Spoilage of fresh turkey and pork sausages: Influence of potassium lactate and modified atmosphere packaging.
Fresh poultry and pork meat products represent highly perishable products which are susceptible to spoil within a few days after production. Lactate addition and modified atmosphere packaging are common preservation strategies used to overcome spoilage. This study aimed to identify the effects of these strategies and their possible interactions on spoilage indicators simultaneously on fresh pork and turkey sausages. Ten batches of raw meat (turkey or pork) sausages were industrially produced with different lactate concentrations (0, 1 or 2% w/w in turkey and 0, 0.57 and 1.13% w/w in pork), packed under different gas mixtures (air, MAP1: 70% O2 - 30% CO2 and MAP2: 50% CO2 - 50% N2) and chill stored during 22 days. Spoilage responses including enumeration of total aerobic mesophilic and lactic acid bacteria, measurement of pH and colour, evaluation of visual defects and off-odour, were monitored. Effects of lactate and modified atmosphere packaging (MAP) as well as random effect of the batch variability were studied using a mixed effect model. Despite initial batch variability, significant effects of lactate and gas packaging were observed but in a different way in turkey and pork. Our results suggest that for fresh turkey sausages, the gas mixture enriched in oxygen enhanced off-odour perception and sausage discolouration from red to dark grey / brown colour. Unlike turkey sausages, in pork sausages, lactate did not significantly influence the monitored spoilage responses, whereas MAP (70% O2-30% CO2) reduced the off-odour perception. The developed model could be useful to estimate the effect of preservation strategies on spoilage occurrence while considering industrial batch variability.


Brain age estimation using multi-feature-based networks.
Studying brain aging improves our understanding in differentiating typical and atypical aging. Directly utilizing traditional morphological features for brain age estimation did not show significant performance in healthy controls (HCs), which may be due to the negligence of the information of structural similarities among cortical regions. For this issue, the multi-feature-based network (MFN) built upon morphological features can be employed to describe these similarities. Based on this, we hypothesized that the MFN is more efficient and robust than traditional morphological features in brain age estimating. In this work, we used six different types of morphological features (i.e., cortical volume, cortical thickness, curvature index, folding index, local gyrification index, and surface area) to build individual MFN for brain age estimation. The efficacy of MFN was estimated on 2501 HCs with T1-weighted structural magnetic resonance imaging (sMRI) data and compared with traditional morphological features. We attained a mean absolute error (MAE) of 3.73 years using the proposed method on an independent test set, whereas a mean absolute error of 5.30 years was derived from morphological features. Our experimental results demonstrated that the MFN is an efficient and robust metric for estimating brain age.


[Primary sinu-nasal melanomas. Clinical aspects, therapy and follow-up].
Primary malignant melanoma of the nasal cavity and paranasal sinuses is a rare entity felt to have a poor prognosis. We examined the frequency and characteristics of this type of melanoma in a defined geographic region over a period of 16 years. Nine patients (eight men, one woman, mean age 62 years) with primary nasal and sinusoidal malignant melanoma were treated between 1985 and 2000 in the Department of Dermatology in cooperation with the Department of Otorhinolaryngology. All patients underwent surgery, eight with clinical complete tumor removal and one with only partial removal. All patients had radiotherapy after surgery. History, potential risk factors, clinical presentation, histological and immunohistochemical data and clinical course were documented. All patients died because of their tumor within the observation period (median survival: 30 months, range 7 to 75 months). There were three different courses of the disease: (1) uncontrollable primary tumor (one patient, survival 11 months); (2) local recurrence with metastasis (five patients, median survival 40.2 months); (3) metastasis after a disease-free interval (three patients, median survival 19.3 months). Malignant melanoma of the nasal cavity and paranasal sinuses is a rare entity which is usually rapidly fatal. Effective treatment approaches are not available.


Changes in puffing behavior among smokers who switched from tobacco to electronic cigarettes.
Nicotine intake from electronic cigarette (e-cigarettes) increases with user's experience. This suggests that smokers who switched from tobacco to electronic cigarettes compensate for nicotine over time to get as much nicotine as they need. One of the mechanisms by which smokers may compensate for nicotine is by modifying their puffing behavior. The aim of the study was to assess the changes in puffing behavior after switching from conventional to electronic cigarettes among regular smokers. Twenty smokers (11 female, aged 31±10, CPD 16±8, FTND 4±3, and exhaled CO 16±17 (mean±SD)) who were naïve to e-cigarettes participated in this study. They were asked to substitute their regular tobacco cigarettes with first generation e-cigarettes (labeled 18mg nicotine) for two weeks. Puffing topography (number of puffs, puff volume, intervals between puffs, and average puff flow rate) was measured at the initial use (baseline), as well as after one and two weeks of product use. We tested changes in puffing topography outcomes using repeated measures ANOVA. We found that after one week of using e-cigarettes, participants significantly increased the average time they puffed on e-cigarettes from 2.2±0.1 (mean±SEM) to 3.1±0.3s (p<0.05). The average puff flow rate decreased from 30.6±2.3 to 25.1±1.8ml/s after one week of e-cigarette use (p<0.05). Our data show that smokers modify their puffing behavior after switching from tobacco to electronic cigarettes by taking longer and slower puffs. The potential reason for changing puffing behavior is to compensate for less efficient nicotine delivery from e-cigarettes.


The relationship among egg size, density and food level on larval development in the wood frog (Rana sylvatica).
Although inter- and intraspecific variation in egg size among amphibians has been well documented, the relationship between egg size and fitness remains unclear. Recent attempts to correlate egg size intraspecifically with larval developmental patterns have been equivocal. In this study the development of larvae derived from large eggs and small eggs, from a single population in Maryland were compared under a range of food levels and larval population densities. Both food level and density had significant effects on the length of the larval period and size at metamorphosis. However, the response among larvae derived from different egg sizes was not additive. At low densities and high food levels, larvae from small eggs had longer larval periods and a larger size at metamorphosis than larvae derived from large eggs. In contrast, at high densities larvae from small eggs had longer developmental periods but were smaller at metamorphosis than larvae from large eggs. In addition, larvae from small eggs were more sensitive to density irrespective of food level. These results suggest that optimal egg size is correlated with environmental factors, which may explain the maintenance of both geographic and within population variation in egg size commonly observed in amphibians.


One-Pot Synthesis of CdTe/ZnS Quantum Dots and their Physico-Chemical Characterization.
A known property of quantum dots (QDs) is their characteristic luminescence, which would make it possible to detect different types of cancers after being functionalized with some type of biological molecule. For this reason, in the present investigation a methodological analysis of the physicochemical characteristics of the CdTe/ZnS core/shell QDs was carried out, using techniques such as Optical Absorbance Spectroscopy (UV-Vis), Molecular Fluorescence, Fourier Transform Infrared Spectroscopy (FT-IR), Dynamic Light Scattering (DLS), X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Zeta Potential that allowed to verify the photoluminescent effectiveness of these semiconductor nanocrystals as an alternative to conventional techniques currently used for the detection of specific cancers smaller than 1 cm. The study consisted of theoretically determining the bandgap energy, the size of the nanocrystals and the molar absorptivity from the wavelength value for the maximum intensity of the excitonic peak. It was also possible to verify the maximum intensity for each sample and thus evaluate its photoluminescent response, as well as it was possible to determine the charge distribution, the hydrodynamic size and the surface composition of each quantum dot. The results obtained correspond to what has been reported in the literature, which makes them good candidates for the detection of cancer in precancerous stages.


The Psychological Toll of Emotion Work in Same-Sex and Different-Sex Marital Dyads.
This study considers how the provision of daily emotion work may affect the psychological well-being of the emotion worker, and how this linkage may vary for men and women in same- and different-sex marriages. Emotion work-work intended to bolster a spouse's well-being by reading and managing the spouse's emotional needs-is common within marital relationships and often gendered, with women more aware of and concerned with emotion work than men. Yet, the psychological cost of performing emotion work is largely unexplored. This study relies on 10 days of daily experiences data from spouses in same- and different-sex marriages (n = 756 individuals). Mixed effects multilevel regression modeling is used to examine how the provision of emotion work is associated with the emotion workers' psychological well-being. Providing emotion work is inversely associated with emotion workers' psychological well-being, especially when provided for a spouse with elevated depressive symptoms. These estimated effects are generally similar for men and women but greater for those married to a man than for those married to a woman, whether in a same- or different-sex marriage. Emotion work appears to adversely affect the worker's own psychological well-being, especially when a spouse has elevated depressive symptoms and when one's spouse is a man. These results point to the importance of dyadic approaches and consideration of gendered relationship dynamics of same- as well as different-sex couples in studies of emotion work and other marital processes.


Exercise Promotion: Reviewing the Importance of Health Professionals' Interpersonal Behaviors on Exercisers' Basic Psychological Needs.
Previous studies have investigated the impact of exercisers' perceptions of health professionals' interpersonal behaviors on exercisers' exercise adherence. From these studies, there is increased interest in developing and evaluating programs to improve health professionals' communication skills and interpersonal behavior. In this narrative review, we provide examples of self-determination theory and newer modifications to it, discuss the empirical conditions that foster optimal exerciser motivation, consider the antecedent factors influencing health professionals' behaviors, and offer practical suggestions to health professionals seeking to promote regular exercise practice. Since exercisers perceive and differentiate health professionals' need-supportive, need-thwarting, and need-passive behaviors, health professionals who can critically and consciously distinguish these different types of behavior are more likely to foster supportive climates and suppress the use of need-thwarting and need-indifferent behaviors. The interpersonal interaction between health professionals and exercisers strongly influences how exercisers will regulate their behavior toward persistent exercise.


Intravascular Leiomyomatosis Extending to Right Atrium: A Rare Caused Syncope.
Intravascular leiomyomatosis (IVL) is a variant of leiomyoma characterized by intravascular proliferation of a histologically benign smooth muscle tumor extending beyond the uterus into distant great vessels or the heart. It is a rare disease and results in death. Here, we reported the case of 48-year-old, otherwise well woman, who presented to the emergency department with syncope. Pulmonary computed tomography (CT) demonstrated a large low-density shadow originating from the inferior vena cava (IVC) extending into the right atrium (RA). Magnetic resonance venography (MRV) showed that a neoplasm was "snakelike," which completely occluded the right internal iliac vein (RIIV), the common iliac vein (CIV), and IVC. A multidisciplinary team of specialists consisting of vascular surgeons, cardiac surgeons, gynecologists, anesthesiologists, and radiologists reviewed the history, clinical examination findings, and diagnostic imaging of the patient. A decision was made to proceed with one-stage surgery (resection of thoracoabdominal tumor extension at one operative setting). After surgery, the patient's vital signs were restored, and her symptoms were disappeared. She was discharged on hospital day 21 without complications. One-stage surgical approach to completely remove an IVL with RA involvement is an optimal choice if the patient's physical condition permits.


