Influence of probiotic supplementation on blood parameters and growth performance in broiler chickens.
Effects of commercial probiotic (Bactocell®) on growth performance and blood parameters were evaluated. A total of 800 one day-old Ross broiler chicks were raised over 42 days. Chicks were wing-banded, weighed individually and randomly allocated into four equally major groups each having two replicates. Chicks of group 1 (control group) were fed the starter and finisher diets that did not supplemented with probiotic. The chicks of groups 2, 3, and 4 were fed the control starter and finisher diets supplemented with 1.6 g, 1 g and 0.8 g of probiotic per kg feed, respectively. Weekly body weight, feed consumption and feed conversion were measured. Blood parameters at 1, 4 and 6 weeks of age including packed cell volume (PCV), haemoglobin (Hb), total protein, albumin, total lipid and cholesterol were determined. All birds were kept under similar environmental, managerial and hygienic conditions. The results of the current study revealed that there was no significant change for Hb and PCV concentrations among different groups at all studied times. Also, total protein, lipids and albumin concentrations were not affected by probiotic supplementation. Chicken fed a diet containing various levels of probiotic showed a significant decrease (p ⩽ 0.05) in cholesterol concentration compared to control group. Probiotic supplementation significantly increased the body weight and daily weight gain of broiler chicks at late ages (3-6 weeks). Also, the birds fed on probiotic levels 1 and 0.8 g/kg diet exhibited higher body weight among chicken groups at 6 weeks of age. Improved feed conversion was noticed in birds fed a diet supplemented with probiotic. There was no significant difference in mortality rate among groups. We concluded that use of selected commercial probiotic resulted in improved performance parameters and reduced serum cholesterol in broiler chickens. Moreover, supplementation of the probiotic to broilers in the levels of 1 and 0.8 g/kg diet was found to be better than control and 1.6 g/kg level indicating that increasing dietary probiotic level does not has the best performance.


Passive control potentials of trees and on-street parked cars in reduction of air pollution exposure in urban street canyons.
This study investigates the passive-control-potentials of trees and on-street parked cars on pedestrian exposure to air pollutants in a street canyon using three-dimensional CFD. Since, according to some studies trees deteriorate air quality and cars parked roadside improve it, the combine as well as separate effects of trees and on-street parked cars have been examined. For this, different tree canopy layouts and parking configurations have been developed and pedestrian exposure for each has been analysed. The results showed, for example, tree crown with high porosity and low-stand density in combination with parallel or perpendicular car parking reduced the pedestrian exposure considerably.


Cytotoxicity assay using a human pluripotent stem cell-derived cranial neural crest cell model.
Cleft lip and palate are the most common congenital abnormalities that occur early in pregnancy. The majority of cranial mesenchyme is derived from cranial neural crest cells that differentiate into odontoblasts, cartilage, craniofacial bone, and connective tissue. A subset of these cells differentiates into cranial ganglia. We have previously reported an induction protocol of cranial neural crest cell-like cells from human pluripotent stem cells. This study tested detection of the cytotoxic sensitivities of dental materials, including titanium ions, palladium ions, and hydroxyethyl methacrylate, on the cell viability of induced cranial neural crest cell-like cells (iNC-LCs) derived from Tic human induced pluripotent stem cell (hiPSC) line. Further, the sensitivity was compared with those of human fetal lung fibroblastic cell line MRC-5, which is origin of Tic hiPSC, and osteoblastic cell line MC3T3-E1 which was derived from mouse calvaria. The results suggested that this cell-based assay system using iNC-LCs is a potential method for in vitro screening as an alternative to animal testing to predict toxic effects of dental materials on early craniofacial development.


Cost-Effectiveness of Cancer Screening: Health and Costs in Life Years Gained.
Studies reporting on the cost-effectiveness of cancer screening usually account for quality of life losses and healthcare costs owing to cancer but do not account for future costs and quality of life losses related to competing risks. This study aims to demonstrate the impact of medical costs and quality of life losses of other diseases in the life years gained on the cost-effectiveness of U.S. cancer screening. Cost-effectiveness studies of breast, cervical, and colorectal cancer screening in the U.S. were identified using a systematic literature review. Incremental cost-effectiveness ratios of the eligible articles were updated by adding lifetime expenditures and health losses per quality-adjusted life year gained because of competing risks. This was accomplished using data on medical spending and quality of life by age and disease from the Medical Expenditure Panel Survey (2011-2015) combined with cause-deleted life tables. The study was conducted in 2018. The impact of quality of life losses and healthcare expenditures of competing risks in life years gained incurred owing to screening were the highest for breast cancer and the lowest for cervical cancer. The updates suggest that incremental cost-effectiveness ratios are underestimated by $10,300-$13,700 per quality-adjusted life year gained if quality of life losses and healthcare expenditures of competing risks are omitted in economic evaluations. Furthermore, cancer screening programs that were considered cost saving, were found not to be so following the inclusion of medical expenditures of competing risks. Practical difficulties in quantifying quality of life losses and healthcare expenditures owing to competing risks in life years gained can be overcome. Their inclusion can have a substantial impact on the cost-effectiveness of cancer screening programs.


Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot.
Diabetic foot is one of the severest complications of diabetes. In severe cases, this disease may be lead to amputation or even death due to secondary infection and ischemic necrosis. Since the ineffectiveness of traditional therapy, autologous stem cell transplantation has been used to treat diabetic foot. This simple, safe, and effective therapy is expected to be applied and promoted in the future.In this review, we described the detailed pathogenesis of diabetic foot and the common clinical treatments currently used. We also revealed vascular remodeling as the potential mechanism of therapeutic functions of adipose-derived stromal vascular fraction (SVF) in treating diabetic foot.


Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus.
Pramlintide delays gastric emptying, possibly by a centrally mediated mechanism. Our aim was to determine whether the effects of pramlintide on gastric emptying differ in people with type 1 or type 2 diabetes who had no history of complications. Using a randomized, three-period, two-dose, crossover design, we studied the effects of 0, 30, or 60 microg t.i.d. pramlintide subcutaneously for 5 days each in six type 1 and six type 2 diabetic subjects. Gastric emptying of solids was measured by 13C-Spirulina breath test. Plasma pancreatic polypeptide (HPP) response to the test meal was also measured. Relative to placebo [t 50% 91 +/- 6 min (means +/- SEM)], pramlintide equally delayed gastric emptying following 30 or 60 microg t.i.d. (268 +/- 37 min, 329 +/- 49 min, respectively; P < 0.01]. Postprandial HPP levels were lower in response to 30 and 60 microg pramlintide compared to placebo. There were no significant differences in the effects on gastric emptying or HPP levels between type 1 and type 2 diabetic subjects. Pramlintide delays gastric emptying in diabetes unassociated with clinically detected complications. Further studies are needed in diabetic patients with impaired gastric motor function.


The first comprehensive phylogenetic and biochemical analysis of NADH diphosphatases reveals that the enzyme from Tuber melanosporum is highly active towards NAD.
Nudix (for nucleoside diphosphatases linked to other moieties, X) hydrolases are a diverse family of proteins capable of cleaving an enormous variety of substrates, ranging from nucleotide sugars to NAD+-capped RNAs. Although all the members of this superfamily share a common conserved catalytic motif, the Nudix box, their substrate specificity lies in specific sequence traits, which give rise to different subfamilies. Among them, NADH pyrophosphatases or diphosphatases (NADDs) are poorly studied and nothing is known about their distribution. To address this, we designed a Prosite-compatible pattern to identify new NADDs sequences. In silico scanning of the UniProtKB database showed that 3% of Nudix proteins were NADDs and displayed 21 different domain architectures, the canonical architecture (NUDIX-like_zf-NADH-PPase_NUDIX) being the most abundant (53%). Interestingly, NADD fungal sequences were prominent among eukaryotes, and were distributed over several Classes, including Pezizomycetes. Unexpectedly, in this last fungal Class, NADDs were found to be present from the most common recent ancestor to Tuberaceae, following a molecular phylogeny distribution similar to that previously described using two thousand single concatenated genes. Finally, when truffle-forming ectomycorrhizal Tuber melanosporum NADD was biochemically characterized, it showed the highest NAD+/NADH catalytic efficiency ratio ever described.


Discovery of selective irreversible inhibitors of B-Lymphoid tyrosine kinase (BLK).
B-lymphoid tyrosine kinase (BLK), a member of the SRC family nonreceptor tyrosine kinase, is involved in the B-cell receptor (BCR) signaling pathway and B cell development and function. Dysregulation of BLK is associated with autoimmune diseases and cancer. However, there is an absence of good tool compounds for BLK, and the molecular mechanisms by which BLK mediates physiological and pathological processes are poorly understood. Herein, we present the discovery of a novel series of selective and irreversible inhibitors of BLK with nanomolar potency against BLK in biochemical and cellular assays. Compound 25 demonstrated potent antiproliferative activities against several B cell lymphoma cell lines. These compounds constitute the first series of selective inhibitors developed for BLK and could help expedite the exploration of BLK functions.


Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming.
The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.


Transport of sodium, water, 3-O-methyl-glucose and L-phenylalanine in vitro in biotin-deficient rats intestine.
In biotin-deficient rats, a decreased intestinal transport of Na+, H2O and L-phenylalanine, and no transport differences of 3-O-methyl-D-glucose were observed. The lower Na+ and L-phenylalanine transport appears to be referable to a decreased energy availability and probably not to the lack of a carrier.


