Identification of 12 Piroplasms Infecting Ten Tick Species in China Using Reverse Line Blot Hybridization.
Piroplasmosis, a disease of domestic and wild animals, is caused by tick-borne protozoa in the genera of Theileria and Babesia. There is limited information available about the prevalence of piroplasmosis in ticks in China, and to assess the potential threat of piroplasmosis in China, we investigated the infections of ovine and bovine Babesia and Theileria species in ticks collected from cattle, yaks, sheep, horses, and camels in several regions of China where tick-borne diseases have been reported. In total, 652 ticks were collected from the animals in 6 provinces of China. Babesia spp. and Theileria spp. were detected with a PCR-RLB method and identified by sequencing. Overall, 157 ticks (24.1%) were infected with 5 Babesia and 4 Theileria species. Among tested tick samples, 134 (20.6%) were single infections with 1 of 7 piroplasm species, with Theileria annulata (118/652, 18.1%) being dominant. Only 23 (3.5%) tick samples were double or triple infected, Theileria luwenshuni and Theileria sinensis (18/652, 2.8%) were frequently observed in co-infections. Some piroplasm species were carried by ticks that were not previously reported to be vectors.


Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions.
We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury. Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded. Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p < 0.05 vs innervated ARF rats). Potassium excretion was significantly lower in denervated group as per fractional (p < 0.05 vs innervated ARF rats) but not absolute potassium excretion (p > 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats). The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions.


Bovine kidney gamma-glutamyltransferase. Solubilized forms, biochemical and immunochemical properties.
By digestion of detergent-solubilized gamma-glutamyltransferase (GGT), isolated from bovine kidney with bromelain, the liberation of 4 protein fragments was demonstrated. The fragment migrating most quickly in gel electrophoresis showed gamma-glutamyltranspeptidase activity and the most slowly migrating fragment showed peptidase activity. Protease-solubilized GGT is a sialoprotein with a molecular weight of 95,000. After treatment with sodium dodecylsulfate it was separated into two unequal subunits with molecular weights of 26,000 and 69,000. Sugar components were found only in the heavy subunit. Some catalytic differences were found between the two solubilized GGT forms. The immunoprecipitate obtained from detergent-solubilized GGT retained about 50% of the initial enzyme activity. The enzyme is inactivated with phenylmethanesulfonyl fluoride in the presence of maleate and with 6-diazo-5-oxo-L-norleucine.


Eμ and 3'RR IgH enhancers show hierarchic unilateral dependence in mature B-cells.
Enhancer and super-enhancers are master regulators of cell fate. While they act at long-distances on adjacent genes, it is unclear whether they also act on one another. The immunoglobulin heavy chain (IgH) locus is unique in carrying two super-enhancers at both ends of the constant gene cluster: the 5'Eμ super-enhancer promotes VDJ recombination during the earliest steps of B-cell ontogeny while the 3' regulatory region (3'RR) is essential for late differentiation. Since they carry functional synergies in mature B-cells and physically interact during IgH locus DNA looping, we investigated if they were independent engines of locus remodelling or if their function was more intimately intermingled, their optimal activation then requiring physical contact with each other. Analysis of chromatin marks, enhancer RNA transcription and accessibility in Eμ- and 3'RR-deficient mice show, in mature activated B-cells, an unilateral dependence of this pair of enhancers: while the 3'RR acts in autonomy, Eμ in contrast likely falls under control of the 3'RR.


COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome.
Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMT(L)) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.


Anaesthetic issues in robotic-assisted minimally invasive surgery.
Over the past decade there has been an exponential increase in the number of robotic-assisted surgical procedures performed in Australia and internationally. Despite this growth, there are no level I or II studies examining the anaesthetic implications of these procedures. Available observational studies provide insight into the significant challenges for the anaesthetist. Most anaesthetic considerations overlap with those of non-robotic surgery. However, issues with limited patient access and extremes of positioning resulting in physiological disturbances and risk of injury are consistently demonstrated concerns specific to robotic-assisted procedures.


Amphotericin B nephrotoxicity.
Nephrotoxicity becomes apparent days to months after the institution of amphotericin B therapy. It is characterized by azotemia, decreased renal plasma flow, decreased glomerular filtration rate, tubular defects, nephrocalcinosis, and diffuse, nonspecific histologic changes. Management consists of minimizing exposure to other nephrotoxins and ensuring adequate hydration.


Casemix Funding Optimisation: Working Together to Make the Most of Every Episode.
Eastern Health, a large public Victorian Healthcare network, conducted a WIES optimisation audit across the casemix-funded sites for separations in the 2009/2010 financial year. The audit was conducted using existing staff resources and resulted in a significant increase in casemix funding at a minimal cost. The audit showcased the skill set of existing staff and resulted in enormous benefits to the coding and casemix team by demonstrating the value of the combination of skills that makes clinical coders unique. The development of an internal web-based application allowed accurate and timely reporting of the audit results, providing the basis for a restructure of the coding and casemix service, along with approval for additional staffing resources and inclusion of a regular auditing program to focus on the creation of high quality data for research, health services management and financial reimbursement.


Why life sciences companies need to tap technology to gain a competitive edge-and what that means for the chief information officers (CIO) role.
Fundamental changes in the marketplace for medicines, as well as the rapid and continuing evolution of technology are bringing new challenges and opportunities for life sciences companies and their contribution to healthcare systems. These changes bring pressure on chief information officers (CIOs) within the healthcare industry to play an increasingly strategic role in advancing business success and delivering digital transformation.


Lipid composition of lees from Sherry wine.
In this paper, we describe the study and characterization of the lipids from lees of Sherry wine, one of the main byproducts from the wine-making industry in the Jerez/Xeres/Sherry denomination of the origin zone in Jerez de la Frontera, Spain. The lipid content, extractability, classification, fatty acid composition, and its main chemical characteristics have been determined in order to evaluate their potential use as a food or food additive.


Cross-functioning between the extraneuronal monoamine transporter and multidrug resistance protein 1 in the uptake of adrenaline and export of 5-(glutathion-S-yl)adrenaline in rat cardiomyocytes.
Isolated heart cells are highly susceptible to the toxicity of catecholamine oxidation products, namely, to catecholamine-glutathione adducts. Although cellular uptake and/or efflux of these products may constitute a crucial step, the knowledge about the involvement of transporters is still very scarce. This work aimed to contribute to the characterization of membrane transport mechanisms, namely, extraneuronal monoamine transporter (EMT), the multidrug resistant protein 1 (MRP1), and P-glycoprotein (P-gp) in freshly isolated cardiomyocytes from adult rats. These transporters may be accountable for uptake and/or efflux of adrenaline and an adrenaline oxidation product, 5-(glutathion-S-yl)adrenaline, in cardiomyocyte suspensions. Our results showed that 5-(glutathion-S-yl)adrenaline efflux was mediated by MRP1. Additionally, we demonstrated that the adduct formation occurs within the cardiomyocytes, since EMT inhibition reduced the intracellular adduct levels. The classical uptake2 transport in rat myocardial cells was inhibited by the typical EMT inhibitor, corticosterone, and surprisingly was also inhibited by low concentrations of another drug, a well-known P-gp inhibitor, GF120918. The P-gp activity was absent in the cells since P-gp-mediated efflux of quinidine was not blocked by GF120918. In conclusion, this work showed that freshly isolated cardiomyocytes from adult rats constitute a good model for the study of catecholamines and catecholamines metabolites membrane transport. The cardiomyocytes maintain EMT and MRP1 fully active, and these transporters contribute to the formation and efflux of 5-(glutathion-S-yl)adrenaline. In the present experimental conditions, P-gp activity is absent in the isolated cardiomyocytes.


[The role of acute phase proteins in the pathogenesis of chronic periapical granuloma].
Alpha-1-antitrypsin, alpha-2-macroglobulin, C-reactive protein, haptoglobin and complement component C 3 concentrations and oxidase activity of ceruloplasmin were studied in sera of 36 patients with chronic periapical granuloma before and after surgical treatment. Mean serum concentrations of the investigated proteins were slightly elevated at diagnosis, with the exception of haptoglobin. Alpha-1-antitrypsin and ceruloplasmin levels decreased significantly 7 days after apicectomy, the four other proteins were unchanged at this sampling time. Each investigated protein decreased significantly 3 months after apicectomy. This is the first longitudinal study of "acute-phase proteins" in chronic periapical granuloma. The results suggest that inflammatory reactions contribute to the maintenance of chronic periapical lesion.


The effects of temperature on the development, fecundity and mortality of Eretmocerus warrae: is Eretmocerus warrae better adapted to high temperatures than Encarsia formosa?
Eretmocerus warrae (Hymenoptera: Aphelinidae) is a parasitoid of the glasshouse whitefly, Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). Here, we compare its potential as a biological control agent at high temperatures to that of Encarsia formosa (Hymenoptera: Aphelinidae), a wasp which is widely sold for control of T. vaporariorum. Eretmocerus warrae attained the highest estimated developmental rate at 31.4 °C and the maximum oviposition rate at 30.5 °C. Developmental times of E. warrae at fluctuating temperatures that simulate night-day patterns were similar to those predicted based on constant temperatures. Above the optimum temperature, E. warrae tolerated higher constant temperatures than En. formosa during development and as adults. Using a ramping temperature approach, the critical thermal maximum for adult E. warrae was significantly higher than that of adult En. formosa. Eretmocerus warrae is better adapted to high temperatures than En. formosa, and could therefore be a complementary or superior biological control agent during summer months in hot regions. © 2018 Society of Chemical Industry.