Upscaling NZ-DNDC using a regression based meta-model to estimate direct N2O emissions from New Zealand grazed pastures.
The availability of detailed input data frequently limits the application of process-based models at large scale. In this study, we produced simplified meta-models of the simulated nitrous oxide (N2O) emission factors (EF) using NZ-DNDC. Monte Carlo simulations were performed and the results investigated using multiple regression analysis to produce simplified meta-models of EF. These meta-models were then used to estimate direct N2O emissions from grazed pastures in New Zealand. New Zealand EF maps were generated using the meta-models with data from national scale soil maps. Direct emissions of N2O from grazed pasture were calculated by multiplying the EF map with a nitrogen (N) input map. Three meta-models were considered. Model 1 included only the soil organic carbon in the top 30cm (SOC30), Model 2 also included a clay content factor, and Model 3 added the interaction between SOC30 and clay. The median annual national direct N2O emissions from grazed pastures estimated using each model (assuming model errors were purely random) were: 9.6GgN (Model 1), 13.6GgN (Model 2), and 11.9GgN (Model 3). These values corresponded to an average EF of 0.53%, 0.75% and 0.63% respectively, while the corresponding average EF using New Zealand national inventory values was 0.67%. If the model error can be assumed to be independent for each pixel then the 95% confidence interval for the N2O emissions was of the order of ±0.4-0.7%, which is much lower than existing methods. However, spatial correlations in the model errors could invalidate this assumption. Under the extreme assumption that the model error for each pixel was identical the 95% confidence interval was approximately ±100-200%. Therefore further work is needed to assess the degree of spatial correlation in the model errors.


[Pharmacodynamic and pharmacokinetic characteristics. Mechanism of action of the new oral anticoagulants].
Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran.


Up regulation of the long non-coding RNA NEAT1 promotes esophageal squamous cell carcinoma cell progression and correlates with poor prognosis.
Dysregulation of NEAT1 plays critical oncogenic roles and facilitates tumorigenesis on various human tumor entities. However, little information is available about the expression pattern of NEAT1 in esophageal squamous cell carcinoma (ESCC). The contributions of this lncRNA to tumorigenesis and progression of ESCC aslo remains unclear. By performing quantitative real-time polymerase chain reaction (qRT-PCR) in 96 cases of ESCC, we found that the expression of NEAT1 was higher in ESCC tissues and cells compared with the normal counterparts. Pearson analysis showed that elevated NEAT1 levels were extraordinarily correlated with the tumor size (P=0.026), lymph node metastasis (P=0.035) and clinical stage (P=0.004). Moreover, Kaplan-Meier curves with the log-rank test showed that higher expression of NEAT1 led to a significantly poorer survival and multivariate Cox proportional hazards analysis revealed that NEAT1 was an independent risk factor of overall survival (OS). We also assessed the function of NEAT1 in vitro by gain-/loss-of-function studies. Results showed that enhanced expression of NEAT1 stimulated the proliferation of ESCC cells, and promoted their ability of forming foci, migration, and invasion. Conversely, knockdown of NEAT1 showed the opposite effect. Overall, our study indicated that the inappropriate activation of NEAT1 predicts poor prognosis and has a crucial regulatory role in in ESCC. Targeting NEAT1 could be a novel therapeutic choice for treating ESCC patients.


Towards a functional model of chronic headaches: investigation of antecedents and consequences.
The traditional approach to classifying headache based on symptoms and assumed mechanisms is criticized as having limited utility when applied to tension-type headache and migraine. The study reported here was designed to explore an alternative method of conceptualizing chronic headaches based on functional characteristics or controlling variables. One hundred and ninety nine chronic headache sufferers completed questionnaires which enquired about the antecedents and consequences of their headaches. An attempt to build a categorical model driven by functional characteristics using cluster analysis was unsuccessful but a subsequent attempt to construct a dimensional model using factor analysis proved more successful. This approach led to the emergence of five antecedent dimensions and six consequences dimensions (three pertaining to the responses of sufferers and three to the reactions of significant others) which were readily identifiable. The functional dimensions were significantly related to traditional diagnostic categories but at a low level. Three functional dimensions predicted response to psychological treatment.


Activatable MRI-monitoring gene delivery for the theranostic of renal carcinoma.
Multifunctional nanocarriers, which can be used for molecular imaging and drug delivery simultaneously, favor the fabrication of theranostic platforms in a less cost- and time-consuming way. Polyethylene glycol (PEG)-modified manganese dioxide (MnO2) nanosheets (PEG-MnO2), used as two-dimensional nanomaterials, not only possess the high surface-to-volume ratio necessary for drug delivery but also display a redoxable property in the tumor microenvironment, producing Mn2+ ions for magnetic resonance imaging (MRI). In this study, we constructed a PEG-MnO2-OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo. This strategy of utilizing PEG-MnO2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T1-weight MRI, illustrating the promising potential of PEG-MnO2 nanosheets for the fabrication of an MRI-based theranostic system.


The evolution of cerebral palsy publications and global productivity: a bibliometric analysis between 1980 and 2019.
Although cerebral palsy (CP), which affects the quality of life of many children and their families, is the most common cause of motor dysfunction in children, no comprehensive bibliometric study has holistically evaluated the publications on CP. This study aimed to analyze the scientific outputs published on CP in pediatrics research between 1980 and 2019 using bibliometric and statistical methods, and reveal new study trends in this field. The literature search was performed in the Web of Science database using the keyword cerebral palsy in the title section of the articles published only in the pediatrics research field. Four-thousand seventy-five publications were obtained in the field of pediatrics research on CP, 3027 of which were articles. We shared abstract information of 3027 articles published between 1980 and 2019 with this comprehensive bibliometric study, which will be a useful guide for physicians and scientists on the global outcomes of CP, and we discussed new trends in this topic. We think that comprehensive bibliometric analyzes on subjects that we frequently encounter in clinics and which are widely researched will contribute to the field.


Considerations for radiotherapy planning with MV photons using dose-to-medium.
Radiotherapy planning considerations were developed for the previous calculation algorithms yielding dose to water-in-water (Dw,w). Advanced algorithms improve accuracy, but their dose values in terms of dose to medium-in-medium (Dm,m) depend on the medium considered. This work aimed to show how mimicking Dw,w planning with Dm,m can introduce new issues. A head and neck case involving bone and metal heterogeneities outside the CTV was considered. Two different commercial algorithms were used to obtain Dm,m and Dw,w distributions. First, a plan was optimised to irradiate the PTV uniformly and get a homogeneous Dw,w distribution. Second, another plan was optimised to achieve homogeneous Dm,m. Both plans were calculated with Dw,w and Dm,m, and the differences between their dose distributions, clinical impact, and robustness were evaluated. Uniform irradiation produced Dm,m cold spots in bone (-4%) and implants (-10%). Uniform Dm,m compensated them by increasing fluence but, when recalculated in Dw,w, the fluence compensations produced higher doses that affected homogeneity. Additionally, doses were 1% higher for the target, and + 4% for the mandible, thus increasing toxicity risk. Robustness was impaired when increased fluence regions and heterogeneities mismatched. Planning with Dm,m as with Dw,w can impact clinical outcome and impair robustness. In optimisation, uniform irradiation instead of homogeneous Dm,m distributions should be pursued when media with different Dm,m responses are involved. However, this requires adapting evaluation criteria or avoiding medium effects. Regardless of the approach, there can be systematic differences in dose prescription and constraints.


Nuclear DNA Content Estimation of Seaweed by Fluorimetry Analysis.
Fluorimetry analysis of nuclear DNA content allows identification of genome size and ploidy levels of different life phases, tissues, and populations in seaweed species. It is an easy method that saves time and resources compared to more complex techniques. Here we describe the methodology for measuring nuclear DNA content in seaweed species by DAPI fluorochrome staining and its comparison with the standard Gallus gallus erythrocytes nuclear content, one of the preferred internal standards. With this methodology, up to a thousand nuclei can be measured in a single staining session, allowing for a quick analysis of the studied species.


Facile green synthesis, analysis, in vitro antidiabetic and antimicrobial activity of ZnO macropores.
Rapid increase in population and development in industry causes many problems such as microbial contaminations and chronic diseases such as diabetes. Materials synthesized at nanoscale are novel antidiabetic and antimicrobial agents. ZnO nanoparticles with macropores characteristics are synthesized by green methods. Turmeric, clove buds and green tea extracts are used as additives. X-ray diffraction results confirmed the hexagonal wurtzite structure of ZnO nanoparticles and crystallinity was quit high in case of green tea extract. Sample synthesized with clove shows relatively higher crystallite size (10.64) which is pertaining to variation in Zn2+ and OH- ions. The nanoparticles are more or less spherical in nature, macropores and clustered together revealed by SEM images. Macroporosity of the sample was further confirmed by nitrogen adsorption-desorption isotherm. The deep absorption band at 605 cm-1 in FTIR spectra attributed the wurtzite-type ZnO. The major dominating sharp peak was detected at 437 cm-1 in Raman spectra which is a feature of the wurtzite hexagonal phase ZnO. UV-Vis spectra showed red shift from wavelength 362 to 375 nm with different plant extracts. Impedance analysis showed a high dielectric constant and low tangent loss in case of green tea extract. ZnO synthesized using green tea exhibited ~ 95% α-glucosidase inhibition activity and 91% α-amylase inhibition activity. Antibacterial results revealed that synthesized ZnO nanoparticles showed activity against Bacillus subtilis and E. coli with inhibition zone 35 mm and 29 mm, respectively.


