Census tract correlates of vape shop locations in New Jersey.
Vape shops are opening across the USA, but little is known about the types of neighborhoods where they are located. This study explores community-level predictors of vape shop locations in New Jersey, USA. Vape shops were identified in July 2015 using a validated systematic online search protocol and geocoded using Google Earth Pro. Multivariable logistic regression identified demographic and other predictors of vape shop presence at the census tract level. Tobacco outlet density was consistently associated with higher odds of vape shop presence after adjusting for covariates (p<0.05). However, factors traditionally associated with tobacco retail were negatively associated with vapor outlets. Census tracts with a higher proportion of non-Hispanic black residents had significantly lower odds of having a vape shop (β=-0.03, p<0.001). Vape shops are commonly located in census tracts where tobacco retail is high, but where fewer racial minorities live. The retail environment may communicate social norms regarding vaping and ultimately influence use behaviors of community residents.


Effect of dietary cation-anion difference and dietary crude protein on milk yield, acid-base chemistry, and rumen fermentation.
Eight primiparous lactating Holstein cows (47 +/- 10 d in milk) fitted with ruminal cannulae were used to determine the effect of dietary cation-anion difference (DCAD) and dietary crude protein (CP) concentration on milk yield and composition, acid-base chemistry, and measures of N metabolism in lactating dairy cows. Treatments were arranged as a 2 x 2 factorial in a randomized complete block design to provide 15 or 17% CP and DCAD of 25 or 50 mEq (Na + K - Cl)/100 g of feed dry matter [15 or 39 mEq (Na + K) - (Cl + S)/100 g of feed dry matter]. High DCAD improved dry matter intake, milk yield, and concentrations of milk fat and protein. An interaction of DCAD and CP was observed for uric acid excretion, an indicator of microbial protein yield. Uric acid excretion was higher for high DCAD than for low DCAD in low CP diets and was similar for low and high DCAD with high CP. Serum bicarbonate concentration, urinary bicarbonate excretion, blood pH, and serum Na were elevated for high DCAD compared with low DCAD. Fractional excretion of Na, K, Cl, and Ca increased for high DCAD. Blood urea N and urinary urea N were greater for high than for low CP diets. No differences due to DCAD were observed for these parameters. Results of this study suggest that, in early lactation cows, blood acid-base chemistry is altered by differences in DCAD that range between the high and low ends of the desired DCAD range. Modifications of acid-base chemistry and the corresponding changes in protein metabolism may allow for more efficient feeding of protein and better nutritional management of the lactating dairy cow.


Evaluation of Ultraviolet-C Light for Rapid Decontamination of Airport Security Bins in the Era of SARS-CoV-2.
Contaminated surfaces are a potential source for spread of respiratory viruses including SARS-CoV-2. Ultraviolet-C (UV-C) light is effective against RNA and DNA viruses and could be useful for decontamination of high-touch fomites that are shared by multiple users. A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of UV-C light for rapid decontamination of plastic airport security bins inoculated at 3 sites with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2, PhiX174, and Phi6, an enveloped RNA virus used as a surrogate for coronaviruses. Reductions of 3 log10 on inoculated plastic bins were considered effective for decontamination. UV-C light administered as 10-, 20-, or 30-second cycles in proximity to a plastic bin reduced contamination on each of the test sites, including vertical and horizontal surfaces. The 30-second cycle met criteria for decontamination of all 3 test sites for all the test organisms except bacteriophage MS2 which was reduced by greater than 2 log10 PFU at each site. UV-C light is an attractive technology for rapid decontamination of airport security bins. Further work is needed to evaluate the utility of UV-C light in real-world settings and to develop methods to provide automated movement of bins through a UV-C decontamination process.


Public Health Practice Report: water supply and sanitation in Chukotka and Yakutia, Russian Arctic.
Information from 2013-2015 have been analysed on water accessibility, types of water service to households, use of water pretreatment, availability of sewerage, use of sewage treatment in Chukotka Autonomous Okrug and Yakutia Republic, based on evaluation information accessible in open sources, such as regional statistics and sanitary-epidemiologic reports. The main causes of the poor state of water supply and sanitation in the study regions include: very limited access to in-home running water (one-quarter of settlements in Chukotka and half of settlements in Yakutia have no regular water supply) and lack of centralised sewerage (78% and 94% of settlements correspondingly have no sewerage); lack of water pretreatment and sewage treatment, outdated technologies and systems; serious deterioration of facilities and networks, frequent accidents; secondary pollution of drinking water. Lack of open objective information on Russian Arctic water supply and sanitation in the materials of the regional and federal statistics hampers the assessment of the real state of affairs. The situation for water and sanitation supply in these Russian Arctic regions remains steadily unfavourable. A comprehensive intervention from national and regional governmental levels is urgently needed.


Evaluation of the macrocyclic antibiotic vancomycin as a chiral selector for capillary electrophoresis.
Vancomycin is one of a family of related macrocyclic glycopeptide antibiotics that were discovered by scientists at the Eli Lilly Company in the 1950s. It has been used to treat severe staphylococcal infections, particularly when bacterial resistance to other antibiotics has developed. Vancomycin is a naturally occurring chiral compound and has a number of stereogenic centers. Furthermore, it contains a variety of functionalities that are known to be useful for enantioselective interactions (e.g., hydrogen bonding groups, hydrophobic pockets, aromatic groups, amide linkages, etc.). The physiochemical properties of vancomycin, including its stability in solution, are discussed as they pertain to capillary electrophoresis. Over 100 racemates were resolved including many nonsteroidal antiinflammatory drugs, antineoplastic compounds and N-derivatized amino acids. Many of these compounds had very high resolution factors. Optimization and the effect of different experimental parameters on the enantioselective separations are discussed.


Epistasis and the Evolution of Antimicrobial Resistance.
The fitness effects of a mutation can depend, sometimes dramatically, on genetic background; this phenomenon is often referred to as "epistasis." Epistasis can have important practical consequences in the context of antimicrobial resistance (AMR). For example, genetic background plays an important role in determining the costs of resistance, and hence in whether resistance will persist in the absence of antibiotic pressure. Furthermore, interactions between resistance mutations can have important implications for the evolution of multi-drug resistance. I argue that there is a need to better characterize the extent and nature of epistasis for mutations and horizontally transferred elements conferring AMR, particularly in clinical contexts. Furthermore, I suggest that epistasis should be an important consideration in attempts to slow or limit the evolution of AMR.


Lost in the mall: misrepresentations and misunderstandings.
Readers of Ethics and Behavior have been treated to a misrepresentation of my research on planting false memories, to a misstatement of the actual empirical finidngs, and to a distortion of the history of the development of the idea for this line of research. The partisan essay by Crook and Dean which appears in this issue ("'Lost in a Shopping Mall' -- A Breach of Professional Ethics") is disturbing not only because of its errors, exaggerations, and omissions, but because, in some instances, the quality of the argument makes one wonder whether these were innocent mistakes or a deliberate attempt to distort my work. Some of these errors can be explained by simple lack of scientific competence. However, others are sufficiently bizarre that they cast doubt on the process that led to the acceptance of a manuscript written by an individual who has continually made her animosity toward me very publicly known (e.g., Boerner, 1996; Neimark, 1996).


The Rating Form of IBD Patient Concerns: Translation, Validation, and First Implementation of the Greek Version.
Background. The rating form of IBD patients' concerns (RFIPC) provides a unique assessment of the worries and concerns of inflammatory bowel disease (IBD) patients. Our aims were primarily to validate the Greek version of RFIPC and secondarily to describe the pattern of Greek patients'concerns. Methods. After translating RFIPC, the questionnaire was given to IBD patients at baseline and after 12 weeks. The questionnaire's measuring properties were evaluated based on the consensus-based standards for the selection of health status measurement instruments (COSMIN) recommendations. Premediated factorial structures were tested for goodness of fit with confirmatory factor analysis (CFA). Results. At baseline, 200 patients (94 with Crohn's disease) completed RFIPC. After 12 weeks, the first 100 patients recompleted the questionnaire. CFA results were consistent with a slightly modified than the original factorial structure. Cronbach's α and intraclass correlation coefficients were high. RFIPC scores negatively affected the quality of life. RFIPC was sensitive to detect important changes in patients' condition and was able to discriminate between remission and active disease. Disease activity, full time employment, celibacy, and low education were associated with higher scores. Conclusion. The Greek version of RFIPC is a reliable, valid, and responsive tool to assess Greek IBD patients' concerns.


Orbital ordering, new phases, and stripe formation in doped layered nickelates.
Ground-state properties of layered nickelates are investigated based on the orbital-degenerate Hubbard model coupled with lattice distortions, by using numerical techniques. The Néel state composed of spin S=1 ions is confirmed in the undoped limit x = 0. At x = 1/2, novel antiferromagnetic states, called CE- and E-type phases, are found by increasing the Hund's coupling. (3x2-r2/3y2-r2)-type orbital ordering is predicted to occur in a checkerboard-type charge-ordered state. At x = 1/3, both Coulombic and phononic interactions are found to be important, since the former stabilizes the spin stripe, while the latter leads to the striped charge order.


Dynamic changes in liver volume calculated using a three-dimensional visualisation system after microwave ablation of hepatocellular carcinomas.
To investigate the changes in liver volume and function after microwave ablation (MWA) of hepatocellular carcinomas (HCCs). We retrospectively analysed 76 patients with 106 nodules who underwent MWA for HCCs ≤5 cm between January 2015 and September 2017. Liver and ablation volumes were calculated using a three-dimensional visualisation system on MRI. Multiple regression analysis was used to estimate the association between the ablation volume and liver volume changes. Deformable image registration (DIR) was performed to confirm the influence of liver volume changes on curative effect evaluation after ablation. The initial liver and tumour volumes were 1262.1 ± 259.91 cm3 (range: 864.9-1966.8) and 2.5 cm3 (interquartile range [IQR]: 1.3-8.8), respectively. Compared to the initial liver volumes, the entire live volume (ELV) increased by 10.1% ± 8.93% (range: -4.9% to 46.68%) on the 3rd day after ablation. Subsequently, it recovered to initial level at the 3rd month and maintained its level during the 1-year follow-up. The median total ablation volume was 34.9 cm3 (IQR: 20.4-65.4) on the 3rd day after ablation, which decreased by 71.2% (IQR: 57.4%-78.1%) 1 year after ablation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (T-Bil) peaked within 3 days after MWA and recovered to normal within 1 month. The ablation volume proportion of the ELV was an independent risk factor for the increase in the ELV and AST, ALT and T-Bil levels within 3 days after ablation. When DIR was conducted to fuse ablation zone and tumour, the reshaped tumour volumes were enlarged by 40% because of the increase in ELV. MWA of HCCs based on the Milan criteria could induce temporary increases in ELV and RLV within 3 days after ablation, but both parameters recovered to initial levels 3 months after ablation. This indicates that MWA of early-stage HCCs would not lead to liver volume loss and could potentially protect liver function. The liver cannot be treated as an incompressible organ after ablation, and the appropriate deformation constraint should be designed for DIR to evaluate ablation margin accurately.


