Downregulation of ABCE1 via siRNA affects the sensitivity of A549 cells against chemotherapeutic agents.
ATP-binding cassette E1 (ABCE1) is involved in several biological functions in cancer cells such as tumor proliferation, antiapoptotic pathway and chemoresistance mechanism. This work aimed to investigate the alterations in chemosensitivity of A549 lung cancer cells for 5-Fluorouracil (5-FU) and irinotecan by silencing ABCE1 using specific small interfering RNAs (siRNA). The cells were treated with low doses of drugs, alone and also their combinations with ABCE1 siRNA. Cytotoxicity, cell proliferation and apoptosis/necrosis evaluations were performed in order to examine the effects of the combined treatment. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the downregulation of ABCE1. We also investigated the levels of B cell lymphoma 2 (Bcl-2) and mammalian target of rapamycin (mTOR) after the treatments by RT-PCR. Downregulation of ABCE1 improved the anticancer effects of 5-FU in inducing cell viability/proliferation inhibition and apoptosis/necrosis, whereas interestingly, almost did not change or slightly reduced the anticancer effects of irinotecan. ABCE1 expression significantly decreased by transfecting the cells with ABCE1 siRNA. Moreover, Bcl-2 and mTOR levels changed after the single or combined therapy in parallel with the apoptotic and antiproliferation effect. In conclusion, the simultaneous treatment of lung cancer cells with ABCE1 siRNA and 5-FU exhibited synergistic or additive effects; however, ABCE1 siRNA and irinotecan had unexpected antagonistic effects. Our findings demonstrate that the strategy of downregulation of ABCE1 may be included in conventional 5-FU chemotherapy for lung cancer, minimizing the usage of 5-FU at high dosages.


[Comparison of trophic status analysis of the Daning River within the Three Gorges Reservoir before and after experimental impoundment].
We evaluated 4-year data set to assess the trophic state and limiting factors of the Three Gorges Reservoir (TGR) during the experimental impounding period (September 2005 to September 2007) and the normal operating period (September 2008 to September 2010). The results indicated that there had been appeared new characteristics in spatial and temporal distribution of trophic state indices after impoundment. The trophic state indices (TSI(TP)) showed increased trend after the TGR impoundment during the study area, but TSI(TN) and TSI(SD) had no significant changes after the TGR impoundment. The values of TSI(CHL) showed increased trend after the TGR impoundment in S1, and the values of TSI(CHL) did not show obvious changes in S2, S3 and S4 after the TGR impoundment. The values of TSI(TN), TSI(TP) and TSI(SD) show similar spatial variances with the highest value in S4, followed in a descending order by S3, S2 and S1. TSI(CHL) in the S2 and S3 were higher than that in S1 and S4. According to the characteristics of water level, the operational period of the TGR classified into following four stages: stage I (pre-November-April), stage II (May-July), stage III (July-September) and stage IV (September-November). The values of TSI(TN) and TSI(TP) in the Daning River and the TGR mainstream showed similar seasonal variances with the highest value in the stage II and III, followed in a descending order by stage I and IV. The values of TSI(CHL) varied substantially among the four stages, with the highest value in stage III, followed by stage II, IV and I. The trophic state indices differences were getting smaller between the four stages after the TGR impoundment. Using Carlson's two-dimensional approach, deviations of the TSI(S) indicated that factors other than phosphorous and nitrogen limited algal growth and that nonalgal particles affected light attenuation. These findings were further supported by the significant correlation among the values of TSI and hydrological factors.


Ulcerative Colitis and Cytomegalovirus Infection: From A to Z.
Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.


Mutagenic safety and fatty liver improvement of nanonized black soybeans in senescence-accelerated prone-8 mice.
Nanotechnology, as a new enabling technology, has the potential to revolutionize food systems. However, much attention has been focused on nanoparticle foods due to their potential physiological properties. This study was aimed to evaluate the mutagenic safety and fatty liver improvement of black soybean in senescence-accelerated mice (SAMP8). The mutagenic activity of black soybeans was investigated using the Ames test (Salmonella Typhimurium TA98, 100, 102, and 1535). Furthermore, senescence-accelerated prone-8 mice (SAMP8) have been reported to display spontaneous fatty liver. Male SAMP8 mice were divided into control and supplemented with 10% micronized or nanonized black soybeans diet and fed for 12 wk. The results revealed that the Ames test of micronized and nanonized black soybeans exhibited no mutagenicity. Administration of black soybeans to mice showed no effects on food intake and body and organ weights. The nanonized black soybean group had a lower degree of spontaneous fatty liver, alanine aminotransferase, and thiobarbituric acid-reactive substance concentrations, and had enhanced superoxide dismutase, catalase, and glutathione peroxidase activities of livers when compared with the SAMP8 control and micronized black soybean groups. The mice fed with black soybeans had significantly lower triglyceride concentrations than the SAMP8 control group. The results of this study suggest that nanonized black soybeans have no side effects and, moreover, may minimize liver lesions in SAMP8 mice.


Curcumin modulates cell type-specific miRNA networks to induce cytotoxicity in ovarian cancer cells.
To understand the epigenetic role of curcumin, a natural polyphenolic compound extracted from the spice Curcuma longa in inducing cytotoxicity in two molecularly distinct ovarian cancer cell lines: PA1 and A2780. An integrated mRNA-miRNA sequence analysis was performed to determine the curcumin-induced mRNA-miRNA regulatory networks in the induction of cytotoxicity. The miRNA-mRNA pathways, the miRNAs and their targets implicated in apoptosis, autophagy, DNA damage, and stemness markers were validated. Gene/miRNA expressions were validated using qPCR and protein expressions by western blotting. Curcumin-induced oncogenic /tumor-suppressor miRNAs were profiled utilising the oncomiRdb database. Similarly, the expressions of oncogenes/tumor suppressor genes were profiled and correlated with the TCGA ovarian cancer dataset. A dual luciferase assay was performed to investigate the interaction of miR-199a-5p to its direct target, DDR1. The expression of several miRNAs demonstrated an inverse correlation with their respective direct targets. In curcumin-treated PA1 cells, miR-335-5p target ATG5 (autophagic), and OCT4 (pluripotent gene) were downregulated, miR-32a target PTEN (tumor suppressor) was upregulated, miR-1285 target P53 (tumor suppressor) was upregulated, and both miR-182-5p and miR-503-3p target BCL2, were down-regulated. Contrastingly, in curcumin-treated A2780 cells, miR-181a-3p target ATG5, miR-30a-5p, and miR-216a target BECN1 (autophagic) were upregulated, and miR-129a-5p target BCL2 were downregulated. The reversal of the oncomiR/TSmiR profile revealed suppression of oncogenic processes by curcumin. Curcumin treatment induced a moderate cisplatin-sensitisation effect and impaired epithelial-to-mesenchymal transition (EMT) characteristics. Curcumin also regulated the miR-199a-5p/DDR1 axis with a decrease in collagen deposition. The activity of curcumin is cell-type specific. Distinct miRNA regulatory networks were activated to induce multiple modes of cellular cytotoxicity in these ovarian cancer cells. This study further highlights the molecular mechanism of curcumin action in ovarian cancers establishing its candidacy as a promising drug candidate.


High-throughput models for exposure-based chemical prioritization in the ExpoCast project.
The United States Environmental Protection Agency (U.S. EPA) must characterize potential risks to human health and the environment associated with manufacture and use of thousands of chemicals. High-throughput screening (HTS) for biological activity allows the ToxCast research program to prioritize chemical inventories for potential hazard. Similar capabilities for estimating exposure potential would support rapid risk-based prioritization for chemicals with limited information; here, we propose a framework for high-throughput exposure assessment. To demonstrate application, an analysis was conducted that predicts human exposure potential for chemicals and estimates uncertainty in these predictions by comparison to biomonitoring data. We evaluated 1936 chemicals using far-field mass balance human exposure models (USEtox and RAIDAR) and an indicator for indoor and/or consumer use. These predictions were compared to exposures inferred by Bayesian analysis from urine concentrations for 82 chemicals reported in the National Health and Nutrition Examination Survey (NHANES). Joint regression on all factors provided a calibrated consensus prediction, the variance of which serves as an empirical determination of uncertainty for prioritization on absolute exposure potential. Information on use was found to be most predictive; generally, chemicals above the limit of detection in NHANES had consumer/indoor use. Coupled with hazard HTS, exposure HTS can place risk earlier in decision processes. High-priority chemicals become targets for further data collection.


Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys.
To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC), we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta). The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1) all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2) with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3) roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4) the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex.