Isolate-specific and broad-spectrum QTLs are involved in the control of clubroot in Brassica oleracea.
Clubroot, caused by Plasmodiophora brassicae, is one of the most damaging diseases of vegetable Brassica crops in the world. In this study, genetic control and mapping of loci implied in quantitative resistance against five isolates of P. brassicae were studied in the F(1) and F(2/3 )progenies of the cross C10 (resistant kale)xHDEM (susceptible broccoli). A genetic map was constructed using RFLP, random and specific PCR-based markers. The 199 loci were assembled into nine linkage groups covering 1,226.3 cM. The F(3) families were assessed for resistance under controlled conditions with four single-spore isolates and one field isolate. A total of nine genomic regions were detected for clubroot resistance. Depending on the isolate, two to five QTLs were identified. The total phenotypic variation accounted for by QTLs ranged from 70% to 88% depending on the isolate. One of the QTLs ( Pb-Bo1) was detected in all isolates and explained 20.7-80.7% of the phenotypic variation. Pb-Bo1 had a major effect on three isolates but this effect was weaker for the last two. Five QTLs with minor effect were identified in only one isolate. To construct clubroot resistant varieties, the existence of both broad-spectrum and isolate-specific QTLs should be taken into account for the choice of genomic regions to use in a marker-assisted selection strategy.


The number of accessible SH-groups in Escherichia coli membrane vesicles is increased by ATP or by formate.
The number of accessible SH-groups was determined in membrane vesicles prepared from Escherichia coli growing in fermentation conditions at slightly alkaline pH on glucose with or without added formate. Addition of ATP or formate to the vesicles caused a approximately 1.4-fold increase in the number of accessible SH-groups. The increase was inhibited by treatment with N-ethylmaleimide or the presence of the F(0)F(1)-ATPase inhibitors N,N(')-dicyclohexylcarbodiimide or sodium azide. The increase in accessible SH-groups was also absent in strains with the ATP synthase operon deleted or with the single F(0) domain cysteine Cysb21 changed to Ala. Using hyc and hyf mutants, it was shown that the increase was also largely dependent on hydrogenase 4 or hydrogenase 3, main components of formate hydrogen lyase, when bacteria were grown in the absence or presence of added formate. These results suggest a relationship between the F(0)F(1)-ATP synthase and hydrogenase 4 or hydrogenase 3 under fermentation conditions.


Can MASCC and CISNE scores predict delays of lung cancer chemotherapy after febrile neutropenia?
Febrile neutropenia (FN) during cancer chemotherapy can lead to morbidity and mortality. The Multinational Association of Supportive Care in Cancer (MASCC) and clinical index of stable febrile neutropenia (CISNE) scores have been widely used to predict the risk of severe medical complications in patients with FN; however, there are few tools for predicting chemotherapy delays or discontinuation after FN. Patients admitted to two university hospitals between 2014 and 2018 with a FN diagnosis during the first cycle of chemotherapy for lung cancer were reviewed retrospectively. Among 539 patients who received 813 courses of chemotherapy for lung cancer, 49 (9%) developed FN during the first treatment cycle. Although all the patients recovered from their primary infection, 19 patients (38.8%) developed serious medical complications, 11 (22.4%) were unable to resume chemotherapy and one (2.0%) declined to resume chemotherapy, and nine (18.4%) died within 90 days. Patients who failed to resume chemotherapy had a lower MASCC score (median 8.5 vs. 17, p < 0.01) and a higher CISNE score (median 3 vs. 1, p < 0.01) at the onset of FN. The specificity to predict the patient who failed to resume chemotherapy was 90% or more with MASCC score ≤9 or CISNE score ≥3, with the sensitivity of 61%. MASCC score ≤ 16 can also be a sensitive indicator with the sensitivity and specificity of 89 and 52%, respectively. The MASCC and CISNE scores are useful in identifying lung cancer patients who are unable to resume chemotherapy as scheduled after the onset of FN.


A review of standardized high-throughput cardiovascular phenotyping with a link to metabolism in mice.
Cardiovascular diseases cause a high mortality rate worldwide and represent a major burden for health care systems. Experimental rodent models play a central role in cardiovascular disease research by effectively simulating human cardiovascular diseases. Using mice, the International Mouse Phenotyping Consortium (IMPC) aims to target each protein-coding gene and phenotype multiple organ systems in single-gene knockout models by a global network of mouse clinics. In this review, we summarize the current advances of the IMPC in cardiac research and describe in detail the diagnostic requirements of high-throughput electrocardiography and transthoracic echocardiography capable of detecting cardiac arrhythmias and cardiomyopathies in mice. Beyond that, we are linking metabolism to the heart and describing phenotypes that emerge in a set of known genes, when knocked out in mice, such as the leptin receptor (Lepr), leptin (Lep), and Bardet-Biedl syndrome 5 (Bbs5). Furthermore, we are presenting not yet associated loss-of-function genes affecting both, metabolism and the cardiovascular system, such as the RING finger protein 10 (Rfn10), F-box protein 38 (Fbxo38), and Dipeptidyl peptidase 8 (Dpp8). These extensive high-throughput data from IMPC mice provide a promising opportunity to explore genetics causing metabolic heart disease with an important translational approach.


Total loss of upper and lower lips: challenges in reconstruction.
A 2-year-old girl lost both lips after an aggressive attack of noma (gangrenous stomatitis). After an unsuccessful attempt to reconstruct her upper lip, a bipedicled chin flap was used to reconstruct both lips. The cosmetic result was good and the functional result was acceptable.


Myocardial backscatter analysis in animal experiments.
This paper describes the instrumentation and data analysis procedures for cardiac tissue characterization by a backscatter method. Experimental results obtained with a 'button' transducer in direct contact with the myocardium are discussed.


Altered photic and non-photic phase shifts in 5-HT(1A) receptor knockout mice.
The mammalian circadian clock located in the suprachiasmatic nucleus (SCN) is thought to be modulated by 5-HT. 5-HT is though to inhibit photic phase shifts by inhibiting the release of glutamate from retinal terminals, as well as by decreasing the responsiveness of retinorecipient cells in the SCN. Furthermore, there is also evidence that 5-HT may underlie, in part, non-photic phase shifts of the circadian system. Understanding the mechanism by which 5-HT accomplishes these goals is complicated by the wide variety of 5-HT receptors found in the SCN, the heterogeneous organization of both the circadian clock and the location of 5-HT receptors, and by a lack of sufficiently selective pharmacological agents for the 5-HT receptors of interest. Genetically modified animals engineered to lack a specific 5-HT receptor present an alternative avenue of investigation to understand how 5-HT regulates the circadian system. Here we examine behavioral and molecular responses to both photic and non-photic stimuli in mice lacking the 5-HT(1A) receptor. When compared with wild-type controls, these mice exhibit larger phase advances to a short late-night light pulse and larger delays to long 12 h light pulses that span the whole subjective night. Fos and mPer1 expression in the retinorecipient SCN is significantly attenuated following late-night light pulses in the 5-HT(1A) knockout animals. Finally, non-photic phase shifts to (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) are lost in the knockout animals, while attenuation of the phase shift to the long light pulse due to rebound activity following a wheel lock is unaffected. These findings suggest that the 5-HT(1A) receptor plays an inhibitory role in behavioral phase shifts, a facilitatory role in light-induced gene expression, a necessary role in phase shifts to 8-OH-DPAT, and is not necessary for activity-induced phase advances that oppose photic phase shifts to long light pulses.


Aspects of folate metabolism in renal failure.
Plasma and urine folate fractions were evaluated after ingestion of radioactive N5-methyl-tetrahydrofolic acid by a normal control (subject I), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radiofolate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject I to be compatible with N5-methyl-tetrahydrofolic acid (peak I). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10-formyl-tetrahydrofolate. Peak I was minimally present in subject 3. This limited study suggest a defect of methyl-tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se. In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks I and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis-resistant (bound plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate 'binder' detected with haemoglobin-coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.


Spatial and temporal distribution of pesticide residues in surface waters in northeastern Greece.
A monitoring study of 147 compounds in surface river waters from northeastern Greece near Greek/Bulgarian/Turkish borders was carried out during 1999-2007. Based on agricultural use eight sampling points along the rivers Ardas, Evros and Erythropotamos were set up, covering the distance from the Greek/Bulgarian borders down to the river's discharge (river's delta) in the Greek territory. In total, 88 sampling events were carried out from 1999 to 2007. Pesticides were extracted by solid-phase extraction (SPE) and analyzed by gas chromatography-mass spectrometry (GC-EI-MS) using a multiresidue in-house analytical method including pesticides belonging to different chemical classes. Aquatic risk concerning the detected pesticides was assessed on the basis of the risk quotient (RQ = PEC/PNEC). From the 28 compounds (pesticides, metabolites and caffeine) that were detected in surface waters of northeastern Greece the soil applied pesticides were the most frequently detected. High pesticide concentrations were detected within 2 months of their application. Extreme pesticide concentrations were detected in the beginning of the irrigation season or just after high rainfall events. Generally, low levels of pesticide residues were found in the first sampling point (Greek/Bulgarian borders) of all rivers, however o',p' DDT, o',p' DDE and gamma-HCH were mainly detected in this sampling point regarded as cross-boundary contamination. The most commonly encountered compounds in the river waters were atrazine, DEA, alachlor, trifluralin, prometryne, molinate, carbofuran, carbaryl and diazinon. Increased loading (primary as well as secondary peaks) seemed to be a consequence of application (timing, rate, frequency) and intense rainfall during the application period. Aquatic risk assessment revealed that from the 28 compounds that were constantly detected 12 showed non-acceptable risk when median concentrations were used as PEC and 18 when extreme concentrations were used as PEC values.


Cytophotometric measurements of the DNA in Hodgkin lymphomas and non-Hodgkin lymphomas.
In smear preparation of lymph nodes excised from 36 patients with a malignant lymphoma the DNA content was estimated in different tumor cells following Feulgen staining by means of quantitative cytophotometric measurements. The tumors investigated included 11 Hodgkin lymphomas and various types of Non-Hodgkin lymphomas (altogether 25). Whereas the small lymphoid cells found in Hodgkin lymphomas show a diploid DNA content with a wide scattering, in the large mononuclear reticular cells (Hodgkin cells) as well as in Sternberg's giant cells only aneuploid DNA values are seen lying in the hyperdiploid, hypertetraploid and hyperoctoploid regions. DNA stemlines are found in the aneuploid regions, but in some cases they are missing. This indicates that we are dealing with malignant tumor cells. In Non-Hodgkin lymphomas with a low grade of malignancy (centrocytic-centroblastic lymphoma, centrocytic lymphoma, CLL) an aneuploid DNA content is found particularly in the large cells (centroblasts, lymphoblasts) with or without a DNA stemline. These cells must be considered as primary malignant tumor cells. In the immunoblastic lymphoma of high malignancy only aneuploid tumor cells are present showing a particularly intense DNA content in the large immunoblasts, whereas a DNA stemline is usually missing. The range of aneuploid values, the number of polyploid tumor cells and the presence or absence of a DNA stemline are important criterions in determining the degree of malignancy. By means of cytophotometric measurements of the DNA content in the tumor cells of malignant lymphomas it is possible to assertain the degree of malignancy and to establish an objective prognosis.