Potential Therapeutic Effect and Mechanisms of Mesenchymal Stem Cells-Extracellular Vesicles in Renal Fibrosis.
Renal fibrosis (RF) is central pathological pathway for kidney diseases, with the main pathological features being the aberrant accumulation of myofibroblasts that produce accumulation of extracellular matrix in the renal interstitium and glomeruli. Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with RF. Current treatment strategies for RF are ineffective. Mesenchymal stem cells (MSCs) have been found to be able to treat organ fibrosis including RF, but they have some safety problems, such as cell rejection, carcinogenicity, and virus contamination, which limit the application of MSCs. However, current studies have found that MSCs may exert their therapeutic effect by releasing extracellular vesicles (EVs). MSC-EVs can transfer functional proteins and genetic material directly to the recipient cells. As non-cell membrane structures, MSC-EVs have the advantages of low immunogenicity, easy preservation, and artificial modification, but do not have the characteristics of self-replication and ectopic differentiation. Therefore, EVs are safer than MSCs for treatment, but might be less effective than MSCs. Recent studies have also found that MSC-EVs can improve renal function and pathological changes of RF. Thus, this review summarizes the therapeutic effect of MSC-EVs on RF and the mechanisms that have been discovered so far, so as to provide a theoretical basis for the further study of the role of MSC-EVs in treating RF diseases.


Interlayer tunneling in counterflow experiments on the excitonic condensate in quantum Hall bilayers.
The effect of tunneling on the transport properties of quantum Hall double layers in the regime of the excitonic condensate at a total filling factor one is studied in counterflow experiments. If the tunnel current I is smaller than a critical I{C}, tunneling is large and is effectively shorting the two layers. For I>I{C} tunneling becomes negligible. Surprisingly, the transition between the two tunneling regimes has only a minor impact on the features of the filling-factor one state as observed in magnetotransport, but at currents exceeding I{C} the resistance along the layers increases rapidly.


Structural pre-organization of peptide nucleic acids.
Introduction of constraint via chemical bridging in the aegPNA leads to the five or six membered cyclic structures that may contribute towards maintaining the balance between rigidity and flexibility of the PNA backbone. The significant promise of our approach to use the naturally occurring trans-4-hydroxy-L-proline to arrive at different chirally pure cyclic PNA analogs and their DNA binding properties will be presented.


Semliki forest virus neurovirulence mutants have altered cytopathogenicity for central nervous system cells.
We have analyzed the pathogenicity and host range properties of four neurovirulence mutants of Semliki Forest virus which, unlike the wild type (WT), allow the survival of weanling mice injected intraperitoneally with 10(2) PFU. The mutant M9 showed a sustained multiplication in the brains of infected mice. It produced paralysis in 35%, and 8% died. Demyelination occurred in 94% of the surviving mice and was associated with the destruction of oligodendrocytes. All of the mutants showed a restricted ability to multiply in BHK, C1300 (neuroblastoma), and G26-24 (oligodendroglioma) cells as compared with the WT, and this was not associated with differential interferon production or action. C1300 cells infected with the mutants survived, whereas WT-infected cells were killed. In G26-24 cells all of the mutants and the WT produced a rapid cytopathic effect which was inhibited by pretreatment with 10 U of mouse interferon. Extensive RNA synthesis was detected for all of the mutants and the WT in BHK and C1300 cells, but it was only detectable in G26-24 cells in small amounts early in the infection. The mutant M4 had a defect in the nucleocapsid assembly, whereas M9 had a defect in total RNA synthesis. M136 was defective in the synthesis of 26S RNA, and M103 showed defective synthesis of viral core protein in C1300 cells. It is concluded that C1300 cells can tolerate viral RNA synthesis by a defective virus without showing a cytopathic effect, but the fully virulent WT virus is cytopathic. G26-24 cells are sensitive to small amounts of viral RNA synthesis. These properties of the WT and mutant viruses correlate with changes produced in the neurons and oligodendrocytes of the central nervous system: the virulence of the WT is due to its ability to destroy both neurons and oligodendrocytes, whereas the demyelination produced by the mutants M9 and M136 is due to the destruction of oligodendrocytes alone.


A comparison of early and delayed arthroscopically-assisted reconstruction of the anterior cruciate ligament using hamstring autograft.
Delayed rather than early reconstruction of the anterior cruciate ligament is the current recommended treatment for injury to this ligament since it is thought to give a better functional outcome. We randomised 105 consecutive patients with injury associated with chondral lesions no more severe than grades 1 and 2 and/or meniscal tears which only required trimming, to early (< two weeks) or delayed (> four to six weeks) reconstruction of the anterior cruciate ligament using a quadrupled hamstring graft. All operations were performed by a single surgeon and a standard rehabilitation regime was followed in both groups. The outcomes were assessed using the Lysholm score, the Tegner score and measurement of the range of movement. Stability was assessed by clinical tests and measurements taken with the KT-1000 arthrometer, with all testing performed by a blinded uninvolved experienced observer. A total of six patients were lost to follow-up, with 48 patients assigned to the delayed group and 51 to the early group. None was a competitive athlete. The mean interval between injury and the surgery was seven days (2 to 14) in the early group and 32 days (29 to 42) in the delayed group. The mean follow-up was 32 months (26 to 36). The results did not show a statistically significant difference for the Lysholm score (p = 0.86), Tegner activity score (p = 0.913) or the range of movement (p = 1). Similarly, no distinction could be made for stability testing by clinical examination (p = 0.56) and measurements with the KT-1000 arthrometer (p = 0.93). Reconstruction of the anterior cruciate ligament gave a similar clinical and functional outcome whether performed early (< two weeks) or late at four to six weeks after injury.


The onset of a peripheral ameloblastoma.
Incipient odontogenic tumors often display intermediate features between two or more lesions leading to diagnosis dilemma. We report the onset of a peripheral ameloblastoma fortuitously found subjacent to a nondysplastic leukoplakia in the region of missing 38 teeth of a 52-year-old man. The aim of this paper is the discussion of the microscopical features observed in the case reported which allowed the establishment of the final diagnosis of an early peripheral ameloblastoma.


Global conditions in the solar corona from 2010 to 2017.
Through reduction of a huge data set spanning 2010-2017, we compare mean global changes in temperature, emission measure (EM), and underlying photospheric magnetic field of the solar corona over most of the last activity cycle. The quiet coronal mean temperature rises from 1.4 to 1.8 MK, whereas EM increases by almost a factor of 50% from solar minimum to maximum. An increased high-temperature component near 3 MK at solar maximum drives the increase in quiet coronal mean temperature, whereas the bulk of the plasma remains near 1.6 MK throughout the cycle. The mean, spatially smoothed magnitude of the quiet Sun magnetic field rises from 1.6 G in 2011 to peak at 2.0 G in 2015. Active region conditions are highly variable, but their mean remains approximately constant over the cycle, although there is a consistent decrease in active region high-temperature emission (near 3 MK) between the peak of solar maximum and present. Active region mean temperature, EM, and magnetic field magnitude are highly correlated. Correlation between sunspot/active region area and quiet coronal conditions shows the important influence of decaying sunspots in driving global changes, although we find no appreciable delay between changes in active region area and quiet Sun magnetic field strength. The hot coronal contribution to extreme ultraviolet (EUV) irradiance is dominated by the quiet corona throughout most of the cycle, whereas the high variability is driven by active regions. Solar EUV irradiance cannot be predicted accurately by sunspot index alone, highlighting the need for continued measurements.


Synthesis and disulfide structure determination of porcine endothelin: an endothelium-derived vasoconstricting peptide.
All disulfide analogs (types A, B and C) of porcine or human endothelin, a 21-amino acid peptide having two intramolecular disulfide bonds, were synthesized and their retention times on HPLC were compared with that of natural endothelin. One of the analogs (type A) having disulfide bonds between positions 1 and 15 and between 3 and 11 was found to be identical with natural endothelin. Random oxidation of fully reduced endothelin formed a mixture of type A and B in a ratio of 3:1, with almost none of type C, which has disulfide bonds between positions 1 and 3 and between 11 and 15. Type A endothelin was also synthesized by the segment condensation procedure in solution applying our maximum protection strategy. This product was found to have full vasoconstricting activity in rat pulmonary artery ring preparations; the potency was as high as that of the natural product.


Markers of systemic involvement in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. It is primarily a pulmonary disease, but it has various extrapulmonary manifestations such as muscular dysfunction and hypotrophy, cachexia or cardiovascular complications. That is why COPD may be considered a systemic disease. Principal mechanisms implicated in these extrapulmonary determinations are systemic inflammation, oxidative stress and neurohormonal activation. Circulating markers involved in these mechanisms can be detected in patients with COPD. We present some of the most important markers of systemic inflammation, oxidative stress and neurohormonal activation and also the clinical implications.


Comparison of 22 species of Mycobacteria by immunodiffusion against an absorbed reference leprosy serum.
Lithium acetate antigenic extracts of 22 species of acetone-treated mycobacteria were tested by immunodiffusion precipitation for reactivity with a pool of sera from treated lepromatous leprosy patients (ARLS). This ARLS had been adsorbed with M. bovis (BCG, M. vaccae, cardiolipin, and lecithin to make it specific for M. leprae when used in an indirect immunofluorescence test. The ARLS produced two precipitin lines with M. leprae extract, one of which formed a line of identity with extracts of M. lepraemurium and M. bovis (BCG). Aso, recognition without reactions of identity was produced between ARLS and M. flavecens, M. gastri, M. gordonae, and M. nonchromogenicum. The ARLS did not recognize the 15 other species including the human pathogens, M. tuberculosis, M. intracellulare, M. kansasii, M. scrofulaceum, and M. marinum. These data suggest that serologic tests for M. leprae infection might be affected by antibodies to antigens shared by M. leprae and other mycobacteria. The significance of these shared antigens will depend upon the prevalence of human immune responses to mycobacteria containing the shared antigens in any given community.


