Heterojunction modification for highly efficient organic-inorganic perovskite solar cells.
Organic-inorganic perovskites, such as CH3NH3PbX3 (X=I, Br, Cl), have emerged as attractive absorber materials for the fabrication of low cost high efficiency solar cells. Over the last 3 years, there has been an exceptional rise in power conversion efficiencies (PCEs), demonstrating the outstanding potential of these perovskite materials. However, in most device architectures, including the simplest thin-film planar structure, a current-voltage response displays an "anomalous hysteresis", whereby the power output of the cell varies with measurement time, direction and light exposure or bias history. Here we provide insight into the physical processes occurring at the interface between the n-type charge collection layer and the perovskite absorber. Through spectroscopic measurements, we find that electron transfer from the perovskite to the TiO2 in the standard planar junction cells is very slow. By modifying the n-type contact with a self-assembled fullerene monolayer, electron transfer is "switched on", and both the n-type and p-type heterojunctions with the perovskite are active in driving the photovoltaic operation. The fullerene-modified devices achieve up to 17.3% power conversion efficiency with significantly reduced hysteresis, and stabilized power output reaching 15.7% in the planar p-i-n heterojunction solar cells measured under simulated AM 1.5 sunlight.


[Textual research on Lu You's poet on diseases during his trip to Nanchang].
By combining textual research on Bing Zhong Zuo (Poet Composed When Falling Ill) in Lu You's Jiannan shigao (Jiannan's Poetry Anthology), with other related historical materials, the geographical and climatic features of Nanchang area in the Southern Song Dynasty and epidemo1ogical characteristics of common diseases such as rheumatism, gastro-enteropathy and pulmonary diseases et al. thus happened can be clearly understood. It reflects the customs of the belief on witchery in medical treatment and the low medical level in Nanchang at that time. Meanwhile, it also reflects Lu You's optimistic attitude on his illness and his quiet, simple and open-minded idea of keeping fit.


Postoperative neovascularization, cerebral hemodynamics, and clinical prognosis between combined and indirect bypass revascularization procedures in hemorrhagic moyamoya disease.
We evaluated what few studies emphasized the postoperative collateral formation and cerebral hemodynamics of hemorrhagic moyamoya disease (MMD). Hemorrhagic MMD patients treated surgically were retrospectively collected and dichotomized into combined bypass (CB) and indirect bypass (IB) groups. CB used superficial temporal artery-to-middle cerebral artery anastomosis combined with encephaloduroarteriomyosynangiosis (STA-MCA+EDAMS), and IB used encephaloduroarteriomyosynangiosis (EDAMS) for revascularization. Postoperative complications and clinical prognosis, as well as pre- and post-operative Modified Rankin Scale (mRS), collateral circulation status, and cerebral hemodynamics were observed and compared between the CB and IB groups. A total of 37 patients with hemorrhagic MMD were identified. Of the 68 cerebral hemispheres, 47(69.1%) were combined revascularization, and the rest were indirect. During an average follow-up of 16.5 ± 8.7 months, the recurrent stroke events were significantly lower, as well as having a postoperative mRS scores≤ 2. A satisfactory postoperative collateral formation, and an improved dilation or extension of the anterior choroidal/posterior communication artery (AchA/PcoA) were significantly higher in the CB group than in the IB group (all P < .05). Compared with preoperative cerebral hemodynamics, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and relative time to peak (rTTP) in the CB group; rCBF, rCBV, and MTT in the IB group were significantly improved (all P < .001). The CB group's postoperative rCBF was significantly improved compared with the IB group (P < .001). STA-MCA bypass combined with EDAMS can obtain better postoperative collateral formation, cerebral hemodynamics, and clinical prognosis than EDAMS alone.


[Design and development of analysis software for acid-base balance disorder based on Visual Basic.NET].
To develop a diagnostic analysis software for determining the type of acid-base balance disorder. Mathematical models were built based on Henderson-Hasselbalch equations and compensation formulas, to determine the important parameters of acid-base balance disorder, and to develope acid-base balance disorder analysis process. The software was compiled using the Visual Basic.NET programming language, and the installation package was generated after debugging. Acid-base balance disorder cases were searched by PubMed, Wanfang and CNKI databases from 1980 to 2015, and the blood gas parameters [pH, arterial partial pressure of carbon dioxide (PaCO2), HCO3- and anion gap (AG)] and the types of acid-base imbalance (literature results) were recorded. All cases were reanalyzed by software and the type of acid-base balance disorder was determined (software diagnostic type). Kappa-test and McNemar-test were performed for the two diagnostic results. The "four parameters-four steps" analysis method was used as the analysis process to judge the types of acid-base balance disorder. "Four parameters" included pH, PaCO2, HCO3- and AG. "Four steps" were outlined by following aspects: (1) according to the pH, combined with PaCO2 and HCO3-, the primary types of acid-base balance disorder was determined; (2) according to the compensation situation, double mixed acid-base balance disorder (DABD) was determined; (3) according to AG value, three mixed acid-base disorders (TABD) were determined; (4) the ratio of ΔAG ↑ /ΔHCO3- ↓ was also calculated to determine whether there was normal AG metabolic acidosis or metabolic alkalosis. The software had the characteristics of simple interface, convenient operation, rapid judgment, and comprehensive analysis. It could judge all acid-base balance disorder types excepted "AG normal metabolic acidosis combined metabolic alkalosis". The software was used to reanalyze 112 cases of acid-base balance disorder reported in the literature, with a consistent rate of 87.50% and better consistency of the diagnostic results (Kappa test: κ = 0.84, P < 0.01; McNemar test: χ2 = 0.87, P = 0.65). The software can be used as an important tool to judge the type of acid-base balance disorder, and provide clinicians with diagnostic reference, which have practical value and application prospect.


Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection.
The advancement of gene therapy has been slowed, in part, by inefficient transduction of targeted cells and poor long-term engraftment of genetically modified cells. Thus, the ability to select for a desired population of cells within a recipient would be of great benefit for improving gene therapy. Proposed strategies for in vivo cell selection using drug resistance genes have had disappointing outcomes and/or require highly genotoxic medications to be effective. We hypothesized that resistance to purine analogs, a well-tolerated, relatively low-toxicity class of medications, could be provided to cells using interfering RNA against hypoxanthine phosphoribosyl transferase. Using a lentiviral vector, we found that interfering RNA-mediated purine analog resistance (iPAR) provided relative resistance to 6-thioguanine (6TG) in murine hematopoietic cells compared with control- and untransduced cells. iPAR attenuated 6TG-induced G(2)/M checkpoint activation, cell-cycle arrest, and apoptosis. Furthermore, in recipients of transplanted bone marrow cells with iPAR, treatment with 6TG resulted in increased percentages of transduced peripheral blood cells and hematopoietic progenitor cells in the bone marrow. Secondary transplantations resulted in higher hematopoietic contributions from 6TG-treated primary recipients relative to phosphate-buffered saline-treated recipients. These findings indicate that iPAR/6TG can be used for in vivo hematopoietic progenitor cell selection.


Association between ambient temperature and chronic obstructive pulmonary disease: a population-based study of the years of life lost.
Limited evidence on the burden of chronic obstructive pulmonary disease (COPD) attributable to ambient temperature. We aim to explore the association between ambient temperature and years of life lost (YLL), and to get a more intuitive understanding of the dangers of COPD in China. Death and meteorological data of 31 Chinese provincial capital cities during 2008-2013 was analyzed in this study. Distributed Lag Non-linear Model (DLNM) was used to estimate the association between ambient temperature and mortality. The attributable fraction (AF) to cold effect ranged from 8.19 (95%CI: -8.52,19.38) to 28.98 (95%CI: -64.78,67.59), while the AF to heat effect varied from 0.02 (95%CI: -0.13,0.05) to 5.73 (95%CI: 0.31,10.22). Cold effect was higher than heat effect on COPD in women and elderly, heat effect was higher in men and younger. Low temperature can cause more serious disease burden of COPD than high temperature.


Combination of Silver Nanoparticles and Vancomycin to Overcome Antibiotic Resistance in Planktonic/Biofilm Cell from Clinical and Animal Source.
This study aims to evaluate the prevalence of multidrug-resistant (MDR) and biofilm-forming pathogens from animal source compared to clinical ones. In addition, to assess the antibacterial and antibiofilm activity of silver nanoparticles (AgNPs) alone and/or mixed with vancomycin. Out of 62 bacterial isolates from animal respiratory tract infection (RTI), 50.00% were defined as MDR, while among human ones, 44.00% were MDR. The bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae were the predominant isolated bacteria from both animal and human origin with frequency percentage of 50.00, 22.32, and 18.75, respectively. Among Staph. aureus strains, mecA gene was detected in 60.00% and 61.54% of animal and human isolates, respectively, while mecALGA251 (mecC) gene was detected in 13.33% and 15.38% of animal and human isolates, respectively. Biofilm formation ability among animal isolates was 83.87%, while among human ones was 86.00%. AgNPs were effective in inhibiting planktonic cells with minimal inhibitory concentration (MIC) values (0.625-10 μg/mL), as well as eradicating biofilm with minimal biofilm eradication concentration values (1.25-10 μg/mL). Noticeable low MIC of AgNPs was required for the isolates from animal source (0.625-5 μg/mL) compared to clinical ones (0.625-10 μg/mL). Remarkable reduction in AgNP effective concentration was observed after combination with 1/4 MIC of vancomycin with minimum recorded concentration of 0.08 μg/mL. In conclusion, the prevalence of MDR among RT pathogens was recorded with high ability to produce biofilm and virulence factors from both animal and human pathogens. AgNPs showed strong antibacterial and antibiofilm activity alone and mixed with vancomycin, with up to fourfold reduction of AgNP inhibitory dose.


