Characterization of primary dental pulp cells in vitro.
This study's purpose was to characterize dental pulp cells from human primary teeth and determine their ability to induce differentiation of oral epithelial cells. Dental pulp cells were isolated from freshly extracted primary incisors, digested with 4 mg/ml collogenase/dispase, and grown in Dulbecco's modified Eagle's medium with 10 percent fetal bovine serum. Stem cell populations were identified by immunocytochemical staining for STRO-1 and CD146 and fluorescence activated cell sorting. To determine whether primary pulp cells can signal epithelium, the pulp cells were grown in coculture with human fetal oral epithelial cells. After 3 days, the cocultured cells were collected and analyzed for amelogenin expression by polymerAse chain reaction (PCR) and immunocytochemical staining. Immunofluorescence and fluorescence activated cell sorting of STRO-1+ cells showed this stem cell population to be approximately 2 percent of the total population. Growth-arrested primary dental pulp cells grown in coculture with oral epithelial cells showed expression of Amelogenin by immunocytochemistry and PCR. Oral epithelial cells alone were amelogenin immunonegative. Primary tooth dental pulp cells contain less than 2 percent stem cells. Cells within the primary tooth pulp can promote epithelial cell differentiation toward an ameloblast phenotype, suggesting the potential use of this heterogeneous population of cells in cell-mediated enamel tissue engineering.


Comparison of patients' views and dentists' evaluations 5 years after complete denture treatment.
This study describes a comparison of patients' views of their dentures and dentists' technical evaluations 5 yr after complete denture treatment. Of the original sample (n = 139) a test group of 92 patients remained available for the actual study 5 yr after treatment. Firstly, the patients filled in a questionnaire regarding their complaints of and (dis)satisfaction with dentures. Secondly, they were examined independently by two experienced dentists in order to evaluate their dentures. Finally, after considering the answers to the questions in the questionnaire and their own dentures' evaluation the dentists proposed a therapy. It was found that patients and dentists agree on assessments of denture retention, but do not agree on assessment of denture aesthetical aspects. Furthermore, it appeared that generally more therapy was rendered by the dentists than could be expected on the basis of their evaluations and the patients' views.


Analysis of Fatty Acids of Some Hyoscyamus, Datura, and Atropa Species from Azerbaijan.
Datura stramonium L., D. stramonium var. tatula (L.) Torr., Hyoscyamus reticulatus L., H. niger L., and Atropa caucasica Kreyer naturally found in Azerbaijan and their seeds possess 17-35% of oils. This study aims to evaluate and determine fatty acids of these plants special to Azerbaijan climate and geography. The presented study is the first to research into fatty acids of A. caucasica, which is an endemic species of Caucasus. Fatty acid seed oils were derivatized to methyl esters and analyzed by gas chromatography equipped with a flame ionization detector, compared with a standard mixture of 37 fatty acid methyl esters. Linoleic (55-79%), oleic (11-26%), palmitic (4-12%), and stearic (2-3%) acids compose 97% of total fatty acids. Other minor compounds, including two trans-fatty acids, were determined in the samples. Significantly high concentration of a medicinally important polyunsaturated fatty acid, e.g. linoleic acid, was observed in all samples. The results of this study showed that these oils are particularly valuable sources of linoleic and oleic acids, which have beneficial effects on cardiovascular diseases and are important compounds for the pharmaceutical and cosmetic industries in the manufacture of liposomes, nano- and microemulsions, soaps, etc.


Flow cytometric analysis of estrogen, progesterone receptor expression and DNA content in formalin-fixed, paraffin-embedded human breast tumors.
Flow cytometric analysis of estrogen (ER) and progesterone (PgR) receptor expression in archival human breast tumors is relatively difficult. We have used enzyme digestion and microwave antigen retrieval procedures for multiparametric flow cytometric analysis of ER and PgR expression and DNA content in nuclei isolated from formalin-fixed/paraffin-embedded primary breast tumors. Deparaffinized rehydrated tissue sections treated with pepsin were subjected to microwave irradiation for unmasking of ER and PgR antigenic sites. Biotinylated ER antibody and streptavidin-fluorescein isothiocyanate (FITC) were used for ER labeling and PgR antibody with phycoerythrin labeled goat anti-mouse antibody was used for PgR labeling. Counter staining with propidium iodide-RNase was used for determination of cellular DNA content. Our results show that enzyme digestion and microwave treatment of formalin-fixed, paraffin-embedded breast tumors can be successfully used for the multiparametric analysis of nuclear hormone receptor expression and DNA content by flow cytometry.


EEG classification for motor imagery BCI using phase-only features extracted by independent component analysis.
The accurate classification of the electroencephalography (EEG) signals is the most important task towards the development of a reliable motor imagery brain-computer interface (MI-BCI) system. In this study, we utilized a publically available BCI Competition-IV 2008 dataset IIa. This study address to the binary classification problem of the motor imagery EEG data by using a sigmoid activation function-based extreme learning machines (ELM). We proposed a novel method of extracting the features from the EEG signals by first applying the independent component analysis (ICA) on the time series data and transforming the ICA time series data into Fourier domain and then extract the phase information from the Fourier spectrum. This phase information was further used to calculate the maximized cross-correlation connectivity matrix. The upper diagonal of this matrix was then vectorized and it serves as the basic feature for the ELM classification framework. By using the phase-only features we achieved 97.80% (p <; 0.0022) nested cross-validated classification accuracy. In addition, this process is relatively computationally inexpensive. Thus, it can be an excellent candidate for the motor imagery BCI applications.


The data base management system alternative for computing in the human services.
The traditional incremental approach to computerization presents substantial problems as systems develop and grow. The Data Base Management System approach to computerization was developed to overcome the problems resulting from implementing computer applications one at a time. The authors describe the applications approach and the alternative Data Base Management System (DBMS) approach through their developmental history, discuss the technology of DBMS components, and consider the implications of choosing the DBMS alternative. Human service managers need an understanding of the DBMS alternative and its applicability to their agency data processing needs. The basis for a conscious selection of computing alternatives is outlined.


Bradyrhizobium as the Only Rhizobial Inhabitant of Mung Bean (Vigna radiata) Nodules in Tropical Soils: A Strategy Based on Microbiome for Improving Biological Nitrogen Fixation Using Bio-Products.
The mung bean has a great potential under tropical conditions given its high content of grain protein. Additionally, its ability to benefit from biological nitrogen fixation (BNF) through association with native rhizobia inhabiting nodule microbiome provides most of the nitrogen independence on fertilizers. Soil microbial communities which are influenced by biogeographical factors and soil properties, represent a source of rhizobacteria capable of stimulating plant growth. The objective of this study is to support selection of beneficial bacteria that form positive interactions with mung bean plants cultivated in tropical soils, as part of a seed inoculation program for increasing grain yield based on the BNF and other mechanisms. Two mung bean genotypes (Camaleão and Esmeralda) were cultivated in 10 soil samples. Nodule microbiome was characterized by next-generation sequencing using Illumina MiSeq 16S rRNA. More than 99% of nodule sequences showed similarity with Bradyrhizobium genus, the only rhizobial present in nodules in our study. Higher bacterial diversity of soil samples collected in agribusiness areas (MW_MT-I, II or III) was associated with Esmeralda genotype, while an organic agroecosystem soil sample (SE_RJ-V) showed the highest bacterial diversity independent of genotype. Furthermore, OTUs close to Bradyrhizobium elkanii have dominated in all soil samples, except in the sample from the organic agroecosystem, where just B. japonicum was present. Bacterial community of mung bean nodules is mainly influenced by soil pH, K, Ca, and P. Besides a difference on nodule colonization by OTU sequences close to the Pseudomonas genus regarding the two genotypes was detected too. Although representing a small rate, around 0.1% of the total, Pseudomonas OTUs were only retrieved from nodules of Esmeralda genotype, suggesting a different trait regarding specificity between macro- and micro-symbionts. The microbiome analysis will guide the next steps in the development of an inoculant for mung bean aiming to promote plant growth and grain yield, composed either by an efficient Bradyrhizobium strain on its own or co-inoculated with a Pseudomonas strain. Considering the results achieved, the assessment of microbial ecology parameters is a potent coadjuvant capable to accelerate the inoculant development process and to improve the benefits to the crop by soil microorganisms.


Efficacy of an olmesartan medoxomil-based treatment algorithm in patients with hypertension and type 2 diabetes: analysis of diurnal blood pressure control as assessed by 24-hour ambulatory blood pressure monitoring.
Secondary, prespecified analysis of a single-arm, open-label study evaluating the efficacy of olmesartan medoxomil (OM) plus hydrochlorothiazide (HCTZ) in patients with hypertension and type 2 diabetes. After placebo run-in, 192 patients received OM 20 mg/day for 3 weeks. If blood pressure (BP) remained ≥120/70 mmHg, patients were uptitrated every 3 weeks to OM 40 mg/day, OM/HCTZ 40/12.5 mg/day, and OM/HCTZ 40/25 mg/day. Efficacy was evaluated by 24-hour ambulatory BP monitoring. Secondary endpoints included changes in ambulatory systolic BP (SBP) and diastolic BP (DBP) during daytime (08:00 to 16:00) and nighttime (22:00 to 06:00), as well as achievement of prespecified ambulatory BP targets in the total cohort and subgroups based on gender, race, hypertension severity, and age (≥65 or <65 years). Dipper status (nocturnal decrease in BP ≥10% of mean daytime BP) was assessed. At baseline, mean ambulatory BP was 151.2 ± 12.7/87.6 ± 9.0 mmHg during the daytime and 140.3 ± 13.1/78.1 ± 8.6 mmHg during the nighttime. Mean daytime and nighttime ambulatory BP was reduced from baseline by 22.3 ± 13.7/12.0 ± 8.9 mmHg and 18.8 ± 12.4/ 10.2 ± 7.2 mmHg, respectively. The reduction in daytime ambulatory SBP was 24.4 ± 11.8 mmHg in Blacks, 21.7 ± 14.2 mmHg in non-Blacks, 23.6 ± 12.3 mmHg in females, 21.2 ± 14.8 mmHg in males, 23.4 ± 11.6 mmHg in patients aged ≥65 years, and 21.9 ± 14.4 mmHg in those aged <65 years. Ambulatory BP targets of <130/80, <125/75, and <120/80 mmHg were reached by 51.7%, 36.0%, and 32.6% of patients during the daytime and 69.8%, 60.5%, and 50.6% of patients during the nighttime. After 12 weeks of treatment, 36.4% of baseline nondippers converted to dippers. OM ± HCTZ effectively lowered ambulatory BP in patients with type 2 diabetes and hypertension, enabling them to achieve ambulatory BP targets during both the daytime and nighttime.


Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease.
This paper describes the identification and optimization of a novel series of DFG-out binding p38 inhibitors as inhaled agents for the treatment of chronic obstructive pulmonary disease. Structure based drug design and "inhalation by design" principles have been applied to the optimization of the lead series exemplied by compound 1a. Analogues have been designed to be potent and selective for p38, with an emphasis on slow enzyme dissociation kinetics to deliver prolonged lung p38 inhibition. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimize systemic exposure and reduce systemically driven adverse events. High CYP mediated clearance and glucuronidation were targeted to achieve high intrinsic clearance coupled with multiple routes of clearance to minimize drug-drug interactions. Furthermore, pharmaceutical properties such as stability, crystallinity, and solubility were considered to ensure compatibility with a dry powder inhaler. 1ab (PF-03715455) was subsequently identified as a clinical candidate from this series with efficacy and safety profiles confirming its potential as an inhaled agent for the treatment of COPD.


The role of surface free energy on the formation of hybrid bilayer membranes.
The interaction of small phospholipid vesicles with well-characterized surfaces has been studied to assess the effect of the surface free energy of the underlying monolayer on the formation of phospholipid/alkanethiol hybrid bilayer membranes (HBMs). The surface free energy was changed in a systematic manner using single-component alkanethiol monolayers and monolayers of binary mixtures of thiols. The binary surfaces were prepared on gold by self-assembly from binary solutions of the thiols HS-(CH(2))(n)()-X (n = 11, X = CH(3) or OH) in THF. Surface plasmon resonance (SPR), electrical capacitance, and atomic force microscopy (AFM) measurements were used to characterize the interaction of palmitoyl,oleoyl-phosphatidylcholine (POPC) vesicles with the surfaces. For all surfaces examined, it appears that the polar part of surface energy influences the nature of the POPC assembly that associates with the surface. Comparison of optical, capacitance, and AFM data suggests that vesicles can remain intact or partially intact even at surfaces with a contact angle with water of close to 100 degrees. In addition, comparison of the alkanethiols of different chain lengths and the fluorinated compound HS-(CH(2))(2)-(CF(2))(8)-CF(3) that characterize with a low value of the polar part of the surface energy suggests that the quality of the underlying monolayer in terms of number of defects has a significant influence on the packing density of the resulting HBM layer.


Treatment of pharyngeal gonorrhea due to beta-lactamase-producing gonococci.
Between March 1978 and October 1980 seven patients with beta-lactamase-producing gonococci in the pharynx were treated wit spectinomycin of cefuroxime or both. One-day treatment with spectinomycin was effective in only one of six patients and with cefuroxime in only one of four patients. Prolonged treatment with cefuroxime was successful in all five cases so treated.


[Assessment of prognostic factors in common ovarian tumors of varying malignancy].
The outcome and prognosis of apparently similar cases of epithelial ovarian cancers with the same histology and stage is highly variable. The objective was to compare survival and prognostic factors of patients treated at the 1st Department of Obstetrics and Gynecology of Semmelweis University between 1993-2003 with the similar data of the 25th Annual Report on the Results of Treatment in Gynecological Cancer of FIGO. In addition, the aim was to assess the prognostic value of MMP activities and fibronectin concentration in ovarian tumour patients. The 25th Annual Report of FIGO included 5694 patients with ovarian tumours from 32 countries diagnosed and treated between 1995 and 1998. Hungary did not participate in this report. Between 1993 and 2003, 180 patients with common epithelial ovarian tumours had been treated at the 1st Department of Obstetrics and Gynecology of Semmelweis University. Treatment and survival data derived from medical record review and from the Population Register Office. In order to compare different prognostic factors, a multivariate Cox proportional regression analysis was performed. The authors measured MMP activities in 33 surgically removed ovarian tumours, serum and ascites by applying zymographic technique. Fibronectin content was determined by Western blot analysis and quantitated by densitometry. The 5-year survival was 90.0% and 30.9% in the case of ovarian tumours with low malignant potential and of epithelial ovarian cancers, respectively. Multivariate analysis identified adverse prognostic factors including advanced age (>60 years) and stage, high grade and suboptimal operation with residual macroscopic disease and the presence of ascites. However, the histological type was not identified to be an adverse prognostic factor in this study. No correlation could be seen between the histology of the ovarian tumours and the elevation of MMP-2/9 activity. More interestingly, however, MMP-9 expression and fibronectin concentration were significantly elevated and the activated forms of both MMP-9 and MMP-2 were more frequent in ovarian cancer patients who developed recurrent disease. A great deal of effort should be devoted to identification of further prognostic factors to improve treatment of ovarian cancer. These prognostic factors might help to identify those ovarian cancer patients at the time of diagnosis whose disease will have unfavourable outcome. Our data support the notion that high expression of MMP-9 and fibronectin indicates poor prognosis of ovarian cancer patients.


Anisotropy, itineracy, and magnetic frustration in high-Tc iron pnictides.
Using first-principles density functional theory calculations combined with insight from a tight-binding representation, dynamical mean field theory, and linear response theory, we have extensively investigated the electronic structures and magnetic interactions of nine ferropnictides representing three different structural classes. The calculated magnetic interactions are found to be short range, and the nearest (J_{1a}) and next-nearest (J2) exchange constants follow the universal trend of J_{1a}/2J_{2} approximately 1, despite their itinerant origin and extreme sensitivity to the z position of As. These results bear on the discussion of itineracy versus magnetic frustration as the key factor in stabilizing the superconducting ground state. The calculated spin-wave dispersions show strong magnetic anisotropy in the Fe plane, in contrast with cuprates.


[Mannatide enhances the efficacy of fractionated and unfractionated radiotherapy in mice bearing Lewis lung cancer].
To investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer. C57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments. MI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05). MI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.


Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development.
Bortezomib-induced peripheral neuropathy (BiPN) occurs in approximately 40% of patients with multiple myeloma. The induction of severe neuropathy entails the dose reduction or complete elimination of bortezomib (BTZ). Interestingly, discontinuation of BTZ mostly results in a reduction or complete resolution of peripheral neuropathy (PN) symptoms. Therefore, it is likely that the BiPN mechanisms are based on temporary/reversible changes such as epigenetic alterations. In this study, we examined the effect of treating nerve cells, differentiated from the Lund human mesencephalic (dLUHMES) cell line, with several low-dose BTZ (0.15 nM) applications. We showed a significant decrease in global histone H3 acetylation as well as histone H3 lysine 9 acetylation. Moreover, analysis of the genetic microarray showed changes mainly in epigenetic processes related to chromatin rearrangement, chromatin silencing, and gene silencing. GSEA analysis revealed three interesting signaling pathways (SIRT1, B-WICH and, b-Catenin) that may play a pivotal role in PN development. We also performed an analysis of the miRNA microarray which showed the interactions of miR-6810-5p with the genes MSN, FOXM1, TSPAN9, and SLC1A5, which are directly involved in neuroprotective processes, neuronal differentiation, and signal transduction. The study confirmed the existence of BTZ-induced complex epigenetic alterations in nerve cells. However, further studies are necessary to assess the reversibility of epigenetic changes and their potential impact on the induction/resolution of PN.


Exquisite selectivity for human toll-like receptor 8 in substituted furo[2,3-c]quinolines.
Toll-like receptor (TLR)-8 agonists activate adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds may be promising candidate adjuvants. We synthesized and evaluated hitherto unexplored furo[2,3-c]quinolines and regioisomeric furo[3,2-c]quinolines derived via a tandem, one-pot Sonogashira coupling and intramolecular 5-endo-dig cyclization strategy in a panel of primary screens. We observed a pure TLR8-agonistic activity profile in select furo[2,3-c]quinolines, with maximal potency conferred by a C2-butyl group (EC50 = 1.6 μM); shorter, longer, or substituted homologues as well as compounds bearing C1 substitutions were inactive, which was rationalized by docking studies using the recently described crystal structure of human TLR8. The best-in-class compound displayed prominent proinflammatory cytokine induction (including interleukin-12 and interleukin-18), but was bereft of interferon-α inducing properties, confirming its high selectivity for human TLR8.


Phototriggered fluorescence color changes in azobenzene-functionalized conjugated polymers.
We report fluorescence studies of phototriggered changes in spectral position and shape for two azobenzene-functionalized poly(p-phenylenevinylene) derivatives, poly(2-methoxy-5-(4-phenylazophenyl-4'-(1,10-dioxydecyl))-1,4-phenylenevinylene) (MPA-10-PPV) and poly(2-hexyloxy-5-(4-phenylazophenyl-4'-(1,10-dioxydecyl))-1,4-phenylenevinylene) (HPA-10-PPV). Upon trans --> cis azobenzene photoisomerization, small (ca. 1 nm) blue shifts in spectral position are observed for MPA-10-PPV in 100% toluene, a good solvent for this polymer. These shifts are reversed upon visible irradiation and can be cycled many times. To probe the dependence of these shifts on initial polymer conformation, a dichloromethane-methanol cosolvent study was performed in which the solvent quality was decreased incrementally to induce a reduction in polymer coil dimensions. Unirradiated dichloromethane solutions of both MPA-10-PPV and HPA-10-PPV showed a red shift and reduction in quantum yield with increasing methanol concentration as expected based on literature results for other poly(p-phenylenevinylene) derivatives. These changes have been attributed to a dramatic conformational collapse by others and occur for these azo polymers over the 30-60% (v/v) methanol range. While little or no light-induced spectral shifting was observed at low (<or=20%) and high (>or=70%) methanol concentrations, significant spectral shifts were observed for both polymers upon azobenzene photoisomerization in solutions with 30-60% methanol, the same range over which the polymer undergoes collapse to a highly coiled state. The largest shifts are visible to the eye, with a 65:35 (v/v) dichloromethane-methanol solution of HPA-10-PPV showing yellow-orange fluorescence when the azobenzenes are trans, green fluorescence when they are cis, and yellow-orange again after the azobenzenes are returned to the trans state. We attribute these color changes to a reversible UV-phototriggered expansion of polymer coil dimensions that occurs as a result of trans --> cis azobenzene side chain isomerization and provide temperature data to support this conclusion.


