake and ACh synthesis per se. Possible significance of these findings in the pharmacological actions of organophosphorus compounds is briefly discussed.


The relationship between heart rate variability and prostaglandin E2 in patients with renal insufficiencies.
To investigate the relationship between heart rate variability (HRV) and prostaglandin E2 (PGE2) in patients with renal insufficiencies. HRV blood and 24-hour urine prostaglandin E2 (PGE2) detection were detected in the following 4 groups of people: group A was a control group comprised of 20 normal individuals; group B had 20 patients with renal disease but exhibiting normal renal function; group C contained 20 patients with renal disease and compensatory renal function; group D had 20 patients demonstrating renal insufficiencies. The indices standard deviation of all NN intervals (SDNN), index of standard deviation of the averages of NN intervals (SDANN), mean of the standard deviation of all NN intervals performed on all 5-minute segments of the entire recording (SDNNindex), square root of the mean of the sum of the squares of differences between adjacent NN intervals (rMSSD) and NN50 count divided by the total number of all NN intervals (PNN50) were used to evaluate HRV, blood and 24-hour urine were determined by specific radioimmunoassay (RIA). PGE2 in blood and urine and HRV exactly within 24 hours in patients with renal insufficiencies, negatively correlated with worsening damage to renal function. There was a slight or moderate correlation between blood and urine PGE2 and the SDNNindex, SDANNindex, SDNN, rMSSD and PNN50 indices (P < 0.05). HRV and cardiac autonomic regulatory functions are decreased in the patients with renal insufficiencies, while lower levels of PGE2 may be a related factor.


Trapped interacting Bose gas in nonextensive statistical mechanics.
We study the Bose-Einstein condensation (BEC) phenomenon in an interacting trapped Bose gas using the semiclassical two-fluid model and nonextensive statistical mechanics. The effects of nonextensivity characterized by a parameter are explored by calculating the temperature dependent thermodynamic properties, fraction of condensed particles, and density distributions of condensed and thermal components of the system. It is found that nonextensivity in the underlying statistical mechanics may have large effects on the BEC transition temperature.


[Study on double feedback current source for biologic impedance measurement].
A double feedback current source for biologic impedance measurement is designed in order to solve the problem on the poor constant-current characteristic under higher frequency and meet the request for the ability to eliminate the direct current signal. The voltage controlled current source based on the second generation current conveyor theory is presented, which has good output impedance and anti-direct current characteristics by using the direct current feedback unit and input buffer. The closed loop control of current amplitude is implemented by means of the direct digital synthesizer and multiplication demodulation technique, which improves the constant-current characteristic of the current source.


The impact of atherosclerotic vascular disease in predicting a stroke, thromboembolism and mortality in atrial fibrillation patients: a systematic review.
Atrial fibrillation (AF) is commonly associated with vascular disease. Although atherosclerotic vascular disease (for example, defined as a myocardial infarction (MI), complex aortic plaque and peripheral arterial disease) has been proposed as a risk factor for a stroke, the co-existence of the two diseases increases the risk of future cardiovascular events. The objective of this study was to conduct a systematic review to assess the impact of atherosclerotic vascular disease on the primary end-point of a stroke, thromboembolism or mortality, in patients with AF. Literature searches were performed electronically, to identify studies published between January 1990and July 2012 examining stroke and thromboembolism in relation to AF and atherosclerotic vascular disease. Nineteen articles satisfied the pre-inclusion criteria. The bibliographies were subsequently screened to retrieve further relevant studies for this review. Peripheral arterial disease significantly increased the stroke risk in all 10 observational studies, within a reported risk range of 1.3- to 2.5-fold. Complex aortic plaque on the descending aorta, as identified by trans-oesophageal echocardiography, was also a significant risk factor. Although a prior myocardial infarction (MI) was validated as a significant predictor of the primary end-point amongst five of the six studies, there was a degree of heterogeneity, owing to the marked difference in population sizes and the use of antithrombotic regimens between studies. Atherosclerotic vascular disease (e.g. peripheral arterial disease, complex aortic plaque and prior MI) are significant predictors of a stroke, thromboembolism and mortality in subjects with AF.


Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure.
Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too.


Inflammation and lithium: clues to mechanisms contributing to suicide-linked traits.
Suicide is one of the leading causes of death in the United States, yet it remains difficult to understand the mechanistic provocations and to intervene therapeutically. Stress is recognized as a frequent precursor to suicide. Psychological stress is well established to cause activation of the inflammatory response, including causing neuroinflammation, an increase of inflammatory molecules in the central nervous system (CNS). Neuroinflammation is increasingly recognized as affecting many aspects of CNS functions and behaviors. In particular, much evidence demonstrates that inflammatory markers are elevated in traits that have been linked to suicidal behavior, including aggression, impulsivity and depression. Lithium is recognized as significantly reducing suicidal behavior, is anti-inflammatory and diminishes aggression, impulsivity and depression traits, each of which is associated with elevated inflammation. The anti-inflammatory effects of lithium result from its inhibition of glycogen synthase kinase-3 (GSK3). GSK3 has been demonstrated to strongly promote inflammation, aggressive behavior in rodents and depression-like behaviors in rodents, whereas regulation of impulsivity by GSK3 has not yet been investigated. Altogether, evidence is building supporting the hypothesis that stress activates GSK3, which in turn promotes inflammation, and that inflammation is linked to behaviors associated with suicide, including particularly aggression, impulsivity and depression. Further investigation of these links may provide a clearer understanding of the causes of suicidal behavior and provide leads for the development of effective preventative interventions, which may include inhibitors of GSK3.


Gold(III)-Catalyzed Decarboxylative C3-Benzylation of Indole-3-carboxylic Acids with Benzylic Alcohols in Water.
A strategy for the gold(III)-catalyzed decarboxylative coupling reaction of indole-3-carboxylic acids with benzylic alcohols has been developed. This cascade reaction is devised as a straightforward and efficient synthetic route for 3-benzylindoles in moderate to excellent yields (50-93%). A Hammett study of the protodecarboxylation gives a negative ρ value, suggesting that there is a buildup of positive charge on the indole ring in the transition state. Furthermore, comparison of initial rates in H2O and in D2O reveals an observed kinetic solvent isotope effect (KSIE = 2.7). This simple protocol, which affords the desired products with CO2 and water as the coproducts, can be achieved under mild conditions without the need for base or other additives in water.


Influence of the facial pattern on ANB, AF-BF, and Wits appraisal.
To assess the correlation between Wits and AF-BF appraisals with the ANB angle, and verify the influence of the facial type on these appraisals. Lateral cephalometric radiographs from 118 untreated individuals were separated into 3 groups according to the facial pattern (brachyfacial, mesofacial, and dolichofacial). The radiographs were digitized and submitted to ANB angle and Wits and AF-BF appraisals on computer software. All radiographs were retraced for intraobserver and interobserver error tests. The Student's t test demonstrated no statistically significant differences on the intraobserver's test (P > .05). There were statistically significant differences in the readings of Wits values of the 3 groups and for AF-BF values in the brachyfacial and mesofacial groups (P <.05). The multiple linear regression tests demonstrated high correlation between ANB and AF-BF for the 3 groups (r2, 0.768). The same result was found for ANB and Wits (r2, 0.624). Facial pattern does not have an influence on the correlation between ANB and AF-BF nor between ANB and Wits, but it does influence the measurements of ANB, AF-BF, and Wits.


Changes in cerebral metabolism in patients with a minimally conscious state responding to zolpidem.
Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS.