Results of a survey of cancer patients' willingness to travel to participate in a clinical trial.
Only 2-3% of cancer patients enrol in a trial. We surveyed patients' willingness to change clinician or treating centre, or to travel, to participate in trials, to improve trial recruitment. Of 188 respondents, 79% were willing to participate in a trial in at least one scenario. Increasing travel time, change in oncologist, private health insurance and out of pocket expenses decreased likelihood of joining a trial. Rural and regional patients, and those from lower socio-economic areas, were more willing to travel. To optimise access to trials, clinicians should refer within and between institutions.


Osteoprotegerin inhibits calcification of vascular smooth muscle cell via down regulation of the Notch1-RBP-Jκ/Msx2 signaling pathway.
Vascular calcification is a common pathobiological process which occurs among the elder population and in patients with diabetes and chronic kidney disease. Osteoprotegerin, a secreted glycoprotein that regulates bone mass, has recently emerged as an important regulator of the development of vascular calcification. However, the mechanism is not fully understood. The purpose of this study is to explore novel signaling mechanisms of osteoprotegerin in the osteoblastic differentiation in rat aortic vascular smooth muscle cells (VSMCs). VSMCs were isolated from thoracic aorta of Sprague Dawley rats. Osteoblastic differentiation of VSMCs was induced by an osteogenic medium. We confirmed by Von Kossa staining and direct cellular calcium measurement that mineralization was significantly increased in VSMCs cultured in osteogenic medium; consistent with an enhanced alkaline phosphatase activity. This osteoblastic differentiation in VSMCs was significantly reduced by the addition of osteoprotegerin in a dose responsive manner. Moreover, we identified, by real-time qPCR and western blotting, that expression of Notch1 and RBP-Jκ were significantly up-regulated in VSMCs cultured in osteogenic medium at both the mRNA and protein levels, these effects were dose-dependently abolished by the treatment of osteoprotegerin. Furthermore, we identified that Msx2, a downstream target of the Notch1/RBP-Jκ signaling, was markedly down-regulated by the treatment of osteoprotegerin. Osteoprotegerin inhibits vascular calcification through the down regulation of the Notch1-RBP-Jκ signaling pathway.


Improving training for sensory augmentation using the science of expertise.
Sensory substitution and augmentation devices (SSADs) allow users to perceive information about their environment that is usually beyond their sensory capabilities. Despite an extensive history, SSADs are arguably not used to their fullest, both as assistive technology for people with sensory impairment or as research tools in the psychology and neuroscience of sensory perception. Studies of the non-use of other assistive technologies suggest one factor is the balance of benefits gained against the costs incurred. We argue that improving the learning experience would improve this balance, suggest three ways in which it can be improved by leveraging existing cognitive science findings on expertise and skill development, and acknowledge limitations and relevant concerns. We encourage the systematic evaluation of learning programs, and suggest that a more effective learning process for SSADs could reduce the barrier to uptake and allow users to reach higher levels of overall capacity.


The functional nitrite reductase activity of the heme-globins.
Hemoglobin and myoglobin are among the most extensively studied proteins, and nitrite is one of the most studied small molecules. Recently, multiple physiologic studies have surprisingly revealed that nitrite represents a biologic reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. These studies suggest a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction. Biophysical and chemical analysis of the nitrite-deoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. The first is that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobin-nitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Third, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of 2 molecules of nitrite into dinitrogen trioxide (N(2)O(3)), an uncharged molecule that may be exported from the erythrocyte. We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart.


[From recognition to practice: The 140th anniversary of the discovery of Clonorchis sinensis].
It has been the 140th anniversary since the discovery of Clonorchis sinensis, of which adult worms were found by McConnell in an oversea Chinese in Calcutta, India, September of 1874. Then, Japanese scholar Kobayashi proved that freshwater fish served as the second intermediate hosts in 1910, while another Japanese parasitologist Muto found that the first intermediate hosts were freshwater snails in 1918. However, the perniciousness has not been recognized until recently. C. sinensis infection was classified as definite carcinogen (group 1) in cholangiocarcinoma in 2009 by the International Agency for Research on Cancer, WHO, and listed as one of the 17 diseases in WHO's first report on neglected tropical diseases in 2010, while its disease burden was published on line in an international journal in 2011. Nevertheless, our awareness on and practices in the control of clonorchiasis still lag behind the reality. Great efforts on research and control of clonorchiasis are especially required in China, since China takes the biggest share in global disease burden of clonorchiasis.


Concepts and tools for gene editing.
Gene editing is a relatively recent concept in the molecular biology field. Traditional genetic modifications in animals relied on a classical toolbox that, aside from some technical improvements and additions, remained unchanged for many years. Classical methods involved direct delivery of DNA sequences into embryos or the use of embryonic stem cells for those few species (mice and rats) where it was possible to establish them. For livestock, the advent of somatic cell nuclear transfer platforms provided alternative, but technically challenging, approaches for the genetic alteration of loci at will. However, the entire landscape changed with the appearance of different classes of genome editors, from initial zinc finger nucleases, to transcription activator-like effector nucleases and, most recently, with the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas). Gene editing is currently achieved by CRISPR-Cas-mediated methods, and this technological advancement has boosted our capacity to generate almost any genetically altered animal that can be envisaged.


Thermodynamically based DNA strand design.
We describe a new algorithm for design of strand sets, for use in DNA computations or universal microarrays. Our algorithm can design sets that satisfy any of several thermodynamic and combinatorial constraints, which aim to maximize desired hybridizations between strands and their complements, while minimizing undesired cross-hybridizations. To heuristically search for good strand sets, our algorithm uses a conflict-driven stochastic local search approach, which is known to be effective in solving comparable search problems. The PairFold program of Andronescu et al. [M. Andronescu, Z. C. Zhang and A. Condon (2005) J. Mol. Biol., 345, 987-1001; M. Andronescu, R. Aguirre-Hernandez, A. Condon, and H. Hoos (2003) Nucleic Acids Res., 31, 3416-3422.] is used to calculate the minimum free energy of hybridization between two mismatched strands. We describe new thermodynamic measures of the quality of strand sets. With respect to these measures of quality, our algorithm consistently finds, within reasonable time, sets that are significantly better than previously published sets in the literature.


The Prevalence of Cigarette and E-cigarette Smoking Among Students in Central and Eastern Europe-Results of the YUPESS Study.
Electronic cigarettes (e-cigarettes) are an alternative to traditional tobacco cigarette smoking. The aim of this study was to assess the prevalence of cigarette smoking and e-cigarette use among university students from Central and Eastern Europe and to investigate personal characteristics associated with cigarette and e-cigarette smoking. A questionnaire-based cross-sectional survey was performed between 2017-2018 among university students in five European countries: Belarus, Lithuania, Poland, Russia, and Slovakia. The questionnaire included 46 questions related to the frequency and habits of traditional cigarettes and e-cigarettes use. Completed questionnaires were obtained from 14,352 students (8800 medical; aged 20.9 ± 2.4 years) with an overall response rate of 72.2%. Two-thirds of the respondents had smoked a traditional tobacco cigarette and 43.7% had used an e-cigarette. Overall current smoking status included 12.3% traditional cigarette smokers, 1.1% e-cigarette users, and 1.8% were dual users with the remainder being non-smokers. Smoking status differed between the research centres (p < 0.001). Females were less likely to try either cigarettes (OR = 0.83) or e-cigarettes (OR = 0.62) and were less likely to be current cigarette (OR = 0.64), e-cigarette (OR = 0.34), or dual users (OR = 0.33) than males. Perception of e-cigarettes significantly differed between smokers and non-smokers (p < 0.001). Among university students, cigarettes are more popular than e-cigarettes.


Principles of safety pharmacology.
Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).


[Male infertility with chromosomal abnormalities. III. 46, XYq-].
A deletion of the long arm of the Y chromosome (46,XYq-) was found in two cases with normal male habitus but with azoospermia. The first case was of a 28-year-old married man, an office worker, complaining of infertility. His height was 153 cm, weight 57 kg and distance of extended hand 152 cm. Both testes were 13 ml in size. The second case was a 32-year-old married man, a fireman, complaining of infertility. His height was 160 cm, weight 64 kg and distance of extended hand 161 cm. Both testes were 10 ml in size. In each case, the external genitalia showed a normal male type, but azoospermia was identified in semen analysis. The testicular biopsy specimens revealed spermatogenic arrest with thickening of basement membrane. Chromosomal analysis showed 46,XYq- karyotype. Basal serum levels of luteinizing hormone and follicle-stimulating hormone were slightly elevated and the serum testosterone level was within normal limits. Eight cases of 46,XYq- karyotype in the Japanese literature including our cases were reviewed.


Biomimetic Synthesis of Complex Flavonoids Isolated from Daemonorops "Dragon's Blood".
The dragonbloodins are a pair of complex flavonoid trimers that have been isolated from the palm tree Daemonorops draco, one of the sources of the ancient resin known as "dragon's blood". We present a short synthesis that clarifies their relative configurations and sheds light on their origin in Nature. This synthesis features biomimetic cascade reactions that involve both ionic and radical intermediates. The biogenetic relationships between dracorhodin, the dracoflavans C, and the dragonbloodins A1 and A2 are discussed.


Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation.
Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge. Intra-nasal administration of OVA and papain preferentially activated Th2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although T-/B-cell-deficient mice showed severely decreased nasal symptoms induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. Similarly, IL-33- and ST2-deficient mice showed decreased OVA-plus-papain-induced nasal symptoms. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain. Dexamethasone ameliorated OVA-alone-induced nasal epithelial thickening. However, OVA-plus-papain-induced nasal epithelial thickening was only partially controlled by dexamethasone. These results demonstrate that IL-33/ST2-pathway-mediated ILC2 activation exacerbated Th2-cell-induced nasal inflammation by producing IL-13. Although Th2-cell-alone-induced nasal inflammation was controlled by corticosteroid treatment, the activation of ILC2s conferred treatment resistance. Therefore, ILC2s and their activators could be therapeutic targets for treatment-refractory nasal allergic disorders.


Drug repositioning for idiopathic epilepsy using gene expression signature data.
Epilepsy is one of the most common neurological disorders, affecting millions of patients with a substantial economic and human burden. About 30-40% of epileptic patients remain un-treated after the therapeutic option. Genetic or idiopathic epilepsy count about 40% of total epilepsy patients, showing a maximum percentage for drug-resistant epilepsy. Since the last century basic approach to understanding disease progression and drug discovery has been through the prism, exploring all possible causes and treatment options. Here we report about the gene expression-based drug repositioning study for epilepsy. Epilepsy gene expression data was retrieved from the Gene Expression Omnibus database, while drugs-associated gene expression data was retrieved from the Connectivity map (CMAP). The study predicted309 drug compounds which can alter genetic epilepsy-mediated gene signature using an in-house developed R-script. These compounds were docked against identified epilepsy targets- Voltage-gated sodium channel subunit α2 (Nav1.2); GABA receptor α1-β1; and Voltage-gated calcium channel α1G (Cav3.1)using Carbamazepine, Clonazepam, and Pregabalin as standard drugs, respectively. Twenty-one predicted drug compounds showed better binding affinity than respective standards against the selected epileptic receptors. Among these drug compounds, Ergocalciferol, Oxaprozin, Flunarizine, Triprolidine and Cyproheptadine have been previously reported for anti-epileptic activities and can be potential hits to target idiopathic epilepsy.


Broad spectrum antibiotics in newborns increase multi-drug resistant infections.
Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4-17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1-34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.


Atractylenolide I Ameliorates Acetaminophen-Induced Acute Liver Injury via the TLR4/MAPKs/NF-κB Signaling Pathways.
Background: Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), induces hepatocyte necrosis, and leads to acute liver failure. Atractylenolide I (AO-I), a phytochemical found in Atractylodes macrocephala Koidz, is known to exhibit antioxidant activity. However, its clinical benefits against drug-induced liver injury remain largely unclear. Purpose: This study aimed at evaluating the protective effects of AO-I against APAP-induced acute liver injury. Methods: C57BL/6 mice were administered 500 mg/kg APAP to induce hepatotoxicity. AO-Ⅰ (60 and 120 mg/kg) was intragastrically administered 2 h before APAP dosing. Liver histopathological changes, oxidative stress and hepatic inflammation markers from each group were observed. Results: We observed that AO-I treatment significantly reversed APAP-induced liver injury, as evidenced by improved plasma alanine transaminase (ALT) level, aspartate aminotransferase (AST) and liver H&E stain. APAP treatment increased liver malondialdehyde (MDA) content and reduced catalase (CAT) and glutathione (GSH) level; however, these effects were alleviated by AO-I intervention. Moreover, AO-I treatment significantly inhibited APAP-induced activation of pro-inflammatory factors, such as IL-1β, IL-6, and TNF-α, at both the mRNA and protein levels. Mechanistic studies revealed that AO-I attenuated APAP-induced activation of TLR4, NF-κB and MAPKs (including JNK and p38). Conclusion: AO-I mediates protective effects against APAP-induced hepatotoxicity via the TLR4/MAPKs/NF-κB pathways. Thus, AO-I is a candidate therapeutic compound for APAP-induced hepatotoxicity.


Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease.
Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs related to impaired oxidative stress, DNA repair, and inflammatory pathways could be replicated in an independent cohort study of donor-matched healthy and atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n = 19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as most central disease-associated DNA methylation biomarkers. Differentially methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and pyrosequencing assays and could be further replicated in blood, aorta tissue and carotid plaque material of atherosclerosis patients. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures (coronary calcium score and carotid intima media thickness) in an independent sample cohort of middle-aged men with subclinical cardiovascular disease in the Aragon Workers' Health Study (n = 24). Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers for early risk stratification and CVD prevention.


A benchmark study of electronic excitation energies, transition moments, and excited-state energy gradients on the nicotine molecule.
In this work, we report a comparative study of computed excitation energies, oscillator strengths, and excited-state energy gradients of (S)-nicotine, chosen as a test case, using multireference methods, coupled cluster singles and doubles, and methods based on time-dependent density functional theory. This system was chosen because its apparent simplicity hides a complex electronic structure, as several different types of valence excitations are possible, including n-π(*), π-π(*), and charge-transfer states, and in order to simulate its spectrum it is necessary to describe all of them consistently well by the chosen method.


Resisted Sprint Training in Youth: The Effectiveness of Backward vs. Forward Sled Towing on Speed, Jumping, and Leg Compliance Measures in High-School Athletes.
Uthoff, A, Oliver, J, Cronin, J, Winwood, P, Harrison, C, and Lee, JE. Resisted sprint training in youth: the effectiveness of backward vs. forward sled towing on speed, jumping, and leg compliance measures in high-school athletes. J Strength Cond Res 35(8): 2205-2212, 2021-Resisted sprinting (RS) is a popular training method used to enhance sprinting performance in youth. However, research has only explored the effects of forward RS (FRS) training. We examined the effects of FRS and backward RS (BRS) and compared these with a traditional physical education curriculum (CON). One hundred fifteen boys (age 13-15 years) were matched for maturity and allocated to either an FRS (n = 34), BRS (n = 46), or CON (n = 35) group. Training groups towed progressively overloaded sleds (20-55% body mass) 2 d·wk-1 for 8 weeks. Pre-training and post-training data were collected for sprinting times over 10 and 20 m, countermovement jump (CMJ) height, and leg stiffness (KN). Performance remained unchanged for the CON group (all p > 0.05), whereas all variables significantly improved (p < 0.05) after BRS, and all but 10-m performance improved after FRS. Compared with the CON, BRS and FRS significantly (p > 0.05) improved CMJ (Effect size [ES] = 0.67 and 0.38) and KN (ES = 0.94 and 0.69), respectively. No differences were found between training groups. The probabilities of improving sprinting performance after BRS (∼70%) were on average ∼10 and ∼8% better than the FRS and CON groups, respectively. The BRS and FRS showed similar probabilities of improving CMJ (75 and 79%) and KN (80 and 81%), respectively, over the CON group. It seems that BRS may be a means to improve sprint performance, and regardless of direction, RS seems to be a beneficial method for improving jumping height and leg stiffness in youth male athletes.


Diagnostic outcomes for molecular genetic testing in children with suspected Ehlers-Danlos syndrome.
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders characterized by hyperextensible skin, hypermobile joints, easy bruisability, and fragility of the connective tissues. The diagnosis is based on clinical assessment and phenotype-guided genetic testing. Most EDS subtypes can be confirmed by genetic testing except for hypermobile EDS. This study explored the utility of applying the 2017 EDS classification criteria and molecular genetic testing in establishing an EDS diagnosis in children. In this retrospective study, we reviewed 72 patients referred to a tertiary care center for evaluation of EDS who underwent one or more forms of genetic testing. Eighteen patients (18/72, 25%) met the clinical criteria for one of the EDS subtypes and of these, 15 (15/18, 83%) were confirmed molecularly. Fifty-four patients (54/72, 75%) had features that overlapped EDS and other syndromes associated with joint hypermobility but did not fully meet clinical criteria. Twelve of them (12/54, 22%) were later shown to have a positive molecular genetic diagnosis of EDS. Different molecular genetic tests were performed on the cohort of 72 patients (EDS panel, n = 44; microarray, n = 25; whole exome sequencing [WES], n = 9; single gene sequencing, n = 3; familial variant testing, n = 10; other genetic panels n = 3). EDS panel was completed in 44 patients (61%), and a molecular diagnosis was confirmed in nine of the patients who satisfied criteria for one of the EDS subtypes (9/12, 75%) and in nine of the patients who did not fully meet criteria (9/32, 28%). We observed a correlation between generalized joint hypermobility, poor healing, easy bruising, atrophic scars, skin hyperextensibility, and developmental dysplasia of the hip with a positive molecular result. This study provides guidance for the use of molecular genetic testing in combination with the 2017 clinical diagnostic criteria in children presenting with EDS characteristics.


Skin cancer: symptoms, mechanistic pathways and treatment rationale for therapeutic delivery.
Cancer is a group of diseases categorized by abandoning escalation and multiplication of abnormal cells. Current topical treatments for skin cancer are mainly in the semisolid dosage forms of 5-fluorouracil, imiquimod, etc. Many surgical treatments are also available these days for the treatment of skin cancer, for example, photodynamic therapy, which is approved by the US FDA. The stratum corneum is the main barrier against permeation of topical formulations developed for skin cancer treatment. Liposomes, thermosensitive stealth liposomes, nanoemulsions and polymeric lipid nanoparticles have been used by several researchers to increase skin permeability. In the present paper, major aspects of formulations developed for skin cancer, various types of skin cancer, its etiology and pathogenesis have been emphasized.


