Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease.
This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt-Koyanagi-Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt-Koyanagi-Harada disease may achieve better control with adalimumab and methotrexate combination therapy.


Neuroprotective Effect of Nypa fruticans Wurmb by Suppressing TRPV1 Following Sciatic Nerve Crush Injury in a Rat.
Peripheral nerve injury can result in severe functional impairment and decreased quality of life due to loss of sensory and motor function. Nypa fruticans wurmb (NF) has been used in diverse folk remedies in East Asia. We have previously shown that Nypa fruticans wurmb extract has antinociceptive and anti-inflammatory effects by suppressing TRPV1 in the sciatic nerve injury. The present study investigated the effects of NF on the control of TRPV1 in relation to neuroprotective effects of a sciatic nerve crush injury. To evaluate the neuroprotective effects, an animal behavior test and a physiological function test were performed. Functional recovery and nerve recovery were improved in the NF and NF + SB (SB366791; TRPV1 antagonist) treated group. In the histomorphology evaluation, the neuronal regenerative effect of NF on the injured sciatic nerve was confirmed via hematoxylin and eosin (H&E) staining. In this study, the NF and NF + SB treated group showed neuroprotective and functional recovery effects from the sciatic nerve crush injury. Furthermore, the expression of NF-κB and iNOS showed a significantly suppressive effect on NF (p < 0.01), SB (p < 0.01), and NF + SB (p < 0.01) treated group at the 7th and 14th day compared to the vehicle group. This study confirmed the neuroprotective effects of NF on suppressing TRPV1 in a sciatic nerve crush injury. The findings of this study establish the effect of NF as a neurotherapeutic agent to protect the peripheral nerve after a sciatic nerve crush injury.


[A technique to design the framework of removable partial denture by multi-stage expert system].
This study aims to apply a new expert system to design removable partial denture (RPD) framework. The RPD design is completed in three steps, namely, "selecting missing teeth", "selecting abutment condition", and "selecting personalized clasp". The system can help auxiliary dentists develop personalized treatment plans to reduce their clinical workload. It can also generate a dental preparation guideline for clinical preparation, which can prevent tooth preparation mistakes. By generating the standard electronic drawings of the framework design, the system can reduce the inconvenience caused by manual drawing, thereby facilitating dentist-technician communication and reducing the rate of remade.


Diabetes and percutaneous coronary intervention in the setting of an acute coronary syndrome.
Diabetes mellitus has reached epidemic proportions worldwide. Patients with diabetes are at increased risk for acute coronary syndromes, and these syndromes lead to frequent morbidity and cardiovascular mortality. Emerging adjunctive pharmacological strategies coupled with the drug-eluting stent platform have resulted in improved adverse event rates for this high-risk group. This review will concentrate on the historical data associated with acute coronary syndromes in diabetes mellitus, focusing on revascularisation, drug-eluting stents and antiplatelet therapies.


[Critical issues in criminal investigations in the ascertainment of causation and liability].
The critical issues still affecting criminal proceedings concerning occupational diseases are discussed, focusing in particular on the following points: determination of cause-effect relationship, finding of guilt, presence of concauses not related to workplace, ascertainment of individual liability and the role of medical sciences.


Sodium and body fluid homeostasis in profiling hemodialysis treatment.
Acute adverse side-effects of hemodialysis such as hypotension, muscle cramps, osmotic imbalance and thirst are induced by the interference with fluid and electrolyte balance occurring during treatment. Changes in osmolarity due to alterations of plasma sodium concentration during hemodialysis strongly influence fluid distribution between extracellular and intracellular fluid volume. Increased sodium dialysate concentration induces fluid shift from the intracellular to the extracellular compartment. This shift leads to a more efficient ultrafiltration by increasing plasma refilling volume but also to an increased thirst. Treatment of hypotension, cramps and nausea with hypertonic saline solution leads also to a considerable retention of sodium. Profiling hemodialysis consists in deliberately changing ultrafiltration and dialysate. sodium in order to combine an efficient ultrafiltration with a balanced sodium handling and to prevent side-effects during treatment. Continuous measurement and control of blood volume seems to be the best method to prevent hypotensive episodes. Profiling of sodium should not be the cause of a positive sodium balance. The clinical benefits of sodium profiling to the patients have still to be proven.


Depression, anxiety and cardiometabolic risk in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is associated with psychological and metabolic disturbances. The aim of this study was to determine whether depression, anxiety and reduced health-related quality of life (HRQOL) are more common in women with PCOS and associated with metabolic risk. The study included 226 PCOS patients and 85 BMI-matched healthy control women. All participants completed standardized questionnaires assessing depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory) and both depression and anxiety (Hospital Anxiety and Depression Scale and General Health Questionnaire). Patients also completed a PCOS HRQOL questionnaire. Hirsutism scores, serum androgens and lipids were obtained. All subjects underwent a standard oral glucose tolerance test. 28.6% of PCOS women versus 4.7% of control women had clinical depression scores indicating an 8.1-fold increased risk of depression in PCOS (P < 0.001). Depression and anxiety scores were higher in PCOS women than controls (P < 0.01 for all subscales). Obese PCOS subjects had higher depression scores and rates than non-obese PCOS women (P < 0.05). Depression scores were significantly correlated with insulin resistance and lipid parameters and with the number of components comprising the metabolic syndrome. Menstrual and hirsutism problems were the most serious concerns followed by emotional problems on the HRQOL. Depression and anxiety are more common in patients with PCOS compared with healthy women. Depression in PCOS might be associated with obesity and metabolic abnormalities including insulin resistance and dyslipidemia.


Estimates of wind power and radiative near-inertial internal wave flux: The hybrid slab model and its application to the North Atlantic.
Energy transfer mechanisms between the atmosphere and the deep ocean have been studied for many years. Their importance to the ocean's energy balance and possible implications on mixing are widely accepted. The slab model by Pollard (Deep-Sea Res Oceanogr Abstr 17(4):795-812, 1970) is a well-established simulation of near-inertial motion and energy inferred through wind-ocean interaction. Such a model is set up with hourly wind forcing from the NCEP-CFSR reanalysis that allows computations up to high latitudes without loss of resonance. Augmenting the one-dimensional model with the horizontal divergence of the near-inertial current field leads to direct estimates of energy transfer spectra of internal wave radiation from the mixed layer base into the ocean interior. Calculations using this hybrid model are carried out for the North Atlantic during the years 1989 and 1996, which are associated with positive and negative North Atlantic Oscillation index, respectively. Results indicate a range of meridional regimes with distinct energy transfer ratios. These are interpreted in terms of the mixed layer depth, the buoyancy frequency at the mixed layer base, and the wind field structure. The average ratio of radiated energy fluxes from the mixed layer to near-inertial wind power for both years is approximately 12%. The dependence on the wind structure is supported by simulations of idealized wind stress fronts with variable width and translation speeds.


Tissue plasminogen activator is endocytosed by mannose and galactose receptors of rat liver cells.
Experiments were carried out to characterize the specificity of uptake of tPA in rat liver cells. Endocytosis in liver endothelial cells of the native carbohydrate variants of tissue plasminogen activator (tPA), and tPA inactivated by diisopropyl fluorophosphate was found to be competitive, suggesting that the determinant being recognized by these cells is different from the active site. Fibronectin and urokinase, which show partial homology with tPA, did not compete with tPA for uptake in liver endothelial cells. Hyaluronic acid, collagen, or IgG, which are endocytosed by specific receptors in liver endothelial cells, did not interfere with the uptake. Reduced endocytosis by liver endothelial cells was observed with tPA modified in the carbohydrate side chains, suggesting that these structures are important for uptake. Ovalbumin, mannan, mannose, fructose, and EDTA, but not galactose, effectively inhibited uptake in liver endothelial cells of both native and diisopropyl fluorophosphate-inhibited tPA, but had very little effect on the uptake of tPA modified in the carbohydrate side chains. Endocytosis of native tPA by parenchymal cells could be inhibited by galactose, ovalbumin, and EDTA, but not by mannose. These results suggest that endocytosis of tPA by liver endothelial cells and parenchymal cells is mediated by the mannose and galactose receptors, respectively.


Immigration policies: a comparative overview.
"This is a short comparative overview of the present immigration policies of certain Western countries which, as regards questions of migration, are comparable. It is based on data provided by the International Centre for Migration Policy Development (ICMPD) in Vienna.... It covers the following European countries: Austria, Denmark, Finland, France, Germany, the Netherlands, Norway, Switzerland, Sweden and the United Kingdom. For comparative purposes it also covers three countries overseas which are regarded as typical countries of immigration: Australia, Canada, and the U.S.A."


Hematology and Clinical Chemistry Reference Ranges for Laboratory-Bred Natal Multimammate Mice (Mastomys natalensis).
Laboratory-controlled physiological data for the multimammate rat (Mastomys natalensis) are scarce, despite this species being a known reservoir and vector for zoonotic viruses, including the highly pathogenic Lassa virus, as well as other arenaviruses and many species of bacteria. For this reason, M. natalensis is an important rodent for the study of host-virus interactions within laboratory settings. Herein, we provide basic blood parameters for age- and sex-distributed animals in regards to blood counts, cell phenotypes and serum chemistry of a specific-pathogen-monitored M.natalensis breeding colony, to facilitate scientific insight into this important and widespread rodent species.