Immunoregulation by Toxoplasma gondii infection prevents allergic immune responses in mice.
Toxoplasma gondii is a ubiquitous intracellular parasite affecting most mammals including humans. In epidemiological studies, infection with T. gondii and allergy development have been postulated to be inversely related. Using a mouse model of birch pollen allergy we investigated whether infection with T. gondii influences allergic immune responses to birch pollen. BALB/c mice were infected with T. gondii oocysts either before or at the end of sensitisation with the major birch pollen allergen Bet v 1 and thereafter aerosol challenged with birch pollen extract. During the acute phase of infection, clinical signs correlated with increased levels of serum TNF-alpha, IL-6, IFN-gamma and anti-Toxoplasma-IgM. In the chronic phase, Toxoplasma-specific serum IgG, brain tissue cysts and high IFN-gamma production in spleen cell cultures were detected. Mice infected prior to allergic sensitisation produced significantly less allergen-specific IgE and IgG1, while IgG2a levels were markedly increased. IL-5 levels in spleen cell cultures and bronchoalveolar lavage fluid were significantly reduced, and airway inflammation was prevented in these mice. Notably, in mice infected at the end of the allergic sensitisation process, systemic and local immune responses to the allergen were markedly reduced. T.gondii infection was associated with up-regulation of Toll-like receptor 2 (TLR2), 4, 9 and 11, as well as T-bet (a differentiation factor for Th1 cells) mRNA expression in splenocytes; moreover, enhanced TGF-beta, IL-10 and Foxp3 mRNA expression in these cells suggested that regulatory mechanisms were involved in suppression of the allergic immune response. Kinetic studies confirmed the induction of Foxp3(+)CD4(+)CD25(+) regulatory T cells preferentially during the chronic phase of T. gondii infection. Our data demonstrate that T. gondii exhibits strong immunomodulating properties which lead to prevention of allergic immune responses and thereby support the hygiene hypothesis.


Optimized preparation of Phragmites australis activated carbon using the Box-Behnken method and desirability function to remove hydroquinone.
In this study, preparation of Phragmites australis activated carbon (PAAC) was optimized and applied for the removal of hydroquinone from aqueous solution. The Box-Behnken surface design (33) was used to statistically visualize the interactions among microwave power (A), microwave radiation time (B) and the ingredient ratio (C) (H3PO4: P. australis powder, in g). The desirability function was utilized to simultaneously optimize the multi-response indicators. A regression analysis showed that the experimental data of BBD optimization experimental results fit well to a quadratic model. PAAC was characterized according to its morphology, structure and composition. Dynamic adsorption data showed that the best fit was obtained by a pseudo-second-order model and the Freundlich isotherm model. The maximum adsorption capacity for hydroquinone adsorption onto PAAC was 156.25 mg/g at 30 ℃ and the adsorption mechanism may be attributed to multi-layer surface and chemisorption via donor-acceptor and coupling interaction of the electron. The present study showed that PAAC has the potential for use as a biosorbent for the adsorption treatment of water pollutants.


The effect of a novel inhibitor of aldehyde dehydrogenase on viral replication.
The effect of AMPAL (4-amino 4-methyl 2-pentyne 1-al), an inhibitor of aldehyde dehydrogenase, on adenovirus type 5 (Ad5) replication was studied. AMPAL at 2 x 10(-4) M clearly reduced the cytopathic effect on HeLa cells but had no effect on cell growth at this concentration. Viral adsorption, penetration and protein synthesis were not affected by adding AMPAL at 2 hr post infection. When viral DNA synthesized in the presence of AMPAL was investigated, no significant inhibition was observed on either synthesis or the physicochemical properties of the neosynthesized DNA. However, there was a 4-fold increase in the amount of condensed DNA. In addition, AMPAL inhibited intracellular viral production (40%) and brought about concomitant inhibition of virus release (70%) into the medium. The absence of a quantitative relationship between the inhibition of viral DNA synthesis on one hand and that of viral production on the other may imply that the antiviral effect of AMPAL is indirectly mediated by the action of the malondialdehyde which has accumulated on some, as not yet identified, membrane constituent.


Membrane Dynamics and Signaling of the Coxsackievirus and Adenovirus Receptor.
The coxsackievirus and adenovirus receptor (CAR) belongs to the immunoglobulin superfamily and acts as a receptor for some adenovirus types and group B coxsackieviruses. Its role is best described in epithelia where CAR participates to tight junction integrity and maintenance. Recently, several studies aimed to characterize its potential interaction with intracellular signaling pathways and highlighted several features linking CAR to gene expression. In addition, the molecular mechanisms leading to CAR-specific membrane targeting via the secretory pathway in polarized cells and its internalization are starting to be unraveled. This chapter discusses the interaction between membrane dynamics, intracellular trafficking, and signaling of CAR.


Characterization of mouse organic anion transporter 5 as a renal steroid sulfate transporter.
A family of organic anion transporters (OAT) recently identified has important roles for the excretion or reabsorption of endogenous and exogenous compounds, and several new isoforms have been reported in this decade. Although the transepithelial transport properties of organic anions are gradually being understood, many portions of their functional characteristics in functions remain to be elucidated. A recently reported new cDNA encoding a mouse OAT5 (mOAT5) was constructed, using 3'-RACE PCR, with the total RNA isolated from a mouse kidney. When mOAT5 was expressed in Xenopus oocytes, mOAT5 transported estrone sulfate, dehydroepiandrosterone sulfate and ochratoxin A. Estrone sulfate uptake by mOAT5 displayed a time-dependent and sodium-independent manner. The Km values of estrone sulfate and dehydroepiandrosterone sulfate were 2.2 and 3.8 microM, respectively. mOAT5 interacted with chemically heterogeneous steroid or organic sulfates, such as nitrophenyl sulfate, methylumbelliferyl sulfate and estradiol sulfates. In contrast to the sulfate conjugates, mOAT5-mediated estrone sulfate uptake was not inhibited by the steroid or organic glucuronides. The mOAT5 protein having about 85 kDa molecular weight was shown to be mainly localized in the apical membrane of the proximal tubules of the outer medulla. These results suggest an important role of mOAT5 for the excretion or reabsorption of steroid sulfates in the kidney.


Acadesine: AICA riboside, ARA 100, arasine, GP 1 110.
Acadesine is an adenosine receptor agonist (ARA) in development for the treatment of ischaemia-reperfusion injury and chronic lymphocytic leukaemia. Schering-Plough is developing the compound as a cardioprotective agent in ischaemia-reperfusion injury. Avancell and Protherics are co-developing acadesine for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL). Clinical development is underway for both indications. In January 2005, PeriCor Therapeutics obtained a sublicense for the worldwide rights to acadesine and three additional ARA compounds from Dr Mangano who was a founder of the company. Dr Mangano acquired the license of worldwide rights for acadesine from Metabasis in November 2000.Previously, in December 1997, all intellectual property rights and data covering acadesine and related ARAs for cardiovascular and cerebrovascular disorders were transferred from the original developer, Gensia Sicor (SICOR), to Metabasis Therapeutics in an asset-liability transfer agreement.Schering-Plough intends to conduct a randomized, placebo-controlled phase III trial, which is required for regulatory approval. The trial will further evaluate acadesine in patients deemed to be at high risk of ischaemic heart disorders. Patients will have either undergone coronary artery bypass graft surgery, or have a history of cardiovascular events (heart attack or stroke). Protherics presented 2-year mortality results from a study of acadesine, investigating long-term mortality after perioperative myocardial infarction, at the 55th Scientific Session of the American College of Cardiology in 2006.Previously, Gensia Sicor conducted clinical trials of acadesine in Canada, the EU and the US; results of these trials were inconclusive. Acadesine has been shown to selectively cause the death of B-cells, whilst sparing T-cells when administered to blood samples taken from patients with B-CLL. Orphan drug status has been granted for acadesine in the EU for the treatment of B-cell chronic lymphocytic leukaemia.


Economic Reliable Arthroscopic Technique for Reduction and Fixation of Acute Acromioclavicular Joint Dislocation.
Separation of the acromioclavicular joint (ACJ) is a common orthopaedic injury among athletes involved in contact sports and victims of motor vehicle accidents. ACJ disruptions are common in athletes. Treatment is guided by the level of injury; grade 1 and 2 injuries are managed nonoperatively. Grades 4-6 are managed operatively, whereas grade 3 is an area of controversy. Several operative techniques have been described to restore anatomy and function. We present a technique that's safe, economic, and reliable in the management of acute ACJ dislocation. It allows intra-articular glenohumeral assessment and relies on a coracoclavicular sling. This is an arthroscopic-assisted technique. It entails a small transverse or vertical incision over distal clavicle 2 cm away from ACJ, which enables us to reduce the ACJ and maintain reduction with a k-wire, checked by the C-arm. Diagnostic shoulder arthroscopy is then performed to assess the glenohumeral joint. The rotator interval is liberated and the coracoid base is exposed, and PROLENE sutures are then passed anterior to the clavicle medial and lateral to the coracoid. It is the used to shuttle polyester tape and ultrabraid as a sling under the coracoid. A tunnel is then made in the clavicle, then one end of suture is passed through the tunnel whereas the other end remains anterior. Several knots are made to ensure it is secured, then the deltotrapezial fascia is closed as a separate layer.