Analysis of 1276 Haplotype-Resolved Genomes Allows Characterization of Cis- and Trans-Abundant Genes.
Many methods for haplotyping have materialized, but their application on a significant scale has been rare to date. Here we summarize analyses that were carried out in 1092 genomes from the 1000 Genomes Consortium and validated in an unprecedented number of 184 PGP genomes that have been experimentally haplotype-resolved by application of the Long-Fragment Read (LFR) technology. These analyses provided first insights into the diplotypic nature of human genomes and its potential functional implications. Thus, protein-changing variants were not randomly distributed between the two homologues of 18,121 autosomal protein-coding genes but occurred significantly more frequently in cis than in trans configurations in virtually each of the 1276 phased genomes. This resulted in global cis/trans ratios of ~60:40, establishing "cis abundance" as a universal characteristic of diploid human genomes. This phenomenon was based on two different classes of genes, a larger one exhibiting cis configurations of protein-changing variants in excess, so-called "cis-abundant" genes, and a smaller one of "trans-abundant" genes. These two gene classes, which together constitute a common diplotypic exome, were further functionally distinguished by means of gene ontology (GO) and pathway enrichment analysis. Moreover, they were distinguishable in terms of their effects on the human interactome, where they constitute distinct cis and trans modules, as shown with network propagation on a large integrated protein-protein interaction network. These analyses, recently performed with updated database and analysis tools, further consolidated the characterization of cis- and trans-abundant genes while expanding previous results. In this chapter, we present the key results along with the materials and methods to motivate readers to investigate these findings independently and gain further insights into the diplotypic nature of genes and genomes.


Usefulness of TC-99M GSA liver scintigraphy for the evaluation of liver regeneration in donors after living-donor liver transplantation.
We evaluated the impact of steatosis on regeneration and function of the remnant liver by using technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy. Twelve living donors were classified into groups with or without mild hepatic steatosis according to the liver-to-spleen attenuation ratio on computed tomography: six donors had a ratio > or = 1.2 (control group) and six had a ratio < 1.20 (fatty liver group). Scintigraphy was performed to determine the hepatic uptake ratio of the tracer (corrected for disappearance from the blood) and the maximum removal rate of the tracer by hepatocytes as parameters of the hepatic functional reserve. The fatty liver group had a significantly lower corrected hepatic uptake ratio and removal rate compared with the control group at 6 and 12 months after partial hepatectomy. The regenerated liver volume estimated by scintigraphy did not differ significantly between the two groups at any time. Because donors with mild hepatic steatosis showed impaired liver regeneration at 1 year after partial hepatectomy, management of these donors requires more care.


Solubility properties in biological media 9: prediction of solubility and partition of organic nonelectrolytes in blood and tissues from solvatochromic parameters.
Solubilities in and partition among human blood, brain, lung, kidney, muscle, and fat tissue are well correlated by linear solvation energy relationships of the form: XYZ = XYZo + mVI/100 + s pi + b beta m where XYZ is the logarithm of the solubility property, VI is the intrinsic (van der Waals') molar volume, pi and beta are the solvatochromic parameters that measure solute dipolarity/polarizability and hydrogen-bond acceptor basicity, respectively, and the subscript m indicates that for self-associating compounds, the parameter applies to the non-self-associated "monomer" solute. The equation for log K(brain--blood) indicates that increasing molar volume favors, whereas increasing dipolarity and hydrogen-bond acceptor basicity oppose, solute transfer from blood into brain.


Critical influenza virus infection.
To determine the risk of death from influenza infection in children with chronic underlying disease. An 18-year retrospective study of children with 'critical' influenza A or B virus infection, defined as requiring admission to intensive care or resulting in death, but excluding laryngotracheobronchitis (LTB). Influenza infection was diagnosed by viral culture and/or immunofluorescence of respiratory secretions. Patients with LTB were analysed separately. There were 27 cases of critical influenza virus infection over the study period, comprising 26 admissions to the intensive care unit (excluding LTB) and one death on the general wards. Thirteen (48%) of the 27 children had chronic underlying disease. In addition, 12 children with LTB were admitted to the intensive care unit. The LTB children were older and less likely to have chronic underlying disease. Nosocomial infection caused seven (26%) of the 27 critical infections. Nine (33%) of the 27 children with critical influenza died. Six (46%) of 13 children with chronic underlying disease and influenza admitted to intensive care died, compared with three of 14 (21%) without any underlying disease (odds ratio = 3.1, 95% confidence interval 0.6-14.0). Critical life-threatening influenza virus infection was uncommon, but the mortality was high (33%), particularly in children with chronic underlying disease. Nosocomial infection with influenza was an important cause of admission to intensive care.


Juxtapapillary choroid is thinner in normal-tension glaucoma than in healthy eyes.
To measure the juxtapapillary choroidal thickness in eyes with normal-tension glaucoma (NTG) and to compare it with healthy eyes. Twelve radial B-scan images of the optic nerve head (ONH) were obtained from 96 patients with NTG and 48 healthy subjects matched by age using swept-source (SS) optical coherence tomography (OCT). The juxtapapillary choroidal thickness was defined as the average choroidal thickness within 500 μm from the border tissue of Elschnig. Choroidal thinning in patients with NTG was assessed by calculating the relative choroidal thickness, defined as the ratio of the measured juxtapapillary choroidal thickness in each meridian to the corresponding value in age-matched healthy controls. Retinal nerve fibre layer (RNFL) damage as reflected by circumpapillary RNFL thickness (measured using spectral-domain OCT) was also assessed. The juxtapapillary choroid was significantly thinner in NTG eyes than in healthy control eyes in the inferotemporal and superotemporal sectors. The relative choroidal thinning was topographically associated with the hemispheric location of dominant RNFL damage. The average juxtapapillary choroidal thickness was not associated with either the global RNFL thickness or the visual field mean deviation. Age and untreated intraocular pressure were significantly associated with the juxtapapillary choroidal thickness in NTG eyes in both univariate and multivariate analyses (all p < 0.05). Decreased microvascular circulation in the ONH as a result of juxtapapillary choroidal thinning could be an important part of the pathogenesis of optic nerve damage in NTG.


Effect of gamma-synuclein silencing on apoptotic pathways in retinal ganglion cells.
gamma-Synuclein (Syn G) is highly expressed in retinal ganglion cells and the loss of these cells in glaucoma is associated with significant reduction of the intracellular Syn G level. However, a causative relationship between these two events has not been established. Here we show that the knockdown of Syn G results in a decreased viability of the immortalized retinal ganglion cells (RGC-5). The Syn G silencing reduces phosphorylation of serine 112 (Ser112) in Bad protein, a member of the Bcl-2 family that plays a critical role in apoptotic cell death signaling. Our gene expression analysis data suggests that changes in Bad phosphorylation status may be caused by a coordinated shift in activities of kinases controlling Bad phosphorylation and phosphatases catalyzing its dephosphorylation. Moreover, increased phosphorylation of Bad-sequestering protein 14-3-3 detected in these cells is also pro-apoptotic. These results suggest that the homeostatic level of Syn G in RGC-5 cells is required for transcriptional regulation of protein kinases and phosphatases, controlling phosphorylation of Bad and 14-3-3. Lowering Syn G causes Bad dephosphorylation, dissociation from phosphorylated 14-3-3, and translocation to mitochondria where it initiates apoptotic death cascade.


Prevalence of poor lipid control in patients with premature coronary artery disease.
Lipid goals have become more stringent in high risk patients. However, no studies have analyzed lipid control defined as the composite achievement of goals in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (Non-HDL-C) and apolipoproteinB-100 (ApoB-100), in patients with premature coronary artery disease (CAD). We aimed to analyze lipid control rates, and the associated factors with its poor achievement in patients with premature CAD. The study included 1196 patients with CAD diagnosed before 55 and 65 years old in men and women, respectively. The American Heart Association/American College of Cardiology (non-strict) and the American Association of Clinical Endocrinologists (strict) criteria were used to analyze lipid control rates. Sociodemographic, dietary-healthy and clinical characteristics of the patients were collected. Participants were 54 ± 8 years old, 19.7% were women, and median CAD evolution was 2.4 years. Non-strict and strict lipid control was achieved in 23.0% and 8.9% of the patients, respectively. Moreover, 46.5% and 62.8% of the patients did not achieve any lipid goal using both criteria. Sociodemographic data were not different among patients who achieved or not lipid control. Treatment adherence<85%, prescription of low- and moderate-intensity statins, and obesity were consistently associated with poor lipid control. Lipid control is suboptimal in patients with premature CAD. Low lipid-lowering treatment adherence, low prescription of high-intensity statins, and obesity were independently associated with poor lipid control. Novel preventive programs and more aggressive pharmacological intervention should be implemented in order to reduce the burden of premature CAD.