A new role for Notch and Delta in cell fate decisions: patterning the feather array.
Chick embryonic feather buds arise in a distinct spatial and temporal pattern. Although many genes are implicated in the growth and differentiation of the feather buds, little is known about how the discrete pattern of the feather array is formed and which gene products may be involved. Possible candidates include Notch and its ligands, Delta and Serrate, as they play a role in numerous cell fate decisions in many organisms. Here we show that Notch-1 and Notch-2 mRNAs are expressed in the skin in a localized pattern prior to feather bud initiation. In the early stages of feather bud development, Delta-1 and Notch-1 are localized to the forming buds while Notch-2 expression is excluded from the bud. Thus, Notch and Delta-1 are expressed at the correct time and place to be players in the formation of the feather pattern. Once the initial buds form, expression of Notch and its ligands is observed within each bud. Notch-1 and -2 and Serrate-1 and -2 are expressed throughout the growth and differentiation of the feathers whereas Delta-1 transcripts are downregulated. We have also misexpressed chick Delta-1 using a replication competent retrovirus. This results in induction of Notch-1 and-2 and a loss of feather buds from the embryo in either large or small patches. In large regions of Delta-1 misexpression, feathers are lost throughout the infected area. In contrast, in small regions of misexpression, Delta-1 expressing cells differentiate into feather buds more quickly than normal and inhibit their neighbors from accepting a feather fate. We propose a dual role for Delta-1 in promoting feather bud development and in lateral inhibition. These results implicate the Notch/Delta receptor ligand pair in the formation of the feather array.


Characterization of cattle in Nigeria--body measurements.
The beef cow breeds Boran, Muturu, and N'Dama, which are widely distributed in southern Nigeria, are described in their phenotypes and their performance characteristics. Body measurements exhibited highly significant differences between the breeds as to body weight, wither height, and body length. The constants are presented for estimating the body weight of these breeds from their heart girth and body length under Nsukka conditions. They can be used for measurements in inches (yielding the body weight in lbs) or in cm (body weight in kg).


Long-term abstinence and predictors of tobacco treatment uptake among hospitalized smokers with serious mental illness enrolled in a smoking cessation trial.
Hospital patients with serious mental illness (SMI) have high rates of smoking. There are few post-discharge treatment models available for this population and limited research on their treatment uptake following discharge. This study is a secondary analysis of an RCT that compared multi-session intensive telephone counseling versus referral to state quitline counseling at two safety net hospitals in New York City. For this analysis, we selected all trial participants with a history of schizophrenia, schizoaffective disorder or bipolar disorder (N = 384) and used multivariable logistic regression to compare groups on self-reported 30-day abstinence at 6 months and to identify patient factors associated with use of tobacco treatment. Analyses found no significant group differences in abstinence 6 months (28% quitline vs. 29% intervention, p > 0.05), use of cessation medications (42% quitline vs. 47% intervention, p > 0.05) or receipt of at least one counseling call (47% quitline vs. 42% intervention, p > 0.05). Patients with hazardous drinking (p = 0.04) or perceived good health (p = 0.03) were less likely to use cessation medications. Homeless patients were less likely to use counseling (p = 0.02). Most patients did not use cessation treatment after discharge, and the intensive intervention did not improve abstinence rates over quitline referral. Interventions are needed to improve use of cessation treatment and long-term abstinence in patients with SMI.


Effect of the damping function in dispersion corrected density functional theory.
It is shown by an extensive benchmark on molecular energy data that the mathematical form of the damping function in DFT-D methods has only a minor impact on the quality of the results. For 12 different functionals, a standard "zero-damping" formula and rational damping to finite values for small interatomic distances according to Becke and Johnson (BJ-damping) has been tested. The same (DFT-D3) scheme for the computation of the dispersion coefficients is used. The BJ-damping requires one fit parameter more for each functional (three instead of two) but has the advantage of avoiding repulsive interatomic forces at shorter distances. With BJ-damping better results for nonbonded distances and more clear effects of intramolecular dispersion in four representative molecular structures are found. For the noncovalently-bonded structures in the S22 set, both schemes lead to very similar intermolecular distances. For noncovalent interaction energies BJ-damping performs slightly better but both variants can be recommended in general. The exception to this is Hartree-Fock that can be recommended only in the BJ-variant and which is then close to the accuracy of corrected GGAs for non-covalent interactions. According to the thermodynamic benchmarks BJ-damping is more accurate especially for medium-range electron correlation problems and only small and practically insignificant double-counting effects are observed. It seems to provide a physically correct short-range behavior of correlation/dispersion even with unmodified standard functionals. In any case, the differences between the two methods are much smaller than the overall dispersion effect and often also smaller than the influence of the underlying density functional.


AlloMap6: an R package for genetic linkage analysis in allohexaploids.
Allopolyploids are a group of polyploids with more than two sets of chromosomes derived from different species. Previous linkage analysis of allopolyploids is based on the assumption that different chromosomes pair randomly during meiosis. A more sophisticated model to relax this assumption has been developed for allotetraploids by incorporating the preferential pairing behavior of homologous over homoeologous chromosomes. Here, we show that the basic principle of this model can be extended to perform linkage analysis of higher-ploidy allohexaploids, where multiple preferential pairing factors are used to characterize chromosomal-pairing meiotic features between different constituent species. We implemented the extended model into an R package, called AlloMap6, allowing the recombination fractions and preferential pairing factors to be estimated simultaneously. Allomap6 has two major functionalities, computer simulation and real-data analysis. By analyzing a real data from a full-sib family of allohexaploid persimmon, we tested and validated the usefulness and utility of this package. AlloMap6 lays a foundation for allohexaploid genetic mapping and provides a new horizon to explore the chromosomal kinship of allohexaploids.


[Neuropsychiatric disturbances in Wilson's disease and use of electroconvulsive therapy: case report].
Wilson's disease consists in a inborn error of metabolism with marked neuropsychiatric manifestations. These manifestations need to be correctly identified and treated. There are four neuropsychiatric symptoms clusters established for Wilson's disease patients: behavior and/or personality disorders, mood disorders, cognitive deficits, and psychotic manifestations. Although such patients are more commonly seen in neurological and hepatological settings, mental health professionals must keep in mind a high level of suspicion, once first presentations may be of psychiatric nature. This study presents a review of literature about neuropsychiatric aspects of Wilson's disease, emphasizing diagnostic issues. It is presented the case of a 26 years old male patient initially with psychiatric polimorfic symptoms. The treatment of this patient with electroconvulsive therapy is presented, adding a report of this therapeutic modality, applied to that case, to the two only previous records in the literature.


[Individualized partial laryngectomy during surgery of epiglottic carcinoma].
To investigate an individualized operative modality of partial laryngectomy for suprahyoid epiglottis centered epiglottic carcinoma. Eleven cases of epiglottic squamous carcinoma which primarily focused in the suprahyoid region were included. Preoperative CT indicated that obvious margin with low density existed in the pre-epiglottic space in 3 cases, and pre-epiglottic space were involved in 8 cases, among which the arytenoid region were involved in 2 cases. An individualized partial laryngectomy was manipulated beyond the safe margin, an arytenoid epiglottic fold-plasty was performed and the remaining epiglottis was fixed to the tongue base. Adjuvant postoperative radiotherapy and chemotherapy were applied to all patients and the follow-up time lasted from 1 to 6 years with mean time of 3 years and 6 months. One patient died of recurrence in the tongue base after one year postoperatively, one was lost to follow-up 2 years after surgery. The overall 3-year survival rate was 81.8%. Nine patients were free from tracheal cannulation within one year postoperatively and the other two patients went on with tracheal tube assisted respiration. Aspiration gradually disappeared within 1-3 months. Individualized partial laryngectomy in treatment of epiglottic carcinoma could preserve more laryngeal tissue and result in better laryngeal function preservation.


Angioplasty for coarctation of the aorta: long-term results.
Balloon coarctation angioplasty (BCA) was performed in seven consecutive patients (five boys and two girls) 18 months to 18 years old (mean 9.5) with isolated discrete unoperated coarctation of the aorta. A No. 8F or 9F catheter was chosen with balloon lengths of 30 or 40 mm and maximum inflation diameters 1 mm less than the smallest measured aortic diameter determined 1 cm proximal to the coarctation site. A 10 sec inflation-deflation cycle of 6 to 8 atmospheres (90 to 120 psi) was performed. The peak systolic pressure gradient (PSG) before BCA ranged from 35 to 70 mm Hg (mean 58), and immediately after BCA it decreased to 0 to 20 mm Hg (mean 7). One to two year follow-up (mean 14 months) of the seven patients revealed a PSG range of 10 to 30 mm Hg (mean 19). Repeat angiography was performed immediately proximal to the coarctation site. Three patients (43%) had evidence of aneurysm formation at or immediately distal to the balloon dilatation site. One patient had coarctation restenosis. While initial results with BCA for unoperated coarctation were encouraging, current data raise serious concerns about its long-term safety and efficacy.


Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.
Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.


Spontaneous reattachment of rhegmatogenous retinal detachment:about 5 cases.
Spontaneous retinal reattachment is very rare in the natural evolution of rhegmatogenous retinal detachment and it is often undervalued. To report some cases of this affection. A retrospective study was conducted reporting five eyes of five patients who presented for acute visual loss in relation with a confirmed rhegmatogenous retinal detachment. Surgical care was delayed because of bacterial or viral conjunctivitis. Following this delay, the preoperative examination rapported a spontaneous retinal reattachment. Each patient underwent Laser exclusion of the dehiscence and a regular follow up: clinical examination and OCT. The incidence of spontaneous retinal reattachment is 3.2% among examined and treated rhegmatogenous retinal detachments in our department during this period. The age of our patients ranged between 20 and 67 years. Retinal detachment was subtotal in all cases. Retinal break was unique in four cases and mostly located in the superior retina. Proliferative vitreoretinopathy was low graded in all cases (A and B). The diagnosis of spontaneous reattachment DRR was often carried out retrospectively on the basis offundus evocative examination signs. According to many authors, it is more observed in myopic eye and if detachment is inferior. In our series, the low PVR seems to have a principal role in physiopathology.


The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.
Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms. The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD. We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables. Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day). Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.


Focal cellular origin and regulation of interstitial collagenase (matrix metalloproteinase-1) are related to menstrual breakdown in the human endometrium.
Recent studies suggest that interstitial collagenase (MMP-1) is an essential enzyme in the early events leading to menstruation. This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-cultured samples. The source of MMP-1 was identified by in situ hybridization and by immunohistochemistry on serial sections. This was compared with the immunolocalization of other MMPs, steroid receptors, macrophages, and laminin. In non-cultured endometrium, MMP-1 was only expressed during the perimenstrual period. It was either restricted to superficial foci of stromal cells or extended towards the entire functional layer. MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles. In cultured non-menstrual explants, MMP-1 expression was induced within two days after deprivation of sex steroids. Both in cultured and non-cultured samples, progesterone receptors were not detectable in epithelial cells at foci of MMP-1 expression. The same stromal cells could synthesize MMP-1, MMP-2 (gelatinase A) and MMP-3 (stromelysin-1), as well as laminin, and did not correspond to macrophages. In conclusion, MMP-1 is focally expressed in stromal cells of the functional layer of the endometrium, when and where steroid receptors disappear, and especially where tissue breakdown is prominent. These observations point to an essential role for MMP-1 in the early stages of menstruation.


[The significance of concurrent vertebrobasilar insufficiency in postanesthesia recovery].
A study of 149 patients was carried out, who had cervical osteochondrosis, by using the stage-based narcosis and general intravenous anesthesia. The parameters of the peripheral velocity of the bloodstream in the direct brain venous sine were examined by transcranial dopplerography. Preoperatively, the patients were shared between 3 groups with due respect to clinical and neurological symptoms as well as to X-ray-registered changes in the cervical spine. While evaluating the intracranial pressure, the cerebral hemodynamics was examined by ophthalmodynamometry procedures (diastolic pressure in the retinal central vein). The anatomotopographic peculiarities of the cervical spine, and in particular, of the spinal artery, vein and sympathetic nerve passage, as observed in the lateral vertebral processes in cases of spine osteochondrosis, aggravate the strangulation and blood circulation disturbances in the basilar and vertebral regions with respect to changes of the head position. Trachea incubation (head extended with anesthetic management), made in patients with the pronounced cervical osteochondrosis (group III), slowed down the peripheral blood flow into the direct brain venous sine; it also caused a higher intracranial pressure versus the parameters observed in the basilar and vertebral deficiency, as well as hemodynamics instability resulting in a late awakening after anesthetic management.


Aboriginal perspectives of diabetes in a remote community in the Northern Territory.
This study explores the knowledge and beliefs of diabetes in a group of Aboriginal people from a remote community in the Northern Territory. Information was gathered from participants through a combination of group discussions, semi-structured interviews and informal conversations. The four themes of explanation of diabetes were: worry, food, family and infections. The most common means of preventing or treating diabetes were stopping worry and changing one's diet. Significantly, few of the participants believed that medication was effective, and weight loss and exercise were not mentioned. The results highlight the miscommunication about diabetes that has occurred in this population. For effective communication and management of diabetes, health information must incorporate the contemporary health beliefs of the clients.


Impact of peripheral artery disease on prognosis in hospitalized heart failure patients.
The impact of peripheral artery disease (PAD) on heart failure (HF) prognosis remains unclear. A total of 388 consecutive decompensated HF patients were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n=101, 26.0%) and HF without PAD (non-PAD group, n=287, 74.0%). We compared clinical features, echocardiographic parameters, cardiopulmonary exercise testing results, laboratory findings, as well as cardiac, non-cardiac, and all-cause mortality between the 2 groups. The PAD group, as compared with the non-PAD group, had (1) higher prevalence of coronary artery disease (40.6 vs. 27.5%, P=0.011) and cerebrovascular disease (34.7 vs. 18.2%, P=0.001); (2) higher tumor necrosis factor-α (1.82 vs. 1.49 pg/ml, P=0.023), C-reactive protein (0.32 vs. 0.19 mg/dl, P=0.045), and troponin T (0.039 vs. 0.021 ng/ml, P=0.019); (3) lower LVEF (42.4 vs. 48.5%, P<0.001); (4) lower peak V̇O2(13.4 vs. 15.9 ml·kg(-1)·min(-1), P=0.001); and (5) higher V̇E/V̇CO2slope (38.8 vs. 33.7, P<0.001). On Kaplan-Meier analysis, cardiac, non-cardiac, and all-cause mortality were significantly higher in the PAD group than in the non-PAD group (P<0.05, respectively). On Cox proportional hazard analysis after adjusting for confounding factors, PAD was an independent predictor of cardiac and all-cause mortality (P<0.05, respectively) in HF patients. PAD was common and an independent predictor of cardiac and all-cause mortality in HF patients.


A comparison of weighted CUSUM procedures that account for monotone changes in population size.
The CUSUM procedure has been popularly used for detecting a shift in the incidence rate of a rare health event. Many CUSUM methods are developed based on a Poisson model with a constant mean number of events. In practice, the expected number of events is likely to vary over time as the population size at risk is not constant but often grows over time. An increase in the baseline incidence rate tends to be masked by the population growth. To efficiently detect an increase in the baseline incidence rate, it is appealing to assign more weight to recent observations and less weight to older observations. This paper compares weighted CUSUM (WCUSUM) and conventional CUSUM procedures in the presence of monotone changes in population size. The simulation results show that the WCUSUM method may be more efficient than the conventional CUSUM methods in detecting increases in the incidence rate, especially for small shifts. An example based on mortality data from New Mexico is used to illustrate the implementation of the WCUSUM method.


A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3).
Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test).


Language context processing deficits in schizophrenia: The role of attentional engagement.
Individuals with schizophrenia exhibit problems in language comprehension that are most evident during discourse processing. We hypothesized that deficits in cognitive control contribute to these comprehension deficits during discourse processing, and investigated the underlying cognitive-neural mechanisms using EEG (alpha power) and ERPs (N400). N400 amplitudes to globally supported or unsupported target words near the end of stories were used to index sensitivity to previous context. ERPs showed reduced sensitivity to context in patients versus controls. EEG alpha-band activity was used to index attentional engagement while participants listened to the stories. We found that context effects varied with attentional engagement in both groups, as well as with negative symptom severity in patients. Both groups demonstrated trial-to-trial fluctuations in alpha. Relatively high alpha power was associated with compromised discourse processing in participants with schizophrenia when it occurred during any early portion of the story. In contrast, discourse processing was only compromised in controls when alpha was relatively high for longer segments of the stories. Our results indicate that shifts in attention from the story context may be more detrimental to discourse processing for participants with schizophrenia than for controls, most likely due to an impaired ability to benefit from global context.