A Multi-Attribute Decision-Making Model for the Selection of Polymer-Based Biomaterial for Orthopedic Industrial Applications.
The potential of quantifying the variations in IR active bands was explored while using the chemometric analysis of FTIR spectra for selecting orthopedic biomaterial of industrial scale i.e., ultra-high molecular weight PE (UHMWPE). The nano composites UHMWPE with multi-walled carbon nano-tubes (MWCNTs) and Mg-silicate were prepared and irradiated with 25 kGy and 50 kGy of gamma dose. Principal component analysis (PCA) revealed that first three principal components (PCs) are responsible for explaining the >99% of variance in FTIR data of UHMWPE on addition of fillers and/or irradiation. The factor loadings plots revealed that PC-1 was responsible for explaining the variance in polyethylene characteristics bands and the IR active region induced by fillers i.e., 440 cm−1, 456 cm−1, from 900−1200 cm−1, 1210 cm−1, 1596 cm−1, PC-2 was responsible for explaining the variance in spectra due to radiation-induced oxidation and cross linking, while the PC-3 is responsible for explaining the variance induced because of IR active bands of MWCNTs. Hierarchy cluster analysis (HCA) was employed to classify the samples into four clusters with respect to similarity in their IR active bands which is further confirmed by PCA. According to multi attribute analysis with PCA and HCA, 65 kGy irradiated sample is optimum choice from the existing alternatives in the group of irradiated pristine UHMWPE, UHMWPE/Mg-silicate irradiated with 25 kGy of gamma dose was the optimum choice for UHWMPE/Mg-silicate nano composites, and UHMWPE/γMWCNTs composites containing 1.0% dof γ MWCNTs for UHMWPE/MWCNTs nanocomposites, respectively. The results show the effectiveness of quantifying the variance for decision as far as optimization of biomaterials in orthopedic industrial applications is concerned.


Identification of a specific assembly of the g protein golf as a critical and regulated module of dopamine and adenosine-activated cAMP pathways in the striatum.
In the principal neurons of striatum (medium spiny neurons, MSNs), cAMP pathway is primarily activated through the stimulation of dopamine D1 and adenosine A(2A) receptors, these receptors being mainly expressed in striatonigral and striatopallidal MSNs, respectively. Since cAMP signaling pathway could be altered in various physiological and pathological circumstances, including drug addiction and Parkinson's disease, it is of crucial importance to identify the molecular components involved in the activation of this pathway. In MSNs, cAMP pathway activation is not dependent on the classical Gs GTP-binding protein but requires a specific G protein subunit heterotrimer containing Gαolf/β2/γ7 in particular association with adenylyl cyclase type 5. This assembly forms an authentic functional signaling unit since loss of one of its members leads to defects of cAMP pathway activation in response to D1 or A(2A) receptor stimulation, inducing dramatic impairments of behavioral responses dependent on these receptors. Interestingly, D1 receptor (D1R)-dependent cAMP signaling is modulated by the neuronal levels of Gαolf, indicating that Gαolf represents the rate-limiting step in this signaling cascade and could constitute a critical element for regulation of D1R responses. In both Parkinsonian patients and several animal models of Parkinson's disease, the lesion of dopamine neurons produces a prolonged elevation of Gαolf levels. This observation gives an explanation for the cAMP pathway hypersensitivity to D1R stimulation, occurring despite an unaltered D1R density. In conclusion, alterations in the highly specialized assembly of Gαolf/β2/γ7 subunits can happen in pathological conditions, such as Parkinson's disease, and it could have important functional consequences in relation to changes in D1R signaling in the striatum.


A "Multi-Heavy-Atom" Approach toward Biphotonic Photosensitizers with Improved Singlet-Oxygen Generation Properties.
Two trispicolinate 1,4,7-triazacyclonane (TACN)-based ligands bearing three picolinate biphotonic antennae were synthetized and their Yb3+ and Gd3+ complexes isolated. One series differs from the other by the absence (L1 )/presence (L2 ) of bromine atoms on the antenna backbone, offering respectively improved optical and singlet-oxygen generation properties. Photophysical properties of the ligands, complexes and micellar Pluronic suspensions were investigated. Complexes exhibit high two-photon absorption cross-section combined either with NIR emission (Yb) or excellent 1 O2 generation (Gd). The very large intersystem crossing efficiency induced by the combination of bromine atom and heavy rare-earth element was corroborated with theoretical calculations. The 1 O2 generation properties of L2 Gd micellar suspension under two-photon activation leads to tumour cell death, suggesting the potential of such structures for theranostic applications.


Psychosocial adjustment and marital intimacy among partners of patients with breast cancer: a comparison study with partners of healthy women.
This cross-sectional study investigated the psychosocial adjustment of 70 partners of patients with breast cancer by comparing their emotional adjustment and quality of life (QoL) with 70 partners of women without cancer. The role of marital intimacy in their adjustment and the moderating effect of group type were analyzed. The partners of patients with breast cancer presented higher levels of anxious and depressive symptomatology; poor social, psychological, general and physical QoL; and higher levels of intimacy. The moderation analysis showed that higher levels of intimacy predicted lower levels of depression and anxiety and greater QoL only among the partners of cancer patients.


[Apropos of 2 cases of severe malaria contracted in the port of Marseille].
Acute Plasmodium falciparum malaria occurred during summer 1993 in two inhabitants living close to Marseille harbour. History of blood transfusion and travel outside France were excluded as was also discarded airport malaria. Entomological investigations confirmed the absence of Anopheles breeding sites in the port area. An hypothesis is a vectorial transmission following introduction of one or several anopheles arrived on a ship coming from tropical Africa. During this season, the weather conditions were favourable to the survival of anopheles and the completion of P. falciparum sporogonic cycle. Physicians were advised to take into consideration malaria in the differential diagnosis of fever from unknown origin in any patient working or living inside or around the harbour area regardless history of previous travel in malaria endemic region.


Solvent-free, microwave-assisted synthesis of thiophene oligomers via Suzuki coupling.
The purpose of this study was to obtain a rapid, efficient, and environmentally friendly methodology for the synthesis of highly pure thiophene oligomers. The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, allowed us to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the targeted product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Thus, for example, quaterthiophene was obtained in 6 min by reaction of 2-bromo-2,2'-bithiophene with bis(pinacolato)diboron (isolated yield 65%), whereas quinquethiophene was obtained in 11 min by reaction of dibromoterthiophene with thienylboronic acid (isolated yield 74%). The synthesis of new chiral 2,2'-bithiophenes is reported. The detailed analysis of the byproducts of some reactions allowed us to elucidate a few aspects of reaction mechanisms. While the use of microwaves proved to be very convenient for the coupling between conventional thienyl moieties, the same was not true for the coupling of thienyl rings to thienyl-S,S-dioxide moieties. Indeed, in this case, the targeted product was obtained in low yields because of the competitive, accelerated, Diels-Alder reaction that affords a variety of condensation products.


Survival of Escherichia coli in Food at Hot-Holding Temperatures.
Foods usually served hot were held at various hot-holding temperatures [40°C (104°F) - 60°C (140°F] and were contaminated with fecal Escherichia coli . The contaminated hot foods were held for 1 h at each of the hot-holding temperatures during which the survival of the pathogen in each food type was evaluated. Results showed that E. coli survived hot-holding temperatures in each food type for the whole period of evaluation. A population increase occurred with time at temperatures below 50°C (122°F), while at and above this temperature there was a decrease in population with increasing time in each food type. A two-way analysis of variance using relative rates of increase or decrease (± b) showed food type to be unimportant for survival of the bacteria. A three-way analysis of variance of the same results using mean log CFU/g food showed holding temperature, food type, holding time, and the interactions of temperature and food type; and temperature and time to be significantly important for survival of the bacteria. The public health significance of these findings are discussed.


Adrenal phaeochromocytoma and neurofibromatosis presenting with hypotension.
We report a case of adrenal phaeochromocytoma with the stigmata of neurofibromatosis, who presented with acute hypotension. The patient later had episodes of hypertension alternating with hypotension, associated with electrocardiographic changes simulating myocardial infarction, and finally a completed stroke. The circumstances illustrate the problem of early recognition of the protean clinical effects of an excess of circulating adrenal medullary hormones. They also emphasise the need to consider phaeochromocytoma as a differential diagnosis of apparent clinical shock.


Contrasting Storage Protein Synthesis and Messenger RNA Accumulation during Development of Zygotic and Somatic Embryos of Alfalfa (Medicago sativa L.).
During development on hormone-free media, somatic embryos pass through distinct morphological stages that superficially resemble those of zygotic embryo development (globular, heart, torpedo, cotyledonary stages). Despite these similarities, they differ from zygotic embryos in the extent of cotyledonary development and the patterns of synthesis and quantitative expression of seed-specific storage proteins (7S, 11S, and 2S proteins). Alfin (7S) is the first storage protein synthesized in developing zygotic embryos (stage IV). The 11S (medicagin) and 2S (Low Molecular Weight, LMW) storage proteins are not detectable until the following stage of development (stage V), although all three are present before the completion of embryo enlargement. Likewise, the 7S storage protein is the first to be synthesized in developing somatic embryos (day 5). Medicagin is evident by day 7 and the LMW protein by day 10. In contrast to zygotic embryos, alfin remains the predominant storage protein in somatic embryos throughout development. Not only are the relative amounts of medicagin and the LMW protein reduced in somatic embryos but the LMW protein is accumulated much later than the other proteins. Quantification of the storage protein mRNAs (7S, 11S, and 2S) by northern blot analysis confirms that there are substantial differences in the patterns of message accumulation in zygotic and somatic embryos of alfalfa (Medicago sativa). In zygotic embryos, the 7S, 11S, and 2S storage protein mRNAs are abundant during maturation and, in particular, during the stages of maximum protein synthesis (alfin, stages VI and VII; medicagin, stage VII; LMW, stage VII). In somatic embryos, the predominance of the 7S storage protein is correlated with increased accumulation of its mRNA, whereas the limited synthesis of the 11S storage protein is associated with much lower steady-state levels of its message. The mRNA for the LMW protein is present already by 3 days after transfer to hormone-free media, yet that protein is not evident on stained gels until day 10. Thus, both transcriptional and posttranscriptional events appear to be important in determining the protein complement of these seed tissues. On the basis of storage protein and mRNA accumulation, mature (14 days) somatic embryos most closely resemble stage VI zygotic embryos. The results of the developmental comparison also suggest that the patterns of synthesis of the individual storage proteins (7S, 11S, or 2S) are regulated independently of each other during embryogenesis in alfalfa.