Predictors of increases in alcohol-related problems among black and white adults: results from the 1984 and 1992 National Alcohol Surveys.
We examined increases in self-reported alcohol-related problems among black and white adult drinkers using data from the 1984 and 1992 National Alcohol Surveys. The objectives of the study were to determine whether alcohol consumption, drinking norm, or socioeconomic status were related to increases in alcohol-related problems. Two types of self-reported alcohol-related problems were analyzed using regression methods: drinking consequences and alcohol dependence symptoms. Results indicated that increases in alcohol consumption were associated with increased drinking consequences for white men, but increased consumption had little affect for black men. Changes in drinking norms regarding non-social drinking were associated with increased in drinking consequences among black men, such norms showed little affect on drinking consequences for white men. Despite substantial increases in alcohol consumption among black women from 1984 to 1992, there were no significant racial/ethnic differences in drinking consequences or alcohol dependence symptoms among women. Changes in socioeconomic status were however related to increases in drinking consequences and alcohol dependence symptoms in women, but not in men. Findings suggest that liberal drinking norms may have greater long term consequences for black than white men. Socioeconomic status, on the other hand, may have greater explanatory power in predicting increases in alcohol-related problems in women than in men.


[A case report of severe laryngeal edema which occured before removal of a laryngeal mask airway].
A 41-year-old woman was scheduled for a partial hip arthroplasty. She was suffering from malignant rheumatoid arthritis for a long time and we recognized her difficult airway. After epidural catheterization, anesthesia was induced with fentanyl, thiopental, and 5% sevoflurane with oxygen. A laryngeal mask airway (LMA ; size 3) was inserted smoothly on third trial after suxamethonium chloride administration. Anesthesia was maintained with fentanyl, vecuronium bromide, sevoflurane with oxygen and epidural anesthesia. No complications were observed during the operation. After reversal of muscle relaxant, spontaneous respiration returned. But inspiratory stridor and chest wall retraction occurred soon, and we found severe epiglottic edema by bronchoscopy. A tracheal tube (ID 5.5 mm) was intubated immediately through the LMA. Twenty hours later the pharyngeal edema was still very severe, and tracheotomy was performed. The edema disappeared three days later. We thought the edema had occurred as a result of blood flow disturbance caused by LMA in narrow pharyngeal space expanding to the epiglottis. It should be kept in mind that severe edema could develop after LMA in malignant rheumatoid arthritis.


Measurement of Oral Moisture on Oral Dryness Patients.
Many elderly patients have oral dryness; thus, it is necessary to evaluate the oral moisture in a clinical setting. The aim of this study was to clarify the importance of controlling the measuring pressure of the oral moisture-checking device. The influence of the measuring pressure of the oral moisture-checking device was examined using agar under 10 measuring pressure conditions (Kruskal-Wallis test). Fifty-five oral dryness patients were examined the lingual moisture using the device with and without a tongue depressor. The tongue depressor was placed underneath the tongue to support it during the measurement. The mean value and the coefficient of variation of five measurements was evaluated (paired t-test or Wilcoxon signed-ranks test). The agar moisture values changed according to the measuring pressure (p < 0.05). The lingual moisture value with the tongue depressor was higher than that without the tongue depressor (p < 0.05). The coefficient of variation with the tongue depressor was smaller than that without the tongue depressor (p < 0.01). The results of this study indicated that the measuring pressure of oral moisture-checking device influenced the measurement value, and it is necessary to support the tongue for the measurement of lingual mucosal moisture in a uniform manner.


AC dielectrophoresis alignment of ZnO nanowires and subsequent use in field-effect transistors.
We report on the dielectrophoresis (DEP) characterization of single crystalline zinc oxide (ZnO) nanowires with variations of the AC electric field and frequency. The alignment yield rate of ZnO nanowires in the gap over the 200 metal electrodes increased with increasing AC electric field and also changed by the applying frequency. Moreover, we demonstrated that the DEP prepared multi-ZnO nanowires field-effect transistors (FETs) exhibited excellent performance with a transconductance of approximately 3 muS and a high drain current of approximately 2.7 x 10(-6) A (V(DS) = 5 V, V(G) = 20 V).


Structure of the Recombinant Neisseria gonorrhoeae Adhesin Complex Protein (rNg-ACP) and Generation of Murine Antibodies with Bactericidal Activity against Gonococci.
Neisseria gonorrhoeae (gonococcus [Ng]) is the causative organism of the sexually transmitted disease gonorrhoea, and no effective vaccine exists currently. In this study, the structure, biological properties, and vaccine potential of the Ng-adhesin complex protein (Ng-ACP) are presented. The crystal structure of recombinant Ng-ACP (rNg-ACP) protein was solved at 1.65 Å. Diversity and conservation of Ng-ACP were examined in different Neisseria species and gonococcal isolates (https://pubmlst.org/neisseria/ database) in silico, and protein expression among 50 gonococcal strains in the Centers for Disease Control and Prevention/Food and Drug Administration (CDCP/FDA) AR Isolate Bank was examined by Western blotting. Murine antisera were raised to allele 10 (strain P9-17)-encoded rNg-ACP protein with different adjuvants and examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and a human serum bactericidal assay. Rabbit antiserum to rNg-ACP was tested for its ability to prevent Ng-ACP from inhibiting human lysozyme activity in vitro. Ng-ACP is structurally homologous to Neisseria meningitidis ACP and MliC/PliC lysozyme inhibitors. Gonococci expressed predominantly allele 10- and allele 6-encoded Ng-ACP (81% and 15% of isolates, respectively). Murine antisera were bactericidal (titers of 64 to 512, P < 0.05) for the homologous P9-17 strain and heterologous (allele 6) FA1090 strain. Rabbit anti-rNg-ACP serum prevented Ng-ACP from inhibiting human lysozyme with ∼100% efficiency. Ng-ACP protein was expressed by all 50 gonococcal isolates examined with minor differences in the relative levels of expression. rNg-ACP is a potential vaccine candidate that induces antibodies that (i) are bactericidal and (ii) prevent the gonococcus from inhibiting the lytic activity of an innate defense molecule.IMPORTANCENeisseria gonorrhoeae (gonococcus [Ng]) is the causative organism of the sexually transmitted disease gonorrhoea, and the organism is listed by the World Health Organization as a high-priority pathogen for research and development of new control measures, including vaccines. In this study, we demonstrated that the N. gonorrhoeae adhesin complex protein (Ng-ACP) was conserved and expressed by 50 gonococcal strains and that recombinant proteins induced antibodies in mice that killed the bacteria in vitro We determined the structure of Ng-ACP by X-ray crystallography and investigated structural conservation with Neisseria meningitidis ACP and MliC/PliC proteins from other bacteria which act as inhibitors of the human innate defense molecule lysozyme. These findings are important and suggest that Ng-ACP could provide a potential dual target for tackling gonococcal infections.


Patient satisfaction in an outpatient parenteral antimicrobial therapy (OPAT) unit practising predominantly self-administration of antibiotics with elastomeric pumps.
Self-administration of antibiotics using elastomeric pumps has become the most frequently used treatment modality at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne. However, it remains unknown how comfortable patients feel using this mode of treatment. A questionnaire was offered to all patients treated at the OPAT unit between June 2014 and December 2015. The questionnaire was distributed to 188 patients and 112 questionnaires were returned. Seventy-one patients were treated by self-administration, 21 attended the OPAT unit on a daily basis, and 20 received their antibiotics from home-care nurses. Overall, 83-97% of the patients gave the highest possible scores to the four items evaluating their global satisfaction. Subjects treated by self-administration gave a significantly better rating to 6 of the 17 semi-quantitative questions than the patients treated at the OPAT unit or by home-care nurses. There was no item which was more poorly rated by patients treated by self-administered OPAT than by the other treatment groups. In conclusion satisfaction was high in all patients treated by OPAT. The particularly high satisfaction of patients treated by self-administration of antibiotics with elastomeric pumps suggests that a significant number of patients are happy to take over some responsibility for their treatment. Patients' capacity to appropriate their care themselves should not be underestimated by health care professionals.