In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite composite for bone regeneration.
Synthetic bone graft substitutes based on composites consisting of a polymer and a calcium-phosphate (CaP) ceramic are developed with the aim to satisfy both mechanical and bioactivity requirements for successful bone regeneration. In the present study, we have employed extrusion to produce a composite consisting of 50 wt.% poly(D,L-lactic acid) (PLA) and 50 wt.% nano-sized hydroxyapatite (HA) powder, achieving homogeneous distribution of the ceramic within the polymeric phase. In vitro, in both a simulated physiological saline (SPS) and a simulated body fluid (SBF), a greater weight loss was observed for PLA/HA than for PLA particles upon 12-week immersion. Furthermore, in SPS, a continuous release of calcium and phosphate from the composite was measured, whereas in SBF, decrease of the amount of the two ions in the solution was observed both for PLA and PLA/HA accompanied with the formation of a CaP layer on the surface. In vitro characterization of the composite bioactivity was performed by culturing human mesenchymal stromal cells (hMSCs) and assessing proliferation and osteogenic differentiation, with PLA as a control. Both PLA/HA composite and PLA control were shown to support hMSCs proliferation over a period of two weeks. In addition, the composite significantly enhanced alkaline phosphatase (ALP) activity of hMSCs in osteogenic medium as compared with the polymer control. A novel implant design was employed to develop implants from dense, extruded materials, suitable for testing osteoinductivity in vivo. In a preliminary study in dogs, PLA/HA composite implants induced heterotopic bone formation upon 12-week intramuscular implantation in all animals, in contrast to PLA control, which was not osteoinductive. Unlike in vitro, a more pronounced degradation of PLA was observed in vivo as compared with PLA/HA composite.


[The approach to the regulation of mercury according to the content of its termoforms in soils and bed loads].
The article contains the results of the ecological and hygienic diagnostics of conditions of lands of areas of different sizes and varying degrees of urbanization, located in different agro-climatic conditions of European Russia (the southern Astrakhan region, he city of Moscow). Assessments of the state of territories use a new approach to rationing of Hg according to quantitative ratios of the content of its thermoforms in soils, grounds and alluvium (in litho substrate). The method of diagnostics is based on known properties of Hg forms: their geochemical activity (migration mobility) and toxicity decline along with the increment of the Hg temperature threshold of the release in the process of continuous warming up of the litho substrate sample (up to 1100°C). Thermoforms are not tied to specific minerals or chemicals and are conditionally designated as FR (Free: <180°C), CL (Chloride: 180-250°C), FS and CS (physically and chemically sorbed: 250-400°C), SU (Sulfide: 400-500°C) IS (isomorphic: >500°C) Hg forms. Among forms, also conditionally according to complexes of low, medium and high temperature variations(FR + CL, FS + CS and SU + IZ, respectively, there are selected groups of «mobile», «sustainable» and «inert» forms. For technogenic Hg there is characterized the predominance in the sample of «mobile» and to lesser extent degree - «stable» thermoforms. The more intensive this predominance is, the higher is environmental hazard. The natural accumulation is diagnosed by the presence and prevalence of the sum of moderate - and high-temperature inert forms of Hg. According to the ratios of Hg content, its forms and groups, as well as the density of correlationships between them, 6 indices of the conditions of soils and alluvium were developed by ourselves.Main coefficients out of indices on informativeness of results of diagnostics are the following factors: Endogenous input, Geochemical activity and Hg mobility. With regard to the combination of variability in indices, the total amount of Hg, the genesis and intensity of its accumulation (natural or anthropogenic), there were also developed ranking scales of the ecological and hygienic condition of the land areas and surface water bodies. As a result, on the base of such approach to the regulation of Hg the information value of assessments of mercury contamination of land significantly increased. At the objects of assessments there were identified following areas: foci of the manifestation of Hg hypolimnetic emanations on the landscape surface - dispersion halos in the areas of the Earth crust fracture (the dome of the Astrakhan gas condensate field); environmentally dangerous (sometimes even at a low total content of Hg) parts of cities, towns, their districts, as well as beds of watercourses and water reservoirs bottom (the Volga river valley and delta, the Lefortovo quarter in Moscow). There was also diagnosed the threshold of the background distribution of gross Hg content detected = 0.2-0.3 mg/kg. Its magnitude is consistent with domestic and abroad safe levels of Hg accumulation in soils = 0.3-0.4 mg/kg. The approach provides the differentiation of the environmental hazard lands. Technology of the approach can be used in the development of normative Document for the diagnosis of environmental and sanitary condition of territories in the system of Classifications of hazard of waste, in decontamination of territories, water areas and land zoning according to the criteria of natural or anthropogenic Hg accumulation.


Detection of two mRNA species at single-cell resolution by double-fluorescence in situ hybridization.
Here we describe a fluorescence in situ hybridization protocol that allows for the detection of two mRNA species in fresh frozen brain tissue sections. This protocol entails the simultaneous and specific hybridization of hapten-labeled riboprobes to complementary mRNAs of interest, followed by probe detection via immunohistochemical procedures and peroxidase-mediated precipitation of tyramide-linked fluorophores. In this protocol we describe riboprobes labeled with digoxigenin and biotin, though the steps can be adapted to labeling with other haptens. We have used this approach to establish the neurochemical identity of sensory-driven neurons and the co-induction of experience-regulated genes in the songbird brain. However, this procedure can be used to detect virtually any combination of two mRNA populations at single-cell resolution in the brain, and possibly other tissues. Required controls, representative results and troubleshooting of important steps of this procedure are presented. After tissue sections are obtained, the total length of the procedure is 2-3 d.


Pathophysiological mechanisms explaining poor clinical outcome of older cancer patients with low skeletal muscle mass.
Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as post-operative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review, we summarize proposed pathophysiological mechanisms underlying the association between low skeletal muscle mass and poor clinical outcomes in older cancer patients including a) systemic inflammation; b) insulin-dependent glucose handling; c) mitochondrial function; d) protein status and; e) pharmacokinetics of anticancer drugs. The mechanisms of altered myokine balance negatively affecting the innate and adaptive immune system, and altered pharmacokinetics of anticancer drugs leading to a relative overdosage of anticancer drugs are best-substantiated. The effects of glucose intolerance and circulating mitochondrial DNA as a consequence of low skeletal muscle mass are topics of interest for future research. Restoring myokine balance through physical exercise, exercise mimetics, neuro-muscular activation and adapting anticancer drug dosing on skeletal muscle mass could be targeted approaches to improve clinical outcomes in older cancer patients with low skeletal muscle mass.


Comparative approaches in social network ecology.
Social systems vary enormously across the animal kingdom, with important implications for ecological and evolutionary processes such as infectious disease dynamics, anti-predator defence, and the evolution of cooperation. Comparing social network structures between species offers a promising route to help disentangle the ecological and evolutionary processes that shape this diversity. Comparative analyses of networks like these are challenging and have been used relatively little in ecology, but are becoming increasingly feasible as the number of empirical datasets expands. Here, we provide an overview of multispecies comparative social network studies in ecology and evolution. We identify a range of advancements that these studies have made and key challenges that they face, and we use these to guide methodological and empirical suggestions for future research. Overall, we hope to motivate wider publication and analysis of open social network datasets in animal ecology.


Nucleophilic Attack on Nitrogen in Tetrazines by Silyl-Enol Ethers.
The nucleophilic addition of silyl-enol ethers to nitrogen in 3-monosubstituted s-tetrazines mediated by BF3 is reported. The preference for this azaphilic addition over the usually observed inverse electron demand Diels-Alder reactions was evaluated theoretically and corroborated by experiments. The substrate dependency of this unusual reaction was rationalized by determination of the activation barriers and on the basis of the activation strain model by employing density functional theory.


Characterization of a highly efficient antibiotic-degrading metallo-β-lactamase obtained from an uncultured member of a permafrost community.
Antibiotic resistance is a major global health problem, one that threatens to derail the benefits garnered from arguably the greatest success of modern medicine, the discovery of antibiotics. Among the most potent agents contributing to antibiotic resistance are metallo-β-lactamases (MBLs). The discovery of MBL-like enzymes in microorganisms that are not in contact with the human population is of particular concern as these proteins already have the in-built capacity to inactivate antibiotics, even though they may not need MBL activity for their survival. Here, we demonstrate that a microbiome from a remote and frozen environment in Alaska harbours at least one highly efficient MBL, LRA-8. LRA-8 is homologous to the B3 subgroup of MBLs and has a substrate profile and catalytic properties similar to well-known members of this enzyme family, which are expressed by major human pathogens. LRA-8 is predominantly a penicillinase, but is also active towards carbapenems, but not cephalosporins. Spectroscopic studies indicate that LRA-8 has an active site structure similar to that of other MBLs (in particular B3 subgroup representative AIM-1), and a combination of steady-state and pre-steady-state kinetic data demonstrate that the enzyme is likely to employ a metal ion-bridging hydroxide to initiate catalysis. The rate-limiting step is the decay of a chromophoric, tetrahedral intermediate, as is observed in various other MBLs. Thus, studying the properties of such "pristine" MBL-like proteins may provide insight into the structural plasticity of this family of enzymes that may facilitate functional promiscuity, while important insight into the evolution of MBLs may also be gained.