Treatment of cachexia with ghrelin in patients with COPD.
Ghrelin is a novel growth hormone (GH)-releasing peptide that also induces a positive energy balance by decreasing fat utility and stimulating feeding through GH-independent mechanisms. We investigated whether ghrelin improves cachexia and functional capacity in patients with COPD. This is an open-label pilot study. Human ghrelin (2 microg/kg bid) was IV administered to seven cachectic patients with COPD for 3 weeks. Food intake, body composition, muscle strength, exercise capacity, pulmonary function, and sympathetic nerve activity were examined before and after ghrelin therapy. A single administration of ghrelin markedly increased serum GH (21-fold). Three-week treatment with ghrelin resulted in a significant increase in mean (+/- SEM) body weight (49.3 +/- 3.6 to 50.3 +/- 3.8 kg; p < 0.05). Food intake was significantly increased during ghrelin therapy. Ghrelin increased lean body mass and peripheral and respiratory muscle strength. Ghrelin significantly increased Karnofsky performance status score and the distance walked in 6 min (370 +/- 30 to 432 +/- 35 m; p < 0.05), although it did not significantly alter pulmonary function. Ghrelin attenuated the exaggerated sympathetic nerve activity, as indicated by a marked decrease in plasma norepinephrine level (889 +/- 123 to 597 +/- 116 pg/mL; p < 0.05). These preliminary results suggest that repeated administration of ghrelin improves body composition, muscle wasting, functional capacity, and sympathetic augmentation in cachectic patients with COPD.


Computational Study of the Malonic Acid Tautomerization Products in Highly Concentrated Particles.
Knowing the tautomeric form of malonic acid (MA) in concentrated particles is critical to understanding its effect on the atmosphere. Energies and vibrational modes of hydrated MA particles were calculated using density functional theory (DFT) at the B3LYP/6-31G(d,p) level and the effective fragment potential (EFP) method. Visualization of the keto and enol isomer vibrational modes enabled the assignment of keto isomer peaks in the 1710-1750 cm-1 range, and previously unidentified experimental IR peaks in the 1690-1710 cm-1 can now be attributed to the enol isomer. Comparison of calculated spectra of pure hydrated enol or keto isomers confirm recent experimental evidence, presented by Ghorai et al. ( J. Phys. Chem. A 2011 , 115 , 4373 - 4380 ) of a shift in the keto-enol tautomer equilibrium when MA exists as concentrated particles.


Dietary vitamin B12 deficiency in an adolescent white boy.
Dietary deficiency of cobalamin resulting in tissue deficiency in white individuals is unusual. However, several patients with dietary deficiency who were neither vegan nor Hindu have been described. This report describes the case of a 14 year old boy who was a white non-Hindu with a very low intake of cobalamin, which was not apparent until a detailed dietary assessment was performed. The patient responded rapidly to a combination of oral and parenteral B12. This case illustrates the fact that severe dietary vitamin B12 deficiency can occur in non-Hindu white individuals. Inadequate dietary content of B12 may not be apparent until a detailed dietary assessment is performed. This patient is likely to have had subclinical vitamin B12 deficiency for several years. Increased vitamin B12 requirements associated with the adolescent growth spurt may have provoked overt tissue deficiency.


Seroprevalence and Trends of Transfusion Transmissible Infections in Blood Donors in Andaman and Nicobar Islands- An Institutional Retrospective Study.
Transfusion Transmissible Infections (TTIs) such as Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C Virus (HCV) and syphilis pose a threat to blood safety in a developing country like India. To determine the prevalence of TTIs among healthy donors in Andaman and Nicobar Islands, India, and to further help in determination of the population subset to be focused on for enhancing blood donor pool. This retrospective cross-sectional study was conducted on all voluntary and replacement donors in a tertiary health care centre in Andaman and Nicobar Islands for a period of three years. Donor blood was screened for HIV, HBV, HCV, Syphilis and malarial parasite using rapid kits and ELISA. Out of 12,118 donors, 97.01% were males and 2.99% were females. 9409 (77.64%) were voluntary donors and 2709 (22.35%) were replacement donors. Majority of the screened donors belonged to 25 to 40 age group. Out of 12,118 donors, 265 (2.18%) were seropositive. Among them, 8 (0.066%) were HIV positive, 15 (0.124%) HCV positive, 128 (1.056%) HBsAg positive, 30 (0.247%) Syphilis positive and 84 (0.693%) were positive for malarial antigen. Yearly prevalence of seropositivity was 2.370%, 2.113% and 2.082% for three consecutive years. With high prevalence of TTIs among healthy donors, safe blood transfusion is still a challenge in developing countries. This continues to place unacceptable burden on health sector. There is a need for encouragement of voluntary blood donation, strict donor selection criteria and sensitive screening tests to minimize TTIs in Indian setting.


Structural basis for the nuclear export activity of Importin13.
Importin13 (Imp13) is a bidirectional karyopherin that can mediate both import and export of cargoes. Imp13 recognizes several import cargoes, which include the exon junction complex components Mago-Y14 and the E2 SUMO-conjugating enzyme Ubc9, and one known export cargo, the translation initiation factor 1A (eIF1A). To understand how Imp13 can perform double duty, we determined the 3.6-Å crystal structure of Imp13 in complex with RanGTP and with eIF1A. eIF1A binds at the inner surface of the Imp13 C-terminal arch adjacent and concomitantly to RanGTP illustrating how eIF1A can be exported by Imp13. Moreover, the 3.0-Å structure of Imp13 in its unbound state reveals the existence of an open conformation in the cytoplasm that explains export cargo release and completes the export branch of the Imp13 pathway. Finally, we demonstrate that Imp13 is able to bind and export eIF1A in vivo and that its function is essential.


[Application of allogenous dural membrane (brefotissue DM) in surgical treatment of retraction pockets of the tympanic membrane].
The tactics of treating patients with retraction pockets of the tympanic membrane is still debatable. When choosing surgical treatment, preference is given to the removal of the retraction pocket with simultaneous reconstruction of the posterior-upper wall of the external auditory canal (retraction area) with a cartilage or fascial flap, autologous bone, or a combination of the above tissues. Considering the well-known negative aspects of the use of all the mentioned grafts, there is a need to find new types of tissues to strengthen the retraction pocket. For example, dura mater brefotissue has good plastic properties, resistance to infection, is easy to prepare, store, and is cheaper than many allografts. Evaluation of the possibility of using dura mater brefotissue in the surgical treatment of patients with retraction pockets of the tympanic membrane. The study included 52 patients who underwent surgery to eliminate the retraction pocket. All of them were divided into 2 groups. In the first - the main (n=25) cartilage of the auricle was used to seal the relaxed part of the tympanic membrane, in the second - the control (n=27) applied tissue of the dura mater. After 1, 3, 6 and 12 months, to assess the result of the intervention, all patients underwent otomicroscopy, audiometry with the calculation of the average sound conduction index for speech frequencies. Fewer cases (4 patients out of 27) had difficulty in graft placement with the use of dura mater compared to the group where cartilage was used (9 patients out of 25). The average duration of graft placement was 8±0.5 minutes in the control group and 2±0.3 minutes in the main group. A stable morphological result was obtained in the group with the use of brefotissue in 26 patients (96%) and only in 20 patients (80%) with the use of cartilage. It is important to note that in the group with the use of brefotissue, in the early postoperative period, there was an increase in the air-bone interval, and 1 month after the operation, the average values increased by 10±0.5 dB. 12 months after the operation, the above parameters returned to preoperative. The conducted study indicates that the dura mater brefotissue, having sufficient strength, the convenience of forming a given shape and placing it in the desired position, can be successfully used in the surgical treatment of patients with retraction pockets of the tympanic membrane.


[Identification of human small supernumerary marker chromosomes and discussion of its research value].
To identify the origin of human small supernumerary marker chromosomes (sSMCs) using fluorescent in situ hybridization (FISH) combined with G-banding karyotype analysis, and to discuss their mechanisms of formation and research value. Cep-FISH and SubcenM-FISH were used to analyze sSMCs in 3 patients for whom the result of G-banding was 47,XN,+mar. The FISH result of case 1 was 47,XY,+mar.ish inv dup(22)(q11.1)(D22Z4++,D14/22Z1+, RP11-172D7-). The marker has formed exclusively by heterochromatin. A boy was delivered later with no apparent clinical abnormalities. The FISH result of case 2 was 47,XX,+mar.ish r(10)(p11.2q11.2) (cep10+, RP11-232C13+, RP11-178A10+)[25]/46,XX[10]. The marker has formed by heterochromatin and nearby centromere. A girl was delivered later with no clinical abnormalities. The FISH result of case 3 was 47,XY,+mar.ish inv dup(22)(q11.1)(D22Z4+,D14/22Z1+). The marker has also formed exclusively by euchromatin. Fetal abnormalities were detected by type B ultrasonography, but were not necessarily related with the marker. The diversity of sSMCs has posed a great challenge for prenatal diagnosis. Identification of sSMCs will require combined karyotype analysis and FISH or other molecular techniques such as microarray based comparative genomic hybridization or sequencing. For its specific structure, the sSMCs may also provide a valuable tool for gene mapping, heterochromatin research and gene therapy.


Coronary atherosclerosis: where are we now?
An attempt is made to present and summarize recent results in atherosclerosis research which may aid to a better understanding of atherogenesis, progression of atherosclerotic lesions and occurrence of myocardial ischemia. Based on selected data from the available literature and the authors' experience, the review focuses the attention on: the atherogenic role of hemodynamic stresses; the onset and fate of early coronary atherosclerotic lesions; the development of lesions of possible clinical significance; the concept of "critical stenosis"; the view that atherosclerosis is a hyperplastic and/or neoplastic disease.


