Contrast-medium-induced acute renal failure and Tamm-Horsfall proteinuria.
An acute obstructive nephropathy due to precipitation of urinary glycoprotein-contrast complexes in the renal tubules has been postulated to explain the episodes of renal failure occasionally seen following intravascular contrast medium administration. In an in vitro study we were unable to produce any precipitation of contrast-glycoprotein complexes over a wide range of concentrations, temperatures and pH values in urine with any urographic contrast agent, conventional or new. Meglumine ioglycamide (Biligram: Schering) alone, the strongly protein-binding agent, exhibited the phenomenon, and only in high concentration. It is concluded that such a mechanism is unlikely to play a role in contrast medium nephrotoxicity, which therefore remains unexplained.


Expression of aryl hydrocarbon receptor in human placentas and fetal tissues.
The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates many biological processes, including fetal development. In this study, we examined AhR protein expression in human placentas from normal (N) and severe preeclamptic (sPE) pregnancies, as well as human fetal tissues from the second trimester of pregnancy, using immunohistochemistry and/or Western blot analysis. In the placentas, the AhR immunoreactivity was present primarily in syncytiotrophoblasts. The AhR staining was also seen in endothelium of large blood vessels in villi and endothelium of umbilical cord arteries and veins. No difference in AhR protein levels was found between N and sPE placentas. In fetal tissues, the AhR immunoreactivity was localized in lung, kidney, esophagus, pancreas, liver, testicle, thymus gland, retina, and choroid, mainly in epithelial cells, whereas it was absent in heart, brain, sclera, and thoracic aorta. These findings suggest that the AhR plays a critical role in syncytiotrophoblasts of human placentas and epithelium of many fetal organs. These data also imply that human placentas and those fetal organs with high AhR expression (e.g., lung, kidney, liver, pancreas, and thymus gland) during fetal development are highly susceptible to environmental toxicants such as dioxin.


Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog.
Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.


Imaging Laser-Triggered Drug Release from Gold Nanocages with Transient Absorption Lifetime Microscopy.
Nanoparticles have shown promise in loading and delivering drugs for targeted therapy. Many progresses have been made in the design, synthesis, and modification of nanoparticles to fulfill such goals. However, realizing targeted intracellular delivery and controlled release of drugs remains challenging, partly because of the lack of reliable tools to detect the drug-releasing process. In this paper, we applied femtosecond laser pulses to trigger the explosion of gold nanocages (AuNCs) and control the intracellular release of loaded aluminum phthalocyanine (AlPcS) molecules for photodynamic therapy (PDT). AuNCs were found to enhance the encapsulation efficiency and suppress the PDT effect of AlPcS molecules until they were released. More importantly, we discovered that the excited-state lifetimes of the AlPcS-AuNC conjugate (∼3 ps) and free AlPcS (∼11 ps) differ significantly, which was utilized to image the released drug molecules using transient absorption lifetime microscopy with the same laser source. This technique extracts information similar to fluorescence lifetime imaging microscopy but is superior in imaging the molecules that hardly fluoresce or are prone to photobleaching. We further combined a dual-phase lock-in detection technique to show the potential of real-time imaging based on the change in transient optical behaviors. Our method may provide a new tool for investigating nanoparticle-assisted drug delivery and release.


Regional Alteration within the Cerebellum and the Reorganization of the Cerebrocerebellar System following Poststroke Aphasia.
Recently, an increasing number of studies have highlighted the role of the cerebellum in language processing. However, the role of neural reorganization within the cerebellum as well as within the cerebrocerebellar system caused by poststroke aphasia remains unknown. To solve this problem, in the present study, we investigated regional alterations of the cerebellum as well as the functional reorganization of the cerebrocerebellar circuit by combining structural and resting-state functional magnetic resonance imaging (fMRI) techniques. Twenty patients diagnosed with aphasia following left-hemispheric stroke and 20 age-matched healthy controls (HCs) were recruited in this study. The Western Aphasia Battery (WAB) test was used to assess the participants' language ability. Gray matter volume, spontaneous brain activity, functional connectivity, and effective connectivity were examined in each participant. We discovered that gray matter volumes in right cerebellar lobule VI and right Crus I were significantly lower in the patient group, and the brain activity within these regions was significantly correlated with WAB scores. We also discovered decreased functional connectivity within the crossed cerebrocerebellar circuit, which was significantly correlated with WAB scores. Moreover, altered information flow between the cerebellum and the contralateral cerebrum was found. Together, our findings provide evidence for regional alterations within the cerebellum and the reorganization of the cerebrocerebellar system following poststroke aphasia and highlight the important role of the cerebellum in language processing within aphasic individuals after stroke.


Low temperature CO oxidation over unsupported nanoporous gold.
Supported Au nanoclusters are well-known for their unusual properties in catalysis. We describe here that nanostructured porous Au made via dealloying represents a new class of unsupported catalysts with extraordinary activities in important reactions such as CO oxidation. Although nanoporous Au may contain some oxides on the surface, our results demonstrate that it is metallic Au that plays the main role in this catalytic reaction. Furthermore, this material has good low-temperature catalytic stability and is extremely CO tolerant.


Adherence to a community-based exercise program is a strong predictor of improved back pain status in older adults: an observational study.
To identify factors that were predictive of improved pain status among older adults with chronic back pain participating in the Adaptive Physical Activity (APA) program and to identify factors that were predictive of adherence to APA. An observational cohort study of 392 older adults (ages 50 to 88) with chronic back pain participating in APA for 12 months. APA was a community-based group exercise program given for 1-hour, twice weekly, in local gyms. Primary outcome measures were improved pain based on a global rating of change evaluation and adherence to the APA program (defined as participation in >75% of exercise sessions). Potential predictor variables were entered into multivariate logistic regression models to determine the most accurate set of variables for predicting improved pain and adherence. Presence of depressive symptoms, poor self-rated health and adherence to APA were the best predictors of improved pain status, with adherence being the strongest predictor [odds ratio: 13.88 (95% confidence interval: 8.17, 23.59)]. Better physical function, longer pain duration, and positive rating of the trainer were all positively associated with adherence to APA; whereas poor self-rated health and further distance from the gym were inversely associated. Given that adherence to APA is the key predictor of improved back pain, future efforts should focus on strategies to improve adherence. Our data suggest that enhanced training of exercise trainers, development of separate classes for people with different functional levels, and use of psychosocial interventions to reduce health pessimism and depression may be potential targets for improving adherence.


A model of effective health policy: the 1983 Orphan Drug Act.
There was a new pharmaceutical policy enacted in 1983 known as the Orphan Drug Act. It was designed to increase the availability of drugs used to treat rare diseases. In the decade prior to 1983, only ten orphan drugs had been marketed. Since 1983, over 200 orphan drugs have been marketed and over 800 have entered the regulatory pipeline. This paper examines a case of government regulation that industry, patients and politicians view as a resounding success. This policy should serve as a model of how to encourage innovation in other under-served areas.


The p75 neurotrophin receptor enhances HIF-dependent signaling in glioma.
Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and -independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75NTR) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro. Expression of p75NTR resulted in increased stabilization of HIF-1α and HIF-2α, and RNAi or pharmacologic targeting of p75NTR diminished HIF stabilization and HIF-dependent signaling at hypoxia. Consequentially, p75NTR inhibition resulted in decreased migration, invasion, and stemness in response to hypoxia, suggesting that p75NTR is a central regulator of hypoxia-induced glioma aggressiveness. Together, our findings support the literature that identifies p75NTR as a potential therapeutic target in brain tumors.


Electrical characteristics of waveguide applicators for medical applications.
This work concerns the electrical properties of waveguide applicators consisting of flanged rectangular waveguides filled with a dielectric, used in medical applications (microwave thermography and local hyperthermia). The reflection coefficient and the near field configuration in lossy materials were obtained in some cases analytically and in some other cases numerically. The validity of these methods was verified experimentally. The study shows that the matching of the applicator and the penetration depth in a lossy material, such as a living tissue, depend not only on the tissue characteristics but also on the characteristics of the applicator itself.


[Computer tomography following renal tumour embolisation (author's transl)].
CT examination of eight patients after palliative embolisation of a malignant renal tumour showed a distinct reduction in renal size, beginning after a week and lasting for two or three months. In the patients who survived for more than six to twelve months, the tumor increased in size, as was shown by an increase of tumour volume and tumour revascularisation which could also be demonstrated by computer tomography. Gas in the tumour after embolisation was seen in four out of six cases within the first week and in another case it persisted for five months, without evidence of the presence of a renal abscess or urinary sepsis.


Pulmonary Embolism and Increased Levels of d-Dimer in Patients with Coronavirus Disease.
We report 3 patients with coronavirus disease who had a decline in respiratory status during their hospital course that responded well to intravenous steroids and interleukin-6 receptor antagonist therapy. These patients later showed development of persistent hypoxia with increased levels of d-dimer levels and were given a diagnosis of pulmonary embolisms.


