The need to improve implementation and use of lifestyle surveillance systems for planning prevention activities: an analysis of the Italian Regions.
To describe the level of use of lifestyle surveillance systems in Italy and to identify predictors of their use by the Italian Regions for planning and monitoring purposes. Data were extracted from the 19 Regional Prevention Plans (RPPs) and the health promotion and prevention projects included in them developed by the Italian Regions within the National Prevention Plan 2010-2013. The 19 RPPs and the 702 projects were appraised using a tool specifically developed for the purpose. Multiple logistic regression was performed to identify predictors of use of surveillance systems in the 359 projects that could use them. The analysis of regional epidemiological contexts does not always rely upon surveillance system data and there were too few projects aimed at the maintenance and the development of these systems. Moreover, fewer than half of projects that could have used surveillance systems for planning and evaluation procedures actually did so, despite the potential value of these data. There was a statistically significant association between Regional Health Care Expenditure (RHCE) and the use of surveillance system data for planning and/or evaluation of the projects (OR 7.81, 95% CI 2.86-21.29). Use of surveillance systems for regional prevention planning in Italy is not optimal due to late implementation, presence of different data collecting systems and RGDP inequalities. There is a pressing need for full implementation of surveillance systems to allow better definition of the priorities and objectives of public health interventions.


Factors Affecting Visual Field Outcome Post-Surgery in Sellar Region Tumors: Retrospective Study.
Despite the broad category of differentials for sellar region, most of them present with similar clinical signs and symptoms. Headache and visual disturbance are among the frequently seen as presenting symptom. Visual field (VF) assessment is one of the crucial component of neuroophtalmologic assessment and mean deviation (MD) value from automated perimetry allows quantification of the visual field defect. We formulated a study to look into the factors that affect the visual field outcome after surgery. All patients with sellar region tumor who has underwent surgery in Queen Elizabeth Hospital from July 2010 to July 2016 were retrospectively analysed through hospital notes. VF assessment via Humphrey visual assessment for these patient pre and post-surgery were reviewed for MD value. Eighty four patients were recruited and out of them, 151 eyes were taken into analysis after excluding eyes with missing data. Mean age of patients were 45.4 years with 70.2% of them were male. Visual disturbance is the commonest presenting symptom with mean duration of symptom prior to surgery is 9.7 months. Majority of them were pituitary adenomas (75%) followed by sellar meningioma (19%), craniopharyngioma (4.8%), and rathke cleft cyst (1.2%). 70.9% of patients showed improvement in VF based on MD outcome. Mean MD for pre surgery and post-surgery were -14.0 dB and -12.4 dB, respectively. Univariate analysis reveals younger age, female sex, shorter duration of symptom, pituitary adenoma, transsphenoidal approach, and transcranial approach favours improvement in VF. Multivariate analysis shows only shorter symptom duration, transphenoidal approach, and transcranial approach are significant for favourable VF outcome when other factors adjusted. Symptom duration and surgical approach were independent factors that affects the visual field after surgery in patients with sellar region tumors.


Medical imaging technology shock and volatility of macro economics: Analysis using a three-sector dynamical stochastic general equilibrium REC model.
The study analysed the medical imaging technology business cycle from 1981 to 2009 and found that the volatility of consumption in Chinese medical imaging business was higher than that of the developed countries. The volatility of gross domestic product (GDP) and the correlation between consumption and GDP is also higher than that of the developed countries. Prior to the early 1990s the volatility of consumption is even higher than GDP. This fact makes it difficult to explain the volatile market using the standard one sector real economic cycle (REC) model. Contrary to the other domestic studies, this study considers a three-sector dynamical stochastic general equilibrium REC model. In this model there are two consumption sectors, whereby one is labour intensive and another is capital intensive. The more capital intensive investment sector only introduces technology shocks in the medical imaging market. Our response functions and Monte-Carlo simulation results show that the model can explain 90% of the volatility of consummation relative to GDP, and explain the correlation between consumption and GDP. The results demonstrated the significant correlation between the technological reform in medical imaging and volatility in the labour market on Chinese macro economy development.


Effect of dialysis on interference by cefoxitin with determination of creatinine.
Interference by cefoxitin with determination of creatinine is less with the Technicon SMAC than with other commercial analytical systems. The SMAC assay involves a single-point kinetic method with dialysis, whereas most other commercial methods are multipoint kinetic without dialysis. The apparent creatinine concentration measured for aqueous solutions of cefoxitin was 73 mmol of creatinine per mole of cefoxitin with the SMAC, 135 mmol/mol with a manual method. Furthermore, we determined for the SMAC that the average fraction of creatinine dialyzed was 0.128 and for cefoxitin, 0.064. Thus, the concentration of and interference by cefoxitin in the reaction mixture for SMAC are reduced by half (i.e., the apparent creatinine concentration for cefoxitin with the manual system multiplied by 0.5 is essentially that noted with the SMAC: 68 vs 73). Thus we conclude that the diminished interference be cefoxitin with determination of creatinine by SMAC is primarily ascribable to the dialysis step.


Imaging for infection: from visualization of inflammation to visualization of microbes.
With the development of high-resolution cross-sectional imaging, anatomic identification of most areas of infection has become routine. Imaging a site of infection allows for diagnosis and treatment. In the past, molecular imaging for infection involved mainly the use of radiolabeled leukocytes for functional targeting at infection sites. With the recent development of functional nuclear imaging, bacterial and viral metabolism can also be imaged directly for potential identification of early infection. Review of pertinent English-language literature. Cross-sectional imaging is used routinely to identify and treat sources of infection in patients with fever, leukocytosis, or unexplained hemodynamic instability. Although ultrasound is preferred for the identification of biliary or hepatic sepsis, computed tomography (CT) has proved to be accurate for the identification and treatment of intra-abdominal fluid collections and abscesses. Biologic imaging is a non-invasive technique that identifies sites of infection in cases in which no definite abnormality is identified via cross-sectional imaging. This is made possible by imaging the accumulation of radioisotopes that have been attached to white blood cells or glucose. Biologic imaging is useful for the identification of anatomic sites where there is inflammation or high metabolic demand. However, a drawback of biologic imaging is that it is not specific for infection. Techniques that image microbes directly increase the specificity of imaging results significantly and can be used to quantify and track infectious processes. For example, radiolabeling of antimicrobial proteins and antibiotics is one technique that has been demonstrated to identify areas of infection accurately in animals but is not currently being used clinically in humans. With the advent of gene therapy, many researchers are inserting the herpes viral thymidine kinase gene into both viruses and bacteria. This allows for tracking of the infectious process by imaging the accumulation of radiolabeled thymidine analogues. This review summarizes standard imaging for infection as it is currently practiced clinically. We will also explore the promising new methods of microbial imaging that are likely to become standards in clinical care in the near future.


Target signatures for laser altimeters: an analysis.
The statistical characteristics of the received signal for short pulse laser altimeters are investigated. Expressions are derived for the mean and temporal covariances of the received pulse for a direct detection receiver. The effects of laser speckle, shot noise, and surface profile of the ground target are considered. The results are used to compute the means and variances of the total received energy, propagation delay, and rms width of the received pulse. These parameters are shown to be directly related to the statistics of the surface profile.


Turning 1 Year of Age in a Low Socioeconomic Environment: A Portrait of Disadvantage.
In the United States today, 16 million children are growing up poor. Few studies report multiple environmental factors associated with poverty during the first year of life and effects on infant development. To evaluate maternal, home, and neighborhood environment of low and higher socioeconomic status (SES) infants from birth to 1 year and to evaluate the impact of SES and environment on infant developmental outcome at 1 year. Low (n = 30) and higher SES (n = 30) African-American mothers and their healthy term gestation female infants were prospectively compared for environmental characteristics and infant developmental outcome. Wechsler Adult Intelligence Scale-IV (WAIS-IV); Beck Depression Inventory; Perceived Stress Scale; Parenting Stress Index-Fourth Edition (PSI-4); Social Support Scale; Home Observation Measurement of the Environment (HOME); Household Food Insecurity (HFI); Concentrated Neighborhood Disadvantage (CND). Bayley Scales of Infant Development Third Edition (BSID-III); Preschool Language Scale (PLS-5). Environmental risk was greater for low compared with higher SES: lower WAIS-IV (p < .001); higher PSI-4 total (p = .003); lower HOME total and 3 subscales (p < .002); higher HFI (p = .012); and higher CND (p = .027). Low SES infant outcomes differed from higher SES: lower BSID-III Cognitive Composite (p = .005), PLS-5 Total Language (p ≤ .017), and Auditory Comprehension (p ≤ .008). In regressions, after controlling for SES, effects of environmental factors were not found. By age 1, low SES infants had been exposed to greater environmental disadvantage and already exhibited poorer developmental functioning than higher SES infants. These findings suggest that support for families and children from impoverished circumstances cannot begin too early.


Design, synthesis, antimicrobial activity and anti-HIV activity evaluation of novel hybrid quinazoline-triazine derivatives.
A series of novel hybrid quinazoline-triazine derivatives was designed and synthesized from cyanuric chloride and anthranilic acid through sequential reactions, which contain different pharmacophores like quinazoline and substituted diaryl triazine (DATA) linked with ethylene diamine. All the newly synthesized compounds were characterized by infrared, (1)H-NMR, (13)C-NMR, MS and elemental analysis. Further, we evaluated the in vitro anti-HIV activity of the newly synthesized compounds against HIV-1 (IIIB) and HIV-2 (ROD) viral strains and as well as in vitro antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae) and two fungi (Aspergillus clavatus, Candida albicans) using the paper agar streak dilution method. The bioassay results indicate that four compounds namely 7d, 7n, 7r and 7s could be considered as possible potential agents.


