Effects of short-term exercise on food intake and the expression of appetite-regulating factors in goldfish.
In mammals, growing evidence indicates that exercise affects food intake, metabolism and the expression and blood levels of appetite regulators. In this study, we examined the effects of short-term (30 min, at low and high water flow) exercise on food intake, glucose levels and the expressions of appetite regulators in goldfish hypothalamus (irisin, orexin, CART, leptin), intestine (CCK, PYY, proglucagon/GLP-1), muscle (irisin) and liver (leptin), of brain-derived neurotrophic factor (BDNF) in brain, interleukin-6 (IL6) in muscle and hypothalamus, and major metabolic enzymes, the glycolytic enzyme glucokinase (GCK) and its regulatory protein (GCKR) in liver, the lipolytic enzyme lipoprotein lipase in intestine and muscle, and trypsin in intestine. Fish submitted to high flow exercise had a lower post-exercise food intake compared to control fish but no differences were seen in glucose levels between groups. Exercise induced an increase in hypothalamic expression levels of CART, IL6 and BDNF, but not orexin, irisin, CRF, leptin and NPY. High flow exercise induced an increase in intestine CCK, PYY and GLP-1, and muscle irisin and IL-6 expression levels. Exercise had no effects on expression levels of hepatic leptin or any of the metabolic enzymes examined. Our results suggest that, in goldfish, short-term exercise might decrease feeding in part by affecting the expressions of myokines and peripheral, but not central appetite regulators or metabolic enzyme/hormones.


Comprehensive analysis of NuMA variation in breast cancer.
A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer. In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910) and unselected (n = 884) breast cancer cases and controls (n = 906), with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors. Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement. Our results do not support the role of NuMA variants as breast cancer susceptibility alleles.


Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates.
Histone deacetylases (HDAC) are involved in the regulation of gene transcription. Aberrant HDAC activity has been associated with tumorigenesis, and, therefore, HDACs are potential targets for the treatment of cancers, including tumors of the central nervous system (CNS). Belinostat is a novel, potent, pan-HDAC inhibitor with antiproliferative activity on a wide variety of tumor cell lines. We studied the cerebrospinal fluid (CSF) penetration of intravenous (IV) belinostat in a non-human primate model as a surrogate for blood:brain barrier penetration. Five adult rhesus monkeys received increasing doses of belinostat (10-60 mg/kg) as a 30-min IV infusion. Serial blood and CSF samples were collected over 48 h. Plasma and CSF concentrations of belinostat were quantified with an LC/MS/MS assay. Pharmacokinetic parameters were calculated using non-compartmental methods, and CSF penetration is expressed as the ratio of the area under the concentration-time curve (AUC) in CSF to the AUC in plasma. Belinostat was cleared rapidly from plasma with a half-life of 1.0 h, a mean residence time of 0.47 h, and a clearance of 425 ml/min/m(2). CSF penetration of belinostat was limited. CSF drug exposure was <1% of plasma drug exposure and <10% of free (non-protein bound) plasma drug exposure. IV belinostat is rapidly cleared from plasma and has limited penetration into the CSF.


Paediatric optical coherence tomography normative databases: A real need.
Optical coherence tomography (OCT) has become an essential tool in paediatric ophthalmology. However, none of the currently available OCT devices include any kind of normative database for the paediatric population, which can lead to important interpretation errors. To review the paediatric OCT normative databases. The applications and implications of the use of paediatric OCT normative databases are reviewed. The paediatric normative databases that have been published so far in scientific literature with different OCT devices for Spanish and European population are presented. The knowledge and interpretation of paediatric OCT normative databases in our daily clinical practice is crucial in order for the correct interpretation of OCT thickness maps.


Inhibitors of N-nitroso compounds-induced mutagenicity.
N-Nitroso compounds are environmental mutagens that are present in the air, water, soil etc. or can be formed by nitrosation of various nitrosatable compounds. The present paper gives a survey of inhibitors of N-nitroso compounds-induced mutagenicity. Inhibitors covered include: thiols, metals, vitamins, phenolic acids, complex mixtures of plant, animal and human origin, organic solvents, inhibitors of mixed-function oxidases etc. Data on inhibitors that prevent the formation of N-nitroso compounds are not covered in this review.


Lucialdehyde B suppresses proliferation and induces mitochondria-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells.
Lucialdehyde B (LB), an effective triterpenoid isolated from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Polyproraceae), exerts cytotoxic activity against nasopharyngeal carcinoma CNE2 cells. To investigate the antiproliferative and pro-apoptotic effects of LB on CNE2 cells and explore its underlying mechanisms. LB concentrations of 5-40 μg/mL were used. Cell proliferation was determined using MTT, CFSE, and colony formation assays. LB-induced apoptosis and cell cycle arrest were measured by flow cytometry after 48-h LB treatments. Fluorescence microscopy and flow cytometry were performed to measure the alteration of MMP, mPTP opening, ROS level, and Ca2+ content in CNE2 cells. Western blotting was performed to evaluate the expression of mitochondrial apoptosis-related and Ras/ERK signaling proteins. IC50 values of LB against CNE2 cells for 24, 48, and 72 h were 25.42 ± 0.87, 14.83 ± 0.93, and 11.60 ± 0.77 μg/mL, respectively. The CFSE assay showed that the cell proliferation index was 12.70 in the LB treatment group and 31.44 in the control group. LB significantly reduced clonogenic capacity, promoted cell apoptosis and induced cell cycle arrest at the G2/M phase. Our observations also revealed that LB induced ROS and calcium aggregation, opening of mPTP, MMP reduction, upregulation of mitochondrial apoptosis-related protein expression and inhibition of Ras/ERK signaling cascades. LB suppresses proliferation and induces mitochondrial-dependent apoptosis in nasopharyngeal carcinoma CNE2 cells. LB may have a potential use as a clinical drug candidate for nasopharyngeal carcinoma treatment.


Auditory space representation in the inferior colliculus of the FM bat, Eptesicus fuscus.
The auditory spatial response areas of 333 inferior collicular (IC) neurons of Eptesicus fuscus were studied under free-field acoustic stimulus conditions. A stimulus was delivered from a loudspeaker placed 14 cm in front of a bat and the best frequency of an encountered neuron was determined. Then a best frequency (BF) stimulus was delivered as the loudspeaker was moved across the frontal auditory space to determine the response center of the neuron. At the response center, the neuron had the lowest minimum threshold. The stimulus was then raised 3-15 dB above the lowest minimum threshold of the neuron and the spatial response area for each stimulus intensity was measured. The response center and spatial response area of a neuron measured with a one-octave downward-sweep FM stimulus were similar to those measured with the pure tone pulse. The spatial response area of a neuron expanded asymmetrically with the stimulus intensity. High BF neurons generally had smaller spatial response areas than low BF neurons had. All 333 response centers were located in the contralateral auditory space. Response centers of low BF neurons tended to be located laterally while those of high BF neurons were located medially. Although each neuron had a point of lowest minimum threshold in the contralateral auditory space, the point-to-point representation of the auditory space was not systematically organized. This representation was not correlated with the recording sites of the neurons in the mediolateral, posteroanterior and dorsoventral axes of the IC.


Tongue Edema Secondary to Suspension Laryngoscopy.
Suspension microlaryngoscopy (SML) is generally a safe, same-day procedure. Complications have been linked to prolonged operative time and substantial force applied to the tongue. This report of two cases describes marked tongue edema following SML, a complication not yet reported in the literature. This is a retrospective review of two cases of severe tongue edema following SML. We reviewed the literature for similar reports and proposed treatment plans. Two patients, age 67 and 75, underwent SML for an interval of 247 minutes and 224 minutes for patient 1 and patient 2 respectively. Both developed severe tongue edema requiring inpatient monitoring and steroids. In both patients, the edema improved over several days and returned to baseline. There are no reported cases of this complication in the literature. Prolonged SML can lead to tongue edema requiring close airway monitoring. The edema was self-limited and resolved with steroids and close monitoring.


Increased myocardial expression of angiopoietin-2 in patients undergoing urgent surgical revascularization for acute coronary syndromes.
Myocardial ischemia triggers the expression of multiple angiogenic factors including vascular endothelial growth factor and its receptors. However, vascular endothelial growth factor does not act in isolation. To identify other genes important in the angiogenic response to clinically relevant myocardial ischemia. Paired intraoperative biopsies of ischemic and nonischemic myocardium were obtained from 12 patients with acute coronary syndromes (ACS) undergoing urgent coronary artery bypass graft surgery. Real-time polymerase chain reaction demonstrated significant upregulation of angiopoietin-2 (Ang-2) in ischemic myocardium, to a greater extent than other classical angiogenic factors. Microarray gene profiling identified Ang-2 to be among the top 10 differentially upregulated genes, in addition to genes involved in inflammation, cell signalling, remodelling and apoptosis. The present document is the first report of microarray analysis of patients with ACS, and supports an important role for Ang-2 in the angiogenic response to severe ischemia in the human heart. Common gene expression patterns in ACS may provide opportunities for targeted pharmacological and cellular intervention.


Iron dose-dependent differentiation and enucleation of human erythroblasts in serum-free medium.
Improvements in ex vivo generation of enucleated red blood cells are being sought for erythroid biology research, toward the ultimate goal of erythrocyte engineering for clinical use. Based upon the high levels of iron-saturated transferrin in plasma serum, it was hypothesized that terminal differentiation in serum-free media may be highly dependent on the concentration of iron. Here adult human CD34(+) cells were cultured in a serum-free medium containing dosed levels of iron-saturated transferrin (holo-Tf, 0.1-1.0 mg/ml). Iron in the culture medium was reduced, but not depleted, with erythroblast differentiation into haemoglobinized cells. At the lowest holo-Tf dose (0.1 mg/ml), terminal differentiation was significantly reduced and the majority of the cells underwent apoptotic death. Cell survival, differentiation and enucleation were enhanced as the holo-Tf dose increased. These data suggest that adequate holo-Tf dosing is critical for terminal differentiation and enucleation of human erythroblasts generated ex vivo in serum-free culture conditions. Published 2013. This article is a US Government work and is in the public domain in the USA.