Spatiotemporal heterogeneity analysis of hemorrhagic fever with renal syndrome in China using geographically weighted regression models.
Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in China. The identification of the spatiotemporal pattern of HFRS will provide a foundation for the effective control of the disease. Based on the incidence of HFRS, as well as environmental factors, and social-economic factors of China from 2005-2012, this paper identified the spatiotemporal characteristics of HFRS distribution and the factors that impact this distribution. The results indicate that the spatial distribution of HFRS had a significant, positive spatial correlation. The spatiotemporal heterogeneity was affected by the temperature, precipitation, humidity, NDVI of January, NDVI of August for the previous year, land use, and elevation in 2005-2009. However, these factors did not explain the spatiotemporal heterogeneity of HFRS incidences in 2010-2012. Spatiotemporal heterogeneity of provincial HFRS incidences and its relation to environmental factors would provide valuable information for hygiene authorities to design and implement effective measures for the prevention and control of HFRS in China.


Acquisition of species-specific perfume blends: influence of habitat-dependent compound availability on odour choices of male orchid bees (Euglossa spp.).
Male orchid bees (Euglossini, Apidae, Hymenoptera) expose species-specific blends of volatile chemicals (perfume bouquets) during their courtship display. The perfumes are acquired by collecting fragrant substances from environmental sources, which are then accumulated in specialised hind leg pouches. To balance the perfume composition, the males need to find and collect the required substances in specific relative amounts while facing seasonal, local or habitat-dependent differences in compound availability. Experience-dependent choice of odours, i.e. 'learned avoidance' of recently collected components, has been proposed as the mechanism that mediates the accumulation of the stereotypical compound ratios. In the present study, we used the presence of certain compounds in male hind leg pouches as proxy for the respective local compound availability, and investigated whether differences in content are correlated with differences in chemical choice assays. Our results suggest that volatile availability differs between localities (n = 16) as well as habitats (n = 2; coastal vs. inland) across the Yucatán peninsula, Mexico, for both studied species. Male Euglossa dilemma showed a pronounced preference for benzyl benzoate and eugenol at locations where those compounds were rare in hind leg extracts, as predicted by the learned avoidance model. No equivalent correlations were found for Euglossa viridissima. This is the first study to combine chemical analyses of perfumes with bioassays of odour choice. It strengthens the view that negative feedback from collected odours modifies future chemical choice and helps males to acquire specific perfume blends.


Waterborne Risperidone Decreases Stress Response in Zebrafish.
The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish.


Comparison of QTc and Troponin Levels in ST Elevation MIs Compared with Non-ST Elevation MIs.
ST elevation myocardial infarctions (STEMIs) and non-ST elevation myocardial infarctions (NSTEMIs) have differences that can be important to differentiate. Our primary hypothesis was that corrected QT (QTc) duration and troponin I levels were higher in STEMIs compared with NSTEMIs. The objective of our study was to compare STEMIs with NSTEMIs for QTc duration and troponin levels. This was a retrospective case-control study of all STEMIs and a random sample of NSTEMIs during a 1-year period. STEMIs were retrieved by searching our electrocardiogram database for all of the cardiology-diagnosed STEMIs. NSTEMIs were found by selecting a randomized sample of all of the patients with a final discharge diagnosis of NSTEMI. Records and electrocardiograms were reviewed for initial troponin I levels and QTc duration. Data extractors were educated formally and a 5% sample was reevaluated by the other extractor as a reliability measure. Data analysis included χ2 tests and parametric or nonparametric analysis, where appropriate. A logistic regression model was created with variables selected a priori for predictors of STEMIs compared with NSTEMIs. A total of 92 STEMIs and 111 NSTEMIs were evaluated, and interrater reliability showed 90% agreement. Patients with NSTEMIs had significantly longer QTc. Troponin I did not differ on univariate analysis. In a logistic model, Hispanics were more likely than whites to have a STEMI (adjusted odds ratio [AOR] 2.2, 95% confidence interval [CI] 1.09-4.5). An increase in troponin I of 1 was associated with a 7% increase in the AOR of a STEMI (AOR 1.7, 95% CI 1.03-1.12) and an increase in QTc by 10 was associated with a 13% decrease in the AOR of a STEMI (AOR 0.87, 95% CI 0.78-0.93). Patients with NSTEMIs had longer QTc intervals and lower troponin I levels than those with STEMIs.


Mechanisms of fibrous cap formation in atherosclerosis.
The fibrous cap is formed by smooth muscle cells that accumulate beneath the plaque endothelium. Cap rupture is the main cause of coronary thrombosis, leading to infarction and sudden cardiac death. Therefore, the qualities of the cap are primary determinants of the clinical outcome of coronary and carotid atherosclerosis. In this mini-review, we discuss current knowledge about the formation of the fibrous cap, including cell recruitment, clonal expansion, and central molecular signaling pathways. We also examine the differences between mouse and human fibrous caps and explore the impact of anti-atherosclerotic therapies on the state of the fibrous cap. We propose that the cap should be understood as a neo-media to substitute for the original media that becomes separated from the surface endothelium during atherogenesis and that embryonic pathways involved in the development of the arteria media contribute to cap formation.


A case of aplastic anemia in a patient with systemic lupus erythematosus.
Abstract A case of aplastic anemia with a 16-year history of systemic lupus erythematosus (SLE) is described. The diagnosis of aplastic anemia was established by bone marrow biopsy. Aplastic anemia is an extremely rare complication of SLE. The pathogenesis of aplastic anemia associated with SLE remains to be clarified.


A soft x-ray probe of a titania photoelectrode sensitized with a triphenylamine dye.
We present a thorough soft x-ray photoelectron spectroscopy (XPS) study of a mesoporous titanium dioxide electrode sensitized with the dye 4-(diphenylamino)phenylcyanoacrylic acid, referred to as "L0." Supported by calculations, the suite of XPS, x-ray absorption spectroscopy, and resonant photoelectron spectroscopy allows us to examine bonding interactions between the dye and the surface and the frontier electronic structure at the molecule-oxide interface. While placing these measurements in the context of existing literature, this paper is intended as a useful reference for further studies of more complex triphenylamine based sensitizers.


Quantification of Penumbral Volume in Association With Time From Stroke Onset in Acute Ischemic Stroke With Large Vessel Occlusion.
The benefit of reperfusion therapies for acute ischemic stroke decreases over time. This decreasing benefit is presumably due to the disappearance of salvageable ischemic brain tissue (ie, the penumbra). To study the association between stroke onset-to-imaging time and penumbral volume in patients with acute ischemic stroke with a large vessel occlusion. A retrospective, multicenter, cross-sectional study was conducted from January 1, 2015, to June 30, 2022. To limit selection bias, patients were selected from (1) the prospective registries of 2 comprehensive centers with systematic use of magnetic resonance imaging (MRI) with perfusion, including both thrombectomy-treated and untreated patients, and (2) 1 prospective thrombectomy study in which MRI with perfusion was acquired per protocol but treatment decisions were made with clinicians blinded to the results. Consecutive patients with acute stroke with intracranial internal carotid artery or first segment of middle cerebral artery occlusion and adequate quality MRI, including perfusion, performed within 24 hours from known symptoms onset were included in the analysis. Time from stroke symptom onset to baseline MRI. Penumbral volume, measured using automated software, was defined as the volume of tissue with critical hypoperfusion (time to maximum >6 seconds) minus the volume of the ischemic core. Substantial penumbra was defined as greater than or equal to 15 mL and a mismatch ratio (time to maximum >6-second volume/core volume) greater than or equal to 1.8. Of 940 patients screened, 516 were excluded (no MRI, n = 19; no perfusion imaging, n = 59; technically inadequate perfusion imaging, n = 75; second segment of the middle cerebral artery occlusion, n = 156; unwitnessed stroke onset, n = 207). Of 424 included patients, 226 (53.3%) were men, and mean (SD) age was 68.9 (15.1) years. Median onset-to-imaging time was 3.8 (IQR, 2.4-5.5) hours. Only 16 patients were admitted beyond 10 hours from symptom onset. Median core volume was 24 (IQR, 8-76) mL and median penumbral volume was 58 (IQR, 29-91) mL. An increment in onset-to-imaging time by 1 hour resulted in a decrease of 3.1 mL of penumbral volume (β coefficient = -3.1; 95% CI, -4.6 to -1.5; P < .001) and an increase of 3.0 mL of core volume (β coefficient = 3.0; 95% CI, 1.3-4.7; P < .001) after adjustment for confounders. The presence of a substantial penumbra ranged from approximately 80% in patients imaged at 1 hour to 70% at 5 hours, 60% at 10 hours, and 40% at 15 hours. Time is associated with increasing core and decreasing penumbral volumes. Despite this, a substantial percentage of patients have notable penumbra in extended time windows; the findings of this study suggest that a large proportion of patients with large vessel occlusion may benefit from therapeutic interventions.


Pulmonary arteriovenous malformations complicated by splenic infarction and abscess.
Pulmonary arteriovenous malformation (PAVM) is an abnormal blood vessel connecting a pulmonary artery and a vein, and is accompanied by paradoxical embolism to other organs due to a right-to-left shunt. We report the case of a 66-year-old woman with PAVM complicated by splenic infarction and abscess. Although the PAVM had been detected on a chest image 2 years previously, and she had been advised to have further investigations, she decided not to follow this further at the time. She then visited our hospital complaining of worsening dyspnoea on exertion. Detailed examinations revealed splenic infarction and abscessation due to PAVM. PAVM embolization was performed after antibiotic treatment. It is very rare for PAVM to be complicated by splenic infarction and abscess. Regardless of its size, embolization of a PAVM as soon as possible can reduce not only the risk of central nervous system complications, but also the risk of splenic infarction and abscess.


