Levels of polychlorinated biphenyls and organochlorine pesticides in serum samples of Egyptian Vulture (Neophron percnopterus) from Spain.
Concentrations of 23 polychlorinated biphenyls (PCBs), p,p'-DDT and two of its metabolites, p,p'-DDE and p,p'-TDE have been measured in serum samples of up to 1 ml of Egyptian Vulture (Neophron percnopterus) gathered from five populations in Spain. SigmaPCB concentrations were found to be in the range 3.2-97 ng/ml, while those of SigmaDDTs ranged from 0.93 to 38 ng/ml. p,p'-DDT/p,p'-DDE ratios higher than one were only found in the Segovia population, which could be an indication of recent use of p,p'-DDT in the area. In all cases, PCB profiles were dominated by congeners 52, 132 + 105, 138, 153 and 180. However, some differences among the five populations studied became evident when their profiles were compared with those of technical PCB mixtures by principal components analysis. The DDT and PCB levels detected in the serums analysed were lower than those previously reported for similar avian species and those reported to have deleterious effects on survival or reproduction of birds.


Expansion of stimulus-evoked metabolic activity in monkey somatosensory cortex after peripheral denervation.
The 2-deoxy-glucose (2DG) technique was used to study changes in stimulus-evoked metabolic activity in the somatosensory cortex of the squirrel monkey Saimiri sciureus after unilateral digit amputation. Two to 52 weeks after digit 2 on the left hand was removed, a somatic stimulus was applied to digit 3 bilaterally. In area 3b corresponding to the deafferented side of the brain, the area of stimulus-evoked metabolic activity was greater than that on the opposite, control side of the brain within the same animal. The extent of the topographic projection map of 2DG label in area 3b on the deafferented side of the brain was 1.92 to 4.75 times greater than that on the control side. There was no difference, however, in the topographical area of stimulus-evoked metabolic activity between the left and right somatosensory cortices in a normal, unoperated animal. These data suggest that the changes in functional organization observed using electrophysiological recordings in somatosensory cortex after peripheral denervation may have a metabolic substrate.


In vitro inhibition of Streptococci binding to enamel acquired pellicle by plant lectins.
Initial colonization of the tooth surface by streptococci involves the attachment of these bacteria to adsorbed salivary components of the acquired pellicle. In dental biofilm this adhesion may also involve lectin-like components, present on the surface of the organisms, which bind to complementary carbohydrates on the surface of the tooth. Therefore, this work aimed to evaluate the potential of six lectins, extracted from seeds of Leguminosae family members, to inhibit the adherence of five streptococci species to acquired pellicle in vitro. The lectins used in this work were extracted from Canavalia ensiformis, Canavalia brasiliensis, Dioclea violacea, Dioclea grandiflora, Cratylia floribunda and Vatairea macrocarpa. Fluorescence micrography was employed to visualize the ability of FITC-labeled lectins to attach to acquire pellicle. Adherence inhibition was performed on saliva-coated microtiter plates at which lectins solutions were previously incubated followed by incubation with the oral streptococci. Glucose-mannose specific lectins attached to acquired pellicle with high intensity, while galactose specific lectins, from V. macrocarpa, exhibits low intensity attachment. All lectins were able to inhibit the adherence of the microorganisms tested (p < 0.01). Our results suggest that lectins may be useful in anti adhesion therapeutics.


Positive association between the plasma levels of 5-hydroxyindoleacetic acid and the severity of depression in patients with chronic obstructive pulmonary disease.
The role of plasma monoamines in patients with chronic obstructive pulmonary disease (COPD) with depression is unclear. To investigate monoamines in 20 depressed patients with COPD, the plasma concentrations of serotonin, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured and compared with those in 50 non-depressed COPD patients, and also with 23 age- and gender-matched non-smokers and 13 smokers as non-depressed healthy controls. Diagnosis of depression was assessed using the Centre for Epidemiologic Studies Depression Scale. Plasma concentrations of monoamines were measured by high-performance liquid chromatography. None of the depressed COPD patients had suicidal ideation. The plasma 5-HIAA level [median, (25% and 75% quartiles)] in depressed COPD patients [6.8 ng/mL, (4.9 and 13.1)] was significantly higher than in non-depressed COPD patients [5.4, (4.2 and 7.5)] (p=0.022) and non-smokers [5.1 (3.8 and 7.2)] (p=0.041), but not smokers [4.7, (4.0 and 6.7)] (p>0.05). The plasma 5-HIAA level (r=0.24, p=0.049) was significantly associated with the severity of depression in patients with COPD. The plasma MHPG level was significantly higher in depressed COPD patients (p=0.043) than in smokers, but was not higher than that in non-depressed COPD patients or non-smokers, although the level of MHPG was not associated with the severity of depression. The plasma 5-HIAA level is increased in depressed COPD patients. Plasma monoamines may be a good biomarker for detection of depression in patients with COPD.


In vivo and in vitro binding of epichlorohydrin to nucleic acids.
Epichlorohydrin (EC) binds to macromolecules of biological relevance in vivo: DNA is less labelled than RNA and proteins, rat organs interact more than mouse organs, stomach is the most labelled organ with liver, kidney and lung involved in decreasing order. Based on the Covalent Binding Index (CBI), EC is a weak-moderate oncogen, just as other chlorinated hydrocarbons such as 1,2-dichloroethane and carbon tetrachloride. An interaction of EC with nucleic acids (DNA and polyribonucleotides) occurs also in vitro. It is mediated either by chemical reactivity per se of the molecule (near-UV (NUV) irradiation does not photoactivate EC) and by enzymatic (microsomal and/or cytosolic) fractions, whose relative effectiveness is variable in relation to the organ tested. The best substrates for interaction are poly(G) and poly(A) when using microsomal and cytosolic fractions, respectively, whereas the labelling of double-stranded DNA is always lower. On the whole, the picture of enzyme (microsome + cytosol)-mediated in vitro interaction is similar to the pattern of in vivo binding, with the exception of rat stomach enzymes which are inactive in vitro.


Dual effect of initial [K] on vascular tone in rat mesenteric arteries.
A slight increase in extracellular concentration of potassium ([K(+)](o)) can act as a vasodilator in rat mesenteric vascular bed. However, in recent years, several groups have failed to consistently observe relaxation of rat mesenteric arteries in these conditions. The aim of the present study was to provide a mechanistic understanding of this discrepancy. In rat small mesenteric arteries, 37 of 40 arteries mounted for measurement of isometric force and pre-contracted with phenylephrine (PE) did not relax when ([K(+)](o) was raised from 5.9 mM (control ([K(+)](o) to 11.2 or 21.2 mM. However, when ([K(+)](o) was briefly lowered to 1.2 mM, increasing ([K(+)](o) to between 5.9 and 41.2 mM evoked relaxation. This relaxation was not reduced by barium or by removal of the endothelium, but was abolished by 0.1 mM ouabain. Raising ([K(+)](o) from concentrations between 0 and 5.9 mM to 13.8 mM elicited a relaxation of PE-induced tone that was inversely proportional to initial ([K(+)](o). Relaxation was associated with a ouabain-sensitive hyperpolarization of smooth muscle cells. In arteries exposed to dihydroouabain (DHO), raising ([K(+)](o) from 5.9 to 13.8 mM and simultaneously washing out DHO resulted in relaxation of PE-induced force. These results suggest that only when the initial ([K(+)](o) is less than approximately 5 mM do small elevations in ([K(+)](o) evoke smooth muscle hyperpolarization and relaxation via activation of Na,K-ATPase, and not inwardly rectifying K(+) channels. Therefore, small differences in the initial ([K(+)](o) (4.6 vs 5.9 mM) can strongly influence the variations of vascular tone to increases in ([K(+)](o).


The influence of temperature on the duration of egg development in West European grasshoppers (Orthoptera: Acrididae).
The relationship between embryonic postdiapause development (PDD) and temperature in ten Acridid species was studied by culturing eggpods from diapause onwards at constant temperatures (ranging from 15.0° C to 37.5° C). In six species PDD was also studied at fluctuating temperatures (12 h at 27.5° C and 12 h at 13.0° C). The PDD duration was strongly temperature dependent in all species studied (Q10 values between 3.0 and 4.1) and differed greatly between species. To assess whether these differences affect habitat determination, PDD duration was related to habitat microclimate. We found that species with a relatively long PDD are restricted to relatively warm grasslands, while species with a short PDD are also found in colder grasslands. Two species have a more limited occurrence than predicted from PDD duration. It is argued that the length of PDD (and consequently hatching date) is crucial to the completion of the annual cycle. The results are applicable to conservation of grasshoppers in grasslands subject to eutrophication. Here increase of vegetation density and height will lead to lower maximum temperatures in the egg environment (i.e. near the soil surface) and consequently to a delay in hatching and loss of thermophilous species. Grassland management rules are proposed that should aid conservation of these species.


A case of blue rubber bleb nevus syndrome with coronary artery fistula to left ventricle.
A 69-year-old female was admitted to the hospital because of tarry stool and dyspnea on exertion. Multiple hemangiomas were noticed on the tongue, right arm and abdomen. Gastrointestinal examination revealed multiple polypoid lesions in the stomach and small intestine. In addition, coronary artery-left ventricular fistula formation and pulmonary arteriovenous malformation were shown by angiography. Compared with other reported cases of blue rubber bleb nevus syndrome, the present case was unique because of the coronary artery-left ventricular fistula, heart failure and the familiar incidence of heart failure.