Artery-only occlusion may provide superior renal preservation during laparoscopic partial nephrectomy.
Artery-only occlusion (AO) has been used during nephron-sparing surgery to reduce ischemic damage. However, this has not been demonstrated in laparoscopic partial nephrectomy (LPN). We compared our experience with AO and both artery and vein occlusion (AV) in LPN to optimize the method of ischemia. This retrospective case-control study identified 25 patients who underwent AO during LPN and matched them to a cohort of 53 patients who underwent LPN with AV. The groups were compared for ischemia time, blood loss, transfusion rate, and renal function. The 2 cohorts were comparable on demographic data. Blood loss was similar, with AO and AV demonstrating equivalent transfusion rates. The 2 cohorts had similar warm ischemia times. Positive margin rate was not affected by venous backflow in the AO cohort (0% AO vs 1.9% AV, P = .679). No significant postoperative change in creatinine (Cr) or creatinine clearance (CrCl) was seen for AO; however, a significant change in Cr and CrCl was seen in AV. AO during LPN does not lead to a greater blood loss or an increased warm ischemia time. The benefit of AO on renal function is significant and requires further investigation.


Styloid-stylohyoid syndrome.
This is a case report of Eagle's syndrome due to osseous metaplasia of the stylohyoid apparatus treated conservatively by injection of a local anesthetic - steroid combination. The incidence, etiopathogenesis, classification, clinical picture and various approaches to treatment of ossified stylohyoid ligament associated with Eagle's syndrome have been discussed. Anterolateral glossodynia, which is a previously unreported finding in Eagle's syndrome, and its possible etiology, has also been discussed.


National Institute for Health and Care Excellence updates the stable chest pain guideline with radical changes to the diagnostic paradigm.
In the 2016 update of the stable chest pain guideline, the National Institute for Health and Care Excellence (NICE) has made radical changes to the diagnostic paradigm that it-like other international guidelines-had previously placed at the centre of its recommendations. No longer are quantitative assessments of the disease probability considered necessary to determine the need for diagnostic testing and the choice of test. Instead, the recommendation is for no diagnostic testing if chest pain is judged to be 'non-anginal' and CT coronary angiography (CTCA) in patients with 'typical' or 'atypical' chest pain with additional perfusion imaging only if there is uncertainty about the functional significance of coronary lesions. The new emphasis on anatomical-as opposed to functional-testing is driven in large part by cost-effectiveness analysis and despite inevitable resource implications NICE calculates that annual savings for the population of England will be significant. In making CTCA the default diagnostic testing strategy in its updated chest pain guideline, NICE has responded emphatically to calls from trialists for CTCA to have a greater role in the diagnostic pathway of patients with suspected angina.


Antiepileptic popular ketogenic diet: emerging twists in an ancient story.
The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.


[Sonographic measurement of gastric emptying time].
Sonography, as a non-invasive procedure, may be used also for studying the gastric emptying time. After 250 ml of a liquid test meal the gastric emptying time was determined in 20 subjects. In each subject the applied test meal could be traced in the prepyloric antrum. When examined at 8.00 a.m. the fluid had left the stomach after an average time of 8.3 min. During the day the emptying time increased to 10.8 min. A second examination on another day after application of 30 mg metoclopramide revealed significantly lower gastric emptying time. Ultrasonography may therefore be used as a sensitive non-invasive method for studying the gastric emptying rate in the fasting state and under pharmacological stimulation.


Role of BGS13 in the Secretory Mechanism of Pichia pastoris.
The methylotrophic yeast Pichia pastoris has been utilized for heterologous protein expression for over 30 years. Because P. pastoris secretes few of its own proteins, the exported recombinant protein is the major polypeptide in the extracellular medium, making purification relatively easy. Unfortunately, some recombinant proteins intended for secretion are retained within the cell. A mutant strain isolated in our laboratory, containing a disruption of the BGS13 gene, displayed elevated levels of secretion for a variety of reporter proteins. The Bgs13 peptide (Bgs13p) is similar to the Saccharomyces cerevisiae protein kinase C 1 protein (Pkc1p), but its specific mode of action is currently unclear. To illuminate differences in the secretion mechanism between the wild-type (wt) strain and the bgs13 strain, we determined that the disrupted bgs13 gene expressed a truncated protein that had reduced protein kinase C activity and a different location in the cell, compared to the wt protein. Because the Pkc1p of baker's yeast plays a significant role in cell wall integrity, we investigated the sensitivity of the mutant strain's cell wall to growth antagonists and extraction by dithiothreitol, determining that the bgs13 strain cell wall suffered from inherent structural problems although its porosity was normal. A proteomic investigation of the bgs13 strain secretome and cell wall-extracted peptides demonstrated that, compared to its wt parent, the bgs13 strain also displayed increased release of an array of normally secreted, endogenous proteins, as well as endoplasmic reticulum-resident chaperone proteins, suggesting that Bgs13p helps regulate the unfolded protein response and protein sorting on a global scale.IMPORTANCE The yeast Pichia pastoris is used as a host system for the expression of recombinant proteins. Many of these products, including antibodies, vaccine antigens, and therapeutic proteins such as insulin, are currently on the market or in late stages of development. However, one major weakness is that sometimes these proteins are not secreted from the yeast cell efficiently, which impedes and raises the cost of purification of these vital proteins. Our laboratory has isolated a mutant strain of Pichia pastoris that shows enhanced secretion of many proteins. The mutant produces a modified version of Bgs13p. Our goal is to understand how the change in the Bgs13p function leads to improved secretion. Once the Bgs13p mechanism is illuminated, we should be able to apply this understanding to engineer new P. pastoris strains that efficiently produce and secrete life-saving recombinant proteins, providing medical and economic benefits.


[Systolic heart failure in the elderly].
Aging is associated with changes in cardiac and vascular structure, promoting the development of heart failure. An increase in vascular stiffness leads to an increase of systolic arterial pressure and pulse wave velocity. This augments the afterload of the heart, which contributes to cardiac hypertrophy and neuroendocrine activation in the elderly. On the molecular level the age-associated changes in the sympathetic nervous system are similar to alterations that can be found in congestive heart failure. Therapy of systolic heart failure does not differ between the elderly and younger patients. All drugs which have shown to improve the prognosis of younger patients are indicated in the elderly as well. This holds true for ACE-inhibitors or angiotensin receptor antagonists, betablockers and aldosterone antagonists. However, comorbidities as well as changes in the pharmacokinetics and pharmacodynamics might require a cautious initiation of the therapy, an individual adjustment of the dosage and a thoroughly monitoring of the elderly patients.


Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds.
Previously, we only apply a traditional Chinese medicine (TCM) Danshen-Chuanxiong-Honghua (DCH) for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA) for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO). We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg) and FA (100 mg/kg) improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.


Emerging Evidence for Infectious Causes of Cancer in the United States.
Worldwide, infectious agents currently contribute to an estimated 15% of new cancer cases. Most of these (92%, or 2 million new cancer cases) are attributable to 4 infectious agents: Helicobacter pylori, human papillomavirus, and hepatitis B and C viruses. A better understanding of how infectious agents relate to the US cancer burden may assist new diagnostic and treatment efforts. We review US-specific crude mortality rates from infection-associated cancers and describe temporal and spatial trends since 1999. We review the US-specific evidence for infection-cancer associations by reporting available estimates for attributable fractions for the infection-cancer associations. Death due to cancers with established infectious associations varies geographically, but estimates for the US attributable fraction are limited to a few observational studies. To describe the burden of infection-associated cancer in the United States, additional observational studies are necessary to estimate the prevalence of infection nationally and within subpopulations. As infectious associations emerge to explain cancer etiologies, new opportunities and challenges to reducing the burden arise. Improved estimates for the United States would help target interventions to higher-risk subpopulations.


Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers.
The combination of atezolizumab and bevacizumab (A + B) is the new standard of care for the systemic first-line treatment of hepatocellular carcinoma (HCC). However, up to now there are only few data on the safety and efficacy of A + B in real life. We included patients with advanced HCC treated with A + B as first-line therapy at four cancer centers in Germany and Austria between December 2018 and August 2021. Demographics, overall survival (OS), and adverse events were assessed until 15 September 2021. We included 66 patients. Most patients had compensated cirrhosis (n = 34; 52%), while Child-Pugh class B cirrhosis was observed in 23 patients (35%), and class C cirrhosis in 5 patients (8%). The best responses included a complete response (CR) in 7 patients (11%), a partial response (PR) in 12 patients (18%), stable disease (SD) in 22 patients (33%), and progressive disease in 11 patients (17%). The median progression-free (PFS) survival was 6.5 months, while the median overall survival (OS) was not reached in this cohort (6-month OS: 69%, 12-month OS: 60%, 18-month OS: 58%). Patients with viral hepatitis seemed to have a better prognosis than patients with HCC of non-viral etiology. The real-world PFS and OS were comparable to those of the pivotal IMBRAVE trial, despite including patients with worse liver function in this study. We conclude that A + B is also highly effective in a real-life setting, with manageable toxicity, especially in patients with compensated liver disease. In patients with compromised liver function (Child B and C), the treatment showed low efficacy and, therefore, it should be well considered before administration to these patients.


