Previous experiments have shown that mice lacking a functional delta-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene ...for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse strain, which also lacks tolerance, exhibit antagonist-induced opioid withdrawal. These data demonstrate that although signaling pathways involving ppENK, DOR, and NMDA receptor are necessary for the expression of morphine tolerance, other pathways independent of these factors can mediate physical dependence. Moreover, these studies illustrate that morphine tolerance can be genetically dissociated from physical dependence, and thus provide a genetic framework to assess more precisely the contribution of various cellular and molecular changes that accompany morphine administration to these processes.
We characterize the chemical composition of Asian continental outflow observed during the NASA Transport and Chemical Evolution over the Pacific (TRACE-P) mission during February-April 2001 in the ...western Pacific using data collected on the NASA DC-8 aircraft. A significant anthropogenic impact was present in the free troposphere and as far east as 150degE longitude reflecting rapid uplift and transport of continental emissions. Five-day backward trajectories were utilized to identify five principal Asian source regions of outflow: central, coastal, north-northwest(NNW), southeast (SE), and west-southwest (WSW). The maximum mixing ratios for several species, such as CO, C2Cl4, CH3Cl, and hydrocarbons, were more than a factor of 2 larger in the boundary layer of the central and coastal regions due to industrial activity in East Asia. CO was well correlated with C2H2, C2H6, C2Cl4, and CH3Cl at low altitudes in these two regions (r(sup 2) approx. 0.77-0.97). The NNW, WSW, and SE regions were impacted by anthropogenic sources above the boundary layer presumably due to the longer transport distances of air masses to the western Pacific. Frontal and convective lifting of continental emissions was most likely responsible for the high altitude outflow in these three regions. Photochemical processing was influential in each source region resulting in enhanced mixing ratios of O3, PAN, HNO3, H2O2, and CH3OOH. The air masses encountered in all five regions were composed of a complex mixture of photcrchemically aged air with more recent emissions mixed into the outflow as indicated by enhanced hydrocarbon ratios (C2H2/CO greater than or equal to 3 and C3H8/C2H6 greater than or equal to 0.2). Combustion, industrial activities, and the burning of biofuels and biomass all contributed to the chemical composition of air masses from each source region as demonstrated by the H6, SO2, and C2Cl4 were compared for the TRACE-P and PEM-West B missions. In the more northern regions, O3, CO, and SO2 were higher at low altitudes during TRACE-P. In general, mixing ratios were fairly similar between the two missions in the southern regions. A comparison between CO/CO2, CO/CH4, C2H6/C3H8, NO(x)/SO2, and NO(y)/(SO2 + nss-SO4) ratios for the five source regions and for the 2000 Asian emissions summary showed vay close agreement indicating that Asian emissions were well represented by the TRACE-P data and tbe emissions inventory.
We have measured the cosmic ray spectrum at energies above 1017eV using the two air fluorescence detectors of the High Resolution Fly's Eye experiment operating in monocular mode. We describe the ...detector, PMT and atmospheric calibrations, and the analysis techniques for the two detectors. We fit the spectrum to models describing galactic and extragalactic sources. Our measured spectrum gives an observation of a feature known as the “ankle” near 3×1018eV, and strong evidence for a suppression near 6×1019eV.
Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous ...from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI.
In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens.
RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade.
RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.
To investigate acceptability and tolerability of diets of different protein and glycemic index (GI) content aimed at weight maintenance following a phase of rapid weight loss, as part of a large ...pan-European dietary intervention trial.
The Diogenes study (www.diogenes-eu.org) consisted of an initial 8-week rapid weight-loss phase (800-1000 kcal/day), followed by a 6-month weight maintenance intervention with five different diets varying in protein and GI content. Measurement of a range of outcomes relating to experience of the Diogenes diets in terms of acceptability, experience and mood were recorded via end of day questionnaires throughout the study.
Weight change during the initial weight loss phase weakly, but positively correlated with acceptability of the programme (r range=-0.08 to 0.2, P 0.05, n=685 on four of five dimensions). Success at weight maintenance positively correlated with acceptance of the programme (r range=-0.21 to -0.34, P<0.001, n=540 for all five dimensions). The diets with higher protein content were more acceptable than the low protein (LP) diets, however, no differences between the high vs low GI diets were found concerning acceptability and tolerability.
Results suggest that moderately high protein diets, compared with LP diets, are more acceptable diets for weight control in overweight individuals.
To explore the clinical characteristics of IgA nephropathy (IgAN) with severe chronic periodontitis and aggressive periodontitis.
A total of 436 hospitalized patients who underwent renal needle ...biopsy in the department of nephrology of China-Japan Friendship Hospital from November 2013 to December 2014 were recruited in the study and blindly had periodontal examination. The patients were divided into IgAN group and non-IgAN group according to the renal pathology. The patients with IgAN were further categorized as non-periodontitis, chronic periodontitis and aggressive peridontitis group by Haas classification. The chronic periodontitis group was continually divided into mild, moderate and severe periodontitis group. The levels of interleukin (IL)-1β and IL-6 in gingival crevicular fluid were analyzed by enzyme-linked immunosorbent assays.
The prevalence of periodontitis in the study was 88.3% (385/436). The prevalence of chronic periodontitis and aggressive periodontitis were higher in patients with IgAN than
Based on an e+e− collision data sample corresponding to an integrated luminosity of 567 pb−1 taken at the center-of-mass energy of s=4.6 GeV with the BESIII detector, we measure the absolute ...branching fraction of the inclusive decay Λc+→Λ+X to be B(Λc+→Λ+X)=(38.2−2.2+2.8±0.9)% using the double-tag method, where X refers to any possible final state particles. In addition, we search for direct CP violation in the charge asymmetry of this inclusive decay for the first time, and obtain ACP≡B(Λc+→Λ+X)−B(Λ¯c−→Λ¯+X)/B(Λc+→Λ+X)+B(Λ¯c−→Λ¯+X)=(2.1−6.6+7.0±1.6)%, a statistically limited result with no evidence of CP violation.
