Association between Dietary Antioxidant Quality Score and Anthropometric Measurements in Children and Adolescents: The Weight Disorders Survey of the CASPIAN-IV Study.
Limited experience exists on the relationship between anthropometric measures and dietary antioxidant intake in the pediatric age group. We aimed to investigate the association of dietary antioxidants intake and anthropometric measurement in children and adolescents. This nationwide study was conducted in 4270 children and adolescents, aged 6-18 years. Demographic and anthropometric data were assessed. Children and adolescents were classified as underweight, healthy weight or overweight/obese based on body mass index percentiles. Dietary intake was obtained by a 168-item semi-quantitative validated food frequency questionnaire. Energy and nutrients intake was estimated using the Nutritionist IV software. Dietary antioxidant quality score (DAQS) was calculated based on the daily dietary intake of selenium, zinc, vitamin A, vitamin C and vitamin E compared with daily recommended intake. After adjustment for age, gender, living area (rural or urban), energy intake and physical activity level, DAQS was positively associated with waist circumference (WC), hip circumference and waist-to-height ratio (WHtR) in under-weight children and adolescents (B = 1.614, 1.634 and 0.01, respectively; all ps < 0.05). Increased DAQS was significantly associated with higher WC and WHtR in normal-weight children and adolescents (B = 0.536 and 0.003, respectively; all ps <0.05). Dietary intakes of some antioxidants were higher in children and adolescents with excess weight. DAQS was correlated with some anthropometric measurements in under-weight and normal-weight subjects. It can provide a novel approach to assess the role of antioxidant intake on health promotion and diet-based therapies in under-weight and normal-weight children and adolescents.


Suspected paraspinal abscess and spinal epidural empyema in a dog.
Epidural spinal cord compression was visualized myelographically in a dog presented for rapid development of paraparesis. A large, fluid-filled pocket in the epaxial musculature was found at surgery and appeared to communicate with the first lumbar vertebra. Unfortunately, cytopathological evaluation of the fluid was not performed. No etiological agents were isolated on aerobic culture. The dog responded well to decompressive surgery and medical therapy consisting of antibiotics, pain medication, and nursing care. In the veterinary literature, only two studies of spinal epidural empyema in the dog have been reported. Of these dogs, one had successful decompressive surgery performed. The other dogs in these two reports were euthanized. The dog presented in this report fully recovered. Spinal epidural empyema should be considered as a differential diagnosis in dogs presenting with a fever and a rapidly progressing myelopathy.


Ligand-assisted Hydride Transfer: A Pivotal Step for CO2 Hydroboration Catalyzed by a Mononuclear Mn(I) PNP Complex.
A mononuclear Mn(I) pincer complex [Mn(Ph2 PCH2 SiMe2 )2 NH(CO)2 Br] was disclosed to catalyze the pinacolborane (HBpin)-based CO2 hydroboration reaction. Density functional calculations were conducted to reveal the reaction mechanism. The calculations showed that the reaction mechanism could be divided into four stages: (1) the addition of HBpin to the unsaturated catalyst C1; (2) the reduction of CO2 to HCOOBpin; (3) the reduction of HCOOBpin to HCHO; (4) the reduction of HCHO to CH3 OBpin. The activation of HBpin is the ligand-assisted addition of HBpin to the unsaturated Mn(I)-N complex C1 generated by the elimination of HBr from the Mn(I) pincer catalyst. The sequential substrate reductions share a common mechanism, and every hydroboration commences with the nucleophilic attack of the Mn(I)-H to the electron-deficient carbon centers. The hydride transfer from Mn(I) to HCOOBpin was found to be the rate-limiting step for the whole catalytic reaction, with a total barrier of 27.0 kcal/mol, which fits well with the experimental observations at 90 °C. The reactivity trend of CO2 , HCOOBpin, HCHO, and CH3 OBpin was analyzed through both thermodynamic and kinetic analysis, in the following order, namely HCHO>CO2 >HCOOBpin≫CH3 OBpin. Importantly, the very high barrier for the reduction of CH3 OBpin to form CH4 reconciles with the fact that methane was not observed in this catalytic reaction.


Methylmercury and total mercury in plant litter decomposing in upland forests and flooded landscapes.
The overall objectives of this study were to examine the effects of flooding on the decomposition and mercury (Hg) content of tissues from plants common to boreal upland forests at the Experimental Lakes Area in northwestern Ontario. We used litterbags to study changes in total Hg (THg), methyl Hg (MeHg), carbon (C), and nitrogen (N) in 12 different plant tissues (birch, alder, blueberry, and Labrador tea leaves, bunchberry plants, jack pine needles, Sphagnum spp., Polytrichum spp., and Pleurozium spp. bryophytes, lichen, and fresh and extensively decomposed wood) placed on unflooded boreal forest soils and in experimentally created reservoirs over an approximately 800 day period. Rates of decomposition (as indicated by differences in the percentage of C and N mass left in the tissues over time) were slower in plant tissues placed on unflooded soils compared to the same tissues that were inundated in reservoirs. Depending on tissue type and initial THg concentrations, decomposing litter on both unflooded and flooded soils was either a source or a sink for THg. Tissues where initial THg concentrations were greater than 30 ng g(-1) represented a source of THg to the surrounding environment, whereas tissues that had initial concentrations of less than 30 ng g(-1) gained THg mass. Initial rates of change in THg were more rapid in plant tissues placed in reservoirs compared to the same plant tissue placed on unflooded soils, but there were no differences in final THg masses after approximately 800 days. Plant tissues placed in reservoirs exhibited large increases in MeHg mass, whereas MeHg mass decreased in the same plants placed on unflooded soils. This is the first study examining THg and MeHg cycling in decomposing plants in upland boreal forests and reservoirs.


[Swanson double-stem silicone implant arthroplasty of first metatarsophalangeal point].
To evaluate the curative effectiveness of Swanson double-stem silicone implant arthroplasty on the reconstruction of first metatarsophalangeal joint. Swanson double-stem silicone implant arthroplasty was performed on 10 patients, 2 males and 8 females, aged 60 (57-75), suffering from diseases of first metatarsophalangeal joint with 13 diseased joints, including hallux valgus with geriatric osteoarthritis (8 cases, 10 joints), rheumatoid arthritis (1 case, 2 joints), and traumatic arthritis (1 case, 1 joint). All patients were followed up for an average of 25 months (12-38 months). Eight patients felt complete satisfaction with the operation, 1 patient showed satisfaction to some extent, and 1 patient was not satisfied because of pain of the first matatarsophalangeal joint due to severe hyperosteogeny surrounding the cut bone face 3 years after the operation. Osteolysis around the silicone implant occurred in 2 cases without clinical symptoms, and no special treatment was given. With the advantages of alleviating pain, preserving the length and alignment of great toe, improving the function of walking, and correcting the deformity, Swanson double-stem silicone implant arthroplasty is effective on reconstruction of the first metatarsophalangeal joint.


Cardiac ryanodine receptor calcium release deficiency syndrome.
Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia, a condition characterized by prominent ventricular ectopy in response to catecholamine stress, which can be reproduced on exercise stress testing (EST). However, reports of sudden cardiac death (SCD) have emerged in EST-negative individuals who have loss-of-function (LOF) RyR2 mutations. The clinical relevance of RyR2 LOF mutations including their pathogenic mechanism, diagnosis, and treatment are all unknowns. Here, we performed clinical and genetic evaluations of individuals who suffered from SCD and harbored an LOF RyR2 mutation. We carried out electrophysiological studies using a programed electrical stimulation protocol consisting of a long-burst, long-pause, and short-coupled (LBLPS) ventricular extra-stimulus. Linkage analysis of RyR2 LOF mutations in six families revealed a combined logarithm of the odds ratio for linkage score of 11.479 for a condition associated with SCD with negative EST. A RyR2 LOF mouse model exhibited no catecholamine-provoked ventricular arrhythmias as in humans but did have substantial cardiac electrophysiological remodeling and an increased propensity for early afterdepolarizations. The LBLPS pacing protocol reliably induced ventricular arrhythmias in mice and humans having RyR2 LOF mutations, whose phenotype is otherwise concealed before SCD. Furthermore, treatment with quinidine and flecainide abolished LBLPS-induced ventricular arrhythmias in model mice. Thus, RyR2 LOF mutations underlie a previously unknown disease entity characterized by SCD with normal EST that we have termed RyR2 Ca2+ release deficiency syndrome (CRDS). Our study provides insights into the mechanism of CRDS, reports a specific CRDS diagnostic test, and identifies potentially efficacious anti-CRDS therapies.


No hybrid snowcocks in the Altai-Hyper-variable markers can be problematic for phylogenetic inference.
A recent article in Ecology and Evolution featured the discovery of hybrid snowcocks (Tetraogallus) and speculated on the hybrid origin of an extant species (T. altaicus). Comprehensive re-analyses of original data from the latter paper reliably refute the phylogenetic hypothesis taken as firm evidence of a past hybridization event in these birds. The new re-analyses showed that there is no evidence of hybridization in these snowcocks from the data available so far.


Nonprogressive Unilateral Intracranial Arteriopathy in Children with Arterial Ischemic Stroke.
The nonprogressive unilateral intracranial arteriopathy known as transient (focal) cerebral arteriopathy is not a well-recognized arteriopathy among practitioners of Korea and Japan, although it cannot be easily differentiated from early moyamoya disease. This review summarizes the nomenclature, pathophysiology, diagnostic evaluation, clinico-radiological features, and management of nonprogressive (reversible or stable) unilateral arteriopathy based on the relevant literature and our own experiences. Nonprogressive unilateral arteriopathy should be strongly suspected in children presenting with basal ganglia infarction and arterial beading. The early identification of patients likely to have nonprogressive or progressive arteriopathy would ensure proper management and guide further research for secondary stroke prevention.