Comparison of Two Different Fibrinogen Concentrates in an in vitro Model of Dilutional Coagulopathy.
Fibrinogen concentrates are widely used to restore clot stability in situations of bleeding. Fibrinogen preparations are produced using different production methods, resulting in different compounds. Thus, different preparations might have a distinct impact on blood coagulation. We tested the effect of fibrinogen concentrates Haemocomplettan® (CSL Behring, Marburg, Germany) and fibryga® (Octapharma GmbH, Langenfeld, Germany) on the impairments induced by 60% dilutional coagulopathy in vitro. The influence of the fibrinogen concentrates fibryga® and Haemocomplettan® on colloid (gelatine, hydroxyethyl starch [HES], albumin)-induced or crystalloid (Ringer's acetate)-induced dilutional coagulopathy was analysed using rotational thromboelastometry (ROTEM®) and standard laboratory tests. The following experimental conditions were analysed in vitro: whole blood, 60% dilution (40% blood and 60% diluent) ± 50 or 100 mg/kg-1 fibryga® or Haemocomplettan®, respectively. Dilution with either diluent resulted in prolonged clotting time (CT) in an extrinsic activated test (CTEXTEM) and decreased maximum clot firmness (MCFFIBTEM) as expressed, e.g., by gelatine: (59.5 s [62/54.8] vs. 95 s [102.8/86.8]; p < 0.001 and 14 mm [16/10.5] vs. 3 mm [4-3]; p < 0.001). Substitution after 60% dilution with HES resulted in no difference between the preparations, except for shorter thrombin time with fibryga® (14 s [15/14] vs. 18 s [18.8/17]; p = 0.0093; low dose). CTEXTEM was higher with Haemocomplettan® in a gelatine-induced dilution (51 s [54.5/47.5] vs. 63 s [71/60.3]; p = 0.0202; low dose) whereas thrombin time was lower with fibryga® (19.5 s [20.8/19] vs. 27 s [29/25.3]; p = 0.0017). In dilution with albumin, differences in CTEXTEM (69 s [76.5/66] vs. 56 s [57/53.3]; p = 0.0114; low dose) and thrombin time (18 s [18/17] vs. 24.5 s [25.8/24]; p = 0.0202; low dose) were seen. In dilution with crystalloid solution, again differences in CTEXTEM (53.5 s [57.8/53] vs. 45 s [47/43]; p = 0.035; low dose) and thrombin time (17 s [17/16] vs. 23.5 s [24/23]; p = 0.0014; low dose) were seen. Fibrinogen levels were more increased by high-dose substitution of both preparations. Based on this data it can be stated that both fibryga® and Haemocomplettan® had the same performance in our in vitro model except for CTEXTEM and thrombin time.


Combined Ex Vivo Organ Perfusion and Mesenchymal Stem Cells Transplantation.
The importance of solid organ transplants is increasing due to the increasing incidence of end-stage organ diseases. With the limitations facing the recruitment of the suitable grafts, ex vivo organ perfusion (EVOP) techniques have been developed to increase the graft acceptance rates and improve the clinical outcomes. The role of mesenchymal stem cells (MSCs) in this regard is not limited to the regenerative ability. MSCs have proved their ability to effectively modulate the immune response and inflammation. Accordingly, the idea of the combined ex vivo organ perfusion and MSCs transplant came to focus. This manuscript reviews some points that should be considered, while applying this technique. The combined EVOP-MSCs is a therapeutic technique that should be soon applied in the practice of solid organ transplants. However, certain remarks should be considered on the pre-clinical levels before taking the studies further into the clinical levels. Although the present report will focus on the lung transplant, the ideas and the remarks are also to be considered for all other solid organ transplants, such as heart, liver and kidney.


[Distortion product of otoacoustic emissions in normal hearing and sensorineural hearing loss].
Based on a variety of experimental and clinical studies the diagnostic significance of transient evoked otoacoustic emissions (TEOAEs) is well established. This is also due to the availability of commercial hardware and software which is optimized for the recording of click-evoked OAEs. In cases with distortion product otoacoustic emissions (DPOAEs) the significance for clinical purposes is not yet clear. This study presents results obtained in normal hearing subjects and patients with sensorineural hearing losses (214 ears). The study focuses on three problems: 1. Incidence of DPOAEs in different groups of hearing loss. 2. Level of DPOAEs at various frequencies in each group of hearing loss. 3. Frequency-specific relationships between hearing loss and DPOAEs. Recording of DPOAEs was performed with the ILO92 system and standard configuration (primary tone level, 70 dB SPL). In normal hearing ears DPOAEs were observed at all frequencies above 1 kHz. In cases with moderate hearing loss the detection rate decreased to about 80%. With further increases in hearing loss the detection rate and level of DPOAEs decreased. At frequencies below 1500 Hz even in normal hearing subjects, the level of DPOAEs only slightly exceeded the noise level. The upper limit of hearing loss for which DPOAEs could be observed depended on frequency. In the low-frequency range DPOAEs were absent in ears with a sensorineural hearing loss greater than 35-45 dB; at frequencies between 4 and 6 kHz DPOAEs were observed even in ears with a hearing loss 65 dB.(ABSTRACT TRUNCATED AT 250 WORDS)


Presence of epidermal growth factor in human tears.
Epidermal growth factor (EGF) is a polypeptide that stimulates the growth of various tissues, including the cornea. The presence of EGF in tears from normal volunteers and in aqueous humor from cataract patients was investigated via human EGF (hEGF)-specific radioimmunoassay. Immunoreactive hEGF was found to be present at similar concentrations in both reflex (ranging from 0.7 to 8.1 ng/ml) and non-reflex tears (ranging from 1.9 to 9.7 ng/ml), but was undetectable in aqueous humor. Immunoreactive EGF in human tears was indistinguishable immunologically, biologically and biochemically from urine EGF and standard hEGF.


The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.
Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death. N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits. A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection. Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.


Cinephotomicrography of dog spinal vessels during cord-damaging decompression sickness.
Thirty-three dogs were anesthetized, laminectomized in the lower thoracic, upper lumbar region, and exposed to simulated 220 ft air dives of 5 to 60 minutes. Cinephotomicrography of the epidural vertebral venous system and dorsal pial vessels was done predive and postdive. The epidural vertebral venous system became blocked by bubbles in 24 animals. Eighteen animals evaluated for clinical and/or pathologic signs of cord damage all manifested positive signs. In 10 dives made by eight dogs, epidural vertebral venous system obstruction did not occur, and signs of cord damage were absent after nine of these dives. After one dive, a dog manifested cervical cord damage remote to the region of epidural vertebral venous system under observation. Acute pulmonary hypertension and central venous congestion were not essential prerequisites for epidural vertebral venous system occlusion to occur. These experiments permit further analysis of the pathogenesis of spinal cord damage in decompression sickness.


New Insights Into PTBP3 in Human Cancers: Immune Cell Infiltration, TMB, MSI, PDCD1 and m6A Markers.
Polypyrimidine tract binding protein 3 (PTBP3) plays a critical role in post-transcriptional regulation. The role of PTBP3 in various human tumours was explored and analysed in this study based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PTBP3 was highly expressed in most tumours, such as breast invasive carcinoma, colon adenocarcinoma and hepatocellular carcinoma. PTBP3 overexpression generally predicts poor overall survival and disease-free survival in patients with adrenocortical carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. However, low PTBP3 expression predicts poor prognosis in kidney renal clear cell carcinoma. We also explored PTBP3 genetic alterations in different tumour tissues. The result found that the frequency of PTBP3 alteration (>4%) was the highest in uterine tumours with "mutation" as the primary type. Furthermore, we found a significant correlation between PTBP3 expression and tumour mutational burden and microsatellite instability in various human tumours, and found that PTBP3 expression was positively correlated with TMB in ACC, STAD, PAAD, LUAD, and SARC. Two enhanced phosphorylation levels of S30 and S426 in colon cancer, ovarian cancer, and uterine corpus endometrial carcinoma were found. Further analysis indicated that PTBP3 expression was positively correlated with the cancer-associated fibroblasts for most tumour types. This study also found a relationship between immune checkpoints and N6-methyladenosine-related markers and PTBP3 expression. Moreover, the "mRNA surveillance pathway" and "RNA degradation" were involved in the functional mechanisms of PTBP3. These results provide new insights for molecular studies, and integrative analysis provided a framework for determining the predictive, prognostic, and therapeutic relevance of PTBP3 in cancer patients.


