Influence of phosphodiesterases on basal and 5-HT₄ receptor facilitated cholinergic contractility in pig descending colon.
This study in pig colon descendens circular muscle investigated the possible role of phosphodiesterases (PDEs) (1) in the control of smooth muscle activity and (2) in the signal transduction of the 5-HT₄ receptors located on the cholinergic neurons. Submaximal cholinergic contractions were electrically induced in colonic circular muscle strips and the influence of the non-selective PDE inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) and selective inhibitors for the 5 classic PDE families (1-5) vinpocetine (PDE1), EHNA (PDE2), cilostamide (PDE3), rolipram (PDE4) and zaprinast (PDE5) was evaluated. IBMX and cilostamide concentration-dependently reduced the amplitude of the cholinergic contractions, as good as abolishing them at 30 and 0.3 μM respectively. EHNA only reduced the contractions significantly at the highest concentration tested (30 μM). IBMX and cilostamide also concentration-dependently inhibited submaximal cholinergic contractions induced with the muscarinic receptor agonist carbachol. The 5-HT₄ receptor agonist prucalopride (1 μM) significantly enhanced the electrically induced cholinergic contractions. IBMX, vinpocetine and EHNA did not influence the facilitating effect of prucalopride but rolipram tended to enhance it. When rolipram was added after prucalopride, the facilitating effect of prucalopride was significantly enhanced. These results suggest that PDE3 is the main regulator of circular smooth muscle activity and that the signal transduction of 5-HT₄ receptors on the cholinergic nerves towards the circular muscle layer is regulated by PDE4 in pig colon descendens.


Small intestinal obstruction due to the metastasis of intrahepatic cholangiocarcinoma: A case report.
The small intestine (SI) does not commonly harbor cancer but is occasionally involved by metastatic cancer from other organs. To manage SI cancer appropriately, surveillance for primary origin outside the SI is essential. This study presents a 54-year-old Thai man diagnosed with SI obstruction which required laparoscopy- assisted partial ileal resection. On the basis of the expression pattern of cytokeratins (CKs) and mucins (MUCs) in the resected SI adenocarcinoma, we suspected this was metastasized from the pancreatobiliary tract. Imaging studies revealed a hepatic segmental atrophy with an occlusion of the posterior segmental blanch of the portal vein without any contrast-enhanced lesions in the liver. Pathology of the liver biopsy revealed intrahepatic cholangiocarcinoma (ICC) with the same expression pattern of CKs and MUCs as the SI adenocarcinoma. Systemic chemotherapy (gemcitabine and cisplatin) was initiated. Despite of the chemotherapy for 20 months, he died of ICC. This is the first case of SI obstruction caused by the metastasis of ICC. We demonstrate that immunohistochemical staining of CKs and MUCs discriminate between primary and metastatic SI cancer and predict its primary origin outside the SI. This case also suggests that a hepatic segmental atrophy with portal vein occlusion would be an atypical but important finding to diagnose ICC.


[Primary malignant lymphomas of the gastrointestinal system].
The Authors describe their experience regarding eight cases of primary malignant gastrointestinal lymphomas. After having briefly reexamined the epidemiology and the problems coming from the discordances that still exist on various systems of classification and of staging, they put in evidence that it is not always possible to reach a sure preoperative diagnosis on such pathology, and they explain some considerations about the diagnosis, the therapy and the prognosis.


Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry to identify patients with chronic obstructive pulmonary disease.
There are currently no blood tests to identify the majority of smokers at risk for chronic obstructive pulmonary disease (COPD). We used plasma protein profiles from surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry to identify a panel of protein biomarkers that can distinguish patients with COPD from closely matched controls. Plasma was obtained from 30 COPD subjects and 30 controls matched for age, sex, and smoking history. Plasma protein profiles were generated using Cu2+-immobilized metal affinity capture (IMAC) and strong anion exchanger (Q10) protein chips. Classification and regression tree (CART) analysis identified a panel of 5 biomarkers using the IMAC protein chip that could distinguish COPD patients from controls with sensitivity and specificity of 91.67% and 88.33%, respectively. The 10-fold cross-validation yielded 81.67% sensitivity and 81.67% specificity. This demonstrates the feasibility of using SELDI as a diagnostic test for COPD; however, larger cohorts will be needed to validate these biomarkers and determine their predictive value longitudinally.