Selenium tissue burden compartmentalization in resident white sturgeon (Acipenser transmontanus) of the San Francisco Bay Delta estuary.
High selenium (Se) loads in the San Francisco Bay Delta are bioaccumulated and biomagnified in food webs and can impair the reproduction of resident oviparous animals such as white sturgeon. The objective of the present study was to determine the Se tissue burden in San Francisco Bay Delta-resident white sturgeon to assess Se bioaccumulation in different organs, including ovaries and liver where egg yolk precursor proteins are synthesized. The authors obtained 54 San Francisco Bay Delta-resident white sturgeon including 26 female and 28 male subadults with immature gonads, 8 females with vitellogenic eggs, and 13 males with maturing gonads. Length, weight, age, reproductive stage of development, and kidney, liver, gonad, and muscle Se concentrations were determined in all fish. Concentrations of Se in muscle, gonads, and liver significantly increased with fish size, whereas kidney Se was not correlated to body size and was at the highest level compared with other organs. There was no difference between the sexes (p > 0.05) in Se concentrations in kidney (12.83 ± 0.51 µg · g(-1) dry wt), liver (11.85 ± 1.04 µg · g(-1) dry wt), and muscle (7.09 ± 0.52 µg · g(-1) dry wt; mean ± standard error, n = 47); but Se concentration was higher in the ovary than in testis (p = 0.04). Females with vitellogenic eggs had higher Se concentrations in the ovaries (20.77 ± 4.11 µg · g(-1) dry wt vs 5.22 ± 2.50 µg · g(-1) dry wt), liver (21.84 ± 2.07 µg · g(-1) dry wt vs 8.03 ± 1.03 µg · g(-1) dry wt), and muscle (10.18 ± 1.93 µg · g(-1) dry wt vs 5.48 ± 0.64 µg · g(-1) dry wt) compared with less advanced, previtellogenic females (p < 0.05). The elevated Se concentrations in the ovaries and liver of vitellogenic San Francisco Bay Delta white sturgeon were comparable with levels previously shown to cause reproductive toxicity in dietary Se experiments with captive white sturgeon.


False hyperchloraemia in a dog secondary to ingestion of horse feed supplemented with potassium bromide.
A dog was presented for acute abdominal distension after inadvertent access to a large amount of dry dog food and possibly horse feed consisting of chaff, pony cubes and vitamin, mineral and yeast supplements. A marked hyperchloraemia and decreased anion gap on blood electrolyte analysis prompted a review of the patient's history for potential ingestion of bromide. It was revealed that the horse feed was supplemented with potassium bromide. The serum bromide level was 23.6 mmol/L. The dog recovered uneventfully. This case report highlights the importance of knowing common interferents of chemical analysis techniques.


Pressure denaturation and aggregation of beta-lactoglobulin studied by intrinsic fluorescence depolarization, Rayleigh scattering, radiationless energy transfer and hydrophobic fluoroprobing.
beta-Lactoglobulin (beta-lg) in aqueous solution under pressure showed a marked depolarization of intrinsic fluorescence assigned to a gradually increased rotational diffusion of tryptophyl moieties in pressure-unfolded states. The corresponding change in anisotropy provided a new and more accurate method for determining denaturation volume which, for beta-lg in neutral aqueous solution with ionic strength 0.16 (NaCl) at 25 degrees C, was delta V degree = -73 (SE 3) ml mol-1, corresponding to half denaturation at 123 MPa. The pressure unfolding led to exposure of hydrophobic regions to the protein-water interface that could be probed by fluorescence intensity of a beta-lg-1-anilinonaphthalene-8-sulphonic acid (ANS) complex with 1:1 stoichiometry, as determined by Job's method of continuous variation. The unfolding of beta-lg impaired the binding capacity of the inner calyx, with a reduction in binding capacity of 50% at 50 MPa, as shown by decreasing cis-parinaric acid fluorescence, decreasing anisotropy and decreasing radiationless energy transfer from tryptophans to this probe with increasing pressure. The pressure-induced reversible exposure of hydrophobic groups to the protein-water interface may, at least partly, explain the initial aggregation reactions, evident from increased Rayleigh scattering from approximately 50 MPa, prior to irreversible pressure-induced gel formation of beta-lg. Using results from this and previous studies, we propose a three step pressure denaturation model for beta-lg for neutral solution at ambient temperature, including an initial pressure-melted state (up to 50 MPa) with partial collapse of the inner calyx and solvent exposure of the free thiol group, followed by a reversible denaturation with exposure of hydrophobic regions (half denaturation at 123 MPa) and with irreversible denaturation with thiol-disulphide exchange becoming increasingly important at higher pressures. Effects of pressure on beta-lg, as measured by fluorescence depolarization, were found for the reversible denaturation steps to be similar to the effects of chemical denaturants but different with respect to shift in ANS emission maxima.


Techniques for High-Quality Ambient Coarse Particle Mass Measurements.
Several recent studies have shown associations between ambient concentrations of particle mass (PM) and rates of morbidity and mortality in the general population. These studies have raised the issue of quality of coarse mass (CM, PM between 2.5 and 10 µm) data used for these purposes. CM data may have precision three or more times worse than the associated PM 2.5 or PM10 data, depending on the measurement method, PM 2.5 to PM 10 ratios, and CM concentrations. CM is measured either as the difference between collocated PM10 and PM2.5 samplers or more directly with a dichotomous (virtual impactor) sampler. CM precision for the difference method is degraded due to the increased errors inherent with using the difference between two independent measurements, as well as the high PM2.5 to PM10 ratios (and low CM concentrations) typical of the eastern United States. The dichotomous sampler (dichot) makes a more direct measurement of CM, but there is a potential for significant postexposure loss of particles from unoiled CM dichot filters, as well as uncertainties in the dichot's CM channel enrichment factor. Compared to the dichot, low-volume inertial impactor samplers such as the Harvard Impactor (HI) or PM2.5 Federal Reference Method (FRM) are simpler to operate and maintain, provide sharper cut points, and do not require oiled filters to prevent loss of CM from the filter during transport. With the recent interest in CM spatial and temporal variability with respect to PM health effects, we have developed modifications to the HI PM method to provide measurements of 24-hour PM with estimated CM precision of better than 5% CV and r2 higher than 0.95, primarily by lowering field blank variability and increasing gravimetric analytical precision. These high-precision PM techniques are not limited to the HI sampler; they can also be applied to the PM2.5 FRM sampler. The measurement methods described here can be applied to future PM studies to avoid the potential problems with exposure assessment caused by CM measurements that have poor precision.


Effect of extrusion temperature on the solubility and molecular weight of lentil bean flour proteins containing low cysteine residues.
Lentil flour was extruded at die temperatures of 135, 160, and 175 degrees C. The soluble protein content in the extrudates decreased by 40.1% in the extracting buffer (1% sodium dodecyl sulfate in 50 mM sodium phosphate buffer, pH 6.9) as the extrusion die temperature was increased to 175 degrees C. The most insoluble proteins in the extrudates extruded at die temperatures of up to 175 degrees C could be resolubilized by using sonication. The total disulfide content and sulfhydryl content in the extrudates decreased. The SDS-PAGEs showed that the molecular weight distribution of proteins in the lentil flour changed little before and after extrusion as well as during reduction. The results from this study show that the extrusion temperature had less effect on the solubility and molecular weight of the lentil proteins, which contain a lower level of cysteine residues than wheat proteins.


Local public services and migration: educational change evidence from Norwegian municipalities.
"We take advantage of a large panel data base covering most Norwegian municipalities during seven years to examine the relationship between local public services and migration to and from municipalities for different age groups. The main innovation of the paper is that we use a survey data set to verify that the input measures employed as explanatory variables in the migration study actually are related to citizen satisfaction with local public services. We find that the results depend crucially on whether the input measures are instrumented. When input measures are instrumented, we find few effects of local public services on migration."


[Getting to know former students of PROFAE nursing courses].
The PROFAE (Professionalization Project in Nursing) was a relevant initiative for professional education. The objectives were to describe the profile of the former students of the technical nursing course of the São Paulo Health Department training centers so as to evaluate the effects of the course for the mobility and professional performance in the working market. Data collection was performed using a questionnaire answered by 216 former students and four focal groups with former students and nurse supervisors. Most respondents were women, with an average age of 42.2. The course received a positive evaluation, and two aspects were pointed out as motivating for searching for it: institutional support and COREN's resolutions. The former students perceive they had more initiative and theoretical preparation after the course. Nursing aide remains as the most common position in the area, thus causing dissatisfaction, because, especially in public services, technician positions are not available.


Rotational and vibrational energy transfer in vibrationally excited acetylene at energies near 6560 cm(-1).
Collisional energy transfer kinetics of vibrationally excited acetylene has been examined for states with internal energies near 6560 cm(-1). Total population removal rate constants were determined for selected rotational levels of the (1,0,1,0(0),0(0)) and (0,1,1,2(0),0(0)) states. Values in the range of (10-18) × 10(-10) cm(3) s(-1) were obtained. Measurements of state-to-state rotational energy transfer rate constants were also carried out for these states. The rotational energy transfer kinetics was found to be consistent with simple energy gap models for the transfer probabilities. Vibrational transfer out of the (0,1,1,2(0),0(0)) state accounted for no more than 16% of the total removal process. Transfer from (1,0,1,0(0),0(0)) to the u-symmetry (0,2,0,3(1),1(-1)), (0,1,1,2(0),0(0)), and (1,1,0,1(1),1(-1)) states was observed. Applying the principle of detailed balance to these data indicated that vibrational transfer to (1,0,1,0(0),0(0)) accounted for ~0.1% of the population loss from (0,2,0,3(1),1(-1)) or (0,1,1,2(0),0(0)), and 3% of the loss from (1,1,0,1(1),1(-1)). Relative rotational transfer probabilities were obtained for transfer to the g-symmetry (1,1,0,2(0),0(0))∕(0,0,2,0(0),0(0)) dyad. These results are related to recent studies of optically pumped acetylene lasers.