Delaying visually guided saccades by microstimulation of macaque V1: spatial properties of delay fields.
Electrical microstimulation of macaque primary visual cortex (area V1) is known to delay the execution of saccadic eye movements made to a punctate visual target placed into the receptive field of the stimulated neurons. We examined the spatial extent of this delay effect, which we call a delay field, by placing a 0.2 degrees visual target at various locations relative to the receptive field of the stimulated neurons and by stimulating different sites within the operculum of V1. A 100-ms train of stimulation consisting of current pulses at or less than 100 microA was delivered immediately before monkeys generated a saccadic eye movement to the visual target. The region of tissue activated was within 0.5 mm from the electrode tip. The depth of stimulation for a given site ranged from 0.9 to 2.0 mm below the cortical surface. The location of the receptive fields of the stimulated neurons ranged from 1.8 to 4.4 degrees of eccentricity from the center of gaze. Within this range, the size of the delay field increased from 0.1 to 0.55 degrees of visual angle. The shape of the field was roughly circular. The size of the delay field increased as the stimulation site was located further from the foveal representation of V1. These results are consistent with the finding that phosphenes evoked by electrical stimulation of human V1 are circular and increase in size as the stimulating electrode is placed more distant from the foveal representation of V1.


Fusion of renal epithelial cells: a model for studying cellular mechanisms of ion transport.
The investigation of epithelial ion transport at the cellular level by means of electrophysiological techniques is hampered by the small size of epithelial cells. Moreover, interpretation of experiments is complex due to poorly defined and highly variable paracellular leaks (shunt pathways). In search of a new experimental approach we developed a technique to isolate renal epithelial cells (diameter approximately equal to 10 micron) from diluting segments of the frog kidney and to fuse them to "giant" cells (diameter approximately equal to 100 micron). These cells generate membrane potentials of -54.1 +/- 1.6 mV (mean +/- SEM; n = 40). They are sensitive to the diuretic drugs furosemide and amiloride and to the K+- and Cl- -permeability blockers Ba2+ and anthracene-9-carboxylic acid. The experiments demonstrate membrane potential measurements in cells isolated from renal epithelium and fused to giant cells. The cells retain their specific membrane properties and could serve as a valuable experimental model in epithelial research.


Changes in Photosystem II Account for the Circadian Rhythm in Photosynthesis in Gonyaulax polyedra.
Cell-free extracts that show activity in photosynthetic electron flow have been prepared from the unicellular dinoflagellate, Gonyaulax polyedra. Electron flow, as O(2) uptake, was measured through both photo-system I and II from water to methyl viologen, through photosystem I alone from reduced 2,6-dichlorophenol indophenol to methyl viologen which does not include the plastoquinone pool or from duroquinol to methyl viologen which includes the plastoquinone pool. Electron flow principally through photosystem II was measured from water to diaminodurene and ferricyanide, as O(2) evolution. Cultures of Gonyaulax were grown on a 12-hour light:12 hour dark cycle to late log phase, then transferred to constant light at the beginning of a light period. After 3 days, measurements of electron flow were made at the maximum and minimum of the photosynthetic rhythm, as determined from measurements of the rhythm of bioluminescence. Photosynthesis was also measured in whole cells, either as (14)C fixation or O(2) evolution. Electron flow through both photosystems and through photosystem II alone were clearly rhythmic, while electron flow through photosystem I, including or excluding the plastoquinone pool, was constant with time in the circadian cycle. Thus, only changes in photosystem II account for the photosynthesis rhythm in Gonyaulax.


Drag Reduction Using Polysaccharides in a Taylor⁻Couette Flow.
Three different polysaccharides, aloe vera, Tamarind powder and pineapple fibers, are utilized as drag reducing agents in a turbulent flow. Using a Taylor⁻Couette setup, consisting of a rotating inner cylinder, for measuring the drag reduction, a range of Reynolds numbers from 4 × 10⁴ to 3 × 10⁵ has been explored in this study. The results are in good agreement with previous studies on polysaccharides conducted in a pipe/channel flow and a maximum drag reduction of 35% has been observed. Further, novel additives such as cellulose nanocrystals (CNC), surfactants and CNC grafted with surfactants are also examined in this study for drag reduction. CNC due to its rigid rod structure reduced the drag by 30%. Surfactant, due to its unique micelle formation showed maximum drag reduction of 80% at low Re. Further, surfactant was grafted on CNC and was examined for drag reduction. However, drag reduction property of surfactant was observed to be significantly reduced after grafting on CNC. The effect of Reynolds number on drag reduction is studied for all the additives investigated in this study.


Examination of the Dimensions of Biological Age.
The concept of biological age has been used more and more frequently in aging research in attempts to measure the progress of the biological aging process as opposed to the simple passage of time. Several approaches to quantify biological age have been utilized, including the use of biomarkers in the form of serum analytes, epigenetic markers, and deficit or frailty indices. Among these methods, the deficit index possesses a theoretical basis grounded in systems biology by incorporating networks, with their emergent properties, to describe the complex aging system. Application of the deficit index in human aging studies points to the increased energetic demands posed by an aging system that is losing integration. Different aspects of mitochondrial function appear to be responsible in males and females. The gut microbiome loses complexity in tandem with the host, as biological age increases, with likely impact on host metabolism and immunity. Specific DNA methylation changes are associated with biological age. They suggest declining connectivity within the aging network, at the cellular level. The deficit/frailty index may account for at least part of the departure at older ages of the observed mortality in the population from the exponential increase modeled by the Gompertz equation.


Do collaterals affect heart rate variability in patients with acute myocardial infarction?
The protective effects and the prognostic importance of collaterals during and after acute myocardial infarction (MI) are under debate and heart rate variability (HRV) is a strong predictor of risk of mortality and arrhythmic events after acute MI. We aimed to examine the effects of collateral circulation on HRV in the early period after acute MI. Sixty-four patients admitted to our clinics who were diagnosed with acute anterior MI and underwent thrombolytic therapy were enrolled in this study. We applied 24 h Holter monitoring for HRV analysis to all patients and compared the patients with and without collaterals to the infarct-related artery. Mean heart rate, low frequency (LF) (day, night and 24 h) and LF/high frequency (HF) (day, night and 24 h) were higher, SD of all NN intervals (SDNN), root mean square of successive differences (RMSSD), number of NN intervals that differed by more than 50 ms from the adjacent interval divided by the total number of all NN intervals (PNN50) and HF night values were lower in patients without collaterals than in those with collaterals. SDNN was negatively correlated with left anterior descending coronary artery (LAD) stenosis, ventricle score indices and left ventricular ejection fraction (LVEF); LF/HF ratio was positively correlated with ventricle score indices and negatively correlated with LVEF and Thrombolysis in Myocardial Infarction flow grade. Linear regression analysis showed that ventricle score index and coronary collaterals affect HRV and LAD stenosis, ventricle score, LVEF and coronary collaterals affect LF/HF ratio. A SDNN <80 ms increased the development of ventricular arrhythmias in the early period by 4.7 fold, a LF/HF ratio >2.7 increased it by 9.8 fold and a LVEF <35% increased it by 12.8 fold, whereas the presence of well-developed collaterals decreased the arrhythmia development by 2.5 fold. The collaterals to the infarct-related artery have great impact on HRV, autonomic nervous system activity and the development of ventricular arrhythmias in patients with acute anterior MI. Our results suggest a protective role of collaterals on myocardial electrophysiology in the early period after acute MI.


Simultaneous expression of the S and L surface antigens of hepatitis B, and formation of mixed particles in the methylotrophic yeast, Hansenula polymorpha.
An expression system has been developed for the methylotrophic yeast Hansenula polymorpha and used to co-express both the L (preS1-S2-S) and S hepatitis B surface antigens (HBsAg) under the control of strong methanol-inducible promoters derived from the methanol oxidase and from the formate dehydrogenase genes. A unique feature of this H. polymorpha expression system is the possibility of integrating up to 100 copies of an expression cassette via a multimeric integration mechanism. Several multimeric integrants containing various numbers of L and S expression cassettes were constructed to give a spectrum of strains characterized by different L to S ratios. The expression level of S antigen was 5-8% of the total soluble cell protein. Analysis by sucrose and CsCl density gradient centrifugation and by particle-specific immunoassays demonstrated that the synthesized HBsAg spontaneously assembled into composite subviral particles containing both S and L proteins. Only a minor portion of the L protein was found to be glycosylated. These H polymorpha-derived composite particles can be used for the production of a hepatitis B virus vaccine with the potential for improved immunogenicity due to the presence of a wider spectrum of epitopes and negligible glycosylation.


Computational investigation of rearrangements in huisgen cycloadducts of azolium N-dicyanomethanide 1,3-dipoles with alkynes: a mechanistic panoply.
The reaction surfaces leading to rearrangements and ring expansions of azapentalene cycloadducts of imidazolo- and triazolodicyanomethanide 1,3-dipoles with alkynes are studied with the B3LYP DFT method using the 6-31G(d) and 6-311+G(2d,p) basis sets. The surprisingly complex surface involves (1) consecutive but not combined pericyclic steps, a coarctate TS, and pseudopericyclic mechanisms, (2) anchimerically assisted H-atom transfer competing effectively with concerted symmetry-allowed sigmatropic steps, and (3) azolium methanide zwitterions and ketenimines as key intermediates. The azolium methanide is identified as the intermediate detected previously in a variable-temperature NMR experiment that converted the unstable cycloadduct to product imine.


Wavelets-a new tool in sleep biosignal analysis.
The wavelet transform is a relatively new approach to data processing which has been applied in different areas such as signal, speech and image processing. In the last decade, many papers have been published on wavelet theory and its applications. The wavelet transform provides an elegant alternative to the classical Fourier or Gabor transforms unifying numerous signal processing techniques in a common framework. The purpose of the present paper is to provide an overview of the applicability of the wavelet transform to EEG signal analysis. In the first part of the paper the mathematical background is summarized. In the second part, applications to the sleep EEG field are presented and discussed. The results of these illustrations demonstrate the usefulness of the wavelet transform to solve various problems including signal parametrization, pattern recognition and biosignal representation.