Comparison of hepatic and nephric total mercury concentrations between feral and ranch American mink (Neovison vison) from northwestern Poland.
For many years the American mink (Neovison vison) has been used in North America (where it originates from) as a sensitive indirect bioindicator in assessing the degree of mercury (Hg) contamination in terrestrial ecosystems. The aim of this paper was the determination of total concentrations of Hg in the liver and kidneys of feral and ranch mink from the Warta Mouth National Park (WMNP) and from farms located in northwestern Poland, for comparison with similar data on American mink from North America. In road-killed feral mink from the WMNP, the mean concentrations were 11.8 and 14.1 mg/kg dry weight in the liver and kidney, respectively. Mean Hg concentrations in feral mink were from 240 to 90 times higher in these two respective tissues than in ranch mink. The feral mink from northwestern Poland had concentrations of hepatic and nephric Hg similar to the highest concentrations that have been recorded over the past several decades in wild American mink from certain areas of Canada and the USA.


Managing OR revenue under new payment models.
Five elements have helped Advocate Lutheran General Hospital control the surgical quality, safety, and cost outcomes that are the focus of new payment models: Single-path scheduling, Document management, Presurgical testing, A daily huddle, Surgical safety initiative.


Polaronic state of conducting oligomer as a new approach to design non-lieaner optical materials: A case study of oligofurans.
The geometric, electronic and nonlinear optical properties of neutral and polaron based oligofurans are studied comparatively. We have reported the role of polaron to trigger the nonlinear optical response of oligofurans (nFu). The polaron based oligomers show excellent opto-electronic properties. The effect of polaron on nFu* chains is measured by electronic properties i.e (ionization energy, electron affinity, band gap) and global reactivity descriptors like softness, hardness and chemical potential than their neutral counterpart. An interesting trends of reactivity descriptors have been observed. Lower band gaps (EH-L = 4.66 and 4.41 eV) are observed for polaronic systems as compared to their neutral counterpart. On the other hand, the TD-DFT study further demonstrated that, as the size of chain increases, the absorption maxima (λmax) also increases with significant reduction in excitation energies (ΔE). Furthermore, the nonlinear optical response is confirmed through the linear polarizability (αo), static first order hyperpolarizability (βo) and dynamic (frequency denepndent) hyperpolarizability. Electric filed induced second harmonic generation (EFISHG) and electro-optic pockle effect (EOPE) at 532 nm and 1064 nm, commonly used lasers frequencies have also been employed. Our results showed that the maximum hyperpolarizabilities are observed for polaron based 7Fu* and 9Fu* i.e 1.3 × 104, and 3.1 × 104 au. This study concluded that these polaron based organic polymers (nFu*) are useful as an efficient NLO material with vast applications in different fields.


The social and health protection of migrants in Chile: qualitative analysis of civil society proposals for constitutional change.
A sustained period of social, economic, and political unrest took place during October of 2019 in Chile. As an institutional solution, the "Agreement for Social Peace and the New Constitution" was signed. In this document, most political parties committed to reestablishing peace and public order in Chile, agreeing on the initiation of a constitutional process. To promote participation of civil society actors, the "Popular Initiative for Norms" was enabled. This was a platform where civilians could submit proposals for constitutional norms to be discussed by the Constitutional Convention. We aimed to analyze proposals related to migrants and migrant health. We conducted a qualitative thematic analysis of the proposals. Sixteen of them were related to migrants, and we analyzed their association to health. We also evaluated their link to the Health Goals 2030 set out by the Chilean Ministry of Health and the Global Action Plan 2019-2023 for Promoting the Health of Refugees and Migrants by the World Health Organization. Four main thematic categories were identified: 1) Humans rights of migrants, refugees, and asylum seekers; 2) Nationality and regularization of migrants and refugees; 3) Political participation and cultural integration of migrants and refugees; and 4) Specific regulations on slavery and human trafficking. These resonated with broader frameworks established in the Health Goals 2030 (Chile) and the Global Action Plan 2019-2023 for Promoting the Health of Refugees and Migrants by the World Health Organization. The 'Popular Initiative for Norms' was a non-binding participatory mechanism. Although the proposals sent through were not guaranteed to be included in the constitutional draft-and despite the final draft being rejected last September 2022-the platform allowed to gain insights into civilian opinions. Our findings showed that there is an incipient yet weak recognition of the rights and situation of migrants in Chile. There was no direct mention of health nor an explicit contemplation of social determinants of health. Despite there being an urgent need to define strategies for migrants' health in Chile, this study demonstrated that civil awareness and interest are still insufficient.


Interaction of lipoprotein lipase with phospholipid vesicles. Role of apolipoprotein C-II and heparin.
Lipoprotein lipase is bound to heparin-like molecules at the surface of capillary endothelial cells. For maximal activity, the enzyme requires apolipoprotein C-II, a protein constituent of triacylglycerol-rich lipoproteins. In this report, the interactions of apolipoprotein C-II, heparin and sonicated vesicles of dipalmitoylphosphatidylcholine with purified bovine milk lipoprotein lipase were studied by gel filtration on Bio-Gel A5m. In the presence of vesicles of dipalmitoylphosphatidylcholine (1 mg), lipoprotein lipase (25 micrograms) associated with phospholipids even in the absence of apolipoprotein C-II. With limited phospholipid (40 micrograms), the amount of enzyme which associated with lipid decreased in the presence of apolipoprotein C-II (20 micrograms). Human plasma apolipoprotein C-III, another protein constituent of triacylglycerol-rich lipoproteins, also caused a decrease in the amount of enzyme associated with phospholipid. These results suggest that apolipoprotein C-II does not increase the activity of the enzyme by facilitating its interaction with a lipid interface. In the absence of lipid, lipoprotein lipase and apolipoprotein C-II (molar ratio, 1 : 1) eluted from Bio-Gel A5m as two separate components. The interaction of heparin with lipoprotein lipase was studied using a specific [3H]heparin, which was isolated by affinity chromatography on immobilized lipoprotein lipase; the [3H]heparin eluted with 0.6 M NaCl. Specific [3H]heparin coeluted with lipoprotein lipase when the enzyme was associated with phospholipid; the [3H]heparin was released from the enzyme by 0.75 M NaCl.


Ontogenetic ritualization of primate gesture as a case study in dyadic brain modeling.
This paper introduces dyadic brain modeling - the simultaneous, computational modeling of the brains of two interacting agents - to explore ways in which our understanding of macaque brain circuitry can ground new models of brain mechanisms involved in ape interaction. Specifically, we assess a range of data on gestural communication of great apes as the basis for developing an account of the interactions of two primates engaged in ontogenetic ritualization, a proposed learning mechanism through which a functional action may become a communicative gesture over repeated interactions between two individuals (the 'dyad'). The integration of behavioral, neural, and computational data in dyadic (or, more generally, social) brain modeling has broad application to comparative and evolutionary questions, particularly for the evolutionary origins of cognition and language in the human lineage. We relate this work to the neuroinformatics challenges of integrating and sharing data to support collaboration between primatologists, neuroscientists and modelers that will help speed the emergence of what may be called comparative neuro-primatology.


Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma.
Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged ≥ 12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 µg (2 inhalations × 90 µg/inhalation) 4 times/day for 12 weeks. In the 40-week open-label phase of the 52-week safety study, patients received albuterol MDPI 180 μg (2 inhalations × 90 μg/inhalation) as needed (PRN). During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of β2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (≤ 1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. The safety profile of albuterol MDPI 180 μg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma.


A review of pharmacological agents for self-injurious behavior.
1. The clinical literature regarding the effects of various psychotropic agents on self-injurious behavior is reviewed. Anecdotal reports, open trials and controlled studies are each reviewed. 2. The absence of controlled studies and the failure to distinguish self-injurious behaviors from other forms of aggression are highlighted. 3. However, the review does raise the possibility that a wide range of agents may be useful for treating self-injurious behaviors and these appear to be similar to the agents used to treat other forms of aggression.


Identification of spinal motoneurones in the weakly electric fish, Eigenmannia virescens.
The motoneurones of the spinal cord in the weakly electric fish, Eigenmannia virescens, were investigated by light microscopical observations. For identification of motoneurones HRP injections were made: (1) in the electric organ, (2) in different parts of the trunk muscle, and (3) in the muscle of the anal fin. When the spinal cord was considered in transverse section: (1) labelled cells (EMN), 20-25 micron, were observed in the first case in the dorsal grey between the central canal and dorsal border of the spinal cord; (2) in the second case, labelled cells (MN1), 35-40 micron, were found in the central grey ventro-laterally, in close vicinity of the ependymal canal; (3) in the last case, labelled cells (MN2), 18-20 micron, were seen in the ventro-lateral part of the anterior horn. When the spinal cord was considered in longitudinal sections, EMNs and MN1 constitute a continuous column along the spinal axis, whereas MN2 show a metametric distribution. The 3 groups of motor cells can be identified in the spinal cord for the whole length of the anal fin, whereas the MN1 and MN2 disappear at the level of the caudal peduncle. The 3 cell types bear dendritic processes; the EMN thin ones and the MN1 and 2 rather large ones. The results indicate that distinct cell groups innervate the electric organ (EMN), the large muscles of the trunk (MN1) and those of the anal fin (MN2).