Distribution and neurochemical characterization of neurons expressing GIRK channels in the rat brain.
G-protein inwardly rectifying potassium (GIRK) channels mediate the synaptic actions of numerous neurotransmitters in the mammalian brain and play an important role in the regulation of neuronal excitability in most brain regions through activation of various G-protein-coupled receptors such as the serotonin 5-HT(1A) receptor. In this report we describe the localization of GIRK1, GIRK2, and GIRK3 subunits and 5-HT(1A) receptor in the rat brain, as assessed by immunohistochemistry and in situ hybridization. We also analyze the co-expression of GIRK subunits with the 5-HT(1A) receptor and cell markers of glutamatergic, gamma-aminobutyric acid (GABA)ergic, cholinergic, and serotonergic neurons in different brain areas by double-label in situ hybridization. The three GIRK subunits are widely distributed throughout the brain, with an overlapping expression in cerebral cortex, hippocampus, paraventricular nucleus, supraoptic nucleus, thalamic nuclei, pontine nuclei, and granular layer of the cerebellum. Double-labeling experiments show that GIRK subunits are present in most of the 5-HT(1A) receptor-expressing cells in hippocampus, cerebral cortex, septum, and dorsal raphe nucleus. Similarly, GIRK mRNA subunits are found in glutamatergic and GABAergic neurons in hippocampus, cerebral cortex, and thalamus, in cholinergic cells in the nucleus of vertical limb of the diagonal band, and in serotonergic cells in the dorsal raphe nucleus. These results provide a deeper knowledge of the distribution of GIRK channels in different cell subtypes in the rat brain and might help to elucidate their physiological roles and to evaluate their potential involvement in human diseases.


Evidence for amino Acid-h co-transport in oat coleoptiles.
Microelectrode and tracer techniques were used to test for possible amino acid-H(+) co-transport in coleoptiles of Avena sativa L. cv. "Garry." The amino acid analogue alpha-aminoisobutyric acid (AIB) caused transient depolarization of the membrane potential. The absolute magnitude of the maximum depolarization was affected by the same factors that affected AIB transport. Both increased with higher concentrations of AIB, increased with higher acidities in the medium, and were enhanced by indoleacetic acid (which hyperpolarized the membrane potential). AIB transport was reduced as K(+) concentrations in the medium were increased and by the metabolic inhibitor NaN(3), both of which reduce membrane potentials. Our data fit an amino acid-H(+) co-transport model in which transport is controlled by both the membrane potential and proton concentration components of the chemical potential difference of protons across the coleoptile cell membrane.


Differences of chronopharmacokinetic profiles between propranolol and atenolol in hypertensive subjects.
Previous studies have shown that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the night dosage than after the morning dosage in nocturnal rodents. The present study examines whether such a difference in chronopharmacokinetic profiles between lipophilic and hydrophilic agents also exists in humans. Propranolol (20 mg), a lipophilic beta-blocker, or atenolol (50 mg), a hydrophilic beta-blocker, was given orally to 13 hypertensive patients at 9:00 AM (day trial) or 9:00 PM (night trial) by a crossover design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, and atenolol were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours after treatment. Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of propranolol in the day trial were significantly greater than those in the night trial. Time to maximum plasma concentration (tmax) was significantly shorter in the day trial. No significant difference was observed in the elimination half-life between the two trials. There were similar administration time-dependent changes in the Cmax for 4-hydroxypropranolol and naphthoxylactic acid. On the other hand, although the Cmax of atenolol was greater and its tmax was shorter in the day trial, the differences did not reach significance. These results suggest that propranolol, but not atenolol is absorbed more rapidly after the morning dosage than after the night dosage. Based on these findings, the authors speculate that the absorption rate of a lipophilic, but not hydrophilic, agent is faster after the morning dosage than after the night dosage in humans.


Eosinophilic Cystitis: A Rare Cause of Nocturnal Enuresis in Children.
Eosinophilic cystitis (EC) is a rare and poorly understood inflammatory condition, characterized by eosinophilic infiltration of all layers of the bladder wall, which mimics bladder tumors. EC may present with symptoms such as increased urination frequency, dysuria, gross/microscopic hematuria, suprapubic pain and urinary retention. We present a 17-year-old male patient, who was continent night and day in his childhood, and was admitted to our clinic for complaints of hematuria and nocturnal enuresis for the past six months. His history and physical examination were unremarkable, and routine hematological and biochemical tests were normal. Cystoscopy revealed a 4 × 3 cm erythematous, polypoidal, solid lesion on the bladder dome. Histopathological examination of the lesion revealed transitional epithelium with stromal edema, where diffuse, dense infiltration of lamina propria by eosinophils and lymphocytes was also seen. According to these findings, a histopathological diagnosis of EC was made, and the patient was treated with corticosteroids, antimicrobial agents and antihistamines. His symptoms dramatically improved and nocturnal enuresis also recovered after treatment. Although it is a rare entity, EC should be kept in mind in the differential diagnosis of patients presenting with dysuria, hematuria and any kind of acquired voiding dysfunction, including frequency, pollakiuria and incontinence.


Influence of Alloying Elements on the Mechanical Properties of Anodized Aluminum and on the Adhesion of Copper Metallization.
The active development of the power electronics market and a constant increase in the prices of components require new materials and approaches, including a power module packaging technology. The use of aluminum instead of copper in the power module baseplate is an interesting and promising solution. The insulated metal baseplate is one of the most extensively developed technologies nowadays. The object of this study is an insulated metal substrate based on anodized aluminum. The main goal of the article is the comparison of copper topology adhesion to an anodized aluminum oxide layer formed on different aluminum alloys with aluminum content of at least 99.3 wt %. Peel test and pull-off adhesions showed a twofold difference for both aluminum alloys. The high ordered defect-free anodized alumina formed on alloys with copper content of 0.06 wt % had a mean pull-off adhesion of 27 N/mm2 and hardness of 489 HV. In the case of the alloy with copper content of around 0.15 wt %, it had hardness of 295 HV and a mean pull-off adhesion of 12 N/mm2. The results of our microstructure investigation showed that anodized alumina based on alloys with copper content of around 0.15 wt % is fragile due to spherical holes. Summing up the results, it can be concluded that not all initial impurities are critical for anodized alumina, but some, specifically copper, dramatically decreased the mechanical properties of anodized alumina.


Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women.
Several studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated. A case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12 were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR A2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Neither dietary intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23-3.83; P trend = 0.010). The MTR 2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01-3.92; P trend = 0.801), and statistically significant interactions with regard to risk were observed between the MTHFR A1298C polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022). MTHFR polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12 had no overall association with breast cancer risk. However, increased risk was observed in total women with the MTR 2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions between MTHFR polymorphisms and B vitamins, warrant further investigation.


A 7-amino-acid insert in the heavy chain nucleotide binding loop alters the kinetics of smooth muscle myosin in the laser trap.
Two smooth muscle myosin heavy chain isoforms differ by a 7-amino-acid insert in a flexible surface loop located near the nucleotide binding site. The non-inserted isoform is predominantly found in tonic muscle, while the inserted isoform is mainly found in phasic muscle. The inserted isoform has twice the actin-activated ATPase activity and actin filament velocity in the in vitro motility assay as the non-inserted isoform. We used the laser trap to characterize the molecular mechanics and kinetics of the inserted isoform ((+)insert) and of a mutant lacking the insert ((-)insert), analogous to the isoform found in tonic muscle. The constructs were expressed as heavy meromyosin using the baculovirus/insect cell system. Unitary displacement (d) was similar for both constructs (approximately 10 nm) but the attachment time (t(on) for the (-)insert was twice as long as for the (+)insert regardless of the [MgATP]. Both the relative average isometric force (Favg(-insert)/Favg(+insert) = 1.1 +/- 0.2 (mean +/- SE) using the in vitro motility mixture assay, and the unitary force (F approximately 1 pN) using the laser trap, showed no difference between the two constructs. However, as under unloaded conditions, t(on) under loaded conditions was longer for the (-)insert compared with the (+)insert construct at limiting [MgATP]. These data suggest that the insert in this surface loop does not affect the mechanics but rather the kinetics of the cross-bridge cycle. Through comparisons of t(on) from d measurements to various [MgATP], we conclude that the insert affects two specific steps in the cross-bridge cycle, that is, MgADP release and MgATP binding.


Effect of ram introduction on the oestrous cycle of springbok ewes (Antidorcas marsupialis).
Springbok are aseasonally breeding wild ungulates that inhabit arid environments, and interest has been shown in domesticating them for agricultural purposes. The present study was conducted for husbandry purposes to determine the effect of introducing a vasectomized ram to an isolated herd of springbok ewes (n = 9). Blood was collected from ewes every third day, before and after introduction of a vasectomized ram. Ewes were subjected to the ram for 42 days. Plasma progesterone was measured by radioimmunoassay and was used to establish the stage of the oestrous cycle. After introduction of the ram, the variation in the timing of the follicular phase between ewes was clearly reduced, compressing the spread of oestrus in the springbok ewes from 11 to 3 days. In seven of the nine ewes, the ram was introduced during the luteal phase of the oestrous cycle, causing this cycle to be significantly longer in duration (P < 0.05) and to have a higher maximum concentration of progesterone (P < 0.001) than cycles before and after introduction of the ram. This finding implies that the mechanism of synchronization operates through a luteotrophic effect. These results indicate that rams may be used successfully to synchronize breeding in springbok.