Methylene volumes in monoglyceride bilayers are larger than in liquid alkanes.
The densities as a function of temperature of four fully hydrated saturated monoglycerides with even chain lengths ranging from eight to fourteen were determined by vibrating tube densitometry and their phase transition temperatures were determined by differential scanning calorimetry (DSC). We find the volume of a methylene group in a monoglyceride bilayer is 2% larger than in liquid alkanes at physiological temperatures, similar to the methylene group volumes found in phosphatidylcholine (PC) bilayers. Additionally, we carefully consider the traditional method of calculating component volumes from experimental data and note potential difficulties in this approach. In the literature, the ratio of terminal methyl volume (CH3) to methylene (CH2) volumes is typically assumed to be 2. By analysis of literature alkane data, we find this ratio actually ranges from 1.9 to 2.3 for temperatures ranging from 0 °C to 100 °C. For a rough sense of scale, we note that to effect a 2% reduction in volume requires of order 200 atmospheres of pressure, and pressures of this magnitude are biologically relevant. For instance, this amount of pressure is sufficient to reverse the effect of anesthesia. The component volumes obtained are an important parameter used for determining the structure of lipid bilayers and for molecular dynamics simulations.


Studies on morphological changes of arteries by administration of soluble immune complexes to low calcium diet bred guinea pigs.--Special reference to the morphological pathogenesis of arteritis.
Guinea pigs bred on a low calcium diet for 5 weeks, were injected soluble immune complexes once and angitis or angiolytic changes of the vascular wall in the lungs were noted. Leucocytic adhesions along the luminal surface of the vascular wall, which were carved with leucocytic reactions, could be noticed. Loosening or duplication of the basement membrane accompanied by protrusion of vascular smooth muscle cells into the subendothelial space could be demonstrated. Above results are thought to be a consequence of the conjugation of immune complexes and the negative charges of acid mucopolysaccharides.


Morusalones A-D, Diels-Alder Adducts with 6/7/6/6/6/6 Hexacyclic Ring Systems as Potential PTP1B Inhibitors from Cell Cultures of Morus alba.
Morusalones A-D (1-4), a new class of Diels-Alder adducts featuring unprecedented 6/7/6/6/6/6 hexacyclic core skeletons with a unique bridged cycloheptenone ring, were isolated from Morus alba cell cultures. The biosyntheses for 1-4 were proposed through an unusual Diels-Alder cycloaddition with quinostilbenes as dienophiles and prenyl 2-phenylbenzofuran as a diene to yield the typical methylhexene unit and a rare intramolecular nucleophilic addition to form the cycloheptenone ring. Compounds 1-4 exhibited protein tyrosine phosphatase 1B inhibitory activity.


Proton affinities of the N- and C-terminal segments arising upon the dissociation of the amide bond in protonated peptides.
Dissociation of the amide bonds in a protonated peptide leads to N-terminal sequence fragments with cyclic structures and C-terminal sequence fragments with linear structures. The ionic fragments containing the N-terminus (bn) have been shown to be protonated oxazolones, whereas those containing the C-terminus (Yn) are protonated linear peptides. The coproduced neutral fragments are cyclic peptides from the N-terminus and linear peptides from the C-terminus. A likely determinant of these structural choices is the proton affinity (PA) of the described peptide segments. This study determines the PA values of such segments (Pep), i.e., cyclic and linear dipeptides and a relevant oxazolone, based on the dissociations of proton-bound dimers [Pep + Bi]H+ in which Bi is a reference base of known PA value (Cooks kinetic method). The dissociations are assessed at different internal energies to thereby obtain both proton affinities as well as entropies of protonation. For species with comparable amino acid composition, the proton affinity (and gas phase basicity) follows the order cyclic peptide << oxazolone approximately linear peptide. This ranking is consistent with dissociation of the protonated peptide via interconverting proton-bound complexes involving N-terminal oxazolone (O) or cyclopeptide (C) segments and C-terminal linear peptide segments (L), viz. O...H+...L reversible C...H+...L. N-terminal sequence ions (bn) are formed with oxazolone structures which can efficiently compete for the proton with the linear segments. On the other hand, N-terminal neutral fragments detach as cyclic peptides, with H+ now being retained by the more basic linear segment from the C-terminus to yield Yn.


A lipid based multi-compartmental system: Liposomes-in-double emulsion for oral vaccine delivery.
The gastric mucosa provides the entry point for the majority of pathogens, as well as being the induction site for protective immunity; however, there remain few examples of oral vaccines due to the challenges presented by the gastrointestinal route. In this study, we develop a lipid-based multi-compartmental system for oral vaccine delivery. Specifically, we have optimised the formulation of a water-in-oil-in-water double emulsion prepared from a triglyceride - soya bean oil, using surfactants Span 80/Tween 80 and Pluronic F127 to stabilise the internal and external water phases, respectively. Into the internal water phase, we also incorporated a PEGylated liposome, prepared using hydrogenated phosphatidyl choline as a carrier for our model protein, FITC-labelled ovalbumin. We demonstrated the successful incorporation of intact liposomes into the internal water phase of the double emulsion using imaging techniques including cryo-SEM and confocal microscopy. Finally, we use in vitro release studies of FITC-ovalbumin, to provide further confirmation of the multi-compartmental structure of the double emulsion system and demonstrate significant extended release of the entrapped model antigen compared with PEG-liposomes; these characteristics are attractive for oral vaccine delivery.


[Nature of the hyperpotassic composition of the medium surrounding individual tissue mechanoreceptors].
The ouabain effect on potassium concentration in the Pacini corpuscle fluid was studied using continuous perfusion of cat's mesenteric receptors with ouabain in Ringer's bicarbonate solution. To check the solution penetration into the corpuscles, Na36Cl and (G-3H)-ouabain were used. 2 . 10(-2) mM ouabain reduced (K+) in corpuscle fluid. The high potassium concentration in Pacini corpuscle fluid seems to be due to Na+--K+-ATPase system.


Immunomodulatory effects of β-defensin 2 on macrophages induced immuno-upregulation and their antitumor function in breast cancer.
Macrophages are mononuclear CD34+ antigen-presenting cells of defense mechanism and play dual roles in tumor burden. The immunomodulatory and their antitumor function of β-defensin 2 is still unclear, despite the accumulating evidence of the response in infection. So, the aim of present study is to elucidate the role of β-defensin 2 on the level of ROS, cytokines, chemokine expression in macrophages and antitumor function in breast cancer. Swiss albino mice were used to harvest PEC macrophages and C127i breast cancer cells line for tumor model was used in this study. Macrophages were harvested and characterized by flow-cytometry using F4/80 and CD11c antibodies. MTT was performed to estimate cytotoxicity and dose optimization of β-defensin 2. Oxidative stress was analyzed by H2O2 and NO estimation followed by iNOS quantified by q-PCR. Cytokines and chemokines estimation was done using q-PCR. Co-culture experiment was performed to study anti-tumor function using PI for cell cycle, Annexin -V and CFSE analysis for cell proliferation. PEC harvested macrophages were characterized by flow-cytometry using F4/80 and CD11c antibodies with the purity of 8% pure population of macrophages. It was found that 99% of cells viable at the maximum dose of 100 ng/ml of β-defensin 2 in MTT. Levels of NO and H2O2 were found to be decreased in β-defensin 2 as compared to control. Expression of cytokines of IFN-γ, IL-1α, TNF-α, TGF-βwas found to be increased while IL-3 was decreased in β-defensin 2 group as compared to control. Levels of chemokines CXCL-1, CXCL-5 and CCL5 increased in treated macrophages while CCL24 and CXCL-15 expression decreased. Adhesion receptor (CD32) and fusion receptor (CD204) were decreased in the β-defensin 2 group as compared to control. Anti-tumor experiment was performed using co-culture experiment apoptosis (Annexin-V) was induced, cell cycle arrest in phage and cell proliferation of C127i cells was decreased. This is the first report of β-defensin 2 modulates macrophage immunomodulatory and their antitumor function in breast cancer. β-defensin 2 as a new therapeutic target for immunotherapy as an adjuvant in vaccines.


Degradation and detoxification of broad-spectrum antibiotics by small molecular intercalated BiOCl under visible light.
In view of the increasing threat of overuse of broad-spectrum antibiotics to water environment, here, a series of small molecular intercalated bismuth oxychloride (SBC-X) composite photocatalysts were successfully constructed by a simple stirring synthesis at room temperature. Among them, SBC-0.5 showed excellent photocatalytic performance against the three target broad-spectrum antibiotics in visible light, which was 3.06 times, 5.93 times and 11.64 times higher than that of monomer for degrading tetracycline, norfloxacin and ciprofloxacin, respectively. Through analysis, it was found that the excellent photocatalytic degradation performance of SBC-0.5 was mainly attributed to the greatly improved specific surface area, which increased to 14 times of monomer, providing a large number of reaction sites for the subsequent photocatalytic degradation. Besides, intercalated molecules as charge transfer bridges between nanosheets greatly accelerated the efficiency of photogenerated charge transfer between layers. Free radical trapping experiments and electron spin resonance indicated that superoxide anion radicals played a major role in the photocatalytic degradation, followed by singlet oxygen. Furthermore, nine potential degradation intermediates were identified, and the toxicity was greatly reduced confirmed by ECOSAR software prediction and soybean seed germination and seeding growth experiment. Our work will provide useful information for the purification of wastewater containing antibiotics.