[Disorders in mucociliary transport. Primary ciliary dyskinesia].
A survey is given of the mucociliary transport in the airways. Disturbances in rheologic qualities (viscosity and elasticity) of the mucuslayer may adversely influence mucociliary transport. This plays a role in cystic fibrosis and chronic bronchitis of other etiology. Disturbances in ciliary action can be secondary to for instance viral infections, inhalated substances and drugs. Inborn errors in the architecture of the cilia may cause immotility or ineffective motility of cilia, resulting in frequent airway infections. The clinical characteristics, diagnostic possibilities and a proposal for therapeutic measures are discussed.


Advances with RNA interference in Alzheimer's disease research.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized clinically by memory and cognitive dysfunction. Unfortunately, there is no effective therapeutic method for AD treatment or ways to halt disease progression. Many mechanisms are involved in the disease, including genes mutation and protein dysfunction. RNA interference (RNAi) technology may potentially be able to control AD. It can inhibit the protein expression of specific genes by activating a sequence-specific RNA degradation process. This is a powerful tool with which to study gene function, investigate the mechanism of the disease, and validate drug targets. In this review, we highlight the advances in RNAi technology in the investigation and treatment of AD.


Pulsed laser deposition chamber for in situ X-ray diffraction.
A sample chamber has been constructed for studying the growth of thin films by pulsed laser deposition in situ with surface X-ray diffraction. The achievable temperature ranges from room temperature to 1073 K in a controlled oxygen environment. The partial pressure of the oxygen background gas covers the range from 0.1 to 10(5) Pa. The first results, showing intensity oscillations in the diffracted signal during homoepitaxial deposition of SrTiO(3), are presented.


Determination of Acid Herbicides Using Modified QuEChERS with Fast Switching ESI(+)/ESI(-) LC-MS/MS.
A method for the determination of 35 acid herbicides in food matrices was developed, validated, and implemented. It utilizes a modified QuEChERS extraction procedure coupled with quantitation by liquid chromatography tandem mass spectrometry (LC-MS/MS). The acid herbicides analyzed are all organic carboxylic acids, including the older chlorophenoxy acid herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D), dicamba, 4-chlorophenoxyacetic acid (4-CPA), quinclorac, and many of the newer imidazolinone herbicides such as imazethapyr and imazaquin. In the procedure, 10 mL of water is added to 5 g of sample and then extracted with 1% formic acid in acetonitrile for 1 min. The acetonitrile phase is salted out of the extract by adding sodium chloride and magnesium sulfate, followed by centrifugation. The acetonitrile is diluted 1:1 with water to enable quantitation by LC-MS/MS using fast switching between positive and negative electrospray ionization modes. The average recoveries for all the compounds except aminocyclopyrachlor were 95% with a precision of 8%. The method detection limits for all residues were less than 10 ng/g, and the correlation coefficients for the calibration curves was greater than 0.99 for all but two compounds tested. The method was used successfully for the quantitation of acid herbicides in the FDA's total diet study. The procedure proved to be accurate, precise, linear, sensitive, and rugged.