[Research Progress of Indocyanine Green Fluorescence Laparoscopic Technique in Clinical Application].
Indocyanine green (ICG) is the most commonly used near-infrared fluorescent (NIRF) dye in clinical practice, and its mediated near-infrared fluorescence imaging technology is gradually applied in clinical practice. It has shown great potential in invasive surgery (MIS) and is expected to become the standard technology for surgical diagnosis and treatment of diseases. The clinical application of ICG fluorescence laparoscopy is reviewed here.


Modification of nerve growth factor receptor properties by wheat germ agglutinin.
PC12 is a nerve growth factor (NGF) responsive cell line which exhibits two classes of NGF receptors distinguishable by different kinetic rate constants, sensitivity to trypsin and resistance to Triton detergent solubilization. Whereas incubation of PC12 cells with wheat germ agglutinin (WGA) prior to addition of 125I-NGF inhibits binding of NGF to both classes of receptors, treatment with WGA subsequent to incubation with NGF does not inhibit NGF binding but causes the class of NGF receptors which exhibit rapid or "Fast" dissociation kinetics prior to lectin treatment to be converted to the form which exhibits "Slow" dissociation kinetics. This WGA-mediated receptor conversion is lectin specific, blocked by N-acetyl-D-glucosamine, occurs at similar rates at 4 and 37 degrees C, and is not impaired by a metabolic poison. NGF receptors converted by WGA, like pre-existing Slow receptors, are resistant to trypsinization and remain associated to Triton X-100 extracted "cytoskeletons." Very similar results were obtained for NGF receptors on a human melanoma cell line A875. These results suggest that Fast and Slow receptors are two interconvertible forms of a single protein, rather than distinct proteins. The significance of the generality of these properties for NGF receptors from diverse species and cell types is discussed.


An investigation into the origins of a series of PM10 anomalies at a remote location in NW England.
Throughout 2004, PM(10) concentrations were measured at 10 min intervals at Hazelrigg, a remote location in NW England. The annual mean concentration was 6.1 microg m(-3) and likely origins were determined using directional and particle size characteristics. The fine temporal resolution of the monitoring also allowed several short periods (< 20 h) of persistently high PM(10) concentration to be identified and then 'typed' by event start time, duration, wind direction and particle size characteristics. A series of night time PM(10) anomalies (concentration < 465 microg m(-3)) of no obvious source were identified, and by elimination assumed to have originated from a ground-based fire of particle-rich fodder. A novel methodology combining Stokes' Law with systematic and rigorous modelling of source strength (using ADMS3.2) was developed to locate a possible burn site. The process was limited by the lack of previous modelling studies related to ground-based fires, and also by the capacity of ADMS3.2 to model sub-hourly time-varying emissions and fluctuations in wind speed and direction in the near field. However, modelling did suggest the source was located <400 m SSE of Hazelrigg, and investigation of this area revealed a burn site where tyres and plastic bags were piled nearby. Few studies have combined directional analysis and modelling to locate a source based on sampled data. This innovative methodology could be used by regulatory bodies to investigate the origins of unidentified PM(10) observed within the particle record.


The intention interference effect.
Intentions have been shown to be more accessible (e.g., more quickly and accurately recalled) compared to other sorts of to-be-remembered information; a result termed an intention superiority effect (Goschke & Kuhl, 1993). In the current study, we demonstrate an intention interference effect (IIE) in which color-naming performance in a Stroop task was slower for words belonging to an intention that participants had to remember to carry out (Do-the-Task condition) versus an intention that did not have to be executed (Ignore-the-Task condition). In previous work (e.g., Cohen et al., 2005), having a prospective intention in mind was confounded with carrying a memory load. In Experiment 1, we added a digit-retention task to control for effects of cognitive load. In Experiment 2, we eliminated the memory confound in a new way, by comparing intention-related and control words within each trial. Results from both Experiments 1 and 2 revealed an IIE suggesting that interference is very specific to the intention, not just to a memory load.


Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma.
Evading antitumor immune responses is an important aspect of the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Invariant CD1d-restricted natural killer T (iNKT) cells play an allegedly pivotal role in such responses via transactivation of immune effector cells. It has been reported that iNKT cells are reduced in peripheral blood of cancer patients compared with healthy controls. Here, we investigated whether the extent of this deficiency affected disease outcome in HNSCC patients. In a prospective study, circulating iNKT cell numbers were evaluated in 47 patients before radiotherapy. Patients were stratified in three groups based on iNKT cell levels, and clinical data were obtained during a median follow-up period of 31 months. A small, compared with an intermediate or large, circulating iNKT cell fraction was significantly associated with decreased 3-year overall survival rate (39% v 75% and 92%, respectively), disease-specific survival rate (43% v 87% and 92%, respectively), and locoregional control rate (31% v 74% and 92%, respectively) in HNSCC patients. Cox regression revealed that the iNKT cell level, as well as clinical T stage, was an independent prognostic parameter even after correction for the confounding effect of age. A severe circulating iNKT cell deficiency was related to poor clinical outcome in HNSCC patients, suggesting their critical contribution to antitumor immune responses. Furthermore, screening for iNKT cell levels may be useful for determining which patients can benefit from immunotherapeutic adjuvant therapies aimed at reconstitution of the circulating iNKT cell pool.


Retention of colonoscopy skills after virtual reality simulator training by independent and proctored methods.
Virtual reality (VR) simulators may enhance surgical resident colonoscopy skills, but the duration of skill retention and the effects of different simulator training methods are unknown. Medical students participating in a randomized trial of independent (automated simulator feedback only) versus proctored (human expert feedback plus simulator feedback) simulator training performed a standardized VR colonoscopy scenario at baseline, at the end of training (posttraining), and after a median 4.5 months without practice (retention). Performances were scored on a 10-point scale based on expert proficiency criteria and compared for the independent and proctored groups. Thirteen trainees (8 proctored, 5 independent) were included. Performance at retention testing was significantly better than baseline (median score 10 vs. 5, P < 0.0001), and no different from posttraining (median score 10 vs. 10, P = 0.19). Score changes from baseline to retention and from posttraining to retention were no different for the proctored and independent groups. Overinsufflation and excessive force were the most common reasons for nonproficiency at retention. After proficiency-based VR simulator training, colonoscopy skills are retained for several months, regardless of whether an independent or proctored approach is used. Error avoidance skills may not be retained as well as speed and efficiency skills.


Economic regulation and hospital behavior: the effects on medical staff organization and hospital-physician relationships.
New forms of payment, growing competition, the continued evolution of multiunit hospital systems, and associated forces are redefining the fundamental relationship between hospitals and physicians. As part of a larger theory of organizational response to the environment, the effects of these external forces on hospital-medical staff organization were examined using both cross-sectional data and data collected at two points in time. Findings suggest that regulation and competition, at least up to 1982, have had relatively little direct effect on hospital medical staff organization. Rather, changes in medical staff organization are more strongly associated with hospital case mix and with structural characteristics involving membership in a multiunit system, size, ownership, and location. The pervasive effect of case mix and the consistent effect of multiunit system involvement support the need for policymakers to give these factors particular attention in considering how hospitals and their medical staffs might respond to future regulatory and/or competitive approaches.


[Adult T-cell leukemia/lymphoma].
Adult T-cell leukemia/lymphoma (ATL) is an extremely refractory peripheral T-cell lymphoma that develops after persistent human T-lymphotropic virus type 1 (HTLV-1) infection. In recent years, the number of HTLV-1 carriers has decreased due to lifestyle changes and different measures. Rapid progression in comprehensive genetic analysis techniques has revealed the molecular basis of ATL. Therefore, in addition to conventional prognostic indices based on clinical parameters, prognostic indices incorporating genetic mutations have been proposed. The standard treatment for untreated aggressive ATL is combination chemotherapy such as VCAP-AMP-VECP or CHOP, followed by allogeneic hematopoietic stem cell transplantation, as appropriate. Combined mogamulizumab and chemotherapy is a promising first-line treatment option for patients not eligible for transplantation. Salvage treatment with lenalidomide, brentuximab vedotin, tucidinostat, and valemetostat, in addition to mogamulizumab, has been introduced over the last decade. Advancements in allogeneic transplantation therapy, including early induction and transplantation with post-transplant cyclophosphamide for GVHD prophylaxis, have also improved patient outcomes. This article highlights recent developments in the field of ATL.