Real-life experiments in supermarkets to encourage healthy dietary-related behaviours: opportunities, challenges and lessons learned.
Supermarkets are the primary source of food for many people yet their full potential as a setting to encourage healthy dietary-related behaviours remains underutilised. Sharing the experiences from research groups who have worked with supermarket chains to evaluate strategies that promote healthy eating could improve the efficiency of building such relationships and enhance the design quality of future research studies. A collective case study approach was used to synthesise experiences of engaging and sustaining research collaborations with national supermarket chains to test the effectiveness of health-focused in-store interventions. The collective narrative covers studies conducted in three high-income countries: Australia, the Netherlands and the United Kingdom. We have distilled our experiences and lessons learned into six recommendations for conducting high quality public health research with commercial supermarket chains. These include: (i) using personal contacts, knowledge of supermarket activities and engaging executive management to establish a partnership and allowing time to build trust; (ii) using scientifically robust study designs with appropriate sample size calculations; (iii) formalising data exchange arrangements and allocating adequate resource for data extraction and re-categorisation; (iv) assessing effects at individual/households level where possible; (v) designing a mixed-methods process evaluation to measure intervention fidelity, dose and unintended consequences; and (vi) ensuring scientific independence through formal contract agreements. Our collective experiences of working in non-financial partnerships with national supermarket chains could be useful for other research groups looking to develop and implement supermarket studies in an efficient manner. Further evidence from real-life supermarket interventions is necessary to identify sustainable strategies that can improve population diet and maintain necessary commercial outcomes.


Sexual satisfaction in marriage as a function of life meaning.
Previous research has demonstrated that male and female who are self-actualized and have a purpose in life tend to have satisfying sex lives. However, some research has suggested that self-actualized male partners tend to have dissatisfied female partners due to high levels of egocentricity in self-actualized males. Two alternative approaches to assessing meaning in life were utilized to further test this hypothesis. Forty-eight married couples were administered the Purpose in Life Test (PIL), Personal Orientation Inventory (POI), Selfism Scale, Sexual Interaction Inventory (SII), and Crowne-Marlowe Social Desirability Scale. The findings show that persons high on PIL and POI scores reported higher levels of sexual enjoyment. Egocentricity was positively correlated with dissatisfaction, however this result was significant for females but not males. Although no relationship was found between personality factors in the female spouse and male enjoyment, male self-actualization, but not egocentricity, was indicative of female dissatisfaction. These results are discussed in light of existing theory and research.


Is Cryotherapy a Genuine Rival to Robotic-assisted Partial Nephrectomy in the Management of Suspected Renal Malignancy? A Systematic Review and Meta-analysis.
We systematically reviewed the world literature and compare oncological outcomes, morbidity, renal function, and perioperative outcome between cryotherapy and robotic-assisted partial nephrectomy (RAPN) for suspected renal malignancy. There was a statistically significant difference in "recurrence rates" between the 2 techniques, favoring the RAPN cohort. There was no statistically significant difference in overall and ≥Clavien 3a complication rates between the 2 techniques. The quality of evidence for recurrence rates, overall complication, and ≥Clavien 3a were "moderate", "low," and "very low," respectively, on GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. If a nephron sparing approach is indicated, RAPN should be the approach of choice.


Antibody-dependent cellular cytotoxicity against tumor cells. I. Cultivated bone marrow-derived macrophages kill tumor targets.
Mouse bone marrow cells are cultivated in a liquid culture system in the presence of fibroblast conditioned medium. Under these conditions, proliferation of macrophage and granulocyte precursor cells is induced. Cells of a 5-day-old culture are shown to act as cytotoxic effector cells against tumor targets such as P815, E14, YAC and L5178Y. The effector cell is of macrophage origin since it is susceptible to treatment with the alloantiserum Mph-1.2 plus complement. The kinetics of the reaction resembles the kinetics for killer (K) lymphocyte lysis. In contrast to bone marrow cells, peritoneal macrophages do not show cytotoxic activity against antibody-coated tumor targets although they are susceptible to activation to cytotoxicity by lymphokines. The possible relationship of bone marrow effector cells and K lymphocytes is discussed.


Symptoms of depression during pregnancy are associated with increased systolic blood pressure responses towards infant distress.
A mother's response towards her infant's distress is important for the mother-infant relationship and infant development. There is evidence that maternal responses are impaired in depressed mothers. Further understanding of how depression disrupts maternal responses is important to direct treatment strategies. There is evidence that maternal responses develop during pregnancy. Further understanding of the relationship between depression and maternal responses during pregnancy is therefore important. We have previously found that depression during pregnancy is associated with reduced attentional engagement with infant distress but is unclear whether this is an insensitive or avoidance response. In the current study, we investigated the impact of anhedonic symptoms of depression on pregnant women's autonomic response towards infant distress. We found that women experiencing anhedonic depressive symptoms during pregnancy had significantly larger systolic blood pressure responses towards infant distress (β, 1.6 mmHg, 95 % CI 0.5 to 2.6, p = 0.004) than non-depressed pregnant women. These results suggest that anhedonic symptoms during pregnancy may be associated with increased sympathetic sensitivity. This suggests that depression is not, at a sympathetic level at least, associated with insensitivity to infant distress and rather depression may be associated with an abnormally sensitive response.


Persistent inhibition of Candida albicans biofilm and hyphae growth on titanium by graphene nanocoating.
Candida albicanscolonizes biomaterial surfaces and are highly resistant to therapeutics. Graphene nanocoating on titanium compromises initial biofilm formation. However, its sustained antibiofilm potential is unknown. The objective of this study was to investigate the potential of graphene nanocoating to decrease long-term fungal biofilm development and hyphae growth on titanium. Graphene nanocoating was deposited twice (TiGD) or five times (TiGV) on grade 4 titanium with vacuum assisted technique and characterized with Raman spectroscopy and atomic force microscope. The biofilm formation and hyphae growth of C. albicans was monitored for seven days by CFU, XTT, confocal, mean cell density and scanning electronic microscopy (SEM). Uncoated titanium was the Control. All tests had three independent biological samples and were performed in independent triplicates. Data was analyzed with one- or two-way ANOVA and Tukey's HSD (α = 0.05). Both TiGD and TiGV presented less biofilms at all times points compared with Control. The confocal and SEM images revealed few adhered cells on graphene coated samples, absence of hyphae and no features of a mature biofilm architecture. The increase in number of layers of graphene nanocoating did not improve its antibiofilm potential. The graphene nanocoating exerted a long-term persistent inhibitory effect on the biofilm formation on titanium. The fewer cells that were able to attach on graphene coated titanium were scattered and unable to form a mature biofilm with hyphae elements. The findings open opportunities to prevent microbial attachment and proliferation on implantable materials without the use of antibiotics.


Geniposide suppresses thermogenesis via regulating PKA catalytic subunit in adipocytes.
Geniposide has been widely found to ameliorate many metabolic diseases. The recruitment and activation of brown/beige adipocytes are effective and promising methods for counteracting obesity and related diseases. However, the effect of geniposide on thermogenesis of adipocytes and its underlying mechanism have not yet been investigated. Here, we demonstrate that geniposide (25 mg/kg) reduces body temperature and cold tolerance of mice via suppressing thermogenic genes in interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT). Consistently, geniposide (20 mg/mL) suppresses thermogenic capacity of adipocytes (brown adipocytes and 3T3L1 preadipocyte cells) in vitro. Mechanistically, geniposide reduces the level of protein kinase A (PKA) catalytic subunit and further suppresses transcription activity and protein stability of uncoupling protein 1 (UCP1), leading to reduction of thermogenic capacity in adipocytes. Moreover, pharmacological PKA activation reverses geniposide-induced UCP1 inhibition, which indicated that geniposide suppresses thermogenesis of adipocytes via regulating PKA signaling. Together, our findings suggest that geniposide is an inhibitor of fat thermogenesis, establishing a novel function characteristic of geniposide.


Dose-volume analysis and the prevention of radiation sequelae in cervical cancer.
We report a 9 year (1975-1983) experience of treatment of carcinoma of the uterine cervix by radiation alone. Computerized dosimetry conforming to the ICRU 38 recommendations was performed for all 348 patients analyzed. Late sequelae were graded as mild (grade 1), moderate (grade 2) and severe (grade 3). The overall rates were grade 3: 9.8%, grade 2: 18%, and grade 1: 19.5%. Of the moderate to severe sequelae, 48% were rectal, 15% rectosigmoid and 21% urinary. The complication rate was highly dependent on the type of intracavitary applicator: lowest for patients treated by two insertions of a standard Fletcher-Suit applicator (grade 3: 5.4%, grade 2: 14.4%) and highest for those receiving uterine stem plus vaginal line sources (grade 3: 29.5%, grade 2: 26%). For 183 patients treated with stem and standard ovoids, moderate and severe rectal and bladder sequelae were analyzed according to critical organ reference doses and reference treatment volumes as defined by ICRU 38, with the addition of a mean rectal dose. Zones of low, moderate and high risk could be defined on dose-volume plots using these parameters. Modification of treatment plans at the Cancer Institute G. F. Leclerc (CGFL) of Dijon according to these concepts produced a reduction in moderate and severe sequelae (grade 3: 14.4-3.4%) without a concurrent increase in pelvic failures. Although the zones of risk proposed can be used directly only with standard Fletcher-Suit applicators and comparable computer dosimetry, the concept can be applied to other systems.


Effect of roasting conditions on the formation and kinetics of furan in various nuts.
In this study, the effect of roasting on the formation of furan in nuts was investigated. Nut samples were roasted at 150-200 °C for 5-25 min. As the roasting temperature and roasting time increased, the levels of furan in the nuts increased up to 348 ng/g. The concentration of furan was 2.76-224, 0.71-69.0, 1.46-348, 2.68-87.0, and 3.70-94.4 ng/g in almonds, peanuts, cashew nuts, hazelnuts, and sacha inchi, respectively. In kinetics analysis, the chemical reaction responsible for the production of furan in nuts followed the zero-order kinetic model, with reaction constants of 3.26 × 10-9 to 16.5 × 10-9mol/L.h at 200 °C. The apparent activation energy (Ea) was 125.0, 93.6, 86.5, 62.0, and 70.1 kJ/mol for almonds, peanuts, cashew nuts, hazelnuts, and sacha inchi, respectively. These results can be used to predict or to calculate furan formation in roasted nuts.


Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth.
In this study, we first describe expression of the paired domain transcription factor PAX2 in the normal and cancerous human breast, then demonstrate in a murine model a novel function for PAX2 in the regulation of progesterone stimulation of secondary ductal growth. In human mammary tissue, PAX2 expression was coincident with sub-populations of mammary ductal cells, some of which possessed an undifferentiated histiotype, and was also found in >50% of the human breast tumors surveyed (n=38). In the mouse, mammary parenchyma with a targeted deletion of PAX2 developed normal ductal systems when grafted into wild-type host mammary fat pads, but failed to undergo higher order side-branching and lobular development in response to progesterone. A previously unsuspected PAX2/WT1 (Wilms' tumor suppressor gene) regulatory axis in the mammary gland was also indicated. Using RT-PCR, a significant reduction in WT1 mRNA expression was detected in the PAX2 mutant glands compared to wild-type counterparts and double-antibody immunohistochemistry detected the co-localization of PAX2 and WT1 in the nuclei of normal and cancerous breast cells. These data indicate a role for PAX2 (and possibly WT1) in the regulation of the progesterone response of the mature mammary gland. The potential contribution of PAX2 to breast tumor pathogenesis is discussed.