Cholesterol absorption inhibitors in development as potential therapeutics.
Drugs that lower low-density lipoprotein cholesterol through their actions in the gastrointestinal tract have been used for > 30 years. Bile acid sequestrants have very excellent safety profiles but their poor tolerability means they have limited clinical use. Recently developed new compounds are better tolerated in clinical trials and show greater benefit in reducing low-density lipoprotein cholesterol level, as compared to "older" sequestrants. Cholesterol absorption inhibitors and bile acid transporter inhibitors have recently been reported to show clinical efficacy and safety as novel gut-acting drugs for lowering cholesterol. Further advances in our understanding of the cholesterol absorption mechanism will provide novel therapeutic targets, such as the ATP-binding cassette transporter. This approach in the treatment of lowering cholesterol appears to play a more significant role in the clinical field of atherosclerotic vascular disease.


Arrhythmogenic Cardiomyopathy - New Insights into Disease Mechanisms and Drug Discovery.
Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disorder characterized by the early appearance of ventricular arrhythmias often out of proportion to the degree of ventricular remodeling and dysfunction. ACM typically presents in adolescence or early adulthood. It accounts for 10% of sudden cardiac deaths in individuals under the age of 18 years. Although there has been significant progress in recognizing the genetic determinants of ACM, how specific gene mutations cause the disease remains poorly understood. Here, we review insights gained from studying the human disease as well as in vivo and in vitro experimental models. These observations have advanced our understanding of the molecular mechanisms underlying the pathogenesis of ACM and may lead to development of new mechanism-based therapies.


Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aβ.
Microglia are the resident immune cells found in our brain. They have a critical role in brain maintenance. Microglia constantly scavenge various waste materials in the brain including damaged or apoptotic neurons and Aβ. Through phagocytosis of Aβ, microglia prevent the accumulation of Aβ plaque in the brain. However, in Alzheimer's disease (AD) patients, chronic exposure to Aβ makes microglia to become exhausted, which reduces their phagocytic activity against Aβ. Since microglia play an important role in Aβ clearance, enhancing microglial phagocytic activity against Aβ is a promising target for AD treatment. Therefore, there is a great need for therapeutic candidate that enhances microglial Aβ clearance while inhibiting microglia's pathogenic properties. In vivo studies were conducted with 5xFAD AD model mice by treating gossypetin for 13 weeks through intragastric administration. Their spatial learning and memory were evaluated through behavior tests such as Y-maze and Morris Water Maze test. Hippocampus and cortex were acquired from the sacrificed mice, and they were used for histological and biochemical analysis. Also, mouse tissues were dissociated into single cells for single-cell RNA sequencing (scRNA-seq) analysis. Transcriptome of microglial population was analyzed. Mouse primary microglia and BV2 mouse microglial cell line were cultured and treated with fluorescent recombinant Aβ to evaluate whether their phagocytic activity is affected by gossypetin. Gossypetin treatment improved the spatial learning and memory of 5xFAD by decreasing Aβ deposition in the hippocampus and cortex of 5xFAD. Gossypetin induced transcriptomic modulations in various microglial subpopulations, including disease-associated microglia. Gossypetin enhanced phagocytic activity of microglia while decreasing their gliosis. Gossypetin also increased MHC II+ microglial population. Gossypetin showed protective effects against AD by enhancing microglial Aβ phagocytosis. Gossypetin appears to be a novel promising therapeutic candidate against AD.


Case report of fatal complication of superior vena cava tear from balloon dilatation of iatrogenic superior vena cava narrowing.
The treatment options for superior vena cava (SVC) obstruction depends on the cause and severity of SVC narrowing. It ranges from conservative medical management to more elaborate endovascular and surgical repair of obstruction. There has always been a concern regarding the possibility of rupture of SVC during balloon dilatation, if the obstruction is secondary to the surgical cause. Very few cases are reported in the literature. We report a case of fatal complication of SVC tear in a 2-month-old child who had iatrogenic SVC narrowing.


Site-selective interactions: squaraine dye-serum albumin complexes with enhanced fluorescence and triplet yields.
We report the effect of steric factors of a few squaraine dyes, bis(2,4,6-trihydroxyphenyl)squaraine (1), bis(3,5-dibromo-2,4,6-trihydroxyphenyl)squaraine (2), and bis(3,5-diiodo-2,4,6-trihydroxyphenyl) squaraine (3), on their binding with human (HSA) and bovine (BSA) serum albumins employing photophysical, chiroptical, biophysical, and microscopic techniques. These dyes interact with serum albumins very efficiently and exhibit site selectivity, involving synergistic effects of hydrophobic, hydrogen bonding, and electrostatic interactions. The association constants of these complexes have been determined and are found to be 4.9 x 10(6) and 4.1 x 10(5) M(-1), respectively, for the dyes 2 and 3 with BSA, while HSA showed relatively higher association constants of 6.0 x 10(6) and 9.9 x 10(5) M(-1). Highly clear distinction in site-selective binding can be ascertained from time-resolved fluorescence, displacement cum fluorimetry, and circular dichroism (CD) studies. The increased affinity toward the major binding site (site II, domain III) over the relatively smaller binding site (site I, domain II) in the serum albumin with the increasing size of the heavy atoms present in 2 and 3 as compared to 1 indicates the importance of steric factors thereby confirming that the dye structure has a predominant role in deciding site selectivity. The distance between the energy donor and acceptor was calculated using Forster theory, which agrees well with the reported site 1 binding agent dansylamine. In contrast, no energy transfer was observed between tryptophan (Trp-214) present in domain II of the albumins and the dyes 2 and 3, indicating that these derivatives bind less efficiently at site I due to steric conatraints but preferentially bind at site II. Laser flash photolysis studies of the dyes 2 and 3 in the presence of HSA exhibited ca. 2.5-fold enhancements in the triplet lifetimes and quantum yields when compared to that obtained in buffer. The uniqueness of these dyes is that they show substituent size-dependent selectivity at site II of serum albumins and signal the event through "turn on" fluorescence intensity as well as enhanced triplet excited state lifetimes and quantum yields, thereby indicating their potential use as NIR noncovalent protein labeling and photodynamic therapeutic agents.


Isolated intraspinal relapse of neuroblastoma after autologous bone marrow transplantation.
Neuroblastoma may present with spinal cord compression due to dumbbell extension of thoracic or abdominal disease. Isolated intraspinal involvement as the sole site of relapse is rare. Two infants with poor-prognosis stage IV neuroblastoma presented early after high-dose therapy and autologous bone marrow transplant with isolated spinal relapse heralded by misleading symptoms. The rarity of such isolated relapses is reviewed, and an etiologic hypothesis is proposed.


Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis.
Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide insights into the mechanisms of tumorigenesis and the risk for disease recurrence in HPV-negative head and neck cancers, originating in the hypopharynx, larynx, and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs in 178 HPV-negative head and neck cancer patients using a quantitative methylation-specific PCR. Promoter methylation was correlated with various clinical characteristics and patient survival. The mean number of methylated TRGs was 14.2 (range, 2-25). In the multivariate Cox proportional hazards analysis, the methylation of COL1A2 and VEGFR1 was associated with poor survival for hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014, respectively. The methylation of p16 and COL1A2 were independent prognostic factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and 3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005 and 5.38; p = 0.029, respectively). Our findings suggest that methylation status of TRGs could serve as important site-specific biomarkers for prediction of clinical outcomes in patients with HPV-negative head and neck cancer.


KIF1A novel frameshift variant p.(Ser887Profs*64) exhibits clinical heterogeneity in a Pakistani family with hereditary sensory and autonomic neuropathy type IIC.
Background: Hereditary sensory and autonomic neuropathies (HSANs) are rare heterogeneous group of neurological disorders caused by peripheral nerve deterioration. The HSANs sub-clinical classes have clinical and genetic overlap which often lead to misdiagnosis. In the present study a Pakistani family with five affected members suffering from severe neuropathy were genetically analyzed to identify the disease causative element in the family.Methods: Genome wide high-density single nucleotide polymorphism (SNP) microarray analysis was carried out followed by whole exome sequencing of the affected proband and another affected sibling. Shared homozygous regions in all severely affected members were identified through homozygosity mapping approach.Results: The largest homozygous region of 14.1 Mb shared by the five severely affected members of the family was identified on chromosome 2. Subsequent exome sequencing identified a novel single nucleotide deletion c.2658del; p.(Ser887Profs*64) in KIF1A. Segregation analysis revealed that this mutation was homozygous in all five affected individuals of the family with severe clinical manifestation, while members of the family that were heterozygous carriers shared abnormal skin features (scaly skin) only with the homozygous affected members.Conclusions: A novel frameshift mutation p.(Ser887Profs*64) in KIF1A is the potential cause of severe HSANIIC in a Pakistani family along with incomplete penetrance in mutation carriers. We demonstrate that using a combination of different techniques not only strengthens the gene finding approach but also helps in proper sub-clinical characterization along with identification of mutated alleles exhibiting incomplete penetrance leading to intrafamilial clinical variability in HSAN group of inherited diseases.