Postnatal Diagnostic Workup in Children With Arthrogryposis: A Series of 82 Patients.
To describe a postnatal series of patients with arthrogryposis multiplex congenita by the causal mechanisms involved. In this single-center study, the local data warehouse was used to identify patients with arthrogryposis multiplex congenita. Patients were classified into different etiologic groups. Of 82 patients included, the most frequent cause of arthrogryposis multiplex congenita was a neuromuscular disorder (39%), including skeletal muscle (n = 19), neuromuscular junction (n = 3), and peripheral nerve (n = 11) involvement. In other subgroups, 19 patients (23%) were classified by disorders in the central nervous system, 5 (6%) in connective tissue, 7 (8.5%) had mixed mechanisms, and 18 (22%) could not be classified. Contractures topography was not associated with a causal mechanism. Cerebral magnetic resonance imaging (MRI), electroneuromyography, and muscle biopsy were the most conclusive investigations. Metabolic investigations were normal in all the patients tested. Targeted or whole exome sequencing diagnostic rates were 51% and 71%, respectively. Thirty-three percent of patients died (early death occurred in patients with polyhydramnios, prematurity, and ventilatory dependency). The benefits of a precise diagnosis in the neonatal period include more tailored management of arthrogryposis multiplex congenita and better genetic information.


[High frequency oscillatory ventilation in the preterm newborn infants with respiratory distress syndrome].
The objective of this study was to evaluate the efficiency and response of gas exchange by the use of high frequency respiratory modalities in cases rescued after failure of conventional mechanical ventilation. A retrospective study of twelve premature infants that required high frequency ventilation (HFV) as rescue therapy for treatment of respiratory distress syndrome (RDS) because of failure of conventional mechanical ventilation (CNV) were studied. The mean weight and gestational age were 1,041 gr (500-1,730) and 28 weeks (26-34), respectively. Fifty percent of the infants weighed less than 1,000 grams. Two different respiratory apparatus were used. Five infants were treated using Infant Star and seven with Babylog 8000. The variables were analyzed by comparison of the means with significance taken as p < 0.05. High frequency ventilation was initiated at 24 hours of life (2-86) and the mean duration was 33 hours (1-133). We saw a significant improvement in oxygenation after starting HFV and during the first and second controls after HFV initiation. PaO2 increased from 59 mmHg to 87 (HFV-initial), 119 mmHg (HFV-first control) and 98 mmHg (HFV second control; p < 0.05). Likewise, a/AO2 increased from 0.087 to 0.13 (HFV-initial), 0.19 (HFV-first control) and and 0.18 (HFV-second control; p < 0.05). The oxygenation index (OI) decreased from 23 to 16 (HFV-initial p < 0.05) and to 11 during the first and second controls (p < 0.01). Despite the improvement in oxygenation, there were no differences in mean airway pressure levels. We did not see any change in PaCO2 levels. The mortality rate was 58%, with a mean age at death of 82 hours of life (6-264). High frequency ventilation might be used as a rescue therapy for treatment of respiratory distress syndrome since there is an improvement in oxygenation.


Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.
Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer.


Nucleophosmin, a critical Bax cofactor in ischemia-induced cell death.
We hypothesized that nucleophosmin (NPM), a nucleolar phosphoprotein, is critical for Bax-mediated cell death. To test this hypothesis, Bax activation was induced by metabolic stress. During stress, nucleolar NPM translocated into the cytosol, NPM-Bax complexes formed, and both NPM and Bax accumulated in mitochondria. Expression of a cytosol-restricted NPM mutant (NPM-ΔNLS), but not a nucleus-restricted NPM mutant, increased NPM-Bax complex formation, mitochondrial NPM and Bax accumulation, mitochondrial membrane injury, caspase 3 activation, and ischemia-induced cell death. Coexpression of NPM-ΔNLS with constitutively active Bax mutants caused nearly universal cell death in the absence of metabolic stress, whereas expression of active Bax or NPM-ΔNLS alone did not. A Bax peptide that disrupts NPM-Bax interaction significantly reduced cell death caused by exposure to metabolic inhibitors in vitro and preserved kidney function after ischemia in vivo. Thus, NPM-Bax interaction enhances mitochondrial Bax accumulation, organelle injury, and cell death. NPM-Bax complex formation is a novel target for preventing ischemic tissue injury.


Association between psychological measures with inflammatory anddisease-related markers of inflammatory bowel disease.
This study aimed at investigating the associations between inflammatory mediators, symptoms and psychological disturbances in inflammatory bowel disease (IBD) patients. IBD patients and patient controls were examined during a single visit to a gastroenterology clinic. Disease activity was assessed using the Mayo index for ulcerative colitis (UC), inflammatory bowel disease questionnaire (IBDQ), Crohn's disease activity index (CDAI) and Crohn's disease endoscopic index of severity (CDEIS). Gene expression of inflammatory mediators were measured in intestinal biopsies and whole blood samples along with circulating concentrations of interleukin (IL)-6, interferon (IFN)γ, C-reactive protein (CRP), kynurenine and tryptophan. Validated depression, anxiety and quality of life scores were used to assess psychological well-being. Patients who were symptomatic had the highest depression and anxiety scores, together with increased intestinal expression of IL-1β, IL-6 and matrix metalloproteinase-9, increased circulating IL-6 and CRP, and an increased circulating kynurenine:tryptophan ratio. Increased Hamilton depression (HAM-D) scores in IBD patients were observed independent of the psychological impact of acute symptoms. Active IBD is associated with symptoms of depression and anxiety and with a raised circulating inflammatory mediator profile. Patients with active IBD exhibiting psychological symptoms should undergo psychological evaluation to ensure the psychological aspects of the condition are considered and addressed.


The thoracodorsal artery perforator flap with a vascularized scapular segment for reconstruction of a composite lower extremity defect.
High-energy trauma resulting in a composite defect of the lower extremity confronts the microvascular surgeon with more difficulties than do free flap reconstruction elsewhere in the body, since the choice of distant recipient vessels is particularly difficult. Combining principles of perforator flap surgery with those of composite tissue transfer, we designed a thoracodorsal artery perforator flap with a vascularized bone segment from the scapula for reconstruction of a composite lower extremity defect in a patient following a paragliding accident. This is the first report on the application of a composite thoracodorsal artery perforator flap with vascularized scapula in lower extremity reconstruction. Among its multiple advantages, such as preservation of latissimus dorsi function, it is a good tool for one-stage reconstruction of traumatic composite lower extremity defects because its low donor site morbidity and long vascular pedicle enables anastomosis placement outside the zone of injury.


[Discussion on research thought of dry granulation of traditional Chinese medicine: research progress at home and abroad based on dry granulation technology].
Dry granulation technology is a great innovation in granulation technology,which saves many intermediate links and reduces many intermediate costs. It is closely related to the characteristics of materials,dry granulation equipment and process. Dry granulation technology is a systematic engineering science covering many technical fields. The process of dry granulation involves complex mathematical model mechanisms of temperature field,pressure field and velocity field,closely related to the characteristics of materials and drying equipment. However,due to the late start of research on dry granulation technology of traditional Chinese medicine,basic research is still weak. The research on dry granulation technology has achieved great results in the fields of food,chemical industry,agriculture and forestry,showing great reference significance. The advantage of dry granulation of traditional Chinese medicine is that it can be directly granulated by adding an appropriate amount of auxiliary materials in the extract powder of traditional Chinese medicine,without the need of wetting,mixing,drying and other processes. The process is simple and can effectively guarantee the quality of traditional Chinese medicine. The granules obtained by the dry granulation technique are important intermediates for preparing the solid preparations of traditional Chinese medicines,which would directly affect the subsequent molding process and the quality of the preparation products. Therefore,based on the characteristics of dry granulation method in traditional Chinese medicine and by referring to the advanced research results of dry granulation technology in other fields,we would discuss the research ideas of dry granulation in traditional Chinese medicine in terms of the mechanism of dry granulation equipment,technology,on-line detection technology and mathematical model of dry granulation process,hoping to provide reference for the research of dry granulation method in traditional Chinese medicine.


[Megakaryocytic pseudomyelosis with severe thrombocytosis].
A 66-year-old female patient complained of loss of body weight and fatigue. The clinical examination revealed a thrombocytosis with a maximum count of 3.200 . 10(9) platelets and a leukocytosis with maximally 25 . 10(9) white cells in the peripheral blood. The bone marrow showed a large increase of megakaryocytes. Under the diagnosis of megakaryocytic myelosis a chemotherapy with 186 mg busulfan was performed. In the course of this treatment the clinical picture of a sepsis occurred which could not be controlled by antibiotics. The patient died four months after her admission to the clinic. The essential findings in autopsy were a caseous tuberculosis of the lymph nodes with haematogenic generalization which appeared as a septic tuberculosa gravissima ("typhobacillosis" Landouzy). The bone marrow was atrophic. Spleen liver and lymph nodes were without evidence for a myeloproliferative disorder. Thus, the initial diagnosis had to be changed to a megakaryocytic pseudomyelosis with massive thrombocytosis as a reaction to the tuberculous infection. The differential diagnosis of megakaryocytic myelosis, other disorders of the myeloproliferative syndrome, and the reactive thrombocytosis are discussed.


A simple and universal gel permeation chromatography technique for precise molecular weight characterization of well-defined poly(ionic liquid)s.
Poly(ionic liquid)s (PILs) are an important class of technologically relevant materials. However, characterization of well-defined polyionic materials remains a challenge. Herein, we have developed a simple and versatile gel permeation chromatography (GPC) methodology for molecular weight (MW) characterization of PILs with a variety of anions. PILs with narrow MW distributions were synthesized via atom transfer radical polymerization, and the MWs obtained from GPC were further confirmed via nuclear magnetic resonance end group analysis.


Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.
Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were prepared and it was found that the 3,5-substituted furan analog had increased activity compared to that of the 2,5-substituted furan isomer. Addition of a methoxy group at C-6 decreased the Src inhibitory activity of the C-7 2,5-substituted furan analog but increased the activity of the C-7 3,5-substituted furan isomer. This compound, 10, was a more potent Src inhibitor than 1 in both enzymatic and cell-based assays. The kinase selectivity profile of 10 was similar to that of 1, with 10 also inhibiting the activity of Abl and Lck. When tested in a solid tumor xenograft model, 10 had comparable oral activity to that of 1.


Endometrial safety of third generation aromatase inhibitors versus tamoxifen in breast cancer patients.
The estrogenic activity of tamoxifen on the uterus increases the risk of developing benign and malignant uterine pathologies in breast cancer patients receiving this drug. This has led to gynecological interventions specifically in symptomatic women to exclude malignant disease. Given this known side effect associated with tamoxifen therapy, newer endocrine therapies such as the third-generation aromatase inhibitors have been compared to tamoxifen also in terms of their uterine effects. To date, studies that have directly compared the uterine effects of tamoxifen with that of aromatase inhibitors generally show that aromatase inhibitors such as anastrozole, letrozole, and exemestane are associated with less uterine pathologies compared to tamoxifen. Furthermore, aromatase inhibitors may even reverse uterine abnormalities induced by tamoxifen. This implies that the absence of a stimulatory effect on the uterus would be one of the benefits gained with aromatase inhibitor therapy and may decrease or even obviate the need for gynecological interventions.


[Ultrastructural study of lymph node cells in experimental burn injury].
Ultrastructure of the lymph nodes was examined in rats with experimental thermal burns of the skin. Ultrastructural studies of lymph node cells demonstrated the signs of destruction at the ultrastructural level. In the authors' opinion, destructive changes in lymph node cells may form the structural basis for secondary immunological deficiency typical for burn injury.


Discovery of two new Andean species of Scolomus (Townes Townes), with a key to all known species (Hymenoptera: Ichneumonidae: Metopiinae).
Scolomus Townes Townes is a widely distributed genus of the family Ichneumonidae, with most species occurring in the New World. Herein two new species from Chile are described and illustrated. Scolomus maculatus sp. nov., which is characterized by a large rhomboid areolet and very wide RS vein in the fore wing, resembling a petiole; head and pronotum green, mesoscutum yellow with dark brown spots on its lateral lobes and around the scutellum. Scolomus clypeatus sp. nov., which is characterized by its wide clypeus, 3.00× as wide as long, with a rectangular aspect; head, mesoscutum, postscutellum and pronotum entirely yellow. The first key to all known species of the genus is also presented.


Ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates: Silica supported bismuth(III)triflate catalyzed synthesis and antioxidant activity.
Novel ethyl-4-(aryl)-6-methyl-2-(oxo/thio)-3,4-dihydro-1H-pyrimidine-5-carboxylates were synthesized from one-pot, three-component Biginelli reaction of aryl aldehydes, ethyl acetoacetate and urea/ thiourea by catalytic action of silica supported Bismuth(III) triflate, a Lewis acid. All the synthesized compounds were structurally characterized by spectral (IR, 1H NMR & 13C NMR spectroscopic and Mass spectrometric) and elemental (C, H & N) analyses. The present protocol has deserved novel as, formed the products in high yields with short reaction times, involved eco-friendly methodology and reusable heterogeneous Lewis acid catalyst. The title compounds were screened for in vitro DPPH free radical scavenging antioxidant activity and identified 4i, 4j, 4h & 4f as potential antioxidants. The obtained in vitro results were correlated with molecular docking, ADMET, QSAR, Bioactivity & toxicity risk studies and molecular finger print properties and found that in silico binding affinities were identified in good correlation with in vitro antioxidant activity and studied the structure activity relationship. The molecular docking study has disclosed strong hydrogen bonding interactions of title compounds with aspartic acid (ASP197) aminoacid residue of 2HCK, a complex enzyme of haematopoietic cell kinase and quercetin. Results of toxicology study evaluated for potential risks of compounds have revealed title compounds as safer drugs. In ultimate the study has established ligand's antioxidant potentiality as they effectively binds with ASP197 amino acid of Chain A hence confirms the inhibition of growth of reactive oxygen species in vivo. In addition, the title compounds have been identified as potential blood-brain barrier penetrable entities and efficient central nervous system (CNS) active neuro-protective antioxidant agents.


[Prokaryotic expression of F10 and preparation of its polyclonal antibody].
To induce the expression of F10 in E.coli and prepare the rabbit polyclonal antibody against it. The gene of F10 was amplified by PCR, and cloned into expression vector pET-GST to construct recombinant expression plasmid pET-GST/F10. The recombinant plasmid was transformed into E.coli BL21 and induced to express recombinant protein with IPTG. The fusion protein was further purified by affinity chromatography and analyzed by SDS-PAGE and Western blot. A rabbit was immunized with the purified F10 fusion protein to produce polyclonal antibody, and the production of antibody was confirmed by ELISA. Restriction enzyme digestion and DNA sequencing analysis suggested that the recombinant expression plasmid contained correct coding region of F10. SDS-PAGE demonstrated that the recombinant protein was expressed with the expected molecular weight at 61 kD. After purified, the purity of the fusion protein was above 90%. Western blot confirmed the recombinant protein was GST/F10 fusion protein. Rabbit polyclonal antibody was obtained, the titer of which was 1:20 000. F10 recombinant expression vector has been successfully constructed and F10 protein has been expressed. The obtained rabbit anti F10 antibody has a high titer and will facilitate the study of the biological function of F10.


Improvements in the color, phytochemical, and antioxidant properties of frozen ripe mango pieces using calcium chloride dipping and chitosan coating.
This study aimed to investigate the influences of a dipping/coating composed of calcium chloride (CaCl2 ) or chitosan on the quality of ripe mango pieces during frozen storage for 6 months. The fruits were dipped in solutions with concentrations of 0.5% and 1% for different times (15 or 30 min for CaCl2 and 1 or 15 min for chitosan). We found that treatment with 1% CaCl2 for 30 min significantly retarded the color changes with the highest L* (p < 0.05) and the lowest of b* and ∆E (p ≥ 0.05). Interestingly, treatment with 0.5% CaCl2 for 30 min significantly preserved the contents of total phenolics and total flavonoids and the antioxidant activities at values higher than the control levels, as determined by DPPH and ABTS assays (p < 0.05). Moreover, treatment with 0.5%-1% chitosan for 1 min effectively delayed the loss of moisture and weight. The results indicate that dipping in CaCl2 is an alternative simple food processing technique for improving the quality of ripe mango pieces during frozen storage that effectively delays the color changes and preserves the antioxidant content and activity. HIGHLIGHTS: The coating of frozen ripe mango pieces with CaCl2 and chitosan was first investigated. CaCl2 effectively retarded the color change during storage and after thawing. Chitosan effectively delayed the loss of moisture and weight of mango pulp. Coating with 0.5% CaCl2 for 30 min maintained the phytochemicals and antioxidant activities. Coating treatment can preserve mango qualities and could be commercialized with cost savings. PRACTICAL APPLICATION: The present article proposes a strategy that effectively delays the physicochemical changes and preserves the nutritional properties of mango fruit and could be commercialized with cost savings. A frozen mango can either be consumed (ready-to-eat frozen mango) or used as a food raw material.


Regional enteritis of the duodenum: a review and report of five cases.
Forty-three cases of regional enteritis of the duodenum were found in the world literature. Regional duodenitis is relatively uncommon; in one large series of 600 cases of regional enteritis only three involved the duodenum.At the University of Alberta Hospital, in a three-year period (1962 to 1965), the authors encountered five patients with regional duodenitis, demonstrating a spectrum of clinical, radiologic and pathologic characteristics of this disease. The description of these patients brings the world's total to 48 reported cases.Two of these patients had symptoms of severe duodenal obstruction and were relieved by bypass procedures and vagotomy; one required surgery because of co-existent obstructive ileal disease: and two patients have improved on corticoids and salicylazosulfapyridine without surgery.In our experience treatment with corticoids and salicylazosulfapyridine is beneficial.Four of the five patients remain in a state of mild to moderate nutritional impairment and have evidence of intestinal malabsorption. In the fifth case the period of followup is too short to permit assessment.


The Bartsocas-Papas syndrome: autosomal recessive form of popliteal pterygium syndrome in a male infant.
We report on an additional patient with the severe autosomal recessive form of the popliteal pterygium syndrome. The patient was diagnosed at birth and had all of the phenotypic manifestations of this rare syndrome. Clinical findings and natural history suggest this is a distinct genetic entity.


Lithotripsy with a Q-switched alexandrite laser system. Preliminary in vivo and in vitro results.
An alexandrite laser system which emits a wavelength of 750 nm, has recently been proposed as a substitute for the pulsed-dye laser (504 nm) for laser lithotripsy. We have carried out in vitro lithotripsy trials in order to evaluate the efficiency of a flashlamp pumped Q-switched alexandrite laser. In the first experiment, we compared the Q-switched alexandrite laser to the pulsed-dye laser with respect to their effectiveness in fragmentizing urinary and model stones (HMT target stones). In the second experiment, we evaluated the effect of Q-switched alexandrite radiation on the urinary wall (bladder, ureter, renal pelvis and liver) of animals (Wistar rats and rabbits) under general anesthesia. In conclusion, the alexandrite laser system is comparable to the pulsed dye laser. The 750-nm wavelength involves minimal risk of damage to the urinary tract and constitutes a safe alternative, especially during blind lithotripsy. It is a compact solid-state system, with no toxic chemical agents as laser material.