Initiating or changing to a fixed-dose combination of Fluticasone propionate/Formoterol over Fluticasone propionate/Salmeterol: A real-life effectiveness and cost impact evaluation.
Asthma has a substantial impact on quality of life and health care resources. The identification of a more cost-effective, yet equally efficacious, treatment could positively influence the economic burden of this disease. Fluticasone propionate/Formoterol (FP/FOR) may be as effective as Fluticasone Salmeterol (FP/SAL). We evaluated non-inferiority of asthma control in terms of the proportion of patients free from exacerbations, and conducted a cost impact analysis. This historical, matched cohort database study evaluated two treatment groups in the Optimum Patient Care Research Database in the UK: 1) an FP/FOR cohort of patients initiating treatment with FP/FOR or changing from FP/SAL to FP/FOR and; 2) an FP/SAL cohort comprising patients initiating, or remaining on FP/SAL pMDI combination therapy. The main outcome evaluated non-inferiority of effectiveness (defined as prevention of severe exacerbations, lower limit of the 95% confidence interval (CI) of the mean difference between groups in patient proportions with no exacerbations is -3.5% or higher) in patients treated with FP/FOR versus FP/SAL. After matching 1:3, we studied a total of 2472 patients: 618 in the FP/FOR cohort (174 patients initiated on FP/FOR and 444 patients changed to FP/FOR) and 1854 in the FP/SAL cohort (522 patients initiated FP/SAL and 1332 continued FP/SAL). The percentage of patients prescribed FP/FOR met non-inferiority as the adjusted mean difference in proportion of no severe exacerbations (95%CI) was 0.008 (-0.032, 0.047) between the two cohorts. No other significant differences were observed except acute respiratory event rates, which were lower for patients prescribed FP/FOR (rate ratio [RR] 0.82, 95% CI 0.71, 0.94). Changing to, or initiating FP/FOR combination therapy, is associated with a non-inferior proportion of patients who are severe exacerbation-free at a lower average annual cost compared with continuing or initiating treatment with FP/SAL.


Transgene-Free Genome Editing in Tomato and Potato Plants Using Agrobacterium-Mediated Delivery of a CRISPR/Cas9 Cytidine Base Editor.
Genome editing tools have rapidly been adopted by plant scientists for gene function discovery and crop improvement. The current technical challenge is to efficiently induce precise and predictable targeted point mutations valuable for crop breeding purposes. Cytidine base editors (CBEs) are CRISPR/Cas9 derived tools recently developed to direct a C-to-T base conversion. Stable genomic integration of CRISPR/Cas9 components through Agrobacterium-mediated transformation is the most widely used approach in dicotyledonous plants. However, elimination of foreign DNA may be difficult to achieve, especially in vegetatively propagated plants. In this study, we targeted the acetolactate synthase (ALS) gene in tomato and potato by a CBE using Agrobacterium-mediated transformation. We successfully and efficiently edited the targeted cytidine bases, leading to chlorsulfuron-resistant plants with precise base edition efficiency up to 71% in tomato. More importantly, we produced 12.9% and 10% edited but transgene-free plants in the first generation in tomato and potato, respectively. Such an approach is expected to decrease deleterious effects due to the random integration of transgene(s) into the host genome. Our successful approach opens up new perspectives for genome engineering by the co-edition of the ALS with other gene(s), leading to transgene-free plants harboring new traits of interest.


Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)-DNA Conjugates.
PEGylation of an oligonucleotide using a brush polymer can improve its biopharmaceutical characteristics, including enzymatic stability and biodistribution. Herein, we quantitatively explore the nuclease accessibility of the nucleic acid as a function of "depth" toward the backbone of the brush polymer. It is found that protein accessibility decreases as the nucleotide is located closer to the backbone. Thus, by moving the conjugation point from the terminus of the nucleic acid strand to an internal position, much smaller brushes can be used to achieve the same level of steric shielding. This finding also makes it possible to assess antisense gene regulation efficiency of these brush-DNA conjugates as a function of their nuclease stability.


Comparison of three methods of myocardial protection.
Ischemic arrest (45 minutes), injection cardioplegia (2-3 ml/kg body weight within 1 minute) using Cardioplegin (magnesium-aspartate-procaine-sorbitol) according to Kirsch (90 minutes), and infusion cardioplegia (30 ml/kg body weight within 5 to 7 minutes) employing solution LK 352 (sodium-potassium-magnesium-aspartate-sorbitol) according to Bretschneider (90 minutes) were investigated in dogs in order to evaluate their efficacy of protection during myocardial ischemia and their effects on post-ischemic cardiac function. Parameters studied were myocardial tissue levels of adenine nucleotides, creatine phosphate, total creatine and glycogen as well as heart rate, systemic pressure, cardiac output, LVEDP, left ventricular pressure-volume-work, dp/dtmax, t-dp/dtmax, (dp/dtmax)/IP, and Vpm. According to biochemical data corrected for differences in myocardial temperature during arrest, myocardial protection during aortic cross-clamping at a core temperature of 30 degrees C was increased 1.8-fold by Cardioplegin and 3.4-fold by LK 352 administration respectively when compared to ischemic arrest. Functional recovery was poor after ischemic arrest and better after Cardiplegin arrest. Infusion cardioplegia with LK 352 did not result in a post-arrest depression of functional parameters.


Distinct roles of β-arrestin 1 and β-arrestin 2 in ORG27569-induced biased signaling and internalization of the cannabinoid receptor 1 (CB1).
The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor primarily expressed in brain tissue that has been implicated in several disease states. CB1 allosteric compounds, such as ORG27569, offer enormous potential as drugs over orthosteric ligands, but their mechanistic, structural, and downstream effects upon receptor binding have not been established. Previously, we showed that ORG27569 enhances agonist binding affinity to CB1 but inhibits G protein-dependent agonist signaling efficacy in HEK293 cells and rat brain expressing the CB1 receptor (Ahn, K. H., Mahmoud, M. M., and Kendall, D. A. (2012) J. Biol. Chem. 287, 12070-12082). Here, we identify the mediators of CB1 receptor internalization and ORG27569-induced G protein-independent signaling. Using siRNA technology, we elucidate an ORG27569-induced signaling mechanism for CB1 wherein β-arrestin 1 mediates short term signaling to ERK1/2 with a peak at 5 min and other upstream kinase components including MEK1/2 and c-Src. Consistent with these findings, we demonstrate co-localization of CB1-GFP with red fluorescent protein-β-arrestin 1 upon ORG27569 treatment using confocal microscopy. In contrast, we show the critical role of β-arrestin 2 in CB1 receptor internalization upon treatment with CP55940 (agonist) or treatment with ORG27569. These results demonstrate for the first time the involvement of β-arrestin in CB1-biased signaling by a CB1 allosteric modulator and also define the differential role of the two β-arrestin isoforms in CB1 signaling and internalization.


Iron intake and associated factors in general Japanese population: NIPPON DATA80, NIPPON DATA90 and national nutrition monitoring.
The purpose of this study was to investigate the dietary iron intake and associated other dietary factors and clinical characteristics among a representative sample cohort of Japanese population. We obtained data from NIPPON DATA80 and 90 that were conducted with the National Nutrition Surveys in 1980 and in 1990. Then we estimated nutrient and food intakes of individuals in the National Nutrition Survey of 1980 and that of 1990, which were adjusted on the basis of data of the National Nutrition Survey of 1995. Finally, we analyzed data for the 10,422 participants (4585 men and 5837 women) in NIPPON DATA80 and 8342 participants (3488 men and 4854 women) in NIPPON DATA90 having dietary iron intake information. In NIPPON DATA80 and 90, there was a significant relationship between the dietary iron intake and age for both men and women. Dietary protein intake was associated with iron intake where as dietary fat intake did not show any association. Regarding the minerals, significant relationships were observed between the different minerals and dietary iron intake. Apart from the food group of milk and dairy products, there were significant differences in other food groups according to quintiles of iron intakes for men and women. We described the mean dietary iron intake and its relation with other dietary factors and clinical characteristics in Japanese adults as the baseline data in NIPPON DATA80 and in NIPPON DATA90.


The efficacy, tolerability, and safety of contemporary antidepressants.
A wide variety of antidepressants are available today for treating major depressive disorder. However, like all medical therapies, antidepressants have several limitations that clinicians should consider when choosing treatments for their patients. This article reviews the efficacy, tolerability, and safety of the newer (ie, posttricyclic era) antidepressants. Specifically, overall efficacy and efficacy in relation to specific depressive symptoms and patient subpopulations, as well as in relation to various psychiatric and medical comorbidities, are addressed, along with tolerability profiles with respect to common side effects, including nausea, fatigue, insomnia, somnolence, sexual dysfunction, and weight gain. Finally, the safety profile of these agents is summarized.


FTIR spectroscopic and theoretical study of the photochemistry of matrix-isolated coumarin.
The infrared spectrum of monomeric unsubstituted coumarin (C9H6O2; 2H-1-benzopyran-2-one), isolated in solid argon at 10 K is presented and assigned. The UV-induced (lambda>200 nm) unimolecular photochemistry of the matrix-isolated compound was studied experimentally. Three main photoreactions were observed: (a) decarboxylation of the compound and formation of benzocyclobutadiene and CO2, with the Dewar form of coumarin as intermediate; (b) isomerization of the compound, leading to production of a conjugated ketene; and (c) decarbonylation, leading to formation of CO and benzofuran complex. Further decomposition of benzofuran to produce ethynol is suggested. Photochannels (a) and (b) correspond to those previously observed for matrix-isolated alpha-pyrone and its sulfur analogs (Phys. Chem. Chem. Phys. 2004, 6, 929; J. Phys. Chem. A 2006, 110, 6415), while route (c) is similar to the UV-induced photochemistry of coumarin in the gaseous phase (J. Phys. Chem. A 2000, 104, 1095). Interpretation of the experimental data is supported by extensive calculations performed at the B3LYP/6-311++G(d,p), MP2/6-31G(d,p) and MP2/6-311++G(d,p) levels.