Analysis of streptokinase by validated liquid chromatography methods and correlation with an in vitro bioassay.
Reversed-phase and size-exclusion liquid chromatography methods were validated for the assessment of streptokinase. The reversed-phase method was carried out on a Jupiter C4 column (250 mm × 4.6 mm id) maintained at 25°C. The mobile phase consisted of 50 mM sodium sulfate solution pH 7.0 and methanol (90:10, v/v), run isocratically at a flow rate of 0.8 mL/min. The size-exclusion method was carried out on a Protein KW 802.5 column (300 mm × 8.0 mm id), at 25°C. The mobile phase consisted of 40 mM sodium acetate solution pH 7.0, run isocratically at a flow rate of 1.0 mL/min. Retention times were 19.3 min, and 14.1 min, and calibration curves were linear over the concentration range of 0.25-250 μg/mL (25.75-25 750 IU/mL) (r2 = 0.9997) and 5-80 μg/mL (515-8240 IU/mL) (r2 = 0.9996), respectively, for reversed-phase and size exclusion, with detection at 220 and 204 nm. Chromatographic methods were employed in conjunction with the in vitro bioassay for the content/potency assessment of Streptokinase, contributing to improve the quality control and ensure the efficacy of the biotherapeutic.


TRESK background potassium channel modifies the TRPV1-mediated nociceptor excitability in sensory neurons.
TWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice. Calcium imaging was used to investigate the role of TRESK channels in the modulation of the response evoked by transient receptor potential vanilloid 1 (TRPV1) receptor stimulation in dorsal root ganglion neurons. Release of calcitonin gene-related peptide from trigeminal afferents and changes in meningeal blood flow were also measured. Experiments were performed on wild-type and TRESK knockout animals. Inhibition of TRESK increased the TRPV1-mediated calcium signal in dorsal root ganglion neurons and potentiated capsaicin-induced increases in calcitonin gene-related peptide release and meningeal blood flow. Activation of TRESK decreased the capsaicin sensitivity of sensory neurons, leading to an attenuation of capsaicin-induced increase in meningeal blood flow. In TRESK knockout animals, TRPV1-mediated nociceptive reactions were unaffected by pretreatment with TRESK modulators. Pharmacological manipulation of TRESK channels influences the TRPV1-mediated functions of nociceptors. Altered TRESK function might contribute to trigeminal nociceptor sensitization in migraine patients.


Immune modulation in primary vaccinia virus zoonotic human infections.
In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4(+) cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.


Nitrosamines, alcohol, and gastrointestinal tract cancer: recent epidemiology and experimentation.
Recent epidemiological and experimental data continues to implicate nitrosamines in causation of gastrointestinal cancers. The evidence is strong for pharynx, esophagus, and stomach, and more problematic for liver, pancreas, and colorectum. Substantial levels of the promutagenic DNA adduct, Ob-methylguanine, in DNA from these organs in patas monkeys after a low dose of N-nitrosodimethylamine confirms the capacity for activation of environmental nitrosamines in these primate tissues. Alcohol is both an independent and a tobacco-interactive risk factor, influencing cancer incidence for oropharynx and esophagus strongly, and for stomach, colorectum, and liver more moderately. In a tabulation of experimental effects of ethanol potentially related to cancer-enhancing effects, toxicokinetic inhibition of hepatic first-pass clearance of nitrosamines is quantitatively greatest, and may be a major part of the mechanism of alcohol's effect on cancer risk for oropharnx, esophagus, and colon. Other operative mechanisms supported by experimental data are induction of activating enzymes, inhibition of DNA repair, and tumor promotion.


Predominance of genotype P[9]G3 in rotavirus gastroenteritis in Polish children.
Rotavirus (RV) infection is the most common cause of gastroenteritis in children. This paper identifies the most common genotypes of rotaviruses isolated from children hospitalized with gastroenteritis and attempts to determine any relationship between infection with a certain rotavirus genotype. The investigated group consisted of 68 consecutive children with rotavirus gastroenteritis (confirmed by an agglutination test). Rotavirus genotype was determined in stool samples obtained from each child. The P[9]VP4 genotype was observed in 41/61 positive samples (over 67.2%) that were permanently associated with the G3 VP7 genotype. Moreover, G3 was determined as the most commonly isolated G type (77.94%). As well as the P[9]G3 type, G3 was also found in the P[4] type (5 cases). Twenty-six out of 61 (42.6%) children in whom rotavirus genotype was determined were co-infected with pathogenic bacteria. No statistical correlation was observed between rotavirus P[9]G3 gastroenteritis and digestive tract co-infection with pathogenic bacteria (p > 0.05). Elevated ALT activity was found in 34/59 (57.6%) cases of rotavirus gastroenteritis. Elevated ALT serum level was found to correlate with P[9]G3 rotavirus genotype but concomitant infections did not. The most common genotype of rotaviruses observed in our group of children, P[9]G3, has rarely been described. Co-infection of the digestive tract with pathogenic bacteria and elevated serum ALT concentrations were found to be the most frequent phenomena. A correlation between P[9]G3 rotavirus genotype and elevated serum ALT level was found, but no significant relationship was identified between concomitant infections and P[9]G3 genotype.


Enzyme-catalyzed O2 removal system for electrochemical analysis under ambient air: application in an amperometric nitrate biosensor.
Electroanalytical procedures are often subjected to oxygen interferences. However, achieving anaerobic conditions in field analytical chemistry is difficult. In this work, novel enzymatic systems were designed to maintain oxygen-free solutions in open, small volume electrochemical cells and implemented under field conditions. The oxygen removal system consists of an oxidase enzyme, an oxidase-specific substrate, and catalase for dismutation of hydrogen peroxide generated in the enzyme catalyzed oxygen removal reaction. Using cyclic voltammetry, three oxidase enzyme/substrate combinations with catalase were analyzed: glucose oxidase with glucose, galactose oxidase with galactose, and pyranose 2-oxidase with glucose. Each system completely removed oxygen for 1 h or more in unstirred open vessels. Reagents, catalysts, reaction intermediates, and products involved in the oxygen reduction reaction were not detected electrochemically. To evaluate the oxygen removal systems in a field sensing device, a model nitrate biosensor based on recombinant eukaryotic nitrate reductase was implemented in commercial screen-printed electrochemical cells with 200 μL volumes. The products of the aldohexose oxidation catalyzed by glucose oxidase and galactose oxidase deactivate nitrate reductase and must be quenched for biosensor applications. For general application, the optimum catalyst is pyranose 2-oxidase since the oxidation product does not interfere with the biorecognition element.


A novel hypothesis regarding the possible involvement of cytosolic phospholipase 2 in insulin-stimulated proliferation of vascular smooth muscle cells.
Insulin (INS) via INS receptor acts as a mitogen in vascular smooth muscle cells (VSMCs) through stimulation of multiple signaling mechanisms, including p42/44 mitogen-activated protein kinase (ERK1/2) and phosphatidyl inositol-3 kinase (PI3K). In addition, cytosolic phospholipase 2 (cPLA2) is linked to VSMCs proliferation. However, the upstream mechanisms responsible for activation of cPLA2 are not well defined. Therefore, this investigation used primary cultured rat VSMCs to examine the role of PI3K and ERK1/2 in the INS-dependent phosphorylation of cPLA2 and proliferation induced by INS. Exposure of VSMCs to INS (100 nM) for 10 min increased the phosphorylation of cPLA2 by 1.5-fold ( p < 0.01), which was blocked by the cPLA2 inhibitor MAFP (10 microM; 15 min). Similarly, the PI3K inhibitor LY294002 (10 microM; 15 min) and ERK1/2 inhibitor PD98059 (20 microM; 15 min) abolished the INS-mediated increase in cPLA2 phosphorylation by 59% (p < 0.001), and by 75% ( p < 0.001), respectively. Further, inhibition of cPLA2 with cPLA2 inhibitor MAFP abolished the INS-stimulated ERK1/2 phosphorylation by 65% ( p < 0.01). Incubation of rat VSMCs with INS resulted in an increase of VSMCs proliferation by 85% ( p < 0.001). The effect of INS on VSMCs proliferation was significantly ( p < 0.01) reduced by pretreatment with MAFP. Thus, we hypothesized that INS stimulates VSMCs proliferation via a mechanism involving the PI3K-dependent activation of cPLA2 and release of arachidonic acid (AA), which activates ERK1/2 and further amplifies cPLA2 activity.


Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA-DoD CARE Consortium.
Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; N = 190) and matched non-contact sport athletes (NCS; N = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all ps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS (p = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS (p = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history (p = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion (p = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.


[Protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats].
Objective: To study the protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats and explore the regulatory mechanism of toll-like receptors 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in this process. Methods: Sixty male SD rats were randomly divided into control group (C), model group (M), low-dose Lycium ruthenicum Murr. juice group (LLM), medium-dose Lycium ruthenicum Murr. juice group (MLM) and high-dose Lycium ruthenicum Murr. juice group (HLM), 12 rats in each group. The group M, LLM, MLM and HLM were treated with 20 ml/kg (8 g/(kg·d)) ethanol (400 g/L) intragastrically and the gavage was divided into two sessions, group C was treated with an equal volume of distilled water at the same time point. Four hours before the first alcohol gavage session, rats in each dose group of Lycium ruthenicum Murr. juice were administered with 2.4, 4.8, 9.6 ml/(kg·d) Lycium ruthenicum Murr. juice respectively, and the other groups were given equal volume of distilled water at the corresponding time points. Four weeks later, the rats were sacrificed 24 hours after the end of the last experiment, blood and liver were collected. The liver index was calculated. The morphology of the liver was observed by HE staining. The expressions of hepatic TLR4, p38 MAPK and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were detected by immunohistochemistry. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The levels of hepatic tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10) and interleukin-18 (IL-18) were detected by enzyme linked immunosorbent assay. Results: Compared with group C, the alcoholic liver injury model was established successfully in Group M. Compared with group M, related indicators in each dose group of Lycium ruthenicum Murr. juice were improved, the improvement of hepatic morphology in group HLM was the most significant, the liver index, the levels of serum ALT, AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-1β, IL-18 were decreased (P< 0.05 or P<0.01), while the level of hepatic IL-10 was increased (P<0.01). Comparison among the dose groups of Lycium ruthenicum Murr. juice, the levels of liver index, serum AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-18 in HLM were lower than those in LLM (P<0.05 or P<0.01); the level of hepatic IL-10 in HLM was higher than that in LLM and MLM (P<0.05 or P<0.01); the other indicators in each dose group had no statistical difference (P>0.05). Conclusion: Lycium ruthenicum Murr. juice can improve the inflammatory stress by regulating TLR4/p38 MAPK signaling pathway, relieve alcoholic liver injury in rats, and the effect of high-dose group is better than the others.