Differential diagnostic value in hepatobiliary disease of serum conjugated bile acid concentrations and some routine liver tests assessed by discriminant analysis.
Serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a HPLC-enzymatic assay in 104 patients with hepatobiliary diseases. The capability of discriminating between four major diagnostic categories by the serum bile acid concentrations, alone and in conjunction with five commonly used biochemical liver tests, was evaluated by stepwise linear discriminant analysis. The serum bile acid pattern alone was inferior to the routine liver tests in separating the diagnostic groups. When the two sets of analytes were combined, the generalized group distance (Rao's V) was significantly increased, showing that the serum bile acid pattern contained discriminatory information in addition to the routine liver tests. The gain in correct reclassification of patients obtained by adding the serum bile acids, however, was only marginal.


Resting metabolic rate of Indian Junior Soccer players: Testing agreement between measured versus selected predictive equations.
Owing to a dearth of research related to Resting Metabolic Rate (RMR) among adolescent athletes in India, our study aimed to document RMR among junior soccer players (JSP) and to identify suitable RMR predictive models for JSP from nine existing equations. Forty Indian JSP (Boys = 21, Girls = 19) representing the under-12 and under-16 age categories were assessed for body composition (skinfold technique) and RMR (oxycon mobile). Two-way ANOVA and ANCOVA were used to examine the differences across age and sex. Bland-Altman plot was used to test agreement between measured vs. predicted RMR using the equations of Cunningham (, The American Journal of Clinical Nutrition, 33), Soares et al. (, European Journal of Clinical Nutrition, 47; 1998, British Journal of Nutrition, 79), Henry (, Public Health Nutrition, 8), and Patil and Bharadwaj (, Journal of Postgraduate Medicine, 59) for non-athletic populations and the equations of De Lorenzo et al. (, The Journal of Sports Medicine and Physical Fitness, 39), Wong et al. (, Singapore Medical Journal, 53), and ten Haaf & Weijs (, PloS One, 9) for adult athletes. RMR showed significant (P < .01) sex differences (Boys: 1343 ± 297.1; Girls: 1135 ± 116.7 kcal·day-1 ). While RMR values adjusted for fat-free mass (FFM) were similar across age and sex. The equation of Soares et al. (, British Journal of Nutrition, 79) for girls and Wong et al. (, Singapore Medical Journal, 53) for boys showed better RMR predictability. FFM explained variation in RMR across age and sex. The FFM-based Soares et al. (, British Journal of Nutrition, 79) equation for girls and body weight-based Wong et al. (, Singapore Medical Journal, 53) equation for boys are best suited for predicting RMR.


Evolution on the X chromosome: unusual patterns and processes.
Although the X chromosome is usually similar to the autosomes in size and cytogenetic appearance, theoretical models predict that its hemizygosity in males may cause unusual patterns of evolution. The sequencing of several genomes has indeed revealed differences between the X chromosome and the autosomes in the rates of gene divergence, patterns of gene expression and rates of gene movement between chromosomes. A better understanding of these patterns should provide valuable information on the evolution of genes located on the X chromosome. It could also suggest solutions to more general problems in molecular evolution, such as detecting selection and estimating mutational effects on fitness.


A combined proximal and distal dislocation of two adjacent metatarsals: double floating metatarsal bones (second-third).
A rare foot injury consisting of an irreducible, closed combined distal and proximal articulation dislocation of two adjacent metatarsals (second and third), called a "double floating metatarsal," was encountered in a 29-year-old man. The anatomy, mechanism of injury, and sequence of the surgical procedure are presented and discussed.


Oral contraceptives and colorectal cancer risk - A meta-analysis and systematic review.
There is limited understanding of the potential relationship between the risk of colorectal cancer and oral contraceptive use among women of different ages. Further investigation on the issue helps develop an informed choice of contraception. Data for this meta-analysis were derived from case-control and cohort studies of colorectal cancer and oral contraceptive use conducted between June 2000 and May 2022. The studies had a very high heterogeneity, as shown by an I2 of 99%, and a confidence interval of 95% was considered significant. Other results from the meta-analysis were as follows; Heterogeneity: Chi2 = 585.13, df = 6 (P < 0.00001). A test of the overall effect of ever use versus never use of oral contraceptives was Z = 21.85 (P < 0.00001). All the studies had a pooled risk ratio (RR) of 0.53. The use of oral contraceptives is associated with reduced risk of developing colorectal cancer. There is a need for further research into the biological mechanisms underlying these relationships, which may lead to insights into potential preventive interventions for colorectal carcinogenesis in women. The keywords used to locate studies included in this meta-analysis include Keywords targeting oral contraceptives included oral contraceptive pills, and birth control pills. Search keywords targeting colorectal carcinogenesis included neoplasms, tumors, or colon and rectal cancer.


Comparison of the biological effects of anemia inducing and polycythemia inducing Friend virus complex.
The comparison of the biological effects of FVP and FVA showed that leukemogenesis appears to be delayed in FVA infected mice as compared to FVP infected animals after injection of comparable quantities of virus as measured in spleen focus forming units. In addition, no CFU-EI, characteristic for FVP induced leukemia, were found in leukemic spleen or bone marrow of FVA infected mice. Since it was possible to distinguish both viruses by their different host ranges, which are helper virus determined, it is suggested that the observed differences, especially the lack of CFU-EI in FVA infected mice, might be due to differences in the helper virus component of the FV complex.


The potential effectiveness of young driver high-performance vehicle restrictions as used in Australia.
Young drivers persistently have higher crash rates despite various countermeasures targeted at their risk factors and exposures. A potentially high risk situation for novice drivers may feasibly include the driving of high performance vehicles, which are subject to restrictions for probationary and restricted drivers in four Australian States. High performance vehicles are capable of high levels of acceleration and speed, which may encourage unsafe driving behaviours, particularly when driven by novice drivers, who may lack appropriate judgement and experience. This research sought to identify potential safety benefits of restrictions on certain vehicles for novice drivers using crash data from Australia and New Zealand, and vehicle licensing data from New Zealand. Data on crashed vehicles and their drivers were analysed to estimate the prevalence of the high performance vehicles in the fleets considered, particularly when driven by young people. By matching New Zealand licensing data with crash data, it was possible to estimate the risk of these high performance vehicles relative to other vehicles in the fleet. For owners aged under 25, a statistically significant 69% elevated injury crash involvement risk ratio was estimated for the high performance vehicles subject to restrictions in Australia in comparison with their risk with other vehicles controlling for other relevant factors (with 95% CI 30-123%, using owners aged 40-59 as a comparison group). Injuries in the vehicles of young owners of high performance vehicles were estimated to increase compared to their rate in other vehicles by 101% (with 95% confidence interval 69-171%, using owners aged 40-59 as a comparison group). Despite the higher relative risk for the high performance vehicles, they were relatively rare in the fleets studied, and the potential reduction in young driver injury rates from banning these vehicles was estimated to range from 0.4% in New Zealand to 2.5% in the Australian States of Queensland and Victoria. In addition, the potential reductions estimated here also depend on unrealistic assumptions of 100% compliance with regulation and the adoption of less risky driving behaviour in response to lower performance vehicles. Although these vehicles have a statistically significantly higher crash and injury risk than other vehicles when owned by young people, there are considerable costs of implementation and ongoing enforcement in imposing vehicle restrictions for young drivers that may not outweigh these potential safety benefits.


Doxycycline hyclate stimulates inducible nitric oxide synthase and arginase imbalance, potentiating inflammatory and oxidative lung damage in schistosomiasis.
We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous inflammation in S. mansoni-infected and doxycycline-treated mice. Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni, (iii) infected + 200 mg/kg praziquantel (Pzt), (iv) and (v) infected + 5 and 50 mg/kg doxycycline. Pzt (reference drug) was administered in a single dose and doxycycline for 60 days. S. mansoni-infection determined extensive lung inflammation, marked recruitment of M2 macrophages, cytokines (IL-4, IL-5, IFN-γ, TNF-α) upregulation, intense eosinophil peroxidase (EPO) levels, arginase expression and activity, reduced iNOS expression and nitric oxide (NO) production. The higher dose of doxycycline aggravated lung granulomatous inflammation, downregulating IL-4 levels and M2 macrophages recruitment, and upregulating iNOS expression, EPO, NO, IFN-γ, TNF-α, M1 macrophages, protein carbonyl and malondialdehyde tissue levels. The number and size of granulomas in doxycycline-treated animals was higher than untreated and Pzt-treated mice. Exudative/productive granulomas were predominant in untreated and doxycycline-treated animals, while fibrotic/involutive granulomas were more frequent in Pzt-treated mice. The reference treatment with Pzt attenuated all these parameters. Our findings indicated that doxycycline aggravated lung granulomatous inflammation in a dose-dependent way. Although Th1 effectors are protective against several intracellular pathogens, effective schistosomicidal responses are dependent of the Th2 phenotype. Thus, doxycycline contributes to the worsening of lung granulomatous inflammation by potentiating eosinophils influx and downregulating Th2 effectors, reinforcing lipid and protein oxidative damage in chronic S. mansoni infection.