ECKN: An Integrated Approach for Position Estimation, Packet Routing, and Sleep Scheduling in Wireless Sensor Networks.
Network lifetime and localization are critical design factors for a number of wireless sensor network (WSN) applications. These networks may be randomly deployed and left unattended for prolonged periods of time. This means that node localization is performed after network deployment, and there is a need to develop mechanisms to extend the network lifetime since sensor nodes are usually constrained battery-powered devices, and replacing them can be costly or sometimes impossible, e.g., in hostile environments. To this end, this work proposes the energy-aware connected k-neighborhood (ECKN): a joint position estimation, packet routing, and sleep scheduling mechanism. To the best of our knowledge, there is a lack of such integrated solutions to WSNs. The proposed localization algorithm performs trilateration using the positions of a mobile sink and already-localized neighbor nodes in order to estimate the positions of sensor nodes. A routing protocol is also introduced, and it is based on the well-known greedy geographic forwarding (GGF). Similarly to GGF, the proposed protocol takes into consideration the positions of neighbors to decide the best forwarding node. However, it also considers node residual energy in order to guarantee the forwarding node will deliver the packet. A sleep scheduler is also introduced in order to extend the network lifetime. It is based on the connected k-neighborhood (CKN), which aids in the decision of which nodes switch to sleep mode while keeping the network connected. An extensive set of performance evaluation experiments was conducted and results show that ECKN not only extends the network lifetime and localizes nodes, but it does so while sustaining the acceptable packet delivery ratio and reducing network overhead.


Effect of injection rate on contrast-enhanced MR angiography image quality: Modulation transfer function analysis.
Contrast-enhanced (CE)-MRA optimization involves interactions of sequence duration, bolus timing, contrast recirculation, and both R1 relaxivity and R2*-related reduction of signal. Prior data suggest superior image quality with slower gadolinium injection rates than typically used. A computer-based model of CE-MRA was developed, with contrast injection, physiologic, and image acquisition parameters varied over a wide gamut. Gadolinium concentration was derived using Verhoeven's model with recirculation, R1 and R2* calculated at each time point, and modulation transfer curves used to determine injection rates, resulting in optimal resolution and image contrast for renal and carotid artery CE-MRA. Validation was via a vessel stenosis phantom and example patients who underwent carotid CE-MRA with low effective injection rates. Optimal resolution for renal and carotid CE-MRA is achieved with injection rates between 0.5 to 0.9 mL/s and 0.2 to 0.3 mL/s, respectively, dependent on contrast volume. Optimal image contrast requires slightly faster injection rates. Expected signal-to-noise ratio varies with both contrast volume and cardiac output. Simulated vessel phantom and clinical carotid CE-MRA exams at an effective contrast injection rate of 0.4 to 0.5 mL/s demonstrate increased resolution. Optimal image resolution is achieved at intuitively low, effective injection rates (0.2-0.9 mL/s, dependent on imaging parameters and contrast injection volume). Magn Reson Med 78:357-369, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


An anion-controlled crystal growth route to Zn2GeO4 nanorods for efficient photocatalytic conversion of CO2 into CH4.
For photoreduction of CO2 into solar fuels driven by photocatalysis, a means to convert solar energy into chemical energy, a semiconductor photocatalyst with a specific crystal surface and high chemical stability is expected to achieve high activity and selectivity. Here, (110) facets exposed Zn2GeO4 nanorods with different aspect ratios were prepared by the ion exchange reaction between Na2GeO3 colloidal solution and various zinc salt solutions. The aspect ratio of Zn2GeO4 can be adjusted in the wide range from 2.5:1 to 20:1, depending on the acid radical. In this synthetic route, the Na2GeO3 precursor is a strong base, but strong acids such as HCl, HNO3 and H2SO4 as by-products were formed, meaning that the Zn2GeO4 single-crystal nanorods have good chemical stability in acid as well as in base. The excellent hydrothermal stability for the Zn2GeO4 nanorods in NaOH solution provides a simple method to obtain a hydroxylated surface for high performance in the photocatalytic conversion of CO2 and H2O to hydrocarbons fuels.