Atovaquone/proguanil for the prophylaxis and treatment of malaria.
Increases in international travel and escalating drug resistance have resulted in a growing number of travelers at risk of contracting malaria. Drug resistance and intolerance to standard agents such as chloroquine, sulfadoxine/pyrimethamine and mefloquine has highlighted the need for new antimalarials. The recently licensed fixed combination of atovaquone and proguanil hydrochloride (Malarone) is a promising new agent to prevent and treat Plasmodium falciparum malaria. Randomized controlled trials have shown that atovaquone/proguanil is well tolerated and efficacious for the prevention and treatment of drug-resistant P. falciparum malaria. Atovaquone/proguanil is active against the liver stage of P. falciparum malaria parasites and when used as a prophylactic agent it can be discontinued shortly after leaving malaria-endemic areas, offering a clear advantage for drug adherence.


Comparison of Peak Ground Reaction Force, Joint Kinetics and Kinematics, and Muscle Activity Between a Flexible and Steel Barbell During the Back Squat Exercise.
The flexible barbell is purported to improve training gains compared with an Olympic steel barbell (SB) during the back squat exercise with Division I collegiate American football programs. The two bars loaded at 30% 1-repetition maximum were compared with ten trained Division I American football players (n = 10; age = 19.5 years; body mass = 89.4 kg; body height = 182.0 cm) completing 10 repetitions of the back squat exercise. Analysis included integrated-peak values of electromyography of the rectus femoris, biceps femoris, rectus abdominis, erector spinae, external oblique, vastus lateralis, ground reaction forces, and joint kinematics and kinetics of the hip, knee, and ankle. The flexible bar elicited significant increases in peak joint kinetics (Hip Moment: 229 ± 54 Nm vs. 209 ± 52 Nm; Hip Power: 494 ± 151 W vs. 382 ± 134 W; Knee Power: 305 ± 108 W vs. 241 ± 63 W), peak vertical ground reaction forces (1195 ± 209 N vs. 1120 ± 203 N), and muscle activity (Vastus Lateralis: 75.7 vs. 66.5%, Rectus Abdominis: 190 vs. 115%, Rectus Femoris: 69.8 vs. 59.9%, External Oblique: 115 vs. 69.0%). Greater vertical ground reaction forces, hip moment, hip power, knee power, and muscle activity of the vastus lateralis, rectus abdominis, rectus femoris, and external oblique suggest the FB provides biomechanical and physiological mechanisms for training gains over the SB for 30% of 1-repetition maximum loads.


Interventional pain management in rheumatological diseases - a three years physiatric experience in a tertiary medical college hospital in bangladesh.
Interventional pain management (IPM) is a branch of medical science that deals with management of painful medical conditions using specially equipped X-ray machines and anatomical landmarks. Interventional physiatry is a branch of physical medicine and rehabilitation that treats painful conditions through intervention in peripheral joints, the spine, and soft tissues. A cross-sectional study was conducted using three years of hospital records (2006 to 2008) from the Physical Medicine and Rehabilitation Department at Chittagong Medical College Hospital in Bangladesh, with a view toward highlighting current interventional pain practice in a tertiary medical college hospital. The maximum amount of intervention was done in degenerative peripheral joint disorders (600, 46.0%), followed by inflammatory joint diseases (300, 23.0%), soft tissue rheumatism (300, 23.0%), and radicular or referred lower back conditions (100, 8.0%). Of the peripheral joints, the knee was the most common site of intervention. Motor stimulation-guided intralesional injection of methylprednisolone into the piriformis muscle was given in 10 cases of piriformis syndrome refractory to both oral medications and therapeutic exercises. Soft tissue rheumatism of unknown etiology was most common in the form of adhesive capsulitis (90, 64.3%), and is discussed separately. Epidural steroid injection was practiced for various causes of lumbar radiculopathy, with the exception of infective discitis. All procedures were performed using anatomical landmarks, as there were no facilities for the C-arm/diagnostic ultrasound required for accurate and safe intervention. A dedicated IPM setup should be a requirement in all PMR departments, to provide better pain management and to reduce the burden on other specialties.


Sponge mesoporous silica formation using disordered phospholipid bilayers as template.
Lecithin/dodecylamine/lactose mixtures in ethanol/aqueous media led to the formation of sponge mesoporous silica (SMS) materials by means of tetraethoxysilane (TEOS) as silica source. SMS materials show a "sponge-mesoporous" porosity with a pore diameter of about 5-6 nm, in accordance to the length of a lecithin bilayer. SMS synthesis was developed to create a new class of powerful biocatalysts able to efficiently encapsulate enzymes by adding a porosity control to the classical sol-gel synthesis and by using phospholipids and lactose as protecting agents for the enzymes. In the present study, the formation of SMS was investigated by using electron paramagnetic resonance (EPR) probes inserted inside phospholipid bilayers. The influence of progressive addition of each component (ethanol, dodecylamine, lactose, TEOS) on phospholipid bilayers was first examined; then, the time evolution of EPR spectra during SMS synthesis was studied. Parameters informative of mobility, structure, order, and polarity around the probes were extracted by computer analysis of the EPR line shape. The results were discussed on the basis of solids characterization by X-ray diffraction, nitrogen isotherm, transmission electron microscopy, and scanning electron microscopy. The results, together with the well-known ability of ethanol to promote membrane hemifusion, suggested that the templating structure is a bicontinuous phospholipid bilayer phase, shaped as a gyroid, resulting of multiple membrane hemifusions induced by the high alcohol content used in SMS synthesis. SMS synthesis was compared to hexagonal mesoporous silica (HMS) synthesis accomplished by adding TEOS to a dodecylamine/EtOH/water mixture. EPR evidenced the difference between HMS and SMS synthesis; the latter uses an already organized but slowly growing mesophase of phospholipids, never observed before, whereas the former shows a progressive elongation of micelles into wormlike structures. SMS-type materials represent a new class of biocompatible materials and open a bright perspective for biomolecule processing for pharmaceutical, biocatalysis, biosensors, or biofuel cell applications.


Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.
ErbBs are receptor tyrosine kinases involved not only in development, but also in a wide variety of diseases, particularly cancer. Their extracellular, transmembrane, juxtamembrane, and kinase folded domains were described extensively over the past 20 years, structurally and functionally. However, their whole C-terminal tails (CTs) following the kinase domain were only described at atomic resolution in the last 4 years. They were shown to be intrinsically disordered. The CTs are known to be tyrosine-phosphorylated when the activated homo- or hetero-dimers of ErbBs are formed. Their phosphorylation triggers interaction with phosphotyrosine binding (PTB) or Src Homology 2 (SH2) domains and activates several signaling pathways controling cellular motility, proliferation, adhesion, and apoptosis. Beyond this passive role of phosphorylated domain and site display for partners, recent structural and function studies unveiled active roles in regulation of phosphorylation and interaction: the CT regulates activity of the kinase domain; different phosphorylation states have different compaction levels, potentially modulating the succession of phosphorylation events; and prolines have an important role in structure, dynamics, and possibly regulatory interactions. Here, we review both the canonical role of the disordered CT domains of ErbBs as phosphotyrosine display domains and the recent findings that expand the known range of their regulation functions linked to specific structural and dynamic features.


Comparison of therapies with torasemide or furosemide in patients with congestive heart failure from a pharmacoeconomic viewpoint.
This observational study compared patients suffering from congestive heart failure (CHF) who were treated with loop diuretics torasemide or furosemide. Data documenting the course of the disease and its associated costs over a period of one year were collected retrospectively. A total of 400 CHF patients, 200 in each treatment group, were included in the analysis. Concomitant ACE inhibitor therapy was received by 46% of patients in both groups. More torasemide-treated patients (38.0%) than furosemide-treated patients (24.5%) achieved an improvement in NYHA class in the one-year period. The main difference between the two groups was the number of CHF-related hospitalisations: 62 vs 324 hospital days due to CHF were necessary among torasemide- and furosemide-treated patients, respectively. Thus torasemide treatment was associated with an 80% reduction in hospital days compared with furosemide. Furthermore, about 30% fewer working days were lost in the torasemide group than in the furosemide group (441 days vs 617 days, respectively). Direct and indirect costs were evaluated, resulting in overall annual costs of DEM 1502 per torasemide-treated patient and DEM 1863 per furosemide-treated patient. A cost-effectiveness analysis showed a difference between the therapies of DEM 3651 in favour of torasemide. In conclusion, treatment with torasemide improved clinical outcome and was more cost-effective than with furosemide.


Exporting analogue behavioral observation from research to clinical practice: useful or cost-defective?
The special section on analogue behavioral observation (ABO) provided an in-depth review of various ABO assessment procedures. Despite their availability, however, these procedures are rarely used in clinical practice. This may result in part from the traditions on which most ABO assessments are based, from distinctions between clinical and research assessment environments, and from the need for more information about the cost-effectiveness of ABO strategies for meeting specific needs of clinicians in applied settings. Suggestions for bridging the research-clinical gap involve investigating more thoroughly when ABO does and does not provide useful information for various purposes in applied settings and increasing accessibility and cost-effectiveness of ABO procedures for practitioners.