Age-related changes in aortic arch geometry: relationship with proximal aortic function and left ventricular mass and remodeling.
We sought to define age-related geometric changes of the aortic arch and determine their relationship to central aortic stiffness and left ventricular (LV) remodeling. The proximal aorta has been shown to thicken, enlarge in diameter, and lengthen with aging in humans. However, no systematic study has described age-related longitudinal and transversal remodeling of the aortic arch and their relationship with LV mass and remodeling. We studied 100 subjects (55 women, 45 men, average age 46 ± 16 years) free of overt cardiovascular disease using magnetic resonance imaging to determine aortic arch geometry (length, diameters, height, width, and curvature), aortic arch function (local aortic distensibility and arch pulse wave velocity [PWV]), and LV volumes and mass. Radial tonometry was used to calculate central blood pressure. Aortic diameters and arch length increased significantly with age. The ascending aorta length increased most, with age leading to aortic arch widening and decreased curvature. These geometric changes of the aortic arch were significantly related to decreased ascending aortic distensibility, increased aortic arch PWV (p < 0.001), and increased central blood pressures (p < 0.001). Increased ascending aortic diameter, lengthening, and decreased curvature of the aortic arch (unfolding) were all significantly associated with increased LV mass and concentric remodeling independently of age, sex, body size, and central blood pressure (p < 0.01). Age-related unfolding of the aortic arch is related to increased proximal aortic stiffness in individuals without cardiovascular disease and associated with increased LV mass and mass-to-volume ratio independent of age, body size, central pressure, and cardiovascular risk factors.


Functional analysis of cis-regulatory regions within the dioxin-inducible CYP1A promoter/enhancer region from zebrafish (Danio rerio).
In vitro mutagenesis was utilized to render the various xenobiotic response elements (XREs) within the zebrafish CYP1A promoter/enhancer region non-functional either independently or in combination. Reporter gene assays revealed that only XRE4, XRE7, and XRE8 contributed to maximal TCDD-mediated induction of luciferase and that the contribution of each XRE to maximal induction was not equal. XRE4 and XRE7 were capable of functioning independently, while XRE8 alone could not support TCDD-mediated induction but was required for the ability of XRE4 and XRE7 to support maximal induction. These results were observed in cell lines derived from human, mouse and zebrafish. Mutagenesis of 3' nucleotides flanking the non-functional XRE5, and functional XRE4 did not alter the function of these XREs in cell culture. In silico analyses revealed the presence of putative Sp1, AP2, CREB, and two HNF-3 transcription factor binding sites that were localized to common positions within the enhancer region of both the mouse and zebrafish CYP1A genes. In vitro mutagenesis of the binding sites showed that loss of the Sp1 or AP2 sites had minimal impact on TCDD-mediated gene induction while loss of the putative CREB site resulted in a modest decrease in basal and inducible activity and mutation of the HNF-3 reduced inducible activity by >90% of controls. Collectively, these findings suggest that the presence of XREs is not the sole determinant for regulation of aryl hydrocarbon receptor (AHR)-mediated gene and do not function in an additive manner.


[Premature rupture of fetal membranes in the midtrimester (II): Antibiotic treatment in a case of intraamniotic infection prior to fetal viability].
A case of a 33 year old woman G7P6A1, with preterm premature rupture of membranes at 20 weeks of gestation and asymptomatic intramniotic infection is reported. At admission, the presence of Klebsiella oxytoca in amniotic fluid was demonstrated by amniocentesis. Parenteral antibiotics were administered with a following demonstration of aseptic fluid. The patient delivered at 29 1/2 weeks of pregnancy. A newborn weighing 1520 with an Apgar score of 8-8 was obtained. The mother had a normal puerperal period without any evidence of infectious morbidity. A clinical sepsis was demonstrated in the newborn with appropriate response to antibiotic therapy. No further complications were observed.


Shared Virtual Reality Experiences during the COVID-19 Pandemic: Exploring the Gratifications and Effects of Engagement with Immersive Videos.
The coronavirus (COVID-19) pandemic and recent economic recession have been impacting many people's mental health. The experience of social distancing created new hardships for people who already reported symptoms of depression or anxiety. In these circumstances, new technologies, such as immersive virtual reality (VR) videos, could serve as useful tools for facilitating interactions, emotional sharing, and information processing within a virtual environment. In this study, researchers aimed to enrich the information processing literature by focusing on the uses and gratifications of 360-degree VR videos during the pandemic. Through employing survey research with 1422 participants located in the U.S. and structural equation modeling for data analysis, this study found that five types of gratification, including utilitarian (i.e., navigation), hedonic (i.e., enjoyment), sensual (i.e., realism), social (i.e., community), and symbolic (i.e., coolness), significantly motivated users to use such immersive videos. Simultaneously, data demonstrated that these five types of gratification could influence users' cognitive engagement with virtual content. In addition, such VR engagement facilitated users' positive attitudes toward immersive videos and continued usage of them. The findings provided practical implications for COVID-19 global recovery as well.


Heart proteins. Prevention of the denaturation of actomyosin by sodium glutamate.
The storage of actomyosin isolated from bovine heart for one week either at +4 degrees or frozen at -5 degrees results in deep structural changes in the molecule of actomyosin, while storage of the actomyosin at the mentioned temperatures in the presence of sodium glutamate preserved the characteristic structure of actomyosin molecule as revealed by electron microscopy.


Determination of operator exposure levels to insecticide during bait applications in olive trees: study of coverall performance and duration of application.
In this study the operator exposure levels during bait applications of an insecticide in olive groves were determined using a whole body dosimetry method for dermal exposure. The study design allowed the roles of application task duration and coverall type to be evaluated as factors influencing operator exposure. Twenty applications were carried out with knapsack sprayers in the Tanagra region of Viotia, Greece, ten of which were for a 1h and ten for a 3h duration. An in-house GC-NPD analytical method was developed and validated for the determination of malathion, the active substance (a.s.) of the insecticide formulation used in field trials. The mean recovery of field-fortified samples was 84% (%RSD=3.0). Field trial results generally indicated lower operator exposure levels than indicated by the most relevant operator exposure predictive model. Residues of malathion on internal dosimeters were compared to those measured on the respective outer coveralls (potential dermal exposure) to evaluate the protective factor of each one of the two coverall types used. Both coverall types provided satisfactory levels of protection and can be considered as suitable protection for the conditions of the application scenario studied. Furthermore, the results indicated that there is not a strong correlation between exposure levels and duration of application.


Sources of organic compounds in fine soil and sand particles during winter in the metropolitan area of Riyadh, Saudi Arabia.
Major advances have been made in molecular marker analysis to distinguish between natural and anthropogenic organic matter inputs to the atmosphere. Resuspension of soil and sand by wind is one of the major mechanisms that produces particle dusts in the atmosphere. Soil and sand samples from the Riyadh area were collected in winter 2002, sieved to remove coarse particles and extracted with a mixture of dichloromethane and methanol (3:1, v:v). The total extracts were analyzed by gas chromatography-mass spectrometry in order to characterize the contents and identify the potential sources of the organic components. The major organic compounds of these extracts were derived from natural biogenic and anthropogenic sources. Organic compounds from natural sources, mainly vegetation, were major in samples from outside the city of Riyadh and included n-alkanes, n-alkanoic acids, n- alkanols, methyl alkanoates, and sterols. Anthropogenic inputs were significant in the fine particles of soil and sand samples collected from populated areas of the city. They consisted mainly of n-alkanes, hopanes, UCM (from vehicular emissions), and plasticizers (from discarded plastics, e.g., shopping bags). Carbohydrates had high concentrations in all samples and indicate sources from decomposed cellulose fibers and/or the presence of viable microbiota such as bacteria and fungi.


Bone lesions in hairy cell leukemia. A case report and response of bone pains to steroids.
An unusual case of hairy cell leukemia is reported. The patient experienced severe bone pains at the sites of the bone lesions caused by infiltration by hairy cells documented histologically. The pains were resistant to various analgesics. Administration of corticosteroids resulted in prompt, full, and sustained response despite the persistence of bone lesions radiographically.


Excessive Maternal Weight and Diabetes Are Risk Factors for Macrosomia: A Cross-Sectional Study of 42,663 Pregnancies in Uruguay.
To evaluate the risk of macrosomia in newborns from women with gestational diabetes, pregestational diabetes, overweight, and obesity in Uruguay in 2012, as well as its association with prolonged pregnancy, maternal age, multiparity, and excessive gestational weight gain (EGWG). We performed a cross-sectional study of 42,663 pregnant women. The risk of macrosomia was studied using logistic regression. Mean maternal age was 26.7 ± 6.8 years. Pregestational overweight and obesity was present in 20.9% and 10.7% of women, respectively. There were 28.1% and 19.8% of women overweight and obese at the end of the pregnancy, respectively. Furthermore, 0.5% had pregestational diabetes and 8.5% were multiparous. Twenty two percent developed gestational diabetes and 44.9% had EGWG. The prevalence of macrosomia was 7.9%, significantly more prevalent in males (10.0% vs. 5.5%, p<0.005). Univariate analysis showed that obesity and overweight pre-pregnancy, obesity and overweight at the end of pregnancy, EGWG, pregestational diabetes, gestational diabetes, multiparity, prolonged pregnancy, and male newborn were strongly associated with macrosomia (p<0.0001). Maternal age >35 years did not increase the risk of macrosomia. After multiple logistic regression macrosomia was more likely in pre-gestational obese women (OR 1.24; CI 1.07-1.44), overweight women at the end of pregnancy (OR 1.66; CI 1.46-1.87), obese women at the end of pregnancy (OR 2.21; CI 1.90-2.58), women with EGWG (OR 1.78; CI 1.59-1.98), pregestational diabetes (OR 1.75; CI 1.15-2.69), gestational diabetes (OR 1.39; CI 1.25-1.53), prolonged pregnancy (OR 2.67; CI 2.28-3.12), multiparity (OR 1.24; CI 1.04-1.48), and male newborn (OR 1.89; CI 1.72-2.08). Maternal overweight, obesity, EGWG, and gestational diabetes are prevalent in Uruguay, increasing the risk of macrosomia. Efforts to implement strategies to decrease the prevalence of overweight and obesity among women of reproductive age are essential to improve maternal and neonatal outcomes.