Hip fracture prevention trial using hip protectors in Japanese nursing homes.
A method to protect the hips during falls could effectively reduce the incidence of hip fractures. We report the results of the first hip protector trial in Japan, performed between July 1996, and September 1999. One hundred and sixty-four elderly female residents of nursing homes, with Activities of Daily Living above the wheelchair level, agreed to participate in this study. Among them, 88 were randomly selected to wear a hip protector and 76 controls did not. All falls and resulting injuries were recorded daily. In anthropometric measurements and ultrasonic bone evaluation, no significant differences were found between the two groups, except in height. During an average of 377 days, the wearers and the non-wearers fell a total of 131 and 90 times, respectively. Among the wearers, there were two non-hip fractures and one hip fracture, so the annual hip fracture rate was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7% per year. The hip fracture rate was significantly lower among the wearers than non-wearers, while the annual number of falls per subject and the distribution of fallers remained the same. According to Cox's proportional hazard regression analysis, the effect of the hip protector on hip fracture prevention was independent of anthropometric data, ultrasonic bone assessment values or number of falls. Moreover, even after limiting the subjects to fallers only, the annual hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a beneficial device for the prevention of hip fractures.


Graft and quality of life outcomes in older recipients of a kidney transplant.
It is well recognized that kidney transplants significantly improve quality of life for patients with end-stage renal disease (ESRD). This benefit is not as clearly documented for older recipients as it is for younger recipients. We looked at outcomes, both medical and psychosocial, in a group of older (> or =65 years) kidney transplant recipients and compared the results to a group of younger recipients (18 to 64 years). From 1990 through 2002, we performed 2,746 kidney transplants at our center: 2,596 (94.5%) in recipients 18 to 64 years old and 150 (5.5%) in recipients 65 years or older. In our retrospective analysis, we determined outcomes such as patient and graft survival rates. To determine whether or not older recipients had an improved health-related quality of life, we used the national SF-36 (short form) questionnaire. We compared those results with a group of younger recipients and with national age-appropriate norms. The mean recipient age was 69.1 years in the older group vs. 42.8 years in the younger group (p < 0.001). Living donors were used in 43.3% of the transplants in the older group vs. 47.5% in the younger group (p < 0.01). At 5 years posttransplant, patient and graft survival rates were 73% and 68% in the older group vs. 86% and 79% in the younger group (p < 0.001). We analyzed the SF-36 responses for all recipients with completed forms: 42 completed forms from the older group vs. 149 from the younger group. The overall benefit to quality of life was similar for both groups. General physical health was rated slightly higher than national norms in both groups. Benefits to mental health were more pronounced in the older group. Kidney transplants can be performed in older recipients with acceptable outcomes. Such recipients enjoy significant benefits to their quality of life after a transplant, similar to benefits seen in younger recipients. Older age, by itself, should not be a contraindication to a transplant.


Inflammatory, Oxidative Stress, and Angiogenic Growth Factor Responses to Repeated-Sprint Exercise in Hypoxia.
The present study was designed to determine the effects of repeated-sprint exercise in moderate hypoxia on inflammatory, muscle damage, oxidative stress, and angiogenic growth factor responses among athletes. Ten male college track and field sprinters [mean ± standard error (SE): age, 20.9 ± 0.1 years; height, 175.7 ± 1.9 cm; body weight, 67.3 ± 2.0 kg] performed two exercise trials in either hypoxia [HYPO; fraction of inspired oxygen (FiO2), 14.5%] or normoxia (NOR; FiO2, 20.9%). The exercise consisted of three sets of 5 s × 6 s maximal sprints with 30 s rest periods between sprints and 10 min rest periods between sets. After completing the exercise, subjects remained in the chamber for 3 h under the prescribed oxygen concentration (hypoxia or normoxia). The average power output during exercise did not differ significantly between trials (p = 0.17). Blood lactate concentrations after exercise were significantly higher in the HYPO trial than in the NOR trial (p < 0.05). Plasma interleukin-6 concentrations increased significantly after exercise (p < 0.01), but there was no significant difference between the two trials (p = 0.07). Post-exercise plasma interleukin-1 receptor antagonist, serum myoglobin, serum lipid peroxidation, plasma vascular endothelial growth factor (VEGF), and urine 8-hydroxydeoxyguanosine concentrations did not differ significantly between the two trials (p > 0.05). In conclusion, exercise-induced inflammatory, muscle damage, oxidative stress, and VEGF responses following repeated-sprint exercise were not different between hypoxia and normoxia.


Refining Immunogenicity through Intradermal Delivery of Outer Membrane Vesicles against Shigella flexneri in Mice.
Shigellosis remains a global health concern, especially in low- and middle-income countries. Despite improvements in sanitation, the absence of a licensed vaccine for human use has prompted global health organizations to support the development of a safe and effective multivalent vaccine that is cost-effective and accessible for limited-resource regions. Outer Membrane Vesicles (OMVs) have emerged in recent years as an alternative to live attenuated or whole-inactivated vaccines due to their immunogenicity and self-adjuvating properties. Previous works have demonstrated the safety and protective capacity of OMVs against Shigella flexneri infection in mouse models when administered through mucosal or intradermal routes. However, some immunological properties, such as the cellular response or cross-protection among different Shigella strains, remained unexplored. In this study, we demonstrate that intradermal immunization of OMVs with needle-free devices recruits a high number of immune cells in the dermis, leading to a robust cellular response marked by antigen-specific cytokine release and activation of effector CD4 T cells. Additionally, functional antibodies are generated, neutralizing various Shigella serotypes, suggesting cross-protective capacity. These findings highlight the potential of OMVs as a promising vaccine platform against shigellosis and support intradermal administration as a simple and painless vaccination strategy to address this health challenge.


Ω-3 index as a prognosis tool in cardiovascular disease.
In 2004, the 'Ω-3 index' was described as the sum of eicosapentaenoic acid (EPA, 20 : 5 n-3) and docosahexaenoic acid (DHA, 22 : 6 n-3) in red blood cells (RBCs) as an index of coronary heart disease mortality. This review outlines new evidence to support the Ω-3 index as a tool to inform disease prognosis. Recent studies have reported differential metabolism of EPA and DHA. High-dose supplementation with EPA and DHA led to increased levels of RBC DHA that were associated with decreased liver fat. EPA and DHA in RBCs were associated with reduced mortality in a prospective study of patients with cardiac disease; the strongest association was with EPA. A diet containing 9.5-g α-linolenic acid lead to an increase in EPA but not DHA status in middle-aged women. Dietary intake or supplementation studies with n-3 fatty acids should include measurement of n-3 status in a standardized way. The Ω-3 index, reflecting EPA and DHA status throughout the body, is convenient and may be appropriate in some cases, but as EPA and DHA assimilate differently in membranes, and have different potency, measurement of individual fatty acid composition in RBCs may be more informative.


Combined Treatments of High Hydrostatic Pressure and CO2 in Coho Salmon (Oncorhynchus kisutch): Effects on Enzyme Inactivation, Physicochemical Properties, and Microbial Shelf Life.
This study focused on applying different high hydrostatic pressure + carbon dioxide (HHP + CO2) processing conditions on refrigerated (4 °C, 25 days) farmed coho salmon (Oncorhynchus kisutch) to inactivate endogenous enzymes (protease, lipase, collagenase), physicochemical properties (texture, color, lipid oxidation), and microbial shelf life. Salmon fillets were subjected to combined HHP (150 MPa/5 min) and CO2 (50%, 70%, 100%). Protease and lipase inactivation was achieved with combined HHP + CO2 treatments in which lipase activity remained low as opposed to protease activity during storage. Collagenase activity decreased approximately 90% during storage when applying HHP + CO2. Combined treatments limited the increase in spoilage indicators, such as total volatile amines and trimethylamine. The 150 MPa + 100% CO2 treatment was the most effective at maintaining hardness after 10 days of storage. Combined treatments limited HHP-induced color change and reduced the extent of changes caused by storage compared with the untreated sample. Microbial shelf life was extended by the CO2 content and not by the HHP treatments; this result was related to an increased lag phase and decreased growth rate. It can be concluded that combining HHP and CO2 could be an effective method of inactivating endogenous enzymes and extend salmon shelf life.


[Spontaneous cytomegalovirus infection of kidney cell cultures of green monkeys].
In subcultivation of 104 batches of primary kidney cell cultures from clinically normal green monkeys 66 batches (47%) showed cytopathic changes indicating spontaneous virus contamination of the cultures. Sixty-six strains were isolated and the properties of 23 cytopathic strains were studied. Electron microscopic examinations of 6 virus isolates identified them as members of the herpesvirus group. Serological examinations of 335 clinically normal green monkeys demonstrated antibodies to one of our virus isolates (No. 8532) in 192 (57.3%) animals. Virus strain 8532 was neutralized by antiserum to green monkey cytomegalovirus M-1. The isolates obtained in the present study exhibit the properties previously unknown for green monkey cytomegalovirus such as the capacity for replication in rabbit, sheep, cow, and piglet cell cultures.