Dissociation of aggregated ferroheme complexes and protoporphyrin IX by water-soluble polymers.
The ferroheme-pyridine complex, ferroheme and protoporphyrin IX form the aggregates by the hydrophobic interaction in aqueous solutions. We found by spectrophotometric and fluorometric measurements that the aggregates dissociated into the monomers by the addition of water-soluble polymers, such as, poly(ethyleneoxide), poly(vinylalcohol), poly(vinylpyrrolidone) and poly(styrene sulfonate). The dissociation by the polymers proceeded as their hydrophobicities increased. The aggregated ferroheme was effectively dissociated by the copolymers of 4-vinylpyridine which were water-soluble polymer-ligands.


Impact of renal function on coronary plaque morphology and morphometry in patients with chronic renal insufficiency as determined by intravascular ultrasound volumetric analysis.
The aim of the present study was to use intravascular ultrasonography (IVUS) to assess plaque morphology and morphometry in patients with varying degrees of chronic renal insufficiency, including end-stage renal disease (ESRD) on dialysis replacement. Cardiovascular disease is the main cause of death for patients with chronic renal insufficiency, particularly in patients with ESRD. The impact of several degrees of renal insufficiency (including ESRD) on coronary plaque characteristics has not been determined. A total of 142 patients who underwent IVUS imaging of a de novo native coronary artery stenosis before percutaneous intervention were matched for age, gender, and diabetes and were grouped according to calculated creatinine clearance (CrCl): CrCl >70 ml/min (n = 39); CrCl 50 to 69 ml/min (n = 41); CrCl <50 ml/min, (n = 37), and ESRD (n = 25). Standard clinical, angiographic, and IVUS parameters were measured. The ESRD group had more African-American (p = 0.002) and hypertensive (p = 0.002) patients. No significant difference was found in any of the IVUS measurements among patients with CrCl >70, 50 to 69, and <50 ml/min: reference and lesion site arterial, lumen, and plaque areas and volumes, and arterial calcium (p = NS for all comparisons). Conversely, patients with ESRD had larger reference segment arterial and lumen areas and volumes; larger lesion site arterial, lumen, and plaque areas; and larger arcs of calcium (p <0.05 for all post hoc comparisons between patients with ESRD and patients with CrCl >70, 50 to 69, and <50 ml/min). Thus, chronic renal insufficiency in the absence of dialysis is not associated with increased reference segment or lesion site plaque burden and calcium. However, the transition to the need for dialysis is associated with progressive calcific atherosclerosis (larger lesion plaque area and calcium).


Disseminated BCG infection revealing a severe combined immunodeficiency: A case report.
Bacillus Calmette Guerin (BCG) vaccine, which is administered to all newborns in Tunisia, can lead to serious complications ranging from local disease to disseminated disease in a group of patients with primary immunodeficiency diseases. A 3-month-old boy presented with persistent fever, hepato-splenomegaly and multiple osteolytic lesions. He was diagnosed with severe combined immunodeficiency disease and disseminated BCG infection. Despite anti-tubercular therapy combined with intravenous immunoglobulin, the evolution was fatal. The case highlights the possible risk of such rare yet lethal complication of BCG vaccine. In suspected cases of primary immunodeficiency disease, inoculation of BCG should be postponed until appropriate screening tests exclude such diagnosis to prevent serious complications.


Accuracy of epidermal growth factor receptor gene mutation analysis by direct sequencing method based on small biopsy specimens from patients with non-small cell lung cancer: analysis of results in 19 patients.
The importance of an epidermal growth factor receptor (EGFR) gene mutation has been recognized in patients with non-small cell lung cancer (NSCLC), and many reports have indicated that the presence of somatic mutations in the EGFR gene is a strong predictor of both clinical and in vitro sensitivity to EGFR tyrosine kinase inhibitors; thus necessitating the standardization of a mutation screening system based on the sources of tissue samples. In this study, we compared the results of EGFR mutation analyses in 19 small biopsy specimens with results obtained in surgical materials from the same patients with NSCLC. We used a laser microdissection method and a direct sequencing method, and we confirmed the accuracy of EGFR mutation analysis with small biopsy specimens. The results obtained from the biopsy specimens were identical to those obtained from the surgical materials in 18 of the 19 patients analyzed. For the 1 patient in whom the results obtained from the two sets of materials were not identical, the number of cancer cells in one bronchoscopic specimen was insufficient to perform analyses of all three exons of interest (i.e., exons 18, 19, and 21), and so only exon 19 was sequenced, and no mutation was demonstrated. We conclude that satisfactory accuracy can be achieved by the genomic analysis of a small biopsy specimen from a patient with NSCLC and we note that it is possible to conduct prospective clinical trials that include patient assignment for treatment based on the results obtained.


[Preliminary note on a model of cup-shaped deformed human erythrocyte].
We have developed a very elementary model for the cup shaped erythrocyte, in order to obtain some geometrical informations about the cellular contour and mould of the membrane, with regard to the territories of the cell, less accessible to the microscopical observation.


An overseas business paradox: Are Japanese general contractors risk takers?
Japanese industries have struggled with stagnation after the collapse of bubble economy in the 1990s. Such a financial crisis has led to overseas business expansion of Japanese industries. This study empirically examines Japanese general contractors' overseas operations over the post-bubble period in relation to their financial status. The result shows that general contractors facing financial distress expand overseas business aggressively, when the domestic market shrinks. This result is opposite to conventional wisdom that stronger entities expand their territories of operations, thus "overseas business paradox." However, it can be considered a new scenario of industries' evolution when a country's economy matures.


Candida caseinolytica sp. nov., a new species of yeast occurring in necrotic tissue of Opuntia and Stenocereus species in the southwestern United States and Baja California, Mexico.
We describe Candida caseinolytica, a new yeast species which occurs in rotting tissues of opuntias and other cacti in the North American Sonoran Desert and a few other localities. This small-celled, slowly growing yeast does not ferment any sugar and assimilates a limited number of carbon compounds, including 2- and 5-ketogluconic acids. It exhibits strong extracellular proteolytic activity on casein at pH 6.5, but gelatin is not hydrolyzed or is only weakly hydrolyzed by a few strains. The type strain of C. caseinolytica is strain UCD-FST 83-438.3 (= ATCC 90546 = CBS 7781).


The dose of direct oral anticoagulants and outcomes of intracerebral hemorrhage: Preliminary findings.
The effect of a direct-acting oral anticoagulant (DOAC) dose on intracerebral hemorrhage (ICH) severity and outcome remains unclear. The aim of this study is to clarify the frequency of off-label dosing of DOAC treatments in ICH patients and compare clinical characteristics. We studied 43 patients with ICH who were treated with DOAC for nonvalvular atrial fibrillation before the onset of ICH. DOAC treatments were categorized into three groups based on the following doses: optimal dose, under-dose, and overdose. Overall, 31 patients were optimally dosed, 10 were under-dosed, and 2 were overdosed. CHADS2 and CHA2DS2-VASc scores were the highest in the overdose group (median, 4, 6, respectively) and the lowest in the optimal dose group (median, 2, 4, respectively) (p = 0.006, p = 0.005, respectively). ICH severity measured using the National Institutes of Health Stroke Scale scores was the highest in the overdose group (median, 26.5) and the lowest in the under-dose group (median, 6.5) (p = 0.244). Larger initial hematoma volume was observed in the overdose group. The ratio of good outcome (modified Rankin Scale score ≤ 2) was higher in the under-dose group (40%) than the other groups, but this difference was not significant. Our study shows only a few patients received overdosing of a DOAC before the onset of ICH, and they were associated with poorer functional outcomes. Conversely, under-dosing was associated with better functional outcomes than the other groups.


Riptide.
In this article the author describes her experience of being diagnosed with breast cancer as a riptide experience. The ocean and many of its characteristics, such as the riptide, are used to describe the powering necessary to prevail during a cancer diagnosis and treatment. Five themes or currents within this riptide experience are identified: a shattered sense of well-being; feelings of anxiety, fear and uncertainty; learning to live one day at a time; the loving attention of family and friends; and,swimming with the turbulent sea. Concepts of powering uncovered in nursing research studies along with other theoretical concepts are presented to develop further these currents.


The size of the population potentially in need of palliative care in Germany--an estimation based on death registration data.
No data exist on the size of the population potentially in need of palliative care in Germany. The aim of this study is to estimate the size of the German population that may benefit from palliative care. Based on existing population-based methods (Rosenwax and Murtagh), German death registration data were analyzed and contrasted with international results. The data include all death cases in 2013 in Germany. According to the method Rosenwax defined, between 40.7% (minimal estimate) and 96.1% (maximal estimate) of death cases could benefit from palliative care. The estimation, based on Murtagh's refined method, results in 78.0% of death cases potentially being eligible for palliative care. The percentage of potential palliative care candidates is conditioned by age. Based on the Murtagh Method, in the age category between 30 and 39 years, a potential demand for palliative care can be found for 40.4% percent of all deaths occurring in this age category, with this number increasing to 80.3% in the age bracket of 80 years and over. An estimation of the size of the population in need is essential for healthcare planning. Therefore, our data serve as a guide and starting point for further research.