Management of severe haemoptysis by bronchial artery embolisation in a patient with cystic fibrosis.
Severe haemoptysis in a patient with cystic fibrosis was successfully treated on two occasions by bronchial artery embolisation.


Chromosomes bearing amplified genes are a preferential target of chemicals inducing chromosome breakage and aneuploidy.
Micronuclei were induced in V79 Chinese hamster cells and in PALA L and MTX M, two derivative cell lines harboring amplified genes, with 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and vinblastine. Spontaneous and induced micronuclei were analyzed for the presence of centromeres by immunofluorescent CREST staining. Micronuclei formed in PALA L cells were also analyzed for the presence of amplified DNA by in situ hybridization with a CAD gene probe. Both cell lines containing amplified genes showed increased micronucleus induction by BCNU and vinblastine. The marker chromosome of PALA L cells was found to be a preferential target for both the clastogenic and the aneugenic action of the two chemicals. DNA amplification seems therefore to be a destabilizing factor of chromosomal structural integrity and mitotic segregation.


Human macrophages armed with murine immunoglobulin G2a antibodies to tumors destroy human cancer cells.
Macrophages isolated from tumor-bearing patients as well as cultured human monocytes express Fc receptors that cross-react strongly with murine immunoglobulins of the G2a but only slightly or not at all with the G1, G2b, or G3 subclasses. Such macrophages in the presence of murine immunoglobulin G2a monoclonal antibodies to tumors mediated the killing of tumor cells in vitro. These data suggest that monoclonal antibodies of the G2a subclass may be useful in the immunotherapy of human cancer.


[The determination of capillary blood glucose using the automatic clinical analyzer (aca) Dupont (author's transl)].
The determination of capillary blood glucose after deproteinization using the aca is described. The method, which uses the hexokinase/glucose-6-phosphate dehydrogenase reaction, is compared with the glucose dehydrogenase method. The comparison shows that glucose values measured in capillary blood are essentially the same in both methods. The requirements for quality control are fulfilled. The method is not influenced by hemolysis, bilirubinemia, and hypertriglyceridemia.


Monovalent and multivalent binding of streptavidin to biotinylated gramicidin affects the kinetic properties of the ion channel.
Biotin-avidin (or streptavidin) high affinity binding has been widely applied as a universal tool for basic research as well as diagnostic and therapeutic purposes. Here we studied the interaction of streptavidin with ionic channels formed by biotinylated gramicidin in planar bilayer lipid membranes (BLM) using the method of sensitized photoinactivation. As shown previously, the addition of streptavidin leads to a profound increase in the lifetime (tau) of gA5XB, a biotinylated analog of gramicidin A with a linker arm of five aminocaproyl groups (Rokitskaya et al. (2000) Biochemistry, 39, 13053-13058). The present study has revealed that the increase in tau is related to multivalent interaction of streptavidin with biotinylated gramicidin, i.e., to formation of a complex of streptavidin with several gramicidin channels, whereas binding of streptavidin to a single channel does not change the value of tau. A rather long linker arm attaching biotin to the C-terminus of gramicidin appeared to be required for the multivalent interaction of streptavidin with gramicidin channels, as the increase in tau was not observed with channels formed by gA2XB, the biotinylated gramicidin analog with a linker arm comprising only two aminocaproyl groups. However, the formation of a stoichiometric (1 : 1) complex of streptavidin with gA2XB apparently occurred. The multivalent interaction of streptavidin with gA5XB disappeared if biotinylated lipids were included into the diphytanoylphosphatidylcholine membrane. It is suggested that the slowing of gramicidin channel kinetics provoked by streptavidin binding is due to membrane-mediated elastic interactions between two neighboring channels.


Loss of PINK1 leads to metabolic deficits in adult neural stem cells and impedes differentiation of newborn neurons in the mouse hippocampus.
Emerging evidence suggests that mitochondrial dynamics regulates adult hippocampal neurogenesis (AHN). Although abnormal AHN has been linked to depression, anxiety, and cognitive dysfunction, which are features of neurodegenerative conditions, including Parkinson's disease (PD), the impact of mitochondrial deficits on AHN have not been explored previously in a model of neurodegeneration. Here, we used PTEN-induced kinase 1-deficient (PINK1-/- ) mice that lacked a mitochondrial kinase mutated in recessive familial PD. We show that mitochondrial defects, elevated glycolysis, and increased apoptosis are associated with impaired but not abrogated differentiation of PINK1-deficient neural stem cells (NSCs) in culture. In the dentate gyrus of PINK1-/- mice, newly generated doublecortin-positive neurons show aberrant dendritic morphology, and their maturation is compromised compared with wild-type mice. In addition, in vivo labeling of NSCs with 5-ethynyl-2'-deoxyuridine shows that proliferating NSC numbers are normal, but the differentiation of NSCs to doublecortin-positive neuroblasts and mature NeuN+ neurons is impeded in PINK1-/- mice. Finally, we demonstrate that home cage activity and corticosterone levels of PINK1-/- mice are normal, thereby excluding reduced physical activity and increased stress as causes of neurogenesis defects. Our results reveal a new and important relationship between mitochondrial dysfunction and impaired AHN in a genetic PD model. Targeting mitochondrial function and metabolism to increase AHN may hold promise for the treatment of affective disorders and the mitigation of related symptoms in PD and other neurodegenerative conditions.-Agnihotri, S. K., Shen, R., Li, J., Gao, X., Büeler, H. Loss of PINK1 leads to metabolic deficits in adult neural stem cells and impedes differentiation of newborn neurons in the mouse hippocampus.


Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial.
Large reductions in transmission of HIV-1 from mother to child have been achieved in more-developed countries due to the use of antiretrovirals. Short-course regimens, suitable for resource-poor countries, have also been shown to significantly reduce peripartum HIV-1 transmission. We assessed the efficacy of short-course regimens with zidovudine and lamivudine in a predominantly breastfeeding population. We did a randomised, double-blind, placebo-controlled trial in South Africa, Uganda, and Tanzania. Between June, 1996, and January, 2000, HIV-1-infected mothers were randomised to one of four regimens: A, zidovudine plus lamivudine starting at 36 weeks' gestation, followed by oral intrapartum dosing and by 7 days' postpartum dosing of mothers and infants; B, as regimen A, but without the prepartum component; C, intrapartum zidovudine and lamivudine only; or placebo. From Feb 18, 1998, onward, women were only randomised to one of the active treatment groups. Primary outcomes were HIV-1 infection and child mortality at week 6 and month 18 after birth. Analysis was by intention to treat of those randomised before Feb 18, 1998. 1797 HIV-1-infected women were identified. Week 6 HIV-1 transmission rates were 5.7% for group A, 8.9% for group B, 14.2% for group C, and 15.3% for the placebo group. Respective relative risks for HIV-1 transmission in the treatment groups compared with placebo were 0.37 (95% CI 0.21-0.65), 0.58 (0.36-0.94), and 0.93 (0.62-1.40). For the combined endpoint of HIV-1 infection and infant mortality at week 6 rates were 7.0%, 11.6%, 17.5%, and 18.1%, respectively, with relative risks of 0.39 (0.24-0.64), 0.64 (0.42-0.97), and 0.97 (0.68-1.38). 1081 (74%) of the women analysed initiated breastfeeding. Based on an interval-censored survival analysis, HIV-1 infection rates at month 18 were 15% (95% CI 9-23), 18% (12-26), 20% (13-30) and 22% (16-30), respectively. Although at week 6 after birth, regimens A and B were effective in reducing HIV-1 transmission, benefits have diminished considerably after 18 months of follow-up. Introduction of short-course regimens to prevent mother-to-child transmission of HIV-1 in less-developed countries should be accompanied by interventions to minimise the risk of subsequent transmission via breastfeeding.


Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase(PI3-kinase) pathway.
Pancreatic stellate cells (PSCs) are implicated as key mediators of pancreatic fibrogenesis and are found in increased numbers in areas of pancreatic injury. This increase in number may be due to increased local proliferation and/or migration of PSCs to affected areas from surrounding tissue. We have recently shown that PSCs can migrate and that this migration is stimulated by PDGF in a predominantly chemotactic manner [Gut 52 (2003) 677]. However, the signalling mechanisms responsible for PDGF-induced PSC migration are not known. (i) To determine whether PDGF-induced PSC migration is mediated by the PI3-kinase pathway. (ii) To investigate whether cell migration is influenced by cell proliferation and whether an interaction exists between the PI3-kinase pathway and the ERK1/2 pathway (known to mediate cell proliferation) in PSCs exposed to PDGF. (i) PI3-kinase activity was assessed by measuring the activation (phosphorylation) of its downstream substrate Akt in rat PSCs incubated with PDGF (10ng/mL) for 5min, 15min, 60min, and 24hr in the presence or absence of the specific PI3-kinase inhibitor wortmannin. (ii) The role of the PI3-kinase pathway in PSC migration was examined by assessing PSC migration through a porous membrane after exposure to PDGF in the presence and absence of wortmannin for 24hr. (iii) The relationship between migration and proliferation was assessed by examining migration of PSCs exposed to PDGF in the presence and absence of mitomycin C, an inhibitor of cell proliferation. (iv) The interaction between PI3-kinase and ERK1/2 was examined by incubation of PSCs with PDGF in the presence and absence of wortmannin, followed by assessment of ERK1/2 activation by western blot. PDGF increased Akt activation in PSCs as early as at 5min of incubation and this increase was sustained for 24hr. Inhibition of PI3-kinase by wortmannin decreased basal as well as PDGF-induced migration and also inhibited ERK1/2 activation. Inhibition of PSC proliferation with mitomycin C significantly reduced (but did not abolish) basal and PDGF-induced PSC migration. (i) The PI3-kinase pathway is induced in PSCs after exposure to PDGF and this induction is sustained for at least 24hr. (ii) The PI3-kinase pathway plays a role in PDGF-induced PSC migration and is partially involved in mediating ERK1/2 activation. (iii) PSC migration is dependent, at least in part, on cell proliferation.