Optimization of expression, purification and secretion of functional recombinant human growth hormone in Escherichia coli using modified staphylococcal protein a signal peptide.
Human Growth Hormone (hGH) is a glycoprotein released from the pituitary gland. Due to the wide range of effects in humans, any disruption in hGH secretion could have serious consequences. This highlights the clinical importance of hGH production in the treatment of different diseases associated with a deficiency of this hormone. The production of recombinant mature hormone in suitable hosts and secretion of this therapeutic protein into the extracellular space can be considered as one of the best cost-effective approaches not only to obtain the active form of the protein but also endotoxin-free preparation. Since the natural growth hormone signal peptide is of eukaryotic origin and is not detectable by any of the Escherichia coli secretory systems, including Sec and Tat, and is therefore unable to secrete hGH in the prokaryotic systems, designing a new and efficient signal peptide is essential to direct hGh to the extracellular space. In this study, using a combination of the bioinformatics design and molecular genetics, the protein A signal peptide from Staphylococcus aureus was modified, redesigned and then fused to the mature hGH coding region. The recombinant hGH was then expressed in E. coli and successfully secreted to the medium through the Sec pathway. Secretion of the hGH into the medium was verified using SDS-PAGE and western blot analysis. Recombinant hGH was then expressed in E. coli and successfully secreted into cell culture medium via the Sec pathway. The secretion of hGH into the extracellular medium was confirmed by SDS-PAGE and Western blot analysis. Furthermore, the addition of glycine was shown to improve hGH secretion onto the culture medium. Equations for determining the optimal conditions were also determined. Functional hGH analysis using an ELISA-based method confirmed that the ratio of the active form of secreted hGH to the inactive form in the periplasm is higher than this ratio in the cytoplasm. Since the native signal protein peptide of S. aureus protein A was not able to deliver hGH to the extracellular space, it was modified using bioinformatics tools and fused to the n-terminal region of hGh to show that the redesigned signal peptide was functional.


Velocity Gradient Power Functional for Brownian Dynamics.
We present an explicit and simple approximation for the superadiabatic excess (over ideal gas) free power functional, admitting the study of the nonequilibrium dynamics of overdamped Brownian many-body systems. The functional depends on the local velocity gradient and is systematically obtained from treating the microscopic stress distribution as a conjugate field. The resulting superadiabatic forces are beyond dynamical density functional theory and are of a viscous nature. Their high accuracy is demonstrated by comparison to simulation results.


Gender Differences in Relation to Body Composition, Insulin Resistance, and Islet Beta Cell Function in Newly Diagnosed Diabetic or Pre-Diabetic Patients.
To assess the correlation between body components with insulin resistance (IR) and islet beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM) or pre-diabetes mellitus (pre-DM) and to explore whether this correlation differs in males and females. 111 newly diagnosed diabetic or pre-diabetic patients were recruited in this cross-sectional study. 75g oral glucose tolerance test was used to determine the diagnosis of DM or pre-DM. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30) was calculated to assess IR and islet beta cell function, respectively. Whole-body and regional lean mass (LM) and fat mass (FM) were obtained by dual-energy X-ray absorptiometry (DEXA). Partial correlation and multiple linear regression analyses were used to determine the associations between body composition, IR, and islet beta cell function. More body fat and appendicular fat was observed in female patients than in male, though with similar BMI. Legs fat % was negatively correlated with HOMA-IR, whereas legs lean % was positively associated with HOMA-IR in females (r = -0.673, p = 0.017; r =0.664, p = 0.018, respectively). The regression analysis showed that legs LM was positively correlated with HOMA-IR in females. However, in male patients, android FM was positively correlated with HOMA-IR (r = 0.462, p = 0.007), and trunk LM was negatively associated with DI30 (r = -0.458, p = 0.007). Nevertheless, no significant correlation was observed between body composition and islet beta cell function in female patients. Android FM was positively correlated with IR only in male patients but not in females. Besides, relative legs fat and LM were independently associated with IR in female patients but not in males. Further studies are needed to explore the underlying mechanism.


Genome-wide DNA profiling better defines the prognosis of chronic lymphocytic leukaemia.
The integration of molecular and clinical information to tailor treatments remains an important research challenge in chronic lymphocytic leukaemia (CLL). This study aimed to identify genomic lesions associated with a poor outcome and a higher risk of histological transformation. A mono-institutional cohort of 147 cases was used as the test series, and a multi-institutional cohort of 176 cases as a validation series. Genomic profiles were obtained using Affymetrix SNP 6.0. The impact of the recurrent minimal common regions (MCRs) on overall survival was evaluated by univariate analysis followed by multiple-test correction. The independent prognostic significance was assessed by multivariate analysis. Eight MCRs showed a prognostic impact: gains at 2p25.3-p22.3 (MYCN), 2p22.3, 2p16.2-p14 (REL), 8q23.3-q24.3 (MYC), losses at 8p23.1-p21.2, 8p21.2, and of the TP53 locus. Gains at 2p and 8q and TP53 inactivation maintained prognostic significance in multivariate analysis and a hierarchical model confirmed their relevance. Gains at 2p also determined a higher risk of Richter syndrome transformation. The prediction of outcome for CLL patients might be improved by evaluating the presence of gains at 2p and 8q as novel genomic regions besides those included in the 'standard' fluorescence in situ hybridization panel.


Effects of selective β1-adrenoceptor blockade on cardiovascular and renal function and circulating cytokines in ovine hyperdynamic sepsis.
Activation of the sympathetic nervous system has beneficial cardiovascular effects in sepsis, but there is also evidence that sympatholytics have beneficial actions in sepsis. We therefore determined the effect of selective β1-adrenoceptor blockade on cardiac and renal function and cytokine release in ovine hyperdynamic sepsis. Hyperdynamic sepsis was induced by infusion of live E. coli for 24 hours in nine conscious sheep instrumented with flow probes on the pulmonary and left renal artery. Cardiovascular and renal function and levels of plasma cytokines were determined in a control group and during selective β1-adrenoceptor blockade with atenolol (10 mg intravenous bolus then 0.125 mg/kg/h) from 8 to 24 hours of sepsis. Hyperdynamic sepsis was characterized by hypotension with increases in cardiac output (CO), heart rate (HR) and renal blood flow (RBF), and acute kidney injury. Atenolol caused sustained reductions in HR (P < 0.001) and CO (P < 0.001). Despite the lower CO the sepsis-induced fall in mean arterial pressure (MAP) was similar in both groups. The sepsis-induced increase in RBF, decrease in renal function and increase in arterial lactate were unaffected by atenolol. Sepsis increased plasma levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10. Atenolol caused a further increase in IL-10, but did not affect levels of TNF-α or IL-6. In sepsis, selective β1-adrenoceptor blockade reduced CO, but not MAP. During sepsis, atenolol did not alter the development of acute kidney injury or the levels of pro-inflammatory cytokines, but enhanced the release of IL-10. Atenolol appears safe in sepsis, has no deleterious cardiovascular or renal effects, and has an anti-inflammatory effect.


Developing a service improvement initiative for people with learning disabilities in hospice settings.
People with learning disabilities are often marginalised in healthcare, including in hospice settings, and as a result may not receive effective end of life care. Research in hospice settings has identified that many staff lack confidence, skills and knowledge in caring for people with learning disabilities, which can have a negative effect on the care these individuals receive. To address these issues, the author has proposed a service improvement initiative, which she developed as part of her learning disability nursing degree programme. This proposed initiative aimed to enhance end of life care for people with learning disabilities through the implementation of a community learning disability link nurse in the hospice setting.


Immunopathology of leishmaniasis: an update.
Leishmaniasis represents a severe, increasing, public health problem. The perspective of its control is highly dependent on research progress, on therapeutic manipulations of the immune system, and on vaccine development. There is a correlation between the clinical outcome of Leishmania infection and the cytokine response profile. While a protective immune response against Leishmania has been clearly identified to be related to the influence of a type-1 response and IFN-gamma production, the precise role of T helper (TH) 2 cytokines in non-healing infections requires further exploration. IL-4 and IL-13 (TH2 cytokines) can promote disease progression in cutaneous leishmaniasis, whereas IL-4 would appear to enhance protective type-1 responses in visceral leishmaniasis. Thus, the TH1/TH2 paradigm of resistance/susceptibility to intracellular parasites is probably an oversimplification of a more complicated network of regulatory/counter regulatory interactions. Moreover, the presence of antigen specific regulatory T cell subsets may provide an environment that contributes to the balance between TH1 and TH2 cells. Finally, the involvement of CD8 positive T cells has been described, but the modality of their function in this kind of infection has not been so far elucidated.


Cytotoxic mechanisms of murine lymphokine-activated killer cells: functional and biochemical characterization of homogeneous populations of spleen LAK cells.
A highly purified population of murine lymphokine-activated killer (LAK) cells was obtained by selecting plastic-adherent splenocytes after incubation in high doses of recombinant IL-2. The population obtained was shown to be more than 95% positive for the cell marker asialo-GM1, and negative for both Lyt-1 (CD5) and Lyt-2 (CD8). The cells presented typical large granular lymphocyte morphology, and killed NK-susceptible target cells in an exclusively calcium-dependent fashion. A target cell DNA fragmentation activity of LAK cells could be detected even before target cell death. The presence of Hanukkah Factor/granzyme A/serine esterase 1, CTLA-1/granzyme B/serine esterase 2, and pore-forming protein (PFP/perforin) in these LAK cells was demonstrated by Northern blot analysis, suggesting that these markers are not exclusively associated with cytotoxic T lymphocytes. On immunoblots, antibodies specific for a lymphocyte PFP/perforin reacted with a 70-kDa protein of LAK cells. PFP/perforin was localized by immunofluorescence to the cell granules. A 50-kDa protein antigenically related to the macrophage cytokine tumor necrosis factor (TNF) was detected by immunoblotting and localized by immunofluorescence to both the cell granules and the cytosol. No RNA for TNF, however, could be detected using TNF-specific probes, suggesting that LAK cells may contain a cytotoxic factor which is related to, but distinct from, TNF. The work presented here demonstrates that cytotoxic mediators identified in cell lines are also present in primary cell cultures.