The effect of magnetic field strength on the positron range and projected annihilation artifact in integrated PET/MR systems: A GATE Monte Carlo study.
With improvements in positron emission tomography/magnetic resonance imaging (PET/MRI) over the last decade, there is a need to investigate the projected annihilation (shine-through) artifact and resolution impact for different PET radiopharmaceuticals, magnetic field (MF) strengths, and tissues. The GATE Monte Carlo (MC) simulation was used to simulate the annihilation distribution of positrons in different tissues and MFs. The positron distribution was studied in magnetic field (MF) intensities up to 15 T for 11 C, 13 N, 15 O, 18 F, 68 Ga, and 82 Rb. Moreover, the image quality in terms of the occurrence of projected annihilation artifacts was investigated using the 4D anthropomorphic digital extended cardiac-torso (XCAT) phantom. Positron ranges were restricted across the directions perpendicular to the MF, but no change along the direction of the MF was detected. The projected annihilation artifacts were observed with the presence of MF in the sagittal and coronal view of PET images prepared from the XCAT phantom. The intensity of artifact was constant in MFs higher than 3 T. The significant effect of the MF on resolution improvement was observed in soft tissue for 68 Ga in 7 T and 82 Rb in 3 and 7 T, while higher MFs have no impact on resolution. The improvement of resolution in the lung tissue was observed for the medium- and high-energy radionuclides in 7 T MF. The MF can create the projected annihilation artifact in the boundary of air cavities and other tissues for medium- and high-energy radionuclides especially for 68 Ga in clinical studies. In addition, the strength of the MFs more than 3 T was ineffective on the intensity of the projected annihilation artifact. In a clinical PET/MR scanner, MF has remarkable spatial resolution improvement in lung tissue, especially for medium- and high-energy radionuclides, and negligible effect in bone and soft tissue for most radionuclides.


Homocysteine content of plasma proteins in ischemic heart disease.
It has been shown previously that accumulation of homocysteine produces atheromatous changes. The present study was done on 26 male survivors of myocardial infarction 2-3 months after the acute phase and 26 healthy males of the same age (30-60 years). The concentrations of homocysteine, its derivatives and other amino acids were determined in acid hydrolyzate of plasma and in deproteinized plasma. The plasma proteins of survivors of myocardial infarction were found to contain a high concentration of homocysteine. The average value was 958 +/- 84 mumol/l of plasma, which was about 25 times the quantity found in the control group. Large differences were also found in alpha-amino adipic acid and cystathionine concentrations. These substances were found in significantly higher concentrations in the plasma of the survivors compared to controls. The high positive correlation between homocysteine and alpha-amino adipic acid level (r = 0.83; P less than 0.001) suggests a common source of these 2 compounds in the analyzed samples. The levels of the other 15 measured amino acids were not significantly different in the 2 groups. The results support the homocysteine theory and suggest a method for more exact diagnosis of atherosclerosis.


Study on the structure, antioxidant activity and degradation pattern of polysaccharides isolated from lotus seedpod.
The lotus (Nelumbo nucifera Gaertn.) is the largest aquatic vegetable in Asia. The lotus seedpod (LS) is an inedible part of the mature flower receptacle of the lotus plant. However, the polysaccharide isolated from the receptacle has been less studied. The purification of LS resulted in two polysaccharides (LSP-1 and LSP-2). Both polysaccharides were found to be medium-sized HG pectin, with a Mw of 74 kDa. Their structures were elucidated via GC-MS and NMR spectrum and proposed as the repeating sugar units of GalA connected via α-1,4-glycosidic linkage, with LSP-1 having a higher degree of esterification. They have certain content of antioxidant and immunomodulatory activities. The esterification of HG pectin would have an adverse effect on these activities. Furthermore, the degradation pattern and kinetics of LSPs by pectinase conformed to the Michaelis-Menten model. There is a large amount of LS, resulting from the by-product of locus seed production, and thus a promising source for the isolation of the polysaccharide. The findings of the structure, bioactivities, and degradation property provide the chemical basis for their applications in the food and pharmaceutical industries.


Antagonism of etonitazene's effects in rats and pigeons.
The effects of etonitazene were studied in the pigeon under a mult FR FI schedule of food presentation and in the rat under a continuous avoidance-escape schedule. A low dose of etonitazene increased rates of responding by pigeons under the FI component of the multiple schedule, whereas higher doses produced dose-related decreases in rates of responding under both components of the multiple schedule. These effects were blocked by cyclazocine. Under the continuous avoidance-escape schedule, etonitazene produced only dose-related decreases in rates of responding by rats, and these decreases were blocked by naloxone.


Immune interventions in COVID-19: a matter of time?
As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.


Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice.
Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflammation, caused by sustained Toll-like receptor 9 activation, on established diastolic heart failure. Diastolic heart failure was established in 8-10 week old cardiomyocyte specific, inducible SERCA2a knock out (i.e., SERCA2a KO) C57Bl/6J mice. Four weeks after conditional KO, mice were randomized to receive Toll-like receptor 9 agonist (CpG B; 2μg/g body weight) or PBS every third day. After additional four weeks, echocardiography, phase contrast magnetic resonance imaging, histology, flow cytometry, and cardiac RNA analyses were performed. A subgroup was followed, registering morbidity and death. Non-heart failure control groups treated with CpG B or PBS served as controls. Our main findings were: (i) Toll-like receptor 9 activation (CpG B) reduced life expectancy in SERCA2a KO mice compared to PBS treated SERCA2a KO mice. (ii) Diastolic function was lower in SERCA2a KO mice with Toll-like receptor 9 activation. (iii) Toll-like receptor 9 stimulated SERCA2a KO mice also had increased cardiac and systemic inflammation. Sustained activation of Toll-like receptor 9 causes cardiac and systemic inflammation, and deterioration of SERCA2a depletion-mediated diastolic heart failure.


Clinical significance of high expression of circulating serum lncRNA RP11-445H22.4 in breast cancer patients: a Chinese population-based study.
Long noncoding RNAs (lncRNAs) have been gradually confirmed to be tumor-associated biological molecules and became interesting new diagnostic targets of cancer. However, the clinical significances of most cancer-related lncRNAs are largely unknown. Here, we evaluated, for the first time, the feasibility and clinical significances of circulating serum lncRNA RP11-445H22.4 as biomarker for the detection of breast cancer (BC). In this study, the relative concentrations of breast cancer-associated lncRNA RP11-445H22.4 were investigated in a total of 136 serum samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlations between the levels of serum lncRNA RP11-445H22.4 in breast cancer patients and the clinicopathological factors of these patients were further analyzed. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. In breast cancer patients, the expression level of lncRNA RP11-445H22.4 is significantly increased (p < 0.001). The sensitivity and specificity of RP11-445H22.4 for BC were 92 and 74 %, respectively. Its expression levels were correlated with estrogen receptor (ER), progesterone receptor (PR), and menopausal status of the breast cancer patients (p < 0.05). For the detection of breast cancer, the use of RP11-445H22.4 showed a remarkable improvement compared with the clinical serum carcinoembryonic antigen. In conclusions, lncRNA RP11-445H22.4 may be a new potential biomarker of breast cancer.


Effect of Pudilan Keyanning antibacterial mouthwash on dental plaque and gingival inflammation in patients during periodontal maintenance phase: study protocol for double-blind, randomised clinical trial.
Plaque control plays a critical role in the prevention and treatment of periodontitis. Antibacterial mouthwash is one of the most important tools for plaque control. Pudilan, including extracts of Scutellaria baicalensis root, Taraxacum mongolicum, Bunge corydalis herb and Isatis indigotica, was reported playing the role of anti-inflammatory and anti-bacterial. However, its effect on dental plaque and periodontal inflammation remains unknown. We aimed to assess the efficacy of Pudilan Keyanning antibacterial mouthwash which contains the active essence of Pudilan and 0.03%-0.06% cetylpyridinium chloride, as well as Pudilan active essence for plaque control and gingival anti-inflammation in patients during periodontal maintenance phase. In this double-blind, randomised, placebo-controlled clinical trial, a total of 120 participants during periodontal maintenance phase will be enrolled. After supragingival scaling, they will be randomly assigned into three groups in a 1:1:1 ratio: the Pudilan Keyanning antibacterial mouthwash group, a chlorhexidine acetate mouthwash (0.12%) group or a placebo group with mouthwash containing the same components as the Pudilan Keyanning mouthwash except for Pudilan active ingredients. They will rinse with mouthwash, respectively, two times per day for 6 weeks. Clinical parameters (such as plaque index, bleeding index) and the level of volatile sulfide in the breath will be measured and analysed. The subgingival plaque will be collected and analysed microbiologically. Questionnaire feedback will be analysed. The study protocol (V.4) was reviewed and approved by the Medical Ethical Committee of Peking University School and Hospital of Stomatology (Ethics Approval No. PKUSSIRB-201950153b). All participants signed a written consent form. ChiCTR2000041253.


Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.
Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured.


Correlated ultrastructural damage between cerebellum cells after early anticonvulsant treatment in mice.
The anticonvulsants phenobarbital and diphenylhydantoin administered early in life to mice resulted in significant and long-lasting ultrastructural damage, including abnormalities of mitochondria, myelin sheaths, and lamellar inclusion bodies inside identified cells throughout the cortical layers of the cerebellum in treated vs control mice. The magnitude, distribution and duration of damage was age and treatment specific. No differences were detected in density of parallel fiber processes nor in synapse density within the molecular layer. Neuron profiles containing damaged organelles were not homogeneously distributed but made up only a small fraction of the total cell population examined. In our experiments, there was an overall within-animal correlation explaining 45% of the magnitude of damage in different cerebellar regions, but between synaptically connected cells, specifically mossy fiber axon varicosities and granule cell dendrite profiles, the subset population ratio of damaged-to-total mitochondria was highly significantly correlated (70-90%; P less than 0.001). We hypothesized that some correlated transneuronal degeneration and death in the central nervous system may have a transynaptically regulated component that first appears as correlated damage between synaptically connected cells, perhaps regardless of the degree of toxicity. The orderly cytoarchitecture and cell connections of the cerebellar cortex can be used to study these patterns of degeneration.