Suicide in early childhood: a brief review.
The rate of suicide in the United States among prepubertal children and young adolescents had increased by 120% from 1980 to 1992. From 1992 to the present the rate has decreased slightly by 33%. We address a brief review of the most relevant findings in literature that are related to the risk of suicide. Although the most reported findings were child mood disorder, any type of family distress and family history of suicide attempts, the severity of those does not seem to increase the risk of suicide. However, there were other environmental factors that may influence the risk of suicide, such as the access to firearms. It is critical to detect risk factors and triggers in prepubertal populations in order to reduce the incidence of suicide in this age group and older age groups.


Preparation and resolution of molecular states by coherent sequences of phase-locked ultrashort laser pulses.
We study the application of nonlinear wave packet interferometry to the preparation and resolution of the overlaps of nonstationary nuclear wave functions evolving in an excited electronic state of a diatomic molecule. It is shown that possible experiments with two phase-locked ultrashort pulsepairs can be used to determine a specific vibrational wave packet state in terms of coherent states of the ground electronic state. We apply this scheme to an idealized molecule with harmonic potential energy surfaces and to the X <-- B transition states of the iodine molecule. Our results indicate that this scheme is very promising as a potential tool to quantum control.


Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice.
The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. Therefore, we investigated the antiinflammatory effects of a respirable p38alpha MAPK antisense oligonucleotide (p38alpha-ASO) in a mouse asthma model. A potent and selective p38alpha-ASO was characterized in vitro. Inhalation of aerosolized p38alpha-ASO using an aerosol chamber dosing system produced measurable lung deposition of ASO and significant reduction of ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4 (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose-dependent inhibition of airway hyperresponsiveness in allergen-challenged mice. Furthermore, inhaled p38alpha-ASO markedly inhibited OVA-induced lung tissue eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph node cells showed that p38alpha-ASO significantly reduced p38alpha MAPK mRNA expression. Nose-only aerosol exposure of mice verified the p38alpha-ASO-induced inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. None of the effects of the p38alpha-ASO were produced by a six-base mismatched control oligonucleotide. These findings demonstrate antisense pharmacodynamic activity in the airways after aerosol delivery and suggest that a p38alpha MAPK ASO approach may have therapeutic potential for asthma and other inflammatory lung diseases.


Benefits of symbiotic ectomycorrhizal fungi to plant water relations depend on plant genotype in pinyon pine.
Rhizosphere microbes, such as root-associated fungi, can improve plant access to soil resources, affecting plant health, productivity, and stress tolerance. While mycorrhizal associations are ubiquitous, plant-microbe interactions can be species specific. Here we show that the specificity of the effects of microbial symbionts on plant function can go beyond species level: colonization of roots by ectomycorrhizal fungi (EMF) of the genus Geopora has opposite effects on water uptake, and stomatal control of desiccation in drought tolerant and intolerant genotypes of pinyon pine (Pinus edulis Engelm.). These results demonstrate, for the first time, that microorganisms can have significant and opposite effects on important plant functional traits like stomatal control of desiccation that are associated with differential mortality and growth in nature. They also highlight that appropriate pairing of plant genotypes and microbial associates will be important for mitigating climate change impacts on vegetation.


Isoflurane Conditioning-Induced Delayed Cerebral Ischemia Protection in Subarachnoid Hemorrhage-Role of Inducible Nitric Oxide Synthase.
Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning-induced protection against delayed cerebral ischemia in a mouse model of SAH. Methods and Results The experiments used 10- to 14-week-old male wild-type (C57BL/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1 hour after SAH with isoflurane 2% for 1 hour. Isoflurane-induced changes in iNOS expression were measured. N-(3-(aminomethyl) benzyl) acetamidine, a highly selective iNOS inhibitor, was injected intraperitoneally immediately after SAH and then daily. Vasospasm, microvessel thrombosis, and neurological assessment was performed. Data were analyzed by 1-way ANOVA and 2-way repeated measures ANOVA followed by Student Newman Keuls comparison test. Statistical significance was set at P<0.05. Isoflurane conditioning downregulated iNOS expression in naïve and SAH mice. N-(3-(aminomethyl) benzyl) acetamidine attenuated large artery vasospasm and microvessel thrombosis and improved neurological deficits in wild-type animals. iNOS knockout mice were significantly resistant to vasospasm, microvessel thrombosis, and neurological deficits induced by SAH. Combining isoflurane with N-(3-(aminomethyl) benzyl) acetamidine did not offer extra protection, nor did treating iNOS knockout mice with isoflurane. Conclusions Isoflurane conditioning-induced delayed cerebral ischemia protection appears to be mediated by downregulating iNOS. iNOS is a potential therapeutic target to improve outcomes after SAH.


The effect of HIV disease on serum markers of hepatitis delta infection in intravenous drug abusers.
The prevalence of serum markers of delta hepatitis was determined prospectively in 82 intravenous drug abusers at various stages of human immunodeficiency virus (HIV) disease. Seventeen were HIV negative, 30 were HIV positive without acquired immunodeficiency syndrome (AIDS) and 35 had been diagnosed as having AIDS. Antihepatitis D virus (HDV) in serum was measured by a commercially available enzyme-linked immunosorbent assay (ELISA) and also by solid phase capture radioimmunoassays (RIAs) for immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-HDV. HDV antigen and hepatitis B virus (HBV) DNA were also measured. Hepatitis B surface antigen (HBsAg) and anti-HBs were determined by using a commercially available RIA. Anti-HDV (RIA) was only detected in serum that contained HBsAg. These anti-HDV (RIA) positive samples also tested positive with the commercial anti-HDV electroimmunoassay. In addition, the commercial anti-HDV ELISA detected anti-HDV in some serum samples that were negative for HBsAg; these anti HDV-positive HBsAg-negative samples were frequently lipemic or contained rheumatoid factor. The prevalence of HBsAg and anti-HBs did not differ significantly with the stage of HIV disease. HBsAg was detected in 3 of 13 (23%) HIV-negative, 5 of 29 (17%) HIV-positive, and 4 of 18 (22%) patients with AIDS. IgG and IgM anti-HDV (RIA) was positive in 2 of 3 HIV-negative and 4 of 5 HIV-positive pre-AIDS HBsAg-positive subjects. However, none of 4 AIDS patients had anti-HDV. The difference between AIDS and non-AIDS patients was statistically significant (Fisher's exact test, p = 0.03). HDV antigen was detected in serum from one AIDS patient.(ABSTRACT TRUNCATED AT 250 WORDS)


Authentication of herbal drug Tukhm-e-balango (Lallemantia royleana Benth.) using microscopic, pharmacognostic, and phytochemical characterization.
The study is aimed to provide a comprehensive account on authentication of herbal drug named as Tukhm-e-balango (Lallemantia royleana Benth.) from the seeds of Ocimum basilicum by using microscopic, pharmacognostic, and phytochemical characterization. The crude medicinal plants and their parts are often adulterated or substituted in market due to improper identification by the consumers while among herbal plant sellers, taxonomic confusion is caused due to morphological similarities of the plant parts and lack of a standard identification system.In microscopy, both herbarium and fresh specimens were studied using qualitative and quantitative morphological characteristics of leaves, seeds, and pollen. For pharmacognosy, solubility, fluorescence, and physicochemical characterizers were analyzed whereas a total phenolic and flavonoids contents was determined in addition to DPPH radical scavenging activity. In current study, microscopic, pharmacognostic, and phytochemical characterization clearly differentiated L. royleana from O. basilicum. The major problem in herbal drug industry is caused due to confusion and controversy of certain synonyms used for more than one or two drugs. Sometimes, under the same common or local name, entirely different taxa are being sold in herbal markets. It is concluded that correct and proper identification of medicinal plants is very crucial to ensure the safety and efficacy of herbal medicines, as many medicinal plants are intentionally or unintentionally adulterated with similar species or varieties. In herbal market, the seeds of L. royleana are adulterated with seeds of O. basilicum due to their similar morphology.


Comparison between Two Scheimpflug Anterior Segment Analyzers.
To compare the anterior segment indices measured by two Scheimpflug camera machines; Galilei and Pentacam. In this observational case series, the anterior segment indices of myopic healthy subjects seeking for refractive surgery were measured by Pentacam and Galilei on the same day. Analyzed parameters were anterior and posterior best fit spheres (BFS), axial curvature, true corneal power, central corneal thickness (CCT), anterior chamber (AC) depth, AC volume, AC angle, and pupil diameter. This study included 176 eyes of 88 participants. Mean radius of the anterior BFS was 7.79 ± 0.34 mm versus 7.75 ± 0.39 mm measured by Pentacam and Galilei, respectively (r = 0.877, P < 0.001). Corresponding values for the mean radius of posterior BFS were 6.42 ± 0.32 and 6.47 ± 0.38 mm, respectively (r = 0.879, P < 0.001). Anterior corneal mean power was 43.8 ± 1.9 diopters (D) with Pentacam and 43.8 ± 2.4 D with Galilei (r = 0.905,P < 0.001). Posterior corneal mean power was measured - 6.3 ± 0.3 and - 6.3 ± 0.4 D using Pentacam and Galilei, respectively (r = 0.873, P < 0.001). True corneal power was 43.9 ± 1.9 D with Pentacam and 43.5 ± 2.3 D with Galilei (r = 0.909, P < 0.001). CCT was 537 ± 44 and 553 ± 51 μm measured by Pentacam and Galilei, respectively (r = 0.796, P < 0.001). AC depth measurements using Pentacam and Galilei were 3.29 ± 0.4 and 3.3 ± 0.38 mm (P < 0.001), respectively; AC volume was 207 ± 50 and 129 ± 39 mm3≥ (P = 0.004), and AC angle was 39.7 ± 9.2 and 54.2 ± 5.2 degrees (P = 0.051), respectively. Average pupil diameter was measured 3.91 ± 1.77 mm by Pentacam and 3.34 ± 0.89 mm by Galilei (P = 0.018). There was a significant correlation between the Pentacam and Galilei in all measured parameters except AC angle, AC volume, and average pupil diameter.