Dynamic chromatic aberration pre-compensation scheme for ultrashort petawatt laser systems.
A novel chromatic aberration pre-compensation scheme for ultrashort petawatt laser systems was proposed. The pre-compensation scheme consists of a convex lens, group of concave lenses, and a spherical reflector combined with a conventional vacuum chamber. It provides a versatile method to accurately compensate the chromatic aberration of an entire laser system via controlling the amount of propagation time delay (PTD) induced by the compensator without changing the input and output beam size. A compensator, tailored based on the proposed scheme, was designed and experimentally evaluated for the Shen-Guang-II 5PW (SG-II 5PW) laser system at Shanghai Institute of Optics and Fine Mechanics (SIOM). The experimental results verified that chromatic aberration in the laser system was almost fully compensated: the size of laser beam focused by an f/2.42 off-axis parabolic mirror (OAP) was reduced tremendously from 32×18μm2to about 4×4μm2at full width at half maximum (FWHM). The proposed scheme provides the flexibility to accurately correct chromatic aberration in high-power laser systems within a wide dynamic range.


Cardiopulmonary bypass is associated with hemolysis and acute kidney injury in neonates, infants, and children*.
This pilot study assesses the degree of hemolysis induced by cardiopulmonary bypass and determines its association with acute kidney injury in pediatric patients. Further, it evaluates the degree to which the use of urinary biomarkers neutrophil gelatinase-associated lipocalin and cystatin C correlate with the presence of acute kidney injury and hemolysis following cardiopulmonary bypass. Prospective observational study. A 13-bed pediatric cardiac ICU in a university hospital. Children undergoing cardiac surgery with the use of cardiopulmonary bypass. None. Blood and urine samples were obtained at multiple time points before and after cardiopulmonary bypass. Hemolysis was assessed by measuring levels of plasma hemoglobin and haptoglobin. Acute kidney injury was defined as a doubling in serum creatinine from preoperative baseline and by using the pediatric-modified RIFLE criteria. Urinary neutrophil gelatinase-associated lipocalin and cystatin C levels were measured. A total of 40 patients (range, 3 d to 4.8 yr) were enrolled. Plasma hemoglobin levels increased markedly on separation from cardiopulmonary bypass with a concurrent decrease in haptoglobin. This was associated with an increase in protein oxidation in the plasma. Hemolysis was more evident in younger patients with a longer duration of bypass and in those requiring a blood-primed circuit. Forty percent of patients had a doubling in serum creatinine and acute kidney injury was developed in 88% of patients when defined by the pediatric-modified RIFLE criteria. Controlling for cardiopulmonary bypass time, persistently elevated levels of plasma hemoglobin were associated with a five-fold increase in acute kidney injury. Further, urinary neutrophil gelatinase-associated lipocalin measured 2 hours after separation from cardiopulmonary bypass was associated with acute kidney injury and with elevations in plasma hemoglobin. Cardiopulmonary bypass in pediatric patients results in significant hemolysis, which is associated with the development of acute kidney injury. The biomarker neutrophil gelatinase-associated lipocalin correlates with both acute kidney injury and hemolysis in this population.


Association of mean platelet volume with presence of non-viable myocardium in ischaemic cardiomyopathy.
Parameters derived from complete blood count, such as mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), have recently been proposed as measures of inflammation in addition to C-reactive protein (CRP), a classical inflammatory marker. Significant association of these parameters with atherosclerosis and complications have increasingly been reported. The aim of the study is to evaluate the relationship between these parameters and the presence of myocardial viability assessed with positron emission tomography (PET) in patients with ischaemic cardiomyopathy (ICM). A total of 122 ICM patients who had undergone PET were enrolled in this study. The patients were dichotomised depending on the presence of transmural scar. Group 1 consisted of 21 patients who had transmural scar tissue only, who were accepted as the group having non-viable myocardium. Group 2 consisted of 101 patients who had hibernation and/or non-transmural scar, who were accepted as the group having viable myocardium. Haematological parameters within 30 days of PET imaging were retrospectively analysed. There were no significant differences between the two groups regarding values of white blood cell, neutrophil, lymphocyte, platelet, haemoglobin, red cell distribution width, CRP, PLR, and NLR. Patients with non-viable myocardium have significantly higher levels of MPV (p = 0.002). In multiple logistic regression analysis, MPV (odds ratio [OR] = 0.373, 95% confidence interval [CI] 0.20-0.69, p = 0.002), was identified as an independent predictor of non-viable myocardium. In receiver-operator characteristic (ROC) analysis, a cut-point of 8.19 identified patients with non-viable myocardium (area under curve: 0.72, 95% CI 0.60-0.84). An MPV value greater than 8.19 demonstrated a sensitivity of 76% and a specificity of 55%. \ CONCLUSIONS: The present study showed that MPV is an inexpensive, clinical, and routinely measurable parameter that is associated with the presence of viable myocardium in ICM.


Autism symptoms, functional impairments, and gaze fixation measured using an eye-tracker in 6-year-old children.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder clinically characterized by abnormalities in eye contact during social exchanges. We aimed to clarify whether the amount of gaze fixation, measured at the age of 6 years using Gazefinder, which is an established eye-tracking device, is associated with ASD symptoms and functioning. The current study included 742 participants from the Hamamatsu Birth Cohort Study. Autistic symptoms were evaluated according to the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the functioning of the participating children in real life was assessed using the Japanese version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). The Gazefinder system was used for gaze fixation rates; two areas of interest (eyes and mouth) were defined in a talking movie clip, and eye gaze positions were calculated through corneal reflection techniques. The participants had an average age of 6.06 ± 0.14 years (males: 384; 52%). According to ADOS, 617 (83%) children were assessed as having none/mild ASD and 51 (7%) as severe. The average VABS-II scores were approximately 100 (standard deviation = 12). A higher gaze fixation rate on the eyes was associated with a significantly lower likelihood of the child being assigned to the severe ADOS group after controlling for covariates (odds ratio [OR], 0.02; 95% confidence interval [CI], 0.002-0.38). The gaze fixation rate on the mouth was not associated with ASD symptoms. A higher gaze fixation rate on the mouth was associated with a significantly lower likelihood of the child being assigned to the low score group in VABS-II socialization after controlling for covariates (OR, 0.18; 95% CI, 0.04-0.85). The gaze fixation rate on the eyes was not associated with functioning. We found that children with low gaze fixation rates on the eyes were likely to have more ASD symptoms, and children with low gaze fixation rates on the mouth were likely to demonstrate poorer functioning in socialization. Hence, preschool children could be independently assessed in the general population for clinically relevant endophenotypes predictive of ASD symptoms and functional impairments.


The origins of the shape bias: Evidence from the Tsimane'.
In the United States, children often generalize the meaning of new words by assuming that objects with the same shape have the same name. We propose that this shape bias is influenced by children's exposure to objects of different categories (artifacts and natural kinds) and language to talk about them. We present a cross-cultural study between English speakers in the United States and Tsimane' speakers in the Bolivian Amazon. We found that U.S. children and adults were more likely to generalize novel labels by shape rather than by material or color, relative to Tsimane' participants. Critically, Tsimane' children and adults systematically avoided generalizing labels to objects that shared no common features with the novel referent. Our results provide initial evidence that the relative exposure to objects of different kinds and language to talk about them can lead to cross-cultural differences on object name learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Prospective study of extended segmentectomy for small lung tumors: the final report.
Minimal resection of small lung tumors is still controversial. This study was conducted to clarify whether this type of operation is acceptable. From January 1992 to December 1994, 73 patients were registered in a multiinstitutional trial of limited resection for peripheral lung tumors less than 2 cm in diameter. The operative procedure consisted of extended segmentectomy in which the cut line of the lung was beyond the burdened segment, confirming N0 disease by intraoperative lymph node examination of frozen sections. The operation was changed to other procedures if the report was positive. All the patients were observed more than 5 years. There were no perioperative deaths and no major complications. A total of 55 patients were finally enrolled in this study. Ten patients died postoperatively, 4 of lung cancer and the remaining 6 died of other diseases, with no signs of recurrence. The 5-year survival rate, excluding these 6 patients, was 91.8%; for all patients including those who died it was 81.8%. A total of 18 patients were not included in this study for various reasons. The decrease in forced vital capacity was 11.3% +/- 9.8% compared with the preoperative value. Extended segmentectomy is an alternative method as a standard operation for patients with small peripheral lung tumors, and the loss of lung function is minimal. However, patient selection must be strict, with intraoperative pathologic examination, and a wide margin to the lesion beyond the burdened segment is mandatory.


Near-Infrared Rewritable, Non-Volatile Subwavelength Absorber Based on Chalcogenide Phase Change Materials.
Chalcogenide phase change materials enable the realization of novel, non-volatile, switchable electronic and photonic devices. In this paper, we propose a type of rewritable, non-volatile near infrared subwavelength absorber based on chalcogenide phase change materials. Our numerical simulations show that nearly perfect absorption more than 0.99 can be realized in the written state while the absorption of as-deposited or erased state is lower than 0.15 in the studied spectral range, leading to high contrast ratio of reflection more than 20 dB. Continuous tuning of the absorption spectra can be realized not only by varying the geometric parameters of the absorber but also by changing the crystallization ratio of the switched Ge 2 Sb 2 Te 5 (GST). The proposed device may find widespread applications in optical modulation, beam steering and so on.


AIDS, otolaryngology and a case of adenoid cystic carcinoma of the parotid arising in a patient with the AIDS-related complex.
The incidence of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) is increasing, and as head and neck manifestations of this entity are common it is important that otolaryngologists have an up-to-date knowledge of this condition. In this paper the epidemiological aspects of the disease are reviewed and the head and neck manifestations discussed. An interesting case of adenoid cystic carcinoma of the parotid arising in a patient with ARC is presented.