Photophysics of xanthone: a quantum chemical perusal.
A theoretical analysis of the chromophore xanthone has been carried out in various cases, starting from the isolated molecule and going on to the extremely polar-protic solvated chromophore. In the gas phase, we find that an El-Sayed forbidden channel with a rate constant of kISC = 2 × 10(11) s(-1) is one of the trend-setting factors in the photophysical kinetics. The fluorescence is found to be quenched in the gas phase and polar-aprotic solvents. The analysis of xanthone in aqueous solution supports the delayed fluorescence model, which has been suggested to explain the high fluorescence quantum yield observed in water. Besides, we present a detailed analysis of the photophysics of xanthone in acetonitrile and methanol.


Sequential column asymmetric catalysis.
Since the introduction of catalysts and reagents on solid-support, researchers have developed new reaction systems to take advantage of their insoluble nature by designing multistep reaction sequences, high-throughput purification techniques, and combinatorial synthesis methods. The continuous flow system is one of these advancements and represents the foundation of a new technique termed sequential column asymmetric catalysis (CAC). In this strategy, reagents and catalysts are attached to a solid-phase support and loaded onto sequentially-linked columns. The substrates are present in the liquid phase that flows through the column. As a substrate encounters each successive column, it grows in complexity. Consequently, one can imagine a number of flow systems that consist of columns attached in series and/or in parallel that synthesize a fairly complex molecule. Herein, we discuss the development of the sequential CAC technique, beginning with the most relevant antecedents.


Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography.
The myocardial infarction (MI) rat model plays a crucial role in modern cardiovascular research, but the inherent heterogeneity of this model represents a challenge. We sought to identify subgroups among the post-MI rats and establish simple noninvasive stratification protocols for such subgroups. Six weeks after induction of MI, 49 rats underwent noninvasive examinations using magnetic resonance imaging (MRI) and echocardiography. Twelve sham-operated rats served as controls. Increased end-diastolic left ventricular (LV) pressure and lung weight served as indicators for congestive heart failure (CHF). A clustering algorithm using 13 noninvasive and invasive parameters was used to identify distinct groups among the animals. The cluster analysis revealed four distinct post-MI phenotypes; two without congestion but with different degree of LV dilatation, and two with different degree of congestion and right ventricular (RV) affection. Among the MRI parameters, RV mass emerged as robust noninvasive marker of CHF with 100% specificity/sensitivity. Moreover, LV infarct size and RV ejection fraction further predicted subgroup among the non-CHF and CHF rats with excellent specificity/sensitivity. Of the echocardiography parameters, left atrial diameter predicted CHF. Moreover, LV end-diastolic diameter predicted the subgroups among the non-CHF rats. We propose two simple noninvasive schemes to stratify post-MI rats, based on the degree of heart failure; one for MRI and one for echocardiography.NEW & NOTEWORTHY In vivo phenotyping of rats is essential for robust and reliable data. Here, we present two simple noninvasive schemes for the stratification of postinfarction rats based on the degree of heart failure: one using magnetic resonance imaging and one based on echocardiography.


Intracranial haemorrhages after Nebo hierochonticus scorpion sting.
A 3-year-old boy, who was previously well, developed acute pulmonary oedema, fundal haemorrhages, temporary blindness and deafness following a Nebo hierochonticus scorpion sting. Cranial CT scan 8 days after admission showed bilaterally symmetrical multiple hyperdense areas with intense enhancement in the cerebellar and cerebral hemispheres consistent with multiple haemorrhages. He made a complete clinical recovery with resorption of the retinal haemorrhages 4 weeks after the scorpion sting. Cranial CT scan 8 months later revealed the intracranial lesions to be hypodense with no contrast enhancement, indicating resorption of the haemorrhages.


Menstrual cycle influences Toll-like receptor responses.
Toll-like receptors (TLRs) are pattern recognition receptors that play an important role as mediators of innate immunity. Human studies have shown changes in endometrial TLR expression during the menstrual cycle and during pregnancy. Our objective was to measure peripheral TLR activity over the course of the menstrual cycle. We recruited 11 healthy females, and using ELISA we measured sex hormone levels and IL-1β, IL-6, IL-8 and TNF-α following stimulation of whole blood with different TLR agonists during follicular, and early and late luteal phases of the menstrual cycle. During the follicular phase, we observed lower levels of IL-6 and TNF-α following stimulation with the TLR2 agonist HKLM when compared with the early luteal phase; lower levels of IL-1β, IL-6 and TNF-α following stimulation with the TLR4 agonist LPS, and lower levels of IL-1β and TNF-α following stimulation with the TLR5 agonist flagellin. Decreased IL-6 levels in the late compared to the early luteal phase were also observed following stimulation with the TLR5 agonist flagellin. Compared with the follicular phase, the late luteal phase of the cycle resulted in decreased levels of IL-1β and TNF-α following stimulation with the TLR1/TLR2 agonist Pam3CSK and the TLR6/TLR2 agonist FSL1, as well as decreased levels of TNF-α following stimulation with the TLR8 agonist ssRNA40. There were no differences in cytokine release across the menstrual cycle following stimulation with the TLR3 agonist polyriboinosinic polyribocytidylic acid, or the TLR7 agonist Imiquimod. This study is the first to demonstrate that TLR responsivity in peripheral blood fluctuates throughout the menstrual cycle.


Artificial Neural Network Algorithms to Predict Resting Energy Expenditure in Critically Ill Children.
Accurate assessment of resting energy expenditure (REE) can guide optimal nutritional prescription in critically ill children. Indirect calorimetry (IC) is the gold standard for REE measurement, but its use is limited. Alternatively, REE estimates by predictive equations/formulae are often inaccurate. Recently, predicting REE with artificial neural networks (ANN) was found to be accurate in healthy children. We aimed to investigate the role of ANN in predicting REE in critically ill children and to compare the accuracy with common equations/formulae. We enrolled 257 critically ill children. Nutritional status/vital signs/biochemical values were recorded. We used IC to measure REE. Commonly employed equations/formulae and the VCO2-based Mehta equation were estimated. ANN analysis to predict REE was conducted, employing the TWIST system. ANN considered demographic/anthropometric data to model REE. The predictive model was good (accuracy 75.6%; R2 = 0.71) but not better than Talbot tables for weight. After adding vital signs/biochemical values, the model became superior to all equations/formulae (accuracy 82.3%, R2 = 0.80) and comparable to the Mehta equation. Including IC-measured VCO2 increased the accuracy to 89.6%, superior to the Mehta equation. We described the accuracy of REE prediction using models that include demographic/anthropometric/clinical/metabolic variables. ANN may represent a reliable option for REE estimation, overcoming the inaccuracies of traditional predictive equations/formulae.


Increased motivational intensity leads to preference for distraction over reappraisal during emotion regulation: Mediated by attentional breadth.
Motivation is considered important in the study of emotion regulation. However, it remains unknown whether and how varied motivation may influence people's emotion regulation choice. To address this question, 51 participants first performed a global-local task that measures attentional breadth. Then, they were required to choose emotion regulation strategies, reappraisal, or distraction, to regulate their emotion in emotional contexts that varied in motivational direction and intensity. We found that distraction was chosen more often over reappraisal in high-intensity-motivated emotion, while the reverse pattern was observed in low-intensity motivated emotion. Besides, withdrawal-motivated emotion was associated with more reappraisal choices than approach-motivated emotion, an effect that, however, vanished when valence was controlled. Furthermore, participants made fewer global choices, which is indicative of narrowed attentional breadth, during high- relative to low-intensity motivated emotional contexts, and attentional breadth partially mediated the effect of motivational intensity on emotion regulation choice. These findings suggest that increased motivation promotes one's choice of distraction over reappraisal during emotion regulation, by narrowing attentional breadth. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subcellular protein localization (cell envelope) in Phaeobacter inhibens DSM 17395.
Phaeobacter inhibens DSM 17395 is a metabolically versatile, secondary metabolite producing and surface colonizing member of the alphaproteobacterial Roseobacter clade. Proteins compartmentalized across the Gram-negative cell envelope are expected to be relevant for the habitat success of P. inhibens DSM 17395. Subcellular fractionation was followed by gel- or nano-LC-based separation of proteins and peptides, respectively. Subsequent MS-based identification of in total 1187 proteins allowed allocation to cytoplasm (303 proteins), cytoplasmic membrane (346), periplasm (325), outer membrane (76), and extracellular milieu (22). Multidimensional scaling was used to visualize the spreading of heuristically allocated proteins across the five different compartments. Experimentally inferred subcellular protein localization was compared with PSORTb prediction of protein secretion and membrane localization. Determined subcellular localizations of identified proteins were interpreted to reconstruct the functional traits of the different cell envelope compartments, in particular protein secretion and sorting, direct effector molecule transit, and cell envelope biogenesis. From a proteogenomic perspective, functional prediction of 74 genes (including 17 coding for proteins of hitherto unknown function) could be refined.


Review on Novel Oral Therapies for Psoriasis.
Currently, several classes of oral therapies for psoriasis are in use, in development, or in investigative stages. Standard non-biologic treatments for psoriasis, such as methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-term use. This review will address the safety and efficacy of existing and novel oral therapies for psoriasis that target inflammatory pathways via modulation of phosphodiesterase 4 (PDE4), Janus kinases (JAKs), sphingosine 1-phosphate (S1P), A3 adenosine receptors, and rho-associated kinase 2 (ROCK2), with an emphasis on JAK inhibitors.