[Therapeutic Drug Monitoring of Antimicrobial Agents].
Antimicrobial dosing can be targeted to achieve pharmacokinetic (PK) -pharmacodynamic parameters at the minimal inhibitory concentration of bacteria. Therapeutic drug monitoring (TDM) of glycopetides [vanco- mycin (VCM) and teicoplanin] and aminoglycosides (gentamicin, tobramycin, and amikacin) makes it possible to optimize dosing in individual patients. TDM of these antimicrobials can improve clinical outcomes, de- crease adverse events, and reduce costs. Therefore, PK-monitoring for VCM and aminoglycosides is rec- ommended in the Antimicrobial Stewardship Program implementing guidelines developed by the Infectious Disease Society of America and the Society for Healthcare Epidemiology of America in 2016. In addition, Clinical practice guidelines for TDM have been developed by the Japanese Society of Chemotherapy and the Japanese Society of TDM since 2012, and they were updated in 2016. The aim of this study was to review TDM of antimicrobial agents. [Review].


Toward understanding the clinical aspects of geriatric case management.
Despite the prominence of complex psychosocial problems in aging clients, geriatric case management has generally emphasized the provision of concrete resources and services as its primary function. However, some of the literature as well as the findings of this study, point to competent case management as being contingent on interventions that successfully address key psychosocial problems. This paper presents a qualitative study involving experienced geriatric care managers. Psychosocial problem and intervention categories are identified as well as overarching themes with significant implications for practice. The paper argues that a grounded, thorough, well-explicated and generalizable model for clinically-focused geriatric case management practice is necessary; it also suggests additional research towards the development of such a model.


Focal choroidal excavation associated with polypoidal choroidal vasculopathy.
A 48-year-old woman presented with blurred vision in her right eye for 6 weeks. Visual acuity was 20/300 and 20/25 in the right and left eyes, respectively. Fundus examination showed subretinal hemorrhage in the superonasal macula in the right eye, whereas the left eye was normal. Fluorescein angiography showed blocked fluorescence from hemorrhage and a round distinct hypofluorescent spot along the inferotemporal arcade. Indocyanine green angiography revealed hyperfluorescent tubular and aneurysmal dilatations consistent with polypoidal choroidal vasculopathy in the superior macula. Spectral-domain optical coherence tomography showed retinal pigment epithelial irregularities and detachment. Scans through the round area of hypofluorescence revealed a conforming focal choroidal excavation and thinning of the underlying choriocapillaries. Because the pathogenesis of focal choroidal excavation is currently unclear, the authors propose the possibility of an acquired etiology related to loss of choriocapillaries from perfusion abnormalities as evidenced here.


[A case of hepatocellular carcinoma associated with multiple pulmonary tumor thrombi and rupture of its right adrenal metastasis].
A 54-year-old man, who had the history of a blood transfusion 29 years ago, was admitted to our hospital because of dyspnea and abdominal fullness. Physical examination revealed jaundice and massive ascites and laboratory data suggested liver cirrhosis. The high level of AFP and a CT scan indicated the association of hepatocellular carcinoma and its metastasis to the right adrenal gland. On the 21st hospital day, he suddenly complained of severe pain in the right upper quadrant and the right flank, and fell into hemorrhagic shock. Blood transfusion was given, but he died on the 24th hospital day. Autopsy revealed liver cirrhosis, accompanied by hepatocellular carcinoma with the metastasis to the right adrenal gland and multiple pulmonary tumor thrombi. Massive hemorrhaging due to rupture of the right adrenal metastasis was seen in the retroperitoneal space.


[Tissue specificity of the human brain protein D2].
Protein D2 was isolated and purified from adult human brain by extraction with Triton X-100 as well as by chromatography on phenyl-sepharose, concanavalin A-sepharose, lysine-sepharose and hydroxylapatite. Specific rabbit antisera against purified protein D2 were raised. Crossed and rocket immunoelectrophoresis revealed an immunoreactive protein D2 in the fetal heart, fetal kidney and adult heart (8-15% of total content in adult brain tissue). Rocket-on-line immunoelectrophoresis revealed additionally small amounts of D2-like antigens in adult kidney (12%), adult liver (1.5%), and in adult lung and spleen (less than 1%). The differences in tissue distribution as revealed by rocket-on-line immunoelectrophoresis suggest the existence of special D2-like protein clone in some tissues with or several immunochemically identical domains.