Bioanalysis young investigator: Alexander Medina-Remón.
Supervisor's supporting comments Alex Medina joined my research group, Natural Antioxidants, in January 2006 to start his PhD program. He has been working intensively and efficiently on several projects; initially for his thesis he developed a new bioanalytical methodology to quantify phenols in urine (Medina-Remón A et al. 2009) to correlate with the hypertension prevention in the PREDIMED study ( www.predimed.org ). Thanks to this new bioanalytical method, we are currently starting collaboration projects with different research centers. In addition, he has been working on other research projects on tomatoes, grapes, citric fruits and wine. Medina is helpful whenever needed and efficient. He has shown himself to be responsible, well-prepared, intelligent, organized and to have very good teaching skills. Moreover, he is patient and able to solve problems calmly, but at the same time, he is enthusiastic about what he does and can transmit this enthusiasm to his colleagues. He is really a thoughtful scientist. I have now contracted him as a Postdoctoral researcher. His responsibilities include leading several master's students and he is writing several papers on the health effects of polyphenols using his method.


Plasma concentrations of tumor necrosis factor-alpha in cats with congestive heart failure.
To determine whether plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) are increased in cats with congestive heart failure (CHF) secondary to cardiomyopathy. 26 adult cats with CHF and cardiomyopathy and 9 healthy control cats. Plasma concentrations of TNF-alpha were measured in cats with CHF and cardiomyopathy. Tumor necrosis factor-alpha was measured by quantifying cytotoxic effects of TNF-alpha on L929 murine fibrosarcoma cells. Concentrations of TNF-alpha were increased (0.13 to 3.6 U/ml) in 10 of 26 cats with CHF but were undetectable in the other 16 cats with CHF and all control cats. In 20 of 26 cats with CHF right-sided heart failure (RHF) was evident; TNF-alpha concentrations were increased in 9 of these 20 cats. The remaining 6 cats had left-sided heart failure (LHF); TNF-alpha concentrations were increased in only 1 of these cats. Age of cats with LHF (mean +/- SD, 12.1+/-6.2 years) was not significantly different from age of the cohort with RHF (10.5+/-5.2 years). Body weight of cats with increased TNFalpha concentrations (5.4+/-1.8 kg) was not significantly different from body weight of cats with CHF that did not have measurable concentrations of TNF-alpha (4.7+/-1.6 kg). Concentrations of TNF-alpha were increased in many cats with CHF. Cats with RHF were most likely to have increased TNF-alpha concentrations. Increased plasma concentrations of TNF-alpha in cats with CHF may offer insights into the pathophysiologic mechanisms of heart failure and provide targets for therapeutic interventions.


Degradation of aliphatic alcohols by human liver alcohol dehydrogenase: effect of ethanol and pharmacokinetic implications.
We have investigated the oxidation of low molecular weight aliphatic alcohols by Class I, II, and III alcohol dehydrogenases (ADH) isolated from human liver. These alcohols are generally present as byproducts of alcoholic beverages and referred to as alcoholic congeners. At concentrations corresponding to those in the blood after ingestion of alcoholic drinks (10-100 microM), the oxidation of propanol-1, isobutanol, 2-methylbutanol-1, and 3-methylbutanol-1 was mediated mainly by the isoenzymes of class I ADH, whereas butanol-1 was metabolized by Class I and II ADH. Class II ADH showed no activity with any of the alcohols at concentrations up to 100 microM. Lineweaver-Burk plots of the Class I ADH-catalyzed oxidation of all the congeners tested were linear in the pharmacokinetically relevant concentration range between 10 and 100 microM. Ethanol at concentrations found in the blood after moderate drinking (2.5-10 mM) caused a concentration-dependent inhibition of the congener oxidation. The experimentally determined kinetic constants were used to simulate the pharmacokinetics of propanol-1 metabolism in a multicompartment model system which accounts for first-pass elimination. The results suggest, in agreement with reported data from drinking experiments, that congener alcohols undergo considerable metabolism during the first liver passage, the extent of the first-pass metabolism depending on the ethanol dose.


[Diagnosis of the bleeding site in gastrointestinal hemorrhage by the determination of the serum urea and creatinine ratios].
Serum urea/creatinine (Ur/Cr) ratios were determined in patients showing massive gastrointestinal (GI) bleeding in order to evaluate the bleeding site. In 36 cases of upper GI bleeding, serum Ur/Cr ratios were 119.1 +/- 4.0. The ratios were 54.1 +/- 12.1 and 58.4 +/- 10.3 in 23 cases of lower GI bleeding and 50 control cases without GI bleeding, respectively. The ratio in the upper GI bleeding cases were significantly higher than those in the lower GI bleeding and the control cases. In all cases of upper GI bleeding, except for 6 cases in which blood volume flowed into the GI tract was small, the ratios were beyond 81. On the other hand, in the lower GI bleeding and the control cases, the ratios were all below 81. Values over 81 in serum Ur/Cr ratios in upper GI bleeding cases continued until the 3rd day after bleeding. These results indicate that determination of serum Ur/Cr ratios is a simple and useful procedure for diagnosis of the bleeding site in cases showing massive GI bleeding.


Does the T-locus in the mouse include ribosomal DNA?
The proportion of rDNA in the mouse genome is shown to have no systematic relation to the T-locus genotype, and hybridization in situ with 125I-RNA does not label chromosome 17, which carries the T-locus. Thus rDNA need no longer be taken into account in explaining the unique properties of the alleles at this locus. The number of genes for rRNA precursor averaged 153 per haploid genome, but a large measure of individual variation is suggested.


Family planning services in the United States.
In recent years the United States has made considerable progress in providing family planning services for those in need. This does not mean, however, that the problems posed by unwanted pregnancies and unwanted births have been completely overcome. Estimates of the number of low-income women needing and receiving family planning services indicate that roughly 3.6 million women at risk of an unwanted pregnancy were receiving family planning services in 1973. This represented almost two-thirds of those in need at the time. Many programs are also seeking to meet the teenage need demonstrated by very high rates of out-of-wedlock births, premarital conceptions, obstetric problems, and legal abortion demands of women 15 to 19 years of age. As of 1973, it appeared that between 1.3 and 2.2 million never-married teenagers were in need of organized family planning services, and that of these, services were being received by between 25 and 42 per cent.


Renal complications of Fabry disease.
Fabry disease is a progressive devastating disease caused by absent or deficient activity of lysosomal enzyme alpha-galactosidase A, with progressive accumulation of globotriaosylceramide (GL-3) within lysosomes in a different cell types. Accumulation of GL-3 and related glycosphingolipids in different cell types may create diverse clinical picture depending on the organ which is dominantly affected. Renal pathology progresses in severity with aging. Globotryaosil ceramide deposits may be found in different cell types within the kidney. Deposition within the glomeruli may be found in endothelial cells, mesangial cells, interstitial cells, with the highest level found within the podocytes. Although Fabry disease is not curable at the moment, availability of enzyme replacement therapy made it possible to treat this group of patients. Two formulations of recombinant human alpha-galactosidase A are present on the market: agalsidase alfa and agalsidase beta. Longer follow-up period is necessary to estimate the impact of ERT on mortality. Patients with end-stage renal disease caused by Fabry disease could be safely treated with enzyme replacement therapy regardless of the method of renal replacement therapy.


Nonsteroidal antiinflammatory agents, XVIII: C-5 functionalized 6,7-diphenyl-2,3-dihydro-1H-pyrrolizines as inhibitors of bovine cyclooxygenase and 5-lipoxygenase.
6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding propionic acid compounds, but they aren't well balanced dual inhibitors as shown for the carboxylic derivatives. A structure activity relationship and the enzyme selectivity are discussed.


Tools for a systematic appraisal of integrated community-based approaches to prevent childhood obesity.
Evaluation and monitoring methods are often unable to identify crucial elements of success or failure of integrated community-wide approaches aiming to tackle childhood overweight and obesity, yet difficult to determine in complex programmes. Therefore, we aimed to systematically appraise strengths and weaknesses of such programmes and to assess the usefulness of the appraisal tools used. To identify strengths and weaknesses of the integrated community-based approaches two tools were used: the Good Practice Appraisal tool for obesity prevention programmes, projects, initiatives and intervention (GPAT), a self-administered questionnaire developed by the WHO; and the OPEN tool, a structured list of questions based on the EPODE theory, to assist face-to-face interviews with the principle programme coordinators. The strengths and weaknesses of these tools were assessed with regard to practicalities, quality of acquired data and the appraisal process, criteria and scoring. Several strengths and weaknesses were identified in all the assessed integrated community-based approaches, different for each of them. The GPAT provided information mostly on intervention elements whereas through the OPEN tool information on both the programme and intervention levels were acquired. Large variability between integrated community-wide approaches preventing childhood obesity in the European region was identified and therefore each of them has different needs. Both tools used in combination seem to facilitate comprehensive assessment of integrated community-wide approaches in a systematic manner, which is rarely conducted. Nonetheless, the tools should be improved in line to their limitations as recommended in this manuscript.