[Spatiotemporal variation of epilithic algae in Xiangxi River system].
Xiangxi River system is the greatest branch in the Hubei reservoir area of the Three Gorges reservoir. In this paper, the epilithic algae in the River and its three major tributaries were investigated from July 2005 to June 2006. A total of 218 taxa were identified, including 183 species of Bacillariophyta, 24 species of Chlorophyta, 10 species of Cyanophyta, and one species of Xanthophyta. The diatom Achnanthes linearis was the most predominant species. The richness and Shannon-Wiener diversity indices varied significantly (or almost significantly) over time and space, and the total average values were 32 and 1.54, respectively. The total averages of annual epilithic algal density and chlorophyll a concentration were 8.75 x 10(9) cells x m(-2) and 14.62 mg x m(-2), respectively. There were significant differences in the algal density and chlorophyll a concentration among different sampling sites, and the maximum values were observed in Gufu River tributary, which were one order of magnitude higher than the minimum ones in Jiuchong River tributary. The algal density and chlorophyll a concentration tended to be higher in winter and spring than in summer and autumn, but no significant differences were observed in various seasons. Epilithic algal density and chlorophyll a concentration were significantly negatively correlated with elevation and water current, but positively correlated with the total nitrogen concentration in water.


Respiratory-function changes in textile workers exposed to synthetic fibers.
The prevalence of respiratory symptoms and acute and chronic changes in ventilatory function were studied in three groups of textile workers: 68 workers with exposure to synthetic fibers only, 30 with previous exposure to cotton, and 77 with previous exposure to hemp. The prevalence of dyspnea, grade 3 to 4, was significantly lower (P less than .01) in workers with a history of exposure to synthetic fibers only than in those previously exposed to hemp or cotton. No case of byssinosis was found in any of the workers studied. Values in ventilatory-function tests (FEV 1.0, FVC and MEF 50%) were significantly reduced during the work shift on Monday and Thursday. The Monday MEF 50% preshift values were significantly lower than expected in all three groups of workers. A comparison of the 1963-1973 data on the 77 workers previously exposed to hemp showed a lower prevalence of most chronic respiratory symptoms and smaller acute FEV1.0 and FVC reductions when they worked with synthetic fibers (1973) than when they were exposed to hemp (1963).


Study on Chemical Profile and Neuroprotective Activity of Myrica rubra Leaf Extract.
The chemical profile of Myrica rubra (a native species in China) leaf extract was investigated by UPLC-PDA-HRMS, and the neuroprotective activity of two characteristic constituents, myricanol and myricetrin, was evaluated with N2a cells using H₂O₂-inducedoxidative challenge through a series of methods, e.g., MTT assay, ROS assay and [Ca2+]i assay. Among the 188 constituents detected in the extract of Myrica rubra leaf, 116 were identified definitely or tentatively by the comprehensive utilization of precise molecular weight and abundant multistage fragmentation information obtained by quadrupole orbitrap mass spectrometry. In addition, 14 potential new compounds were reported for the first time. This work established an example for the research of microconstituents in a complex analyte and revealed that suppression of H₂O₂-induced cytotoxicity in N2a cells was achieved by the pretreatment with myricanol. The evidence suggested myricanol may potentially serve as a remedy for prevention and therapy of neurodegenerative diseases induced by oxidative stress.


Degradation of organic pollutants mediated by extracellular peroxidase in simulated sunlit humic waters: A case study with 17β-estradiol.
A growing body of research indicated that natural processes such as photolysis, biotransformation and sorption contribute to natural attenuation of organic compounds in natural waters. Here we report another potential natural reaction involving induction by extracellular peroxidase (POD) in sunlit humic waters. The degradation behavior of a natural estrogen 17β-estradiol (E2) in waters containing both horseradish peroxidase (HRP) and Suwannee River humic acid (SRHA) were studied under simulated sunlight. Significant enhancement of E2 degradation was observed in the presence of HRP as compared to direct and SRHA-inducted photolysis, resulting from the efficient degradation of E2 induced by HRP using photoproduced H2O2. The contribution of direct photolysis, indirect photolysis and enzymatic degradation to E2 degradation was calculated as 36.6, 31.7 and 31.7%, respectively. Lower yields of hydroxylation products and several new dimer products in E2+SRHA+HRP system relative to E2+SRHA system indicated that E2 degradation was primarily mediated by HRP, revealing the presence of HRP strongly affected the degradation pathway of E2. Take naturally occurring POD into consideration, enzymatic degradation may be an important attenuation pathway of E2 and other contaminants that are sensitive to peroxidases in certain waters such as humic rich freshwater system.


Design Challenges of an Episode-Based Payment Model in Oncology: The Centers for Medicare & Medicaid Services Oncology Care Model.
The Centers for Medicare & Medicaid Services developed the Oncology Care Model as an episode-based payment model to encourage participating practitioners to provide higher-quality, better-coordinated care at a lower cost to the nearly three-quarter million fee-for-service Medicare beneficiaries with cancer who receive chemotherapy each year. Episode payment models can be complex. They combine into a single benchmark price all payments for services during an episode of illness, many of which may be delivered at different times by different providers in different locations. Policy and technical decisions include the definition of the episode, including its initiation, duration, and included services; the identification of beneficiaries included in the model; and beneficiary attribution to practitioners with overall responsibility for managing their care. In addition, the calculation and risk adjustment of benchmark episode prices for the bundle of services must reflect geographic cost variations and diverse patient populations, including varying disease subtypes, medical comorbidities, changes in standards of care over time, the adoption of expensive new drugs (especially in oncology), as well as diverse practice patterns. Other steps include timely monitoring and intervention as needed to avoid shifting the attribution of beneficiaries on the basis of their expected episode expenditures as well as to ensure the provision of necessary medical services and the development of a meaningful link to quality measurement and improvement through the episode-based payment methodology. The complex and diverse nature of oncology business relationships and the specific rules and requirements of Medicare payment systems for different types of providers intensify these issues. The Centers for Medicare & Medicaid Services believes that by sharing its approach to addressing these decisions and challenges, it may facilitate greater understanding of the model within the oncology community and provide insight to others considering the development of episode-based payment models in the commercial or government sectors.


Chair dental anaesthesia: a survey of current and intended practice in Mersey Region.
We performed a questionnaire survey to establish the current and intended practice of chair dental anaesthesia amongst recently appointed consultants, and senior registrars within the Mersey Region. Only 26% of the consultants surveyed practised chair dental anaesthesia, however, more consultants would have had their anaesthetic sessions allowed. Consultants performed 4.62 +/- 3.5 sessions per month and anaesthetised 8.0 +/- 2.27 patients per session. Cases were mostly performed in community dental centres. The most common reason for discontinuing the practice of chair dental anaesthesia was the Poswillo report and its implications. Sixty-eight per cent of senior registrars declared an interest in chair dental anaesthesia. This group had received significantly more training (p < 0.005) in dental anaesthesia than those with no interest. Most anaesthetists (52/71) felt that chair dental anaesthesia was acceptable in centres approved to Poswillo standards; 16 anaesthetists felt that it should be confined to a hospital environment and three felt that it should not be performed at all.


3D Graphene-Infused Polyimide with Enhanced Electrothermal Performance for Long-Term Flexible Space Applications.
Polyimides (PIs) have been praised for their high thermal stability, high modulus of elasticity and tensile strength, ease of fabrication, and moldability. They are currently the standard choice for both substrates for flexible electronics and space shielding, as they render high temperature and UV stability and toughness. However, their poor thermal conductivity and completely electrically insulating characteristics have caused other limitations, such as thermal management challenges for flexible high-power electronics and spacecraft electrostatic charging. In order to target these issues, a hybrid of PI with 3D-graphene (3D-C), 3D-C/PI, is developed here. This composite renders extraordinary enhancements of thermal conductivity (one order of magnitude) and electrical conductivity (10 orders of magnitude). It withstands and keeps a stable performance throughout various bending and thermal cycles, as well as the oxidative and aggressive environment of ground-based, simulated space environments. This makes this new hybrid film a suitable material for flexible space applications.


[Clinical analysis of 15 cases of Paget's disease of the scrotum].
To study the clinicopathologic features and treatment of Paget's disease of the scrotum. Fifteen cases of Paget's disease of the scrotum, pathologically diagnosed and successfully treated by surgery from 1987 to 2003, were studied retrospectively. Typical pathological features were observed in all the patients. Thirteen cases were followed up for 0. 5 approximately 13 years, of whom 1 case relapsed within 3 years, 2 died of metastasis after 2 years, and 3 died of cardiovascular diseases, with no recurrence in the others. Early biopsy and extensive excision of the scrotal lesion is the first choice of treatment for Paget's disease, with good operative effect and satisfactory prognosis. A 2nd operation could be considered for patients of local relapse.