Hepatitis B virus genotypes: a South Pacific perspective.
87-91% but still, 0.6% of those that did respond to vaccination became infected. The infection rate of the vaccinated populations in the Pacific Islands ranged between 0.7 and 3.8%, which is comparable to Taiwan. A vigorous polyclonal response This communication discusses the current status of research in the hepatitis B virus in relation to the South Pacific. The hepatitis B virus (HBV) is a small DNA virus--3200 nucleotides. It has a circular genome and replicates through an RNA intermediate giving this DNA virus many characteristics similar to RNA viruses. Viral genomes can be single-stranded (+ or - sense) or double-stranded. If not vaccinated, infants born to HBeAg positive mothers (i.e. with high viral titer) have a 90% chance of being infected and becoming HBV carriers themselves. Mutants that affect the major antigenic determinant in HBV surface antigens are probably responsible for HBV infection despite immunization and mutants in the polymerase protein may render HBV resistant to therapy with nucleoside analogs. Within HBV seven genotypes A-G have been reported that is, HBV genotype A (HBVA), HBV genotype B (HBVB) etc. HBV is endemic worldwide with an estimated that 5% of the worlds population being carriers. Before the introduction of vaccination programs carrier rates varied between 5-30% in communities of these ethnic groups, and in some cases 80-90% of a community tested positive for HBV markers (i.e. were infected or had been infected). In Taiwan, of vaccinated babies born to HBV positive mothers, the proportion of those that responded to vaccination varied between will usually result in an acute infection and viral clearance. An associated problem with HBV, in the South Pacific, is the hepatitis delta virus (HDV). HDV is a satellite viroid-like RNA virus that requires HBV for replication. It can either co-infect with, or super-infect upon HBV infection resulting in acute infection and/or chronic infection respectively.


Effect of caries disclosing agents on bond strengths of total-etch and self-etching primer dentin bonding systems to resin composite.
This study examined the effect of caries disclosing dyes on composite to dentin shear bond strengths of a total etch, one-bottle and two self-etching, non-rinsing primer dental adhesives. Two caries disclosing dyes were evaluated, Seek and Snoop, with three dentin adhesives, Prime & Bond NT, Prompt L-Pop and Clearfil SE Bond. Extracted human molars stored in 0.2% sodium azide were sectioned longitudinally to expose dentin and embedded in acrylic, leaving the dentin exposed. Each dentin adhesive had three test groups (n=12); a control and one with each of the caries disclosing dyes. The control group had the dentin conditioned and the adhesive applied following the manufacturer's instructions. The caries disclosing dye groups had the dentin first treated for 10 seconds with the disclosing dye, rinsed, then the dentin adhesives were applied as in the controls. A column of Tetric Ceram was bonded after dentin adhesive placement to each specimen and light cured. Specimens were stored in room temperature water for 24 hours, thermocycled for 1,000 cycles between 5 degrees C and 55 degrees C and tested in shear until failure. Mean +/- SD shear bond values (SBV) were determined in MPa. A one-way ANOVA and Student Neuman Keuls multiple comparison test within each DBS were performed at a significance level ofp<0.05 to analyze the caries disclosing dyes input on SBV versus the controls. Surface analysis to determine the nature of the type of dentin/composite fracture/ separation was also performed. For the fracture analysis data, a Chi-Square test was performed at a significance level of p<0.05. The results of this study indicate that using the two tested caries disclosing dyes, with a total etch, one bottle and two self-etching, non-rinsing primer dental adhesives did not negatively affect the dentin-to-composite shear bond strengths of the three tested dentin bonding systems (p>0.05).


A renal transplant patient with abdominal discomfort, vomiting and diarrhoea for 1 week.
The patient is a 61-year-old diabetic male with history of renal transplant who presented to the emergency department with complaints of intermittent abdominal discomfort accompanied by multiple episodes of vomiting and diarrhoea. He had delayed seeking medical attention until his friends insisted that he come to the emergency department, since the abdominal discomfort was worsening. The patient's ECG revealed an ST-segment elevation myocardial infarction.


Palliative treatment of advanced colorectal carcinoma with the YAG laser.
The Nd-YAG laser was used to provide palliative treatment for eight patients (two women and six men), ranging in age from 53 to 76 years, who had locally advanced colorectal cancer. The main indications for treatment were obstruction, bleeding and copious rectal mucus discharge. Only one complication, a Staphylococcus aureus infection, followed the treatment; the infection was easily controlled. The laser treatment was considered to ease the symptoms in five patients, but survival was not influenced by the treatment. This form of palliation must be evaluated in larger numbers of patients to assess its real value in advanced colorectal cancer.


Victimization and PTSD-like states in an Icelandic youth probability sample.
Although adolescence in many cases is a period of rebellion and experimentation with new behaviors and roles, the exposure of adolescents to life-threatening and violent events has rarely been investigated in national probability studies using a broad range of events. In an Icelandic national representative sample of 206 9th-grade students (mean = 14.5 years), the prevalence of 20 potentially traumatic events and negative life events was reported, along with the psychological impact of these events. Seventy-four percent of the girls and 79 percent of the boys were exposed to at least one event. The most common events were the death of a family member, threat of violence, and traffic accidents. The estimated lifetime prevalence of posttraumatic stress disorder-like states (PTSD; DSM-IV, APA, 1994 1) was 16 percent, whereas another 12 percent reached a sub-clinical level of PTSD-like states (missing the full diagnosis with one symptom). Following exposure, girls suffered from PTSD-like states almost twice as often as boys. Gender, mothers' education, and single-parenthood were associated with specific events. The odds ratios and 95% CI for PTSD-like states given a specific event are reported. Being exposed to multiple potentially traumatic events was associated with an increase in PTSD-like states. The findings indicate substantial mental health problems in adolescents that are associated with various types of potentially traumatic exposure.


IL-23/Th17 Axis: A Potential Therapeutic Target of Psoriasis.
Psoriasis is an immune-mediated skin disease that leads to the initiation of abnormal production of inflammatory mediators and keratinocytes hyper-proliferation. Th-1 cell expressing cytokines such as IL-1β and TNF-α have been the important hallmarks in the management of psoriasis. However, investigations carried out in the previous few years underline the involvement of another subset of T helper cells, i.e. Th-17 in psoriasis exacerbation, and hence have become the point of focus now. The immunopathogenesis of Th-17 is the result of the IL-23/Th-17 axis. It involves the release of IL-17 and IL-22 in response to the activated NF-kβ dependent activation of IL-23. The function of human Th-17 cells, as well as the crucial role of IL-23/Th-17 axis in the exacerbation of psoriasis and treatment, have been well explored. Therefore, considering IL-23/Th17 axis as a pertinent therapeutic target in immune driven disorders, extensive investigations are now highlighting the utility of biopharmaceuticals and/or biological agents acting on these targets. Here, we review the IL-23/Th-17 axis based therapeutic targets, different types of active moieties based on their source of availability and most useful USFDA approved Mabs targeting the IL-23/Th17 axis in psoriasis for a better understanding of the future possibilities in this area.