Interactive effects of photon fluence rates and drought on CAM-cycling in Delosperma tradescantioides (Mesembryanthemaceae).
The ability of photosynthesis and CAM to acclimate to low (220 µmol m-2 s-1 ; LL) and relatively high (550 µmol m-2 s-1 ; HL) photosynthetic photon flux densities (PPFD) was investigated in the CAM-cycling species Delosperma tradescantioides by means of CO2 gas exchange and chlorophyll fluorescence analysis. Furthermore, the influence of short-term drought on malic acid accumulation and the activity of photosystem II (PSII) was studied to assess the possible interactions between drought and the prevailing PPFD in this species. HL plants showed features of sun versus shade acclimation relative to LL plants. Nocturnal malic acid accumulation (Δ-malate) and leaf water content also tended to be higher in HL plants. Irrespective of the PPFD during growth, the weak Δ-malate doubled within 3 days of drought. Despite largely restricted CO2 uptake, photosynthetic activity as estimated from fluorescence analysis declined only ca 5%. After 7 days of drought, when plants showed CAM-idling and Δ-malate had decreased again, potential carbon assimilation was still ca 84% of that in well-watered plants and remained relatively constant throughout the day. Decarboxylation of malic acid accounted for ca 23% of potential assimilation assuming total oxidation of a maximum portion of this organic acid. Drought did not affect predawn maximum photochemical efficiency (Fv /Fm ). Nonphotochemical quenching (qN) increased (24%) in response to desiccation and resulted in a more or less constant reduction state of PSII. This increase in qN resulted mainly from the change in its fast-relaxing component (qNF), while the slow component (qNS) was significant only at or above saturating PPFD in both HL and LL plants. The photon response characteristics of PSII, which differed between LL and HL plants, were unaffected by short-term drought. Photon harvesting and photon use were always adjusted to guarantee a low reduction state of PSII. Results suggest that in both LL and HL plants CAM-cycling may help to stabilize photosynthesis but to a large extent by other means than simply providing internally derived CO2 .


Ionic Specificity in Rapid Coagulation of Silica Nanoparticles.
The Smoluchowski theory has been widely accepted as the basic theory to estimate the rapid coagulation rate of colloidal particles in electrolyte solutions. However, because the size and specificity of molecules and ions are not taken into account, the theory is applicable only if the particle size is large enough to neglect the effects caused by the structured layers composed of water molecules, ions, and hydrated ions adsorbed on the colloidal surface. In the present study, the rapid coagulation rates of silica nanoparticles in concentrated chloride and potassium solutions were measured by using a low-angle light-scattering apparatus, and the dependence of the experimental value of rapid coagulation rate, KER, on the particle diameter, Dp, and also on the Gibbs free energy of hydration of ions, ΔGhyd, was investigated extensively. The following were found. (1) When the particle size was small enough, the value of KER reduced exponentially not only with the decreasing particle size but also with the increasing value of (-ΔGhyd) of cations (counterions) in the case of chloride solutions and with that of anions (coions) in the case of potassium solutions. (2) Silica nanoparticles of Dp ≲ 70 nm in 1 M KNO3 and KSCN solutions did not coagulate at all, although they coagulated at Dp ≳ 100 nm as in the other potassium solutions. These unexpected phenomena were explained by the proposed mechanisms.


Immobilization of Arthrobacter simplex in a thermally reversible hydrogel: effect of temperature cycling on steroid conversion.
Arthrobacter simplex cells, which convert the steroid hydrocortisone to prednisolone, have been entrapped in a thermally reversible hydrogel. Such hydrogels exhibit a lower critical solution temperature (LCST) wherein the gel shrinks and deswells when it is warmed through its LCST, and then reversibly expands and reswells when it is cooled below the LCST. The immobilized cell-hydrogel system has been thermally cycled between two temperatures, each below the LCST. The upper temperature was selected to be just below the LCST, where the gel deswells but does not collapse, as it does at the LCST. The thermal cycling acts like a "hydraulic pump" which enhances mass transfer of the substrate (hydrocortisone) in and the product (prednisolone) out of the gel, thereby increasing steroid conversion dramatically relative to isothermal operation at either the upper or lower temperature. The increased conversion can also be due in part to reduced product inhibition. Mass transfer resistance and product inhibition are among the most serious problems in immobilized biocatalyst technology and thermal cycling of LCST hydrogels is both a novel and useful approach to minimizing these problems.


Phenol Abatement by Titanium Dioxide Photocatalysts: Effect of The Graphene Oxide Loading.
Hetero-photocatalytic graphene-TiO2 materials have, in the literature, been found to possess better photocatalytic activity for environmental applications compared to pure TiO2. These types of materials can be prepared in different ways; however, their photocatalytic performance and quality are not easily controlled and reproduced. Therefore, we synthetized graphene oxide-TiO2 nanoparticles by sol-gel reaction from TiCl4, as precursor, with two different methods of synthesis and with a graphene oxide (GO) loading ranging from 0 to 1.0. This approach led to a good adhesion of GO to TiO2 through the Ti-O-C bonding, which could enhance the photocatalytic performances of the materials. Overall, 0.05 wt % GO loading gave the highest rate in the photodegradation of phenol under visible light, while higher GO loadings had a negative impact on the photocatalytic performances of the composites. The 0.05 wt % GO-TiO2 composite material was confirmed to be a promising photocatalyst for water pollutant abatement. The designed synthetic approach could easily be implemented in large-scale production of the GO-TiO2 coupling materials.


Computed tomography findings of spontaneous porto-pulmonary shunts in 3 patients with portal hypertension.
Spontaneous portopulmonary shunts in the setting of cirrhosis have been associated with the embolization of gelfoam during the treatment of esophageal varices, resulting in strokes. Currently there is minimal data describing the prevalence of spontaneous portopulmonary shunts. Our aim is to demonstrate computed tomography (CT) imaging findings of spontaneous portopulmonary venous anastomoses in patients with underlying portal hypertension. Clinical cases with accompanying CT images are presented and described. A review of the literature is discussed. CT is a useful method for identifying shunting, both spontaneous and surgical, of the portal circulation secondary to hypertension. A less known type of anastomosis involves the pulmonary circulation, specifically the pulmonary veins and left atrium, that can also be recognized with CT.


[Study and analysis on the quantitive detection of EBV-DNA in adenoidal hypertrophic and tonsillitis tissues of children].
To investigate the epidemiology of EBV in adenoidal hypertrophy and chronic tonsillitis and discuss the affection of EBV on the nosogenesis of adenoidal hypertrophy and tonsillitis of children. Fifty-two children with chronic tonsillitis and/or adenoidal hypertrophy had the operations of the tonsillectomy and/or the adenoidectomy. These tissues resected and plasma of all cases were detected to find EBV-DNA by RQ PCR. The infection rate of EBV in the tissues of adenoidal hypertrophy and tonsillitis of children was 51.9%. The boys' infection rate of EBV was 50.0%, and the girls' infection rate of EBV was 55.6%, which had not significantly different. The EBV infection rate in the tissues of tonsillitis was 40.4%, The EBV infection rate in the tissues of adenoidal hypertrophy was 48.9%, which had not significant difference. The school age group (7- to 14-years-old) presented higher infection rate of EBV in the tissues of adenoid and tonsil (65.5%) than the pre-school children group (2- to 6-years-old) (34.8%). Comparing the copies numbers of EBV-DNA in the different degrees of adenoidal hypertrophy, we found that the copies numbers of EBV-DNA in the severe hypertrophy group were higher than the midrange and slight hypertrophy groups (P<0.05). Meanwhile we detected EBV-DNA in these childrens' blood plasma by RQ-PCR. No blood plasma was detected EBV-DNA copies higher than normal (< 1 x 10(3) copies/ml). The tissues of adenoidal hypertrophy and tonsillitis had same sensitivity to EBV. There was not significant difference between the infection rates of the boys and girls with adenoidal hypertrophy and/or tonsillitis. With these children growing up and the course of diseases prolonging, the infection rate of EBV increased correspondingly. There was a certain correlation between the hypertrophy of adenoid and EBV. There were no EBV-DNA fragments in blood plasma of the children with adenoidal hypertrophy and/or tonsillitis. So there were essential different between benign hyperplasia and nasopharyngeal carcinoma.


Enhancing resident training in abortion and contraception through hospital-community partnership.
The study was undertaken to assess the efficacy of a hospital-community rotation in abortion and contraception. The program was developed and implemented by the Planned Parenthood League of Massachusetts (PPLM) and the Department of Obstetrics and Gynecology at Baystate Medical Center in November 2000. Abortion and contraceptive training is integrated into postgraduate year 3 and includes didactic presentations and 10 mandatory clinical sessions in first trimester abortion care. Five residents complete the program annually. Before rotation, residents report their competence in first-trimester abortion procedure as 2 on a scale of 1 to 5 (1=not at all comfortable, 5=very comfortable). After rotation, the reported competency rating is 4.5 on the same scale. Residents, trainers, and staff report high satisfaction with the program. A collaborative hospital-community rotation in abortion and contraception increases residents' clinical competence in these areas and is highly acceptable to residents, faculty, and staff.