"Thiocyanate gold": small (2-3 nm) colloidal gold for affinity cytochemical labeling in electron microscopy.
Reduction of HAuCl4 by NaSCN or KSCN produces colloidal gold particles of 2.6 nm in diameter and homogeneous in size (coefficient of variation approximately 15%). The AuSCN sol forms protein-gold complexes. The amount of protein required to form an AuSCN-protein complex is best determined in the electron microscope, where serial dilutions of protein with gold sol are inspected for the presence of aggregates. By immuno-electron microscopy SCN-gold complexed to protein A is active and visible as is shown by revealing alpha-amylase in rat pancreatic acinar cells.


Indirectly detected through-bond chemical shift correlation NMR spectroscopy in solids under fast MAS: studies of organic-inorganic hybrid materials.
Indirectly detected, through-bond NMR correlation spectra between (13)C and (1)H nuclei are reported for the first time in solid state. The capabilities of the new method are demonstrated using naturally abundant organic-inorganic mesoporous hybrid materials. The time performance is significantly better, almost by a factor of 10, than in the corresponding (13)C detected experiment. The proposed scheme represents a new analytical tool for studying other solid-state systems and the basis for the development of more advanced 2D and 3D correlation methods.


Tumor-induced remote ECM network orientation steers angiogenesis.
Tumor angiogenesis promotes tumor growth and metastasis. Here, we use automated sequential microprinting of tumor and endothelial cells in extracellular matrix (ECM) scaffolds to study its mechanical aspects. Quantitative reflection microscopy shows that tumor spheroids induce radial orientation of the surrounding collagen fiber network up to a distance of five times their radius. Across a panel of ~20 different human tumor cell lines, remote collagen orientation is correlated with local tumor cell migration behavior. Tumor induced collagen orientation requires contractility but is remarkably resistant to depletion of collagen-binding integrins. Microvascular endothelial cells undergo directional migration towards tumor spheroids once they are within the tumor-oriented collagen fiber network. Laser ablation experiments indicate that an intact physical connection of the oriented network with the tumor spheroid is required for mechanical sensing by the endothelial cells. Together our findings indicate that, in conjunction with described activities of soluble angiogenic factors, remote physical manipulation of the ECM network by the tumor can help to steer angiogenesis.


Most treatments to control freshwater algal blooms are not effective: Meta-analysis of field experiments.
Harmful algal blooms negatively impact freshwater, estuarine, and marine systems worldwide, including those used for drinking water, recreation, and aquaculture, through the production of toxic and nontoxic secondary metabolites as well as hypoxic events that occur when algal blooms degrade. Consequently, water resource managers often utilize chemical, bacterial, physical, and/or plant-based treatments to control algal blooms and improve water quality. However, awareness of available treatments may be limited, and there is ambiguity among the effects of algal bloom treatments across studies. Such variation within the literature and lack of knowledge of other tested treatments leave uncertainty for water resource managers when deciding what treatments are best to control algal blooms and improve water quality. Our primary objective was to synthesize data from 39 published and unpublished studies that used one of 28 chemical, bacterial, physical, and/or plant-based treatments in field experiments on various water quality measurements, including phytoplankton pigments and cell density, cyanobacterial toxins (microcystin), and common off-flavors (i.e., taste and odor compounds; geosmin and 2-methylisoborneol). We hypothesized that treatments would improve water quality. Across all studies and treatment types (227 effect sizes), water quality improvements were observed when measured at the time of greatest decline following treatment or at the end of the experiment. However, these findings were primarily mediated by only four chemicals, namely copper sulfate, hydrogen peroxide, peracetic acid, and simazine. None of the bacterial, physical, or plant-based treatments were shown to significantly improve water quality by themselves. Results from this synthesis quantitatively showed that most treatments fail to improve water quality in the field and highlight the need for more research on existing and alternative treatments.


Comparative analysis and chemical profiling of different forms of Peucedani Radix.
Peucedani Radix, derived from roots of Peucedanum praeruptorum Dunn, is a well-known herb used for centuries in traditional Chinese medicine, which is rich in various coumarins. Four different forms including "earthworm head", "bamboo-like", taproots and multi-branched roots have occurred in current producing areas, but the differences in their external features and chemistry have not been concerned till now. In this study, the morphological and microscopic characters of "earthworm head" and "bamboo-like" roots were compared in detail, and qualitative and quantitative characterization of main active coumarins in different forms of Peucedani Radix have been developed by UPCL-Q/TOF-MS and HPLC-DAD, respectively. The results showed that both "earthworm head" and "bamboo-like" consisted of rhizome and root, exhibiting distinct features from normal taproots. Moreover, 53 coumarins including simple coumarins, furanocoumarins and pyranocoumarins were identified or putatively characterized from the four forms samples under the established UPLC-Q/TOF-MS conditions. In addition, the developed quantitative method was successfully applied to simultaneously determine eight main coumarins in 24 batches of four forms Peucedani Radix and 12 batches of dissected "earthworm head" and "bamboo-like" samples. The quantitative results proved that wild "earthworm head" showed higher content of active coumarins and the "bamboo-like" was a rich source of coumarins in cultivated samples, especially for furanocoumarins. These findings would provide reasonable basis for further quality evaluation, grades classification and comprehensive utilization of P. praeruptorum resources.


Engaging the families of substance abusing adolescents in family therapy.
This article discusses three major topics: First, the family processes one typically finds in families with a substance abusing adolescent are described. These processes include pseudo-separation and defensive delineation. A case vignette is used to illustrate these processes. Second, an overview of the importance of family therapy in treating substance abusing adolescents is provided. Third, specific principals and techniques for involving families in family therapy are described. This area includes a discussion of such topics as using the initial telephone contact to join with and involve the family, and suggestions for handling some typical problems which the therapist may encounter in the initial interview. These problems or resistances must be handled sensitively if the family is to remain in treatment. This is an important area since involving the families of substance abusing adolescents in treatment can be quite difficult and there is little practical literature available.


Environmental lead exposure aggravates the progression of Alzheimer's disease in mice by targeting on blood brain barrier.
Alzheimer's disease (AD) is a neurodegenerative disease that can be induced by heavy metals such as lead. However, there is limited information on the role of blood-brain barrier (BBB) in lead induced AD-like pathology. This study investigates the potential mechanism of lead exposure aggravating the progression of Alzheimer's disease in mice through the BBB. 200 mg/L and 500 mg/L lead acetate were given to C57BL/6J and APP/PS1 mice through drinking water from a week before mating, until the offspring were 7-months-old. 8 female juvenile mice in each group were selected for this investigation. Lead exposure increased blood lead concentration which revealed the internal exposure level, accelerated Aβ1-42 deposition in APP/PS1 mouse cortexes and abnormal change in Zonula Occludin-1 (ZO-1) and Claudin-5 protein. It also increased the expression of p-tau in both the C57BL/6J and APP/PS1 mice, and decreased mRNA and protein expression in low-density lipoprotein receptor (LRP-1). Additionally, it increased the mRNA and protein expression of amyloid beta precursor protein (APP) and beta secretase 1 (BACE-1). The activated astrocytes increased in the brains of APP/PS1 mice, and coalesced around the Aβ1-42 deposition after lead exposure. The main vessels in deutocerebrum were attached with Aβ1-42 deposition. These results offer insight into the mechanism of preventing lead induced AD through cerebrovascular pathways.


Differences between men and women in substance use: the role of educational level and employment status.
To determine differences between men and women in hazardous drinking, heavy cannabis use and hypnosedative use according to educational level and employment status in the economically active population in Spain. Cross-sectional study with data from 2013 Spanish Household Survey on Alcohol and Drugs on individuals aged 25-64 [n=14,113 (women=6,171; men=7,942)]. Dependent variables were hazardous drinking, heavy cannabis use and hypnosedative consumption; the main independent variables were educational level and employment situation. Associations between dependent and independent variables were calculated with Poisson regression models with robust variance. All analyses were stratified by sex. Hazardous drinking and heavy cannabis use were higher in men, while women consumed more hypnosedatives. The lower the educational level, the greater the gender differences in the prevalence of this substances owing to different consumption patterns in men and women. While men with a lower educational level were higher hazardous drinkers [RII=2.57 (95%CI: 1.75-3.78)] and heavy cannabis users [RII=3.03 (95%CI: 1.88-4.89)] compared to higher educational level, in women the prevalence was the same. Women with a lower education level and men with a higher education level had higher hypnosedative consumption. Unemployment was associated with increased heavy cannabis use and hypnosedative use in both women and men and with lower hazardous drinking only in women. There are differences between men and women in the use of psychoactive substances that can be explained by the unequal distribution of substance use in them according to educational level. Unemployment was associated with substance use in both men and women.


Synthesis and reaction of 4'-hydroperoxynucleosides. A model for oxidative degradation of DNA by action of bleomycins.
The reaction of 1-(3-O-benzoyl-2,5-dideoxy-beta-D-glycero-pent-4-enofuranosyl)t hym ine (1a) with anhydrous hydrogen peroxide in the presence of a catalytic amount of trifluoroacetic acid leads to the formation of 3'-O-benzoyl-5'-deoxy-4'-hydroperoxythymidines (2a) and (3a). It has been demonstrated that the hydroperoxide 2a is capable of undergoing a Criegee-type rearrangement to lead ultimately to thyminylpropenal, whereas the reduction of 2a gives free thymine exclusively.