AVP-923, a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect and neuropathic pain.
AVANIR Pharmaceuticals Inc, under license from Irisys Research & Development, is developing AVP-923 (Zenvia, Neurodex) for the treatment of pseudobulbar affect (PBA; in collaboration with Medison Pharma Ltd) and neuropathic pain associated with diabetic peripheral neuropathy. PBA, the main indication of AVP-923, is a neurological disorder characterized by uncontrollable and unpredictable episodes of laughing and/or crying. AVP-923 consists of a combination of the NMDA antagonist/sigma1 receptor agonist dextromethorphan hydrobromide (DM) and the cytochrome P450 2D6 (CYP2D6) enzyme inhibitor quinidine sulfate (Q). DM has been under investigation for several years as a neuroprotective agent in stroke, neurosurgery and amyotrophic lateral sclerosis (ALS); however, it is rapidly metabolized by CYP2D6, reducing the drug's bioavailability at neuronal targets. The inclusion of Q inhibits the rapid first-pass metabolism of DM to increase systemic concentrations of the drug in the plasma and, in theory, increase the potential efficacy. The initial clinical data for AVP-923 in the treatment of PBA demonstrated the combination was effective, but exhibited significant side effects. Of particular concern to the FDA were increased QTc intervals reported in patients dosed with a 30-/30-mg dose of DM/Q. A subsequent phase III clinical trial assessing a lower dose of AVP-923 (20 or 30 mg DM/10 mg Q) for the treatment of PBA in patients with ALS or multiple sclerosis was implemented by AVANIR and demonstrated a favorable safety profile of AVP-923 while maintaining efficacy. Pending approval of the data from the FDA, AVP-923 would be the first FDA-approved treatment for PBA.


A Direct Comparison of the Effects of the Antiretroviral Drugs Stavudine, Tenofovir and the Combination Lopinavir/Ritonavir on Bone Metabolism in a Rat Model.
Antiretroviral (ARV) treatment may induce metabolic complications in HIV patients on long-term therapy that can affect bone health. In this study, the effects of the ARVs Stavudine (d4T), Tenofovir (TDF) and Lopinavir/ritonavir (LPV/r) on bone metabolism and lipodystrophy were directly compared in rats to negate the consequences of HIV-associated confounding factors. Healthy 12-14-week-old male Wistar rats (n = 40) were divided into four treatment groups and received an oral animal equivalent dose of either Stavudine (6.2 mg/kg/day), TDF (26.6 mg/kg/day), LPV/r (70.8 mg/kg/day) or water (Control 1.5 mL water/day) for a period of 9 weeks. Whole-body DXA measurements, a biomechanical three-point breaking test and histomorphometric analysis were performed on the femurs and tibias at the end of the treatment period. Stavudine monotherapy was found to be associated with decreased femoral bone mineral density that translated into reduced bone strength, whereas histomorphometric analysis demonstrated that Stavudine induces an imbalance in bone metabolism at tissue level, evident in higher resorption (eroded surfaces, osteoclast surfaces and osteoclast number) and lower formation parameters (osteoblast surfaces and osteoid surfaces). This was less clear in the rats treated with either TDF or LPV/r. Furthermore, both Stavudine and TDF treatment resulted in significant bone marrow adiposity, although no significant redistribution of body fat was noted in the treated rats compared to controls. The data from this study suggest that in the absence of HIV-associated factors, LPV/r is less detrimental to bone metabolism compared to Stavudine and TDF.


SLICER: A Seamless Gene Deletion Method for Deinococcus radiodurans.
Deinococcus radiodurans' high resistance to various stressors combined with its ability to utilize sustainable carbon sources makes it an attractive bacterial chassis for synthetic biology and industrial bioproduction. However, to fully harness the capabilities of this microbe, further strain engineering and tool development are required. Methods for creating seamless genome modifications are an essential part of the microbial genetic toolkit to enable strain engineering. Here, we report the development of the SLICER method, which can be used to create seamless gene deletions in D. radiodurans. This process involves (a) integration of a seamless deletion cassette replacing a target gene, (b) introduction of the pSLICER plasmid to mediate cassette excision by I-SceI endonuclease cleavage and homologous recombination, and (c) curing of the helper plasmid. We demonstrate the utility of SLICER for creating multiple gene deletions in D. radiodurans by sequentially targeting 5 putative restriction-modification system genes, recycling the same selective and screening markers for each subsequent deletion. While we observed no significant increase in transformation efficiency for most of the knockout strains, we demonstrated SLICER as a promising method to create a fully restriction-minus strain to expand the synthetic biology applications of D. radiodurans, including its potential as an in vivo DNA assembly platform.


Clinical survey on type of restoration in deciduous teeth.
This study was conducted in 533 children with 1,634 treated teeth who visited the Pediatric Dentistry Department at the Chiba Hospital of Tokyo Dental College between January and December, 2003. Restorations on deciduous tooth were categorized by age of patient and tooth type. The following observations were made: Children aged 4 (17.9%) visited the clinic most frequently and this group had the highest number of deciduous restorations (21.3%). Among the 1,634 deciduous teeth restored, metal inlays were provided in 29.4% of total teeth restored, composite resin restorations in 27.2%, stainless-steel crowns in 25.7%, composite resin full crowns in 7.7%, glass-ionomer cement restorations in 6.6%, and amalgam restorations in 3.4%. By age, composite resin was most frequently used in children aged 1 to 3. In children aged 5 to 9, metal inlay was most frequently used. Those aged 4 received mostly stainless-steel crowns. Composite resin restorations were used mostly in anterior deciduous teeth, and metal inlays mostly in deciduous molars. Previous research indicated an increasing trend towards composite resin restorations and composite resin full crowns. The present study also confirmed such a trend. While the use of metal inlays and stainless-steel crowns tended to increase until 1987, the present study indicated a trend to decrease.


[Subacute sclerosing panencephalitis (SSPE) in Poland in the years 1993-1995. The sixth stage of epidemiological research].
Data was collected about 49 newly diagnosed cases of SSPE in the years 1993-1995 in Poland. In the analyzed period of time a falling of tendency the incidence of SSPE was maintained. Overall incidence--0.42 per million population, was lower than the incidence in years 1990-1992, when it was 0.72. The tendency of a shift towards older age group was maintained--the peak incidence was observed among 19 year olds, as opposed to 15 year olds in the previous analyzed time period. The authors explain the dropping SSPE incidence in Poland with a drop in measales incidence, which is a consequence of growing measles vaccine coverage rates. The influence of a big measles epidemic which occurred in 1989-1990 on a potential rise in number of SSPE cases has not been noted, but further observations are needed.


Aerosol-assisted atmospheric cold plasma deposition and characterization of superhydrophobic organic-inorganic nanocomposite thin films.
A facile atmospheric pressure cold plasma process is presented to deposit a novel organic-inorganic hydrocarbon polymer/ZnO nanoparticles nanocomposite coating. Specifically, this method involves the utilization of an atmospheric pressure dielectric barrier discharge (DBD) fed with helium and the aerosol of a dispersion of oleate-capped ZnO nanoparticles (NPs) in n-octane. As assessed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, the deposited nanocomposite coating combines the chemical features of both the oleate-capped ZnO NPs and the polyethylene-like organic component originated from the plasma polymerization of n-octane. Additionally, scanning electron microscopy (SEM) and transmission scanning electron microscopy (TSEM) confirm the synthesis of hierarchical micro/nanostructured coatings containing quasi-spherical NPs agglomerates. The polyethylene-like polymer covers the NPs agglomerates to different extents and contributes to their immobilization in the three-dimensional network of the coating. The increase of both the deposition time (1-10 min) and the NPs concentration in the dispersion (0.5-5 wt %) has a significant effect on the chemical and morphological structure of the thin films and, in fact, results in the increase the ZnO NPs content, which ultimately leads to superhydrophobic surfaces (advancing and receding water contact angles higher than 160°) with low hysteresis due to the hierarchical multiscale roughness of the coating.


The marriage of surgical simulation and telementoring for damage-control surgical training of operational first responders: A pilot study.
Hemorrhage is the leading cause of preventable posttraumatic death. Many such deaths may be potentially salvageable with remote damage-control surgical interventions. As recent innovations in information technology enable remote specialist support to point-of-care providers, advanced interventions, such as remote damage-control surgery, may be possible in remote settings. An anatomically realistic perfused surgical training mannequin with intrinsic fluid loss measurements (the "Cut Suit") was used to study perihepatic packing with massive liver hemorrhage. The primary outcome was loss of simulated blood (water) during six stages, namely, incision, retraction, direction, identification, packing, and postpacking. Six fully credentialed surgeons performed the same task as 12 military medical technicians who were randomized to remotely telementored (RTM) (n = 7) or unmentored (UTM) (n=5) real-time guidance by a trauma surgeon. There were no significant differences in fluid loss between the surgeons and the UTM group or between the UTM and RTM groups. However, when comparing the RTM group with the surgeons, there was significantly more total fluid loss (p = 0.001) and greater loss during the identification (p = 0.002), retraction (p = 0.035), direction (p = 0.014), and packing(p = 0.022) stages. There were no significant differences in fluid loss after packing between the groups despite differences in the number of sponges used; RTM group used more sponges than the surgeons and significantly more than the UTM group (p = 0.048). However, mentoring significantly increased self-assessed nonsurgeon procedural confidence (p = 0.004). Perihepatic packing of an exsanguinating liver hemorrhage model was readily performed by military medical technicians after a focused briefing. While real-time telementoring did not improve fluid loss, it significantly increased nonsurgeon procedural confidence, which may augment the feasibility of the concept by allowing them to undertake psychologically daunting procedures.


Evidence for a critical role of diet in the development of insulin-dependent diabetes mellitus.
The role of diet in human insulin-dependent diabetes mellitus (IDDM) has not been properly examined, mainly due to a lack of reliable markers to identify prospective diabetics and the difficulties in obtaining accurate and representative dietary information. Nonetheless, there is some circumstantial evidence suggesting a role for diet in human IDDM. The validity of this relationship in humans must await a sufficiently large, well designed prospective study or the discovery of better markers for diabetes predisposition. The recent availability of the spontaneously diabetic BB rat has permitted prospective studies under controlled conditions which indicate diet, particularly dietary proteins, such as wheat gluten or cow's milk proteins may be prerequisites for maximum expression of the insulin-dependent syndrome in these animals. The early suckling and/or post-weaning period appears to be important and may be the crucial time when these proteins or portions of them pass the gastrointestinal barrier and initiate a process, possibly immunological, which results in destruction of the beta cells of the pancreas.