Relations of singing talent with voice onset time of trained and untrained female singers.
This study examined phonatory-articulatory timing during sung productions by trained and untrained female singers with and without singing talent. 31 untrained female singers were divided into two groups (talented or untalented) based on the perceptual judgments of singing talent by two experienced vocal instructors. In addition to the untrained singers, 24 trained female singers were recorded singing America the Beautiful, and voice onset time was measured for selected words containing /p, b, g, k/. Univariate analyses of variance indicated that phonatory-articulatory timing, as measured with voice onset time, was different among the three groups for /g/, with the untrained-untalented singers displaying longer voice onset time than the trained singers. No other significant differences were observed across the other phonemes. Despite a significant difference observed, relatively small effect sizes and statistical power make it difficult to draw any conclusions regarding the usefulness of voice onset time as an indicator of singing talent.


The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the management of pain and inflammation. However, little remains known about the effects of NSAIDs on synovitis of the human temporomandibular joint (TMJ). The aims of this study were to investigate the potential anti-inflammatory effects of NSAIDs on synovitis of the TMJ and the inflammatory effects of PGE2 on fibroblast-like synoviocytes (FLS) derived from the TMJ. Human synovial tissue was obtained from patients with internal derangement who underwent arthroscopy of the TMJ. FLSs were prepared from the tissues using the outgrowth method. A COX inhibitor (indomethacin or celecoxib) was added to the IL-1β-stimulated cells in culture. The cells were also stimulated with PGE2 or an EP agonist. The PGE2 production and COX-2 and IL-6 expression levels were examined using enzyme-linked immunosorbent assays, real-time PCR, and a microarray analysis. COX inhibitors decreased not only PGE2 production, but also the expression of COX-2 and IL-6 in FLS stimulated with IL-1β. EP2 and EP4 were both expressed in the FLS, and the treatment with EP2 and EP4 agonists induced IL-6 production in these cells. The COX inhibitors indomethacin and celecoxib reduce the expression of inflammatory factors, such as COX-2 and IL-6, in FLS from the TMJ via suppression of PGE2 production. EP2 and EP4 were the main receptors for PGE2 present in the FLS. The approach used in this study may be useful for revealing how drugs such as NSAIDs affect the cellular functions of FLS from the TMJ.


Peer tutoring improves student performance in an advanced physiology course.
Effectiveness of a peer tutoring system developed for an advanced physiology course was assessed in terms of academic performance and perceived value. Forty-five students took the course without the peer tutoring system, and sixty-nine students took the course with peer tutoring. Grades from both groups of students were compared with grades earned in an introductory physiology course. Tutored students were asked how much they valued the peer tutoring. There was a decline in grades received by the students in the advanced physiology course compared with their scores in the introductory physiology course in both tutored and untutored groups. However, the decline in the tutored group was significantly (P = 0.015) less than that in the untutored group of students. Tutored students reacted very favorably to the tutoring sessions and expressed a desire to see tutoring expanded to other courses. This was the first demonstration of the effectiveness of peer tutoring in college science teaching. Peer tutoring appears to be effective in enhancing student performance as well as being perceived as beneficial by the students.


VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases.
V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator (NCR) involved in inhibition of T cell-mediated immunity. Expression changes of other NCRs (PD-1, PD-L1/L2, CTLA-4) during inflammation of the central nervous system (CNS) were previously demonstrated, but VISTA expression in the CNS has not yet been explored. Here, we report that in the human and mouse CNS, VISTA is most abundantly expressed by microglia, and to lower levels by endothelial cells. Upon TLR stimulation, VISTA expression was reduced in primary neonatal mouse and adult rhesus macaque microglia in vitro. In mice, microglial VISTA expression was reduced after lipopolysaccharide (LPS) injection, during experimental autoimmune encephalomyelitis (EAE), and in the accelerated aging Ercc1 Δ/- mouse model. After LPS injection, decreased VISTA expression in mouse microglia was accompanied by decreased acetylation of lysine residue 27 in histone 3 in both its promoter and enhancer region. ATAC-sequencing indicated a potential regulation of VISTA expression by Pu.1 and Mafb, two transcription factors crucial for microglia function. Finally, our data suggested that VISTA expression was decreased in microglia in multiple sclerosis lesion tissue, whereas it was increased in Alzheimer's disease patients. This study is the first to demonstrate that in the CNS, VISTA is expressed by microglia, and that VISTA is differentially expressed in CNS pathologies.


DDB1-DDB2 (xeroderma pigmentosum group E) protein complex recognizes a cyclobutane pyrimidine dimer, mismatches, apurinic/apyrimidinic sites, and compound lesions in DNA.
The DDB protein complex, comprising the subunits DDB1 and DDB2, binds tightly to UV light-irradiated DNA. Mutations in DDB2 are responsible for xeroderma pigmentosum group E, a disorder with defects in nucleotide excision repair of DNA. Both subunits are also components of a complex involved in ubiquitin-mediated proteolysis. Cellular defects in DDB2 disable repair of the major UV radiation photoproduct in DNA, a cyclobutane pyrimidine dimer, but no significant direct binding of DDB to this photoproduct in DNA has ever been demonstrated. Thus, it has been uncertain how DDB could play a specific role in DNA repair of such damage. We investigated DDB function using highly purified proteins. Co-purified DDB1-DDB2 or DDB reconstituted with individual DDB1 and DDB2 subunits binds to damaged DNA as a ternary complex. We found that DDB can indeed recognize a cyclobutane pyrimidine dimer in DNA with an affinity (K(app)a) 6-fold higher than that of nondamaged DNA. The DDB1-DDB2 complex also bound with high specificity to a UV radiation-induced (6-4) photoproduct and to an apurinic site in DNA. Unexpectedly, DDB also bound avidly to DNA containing a 2- or 3-bp mismatch (and does not bind well to DNA containing larger mismatches). These data indicate that DDB does not detect lesions per se. It instead recognizes other structural features of damaged DNA, acting as a sensor that probes DNA for a subset of conformational changes. Lesions recognized may include those arising when translesion polymerases such as POLH incorporate bases across from DNA lesions caused by UV radiation.


Rehbein's procedure in 73 cases of Hirschsprung's disease.
The principle for treatment of Hirschsprung's disease by Rehbein's procedure is to remove the aganglionic narrow segment including the dilated sigmoid colon by dissection of the upper rectum deep down into the pelvic cavity about 2 cm from peritoneal reflection and to elimination of the achalasia of internal anal sphincter by vigorous dilatation. Between August 1987 and April 2000, 73 cases of Hirschsprung's disease (50 boys and 23 girls) were operated on by Rehbein's procedure at the Pediatric Surgical Unit, Ratchaburi Hospital. The age varied from 7 months to 10 years. 55 cases showed very good results by daily stool evacuation without any help, occasional laxative or enema in 15 cases, giving laxative or enema regularly in 2 cases and no adequate bowel evacuation despite giving laxative or enema in I case. In conclusion, Rehbein's procedure is technically simple and has good results. It should be another treatment of choice for Hirschsprung's disease.