Interleukin-1 production and cell-activation response to cytomegalovirus infection of vascular endothelial cells.
Human cytomegalovirus (HCMV) is a source of major complications in immunosuppressed individuals, and endothelial involvement in HCMV infection is well documented. Traditionally laboratory strains of HCMV have been used in experimental investigations in vitro; however the continuous propagation of these strains in fibroblasts have attenuated the virus making it unsuitable for infecting other cell systems such as endothelial cells. In this study a recent clinical isolate of HCMV was propagated through several passages in endothelial cells and was used to investigate the effect of HCMV infection of human umbilical vein endothelial cells (HUVEC) on IL-1 production and cell proliferation. Infection of HUVEC with the clinical isolate of HCMV (at multiplicity of infection 5:1) suppressed the production of IL-1 alpha (82%) and IL-1 beta (99%) at 5 h post infection; the levels returned to that of the control within 24h post infection. Ultraviolet inactivated (but not heat killed) virus produced similar suppression confirming that a thermolabile viral structural protein or intact virion were responsible for this suppression. Infection of HUVEC with the clinical isolate increased the number of these cells and the rate of their proliferation. An increase of infected HUVEC number under quiescent growth conditions continued as the infection progressed (6-10 days post infection), exhibiting, at 3 days post infection, 5 times the number of uninfected HUVEC (control) which did not tolerate the quiescent culture conditions for more than 4 days. Live virus is responsible for this increase because UV-inactivated virus did not maintain the proliferation of HUVEC. These studies suggest that while infection of HUVEC with a recent clinical isolate of HCMV suppressed the production of IL-1 at early hours after infection, it increased the proliferation of these cells at later stages of infection.


Obturator dislocations of the hip associated with pelvic ring injuries: Case report and review of the literature.
An obturator hip dislocation with an associated open book pelvic ring injury is an extremely rare injury pattern. This case report will discuss challenges to closed reduction, acute management strategies and review the literature on combined hip dislocations and open book pelvic ring injuries. This injury pattern presents unique reduction challenges that should be recognized early in order to provide effective resuscitation and preserve the femoral head blood supply. Failing to close reduce the hip delays reducing the pelvic ring volume because sheets and binders are precluded from working effectively.


[Results of acute myeloid leukemia treatment. Analysis of 63 patients between 2010-2014].
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, emphasizing its high recurrence rate despite hematopoietic cell transplantation (HCT). To report the results of AML treatment at the Catholic University of Chile Clinical Hospital. Review of medical records of patients with AML. 63 patients, median age 55.4 years (range:16-89), treated between 2010 and 2014. Admission laboratory values showed (median values): leukocytes 45.989/mm³, hemoglobin 9.1 g/dl, platelets 75.548/mm³, peripheral blood blasts 38% and bone marrow blasts 74%. According to cytogenetic risk classification we observed the following groups: favorable 8% (n = 5), intermediate 51% (n = 32), unfavorable 13% (n = 8) and unknown 28% (n = 17). Seventy five percent of patients received induction chemotherapy and 25% palliative care. Median survival of treated and palliative care patients was 27.3 and 1 month respectively. Induction chemotherapy (IC) mortality (ICM) was 4.2%. Seventy percent (n = 33) of patients who received IC had complete response (CR) with a 3-year relapse free survival (RFS) of 25% and overall survival (OS) of 31%. Multivariate analysis demonstrated that achievement of CR, cytogenetic risk group and receiving consolidation chemotherapy were significantly associated with better RFS and OS. AML treatment with standard chemotherapy in our center achieves similar results to what has been described in international series regarding induction rates and ICM, however RFS and OS are still very low, especially in intermediate and high cytogenetic risk groups.


Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort.
The root extract of Peucedanum ostruthium (PO-E) was identified as a promising antibacterial source from a screening of 158 extracts against Staphylococcus aureus. It has also recently been shown to significantly decrease the survival of the nematode Caenorhabditis elegans. We used the biochemometric approach ELINA to investigate the phytochemical characteristics of the multicomponent mixture PO-E to identify the anti-infective constituent(s) targeting S. aureus and C. elegans.1H NMR spectra of PO-E-derived microfractions were correlated with their respective bioactivity data. Heterocovariance analyses unambiguously identified ostruthin as an anti-staphylococcal constituent, which potently also inhibited Enterococcus spp.. ELINA demonstrated that anthelmintic activity was due to a combinatorial effect of ostruthin and isoimperatorin. A C. elegans-based survival and motility assay confirmed that isoimperatorin, imperatorin, and verapamil modulated the susceptibility of ostruthin. The combinatorial effect of these natural products was shown in larvae studies to be related to the function of the nematodes' efflux pump.


Evaluation of QT Liability for PF-05251749 in the Presence of Potential Circadian Rhythm Modification.
PF-05251749 is a dual inhibitor of casein kinase 1 δ/ε, key regulators of circadian rhythm. As a result of its mechanism of action, PF-05251749 may also change the heart rate corrected QT (QTc) circadian rhythm, which may confound detection of drug-induced QTc prolongation. In this analysis, a nonlinear mixed effect model including a multioscillator function was developed in addition to fitting the prespecified linear mixed effect concentration-QTc model, to identify QTc liability of PF-05251749 in the presence of potential circadian rhythm change. The modeling results suggested lack of clinically meaningful QTc prolongation (upper bound of 90% confidence interval for ∆∆QTc < 10 milliseconds) and that the drug-induced QTc circadian rhythm change was not present. However, simulation results indicated that inference of drug-induced QTc prolongation could be misleading if the drug effect on QTc circadian rhythm is not properly addressed. The modeling and simulation results suggest that prespecification of the concentration-QTc model should be reconsidered for drugs with circadian rhythm modulation potential.


A repeated 28-day oral dose toxicity study of nonylphenol in rats, based on the 'Enhanced OECD Test Guideline 407' for screening of endocrine-disrupting chemicals.
A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the 'Enhanced OECD Test Guideline 407' paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.


Physical activity and associations with health-related quality of life in adults born small for gestational age at term: a prospective cohort study.
Adults born small for gestational age (SGA) have increased risk of adverse health outcomes. Physical activity (PA) is a key determinant of health and health-related quality of life (HRQoL). We aimed to investigate if being born SGA at term is associated with lower objectively measured and self-reported PA during adulthood. We also examined if objectively measured and self-reported PA were associated with HRQoL. As part of the 32-year follow-up in the NTNU Low Birth Weight in a Lifetime Perspective study, SGA and non-SGA control participants wore two tri-axial accelerometers for seven days (37 SGA, 43 control), and completed the International Physical Activity Questionnaire (IPAQ) (42 SGA, 49 control) and the Short Form 36 Health Survey (SF-36) (55 SGA, 67 control). Group differences in objectively measured daily metabolic equivalent of task (MET) minutes spent sedentary (lying, sitting), on feet (standing, walking, running, cycling), on the move (walking, running, cycling) and running/cycling, and group differences in self-reported daily MET minutes spent walking and in moderate and vigorous PA were examined using linear regression. Associations with SF-36 were explored in a general linear model. Mean (SD) daily MET minutes on the move were 218 (127) in the SGA group and 227 (113) in the control group. There were no group differences in objectively measured and self-reported PA or associations with HRQoL. In the SGA group, one MET minute higher objectively measured time on the move was associated with 4.0 (95% CI: 0.6-6.5, p = 0.009) points higher SF-36 physical component summary. We found no differences in objectively measured and self-reported PA or associations with HRQoL between term-born SGA and non-SGA control participants in adulthood.


New product development: Cellulose/egg white protein blend fibers.
The aim of the research was to form mixed cellulose/egg white isolate (EWI) fibers. Cellulose was dissolved in the Schweitzer's reagent. The blend fibers were obtained by simultaneous cellulose fiber formation and acid-induced gelation of EWI in 33% sulphuric acid solution. Increased storage modulus was noted for the blend fibers in comparison to the cellulose fibers. EWI alone formed fibers which were composed of microfibers with the average diameter of about 80 nm. Cellulose fibers had a loose microstructure with about 10 μm gaps and rough surface. The addition of EWI caused that the surface of the fiber was even more rough with a tendency to form microfibers, which were not observed for cellulose alone. EWI protein molecules had the tendency to bridge the voids between cellulose microfibers. Protein in the blend fibrils formed more branched aggregates than in the EWI fibrils, which was probably caused by interactions with copper ions. Both in cellulose and cellulose/EWI fibrils, the cellulose crystallized in cellulose II monoclinic system. Reduction in COH groups was noted, which was probably caused by interactions between the cellulose and proteins molecules. EWI/cellulose interactions caused formation of β-sheet type structures.


Goldenhar syndrome and medulloblastoma: a coincidental association? The first case report.
Features of Goldenhar syndrome include several craniofacial anomalies of structures derived from the first and second pharyngeal arches, as well as vertebral, cardiac and renal systems abnormalities. In addition, Goldenhar patients were reported to manifest a variety of central nervous system anomalies and several types of neoplasias. The first case of medulloblastoma in a patient with Goldenhar syndrome is presented here. There is no clear association between these two pathologies. We speculate that aberrant events during the migration of neural crest cells in early stages of development could be the basis of an association between medulloblastoma and Goldenhar syndrome. The case history suggests other possible etiological contributing factors to the development of medulloblastoma, such as patient's history of trauma and/or early childhood exposure to ionizing radiation.


A method for the analysis of chlorhexidine in serum.
A colorimetric method for the determination of chlorhexidine in serum or plasma has been elaborated; the limit of detection of the method is 25 ng/ml, based on 10 ml of serum or plasma.