Coping and caring in different ways: understanding and meaningful involvement.
The experience of having a baby in the neonatal intensive care unit (NICU) is frightening and creates uncertainty for families. Each parent copes with the challenge in his or her own way. Nurses can play an important role in helping parents find their own unique paths to meaningful involvement in caring for their infant by utilizing five frameworks in the assessment and planning process. The frameworks include: (a) family-centered care, (b) a cultural context, (c) loss and grief issues, (d) personal style considerations, and (e) reflections on the caregiver's own value system. The stories of three families illustrate individual coping styles and the application of these frameworks in understanding family coping in the NICU. A list of suggested questions identifying family background and strengths can assist in applying the five frameworks in assessment. A list of areas of potential parental involvement can assist nurses in helping families determine the ways in which they would like to be involved in their infant's care while in the NICU.


Guiding flying-spot laser transepithelial phototherapeutic keratectomy with optical coherence tomography.
To analyze transepithelial phototherapeutic keratectomy (PTK) results using optical coherence tomography (OCT) and develop a model to guide the laser dioptric and depth settings. Casey Eye Institute, Portland, Oregon, USA. Prospective nonrandomized case series. Patients with superficial corneal opacities and irregularities had transepithelial PTK with a flying-spot excimer laser by combining wide-zone myopic and hyperopic astigmatic ablations. Optical coherence tomography was used to calculate corneal epithelial lenticular masking effects, guide refractive laser settings, and measure opacity removal. The laser ablation efficiency and the refractive outcome were investigated using multivariate linear regression models. Twenty-six eyes of 20 patients received PTK to remove opacities and irregular astigmatism due to scar, dystrophy, radial keratotomy, or previous corneal surgeries. The uncorrected distance visual acuity and corrected distance visual acuity were significantly improved (P < .01) by 3.7 Snellen lines and 2.0 Snellen lines, respectively, to a mean of 20/41.2 and 20/22.0, respectively. Achieved laser ablation depths were 31.3% (myopic ablation) and 63.0% (hyperopic ablation) deeper than the manufacturer's nomogram. The spherical equivalent of the corneal epithelial lenticular masking effect was 0.73 diopter ± 0.61 (SD). The refractive outcome highly correlated to the laser settings and epithelial lenticular masking effect (Pearson R = 0.96, P < .01). The ablation rate of granular dystrophy opacities appeared to be slower. Smoothing ablation under masking fluid was needed to prevent focal steep islands in these cases. The OCT-measured ablation depth efficiency could guide opacity removal. The corneal epithelial lenticular masking effect could refine the spherical refractive nomogram to achieve a better refractive outcome after transepithelial ablation.


The Effect of an Electronic Passive Prompt Intervention on Prolonged Occupational Sitting and Light-Intensity Physical Activity in Desk-Based Adults Working from Home during COVID-19 in Ireland.
This study aimed to assess the effect of passive prompts on occupational physical behaviours (PBs) and bouts of prolonged sitting among desk-based workers in Ireland who were working from home during the COVID-19 pandemic. Electronic passive prompts were delivered every 45 min, asking participants to walk for five minutes, during working hours. Twenty-eight participants (aged 30-67 years) completed the six-week intervention between October 2020 and April 2021. PBs were measured using an activPAL3TM accelerometer, following a 24 h wear protocol, worn for the duration of the study. Participants were highly sedentary at both baseline (77.71% of work hours) and during the intervention (75.81% of work hours). However, the number of prolonged occupational sedentary bouts > 90 min was reduced compared to baseline (0.56 ± 0.08 vs. 0.77 ± 0.11, p = 0.009). Similar reductions were observed in the time spent in sustained sitting > 60 and >90 min when compared to baseline sedentary patterns (60 min: -31.27 ± 11.91 min, p = 0.014; 90 min: -27.97 ± 9.39 min, p = 0.006). Light-intensity physical activity (LIPA) significantly increased during the intervention (+14.29%, p = 0.001). This study demonstrates that passive prompts, delivered remotely, can both reduce the number and overall time spent in prolonged bouts of occupational sedentary behaviour and increase occupational LIPA.


Crash test-based assessment of injury risks for adults and children when colliding with personal mobility devices and service robots.
Autonomous mobility devices such as transport, cleaning, and delivery robots, hold a massive economic and social benefit. However, their deployment should not endanger bystanders, particularly vulnerable populations such as children and older adults who are inherently smaller and fragile. This study compared the risks faced by different pedestrian categories and determined risks through crash testing involving a service robot hitting an adult and a child dummy. Results of collisions at 3.1 m/s (11.1 km/h/6.9 mph) showed risks of serious head (14%), neck (20%), and chest (50%) injuries in children, and tibia fracture (33%) in adults. Furthermore, secondary impact analysis resulted in both populations at risk of severe head injuries, namely, from falling to the ground. Our data and simulations show mitigation strategies for reducing impact injury risks below 5% by either lowering the differential speed at impact below 1.5 m/s (5.4 km/h/3.3 mph) or through the usage of absorbent materials. The results presented herein may influence the design of controllers, sensing awareness, and assessment methods for robots and small vehicles standardization, as well as, policymaking and regulations for the speed, design, and usage of these devices in populated areas.


Laboratory investigations in Balkan endemic nephropathy.
Serum samples from three patients with Balkan endemic nephropathy (BEN) were inoculated intraperitoneally to guinea pigs. After a very long incubation period (58-273 days) the animals developed an experimental disease characterized by apathy, tremor, convulsions and a fatal outcome. The disease could be serially propagated, the same clinical symptoms being recorded at each of the three passages performed. The morphological features of the experimental disease included glomerular and tubular lesions and the presence of interstitial fibrous and lymphoplasmocytic reactions. Different hypotheses on the etiology of BEN are discussed.


Evaluation of the impacts of photodynamic therapy on the prognosis of patients with hrHPV infection based on BTNL8 expression.
The aim of this study was to evaluate the prognostic value of Butyrophilin-like protein 8 (BTNL8) expression in high-risk HPV (hrHPV) infection treated with photodynamic therapy. A total of 93 patients with hrHPV infection were enrolled as research study subjects, along with 69 healthy women who served as controls. Serum samples were obtained from each participant, and BTNL8 levels were quantified. The patients were divided into high- and low-expression groups (n = 45 and n = 48, respectively), and both groups underwent photodynamic therapy. We recorded the following data: BTNL8 expression pre-treatment and at 3/6 months post-treatment, HPV negative conversion ratio, regression rate of low-grade squamous intraepithelial lesions (LSIL), incidence of adverse reactions, complication rate, serum inflammatory factors, persistence of HPV positivity, LSIL residue or recurrence, and incidence of high-grade cervical intraepithelial lesions (HCIL). Patients with HPV infection exhibited higher BTNL8 expression than healthy individuals. Compared to the low-expression group, the high-expression group showed increased HPV negative conversion ratios, LSIL regression rates, and levels of IL-17 and IL-23. This group also demonstrated decreased total complication rate, HPV positivity persistence, LSIL residue or recurrence, and IL-10 levels. Additionally, there was no significant difference between the two groups in terms of the number of adverse reactions and cases with LSIL residue/recurrence. Serum BTNL8 expression may serve as a valuable tool for early screening and prognosis monitoring of patients with hrHPV infection.


Reaction landscape of a pentadentate N5-ligated Mn(II) complex with O2˙- and H2O2 includes conversion of a peroxomanganese(III) adduct to a bis(μ-oxo)dimanganese(III,IV) species.
Herein we describe the chemical reactivity of the mononuclear [Mn(II)(N4py)(OTf)](OTf) (1) complex with hydrogen peroxide and superoxide. Treatment of 1 with one equivalent superoxide at -40 °C in MeCN formed the peroxomanganese(III) adduct, [Mn(III)(O2)(N4py)](+) (2) in ~30% yield. Complex 2 decayed over time and the formation of the bis(μ-oxo)dimanganese(III,IV) complex, [Mn(III)Mn(IV)(μ-O)2(N4py)2](3+) (3) was observed. When 2 was formed in higher yields (~60%) using excess superoxide, the [Mn(III)(O2)(N4py)](+) species thermally decayed to Mn(II) species and 3 was formed in no greater than 10% yield. Treatment of [Mn(III)(O2)(N4py)](+) with 1 resulted in the formation of 3 in ~90% yield, relative to the concentration of [Mn(III)(O2)(N4py)](+). This reaction mimics the observed chemistry of Mn-ribonucleotide reductase, as it features the conversion of two Mn(II) species to an oxo-bridged Mn(III)Mn(IV) compound using O2(-) as oxidant. Complex 3 was independently prepared through treatment of 1 with H2O2 and base at -40 °C. The geometric and electronic structures of 3 were probed using electronic absorption, electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), variable-temperature, variable-field MCD (VTVH-MCD), and X-ray absorption (XAS) spectroscopies. Complex 3 was structurally characterized by X-ray diffraction (XRD), which revealed the N4py ligand bound in an unusual tetradentate fashion.


A group randomized trial to improve safe use of nonsteroidal anti-inflammatory drugs.
To determine whether audit/feedback and educational materials improve adherence to recommendations for laboratory monitoring and cytoprotective agents to detect and prevent adverse events caused by nonsteroidal anti-inflammatory agents (NSAIDs). Controlled, cluster-randomized trial. Physicians commonly prescribing NSAIDs were identified within a large managed care organization and randomized to a control or an intervention group (audit/feedback with peer-derived benchmarks and continuing medical education). Medical records were examined 10 months before and after the intervention for clinical data and receipt of complete blood count (CBC), creatinine testing, and cytoprotective agents (process measures). Primary analysis compared intervention versus control physicians among those who initially performed below a peer-derived benchmark. General estimating equations accounted for patient clustering. Of 101 physicians initially randomized, 85 remained eligible (38 internists, 36 family physicians, 11 rheumatologists) postintervention. Mean percent change in performance between intervention and control physicians for CBC monitoring was 16% versus 10%; for creatinine monitoring, 0% versus 17%; and use of cytoprotective agents, -3% versus -1%. None of these changes were significant. Rheumatology specialty, number of NSAID prescriptions and physician visits, and patient risk factors for NSAID-related toxicity were more strongly associated with improved safety practices than the intervention. Audit/feedback and educational materials had no observed effect on improving NSAID-related safety practices. Potentially contributing factors include high baseline performance (ceiling effect), dilution of the intervention effect by case mix and provider factors, nonreceipt of intervention materials, and diverse indications for lab tests.


Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway.
Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is known to exhibit anticancer properties against a variety of carcinomas. Previous experimental evidence suggests that lifestyle and dietary habits affect the risk of prostate cancer to a certain extent. As the effect of tangeretin on prostate cancer is unexplored, the present study investigated the effect of tangeretin on androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin reduced the cell viability of PC-3 cells in a dose- and time-dependent manner, with the half-maximal inhibitory concentration (IC50) observed at 75 µM dose following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be ~65 µM. Expression levels of the mesenchymal proteins including vimentin, cluster of differentiation 44 and Neural cadherin in PC-3 cells were reduced by tangeretin treatment, whereas those of the epithelial proteins, including Epithelial cadherin and cytokeratin-19 were upregulated. Treatment of PC-3 cells also resulted in the downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Therefore, it may be concluded that tangeretin induces reprogramming of epithelial-mesenchymal transition in PC-3 cells by targeting the PI3K/Akt/mTOR signaling pathway.


A Review of the Research in Emotionally Focused Therapy for Couples.
Emotionally Focused Therapy for Couples (EFT) is a brief evidence-based couple therapy based in attachment theory. Since the development of EFT, efficacy and effectiveness research has accumulated to address a range of couple concerns. EFT meets or exceeds the guidelines for classification as an evidence-based couple therapy outlined for couple and family research. Furthermore, EFT researchers have examined the process of change and predictors of outcome in EFT. Future research in EFT will continue to examine the process of change in EFT and test the efficacy and effectiveness of EFT in new applications and for couples of diverse backgrounds and concerns.


Insufficiency of the Kanagawa hemolytic test for detecting pathogenic Vibrio parahaemolyticus in Shanghai, China.
We evaluated the Kanagawa hemolytic test and tdh gene test for accuracy in identifying pathogenic Vibrio parahaemolyticus isolates in Shanghai. One hundred and seventy-two V. parahaemolyticus isolates were collected from diarrhea patients, freshly harvested sea fish, or fresh water samples. Statistical data for the Kanagawa hemolytic test and tdh gene test were compared. There were 83.51% isolates (81/97) from patients and 22.22% isolates (10/45) from sea-fish positive for the tdh gene. However, none of 30 isolates from fresh water samples were tdh-positive. Positive Kanagawa hemolytic tests were obtained in 88.66%, 46.67%, and 76.67% of isolates, which were from patients, sea fish, and fresh water samples, respectively. Positive rates of the Kanagawa hemolytic tests and the tdh gene tests were significantly different in isolates from those 3 sources (P < 0.001). The tdh gene test showed higher specificity than the Kanagawa hemolytic test on identifying pathogenic V. parahaemolyticus isolates in Shanghai, China.


Fourier transform microwave and millimeter-wave spectroscopy of bromoiodomethane, CH2BrI.
Bromoiodomethane, CH2BrI, is a molecule of natural origin emitted in significant amount into the marine boundary layer. It can easily be decomposed by solar radiation, releasing Br and I atoms in the troposphere, which in turn impacts the atmospheric chemistry. Spectroscopy is an invaluable tool to monitor species present in the atmosphere. Since no high-resolution spectroscopic studies are available for this dihalomethane, we have investigated the rotational spectra of the two bromine isotopologues of CH2BrI in its vibrational ground state in the microwave and millimeter-wave regions. Transitions of b-type have been recorded by Fourier transform microwave spectroscopy below 25 GHz while both a- and b-type spectral lines have been measured below 230 GHz. Observed transitions correspond to energy levels with J ≤ 132 and Ka ≤ 14. Molecular constants including those describing the nuclear quadrupole coupling tensors for (79)Br, (81)Br, and (127)I were accurately determined from the least-squares analysis of a total of 1873 distinct transition frequencies (of which 943 belong to the CH2(79)BrI isotopologue). An experimental (r0) structure of the title species has been derived from the two sets of rotational constants.


Dietary Misconceptions.
Patients' misconceptions concerning peptic ulcer diets may lead them to observe a more strict diet than intended by the physician. In some cases the diet was impossible to follow.


The effect of Rapid Access Prostate Clinics on the outcomes of Gleason 7 prostate cancer: does earlier diagnosis lead to better outcomes?
Rapid Access Prostate Clinics (RAPC) were introduced in Ireland by the National Cancer Control Programme bringing about expedited referral pathways and increased detection rates of prostate cancer. Lower Gleason (G) grade at diagnosis due to RAPC has been previously reported but grade at prostatectomy has not been assessed. The aim of this study was to assess the impact of RAPC on the outcomes of patients with G7 disease on radical prostatectomy (RP). A retrospective analysis was carried out of all RPs performed over a 9-year period (2006-2014). Outcomes for G7 prostatectomies were compared before and after the introduction of the RAPC, with a further sub-analysis of G4 + 3 versus G3 + 4. The primary outcome was biochemical recurrence (BCR). Other outcomes were adjuvant/salvage radiotherapy, extra prostatic extension, positive surgical margins, seminal vesicle involvement and tumour stage. In total, 240 RPs were performed with 167 cases graded G7 (70 graded G4 + 3 and 97 graded G3 + 4). Since the introduction of RAPC the proportion of G4 + 3 compared to G3 + 4 has increased from 37.9 to 42%. There was no statistical difference in outcomes for G4 + 3 treated before and after the introduction of RAPC. G4 + 3 was associated with higher rates of BCR (24.4 vs. 0%, p < 0.0001, radiotherapy (41.1 vs. 4.8%, p < 0.0001) and worse histological features than G3 + 4. Despite the benefits in diagnosis of prostate cancer brought about by RAPC in Ireland, this has not translated to a lower grade for surgically treated patients. There has been no improvement in outcomes especially for higher grade G4 + 3 disease.


[The effectiveness of antibiotic treatment for Salmonella enteritis and Salmonella excretors].
The role of antibiotic treatment was evaluated in 190 hospitalized patients with Salmonella enteritis and 80 with asymptomatic Salmonella infection (without typhoid or paratyphoid). The results indicate that antibiotic treatment does not shorten the duration of excretion (compared with non-treated patients). Because of the danger of prolonged bacterial excretion under antibiotic treatment in complication-free Salmonella enteritis as well as the possible development of resistant Salmonella strains, antibiotic treatment of Salmonella infections (other than typhoid or paratyphoid) should be limited to systemic forms. Treatment of complication-free Salmonella enteritis and Salmonella excretors should be limited to intestine-cleansing measures.


Measuring Within-Session and Between-Session Compliance in Hoarding Disorder: A Preliminary Investigation of the Psychometric Properties of the CBT Compliance Measure (CCM) and Patient Exposure/Response Prevention Adherence Scale for Hoarding (PEAS-H).
Hoarding disorder (HD) is a new psychiatric diagnosis in Diagnostic and Statistical Manual of Mental Disorders-Fifth edition and preliminary evidence suggests that cognitive-behavioral treatments are effective in treating this condition. However, it has been demonstrated that individuals with HD generally display poor compliance during treatment, which may lead to poor outcomes. Treatment compliance can be conceptualized as either within-session or between-session compliance, but currently there are no validated measures of within-session or between-session compliance specifically for HD. The aim of this study was to provide an initial validation of the CBT Compliance Measure and the Patient Exposure/Response Prevention Adherence Scale for Hoarding in a sample of participants with HD who were undergoing group cognitive behavioral therapy (CBT) for HD (N = 70). Both measures, which were administered at each relevant treatment session, demonstrated a unidimensional structure, good reliability, as well as predictive validity, and are thus promising in the measurement of within-session and between-session compliance with CBT for HD.


Cellular transcription factor Sp1 recruits simian virus 40 capsid proteins to the viral packaging signal, ses.
Simian virus 40 (SV40) capsid assembly occurs in the nucleus. All three capsid proteins bind DNA nonspecifically, raising the dilemma of how they attain specificity to the SV40 minichromosome in the presence of a large excess of genomic DNA. The SV40 packaging signal, ses, which is required for assembly, is composed of multiple DNA elements that bind transcription factor Sp1. Our previous studies showed that Sp1 participates in SV40 assembly and that it cooperates in DNA binding with VP2/3. We hypothesized that Sp1 recruits the capsid proteins to the viral minichromosome, conferring upon them specific DNA recognition. Here, we have tested the hypothesis. Computer analysis showed that the combination of six tandem GC boxes at ses is not found at cellular promoters and therefore is unique to SV40. Cooperativity in DNA binding between Sp1 and VP2/3 was not abolished at even a 1,000-fold excess of cellular DNA, providing strong support for the recruitment hypothesis. Sp1 also binds VP1 and cooperates with VP1 in DNA binding. VP1 pentamers (VP1(5)) avidly interact with VP2/3, utilizing the same VP2/3 domain as described for polyomavirus. We conclude that VP1(5)-VP2/3 building blocks are recruited by Sp1 to ses, where they form the nucleation center for capsid assembly. By this mechanism the virus ensures that capsid formation is initiated at a single site around its minichromosome. Sp1 enhances the formation of SV40 pseudovirions in vitro, providing additional support for the model. Analyses of Sp1 and VP3 deletion mutants showed that Sp1 and VP2/3 bind one another and cooperate in DNA binding through their DNA-binding domains, with additional contacts outside these domains. VP1 contacts Sp1 at residues outside the Sp1 DNA-binding domain. These and additional data allowed us to propose a molecular model for the VP1(5)-VP2/3-DNA-Sp1 complex.


Transition from a failing dentition to a removable implant-supported prosthesis: a staged approach.
Patients with hopeless dentition often present difficulties in the management of the transitional phase to the final restoration. This article describes a staged approach to achieve a full-arch, implant-supported, removable prosthesis in patients with a hopeless dentition. The approach described allows the clinician to proceed in a staged manner and facilitate prosthetic steps by keeping fixed references for vertical dimension. This technique includes initial conservative periodontal care and, afterward, extraction of some strategic teeth, while others are temporarily maintained. At this point, the implants are positioned, and during the healing period, the remaining natural abutments are used for occlusal reference and to stabilize the removable provisional prosthesis. After osseointegration of the implants, the residual teeth are extracted and the final prosthesis is delivered. The main advantages of the technique include maintenance of function during treatment, stabilization of the removable provisional (especially in the mandibular arch), prosthetic-guided insertion of implants, and easier retrieval of prosthetic references. The main drawbacks are longer treatment time and the need for two surgical steps.


Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden.
While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble Aβ increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of Aβ dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 μm near Aβ deposits in the brain. In the gut, sepsis negatively modulated the α- and β-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.


The effects of dexfenfluramine administration on brain serotonin immunoreactivity and lipid peroxidation in mice.
Obesity continues to be an increasing health problem in worldwide and antiobesity drugs have commonly been used by obese patients. During the use of anorectic drugs, the antioxidant defense may be affected, especially by reactive oxygen species. It was decided to investigate the effects of dexfenfluramine on body weight, daily food intake, brain thiobarbituric acid-reactive substances (TBARS), glutathione (GSH) and nitric oxide (NO) levels, and 5-HT immunoreactivity. Mice were divided into two groups each containing 8 Swiss Albino adult (6 months) mice. Group 1, untreated, was used as a control; group 2 was treated with dexfenfluramine 0.4 mg/kg per day intraperitoneally for 7 days. Brain TBARS and GSH levels were assayed spectrophotometrically. The stable end-products of NO, nitrite and nitrate, were analyzed spectrophotometrically. Brain tissue 5-HT immunoreactivity was observed using an immunohistochemical method. There were significant decreases in body weight in the dexfenfluramine group (p < 0.05). Although brain GSH and NO(x) levels decreased significantly, brain TBARS levels increased in the dexfenfluramine group (p < 0.05). Brain 5-HT immunoreactivity also increased in the dexfenfluramine-treated group compared to control. In conclusion, our findings show that dexfenfluramine is effective in achieving weight loss and also increases lipid peroxidation in mouse brain.


A 16S rDNA-based PCR method for rapid and specific detection of Clostridium perfringens in food.
A 16S rDNA-based polymerase chain reaction (PCR) method was developed for the rapid and specific detection of Clostridium perfringens in food. The PCR primers were designed by a GenBank computer search and they are complementary only with the 16S rRNA gene of C. perfringens by sequence alignment. The PCR product is a 279 BP DNA fragment. All C. perfringens strains tested were positive in the PCR assay and all other species tested were negative, including 11 other species of Clostridium and 38 species of other common bacteria. As few as two cells of C. perfringens in pure culture were detectable. High numbers of other bacterial species did not interfere with the detection of C. perfringens. The PCR amplification required only 30 min to complete. The method can be used for detection of C. perfringens in contaminated food. Samples from 100 g of chicken drumsticks which were inoculated with 20, 200 or 2000 cells of C. perfringens were subjected to the PCR assay and all produced positive results.


Dynamic spatiotemporal analysis of indigenous dengue fever at street-level in Guangzhou city, China.
This study aimed to investigate the spatiotemporal clustering and socio-environmental factors associated with dengue fever (DF) incidence rates at street level in Guangzhou city, China. Spatiotemporal scan technique was applied to identify the high risk region of DF. Multiple regression model was used to identify the socio-environmental factors associated with DF infection. A Poisson regression model was employed to examine the spatiotemporal patterns in the spread of DF. Spatial clusters of DF were primarily concentrated at the southwest part of Guangzhou city. Age group (65+ years) (Odd Ratio (OR) = 1.49, 95% Confidence Interval (CI) = 1.13 to 2.03), floating population (OR = 1.09, 95% CI = 1.05 to 1.15), low-education (OR = 1.08, 95% CI = 1.01 to 1.16) and non-agriculture (OR = 1.07, 95% CI = 1.03 to 1.11) were associated with DF transmission. Poisson regression results indicated that changes in DF incidence rates were significantly associated with longitude (β = -5.08, P<0.01) and latitude (β = -1.99, P<0.01). The study demonstrated that social-environmental factors may play an important role in DF transmission in Guangzhou. As geographic range of notified DF has significantly expanded over recent years, an early warning systems based on spatiotemporal model with socio-environmental is urgently needed to improve the effectiveness and efficiency of dengue control and prevention.


[The application of the physical factors for the medical rehabilitation of the children presenting with neurogenic dysfunction of the bladder].
This article describes the modern technologies for the medical rehabilitation of the children presenting with neurogenic dysfunction of the bladder aimed at improving the act of urination at all levels of innervation. The most frequent variant of neurogenic dysfunction of the bladder in the children is the hyper-reflexive one; it is this variant in which the most pronounced disorders of urodynamics due to intravesical hypertension and detrusor hypoxia are observed. The urodynamic disorders are known to contribute to the formation of the characteristic clinical picture associated with the hyper-reflexive urinary bladder dysfunction in the children characterized by the mandatory urination syndrome, pollakiuria, imperative urges, and mandatory urinary incontinence in the combination with enuresis. The treatment of urinary bladder dysfunction includes both behavioural and medication therapeutic modalities. The "golden standard" for the pharmacotherapy of neurogenic bladder dysfunction of the hyper-reflexive type in the childhood is the use of M-cholinoblockers, such as oxybutynin. The popularity of the physiotherapeutic methods is attributable to their influence on the main links of pathogenesis, the absence of side effects, and the possibility of application in the children of the early age. The combined treatment of neurogenic bladder dysfunction includes the use of a wide range of physiotherapeutic methods the action of which is aimed at regulating the act of urination at all levels of innervation of the bladder, normalizing the tone of the muscles of the bladder, eliminating sphincter insufficiency, improving circulation and accelerating the maturation of the neuromuscular apparatus of the pelvic organs. At present, the natural and preformed methods of physiotherapy are finding the wide application for the management of neurogenic dysfunction of the bladder in the children in the conjunction with therapeutic physical exercises, massage, and the biological feedback (BFB) technique.


Dose Mapping After Endoradiotherapy with 177Lu-DOTATATE/DOTATOC by a Single Measurement After 4 Days.
Dosimetry of organs and tumors helps to assess risks and benefit of treatment with 177Lu-DOTATATE/DOTATOC. However, it is often not performed in clinical routine because of additional efforts, the complexity of data collection and analysis, and the additional burden for the patients. Aiming at a simplification of dosimetry, we analyzed the accuracy of a theoretically substantiated approximation, which allows the calculation of absorbed doses from a single measurement of the abdominal activity distribution. Methods: Activity kinetics were retrospectively assessed from planar images in 29 patients with neuroendocrine tumors (NETs; n = 21) or meningioma (n = 8) after the administration of 177Lu-DOTATATE (n = 22) or 177Lu-DOTATOC (n = 7). Mono- or biexponential functions were fitted to measured data in 54 kidneys, 25 livers, 27 spleens, and 30 NET lesions. It was evaluated for each fit function how well the integral over time was represented by an approximation calculated as the product of the time tl of a single measurement, the expected reading at time tl, and the factor 2/ln(2). Tissue-specific deviations of the approximation from the time integral were calculated for time points tl of 24, 48, 72, 96, 120, and 144 h. Results: The correlation between time integral and approximation improved with increasing time tl Pearson r exceeded 0.95 for a tl of 96 h or more in all tissues. The lowest maximum errors were observed at a tl of 96 h, with deviations of the approximation from the time integral of median +5% (range, -9% to +17%) for kidneys, +6% (range, -7% to +12%) for livers, +8% (range, +2% to +20%) for spleens, and +6% (range, -11% to +16%) for NET lesions. Accuracy was reduced for measurements after 72 or 120 h. For measurements after 24, 48, and 144 h, the approximation led to large deviations for some of the patients, in particular unacceptable underestimates of the absorbed dose to the kidneys. Conclusion: A single quantitative measurement of the abdominal activity concentration by SPECT/CT 4 d after the administration of 177Lu-DOTATATE/DOTATOC provides a 3-dimensional dose map and can be used to estimate the doses actually absorbed in the treatment cycle with minor additional resources and effort.


A simple and versatile route to stable quantum dot-dye hybrids in nonaqueous and aqueous solutions.
Hybrid systems consisting of core/shell semiconductor quantum dots (QDs) and organic rylene dyes have been prepared and characterized. Complex formation is mediated by bidentate carboxylate moieties covalently linked to the dye molecules. The complexes were very stable with respect to time (at least months), dilution (sub nM), and precipitation. After preparation in organic solvent, complexes could be easily transferred into water. The strong quenching of QD emission by the dye molecules (transfer efficiencies up to 95%) was satisfactorily modeled by an FRET process. Single complexes immobilized in thin polymer films were imaged by confocal fluorescence microscopy.


Direct observation of long-range assisted formation of Ag clusters on Si(111)7 x 7.
Formation of Ag clusters on reconstructed surface Si(111)7 x 7 was for the first time observed in real time during deposition by means of scanning tunneling microscopy. The sequences of images taken at room temperature show mechanisms controlling the growth and behavior of individual Ag adatoms. Obtained data reveal new details of attractive interaction between adsorbates occupying adjacent half-unit cells of the 7 x 7 reconstruction. Time evolution of growth characteristics was simulated by means of a simple model. The growth scenario observed in vivo is discussed with respect to previously reported models based on data obtained after finishing the deposition--post-mortem.


Compassion fatigue among nurses working in a long-term care facility: The Israeli experience.
Nurses working in a long-term care facility could be at risk of developing compassion fatigue due to the nature of their work. In this descriptive, cross-sectional survey, we explored the level of compassion fatigue among nurses working in a long-term care facility, as well as the associated sociodemographic and occupational factors. In total, 103 nurses employed in various departments of a long-term care facility in central Israel completed the Hebrew version of the Professional Quality of Life Scale R-IV. Nurses scored moderate-high on the compassion fatigue (mean = 3.6, standard deviation = .5), burnout (mean = 3.5, standard deviation = .5), and compassion satisfaction (mean = 3.8, standard deviation = .5) scales. Older nurses scored lower on compassion fatigue, while nurses with higher qualifications scored higher on compassion satisfaction. In this study, we implicate that it is necessary to raise awareness about compassion fatigue, both in nursing education and training and in long-term care organizations. It is necessary to improve understanding of this phenomenon in order to help nurses acquire appropriate coping skills to address this critical issue.