Acute renal failure in Kuwait--a prospective study.
This prospective study was conducted over a period of 18 months (February 1989 to July 1990) in the State of Kuwait. It covered a population of 1,024,211 and eight multidisciplinary hospitals with an in-patient admission of 118,079 per year. Two hundred and twenty-six adult patients with acute renal failure (ARF) were seen and followed up by nephrologists. This made the calculated annual incidence of ARF 14.7 per 100,000 population, nearly five times that reported by the EDTA registry (Biesenbach et al. 1991). Drugs, sepsis and volume depletion were the most frequent causes, with sepsis resulting in 36% cause specific mortality compared to zero mortality with the other two. The overall mortality rate was only 14% which clearly indicated a markedly improved prognosis in cases of ARF. The prognosis in ARF depended on two major factors, viz. the type of aetiological insult and the presence of predisposing associated medical illnesses. Multiple insults, though common, do not affect the mortality rate. Secondary sepsis or gastrointestinal bleeding as a cause of death in ARF was rarely seen in our study. Those who required dialytic support for renal failure had a 45% patient mortality rate in general. Over 40% of our patients were 60 years or older compared with only 3.5% in the local population. This indicated old age as a major risk factor in the development of ARF. The overall mortality in the elderly did not differ from that in the young, but sepsis in the elderly carried a mortality rate of 60% compared to only 14.8% in the younger age group.


A variable-wavelength-based approach of phase retrieval for contrast transfer function based methods.
X-ray phase-contrast imaging has emerged as an important method for improving contrast and sensitivity in the field of X-ray imaging. This increase in the sensitivity is attributed to the fact that, in the hard X-ray regime, the phase shift is more prominent as compared with the attenuation for materials having a low X-ray absorption coefficient. Among all the methods using the X-ray phase-contrast technique, in-line phase-contrast imaging scores over the other methods in terms of ease of implementation and efficient use of available X-ray flux. In order to retrieve the projected phase map of the object from the recorded intensity pattern, a large number of algorithms have been proposed. These algorithms generally use either the transport of intensity or contrast transfer function based approach for phase retrieval. In this paper it is proposed to use multiple wavelengths for phase retrieval using the contrast transfer function based formalism.


Spontaneous autoimmunity sufficiently potent to induce diabetes mellitus is insufficient to protect against insulinoma.
Intact tolerogenic mechanisms preclude effective immunity against tumors, as most tumor Ags differ little from normal host Ags. In contrast, when tolerance fails, the immune system becomes inappropriately activated against an autoantigen. We postulated that CD8(+) T cells activated during autoimmunity are capable of protecting against tumors that express the targeted autoantigen. To test this hypothesis, double-transgenic 8.3-NOD-RIPTAg mice were developed (where NOD is nonobese diabetic, RIP is rat insulin promoter, and TAg is large T Ag). In this model, individuals with the RIPTAg transgene develop insulinoma; those expressing a transgenic TCR (8.3-TCR) recognizing the islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP) harbor a peripheral immune system dominated by diabetogenic CD8(+) T cells. Although tumor emergence was significantly slower in 8.3-NOD-RIPTAg mice compared with NOD-RIPTAg mice, all 8.3-NOD-RIPTAg mice eventually developed insulinoma. Tumor emergence was not secondary to clonal deletion or anergy. Ag loss and MHC down-regulation were not apparent. Endogenous 8.3-TCR CD8(+) T cells were recruited to the tumor site and proliferated upon arrival to the tumor, although they were notably absent from the central parts of more advanced tumors. These results demonstrate that a breakdown of tolerance capable of causing autoimmune disease is insufficient for effective tumor immunity. Alterations in the tumor microenvironment may inhibit efficient and comprehensive delivery of CD8(+) T cells to all regions of the tumor. These data suggest that any immunotherapeutic strategy for cancer must involve enhancement of a proinflammatory tumor microenvironment in addition to inhibition of tolerogenic mechanisms.


Phosphatidylserine, a putative inhibitor of tumor necrosis factor, prevents autoimmune demyelination.
We tested the effect of bovine cortex phosphatidylserine (BC-PS), a membrane phospholipid known to inhibit the release of the cytokine tumor necrosis factor (TNF), in SJL/J mice sensitized for adoptively transferred experimental autoimmune encephalomyelitis (EAE). Control, sensitized mice developed severe clinical and histologic EAE within 6 to 9 days, whereas only 20% of mice given BC-PS displayed clinical signs that were much less severe and minimal CNS pathology. Cessation of BC-PS treatment after 15 to 40 days led to disease within 1 to 2 weeks, but when treatment was more prolonged, animals remained healthy after cessation. Serial transfer of spleen cells (SC) from BC-PS-treated and control animals into naive recipients resulted in acute EAE within 6 to 7 days with cells from either donor type. Animals treated late with BC-PS failed to relapse and generally remained healthier than controls did over a 40-day period of observation. Cultures of lymph node cells or SC from BC-PS-treated and control animals showed an 80 to 90% reduction in TNF production in the BC-PS-treated group. Thus, we demonstrate that PS can abrogate or significantly reduce the severity of EAE without permanently inhibiting effector T cells. The approach might be considered a candidate for future therapies of relevance to MS.


Oxidized LDLs influence thrombotic response and cyclooxygenase 2.
Oxidative modification of low-density lipoproteins (LDLs) plays a key role in the development of atherosclerosis and the onset of coronary artery disease. LDL oxidation alters the antithrombotic balance of human endothelial cells inducing surface tissue factor (TF) pathway activity, which results in enhanced fibrin deposition. Fibrinolysis, which is strictly regulated by plasminogen activator inhibitor-1 (PAL-1) and tissue-type plasminogen activator (tPA). Is also dysregulated by LDL oxidation with a net increase in the inhibitory rate. Oxidized LDLs (oxLDLs) also affect many aspects of macrophage function linked to the inflammatory response of these cells, In particular, oxLDLs downregulate inducible cyclooxigenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide. This observation may support the hypothesis that, within atheromata, the transformation macrophages into foam cells results in the attenuation of the inflammatory response, thus contributing to the progression of athrogenesis. Among lipid constituents of oxLDLs, Ox-PAPC, a mixture of oxidized arachidonic acid-containing phospholipids, prevents Cox-2 expression, suggesting that it could be considered responsible for the biological activity of oxLDLs.


Genome-wide association mapping for component traits of drought and heat tolerance in wheat.
Identification of marker trait association is a prerequisite for marker-assisted breeding. To find markers linked with traits under heat and drought stress in bread wheat (Triticum aestivum L.), we performed a genome-wide association study (GWAS). GWAS mapping panel used in this study consists of advanced breeding lines from the IARI stress breeding programme produced by pairwise and complex crosses. Phenotyping was done at multi locations namely New Delhi, Karnal, Indore, Jharkhand and Pune with augmented-RCBD design under different moisture and heat stress regimes, namely timely sown irrigated (IR), timely sown restricted irrigated (RI) and late sown (LS) conditions. Yield and its component traits, viz., Days to Heading (DH), Days to Maturity (DM), Normalized Difference Vegetation Index (NDVI), Chlorophyll Content (SPAD), Canopy temperature (CT), Plant Height (PH), Thousand grain weight (TGW), Grain weight per spike (GWPS), Plot Yield (PLTY) and Biomass (BMS) were phenotyped. Analysis of variance and descriptive statistics revealed significant differences among the studied traits. Genotyping was done using the 35k SNP Wheat Breeder's Genotyping Array. Population structure and diversity analysis using filtered 10,546 markers revealed two subpopulations with sufficient diversity. A large whole genome LD block size of 7.15 MB was obtained at half LD decay value. Genome-wide association search identified 57 unique markers associated with various traits across the locations. Twenty-three markers were identified to be stable, among them nine pleiotropic markers were also identified. In silico search of the identified markers against the IWGSC ref genome revealed the presence of a majority of the SNPs at or near the gene coding region. These SNPs can be used for marker-assisted transfer of genes/QTLs after validation to develop climate-resilient cultivars.


Acetazolamide triggers death inducing autophagy in T-47D breast cancer cells.
The inhibitory effects of acetazolamide on the growth and proliferation of epithelial breast cancer cells (T-47D) were investigated. Analysis of morphological changes indicated little apoptosis in T-47D cells incubated with acetazolamide, according to data from flow cytometry, DNA laddering, and expression of AIF. However, an increase in caspase-3 activity was detected in cells. This was concomitant with an increase in DFF45/DFF40 ratio leading to inhibition of caspase-3 activity, DNA fragmentation and progression of apoptosis. Flow cytometry also confirmed that acetazolamide had no significant effect on cell cycle progression. These results are consistent with lack of change in the expression of cell cycle regulatory proteins p21, p27, cdc2 and cyclinD1. Increased expression of ATG5, p53 and DRAM, along with an increase in BCLN1/Bcl-2 ratio, indicated that acetazolamide inhibited the proliferation of T-47D cells by inducing autophagy. Increased expression of PTEN, along with decreased expression of Akt1, also showed that acetazolamide treatment resulted in death inducing autophagy. Collectively the results indicate that autophagy is an adequate mechanism mediating the anti-cancer effects of acetazolamide in T-47D cells through engagement of p53/DRAM pathway and attenuation of Akt survival signalling.


Constitutional chromosome anomalies in patients with cerebral gigantism (Sotos syndrome).
Two boys are presented with the clinical features of cerebral gigantism and chromosomal variants which have not been described so far in this syndrome. In the first boy a de novo pericentric inversion of chromosome Y was found, the karyotypes of all other investigated family members were normal. The patient had an obstructive hypertrophic cardiomyopathy and atrial septal defect type II. The second boy had inherited pericentric inversion of the heterochromatic region of chromosome 9 from his mother. This chromosome 9 variant was also found in his sister who had a similar phenotype but without gigantism. Endocrine evaluation demonstrated normal results in both boys. The intellectual achievement in both cases was average.