Source apportionment of PM(10) and PM(2.5) using positive matrix factorization and chemical mass balance in Izmir, Turkey.
Atmospheric particulate matter (PM) fractions (PM(10) and PM(2.5)) were sampled concurrently between June 2004 and May 2005 at two sites (urban and suburban) in Izmir, Turkey. The elemental composition of PM (Al, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sr, V, and Zn) was determined using inductively coupled plasma-optical emission spectrometer. Elemental compositions of several PM sources were also characterized. Positive matrix factorization (PMF) and chemical mass balance modeling (CMB) were applied to determine the PM sources and their contributions to air concentrations. The major contributors to PM were fossil fuel burning, traffic emissions, mineral industries and marine salt according to the PMF results. However, undetermined parts were more than 40%. On the other hand, the contributions to PM could be determined completely by CMB, and the dominant contributor was traffic with >70% at the two sites. Fossil fuel burning, mineral industries, marine salt and natural gas-fired power plant were the minor contributors.


Advances in Ventricular Arrhythmia Ablation for Brugada Syndrome.
Three decades have passed since the Brugada syndrome (BrS) clinical entity was introduced in the early 1990s. During the first 2 decades, treatment of patients with BrS was challenging because there were limited treatment options, and an implantable cardioverter-defibrillator was the only choice for high-risk patients with BrS, that is, those who had aborted sudden cardiac death or had previous ventricular fibrillation episodes. In this article, the authors focus on these advances and how to treat patients with BrS with catheter ablation.


DNA methylation and mutation.
5-Methylcytosine (5mC) in DNA is produced by post-synthetic modification of cytosine residues, and it occurs primarily in CpG doublets in the mammalian genome. 5mC is a mutable site, because it can undergo spontaneous deamination to thymine. There is a repair mechanism which specifically recognises G.T mispairs, and replaces thymine with cytosine. However, this repair is not fully efficient, because the 5mC-->T transition mutation occurs about 10 times as frequently as other transitions. Such mutations are frequently seen in inherited diseases, and mutations in the p53 gene in tumours are also very commonly in 5mCpG doublets. As well as mutations, there can also be heritable changes in DNA methylation, known as epimutations, which may be of particular significance in somatic cells. Whereas the pattern of DNA methylation is very constant for any one cell type, the pattern becomes very variable in tumour cells. The breakdown of the normal controls of DNA methylation in tumorigenesis can lead to increased gene expression or to gene silencing. DNA damage increases not only mutation, but also heritable changes in methylation. At present, little is known about the ability of DNA repair to preserve the normal pattern of methylation in somatic cells.


Synthesis and Antiviral Evaluation of 3'-Fluoro-5'-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents.
Carbocyclic nucleoside analogues are an essential class of antiviral agents and are commonly used in the treatment of viral diseases (hepatitis B, AIDS). Recently, we reported the racemic synthesis and the anti-human immunodeficiency virus activities (HIV) of 3'-fluoro-5'-norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base. Based on these results, the corresponding racemic norcarbocyclic nucleoside phosphonates bearing pyrimidine bases were synthesized. The prepared compounds were evaluated against HIV, but none of them showed marked antiviral activity compared to their purine counterparts.


On the possible amyloid origin of protein folds.
The diversity of protein folds is derived from the diversity of the underlying proteome. Such diversity must have originated from a so-called common ancestor: a hypothetical fold whose identity will, in all likelihood, never be known. Nonetheless, hypotheses exist to explain the evolution of protein folds. When formulating such hypotheses as done here, the entire repertoire of polypeptide structure, from well-defined tertiary structures and molten globule states to intrinsically disordered proteins and oligomeric aggregates, is worth considering. It is the aim of this short essay to discuss the hypothesis that one type of protein aggregate-the cross-β-sheet motif-was the first functional protein fold, that is, the common ancestor fold. Support for this hypothesis comes from the observations that (i) short peptides with simple amino acid sequences are able to form the cross-β-sheet structure, (ii) amyloids can be very stable under harsh conditions, (iii) amyloids can self-assemble in complex mixtures, (iv) amyloids have many potent activities that are attributable to the inherent repetitiveness of the structure, and (v) the proteomes of modern organisms appear to have evolved away from the more amyloidogenic sequences of older organisms, suggesting that amyloids were more ubiquitous earlier in the evolution of modern protein folds.


Polyclonal antibodies against human fibroblast collagenase and the design of an enzyme-linked immunosorbent assay to measure TIMP-collagenase complex.
A polyclonal antibody has been raised against purified human fibroblast collagenase and characterised. This antibody has been used in combination with a monoclonal anti-TIMP antibody in a double antibody sandwich ELISA to measure TIMP-collagenase complex. The assay range was 5-50 ng/ml complex, quantitated in terms of the TIMP component. The assay can measure complex even in the presence of at least a 40-fold excess of free TIMP. The level of TIMP-collagenase complex has been measured in serial samples of synovial fluid from two patients with septic arthritis; high levels of complex are found in some samples, and the level of complex shows an inverse relationship with the level of free TIMP.


Clinical pharmacokinetics of ciclosporin A in bone marrow transplantation patients.
Ciclosporin A (CsA) plasma concentrations were monitored by radioimmunoassay after administration IV and PO to 15 patients before allogeneic bone marrow transplantation. The clearance (10.4 +/- 5.41 1/h), half-life (26.4 +/- 14.6 h), and bioavailability (16% +/- 10%) calculated directly from experimental data showed wide interindividual variations. The kinetics after IV infusion, monitored over 2-5 days, appeared to be triphasic. A three-compartment open mamillary model was thus used to simulate the distribution and elimination kinetics of CsA. The distributive delay between administration PO and absorption in the plasma was approximated using a series of six additional compartments connected with a single transfer rate constant. Then, for each patient, the experimental data corresponding to both IV and PO administration were fitted using a single set of rate constants. Clearance and bioavailability calculated from model parameters correlated well with direct estimations obtained from the areas under the concentration time curves. Drug monitoring and linear modeling will be used in an attempt to achieve stable predetermined plasma concentrations of CsA in bone marrow transplantation patients receiving the drug either IV or PO.


Neuronal expression of keratinocyte-associated transmembrane protein-4, KCT-4, in mouse brain and its up-regulation by neurite outgrowth of Neuro-2a cells.
One group of proteins that regulates neurite outgrowth and maintains neuronal networks is the immunoglobulin superfamily (IgSF). We previously identified a new member of the IgSF, keratinocyte-associated transmembrane protein-4 (KCT-4), by the signal sequence-trap method from primary cultured human keratinocytes. The KCT-4 mRNA has been found to be highly expressed in the adult human brain, although it is also distributed in various tissues. In the present study, to gain insight into the role of KCT-4 in the nervous system, we examined the expression profile and localization of KCT-4 mRNA in mouse brain. We also evaluated changes in KCT-4 mRNA expression in the differentiation of the neuroblastoma cell line Neuro-2a as the in vitro model of neurite outgrowth. KCT-4 mRNA was detected broadly in various regions of the adult mouse brain by RT-PCR. In situ hybridization revealed that it was expressed highly selectively by neurons but not by glial cells. Moreover, expression of KCT-4 mRNA was induced by neurite outgrowth of Neuro-2a. These data suggest that KCT-4 participates in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.


Outcome of Second Allogeneic Hematopoietic Cell Transplantation after Relapse of Myeloid Malignancies following Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort on Behalf of the Grupo Español de Trasplante Hematopoyetico.
Allogeneic stem cell transplantation (allo-HCT) represents the most effective immunotherapy for acute myeloid leukemia (AML) and myeloid malignancies. However, disease relapse remains the most common cause of treatment failure. By performing a second allo-HCT, durable remission can be achieved in some patients. However, a second allo-HCT is of no benefit for the majority of patients, so this approach requires further understanding. We present a retrospective cohort of 116 patients diagnosed with AML, myelodysplastic syndromes, and myeloproliferative disorders who consecutively underwent a second allo-HCT for disease relapse. The median age was 38 years (range, 4 to 69 years). Sixty-three patients were alive at last follow-up. The median follow-up of the whole cohort was 193 days (range, 2 to 6724 days) and the median follow-up of survivors was 1628 days (range, 52 to 5518 days). Overall survival (OS) at 5 years was 32% (SE ± 4.7%). Multivariate analysis identified active disease status (P < .001) and second allo-HCT < 430 days (the median of the time to second transplantation) after the first transplantation (P < .001) as factors for poor prognosis, whereas the use of an HLA-identical sibling donor for the second allo-HCT was identified as a good prognostic factor (P < .05) for OS. The use of myeloablative conditioning (P = .01), active disease (P = .02), and a donor other than an HLA-identical sibling (others versus HLA-identical siblings) (P = .009) were factors statistically significant for nonrelapse mortality in multivariate analysis. Time to second transplantation was statistically significant (P = .001) in the relapse multivariate analysis, whereas multivariate analysis identified active disease status (P < .001) and time to second transplantation (P < .001) as poor prognosis factors for disease-free survival. This study confirms active disease and early relapse as dismal prognostic factors for a second allo-HCT. Using a different donor at second allo-HCT did not appear to change outcome, but using an HLA-identical sibling donor for a second transplantation appears to be associated with better survival. Further studies are warranted.