Intraocular pressure in exfoliation syndrome.
Two studies, both retrospective, were done at our institution. The first study evaluated 100 consecutive patients with exfoliation (EX) syndrome found as an incidental finding in a private, general ophthalmology practice, to determine the incidence of glaucoma. The second determined the long-term course of EX as it relates to the onset of elevated intraocular pressure (IOP). In the first study, of 124 eyes having EX 78% had normal IOP, 15% had intraocular pressure greater than 22 mm Hg but no cupping or field loss (ocular hypertension or glaucoma suspect), and 7% had glaucoma. In the second study 347 patients who initially had normal IOPs and either unilateral or bilateral EX were followed over time. Elevated IOP developed in 35 patients (44 eyes) during the study. The cumulative probability for eyes with EX to develop elevated intraocular pressure was 5.3% in 5 years and increased to 15.4% in 10 years. These probabilities predict that patients with EX have a higher incidence of developing elevated intraocular pressure than would be expected in patients without EX of similar age.


Decreased width of the spinal canal in patients with chronic symptoms after whiplash injury.
The sagittal diameter of the cervical spinal canal was measured on standard lateral radiographs of 48 consecutive patients with acute whiplash injury. A follow-up was done 12 months after injury. The purpose of this study was to evaluate the relationship between spinal canal width and chronic symptoms after whiplash injury. A narrow sagittal diameter of the cervical spinal canal has been correlated with neurologic deficits in degenerative conditions and after fractures. The authors are not aware of previous studies on whiplash patients related to this area. Forty-eight consecutive patients were evaluated for whiplash trauma after car accidents. Twenty-four patients (12 men and 12 women; mean age, 37 years) had persistent symptoms after 12 months, while 24 patients (12 men and 12 women; mean age, 34 years) were asymptomatic. All measurements were done from standard lateral radiographs with a graphic digitizer connected to a microcomputer. Three anteroposterior and one oblique measurement of the canal were reconstructed for each vertebrae from C2-C6. Multivariate analysis of variance was used to evaluate any association between gender, remaining symptoms at follow-up, and the recorded values of the spinal canal width. The spinal canal was significantly smaller in the patients with persistent symptoms than in the asymptomatic group. A significant difference also was found between men and women. Narrow diameter of the cervical spinal canal is unfavorable in patients with whiplash.


Peptides and peptidomimetics in the p53/MDM2/MDM4 circuitry - a patent review.
Restoration of the p53 tumor suppressor function is an attractive anticancer strategy. Despite the development of several therapeutics targeting the two main p53 negative regulators, MDM2 and MDM4, no one has yet reached clinical application. In the past, several efforts have been employed to develop more specific and efficient compounds that can improve and/or overcome some of the features related to small molecule compounds (SMC). Peptides and peptidomimetics are emerging as attractive molecules given their increased selectivity, reduced toxicity and reduced tendency to develop tumor-resistance compared to SMC. Area covered: This article reviews publications and patents (publicly available up to April 2016) for peptides and derivatives aimed to reactivate the oncosuppressive function of p53, with a particular focus on inhibitors of MDM2/MDM4. Emphasis is placed on the efficacy of these compounds compared to the p53-reactivating small molecules developed so far. Expert opinion: A number of promising peptides for p53 reactivation in cancer therapy have been developed. These compounds appear to possess improved features compared to SMC, especially for their ability to simultaneously target the MDM2/MDM4 inhibitors, and their increased specificity.


Health-related quality of life assessed by Gout Impact Scale (GIS) in Chinese patients with gout.
The Gout Impact Scale (GIS) is a disease-specific health-related quality of life (HR-QoL) measurement for patients with gout. This study aimed to investigate the quality of life in Chinese patients with gout and potential risk factors for poorer HR-QoL by GIS. Adults with gout from February 2017 to February 2019 were invited to complete a questionnaire containing the GIS, social demographic characteristics, clinical information and gout-specific questions. Pearson/Spearman correlation and linear regression were used to analyze the data. A total of 413 patients were included in the analysis (mean age, 51.85 years; 96.4% male). The mean (SD) score of GIS total was 56.79 ± 15.45. Worse gout-specific HR-QoL was associated with anxiety (p < .05), depression (p < .05) and fatigue (p < .05). The effectiveness and global satisfaction of Treatment Satisfaction Questionnaire for Medication (TSQM) were negatively related to each dimension of GIS. Age (B = -0.251, p = .013), fatigue (B = 1.850, p < .001) and depression (B = 9.068, p = .042) were independent predictors of GIS total score. Gout-specific HR-QoL is impaired by social demographic and clinical characteristics, highlighting the importance of psychological factors (fatigue and depression) and patient-reported outcomes (patients' satisfaction and confidence in gout treatment). These findings suggest that more studies should focus on disease-specific HR-QoL.


High flow insufflation for the maintenance of the pneumoperitoneum during bariatric surgery.
Minimally invasive bariatric procedures next to becoming more and more popular have established a new field of applications for carbon dioxide (CO2) insufflators. In laparoscopic bariatric procedures, gas is used to insufflate the peritoneal cavity and increase the intra-abdominal pressure up to 15 mm Hg for optimal exposure and a suitable operating field. The increased intra-abdominal pressure during pneumoperitoneum can reduce femoral venous flow, intra-operative urine output, portal venous flow, respiratory compliance,and cardiac output. However, clinical complications related to these effects are rare. Yet, surgeons should be constantly aware that the duration of an operation is an important factor in reducing the patient's exposure to CO2 pneumoperitoneum and its adverse effects. The optimized performance of the bariatric high flow insufflator allows reaching stable abdominal pressure conditions quicker and at a higher level than a common insufflator. Therefore, high flow insufflators offer great advantages in maintaining intra-abdominal pressure and temperature in comparison to conventional insufflators and thus enhance laparoscopic bariatric surgery by potentially reducing the operating time and the undesirable effects of CO2 pneumoperitoneum.


[The French character of the pioneers of the Saint Lawrence valley].
The origin of migrants to the Saint Lawrence valley in Canada prior to 1765 is explored. The author presents data concerning the sex and language distribution of the migrant population. "Immigrants who settled in the Saint Lawrence valley before 1765 were [primarily of] French origin. Many came from provinces where, at least in the rural areas, French was still not the dominant language. Pioneer families who arrived before 1680 had a relatively large linguistic homogeneity. Close to 40% originated from large or medium sized cities, and this proportion is close to 50% in the case of women." (SUMMARY IN ENG AND SPA)


Mutational analysis of inherited epilepsies.
Single-gene mutations in mice initiate specific heritable neuronal diseases featuring different patterns of epilepsy. Thirteen chromosomal loci for convulsive seizures and four loci for spike-wave seizures have been assigned. Within this genetic framework, a few general principles are emerging. Mutations located on different chromosomes may result in identical seizure patterns. Interactions between specific genes, demonstrated by the synthesis of compound heterozygotes, can express intermediate syndromes. Interactions with unknown genes in the background can mask neurological disease expression. Analysis of the cellular phenotypes of epileptic mutants is a direct strategy to define naturally occurring defects in central synaptic pathways involved in cortical synchronization. In one allele of the tottering locus, a pathogenetic lesion linking noradrenergic hyperinnervation with cortical spike-wave discharges has been identified. The tottering gene initiates an overgrowth within all target innervation areas of axon terminals originating from the locus coeruleus (LC). Selective neonatal denervation of the excess noradrenergic axons permanently prevents the subsequent appearance of cortical spike-wave seizures in the adult animal. Partial lesions of central noradrenergic afferent fibers in adults temporarily reverse the seizure disorder. Other criteria defining the relationship between the mutant gene and the electrophysiologic traits and the role of central noradrenergic pathways in neuronal synchronization are reviewed. Isolating and tracing the developmental expression of epileptic mutations permits a formal classification of gene-linked excitability defects, a derivation of basic rules governing their inheritance, and the design of strategies to correct the gene error. By allowing phenotypic comparisons with over 60 known human inherited neurological diseases associated with seizures, these models may directly contribute to advances in the clinical management of epileptic gene expression.


Use of media and public-domain Internet sources for detection and assessment of plant health threats.
Event-based biosurveillance is a recognized approach to early warning and situational awareness of emerging health threats. In this study, we build upon previous human and animal health work to develop a new approach to plant pest and pathogen surveillance. We show that monitoring public domain electronic media for indications and warning of epidemics and associated social disruption can provide information about the emergence and progression of plant pest infestation or disease outbreak. The approach is illustrated using a case study, which describes a plant pest and pathogen epidemic in China and Vietnam from February 2006 to December 2007, and the role of ducks in contributing to zoonotic virus spread in birds and humans. This approach could be used as a complementary method to traditional plant pest and pathogen surveillance to aid global and national plant protection officials and political leaders in early detection and timely response to significant biological threats to plant health, economic vitality, and social stability. This study documents the inter-relatedness of health in human, animal, and plant populations and emphasizes the importance of plant health surveillance.


Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation.
In this study, we present evidence for the critical role of proteinase-3 (PR3) in the proliferation of myeloid cells via the proteolytic regulation of the cyclin-dependent kinase inhibitor p21(waf1). Expression of recombinant PR3 in rat (RBL) or human (HMC1) mast cell lines increased bromodeoxyuridine incorporation and CDK2 activity compared with RBL and HMC1 cells transfected with an enzymatically inactive PR3 mutant (PR3(S203A)) or with human neutrophil elastase. Western blot analysis of p21(waf1) showed an absence of detectable protein, despite normal levels of p21 mRNA. Ectopic overexpression of p21 restored normal levels of p21 in the RBL/PR3/p21 double transfectants and reverted the proliferative effect of PR3. Inhibition of the 26 S proteasome by lactacystin or of caspases by benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone did not inhibit p21 proteolysis. p21 cleavage correlated with PR3 expression in HMC1 cells infected with recombinant adenoviral vector Ad/PR3. During in vitro studies, purified p21 was cleaved by PR3, resulting in a 10-kDa p21 fragment. Employing double immunofluorescence confocal microscopy, subcellular fractionation, and co-immunoprecipitation, we found that PR3 and p21 colocalized in the cytosol. In human neutrophils treated with tumor necrosis factor-alpha, which induces PR3 re-expression, we observed that p21 disappeared and was reversed by Pefabloc, a serine proteinase inhibitor. The physiopathological implications of the cleavage of p21 by PR3 have to be determined.


Magnetic resonance angiography of thromboembolic stroke in rats: indicator of recanalization probability and tissue survival after recombinant tissue plasminogen activator treatment.
Magnetic resonance angiography (MRA) was performed in a thromboembolic stroke model of the rat to characterize intracranial vessel occlusion patterns and to test its predictive power for tissue recovery after recombinant tissue plasminogen activator (rt-PA) treatment. After rt-PA-treated selective middle cerebral artery (MCA) occlusion, full recanalization was observed in two of three animals, whereas additional occlusion of the circle of Willis (CW) resulted in full vascular flow restitution in only one of six rats. Tissue reperfusion markedly lagged the onset of treatment, and the delay correlated with the pattern of vessel occlusion (20 to 23 minutes for selective MCA occlusion vs. 71 to 79 minutes for combined MCA/CW occlusion). In lateral cortex and striatum the apparent diffusion coefficient decreased to 78 +/- 15% of control after embolization, recovered to 80% to 85% after rt-PA treatment of selective MCA occlusion, but further declined to 66% to 69% after combined MCA/CW occlusion. Correspondingly, T2 relaxation time increased to 107% to 118% of control after selective MCA occlusion and to 112% to 124% after combined MCA/CW occlusion in these regions. The present investigation shows that MRA provides valuable information on the severity of thromboembolic stroke and has the power to predict, before the initiation of treatment, the functional tissue outcome after rt-PA-induced thrombolysis.


Alcohol and Relatively Pure Cannabis Use, but Not Schizotypy, are Associated with Cognitive Attenuations.
Elevated schizotypy relates to similar cognitive attenuations as seen in psychosis and cannabis/polydrug use. Also, in schizotypal populations cannabis and polydrug (including licit drug) use are enhanced. These cognitive attenuations may therefore either be a behavioral marker of psychotic (-like) symptoms or the consequence of enhanced drug use in schizotypal populations. To elucidate this, we investigated the link between cognitive attenuation and cannabis use in largely pure cannabis users (35) and non-using controls (48), accounting for the potential additional influence of both schizotypy and licit drug use (alcohol, nicotine). Cognitive attenuations commonly seen in psychosis were associated with cannabis and alcohol use, but not schizotypy. Future studies should therefore consider (i) non-excessive licit substance use (e.g., alcohol) in studies investigating the effect of cannabis use on cognition and (ii) both enhanced illicit and licit substance use in studies investigating cognition in schizotypal populations.


Salivary microbiome profiles for different clinical phenotypes of pituitary adenomas by single-molecular long-read sequencing.
The gut and salivary microbiomes have been widely reported to be significantly associated with a number of neurological disorders. The stability of the microbiome in the oral cavity makes it a potentially ideal sample that can be conveniently obtained for the investigation of microbiome-based pathogenesis in diseases. In the present study, we used a single-molecule long-read sequencing technique to study the distribution of the salivary microbiota in patients with pituitary adenoma (PA) and healthy individuals, as well as among four clinical phenotypes of PA. We found that the diversity of salivary microbes was more abundant in PA patients than in healthy individuals. We also observed some unique genera in different PA phenotypes. The bioinformatics-based functional predictions identified potential links between microbes and different clinical phenotypes of PA. This study improves the existing understanding of the pathogenesis of PA and may provide diagnostic and therapeutic targets for PA.


A Review on the Development of Earthquake Warning System Using Low-Cost Sensors in Taiwan.
Seismic instrumentation for earthquake early warnings (EEWs) has improved significantly in the last few years, considering the station coverage, data quality, and the related applications. The official EEW system in Taiwan is operated by the Central Weather Bureau (CWB) and is responsible for issuing the regional warning for moderate-to-large earthquakes occurring in and around Taiwan. The low-cost micro-electro-mechanical system (MEMS)-based P-Alert EEW system is operational in Taiwan for on-site warnings and for producing shakemaps. Since 2010, this P-Alert system, installed by the National Taiwan University (NTU), has shown its importance during various earthquakes that caused damage in Taiwan. Although the system is capable of acting as a regional as well as an on-site warning system, it is particularly useful for on-site warning. Using real-time seismic signals, each P-Alert system can provide a 2-8 s-long warning time for the locations situated in the blind zone of the CWB regional warning system. The shakemaps plotted using this instrumentation help to assess the damage pattern and rupture directivity, a key feature in the risk mitigation process. These shakemaps are delivered to the intended users, including the disaster mitigation authorities, for possible relief purposes. Earlier, the network provided only peak ground acceleration (PGA) shakemaps, but has now been updated to include peak ground velocity (PGV), spectral acceleration (Sa) at different periods, and CWB intensity maps. The PGA and PGV shakemaps plotted using this network have proven helpful in establishing the fact that PGV is a better indicator of damage detection than PGA. This instrumentation is also useful in structural health-monitoring and estimating co-seismic deformations. Encouraged by the performance of the P-Alert network, more instruments are installed in Asia-Pacific countries.


An Introduction and Illustration of Bayesian Modeling in Couple and Family Therapy Research.
Bayesian modeling is becoming increasing popular as a method for data analyses in the social sciences and can move couple, marriage, and family therapy (C/MFT) research forward. Bayesian modeling helps researchers better understand the uncertainty of findings and incorporate previous research into analyses. Other benefits of Bayesian modeling are the straightforward interpretation of findings, high-quality inferences even with small samples (in combination with an informative prior), and the ability to work with complex data structures (observations nested in relationships and time points) which are common in C/MFT research. This article introduces the benefits of Bayesian modeling and provides an example of an Actor-Partner Interdependence Model using R. Information on how to conduct the same analyses using Stata and MPlus is provided in the Supplemental Information.


The feasibility of implementing an English language version of GLA:D Back.
Evidenced-based clinical guidelines for the treatment of low back pain (LBP) consistently suggest educating patients about their back pain, its natural course, and providing advice to keep active and continue working. Despite this evidence, clinicians routinely do not follow these recommendations resulting in ineffective and fragmented care. GLA:D® Back, a standardized care package, was originally developed in Denmark to assist clinicians in implementing evidence-based care. This study will evaluate the feasibility of implementing the English version of the Danish GLA:D® Back program in Alberta, Canada. Thirty-five clinicians from nineteen clinics in Alberta, Canada, participated. Feasibility of program implementation, our primary objective, was evaluated within 3 months. Feasibility success was defined as 50% clinician/clinic adoption in addition to 66-88 enrolled participants registered in the database. Our secondary objectives included collecting data pertaining to clinician confidence, attitudes and behaviour of treating patients, perceived barriers and facilitators of program in addition to collecting patient-data regarding pain, function, general health and self-efficacy. The majority of the clinics (15/19, 79%) offered GLA:D® Back to their patients within the study period. Of the participating clinicians, GLA:D® Back was delivered by (25/35, 71%) of clinicians. In total, 78 patients were enrolled in the program and (69/78, 88%) participants attended the final assessment. Secondarily, clinicians demonstrated a biomedical and behavioural orientation along with high confidence when treating LBP patients while patient outcomes trended toward improvement. The English translation of the Danish GLA:D Back program was feasible for Albertan clinicians to implement into practice in both urban and rural settings.


Hydrothermal Ore Deposits in the Western United States: A NewConcept of Structural Control of Distribution.
Empirical plotting of four sets of equidistantly spaced shear stress trajectories, based on regularities in distribution of actual faults and ore veins in the continental area and on the landward prolongation of the big fracture zones of the northeastern Pacific, givesrise to a prospecting net for the western United States. Preferential accumulation of big ore deposits (including such deposits as Bingham and Tintic) along landward prolongation of the main fracture zones of northeastern Pacific, in the vicinity of intersections of four systems of trajectories, and along boundaries of crustal blocks suggests several possibilities for prospecting for unknown hydrothermal deposits in the Cordilleran part of the United States.


German consumer evaluations of milk in blind and nonblind tests.
Greater differentiation is being made between types of milk according to product and process characteristics. This study investigated consumer preferences for 4 different types of milk in packaging-blind and nonblind experiments. The taste of long-life milk, conventional fresh whole milk, pasture-based milk, and organic milk was assessed by 138 randomly selected respondents. The average taste of packaging-blind versus nonblind milk types was statistically significantly different for each of the 4 milk types. Consumers appeared to be influenced by the milk's packaging and related credence-good attributes. It is noteworthy that the taste of organic milk during the blind tasting was given a lower rating, and the taste of long-life milk or UHT milk a higher rating, than when respondents were aware of the respective milk types. The study estimated multilevel mixed-effects logistic regression models with the response variable buying decision. Of all the factors studied in the blind and nonblind tasting of almost all milk types, buying decisions were influenced most by taste, overall assessment and income.


Inherent optical properties of Jerlov water types.
The diffuse attenuation coefficient Kd(λ) was first expressed in terms of the inherent optical properties (IOPs) of water according to well-established empirical bio-optical models. Boltzmann simulated annealing was then used to find the best sets of IOPs to fit Kd(λ) spectra to the reference spectra Kd0(λ) that define the Jerlov water types. Absorption a(λ) and scattering b(λ) coefficients were thus obtained for all Jerlov water types over the wavelength range 300-700 nm. The chlorophyll concentrations corresponding to the Jerlov water types were also obtained via bio-optical models. The result is a self-consistent set of spectral IOPs, chlorophyll concentrations, and Jerlov water types useful for a variety of underwater optical communications and remote sensing applications.