High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged Caucasian populations.
Plasma aldosterone and renin levels have been associated with blood pressure increase and 3-4 year incidence of hypertension in a middle-aged North American community in Framingham. To confirm these findings in a different population, a nested case-control study was performed in a national sample of 1984 French non-hypertensive volunteers aged 45-64 year and followed for 5 years. Cases and controls (individuals becoming hypertensive or remaining non-hypertensive on follow-up) were individually matched on sex, diastolic and systolic pressures at baseline. Multivariable regression models show that plasma aldosterone and renin are respectively positively and negatively associated with the increase in systolic pressure (P=0.01 and 0.001) and the risk of hypertension (22% increase and 16% decrease per s.d. increment in the log, P=0.04 and 0.07). These associations are mostly observed in the lowest tertiles of dietary sodium and potassium intakes where plasma aldosterone is positively associated with the increase in systolic pressure (P=0.01 and 0.08) and the risk of hypertension (59 and 69% increase per s.d. increment in the log, P=0.02 and 0.01), whereas plasma renin is negatively associated with the increase in systolic pressure (P=0.0004 and 0.004) and the risk of hypertension (31 and 28% decrease per s.d. increment in the log, P=0.03 and 0.05). These results reinforce the hypothesis that high plasma aldosterone and low plasma renin levels precede blood pressure increase and the occurrence of hypertension in middle-aged Caucasian populations.


Critical role of information and communication technology in nursing during the COVID-19 pandemic: A qualitative study.
To examine the need for information and communication technology (ICT)-based nursing care in improving patient management during the pandemic. Maintaining traditional approaches to nursing in the ongoing coronavirus disease (COVID-19) pandemic predisposes health care systems to a risk of diminished quality of care. Using ICT (real-time videoconferencing, mobile robots and artificial intelligence) could reduce burnout and infection risks by minimizing face-to-face contact. Qualitative descriptive design with content analysis. Overall, 24 participants (14 nurses, six medical/nursing informatics experts and four technology experts) were interviewed. Three main themes were extracted: emerging challenges for nurses due to COVID-19, impact of new technology on patient and nurse experiences and concerns with implementation of technology. A significant portion of nurses' work was unrelated to professional nursing, causing burnout. ICT could help reduce nurses' burden by facilitating environmental management and non-contact communication and providing emotional support for patients. Establishing an ICT-based nursing care system that considers the physical environment and communication infrastructure of health care institutions, user's digital health literacy and user safety to effectively manage non-nursing care-related activities and undertake tasks that can be delegated may improve the quality of care for quarantined patients and reduce risk of cross-infection.


The role of combination anthelmintic formulations in the sustainable control of sheep nematodes.
Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.


Co-digestion of sewage sludge and sterilized solid slaughterhouse waste: methane production efficiency and process limitations.
The rendering product of Category 2 and 3 Animal By-Products is known as sterilized mass (SM) and it is mainly composed of fat and proteins, making it interesting substrate for anaerobic digestion. Batch and semi-continuous laboratory experiments were carried out to investigate the effect of SM addition in co-digestion with sewage sludge on methane production and possible process limitations. Results showed that SM addition in the feed mixture up to 5% (w/w), corresponding to 68.1% of the organic loading, increased methane production 5.7 times, without any indication of process inhibition. Further increase of SM addition at 7.5% (w/w) caused methane production decrease and volatile solids removal reduction, that was mainly related to remarkably increased free ammonia concentration in the digester of 596.5±68.6 gNH3 L(-1). Sterilized mass addition of 10% (w/w) caused intensive foaming, LCFA accumulation of 9172±701.2 mgCOD-LCFA g(-1) sample and termination of the experiment.


Comparative summer dynamics of surface cyanobacterial communities in two connected lakes from the west of Ireland.
The eutrophication of lakes is typically associated with high biomass proliferations of potentially toxic cyanobacteria. At a regional level, the sustainable management of water resources necessitates an approach that recognises the interconnectivity of multiple water systems within river catchments. This study examined the dynamics in summer diversity of planktonic cyanobacterial communities and microcystin toxin concentrations in two inter-connected lakes from the west of Ireland prone to nutrient enrichment. DGGE analysis of 16S rRNA gene amplicons of genotype-I cyanobacteria (typically spherical) showed changes in the communities of both Lough Corrib and Ballyquirke Lough throughout the summer, and identified cyanobacterial genotypes both unique and shared to both lakes. Microcystin concentrations, estimated via the protein phosphatase 2A inhibition assay, were greater in August than in July and June in both lakes. This was concomitant to the increased occurrence of Microcystis as evidenced by DGGE band excision and subsequent sequencing and BLAST analysis. RFLP analysis of PCR amplified mcy-A/E genes clustered together the August samples of both lakes, highlighting a potential change in microcystin producers across the two lakes. Finally, the multiple factor analysis of the combined environmental data set for the two lakes highlighted the expected pattern opposing greater water temperature and chlorophyll concentration against macronutrient concentrations, but also indicated a negative relationship between microcystin concentration and cyanobacterial diversity, possibly underlining allelopathic interactions. Despite some element of connectivity, the dissimilarity in the composition of the cyanobacterial assemblages and the timing of community change in the two lakes likely were a reflexion of niche differences determined by meteorologically-forced variation in physico-chemical parameters in the two water bodies.


Scalp recorded somatosensory evoked potentials to posterior tibial nerve stimulation in humans.
The somatosensory evoked potentials (SEPs) produced by stimulation of the right and left posterior tibial nerves individually and also by their simultaneous stimulation were recorded in 84 adult normal subjects up to 150 msec after the stimulus by electrodes placed on the cranial vertex and by rows of electrodes over the sagittal and coronal lines using references on the ear or in the nasopharynx. The statistical distribution of the latencies of their different peaks was established. The effect of simultaneous stimulation of right and left posterior tibial nerves on the early SEP components was described. Some details of the anatomy of the rolandic sulcus were inferred from the amplitude distribution of these potentials.


The impact of voluntary exercise on mental health in rodents: a neuroplasticity perspective.
There is growing interest in the effects of voluntary wheel running activity on brain and behaviour in laboratory rodents and their implications to humans. Here, the major findings to date on the impact of exercise on mental health and diseases as well as the possible underlying neurobiological mechanisms are summarised. Several critical modulating factors on the neurobehavioural effects of wheel running exercise are emphasized and discussed--including the amount of wheel running, sex and strain/species differences. We also reported the outcome of an empirical investigation of the impact of wheel running exercise on the expression of both cognitive and non-cognitive phenotypes in a triple (3 x Tg-AD) transgenic mouse model for Alzheimer's disease (AD). Clear sex- and paradigm-specific effects of exercise on the genetically determined phenotypes are illustrated, including the efficacy of wheel running activity in attenuating the sex-specific cognitive deficits. It is concluded that the wheel running paradigm represents a unique environmental manipulation for the investigation of neurobehavioural plasticity in terms of gene-environment interactions relevant to the pathogenesis and therapies of certain neuropsychiatric conditions.


Retraction Note: Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging.
An amendment to this paper has been published and can be accessed via the original article.


Iron uptake system mediates nitrate-facilitated cadmium accumulation in tomato (Solanum lycopersicum) plants.
Nitrogen (N) management is a promising agronomic strategy to minimize cadmium (Cd) contamination in crops. However, it is unclear how N affects Cd uptake by plants. Wild-type and iron uptake-inefficient tomato (Solanum lycopersicum) mutant (T3238fer) plants were grown in pH-buffered hydroponic culture to investigate the direct effect of N-form on Cd uptake. Wild-type plants fed NO₃⁻ accumulated more Cd than plants fed NH₄⁺. Iron uptake and LeIRT1 expression in roots were also greater in plants fed NO₃⁻. However, in mutant T3238fer which loses FER function, LeIRT1 expression in roots was almost completely terminated, and the difference between NO₃⁻ and NH₄⁺ treatments vanished. As a result, the N-form had no effect on Cd uptake in this mutant. Furthermore, suppression of LeIRT1 expression by NO synthesis inhibition with either tungstate or L-NAME, also substantially inhibited Cd uptake in roots, and the difference between N-form treatments was diminished. Considering all of these findings, it was concluded that the up-regulation of the Fe uptake system was responsible for NO₃⁻-facilitated Cd accumulation in plants.


Psychometric properties of the SCOFF questionnaire (Chinese version) for screening eating disorders in Hong Kong secondary school students: a cross-sectional study.
Eating disorders are affecting an increasing number of high school students in Western and Asian countries. The availability of an effective screening tool is crucial for early detection and prompt intervention. The objective of this study was to examine the validity and reliability of the SCOFF questionnaire for screening eating disorders in Hong Kong high school students. This study adopted a cross-sectional design to examine the psychometric properties of the SCOFF questionnaire. A panel of 7 experts and 936 students of a high school participated in the study. The SCOFF questionnaire was translated into Chinese and back-translated into English to ensure the linguistic equivalence. A panel of 7 experts involved in the content validation of the SCOFF questionnaire. The Eating Disorder Examination-Questionnaire (EDE-Q) was used as the "reference standard" to assess its concurrent validity in 936 students of a high school. Its reliability was examined by internal consistency and the test-retest method at a 2-week interval and with 38 students. The SCOFF questionnaire achieved an agreement of 86-100% among the experts for the content relevance. Of 812 students (86.8%) who responded to this study, their SCOFF scores correlated significantly with their global scores on the EDE-Q (r=0.5, P<0.01). Students identified as potentially having eating disorders had significantly higher scores in the EDE-Q than those not identified as such by SCOFF. The SCOFF questionnaire demonstrated moderate test-retest reliability (ICC=0.66) and an acceptable internal consistency reliability (Cronbach's alpha=0.44-0.57) in comparing with previous studies. The SCOFF questionnaire has acceptable psychometric properties in the Chinese culture. It will be useful for detecting potential eating disorders and assisting health promotion activity.