[TGF-β1 activates NOX4/ROS pathway to promote the invasion and migration of cervical cancer cells].
Objective To investigate the role of transforming growth factor β1/nicinamide adenine dinucleotide phosphate oxidase/reactive oxygen species (TGF-β1/NOX4/ROS) signaling pathway in the invasion and migration of cervical cancer cells. Methods The cultured SiHa, CaSki, HeLa, C4-I and C33A cervical cancer cells were treated with 5 ng/mL TGF-β1 for 4 hours or 8 hours. ROS levels in these cervical cancer cells were detected using 2', 7'-dichlorofluorescein diacetate (DCFH-DA) staining combined with flow cytometry. After the transfection of NOX4 small interfering RNA (NOX4-siRNA) into HeLa cells or using of NOX4 signaling pathway inhibitor diphenylidene iodine chloride (DPI), NOX4 protein expression was measured by Western blotting, and the effect of TGF-β1 on migration and invasion ability of cervical cancer cells were analyzed by TranswellTM assay. Results TGF-β1 significantly up-regulated NOX4 protein expression, increased ROS production in HPV-positive cervical cancer cells (SiHa, CaSki, HeLa and C4-I) and promoted the migration and invasion abilities of cervical cancer cells. Silencing the NADPH oxidase gene or using the NOX4 pathway inhibitor DPI could reverse this effect. Conclusion TGF-β1 can activate NOX4/ROS signaling pathway to enhance the invasion and migration abilities of cervical cancer cells.


The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS.
To date, several classes of enzymes have been shown to affect transcription by catalyzing the modifications of nucleosomes via methylation. Employing our global proteomic screen, GPS, we have determined that the loss of Bur2, a component of the Bur1/Bur2 cyclin-dependent protein kinase, results in a decrease in histone H3(K4) methylation catalyzed by COMPASS. Furthermore, Bur1/Bur2 is required for histone H2B monoubiquitination by Rad6/Bre1. The effect on histone monoubiquitination and methylation is the result of defective Bur1/Bur2-mediated phosphorylation of Rad6 on its serine residue 120 and proper recruitment of the Paf1 complex to chromatin. We have also demonstrated that serine 120 of Rad6 is required for histone H2B monoubiquitination and the regulation of gene expression in vivo. Our results identify in vivo substrates for Bur1/Bur2, thus linking its role to transcriptional elongation and demonstrating a potential activation mechanism for histone H2B monoubiquitination by the Rad6/Bre1 complex.


Analysis of Factors Influencing Telemedicine-Based Psychiatric Extended Care and Care of Psychiatric Patients.
The aim of this paper is to understand the current situation of the care burden of patients with mental illness in remission and the factors affecting it in order to provide a scientific basis for targeted interventions. This paper reviews the concept of telemedicine, the application of telemedicine in home hospice care, and the remaining problems and improvement strategies of telemedicine in home hospice care, with the aim of providing a reference for the application of telemedicine in home hospice care in China. The Zarit Burden Scale, Family Care Scale, and Social Functioning Scale were used to conduct one-to-one interviews with 201 schizophrenic patients in remission and their primary caregivers in Hubei Province. Among them, 66, 72, and 25 cases (32.8%, 35.9%, and 12.4%) had mild, moderate, and severe burdens, respectively. Caregivers' family care and patients' social functioning were generally poor. The results of multiple linear regression analysis showed that caregiver age, caregiver education, caregiver family care, patient medical costs, and patient social functioning were factors influencing the burden of care for patients with schizophrenia in remission (P < 0.05). The government, mental health centers, and families should understand the level of caregiving burden of patients with schizophrenia in remission and the factors influencing it and provide targeted measures to reduce the caregiving burden.


Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase.
The pathway of the oxidation of propionate to pyruvate in Escherichia coli involves five enzymes, only two of which, methylcitrate synthase and 2-methylisocitrate lyase, have been thoroughly characterized. Here we report that the isomerization of (2S,3S)-methylcitrate to (2R,3S)-2-methylisocitrate requires a novel enzyme, methylcitrate dehydratase (PrpD), and the well-known enzyme, aconitase (AcnB), of the tricarboxylic acid cycle. AcnB was purified as 2-methylaconitate hydratase from E. coli cells grown on propionate and identified by its N-terminus. The enzyme has an apparent Km of 210 micro m for (2R,3S)-2-methylisocitrate but shows no activity with (2S,3S)-methylcitrate. On the other hand, PrpD is specific for (2S,3S)-methylcitrate (Km = 440 micro m) and catalyses in addition only the hydration of cis-aconitate at a rate that is five times lower. The product of the dehydration of enzymatically synthesized (2S,3S)-methylcitrate was designated cis-2-methylaconitate because of its ability to form a cyclic anhydride at low pH. Hence, PrpD catalyses an unusual syn elimination, whereas the addition of water to cis-2-methylaconitate occurs in the usual anti manner. The different stereochemistries of the elimination and addition of water may be the reason for the requirement for the novel methylcitrate dehydratase (PrpD), the sequence of which seems not to be related to any other enzyme of known function. Northern-blot experiments showed expression of acnB under all conditions tested, whereas the RNA of enzymes of the prp operon (PrpE, a propionyl-CoA synthetase, and PrpD) was exclusively present during growth on propionate. 2D gel electrophoresis showed the production of all proteins encoded by the prp operon during growth on propionate as sole carbon and energy source, except PrpE, which seems to be replaced by acetyl-CoA synthetase. This is in good agreement with investigations on Salmonella enterica LT2, in which disruption of the prpE gene showed no visible phenotype.


Epr1, a UPR-upregulated soluble autophagy receptor for reticulophagy.
The endoplasmic reticulum (ER) is a major site of protein folding. Perturbations in the folding capacity of the ER result in ER stress. ER stress triggers autophagic degradation of the ER (reticulophagy). Molecular mechanisms underlying ER stress-induced reticulophagy remain largely unknown. Our recent study identified a soluble protein, Epr1, as an autophagy receptor for ER stress-induced reticulophagy in the fission yeast Schizosaccharomyces pombe. Epr1 can interact simultaneously with Atg8 and a VAP family integral ER membrane protein, and thereby act as a bridging molecule between them. VAP family proteins contribute to reticulophagy by not only connecting Atg8 to the ER membrane through Epr1, but also by supporting the ER-plasma membrane contact. The expression of Epr1 is upregulated during ER stress in a manner dependent on the unfolded protein response (UPR) regulator Ire1. Ire1 promotes reticulophagy by upregulating Epr1.


Gastric lymphoma: a clinical study of 28 cases and an evaluation of prognostic factors.
The charts of 28 patients with primary gastric lymphoma referred to our department from 1972 through 1980 were reviewed and analysed with regard to prognostic factors and treatment. Stage, histology and depth of penetration were found to correlate strongly with survival. The two year survival was 89% for stages I and II1 versus 44% for stages II2-IV (p less than 0.05), 100% for lymphocytic and mixed types versus 56% for histiocytic types (p less than 0.05), and 100% for tumors confined to the submucosa and muscularis propria versus 53% for those with deeper penetration (p less than 0.02). Age, sex and microscopic features were not found to have prognostic significance. Since stage, histologic type and depth of penetration were each found to have their own prognostic value, a classification system unifying all three parameters is proposed, based on which a rational therapeutic approach for patients with gastric lymphoma can be attempted.


Detection of porcine rotavirus from tissue and faecal specimens.
Porcine small intestinal sub-mucosa is a cell-free collagen matrix that has demonstrated its ability as a scaffold material. Transplantation poses special hazards because grafted tissues and organs transmit pathogens efficiently, especially viruses. Rotavirus is thought to be confined to the intestine, causing acute diarrhoea. The purpose of this study was to evaluate the porcine intestinal tissue scaffold for Rotavirus and to study the incidence of this virus among pig herds. Only one isolate was successfully adapted to grow in cell line MA 104 from faecal samples. This isolate was further confirmed by reverse transcriptase polymerase chain reaction and sequence analysis.


The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial.
This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. The present study failed to confirm the superiority of the no touch.


Semen characterization and sperm storage in Cabot's Tragopan.
The semen quality of Cabot's Tragopan, the dependence of sperm yields on frequency of semen collection, and the duration of sperm storage in females were investigated. The results are as follows: 1) The average duration of the period in which Cabot's Tragopan can produce an ejaculate was about 70 d. The ejaculate volume ranged from 15 to 100 microL. The average concentration of the ejaculate was 2.31 x 10(9) mL(-1). There were 11.69 (+/- 0.77)% abnormal spermatozoa per ejaculate. Three of 11 males yielded more than 50 microL of semen per collection most of the time. 2) The ejaculate volumes, the concentration, the total number of sperm per ejaculate, and the daily sperm output were all markedly affected by the frequency of semen collection (P < 0.01). However, no significant difference was detected in characters between the 2 groups with relatively low collection frequency (P > 0.05) except the daily sperm output (P < 0.01). The highest frequency of semen collection did not yield more sperm. 3) The average duration of the period in which the female laid fertilized eggs after single insemination was 19.85 +/- 3.08 d (range 9 to 32 d, n = 7). This value was affected by the rhythm of egg laying and varied among individuals. All of the results will facilitate design of the optimal artificial insemination strategy and help to achieve the ultimate aim of ex situ conservation.


Genetic diversity and evolution of the human leptin locus tetranucleotide repeat.
To better understand the evolutionary history of the gene region containing the multifunctional adipose tissue hormone leptin, we genotyped 1,957 individuals from 12 world populations for a highly variable tetranucleotide repeat polymorphism located 476 bp 3' of exon 3 of the leptin gene. Common alleles shared among populations, alleles specific to geographically defined populations, and the homologous alleles in the common and pygmy chimpanzee, the gorilla and the orangutan, were sequenced to define the allelic variation at the nucleotide level. These data reveal a common set of alleles shared among world populations, presumed to have arisen from a great ape ancestral allele prior to the divergence of the major geographical subdivisions of the human population, a subset of alleles specific to populations of African ancestry and a second set of alleles that arose by tandem duplication of the core repeat unit following the separation of African and non-African populations. These findings emphasize the complex evolutionary history of this locus and raise cautions about the pooling of alleles at this locus in association studies.