LC-MS bioanalysis of intact proteins and peptides.
Bioanalysis assays that reliably quantify biotherapeutics and biomarkers in biological samples play pivotal roles in drug discovery and development. Liquid chromatography coupled with mass spectrometry (LC-MS), owing to its superior specificity, faster method development and multiplex capability, has evolved as one of the most important platforms for bioanalysis of biotherapeutics, particularly new scaffolds such as half-life extension platforms for proteins and peptides, as well as antibody drug conjugates. Intact LC-MS analysis is orthogonal to bottom-up surrogate peptide approach by providing whole molecule quantitation and high-level sequence and structure information. Here we review the latest development in LC-MS bioanalysis of intact proteins and peptides by summarizing recent publications and discussing the important topics such as the comparison between top-down intact analysis and bottom-up surrogate peptide approach, as well as simultaneous quantitation and catabolite identification. Key bioanalytical issues around intact protein bioanalysis such as sensitivity, data processing strategies, specificity, sample preparation and LC condition are elaborated. For peptides, topics including quantitation of intact peptide vs. digested surrogate peptide, metabolites, sensitivity, LC condition, assay performance, internal standard and sample preparation are discussed.


[Surgical Treatment of Papillary Fibroelastoma Developed in the Left Ventricle].
Papillary fibroelastomas are rare benign cardiac tumors, which generally arise from the valvular endocardium. Although they have little hemodynamics effects, they can cause some life threatening events such as cerebral embolization. We herein report a case of 68-year-old female with a mobile left ventricular mass of 10 mm in diameter. It was accidentally found on the anterior papillary muscle by echocardiography under evaluation of the angina pectoris. Resection of the left ventricular mass was performed through the mitral valve. Coronary artery bypass grafting to left anterior descending artery was also performed using the left intra-thoracic artery. Pathological finding of the tumor was papillary fibroelastoma. Post-operative course was uneventful, with no recurrence about a year.


Is this radiograph really necessary?
While agreeing that overutilization of radiological diagnosis creates an unnecessary increase in both medical costs and patient exposure, the author calls for a more sensible and economical approach to the number of radiographs taken as part of any given study, noting that in many cases the number could be cut in half without any loss of diagnostic efficiency. By limiting the number of views per study, the radiologist would be able to remain in a safe medico-legal situation without reducing his ability to function as a diagnostician.


Difluoro-[2-(quinolin-2-yl)phenolato]borane.
The title compound, C(15)H(10)BF(2)NO, was synthesized by the reaction of 2-(quinolin-2-yl)phenol and boron trifluoride etherate. The quinoline ring system and the benzene ring are twisted, making a dihedral angle of 8.3 (2)°. In the crystal, π-π inter-actions between the aromatic rings [centroid-centroid distance = 3.638 (9) Å] link the mol-ecules into chains propagating in [100].


Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity.
A novel hypothalamic neuropeptide of the RFamide family, comprising 26 amino acids residues and thus termed 26RFa, has been recently characterized in human, and was found to be the endogenous ligand for the orphan G protein-coupled receptor GPR103. Intracerebroventricular injection of 26RFa provokes a robust increase in food intake in rodents. In the present study, we have investigated the solution conformation of 26RFa by using two-dimensional NMR spectroscopy in different media. In water, 26RFa exhibits mainly a random coil conformation although the presence of a nascent helix was detected between residues 6 and 15. In methanol, 26RFa adopts a well-defined conformation consisting of an amphipathic alpha-helical structure (Pro4-Arg17), flanked by two N- and C-terminal disordered regions. The strong conservation, from amphibians to mammals, of the amino acid sequence corresponding to the amphipathic helix and to the C-terminal flexible octapeptide of 26RFa, suggests that these two domains are crucial for the interaction of the peptide with its receptor.


One-year outcomes of intravitreal conbercept combined rescue therapy for polypoidal choroidal vasculopathy in a Chinese population: a real-life clinical data.
To evaluate the real-life clinical outcomes of intravitreal injection of conbercept combined rescue therapy for polypoidal choroidal vasculopathy (PCV). This was an open label, single center, and interventional study. All enrolled patients were treated initially with three consecutive monthly intravitreal conbercept injections (0.5 mg). Additional conbercept injections were administered upon substantial polyp regression with improved visual acuity (VA). Eyes with partial or no polyp regression and poor VA were rescue treated with photodynamic therapy (PDT) for subfoveal polyps or thermal laser photocoagulation for extrafoveal polyps. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and polyp regression were observed as primary outcomes. Side effects were also collected during the follow-up period. A total of 56 eyes (56 patients) with PCV were included. BCVA increased significantly from the baseline of 43.52±24.21 letters to 55.88±21.94 letters (P<0.001) at 12mo, while CFT decreased significantly from 457.41±207.86 µm to 247.98±127.08 µm (P<0.001). All patients showed polyp regression. Twenty-three eyes achieved complete polyp regression after the three initial injections, which increased to 44 eyes at 12mo. Seventeen eyes underwent rescue therapy, among which 2 eyes treated with PDT and 15 eyes treated with laser photocoagulation. A mean of 4.30±1.43 injections were given per eye. No intraocular inflammation, retinal or vitreous hemorrhage, or systemic complication occurred. Conbercept is an effective and safe option for the treatment of PCV in Chinese population. The treatment regimen of three initial conbercept injections followed by additional injections or rescue therapies is efficacious for treating PCV.


Effect of dietary methionine status on response of chicks to coccidial infection.
Three experiments determined if the methionine requirement of broiler chicks was affected by coccidial infection. Chicks were fed a corn-soy or a corn-soy-pea basal diet containing 0.73% and 0.62% total sulfur amino acids (TSAA), respectively. Levels of 0 to 0.45% DL-methionine were added, with and without 0.01% monensin sodium. In two experiments, the chicks were inoculated at two weeks of age with a mixture of oocysts of E. acervulina, E. maxima, E. tenella, E. necatrix and E. brunetti. Lesion scores on the intestines and ceca, and blood carotenoid levels were determined at three weeks. The experiments were terminated at four weeks. A level of methionine greater than 0.47% and of TSAA greater than 0.83% was necessary to obtain maximum growth rate in uninoculated chicks. No evidence of dermatitis was observed. Growth rate and feed efficiency of chicks infected with coccidiosis were more severly depressed when the diet was not supplemented with methionine. Infections of coccidia and low levels of methionine, which in themselves did not produce any significant change in weight gain, did give a significant weight depression in combination. Adding monensin to the diet prevented a reduction in growth rate and feed efficiency of inoculated chicks fed adequate methionine. Monensin did not completely prevent the adverse effects of a coccidial infection, based on feed efficiency, when chicks were fed diets inadequate in methionine. Blood carotenoid levels were not affected by methionine level, but were significantly lowered by coccidial infection in the absence of monensin. Intestinal and cecal lesions in inoculated chicks were significantly reduced by including monesin in the diet. Although the coccidial infection more severly affected the performance of chicks fed diets deficient in methionine, satistical analysis of pooled data indicated no difference in the quantitative requirement of chicks for methionine. Therefore, a level of methionine and cystine adequate for optimum growth under the coccidial-free conditions should be adequate for chicks when infected with coccidia.


It can work: Open employment for people with experience of mental illness.
Previous research has tended to focus on the barriers to employment for people with mental illness and the extra support they may need. This research contributes to the knowledge base pertaining to this population by looking at successful employment relationships in New Zealand. To describe factors enabling and/or sustaining the open employment of people with experience of mental illness. Fifteen pairs of employers and employees were interviewed individually but consecutively (using a semi-structured interview schedule) about their perceptions of the critical factors that enabled and sustained the employee's employment. Employee participants were recruited by advertisement, with employers approached through their employees. Transcripts were analysed using a thematic analysis. Themes raised in the interviews included the meaning of work, disclosure of mental illness, the benefits of working, special arrangements or accommodations, the work environment and key things employers and employees do to sustain successful employment. Four critical success factors were identified relating to disclosure, the employment relationship, freedom from discrimination and workplace flexibility.


Alterations in synaptonemal complex coding genes and human infertility.
About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid gametes for fertilization and errors in meiosis are associated with human infertility in both males and females. Successful meiosis relies on the assembly of the synaptonemal complex (SC) between paired homologous chromosomes during the meiotic prophase. The SC is ultrastructurally and functionally conserved, promoting inter-homologous recombination and crossover formation, thus critical for accurate meiotic chromosome segregation. With whole-genome/exome sequencing and mouse models, a list of mutations in SC coding genes has been linked to human infertility. Here we summarize those findings. We also analyzed SC gene variants present in the general population and presented complex interaction networks associated with SC components. Whether a combination of genetic variations and environmental factors causes human infertility demands further investigations.