Fourier-transform spectroscopy of (4)1Σ+ → A1Σ+ - b3Π, A1Σ+ - b3Π → X1Σ+, and (1)3Δ1→b3Π(0±) transitions in KCs and deperturbation treatment of A1Σ+ and b3Π states.
High resolution Fourier-transform spectroscopy data of term values in the spin-orbit (SO) coupled first excited A(1)Σ(+) and b(3)Π states in KCs were obtained from (4)(1)Σ(+) → A(1)Σ(+) - b(3)Π, A(1)Σ(+) - b(3)Π → X(1)Σ(+), and (1)(3)Δ1→b(3)Π(0(±)) spectra of laser-induced fluorescence (LIF). About 3000 new rovibronic term values of the A(1)Σ(+) and b(3)Π(Ω) states were obtained with an uncertainty about 0.01 cm(-1) and added to the previously obtained 3439 term values in Kruzins et al. [Phys. Rev. A 81, 042509 (2010)] and 30 term values of the b(3)Π(0(+)) state levels below the A(1)Σ(+) state in Tamanis et al. [Phys. Rev. A 82, 032506 (2010)]. The data field was extended considerably, going down to vibrational level v(b) = 0 and up in energy to 13,814 cm(-1), as compared to previously achieved v(b) = 14 and E = 13,250 cm(-1). Overall 6431 e-symmetry term values of (39)K(133)Cs were included in 4 × 4 coupled-channel deperturbation analysis. The analytical Morse-Long-Range (MLR) function yielded empirical diabatic potentials for the A(1)Σ(+) and b(3)Π(0(+)) states while the morphing of the SO ab initio points [J. T. Kim et al., J. Mol. Spectrosc. 256, 57 (2009)] provided the empirical diagonal and off-diagonal SO functions. Overall 98.5% of the fitted term values were reproduced with a rms (root mean square) uncertainty of 0.004 cm(-1). The reliability of the model is proved by a good agreement of predicted and measured term values of the (41)K(133)Cs isotopologue, as well as of measured and calculated intensities of (4)(1)Σ(+) → A(1)Σ(+) - b(3)Π LIF progressions. Direct-potential-fit of low-lying v(b) levels of the b(3)Π(0(-)) component yielded the MLR potential which represents the 204 f-symmetry experimental term values with a rms uncertainty of 0.002 cm(-1). The Ω-doubling of the b(3)Π0 sub-state demonstrates a pronounced vb-dependent increase.


Oxidative stress and lipids in diabetes: a role in endothelium vasodilator dysfunction?
Endothelial dysfunction is a key feature of diabetes mellitus and is thought to be the major cause of vascular complications associated with the disease. The vascular endothelium demonstrates impaired synthesis of vasodilators and increased release of procoagulants and vasoconstrictors, defects which theoretically could explain the increased incidence of atherosclerosis and hypertension found within this patient group. The pathways mediating endothelial cell layer dysfunction are unknown, although many candidates have been proposed. This review concentrates on the hypothesis that increased oxidative stress combined with abnormal plasma lipid composition leads to reduced synthesis of endothelial vasodilators and hence endothelial dysfunction. Free radical generation is undoubtedly raised in diabetes but the evidence for decreased antioxidant status is debatable. The role of antioxidant and lipid-lowering therapy is considered, but few studies have directly investigated the effect of treatment on vascular function. Concern arises from individual studies of vitamin E in diabetic animals which have proved deleterious. Current literature implies that a combination therapy of vitamin E and vitamin C may be beneficial, but this needs to be investigated further in both animal and human diabetes.


Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals.
Inhibitor of histone deacetylases (HDACIs) have great therapeutic value for triple negative breast cancer (TNBC) patients. Interestingly, our present study reveals that suberoyl anilide hydroxamic acid (SAHA), one of the most advanced pan-HDAC inhibitor, can obviously promote in vitro motility of MDA-MB-231 and BT-549 cells via induction of epithelial-mesenchymal transition (EMT). SAHA treatment significantly down-regulates the expression of epithelial markers E-cadherin (E-Cad) while up-regulates the mesenchymal markers N-cadherin (N-Cad), vimentin (Vim) and fibronectin (FN). However, SAHA has no effect on the expression and nuclear translocation of EMT related transcription factors including Snail, Slug, Twist and ZEB. While SAHA treatment down-regulates the protein and mRNA expression of FOXA1 and then decreases its nuclear translocation. Over-expression of FOXA1 markedly attenuates SAHA induced EMT of TNBC cells. Further, silence of HDAC8, while not HDAC6, alleviates the down-regulation of FOXA1 and up-regulation of N-Cad and Vim in MDA-MB-231 cells treated with SAHA. Collectively, our present study reveals that SAHA can promote EMT of TNBC cells via HDAC8/FOXA1 signals, which suggests that more attention should be paid when SAHA is used as anti-cancer agent for cancer treatment.


Reality confusion in spontaneous confabulation.
A woman produced spontaneous confabulations after rupture of an anterior communicating artery aneurysm. She confused currently irrelevant with currently relevant information in implicit memory; confabulations about people concerned only new acquaintances; false reality could be induced by an intensive 5-minute discussion; and in a recognition task, she confused false repetitions in another modality with real item repetitions. The findings support the theory that the defect causing spontaneous confabulation precedes conscious memory processing.


Glucose-regulated protein 78 and platelet deposition: effect of rosuvastatin.
To investigate the effect of rosuvastatin on platelet deposition under controlled shear rate conditions and to identify new platelet proteins involved in the interaction with the activating substrate. Platelet-vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulating blood cells and proteins. Blood was perfused over type I collagen at different wall shear rates, and platelet deposition was measured by confocal microscopy. Perfused effluent blood was collected, platelets were sequentially extracted based on differential protein solubility, and proteins were separated by 2D gel electrophoresis. Blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase significantly reduced platelet deposition and modulated the expression pattern of 18 proteins in the platelet subproteome. Among them, an increase in platelet surface 78-kDa glucose-regulated protein (GRP78), a stress-inducible multifunctional endoplasmic reticulum protein, was clearly apparent. Immunoprecipitation of platelet GRP78 revealed its interaction with tissue factor. Moreover, blockade of surface GRP78 resulted in a substantial increase in platelet deposition and tissue factor procoagulant activity and in a decrease in clotting time. These findings demonstrate that blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase reduces platelet deposition and inhibits GRP78 translocation from the platelet surface after shear and collagen activation. For the first time to our knowledge, this study reports on the presence and functional role of GRP78 in platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone.


A pilot study to investigate effects of inulin on Caco-2 cells through in vitro metabolic fingerprinting.
Metabolic fingerprints are novel measurement tools to evaluate the biochemical status of a living organism by using 1H NMR and multivariate data analysis (MVDA). In this way, a quick evaluation of changes in health or diseased state can be made, reflected in alterations of metabolic patterns. Normally, metabolic fingerprinting is based on in vivo studies. These studies often represent a labor-intensive and expensive manner of investigation. In vitro studies are not hampered by these disadvantages, thus constituting an interesting alternative. In this research, results are presented of a pilot experiment in which metabolic fingerprinting was combined with an in vitro model. For this purpose, differentiated Caco-2 cells were exposed to inulin and its fermentative metabolites, both dissolved in culture medium. Cells were incubated for 0 or 48 h. Cell fractions were analyzed by NMR, then subsequently with MVDA. Differences in treatment provided detectable variations in the time of metabolic patterns of cell contents. Results indicated that glucose metabolism linked to glutamate was of major importance in the effects of inulin and its metabolites on Caco-2 cells under the conditions of our study. Metabolic fingerprinting in combination with an in vitro model appears to be a feasible technique with which to visualize metabolic patterns of cell contents and provides an efficient place for the generation of hypotheses about the metabolic pathways involved. In vitro metabolic fingerprinting may be of great benefit in the future for a better understanding of the relationship between nutrition and health.


Larval dispersal in three coral reef decapod species: Influence of larval duration on the metapopulation structure.
Most coral-associated decapod species have non-migratory adult populations and depend on their planktonic larvae for dispersal. This study examined the metapopulation structure of three decapod species with different pelagic larval duration (PLD) from twelve coral reef complexes of the Gulf of Mexico. The dispersion of larvae was analyzed through the use of a realistic numerical simulation of the Gulf of Mexico with the Hybrid Coordinate Ocean Model. To study the transport and dispersion of particles in near-surface waters, a particle-tracking subroutine was run using as input the currents from the model. The simulation consisted of the launch of 100 passive particles (virtual larvae) every 24 hours from each reef throughout five years, and tracked for as long as 210 days. Results indicated that species with a short PLD, Mithraculus sculptus (PLD 8‒13 days), had a weak connection among the reefs, but higher self-recruitment, especially on the narrow western shelf. The species with a longer PLD, Dromia erythropus (28‒30 days), had a stronger connection among neighboring reefs (< 300 km). Finally, the species with an even longer PLD, Stenopus hispidus (123‒210 days), had a wider potential distribution than the other species. Circulation on synoptic, seasonal and interannual scales had differential effects on the larval dispersal of each species. The metapopulation structure of M. sculptus and D. erythropus seemed to combine features of the non-equilibrium and the patchy models, whereas that of S. hispidus presumably fit to a patchy model. These findings support previous observations that indicate that species with longer PLD tend to occupy larger areas than species with short PLD, although recruitment of juveniles to the adult populations will also depend on other factors, such as the availability of suitable habitats and the ability to colonize them.