[Effect and significance of tetrandrine on epidermal growth factor and its receptor in the lung of congenital diaphragmatic hernia rat model].
To investigate the effect of the traditional Chinese medicine "Tetrandrine"(TET) and its significance on epidermal growth factor (EGF) and its receptor (EGFR) in the lung of nitrofen-induced congenital diaphragmatic hernia (CDH) rat model. Twenty female rats were given maternal administration of a single oral dose (115 mg/rat) of nitrofen to induce CDH at 9.5 days after pregnancy and were divided into normal solution group (NS, n=5), dexamethasone group (Dex, n=5), tetrandrine group (TET, n=5) and Dex+TET group (n=5) at 18.5 days; 4 rats were given edible oil as controls. All fetuses were delivered by cesarean section at 21.5 days. Lung histologic evaluations and EGF, EGFR immunohistochemical staining and image analysis were performed. CDH was observed in 64 of the 137 rat fetuses (46.7%) in the experimental groups; no CHD was observed in 36 rat fetuses of control group. The lungs of CDH fetuses showed marked hypoplasia in NS group, in contrast to improved mesenchymal differentiation in that of Dex, TET, Dex+TET groups. The expression of EGF was weaker and weaker and that of EGFR was stronger and stronger as following order: NS, TET, DEX, T+D and control groups; showing significant differences between them (P<0.05). Prenatal TET administration shows marked improvement in pulmonary hypoplasia through pre-regulating crest-time of EGF expression and up-regulating EGFR expression in the lungs of nitrofen-induced CDH rat model. A combination of TET and Dex would generate evident synergistic effect.


Risk assessment for Helicoverpa zea (Lepidoptera: Noctuidae) resistance on dual-gene versus single-gene corn.
Recent Environmental Protection Agency (EPA) decisions regarding resistance management in Bt-cropping systems have prompted concern in some experts that dual-gene Bt-corn (CrylA.105 and Cry2Ab2 toxins) may result in more rapid selection for resistance in Helicoverpa zea (Boddie) than single-gene Bacillus thuringiensis (Bt)-corn (CrylAb toxin). The concern is that Bt-toxin longevity could be significantly reduced with recent adoption of a natural refuge for dual-gene Bt-cotton (CrylAc and Cry2Ab2 toxins) and concurrent reduction in dual-gene corn refuge from 50 to 20%. A population genetics framework that simulates complex landscapes was applied to risk assessment. Expert opinions on effectiveness of several transgenic corn and cotton varieties were captured and used to assign probabilities to different scenarios in the assessment. At least 350 replicate simulations with randomly drawn parameters were completed for each of four risk assessments. Resistance evolved within 30 yr in 22.5% of simulations with single-gene corn and cotton with no volunteer corn. When volunteer corn was added to this assessment, risk of resistance evolving within 30 yr declined to 13.8%. When dual-gene Bt-cotton planted with a natural refuge and single-gene corn planted with a 50% structured refuge was simulated, simultaneous resistance to both toxins never occurred within 30 yr, but in 38.5% of simulations, resistance evolved to toxin present in single-gene Bt-corn (CrylAb). When both corn and cotton were simulated as dual-gene products, cotton with a natural refuge and corn with a 20% refuge, 3% of simulations evolved resistance to both toxins simultaneously within 30 yr, while 10.4% of simulations evolved resistance to CrylAb/c toxin.


[A case of pancreatic cancer with invasion to the wall of the intrahepatic bile duct].
Presented here is the case of a 69-year-old woman with pancreatic cancer. Efforts were made to discover the origin of the cancer but without success. Tumor nodules were scarcely observed in the pancreas macroscopically at autopsy, while histological examination of the pancreas revealed the presence of a well-differentiated adenocarcinoma (duct cell carcinoma). The invasion to the wall of the intrahepatic bile duct was also observed microscopically.


Differential binding to human mammary and nonmammary tumors of monoclonal antibodies reactive with carcinoembryonic antigen.
Splenic lymphocytes of mice immunized with membrane enriched fractions of human mammary carcinomas were fused with the NS-1 nonsecretory++ myeloma cell line. The resulting hybridomas were screened for the synthesis of immunoglobulins reactive with human mammary tumor associated antigens, and two IgG monoclonal antibodies (B1.1 and F5.5) were identified as being reactive with purified carcinoembryonic antigen (CEA). These antibodies were shown to bind to different epitopes on CEA based on their differential reactivities to five different purified CEA preparations, and their differential binding to the surface of tumor cells derived from various organ sites. Monoclonal B1.1 bound equally to the surface of human breast, colon, and melanoma cell lines. Monoclonal F5.5, on the other hand, did not react with the surface of melanoma cell lines, and showed a differential binding to breast carcinoma versus colon carcinoma cells. Monoclonals F5.5 and B1.1 were both used in immunoperoxidase studies with fixed tissue sections of a variety of histologic types of human mammary carcinomas and were shown to be reactive with 55% and 66%, respectively, of tumor masses.


Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to tetrachlorodibenzo-p-dioxin (TCDD).
In utero exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was found to alter expression of murine thymocyte fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 1.5, or 3.0 micrograms TCDD/kg/day in corn oil on gestational days (gd) 6-14. Offspring were examined on gd 18 and postnatally on d6, d14, and d21, and at 7, 8, and 10 weeks of age. Severe thymic atrophy and cellular depletion were found both pre- and postnatally in TCDD-exposed mice. Immunocytochemical localization of the Thy 1.2 antigen on gd 18 thymocytes revealed no TCDD-related changes in cellular distribution. Flow cytometric analysis, however, indicated that the TCDD treatment resulted in a significant decrease in the percentage of CD4+8+ fetal thymocytes, as well as significantly increased CD4-8- and CD4-8+ thymocytes. The increased CD4-8+ population after TCDD was not from induction of Ts cells. At 7-8 weeks postnatally, no differences existed between control and treatment groups in mitogen responses and antibody plaque response. However, altered thymocyte antigen expression was found to correlate with altered postnatal immune function, as evidenced by decreased cytotoxic T lymphocyte response at 8 weeks of age. Taken together, these results indicate that immunosuppression following prenatal exposure to TCDD can be readily detected by qualitative and quantitative changes in the cell surface phenotype of fetal thymocytes. Furthermore, the observed altered distribution suggests that TCDD inhibits normal thymocyte maturational processes.


Azithromycin-induced cholestatic hepatitis.
Since its introduction >20 years ago, Azithromycin has been widely used owing to its broad spectrum and good tolerability, especially when used for <7 days. In literature, there are only very few, sporadic reports available of patients developing cholestatic hepatitis following treatment with it. The current case study describes a 69-year old patient, with a medical history that included significant alcohol consumption, who presented with jaundice following a 3-day course of Azithromycin. Following a transjugular liver biopsy, he was managed with a short course of corticosteroids and his liver function gradually improved and finally normalized ~2 months after discontinuation of Azithromycin.


Cannabinoids reduce fertility of sea urchin sperm.
Cannabinoids are potent pharmacological substances derived from marihuana. The effects of delta 9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) on fertilization in the sea urchin Strongylocentrotus purpuratus were investigated. Insemination of THC-treated eggs (5-400 microM) with excess sperm did not result in polyspermic fertilization. At minimal sperm densities, THC (0.1-10 microM) inhibited fertilization in a dose-dependent manner. Pretreatment of eggs with THC did not reduce their receptivity to sperm. Pretreatment of sperm with THC reduced their fertilizing capacity. The concentration of THC required to reduce sperm fertility by 50% was 1.1 +/- 1.1 microM. The fertilizing capacity of THC-treated sperm depended on concentration of sperm and duration of pretreatment. The fertility of sperm at minimal densities was reduced by 50% at 129.3 +/- 43 s treatment with 10 microM THC. The adverse effect of THC on sperm fertility was reversible. CBN and CBD at comparable concentrations (0.1-10 microM) inhibited fertilization in a manner similar to THC. First division was not delayed in zygotes that were fertilized with sperm pretreated with 10 microM THC. These studies show that cannabinoids directly affect the process of fertilization in sea urchins by reducing the fertilizing capacity of sperm.


Expanding transcatheter aortic valve replacement into uncharted indications.
Since the first-in-man transcatheter delivery of an aortic valve prosthesis in 2002, the landscape of aortic stenosis therapeutics has shifted dramatically. While initially restricted to non-surgical cases, progressive advances in transcatheter aortic valve replacement and our understanding of its safety and efficacy have expanded its use in intermediate and possibly low surgical risk patients. In this review, we explore the past, present, and future of transcatheter aortic valve replacement.