A prospective trial of analgesia following endoscopic totally extraperitoneal (TEP) inguinal hernioplasty.
The extraperitoneal instillation of bupivacaine has been shown to be superior to the use of a placebo for postoperative analgesia following endoscopic extraperitoneal inguinal hernioplasty. The objective of the present study was to compare the efficacy of postoperative analgesia by local wound infiltration to instillation of the extraperitoneal space with bupivacaine. Between 1 September 1999 and 2 June 2000, a total of 100 patients who underwent unilateral endoscopic extraperitoneal inguinal hernioplasties were recruited to receive either local wound infiltration with 10 ml of 0.5% bupivacaine (group I, n = 50) or instillation of the extraperitoneal space with 40 ml of 0.25% bupivacaine after mesh placement (group II, n = 50). Daily postoperative pain was assessed by visual analogue pain score on a scale from 0 to 10 at rest and upon coughing. Total amount of oral analgesic consumed and clinical outcomes of the two groups were compared. A comparison of daily pain scores of the two groups at rest and upon coughing showed no significant difference (p = ns). The mean number of oral analgesic tablets consumed were 3.2 +/- 0.5 (SEM) and 3.3 +/- 0.5 (SEM) in groups I and II, respectively (p = ns). During follow-up, asympatomatic groin collections were more common in group II (n = 4) than group I (n = 2) (p = ns). Compared to local wound infiltration with bupivacaine, the extraperitoneal instillation of bupivacaine did not bestow any additional analgesic benefits. Therefore, the routine infiltration of skin incisions with bupivacaine is recommended after endoscopic extraperitoneal inguinal hernioplasty.


BAG-1 interacts with the p50-p50 homodimeric NF-κB complex: implications for colorectal carcinogenesis.
Understanding the mechanisms that promote aberrant tumour cell survival is critical for the determination of novel strategies to combat colorectal cancer (CRC). We have recently shown that the anti-apoptotic protein BAG-1, highly expressed in pre-malignant and CRC tissue, can potentiate cell survival through regulating NF-κB transcriptional activity. In this study, we identify a novel complex between BAG-1 and the p50-p50 NF-κB homodimers, implicating BAG-1 as a co-regulator of an atypical NF-κB pathway. Importantly, the BAG-1-p50 complex was detected at gene regulatory sequences including the epidermal growth factor receptor (EGFR) and COX-2 (PTGS2) genes. Suppression of BAG-1 expression using small interfering RNA was shown to increase EGFR and suppress COX-2 expression in CRC cells. Furthermore, mouse embryonic fibroblasts derived from the NF-κB1 (p105/p50) knock-out mouse were used to demonstrate that p50 expression was required for BAG-1 to suppress EGFR expression. This was shown to be functionally relevant as attenuation of BAG-1 expression increased ligand activated phosphorylation of EGFR in CRC cells. In summary, this paper identifies a novel role for BAG-1 in modulating gene expression through interaction with the p50-p50 NF-κB complexes. Data presented led us to propose that BAG-1 can act as a selective regulator of p50-p50 NF-κB responsive genes in colorectal tumour cells, potentially important for the promotion of cell survival in the context of the fluctuating tumour microenvironment. As BAG-1 expression is increased in the developing adenoma through to metastatic lesions, understanding the function of the BAG-1-p50 NF-κB complexes may aid in identifying strategies for both the prevention and treatment of CRC.


Monitoring the presence of trypanosomes' DNA - Including Trypanosoma brucei gambiense DNA - From the midguts of riverine Glossina trapped in the south east outskirts of Kinshasa City (Democratic Republic of Congo).
Even if the number of Human African Trypanosomiasis (HAT) cases from Kinshasa province in DRC is going towards elimination for the last decade, cases still occur in the periphery of the city. The diagnosis of 21 cases in the south periphery of Kinshasa, between 2015 and 2017 gives evidence of the existence of an active focus in this area. Here, we present the results of a punctual entomological survey that was realized in july 2014 in the outskirts of the southeast of Kinshasa. Using pyramidal traps, we caught tsetse flies during 2 days, dissecting the fresh ones for further molecular analysis. The average Apparent Density of flies per Trap and per Day was three with a maximum of 5.6 flies in Nganda PIO. Polymerase chain reaction analysis of the midguts provided evidence of a high prevalence (57.2%) of infected flies. Ninety three percent of the trypanosomes that were identified belonged to the Nanomonas species, but Trypanozoon trypanosomes were also present in 24% of the infected flies, including mixed infections with Nanomonas, including 3 flies carrying Trypanosoma brucei gambiense, the human pathogen of trypanosomiasis. These results show that at the time of the field's study there was an active reservoir of trypanosomes, closed to pigsties, knowing that pig is a potential animal reservoir. It also demonstrates that xenomonitoring using the entomological approach can be an efficient tool for monitoring sleeping sickness. Finally, results are discussed in the frame of WHO's HAT elimination project. Regarding Kinshasa, it points out the need of regular epidemiologic surveys.


Sulfurospirillum oryzae sp. nov., A Novel Nitrogen-Fixing Bacterium Isolated from Paddy Soil.
An anaerobic, Gram-staining-negative, rod shaped, nitrogen-fixing strain designed SG202T, was isolated from paddy soil collected from Fujian Province in China. Strain SG202T showed the highest 16S rRNA gene sequence similarity with the type strain Sulfurospirillum multivorans DSM 12446T (98.5%). Phylogenetic trees based on 16S rRNA gene sequences and conserved core genes from genomes indicated that strain SG202T branched with members of the genus Sulfurospirillum. Growth was observed at 25-37 °C (optimum 30 °C), pH 6.0-10.5 (optimum 7.5), and 0-0.6% (w/v) NaCl (optimum 0.2%). Strain SG202T contained MK-6 as the menaquinone and C16:1ω7c (40.6%), C16:0 (33.3%), C18:1ω7c (13.6%) and C14:0 (9.0%) as the major fatty acids. The genomic DNA G+C content was 39.0%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain SG202T and its closely related species S. multivorans DSM 12446T, Sulfurospirillum halorespirans DSM 13726T, Sulfurospirillum arsenophilum DSM 10659T and Sulfurospirillum diekertiae ACSDCET were 81.3, 81.5, 84.4, 82.2% and 24.5, 24.5, 27.9, 25.2%, respectively. All these values were lower than the recommended species delineation thresholds of ANI (95-96%) and dDDH (70%). Strain SG202T possessed core genes (nifHDK) of nitrogen fixation, and nitrogenase activities (3470.45 μmol C2H4 g-1 protein h-1) was examined using the acetylene reduction assay. Based on the observed physiological properties, chemotaxonomic characteristics and genome analysis, strain SG202T is recognized as a novel species of the genus Sulfurospirillum, for which the name Sulfurospirillum oryzae sp. nov. is proposed. The type strain is SG202T (= GDMCC 1.3379T= JCM 35596T).


Ion interactions in (1-13C)D-Val8 and D-Leu14 analogs of gramicidin A, the helix sense of the channel and location of ion binding sites.
Ion-induced chemical shifts in the carbonyl carbon resonances of synthesized ad verified (1-13C)D-Val8 gramicidin A and (1-13C)D-Leu14 gramicidin A are utilized in combination with the previously determined location of the ion binding sites of the gramicidin A channel (using the carbonyls of L-residues) to determine that the helix sense of the gramicidin A channel) is left-handed. Having resolved the handedness issue, the location of the ion binding sites (which are fundamental to understanding the mechanism of ion transport) are further delineated with the results indicating two sites separated by just over 20 A. Furthermore, the demonstration that the divalent barium ion interacts at the binding site while not being transported through the channel is used to argue that the mechanism of monovalent vs. divalent cation selectivity is due to the positive image force contribution to the central barrier.


Degradation of tetracycline by UV/Fe3+/persulfate process: Kinetics, mechanism, DBPs yield, toxicity evaluation and bacterial community analysis.
As a widely produced and used antibiotic, tetracycline (TC) has been frequently found in rivers, soil and drinking water. In this study, the degradation of TC was investigated by UV/Fe3+/persulfate (PS) coupled process. The degradation behavior was well fitted with pseudo-first-order model. Hydroxyl radicals (·OH), sulfate radicals (SO4-·) and superoxide radical (O2-·) were identified as the primary reactive oxygen species (ROS) in UV/Fe3+/PS process, the contribution to TC degradation were found to be 41.94%, 33.94% and 17.44% at pH 3.0, respectively. Fe(IV) generated from the system also played a crucial role in TC removal. The effects of process parameters (PS/Fe3+ dosages, pH, humic acid, Cl-, HCO3-, NO3- and CO32-) on degradation were investigated. It was found that the degradation of TC was highly pH-dependent, and the optimal performance was obtained at pH 3.0. Except for Cl-, the presence of HA, HCO3-, NO3- and CO32- inhibited TC degradation. The possible transformation pathway involving the hydroxylation, N-demethylation, hydrogenation and dehydroxylation was proposed. Furthermore, the toxicity and mutagenicity of TC and transformation products (TPs) were estimated using ECOSAR and TEST softwares, demonstrating that the toxicity level of most TPs was lower/equal to their precursors. The evaluation of DBPs showed that UV/Fe3+/PS process could reduce the potential of DBPs formation, especially for TCAA and TCM. Microbial community composition was analyzed by 16 S rDNA sequencing, and the relative abundance of ARG-carrying opportunistic pathogens was significantly declined after UV/Fe3+/PS treatment. In general, this study provides an economical, efficient and safe strategy for TC removal.


Chimeric viruses between Rocio and West Nile: the role for Rocio prM-E proteins in virulence and inhibition of interferon-α/β signaling.
Mosquito-transmitted flavivirus Rocio (ROCV) was responsible for an outbreak of encephalitis in the Ribeira Valley, located in the south coast of Sao Paulo State, Brazil, in 1975-1976. ROCV also causes fatal encephalitis in adult mice. Seroprevalence studies in humans, horses and water buffaloes in different regions of Brazil have suggested that ROCV is still circulating in the country, indicating the risk of re-emergence of this virus. West Nile virus (WNV) is also a mosquito-transmitted encephalitic flavivirus, however, WNV strains circulating in Australia have not been associated with outbreaks of disease in humans and exhibit low virulence in adult mice. To identify viral determinants of ROCV virulence, we have generated reciprocal chimeric viruses between ROCV and the Australian strain of WNV by swapping structural prM and E genes. Chimeric WNV containing ROCV prM-E genes replicated more efficiently than WNV or chimeric ROCV containing WNV prM-E genes in mammalian cells, was as virulent as ROCV in adult mice, and inhibited type I IFN signaling as efficiently as ROCV. The results show that ROCV prM and E proteins are major virulence determinants and identify unexpected function of these proteins in inhibition of type I interferon response.