The Efficacy of Transrectal Ultrasound Guided Biopsy Versus Transperineal Template Biopsy of the Prostate in Diagnosing Prostate Cancer in Men with Previous Negative Transrectal Ultrasound Guided Biopsy.
We have previously demonstrated that transperineal template prostate biopsy (TPTPB) has a significantly higher cancer detection rate compared to transrectal ultrasound guided (TRUS) biopsy in biopsy naive men with a PSA < 20 ng/mL. We, therefore, performed a prospective study to determine whether TPTPB is still superior to TRUS biopsy in the detection of prostate cancer in men with persistently elevated PSA after one previous negative set of TRUS biopsies. 42 patients with a background of one previous negative set of TRUS biopsy, persistently elevated PSA (but < 20 ng/mL) and benign feeling digital rectal examination (DRE) underwent simultaneous standard 12-core TRUS biopsy and 36-core TPTPB under general anaesthesia. We determined the prostate cancer detection rate between the two diagnostic modalities. Mean age was 65 years (range: 50-75), mean prostate volume was 59 cc (range: 21-152), mean PSA is 8.3 ng/L (range: 4.4-19), mean time difference between the study and the previous TRUS biopsy was 33 months (range: 1-150) with mean PSA velocity of 0.7 ng/mL/year (range: 0-8). Out of the 42 patients, 22 (52%) had benign pathology. Of the 20 patients (48%) diagnosed with prostate cancer, 4 (10%) had positive results in both TRUS biopsy and TPTPB, 1 (2%) had positive result in TRUS biopsy with negative TPTPB, while 15 (36%) had negative TRUS biopsy with positive TPTPB. Hence, TRUS biopsy detected cancer in 5/42 (12%) patients versus (19/42) 45% detected by TPTPB (P < 0.01). 13/19 (68%) of cancers detected by TPTPB had Gleason score ≥7. A total of 82/141 (58%) of positive cores was found in the anterior zone. One patient (2%) experienced urosepsis, 2 (5%) temporary urinary retention, 14 (34%) mild haematuria and 13 (32%) haematospermia. TPTPB still shows a significantly higher prostate cancer detection rate compared to TRUS biopsy (12% versus 45%, P < 0.01) in men with a previous set of negative TRUS biopsy, persistently elevated PSA (but < 20 ng/mL) and benign feeling prostate on DRE.


Incomplete Suppression of HIV-1 by SAMHD1 Permits Efficient Macrophage Infection.
Sterile alpha motif and histidine/aspartic acid domain-containing protein (SAMHD1) is a dNTP triphosphorylase that reduces cellular dNTP levels in non-dividing cells, such as macrophages. Since dNTPs are required for reverse transcription, HIV-2 and most SIVs encode a Vpx protein that promotes proteasomal degradation of SAMHD1. It is unclear how HIV-1, which does not appear to harbor a SAMHD1 escape mechanism, is able to infect macrophages in the face of SAMHD1 restriction. To assess whether HIV-1 had a mechanism to negate SAMHD1 activity, we compared SAMHD1 and dNTP levels in macrophages infected by HIV-1 and SIV. We examined whether macrophages infected by HIV-1 still harbored antiviral levels of SAMHD1 by assessing their susceptibility to superinfection by vpx-deleted SIV. Finally, to assess whether HIV-1 reverse transcriptase (RT) has adapted to a low dNTP environment, we evaluated SAMHD1 sensitivity of chimeric HIV-1 and SIV variants in which the RT regions were functionally exchanged. Here, we demonstrate that HIV-1 efficiently infects macrophages without modulating SAMHD1 activity or cellular dNTP levels, and that macrophages permissive to HIV-1 infection remained refractory to superinfection by vpx-deleted SIV. Furthermore, through the use of chimeric HIV/SIV, we demonstrate that the differential sensitivity of HIV-1 and SIV to SAMHD1 restriction is not dictated by RT. Our study reveals fundamental differences between HIV-1 and SIV in the strategy used to evade restriction by SAMHD1 and suggests a degree of resistance of HIV-1 to the antiviral environment created by SAMHD1. Understanding how these cellular restrictions antagonize viral replication will be important for the design of novel antiviral strategies.


Surgery in Mongolia.
Western-style medicine in Mongolia was introduced in 1922. Today the health service structure is well adapted to the needs of the country. Surgery in Mongolia is performed by more than 300 surgeons who serve a population of 2.5 million people. The differences in geographical and settlement conditions create significant disparities in health needs between rural and urban populations. In this report we give an overview of the development and current status of medical service, disease patterns, and medical educational systems, including surgical specialty training.


Evaluation of an interprofessional continuing professional development course on comprehensive diabetes care: A mixed-methods approach.
Since there are only 33 endocrinologists within the Department of Defence and over 150 000 beneficiaries with diabetes, most patients with diabetes will be treated by primary care providers (PCPs). Comprehensive diabetes care visits are extensive and the clinical practice guidelines (CPGs) routinely change; thus, providing current evidence-based care is difficult. Most professional development courses aim to update PCPs on CPGs but are often inadequate as they focus on only the PCPs (not the interdisciplinary team) without a plan to implement changes into practice. To evaluate the biannual (twice yearly), 3-day, interprofessional Diabetes Champion Course (DCC) developed by the US Air Force Diabetes Center of Excellence on comprehensive diabetes care. A mixed-methods approach was used to evaluate three iterations of the DCC course (Sept 2014-Sept 2015). Quantitatively, pre-course and post-course surveys were used to obtain impact on knowledge, skills, and intention to change clinical practice. Qualitatively, semi-structured phone interviews were conducted with participants to obtain benefits to their clinic related to attending the DCC and barriers to implementation of the CPG process improvement project. Twelve of 19 responding clinics (63%) reported implementing all or part of their original CPG project developed at the DCC, and 17 of 19 clinics (89%) reported improvements associated with attending the DCC. Post-course surveys, from on location participants, revealed significant improvements in knowledge (P < 0.01). Likewise, foot exam skills and ability to demonstrate glucose meters to patients improved. Even with high pre-course confidence, 97% of providers reported acquiring new knowledge about prescribing and titrating insulin. The DCC is innovative as it employs a team-based, interprofessional, didactic, and interactive approach that is effective in improving knowledge, skills, and intention to change clinical practice, which should translate to better care for patients with diabetes.


Thermodynamics of carbon monoxide adsorption on polycrystalline titania studied by static adsorption microcalorimetry.
The adsorption of CO on polycrystalline TiO2 was investigated by static adsorption microcalorimetry. The initial differential heat of adsorption (qdiff,0) of CO on polycrystalline titania is 40 kJ/mol, and the standard adsorption entropy (Deltas0) is -104 J mol(-1) K(-1). These results are consistent with those derived from temperature-programmed desorption and FTIR results in the literature. The good reproducibility of the isotherms and the stable qdiff indicate that the lattice oxygen and hydroxyl groups on titania surface are basically not reactive to adsorbed CO.


Decreasing LDL cholesterol and medication cost with every-other-day statin therapy.
Statins are administered daily, but because of their long half-lives, atorvastatin and rosuvastatin can be given every other day (q.o.d.). We examined the effect of q.o.d. statin therapy in 25 patients treated with either atorvastatin (mean dose, 18.8 mg q.o.d.) or rosuvastatin (mean dose, 9.7 mg q.o.d.). Low-density lipoprotein cholesterol decreased 43%, triglycerides (mean +/- SEM) decreased 22%+/-6%, and high-density lipoprotein cholesterol increased 9%+/-6% with q.o.d. atorvastatin (n=9; p<0.05 for all). Low-density lipoprotein cholesterol decreased 28%, triglycerides decreased 15%+/-6%, and high-density lipoprotein cholesterol increased 10%+/-5% with rosuvastatin q.o.d. (n=16; p<0.05 for all). We conclude that q.o.d. treatment with long-acting statins significantly improves serum lipid levels.


Rhabdomyosarcoma of extrahepatic biliary tree: initial treatment with chemotherapy and conservative surgery.
The very low frequency of rhabdomyosarcoma (RMS) of the extrahepatic biliary tree has impeded the development of a standardized form of treatment. Based on the good response of embryonal RMS to chemotherapy, we used a multi-drug protocol as the initial treatment of a 3-year-old girl after obtaining adequate transparietohepatic biliary drainage. The treatment achieved complete remission. Later conservative laparoscopic surgery revealed only residual scar tissue. The patient is alive and well 1 year after remission. Management of this difficult tumor using modern less invasive techniques for diagnosis and treatment, with the help of preoperative chemotherapy, prevented extensive damage to the biliary tree and allowed complete recovery.