Computation of the physio-chemical properties and data mining of large molecular collections.
Very large data sets of molecules screened against a broad range of targets have become available due to the advent of combinatorial chemistry. This information has led to the realization that ADME (absorption, distribution, metabolism, and excretion) and toxicity issues are important to consider prior to library synthesis. Furthermore, these large data sets provide a unique and important source of information regarding what types of molecular shapes may interact with specific receptor or target classes. Thus, the requirement for rapid and accurate data mining tools became paramount. To address these issues Pharmacopeia, Inc. formed a computational research group, The Center for Informatics and Drug Discovery (CIDD).* In this review we cover the work done by this group to address both in silico ADME modeling and data mining issues faced by Pharmacopeia because of the availability of a large and diverse collection (over 6 million discrete compounds) of drug-like molecules. In particular, in the data mining arena we discuss rapid docking tools and how we employ them, and we describe a novel data mining tool based on a ID representation of a molecule followed by a molecular sequence alignment step. For the ADME area we discuss the development and application of absorption, blood-brain barrier (BBB) and solubility models. Finally, we summarize the impact the tools and approaches might have on the drug discovery process.


Genotoxicity assessment of the flavouring agent, perillaldehyde.
Perillaldehyde, a natural monocyclic terpenoid found most abundantly in the herb perilla, has a long history of use as a flavouring ingredient to add spiciness and citrus taste to foods. Previously, it was judged to be safe by several international expert panels. To confirm the safety of flavourings placed on the European Union list of flavourings, perillaldehyde was selected by the European Food Safety Authority as a representative of a subgroup of alicyclic aldehyde flavouring substances to be evaluated for genotoxic potential. Perillaldehyde was tested in a bacterial reverse mutation assay, an in vitro micronucleus assay in human lymphocytes, an HPRT assay in mouse lymphoma cells, and a micronucleus/comet assay in Han Wistar rats. In contrast to previously published results, perillaldehyde induced mutation in Salmonella typhimurium strain TA98 in the absence of metabolic activation. The comet assay was negative for duodenum and weakly positive for liver but only at a hepatotoxic dose of perillaldehyde. All other genotoxicity assays were negative. These data do not provide an indication of any genotoxic potential for perillaldehyde, and they provide the primary basis for recent scientific opinions regarding perillaldehyde genotoxicity announced by several international organizations responsible for safety assessment of food additives and flavourings.


Ipsilateral breast tumor recurrence following breast-conserving surgery for early-stage invasive cancer.
Ipsilateral breast tumor recurrence (IBTR) following conservative surgery and radiation for early stage invasive cancer occurs in approximately 15% of all patients at 10 years and is diminished with surgical excisions which achieve negative margins. Treatment strategies of breast-conserving surgery with or without radiation that result in IBTR rates of 30 40% will impact negatively on survival and the magnitude of this effect will be influenced by the predominant pattern of local failure as well as initial and subsequent distant metastases. Optimal local control in early-stage invasive breast cancer is important to minimize the risk of a salvage mastectomy and maximize the potential for long-term survival.


Failed Trapeziectomy Treated by Thumb Metacarpal Base Arthrodesis: A Case Series.
Trapeziometacarpal joint arthritis is a prevalent condition with a preponderance to women. Most cases are asymptomatic, but typical symptoms are pain, reduced dexterity, and functional decline. Trapeziectomy is the most common surgical treatment in the United Kingdom for patients who remain significantly symptomatic despite nonoperative measures, and this generally produces acceptable outcomes; however, a proportion of patients remain significantly symptomatic. The authors present a case series of 4 patients who underwent successful thumb metacarpal base to index metacarpal base arthrodesis with either distal radial or iliac crest bone grafting. Three of these patients had persisting symptoms after a primary trapeziectomy and 1 patient had gross subluxation of the thumb related to rheumatoid arthritis. Technically, this is a simple procedure to perform. All patients had improved symptoms with satisfactory functional outcomes and an improved cosmetic appearance of the hand.


Study on the role of Hsa-miR-31-5p in hypertrophic scar formation and the mechanism.
Hypertrophic scar (HS) formation is associated with the fibrosis of fibrocytes caused by excessive extracellular matrix (ECM) synthesis and deposition, the initial event of HS formation. Our high throughput screen of miRNA expression profiles identified hsa-miR31-5p, whose transcription level was most differentially in normal skin fibroblasts (NS) and HS among other miRNAs. The level of hsa-miR31-5p in HS was significantly higher than in NS. In-vitro functional experiments showed hsa-miR31-5p knockdown remarkably suppressed the proliferation of hypertrophic scar fibroblasts (HSFBs) under hypoxia, promoted cell invasion, and inhibited the expression of Collagen I and III and Fibronectin (FN), suggesting that hsa-miR31-5p knockdown effectively reduces HS formation caused by excessive ECM synthesis and deposition in HSFBs under hypoxia. Mechanism study showed that the regulation of HS formation by hsa-miR31-5p was mediated by its target gene, factor-inhibiting HIF-1 (FIH): under hypoxia, hsa-miR31-5p down-regulated FIH and thus increased the level of hypoxia inducible factor-1α (HIF-1α), which subsequently activated the HIF-1α fibrosis regulation pathway in HSFBs, and stimulated the proliferation and ECM synthesis in HSFBs, eventually resulting in fibrosis and scar formation. The data also show that knockdown of hsa-miR31-5p in HSFBs impaired the trend of increased proliferation, reduced invasion and excessive ECM synthesis and deposition caused by HIF-1a activation under hypoxia through upregulating FIH, indicating that knockdown of hsa-miR31-5p effectively inhibits the formation of HS. In conclusion, hsa-miR31 -5p plays an important role in HS formation by inhibiting FIH and regulating the HIF-1α pathway. Therefore, hsa-miR31 -5p may be a novel therapeutic target for HS.


Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat.
Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep. This study used between-groups and within-groups designs. University of Michigan. Adult male Sprague Dawley rats (n = 40). Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions. Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine level. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus. Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.


Value of the peroral pneumocolon in children.
This is the first study in children of the use of the peroral pneumocolon, which entails insufflation of air per rectum to examine the terminal ileum and cecum in conjunction with a conventional barium follow-through examination. Of 1188 conventional barium follow-through examinations performed during 2 1/2 years, results were ambiguous in 13 patients, who then underwent a peroral pneumocolon study. This study showed terminal ileitis in six patients, confirming the diagnosis of Crohn disease in five and Behçet syndrome in the other. In four patients peroral pneumocolon findings were normal. More extensive cecal or proximal ileal disease was shown in three patients by peroral pneumocolon, and fistulae suspected on conventional study were confidently excluded in two others. In all 13 the examination was well tolerated, and avoided further, more invasive procedures. The peroral pneumocolon is a useful procedure in children for these indications.


Disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets.
Energy depletion induces the formation of disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets. The disulfide type polymers, formed following incubation at 37 degrees C in the absence of adenosine triphosphate (ATP)-generating precursors, are composed of cytoskeletal proteins and are associated with a decrease of reduced glutathione levels accompanying ATP depletion. The maintenance of ATP and reduced glutathione levels to, respectively, 34% and 47% of their original values is sufficient to prevent the formation of both polymer types. The transglutaminase-type cross-links are formed in the presence of calcium in either "energy-depleted" or thrombin stimulated platelets. 125I-surface-labeled membrane proteins, presumably transmembrane proteins, are incorporated into the transglutaminase-catalyzed cross-linked polymer of thrombin-stimulated platelets. Glycoproteins IIb and IIIa are not essential to the polymer formation, since thrombasthenic platelets treated with thrombin exhibit the same type of labeled polymer. The transglutaminase-catalyzed polymer formation following thrombin stimulation of platelets is inhibited by a calcium channel blocker, an intracellular calcium antagonist, as well as other inhibitors such as indomethacin, dibutyryl cyclic AMP, and prostaglandin E1. Although the evidence points to the formation of transglutaminase-catalyzed cross-linking in the cytoplasmic compartment, additional cross-linking of extruded components cannot be excluded.


Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma.
Alterations in DNA methylation in malignant diseases have been heralded as promising targets for diagnostic, prognostic, and predictive values. This study was based on epigenetic alterations and immune cell infiltration analysis to investigate the mechanism of CD3D methylation in uveal melanoma (UM). Bioinformatics analysis was performed on transcriptome data, 450 K methylation data, and clinical information of UM patients from the TCGA database. Stromal and immune cell infiltration was evaluated by calculating the StromalScore and ImmuneScore of UM samples. UM samples were divided into high and low StromalScore and ImmuneScore groups, followed by differential and enrichment analyses. PPI network construction and correlation analysis was used to identify the core prognosis-related genes. The bioinformatics analysis results were confirmed in UM cell experiments. StromalScore and ImmuneScore were significantly associated with the prognosis of UM patients. CD3D, IRF1, CCL3, and FN1 were identified as core genes driven by methylation that affected the prognosis of UM patients. CD3D expression showed the highest correlation with its methylation and was closely related to the four key immune cells in UM development. CD3D was hypomethylated and abundantly expressed in UM cells, while silencing of CD3D inhibited the proliferation, migration, and invasion of UM cells in vitro. In summary, this study identifies hypomethylation of CD3D promoter in UM, which was associated with immune cell infiltration of UM.


Using fMRI to Constrain Theories of Cognition.
Research on cognition often leads to debates that are centered on how many processes exist and how they interact to guide behavior. These debates occur across a range of domains and are often difficult to resolve with behavioral data because similar behavioral predictions can be made by models with different core assumptions. Such model mimicry limits researchers' ability to find differential support for one type of model over the other using behavioral data alone. We argue that functional neuroimaging can help overcome this problem by providing additional dependent measures to constrain model testing. Recent advances in analysis, like multivariate approaches, expand the amount and type of data available for model testing. We illustrate the benefits of this approach by highlighting imaging results that directly speak to the debate over the nature of recollection processes in memory. These results show how functional neuroimaging can advance studies of cognition by providing richer data sets for contrasting cognitive models.