Retention versus sacrifice of the posterior cruciate ligament in total knee replacement for treatment of osteoarthritis and rheumatoid arthritis.
The functional and clinical results to support the choice whether or not to retain the posterior cruciate ligament (PCL) during total knee arthroplasty have not been gathered and analysed so far. There are at least some trials showing no difference. To identify the difference in functional, clinical, and radiological outcome between retention and sacrifice of the PCL in total knee arthroplasty in patients with osteoarthrosis and other non-traumatic diseases. A search was conducted in MEDLINE(Through PubMed; 1966 - March 2004), EMBASE (1980 - March 2004), Cochrane Central Register of Controlled Trials (CENTRAL Issue 2004 - 1), and Current Contents (1996 - March 2004). Also, references of selected articles were checked and citation tracking on the articles selected was performed. Randomised controlled trials comparing retention to sacrifice of the PCL during total knee arthroplasty with regard to functional, radiological and clinical outcome in patients with osteoarthritis and other non-traumatic diseases were selected by two independent reviewers. Methodological quality was assessed with the checklist by van Tulder and the Jadad list. Data was collected with a predeveloped form. Meta-analysis was performed with subgroup analyses on age, gender, disease severity, and follow-up time, if allowed by adequate power. Eight randomised controlled trials were found. Two treatment options were compared against PCL retention: PCL sacrifice without additional stabilisation (post and cam mechanism) (2 studies), and PCL sacrifice with posterior stabilized design (5 studies). One study included all three options. Range of motion was found to be 8.1 degrees higher in the posterior stabilized group compared to the PCL retention group (p=0.01, 95% confidence interval [1.7, 14.5]), although the heterogeneity was high (I(2 )= 66.3%). PCL resection without substituting the PCL with a posterior stabilised prosthesis showed no difference compared to PCL retention (p=0.31, I(2) = 83.2%). On clinical scores, only Hospital for Special Surgery score revealed a significant difference of 1.6 points (p=0.03, 95% confidence interval [-3.1, -0.1]) between PCL retention versus PCL sacrifice and substitution combined favouring the latter group. The necessary subgroup analyses could not be performed for the clinical scores. These results should be interpreted with caution as the methodological quality of the studies was highly variable. We conclude that there is, so far, no solid base for the decision to either retain or sacrifice the PCL with or without use of a posterior stabilized design during total knee arthroplasty. The technique of PCL retention is difficult because the normal configuration and tension need to be reproduced with ligament tensioners. Knowledge of the technique needs to be improved before it can yield superior results compared to the more straightforward techniques of PCL sacrifice or use of a posterior stabilized design. Also, studies evaluating the effect of both techniques should address the right outcome parameters such as range of motion, contact position, and anterior-posterior stability. Suggestions are given to improve future research on this specific topic of knee arthroplasty.


Endovascular uterine artery interventions.
Percutaneous vascular embolization plays an important role in the management of various gynecologic and obstetric abnormalities. Transcatheter embolization is a minimally invasive alternative procedure to surgery with reduced morbidity and mortality, and preserves the patient's future fertility potential. The clinical indications for transcatheter embolization are much broader and include many benign gynecologic conditions, such as fibroid, adenomyosis, and arteriovenous malformations (AVMs), as well as intractable bleeding due to inoperable advanced-stage malignancies. The most well-known and well-studied indication is uterine fibroid embolization. Uterine artery embolization (UAE) may be performed to prevent or treat bleeding associated with various obstetric conditions, including postpartum hemorrhage (PPH), placental implantation abnormality, and ectopic pregnancy. Embolization of the uterine artery or the internal iliac artery also may be performed to control pelvic bleeding due to coagulopathy or iatrogenic injury. This article discusses these gynecologic and obstetric indications for transcatheter embolization and reviews procedural techniques and outcomes.


Longitudinal monitoring of intracranial arterial stenoses with transcranial Doppler ultrasonography.
The natural history of intracranial arterial stenoses remains relatively unknown. To monitor the progression of these lesions over time, the authors reviewed transcranial Doppler (TCD) laboratory reports at five hospitals for patients with angiographically documented intracranial arterial stenoses along the internal carotid artery distribution, and at least two TCD studies conducted more than 2 months apart. Twenty-two patients (19 men and 3 women; mean age, 64 years) with 29 stenoses were identified. The findings were compared to reproducibility data obtained from 11 age-matched control subjects with repeat TCD studies. During a mean follow-up period of 21 months, peak systolic flow velocities corresponding to the areas of stenosis increased in 9 arteries with lesions, and new collateral flow patterns, indicating further hemodynamic compromise distal to the lesions, developed in 2; one of the latter also had increased corresponding velocities. Thus, 10 (35%) arteries with lesions had TCD evidence of progression. Flow velocities remained the same in 13 (45%) stenotic vessels and dropped in 2 (7%). Findings were considered inconclusive for 4 lesions (14%). These findings suggest that intracranial arterial stenoses are dynamic lesions, and that they can evolve and cause further reductions of the arterial diameters after relatively short periods of time. TCD can noninvasively detect their hemodynamic effects.


MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke.
Monocarboxylate transporter 2 (MCT2) is the predominant monocarboxylate transporter expressed by neurons. MCT2 plays an important role in brain energy metabolism. Stroke survivors are at high risk of cognitive impairment. We reported previously that stroke-induced cognitive impairment was related to impaired energy metabolism. In the present study, we report that cognitive function was impaired after stroke in rats. We found that MCT2 expression, but not that of MCT1 or MCT4, was markedly decreased in the rat hippocampus at 7 and 28 days after transient middle cerebral artery occlusion (tMCAO). Moreover, MCT2 overexpression promoted recovery of cognitive function after stroke. The molecular mechanism underlying these effects may be related to an increase in adenosine monophosphate-activated protein kinase-mediated mitochondrial biogenesis induced by overexpression of MCT2. Our findings suggest that MCT2 activation ameliorates cognitive impairment after stroke.


Characterization of the association between cigarette smoking intensity and urinary concentrations of 2-hydroxyethyl mercapturic acid among exclusive cigarette smokers in the National Health and Nutrition Examination Survey (NHANES) 2011-2016.
2-Hydroxyethyl mercapturic acid (2HEMA, N-acetyl-S-(2-hydroxyethyl)-L-cysteine) is a urinary metabolite of several volatile organic compounds including acrylonitrile and ethylene oxide, which are found in cigarette smoke. We measured 2HEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey (2011-2016) from eligible participants aged >12 years (N = 7,416). We developed two multiple linear regression models to characterize the association between cigarette smoking and 2HEMA concentrations wherein the dependent variable was 2HEMA concentrations among participants who exclusively smoked cigarettes at the time of specimen collection and the independent variables included sex, age, race/ethnicity, creatinine, diet, and either cigarettes smoked per day (CPD) or serum cotinine. We detected 2HEMA in 85% of samples tested among exclusive cigarette smokers, and only 40% of specimens from non-smokers. When compared to exclusive cigarette smokers who smoked 1-9 CPD, smoking 10-19 CPD was associated with 36% higher 2HEMA (p < 0.0001) and smoking >19 CPD was associated with 61% higher 2HEMA (p < 0.0001). Additionally, 2HEMA was positively associated with serum cotinine. This study demonstrates that cigarette smoking intensity is associated with higher urinary 2HEMA concentrations and is likely a major source of acrylonitrile and/or ethylene oxide exposure.


Implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital.
The development and implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital are described. A multidisciplinary team was formed to address the feasibility of converting from the standard 30-minute infusion to an extended infusion of piperacillin- tazobactam. Before hospitalwide implementation, feasibility studies were performed in a subset of patients to identify potential barriers to program implementation. On the day of hospitalwide conversion, the orderables for piperacillin-tazobactam were reprogrammed in the computerized prescriber-order-entry system to allow separate options for the 30-minute infusion (for pediatric patients) and the extended-infusion regimen. After selecting the orderable for the extended-infusion regimen, an electronic message appeared to remind prescribers of the rationale for this change and recommended indications for piperacillin-tazobactam. Program success was prospectively evaluated on 11 weekdays after hospitalwide conversion for all 96 adult inpatients receiving piperacillin-tazobactam. Of the 194 piperacillin-tazobactam doses observed, 90% were appropriate, with compliance increasing to 100% by the end of the observation period. There was near-complete cessation of the every-6-hour dosage interval and a marked increase in the every-8-hour and every-12-hour dosage intervals. The number of piperacillin-tazobactam doses per 1000 patient-days significantly decreased during the postimplementation period. During the postimplementation period, pharmacy expenditures related to piperacillin-tazobactam decreased by 18% and the total number of grams of piperacillin-tazobactam purchased decreased by 24%. A hospitalwide program for the administration of extended-infusion piperacillin-tazobactam was safely and successfully implemented using a multi-disciplinary approach in an urban teaching hospital.


Ultrarelativistic particle collisions.
We present results from numerical solution of the Einstein field equations describing the head-on collision of two solitons boosted to ultrarelativistic energies. We show, for the first time, that at sufficiently high energies the collision leads to black hole formation, consistent with hoop-conjecture arguments. This implies that the nonlinear gravitational interaction between the kinetic energy of the solitons causes gravitational collapse, and that arguments for black hole formation in super-Planck scale particle collisions are robust.


Clinical Utility of Liquid Biopsy to Identify Genomic Heterogeneity and Secondary Cancer Diagnoses: A Case Report.
Liquid biopsy is a valuable tool in advanced and metastatic cancers for detection of genomic alterations in tumors that facilitate personalized targeted therapy approaches. Analyzing circulating tumor DNA (ctDNA) using next-generation sequencing (NGS) provides an opportunity to detect tumor genomic changes during therapy and capture inter- and intra-heterogeneity of genomically divergent cancer cell evolution. Herein, we present a patient with metastatic castration-resistant prostate cancer, with progression to soft tissues, bone, and regional lymph nodes, who was treated with abiraterone plus prednisone, with excellent prostate-specific antigen response. At the time of progression, NGS analysis of ctDNA using the FoundationOne®Liquid test revealed a CHEK2 mutation and a BRAF V600E mutation, the latter being exceedingly rare in prostate cancer. At the time of biochemical recurrence, the patient was referred to hematology for evaluation of chronic but stable thrombocytopenia prior to initiating new systemic therapy. Results of a bone marrow biopsy were consistent with hairy-cell leukemia, where the BRAF V600E mutation is considered the disease-defining mutation detectable in nearly all cases at diagnosis. In this case, liquid biopsy served as a noninvasive, highly sensitive approach to help reveal tumor genomic heterogeneity but also identified an unexpected genomic alteration leading to secondary cancer diagnosis and changes to treatment-related decision-making.