Diphtheria toxin prevents catecholamine desensitization of A431 human epidermoid carcinoma cells.
We proposed that a rapidly turning over protein, induced in response to catecholamine stimulation of C6-2B rat astrocytoma cells, inhibits subsequent hormonal activation of adenylate cyclase. Studies upon which our hypothesis is based and confirmatory work in a variety of other cell lines and in vivo have utilized actinomycin D and cycloheximide to inhibit RNA and protein synthesis, respectively. These inhibitors, however, are not specific and have been reported also to interfere with other cellular processes. Diphtheria toxin is a specific protein synthesis inhibitor that acts only by ADP-ribosylating elongation factor 2, thus preventing peptide chain elongation. We thus tested whether diphtheria toxin could prevent catecholamine-induced desensitization in A431 human epidermoid carcinoma cells. The toxin inhibited protein synthesis and altered the time course of isoproterenol-stimulated cAMP accumulation as did the less-specific protein synthesis inhibitor cycloheximide. Cellular cAMP content after a 30-min exposure to isoproterenol was similar in control and in toxin-treated cells. However, after 4 hr of treatment with isoproterenol, toxin-treated cells accumulated up to six times more cAMP than controls. When cells or cell-free adenylate cyclase preparations were rechallenged with agonists, toxin-mediated inhibition of protein synthesis prevented desensitization. These results show that diphtheria toxin, a specific inhibitor of protein synthesis, can interfere with the normal physiological regulation of cAMP metabolism in eukaryotic cells and provide compelling evidence that catecholamine stimulation of adenylate cyclase promotes the synthesis of a protein(s) that, in some way, inhibits hormone-stimulated adenylate cyclase.


Real-time SPARSE-SENSE cine MR imaging in atrial fibrillation: a feasibility study.
Background Cardiac magnetic resonance imaging (MRI) relies on correct ECG-gating, which is hindered in arrhythmia. Purpose To examine whether a prototype free-breathing real-time cine sequence using SPARSE-SENSE (SPARSE) improves left ventricular quantification in atrial fibrillation. Material and Methods On a 1.5T MR system left ventricular short-axis stacks were acquired of the SPARSE sequence and of a "reference" steady-state free precession (SSFP) sequence with arrhythmia rejection in 20 patients with atrial fibrillation. Two radiologists independently rated arrhythmia-caused artifact severity in both sequences using a 4-point scale. Coefficients of variation of myocardial signal intensity for both sequences were acquired. Volumetry was performed twice by one reader and once by another reader. Correlation between artifact severity and employed sequence was analyzed by modified Fisher's exact test. Coefficients of variation and volumetric data were compared by paired t-test and intraclass correlation. Results Median arrhythmia-caused artifact severity was 2 in both readers for SSFP and 0 (reader 1)/1 (reader 2) for SPARSE, being significantly lower in SPARSE ( P < 0.001). Mean coefficient of variance was significantly smaller in SPARSE (0.11 ± 0.04) compared to SSFP (0.22 ± 0.13, P = 0.003), which was interpreted as a hint for fewer artifacts in SPARSE. Only a small difference of 9 ± 15 mL was seen for end-systolic volume ( P = 0.019) between sequences, otherwise no significant difference was detected (end-diastolic volume, P = 0.200; stroke volume, P = 0.554; ejection fraction, P = 0.136; myocardial mass, P = 0.353). Intraclass correlation between sequences was good to excellent (range, 0.80-0.97). Conclusion Real-time MRI with SPARSE data sampling is promising in atrial fibrillation because it reduces arrhythmia-caused artifacts.


Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis.
Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84-20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52-18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29-2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.


New targeted approaches for epigenetic age predictions.
Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis. In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands.


Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause Women Affected With Low Bone Density.
Physical activity and mental health could be affected by osteoporosis and various therapeutic options such as calcitonin may influence Quality Of Life (QOL) of these patients with Low Bone Density (LBD). This study aimed to evaluate the effect of nasal calcitonin on QOL in post menopause women with LBD. This clinical trial study was performed on one hundred and fifteen menopause women with LBD less than 1 SD in Bone Mineral Densitometry (BMD) referred to Baqiyatallah Hospital in Tehran, Iran, during 2009 - 2010. They were assigned to receive 200 IU calcitonin nasal spray along with calcium (1000 mg) and vitamin D (400 IU) for 6 months. Quality of life was assessed by Short-Form 36 (SF-36) questionnaire (Persian-validated version). The mean age (± SD) of the participants was 58.75 ± 8.15 years. Intranasal spray of calcitonin increased QOL scores significantly (88.05 ± 15.63 vs. 92.15 ± 13.22, P value = 0.000). Bone mineral density of spine was increased from 0.834 ± 0.11 to 0.12 ± 0.852 and this difference in BMD of lumbar spine was statistically significant (P value: 0.003) but not significant in femur's BMD (P value = 0.061). In comparison with BMD indexes, The QOL scores especially Mental Health domain changes had only a significant correlation with the changes of total T score in BMD (P = 0.031, Coefficient Correlation = 0.248). It seems that nasal spray of calcitonin can effectively improve QOL of women with LBD and QOL changes were not influenced by clinical or para-clinical alteration. Mental health domain must be more considered in further studies as a predicting domain for Health-Related Quality of Life (HR-QOL) changes.


Improving border irrigation performance with predesigned varied-discharge.
Insufficient water resources restrict wheat production in the North China Plain, so it is urgent and essential to improve the border irrigation performance and water use efficiency. This study developed a predesigned varied-discharge irrigation scheme in the closed-ended border. Field treatments, including continuous-discharge (CD), increased-discharge (ID) and decreased-discharge (DD) border irrigation tests, were conducted to evaluate the irrigation performance of the proposed varied-discharge scheme. The DD border irrigation treatment had great application efficiency (AE), distribution uniformity (DU) and requirement efficiency (RE), and its comprehensive evaluation indicator (Y) was also significantly higher than other treatments. DD treatment achieved the average AE, DU, RE and Y values of 91.4%, 95.5%, 99.5% and 95.4%, respectively. Furthermore, the hydraulic simulation model WinSRFR was used to optimize the scheme of predesigned varied-discharge border irrigation, and sensitivity analyses of infiltration parameters, roughness coefficient, slope and inflow rate were carried out. The results indicate that the predesigned varied-discharge border irrigation scheme can improve the irrigation performance, and the DD border irrigation scheme has more satisfactory robustness than that of the ID border irrigation scheme.


18F-Labeled Carboplatin Derivative for PET Imaging of Platinum Drug Distribution.
Increasing evidence indicates that reduced intracellular drug accumulation is the parameter most consistently associated with platinum drug resistance, emphasizing the need to directly measure the intratumor drug concentration. In the era of precision medicine and with the advent of powerful imaging and proteomics technologies, there is an opportunity to better understand drug resistance by exploiting these techniques to provide new knowledge on drug-target interactions. Here, we contribute to this endeavor by reporting on the development of an 18F-labeled carboplatin derivative (18F-FCP) that has the potential to image drug uptake and retention, including intratumoral distribution, by PET. Methods: Fluorinated carboplatin (19F-FCP) was synthesized using 19F-labeled 2-(5-fluoro-pentyl)-2-methyl malonic acid (19F-FPMA) as the labeling agent to coordinate with the cisplatin-aqua complex. It was then used to treat cell lines and compared with cisplatin and carboplatin at different concentrations. Manual radiosynthesis and characterization of 18F-FCP were performed using 18F-FPMA for coordination with the cisplatin-aqua complex. Automated radiosynthesis of 18F-FCP was optimized on the basis of manual synthesis procedures. The stability of 18F-FCP was verified using high-performance liquid chromatography. 18F-FCP was evaluated using ex vivo biodistribution and in vivo PET imaging in non-tumor-bearing animals as well as in KB-3-1 and COLO-205 tumor xenograft-bearing nude mice. Results: In vitro cytotoxicity studies demonstrated that 19F-FCP has an antitumor activity profile similar to that of the parent drug carboplatin. In vivo plasma and urine stability analysis showed intact 18F-FCP at 24 h after injection. PET imaging and biodistribution studies showed fast clearance from blood and major accumulation in the kidneys, indicating substantial renal clearance of 18F-FCP. Using 18F-FCP PET, we could image and identify the intratumor drug profile. Conclusion: Our results demonstrated that 19F-FCP, like carboplatin, retains antitumor activity in various cell lines. 18F-FCP could be a useful imaging tool for measuring the intratumor drug distribution. This strategy of using a new therapeutic carboplatin derivative to quantify and track platinum drugs in tumors using PET has the potential to translate into a clinically useful imaging tool for individual patients.


Biodegradation of the aromatic fraction from petroleum diesel fuel by Oerskovia sp. followed by comprehensive GC×GC-TOF MS.
Polycyclic aromatic hydrocarbons (PAHs) from petroleum and fossil fuels are one of the most dominant pollutants in the environment. Since aromatic fraction from petroleum diesel fuel is mainly composed of PAHs, it is important to discover new microorganisms that can biodegrade these compounds. This article describes the biodegradation of the aromatic fraction separated from petroleum diesel fuel using the strain Oerskovia sp. CHP-ZH25 isolated from petroleum oil-contaminated soil. The biodegradation was monitored by gravimetry and GC × GC-TOF MS. An innovative method was applied to visualize degraded compounds in the data provided by a GC × GC-TOF MS. It was shown that Oerskovia sp. CHP-ZH25 degraded 77.4% based on gravimetric analysis within 30 days. Average rate of degradation was 14.4 mg/L/day, 10.5 mg/l/day and 4.0 mg/l/day from 0 to 10 day, 10-20 and 20-30 day, respectively. The order of PAH degradation based on decrease in peak volume after 30 days of incubation was as follows: dibenzothiophene derivatives > benzo[b]thiophene derivatives > naphthalene derivatives > acenaphthene derivatives > acenaphthylene/biphenyl derivatives > fluorene derivatives > phenanthrene/anthracene derivatives. Here we demonstrated that Oerskovia sp. CHP-ZH25 could potentially be a suitable candidate for use in bioremediation of environments polluted with different PAHs.


Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?
To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.


Availability of irrigation water for domestic use in Pakistan: its impact on prevalence of diarrhoea and nutritional status of children.
This study assessed whether availability of water for domestic use had any impact on nutritional status of children in an area where people depend on irrigation water for all their domestic water needs. During May 1998-April 1999, data on the occurrence of diarrhoea among 167 children aged less than five years were collected from 10 villages in the command area of the Hakra 6R canal in southern Punjab, Pakistan. Anthropometric measurements were taken at the end of the study period. Additional surveys were conducted to collect information on the availability of water, sanitary facilities, hygiene, and socioeconomic status. Height-for-age and longitudinal prevalence of diarrhoea were used as outcome measures. Quantity of water available in households was a strong predictor of height-for-age and prevalence of diarrhoea. Children from households with a large storage capacity for water in the house had a much lower prevalence of diarrhoea and stunting than children from families without this facility. Having a toilet was protective for diarrhoea and stunting. Increased quantity of water for domestic use and provision of toilet facilities were the most important interventions to reduce burden of diarrhoea and malnutrition in this area. An integrated approach to water management is needed in irrigation schemes, so that supply of domestic water is given priority when allocating water in time and space within the systems.


Optimization of enzymatic clarification of green asparagus juice using response surface methodology.
Enzymatic clarification conditions for green asparagus juice were optimized by using response surface methodology (RSM). The asparagus juice was treated with pectinase at different temperatures (35 °C-45 °C), pH values (4.00-5.00), and enzyme concentrations (0.6-1.8 v/v%). The effects of enzymatic treatment on juice clarity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity were investigated by employing a 3-factor central composite design coupled with RSM. According to response surface analysis, the optimal enzymatic treatment condition was pectinase concentration of 1.45%, incubation temperature of 40.56 °C and pH of 4.43. The clarity, juice yield, and soluble solid contents in asparagus juice were significantly increased by enzymatic treatment at the optimal conditions. DPPH radical-scavenging capacity was maintained at the level close to that of raw asparagus juice. These results indicated that enzymatic treatment could be a useful technique for producing green asparagus juice with high clarity and high-antioxidant activity. Treatment with 1.45% pectinase at 40.56 ° C, pH 4.43, significantly increased the clarity and yield of asparagus juice. In addition, enzymatic treatment maintained antioxidant activity. Thus, enzymatic treatment has the potential for industrial asparagus juice clarification.


The development of busulfan/cyclophosphamide preparative regimens.
Bone marrow transplantation (BMT) preparative regimens consisting of busulfan (Bu) and cyclophosphamide (Cy) were developed as an alternative to preparative regimens based on total body irradiation (TBI). Animal studies demonstrated that Bu had a high level of myeloablative and antileukemic activity, but little immunosuppressive effect. In contrast, Cy was sufficiently immunosuppressive to allow allogeneic marrow engraftment in animal systems. In both animals and humans, the combination of Bu and Cy results in effective eradication of the host's bone marrow and suppression of the immune response, thus allowing engraftment by either allogeneic or autologous marrow. A number of BMT preparative regimens have been developed for use in leukemic patients. These regimens differ primarily in the myeloablative agent used (Bu or TBI) and the dose of Cy. Although few comparative studies have been conducted, BuCy regimens appear to be similar in efficacy to those containing Cy and TBI. In addition to its use in leukemic patients, BuCy BMT preparative regimens also have been used in patients with nonmalignant lymphohematopoietic disorders or other malignant diseases.


[Architectural and structural craniofacial analysis (lateral view). Theoretical principles. Some example of its use in maxillofacial surgery (author's transl)].
Based upon the study of mutual equilibrium of the various bony structures of the skull and face, cranio facial architectural and structural analysis studies successively the skull (vault and base), then the face in relation to the skull and to the cranio-spinal joint. Its value lies in avoiding statistical averages rather relying upon individual measurements, influenced by the special features of each skeleton. It places the dentition within its cephalic context, thereby making it possible to demonstrate certain pathogenic factors of dento-facial dysmorphoses, not demonstrated by traditional types of orthodontic analysis. It is particularly useful to the maxillofacial surgeon in clearly demonstrating all maxillfacial amlformations and the pathological equilibria which it must transform. In the most severe types of craniofacial dysmorphosis it offers better possibilities than other methods of analysis of detecting the various cranial and facial abnormalities which characterise these conditions.


Simultaneous Placement of Endosseous Implants in Free Fibula Flap for Reconstruction of Mandibular Resection Defects.
Functional reconstruction of the jaw defect due to tumor resection poses a challenging problem in maxillofacial surgery. Large bone defects in the mandible due to ablation for tumors may generate a series of problems, as far as function and esthetics of the patient is concerned. The use of free bone flaps for mandibular reconstruction has the obvious advantage of being a well vascularized tissue that can withstand the hostile environment of the oral cavity. Fibular bone presents favorable conditions for implant-supported prosthetic rehabilitation, due to its diameter and the good quality of its cortical bone. The outcome of current study supports the use of simultaneous placement of endosseous implants in free fibula flap for reconstruction of mandibular resection defects with better clinical, aesthetic, and functional outcomes.


Approximate solutions of the Bloch-McConnell equations for two-site chemical exchange.
Approximate formulas for the transverse-relaxation rate constant and resonance frequency have been derived for nuclear spins subject to two-site chemical exchange. The new results are more accurate than previous approximations when chemical exchange does not approach the fast-exchange limit or when site populations are not highly asymmetric. Results are derived from an effective average evolution operator that contains contributions from both exact eigenvalues of the Bloch-McConnell equations. These expressions are useful for interpretation of chemical exchange processes in NMR spectroscopy.


Biomolecules and nutritional quality of soymilk fermented with probiotic yeast and bacteria.
Soymilk was fermented with five isolates of probiotic lactic acid bacteria and in combination with probiotic yeast Saccharomyces boulardii. Nutritional profile like fat, protein, ash, pH, acidity, polyphenol, and protein hydrolysis were analyzed. Polyphenol content decreased from 265.88 to 119 microg/ml with different cultures. Protein hydrolysis ranged from 2.46 to 2.83 mmol l(-1) with different cultures. The antioxidant activity was assessed using different methods like 1, 1-diphenyl-2-picrylhydrazyl free radical-scavenging assay, inhibition of ascorbate autoxidation, and measurement of reducing activity. The activities varied with the starters used but, nevertheless, were significantly higher than those found in unfermented soymilk. Bioconversion of the isoflavone glucosides (daidzin + genistin) into their corresponding bioactive aglycones (daidzein + genistein) was observed during soymilk fermentation. Total glucosides in soyamilk were 26.35 mg/100 ml. In contrast, aglycones genistein and daidzein were quantitatively lesser accounting 2.91 mg/100 ml (genistein 1.17 mg/100 ml and daidzein 1.19 mg/100 ml). Soymilk fermented with probiotic cultures resulted in the reduction of glycosides ranging from 0.40 mg to 1.36 mg/100 ml and increase in aglycones ranging from 6.32 mg to 13.66 mg/100 ml.


Natural history of extensive diaphragmatic injury on the right side: experimental study in rats.
To evaluate the natural healing of the rat diaphragm that suffered an extensive right penetrating injury. Animals were submitted to an extensive penetrating injury in right diaphragm. The sample consisted of 40 animals. The variables studied were initial weight, weight 21 days after surgery; healing of the diaphragm, non-healing of the diaphragm, and herniated abdominal contents into the chest. Ten animals were used as controls for weight and 30 animals were operated. Two animals died during the experiment, so 28 animals formed the operated group; healing of the diaphragm occurred in 15 animals (54%), 11 other animals showed diaphragmatic hernia (39%) and in two we observed only diaphragmatic injury without hernia (7%). Among the herniated organs, the liver was found in 100% of animals, followed by the omentum in 77%, small bowel in 62%, colon in 46%, stomach in 31% and spleen in 15%. The control group and the diaphragmatic healing subgroup showed increased weight since the beginning of the study and the 21 days after surgery (p <0.001). The unhealed group showed no change in weight (p = 0.228). there is a predominance of spontaneous healing in the right diaphragm; animals in which there was no healing of the diaphragm did not gain weight, and the liver was the organ present in 100% the diaphragmatic surface in all rats with healed diaphragm or not.


Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite.
The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (-SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 +/- 129.3 to 2,928.6 +/- 502.0 nM and from 3.8 +/- 0.7 to 9.0 +/- 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and -SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 +/- 66.0 and 253.6 +/- 55.3 microl.min(-1).g kidney wt(-1) in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl(2) 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 +/- 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl(2) administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 +/- 445.6 nM and 6.3 +/- 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 +/- 45.2 microl.min(-1).g kidney wt(-1)). These beneficial effects of CoCl(2) on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.