Psychostimulant effects on neuropsychological, intellectual, and achievement measures for children and adolescents with Attention Deficit Hyperactivity Disorder.
This study compared the performance of medicated (n=57) and non-medicated (n=20) subjects with Attention Deficit Hyperactivity Disorder (ADHD) on neuropsychological, intellectual, and achievement measures. The Wechsler Intelligence Scale for Children (Revised or 3rd Edition), appropriate Halstead Reitan Neuropsychological Test Battery, and individual achievement tests were administered to subjects between the ages of 9 and 16 years (M=12.8) Initially, 26 subtest scores were analyzed using multivariate profile analysis. The two groups were found to be parallel (i e, similar in pattern of performance) and coincident (i.e., similar in level of performance). This suggests that the subjects in the two groups displayed a similar pattern of performance on these neuropsychological, intellectual, and achievement measures. The results are discussed in relation to previous research, current etiological models, and the assessment and treatment of ADHD.


Efficient Bioproduction of Human Milk Alpha-Lactalbumin in Komagataella phaffii.
Alpha-lactalbumin (α-LA; the most abundant whey protein in human milk) contributes to infant development, providing bioactive peptides and essential amino acids. Here, Komagataella phaffii (K. phaffii) was selected as the production host. We found that the K. phaffii host X33 was suitable for expressing the target protein, yielding 5.2 mg·L-1 α-LA. Thereafter, several secretory signal peptides were applied to obtain a higher titer of α-LA. The strain with α-factor secretory signal peptide secreted the highest extracellular titer. Additionally, promoters AOX1, GAP, and GAP(m) were compared and applied. The strain with the promoter AOX1 produced the highest extracellular titer. In addition, coexpressing human protein disulfide isomerase A3 (hPDIA3) increased the titer by 27%. Human α-LA production by the strain X33-pPICZαA-hLALBA-hPDIA3 reached 56.3 mg·L-1 in a 3 L bioreactor. This is the first report of successful secretory human α-LA expression in K. phaffii and lays foundations for the simulation of human milk for infant formulas and further development of bioengineered milk.


Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.
Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is associated with reduced lung compliance and hypoxemia. Curcumin exhibits potent anti-inflammatory properties but has poor solubility and rapid plasma clearance. To overcome these physiochemical limitations and uncover the full therapeutic potential of curcumin in lung inflammation, in this study we utilized a novel water-soluble curcumin formulation (CDC) and delivered it directly into the lungs of C57BL/6 mice inoculated with a lethal dose of Klebsiella pneumoniae (KP). Administration of CDC led to a significant reduction in mortality, in bacterial presence within blood and lungs, as well as in lung injury, inflammation, and oxidative stress. The expression of Klebsiella hemolysin gene; TNF-α; IFN-β; nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; hypoxia-inducible factor 1/2α; and NF-κB were also decreased following CDC treatment, suggesting modulation of the inflammasome complex and hypoxia signaling pathways as an underlying mechanism by which CDC reduces the severity of pneumonia. On a cellular level, CDC led to diminished cell death, improved viability, and protection of human lung epithelial cells in vitro. Overall, our studies demonstrate that CDC administration improves cell survival and reduces injury, inflammation, and mortality in a murine model of lethal gram-negative pneumonia. CDC, therefore, has promising anti-inflammatory potential in pneumonia and likely other inflammatory lung diseases, demonstrating the importance of optimizing the physicochemical properties of active natural products to optimize their clinical application.-Zhang, B., Swamy, S., Balijepalli, S., Panicker, S., Mooliyil, J., Sherman, M. A., Parkkinen, J., Raghavendran, K., Suresh, M. V. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.


Popliteal artery branching patterns detected by digital subtraction angiography.
To describe the popliteal and distal branching patterns detected by digital subtraction angiography. The popliteal branching patterns were analyzed in 535 extremities (270 right, 265 left). Of these, 226 limbs were evaluated bilaterally, while 83 were evaluated unilaterally. The branching patterns were classified according to the level of branching and the presence of hypoplasia or aplasia of the distal branches. Four hundred and seventy-two (88.1%) limbs had a normal level of popliteal artery branching. Type IA was the most frequently encountered pattern. High division of the popliteal artery was seen in 30 (5.6%) limbs. Type IIA was the most frequently encountered pattern among these limbs. Type IIC was not seen. We encountered a new pattern characterized by high division of the peroneal artery with a trifurcation pattern and an anterior tibial artery with a proximal medial course and a distal lateral course. We called this pattern Type IID. Thirty-three (6.1%) limbs exhibited hypoplasia/aplasia of the distal branches. Type IIIA was the most frequently encountered pattern among these limbs. Variations that occur in nearly 10% of patients should be understood because they may affect the choice of management strategy.


Social support and the course of bipolar disorder.
The current study prospectively examined the impact of social support on symptom severity and recovery from episodes in bipolar disorder, both as a direct influence and as a buffer of life events. Fifty-nine individuals with Bipolar I disorder were followed longitudinally with monthly symptom severity interviews. Social support was measured by the Interpersonal Support Evaluation List and the Interview Schedule for Social Interaction, and life events were assessed using the Life Events and Difficulties Schedule. Individuals with low social support took longer to recover from episodes and were more symptomatic across a 6-month follow-up. Results suggest a polarity-specific effect, in that social support influences depression but not mania. Discussion focuses on theoretical implications of a series of polarity-specific findings within the field.


Cervical cancer screening programme attendance and compliance predictors regarding Colombia's Amazon region.
Cervical cancer (CC) promotion and prevention (P&P) programmes' challenge lies in guaranteeing that follow-up strategies have a real impact on reducing CC-related mortality rates. CC P&P programme compliance and coverage rates are relevant indicators for evaluating their success and good performance; however, such indicators' frequency rates are considerably lower among women living in rural and border areas. This study was aimed at identifying factors associated with CC screening programme attendance for women living in Colombia's Amazon region. This study (qualitative and quantitative phases) was carried out between September 2015 and November 2016; women residing in the border towns of Leticia and Puerto Nariño participated in it. The first phase (qualitative) involved interviews and focus group discussions; this led to establishing factors related to CC P&P programme attendance which were used in the quantitative phase for designing a survey for determining the strength of association in a logistic regression model. The terms attendance and compliance were considered to apply to women who had followed the 1-1-3 scheme throughout their lives, i.e. a cytology examination every 3 years after receiving two consecutive negative annual cytology results. Inclusion criteria were met by 309 women (≥18-year-olds having an active sexual life, having resided in the target community for at least one year); 15.2% had suitable P&P programme follow-up. Screening programme attendance was positively associated with first intercourse after becoming 20 years-old (aOR: 3.87; 1.03-9.50 95%CI; p = 0.045), frequent contraceptive use (aOR: 3.11; 1.16-8.33 95%CI; p = 0.023), awareness of the age to participate in P&P programmes (aOR: 2.69; 1.08-6.68 95%CI; p = 0.032), awareness of cytology's usefulness in identifying cervical abnormalities (aOR: 2.43; 1.02-5.77 95%CI; p = 0.043) and considering cytology important (aOR: 2.64; 1.12-6.19 95%CI; p = 0.025). Women living in rural areas had a lower probability (aOR 0.43: 0.24-0.79 95%CI; p = 0.006) of adhering to CC P&P programmes. This study's findings suggested the need for including novel strategies in screening programmes which will promote CC P&P activities going beyond hospital outpatient attendance to reach the most remote or widely scattered communities, having the same guarantees regarding access, opportunity and quality. Including education-related activities and stimulating the population's awareness regarding knowledge about CC prevention could be one of the main tools for furthering the impact of attendance at and compliance with P&P programmes.


[Research advances on assisted analgesic and sedative treatment of burn children].
Burn children would experience pain and anxiety during treatment and rehabilitation, thus analgesic and sedative treatment should be applied throughout the whole process of burn treatment. Due to the unique physiological and psychological status of burn children, analgesic and sedative treatment for burn children is a relatively complex process compared with that for adult burn patients. Therefore, how to provide the effective and safe analgesic and sedative treatment for burn children is a clinical challenge. This paper reviewed the related progress of assisted analgesic and sedative treatment of burn children, in order to provide a reference for clinical treatment.


Role of balloon enteroscopy for obscure gastrointestinal bleeding in those with surgically altered anatomy: A systematic review.
Obscure gastrointestinal (GI) bleeding is defined as persistent bleeding despite negative evaluation with both esophagogastroduodenoscopy and colonoscopy and can be secondary to small intestinal pathology. Standard endoscopy as well as push endoscopy can be a challenge in those with altered anatomy given inaccessible areas as well as perforation risk. Single and double balloon enteroscopy can be warranted in this patient population in instances of obscure GI bleed. To assess the safety and diagnostic efficacy of balloon enteroscopy for obscure GI bleeding in patients with surgically altered anatomy. A search was conducted through PubMed, MEDLINE, Google Scholar, Scopus, and Embase with the key words "enteroscopy," "obscure bleeding," and "altered anatomy," to identify relevant articles in English with no restricted time frame. A search within the Reference Citation Analysis database was conducted to ensure inclusion of the latest high impact articles. Study types included in the review were prospective and retrospective reviews, case series, and case reports. The reference lists of these papers were also reviewed to find further papers that were applicable. The authors extracted the data from the studies that fit inclusion criteria. Data of interest included type of study, type of procedure, and type of altered anatomy, as well as the number of patients with any diagnostic or therapeutic intervention. Data was also recorded on procedure tolerance and complications. The data was analyzed with descriptive statistics. Our literature search yielded 14 studies that were included. There were 68 procedures performed with 61 unique patients subjected to these procedures. Forty-four (65%) of the procedures were double balloon, 21 (31%) were single balloon, and 3 (4%) were classified as through the scope balloon assisted. The most common altered anatomy types included Gastric Bypass Roux-en-Y, Pylorus Sparing Whipple, Orthotopic Liver Transplantation with Roux-en-Y, and Gastrojejunostomy Roux-en-Y. The procedures were successfully performed in each patient. There were 5 (7%) procedures that were complicated by perforation. Amongst the available data, the diagnostic yield was 48/59 (81%) and a therapeutic yield of 39/59 (66%). One patient was recommended surgical revision of their altered anatomy following enteroscopy. Balloon enteroscopy is a useful diagnostic modality in investigating obscure GI bleeding within those with surgically altered anatomy; however, precautions must be taken as this population may have increased perforation risk.