Quantitative assessments of the effect of bilateral subthalamic stimulation on multiple aspects of sensorimotor function for patients with Parkinson's disease.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of advanced Parkinson's disease. Most studies have evaluated the effectiveness of DBS of the STN using clinical motor scores or simple timed tests of motor function. There have been few studies that quantitatively assessed the outcome of STN DBS using multiple testing paradigms. In the current study, 11 patients who had bilateral STN DBS were quantitatively evaluated under four conditions using gait, postural control, and gait initiation. The four conditions included the medication on/stimulation on (M_on/S_on), medication on/stimulation off (M_on/S_off), medication off/stimulation on (M_off/S_on), and medication off/stimulation off (M_off/S_off) conditions. DBS of the STN significantly increased walking speed with and without levodopa, but had no influence on the cadence. The addition of levodopa had a minimal additional effect on walking speed. The effect of STN DBS on gait initiation approached the significant level. The mean values of lateral body sway during quiet standing increased moderately with medication and/or DBS, but the changes were not statistically significant. Future studies need to determine whether or not there is a potential negative effect of STN DBS on the postural control.


IFNγ induces Bcl3 expression by JAK1/STAT1/p65 signaling, resulting in increased IL-8 expression in ovarian cancer cells.
We have recently shown that IFNγ, produced during cancer therapy, induces expression of the Bcl3 proto-oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation, migration, and invasion, but the mechanisms are unknown. Here, we demonstrate that the IFNγ-induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFκB. Furthermore, the IFNγ-induced Bcl3 expression is associated with an increased occupancy of Ser-727 phosphorylated STAT1 and acetylated histone H3 at the Bcl3 promoter. Our data indicate that Bcl3 promotes expression of the pro-inflammatory chemokine interleukin-8 (IL-8) in OC cells. These findings identify Bcl3 as a novel target of IFNγ/JAK1/STAT1 signaling and suggest that targeting the JAK1/STAT1 pathway may suppress IFNγ-induced Bcl3 expression in OC.


Comparative pathology of Prudhoe Bay crude oil and inert shell sealants in chicken embryos.
Pathological changes and body weights were compared in 9-day-old chicken embryos exposed to Prudhoe Bay Crude Oil (PBCO), pharmaceutical mineral oil, or a sealing film on the eggshell. Embryos exposed to 10 or 20 microliters PBCO developed marked ascites or subcutaneous edema, extensive liver necrosis, dilation of the heart, and cellular casts and mineralization in renal tubules. Wet and dry body weights were normal or above normal in embryos exposed to PBCO. No changes were found in embryos exposed to 10 microliters mineral oil; embryos exposed to 20 microliters mineral oil had slight dilation of the heart. Very few embryos survived in eggs that were wrapped in sealing film. All embryos that did survive had greatly reduced body weight and marked dilation of the heart. Four of these embryos had vacuolation of hepatocytes at the surface of the liver, one had superficial liver necrosis, and one embryo had slight ascites. These results indicate that the mechanism of the toxic action of PBCO on the avian embryo involves more than simple physical sealing of the shell.


Ultrasonography and computer tomography in orbital diagnosis. With special reference to dysthyroid ophthalmopathy.
A report is given on a series of 162 patients referred for ultrasound examination (US, A-mode) due to orbital disease. 101 also had computerized tomography (CT, Emi scanner Mark I, 160 X 160 matrix, 8 mm sections), the results of which were emphasized in a recent publication (Gyldensted et al. 1977). The present approach is primarily clinical. With histopathological confirmation in only 40% of the cases, it is difficult to give exact values for diagnostic accuracy, but it appeared to be above 90% for CT, and close to this value for US (depending on, of course, how specified the diagnostic predictions were). Dysthyroid ophthalmopathy (DO, orbital Graves' disease, endocrine exophthalmos) was the most frequent cause of unilateral protrusion (24 cases). In some such cases "tumour-positive" CT scans represent a diagnostic pitfall, unless the examiner is familiar with the clinical features of DO. In the present series, for example, one of the DO cases had transcranial exploration of the orbit. The two--indeed valuable--non-invasive methods (CT and US) should be assessed in combination, and also combined with the classic clinical evaluation of the patient.


Measurement of ultrasonic nonlinear parameter in excised fat tissues.
This paper reports sound speed co, adiabatic acoustic nonlinear parameter B/A, and isothermal nonlinear parameter (B/A)' of 33 samples of excised human and animal fats and some simple mixtures, e.g., skim milk and powdered milk. Tissues were obtained from different parts of the body and the measurements were made in the temperature range of 20 degrees C to 37 degrees C. All the fats were highly nonlinear. Although there was a considerable overlap in the values of acoustic nonlinearity of different body fats, in general their values followed the order: mesenteric fat greater than subcutaneous fat greater than omentum fat greater than breast fat. Temperature coefficients of co and B/A, and the difference between adiabatic and isothermal nonlinearity, correlated highly with water/fat content of tissues. A reciprocal relationship between B/A and co, similar to that proposed for liquids, was observed for soft tissues but not for solutions of powdered milk in skim milk. No significant correlation was observed between acoustic measurements and the age of human subjects from which fat tissues were obtained.


Phase I and Pharmacokinetic Study of Romidepsin in Patients with Cancer and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study.
Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.


Appetite-modifying effects of bombesin receptor subtype-3 agonists.
Studies on bombesin-like peptides (BLP) and their respective mammalian receptors (Bn-r) have demonstrated a significant biological impact on a broad array of physiological and pathophysiological conditions. Pharmacological experiments in vitro and in vivo as well as utilization of genetic rodent models of the gastrin-releasing peptide receptor (GRP-R/BB2-receptor), neuromedin B receptor (NMB-R/BB1-receptor), and the bombesin receptor subtype-3 (BRS-3/BB3-receptor) further delineated their role in health and disease. All three mammalian bombesin receptors have been shown to possess some role in the regulation of energy balance and appetite and satiety. Compelling experimental evidence has accumulated indicating that the orphan BRS-3 is an important regulator of body weight, energy expenditure, and glucose homeostasis. BRS-3 possesses no high affinity to the endogenous bombesin-like peptides (BLP) bombesin, GRP, and NMB, and its endogenous ligand remains unknown. Recently, the synthesis of novel, selective high-affinity BRS-3 agonists and antagonists has been accomplished and has demonstrated that BRS-3 regulates energy balance independent of other established pathways. Accordingly, the availability of new BRS-3 selective agonists and antagonists will facilitate further elucidation of its role in energy homeostasis and provides a potential approach for the pharmacological treatment of obesity.


Intracavitary heart fibroma. A case of successful total excision.
Tumors of the heart are relatively rare events and fibromas represent no more than 5% of these. A central source of peripheral embolization suggests the possibility to kept in mind in the absence of other causes and is therefore worthy of closer investigation.


[Pathophysiology of venous thrombosis (author's transl)].
The pathophysiology of venous thrombosis is determined mainly by the triad of Virchow (hypocirculation, endothelial lesion of vessels, coagulation disturbances). Various predisposing factors are known. Thrombocytes are of utmost importance in the initial phase of thrombus formation, while fibrin and red cells influence the length of the clot and the extent of pulmonary embolism. Postoperative venous thrombosis occurs more frequently and earlier than hitherto thought (radiofibrinogen test). General prophylaxis is indicated for its effective prevention.


Characterization and expression analysis of basic leucine zipper (bZIP) transcription factors responsive to chilling injury in peach fruit.
Peach (Prunus persica L.) is prone to chilling injury as exhibited by inhibition of the ethylene production, failure in softening, and the manifestation of internal browning. The basic leucine zipper (bZIP) transcription factors play an essential role in regulatory networks that control many processes associated with physiological, abiotic and biotic stress responses in fruits. Formerly, the underlying molecular and regulatory mechanism of (bZIP) transcription factors responsive to chilling injury in peach fruit is still elusive. In the current experiment, the solute peach 'Zhongyou Peach No. 13' was used as the test material and cold storage at low temperature (4 °C). It was found that long-term low-temperature storage induced the production of ethylene, the hardness of the pulp decreased, and the low temperature also induced ABA accumulation. The changes of ABA and ethylene in peach fruits during low-temperature storage were clarified. Since the bZIP transcription factor is involved in the regulation of downstream pathways of ABA signals, 47 peach bZIP transcription factor family genes were identified through bioinformatics analysis. Further based on RT-qPCR analysis, 18 PpbZIP genes were discovered to be expressed in refrigerated peach fruits. Among them, the expression of PpbZIP23 and PpbZIP25 was significantly reduced during the refrigeration process, the promoter analysis of these genes found that this region contains the MYC/MYB/ABRES binding element, but not the DRES/CBFS element, indicating that the expression may be regulated by the ABA-dependent cold induction pathway, thereby responding to chilling injury in peach fruit. Over investigation will provide new insights for further postharvest protocols related to molecular changes during cold storage and will prove a better cope for chilling injury.


Outcomes Among High-Risk and Standard-Risk Multiple Myeloma Patients Treated With High-Dose Chemotherapy and Autologous Hematopoietic Stem-Cell Transplantation.
Conventional cytogenetics and interphase fluorescence in-situ hybridization (FISH) identify a high-risk multiple myeloma population characterized by poor response and short survival. We compared outcomes between high-risk and standard-risk myeloma patients who underwent autologous hematopoietic stem-cell transplantation (auto-HCT) at our institution between January 2005 and December 2009. High-risk myeloma was defined as -13/del(13q) or hypodiploidy in at least 2 metaphases of conventional cytogenetics, or -17/del(17p), t(4;14), t(14;16), t(14;20), hypodiploidy (< 45 chromosomes excluding -Y), or chromosome 1 abnormalities (+1q, -1p, t(1;x)) on FISH or conventional cytogenetics. Of 670 myeloma patients, 74 (11%) had high-risk myeloma. These high-risk patients had significantly lower overall response rates (74% vs. 85%; P < .01), shorter median progression-free survival (10.3 vs. 32.4 months; P < .001), and shorter overall survival (28 months vs. not reached; P < .001) than the standard-risk patients. Having only 1 high-risk cytogenetic abnormality or experiencing at least very good partial remission after auto-HCT independently predicted improved progression-free survival and overall survival (P < .05) in high-risk patients. Even in an era of novel therapies, cytogenetically identified high-risk myeloma patients have worse prognoses than standard-risk myeloma patients after auto-HCT, and having more than 1 high-risk cytogenetic abnormality further reduces survival.