Exosomes derived from TGF-β1-pretreated mesenchymal stem cells alleviate biliary ischemia-reperfusion injury through Jagged1/Notch1/SOX9 pathway.
This study aimed to evaluate the efficacy of exosomes (EXO) derived from TGF-β1-pretreated mesenchymal stem cells (MSCs) on biliary ischemia reperfusion injury (IRI) and further reveal the possible mechanisms. Bone marrow-derived MSCs were treated with exogenous TGF-β1, Jagged1/Notch1/SOX9 pathway inhibitor LY450139, or their combination. Then, EXO were isolated from the culture supernatants and further characterized. After establishing IRI model of biliary epithelial cells (EpiCs), EXO derived from differently-treated MSCs were applied to detect their protective effects on EpiCs, and LY450139 was applied in EpiCs to detect the possible mechanisms after treatment with MSCs-EXO. EXO derived from differently-treated MSCs were further injected into the hepatic artery immediately after establishment of intrahepatic biliary IRI for animal studies. Pretreatment with TGF-β1 significantly enhanced MSCs-EXO production and elevated the levels of massive miRNAs associated with anti-apoptosis and tissue repair, which were evidently decreased after TGF-β1 plus LY450139 cotreatment. Notable improvement was observed in EpiCs after MSCs-EXO treatment, evidenced by reduced cellular apoptosis, increased cellular proliferation and declined oxidative stress, which were more evident in EpiCs that were treated with EXO derived from TGF-β1-pretreated MSCs. However, application of EXO derived from TGF-β1 plus LY450139-cotreated MSCs reversely enhanced cellular apoptosis, decreased cellular proliferation and anti-oxidants production. Interestingly, LY450139 application in EpiCs after treatment with MSCs-EXO also reversed the declined cellular apoptosis and enhanced oxidative stress induced by TGF-β1 pretreatment. In animal studies, administration of EXO derived from TGF-β1-pretreated MSCs more effectively attenuated biliary IRI through reducing oxidative stress, apoptosis, inflammation and enhancing the expression levels of TGF-β1 and Jagged1/Notch1/SOX9 pathway-related markers, which were reversed after administration of EXO derived from TGF-β1 plus LY450139-cotreated MSCs. Our results provided a vital insight that TGF-β1 pretreatment endowed MSCs-EXO with stronger protective effects to improve biliary IRI via Jagged1/Notch1/SOX9 pathway.


Sleep-Related Problems and Pediatric Anxiety Disorders.
Sleep-related problems are highly prevalent among childhood and adolescent anxiety disorders. The objective of this review was to summarize the relevant clinical research literature as it pertains to the nature of the association between sleep-related problems and youth anxiety, developmental factors relevant to this association, and intervention efforts to target comorbid sleep challenges and anxiety. Limitations of the literature and future directions are discussed.


Comminuted radial head fractures treated with pyrocarbon prosthetic replacement.
We had evaluated our experience in the treatment of displaced and comminuted radial head fractures with pyrocarbon radial head prosthesis. From May 2003 to July 2008, radial head prostheses were performed in 47 patients. There were 29 female and 18 male with mean age 51 (34-70 years). The follow-up was a mean of 48 (12-60 months). Fractures of the radial head have been classified by Hotchkiss. The indications for a radial head replacement were type III fractures in 27 cases, type IV fractures in ten cases, comminuted radial fracture associated with disruption of the medial collateral ligament in three cases, Monteggia variant in five cases, and Essex-Lopresti in two cases. Functional outcomes were assessed by visual analog scales (VAS) of pain, joint motion and stability, and using the Mayo Elbow Performance Index. The mean VAS score for elbow pain was 1 (0.5-2.1). Patients showed an average arc of motion from 6° to 140°, with 75° of pronation and 67° of supination. By using the Mayo Elbow Performance Index, 42 patients had good/excellent results, with three fair and two poor outcomes. Complications were two implant dislocations, one elbow stiffness, one dissociation of the implant, one stem rupture, and two posterior interosseous nerve palsy that recovered from 5 to 8 weeks. We had not seen persistent instability, infection, synostosis, severe degenerative changes, or impingement. The treatment of comminuted radial head fracture with pyrocarbon implant usually gives an optimal result depending on the severity of the initial injury and the presence of associated lesions. The size of the prosthesis is often overestimated, causing restriction in motion due to impingement, overstuffing, or dislocations.


Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar and Long-Evans rats with different aryl hydrocarbon receptor (AhR) structures.
Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W) and dioxin-sensitive Long-Evans (L-E) rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM) and dose-response modeling. The strongest effects were shown by L-E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS) in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs) for cranial size reduction in L-E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L-E rats, respectively), most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L-E rats had vaults and bases of comparable size, the face was 6.4% larger in L-E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR) that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on the mammalian skeleton.


Neutrophil infiltration of the colon is independent of the FPR1 yet FPR1 deficient mice show differential susceptibilities to acute versus chronic induced colitis.
The receptor for formylated peptides, formyl peptide receptor 1 (FPR1), potently activates and serves as a chemoattractant receptor for neutrophils. Given the abundance of neutrophils in the inflamed colon, our aim was to determine if the FPR1 mediates colonic neutrophil migration, using the dextran sodium sulfate (DDS)-induced model of colitis. Formyl peptide receptor 1 gene-deficient mice were administered DDS in drinking water for a single 5-day period (acute) or in two 5-day periods separated by 16 days (chronic). At the end of the treatment their colons were excised, measured, and prepared for histological evaluation. FPR1(-/-) mice experienced less severe acute colonic pathology than C57BL/6 (wildtype) mice. The opposite was observed following the second colitis cycle, with FPR1(-/-) mice developing worse pathology than wildtype mice. Both strains had similar numbers of infiltrating neutrophils in ulcerated areas of the colon after a single DSS cycle, but FPR1(-/-) mice had significantly more neutrophils in the ulcerated mucosa after two cycles. There was no difference in the capacity of neutrophils from each strain to migrate to chemoattractants. Since the FPR1(-/-) mice had larger ulcers compared to the wildtype mice, we propose that the FPR1(-/-) mice failed to recover at the same rate as wildtype mice. This apparent difference in restitution could not be attributed to observable differences in annexin A1. We conclude that neutrophil migration into the inflamed mouse colon does not depend on FPR1 but that FPR1 contributes in other pathological mechanisms that are harmful during acute inflammation but protective during chronic inflammation.


Mixed genotypes infection with hepatitis D virus.
Heterogeneity of hepatitis C viral (HCV) genomes results in escape from immune clearance. Super-infection or mixed infection of different genotypes of HCV are seen commonly in humans. Hepatitis D virus (HDV) is classified into 3 genotypes. This study was planned to investigate if mixed genotypes infection of HDV occurs in humans. HDV genotyping based on restriction fragment length polymorphism (RFLP) was used to screen 60-99 HDV clones from each case of 7 prostitutes and 11 patients. Mixed infections were diagnosed by the finding of two or more different RFLP patterns in a case and were confirmed by sequencing. Five prostitutes had mixed infections of genotypes IIa and IIb HDV, while only 2 patients had mixed infections of genotypes I and II HDV (P< 0.05). The heterogeneity in nucleotide sequence was generally below 2% among HDV quasi-species from the same subject, while the heterogeneity was 27.7% between genotypes I and II HDV, and 22.8% between genotypes IIa and IIb HDV from a subject with mixed infection. Multiple HDV clones from the spouses of the 2 index cases were also analyzed. One spouse had mixed infection and the other did not, corresponding to the index cases. In cases with mixed genotypes infections, the prevalence of the minor strain was less than 10% of the total colony population analyzed.


Amitriptyline modulation of Na(+) channels in rat dorsal root ganglion neurons.
The effects of amitriptyline, a tricyclic antidepressant, on tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp method. Amitriptyline blocked both types of Na(+)currents in a dose-and holding potential-dependent manner. At the holding potential of -80 mV, the apparent dissociation constants (K(d)) for amitriptyline to block tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) channels were 4.7 and 105 microM, respectively. These values increased to 181 and 193 microM, respectively, when the membrane was held at a potential negative enough to remove the steady-state inactivation. Amitriptyline dose-dependently shifted the steady-state inactivation curves in the hyperpolarizing direction and increased the values of the slope factors for both types of Na(+) channels. The voltage dependence of the activation of both types of Na(+) channels was shifted in the depolarizing direction. It was concluded that amitriptyline blocked the two types of Na(+) channels in rat sensory neurons by modulating the activation and the inactivation kinetics.


Identification of hemolytic granules isolated from human myocardial cells.
Human myocardial cells from fresh autopsy material contained granules which possessed hemolytic activity against guinea pig and rabbit erythrocytes. The hemolytic granules, which had a density of 1.02 and a diameter of 200-300 nm, were recovered as a microsome fraction from subcellular homogenates of human myocardial cells by differential centrifugation in 300 mM sucrose containing 0.1 mM PMSF and 10 mM EDTA. The membrane lesions caused by the granules were ring-like structures with an internal diameter of about 10-17 nm, analogous to that caused by perforin- and complement-induced lysis. However, the requirement for divalent cation differed from that for perforin-induced lysis, since the microsome-mediated lysis occurred in the presence of EDTA.