Differential localisation of the metabotropic glutamate receptor mGluR1a and the ionotropic glutamate receptor GluR2/3 in neurons of the human cerebral cortex.
Specimens of human cerebral cortex were obtained during neurosurgical operations and studied by immunocytochemistry and electron microscopy, using antibodies to the metabotropic glutamate receptor subunit mGluR1a and the ionotropic glutamate receptor GluR2/3. A small number of non-pyramidal neuronal cell bodies were labelled for mGluR1a. Double immunolabelling with mGluR1a and GluR2/3 showed that most pyramidal cell bodies were labelled for GluR2/3 but not for mGluR1a. Despite the non-colocalisation of these two receptor subtypes in cell bodies, however, many dendrites and dendritic spines were double-labelled for mGluR1a and GluR2/3 at electron microscopy. As there is evidence that most neurons positive for GluR2/3 are pyramidal cells, this suggests that mGluR1a is present in dendrites of pyramidal neurons, despite absent or low levels of immunoreactivity in their cell bodies.


Dissemination, use, and impact of a community-based, conversational advance care planning intervention: ripple effects of the Swedish DöBra cards.
Despite increasing interest in community-based advance care planning interventions, few studies investigate the societal impact of such initiatives. The DöBra cards, a Swedish adaptation of the GoWish cards, were first used for advance care planning conversations in a participatory action research project and later, due to popular demand, made available for purchase by the general public. We explore how the DöBra cards were disseminated and used publicly, to understand their impact in the community. We used Ripple Effects Mapping to follow three dissemination ripples, based on interviews with 20 participants, analyzed with directed content analysis. Key factors influencing dissemination of the DöBra cards included 'champions' with a mandate within their context or organization, policy documents including use of the cards, media coverage, and presentations of the cards in various settings. The DöBra cards were adapted for use individually and in groups in different private, professional, and organizational settings. Perceived benefits of the cards included acting as an icebreaker in initiating end-of-life conversations and having preformulated statements to reflect upon. Other positive experiences included discussions on different interpretations of card statements, thus opening new perspectives regarding end-of-life. The DöBra cards functioned both as means to raise end-of-life issues in different contexts, and as an end in themselves, for example, by facilitating advance care planning conversations for those with serious disease. Impact also included personal development and strengthening of private and professional relationships, with potential to affect end-of-life care. The broad dissemination of the DöBra cards influenced capacity-building in dealing with end-of-life issues in communities, as the topic of dying and death was brought to agendas in new contexts.


Inhibited hypothalamic-pituitary-thyroid axis in type I pseudohypoparathyroidism.
To assess the hypothalamic-pituitary-thyroid axis in two patients with the diagnosis of type I pseudohypoparathyroidism established previously by characteristic clinical features and laboratory findings, including low serum Ca++, high parathyroid hormone concentration, and subnormal urinary cyclic adenosine monophosphate (cAMP) responses to exogenous administration of parathyroid hormone. We determined serum thyroxine, triiodothyronine (T(3)), T(3) resin uptake, and 24-hour thyroidal uptake of 123 I before and after subcutaneous administration of thyroid-stimulating hormone (TSH), 10 U daily for 3 days. Serum TSH levels were determined before and again at 15, 30, 45, and 60 minutes after intravenous administration of thyrotropin-releasing hormone (TRH) (400 microg) after an overnight fast. Values noted in the two patients with type I pseudohypoparathyroidism were compared with those obtained in 10 normal volunteer control subjects. Serum thyroxine (T(4)), triiodothyronine (T(3)), T(3) resin uptake, and 24-hour 123 I uptake values for both patients with type I pseudohypoparathyroidism were within the normal ranges (5.5 to 11.5 microg/dL for T(4), 90 to 190 ng/dL for T(3), 35 to 45% for T(3) resin uptake, and 10 to 35% for 24-hour 123I uptake). Their responses to administration of TSH, however, were all significantly lower in comparison with the mean values for the 10 healthy control subjects. Basal TSH was higher in both patients with type I pseudohypoparathyroidism than in normal subjects, but TSH responses after administration of TRH, although not significantly different from normal, were blunted in relationship to the basal concentrations, as expressed as a percentage increase in TSH as well as a cumulative TSH response. The responses of pituitary thyrotrophs to TRH and the thyroid gland to TSH were both considerably inhibited in the patients with type I pseudohypoparathyroidism in comparison with normal control subjects. This finding may be yet another evidence of the lack of adequate generation of cAMP, an important second messenger needed for normal functioning of most polypeptide hormones, including TRH and TSH, in this syndrome.


Cannabidiol effects on cognition in individuals with cocaine use disorder: Exploratory results from a randomized controlled trial.
Cocaine use disorder (CUD) is associated with various cognitive deficits that impede patients' functionality, prognosis and therapeutic outcomes. New pharmacological treatments for CUD that could improve cognition are needed. To explore whether cannabidiol (CBD) is superior to placebo to improve cognitive functioning in individuals with CUD. We conducted an exploratory analysis of a single site, randomized, double-blind, placebo-controlled trial evaluating CBD's efficacy in reducing craving, cocaine use and relapse in individuals with CUD. Seventy-eight individuals diagnosed with CUD were randomized to receive either CBD (800 mg) or placebo for 92 days. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess inhibition (Stop Signal Task; SST), risky decision making (Cambridge Gambling Task; CGT) and visual memory (Pattern Recognition Memory; PRM). This assessment was made on day 1, day 7 and at week 6. We controlled for sex, severity of dependence and baseline cognitive scores in our generalized estimating equation models. Both groups performed similarly on the PRM (correct answers: p = 0.080), SST (stop signal reaction time: p = 0.644) and CGT (quality of decision making: p = 0.994; deliberation time: p = 0.507; delay aversion: p = 0.968; risk taking: p = 0.914) tests. We found no evidence for 800 mg of CBD to be more efficacious than placebo for improving cognitive outcomes. Clinical trials evaluating pharmacological treatments for CUD should continue to be a research priority.


Zn(II) biosorption properties of Botrytis cinerea biomass.
The study was aimed of determining the Zn(II) sorption performance of Botrytis cinerea (B. cinerea) biomass as a new biosorbent. Heat inactivated biomass was used in the determination of optimum conditions. The rate and extent of accumulation were effected by pH, contact time and initial zinc ion concentrations. The uptake capacity of B. cinerea was increased by chemical and physical pretreatment of the cells when compared with the native biomass. The maximum removal of Zn(II) at pH 5.0-6.0 was found to be 12.98+/-0.9623 mg g-1 at initial Zn(II) ion concentration of 100 mg l-1 by heat inactivated biomass. Freundlich and Langmuir isotherm models were used to evaluate the data and regression constants were derived. The biosorbent was regenerated using 10 mM HCl solution, with up to 98% recovery and reused five times in biosorption-desorption cycles successively. Competitive biosorption experiments were performed with zinc in the presence of copper, cadmium and nickel ions simultaneously. The nature of the possible cell-metal ions interactions was also evaluated by chemical and instrumental analysis including infrared spectroscopy, scanning electron microscopy and X-ray energy dispersion analysis.


Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.
Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ)-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1β, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis. The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD.


Mucosal-associated Invariant Cells are Deficient in Systemic Sclerosis.
Systemic sclerosis (SSc) is an autoimmune disease, characterized by fibrosis of the skin and other organs, vascular impairment and deficient immune responses. Mucosal-associated invariant T cells (MAIT) have been involved in various inflammatory and autoimmune diseases. The aims of this study were to determine the frequencies of MAIT cells in the blood of patients with systemic sclerosis (SSc) and to compare their distribution in different types of SSc. Blood samples from patients with SSc and healthy controls were examined by flow cytometer to analyse the frequencies of MAIT and γδ T cells. We demonstrate that in SSc the frequencies and absolute numbers of MAIT and γδ T cells are significantly reduced in comparison with healthy controls. MAIT and γδ T cells did not correlate with C-reactive protein, BNP, pulmonary involvement or median skin fibrosis scale, steroid amount or disease duration. In addition, MAIT and γδ T cells decrease did not stratify with gender, interstitial lung disease or active digital ulcers. Functional studies are necessary to determine the signification of MAIT cells decrease in systemic sclerosis.


Application of headspace and direct immersion solid-phase microextraction in the analysis of organothiophosphates related to the Chemical Weapons Convention from water and complex matrices.
The successful application of headspace (HS) and direct immersion (DI) solid phase microextraction (SPME) for the unambiguous identification and characterization of a series of toxic thiophosphate esters, such as Amiton (I), from aqueous phases and complex matrices (e.g. grass and foliage) has been demonstrated. A Thermo Scientific gas chromatograph (GC) - tandem mass spectrometer (MS/MS) system with a TriPlus RSH® autosampler and a SPME tool was used to investigate the effect of different parameters that influence the extraction efficiency: e.g. pH of the sample matrix and extraction temperature. The developed methods were employed for the detection of several Amiton derivatives (Schedule II of the CWC) that are structurally closely related to each other; some of which are new and have not been reported in literature previously. In addition, a novel DI SPME method from complex matrices for the analysis of organophosphates related to the CWC was developed. The studies clearly show that DI SPME for complex matrices is superior to HS extraction and can potentially be applied to other related compounds controlled under the CWC.