To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models.
This retrospective, historical-control study was performed in a cohort of adult cardiac surgical ...patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015–June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality.
Tertiary Zhongshan Hospital (Fudan University, China).
Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery.
Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists.
Successful extubation, ICU LOS and in-hospital mortality.
A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p=0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19h; p<0.001). In relation to patients with MV duration >48h, those in phase II had a comparatively higher successful extubation rate (p=0.033), shorter ICU LOS (p=0.038) and a significant decrease in in-hospital mortality (p=0.039).
The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery.
Comparar el manejo entre intensivistas y cirujanos de pacientes de cirugía cardíaca en la unidad de cuidados intensivos.
Este estudio de control retrospectivo se llevó a cabo con una cohorte de pacientes adultos de cirugía cardíaca. Durante la primera fase (de marzo a agosto de 2015), los cirujanos cardíacos estuvieron a cargo del manejo médico en la unidad; y durante la segunda fase (septiembre de 2015 a junio de 2016), lo hicieron intensivistas. Comparamos las fases en cuanto al número de extubaciones exitosas, el tiempo de estancia y la mortalidad.
Hospital Zhongshan de la Universidad de Fudan, China.
Adultos admitidos secuencialmente a la unidad de cuidados intensivos cardíacos después de intervenciones quirúrgicas.
Manejo médico por cirujanos en la primera fase, y por intensivistas en la segunda fase.
Extubación exitosa, tiempo de estancia en la unidad de cuidados intensivos y mortalidad.
Participaron 1.792 pacientes en la fase i y 3.007 en la fase ii. Los pacientes de la fase ii tuvieron más extubaciones exitosas (99,17 frente al 98,55%, p=0,043), y necesitaron menos tiempo de ventilación mecánica (mediana de 18 frente a 19h, p<0,001). De entre los pacientes con ventilación mecánica de más de 48h, los de la fase iifueron extubados exitosamente más veces, tuvieron una estancia más corta (p=0,038), y una menor mortalidad (p=0,039).
El manejo médico por intensivistas aumentó significativamente el número de extubaciones exitosas y disminuyó el tiempo de ventilación mecánica.
Abstract Background This paper presents two replications of a heuristic model for measuring environment in studies of gene–environment interplay in the etiology of young adult problem behaviors. ...Methods Data were drawn from two longitudinal, U.S. studies of the etiology of substance use and related behaviors: the Raising Healthy Children study (RHC; N = 1040, 47% female) and the Minnesota Twin Family Study (MTFS; N = 1512, 50% female). RHC included a Pacific Northwest, school-based, community sample. MTFS included twins identified from state birth records in Minnesota. Both studies included commensurate measures of general family environment and family substance-specific environments in adolescence (RHC ages 10–18; MTFS age 18), as well as young adult nicotine dependence, alcohol and illicit drug use disorders, HIV sexual risk behavior, and antisocial behavior (RHC ages 24, 25; MTFS age 25). Results Results from the two samples were highly consistent and largely supported the heuristic model proposed by Bailey et al. (2011). Adolescent general family environment, family smoking environment, and family drinking environment predicted shared variance in problem behaviors in young adulthood. Family smoking environment predicted unique variance in young adult nicotine dependence. Family drinking environment did not appear to predict unique variance in young adult alcohol use disorder. Conclusions Organizing environmental predictors and outcomes into general and substance-specific measures provides a useful way forward in modeling complex environments and phenotypes. Results suggest that programs aimed at preventing young adult problem behaviors should target general family environment and family smoking and drinking environments in adolescence.
Background: Sublingual-swallow immunotherapy was recently recognized in the World Health Organization Position Paper (Allergen immunotherapy: therapeutic vaccines for allergic diseases) “as a viable ...alternative to parenteral injection therapy to treat allergic diseases” in adults. More controlled studies were required to assess the efficacy and safety of this treatment in children.
Objective: This study was carried out to assess the clinical efficacy and safety profile of sublingual-swallow immunotherapy with high-dose allergen in children with allergies.
Methods: We used a double-blind placebo-controlled design. Forty-one children with
Parietaria -induced rhinoconjunctivitis were randomized to receive sublingual standardized
Parietaria judaica extract (n = 20) or placebo (n = 21) for 2 years. The cumulative dose of allergen was 375 times higher than that used in parenteral immunotherapy and the cumulative dose of Par j 1 major allergen was 52.5 mg over 2 years. The main efficacy assessment criteria were symptoms and rescue medication scores recorded on the patients’ diary cards. Secondary criteria were changes in skin and conjunctival specific reactivity as well as blood parameters, analyzed after 1 and 2 years of immunotherapy. The safety of the treatment was assessed by evaluating the frequency and severity of adverse effects.
Results: A significant reduction in rhinitis symptoms was observed in the active treatment group during the second season (
P = .02), with no difference in medication scores. A significant decrease in skin reactivity (
P = .002 after 2 years of treatment) and an increase in the threshold dose for conjunctival allergen provocation test (
P = .02) were observed in the active treatment group compared with the group receiving placebo. A significant increase in specific IgG
4 levels (
P = .02) was also observed in the active group. Immunotherapy was well tolerated.
Conclusion: Sublingual-swallow immunotherapy in
Parietaria -allergic children provided a clinical benefit and a decreased specific reactivity to the allergen. The safety profile of this treatment, which constitutes an important issue, indicated good tolerance and compliance. (J Allergy Clin Immunol 1999;104:425-32.)
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