[Clinical application and observation of injectable modified sodium hyaluronate gel filler for facial cosmetic surgery].
Objective: To evaluate the clinical effect of injectable modified sodium hyaluronate gel filler in the treatment of facial profile modification and rejuvenation. Methods: A total of 125 patients who received facial injection of hyaluronate gel from October 2013 to October 2015 were collected. The patients included 62 cases for rhinoplasty, 28 for chin augmentation, 20 for nasolabial fold correction and 15 for lacrimal groove correction. The post-operation results, satisfaction survey and adverse reaction were observed. Results: All the injected positions improved immediately, and the instant average satisfaction score was 9.3±0.7, followed by 8.1±0.7 after 3 months, 6.9±0.8 after 6 month and 5.2±0.8 after 1 year. Thirty cases exhibited swelling, 5 cases bruised, and they all recovered within one week. Conclusions: Sodium hyaluronate is effective and stable in the treatment of facial contour modification and rejuvenation.


Replication of cowpox virus in macrophages is dependent on the host range factor p28/N1R.
Zoonotic orthopoxvirus infections continue to represent a threat to human health. The disease caused by distinct orthopoxviruses differs in terms of symptoms and severity, which may be explained by the unique repertoire of virus factors that modulate the host's immune response and cellular machinery. We report here on the construction of recombinant cowpox viruses (CPXV) which either lack the host range factor p28 completely or express truncated variants of p28. We show that p28 is essential for CPXV replication in macrophages of human or mouse origin and that the C-terminal RING finger domain of p28 is necessary to allow CPXV replication in macrophages.


Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.
apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.


Flavobacterium covae is the predominant species of columnaris causing bacteria impacting the channel catfish (Ictalurus punctatus) industry in the southeastern USA.
Columnaris disease is a leading cause of disease related losses in the catfish industry of the Southeastern USA. The term 'columnaris causing bacteria' (CCB) has been coined in reference to the four described species that cause columnaris disease, Flavobacterium columnare, F. covae, F. davisii, and F. oreochromis. Historically, F. columnare, F. covae, and F. davisii have been isolated from columnaris disease cases in the catfish industry; however, there is a lack of knowledge of which CCB species are most prevalent in farm-raised catfish. The current research objectives were (1) sample columnaris disease cases from the US catfish industry and identify species of CCB involved, and (2) determine the virulence of the four CCB species in channel catfish in controlled laboratory challenges. Bacterial isolates or swabs of external lesions from catfish were collected from 259 columnaris disease cases in Mississippi and Alabama from 2015-0027. DNA extracted from the samples were analyzed using a CCB-specific multiplex PCR to identify the CCB present in each diagnostic case. Results demonstrated that F. covae is the predominant species of CCB impacting the US catfish industry, present in 94.2% (n = 244) of diagnostic case submissions. Challenge experiments demonstrated F. covae and F. oreochromis were highly virulent to channel catfish resulting in near 100% mortality for most isolates. In contrast, F. columnare and F. davisii were less virulent resulting in less than 40% mortality for most isolates. Collectively, these results demonstrate F. covae is the predominant CCB in the US catfish industry and research aimed at developing new control and prevention strategies should target this bacterial species. The methods described herein can be used to continue monitoring the prevalence of CCB in the catfish industry and can be easily applied to other industries to identify which Flavobacterium species have the greatest impact.


Back to the garden: communes, the environment, and antiurban pastoralism at the end of the sixties.
This essay examines the complicated relationship among hippie communes, the environmental movement, and New Left and Black Power militants in the late 1960s and early 1970s. In those relationships lie the roots of the divide that separated environmental issues on one hand and urban issues on the other during the 1970s and beyond. This essay examines how the fight between militants and back-to-the-land communards and environmentalists, between what we might call urban progressives and antiurban progressives, was staged as a fight between those who cared about the issues of the city and those who turned their backs on them. In this way, this essay locates the city more centrally in politics of the era.


THE HERITABLE BASIS OF VARIATION IN LARVAL DEVELOPMENTAL PATTERNS WITHIN POPULATIONS OF THE WOOD FROG (RANA SYLVATICA).
This study compares the heritable basis of variation in larval developmental patterns of mountain and lowland populations of the wood frog, Rana sylvatica. Additive genetic variances, heritabilities, and genetic correlations for larval developmental time and size at metamorphosis are estimated from half-sib and full-sib crosses. Considerable additive-genetic variances and high heritabilities are revealed for developmental time in both the mountain and the lowland population. There was a high level of additive-genetic variance and high heritability for body size at metamorphosis in the mountain population, but these were very low in the lowland population. The genetic correlations between developmental rate and larval body size are negative for the mountain population and near zero for the lowland population. It is argued that the differences in genetic structure between these two populations reflect differences in the selective regimes of their respective environments.


Genome-Wide Methylation Study Identifies an IL-13-induced Epigenetic Signature in Asthmatic Airways.
Epigenetic changes to airway cells have been proposed as important modulators of the effects of environmental exposures on airway diseases, yet no study to date has shown epigenetic responses to exposures in the airway that correlate with disease state. The type 2 cytokine IL-13 is a key mediator of allergic airway diseases, such as asthma, and is up-regulated in response to many asthma-promoting exposures. To directly study the epigenetic response of airway epithelial cells (AECs) to IL-13 and test whether IL-13-induced epigenetic changes differ between individuals with and without asthma. Genome-wide DNA methylation and gene expression patterns were studied in 58 IL-13-treated and untreated primary AEC cultures and validated in freshly isolated cells of subjects with and without asthma using the Illumina Human Methylation 450K and HumanHT-12 BeadChips. IL-13-mediated comethylation modules were identified and correlated with clinical phenotypes using weighted gene coexpression network analysis. IL-13 altered global DNA methylation patterns in cultured AECs and were significantly enriched near genes associated with asthma. Importantly, a significant proportion of this IL-13 epigenetic signature was validated in freshly isolated AECs from subjects with asthma and clustered into two distinct modules, with module 1 correlated with asthma severity and lung function and module 2 with eosinophilia. These results suggest that a single exposure of IL-13 may selectively induce long-lasting DNA methylation changes in asthmatic airways that alter specific AEC pathways and contribute to asthma phenotypes.


Cysteine Biosynthesis Controls Serratia marcescens Phospholipase Activity.
Serratia marcescens causes health care-associated opportunistic infections that can be difficult to treat due to a high incidence of antibiotic resistance. One of the many secreted proteins of S. marcescens is the PhlA phospholipase enzyme. Genes involved in the production and secretion of PhlA were identified by screening a transposon insertion library for phospholipase-deficient mutants on phosphatidylcholine-containing medium. Mutations were identified in four genes (cyaA, crp, fliJ, and fliP) that are involved in the flagellum-dependent PhlA secretion pathway. An additional phospholipase-deficient isolate harbored a transposon insertion in the cysE gene encoding a predicted serine O-acetyltransferase required for cysteine biosynthesis. The cysE requirement for extracellular phospholipase activity was confirmed using a fluorogenic phospholipase substrate. Phospholipase activity was restored to the cysE mutant by the addition of exogenous l-cysteine or O-acetylserine to the culture medium and by genetic complementation. Additionally, phlA transcript levels were decreased 6-fold in bacteria lacking cysE and were restored with added cysteine, indicating a role for cysteine-dependent transcriptional regulation of S. marcescens phospholipase activity. S. marcescenscysE mutants also exhibited a defect in swarming motility that was correlated with reduced levels of flhD and fliA flagellar regulator gene transcription. Together, these findings suggest a model in which cysteine is required for the regulation of both extracellular phospholipase activity and surface motility in S. marcescensIMPORTANCESerratia marcescens is known to secrete multiple extracellular enzymes, but PhlA is unusual in that this protein is thought to be exported by the flagellar transport apparatus. In this study, we demonstrate that both extracellular phospholipase activity and flagellar function are dependent on the cysteine biosynthesis pathway. Furthermore, a disruption of cysteine biosynthesis results in decreased phlA and flagellar gene transcription, which can be restored by supplying bacteria with exogenous cysteine. These results identify a previously unrecognized role for CysE and cysteine in the secretion of S. marcescens phospholipase and in bacterial motility.


Vascular relaxation induced by Eucommiae Ulmoides Oliv. and its compounds Oroxylin A and wogonin: implications on their cytoprotection action.
The vascular relaxation action of Eucommiae Ulmoides Oliv. also known as Duzhong has been seen on arteries of the heart such as the aorta and the coronary artery which are elastic in nature. Duzhong is historically an active ingredient commonly used in hypertensive herbal prescriptions in China. This work investigated the vasodilating effect of Duzhong and its compounds (wogonin 10 μM and oroxylin-A) in the isolated intact rat heart, perfused retrograde according the method of Langendorff and the cytoprotective effect in EA.hy926 cell lines Coronary perfusion pressure was monitored with a pressure transducer connected to a side-arm of the aortic perfusion cannula. Duzhong induced vasorelaxation in a dose dependent manner, on precontracting the vessels with endothelin-1, Duzhong 10 mg/ml, wogonin 10 μM and oroxylin-A 10 μM could significantly lower the perfusion pressure in reference to positive control SNP, Duzhong induced vasodilation was not inhibited by L-NAME (nitric oxide inhibitor), but was significantly inhibited by Tetraethyl ammonium (TEA, a K(+) channel blocker and almost abolished by potassium chloride. The underlying mechanism was carried out in EA.hy926 cell lines. When these cells were treated with H2O2, there was higher expression of NOX-4, TNF-α and COX-2 mRNA. However, wogonin treatment attenuated the mRNA of NOX-4, TNF-α and COX-2. Wogonin also upregulated the mRNA expression of CAT, SOD-1 and GSR in oxidative stress induced by H2O2 EA.hy926 cells. Duzhong and compounds can exert an in vitro relaxation effect of the coronary artery and improve the heart function in Langendorff apparatus. This action appears to be endothelium dependent but not NO mediated. Cell culture findings indicated that wogonin can exert vascular and cellular protection by scavenging Reactive Oxygen Species.