Quantum Router for Single Photons Carrying Spin and Orbital Angular Momentum.
Quantum router is an essential element in the quantum network. Here, we present a fully quantum router based on interaction free measurement and quantum dots. The signal photonic qubit can be routed to different output ports according to one control electronic qubit. Besides, our scheme is an interferometric method capable of routing single photons carrying either spin angular momentum (SAM) or orbital angular momentum (OAM), or simultaneously carrying SAM and OAM. Then we describe a cascaded multi-level quantum router to construct a one-to-many quantum router. Subsequently we analyze the success probability by using a tunable controlled phase gate. The implementation issues are also discussed to show that this scheme is feasible.


Rating scales for hyperactivity: concurrent validity, reliability, and decisions to label for the Conners and Davids Abbreviated Scales.
Rating scales have become the instrument of choice in labeling and assessing change in behavior of hyperactive children. However, several criticisms have recently have levied against their use. The present investigation examined the concurrent validity, and inter- and intrarater reliability for the Abbreviated Teacer Questionnaire (ATQ, Conners, 1973) and the Rating Scales for Hyperkinesis (Davids, 1971). Sixteen teachers from two special and two regular schools (grades 1-4) rated 211 normal and 49 special children using both scales. High correlations were found suggesting excellent predictability between scales and considerable stability across time and rater. Lower scores on a subsequent rating relative to an initial rating were demonstrated, dependent on time between ratings but independent of (a) teacher expectation of treatment gains, (b) bias produced by rating selected children, and (c) whether children were hyperactive or normal. Use of initial and infrequent rating scores versus subsequent, closely spaced ratings was related to the rater's objective (e.g., diagnosis, treatment, or assessment).


Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs.
The migration of B cells into secondary lymphoid organs is required for the generation of an effective immune response. Here we analyzed the involvement of SWAP-70, a Rac-interacting protein involved in actin rearrangement, in B cell entry into lymph nodes. We noted reduced migration of Swap70-/- B cells into lymph nodes in vivo. Swap70-/- B cells rolled and adhered, yet accumulated in lymph node high endothelial venules. This defect was not due to impaired integrin expression or chemotaxis. Instead, Swap70-/- B cells aberrantly regulated integrin-mediated adhesion. During attachment, Swap70-/- B cells showed defective polarization and did not form uropods or stabilize lamellipodia at a defined region. Thus, SWAP-70 selectively regulates processes essential for B cell entry into lymph nodes.


Purification and characterization of photosystem I and photosystem II core complexes from wild-type and phycocyanin-deficient strains of the cyanobacterium Synechocystis PCC 6803.
Highly photoactive Photosystem I (PS I) and Photosystem II (PS II) core complexes have been isolated from the cyanobacterium Synechocystis Pasteur Culture Collection (PCC) 6803 and a phycocyanin-deficient mutant, enriched in PS II. Cell breakage using glass beads was followed by sucrose density gradient centrifugation and two high-performance liquid chromatography steps involving anion-exchange and hydroxyapatite. The PS I core complex has an apparent molecular mass of 300 +/- 20 kDa (including a detergent shell of about 50 kDa) and contains subunits of approximately 60, approximately 60, 18.5, 18.5, 16, 15, 10.5, 9.5, and 6.5 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblots; its antenna size is 75 +/- 5 chlorophyll/P-700. The PS II core complex has an apparent molecular mass of 310 +/- 20 kDa (including the detergent shell); subunits of 43, 37, 33, 29, and 10-11 kDa were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The antenna size of the average PS II complex is 45 +/- 5 chlorophyll/primary quinone electron acceptor (QA). This preparation procedure also yields, as a byproduct, a highly purified cytochrome b6f complex. This complex contains four subunits of 38, 24, 19, and 15 kDa and b- and c-type cytochromes in a ratio of 2:1. Its apparent molecular mass of 180 +/- 20 kDa (including the detergent shell) is consistent with a monomeric complex.


Electroretinogram abnormalities in nonanterior childhood uveitis.
A major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full-field electroretinography (ERG). Cross-sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score. The ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b-wave (37%; n = 23/63) and an abnormal 30-Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00-0.15 LogMAR). The ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long-term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies.


Women's perceptions and experiences of group cognitive behaviour therapy and other group interventions for postnatal depression: a qualitative synthesis.
This paper is a report of a systematic review that aimed to synthesize qualitative evidence relating to women's perceptions and experiences of group cognitive behaviour therapy and other group interventions for postnatal depression. Postnatal depression may occur in women following childbirth, resulting in a range of distressing symptoms such as sadness, fatigue, and feelings of inability to look after their baby. Women tend to prefer psychological interventions. However, access to individual psychological therapy is limited by cost, waiting times, and availability of therapists. A comprehensive literature search was conducted in 17 major psychological, medical, health-related and health economics electronic bibliographic databases. A qualitative evidence synthesis was conducted using thematic synthesis. Databases were searched from 1966-January 2008. A total of 116 full papers were screened against the inclusion criteria. Included papers were quality assessed. The original review protocol was restricted to evidence on group cognitive behaviour therapy. However, due to the paucity of evidence, the inclusion criteria were broadened to include other group interventions. A thematic synthesis was undertaken of the data extracted from the included papers. Six studies were included. Specific benefits were that treatment enabled women to develop better relationships with their baby and understand postnatal depression. Negative aspects of treatment included difficulties in applying cognitive behavioural techniques, and unfavourable social comparisons with other group members. Women have contrasting perceptions and experiences of group treatment. This suggests that greater attention should be focused on identifying those most likely to benefit from these treatments in a group environment.


SGA subtypes and mortality risk among singleton births.
To determine whether early mortality (first year of life) risks among small for gestational age (SGA) neonates were similar regardless of SGA subtype based on three chronological classifications (term, preterm and post-term). Retrospective cohort study on all singleton live births in the United States from 1995 to 1999 inclusive. Adjusted risk estimates were computed from logistic regression models using non-SGA infants as the referent. When SGA infants were compared as a homogeneous entity to non-SGA infants, the risks for infant, neonatal and post-neonatal mortality were significantly greater in SGA infants [AOR (adjusted odds ratio)=3.0, 95% CI (confidence interval)=2.9-3.0 for infant mortality; AOR=3.2, 95% CI=3.1-3.2 for neonatal mortality; and AOR=2.6, 95% CI=2.6-2.7 for post-neonatal mortality]. However, heterogeneity existed in terms of mortality risk thresholds across SGA babies. The most remarkable risk magnitude was observed among preterm SGA infants [infant mortality AOR=13.8, 95% CI=13.6-14.1; neonatal death AOR=17.4, 95% CI=17.0-17.7; and post-neonatal death AOR=7.4, 95% CI=7.1-7.6]. The adjusted odds ratio for term and post-term SGA infants were comparable regardless of the period during infancy, and were much less than those observed for preterm SGA infants. SGA is a heterogeneous disease in terms of prognosis for survival. Preterm SGA infants bear an extremely high risk for mortality during infancy, and counseling of affected parents should reflect this risk divergence.


Host defense effector molecules in mucosal secretions.
Mucosal secretions contain a range of defense effector molecules including antimicrobial peptides and proteinase inhibitors. These molecules play a central role in host defense against infection, and in a variety of immune and inflammatory reactions. The aim of this study was to analyze the levels of neutrophil defensins, the cathelicidin hCAP-18/LL-37, and the proteinase inhibitors secretory leukocyte proteinase inhibitor, SKALP/elafin and cystatin M/E in various mucosal secretions and urine. We show here that especially seminal plasma is characterized by high concentrations of hCAP-18/LL-37, SLPI, SKALP/elafin and cystatin M/E. The results of this study demonstrate that each mucosal secretion is characterized by a unique profile of effector molecules, which may supply individual mucosal secretions with specific properties related to the control of local infection and inflammation.


Methionine adenosyltransferase: structure and function.
Methionine adenosyltransferase (MAT), a key enzyme in metabolism, catalyzes the synthesis of one of the most important and pivotal biological molecules, S-adenosyl-methionine. In every organism studied thus far, MAT exists in multiple forms; most are encoded by related, but distinct genes. Molecular and immunological studies revealed the presence of considerable conservation in the structure of MAT from different species; however, the various MAT isozymes differ in their physical and kinetic properties in ways that allow them to be regulated differently. Recent studies suggest that human MAT is composed of nonidentical subunits that can assume multiple states of aggregation, each with different kinetic characteristics. The tissue distribution of MAT isozymes and the ability of cells within the same tissue to switch between the different forms of MAT suggest that this mode of regulation is important for cellular function and differentiation. Therefore, understanding the regulation and structure-function relationship of this fascinating enzyme should help us clarify its role in biology and may provide us with tools to effectively manipulate its activity in clinical situations such as cancer, autoimmunity and organ transplantation.