Hemorheological and hemodynamic effects of high molecular weight polyethylene oxide solutions.
Hemorheological and hemodynamic effects of high molecular weight polyethylene oxide (PEO) solutions have been studied in vitro and in vivo at 30 experimental dogs. The rheological behaviour of the PEO solutions and of blood samples has been assessed by rotational viscometers at 20 degrees C, 25 degrees C and 37 degrees C. An addition of PEO solutions to the blood in vitro has modified its rheological behavior, depending on the shear rates, concentration and temperature. Saline with aqueous PEO solutions at the concentration of 500 ppm has been infused into the blood circulation of the experimental dogs to achieve the total concentration in blood of 20-30 ppm. The following parameters cardiac output, mean arterial blood pressure, central venous pressure, pulse frequency, blood volume flow in the femoral artery, total vascular resistance and blood viscosity before and after the infusion of PEO solutions have been studied. The main observed effect was a decrease of the hemodynamic resistance in the cardiovascular system up to 40% below the baseline after infusion of PEO solutions.


High nucleotide and amino acid sequence similarities in tumour necrosis factor-alpha amongst Indian buffalo (Bubalus bubalis), Indian cattle (Bos indicus) and other ruminants.
Tumour necrosis factor-alpha (TNF-alpha) mRNA from Indian water buffalo (Bubalus bubalis) and Indian cattle (Bos indicus) was reverse transcribed and amplified using reverse transcriptase-polymerase chain reaction (RT-PCR). The nucleotide sequences of cDNAs were determined after cloning into pGEM-T-Easy vector (Promega, Madison, WI) and compared with reported nucleotide sequences of TNF-alpha cDNA from other species. The nucleotide sequences of TNF-alpha from Indian cattle revealed significantly high similarities at nucleotide (99.2%) and amino acid (100%) levels with those of cattle (Bos taurus; Zebu). The sequences from buffalo had 98.4% nucleotide and 99.1% amino acid similarities with Indian cattle, indicating functional cross-reactivity. One amino acid deletion at position 63 and one substitution (A-->P) at position 64 were observed in buffalo compared with Indian cattle. The amino acid deletion at position 63 was predicted due to differences in pre-mRNA splicing.


Models of the cellular mechanism underlying propagation of epileptiform activity in the CA2-CA3 region of the hippocampal slice.
We have shown experimentally in the previous paper that spontaneous epileptiform activity, as recorded by extracellular field potentials, propagates smoothly across the CA2-CA3 region of the convulsant-treated hippocampal slice of the guinea pig at velocities of about 0.1 m/s. In the present paper, we used computer simulations of either 500 or 1000 cell arrays of model neurons to examine possible mechanisms underlying this propagation. We show that propagation of epileptiform field potentials can be explained plausibly by slow conduction along axons interconnecting CA2-CA3 neurons, provided that there are sufficiently many interconnections. This propagation can take place even if the interconnections occur randomly. The number of interconnections required decreases as the number of synchronously activated cells initiating a population burst increases. Axonal propagation at 0.1 m/s appears to be a plausible assumption, since conduction velocities along Schaffer collaterals have been experimentally estimated to be as slow as 0.2 m/s, and small recurrent collaterals are likely to conduct more slowly than the main axonal branches. If spontaneous synchronized population bursts are initiated by activity in four or fewer cells, then our model requires, for smooth field potential propagation, more interconnections than are believed to occur on the basis of dual intracellular recording.


High-Temperature Stable Anatase Titanium Oxide Nanofibers for Lithium-Ion Battery Anodes.
Control of the crystal structure of electrochemically active materials is an important approach to fabricating high-performance electrodes for lithium-ion batteries (LIBs). Here, we report a methodology for controlling the crystal structure of TiO2 nanofibers by adding aluminum isopropoxide to a common sol-gel precursor solution utilized to create TiO2 nanofibers. The introduction of aluminum cations impedes the phase transformation of electrospun TiO2 nanofibers from the anatase to the rutile phase, which inevitably occurs in the typical annealing process utilized for the formation of TiO2 crystals. As a result, high-temperature stable anatase TiO2 nanofibers were created in which the crystal structure was well-maintained even at high annealing temperatures of up to 700 °C. Finally, the resulting anatase TiO2 nanofibers were utilized to prepare LIB anodes, and their electrochemical performance was compared to pristine TiO2 nanofibers that contain both anatase and rutile phases. Compared to the electrode prepared with pristine TiO2 nanofibers, the electrode prepared with anatase TiO2 nanofibers exhibited excellent electrochemical performances such as an initial Coulombic efficiency of 83.9%, a capacity retention of 89.5% after 100 cycles, and a rate capability of 48.5% at a current density of 10 C (1 C = 200 mA g-1).


Transgenic hybrid poplar for sustainable and scalable production of the commodity/specialty chemical, 2-phenylethanol.
Fast growing hybrid poplar offers the means for sustainable production of specialty and commodity chemicals, in addition to rapid biomass production for lignocellulosic deconstruction. Herein we describe transformation of fast-growing transgenic hybrid poplar lines to produce 2-phenylethanol, this being an important fragrance, flavor, aroma, and commodity chemical. It is also readily converted into styrene or ethyl benzene, the latter being an important commodity aviation fuel component. Introducing this biochemical pathway into hybrid poplars marks the beginnings of developing a platform for a sustainable chemical delivery system to afford this and other valuable specialty/commodity chemicals at the scale and cost needed. These modified plant lines mainly sequester 2-phenylethanol via carbohydrate and other covalently linked derivatives, thereby providing an additional advantage of effective storage until needed. The future potential of this technology is discussed. MALDI metabolite tissue imaging also established localization of these metabolites in the leaf vasculature.


The real "danger" lies in the failure to confront fundamentals.
Can we formulate a framework that would provide an agreed upon basis for discussions of immune behaviour? An attempt to do this is, in the end, the main goal of this essay. If you tell a physicist that you have invented a perpetual motion machine, he would not spend any time trying to reveal the flaw. Rather, he would shrug you off because in his framework, such a machine is an impossibility. However, immunologists lacking an agreed upon, preferably default, framework spend their time chasing into dead-end alleys or take refuge in descriptive empiricism. This will be illustrated using Danger theory, which ignores fundamentals to generate a framework believed to obviate the need for a Self (S)-Nonself (NS) discrimination and which is claimed to be bolstered with monogamous data (observation married to a single explanation). The arguments presented here apply to all NS-marker theories (pathogenicity, discontinuity, localization, danger, etc.).


Total intravenous anaesthesia and the use of an intubating laryngeal mask in a patient with osteogenesis imperfecta.
Osteogenesis imperfecta is a genetically determined rare disease of the connective tissue, associated with abnormalities of type 1 collagen. The primary bone lesion is the lack of normal ossification of the endochondrial bone. Patients with osteogenesis imperfecta present several problems for anaesthetists. They have a tendency to develop malignant or non-malignant hyperthermia. During laryngoscopy and tracheal intubation, the mandible, teeth and cervical spine may be fractured or injured, and mucosal bruising or bleeding may occur. Renal or ureteral stones are common. The main problems are thus with airway control and intubation, and the risk of anaesthetic agents triggering malignant hyperthermia. We describe the successful anaesthetic management of a patient with osteogenesis imperfecta, undergoing nephrolithotomy and ureterolithotomy with total intravenous anaesthesia including propofol, remifentanil and cisatracurium, using an intubating laryngeal mask.