Facile Preparation of Self-Assembled Polydopamine-Modified Electrospun Fibers for Highly Effective Removal of Organic Dyes.
Polydopamine (PDA) nanoparticles can be used as an adsorbent with excellent adsorption capacity. However, nanosized adsorbents are prone to aggregation and thus are severely limited in the field of adsorption. In order to solve this problem, we utilized polydopamine in-situ oxidation self-polymerization on the surface of polycaprolactone (PCL)/polyethylene oxide (PEO) electrospun fiber after solvent vapor annealing (SVA) treatment, and successfully designed and prepared a PCL/PEO@PDA composite membrane. The SVA treatment regulated the microscopic morphology of smooth PCL/PEO electrospun fibers that exhibited a pleated microstructure, increasing the specific surface area, and providing abundant active sites for the anchoring of PDA nanoparticles. The PCL/PEO@PDA composite obtained by chemical modification of PDA demonstrated numerous active sites for the adsorption of methylene (MB) and methyl orange (MO). In addition, the PCL/PEO@PDA composites were reusable several times with good reutilization as adsorbents. Therefore, we have developed a highly efficient and non-agglomerated dye adsorbent that exhibits potential large-scale application in dye removal and wastewater purification.


Myocardial Infarction With Non-obstructive Coronary Arteries - Diagnosis and Management.
MI with non-obstructive coronary arteries (MINOCA) is an enigma that is being increasingly recognised with the frequent use of angiography following acute MI. To diagnose this condition, it is important to determine the multiple potential underlying mechanisms that may be responsible, many of which require different treatments. This review evaluates the contemporary diagnosis and management of MINOCA.


Idiopathic myelofibrosis associated with primary biliary cirrhosis.
A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid worsening of the patient's clinical condition was noted, with an increase in the constitutional symptoms and need for frequent packed RBC transfusions, and she finally died from an infectious complication. This case represents a new association of IM with an autoimmune disease, supporting the hypothesis of a possible immune basis of IM in some cases.


True precocious puberty complicating congenital adrenal hyperplasia: treatment with a luteinizing hormone-releasing hormone analog.
Congenital adrenal hyperplasia (CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen four such children (three boys and one girl) who had the diagnosis of CAH made between the ages of 3 and 6 yr. These patients were treated with standard doses of hydrocortisone and fludrocortisone. A diagnosis of true precocious puberty was made because of testicular enlargement in the boys, breast development in the girl, progressive pubic hair development, rapid growth, and rapid bone age maturation. Plasma steroid levels were elevated for age, and gonadotropin levels were within the normal pubertal range, both basally and in response to LHRH stimulation. We treated these children with daily sc injections of a LHRH analog (LHRHa) for 6-18 months in addition to the standard hydrocortisone and fludrocortisone therapy for CAH. LHRHa significantly decreased basal plasma LH and FSH, peak LH and FSH responses to native LHRH, and testosterone levels. Testis size decreased in the males, and breast development regressed in the female. LHRHa therapy led to significant decreases in linear growth rate, ulnar growth rate, and rate of bone age advancement. These results suggest that LHRHa is an effective adjunct to hydrocortisone and fludrocortisone in the treatment of true precocious puberty complicating CAH.


Differentiation and Identification of Cachaça Wood Extracts Using Peptide-Based Receptors and Multivariate Data Analysis.
It is becoming increasingly important to differentiate complex mixtures, especially in forensics. Cachaça, the most popular alcoholic beverage in Brazil, is made from distilled and fermented sugar cane juice. It contains a mixture of naturally occurring polyphenols known as tannins, whose composition is dictated by the type of wood used to age the beverage. These tannins can be differentiated in an Indicator Displacement Assay (IDA) using peptide-based ternary sensing ensembles. This investigation demonstrates a technique for fingerprinting the identity of the woods used to age cachaças. Unknown cachaça samples were tested against a training set of Brazilian woods in addition to oaks from different countries. Results obtained from the analysis showed that 62.5% of the samples were correctly identified. Furthermore, four samples anonymously added to the pool of unknowns from the training set were identified with 100% accuracy, emphasizing both the promising results obtained from this method of differentiation and the importance of analyzing same-age samples.


Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.
Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.


[Perioperative removal of body piercing].
The remaining of piercing in intraoperative can cause damages. This paper had as purpose defining the nursing interventions in the intraoperative and evaluates the complications caused by piercing in the intraoperative. This literature review had 16 articles published from 1994 to 2006. Nine articles (56.2%) were about nursing interventions in the intraoperative, four (25.0%) were concerning complications in the intraoperative and three (18.8%) were about the use of piercing in the intraoperative, not presenting complications. We concluded that wearing oral piercing in the intraoperative increases the risk of swallowing and injuries. Furthermore, wearing body jeweIry can cause injuries on the skin during the patient's moving and burns after electrosurgery. Therefore, it is necessay to withdraw the piercing in the preoperative.


Climate Change and Crop Exposure to Adverse Weather: Changes to Frost Risk and Grapevine Flowering Conditions.
The cultivation of grapevines in the UK and many other cool climate regions is expected to benefit from the higher growing season temperatures predicted under future climate scenarios. Yet the effects of climate change on the risk of adverse weather conditions or events at key stages of crop development are not always captured by aggregated measures of seasonal or yearly climates, or by downscaling techniques that assume climate variability will remain unchanged under future scenarios. Using fine resolution projections of future climate scenarios for south-west England and grapevine phenology models we explore how risks to cool-climate vineyard harvests vary under future climate conditions. Results indicate that the risk of adverse conditions during flowering declines under all future climate scenarios. In contrast, the risk of late spring frosts increases under many future climate projections due to advancement in the timing of budbreak. Estimates of frost risk, however, were highly sensitive to the choice of phenology model, and future frost exposure declined when budbreak was calculated using models that included a winter chill requirement for dormancy break. The lack of robust phenological models is a major source of uncertainty concerning the impacts of future climate change on the development of cool-climate viticulture in historically marginal climatic regions.


Welfare assessment of broiler breeders that are food restricted after peak rate of lay.
1. Broiler breeder females were reared on one of three growth curves (ad libitum, conventional or modified restriction) and given rations containing a high or low concentration of crude protein. After the peak rate of lay they were fed ad libitum or a decreasing quantity of food in response to declining egg production. The welfare of the birds was assessed by determining the changes in indices of welfare at 36, 48 and 60 weeks of age. 2. Body weight increased rapidly in restricted birds fed ad libitum post-peak and water intake declined. 3. Post-peak food restriction was associated with a decrease in resting and increased drinking and spot-pecking activities. Birds that were food restricted during rearing spent more time foraging and spot-pecking at 36 and 48 but not 60 weeks of age. 4. Immune function increased with age but was not affected by the experimental treatments. The heterophil-lymphocyte ratio in birds fed ad libitum during rearing was numerically lower at 36 and higher at 48 and 60 weeks of age compared with restricted birds. 5. There was no effect of treatment on plasma corticosterone concentration. Creatine kinase activity was high at 60 weeks in treatments that were characterised by poor reproductive status and the activities of other enzymes reflected differences in reproductive status and mortality. 6. There was no long-term welfare or production advantage from feeding low protein rations or more generous feeding during the rearing period compared with conventional food restriction programmes.


Enhancing the social capital in industrial work teams: results from a participatory intervention.
We investigated the effects of an intervention aiming at enhancing four types of team-level social capital (bonding, bridging and two types of linking social capital) in six dairy plants with a total of 60 teams. Social capital and work engagement was assessed in baseline and follow-up surveys. The follow-up period was approximately 20 months, comprising an intervention period of 12 months. Intervention effects were assessed by comparing changes in team-level mean-scores for teams that had developed action plans with teams that had not. Results show that teams that had developed action plans generally showed a larger increase in social capital and work engagement than other teams. Differences were statistically significant for linking social capital towards the workplace as a whole and work engagement. However, effect sizes indicate an effect of the action plans despite the lack of statistical significance. Moreover, the self-reported level of implementation of the action plans was associated with the size and direction of the observed change.


A quantitative assessment of the consequences of allowing dose heterogeneity in prostate radiation therapy planning.
Target dose uniformity has been historically an aim of volumetric modulated arc therapy (VMAT) planning. However, for some sites, this may not be strictly necessary and removing this constraint could theoretically improve organ-at-risk (OAR) sparing and tumor control probability (TCP). This study systematically investigates the consequences of PTV dose uniformity that results from the application or removal of an upper dose constraint (UDC) in the inverse planning process for prostate VMAT treatments. OAR sparing, target coverage, hotspots, and plan complexity were compared between prostate VMAT plans with and without the PTV UDC optimized using the progressive resolution optimizer (PRO, Varian Medical Systems, Palo Alto, CA). Removing the PTV UDC, the median D1cc reached 144.6% for the CTV and the PTV, and an average increase of 3.2% TCP was demonstrated, while CTV and PTV coverage evaluated by D99% was decreased by less than 0.6% with statistical significance. Moreover, systematic improvement in the rectum dose volume histograms was shown (a 5-10% decrease in the volume receiving 50% to 75% prescribed dose), resulting in an average decrease of 1.3% (P < 0.01) in the rectum normal tissue complication probability. Additional consequences included potentially increased dose to the urethra as evaluated by PTV D0.035cc (median: 153.4%), delivering 283 extra monitor units (MUs), and slightly higher degrees of modulation. In general, the results were consistent when a different optimizer (Photon Optimizer, Varian Medical Systems) was used. In conclusion, removing the PTV UDC is acceptable for localized prostate cases given the systematic improvement of rectal dose and TCP. It can be particularly useful for cases that do not meet the rectum dose constraints with the PTV UDC on. This comes with the foreseeable consequences of increased dose heterogeneity in the PTV and an increase in MUs and plan complexity. It also has a higher requirement for reproducing the position and size of the target and OARs during treatment. Finally, with the PTV UDC completely removed, in some cases the maximum doses within the PTV did approach levels that may be of concern for urethral toxicity and therefore in clinical implementation it may still be necessary to include a PTV UDC, but one based on limiting toxicity rather than enforcing dose homogeneity.