A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet.
Epstein-Barr virus (EBV) is a herpes virus known to cause infectious mononucleosis and several other human disorders. Ocular EBV infections that have been reported include uveitis, retinal vasculitis, and acute retinal necrosis (ARN). ARN is usually caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV). ARN that is caused by EBV (EBV-ARN) is rarely seen, and only a few cases have been reported. The visual prognosis for EBV-ARN is poor, and no treatment strategy has been established. We report on a patient who was treated successfully for EBV-ARN. An 80-year-old female who had been treated with prednisolone at 5 mg/day and methotrexate at 2 mg/week for rheumatoid arthritis visited our hospital because of blurred vision in her left eye. Her left visual acuity was 20/50, and extensive white-yellowish retinal lesions at the temporal periphery with retinal hemorrhages were seen through vitreous haze. The DNA sequence of EBV, but not of HSV, VZV, or cytomegalovirus, was detected by a polymerase chain reaction (PCR) assay in the aqueous humor (4.2 × 106 copies/ml), with EBV also being positive in serum (3.5 × 102 copies/ml). The patient received 2 mg of intravitreal ganciclovir injections twice with a 3-day interval and intravenous infusion of acyclovir at 750 mg/day for 7 days; however, the retinal white lesions expanded rapidly, then dose of prednisolone was increased (40 mg/day) and vitrectomy was performed 10 days after the initial visit. After the surgery, the retinal lesion continued to enlarge. Vitreous samples showed high copies of EBV (1.2 × 108 copies/ml). Following treatment with intravenous foscarnet (4800 mg/day), which replaced the acyclovir application, the retinal white lesions gradually diminished, leaving retinal scars. To date, the patient has developed no retinal detachment and shows visual acuity over 6/60 in the left eye along with silicone oil. We experienced a case of EBV-ARN that was refractory to systemic acyclovir and topical ganciclovir but responded effectively to systemic foscarnet after vitrectomy. Although the clinical management remains challenging in this disease, foscarnet is considered to be one of the candidate drugs for EBV infections.


Edge-on bonding of benzene molecules in the second adsorbed layer on Cu(110).
The bilayer of benzene on Cu(110) was studied with temperature-programmed desorption (TPD), time-of-flight electron stimulated desorption ion angular distribution (TOF-ESDIAD), and scanning tunneling microscopy (STM). TPD spectra show that three well-defined adsorption states exist. The alpha layer corresponds to the first layer containing flat-lying benzene molecules. As coverage increases, the beta layer forms on top of the alpha layer, and eventually, a multilayer, gamma, forms. TPD measurements show that the number of benzene molecules in the beta layer is equal to the number of benzene molecules in the alpha layer. ESDIAD measurements establish that the orientation of the benzene molecules in the beta layer is edge-on, with two C-H bonds directed toward the surface. STM images of the beta layer reveal closely spaced edge-on benzene molecules arranged in repeating hexagons, as well as loosely spaced benzene molecules with greater apparent height, which are also edge-on species. Correlation between the different measurements suggests a structural model for the benzene bilayer.


Revisiting the role of durable polymers in cardiovascular devices.
Polymers are an essential component of drug-eluting stents (DES) used to control drug release but remain the most controversial component of DES technology. There are two types of polymers employed in DES: durable polymer based DES (DP-DES) and biodegradable polymer DES (BP-DES). First-generation DES were exclusively composed of DP and demonstrated increased rates of late stent failure due in part to poor polymer biocompatibility. Newer generations DES use more biocompatible durable polymers or biodegradable polymers. Areas covered: We will cover issues identified with 1st-generation DP-DES, areas of success and failure in 2nd-generation DP-DES and examine the promise and shortcomings of BP-DES. Briefly, fluorinated polymers used in 2nd-generation DP-DES have excellent anti-thrombogenicity and better biocompatibility than 1st-generation DES polymers. However, these devices lead to persistent drug exposure to the endothelium which impairs endothelial function and predisposes towards neoatherosclerosis. Meanwhile, BP-DES has shortened the duration of drug exposure which might be beneficial for endothelial functional recovery leading to less neoatherosclerosis. However, it remains uncertain whether the long-term biocompatibility of bare metal surfaces is better than that of polymer-coated metals. Expert commentary: Each technology has distinct advantages, which can be optimized depending upon the particular characteristics of the patient being treated.


Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium.
Afadin is an actin filament-binding protein that acts cooperatively in cell adhesion with the cell adhesion molecule nectin, and in directional cell movement with the small G protein Rap1 in a nectin-independent manner. We studied the role of afadin in the organization of the small intestinal epithelium using afadin conditional gene knockout (cKO) mice. Afadin was localized at adherens junctions of all types of epithelial cells throughout the crypt-villus axis. Paneth cells were localized at the base of the crypt in control mice, but not confined there, and migrated into the villi in afadin-cKO mice. The distribution of other types of epithelial cells did not change significantly in the mutant mice. The Paneth cells remaining in the crypt exhibited abnormal shapes, were buried between adjacent cells, and did not face the lumen. In these cells, the formation of adherens junctions and tight junctions was impaired. Rap1 and EphB3 were highly expressed in control Paneth cells but markedly down-regulated in the afadin-deficient Paneth cells. Taken together, the results indicate that afadin plays a role in the restricted localization of Paneth cells at the base of the crypt by maintaining their adhesion to adjacent crypt cells and inhibiting their movement toward the top of villi.


Office dilation of the female urethra: a quality of care problem in the field of urology.
Historically dilation of the female urethra was thought to be of value in the treatment of a variety of lower urinary tract symptoms. Subsequent work has more accurately classified these complaints as parts of various diseases or syndromes in which scant data exist to support the use of dilation. Yet Medicare reimbursement for urethral dilation remains generous and we describe practice patterns regarding female urethral dilation to characterize a potential quality of care issue. Health care use by females treated with urethral dilation was compiled using a complementary set of databases. Data sets were examined for relevant inpatient, outpatient and emergency room services for women of all ages. Female urethral dilation is common (929 per 100,000 patients) and is performed almost as much as treatment for male urethral stricture disease. Approximately 12% of these patients are subjected to costly studies such as retrograde urethrography. The overall national costs for treatment exceed $61 million per year and have increased 10% to 17% a year since 1994. A diagnosis of female urethral stricture increases health care expenditures by more than $1,800 per individual per year in insured populations. Urethral dilation is still common despite the fact that true female urethral stricture is an uncommon entity. This scenario is likely secondary to the persistence of the mostly discarded practice of dilating the unstrictured female urethra for a wide variety of complaints despite the lack of data suggesting that it improves lower urinary tract symptoms.


Enantioselective Construction of Quinoxaline-Based Heterobiaryls and P,N-Ligands via Chirality Transfer Strategy.
Central-to-axial chirality transfer via C-N single bond oxidation was first achieved as a versatile and conceptually distinct strategy to prepare a new family of axially chiral heteroaromatic biaryl backbones and P,N-ligands (named as Quinoxalinaps) in gram scale. Two atropisomers of Quinoxalinaps (ee >99%) were readily accessed from the same precursor enantiomer by a simple dehydrogenative oxidation with MnO2 and t-BuOOH under mild conditions. Phosphine could be introduced into the ligands before or after the chirality control process. Moreover, these Quinoxalinap P,N-ligands performed well for both asymmetric reactions of the CuBr-catalyzed alkyne conjugate addition with up to -94% ee and AgOAc-catalyzed glycinate imine [3 + 2] annulation with 90% ee, respectively.


[Relationships between light and physiological characters of five climbing plants].
Studies on the photosynthetic and respiratory rates, light utilization efficiencies and light compensations of five climbing plants showed that the diurnal variations of photosynthetic rates presented double peak, the first peak was between 10:00 to 12:00, and the second was between 14:00 to 16:00. The phenomenon of "noon break" was obvious. The diurnal variations of respiration rates also presented double peak, the first peak was between 11:00 to 13:00, and the second was between 14:00 to 17:00. The light compensation point of Hedera nepatensis, H. helix, Parthenocissus tricuspidata, P. quinuefolia and Wisteria sinensis was 5.73, 5.07, 9.96, 6.40 and 18.93 micromol x m(-2) x s(-1), respectively, and the light utilization efficiency of W. sinensis was higher under strong light, P. quinuefolia was the second, but that of H. helix was higher under weak light. The results showed that Wisteria sinensis was a typical heliophytic plant, Parthenocissus tricuspidata and P. quinuefolia were neuter plants, and Hedera nepalensis and H. helix were typical sciophytic plants.


A standlard for ultraviolet radiation.
Photoemission diode standards for accurately measuring monochromatic ultraviolet light intensity (3000 A-11OO A) are described that are also blind to visible ligh (lambda> 3600 A). The standard uses an opaque photocathode of Cs(2)Te and is unique because of its combination of thinness (19 mm), high sensitivity (Q.E. > 10%), time stability, and uniformity of response. Design criteria, construction methods, and difficulties overcome in obtaining a stable, unform, high yield photocathode responses are discussed. Cs(2)Te is discussed in terms of a model for high yield photoemitters.


An unusual presentation of a large left ventricular pseudoaneurysm.
Left ventricle pseudoaneurysm is an infrequent complication of myocardial infarction, and is most commonly localized in the inferoposterior left ventricular segments. We describe a patient post anterior myocardial infarction, who presented with pulmonary edema and a large pseudoaneurysm of the anterolateral wall with involvement of the anterolateral papillary muscle, resulting in severe mitral regurgitation. The patient underwent successful operation and is currently well.