Delayed postoperative cardiac tamponade mimicking severe tricuspid valve stenosis.
A patient developed acute, severe hemodynamic deterioration five days after an aortic valve replacement. Cardiac catheterization revealed a markedly elevated right atrial pressure but a normal right ventricular end-diastolic pressure. Angiography revealed an extrinsic mass causing compression of the right atrium and the tricuspid anulus. A large clot overlying the right atrium and ventricle was found at emergency surgery. Postoperative cardiac tamponade may result in an atypical hemodynamic presentation when there is selective compression of one chamber or of a valve anulus.


Effect of Insurance Reimbursement Status on Pre- and Postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Scores After Arthroscopic Rotator Cuff Repair.
Previous studies reported inferior patient-reported outcomes (PROs) after arthroscopic rotator cuff repair for patients receiving workers' compensation (WC) relative to patients with commercial insurance. The extent to which alternative insurance reimbursement, including Medicaid and Medicare, influences outcomes after arthroscopic rotator cuff repair remains understudied. Compared with patients with commercial insurance reimbursement, patients with WC or government-issued reimbursement would report lower pre- and postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) scores, report higher pre- and postoperative PROMIS Depression (D) and Pain Interference (PI) scores, and experience smaller levels of improvement in all PROMIS domains with surgical intervention. Cohort study; Level of evidence, 3. Demographic and surgical data were extracted from the medical record, and PROMIS domains were prospectively collected. Patients were divided into cohorts based on insurance reimbursement status. Differences between insurance-based cohorts for baseline variables, pre- and postoperative PROMIS scores, and change from baseline to final follow-up (delta) for PROMIS scores were evaluated using Kruskal-Wallis or chi-square tests. Mixed-effects linear regression models were performed to assess the influence of insurance while controlling for other variables. Survival analysis was performed to determine time to achieve minimal clinically important difference (MCID) for each PROMIS domain per cohort. 1252 patients underwent arthroscopic rotator cuff repair, met inclusion criteria, and completed PROMIS questionnaires. Statistically significant differences were noted in demographic variables including age (P < .001), sex (P < .001), ethnicity (P < .001), and body mass index (P < .001) between insurance-based cohorts. Unadjusted analysis revealed significantly higher PF scores and lower PI and D scores for the group with commercial insurance relative to those with Medicare, Medicaid, and WC at 6- and 12-month follow-up (P < .01 all comparisons), except for the Medicare versus commercial subcohort analysis for PI at 6 months (P = .28). These differences persisted for the Medicare, Medicaid, and WC groups (P < .03 all comparisons) after adjustment for confounding variables in linear regression. The baseline characteristics of patients undergoing arthroscopic rotator cuff repair differed based on insurance reimbursement. Patients with commercial insurance reported improved physical function, decreased pain interference, and improved mood (less depression) relative to patients with government-issued and WC insurance, with maximum improvement 6 to 12 months postoperatively. There were few significant differences between insurance groups in change of PROMIS scores from preoperative to postoperative intervals, indicating that differences in the baseline demographic and surgical characteristics of these groups accounted for differences in response to surgery.


Gene expression, cell localization, and evolution of rodent submandibular gland androgen-binding protein.
A small dimeric androgen-binding protein (Abp) secreted by mouse (Mus) submandibular salivary glands has been hypothesized to function in mate-selection. The alpha-subunit (Abpa) evolves rapidly under natural selection. However, cellular site(s) of synthesis, mode of function, and patterns of evolution of this biologically important protein are otherwise unknown. We used a radiolabeled riboprobe and in situ hybridization to mouse (Mus) Abpa mRNA to localize Abpa synthesis to submandibular gland acinar cells. We next used a quantitative fluorescent thermal cycler (real-time PCR) to determine relative expression levels (normalized with a constitutively expressed ribosomal gene [S15/rig; rat insulinoma gene]) in male, female, and sexually immature European striped field mice (Apodemus agrarius). We hypothesized that gender or age-related differences might occur in production of a salivary protein related to sexual selection, but found no significant differences within our sample. Finally, we also used reverse transcription-PCR of mRNAs isolated from submandibular salivary glands to determine the Abpa allele in the striped wood mouse and compare it to published information on the homologue in Mus musculus domesticus.


A First-in-Man Study with 4-Fluoroamphetamine Demonstrates it Produces a Mild Psychedelic State.
The phenethylamine 4-fluoroamphetamine (4-FA) is a so-called novel psychoactive substance with a chemical structure resembling that of amphetamine and MDMA. Since 4-FA users report their subjective experience ranges between the effects induced by amphetamine and MDMA, and it is known that both substances can produce an altered state of consciousness, this study tests whether 4-FA induces a psychedelic state. A placebo-controlled two-way crossover study in 12 healthy poly-drug users was conducted to test subjective and behavioral effects of 4-FA. 4-FA concentrations were determined in serum up to 12 hours after administration and a series of questionnaires and the picture concept test were administered between one hour and 11 hours post-administration. Findings showed that 4-FA induced a psychedelic state which was highest one hour after 4-FA administration, at peak 4-FA serum concentrations. The 4-FA-induced psychedelic state decreased over time and was in general associated with the decreasing 4-FA serum concentrations. There was no 4-FA-induced change in creative (flexible) thinking. It is concluded that while the 4-FA-induced psychedelic state is mild in intensity and in between that produced by amphetamine and MDMA as hypothesized, more research is needed to indicate whether 4-FA can change creative thinking.


Diffuse low-grade glioma mimicking ischaemic infarct: a case report.
Diffuse Low-Grade Gliomas (LGGs) include World Health Organization (WHO) grade II diffuse astrocytoma, oligodendroglioma and oligoastrocytoma. Since the neurological symptoms of LGGs are often subtle and deceptive, LGGs are easily overlooked at their early stage. Here, we report a case of a 49-year-old female with symptoms and imaging manifestations mimicking ischaemic infarct. After treatments for ischaemic stroke, the symptoms initially fluctuated and then aggravated. In addition, we found that the locations of the lesions did not match the vascular distribution and no obvious abnormalities were observed by Computed Tomography (CT) angiography and transcranial Doppler. The results from the Magnetic Resonance Spectroscopy (MRS) and from the stereotactic biopsy directed to the final diagnosis of WHO grade II, isocitrate dehydrogenase (IDH)-wild-type diffuse astrocytoma. This is the first reported LGG case with a stroke-like onset. This case illustrates how easy it is to misdiagnose an LGG as a stroke if just using cerebral CT and magnetic resonance imaging. MRS and biopsy can assist with the differential diagnosis process thereby avoiding inappropriate or delayed treatments.


Oxygen-limited nitrification and denitrification in a lab-scale rotating biological contactor.
Rotating Biological Contactors (RBC) treating highly nitrogenous wastewaters are known to give rise to nitrogen losses, generally assumed to be due to concomitant nitrification and denitrification. In this study, a lab-scale nitrifying RBC reactor was shown to bring about losses of nitrogen of the order of 10 to 20% at ammonium loading rates of up to 2129 mg N m(-2) d(-1), when no extra carbon source was added. These higher removal values could be due to Oxygen-Limited Autotrophic Nitrification and Denitrification (OLAND), because the reactor was operated at oxygen limitation. When methanol was added as a soluble organic carbon source to further diminish oxygen transfer into the deeper parts of the biofilm, the RBC achieved 84% nitrogen removal (loading rate 2300 mg N m(-2) d(-1)) at a COD/N ratio of 3.1. The latter also suggests that the process was occurring parallel to conventional denitrification.


Imperfect synchrony in animal displays: why does it occur and what is the true role of leadership?
Synchrony can be defined as the precise coordination between independent individuals, and this behaviour is more enigmatic when it is imperfect. The traditional theoretical explanation for imperfect synchronous courtship is that it arises as a by-product of the competition between males to broadcast leading signals to attract female attention. This competition is considered an evolutionary stable strategy maintained through sexual selection. However, previous studies have revealed that leading signals are not honest indicators of male quality. We studied imperfect courtship synchrony in fiddler crabs to mainly test whether (i) signal leadership and rate are defined by male quality and (ii) signal leadership generates synchrony. Fiddler crab males wave their enlarged claws during courtship, and females prefer leading males-displaying ahead of their neighbour(s). We filmed groups of waving males in the field to detect how often individuals were leaders and if they engaged in synchrony. Overall, we found that courtship effort is not directly related to male size, a general proxy for quality. Contrary to the long-standing assumption, we also revealed that leadership is not directly related to group synchrony, but faster wave rate correlates with both leadership and synchrony. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


RISK OF INTRAOCULAR INFLAMMATION AFTER INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS: A Meta-analysis.
This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration. A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model. Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points. There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.