Enzyme replacement therapy for lysosomal storage diseases.
Enzyme replacement therapy (ERT) has been approved for 6 lysosomal storage diseases (LSDs) worldwide including Japan. These diseases include Gaucher disease (GD), Fabry disease, mucopolysaccharidosis (MPS) types I, II, and VI, and Pompe disease (PD). The efficacy and safety of ERT for LSDs has been confirmed by extensive clinical trials. However, there are still obstacles to successful ERT, such as immune reactions against the infused enzyme, mistargeting of enzymes rather than lysosomes, and intractable tissues. Regarding immune reactions, a negative impact of antibody formation on therapeutic effect has been reported for GD, Fabry disease, MPS type I, and PD. In PD, mistargeting of the enzyme was reported in a mouse model due to autophagic build up. Another challenge is intractable tissues, such as the brain and bone, which are key tissues in LSDs. Thus, control of immune reactions against therapeutic enzymes and control of autophagic build up are key issues to maximize the efficacy of ERT. Finally, the development of a new enzyme that effectively targets the brain and bone is very important to improve the quality of life of patients with LSDs.


Self-Assembled Hyaluronic Acid Nanoparticles for pH-Sensitive Release of Doxorubicin: Synthesis and In Vitro Characterization.
The nanoparticulate drug delivery systems (NDDS) demonstrate a relatively ideal therapeutic efficacy during cancer therapy Regarding the high tumor-target capacity and efficient drug release at the tumor site. Thus, in the present study, a novel macromolecular prodrug conjugates was designed and developed, which can target CD44-overexpressed tumor cells in addition to releasing doxorubicin (Dox) that is passively triggered by the acidic microenvironment of tumor cells. Briefly, the best reaction route from three different alternatives was selected and then the synthetic reaction conditions to get grafted hyaluronic acid products were optimized. Through constructing a schiff base covalent bond conjugation between grafted hyaluronic acid and Dox, the macromolecular prodrug micelles were endowed with acid-sensitive character. This character resulted in a delayed release at pH 7.4 and expedited release at pH 5.0. This was proved by the release experiments in vitro. In the aspect of nanostructure, the polymer prodrug can self-assembly into the core-shell structure nanoparticles in aqueous solution with the hyaluronic acid as the hydrophilic shell and doxorubicin as the hydrophobic core. By optimizing the process of preparation, nanoparticles showed the mean size of around 200 nm and a narrow particle size distribution which were verified by dynamic light scattering (DLS) and transmission electron microscopy (TEM). CCK-8 assays and fluorescence microscope experiments showed that the polymer prodrug nanoparticles possessed an enhanced targeting ability and antitumor activity toward HeLa cells.


Generation of solitons and breathers in the extended Korteweg-de Vries equation with positive cubic nonlinearity.
The initial-value problem for box-like initial disturbances is studied within the framework of an extended Korteweg-de Vries equation with both quadratic and cubic nonlinear terms, also known as the Gardner equation, for the case when the cubic nonlinear coefficient has the same sign as the linear dispersion coefficient. The discrete spectrum of the associated scattering problem is found, which is used to describe the asymptotic solution of the initial-value problem. It is found that while initial disturbances of the same sign as the quadratic nonlinear coefficient result in generation of only solitons, the case of the opposite polarity of the initial disturbance has a variety of possible outcomes. In this case solitons of different polarities as well as breathers may occur. The bifurcation point when two eigenvalues corresponding to solitons merge to the eigenvalues associated with breathers is considered in more detail. Direct numerical simulations show that breathers and soliton pairs of different polarities can appear from a simple box-like initial disturbance.


Pityriasis versicolor: Current concepts in Aetiology and Management.
Pityriasis versicolor occurs commonly in this environment. It is characterised by fine scaly macular eruption and has a chronic relapsing nature. It is due to infection with malassezia. Recently with the aid of sequencing of the sub-unit rRNA and nuclear DNA complimentary studies, the malassezia species have been classified into seven. Malassezia (M) furfur, M. Symboidalis, M. Obtuse, M. globosa, M. restricta, M. sloofiae and M. pachydermatitis. M. globosa has been linked to development of pityriasis versicolor. Despite extensive work, factors which change the organism from its commensally to its pathogenic state are yet to be identified, although a genetic factor appears to be involved as familial cases occur. However factors such as hyper-hidrosis, depressed immunity, and occlusion of the skin, malnutrition and abuse of corticosteroids have been observed to be contributory. For many years topical therapy was the main stay of treatment that contributed to the high relapse after treatment. Presently management includes the use of both systemic and topical anti-fungals. Prophylactic treatment is now advocated in preventing relapses, which occurs commonly. pityriasis versicolor, current views, aetiology, management.


Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group.
Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients. The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods. Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes. Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.


[Synthesis and vasodilative activities of benzamide derivatives].
Twenty two benzamide derivatives were synthesized of which twenty one were not reported before. Vasodilative activity screening in vitro has shown that most of the compounds possess various activities, among which compound H1, H11, H17, E1, E3 demonstrated a superior pharmacological profile to the lead compound when inhibiting effect on the noradrenaline (10(-7) mol.L-1) induced contraction of rat aortic strip was chosen as the evaluation criterion, while H7,15, E7 exerted significant inhibiting action toward 85.7 mmol.L-1 KCl induced contraction of rat aortic strip. Further evaluation assays for their KCO potentials showed that E1 might be an ATP sensitive KCO. Preliminary structure-activity relationships of this kind of aromatic amides are discussed herein.


New records of bats and terrestrial small mammals from the Seli River in Sierra Leone before the construction of a hydroelectric dam.
Sierra Leone is situated at the western edge of the Upper Guinean Forests in West Africa, a recognised biodiversity hotspot which is increasingly threatened by habitat degradation and loss through anthropogenic impacts. The small mammal fauna of Sierra Leone is poorly documented, although bats and rodents account for the majority of mammalian diversity. Based on morphological, genetic and echolocation data, we recorded 30 bat (Chiroptera), three shrew (Soricomorpha) and eleven rodent (Rodentia) species at the Seli River in the north of the country in 2014 and 2016, during a baseline study for the Bumbuna Phase II hydroelectric project. In 2016, 15 bat species were additionally documented at the western fringe of the Loma Mountains, a recently established national park and biodiversity offset for the Bumbuna Phase I dam. Three bat species were recorded for the first time in Sierra Leone, raising the total number for the country to 61. Further, two bat species are threatened and endemic to the Upper Guinean Forest and several taxa of small mammals are poorly known or represent undescribed species. Overall, the habitats of the project area supported a species-rich small mammal fauna including species of global conservation concern. Suitable mitigation measures and/or offsets are necessary to maintain biodiversity and ecosystems in a region that is under high human pressure.


Time Course of Cultural Differences in Spatial Frequency Use for Face Identification.
Several previous studies of eye movements have put forward that, during face recognition, Easterners spread their attention across a greater part of their visual field than Westerners. Recently, we found that culture's effect on the perception of faces reaches mechanisms deeper than eye movements, therefore affecting the very nature of information sampled by the visual system: that is, Westerners globally rely more than Easterners on fine-grained visual information (i.e. high spatial frequencies; SFs), whereas Easterners rely more on coarse-grained visual information (i.e. low SFs). These findings suggest that culture influences basic visual processes; however, the temporal onset and dynamics of these culture-specific perceptual differences are still unknown. Here, we investigate the time course of SF use in Western Caucasian (Canadian) and East Asian (Chinese) observers during a face identification task. Firstly, our results confirm that Easterners use relatively lower SFs than Westerners, while the latter use relatively higher SFs. More importantly, our results indicate that these differences arise as early as 34 ms after stimulus onset, and remain stable through time. Our research supports the hypothesis that Westerners and Easterners initially rely on different types of visual information during face processing.


The Role of Autophagy and Apoptosis in Affected Skin and Lungs in Patients with Systemic Sclerosis.
Systemic sclerosis (SSc) is a complex autoimmune inflammatory disorder with multiple organ involvement. Skin changes present the hallmark of SSc and coincide with poor prognosis. Interstitial lung diseases (ILD) are the most widely reported complications in SSc patients and the primary cause of death. It has been proposed that the processes of autophagy and apoptosis could play a significant role in the pathogenesis and clinical course of different autoimmune diseases, and accordingly in SSc. In this manuscript, we review the current knowledge of autophagy and apoptosis processes in the skin and lungs of patients with SSc. Profiling of markers involved in these processes in skin cells can be useful to recognize the stage of fibrosis and can be used in the clinical stratification of patients. Furthermore, the knowledge of the molecular mechanisms underlying these processes enables the repurposing of already known drugs and the development of new biological therapeutics that aim to reverse fibrosis by promoting apoptosis and regulate autophagy in personalized treatment approach. In SSc-ILD patients, the molecular signature of the lung tissues of each patient could be a distinctive criterion in order to establish the correct lung pattern, which directly impacts the course and prognosis of the disease. In this case, resolving the role of tissue-specific markers, which could be detected in the circulation using sensitive molecular methods, would be an important step toward development of non-invasive diagnostic procedures that enable early and precise diagnosis and preventing the high mortality of this rare disease.