Depression and APOEε4 Status in Individuals with Subjective Cognitive Decline: A Meta-Analysis.
To evaluate the associative role of depression and apolipoprotein E epsilon 4 allele (APOEε4) in subjective cognitive decline (SCD) and its progression to objective cognitive decline. After literature search in electronic databases, studies were selected by following precise eligibility criteria. Meta-analyses were performed to examine the role of APOEε4 and depression in SCD or its progression to mild cognitive impairment (MCI) or dementia. APOEε4 positivity was not different between SCD and normal individuals but was significantly higher in individuals with SCD plus than in normal individuals [odds ratio: 2.39 (95% CI: 1.87, 3.05); p<0.00001] and in SCD converters than in non-converters [odds ratio: 5.19 (95% CI: 2.36, 11.42); p<0.00001]. Depression was significantly higher in individuals with SCD [standardized mean difference: 0.63 (0.45, 0.82); p<0.00001] and SCD plus [standardized mean difference: 0.83 (0.43, 1.22); p<0.0001] than in normal individuals. However, depression was not different between SCD and MCI or between SCD converters and non-converters. Age of SCD converters was higher than non-converters [mean difference: 2.95 years (0.58, 5.31)]. Whereas APOEε4 positivity was higher in SCD plus and SCD converters, depression was higher in SCD and SCD plus but was not different between SCD and MCI.


Promoting Global Health.
The Editor-in-Chief of the International Journal of MCH and AIDS (IJMA) is a member of the World Association of Medical Editors (WAME). The Editorial Board of IJMA believes it is important that the statement on promoting global health and this accompanying editorial is brought to the attention of our readers. Medical journal editors have a social responsibility to promote global health by publishing, whenever possible, research that furthers health worldwide.


Overexpression of HVA1 Enhances Drought and Heat Stress Tolerance in Triticum aestivum Doubled Haploid Plants.
Plant responses to multiple environmental stresses include various signaling pathways that allow plant acclimation and survival. Amongst different stresses, drought and heat stress severely affect growth and productivity of wheat. HVA1, a member of the group 3 LEA protein, has been well known to provide protection against drought stress. However, its mechanism of action and its role in other stresses such as heat remain unexplored. In this study, doubled haploid (DH) wheat plants overexpressing the HVA1 gene were analyzed and found to be both drought-and heat stress-tolerant. The transcriptome analysis revealed the upregulation of transcription factors such as DREB and HsfA6 under drought and heat stress, respectively, which contribute toward the tolerance mechanism. Particularly under heat stress conditions, the transgenic plants had a lower oxidative load and showed enhanced yield. The overexpression lines were found to be ABA-sensitive, therefore suggesting the role of HsfA6 in providing heat tolerance via the ABA-mediated pathway. Thus, apart from its known involvement in drought stress, this study highlights the potential role of HVA1 in the heat stress signaling pathway. This can further facilitate the engineering of multiple stress tolerance in crop plants, such as wheat.


[Status of ultrasound diagnosis in differential cholestasis diagnosis].
Differentiating between the hepatocellular "internal" and the "surgical" or "endoscopic" cholestasis syndrome has become a domain of sonography. There is a 92 to 99% success rate, due to the possibility of diagnosing by means of sonography dilations of the gall bladder, the extrahepatic biliary tract and the intrahepatic bile ducts, as well as numerous diseases of the hepatobiliary system and of the pancreas. Congested intra- and extrahepatic bile ducts indicate the presence of a deep-seated distal obstruction, such s a prepapillary concrement, an inflammatory or malignant papillary stenosis or of a process in the area of the head of the pancreas. If the intrahepatic bile ducts alone are dilated the obstructive process has to be assumed near the portal fissure of the liver. Frequent causes are directly demonstrable tumors or metastases on the hilum or high-lying concrements. By using sonography, the level of obstruction can be determined correctly in about 90% of cases, while the cause of obstruction can be diagnosed in about 60 to 70%. In most cases intrahepatic cholestase can only be demonstrated indirectly through the absence of a bile duct dilation. Characteristic diffuse changes in the liver (e.g. fatty liver, cirrhosis, cardiac liver) or intrahepatic space claims-may be in combination with an ultrasound-directed puncture-may support or confirm the diagnosis.


Definition of medical event is to be based on the total source strength for evaluation of permanent prostate brachytherapy: A report from the American Society for Radiation Oncology.
The Nuclear Regulatory Commission deems it to be a medical event (ME) if the total dose delivered differs from the prescribed dose by 20% or more. A dose-based definition of ME is not appropriate for permanent prostate brachytherapy as it generates too many spurious MEs and thereby creates unnecessary apprehension in patients, and ties up regulatory bodies and the licensees in unnecessary and burdensome investigations. A more suitable definition of ME is required for permanent prostate brachytherapy. The American Society for Radiation Oncology (ASTRO) formed a working group of experienced clinicians to review the literature, assess the validity of current regulations, and make specific recommendations about the definition of an ME in permanent prostate brachytherapy. The working group found that the current definition of ME in §35.3045 as "the total dose delivered differs from the prescribed dose by 20 percent or more" was not suitable for permanent prostate brachytherapy since the prostate volume (and hence the resultant calculated prostate dose) is dependent on the timing of the imaging, the imaging modality used, the observer variability in prostate contouring, the planning margins used, inadequacies of brachytherapy treatment planning systems to calculate tissue doses, and seed migration within and outside the prostate. If a dose-based definition for permanent implants is applied strictly, many properly executed implants would be improperly classified as an ME leading to a detrimental effect on brachytherapy. The working group found that a source strength-based criterion, of >20% of source strength prescribed in the post-procedure written directive being implanted outside the planning target volume is more appropriate for defining ME in permanent prostate brachytherapy. ASTRO recommends that the definition of ME for permanent prostate brachytherapy should not be dose based but should be based upon the source strength (air-kerma strength) administered.


Congenital Babesiosis After Maternal Infection With Borrelia burgdorferi and Babesia microti.
We describe the cases of 2 infants with congenital babesiosis born to mothers with prepartum Lyme disease and subclinical Babesia microti infection. The infants both developed anemia, neutropenia, and thrombocytopenia, and 1 infant required red blood cell transfusion. Both infants recovered with treatment. Additional studies are warranted to define the optimal management strategy for pregnant women with early Lyme disease in geographic areas in which B microti infection is endemic.


Randomized Trial of a Palliative Care Intervention to Improve End-of-Life Care Discussions in Patients With Metastatic Breast Cancer.
Studies show that early, integrated palliative care (PC) improves quality of life (QoL) and end-of-life (EoL) care for patients with poor-prognosis cancers. However, the optimal strategy for delivering PC for those with advanced cancers who have longer disease trajectories, such as metastatic breast cancer (MBC), remains unknown. We tested the effect of a PC intervention on the documentation of EoL care discussions, patient-reported outcomes, and hospice utilization in this population. Patients with MBC and clinical indicators of poor prognosis (n=120) were randomly assigned to receive an outpatient PC intervention (n=61) or usual care (n=59) between May 2, 2016, and December 26, 2018, at an academic cancer center. The intervention entailed 5 structured PC visits focusing on symptom management, coping, prognostic awareness, decision-making, and EoL planning. The primary outcome was documentation of EoL care discussions in the electronic health record (EHR). Secondary outcomes included patient-report of discussions with clinicians about EoL care, QoL, and mood symptoms at 6, 12, 18, and 24 weeks after baseline and hospice utilization. The rate of EoL care discussions documented in the EHR was higher among intervention patients versus those receiving usual care (67.2% vs 40.7%; P=.006), including a higher completion rate of a Medical Orders for Life-Sustaining Treatment form (39.3% vs 13.6%; P=.002). Intervention patients were also more likely to report discussing their EoL care wishes with their doctor (odds ratio [OR], 3.10; 95% CI, 1.21-7.94; P=.019) and to receive hospice services (OR, 4.03; 95% CI, 1.10-14.73; P=.035) compared with usual care patients. Study groups did not differ in patient-reported QoL or mood symptoms. This PC intervention significantly improved rates of discussion and documentation regarding EoL care and delivery of hospice services among patients with MBC, demonstrating that PC can be tailored to address the supportive care needs of patients with longer disease trajectories. ClinicalTrials.gov identifier: NCT02730858.


Osteoporosis and its relationship to oral bone loss.
Osteoporosis, an age-related condition, is classified into primary and secondary types. Primary osteoporosis encompasses the postmenopausal and senile types; secondary osteoporosis occurs "secondary" to endocrine and renal diseases. Subjects affected by osteoporosis have an overall reduced bone mass and become highly susceptible to bone fractures. Dual energy x-ray absorptiometry is the method most often used to determine the risk for osteoporotic fractures. In the past decade, a number of studies have suggested a possible correlation between systemic osteoporosis and alveolar bone loss in periodontal disease pathogenesis. It appears that a clear correlation between periodontal health and the general mineral status of the skeleton is still lacking. This review addresses the pathogenesis of osteoporosis and emphasizes the multifactorial nature of bone loss. The current concepts in alveolar bone loss resulting from osteoporosis and its implications as a risk factor in periodontal disease development are also presented.


Multiwalled carbon nanotube buckypaper: toxicology and biological effects in vitro and in vivo.
We evaluated the effect of buckypaper (BP) on cancer and primary cell lines in vitro and in vivo in laboratory rats. BP is an innovative material with interesting physical/chemical properties that has possible pharmacological and prosthetic employment. Given that precautions need to be taken where carbon nanotubes are injected into human body for drug delivery, as contrast agent-carrying entities for MRI or as the material of a new prosthesis generation, we assessed the toxicity of BP carbon nanotubes. BP has structural resemblance to asbestos, whose toxicity has been linked to cancer. BP decreased proliferation of human colorectal, breast and leukemic cancer cell lines in vitro. However, BP had no effect on the proliferation and viability of normal human arterial smooth muscle cells and human dermal fibroblasts in vitro. in vivo, BP induced a moderate inflammatory reaction but had no mutagenic effects. After BP implantation the animals showed an inflammatory reaction followed 2 weeks later by a cicatrization reaction with the organization and fibrosis of the scar. These results show a low toxicity of BP both in vitro and in vivo.