Snakes and Souks: Zoonotic pathogens associated to reptiles in the Marrakech markets, Morocco.
The world-famous markets of Marrakech, also known in Arabic as souks, harbor a vast diversity of reptiles that are sold for medicinal/magic/pet purposes or used for snake charming. This unique epidemiological context has never been studied considering the interactions of humans, reptiles, and zoonotic pathogens. Thus, the aim of this study was to identify the parasites and pathogens present in blood and feces associated with handled reptiles in the markets of Marrakech to assess the risk of zoonotic transmission within the reptile-human interface. Privately owned reptiles (n = 118), coming from vendors or snake charmers, were examined and blood and feces sampled. DNA was extracted and molecular screening (cPCR, nPCR, qPCR, dqPCR) was performed aiming to identify potentially zoonotic pathogens (i.e., Anaplasma/Ehrlichia spp., Rickettsia spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, Babesia/Theileria spp., Cryptosporidium spp., Giardia spp., Leishmania spp., Cestoda). Overall, 28.9% (34/118) of reptiles were positive for at least one pathogen. In blood, Anaplasma spp. were detected in four snakes, with two Montpellier snakes positive for Anaplasma phagocytophilum, while Rickettsia spp. were detected in one Mediterranean chameleon and four puff adders. Leishmania tarentolae was molecularly detected in a Mediterranean chameleon and a Montpellier snake. In feces, the cox1 gene generated a myriad of sequences for nematodes, cestodes, fungi and bacteria. Importantly, Proteus vulgaris was identified from a Mediterranean chameleon. Cryptosporidium spp. nPCR yielded a positive sample (i.e., Cryptosporidium sp. apodemus genotype I) from a Moroccan worm lizard, as well as for bacteria such as Pseudomonas aeruginosa in an Egyptian cobra, and Morganella morganii from a puff adder. Results from this study demonstrated the risk of zoonotic transmission of microorganisms and parasites present in blood and feces from reptiles that are brought to the souks in Marrakech, Morocco, to be sold for medicinal purposes or used for snake charming, being in direct and straight contact with humans.


HIV-infected psychiatric patients: beyond confidentiality.
The AIDS epidemic calls for an ethical analysis of conflicting obligations surrounding HIV-infected psychiatric patients and confidentiality, as well as issues that go beyond confidentiality. Although laws pertaining to HIV infection have been enacted in a number of states, these statutes leave much discretion to health professionals. The ethical principle known as "the harm principle" can permit disclosure of confidential information and detention or isolation of psychiatric patients who pose a threat of infecting other patients. From an ethical point of view, however, the circumstances under which traditional protections may be weakened or abandoned remain limited.


Chemokines and their receptors: drug targets in immunity and inflammation.
The chemokine system coordinates leukocyte migration in immunity and inflammation and is implicated in the pathogenesis of many human diseases. Although several successful strategies have been identified to develop drugs targeting chemokines and their receptors, this has not yet resulted in many new therapeutics. This is likely due to a complexity of the chemokine system, which was not initially appreciated, that is characterized by redundancy, pleiotropy, and differences among species. Nevertheless, our understanding of chemokine biology is continuing to grow and several promising drugs are currently being tested in late-stage clinical trials. In this review, we examine the role of chemokines in health and diseases and discuss strategies to target the chemokine system.


Prognosis of incidental prostatic cancer in Aust-Agder County, Norway.
The clinical significance of dividing incidental prostatic cancer into T0 focal (A1) and T0 diffuse (A2) is well documented, but criteria for the distinction vary considerably. Eighty-four patients with incidental prostatic cancer over a 5-year period comprise all newly diagnosed cases from an area of 94,000 inhabitants in the Aust-Agder County in Norway. This represents 13% of the patients operated upon for apparently benign prostatic hyperplasia. Of these patients, 80 with a mean age of 73.9 years did not receive any additional treatment after prostatectomy until progression (deferred treatment) and were followed up for 2-7 years. Three chips or less of well-differentiated cancer were defined as T0 focal (n = 18), all other cases were T0 diffuse (n = 62). Sixty-nine patients (86%) were free of progression. Eighteen patients died of causes unrelated to prostatic cancer. Progression occurred in 11 patients (14%) at a mean time interval of 39 months after diagnosis, and 3 patients died of prostatic cancer. Related to grade, progression occurred in 2% of the G1 tumors, in 25% of G2, and in 40% of the G3 tumors. When a tumor volume of 25% was chosen as level of distinction between T0 focal and T0 diffuse, 25 patients (31%) changed the stage to T0 focal without any impact on prognosis.


[Clinical characteristics of early-onset type 2 diabetes and risk factors associated with its chronic complications].
To investigate the clinical characteristics of early-onset type 2 diabetes (EOD) and the risk factors associated with its chronic complications. A total of 2713 T2DM patients were recruited and divided into two groups: early- and late-onset groups EOD group (diagnosed at the age <or= 40) and late-onset type 2 diabetes (LOD) group (diagnosed at the age > 40). The clinical characteristics were compared between two groups, and the risk factors were analyses within the early-onset group. (1) The EOD patients were characterized by significantly higher levels of triglycerides (2.5 +/- 2.4 mmol/L vs 1.9 +/- 1.5mmol/L, P < 0.01) and BMI (24.4 kg/m(2) +/- 4.6 kg/m(2) vs 23.6 kg/m(2) +/- 3.7 kg/m(2), P < 0.01), higher rates of smoking (29.2% vs 22.0%, P < 0.01), family history of diabetes (28.6% vs 13.1%, P < 0.01), and higher prevalence of metabolic syndrome (18.9% vs 10.7%, P < 0.01), higher proportion of patients with unacceptable HbA1c (>7.0%) (77.3% versus 72.7%, P < 0.05) and fasting blood glucose >or= 7.0 mmol/L, (80.8% versus 74.6%, P < 0.05). (2) The prevalence rates of microvascular complications were higher than those of macrovascular complications in the EOD group, and the prevalence rates of pain, anesthesia, diarrhea, and nephropathy were 10.6%, 6.20%, 6.00%, and 13.00% respectively, all significantly higher than those of the LOD group (7.10%, 2.80%, 3.70%, and 8.00% respectively, P < 0.05, < 0.01, < 0.05, and < 0.01). Linear regression analysis showed that certain subsets of chronic complications were associated with onset age, diabetes duration, hypertension, family history and high level of triglyceride. Early-onset DM patients present the clinical features of poorer metabolic profiles, which may contribute to the development of certain subsets of microvascular complications. Late-onset patients tend to be complicated with macrovascular diseases, such as cerebrovascular disease, angiocardiopathy, etc. Multiple factor comprehensive control is important for the prevention of the complications.


Integrative analyses of biomarkers and pathways for heart failure.
Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated. The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF. We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine/threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules. The enrichment pathway of DEGs and GO may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.


Is dedicated extremity 1.5-T MRI equivalent to standard large-bore 1.5-T MRI for foot and knee examinations?
The purpose of this study was to prospectively compare dedicated extremity MRI and standard large-bore MRI of the lower extremities in the same patients. Sixty-nine patients (27 feet and 42 knees) were examined both with extremity 1.5-T MRI and standard 1.5-T MRI. Scanning duration was measured, and patients completed a detailed questionnaire after each examination (4-point scale). Two readers assessed image quality parameters. Data were analyzed with the paired Student t test, Wilcoxon signed rank test, and chi-square test. Scanning duration was significantly longer for extremity MRI (foot, 29.9±5.5 minutes; knee, 30.4±5.6 minutes) than for standard MRI (foot, 21.9±5.0 minutes; knee, 20.5±3.9 minutes) (p<0.001 for all comparisons). Acoustic noise reported by the patient was significantly lower on extremity MRI (foot, 1.9±0.9; knee, 2.1±0.7) compared with standard MRI (foot, 2.9±1.0; knee, 2.9±0.8) (p<0.001 for all). Patient satisfaction for both systems was high (1.4-1.6 for all, p=0.2-1.0). Image quality and fat suppression were equally good for both scanners for foot examinations (p≥0.48). Knee examinations generally featured good image quality on both systems, but standard MRI had superior image quality (p≤0.01) and fat suppression (p≤0.001) compared with extremity MRI. More motion artifacts were present on extremity MRI than on standard MRI, which was significant for the knee (p≤0.04) but not for the foot (p≥0.32). Extremity MRI featured less acoustic noise than standard MRI, but examination duration was longer on extremity MRI. Patient satisfaction was high for both scanners. For foot examinations, image quality on extremity MRI was equivalent to standard MRI. Image quality for knee examinations was better on standard MRI compared with extremity MRI, but overall it was good on both systems.


Amifostine impairs p53-mediated apoptosis of human myeloid leukemia cells.
Amifostine is used as a cytoprotective agent in cancer treatments. Amifostine protects from apoptosis in some models and has been used as hematopoiesis stimulator in myeloid malignancies. As the apoptosis induced by many antitumoral agents is mediated by p53, we studied the effect of amifostine on p53-mediated apoptosis. We used human myeloid leukemia K562 and NB4 cells expressing the temperature-conditional p53-Val(135) mutant. Both cell lines undergo apoptosis at 32 degrees C due to the presence of p53 in wild-type conformation. We found that amifostine dramatically reduced apoptosis by p53 in both cell lines, as assessed by cell morphology, annexin V binding, fraction of sub-G(1) cells, and DNA laddering. To explore the mechanism responsible for this apoptosis protection, we tested the effect of amifostine on p53 transcriptional activity. We found that amifostine reduced p53-mediated transactivation of target promoters in NB4 and K562. Macroarray analysis confirmed that several p53 target genes as p21(Waf1), mdm2, gadd45, pig8, and pig3 were down-regulated at the mRNA level by amifostine in NB4 and K562. Also, c-myc was up-regulated by amifostine in K562 in the presence of p53, consistently with the impairment of p53-mediated apoptosis exerted by c-Myc in these cells. We conclude that amifostine impairs p53-dependent apoptosis of myeloid leukemia cells by reducing the activation of apoptosis-related genes. Our results open the possibility that amifostine could reduce the effectiveness of antitumoral treatments when it is dependent on active p53.