[Development of chow for Mongolian gerbils suitable for the conditions of space flight].
One of formidable issues of experiments with animals in space flight is water supply. For Mongolian gerbils (Meriones unguiculatus), classed as cricetid rodents, water in chow is enough. These animals are a new object for space biology. Our purpose was to compose a full-value formula and design a chow making and long-term storage technology to provide Mongolian gerbils for in microgravity. The chow is required to have a 28-d shelf life. To assess the chow suitability on autonomous space fight, the gerbils we house in a cage with the geometry reproducing the current design of the future space animal module. The assessment was performed with adult male gerbils weighing 50.5 +/- 3.4 g on the average. The animals ate up 40.1 +/- 3.9%, i.e. less than 50% of the feed all through the period of experiment. However, by the end of the experiment the body mass and exterior remained essentially unchanged In was concluded that the chow formula can be prescribed to Mongolian gerbils housed in self-contained modules.


Nanovesicle-based bioelectronic nose for the diagnosis of lung cancer from human blood.
A human nose-mimetic diagnosis system that can distinguish the odor of a lung cancer biomarker, heptanal, from human blood is presented. Selective recognition of the biomarker is mimicked in the human olfactory system. A specific olfactory receptor recognizing the chemical biomarker is first selected through screening a library of human olfactory receptors (hORs). The selected hOR is expressed on the membrane of human embryonic kidney (HEK)-293 cells. Nanovesicles containing the hOR on the membrane are produced from these cells, and are then used for the functionalization of single-walled carbon nanotubes. This strategy allows the development of a sensitive and selective nanovesicle-based bioelectronic nose (NvBN). The NvBN is able to selectively detect heptanal at a concentration as low as 1 × 10(-14) m, a sufficient level to distinguish the blood of a lung cancer patient from the blood of a healthy person. In actual experiments, NvBN could detect an extremely small increase in the amount of heptanal from human blood plasma without any pretreatment processes. This result offers a rapid and easy method to analyze chemical biomarkers from human blood in real-time and to diagnose lung cancer.


Recovery period after profound hypoglycemia. Influence of some metabolic modulators on the cerebral endogenous substrate utilization.
The content of "energy-rich" phosphates was markedly decreased in rat cerebral cortex after 20 min of severe hypoglycemia, followed by partial restitution during the recovery period. The adenine nucleotide pool remained reduced even if the energy charge returned to normal. During hypoglycemia the non-glucose endogenous substrates were provided by glycolytic intermediates, by Krebs' cycle intermediates and by related amino acids. Other substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20 min period of post-hypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, the amino acid pool size being still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency towards normalization of the free fatty acid cerebral content. During the post-hypoglycemic recovery, treatment with some specific metabolic modulators (i.e., uridine, L-acetylcarnitine, hopantenate, 6-amino-nicotinamide) suggests the possibility of an alternative cerebral substrate utilization due to the modulation of the cerebral biochemical machinery. Thus, increased carbohydrate utilization by hopantenate was consistent with decreased lipid breakdown, while increased carbohydrate utilization by uridine was concomitant with decreased amino acid degradation. On the other hand, decreased cerebral carbohydrate utilization by 6-aminonicotinamide was concomitant with increased lipid and amino acid breakdown. Furthermore, the increased loss of cerebral phospholipids and fatty acids by L-acetylcarnitine occurred in the presence of a large glucose availability and was concomitant with an extensive reduction on cerebral glycolytic flux.


Small bowel adenocarcinoma: a case of atypical CT scan appearance.
A 73-year-old man presented to the surgical assessment unit with recurrent episodes of central abdominal pain and vomiting for 18 months. He has the past medical history (PMH) of hypertension and has been using his denture for 35 years; he had no past surgical history; he drinks alcohol socially and not a smoker. This patient was investigated for iron deficiency anaemia with upper and lower gastrointestional endoscopy, as the patient had positive faecal occult blood; rectal biopsy showed no sign of inflammation and no evidence of malignancy; blood investigation showed Hb 9.8 g/dl, white cell count 14.8, mean cell volume 86.3, mean cell haemoglobin 26.9 and C reactive protein 13. This patient underwent a CT scan of the chest, abdomen and pelvis; the latest one showed that there is a short segment of the middle part of the small bowel that looks thickened and within which there is a high-density calcified shadow which is reported as an ingested foreign body or a tooth fragment; the patient underwent laparotomy and the histology results revealed 30 mm well differentiated/moderately differentiated adenocarcinoma.


Beneficial effects of lipidic extracts of saladette tomato pomace and Serenoa repens on prostate and bladder health in obese male Wistar rats.
Obesity is associated with increased risk of a number of serious medical conditions, including urological disorders. This study investigated the effect of lipidic extracts of saladette tomato pomace (STP) and Serenoa repens (SR) on the prostate and bladder in a rat obese model induced by high-carbohydrate diet. High-sucrose-fed rats showed higher prostate weight as well as increased contractility and stromal and epithelial hyperplasia in the prostate. Treatment with STP and SR improved contractility and diminished hyperplasia and hypertrophy in the prostate. Obese animals also showed impaired bladder contractility, but neither extract reversed this deterioration. In the histological study, a disarray in the process of smooth muscle cell proliferation with non-parallel fibers was observed; interestingly, treatment with STP and SR led to improvement in this derangement. These findings indicated impaired contractility and hyperplasia in the prostate and bladder of obese rats induced by high sucrose. STP and SR could enhance prostate function by reducing contractility and hyperplasia and improve smooth muscle fiber structure and decrease cell proliferation in the bladder, suggesting their possible health-beneficial effects on lower urinary tract symptoms. © 2017 Society of Chemical Industry.


Fundamental change in the nature of chemical bonding by isotopic substitution.
Isotope effects are important in the making and breaking of chemical bonds in chemical reactivity. Here we report on a new discovery, that isotopic substitution can fundamentally alter the nature of chemical bonding. This is established by systematic, rigorous quantum chemistry calculations of the isotopomers BrLBr, where L is an isotope of hydrogen. All the heavier isotopomers of BrHBr, BrDBr, BrTBr, and Br(4)HBr, the latter indicating the muonic He atom, the heaviest isotope of H, can only be stabilized as van der Waals bound states. In contrast, the lightest isotopomer, BrMuBr, with Mu the muonium atom, alone exhibits vibrational bonding, in accord with its possible observation in a recent experiment on the Mu+Br2 reaction. Accordingly, BrMuBr is stabilized at the saddle point of the potential energy surface due to a net decrease in vibrational zero point energy that overcompensates the increase in potential energy.


Cigarette smoking habits, attitudes and associated social factors in adolescents.
Cigarette smoking habits and attitudes and associated social factors of 997 third and fourth form pupils were studied, using an interviewer administered questionnaire, in two co-educational secondary schools as part of a smoking intervention programme. Overall, 32 percent of the pupils were regular smokers with 15% smoking more than two cigarettes per day. The majority of smokers began smoking before secondary school; boys started earlier than girls,nd heavy smokers earlier than light smokers. The commonest reason for giving up smoking was personal dislike. Heavy smokers were more likely to have respiratory symptoms than other pupils. The smoking habits of the pupils were related to those of their parents, siblings and friends. The majority of pupils thought cigarette smoking bad for their health irrespective of their own smoking habits.