Macroscopic Alignment and Assembly of π-Conjugated Oligopeptides Using Colloidal Microchannels.
One-dimensional (1-D) supramolecular self-assembly offers a powerful strategy to achieve long-range unidirectional ordering of organic semiconducting materials via noncovalent interactions. Using a hierarchical assembly, electronic and optoelectronic materials can be constructed for applications including organic conducting nanowires, organic field-effect transistors (OFETs), and organic light-emitting devices (OLEDs). Despite recent progress, it remains challenging to precisely align and assemble 1-D structures over large areas in a rapid and straightforward manner. In this work, we demonstrate a facile strategy to macroscopically align supramolecular fibers using a templating method based on sacrificial colloidal microchannels. Through use of this approach, colloidal microchannels are generated on a solid surface using a simple fabrication method, followed by the spontaneous self-assembly of π-conjugated oligopeptides inside large arrays of microchannels triggered by solvent evaporation. Following oligopeptide assembly and removal of sacrificial microchannels, the structural properties of oligopeptide fibers were characterized using atomic force microscopy (AFM), atomic force microscope-infrared spectroscopy (AFM-IR), photoinduced force microscopy (PiFM), fluorescence polarization microscopy, and electron microscopy. These results reveal the macroscopic alignment of oligopeptide fibers into ordered structures over millimeter length scales, facilitated by colloidal microchannel templating. In addition, the charge transport properties (I-V curves) of π-conjugated oligopeptides assembled using this method were determined under a wide range of applied voltages using interdigitated array electrodes and conductive AFM. Overall, this work illustrates a simple yet robust strategy to pattern 1-D supramolecular fibers over large areas, thereby offering new routes for assembling materials for organic electronics.


Quantitative planar imaging method for measurement of renal activity by using a conjugate-emission image and transmission data.
We are proposing a method to accurately measure renal activity in renography using Tc-99m labeled tracers. This method uses a conjugate-view image and transmission data for attenuation correction, the triple energy window (TEW) method for scatter correction, and background correction techniques that consider the source volume for accurate background activity correction. To examine this method in planar imaging, we performed two renal phantom studies with various uniform background activity concentrations. One study used two ideal box-shaped kidney phantoms with a thickness of 2 or 4 cm in a water tank and the other study employed two real kidney-shaped phantoms in a fillable abdominal cavity. For these studies the kidney phantom-to-background activity concentration ratio (S) was changed from 5 to infinity. The transmission data were obtained with an external Tc-99m line array source. The anterior- and posterior-view emission images were acquired with a dual-headed gamma camera simultaneously and the TEW method was used to correct scatter for the emission and transmission images. The results showed that this method with both the accurate background correction and scatter correction could give depth-independent count rates and could estimate the true count rate with errors of less than 5% for all S values. However, if either accurate background correction or scatter correction was performed alone, the absolute error increased to about 50% for the smaller S values. Our proposed method allows one to accurately and simply measure the renal radioactivity by planar imaging using the conjugate-emission image and transmission data.


Effect of Oxygen Mole Fraction on Static Properties of Pressure-Sensitive Paint.
The effects of the oxygen mole fraction on the static properties of pressure-sensitive paint (PSP) were investigated. Sample coupon tests using a calibration chamber were conducted for poly(hexafluoroisopropyl methacrylate)-based PSP (PHFIPM-PSP), polymer/ceramic PSP (PC-PSP), and anodized aluminum PSP (AA-PSP). The oxygen mole fraction was set to 0.1-100%, and the ambient pressure (Pref) was set to 0.5-140 kPa. Localized Stern-Volmer coefficient Blocal increased and then decreased with increasing oxygen mole fraction. Although Blocal depends on both ambient pressure and the oxygen mole fraction, its effect can be characterized as a function of the partial pressure of oxygen. For AA-PSP and PHFIPM-PSP, which are low-pressure- and relatively low-pressure-type PSPs, respectively, Blocal peaks at PO2ref<12 kPa. In contrast, for PC-PSP, which is an atmospheric-pressure-type PSP in the investigated range, Blocal does not have a peak. Blocal has a peak at a relatively high partial pressure of oxygen due to the oxygen permeability of the polymer used in the binder. The peak of SPR, which is the emission intensity change with respect to normalized pressure fluctuation, appears at a lower partial pressure of oxygen than that of Blocal. This is because the intensity of PSP becomes quite low at a high partial pressure of oxygen even if Blocal is high. Hence, the optimal oxygen mole fraction depends on the type of PSP and the ambient pressure range of the experiment. This optimal value can be found on the basis of the partial pressure of oxygen.


Linear and nonlinear elastic modulus imaging: an application to breast cancer diagnosis.
We reconstruct the in vivo spatial distribution of linear and nonlinear elastic parameters in ten patients with benign (five) and malignant (five) tumors. The mechanical behavior of breast tissue is represented by a modified Veronda-Westmann model with one linear and one nonlinear elastic parameter. The spatial distribution of these elastic parameters is determined by solving an inverse problem within the region of interest (ROI). This inverse problem solution requires the knowledge of the displacement fields at small and large strains. The displacement fields are measured using a free-hand ultrasound strain imaging technique wherein, a linear array ultrasound transducer is positioned on the breast and radio frequency echo signals are recorded within the ROI while the tissue is slowly deformed with the transducer. Incremental displacement fields are determined from successive radio-frequency frames by employing cross-correlation techniques. The rectangular regions of interest were subjectively selected to obtain low noise displacement estimates and therefore were variables that ranged from 346 to 849.6 mm2 . It is observed that malignant tumors stiffen at a faster rate than benign tumors and based on this criterion nine out of ten tumors were correctly classified as being either benign or malignant.


Impact of intrauterine and post-natal nutritional determinants on blood pressure at 4 years of age.
To prospectively study how the early nutritional environment can programme blood pressure in a well-nourished population of children. By means of multivariate modelling, we assessed whether gestational and post-natal dietary intakes and growth influence childhood blood pressure programming in a cohort of 109 healthy mother-child pairs. They had been followed from early pregnancy until the children reached 4 years of age. Dietary intakes were evaluated using 3-day food diaries. Blood pressure levels in the children were measured using an automated oscillometric DINAMAP ProCare 100 (Criticon, Tampa, FL, USA) at the age of 4 years. In the final multivariate model, the predictor variables of childhood systolic blood pressure were maternal dietary carbohydrate and fat intake during pregnancy, as well as childhood weight and dietary fat intake at 4 years of age. Systolic blood pressure levels in the children were found to be positively associated with the maternal carbohydrate intake (P = 0.003), whereas blood pressure levels were lowest in children exposed to the middle tertile of maternal dietary fat intake during pregnancy (P = 0.003) and whose own dietary fat intake was in the middle tertile at the age of 4 years (P = 0.013). The model also showed that heavier children have a higher systolic blood pressure (P < 0.001). None of the maternal clinical characteristics fulfilled the criterion to be included in the model. The only determinant underlying childhood diastolic blood pressure was childhood weight at 4 years of age (r = 0.289, P = 0.026). Interventions focusing on cardiovascular health in young women during pregnancy and their children should be considered to reduce cardiovascular diseases risk factors in these children.


Meta-analysis of the association between the inflammatory potential of diet and colorectal cancer risk.
The inflammatory potential of diet has been inconsistently linked to colorectal cancer (CRC) risk. This meta-analysis aimed to evaluate the association of the inflammatory potential of diet, as estimated by the dietary inflammatory index (DII) score, with CRC risk. The PubMed and Embase databases were searched for relevant studies from inception to February 2017. All cohort and case-control studies investigating the association of the DII score with CRC risk were selected. Four prospective cohorts and four case-control studies, which enrolled a total of 880,380 participants, were included. The pooled adjusted risk ratio (RR) of CRC for the highest DII score versus the lowest category was 1.43 (95% confidence interval [CI]: 1.26-1.62). When stratified by study design, the RRs for the case-control and cohort studies were 1.27 (95% CI: 1.16-1.38) and 1.81 (95% CI: 1.48-2.22), respectively. Subgroup analysis showed that individuals with the highest category of DII score were independently associated with CRC risk in men (RR=1.51; 95% CI: 1.29-1.76), women (RR=1.25; 95% CI: 1.10-1.41), colon cancer (RR=1.39; 95% CI: 1.19-1.62), and rectal cancer (RR=1.32; 95% CI: 1.01-1.74). However, the pooled RR was 1.07 (95% CI: 0.87-1.31) for rectal cancer among the prospective cohort studies. As estimated by a high DII score, pro-inflammatory diet is independently associated with increased CRC risk. This finding confirms that low inflammatory potential diet may reduce CRC risk. However, the gender- and cancer site-specific associations of the DII score with CRC risk need to be further investigated.