Substance Use in Adults With Type 1 Diabetes in the T1D Exchange.
The purpose of the study was to evaluate frequency of use and problem use of psychoactive substances in adults with type 1 diabetes (T1D). Standardized instruments for assessing tobacco, alcohol, and other psychoactive substance use were emailed to 4311 adult participants at 69 T1D Exchange Registry Exchange Registry centers. A total of 936 respondents (61% female, 90% non-Hispanic white, age 38 ± 16 years) completed the survey. In the sample, 166 (18%) reported past-year use of tobacco and 51 (5%) reported daily use. Past-year alcohol use was reported by 742 (79%) participants, past-month use by 592 (63%), and daily/near-daily use by 87 (9%); 174 (19%) were classified as binge drinkers and 93 (11%) as problem drinkers. Nonprescription use of another psychoactive substance in the past year was reported by 228 (24%), with 167 (18%) indicating they used marijuana, 67 (7%) opioids, 45 (5%) sedatives, and 37 (4%) stimulants. Past-year problem use of these substances was noted in 31 (3%) respondents. Adults with T1D in the United States use substances at rates that meet or exceed the general population; problematic use occurs at rates similar to the general population. These data delineate the need to inquire about regular, intermittent, and problematic use of nicotine and other substances in individuals with T1D. A better understanding of the impact of moderate and occasional use of substances on T1D management and clinical outcomes is needed.


The effect of treatment with clofibrate on hepatic triglyceride and lipoprotein lipase activities of post heparin plasma in male patients with hyperlipoproteinemia.
Twelve male patients with hyperlipoproteinemia were treated with clofibrate, 1 g twice daily. Serum triglyceride concentration decreased on the average 28 +/- 6%. No significant change of serum cholesterol concentration occurred. Post heparin plasma lipoprotein lipase activity isolated and partially purified by heparin Sepharose affinity chromatography was determined quantitatively. During the clofibrate treatment this enzyme activity increased 48 +/- 9%. The post heparin hepatic triglyceride lipase did not change significantly. The possibility that the serum triglyceride-lowering effect of clofibrate might partly be explained by an increased removal rate of triglyceride rich lipoproteins through increased lipoprotein lipase activity is discussed.


Young adults with nonalcoholic fatty liver disease, defined using the fatty liver index, can be at increased risk of myocardial infarction or stroke.
To investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and cardiovascular events among a nationally representative sample of young adults in Korea. This population-based cohort study from the Korean National Health Insurance Service included adults who were aged 20 to 39 years when they underwent a health examination between 2009 and 2012. NAFLD was defined as a fatty liver index (FLI) ≥60, and participants were divided into three groups according to FLI (<30, 30-59 and ≥60) to investigate the dose-dependent effect of FLI score. Among 5 324 410 participants, 9.8% had an FLI ≥60. There were 13 051 myocardial infarctions (MIs; 0.39%) and 8573 strokes (0.26%) during a median follow-up of 8.4 years. In multivariable analysis, NAFLD was associated with a higher risk of MI and stroke (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.61-1.77 and HR 1.73, 95% CI 1.63-1.84, respectively). MI and stroke had dose-dependent relationships with FLI (HR 1.28 in participants with FLI 30-59 and 1.73 in those with FLI ≥60 for MI and HR 1.18 in participants with FLI 30-59 and 1.41 in those with FLI ≥60 for stroke, respectively). Nonalcholic fatty liver disease was an independent predictor of MI and stroke in young adults. These results suggest that primary prevention of cardiovascular disease should be emphasized in young adults with NAFLD.


The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia.
Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22-0.89) was significantly associated with 30-day mortality. Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.


Gene transfer of dimethylarginine dimethylaminohydrolase-2 improves the impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells induced by lysophosphatidylcholine.
Dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for the metabolism of nitric oxide (NO) synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA), and DDAH2 is the predominant isoform in vascular endothelium. Lysophosphatidylcholine (LPC) and ADMA are implicated in endothelial dysfunction of atherosclerosis. This study was to examine changes in DDAH/ADMA/NOS/NO pathway in endothelial cells after exposure to LPC and investigate whether DDAH2 gene transfer could reverse LPC-induced changes. Human endothelial cell line ECV304 cells were transfected with recombinant pcDNA3.1-hDDAH2 plasmid and incubated with 3 micromol/L LPC for 48 h. Cells were harvested for assays of DDAH transcription, DDAH and NOS activities. The culture medium was collected for measurements of ADMA and nitrite/nitrate concentrations. LPC treatment suppressed DDAH2 transcription and DDAH activity in parallel with increased ADMA concentration, inhibited NOS activity and decreased NO metabolites content. DDAH2 gene transfer not only prevented the suppression of DDAH activity and the elevation of endogenous ADMA, but also attenuated the inhibition of NOS activity and the reduction of NO level induced by LPC in endothelial cells. These results suggest that LPC induces impairments of DDAH/ADMA/NOS/NO pathway, and DDAH2 gene transfer could improve the LPC-elicited impairments in endothelial cells.


The effect of motor-response-deprivation on contingent negative variation (CNV): the morphology.
Eighty-four healthy subjects (47 males and 37 females) ranging in age between 9 and 76 years were employed in a study of the relations of the CNV morphology with the CNV amplitude, the reaction time and the MPI score. The results were as follows: 1. We classified a new type of Plateau (P) in the negative-going limb (NGL) types. 2. There was no sex difference in the NGL types, but the positive-going limb (PGL) types were influenced by age, and the type II tended to increase between the ages of 40--59 years old. 3. As a whole, the type B in the NGL and the type I in the PGL were most prominent regardless of age, session or paradigm. The type FD was very rare and appeared only in the session N. The types III and IV failed to be found in any healthy subjects. 4. Using the matched control study, the relations of the morphology with the CNV amplitude, the reaction time and the MPI score were analyzed. The conventional CNV amplitude in the sessions C and R increased in the sequences of the types B-A-P and the types I-II, and the CNV amplitudes in the session N increased in the sequences of the types A-B-P and II-I. The reaction time in the sessions C and R tended to prolong in the sequences of the types P-B-A and II-I. With the MPI, as the N-score increased with a decrease of the E-score, the NGL types changed from the type P to A through B in the conventional CNV and from the type A to B or P in the session N, while the PGL types changed from the type I to II in the conventional CNV and from the type II to I in the session N. 5. We suggest that there is a twofold arousal process, specific (task-relevant) and general, behind these types and that the dynamic balance of this process may influence psychological manifestations.


[The role of serotonin in regulating lipid metabolism in rat liver].
Serotonin is shown to have different effects on the lipid fractions metabolism in the rat liver homogenate and mitochondria depending upon the serotonin concentration. The low serotonin concentration (0.2 mg per 100 g of weight) enhanced lipogenesis in the rat liver; on the contrary, the high serotonin concentration (2 mg per 100 g), as a rule, inhibited this process. It is supposed that the serotonin effect is mediated by the adenyl cyclase system in a cell.


Preliminary Study of the Autism Self-Efficacy Scale for Teachers (ASSET).
The purpose of the current study was to evaluate a new measure, the Autism Self-Efficacy Scale for Teachers (ASSET) for its dimensionality, internal consistency, and construct validity derived in a sample of special education teachers (N = 44) of students with autism. Results indicate that all items reflect one dominant factor, teachers' responses to items were internally consistent within the sample, and compared to a 100-point scale, a 6-point response scale is adequate. ASSET scores were found to be negatively correlated with scores on two subscale measures of teacher stress (i.e., self-doubt/need for support and disruption of the teaching process) but uncorrelated with teacher burnout scores. The ASSET is a promising tool that requires replication with larger samples.


[The leprosy "drama": Governador Valadares, public health policies, and their territorial implications in the 1980s].
The incidence of leprosy in Governador Valadares, Brazil, in the 1980s spurred this town to pioneer the introduction of polychemotherapy. The aim of this research was to understand how the different actors involved in this context interacted, especially the employees and patients at the Special Public Health Service. To identify the territories that these interactions inevitably constituted, a variety of theoretical instruments were used, including dramatism (Burke) and performance (Turner). By taking a theatrical metaphor, we sought to find out the dynamics by which the different actors took the stage and established their most significant relationships in a dynamic process of constituted and reconstituted territories.


Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice.
Obesity is associated with accumulation of macrophages in white adipose tissue (WAT), which contribute to the development of insulin resistance. Germ-free (GF) mice have reduced adiposity and are protected against diet-induced obesity, To investigate whether the gut microbiota and, specifically, gut-derived lipopolysaccharide (LPS) promote WAT inflammation and contribute to impaired glucose metabolism. Macrophage composition and expression of proinflammatory and anti-inflammatory markers were compared in WAT of GF, conventionally raised and Escherichia coli-monocolonised mice. Additionally, glucose and insulin tolerance in these mice was determined. The presence of a gut microbiota resulted in impaired glucose metabolism and increased macrophage accumulation and polarisation towards the proinflammatory M1 phenotype in WAT. Monocolonisation of GF mice for 4 weeks with E. coli W3110 or the isogenic strain MLK1067 (which expresses LPS with reduced immunogenicity) resulted in impaired glucose and insulin tolerance and promoted M1 polarisation of CD11b cells in WAT. However, colonisation with E. coli W3110 but not MLK1067 promoted macrophage accumulation and upregulation of proinflammatory and anti-inflammatory gene expression as well as JNK phosphorylation. Gut microbiota induced LPS-dependent macrophage accumulation in WAT, whereas impairment of systemic glucose metabolism was not dependent on LPS. These results indicate that macrophage accumulation in WAT does not always correlate with impaired glucose metabolism.