Anion receptor and heavy metal-free redox mediator decorated separator for lithium-sulfur batteries.
The adsorption-catalysis synergy for accelerated conversion of polysulfides is critical toward the electrochemical stability of lithium-sulfur battery (LSB). Herein, a non-metallic polymer network with anion receptor units, trifluoromethanesulfonyl (CF3SO2-) substituted aza-ether, was in-situ integrated on PE separator, working as an efficient host for anchoring lithium thiophosphates (LPS) as redox mediators and polysulfides through Lewis acid-base interaction. The anchored LPS on the modified PE separator displayed a robust chemical adsorption ability towards polysulfides through the formation of SS bond. Meanwhile, LPS decreased the energy barrier of Li2S nucleation and promoted redox reaction kinetics. The battery with LPS decorated separator revealed a long cycling lifespan with a per cycle decay of 0.056 % after 600 cycles, and a competitive initial capacity of 889.1 mAh/g when the of sulfur cathode increased to 3 mg cm-2. This work developed a new design strategy to promote the utilization of lithium phosphorus sulfide compounds in LSB.


Trophoblast lineage-specific differentiation and associated alterations in preeclampsia and fetal growth restriction.
The human placenta is a poorly-understood organ, but one that is critical for proper development and growth of the fetus in-utero. The epithelial cell type that contributes to primary placental functions is called "trophoblast," including two main subtypes, villous and extravillous trophoblast. Cytotrophoblast and syncytiotrophoblast comprise the villous compartment and contribute to gas and nutrient exchange, while extravillous trophoblast invade and remodel the uterine wall and vessels, in order to supply maternal blood to the growing fetus. Abnormal differentiation of trophoblast contributes to placental dysfunction and is associated with complications of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). This review describes what is known about the cellular organization of the placenta during both normal development and in the setting of PE/FGR. It also explains known trophoblast lineage-specific markers and pathways regulating their differentiation, and how these are altered in the setting of PE/FGR, focusing on studies which have used human placental tissues. Finally, it also highlights remaining questions and needed resources to advance this field.


Late HIV diagnosis is a major risk factor for intensive care unit admission in HIV-positive patients: a single centre observational cohort study.
HIV positive patients are at risk of infectious and non-infectious complications that may necessitate intensive care unit (ICU) admission. While the characteristics of patients requiring ICU admission have been described previously, these studies did not include information on the denominator population from which these cases arose. We conducted an observational cohort study of ICU admissions among 2751 HIV positive patients attending King's College Hospital, South London, UK. Poisson regression models were used to identify factors associated with ICU admission. The overall incidence rate of ICU admission was 1.0 [95% CI 0.8, 1.2] per 100 person-years of follow up, and particularly high early (during the first 3 months) following HIV diagnosis (12.4 [8.7, 17.3] per 100 person-years compared to 0.37 [0.27, 0.50] per 100 person-years thereafter; incidence rate ratio 33.5 [23.4, 48.1], p < 0.001). In time-updated analyses, AIDS and current CD4 cell counts of less than 200 cells/mm3 were associated with an increased incidence of ICU admission while receipt of combination antiretroviral therapy (cART) was associated with a reduced incidence of ICU admission. Late HIV diagnosis (initial CD4 cell count <350 or AIDS within 3 months of HIV diagnosis) applied to 81% of patients who were first diagnosed HIV positive during the study period and who required ICU admission. Late HIV diagnosis was significantly associated with ICU admission in the first 3 months following HIV diagnosis (adjusted incidence rate ratio 8.72, 95% CI 2.76, 27.5). Late HIV diagnosis was a major risk factor for early ICU admission in our cohort. Earlier HIV diagnosis allowing cART initiation at CD4 cell counts of 350 cells/mm3 is likely to have a significant impact on the need for ICU care.


Inhibition of Borna disease virus replication by ribavirin in persistently infected cells.
Ribavirin at concentrations from 1 to 10 micrograms/ml exhibited inhibitory effects on transcription of Borna disease virus (BDV) in persistently infected cells. Our present study indicates that ribavirin is a candidate anti-BDV drug.


Structural and phylogenetic comparison of napsin genes: the duplication, loss of function and human-specific pseudogenization of napsin B.
Aspartic proteinases form a widely distributed protein superfamily, including cathepsin D, cathepsin E, pepsins, renin, BACE and napsin. Human napsin genes are located on human chromosome 19q13, which comprises napsin A and napsin B. Napsin B has been annotated as a pseudogene because it lacks an in-frame stop codon; its nascent chains are cotranslationally degraded. Until recently, there have been no studies concerning the molecular evolution of the napsin protein family in the human genome. In the present study, we investigated the evolution and gene organization of the napsin protein family. Napsin B orthologs are primarily distributed in primates, while napsin A orthologs are the only napsin genes in other species. The corresponding regions of napsin B in the available sequences from primate species contain an in-frame stop codon at a position equivalent to that of human napsin A. In addition, a rare single-nucleotide polymorphism (SNP) that creates a proper stop codon in human napsin B was identified using HapMap populations. Recombinant protein expression and three-dimensional comparative modeling revealed that napsin B exhibits residual activity toward synthetic aspartic protease substrates compared with napsin A, presumably through a napsin B-specific Arg287 residue. Thus, napsin B was duplicated from napsin A during the early stages of primate evolution, and the subsequent loss of napsin B function during primate evolution reflected ongoing human-specific napsin B pseudogenization.


[Prognostic factors in prostate cancer].
Since several therapeutic options are currently available for clinically organ-confined prostate cancer, morphological parameters have rapidly emerged as prognostic factors to stratify patients into different therapeutic modalities. In addition to the PSA value, pathologic stage, as defined by the TNM system, Gleason grade and the surgical margin status, other markers have prognostic implications. This includes the percent pattern 4/5 cancer, tumor volume, intraductal spread, large volume perineural invasion and molecular markers. This review discusses the methods of sampling and reporting in prostate pathology with an emphasis on well established and new prognostic factors.


The Equivalence Between Unit-Cell Twinning and Tiling in Icosahedral Quasicrystals.
It is shown that tiling in icosahedral quasicrystals can also be properly described by cyclic twinning at the unit cell level. The twinning operation is applied on the primitive prolate golden rhombohedra, which can be considered a result of a distorted face-centered cubic parent structure. The shape of the rhombohedra is determined by an exact space filling, resembling the forbidden five-fold rotational symmetry. Stacking of clusters, formed around multiply twinned rhombic hexecontahedra, keeps the rhombohedra of adjacent clusters in discrete relationships. Thus periodicities, interrelated as members of a Fibonacci series, are formed. The intergrown twins form no obvious twin boundaries and fill the space in combination with the oblate golden rhombohedra, formed between clusters in contact. Simulated diffraction patterns of the multiply twinned rhombohedra and the Fourier transform of an extended model structure are in full accord with the experimental diffraction patterns and can be indexed by means of three-dimensional crystallography. The alternative approach is fully compatible to the rather complicated descriptions in a hyper-space.


Host-derived bacillus spp. as probiotic additives for improved growth performance in broilers.
In recent years, the utilization of antibiotics in animal feed has been restricted, probiotics have been increasingly used to replace antibiotics in maintaining animal health. The aim of this study was to screen and evaluate probiotics with excellent probiotic potential from the gut of healthy goslings for clinical application. Thirteen strains of Bacillus (named AH-G201 to AH-G2013), including 2 strains of Bacillus subtilis (B. subtilis), 6 strains of Bacillus licheniformis (B. licheniformis) and 5 strains of Bacillus amyloliquefaciens (B. amyloliquefaciens), were isolated and identified. Then, acid and bile salts tolerance tests were performed to screen probiotics strains that could survive under different environments. The effects of screened probiotics on the growth of pathogenic Escherichia coli (E. coli) and Salmonella were assessed. Furthermore, we performed the drug resistance tests and safety tests in animals. The results showed that B. Subtilis AH-G201, B. licheniformis AH-G202 and AH-G204 exhibited higher gastrointestinal resistance under in vitro conditions, and showed a moderate level of resistance to the tested antibiotics. Importantly, AH-G201 and AH-G202 showed 24 to 60% inhibition rate against pathogenic E. coli and Salmonella. Moreover, the safety analysis of AH-G201 and AH-G202 suggested that the 2 probiotics strains have no adverse effects on body weight gain and feed intake in the broilers, and in addition, they have significantly improved growth performance. Finally, we analyzed effects of B. Subtilis AH-G201and B. licheniformis AH-G202 on growth performance, immune organ index and the feces microbes of broilers. The results showed that broilers fed with high doses (5 × 109 CFU/mL, for single strain) of a mixture of AH-G201 and AH-G202 exhibited good growth performance, and exhibited the greatest gain in spleen weight and the highest lactic acid bacteria counts. These findings indicate that the combined addition of B. Subtilis AH-G201 and B. licheniformis AH-G202 has the potential to replace antibiotics and to improve the growth performance of broilers.