Reinforcement learning: Computational theory and biological mechanisms.
Reinforcement learning is a computational framework for an active agent to learn behaviors on the basis of a scalar reward signal. The agent can be an animal, a human, or an artificial system such as a robot or a computer program. The reward can be food, water, money, or whatever measure of the performance of the agent. The theory of reinforcement learning, which was developed in an artificial intelligence community with intuitions from animal learning theory, is now giving a coherent account on the function of the basal ganglia. It now serves as the "common language" in which biologists, engineers, and social scientists can exchange their problems and findings. This article reviews the basic theoretical framework of reinforcement learning and discusses its recent and future contributions toward the understanding of animal behaviors and human decision making.


Benzo[a]pyrene sourcing and abundance in a coal region in transition reveals historical pollution, rendering soil screening levels impractical.
Benzo[a]pyrene (BaP) is a hazardous compound for human health and for environmental compartments. Its transfer and deposition through the atmosphere affects soil quality. In this context, we quantified the content of BaP and other Polycyclic Aromatic Hydrocarbons (PAHs) in the soils of a prominent Coal Region in Transition to test whether the soil screening levels in force are realistic and whether they reflect the complexity of regions closely linked to heavy industries and mining. In this regard, soil screening levels are thresholds often established without considering historical anthropogenic activities that affect soil (diffuse pollution). The 150 soil samples studied showed a notable content of high molecular weight PAHs, and BaP surpassed the threshold levels in practically the entire area. PAH-parent diagrams revealed a relatively homogenous fingerprint of four clusters obtained in a multivariate statistical study. In addition, molecular diagnostic ratios pointed to coal combustion as the main pollution source, whereas only some outliers appeared to be related to specific spills. A BaP threshold was calculated to be 0.24 mg kg-1, over 10 times the limit established in Spain. Finally, a factor analysis revealed a positive correlation of BaP with elements usually emitted in coal combustion processes, such as Tl and V. This observation fosters the hypothesis of a historical and indelible pollution fingerprint in soils whose sources, characteristics and potential environmental and health concerns deserve further attention. All things considered, caution should be taken when using soil screening levels in regions associated with coal exploitation and heavy industry.


Occurrence of breathing disorders during CPAP administration in obstructive sleep apnoea syndrome.
The spectrum of breathing events during sleep in patients with obstructive sleep apnoea syndrome (OSAS) after the abolition of obstructive apnoeas has been extensively studied in tracheostomized patients, but has received much less attention in patients submitted to continuous positive airway pressure (CPAP). We analysed the breathing pattern during sleep in forty patients while CPAP was administered. A regular breathing pattern throughout the sleep study was observed in 15 patients. In the remaining 25 subjects, one or more of the following events was observed: central apnoeas, hypopnoeas, periodic breathing, prolonged oxyhaemoglobin desaturations. Central apnoeas during non-rapid eye movement (NREM) sleep appeared almost exclusively after arousals or wakefulness periods; their prevalence did not significantly differ between subjects who showed and who did not show similar events before CPAP. Central apnoeas in rapid eye movement (REM) sleep had a random occurrence. Hypopnoeas were found only in REM sleep, and, like central apnoeas, occurred randomly; in one patient they had a prolonged duration (up to 110 s). Periodic breathing was observed in only two subjects, one of whom had congestive heart failure: it was limited to NREM sleep and was not associated with arousals or shifts in sleep stage. Prolonged oxyhaemoglobin desaturations were found mainly in REM sleep; most subjects with such abnormalities had daytime blood gas alterations. In conclusion, abnormalities of the breathing pattern of patients with OSAS can be observed during CPAP and after tracheostomy, but periodic breathing is less common than is reported after tracheostomy, and is probably caused by different mechanisms.


Two distinct Staufen isoforms in Xenopus are vegetally localized during oogenesis.
Localization of mRNA is an important way of generating early asymmetries in the developing embryo. In Drosophila, Staufen is intimately involved in the localization of maternally inherited mRNAs critical for cell fate determination in the embryo. We show that double-stranded RNA-binding Staufen proteins are present in the oocytes of a vertebrate, Xenopus, and are localized to the vegetal cytoplasm, a region where important mRNAs including VegT and Vg1 mRNA become localized. We identified two Staufen isoforms named XStau1 and XStau2, where XStau1 was found to be the principal Staufen protein in oocytes, eggs, and embryos, the levels of both proteins peaking during mid-oogenesis. In adults, Xenopus Staufens are principally expressed in ovary and testis. XStau1 was detectable throughout the oocyte cytoplasm by immunofluorescence and was concentrated in the vegetal cortical region from stage II onward. It showed partial codistribution with subcortical endoplasmic reticulum (ER), raising the possibility that Staufen may anchor mRNAs to specific ER-rich domains. We further showed that XStau proteins are transiently phosphorylated by the MAPK pathway during meiotic maturation, a period during which RNAs such as Vg1 RNA are released from their tight localization at the vegetal cortex. These findings provide evidence that Staufen proteins are involved in targeting and/or anchoring of maternal determinants to the vegetal cortex of the oocyte in Xenopus. The Xenopus oocyte should thus provide a valuable system to dissect the role of Staufen proteins in RNA localization and vertebrate development.


Changes in EEG during graded exercise on a recumbent cycle ergometer.
Previous studies have shown changes in brain activity as a result of exercise; however, few studies have examined changes during exercise. The purpose of this study was to examine brain activity during a graded exercise test. Twenty male participants performed a graded exercise test on a recumbent cycle ergometer. Exercise intensity was set initially at 50W and was increased by 50W every 2 minutes until volitional fatigue was reached. Electroencephalography (EEG) was measured prior to the onset of exercise, during the last minute of each stage of exercise, immediately post-exercise, and 10 minutes into recovery. EEG was recorded from 8 scalp sites leading to analysis of alpha 1, alpha 2, beta 1, beta 2, and theta activities. Expired air was collected and analyzed for ventilation rate (VE), VO2, % of peak VO2, and Respiratory Exchange Ratio (RER). No differences were seen in EEG between the hemispheres of the brain. There was, however, a significant increase in brain activity across the spectrum occurring at 200 W through immediately post-exercise. Brain activity returned to pre- exercise levels by 10 minutes post. VO2, % of peak VO2 and RER increased linearly with exercise intensity. VE increased linearly through 200 W; however, a disproportionate increase was seen in VE from 200 W to peak exercise. The results of this investigation demonstrate that brain activity may be related to exercise intensity. Future research will want to examine how these changes in brain activity influence affective, perceptual and cognitive changes often associated with exercise. Efforts will also need to be made to determine if changes in brain activity during exercise are mediated by central (within the brain) or peripheral mechanisms. Key pointsEEG can be recorded during exercise.Brain EEG activity increases during exercise and may be related to exercise intensity.Brain EEG activity returns to resting levels quickly after the cessation of exercise.


Cytarabine-related lung infiltrates on high resolution computerized tomography: a possible complication with benign outcome in leukemic patients.
Potentially fatal lung toxicity occurs in 12-20% of leukemic patients treated with cytarabine especially at intermediate to high doses, usually presenting as noncardiogenic pulmonary edema (NCPE). Anecdotally the association between cytarabine and the onset of bronchiolitis obliterans organizing pneumonia (BOOP) has been reported. We describe here three cases of patients affected by acute myeloid leukemia (AML) treated with chemotherapeutic regimens including high dose cytarabine, who developed early onset of fever, mild dyspnea, moderate hypoxemia on arterial blood gas analysis and lung infiltrates documented by high-resolution computerized tomography (HRCT), with a more indolent behaviour and a benign clinical outcome, compared with similar cases previously reported in the literature. Our cases widen the spectrum of clinical features of cytarabine-related toxicity in leukemic patients.


VP23R of infectious spleen and kidney necrosis virus mediates formation of virus-mock basement membrane to provide attaching sites for lymphatic endothelial cells.
Putative open reading frames (ORFs) encoding laminin-like proteins are found in all members of the genus Megalocytivirus, family Iridoviridae. This is the first study that identified the VP23R protein encoded by ORF23R of the infectious spleen and kidney necrosis virus (ISKNV), a member of these genes of megalocytiviruses. The VP23R mRNA covering the ISKNV genomic coordinates 19547 to 22273 was transcribed ahead of the major capsid protein. Immunofluorescence analysis demonstrated that VP23R was expressed on the plasma membrane of the ISKNV-infected cells and could not be a viral envelope protein. Residues 292 to 576 of VP23R are homologous to the laminin γ1III2-6 fragment, which covers the nidogen-binding site. An immunoprecipitation assay showed that VP23R could interact with nidogen-1, and immunohistochemistry showed that nidogen-1 was localized on the outer membrane of the infected cells. Electron microscopy showed that a virus-mock basement membrane (VMBM) was formed on the surface of the infected cells and a layer of endothelial cells (ECs) was attached to the VMBM. The VMBM contained VP23R and nidogen-1 but not collagen IV. The attached ECs were identified as lymphatic endothelial cells (LECs), which have unique feature of overlapping intercellular junctions and can be stained by immunohistochemistry using an antibody against a specific lymphatic marker, Prox-1. Such infection signs have never been described in viruses. Elucidating the functions of LECs attached to the surface of the infected cells may be useful for studies on the pathogenic mechanisms of megalocytiviruses and may also be important for studies on lymphangiogenesis and basement membrane functions.


Red macroalgae in the genomic era.
Rhodophyta (or red algae) are a diverse and species-rich group that forms one of three major lineages in the Archaeplastida, a eukaryotic supergroup whose plastids arose from a single primary endosymbiosis. Red algae are united by several features, such as relatively small intron-poor genomes and a lack of cytoskeletal structures associated with motility like flagella and centrioles, as well as a highly efficient photosynthetic capacity. Multicellular red algae (or macroalgae) are one of the earliest diverging eukaryotic lineages to have evolved complex multicellularity, yet despite their ecological, evolutionary, and commercial importance, they have remained a largely understudied group of organisms. Considering the increasing availability of red algal genome sequences, we present a broad overview of fundamental aspects of red macroalgal biology and posit on how this is expected to accelerate research in many domains of red algal biology in the coming years.