Anorexia of Aging - An Updated Short Review.
The anorexia of aging affects approximately a quarter of older people and is a major contributor to the development of under-nutrition and many other adverse health outcomes in older people. Despite the high prevalence, the anorexia of aging is frequently overlooked by clinicians and, of even more concern, it is commonly accepted as inevitable and a part of 'normal' aging. Early identification of risk coupled with efforts to mitigate these risks through appropriate interventions might stem the deleterious consequences of the anorexia of aging. This review aims to provide an update on the current knowledge base whilst making some practical suggestions that may be of use in clinical practice. Interventions such as exercise and good nutrition remain the preferred treatment while pharmacological options, whilst they continue to be trialed, are not currently recommended for routine clinical use.


π-Conjugated Copper Phthalocyanine Nanoparticles as Highly Sensitive Sensor for Colorimetric Detection of Biomarkers.
Though numerous nanomaterials with enzyme-like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π-d delocalization effect of electrons, excellent metal-chelating property, high electron transferability, and good chemical stability of π-conjugated phthalocyanine, the design of the copper phthalocyanine-based conjugated polymer nanoparticles (Cu-PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu-PcCP NPs are synthesized through a simple microwave-assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu-PcCP NPs demonstrate excellent peroxidase-like detecting activity and also great substrate selectivity than most of the reported Cu-based nanomaterials. The Cu-PcCP NPs can achieve a detection limit of 4.88 μM for the H2 O2 , 4.27 μM for the L-cysteine, and 21.10 μM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme-like nanomaterials. Moreover, Cu-PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π-conjugated copper-phthalocyanine nanoparticles not only overcome the current limitation of polymeric material-based sensors but also provide a new direction for designing next-generation enzyme-like nanomaterial-based colorimetric biosensors.


Craniofacial growth variations in nasal-breathing, oral-breathing, and tracheotomized children.
Childhood oral breathing can alter muscular balance and lead to facial deformities. No articles in the literature have reported on the alteration of facial growth patterns in patients who have received tracheotomies. The purpose of this study was to evaluate craniofacial developmental consequences originating from variations in breathing mechanisms in children who are nasal breathers or oral breathers, and those who have been tracheotomized. The sample was divided into 3 groups of 10 each. The nasal group had a mean age of 13.9 years, the oral group had a mean age of 12.7 years, and the tracheotomy group had a mean age of 12.8 years. The masseter and suprahyoid muscles were evaluated with electromyography. The following measurements were made: facial, maxillary, and mandibular widths; nasion-sella-gnathion angle; and facial index. The tracheotomized group was similar to the nasal group for greater activity of the masseter muscles than of the suprahyoid muscles during mastication, as well as in the measurements of facial, maxillary, and mandibular widths. The oral group showed reductions in each category. The tracheotomized group was similar to the oral group during maximum dental occlusion for significantly higher activity of the suprahyoid muscles compared with the masseter muscles, with reductions in vertical values. A childhood tracheotomy might affect facial development in a way comparable with that of oral breathers, including abnormal facial growth variations.


Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation.
We have previously successfully expanded functional T-cells in vitro from cord blood grafts used for clinical transplantation, with the aim of creating donor lymphocyte infusions to treat e.g. malignant relapse. Here we show that the T-cell expansion in addition might work as a prognostic tool for complications after transplantation. We used multi-color flow cytometry to correlate in vitro phenotypical and functional data from 33 expansions to clinical outcome post-transplantation. Higher levels of CD69+ activated T-cells in the expansion were associated with prolonged survival of the patient. In addition, we found a correlation between T-cell expansions containing relatively high levels of effector memory T-cells and graft vs. host disease and relapse. Our data suggest that expansions of cord blood T-cells from the graft might not only be used as donor lymphocyte infusions, but also as in vitro indicators that could give essential information on how to manage cord blood transplanted patients.


Mechanism of blood pressure reduction by teprotide (SQ 20881) in rats.
The mechanism by which the angiotensin converting enzyme inhibitor, teprotide (SQ 20881), lowers blood pressure was assessed in anesthetized normotensive and spontaneously hypertensive (SHR) rats. Teprotide always was administered at a maximally effective dose of 1 mg/kg. In six normal Wistar rats, teprotide lowered blood pressure only after sodium depletion, an effect which was abolished by bilateral nephrectomy. Saralasin infusion (5 microgram/kg/min) into salt-depleted normal rats induced a blood pressure effect similar to that of teprotide. When administered in addition to saralasin infusion, teprotide did not reduce blood pressure further in normal rats or in SHR. When blood pressure of normal rats was raised by angiotensin II infusion (200 ng/kg/min), teprotide did not affect the induced blood pressure increase. In contrast, the pressure rise induced by angiotensin I infusion (230 ng/kg/min) was reversed by saralasin, but again concomitant administration of teprotide did not induce further blood pressure reduction. Thus, under the particular conditions of the present study, teprotide did not appear to exert its hypotensive effect by any mechanism other than inhibition of the renin-angiotensin system. Furthermore, given at a maximally effective dose to the rat, it produced no greater vasodepressor effect than did saralasin.


Nano-engineered materials for sensing food pollutants: Technological advancements and safety issues.
Food spoilage and safety are key concerns of the modern food sector. Among them, several types of polluting agents are the prime grounds of food deterioration. In this context, nanotechnology-based measures are setting new frontiers to strengthen food applications. Herein, we summarize the nanotechnological dimension of the food industry for both processing and packaging applications. Active bioseparation, smart delivery, nanoencapsulation, nutraceuticals, and nanosensors for biological detection are a few emerging topics of nanobiotechnology in the food sector. The development of functional foods is another milestone set by food nanotechnology by building the link between humans and diet. However, the establishment of optimal intake, product formulations, and delivery matrices, the discovery of beneficial compounds are a few of the key challenges that need to be addressed. Nanotechnology provides effective solutions for the aforementioned problem giving various novel nanomaterials and methodologies. Various nanodelivery systems have been designed, e.g., cochleate, liposomes, multiple emulsions, and polysaccharide-protein coacervates. However, their real applications in food sciences are very limited. This review also provides the status and outlook of nanotechnological systems for future food applications.


Strong bending of purple membranes in the M-state.
Structure changes of purple membranes during the photocycle were analysed in solution by measurements of the electric dichroism. The D96N-mutant was used to characterize the M-state at neutral pH. The transition from the resting state to 61% photo-stationary M-state is associated with a strong reduction of the dichroism decay time constant by a factor of approximately 2. Because the change of the time constant is independent of the bacteriorhodopsin concentration, the effect is not attributed to light-induced dissociation but to light-induced bending of purple membranes. After termination of light-activation the dichroism decay of the resting state is restored with a time constant close to that of the M-state decay, which is more than two orders of magnitude slower than proton transfer to the bulk. Thus, bending is not due to asymmetric protonation but to the structure of the M-state. A very similar reduction of decay time constants at a corresponding degree of light-activation was found for wild-type bacteriorhodopsin at pH-values 7.8-9.3, where the lifetime of the M-state is extended. Light-induced bending is also reflected in changes of the stationary dichroism, whereas the overall permanent dipole moment remains almost constant, suggesting compensation of changes in molecular and global contributions. Bead model simulations indicate that disks of approximately 1 microm diameter are bent at a degree of photo-activation of 61% to a radius of approximately 0.25 microm, assuming a cylindrical bending modus. The large light-induced bending effect is consistent with light-induced opening of the protein on the cytoplasmic side of the membrane detected by electron crystallography, which is amplified due to coupling of monomers in the membrane. Bending may function as a mechanical signal.


Double-Organ Bias in Controlled Trials on Eyelid Ptosis.
Proper statistical analysis is an essential element in the evaluation of clinical trial outcomes. We had the informal observation that double-organ bias was a neglected issue during the statistical analyses of clinical trials on eyelid ptosis. The aim of this study was to formally document the prevalence of this bias in these studies. Clinical trials on eyelid ptosis, published in the last 20 years, were searched in PubMed with the terms; "((blepharoptosis) OR upper eyelid ptosis) OR eyelid ptosis" and with the filters "Randomized Controlled Trial (RCT), Clinical Trial, Humans." Two independent observers evaluated the articles for eligibility, field of the journal, field of the authors, presence of randomization, type of the study (surgical, medical), and statistical approach to double organ bias. The PubMed search yielded 101 articles and 23 of them met the above-mentioned criteria. In 3 articles, primary outcome measure was not related with the eyes. Among the remaining 20 articles, 14 (70%) had double-organ bias in the statistics. The bias was slightly less common in randomized trials (60% vs. 80%), but the difference was not statistically significant. Its prevalence was similar between ophthalmology journals and the rest (p = 0.64). Interestingly, the bias tended to be more in Q1 journals (87.5%) compared to Q2 and Q3 journals (58.3%) and median impact factor was higher in biased articles (1.82 vs. 1.29), but the differences weren't statistically significant (p = 0.32, p = 0.24). There was no difference between the last 2 decades (66.6% vs. 75%, p = 0.64). The prevalence of the double-organ bias was very high in published clinical trials on eyelid ptosis (70%) and even among RCTs (60%). The prevalence of the bias didn't prevent publication in higher impact factor journals and didn't change between journals from different disciplines or over time.