Early Breast Milk Pumping Intentions Among Postpartum Women.
Milk expression has become common, but little is known about women's intentions and motivations for pumping. Our objectives were to measure, among newly postpartum women, intentions related to breast milk feeding and pumping, reasons for intending to pump, and timing of pumping initiation. We conducted a cross-sectional study at a large university hospital in 2015 using a convenience sample of 100 women before their discharge following delivery, who intended to feed their infant breast milk for at least 6 months. All participants planned to feed their baby at the breast. Ninety-eight percent said that they would use a breast pump to express milk for their baby, with most of this subset (69%) intending to start within weeks of delivery. Over a quarter of participants (29%) had already initiated pumping or intended to initiate within the subsequent few days. Primiparae were more likely to report having already started pumping at the time of the interview. For all women, the most common reason for pumping was to keep up their milk supply. Women who started pumping while in the hospital also noted that they pumped to increase their milk supply and overcome latch difficulties. The common intention to use a breast pump so early after delivery indicates a need for increased lactation support to reduce concerns about having an insufficient milk supply immediately following delivery. Additionally, clinicians who help facilitate breastfeeding should be aware of how early women intend to use a breast pump.


Cubic Nanostructures of Nickel-Cobalt Carbonate Hydroxide Hydrate as a High-Performance Oxygen Evolution Reaction Electrocatalyst in Alkaline and Near-Neutral Media.
Catalyst development for the efficient direction of electrocatalytic water splitting with much less overpotential is crucial for meeting large-scale hydrogen generation. Being highly abundant and cost-effective, 3d transition-metal-based catalysts show promising activities in alkaline conditions. In this work, bimetallic nickel-cobalt carbonate hydroxide hydrate (NiCoCHH) was prepared by a co-precipitation method with varying molar ratios of Ni/Co of 0.5:1, 1:1, and 1.5:1, which were analyzed for oxygen evolution reaction (OER) study in both alkaline (1 M KOH) and near-neutral (1 M NaHCO3) media. For OER in 1 M KOH, NiCoCHH 1:1 required overpotential of just 238 mV at 10 mA cm-2 current density compared to other ratios of 0.5:1 and 1.5:1, which required 290 and 308 mV, respectively. Similarly, in 1 M NaHCO3, NiCoCHH 1:1 required an overpotential of 623 mV to reach 10 mA cm-2. A post-OER study confirmed the formation of NiOOH during OER. The observed faradaic efficiency was nearly 95.21% for the NiCoCHH 1:1 catalyst. A two-electrode setup with NiCoCHH 1:1∥Pt required just 312 mV as an overpotential at 10 mA cm-2. These kinds of comparative studies can be used in other 3d transition-metal-based catalysts for OER in the future.


Money, politics, and medicine: the American Medical PAC's strategy of giving in U.S. house races.
We examine contributions by the American Medical Association's political action committee (AMPAC) to candidates for seats in the U.S. House of Representatives during two electoral cycles (1989-1990 and 1991-1992). In contrast to earlier studies, we do not find any systematic evidence to support the conventional wisdom that AMPAC contributes to influence legislators' positions on roll call votes or that AMPAC's contribution decisions are influenced by legislators' voting positions. We do find that AMPAC contributes to promote access to decision makers and to help elect (or reelect) legislators who would be expected to be more generally sympathetic to the economic and practice concerns of AMA physicians. As points of comparison, we also examine contributions from the top five tobacco PACs and the National Rifle Association's (NRA) PAC and find that legislators' roll call voting positions are strongly related to contributions received from these organizations.


Light induction of phosphoenolpyruvate carboxylase in etiolated maize leaf tissue.
An antibody for phosphoenolpyruvate carboxylase was used to isolate and to quantitate the enzyme from greening maize (cv. KOU 6) leaves. The increase in enzyme activity during greening was due to de novo synthesis, which was paralleled by increases in enzyme protein and incorporation of leucine. The light-induced activity was due to one specific isoenzyme. The action spectrum for enzyme synthesis had red and blue peaks.


Stretching lattice models of protein folding.
A new class of experiments that probe folding of individual protein domains uses mechanical stretching to cause the transition. We show how stretching forces can be incorporated in lattice models of folding. For fast folding proteins, the analysis suggests a complex relation between the force dependence and the reaction coordinate for folding.


Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors.
The precursor protein proopiomelanocortin (POMC) produces many biologically active peptides via a series of enzymatic steps in a tissue-specific manner, yielding the melanocyte-stimulating hormones (MSHs), corticotrophin (ACTH) and beta-endorphin. The gene for alpha-MSH is encoded for by the POMC gene, but alpha-MSH cannot be produced from POMC gene transcription and translation without these specific post-translational proteolytic steps taking place. The MSHs and ACTH bind to the extracellular G-protein-coupled melanocortin receptors (MCR), of which there are five subtypes. Two (MC1R and MC5R) show widespread cutaneous expression. ACTH and alpha-MSH bind to MC1R to influence both pigmentation and the immune system. MC5R regulates the sebaceous glands. Mutations in the MC1R gene lead to fair skin and red hair in humans, which is also seen with inactivating human POMC gene mutations. MC1R mutant receptor expression can also correlate with an increased incidence of the three commonest forms of skin cancer. Other mutations can occur in the POMC system or parallel interacting pathways, such as in prohormone convertase 1 and agouti signalling protein, a human homologue of murine agouti protein. However, they do not necessarily affect skin colour or function in humans, and further studies are needed to clarify these observations.


Stability of microsatellites and minisatellites in Bloom syndrome, a human syndrome of genetic instability.
Bloom syndrome (BS) is a human cancer-prone genetic disorder essentially characterized by a generalized genetic instability including a high level of sister chromatid exchanges (SCEs). Although mutator and hyper-Rec phenotypes of BS cells present analogies with those of bacteria and yeast defective in DNA mismatch repair, we report that (CA)(n) microsatellite alterations are undetectable in BS cells. Thus, our results suggest that the origin of BS mutator phenotype is not a major defect in DNA mismatch repair, allowing us to eliminate an attractive hypothesis for the pleiotropy of BS. We previously suggested that at least some of the intra-allelic rearrangements occurring in minisatellites could result from unequal SCEs. Although SCEs are abnormally frequent in BS cells, the present study failed to show any significant variation of the mutation rates of the two hypermutable minisatellites we analyzed. Thus, our results show that, in spite of an overall genetic instability, alterations in structural motifs known to be predisposed to instability by different mechanisms are undetectable in BS cells.


[Study of the antigenic structure of the E1 glycoprotein of the Venezuelan equine encephalomyelitis virus using monoclonal antibodies].
The collection of eight rat and mouse hybridomas secreting the high affinity monoclonal antibodies to glycoprotein E1 of the Venezuelan equine encephalomyelitis has been obtained. The antigenic structure of E1 protein has been studied with the use of these antibodies for the strains Trinidad, TC-83 and 230 of the virus. Antigenic map of glycoprotein E1 based on competition radioimmunoanalysis is proposed. Five sites are mapped including eight epitopes binding monoclonal antibodies. Antibodies to sites E1-1, E1-3 and E1-5 are crossreactive in interaction with the virus of Venezuelan equine encephalomyelitis, while antibodies to site E1-5 interact also with the virus of tick-borne encephalitis. Antibodies to site E1-1 possess the protective effect and lack the neutralizing effect in tissue cultures. Antibodies to all sites of E1 protein are devoid of ability to neutralize the Venezuelan equine encephalitis virus.


High-performance and flexible thermoelectric films by screen printing solution-processed nanoplate crystals.
Screen printing allows for direct conversion of thermoelectric nanocrystals into flexible energy harvesters and coolers. However, obtaining flexible thermoelectric materials with high figure of merit ZT through printing is an exacting challenge due to the difficulties to synthesize high-performance thermoelectric inks and the poor density and electrical conductivity of the printed films. Here, we demonstrate high-performance flexible films and devices by screen printing bismuth telluride based nanocrystal inks synthesized using a microwave-stimulated wet-chemical method. Thermoelectric films of several tens of microns thickness were screen printed onto a flexible polyimide substrate followed by cold compaction and sintering. The n-type films demonstrate a peak ZT of 0.43 along with superior flexibility, which is among the highest reported ZT values in flexible thermoelectric materials. A flexible thermoelectric device fabricated using the printed films produces a high power density of 4.1 mW/cm(2) with 60 °C temperature difference between the hot side and cold side. The highly scalable and low cost process to fabricate flexible thermoelectric materials and devices demonstrated here opens up many opportunities to transform thermoelectric energy harvesting and cooling applications.


Internal Light Source-Driven Photoelectrochemical 3D-rGO/Cellulose Device Based on Cascade DNA Amplification Strategy Integrating Target Analog Chain and DNA Mimic Enzyme.
In this work, a chemiluminescence-driven collapsible greeting card-like photoelectrochemical lab-on-paper device (GPECD) with hollow channel was demonstrated, in which target-triggering cascade DNA amplification strategy was ingeniously introduced. The GPECD had the functions of reagents storage and signal collection, and the change of configuration could control fluidic path, reaction time and alterations in electrical connectivity. In addition, three-dimentional reduced graphene oxide affixed Au flower was in situ grown on paper cellulose fiber for achieving excellent conductivity and biocompatibility. The cascade DNA amplification strategy referred to the cyclic formation of target analog chain and its trigger action to hybridization chain reaction (HCR), leading to the formation of numerous hemin/G-quadruplex DNA mimic enzyme with the presence of hemin. Subjected to the catalysis of hemin/G-quadruplex, the strong chemiluminiscence of luminol-H2O2 system was obtained, which then was used as internal light source to excite photoactive materials realizing the simplification of instrument. In this analyzing process, thrombin served as proof-of-concept, and the concentration of target was converted into the DNA signal output by the specific recognition of aptamer-protein and target analog chain recycling. The target analog chain was produced in quantity with the presence of target, which further triggered abundant HCR and introduced hemin/G-quadruplex into the system. The photocurrent signal was obtained after the nitrogen-doped carbon dots sensitized ZnO was stimulated by chemiluminescence. The proposed GPECD exhibited excellent specificity and sensitivity toward thrombin with a detection limit of 16.7 fM. This judiciously engineered GPECD paved a luciferous way for detecting other protein with trace amounts in bioanalysis and clinical biomedicine.