The effects of precepting on and the support desired by community-based preceptors in Iowa.
To survey community-based family physician-preceptors about teaching costs, issues, and support desired. In late 1994 a questionnaire was mailed to all 139 community family physicians who served as preceptors for the University of Iowa College of Medicine's third-year family practice preceptorship. The questionnaire contained items regarding teaching costs and the kinds of assistance desired from the university, the difficult and enjoyable aspects of precepting, and demographic data. Analyses were done to explore the associations between the preceptors' demographic variables and the effects of precepting on number of patients seen, practice income, and time spent at work. Also tested were the associations between the demographic variables and the kinds of support desired. In all, 130 surveys were returned, for a response rate of 94%. Nearly all of the respondents were Caucasian, male, and residency trained; 61% were in group practices. While precepting, 87% spent more time at work, 31% saw fewer patients, and 25% lost practice income; mean daily cost estimates of precepting were 51 more minutes at work, 1.4 fewer patients seen, and $34 in lost income. The support the preceptors were most interested in receiving was training in and access to computer-based information. Financial compensation was desired more often by the physicians whose first year of practice was after 1977 (p = .009). Motivations for precepting included positive interactions with students and enjoyment of teaching. Time concerns were overwhelmingly the most difficult aspect of precepting. The physicians-many of whom noted their enjoyment of teaching for its intrinsic rewards-spent a significant amount of extra time teaching while precepting, and thus both lost income and saw fewer patients. Medical schools need to recognize the valuable contributions of preceptors and find ways to support them.


Heat destruction of some bacterial strains attached to broiler skin.
1. Heat destruction of bacteria attached to the skin did not occur at a logarithmic rate provided the temperature was above 51 degrees C. 2. It was concluded that the bacteria are protected by their location in the skin surface rather than by polymers produced during attachment. 3. An analogous process is considered to take place during the scalding of broilers, since bacteria which survived were difficult to remove from the carcasses during further processing.


An Investigation of Sodium Fusidate and Recombinant Cytochrome P450 Enzymes Inhibition In-Vitro.
Sodium fusidate (fusidic acid) is an antimicrobial agent that is used in the treatment of staphylococcal and streptococcal infections. Several case reports have noted a drug interaction between sodium fusidate and CYP3A4 metabolised statins, leading to statin toxicity. It is unclear whether sodium fusidate has the potential to cause interactions with other cytochrome P450 enzymes. To investigate the effects of sodium fusidate on recombinant cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) in-vitro. A range of sodium fusidate concentrations (0.1µM, 1µM, 10µM, 100µM, 300µM, 1000µM and 10000µM) were tested to examine its activity on rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 and rCYP3A4 using a luminescent assay with a luciferin substrate. Sodium fusidate inhibited all enzymes at tested concentrations which are relevant to those likely to be achieved in clinical practice. Further, sodium fusidate was found to be a time-dependent inhibitor of all the tested isoenzymes, with the exception of rCYP2C9. These findings suggest that there is a potential for sodium fusidate to cause drug interactions when used with other agents that are substrates for rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 or rCYP3A4. Understanding the basis of this potential drug interaction will assist in safer use of sodium fusidate in clinical practice.


[Establishment and applications of the spatial database of land resources information in Anshun, Guizhou Province].
For the purpose of managing and processing land resources and environment information, a spatial database of land information in Anshun City, Guizhou Province, which involved present data and the investigated information by remote sensing, was established under the supporting of PAMAP GIS 4.2. The spatial database could provide the functionality of querying for spatial data and its associated attributes, conversion between the different data formats, mapping the digital terrain, fast and accurate analysis on soil resources, land assessment and management application, and soil erosion risk mapping. The establishment of this spatial database was expected to play an important role in territorial planning, agricultural sustainable development, spatial assessment of ecological environment, and so on.


Nurses' implementation of guidelines for ventilator-associated pneumonia from the Centers for Disease Control and Prevention.
Ventilator-associated pneumonia accounts for 47% of infections in patients in intensive care units. Adherence to the best nursing practices recommended in the 2003 guidelines for the prevention of ventilator-associated pneumonia from the Centers for Disease Control and Prevention should reduce the risk of ventilator-associated pneumonia. To evaluate the extent to which nurses working in intensive care units implement best practices when managing adult patients receiving mechanical ventilation. Nurses attending education seminars in the United States completed a 29-item questionnaire about the type and frequency of care provided. Twelve hundred nurses completed the questionnaire. Most (82%) reported compliance with hand-washing guidelines, 75% reported wearing gloves, half reported elevating the head of the bed, a third reported performing subglottic suctioning, and half reported having an oral care protocol in their hospital. Nurses in hospitals with an oral care protocol reported better compliance with hand washing and maintaining head-of-bed elevation, were more likely to regularly provide oral care, and were more familiar with rates of ventilator-associated pneumonia and the organisms involved than were nurses working in hospitals without such protocols. The guidelines for the prevention of ventilator-associated pneumonia from the Centers for Disease Control and Prevention are not consistently or uniformly implemented. Practices of nurses employed in hospitals with oral care protocols are more often congruent with the guidelines than are practices of nurses employed in hospitals without such protocols. Significant reductions in rates of ventilator-associated pneumonia may be achieved by broader implementation of oral care protocols.


A role for nonapeptides and dopamine in nest-building behaviour.
During nest building in zebra finches (Taeniopygia guttata), several regions in the social behaviour network and the dopaminergic reward system, which are two neural circuits involved in social behaviour, appear to be active in male and female nest-building finches. Because the nonapeptides, mesotocin and vasotocin and the neurotransmitter, dopamine, play important roles in avian social behaviour, we tested the hypothesis that mesotocinergic-vasotocinergic and dopaminergic neuronal populations in the social behaviour network and dopaminergic reward system, respectively, are active during nest building. We combined immunohistochemistry for Fos (an indirect marker of neuronal activity) and vasotocin, mesotocin or tyrosine hydroxylase on brain tissue from nest-building and non-nest-building male and female zebra finches and compared Fos immunoreactivity in these neuronal populations with the variation in nest-building behaviour. Fos immunoreactivity in all three types of neuronal populations increased with some aspect of nest building: (i) higher immunoreactivity in a mesotocinergic neuronal population of nest-building finches compared to controls; (ii) increased immunoreactivity in the vasotocinergic neuronal populations in relation to the amount of material picked up by nest-building males and the length of time that a male spent in the nest with his mate; and (iii) increased immunoreactivity in a dopaminergic neuronal population in relation to the length of time that a male nest-building finch spent in the nest with his mate. Taken together, these findings provide evidence for a role of the mesotocinergic-vasotocinergic and dopaminergic systems in avian nest building.


Hypernatremia in the geriatric population.
Hypernatremia in the geriatric population is a common disorder associated with significant morbidity and mortality. Older people are predisposed to developing hypernatremia because of age-related physiologic changes such as decreased thirst drive, impaired urinary concentrating ability, and reduced total body water. Medications may exacerbate this predisposition. Hypernatremia and dehydration occurring in nursing homes are considered indicators of neglect that warrant reporting, but there are other nonavoidable causes of hypernatremia, and consideration at time of presentation is essential to prevent delay in diagnosis and management. We describe a case illustrating the importance of the consideration of alternate explanations for hypernatremia in a nursing home resident, followed by a review of hypernatremia in the elderly population, to underscore that neglect is the etiology of exclusion after alternatives have been considered.


Correlation between electromyography and quantitative ultrasonography of facial muscles in patients with facial palsy.
In this study we correlated results of ultrasonographic muscle thickness and contractility with facial electromyography (EMG) in patients with unilateral peripheral acute or chronic facial palsy. Two hundred twenty measurements of 4 facial muscles (frontalis, orbicularis oculi, zygomaticus, and orbicularis oris) were performed in 44 patients. Facial muscle thickness at rest and during muscle contraction correlated best with EMG insertional activity, and facial muscle contractility correlated with EMG voluntary activity. The correlation was much higher at >14 days after onset of facial palsy. The orbicularis oris, followed by the frontalis muscle, showed the best correlation between ultrasound and EMG. Quantitative ultrasound of facial muscles helps confirm the results of facial EMG and is of particular additional value in the first 14 days after onset when the reliability of EMG is low.


Kinetic dielectric decrement revisited: phenomenology of finite ion concentrations.
With the help of a recently developed non-equilibrium approach, we investigate the ionic strength dependence of the Hubbard-Onsager dielectric decrement. We compute the depolarization of water molecules caused by the motion of ions in sodium chloride solutions from the dilute regime (0.035 M) up close to the saturation concentration (4.24 M), and find that the kinetic decrement displays a strong non-monotonic behavior, in contrast to the prediction of available models. We introduce a phenomenological modification of the Hubbard-Onsager continuum theory, which takes into account the screening due to the ionic cloud at the mean-field level and, which is able to describe the kinetic decrement at high concentrations including the presence of a pronounced minimum.


UV exposure and protection against allergic airways disease.
Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity. Allergen-specific IgE levels control the immediate response whilst the interplay between airway mucosal antigen presenting cells, Th2 effector cells and CD4+CD25+ regulatory T cells control the late phase, cell-mediated response. Using two experimental systems in mice with ovalbumin and papain, respectively, as the allergens, UV irradiation of skin prior to allergen sensitisation reduced the expression of allergic airways disease, particularly the late phase response. In this review, the reduced Th2-driven, asthma-like responses in respiratory tissues of UV-irradiated mice are detailed. Possible mechanisms of UV regulation are debated. The potential beneficial effects of UV irradiation of skin in controlling allergic airways disease are discussed. This review gives some scientific understanding to century-old anecdotal reports that beach and mountain resort holidays associated with increased UV exposure are beneficial in asthma treatment.