Squamous cell carcinoma arising from recurrent anal fistula.
Here, we report on a patient with squamous cell carcinoma (SCC) arising from recurrent anal fistula. The patient was a 57-year-old woman who had 32-year history of having a recurrent perianal abscesses that ruptured spontaneously. Six months before her admission to our hospital, anal pain developed. She had no history of inflammatory bowel disease. Physical examination revealed three external fistulous openings at the two o'clock position, 2 cm from the anal verge. One internal opening in the lower rectum was found with proctoscopy. The patient underwent fistulectomy. Microscopic examination showed SCC arising from the anal fistula, which was accompanied by vessel invasion. The tumor was observed to be continuous from the external opening but was not exposed to the internal opening of the rectal mucosa. Because human papillomavirus (HPV) infection was suspected, immunohistochemical analysis was performed, but showed no HPV infection. Two weeks after fistulectomy, abdominoperineal resection with lymph node dissection was performed. Histopathological examination revealed no remnant cancer tissue or lymph node metastasis. She was discharged after surgery without complications. Eight years after the operation, she complained of constant pain during micturition. Urological examination revealed urinary bladder cancer, and transurethral resection of the bladder tumor was performed. Histopathological examination revealed transitional cell carcinoma of the urinary bladder. Two years later, the patient died of metastatic urinary bladder cancer, without recurrence of the fistula cancer. Because the patients mother had died of urinary bladder cancer and she herself had metachronous urinary bladder cancer in addition to fistula cancer, we investigated whether microsatellite instability (MSI) and chromosomal instability correlated with fistula cancer development. Immunohistochemical analysis of formalin-fixed, paraffin-embedded surgical tumor specimens for p53, MLH1, and MSH2 was performed. The tumor specimens showed no MLH1 expression but did show normal MSH2 expression. p53 was not expressed. Five microsatellite loci were examined using the tumor specimens to detect MSI, namely two loci with mononucleotide runs (i.e., BAT25 and BAT26) and three loci with dinucleotide repeats (i.e., APC, Mfd15, and D2S123). The tumor specimens showed alternations in the repeated sequences of two loci (i.e., BAT26 and D2S123). As a result, the tumor was classified as MSI-H (high) according to the Bethesda criteria. Our patient had MSI and one of the smallest reported SCCs arising from recurrent anal fistulae.


An Assessment of Direct Restorative Material Use in Posterior Teeth by American and Canadian Pediatric Dentists: III. Preferred Level of Participation in Decision-making.
The purpose of this study was to assess Canadian and American pediatric dentists' preferred level of participation in clinical decision-making. A web-based survey was used to collect the opinions of all active Royal College of Dentists of Canada members and American Academy of Pediatric Dentistry members on the use of direct restorative materials in posterior teeth (n equals 4,648; 19.3 percent response rate). The main survey also included a domain to elicit participants' preferred role in clinical decision-making, ranging from an active role (the dentist takes the primary role in decision-making while considering patients/caregivers opinions) to a passive role (the dentist prefers to have the patient guide the decision-making). Bivariate and multivariate analyses for the preferred role and its predictor were performed (two-tailed P<0.05). Fifty-eight percent of participants preferred an active role. The passive role was chosen three times more by those who worked in a hospital-based setting (odds ratio [OR] equals 3.15, 95 percent confidence interval [CI] equals 1.13 to 8.79) or a university-based setting versus a combined setting (OR equals 3.61, 95 percent CI equals 1.11 to 11.77). The majority of participants preferred an active role in decision-making, a role that may not be consistent with a patient-centered practice that emphasizes patient autonomy in decision-making.


Catechin-Bound Ceanothane-Type Triterpenoid Derivatives from the Roots of Zizyphus jujuba.
Three unprecedented ceanothane-type triterpenoids, ent-epicatechinoceanothic acid A (1), ent-epicatechinoceanothic acid B (2), and epicatechino-3-deoxyceanothetric acid A (3), containing C-C bond linkages with catechin moieties, were isolated from the roots of Zizyphus jujuba. Their chemical structures, including absolute configurations, were established by spectroscopic analysis and calculation of their ECD spectra. A possible biogenetic pathway for C-C bond formation between the catechin and the triterpenoid moieties is presented. Compound 1 was evaluated for its antiproliferative activity on HSC-T6 hepatic stellate cells.


Rural-urban comparison in prevalence of overweight and obesity among adolescents in Shandong, China.
Prevalence of overweight and obesity has increased in both developed and developing countries. The increasing global prevalence of overweight and obesity among children and adolescents constitutes a public health crisis. The present study assessed the rural-urban differences in prevalence of overweight and obesity among adolescents in Shandong Province, China from 1985-2010. The BMI of adolescents aged 7-18 years was calculated using data from five national repeated cross-sectional surveys on students' constitution and health carried out by the government in 1985, 1995, 2000, 2005 and 2010 in Shandong Province, China. The prevalence of overweight and obesity was obtained according to the WGOC (Working Group on Obesity in China) reference norm and the International Obesity Task Force (IOTF) cut-offs. In the past 25 years, The prevalence of overweight and obesity increased rapidly: The rate of overweight plus obesity by WGOC reference norm increased from 3.60% (Urban male), 3.03% (Urban female), 0.77% (Rural male) and 1.47% (Rural female) in 1985 to 36.57% (Urban male), 19.39% (Urban female), 29.59% (Rural male) and 18.76% (Rural female) in 2010, respectively. The increasing trend is similar using IOTF cut-offs. Differences in prevalence by year of overweight and obesity between urban and rural areas were observed. Overweight and obesity increased remarkably among Shandong adolescents from 1985-2010 and has become a serious public health problem. Comprehensive evidence-based strategies of intervention should be introduced, including periodic monitoring.


Gastric inhibitory polypeptide secretion after radical pancreatoduodenectomy.
To elucidate the role of gastric inhibitory polypeptide (GIP) in the alteration of insulin secretion following pancreatoduodenal resection, in which the main sources of GIP are removed, plasma levels of GIP were measured for 180 minutes after oral glucose administration, both before and after radical pancreatoduodenectomy in nine patients with periampullary cancer. Fasting plasma levels of GIP remained much the same before and after surgery, and were not different from those in normal controls. The levels of GIP after glucose ingestion were significantly greater in the preoperative patients than in normal controls throughout 180 minutes. After pancreatoduodenectomy, the postglucose levels significantly diminished but remained within normal limits. Changes in plasma levels of insulin early after glucose ingestion in these patients, however, were significantly less both before and after surgery than in normal controls, and were not concomitant with the initial increase in plasma GIP. On the other hand, plasma levels of insulin greatly increased immediately after glucose ingestion in accordance with a rapid elevation of plasma GIP in 11 gastrectomized patients in whom the duodenum and the pancreas were preserved intact and who served as the control group. Thus, the diminution in GIP secretion following pancreatoduodenectomy may relate to the lack of main sources of this gut hormone and not to factors involved in the reconstruction of the alimentary tract. We conclude that the impaired insulin secretion following oral glucose ingestion in patients before and after pancreatoduodenectomy does not relate to the secretion of GIP.


Effect of lidocaine with adrenaline and landiolol on hemodynamics in spontaneously hypertensive rats.
Administration of local anesthetics with adrenaline can cause tachycardia and hypertension. This study assessed whether combined administration of landiolol with adrenaline and lidocaine would induce local anesthesia without causing hemodynamic changes. Normal saline (NS), lidocaine with adrenaline (LA), and lidocaine with adrenaline and landiolol (LLA) were injected into Wistar Kyoto (WKY/Izm) or spontaneously hypertensive (SHR/Izm) rats, followed by measurement of the pulse rate (PR), and the systolic, diastolic and mean blood pressures (SBP, DBP and MBP). In the LLA group, the increase in PR was significantly suppressed in both SHR/Izm and WKY/Izm rats relative to those in the LA group. Although SBP was significantly reduced in WKY/Izm rats given LLA, relative to those given NS or LA, it was elevated in SHR/Izm rats given LLA. Landiolol-induced changes in PR may be due to blockade of adrenaline-induced β1 receptor stimulation, which suppresses cardiac hyperactivity, whereas the early surge of blood pressure in SHR/Izm rats given LLA may be due to the dominant alpha-adrenergic effects of β1 receptor inhibition. The anti-adrenergic effects of LLA were safe and effective in WKY/Izm rats, although the unexpected early hypertensive surge in SHR/Izm rats indicates the need for caution.


Dermatomyositis complicated by acute granulocytic leukeumia.
In this case of dermatomyositis, the patient's clinical course was complicated by the development of acute granulocytic leukemia. Various malignancies complicating dermatomyositis have been reported in the literature. Rarely have these been of the hematopoietic system.