Design and validation of a multiphase 3D model to simulate tropospheric pollution.
This work presents the Transport and Chemical Aerosol Model (TCAM) formulation and its validation in the frame of CityDelta-CAFE project. TCAM is a 3D eulerian multiphase model simulating tropospheric secondary pollution at mesoscale. It is included in the GAMES (Gas Aerosol Modelling Evaluation System) modelling system, designed to support the analysis of secondary pollution dynamics and to assess the impact of emission control strategies. The presented validation assessment has been performed in the frame of the CityDelta II project over the Milan domain and concerns both gas and aerosol 1999 simulations. Ozone, nitrogen oxides and aerosol computed and observed patterns have been compared and analysed by means of statistical indicators showing high model performances for both winter and summer pollution regimes.


Comparison of E-Z Derm and Jelonet dressings for partial skin thickness burns.
A prospective, randomized trial of 32 patients with partial skin thickness burns is reported comparing E-Z Derm with Jelonet as a burn dressing. The bacterial colonization rate, need for surgical treatment, time for spontaneous healing, analgesic requirements and frequency of dressing changes were assessed in each group. No statistically significant differences were found between the two groups, for any of these factors.


MRI reveals differential regulation of retinal and choroidal blood volumes in rat retina.
The retina is nourished by two unique (retinal and choroidal) circulations. The lack of depth-resolved blood volume (BV) imaging techniques hampers investigation of vascular-specific regulation of the retina in vivo. This study presents a high-resolution, laminar-specific magnetic resonance imaging (MRI) study to image retinal and choroidal BVs, their responses to physiologic challenges in normal and Royal-College-of-Surgeons (RCS) rats (a model of retinal degeneration). Retinal and choroidal BVs were imaged by MRI (30×30×800 μm) with intravascular administration of monocrystalline iron oxide nanocolloid (MION) contrast agent. Relative baseline BV and BV changes due to physiologic challenges were calculated in normal and RCS rat retinas. BV-MRI revealed two well-resolved retinal and choroidal vascular layers located on either side of the retina and an intervening avascular layer. The ratio of choroidal:retinal BV in normal rats at baseline was 9.8±3.2 in control rat retinas (N=7). Hyperoxia decreased retinal BV (-51±17%, p<0.05) more than choroidal BV (-28±14%), and hypercapnia increased retinal BV (52±11%, p<0.01) more than choroidal BV (12±11%). BV-MRI in degenerated retinas of RCS rats (N=7) revealed thinning of the avascular layer and an increase in relative baseline retinal and choroidal BVs. Only hypercapnia-induced BV changes in the retinal vasculature of RCS rats were significantly different (smaller) from controls (p<0.05). These findings suggest that BV in both retinal vasculatures is regulated. The relative baseline BV in both vasculatures increased in retinal degeneration. BV-MRI provides clinically relevant data that may prove useful for early detection and longitudinal probing of retinal diseases, and could complement optical imaging techniques.


Cellular distributions of AMPA glutamate receptor subunits in fetal ventral mesencephalon transplants in the dopamine-depleted striatum of a rat.
To demonstrate the cellular distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits (GluR1, GluR2/3, and GluR4) in the intrastriatal grafts of a rat model of Parkinson's disease, immunocytochemistry was performed in 6-hydroxydopamine rats with intrastriatal transplants of fetal ventral mesencephalon (VM). In the fetal VM (at embryonic day 15) in which the tyrosine hydroxylase (TH) immunoreactivity was intensely observed, no GluR subunit immunoreactivity was detected. Within the intrastriatal fetal VM grafts containing TH-positive cells, a large number of cells immunoreactive for GluR1 and GluR2/3 were observed. However, the GluR1- and GluR2/3-positive cells tended to locate homogeneously within the grafts and were composed of various cell sizes and shapes, mainly medium-sized and aspiny cells. Weak GluR4-positive cells were seen in the grafts, although in some cases the staining was too faint to see any immunoreactive cells at all. Double immunostaining revealed that a part of TH-positive cells in the grafts was also immunopositive for GluR1 or GluR2/3. Both dopaminergic neurons and nondopaminergic neurons in the VM transplants appear to be modified functionally by glutamatergic afferents via various glutamate receptors, including GluR1 and GluR2/3 and, to a lesser extent, GluR4.


Appraisal of anti-inflammatory and immunomodulatory potential of ramipril against Freund's adjuvant-provoked arthritic rat model.
Because of evident role of renin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with an increase in anti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.


The locus of semantic priming in RSVP target search.
At what stage does semantic priming affect accuracy in target search? In two experiments, participants viewed two streams of stimuli, each including a target word among distractors. Stimulus onset asynchronies (SOAs) between the targets (T1 and T2) ranged from 53 to 213 msec. A word semantically related to one or neither of the targets preceded each trial. In Experiment 1, participants were instructed to report both targets. Although more primed than unprimed targets were reported, there was no cost for unprimed words. A strong interaction between SOA and T1 versus T2 was found, but priming did not interact with either variable. In Experiment 2, only related targets were reported. Performance was similar to that for primed targets in Experiment 1. Semantic priming does not seem to modulate how attentional resources are initially allocated between targets, but instead affects a later stage of processing, the point at which a target word reaches lexical identification.


Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation.
Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders.


Detection of drug-dependent antibodies by the 51Cr platelet lysis test: documentation of immune thrombocytopenia induced by diphenylhydantoin, diazepam, and sulfisoxazole.
Sudden, severe thrombocytopenia developed in each of three patients receiving diphenylhydantion, diazepam, and sulfisoxazole, respectively. Recovery followed discontinuance of the drugs. An antiplatelet antibody requiring the presence of an appropriate drug for interaction with platelets was deomonstrated in each case by the 51Cr platelet lysis test using normal, paroxysmal nocturnal hemoglobinuric, or enzyme-treated normal platelets as target cells. These antibodies could not be detected by techniques that depend on clot retraction inhibition, complement fixation, or platelet factor-3 activation. Quinine-and quinidine-dependent antiplatelet antibodies in the serum of 16 patients who developed acute thrombocytopenia while taking either quinine or quinidine could be demonstrated readily with the 51Cr platelet lysis test and could also be detected by other methods employed.


Efficiency of reactive nitrogen removal in a model Mediterranean high-mountain lake and its downwater river ecosystem: Biotic and abiotic controls.
High-mountain lakes and rivers are usually oligotrophic and strongly influenced by atmospheric transport processes. Thus, wet deposition of reactive N species (Nr), mainly in the form of nitrate (NO3-), is a major source of N input in these high-mountain ecosystems. Bacterial denitrifiers are thought to be largely responsible for reduction of NO3- to nitrous oxide (N2O) and molecular dinitrogen (N2) as main biological pathway of N removal in these ecosystems. Nitrifiers, through the oxidation of ammonium to NO3-, can also be a source of NO3- and N2O. However, there is uncertainty regarding the abiotic and biotic factors controlling Nr elimination from aquatic ecosystems at different altitudes and seasons. We examined the efficiency of Nr removal as N2O and N2 (total removal) or N2 only (clean removal) in a model lake and its downwater river ecosystem (Sierra Nevada, Spain) representative of Mediterranean high-mountain freshwater ecosystems along an altitudinal gradient during the warm period of the year. Denitrification activity and the abundance of nitrifiers and denitrifiers in sediments were measured at thaw, mid ice-free and late ice-free periods. We found the efficiency of total and clean removal of Nr increased from the downwater river to the high-mountain lake. Regardless of the location, the efficiency of total removal of Nr decreased over the ice-free period whereas that of clean removal of Nr peaked at mid ice-free period. The efficiency of total removal of Nr was mainly controlled by the abundance of archaeal nitrifiers and bacterial denitrifiers. Abiotic (ammonium and NO3- concentration) and biotic (mainly nosZI-type denitrifiers) factors drove changes in the efficiency of clean removal of Nr. Our results suggest that abiotic and biotic factors can control the efficiencies of Nr removal in Mediterranean high-mountain lakes and their downwater rivers, and that these efficiencies increase with altitude and vary over the ice-free period.


Acetylaminofluorene-labelled ribosomal RNA for use in molecular epidemiology and taxonomy.
The use of acetylaminofluorene-labelled 16 + 23S rRNA (from Escherichia coli) is described for determining rRNA-gene-restriction patterns. The labelled probe allowed molecular fingerprinting of bacteria belonging to diverse phylogenetic branches (Enterobacteriaceae, Haemophilus, Pseudomonas, Acinetobacter, Brucella, Leptospira, Cytophaga, Campylobacter, Methylophaga). The labelled probe can be stored frozen (-20 degrees C) for at least a year and can endure vacuum dessication, ethanol precipitation or lyophilization.


Pathogenesis of delusions.
This overview of attempts to shed light on the pathogenesis of delusions provides a sense of promise, because we are grappling with the right problems, and reasons for both optimism and skepticism. Optimism is justified because some of the approaches have yielded empirical support and can be tested profitably in research. Skepticism is warranted because we remain unclear about precisely what delusions are; and we have as yet no means of identifying them with a laboratory test. Hence, we must rely on the problematic nature of clinical observation of the inner experiences of patients to make progress. The different mechanisms proposed still require considerable testing, but scrutiny of current results suggests that anomalous experience as a stimulus for delusion formation has been better documented than proposals invoking disordered reasoning or motivational deviances. Nevertheless, no view is as yet established, and each may have some relevance to solving the delusion puzzle.