Gene therapy for the hemoglobin disorders.
The hemoglobin disorders of beta-thalassemia and sickle cell disease together constitute the most prevalent group of human monogenic diseases. Although curative allogeneic stem cell transplantation therapy and palliative therapies have been developed for these disorders, the majority of patients still suffer significant morbidity and early mortality. The development of therapeutic approaches based on genetic manipulation of autologous stem cells therefore remains an attractive alternative. In the past 4 years, significant advances have been made toward this goal using lentiviral vectors to obtain high-level expression of complex globin gene cassettes. Therapeutic correction in murine models of both beta-thalassemia and sickle cell anemia has been achieved using this approach. These advances, coupled with progress in the ability to achieve in vivo selection of genetically modified cells, can now be evaluated in the well-developed nonhuman primate autologous transplant model. The goal in these studies is to provide preclinical safety and efficacy data prior to human clinical trials in order to maximize the likelihood of success in the context of an acceptable risk to benefit ratio. Here we review progress in each of these areas.


Young children's use of features to reorient is more than just associative: further evidence against a modular view of spatial processing.
Proponents of a geometric module have argued that instances of young children's use of features as well as geometry to reorient can be explained by a two-stage process. In this model, only the first stage is a true reorientation, accomplished by using geometric information alone; features are considered in a second stage using association (Lee, Shusterman & Spelke, 2006). This account is contradicted by the data from two experiments. Experiment 1a sets the stage for Experiment 1b by showing that young children use geometric information to reorient in a complex geometric figure without a single principal axis of symmetry (an octagon). In such a figure, there are two sets of geometrically congruent corners, with four corners in each set. The addition of a colored wall leads to the existence of three geometrically congruent but, crucially, all unmarked corners; using the colored wall to distinguish among them could not be done associatively. In Experiment 1b, both 3- and 5-year-old children showed true non-associative reorientation using features by performing at above-chance levels on all-white trials. Experiment 2 used a paradigm without distinctive geometry, modeled on Lee et al. (2006), involving an equilateral triangle of hiding places located within a circular enclosure, but with a large stable feature rather than a small moveable one. Four-year-olds (the age group studied by Lee et al.) used features at above-chance levels. Thus, features can be used to reorient, in a way not dependent on association, in contradiction to the two-stage version of the modular view.


In vivo anti-inflammatory effect and toxicological screening of Maytenus heterophylla and Maytenus senegalensis extracts.
Maytenus heterophylla (Eckl & Zeyh.) Robson and Maytenus senegalensis (Lam). Exell are two African medicinal plants used to treat painful and inflammatory diseases. We evaluated the in vivo (per os) anti-inflammatory activity of M. heterophylla leaf, stem and root extracts and of M. senegalensis leaf and stem extracts. Additionally, we assessed their in vivo acute and sub-acute toxicities. Anti-inflammatory activities of ethanol extracts were determined in Wistar albino rats, by the carrageenan-induced paw oedema method. Acute and sub-acute toxicity screening of the extracts was evaluated in adult male CD-6 mice. Leaf extracts of M. heterophylla and M. senegalensis exhibited significant anti-inflammatory activity (120 mg/kg, per os), reducing oedema by 51% and 35%, respectively. While M. heterophylla extracts at 1200 mg/kg have shown to be non-toxic, M. senegalensis extracts indicated some toxicity. Our results show a significant anti-inflammatory effect of both M. heterophylla and M. senegalensis leaf extracts in a local model of acute inflammation and suggest the absence of acute and sub-acute toxicity signs of the M. heterophylla leaf extract (but not of M. senegalensis). Ongoing studies will surely shed some light into the mechanism of action of this active extract and establish its chemical fingerprint.


Conformational propensities and residual structures in unfolded peptides and proteins.
Ample evidence gathered over the last ten years indicates that unfolded and naturally disordered proteins and peptides can show local order in that short segments can adopt turn or polyproline II-like conformations. These findings show that unfolded states cannot be described by the so-called random coil model which assumes that individual amino acid residues sample the entire sterically accessible parts of the Ramachandran with very similar probabilities. This article reviews the experimental evidence for the notion that amino acid residues have different propensities for polyproline II, β-strand, helical and turn conformations in water. These propensities are changed by interactions with nearest neighbours. We show that for a substantial number of residues the conformational propensities in the unfolded state correlate with values for helix propagation and the Chou-Fasman propensities for β-strands. Based on the presented results we hypothesize that the conformational distributions of a representative set of short peptides could be used for predicting structural distributions of disordered peptides and proteins in the future.


Rapid Detection of Equine Piroplasms Using Multiplex PCR and First Genetic Characterization of Theileria haneyi in Egypt.
Equine Piroplasmosis (EP) is an infectious disease caused by the hemoprotozoan parasites Theileria equi, Babesia caballi, and the recently identified species T. haneyi. Hereby, we used a multiplex PCR (mPCR) targeting the 18S rRNA gene of T. equi and B. caballi for the simultaneous detection of EP in Egyptian equids and examined the presence of T. haneyi infections in Egypt. Blood samples from 155 equids (79 horses and 76 donkeys) collected from different governorates of Egypt were examined by mPCR and PCR targeting T. hayeni. The mPCR method revealed a prevalence of T. equi of 20.3% in horses and of 13.1% in donkeys and a prevalence of B. caballi of 1.2% in horses. B. caballi was not detected in donkeys in the current study. The mPCR method also detected coinfections with both species (2.5% and 1.3% in horses and donkeys, respectively). Additionally, we report the presence of T. haneyi in Egypt for the first time in 53.1% of the horse and 38.1% of the donkey tested samples. Coinfection with T. haneyi and T. equi was found in 13.5% of the samples, while infection with the three EP species was found in 1.9% of the samples.


[Perivascular tissue vibrations: a criterium for high-grade stenoses of the internal carotid artery].
Perivascular tissue vibrations, an artefact of the colour Doppler method, are already known to be a sonographic sign of stenosis but have not yet been investigated systematically in the examination of the internal carotid artery. The present study is intended to assess the value of this artefact in the diagnosis of stenosis of the internal carotid artery. A total of 167 consecutive cases including a stenosis of the internal carotid artery of at least 50% were diagnosed according to the usual haemodynamic criteria using Doppler and duplex sonography and classified into 10% categories. Intermediate groups were formed for findings that could not be assigned unambiguously. By means of suitable apparatus settings each finding was examined to test whether a perivascular colour artefact was detectable. In the stenosis categories of 50% to 70% no perivascular colour artefact was found, whereas in the stenosis categories of 80% to 90% this was the case in 80% of the findings, and in the intermediate 75% category in 42% of the findings. The perivascular colour artefact was recognizable even under poor sonographic conditions. When a perivascular colour artefact is seen the diagnosis of a high-degree stenosis (or an AV fistula) is certain. The phenomenon is particularly valuable as a supplementary criterion of stenosis in cases of unfavourable sonographic conditions. However, the perivascular colour artefact may only be used to confirm, but never to exclude, a high-degree stenosis.


Cocaine alters the respiratory burst and phagocytic activity of murine macrophages.
The effects of cocaine on the respiratory burst (RB) and the phagocytic activity of murine macrophages (M phi) were studied. C57BL/6 mice were injected intraperitoneally with various concentrations of cocaine or appropriate vehicle. Peritoneal and alveolar M phi were isolated from mice and cultured in vitro. Both alveolar and peritoneal M phi from cocaine-exposed mice exhibited an increase in the RB when compared with M phi from saline-injected controls. This increase in the RB was apparent 60 min after injection and persisted for at least 48 hr. Injection of the cocaine metabolites, ecgonine methyl ester hydrochloride and ecgonine hydrochloride, did not affect the RB. The increase in the RB was correlated with an increase in phagocytosis of opsonized zymosan in vitro. However, an in vivo phagocytic assay using mice injected ip with cocaine, which was subsequently followed by sheep erythrocytes, demonstrated the opposite effect. Fewer peritoneal M phi from cocaine-injected mice were observed with ingested erythrocytes. These data underscore the complex effects of cocaine on M phi functions.


Complex regional pain syndrome patient treated with a below knee amputation, implanting nerves directly into muscle: A case report.
Persistent, disabling lower extremity pain, outside the distribution of a single nerve, is termed chronic regional pain syndrome (CRPS), but, in reality, this chronic pain is often due to multiple peripheral nerve injuries. It is the purpose of this report to describe the first application of the "traditional," nerve implantation into muscle, usually used in the treatment of a painful neuroma, as a pre-emptive surgical technique in doing a below knee amputation (BKA). In 2011, a 51-year-old woman developed severe, disabling CRPS, after a series of operations to treat an enchondroma of the left fifth metatarsal. When appropriate peripheral nerve surgeries failed to relieve distal pain, a BKA was elected. The approach to the BKA included implantation of each transected peripheral nerve directly into an adjacent muscle. At 5.0 years after the patient's BKA, the woman reported full use of this extremity, using the prosthesis, and was free of phantom limb and residual limb pain. This anecdotal experience gives insight that long-term relief of lower extremity CRPS can be achieved by a traditional BKA utilizing the approach of implanting each transected nerve into an adjacent muscle.