In vitro attachment to a human cell line of Escherichia coli strains causing urinary-tract infection: occurrence of fimbriae (pili) in adhesive and non-adhesive strains.
In this study, 20 strains of Escherichia coli isolated from infected urinary-tract were screened for the occurrence of haemagglutinating (HA) activity and for the possible relationship between a fimbriate surface structure and adhesion ability to the surface of a human cell line. Only 8 of the 20 adhesive strains agglutinated human or guinea-pig erythrocytes or both. In 7 of the 8 strains, the haemagglutinating activity with human erythrocytes was D-mannose-resistant; one strain was D-mannose-sensitive with guinea-pig red blood cells (RBC). In 40 non-adhering E. coli isolated from urine, D-mannose-resistant HA was rarely detected; in contrast, agglutination of guinea-pig was more frequent and D-mannose-sensitive when it occurred. No correlation was found between the degree of HA activity and the ability to adhere. Moreover at low growth temperature (18 degrees c), haemagglutinin was absent in all the strains tested, whereas residual adhesion capacity could be detected in some strains. Similar results were recorded after heating the bacterial suspension at 65 degrees C. Generally pili detected by electron microscopy were present at the surface of the strains which agglutinated RBC. There is no correlation between the presence of fimbriae or pili and adhesion of E. coli to the human cell line used in this study. A range of distinct mechanisms of E. coli adhesion appeared to be involved in the phenomenon described in this report.


Lymphotropic strain SL3 of Aleutian disease virus: identification of replicative form DNA, molecular cloning and expression of capsid-specific proteins.
Replicative form (RF) DNA of the lymphotropic strain SL3 of Aleutian disease virus was isolated from infected cell cultures. A novel intermediate of about 7.6 kilobases was demonstrated in Hirt lysates in addition to single-stranded viral, double-stranded monomer and dimer RF DNA. The monomer RF DNA exhibited a length heterogeneity of 70 bp and 160 bp at its 3' and 5' termini. The two major monomer RF DNA species each contained hairpins in the extended or the foldback configurations. A central fragment between map units 0.15 and 0.88 was cloned into plasmid pUC18. The recombinant clone expressed virus-specific proteins ranging from 32,000 to 74,000 mol. wt.


Enhanced photocatalytic oxygen evolution by crystal cutting.
Uniformly cut In2O3 truncated octahedrons are fabricated on a large scale by a simple chemical vapor deposition (CVD) technique. This theoretical analysis predicts that the emergence of {100} facets on the In2O3 truncated octahedrons enhances oxygen evolution significantly in photocatalysis and experimental photoelectrochemical measurements are consistent.


Expression of the Na+-K+-2Cl(-)-cotransporter 2 in the normal and pressure-induced ischemic rat retina.
To evaluate the expression of the Na(+)-K(+)-2Cl(-)-cotransporter 2 (NKCC2) in the ischemic rat retina. Retinal ischemia was induced by pressures 90 to 120 mmHg, above systemic systolic pressure. Immunohistochemistry and western blot analysis were performed. NKCC2 is expressed in the normal retina and its expression is increased by ischemia caused by intraocular pressure elevation. NKCC2 immunoreactivity was observed mainly in axon bundles of ganglion cells and horizontal cell processes in the retina. NKCC2 expression continuously increased with a peak value 3 days (to 415% of normal levels) after ischemic injury, and then gradually decreased to 314% of controls until 2 weeks post injury. The mean density of NKCC2-labeled ganglion cells per mm(2) changed from 1,255 ± 109 in normal retinas to 391 ± 49 and 185 ± 37 at 3 days and 2 weeks after ischemia, respectively (p < 0.05), implying cell death of ganglion cells labeled with NKCC2. Taken together, these results suggest that NKCC2, which is expressed in retinal ganglion and horizontal cells, may contribute to cell death by ischemic injury in the retina, although the molecular mechanisms involved remain to be clarified.


Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.
Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.


Telomerase activation. One step on the road to cancer?
Ever since the discovery that telomeres are short in cancer cells and telomerase is activated in immortal cells, telomerase has been an oncogene wannabe. Oncogenes have been the glamour genes of molecular biology for 20 years, garnering flashy headlines and name recognition. More recently, tumor-suppressor genes have joined oncogenes on center stage. Recent evidence has shown that MYC upregulates the catalytic subunit of telomerase, TERT, and that TERT cooperates with HPV E7 in cell immortalization. This evidence now supports the placement of telomerase among the cancer gene elite.


[A study of the efficacy of new methods of laboratory diagnosis of pseudotuberculosis].
A total of 188 patients with sporadic pseudotuberculosis were examined with the use of new rapid methods for serologic indication, i.e. enzyme immunoassay, antibody neutralization test. Combined examinations of the patients' blood serum, urine, saliva, and coprofiltrate samples have detected Y. pseudotuberculosis (serologic variant 1) antigens in 175 (93.1%) patients. Coprofiltrate and saliva examinations were found the most effective if carried out over the febrile period and 5 days after it. The methods' efficacies were still high when the patients were examined during disease recurrence. Enzyme immunoassay has proved to be the most sensitive and specific technique.


Interesting detector shapes for third generation CT scanners.
To discuss options in designing detector shapes in third generation CT and to quantify potential cost savings for compact third generation CT systems, and to extend the work from two-dimensional fan-beam CT to three-dimensional cone-beam CT for circular, sequential, and spiral scan trajectories. Third generation CT scanners typically comprise detectors which are flat or whose shape is the segment of a cylinder or a sphere that is focused onto the focal spot of the x-ray source. There appear to be two design criteria that favor this choice of detector shape. One is the possibility of performing fan-beam and cone-beam filtered backprojection in the native geometry (without rebinning) and the other criterion could be to enable the early use of focused antiscatter grids. It is less known, however, that other detector shapes may also have these properties. While these designs have been evaluated for 2D CT from a theoretical standpoint more than one decade ago the authors revisit and generalize these considerations, extend them to 3D circular, sequential, and spiral cone-beam CT and propose an optimal design in terms of detector costs while keeping image quality constant. Their considerations and conclusions are based on considering the sampling density of the x-rays, including the effects of finite focal spot and finite detector element size. Proposing image reconstruction algorithms or numerically evaluating the results by reconstructing simulated projection data is not within the scope of this work. If the detector arc is curved to be nearly concentric with the circle describing the edge of the field of measurement significantly less detector area and detector pixels are required compared to today's third generation CT systems where the detector arc is centered about the focal spot. Combined with a detector that just covers the spiral Tam window cost savings of 60% or more are possible in compact CT systems. In terms of practicability the new designs appear to be nearly as easy to realize as today's third generation systems. Compact CT systems, which require the focal spot to be mounted close to the edge of the field of measurement, may significantly benefit from using detector shapes other than the typical equiangular detector that is focused onto the focal spot.


Deviation from van't Hoff Behavior of Solids at Low Temperature.
As a sequel to results obtained on the low-temperature behavior of liquids, a similar study is presented for solids. A molecule in a solid interacts with the other molecules of the crystal so that it is subjected to a specific multimolecular potential, kT0. At temperature T < T0, the molecules are localized, and at T > T0, they can participate in processes like self-diffusion and evaporation. As a consequence, the van't Hoff equation is disobeyed at a low temperature and properties like vapor pressure, diffusion rate, or reactivity are zero below the specific temperature, T0, which here can be interpreted as a temperature of thermal stability of the solid. To account for this view, the van't Hoff equation, represented by the green curve in the figure, is extended with a suitable pre-exponential factor, leading to the red curve. Three examples, taken from the literature, are analyzed to demonstrate its applicability. These examples are: the thermal dissociation of calcium carbonate, the sublimation equilibrium pressure of naphthalene, and that of ice. For some other solids, equilibria and dynamic properties, X(T), are examined by means of extrapolations in the X(T) versus T domain, showing the presence of an arrest temperature, which coincides, within experimental accuracy, with the T0 value obtained from the corresponding vapor pressure. As with liquids, kT0 is found to be proportional to the molecular pair potential.


Living with Menière's disease.
This article offers a personal perspective of living with Meniere's disease. Symptoms, interventions, and complications are also discussed. Specific attention is given to the physical and emotional challenges of living with this disease.


Cooperation of Pax2 and Pax5 in midbrain and cerebellum development.
Midbrain and cerebellum development depends on an organizing center that is located at the midbrain-hindbrain junction of the vertebrate embryo. Expression of the two closely related transcription factors Pax2 and Pax5 overlaps spatially and temporally in this region of the developing central nervous system. To study a possible interaction of these transcription factors in midbrain and cerebellum patterning, we have generated Pax5, Krd double mutant mice. The transgene-induced Krd mutation corresponds to an approximately 7-centimorgan chromosome 19 deletion that eliminates the entire Pax2 locus. The heterozygous Krd mutation deleting one Pax2 allele had no effect on midbrain and cerebellum development. Moreover, only minor developmental defects were previously observed at the midline of the inferior colliculus and anterior cerebellum in mice that were homozygous for a targeted Pax5 mutation. Similar morphological alterations were observed in 80% of all compound heterozygous Pax5 (+/-) Krd (+/-) mice. However, in the remaining 20% of compound heterozygotes, the inferior colliculi were missing, and the vermis of the cerebellum was severely disrupted due to the failure of the cerebellar primordia to fuse at the midline. Inactivation of the second Pax5 allele in Pax5 (-/-) Krd (+/-) mice resulted in complete loss of the posterior midbrain and cerebellum, as the tissue originating from the midbrain-hindbrain boundary region was deleted in the embryo as early as day 9.5. On the basis of these data, we propose that the cooperation of Pax2 and Pax5 is essential for normal functioning of the organizing center at the midbrain-hindbrain junction.


G2019S dardarin substitution is a common cause of Parkinson's disease in a Portuguese cohort.
LRRK2 mutations have recently been described in families with Parkinson's disease. Here we show that one of them (G2019S) is present in 6% (7 of 124) unrelated cases of disease in a clinic-based sample series from central Portugal, but not present in 126 controls from the same population. Thus, LRRK2 mutations appear to be a common cause of typical Parkinson's disease and as such will alter clinical practice.