Establishment of MELD-lactate clearance scoring system in predicting death risk of critically ill cirrhotic patients.
To develop a scoring system related to the lactate clearance (ΔLA) to predict the mortality risk (MELD-ΔLA) for critically ill cirrhotic patients. In this retrospective cohort study, 881 critically ill cirrhotic patients from the Medical Information Mart for Intensive Care (MIMIC-III) database were included eventually. The outcomes of our study were defined as ICU death, 28-day, 90-day and 1-year mortality. Predictors were identified by multivariate Cox analysis to develop the predictive scoring system. The C-index and area under the curve (AUC) of receiver operator characteristic curve (ROC) were used to identify the predicting performance of the MELD-ΔLA, sequential organ failure assessment (SOFA), chronic liver failure-sequential organ failure assessment (CLIF-SOFA), the model for end-stage liver disease (MELD), Child-Pugh, chronic liver failure consortium acute-on-chronic liver failure (CLIF-C ACLF), chronic liver failure consortium-acute decompensation (CLIF-C AD) and MELD-Na scoring systems. Additionally, subgroup analysis was also performed based on whether critically ill cirrhotic patients underwent liver transplantation. Creatinine, bilirubin, international normalized ratio (INR), lactate first, ΔLA and vasopressors were closely associated with ICU death of liver critically ill cirrhotic patients. The C-index of the MELD-ΔLA in ICU death was 0.768 (95% CI 0.736-0.799) and the AUC for the MELD-ΔLA scoring system in predicting 28-day, 90-day, and 1-year mortality were 0.774 (95% CI 0.743-0.804), 0.765 (95% CI 0.735-0.796), and 0.757 (95% CI 0.726-0.788), suggested that MELD-ΔLA scoring system has a good predictive value than SOFA, CLIF-SOFA, MELD, Child-Pugh, CLIF-C ACLF, CLIF-C AD) and MELD-Na scoring systems. Additionally, the study also confirmed the good predictive value of MELD-ΔLA scoring system for critically ill cirrhotic patients regardless of undergoing liver transplantation. The developed MELD-ΔLA score is a simple scoring system in predicting the risk of ICU death, 28-day, 90-day and 1-year mortality for critically ill cirrhotic patients, which may have a good predictive performance.


Longitudinal Study of Type I Interlay Tympanoplasty.
The aim of the present study was to access success rate of tympanoplasty and complications with interlay technique of tympanoplasty. This Longitudinal Prospective study was carried out in the Department of Otorhinolaryngology and Head and Neck Surgery, Era's Lucknow Medical College, Lucknow. 50 patients aged between 10 and 50 years of chronic otitis media mucosal type disease with dry ears were selected. Otomicroscopic, tunning fork test, pure tone audiometry were done in all patients. All patients underwent interlay tympanoplasty. Patients were followed up regularly for a minimum period of 1.5 years. Successful graft uptake was noted in 48 (96%) cases. Interlay tympanoplasty results in excellent graft uptake and good post operative Air Bone Gap closure.


Behavioral medicine in Russian family medicine.
The Russian Federation's recently adopted family medicine as a specialty, but with little or no training in psychosocial and behavioral issues, unlike many training programs in other countries. The purpose of this qualitative study was to explore the perceptions and experiences of Russian primary care physicians regarding the practice of behavioral medicine and psychosocial methods. Semi-structured in-depth interviews were conducted with ten Russian family physicians. Examination of key words, phrases, and concepts used by the physicians revealed five themes that physicians related to their incorporation of psychosocial/behavioral medicine methods: (1) factors limiting the practice of behavioral medicine (inadequate training; cultural barriers); (2) demand for behavioral medicine services; (3) patient-doctor issues related to behavioral medicine (e.g., communication); (4) physician's role strain; and (5) intuition and experience. These findings suggest that Russia's new family physicians would benefit from residency and post-graduate curricula in behavioral sciences, tailored to their unique needs.


Progress in Expression Pattern and Molecular Regulation Mechanism of LncRNA in Bovine Mastitis.
Bovine mastitis is an inflammatory disease caused by pathogenic microbial infection, trauma, or other factors. Its morbidity is high, and it is difficult to cure, causing great harm to the health of cows and the safety of dairy products. Susceptibility or resistance to mastitis in individual cows is mainly determined by genetic factors, including coding genes and non-coding genes. Long non-coding RNAs (lncRNAs) are a class of endogenous non-coding RNA molecules with a length of more than 200 nucleotides (nt) that have recently been discovered. They can regulate the immune response of humans and animals on three levels (transcription, epigenetic modification, and post-transcription), and are widely involved in the pathological process of inflammatory diseases. Over the past few years, extensive findings revealed basic roles of lncRNAs in inflammation, especially bovine mastitis. This paper reviews the expression pattern and mechanism of long non-coding RNA (lncRNA) in inflammatory diseases, emphasizes on the latest research progress of the lncRNA expression pattern and molecular regulatory mechanism in bovine mastitis, analyzes the molecular regulatory network of differentially expressed lncRNAs, and looks forward to the research and application prospect of lncRNA in bovine mastitis, laying a foundation for molecular breeding and the biological therapy of bovine mastitis.


Pre-symptomatic Caspase-1 inhibitor delays cognitive decline in a mouse model of Alzheimer disease and aging.
Early therapeutic interventions are essential to prevent Alzheimer Disease (AD). The association of several inflammation-related genetic markers with AD and the early activation of pro-inflammatory pathways in AD suggest inflammation as a plausible therapeutic target. Inflammatory Caspase-1 has a significant impact on AD-like pathophysiology and Caspase-1 inhibitor, VX-765, reverses cognitive deficits in AD mouse models. Here, a one-month pre-symptomatic treatment of Swedish/Indiana mutant amyloid precursor protein (APPSw/Ind) J20 and wild-type mice with VX-765 delays both APPSw/Ind- and age-induced episodic and spatial memory deficits. VX-765 delays inflammation without considerably affecting soluble and aggregated amyloid beta peptide (Aβ) levels. Episodic memory scores correlate negatively with microglial activation. These results suggest that Caspase-1-mediated inflammation occurs early in the disease and raise hope that VX-765, a previously Food and Drug Administration-approved drug for human CNS clinical trials, may be a useful drug to prevent the onset of cognitive deficits and brain inflammation in AD.


City planning as preventive medicine.
The health and well-being of rapidly growing urban populations is a global health issue. Cities in the global north and south are faced with rising health inequities - or avoidable differences in health determinants and outcomes based on place, social status and ethnicity. This commentary suggests that focusing only on treatment interventions in cities is likely to fail because populations will be forced to go back into the urban living and working conditions that likely made them sick in the first place. City planning as preventive medicine includes taking a relational and systems approach to urban health, requiring health assessments for all urban policy making, promoting neighborhood health centers as engines of community economic development and gathering place-based health indicator data to track progress and adapt interventions over time as conditions change.


Association of clinical signs with endoscopic findings in horses with nasopharyngeal cicatrix syndrome: 118 cases (2003-2008).
To characterize the associations between clinical signs of nasopharyngeal cicatrix syndrome (NCS) and endoscopic findings in horses. Retrospective, case-control study. 239 horses (118 case horses and 121 control horses). Medical records of horses that had an endoscopic evaluation of the upper airway performed between January 2003 and December 2008 were reviewed. Clinical signs and the appearance and anatomic locations of lesions identified during endoscopic evaluation were reviewed and recorded for each horse. The associations between clinical signs and endoscopic findings were evaluated by the use of a prospective logistic model that used a Bayesian method for inference and was implemented by a Markov chain Monte Carlo method. Nasal discharge was associated with acute inflammation of the pharynx and larynx. Exercise intolerance was associated with circumferential pharyngeal lesions. Respiratory noise was associated with chronic scarring of the pharynx, a combination of pharyngeal and laryngeal scarring, and circumferential scarring of the pharynx. Respiratory distress was associated with acute inflammation of all portions of the airway, especially when there was preexisting scarring and narrowing of the airway by ≥ 50%. Cough did not have any significant association with NCS, compared with results in control horses. Associations between the endoscopic appearance of NCS lesions and relevant clinical signs will help practitioners identify horses with NCS and allow them to select appropriate treatment.


Impact of Preoperative Weight Loss on Postoperative Weight Loss Revealed from a Large Nationwide Quality Registry.
Weight loss before bariatric surgery is not mandatory, but questions remain as to whether preoperative weight loss has an impact on weight loss after surgery. Most studies have small sample sizes. The objective was to evaluate the relationship between preoperative and successful postoperative weight loss defined as ≥25% total weight loss (TWL) at 1 and 2 years after primary bariatric surgery with regard to the obesity-related comorbidities. Data were extracted from a large nationwide quality registry of patients who underwent a sleeve gastrectomy (SG) or gastric bypass (GBP) between January 2015 and January 2018. Patients with completed screening and preoperative and postoperative data were included. A multivariate logistic regression analysis was performed for each technique and follow-up years separately. In total, 8751 were included in the analysis. Patients with preoperative weight loss were more likely to achieve ≥25% postoperative TWL in both procedures. Patients with higher preoperative weight loss of 5-10% had an increased likelihood for achieving 25% TWL compared to 0-5%, OR 1.79 (CI (1.42-2.25), p < 0.001) vs 1.25 (CI (1.08-1.46), p < 0.004) for the GBP group for year 2 postoperative. This was the same for the SG group at year 2, OR 1.30 (CI (1.03-1.64), p < 0.029) vs 1.14 (CI (0.94-1.38), p < 0.198). Patients with preoperative weight loss were more likely to achieve ≥25% postoperative TWL at 1 and 2 years after surgery in both procedures; moreover, the extent of preoperative weight loss contributes to the significance and odds of this success.


Prospective applications of two-dimensional materials beyond laboratory frontiers: A review.
The development of nanotechnology has been advancing for decades and gained acceleration in the 21st century. Two-dimensional (2D) materials are widely available, giving them a wide range of material platforms for technological study and the advancement of atomic-level applications. The design and application of 2D materials are discussed in this review. In order to evaluate the performance of 2D materials, which might lead to greater applications benefiting the electrical and electronics sectors as well as society, the future paradigm of 2D materials needs to be visualized. The development of 2D hybrid materials with better characteristics that will help industry and society at large is anticipated to result from intensive research in 2D materials. This enhanced evaluation might open new opportunities for the synthesis of 2D materials and the creation of devices that are more effective than traditional ones in various sectors of application.