Conservation of IRE1-regulated bZIP74 mRNA unconventional splicing in rice (Oryza sativa L.) involved in ER stress responses.
Protein folding in the endoplasmic reticulum (ER) is a fundamental process in plant cells that is vulnerable to many environmental stresses. When unfolded or misfolded proteins accumulate in the ER, the well-conserved unfolded protein response (UPR) is initiated to mitigate the ER stress by enhancing the protein folding capability and/or accelerating the ER-associated protein degradation. Here, we report the conservation of the activation mechanism of OsbZIP74 (also known as OsbZIP50), an important ER stress regulator in monocot plant rice (Oryza sativa L.). Under normal conditions, OsbZIP74 mRNA encodes a basic leucine-zipper transcription factor with a putative transmembrane domain. When treating with ER stress-inducing agents such as tunicamycin and DTT, the conserved double stem-loop structures of OsbZIP74 mRNA are spliced out. Thereafter, the resulting new OsbZIP74 mRNA produces the nucleus-localized form of OsbZIP74 protein, eliminating the hydrophobic region. The activated form of OsbZIP74 has transcriptional activation activity in both yeast cells and Arabidopsis leaf protoplasts. The induction of OsbZIP74 splicing is much suppressed in the OsIRE1 knock-down rice plants, indicating the involvement of OsIRE1 in OsbZIP74 splicing. We also demonstrate that the unconventional splicing of OsbZIP74 mRNA is associated with heat stress and salicylic acid, which is an important plant hormone in systemic acquired resistance against pathogen or parasite.


Electrophilic intermediates and their reactions in superacids.
Acid-catalyzed reactions have played a major role in hydrocarbon chemistry involving electron-deficient intermediates such as carbocations, carbodications, onium ions, etc. The pioneering discovery of the use of superacids by George A. Olah, in the early 1960s, to characterize such intermediates under so-called long-lived stable ion conditions led to the understanding of their structures and reactivity patterns much more clearly. Continuing studies in this area in the past 30 years have resulted in a paradigm shift in comprehending the stability and reactivity of electrophilic intermediates in superacid media.


Assessment of "optimal" beta blockade in treating patients with angina pectoris.
Assessment of optimal beta blockade in treating patients with angina pectoris remains a challenge. Reduction in resting heart rate is a poor guide to therapy; the dose response curves are flat and drugs with intrinsic sympathomimetic activity may not lower resting heart rates despite their efficacy. Log plasma concentrations of beta blockers correlate with reduction in exercise tachycardia but not with improvement in exercise tolerance of reduction in myocardial ischaemia. Although useful, reduction in frequency of anginal attacks and nitroglycerin consumption during therapy is a poor guide in assessing optimal beta blockade. The best way to assess optimal therapy is to demonstrate maximum increase in exercise performance in association with reduction in myocardial ischaemia and adequate suppression of exercise-induced increase in heart rate and blood pressure. This requires repeated exercise testing at multiple work loads after various doses of the drug until there is no further increase in exercise duration or reduction in heart rate. When given in optimal and equipotent doses all beta blockers are equally effective antianginal agents and can be prescribed twice daily.


Quantitative evaluation of regional pulmonary ventilation using PET and nitrogen-13 gas.
A new quantitative method, "Simultaneous Exponential Equation method" (SEE), has been developed for the analysis of pulmonary ventilation studies using 13N-labeled nitrogen gas and positron emission computed tomography. This method uses Kety's model assuming insolubility of nitrogen gas in blood or tissues. Activity in poorly ventilated regions does not reach the equilibrium in the so-called equilibrium scan (EQ) performed following 3 or 4 min of washin. Therefore EQ images do not represent lung volume images nor do they provide the initial value of washout phase. Our method corrects for these transient phenomena observed during EQ scan and yields idealistic equilibrium state images (lung volume images) as well as more accurate regional ventilatory time constants than a modified Stewart-Hamilton (A/H) method and tomograms of high resolution.


Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions.
Preclinical evaluation of tuberculosis drugs is generally limited to mice. However, necrosis and hypoxia, key features of human tuberculosis lesions, are lacking in conventional mouse strains. We used C3HeB/FeJ mice, which develop necrotic lesions in response to Mycobacterium tuberculosis infection. Positron emission tomography in live infected animals, postmortem pimonidazole immunohistochemistry, and bacterial gene expression analyses were used to assess whether tuberculosis lesions in C3HeB/FeJ are hypoxic. Efficacy of combination drug treatment, including PA-824, active against M. tuberculosis under hypoxic conditions, was also evaluated. Tuberculosis lesions in C3HeB/FeJ (but not BALB/c) were found to be hypoxic and associated with up-regulation of known hypoxia-associated bacterial genes (P < .001). Contrary to sustained activity reported elsewhere in BALB/c mice, moxifloxacin and pyrazinamide (MZ) combination was not bactericidal beyond 3 weeks in C3HeB/FeJ. Although PA-824 added significant activity, the novel combination of PA-824 and MZ was less effective than the standard first-line regimen in C3HeB/FeJ. We demonstrate that tuberculosis lesions in C3HeB/FeJ are hypoxic. Activities of some key tuberculosis drug regimens in development are represented differently in C3HeB/FeJ versus BALB/c mice. Because C3HeB/FeJ display key features of human tuberculosis, this strain warrants evaluation as a more pathologically relevant model for preclinical studies.


Nicotine gum dose and weight gain after smoking cessation.
The authors examined weight gain in 79 abstinent cigarette smokers during treatment with placebo or with 2 mg or 4 mg of nicotine gum. Results indicated that nicotine gum suppressed weight gain in a linear fashion with increasing nicotine dose. At 90 days postcessation, placebo gum users gained 3.7 kg, 2-mg gum users gained 2.1 kg, and 4-mg gum users gained 1.7 kg. Assessment of nicotine replacement by means of pre- and postcessation salivary continue levels revealed that smokers who replaced a greater percentage of their baseline continue levels during treatment gained less weight. Percentage of baseline cotinine replaced remained related to weight gain after the number of pieces of gum used was controlled. Implications for smokers hoping to minimize postcessation weight gain are discussed.


LncRNA HOXA10-AS Activated by E2F1 Facilitates Proliferation and Migration of Nasopharyngeal Carcinoma Cells Through Sponging miR-582-3p to Upregulate RAB31.
Nasopharyngeal carcinoma (NPC) is a kind of head and neck cancer with a characteristic regional distribution. Increasing evidence has illustrated that long noncoding RNAs (lncRNAs) exert the regulatory function in tumor development. Nevertheless, the specific functions of lncRNA HOXA10 antisense RNA (HOXA10-AS) in NPC remain to be clarified. In this research, quantitative reverse transcription polymerase chain reaction detected HOXA10-AS expression in NPC cells. Cell counting kit-8, colony formation, and transwell assays were utilized to measure the proliferation and migration of NPC cells. Moreover, mechanism assays detected the interaction of different genes. Briefly, HOXA10-AS was highly expressed in NPC cells. HOXA10-AS down-regulation restrained NPC cell proliferation and migration. Further, HOXA10-AS could bind to miR-582-3p by acting as a competing endogenous RNA. Besides, Ras-related protein Rab-31 (RAB31) was proven as the target gene of miR-582-3p. Additionally, E2F transcription factor 1 (E2F1) acted as a transcription factor to activate HOXA10-AS expression. In the final rescue assays, we observed that the effect of HOXA10-AS depletion on NPC cell growth could be fully reversed by RAB31 overexpression or miR-582-3p inhibition. In short, our research proved that HOXA10-AS activated by E2F1 facilitated proliferation and migration of NPC cells through sponging miR-582-3p to upregulate RAB31.


Low-grade endometrial stromal sarcoma with intracaval or intracardiac extension: a retrospective study of eight cases.
This study aimed to improve the knowledge of low-grade endometrial stromal sarcoma (LG-ESS) with intracaval or intracardiac extension and tried to identify the potential risk factors and optimal treatment method influencing prognosis. We performed a retrospective review of eight LG-ESS patients with intracaval or intracardiac extension who underwent treatment at Peking Union Medical College Hospital between 2012 and 2020. The median age at diagnosis was 44 years, ranging from 28 to 56 years. Abnormal uterine bleeding was the most common intimal symptom (3/8), followed by low back discomfort (2/8), edema of the lower limbs (2/8), abdominal pain (1/8), and dyspnea (1/8). All patients underwent resection of the intravascular and extravascular portions of the tumor. Two patients were in stage IIIC, and six were in stage IVB. After surgery, four patients received adjuvant radiotherapy, of whom three also received letrozole. One patient was treated with letrozole alone, and one patient received medroxyprogesterone. The average follow-up time was 34.5 months, ranging from 6 to 98 months. No patients died or relapsed during the follow-up period. LG-ESS with intracaval or intracardiac extension is an uncommon type of tumor which is easily misdiagnosed and can only be diagnosed by histological evaluation after surgery. Complete tumoral excision followed by adjuvant therapy may benefit patient survival time. Long-term follow-up is essential due to the high rate of late recurrence.


Atherothrombosis and oxidative stress: the connection and correlation in diabetes.
Hyperglycaemia-induced depletion of reduced glutathione (GSH) causes erythrocyte oxidative stress (EOS), which leads to vascular events including exacerbation of thrombotic events evidenced by changes in D-dimer level. It would, therefore, appear that there is a complex link between GSH and D-dimer, which are part of an emerging array of biomarkers associated with diabetes. The objective of this study was to investigate evidence of correlation between levels of plasma D-dimer and erythrocyte GSH in diabetes disease progression. A cohort of 69 subjects were selected based on medical history plus clinical findings and equally divided into control, prediabetes and diabetes groups, matched for age and sex. Plasma D-dimer and erythrocyte reduced glutathione (GSH) were determined and separated into quartiles as a means of indicating disease severity. Statistical analysis was by Pearson's correlation coefficient. Of the three groups, only the diabetes group showed any correlation between GSH and D-dimer. Of importance is that for increasing GSH, the second quartile range of GSH (xbar +/- SD = 45 +/- 22 mg/100ml) showed a statistically significant negative correlation for ranked D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = -0.88; P < 0.02). The fourth quartile GSH range (xbar +/- SD = 79 +/- 40 mg/100 ml) showed a statistically significant positive correlation with D-dimer (xbar +/- SD = 1055 +/- 828 microg/l; r = 0.91; P < 0.02). Thus, within the diabetes group only, the increasing level of oxidative stress as measured by GSH first indicates a reduction in D-dimer followed by a rise in D-dimer, which led to the proposal of a two-part process of atherosclerosis that reconciles previous contradictory findings. This study provides not only evidence of a correlation between oxidative stress level and fibrinolysis in diabetes, but also an explanation of why previous studies have found both hypo- or hyperfibrinolysis associated with diabetes.