Important disease conditions of newly cultured species in intensive freshwater farms in Greece: first incidence of nodavirus infection in Acipenser sp.
We describe here the main pathological conditions of freshwater fish recently introduced for intensive rearing (open ponds and recirculating freshwater systems) in Greece. Sturgeon were susceptible to skeletal abnormalities of the spine (scoliosis and lordosis) of unknown aetiology. Horizontal transmission of nodavirus from infected sea bass to sturgeon was detected for the first time. This caused serious pathology and clinical signs, such as lethargy and imbalance, leading to secondary infections with Aeromonas hydrophila and Trichodina sp. and chronic, but steady, mortality. Sea bass were very susceptible to nodavirus infection, monogenean infections and gas bubble disease. Mullet reared under recirculated and open-flow conditions were very sensitive to Chilodonella sp. infection, whereas catfish were susceptible to infection with Ichthyophthirius sp. leading to secondary infections with A. hydrophila, Saprolegnia sp. and Myxobacteria spp. Tilapia were very susceptible to gas bubble disease and A. hydrophila. This bacterium was associated with management manipulations for all species and fully responsive to corrective hygiene methods.


Posttraumatic Delayed Jugular Foramen Syndrome in a Toddler.
Multiple lower cranial nerve palsies have been attributed to occipital condyle fractures in older children and adults, but no clinical details of other possible mechanisms have been described in infants. A 33-month-old boy suffered blunt head trauma. A bilateral skull base fracture was diagnosed, with favorable outcome during the first days after trauma. On the sixth day, the patient began to refuse drinking and developed hoarseness. Physical examination and additional investigations revealed paralysis of left VII, IX, X, and XI cranial nerves. A follow-up computed tomography (CT) scan disclosed a left petrous bone fracture involving the lateral margin of the jugular foramen, and a cranial magnetic resonance imaging (MRI) study showed a left cerebellar tonsil contusion. He improved after methylprednisolone was started. Three months later, he was asymptomatic, although mild weakness and atrophy of the left sternocleidomastoid and trapezius muscles remained 1 year later. A posttraumatic "jugular foramen syndrome" is rare in children, but it has been reported shortly after occipital condyle fracture, affecting mainly IX, X, and XI cranial nerves. In this toddler, delayed symptoms appeared with unilateral involvement. While an occipital fracture was ruled out, neuroimaging findings suggest the hypothesis of a focal contusion as a consequence of a coup-contrecoup injury. This exceptional case highlights the importance of gathering physical examination, anatomical correlation, and neuroimaging to yield a diagnosis.


No loss of chance of diabetic retinopathy screening by endocrinologists with a digital fundus camera.
To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance." In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of "loss of chance," i.e., missed diagnoses that required ophthalmologist referrals. The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training. The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.


The role of heterologous nifAc product in the regulation of nif expression in Agrobacterium tumefaciens.
The plasmids pCK5, pCK3, pSZ36, and pSZ23-CA, which carried constitutive nifAc gene of Azotobacter chroococcum and Klebsiella pneumoniae were transferred into A. tumefaciens C58/pGV3850 with triparental mating. The growth rate of these transconjugants was similar to the wild type. Nitrogenase synthesis was demonstrated by Western blotting, in the presence of 10 mmol/L NH4+, and the nitrogenase activity was restored to 73%, 24%, 11%, and 62%, respectively. The results showed that the regulative gene of nitrogen fixation in A. chroococcum and K. pneumoniae played a regulative role for the expression of A. tumefaciens nitrogen fixation gene. Among them, the role of A. chroococcum nifAc gene was the strongest, the fusion plasmid pSZ23-CA which carried nifA-ntrC gene of K. pneumoniae was stronger, and the nifAc gene of K. pneumoniae was weak.


Synergistic enhancement of MRI with Gd-DTPA and magnetization transfer.
Magnetization transfer (MT) between protons of macromolecules and protons of water molecules is a recently introduced mechanism for tissue contrast in MR imaging. The MT effect is strong in tissues where there is an efficient cross relaxation between macromolecular protons and water protons and where this interaction is the dominant source of relaxation. Paramagnetic ions shorten relaxation times and decrease the MT effect. These two facts led to the assumption that, in the case of contrast enhanced MRI, the combination of the T1-weighted imaging method and the MT technique may yield increased contrast, compared with standard methods. The synergistic effect is demonstrated in this work with studies of egg white samples and by imaging three patients with different brain pathologies. The lesion-to-white matter contrasts, with standard T1-weighted sequences with and without the MT effect, were compared before and after the introduction of Gd-DTPA. In each case the synergistic effect of T1 weighting and MT improved the contrast enhancement provided with Gd-diethylenetriamine pentaacetic acid.


[Case report: facial skin metastasis from rectal adenocarcinoma].
This case report describes an 82 year old male who sought medical attention for changes in bowel habits. Colonoscopy revealed a tumor located 10 to 15cm from the anus. Biopsy showed signetring cell adenocarcinoma. The tumor was not resected due peritoneal dissemination and a tumor invasion into the urinary bladder, found intraoperatively. During hospital stay a skin lesion of the face was removed at the request of the patient. Biopsy showed metastatic signetring adenocarcinoma. Colorectal metastatic lesions to the skin are rare findings, especially metastasis to the face. Skin examination in patients with suspected or known malignancies is an important part of the clinical examination. Key words: Rectal cancer, metastases, skin.


Transsexualism in Hindu Mythology.
In spite of India showing progress in various medical, economic and social fronts, the care of the transgender individual is still encumbered by the various biases and taboos that people hold. But, this was not true in the antiquity. Hindu mythology holds transgender individuals in a status equal to other genders. This brief review of the various references of transgender individuals in Hindu mythology throws light on the various ways the topic of transsexualism and changing gender was addressed.


Drift Reduction in Pedestrian Navigation System by Exploiting Motion Constraints and Magnetic Field.
Pedestrian navigation systems (PNS) using foot-mounted MEMS inertial sensors use zero-velocity updates (ZUPTs) to reduce drift in navigation solutions and estimate inertial sensor errors. However, it is well known that ZUPTs cannot reduce all errors, especially as heading error is not observable. Hence, the position estimates tend to drift and even cyclic ZUPTs are applied in updated steps of the Extended Kalman Filter (EKF). This urges the use of other motion constraints for pedestrian gait and any other valuable heading reduction information that is available. In this paper, we exploit two more motion constraints scenarios of pedestrian gait: (1) walking along straight paths; (2) standing still for a long time. It is observed that these motion constraints (called "virtual sensor"), though considerably reducing drift in PNS, still need an absolute heading reference. One common absolute heading estimation sensor is the magnetometer, which senses the Earth's magnetic field and, hence, the true heading angle can be calculated. However, magnetometers are susceptible to magnetic distortions, especially in indoor environments. In this work, an algorithm, called magnetic anomaly detection (MAD) and compensation is designed by incorporating only healthy magnetometer data in the EKF updating step, to reduce drift in zero-velocity updated INS. Experiments are conducted in GPS-denied and magnetically distorted environments to validate the proposed algorithms.


Association Between Behavioral Dysexecutive Syndrome and the Health-Related Quality of Life Among Stroke Survivors.
Behavioral dysexecutive syndrome (BDES) is one common neuropsychiatric comorbidity after stroke. Despite evidences suggesting the adverse effect of BDES on the survivors' outcome, little is known about the association between BDES and the health-related quality of life (HRQoL) among stroke survivors and how BDES impacts the HRQoL. This study aimed to address these questions. This study included 219 patients with acute ischemic stroke consecutively admitted to a regional hospital in Hong Kong. BDES was defined as a Chinese version of the Dysexecutive Questionnaire (DEX) score of ≥20 assessed at three months after stroke. The HRQoL was assessed with the Chinese version of the Stroke-Specific Quality of Life (SSQoL) questionnaire encompassing 12 domains. Multivariate linear regression models were employed to examine the association between BDES symptoms and the SSQoL total and domain scores. Structural equation model (SEM) was further constructed to delineate the linking pathways linking BDES and the HRQoL. The study sample compromised mainly older patients with mild to moderate ischemic stroke. Compared with patients without BDES, those with BDES exhibited poorer performances regarding with the summarized SSQoL (226.2 ± 18.8 vs. 200.3 ± 29.8, p < 0.001) and almost all domains. The BDES symptoms were independently contributed to the whole HRQoL (SSQoL total score) (β = -0.20, p = 0.002), specifically to the domains in personality (β = -0.34, p < 0.001), language (β = -0.22, p = 0.01), and work/productivity (β = -0.32, p < 0.001), after adjusting demographic and clinical characteristics in linear models. The impacts of the BDES symptoms on the HRQoL were mainly explained by the indirect path mediated by depression and anxiety (path coefficient = -0.27, p < 0.05) rather than physical disability, while the resting was elucidated by the path directly linking BDES to the HRQoL (path coefficient = -0.17, p < 0.05). The present study preliminarily demonstrated a potential association between BDES and a lower level of the HRQoL, predominantly in domains of personality, language, and work/productivityafter acute ischemic stroke. This study also offered insights into the underlying mechanisms linking BDES and the HRQoL, implicating that integrative psychological therapies were urged to achieve better HRQoL after stroke.


A Unique Case of Erdheim-Chester Disease With Cervical and Lumbosacral Nerve Involvement: FDG PET/CT Finding.
Cervical and lumbosacral nerve roots and plexus involvement in Erdheim-Chester disease (ECD) is rare. A 50-year-old man with progressive edema in bilateral lower extremities, numbness, weakness, and muscle atrophy of upper limb for 2 years had been misdiagnosed of neuritis or cervical spondylosis until he presented bone pain. In addition to bilateral symmetric involvement in long bones, bilateral hypermetabolism in cervical and lumbosacral nerve roots was found by FDG PET/CT scan. ECD was diagnosed by bone biopsy. This case reported the rare peripheral neural involvement and highlighted the advantage of FDG PET/CT scan in evaluating the multisystem involvement of ECD.