Dissociating the effects of habituation, black walls, buspirone and ethanol on anxiety-like behavioral responses in shoaling zebrafish. A 3D approach to social behavior.
Understanding the different patterns of anxiety-like behavioral responses is of great interest for pharmacological and genetic research. Here we report the effects of 3.5-hr habituation, buspirone and ethanol on those responses in shoaling zebrafish (Danio rerio). Since in these experiments we used a container with white walls, the effects of black-vs.-white walls were tested in a separate experiment. An important objective was to determine whether factors unrelated to anxiety played a role in modulating the responses. The anxiety-like behavioral responses studied here are social cohesion, distance from bottom and bottom-dwell time, radial distribution (to study thigmotaxis), transparent-wall preference (to study escape responses), locomotion and freezing. The experimental conditions yielded distinctly different response patterns. Thigmotaxis was the most obvious response to white walls and it was significantly reduced after 3.5-hr habituation. It was not affected by any of the drugs. The reduction of social cohesion after 3.5-hr habituation and in the 0.5% ethanol group was probably the most interesting effect seen in this study. A role of anxiety herein was suggested but could not be established with certainty. Other hypotheses were also discussed. The large increase of distance-from-bottom resulting in swimming close to the water surface, which occurred in both buspirone groups and in the 0.5%-ethanol group, is most likely not an anxiolytic response, because of the discrepancy with the in the literature well-established time-course and the absence of any effect of 3.5-hr habituation or black walls on vertical measures. Finally, locomotion and duration freezing could not be specifically taken as indicators for the state of anxiety and the results concerning transparent-wall preference were not sufficient clear. We conclude that the neuronal and ethological mechanisms underlying the effects of habituation, white-aversion, buspirone and ethanol on anxiety-like behavioral responses are complex and need further exploration.


Lack of knowledge of glycosylated hemoglobin in patients with diabetic retinopathy.
We surveyed 220 patients with diabetic retinopathy attending a tertiary eye hospital in Australia, and found that knowledge of HbA(1c), and the proportion achieving target level of <7%, remained low in patients with diabetic retinopathy. These data re-emphasize the gap between clinical guidelines and actual management of patients with diabetes.


Simplified method of determining left ventricular ejection fraction from a radionuclide bolus.
A method which does not require an online computer has been developed to measure left ventircular ejection fraction from a bolus of 99mTc-pertechnetate. The passage of the bolus through the cardiac chambers was imaged using a gamma camera and recorded on video tape. On replay a region of interest corresponding to the left ventricle was selected directly at the gamma camera console. Counts detected in this region were analysed in 30ms intervals. The data were corrected for the contribution from extra-cardiac activity and were then digitally filtered to remove statistical noise. Ejection fractions measured in 13 patients by this technique agreed well with those determined by contrast ventriculography (r=0.97, P less than 0.001).


Effects of load on ground reaction force and lower limb kinematics during concentric squats.
The purpose of this study was to examine the effects of external load on vertical ground reaction force, and linear and angular kinematics, during squats. Eight males aged 22.1 +/- 0.8 years performed maximal concentric squats using loads ranging from 7 to 70% of one-repetition maximum on a force plate while linear barbell velocity and the angular kinematics of the hip, knee and ankle were recorded. Maximum, average and angle-specific values were recorded. The ground reaction force ranged from 1.67 +/- 0.20 to 3.21 +/- 0.29 times body weight and increased significantly as external load increased (P < 0.05). Bar linear velocity ranged from 0.54 +/- 0.11 to 2.50 +/- 0.50 m x s(-1) and decreased significantly with increasing external load (P < 0.05). Hip, knee and ankle angles at maximum ground reaction force were affected by external load (P < 0.05). The force-barbell velocity curves were fitted using linear models with coefficients (r2) ranging from 0.59 to 0.96. The results suggest that maximal force exertion during squat exercises is not achieved at the same position of the lower body as external load is increased. In contrast, joint velocity coordination does not change as load is increased. The force-velocity relationship was linear and independent from the set of data used for its determination.


Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis.
Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. A total of 466 LT recipients were identified (study group n = 108; control group n = 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p = 0.001) and of septic shock (8% vs. 2%, p = 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio = 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p = 0.579) and 5-year survival rates (76% vs. 75%, p = 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.


Association of extent of resection and functional outcomes in diffuse low-grade glioma: systematic review & meta-analysis.
Surgical resection offers survival benefits in patients with diffuse low-grade glioma (DLGG) but its association with functional outcomes is uncertain. This systematic review assessed functional outcomes associated with extent of resection (EoR) in adults with DLGG. We searched Medline, Embase and CENTRAL on the 19th of February 2021 for observational studies reporting functional outcomes after surgical resection for patients aged ≥ 18 years with a new diagnosis of supratentorial DLGG according to any World Health Organization classification of primary brain tumors. The Newcastle-Ottawa Scale (NOS) informed our risk of bias assessments. The proportion of patients returning to work within 12 months entered a random-effects meta-analysis. PROSPERO registration number CRD42021238387. There were seven eligible moderate to high-quality (NOS > 6) observational studies identified from 1,183 records involving 234 patients with DLGG. Functional outcomes reported included neurocognition (n = 2 studies), performance status (n = 3), quality of life (QoL) (n = 1) and return to work (n = 6). The proportion of patients who returned to work within 12 months of surgery was 84% (95% confidence interval [CI] 50-96%, I-squared = 38%, 5 studies) for gross total resection, 66% (95% CI 14-96%, I2 = 57%, 5 studies) for subtotal resection, and 31% (95% CI 4-82%, I2 = 0%, 4 studies) for partial resection. There was insufficient data on other functional outcomes for quantitative synthesis. A higher proportion of DLGG patients returned to work following gross total resection compared with those who had a subtotal or partial resection. Further studies with standardized assessments can clarify the association between EoR and different functional outcomes.


Nuclear proteins that interact with the beta maj globin promoter start to accumulate in MEL cells within 12 hours of induction and RNA copies of the promoter successfully compete their binding in vitro.
The induction of differentiation in mouse erythroleukemia (MEL) cells by dimethylsulfoxide (DMSO) is characterized by increased transcription of globin genes. We have determined that DMSO treated cells increase the levels of nuclear factors capable of overall interactions with the beta maj globin promoter during the initial 24 h post induction, as measured by gel mobility analysis. Two unprocessed beta maj globin mRNA precursors, which are present in MEL cell nuclei early in differentiation, were previously shown to contain the 5' promoter flanking region, and thereby provided the nucleus with a pool of regulatory sequences in multiple RNA copies. We have studied the effect of RNA copies of the promoter region on binding interactions between DNA sequences of the beta maj globin promoter and nuclear factors that interact with these sequences. The promoter region RNA transcripts competed effectively for DNA binding proteins in vitro, while the antisense RNA from the same region did not. The most pronounced competition was observed with proteins from 12 h after DMSO induction, when the concentration of the DNA binding proteins was still increasing. Since the 'upstream' transcripts predominate at 12 h after DMSO induction, these results indicate that the promoter region transcripts may influence the equilibrium of binding between the beta maj globin promoter and the nuclear factors that bind to this region during DMSO induction.


The organization of reticulo-olivo-cerebellar circuits in the North American opossum.
By employing the autoradiographic method we have determined that the inferior olivary nucleus receives input from the reticular formation of the midbrain, pons and, probably, the medulla. The remarkable thing about such connections is that they are not diffuse, but targeted in large part on restricted portions of the caudal acessory nuclei. From our previous studies it is clear that some of the olivary regions receiving reticular input also receive projections from the cerebral cortex, the spinal cord and the dorsal column nuclei. In addition, the HRP technique reveals that these same olivary regions relay to parts of the spinal cerebellum, i.e. to restricted zones of the anterior lobe (present study). Taken together these observations suggest that some reticulo-olivo-cerebellar connections provide indirect routes through which cortical and spinal information gains access to the spinal cerebellum. Such circuits have also been suggested by the physiological literature. Of particular interest, however, was our finding that several reticular areas of the midbrain and pons project to the portion of the medial acessory nucleus which relays in turn to auditory-visual areas of the cerebellar vermis (declive, folium and tuber). It would appear that at least some reticulo-olivo-cerebellar circuits are significant in the organization of motor responses to visual and/or auditory stimuli.


Handling Golgi-impregnated tissue for light microscopy.
The use of cyanocrylic glue to fix pieces of Golgi-stained nervous tissue on a paraffin blank is proposed for obtaining thick sections of unembedded tissue with a sliding microtome. This procedure makes correct orientation of the tissue easy during sectioning and makes it possible to obtain tissue sections quickly. The sections are flat-mounted using epoxy resin, resulting in permanent preparations with excellent optical properties and enabling further thin-sectioning for light and electron microscopic studies.


"We weren't the sort that wanted intimacy every night": Birth control and abstinence in England, c.1930-60.
This article presents an exploration of qualitative evidence on the relationship between birth control and abstinence from an oral history project, which interviewed middle and working-class English men and women, who had married between the late 1920s and the early 1950s. Among the working classes the assumption that men were responsible for birth control choices and the disadvantages that contraceptive methods of all types posed, combined with the fear of pregnancy, acted as a disincentive to have sex and resulted in forms of partial abstinence. Among the middle classes, women had much more access to birth control information and as a consequence a greater range of methods was used, including more female methods. However, the reluctance of couples to discuss sexual matters, and some continued preference for male methods meant that while condoms were the most regularly used middle-class male method, both withdrawal and abstinence were also in evidence. Moreover, although partners were more likely to discuss birth control at the start of their marriages, they were less likely to agree that contraception was a male responsibility and there was greater potential for conflict over contraceptive methods, not infrequently resulting in abstinence. The evidence suggests that sexual and contraceptive practices in marriages in England at the end of the secular fertility decline do not present a picture which straightforwardly correlates with the assumptions represented by the popular thesis that this period of increased fertility control was closely associated with the rise of companionate marriage.