[Chronic obstructive pulmonary disease in France: the patients' perspective. Results of an international survey (Confronting COPD)].
Chronic obstructive pulmonary disease (COPD) has become a real public health problem throughout the world. In spite of its association with high rates of morbidity and mortality, it is not accorded sufficient attention. In this paper, we present the results of the French part of the international survey "Confronting COPD in North America and Europe" concerning the impact of COPD from the perspective patients'. Subjects were randomly recruited by means of telephone questionnaires. Patients included in the survey were to be aged > or =45 years with a cumulative cigarette consumption of > or =10 packets-yrs, and having been diagnosed with COPD, emphysema or chronic bronchitis, or whose symptoms fulfilled a definition of chronic bronchitis. According to this survey, the prevalence of COPD among smokers (mean number of packets per year: 38.2 +/- 26.1) was 3.2%. COPD was undiagnosed in 17% of patients in spite of the presence of characteristic symptoms. Respiratory difficulties had a marked adverse effect on the quality of life although patients tended to play down the severity of their problems. This survey reveals that COPD appears to be under-diagnosed and under-treated in France, as shown by the results of the same survey in the other 7 countries taking part. Considerable efforts are thus required to improve the speed and precision of diagnosis and to improve management of these patients.


Fourier rebinning and consistency equations for time-of-flight PET planograms.
Due to the unique geometry, dual-panel PET scanners have many advantages in dedicated breast imaging and on-board imaging applications since the compact scanners can be combined with other imaging and treatment modalities. The major challenges of dual-panel PET imaging are the limited-angle problem and data truncation, which can cause artifacts due to incomplete data sampling. The time-of-flight (TOF) information can be a promising solution to reduce these artifacts. The TOF planogram is the native data format for dual-panel TOF PET scanners, and the non-TOF planogram is the 3D extension of linogram. The TOF planograms is five-dimensional while the objects are three-dimensional, and there are two degrees of redundancy. In this paper, we derive consistency equations and Fourier-based rebinning algorithms to provide a complete understanding of the rich structure of the fully 3D TOF planograms. We first derive two consistency equations and John's equation for 3D TOF planograms. By taking the Fourier transforms, we obtain two Fourier consistency equations and the Fourier-John equation, which are the duals of the consistency equations and John's equation, respectively. We then solve the Fourier consistency equations and Fourier-John equation using the method of characteristics. The two degrees of entangled redundancy of the 3D TOF data can be explicitly elicited and exploited by the solutions along the characteristic curves. As the special cases of the general solutions, we obtain Fourier rebinning and consistency equations (FORCEs), and thus we obtain a complete scheme to convert among different types of PET planograms: 3D TOF, 3D non-TOF, 2D TOF and 2D non-TOF planograms. The FORCEs can be used as Fourier-based rebinning algorithms for TOF-PET data reduction, inverse rebinnings for designing fast projectors, or consistency conditions for estimating missing data. As a byproduct, we show the two consistency equations are necessary and sufficient for 3D TOF planograms. Finally, we give numerical examples of implementation of a fast 2D TOF planogram projector and Fourier-based rebinning for a 2D TOF planograms using the FORCEs to show the efficacy of the Fourier-based solutions.


Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.
Nonketotic hyperglycinemia (NKH) is caused by deficient glycine cleavage enzyme activity and characterized by elevated brain glycine. Metabolism of glycine is connected enzymatically to serine through serine hydroxymethyltransferase and shares transporters with serine and threonine. We aimed to evaluate changes in serine and threonine in NKH patients, and relate this to clinical outcome severity. Age-related reference values were developed for cerebrospinal fluid (CSF) serine and threonine from 274 controls, and in a cross-sectional study compared to 61 genetically proven NKH patients, categorized according to outcome. CSF d-serine and l-serine levels were stereoselectively determined in seven NKH patients and compared to 29 age-matched controls. In addition to elevated CSF glycine, NKH patients had significantly decreased levels of CSF serine and increased levels of CSF threonine, even after age-adjustment. The CSF serine/threonine ratio discriminated between NKH patients and controls. The CSF glycine/serine aided in discrimination between severe and attenuated neonates with NKH. Over all ages, the CSF glycine, serine and threonine had moderate to fair correlation with outcome classes. After age-adjustment, only the CSF glycine level provided good discrimination between outcome classes. In untreated patients, d-serine was more reduced than l-serine, with a decreased d/l-serine ratio, indicating a specific impact on d-serine metabolism. We conclude that in NKH the elevation of glycine is accompanied by changes in l-serine, d-serine and threonine, likely reflecting a perturbation of the serine shuttle and metabolism, and of one-carbon metabolism. This provides additional guidance on diagnosis and prognosis, and opens new therapeutic avenues to be explored.


Identification and analysis of copine/BONZAI proteins among evolutionarily diverse plant species.
Copines are evolutionarily conserved calcium-dependent membrane-binding proteins with potentially critical biological functions. In plants, the function of these proteins has not been analyzed except for in Arabidopsis thaliana where they play critical roles in development and disease resistance. To facilitate functional studies of copine proteins in crop plants, genome-wide identification, curation, and phylogeny analysis of copines in 16 selected plant species were conducted. All the identified 32 plant copines have conserved features of the two C2 domains (C2A and C2B) and the von Willebrand factor A (vWA) domain. Different from animal and protozoa copines, plant copines have glycine at the second residue potentially acquiring a unique protein myristoylation modification. Phylogenetic analysis suggests that copine was present as one copy when evolving from green algae to basal flowering plants, and duplicated before the divergence of monocots and dicots. In addition, gene expression and protein localization study of rice copines suggests both conserved and different properties of copines in dicots and monocots. This study will contribute to uncovering the role of copine genes in different plant species.


Antinociception and side effects of liposome-encapsulated alfentanil after spinal delivery in rats.
We investigated the spinal antinociceptive and supraspinally mediated side effects of intrathecal (IT) alfentanil after delivery in saline or when encapsulated in liposomes of different lipid constituencies in rats. Rats prepared with chronic IT catheters received IT injections of alfentanil (1, 3, 10, 30, or 50 micrograms) prepared in either saline or in one of three liposome formulations (dipalmitoyl phosphatidyl choline [DPPC], DPPC containing 20% by weight of dipalmitoyl phosphatidyl glycerol [DPPC-DPPG], or DPPC containing 20 weight percent of cholesterol [DPPC-CHOL]). Antinociception was measured by hot-plate (HP) test (52.5 degrees C). In separate groups of halothane-anesthetized rats, plasma alfentanil concentrations were measured (2-120 min) after 50 micrograms IT alfentanil given in either saline or liposomes. Antinociception was measured by tail withdrawal upon its immersion in water 52.5 degrees C. Supraspinal side effects of the drug were tested by measuring catalepsy and the eye blink evoked by touching the cornea. IT alfentanil in saline produced a dose-dependent increase in the HP response latency and this effect was accompanied by a similar dose-dependent increase in the incidence of catalepsy and blockade of corneal responses, indicating a rapid supraspinal redistribution. The HP dose-response curve for IT alfentanil delivered in liposomes was shifted slightly to the right, as compared to saline vehicle, but liposome encapsulation totally abolished the side effects that were otherwise observed at the highest IT alfentanil dose.(ABSTRACT TRUNCATED AT 250 WORDS)


[The dual function of the proliferating cell nuclear antigen (PCNA) in the response of human cells to UV damages].
An auxiliary protein of DNA polymerases delta and epsilon, the proliferating cell nuclear antigen (PCNA), is necessary for efficient DNA replication in vivo and in vitro, and also for the repair synthesis in vitro, but its role in the excision repair of genome in vivo is not exactly established. In S-phase of unirradiated cells, PCNA is tightly bound to focal centers of DNA replication and is not removed by treatment with detergent Triton X-100, but is completely extracted from non-S-phase cells by the indicated detergent. It was shown earlier that after UV-irradiation PCNA could not be removed by the detergent even from non-S-phase cells. It was interpreted as the evidence of PCNA integration into the repair complex and of the participation of this protein in repair synthesis in vivo. In the present work the data were obtained indicating that the role of PCNA in cell response to UV-damage was not confined only to its possible involvement in repair synthesis. With the help of confocal microscopy it was established that in Triton X-100-extracted normal cells PCNA did not colocalize with the well known excision repair protein XPB/ERCC3, defective in cells from Xeroderma pigmentosum (complementation group B) patients. XPB-protein is induced by UV-irradiation in normal cells, and this induction is not observed in repair deficient cells. However, in such cells UV-light induces a detergent-resistant form of PCNA, and this form is obviously not connected with repair. It cannot be excluded that a rapid PCNA immobilization immediately after UV-irradiation of cells is needed for the facilitation of photochemical damage bypass during the subsequent replication of genome.


Similar tactile distance anisotropy across segments of the arm.
A substantial literature has described anisotropy of tactile distance perception across many body parts. In general, the distance between two touches is felt as larger when the touches are oriented with the mediolateral axis of the limbs than when oriented with the proximodistal axis. In this study, we investigated tactile distance perception across the arm, measuring anisotropy on the upper arm, forearm, and hand dorsum. Participants made forced-choice judgments of which of two pairs of tactile distances felt larger and anisotropy was measured using the method of constant stimuli. Clear anisotropy was found on all three regions of the arm. There was no apparent difference in the magnitude of anisotropy across segments of the arm. We further measured the physical curvature of the arm and show that this cannot account of the perceptual anisotropy observed.