Astrocytes derived from ASD individuals alter behavior and destabilize neuronal activity through aberrant Ca2+ signaling.
The cellular mechanisms of autism spectrum disorder (ASD) are poorly understood. Cumulative evidence suggests that abnormal synapse function underlies many features of this disease. Astrocytes regulate several key neuronal processes, including the formation of synapses and the modulation of synaptic plasticity. Astrocyte abnormalities have also been identified in the postmortem brain tissue of ASD individuals. However, it remains unclear whether astrocyte pathology plays a mechanistic role in ASD, as opposed to a compensatory response. To address this, we combined stem cell culturing with transplantation techniques to determine disease-specific properties inherent to ASD astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. These in vivo phenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neurons in vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+ fluctuations in chimeric brains. Genetic modulation of evoked Ca2+ responses in ASD astrocytes modulates behavior and neuronal activity deficits. Thus, this study determines that astrocytes derived from ASD iPSCs are sufficient to induce repetitive behavior as well as cognitive deficit, suggesting a previously unrecognized primary role for astrocytes in ASD.


Conformations of banana-shaped molecules studied by 2H NMR spectroscopy in liquid crystalline solvents.
ClPbis11BB and Pbis11BB, two banana-shaped mesogens differing by a chlorine substituent on the central phenyl ring, show a nematic and a B2 phase, respectively. To obtain information on the structural features responsible for their different mesomorphic behavior, a study of the preferred conformations of these mesogens has been performed by NMR spectroscopy in two nematic media (Phase IV and ZLI1167), which should mimic the environment of the molecules in their own mesophases, avoiding problems of sample alignment by a magnetic field. To this aim, 2H NMR experiments have been performed on selectively deuterated isotopomers of ClPbis11BB and Pbis11BB and of two parent molecules, ClPbisB and PbisB, assumed as models in previous theoretical and experimental conformational studies. We found that only a limited number of conformations is compatible with experimental data, often very different from those inferred from theoretical calculations in vacuo, indicating a strong influence of the liquid crystalline environment on molecular conformation. No significant differences between chlorinated and non-chlorinated molecules were found, this suggesting that chlorine does not change the molecular conformational equilibrium, as previously proposed.


Insights into acetate toxicity in Zymomonas mobilis 8b using different substrates.
Lignocellulosic biomass is a promising renewable feedstock for biofuel production. Acetate is one of the major inhibitors liberated from hemicelluloses during hydrolysis. An understanding of the toxic effects of acetate on the fermentation microorganism and the efficient utilization of mixed sugars of glucose and xylose in the presence of hydrolysate inhibitors is crucial for economic biofuel production. A new microarray was designed including both coding sequences and intergenic regions to investigate the acetate stress responses of Zymomonas mobilis 8b when using single carbon sources of glucose or xylose, or mixed sugars of both glucose and xylose. With the supplementation of exogenous acetate, 8b can utilize all the glucose with a similar ethanol yield, although the growth, final biomass, and ethanol production rate were reduced. However, xylose utilization was inhibited in both media containing xylose or a mixed sugar of glucose and xylose, although the performance of 8b was better in mixed sugar than xylose-only media. The presence of acetate caused genes related to biosynthesis, the flagellar system, and glycolysis to be downregulated, and genes related to stress responses and energy metabolism to be upregulated. Unexpectedly, xylose seems to pose more stress on 8b, recruiting more genes for xylose utilization, than does acetate. Several gene candidates based on transcriptome results were selected for genetic manipulation, and a TonB-dependent receptor knockout mutant was confirmed to have a slight advantage regarding acetate tolerance. Our results indicate Z. mobilis utilized a different mechanism for xylose utilization, with an even more severe impact on Z. mobilis than that caused by acetate treatment. Our study also suggests redox imbalance caused by stressful conditions may trigger a metabolic reaction leading to the accumulation of toxic intermediates such as xylitol, but Z. mobilis manages its carbon and energy metabolism through the control of individual reactions to mitigate the stressful conditions. We have thus provided extensive transcriptomic datasets and gained insights into the molecular responses of Z. mobilis to the inhibitor acetate when grown in different sugar sources, which will facilitate future metabolic modeling studies and strain improvement efforts for better xylose utilization and acetate tolerance.


Study of arsenic-protein binding in serum of patients on continuous ambulatory peritoneal dialysis.
Arsenic (As) bound to serum proteins in patients on continuous ambulatory peritoneal dialysis (CAPD) was studied. A prior experiment by ultrafiltration showed that 5.57% of total As was bound to serum proteins for 14 CAPD patients. Further identification of the As species and protein molecules in serum of three CAPD patients with high As concentrations was carried out by combining the separation methods of size-exclusion, anion-exchange, and affinity fast-protein liquid chromatography, detected by hydride generation atomic absorption spectrometry. The results indicated that only inorganic As species are bound to serum proteins. Transferrin is the main carrier. The concentrations of As bound to proteins in serum for the three patients were 0.44 +/- 0.12, 0.19 +/- 0.09, and 0.59 +/- 0.09 microg/L (n = 3), respectively.


Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and Clinical Populations: An Overview.
Transcranial direct current stimulation (tDCS) is a neuromodulatory approach that is affordable, safe, and well tolerated. This review article summarizes the research and clinically relevant findings from meta-analyses and studies investigating the cognitive effects of tDCS in healthy and clinical populations. We recapitulate findings from recent studies where cognitive performance paired with tDCS was compared with performance under placebo (sham stimulation) in single sessions and longitudinal designs where cognitive effects were evaluated following repeated sessions. In summary, the tDCS literature currently indicates that the effects of tDCS on cognitive measures are less robust and less predictable compared with the more consistent effects on motor outcomes. There is also a notable difference in the consistency of single-session and longitudinal designs. In single-session tDCS designs, there are small effects amid high variability confounded by individual differences and potential sham stimulation effects. In contrast, longitudinal studies provide more consistent benefits in healthy and clinical populations, particularly when tDCS is paired with a concurrent task. Yet, these studies are few in number, thereby impeding design optimization. While there is good evidence that tDCS can modulate cognitive functioning and potentially produce longer-term benefits, a major challenge to widespread translation of tDCS is the absence of a complete mechanistic account for observed effects. Significant future work is needed to identify a priori responders from nonresponders for every cognitive task and tDCS protocol.


Effects of fat type and emulsifier in feed on growth performance, slaughter traits, and lipid metabolism of Cherry Valley ducks.
A 2-factor test design was used to investigate the effect of an emulsifier (Aldo®, Lonza, America) (200 g/t) in the diet of Cherry Valley meat ducks to replace some of 2 different oils (animal fat and vegetable oil) on meat production performance, slaughter traits, and fat metabolism. The 900 healthy 18-day-old ducks were grouped into 6 treatments, each with 5 replicates and 30 meat ducks per replicate. The 2 fat sources were established as a positive control group, a negative control group (positive control group-some oil (equivalent to metabolic energy of 50 kcal/ton)), and an emulsifier group (negative control group + 200 g/ton Aldo). The results showed that addition of different fat sources in feed had no significant effect on growth performance, carcass properties, and fat metabolism of 18- to 42-day-old meat ducks (P > 0.05). Reducing the amount of oil used in the feed lowered the growth performance, carcass properties, and affected fat metabolism of meat ducks. However, in feeds with 2 fat sources, some oils were replaced by adding Aldo without affecting growth performance and carcass properties of meat ducks, and improved their fat metabolism, reduced triglycerides (TG) in serum, and increased activity of lipoprotein and hepatic lipases in liver and of pancreatic lipase. Thus, addition of Aldo to a low fat diet could improve growth performance, carcass quality, and lipid metabolism, and promote digestion and absorption of fat for meat ducks.


Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox.
Histone lysine demethylases facilitate the activity of oncogenic transcription factors, including possibly MYC. Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed. We also identified the approved small-molecule antifungal agent ciclopirox as a novel pan-histone demethylase inhibitor. Ciclopirox targeted several histone demethylases, including KDM4B implicated in MYC function. Accordingly, ciclopirox inhibited Myc signaling in parallel with mitochondrial oxidative phosphorylation, resulting in suppression of neuroblastoma cell viability and inhibition of tumor growth associated with an induction of differentiation. Our findings provide new insights into epigenetic regulation of MYC function and suggest a novel pharmacologic basis to target histone demethylases as an indirect MYC-targeting approach for cancer therapy. Cancer Res; 77(17); 4626-38. ©2017 AACR.


High yield expression, refolding, and characterization of recombinant interferon alpha2/alpha8 hybrids in Escherichia coli.
Interferons (IFNs) are a family of pleiotropic cytokines used for the treatment of various viral infections and cancers. The low-cost production of IFNs with high biological value and the discovery of IFNs with improved properties are important for the treatment of these diseases as well as for understanding the physiological functions of these compounds. We describe a protein expression system for the production of IFNs alpha2, alpha8, and their hybrids in insoluble form in Escherichia coli, coupled to an efficient two-step optimized refolding and histidine-tag purification protocol. The expressed IFNs were of high biological value, as shown in antiviral and antiproliferative assays and some had specific activities higher than those of the commercially available interferon preparations and exhibited novel properties. This time-efficient, optimized protein expression method allows for the production of not just a single interferon subtype but several native and hybrid IFNs with relatively high yield and low cost that can be used in functional and potentially clinical assays.