[CLPB gene mutations analysis in a case of type 3-methylglutaconic aciduria].
To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene. Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis. NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant. Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.


Multivalent interactions between lectins and supramolecular complexes: Galectin-1 and self-assembled pseudopolyrotaxanes.
Supramolecular chemistry has been employed to develop flexible and adaptable multivalent neoglycoconjugates for binding galectin-1 (Gal-1). Gal-1, a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Self-assembled pseudopolyrotaxanes consisting of lactoside-displaying cyclodextrin (LCD) "beads" threaded onto polyviologen "strings" display mobile ligands as a result of cyclodextrin rotation about, and limited translation along, the polymer chain. The pseudopolyrotaxanes rapidly and efficiently precipitate Gal-1 and provide valency-corrected enhancements of up to 30-fold compared to native lactose and 20-fold over free LCD in a T-cell agglutination assay. A supramolecular statistical effect was observed, wherein the efficacy of Gal-1 inhibition correlates with the number of ligands connected to each other solely through mechanical and noncovalent interactions. Such flexible and adaptable self-assembled pseudopolyrotaxanes show promise for the study of multivalent interactions and targeting of therapeutically relevant lectins.


Structure and cation ordering in spinel-type TcCo2O4. An example of a trivalent technetium oxide.
The structure of TcCo(2)O(4) has been determined using a combination of synchrotron X-ray and neutron powder diffraction methods. It has an inverse spinel structure where the Tc occupies the octahedral sites. Both the refined Tc-O distance and X-ray absorption spectra suggest the Tc is predominantly trivalent.


Noise reduction in wide-bore magnets using a patient cage.
Significant rf noise reduction is demonstrated by enclosing the patient in a conducting cage grounded to the magnet bore in a 22-cm-bore spectrometer system capable of examining magnetic images and spectroscopy of human limbs. This method of noise reduction was found to be reliable, simple, and efficient for dealing with ambient rf noise in an unshielded room.


Late degeneration in rabbit tissues after irradiation by heavy ions.
In 1974, using the rabbit as a model, we began long-term experiments designed to help in the evaluation of the hazards to man from extended exposure to heavy ions in space. Such exposure would occur, for example, during the construction of solar power stations in stationary orbits or on round trips to Mars. Our experiments with 400 MeV/nucleon Ne ions and 570 MeV/nucleon Ar ions have shown that true late effects of a degenerative nature are manifested only years after irradiation. At the appropriate doses (the high end of the experimental dose range), the magnitudes of the late effects are comparable with those encountered in human patients given radiation therapy with neutrons. Such comparisons show that the rabbit experiments are applicable to man. Given that basis, the results from the low end of the experimental dose range lead to the conclusion that astronauts subjected to the radiation fluxes anticipated during flights of the above duration could experience late radiation effects one or more decades after exposure. Late degenerative changes will occur in tissues of the central nervous system, terminally differentiating systems and stem cell populations. The studies also indicate that individual tissues may be "prematurely aged" by radiation in the sense that the "life spans" of those tissues can be decreased without the appearance of malignancies.


Five-year performance monitoring of a high-density polyethylene (HDPE) cover system at a reclaimed mine waste rock pile in the Sydney Coalfield (Nova Scotia, Canada).
Cover systems are commonly placed over waste rock piles (WRPs) to limit atmospheric water and oxygen ingress and control the generation and release of acid mine drainage (AMD) to the receiving environment. Although covers containing geomembranes such as high-density polyethylene (HDPE) exhibit the attributes to be highly effective, there are few, if any, published studies monitoring their performance at full-scale WRPs. In 2011, a HDPE cover was installed over the Scotchtown Summit WRP in Nova Scotia, Canada, and extensive field performance monitoring was conducted over the next five years. A range of parameters within the atmosphere, cover, waste rock, groundwater and surface water, were monitored and integrated into a comprehensive hydrogeochemical conceptual model to assess (i) atmospheric ingress to the waste rock, (ii) waste rock acidity and depletion and (iii) evolution of groundwater and surface water quality. Results demonstrate that the cover is effective and meeting site closure objectives. Depletion in oxygen influx resulted in slower sulphide oxidation and AMD generation, while a significant reduction in water influx (i.e. 512 to 50 mm/year) resulted in diminished AMD release. Consistent improvements in groundwater quality (decrease in sulphate and metals; increase in pH) beneath and downgradient of the WRP were observed. Protection and/or significant improvement in surface water quality was evident in all surrounding watercourses due to the improved groundwater plume and elimination of contaminated runoff over previously exposed waste rock. A variably saturated flow and contaminant transport model is currently being developed to predict long-term cover system performance.


Imaging characteristics predicting elevated detrusor pressures in patients with spina bifida.
Patients with spina bifida require urologic follow up with assessments of bladder and renal function. The ideal screening protocol for bladder compliance remains controversial. This study assessed associations between bladder end filling pressure (EFP) and detrusor leak point pressure (DLPP) on urodynamic studies (UDS) and findings from renal bladder ultrasounds (RBUS) and voiding cystourethrograms (VCUG). Pediatric spina bifida patients who underwent RBUS and/or VCUG within six months of UDS at a single institution from 2015 to 2021 were retrospectively reviewed. Demographics, VCUG and RBUS results, and UDS EFP and DLPP were recorded. Multiple linear regression analyses and Pearson chi-square tests were conducted to correlate RBUS and VCUG findings with DLPP/EFP. 129 patients were included. In adjusted analyses, moderate to severe hydronephrosis on RBUS was significantly associated with elevations in mean DLPP/EFP (p = 0.006). Patients with round bladders had significantly lower mean DLPP/EFP than patients with elongated or conical bladders (p < 0.0001). The presence of trabeculations was associated with increased mean DLPP/EFP (p < 0.0001) and increases in severity of trabeculations were associated with higher DLPP/EFP (p < 0.0001). The presence of vesicoureteral reflux (VUR) on VCUG was not associated with significant differences in mean DLPP/EFP (p = 0.20). Abnormal bladder shape and trabeculations on VCUGs in spina bifida patients had significant associations with increased mean bladder pressures on UDS. Assessment of bladder shape and contour by VCUG may be a valuable screening tool in conjunction with routine RBUS in determining the need for further assessment of bladder pressures in patients with spina bifida.


Assessing justice in California's transition to electric vehicles.
Passenger vehicles are an essential form of transportation and contribute significantly to greenhouse gas emissions and criteria air pollution. The health and climate effects associated with their use disproportionately impact low-income communities and people of color. A shift from conventional vehicles to zero-emission vehicles is essential to meet climate targets and reduce inequities. The transition to clean transportation is an opportunity to uplift underserved and marginalized communities while building a sustainable transportation system. We assess justice in California's transition to electric passenger vehicles by analyzing publicly available data on electric vehicle adoption and rebate use to measure justice in three areas: distribution of electric vehicles, allocation of state incentives, and the social and historical context of redlining. We find electric vehicle adoption and rebate use are lower in low-income and Latino-majority ZIP codes and in formerly redlined neighborhoods, indicating that California's electric vehicle transition has not been just thus far.


25OH Vitamin D Is No Associated with Muscle Function Loss in Adults and Elderly Patients Undergoing Hemodialysis.
In patients with chronic kidney disease, sarcopenia is associated with dialysis treatment, accelerated protein catabolism, and high energy demand. Thus, this study aimed to assess the association between 25-OH vitamin D concentrations and muscle function in patients undergoing hemodialysis. A cross-sectional study. Performed in a hemodialysis clinic. 79 adult and elderly patients undergoing hemodialysis. The sample was divided according to the SARC-F definition, being 55 patients allocated in the SARC-F <4 group and 24 in the SARC-F ≥4 group. Normal 25-OH vitamin D concentrations was considered when ≥30 ng/dL. Vitamin D concentrations and number of patients with low or normal muscle function did not differ between the groups. There was no correlation between SARC-F and 25-OH vitamin D levels (r: -0.09, p=0.42). 25-OH vitamin D has no association with muscle function loss in adults and elderly patients undergoing hemodialysis.


Exploring the health burden of cumulative and specific adverse childhood experiences in New Zealand: Results from a population-based study.
Adverse childhood experiences (ACEs) can influence later health, but there are gaps in understanding how ACEs may interact with Positive Childhood Experiences (PCEs). Additionally, there are gaps in understanding how ACEs impact on positive markers of health. To explore associations of ACEs with both negative and positive markers of physical and mental health in adulthood and to examine whether positive childhood experiences (PCEs) can mitigate the negative effects of ACEs on health. 2887 participants (1464 female, 1423 male) from the 2019 New Zealand Family Violence Survey, a population-based study conducted in New Zealand between March 2017-March 2019. Multivariable logistic regressions were conducted to ascertain how both ACE score and ACE subtypes influenced the odds of experiencing adverse and positive mental and physical health after adjusting for socio-demographic predictors. A combined ACE-PCE variable was created and included in the multivariable logistic regression models to examine whether PCEs can mitigate the negative effects of ACEs. Findings indicated that respondents with higher ACE scores had an increased likelihood of reporting each adverse outcome. Higher ACE scores had the strongest association with poor mental health followed by disability and chronic physical health conditions. Respondents with higher ACE scores had a decreased likelihood of reporting each positive health outcome. Exposure to ACEs was detrimental to health even in the presence of PCEs, with minimal effects observed from PCEs given the limited variance observed from its assessment. This study documents the deleterious impacts of ACEs on a wide range of health outcomes and demonstrates that these effects are persistent. Findings should provide the impetus for widespread prevention and intervention initiatives that seek to address ACEs. Further exploration of PCEs with a more complete assessment is needed to determine if they can mitigate the detrimental consequences of ACEs.


Applying a large, statewide database to the assessment, stressor diagnosis, and restoration of stream fish communities.
In this report, predictions of the species that were expected to occur at stream sites were generated and probable stressors to fish species that were predicted to occur but were absent were diagnosed. Predictions were generated based on the hierarchical screening method of Smith and Powell (1971, Am. Mus. Novit. 2458, 1-30), using fish abundance in conjunction with 25 environmental variables at 895 sites. The sites were sampled throughout Maryland and represent the entire range of environmental quality from severely degraded to minimally degraded. Stressor variable values that exceeded tolerance thresholds for species that were expected to occur, but were absent, were considered to be probable stressors. This method was tested for efficacy in stream site assessments and stressor diagnosis using an independent data set. Sites that were classified as degraded according to the IBI and to non-biological criteria had fewer predicted species present compared to minimally influenced sites, indicating that the proportion of predicted species present accurately represents the biological integrity of a stream site. The nine stressors that were applied to the test data set accounted for species absences in 43.7% of degraded sites. Impervious land cover was the most common stressor identified. In addition to assessing stream biological integrity and identifying stressors to fish species, this approach also provides tolerance thresholds for predicted fish species that are useful endpoints necessary to plan effective restoration of fish species in Maryland.


Source of arsenic-bearing pyrite in southwestern Vermont, USA: sulfur isotope evidence.
Arsenic-bearing pyrite is the source of arsenic in groundwater produced in late Cambrian and Ordovician gray and black slates and phyllites in the Taconic region of southwestern Vermont, USA. The aim of this study is to analyze the sulfur isotopic composition of this pyrite and determine if a relationship exists between pyrite δ(34)S and arsenic content. Pyrite occurs in both sedimentary/diagenetic (bedding-parallel layers and framboids) and low-grade metamorphic (porphyroblast) forms, and contains up to >2000 ppm As. The sulfur isotopic composition of arsenic-bearing pyrite ranges from -5.2‰ to 63‰. In the marine environment, the sulfur in sedimentary pyrite becomes increasingly enriched in (34)S as the geochemical environment becomes increasingly anoxic. There is a positive correlation between δ(34)S and arsenic content in the Taconic pyrite, suggesting that uptake of arsenic by pyrite increased as the environment became more reducing. This increased anoxia may have been due to a rise in sea level and/or tectonic activity during the late Cambrian and Ordovician. Low-grade metamorphism appears to have little effect on sulfur isotope composition, but does correlate with lower arsenic content in pyrite. New groundwater wells drilled in this region should therefore avoid gray and black slates and phyllites that contain sedimentary/diagenetic pyrite with heavy δ(34)S values.


Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study.
The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts. Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids. After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P < .0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P > .05). We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.


Effects of S(+)-efonidipine on the rabbit sinus node action potential and calcium channel subunits Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1.
The effect of S(+)-efonidipine on sinus node action potential and calcium channel α-subunits was examined. The slope of the phase 4 depolarization of isolated rabbit sinus node tissue was significantly reduced by S(+)-efonidipine (1 μM), slightly reduced by nifedipine (1 μM), but was not affected by R(-)-efonidipine. S(+)-efonidipine (1 μM), inhibited the expressed Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1 channel currents by 75.7%, 75.3% and 94.0%, nifedipine 84.0%, 43.2% and 14.9%, and R(-)-efonidipine 30.0%, 19.6% and 92.8%, respectively. Thus, the prolongation of the phase 4 depolarization of the rabbit sinus node by S(+)-efonidipine may be explained by blockade of the Ca(V)1.3 channel current.


"Emotions guide us": behavioral and MEG correlates.
Affectively salient stimuli are capable of capturing attentional resources which allow the brain to change the current course of action in order to respond to potentially advantageous or threatening stimuli. Here, we investigated the behavioral and cerebral impact of peripherally presented affective stimuli on the subsequent processing of foveal information. To this end, we recorded whole-head magnetoencephalograms from 12 participants while they made speeded responses to the direction of left- or right-oriented arrows that were presented foveally at fixation. Each arrow was preceded by a peripherally presented pair of pictures, one emotional (unpleasant or pleasant), and one neutral. Paired pictures were presented at 12° of eccentricity to the left and right of a central fixation cross. We observed that the participants responded more quickly when the orientation of the arrow was congruent with the location of the previously presented emotional scene. Results show that non-predictive emotional information in peripheral vision interferes with subsequent responses to foveally presented targets. Importantly, this behavioral effect was correlated with an early (∼135 msec) increase of left fronto-central activity for the emotionally congruent combination, whose cerebral sources were notably located in the left orbitofrontal cortex. We therefore suggest that the prior spatial distribution of emotional salience, like physical salience, grabs attentional resources and modifies the performance in the center of the visual field. Thus, these data shed light on the neurobehavioral correlates of the emotional coding of visual space.


Induction of rat liver glutathione transferase subunit 7 by lead nitrate.
The effect of a single dose of lead nitrate (10 microM/100 g body wt), a hepatic mitogen, on rat liver glutathione transferase (GST) subunit expression was investigated. Using SDS-polyacrylamide gel electrophoresis and Western blot technique evidence for the induction of GST 7-7 is shown. This occurrence is identical to that observed in preneoplastic nodules generated in rat liver by different models of chemical carcinogenesis, suggesting that lead nitrate may be a very simple model for investigation of the mechanism of glutathione transferase 7-7 gene expression in chemical hepatocarcinogenesis.


A novel C-type lectin activates the complement cascade in the primitive oyster Crassostrea gigas.
The ancient origin of the lectin pathway of the complement system can be traced back to protochordates (such as amphioxus and tunicates) by the presence of components such as ficolin, glucose-binding lectin, mannose-binding lectin-associated serine protease (MASP), and C3. Evidence for a more primitive origin is offered in the present study on the Pacific oyster Crassostrea gigas. C3 protein in C. gigas (CgC3) was found to be cleaved after stimulation with the bacteria Vibrio splendidus. In addition, we identified a novel C-type lectin (defined as CgCLec) with a complement control protein (CCP) domain, which recognized various pathogen-associated molecular patterns (PAMPs) and bacteria. This protein was involved in the activation of the complement system by binding CgMASPL-1 to promote cleavage of CgC3. The production of cytokines and antibacterial peptides, as well as the phagocytotic ratio of haemocytes in CgCLec-CCP-, CgMASPL-1-, or CgC3-knockdown oysters, decreased significantly after V. splendidus stimulation. Moreover, this activated CgC3 participated in perforation of bacterial envelopes and inhibiting survival of the infecting bacteria. These results collectively suggest that there existed an ancient lectin pathway in molluscs, which was activated by a complement cascade to regulate the production of immune effectors, phagocytosis, and bacterial lysis.


Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import.
In mammalian cells, one-third of all polypeptides are transported into or across the ER membrane via the Sec61 channel. While the Sec61 complex facilitates translocation of all polypeptides with amino-terminal signal peptides (SP) or transmembrane helices, the Sec61-auxiliary translocon-associated protein (TRAP) complex supports translocation of only a subset of precursors. To characterize determinants of TRAP substrate specificity, we here systematically identify TRAP-dependent precursors by analyzing cellular protein abundance changes upon TRAP depletion using quantitative label-free proteomics. The results are validated in independent experiments by western blotting, quantitative RT-PCR, and complementation analysis. The SPs of TRAP clients exhibit above-average glycine-plus-proline content and below-average hydrophobicity as distinguishing features. Thus, TRAP may act as SP receptor on the ER membrane's cytosolic face, recognizing precursor polypeptides with SPs of high glycine-plus-proline content and/or low hydrophobicity, and triggering substrate-specific opening of the Sec61 channel through interactions with the ER-lumenal hinge of Sec61α.


Purification and characterization of the E1 component of the Clostridium magnum acetoin dehydrogenase enzyme system.
In Clostridium magnum strain Wo Bd P1 the formation of the enzyme components of the acetoin dehydrogenase enzyme system E1 (acetoin:2,6-dichlorophenolindophenol oxidoreductase Ao:DCPIP OR), E2 (dihydrolipoamide acetyltransferase DHLTA) and E3 (dihydrolipoamide dehydrogenase DHLDH) were induced during growth on acetoin. Ao:DCPIP OR was purified from acetoin-grown cells in two steps by chromatography on DEAE-Sephacel and on Mono Q HR. Native Ao:DCPIP OR exhibited a M(r) of 138,000; it consisted of two different subunits of M(r) alpha 38,500 and M(r) beta 34,000, and it occurred most probably in a tetrameric alpha 2 beta 2 structure. The N-terminal amino acid sequences of the alpha- and beta-subunits revealed homologies to the N-termini of the corresponding subunits of Ao:DCPIP OR from Pelobacter carbinolicus and from Alcaligenes eutrophus; furthermore, the N-terminus of the beta-subunit exhibited homologies to the N-termini of beta-subunits from different 2-oxo acid dehydrogenases.