[Prevalence and risk factors for bacteriuria in patients with cirrhosis].
Bacterial infections occur frequently in patients with cirrhosis and may worsen the disease outcome. We investigated the prevalence of bacteriuria in 500 consecutive patients with cirrhosis, in different Child-Pugh stages (41.4% A; 40.8% B; 17% C) and analysed the associated risk factors. Most of the cirrhosis cases were virus related; alcohol abuse was recorded in 6.2% of the patients. Bacteriuria was detected in 139 (27.8%) cases: 32.4% were more than 100,000 cfu/ml; 7.9% between 100,000 and 1.000,000 cfu/ml and the remaining cases more than 1000,000 cfu/ml. Escherichia coli was the most frequent isolated agent (84.5%); Proteus spp. strains were detected only in bacteriuria with more than 100,000 cfu/ml. At univariate analysis, female gender, age and presence of diabetes were significantly associated to bacteriuria, while Child-Pugh stage and the presence of hepatocellular carcinoma were not. In a multivariate model, only female gender and diabetes were significantly associated to bacteriuria. These results indicate that advanced cirrhosis was not a risk for bacteriuria, that was associated rather to gender and diabetes, which are common risk factors for bacteriuria in non-cirrhotic patients.


Food quality score and the risk of coronary artery disease: a prospective analysis in 3 cohorts.
Currently, there are few diet quality assessment tools that are predictive of coronary artery disease (CAD) risk that do not require nutrient analysis and substantial time to administer in clinical settings. To inform the development of such a tool, we prospectively examined the association between a food-based diet quality score and risk of CAD in 3 separate large US cohort studies. Between 1984 and 2012, 71,415 women (aged 43-63 y in 1984), 42,945 men (aged 40-75 y in 1986), and 93,131 younger women (aged 27-44 y in 1991) without a history of cardiovascular disease were followed up to 28 y. Diet was assessed ≤7 times by using repeated food-frequency questionnaires. We computed the Food Quality Score (FQS) for each individual based on food groups previously associated with less weight gain. A higher score represented a healthier diet. The FQS and CAD association was modeled with the Cox proportional hazard model, controlling for potential confounders. We also compared the magnitude of association with CAD for the FQS and other diet quality scores. We ascertained 6817 incident total CAD events, with 4588 cases of nonfatal myocardial infarction and 2131 fatal CAD events. Comparing top to bottom deciles, pooled RRs of the FQS were 0.61 (95% CI: 0.54, 0.69; P-trend < 0.001) for total CAD. These associations were independent of established cardiovascular disease risk factors including body weight, physical activity, and smoking. The magnitude of the RR for 1 SD of the FQS and CAD was generally similar to established diet scores that require detailed nutrient analysis, including the Alternate Healthy Eating Index-2010, the Dietary Approaches to Stop Hypertension score, and the alternate Mediterranean diet score. A higher food-based diet quality score was associated with lower risk of CAD and was comparable with established diet scores.


Cellulose synthase 'class specific regions' are intrinsically disordered and functionally undifferentiated.
Cellulose synthases (CESAs) are glycosyltransferases that catalyze formation of cellulose microfibrils in plant cell walls. Seed plant CESA isoforms cluster in six phylogenetic clades, whose non-interchangeable members play distinct roles within cellulose synthesis complexes (CSCs). A 'class specific region' (CSR), with higher sequence similarity within versus between functional CESA classes, has been suggested to contribute to specific activities or interactions of different isoforms. We investigated CESA isoform specificity in the moss, Physcomitrella patens (Hedw.) B. S. G. to gain evolutionary insights into CESA structure/function relationships. Like seed plants, P. patens has oligomeric rosette-type CSCs, but the PpCESAs diverged independently and form a separate CESA clade. We showed that P. patens has two functionally distinct CESAs classes, based on the ability to complement the gametophore-negative phenotype of a ppcesa5 knockout line. Thus, non-interchangeable CESA classes evolved separately in mosses and seed plants. However, testing of chimeric moss CESA genes for complementation demonstrated that functional class-specificity is not determined by the CSR. Sequence analysis and computational modeling showed that the CSR is intrinsically disordered and contains predicted molecular recognition features, consistent with a possible role in CESA oligomerization and explaining the evolution of class-specific sequences without selection for class-specific function.


Three years' follow-up from the ATAC trial is sufficient to change clinical practice: a debate.
Tamoxifen is currently the adjuvant treatment of choice for postmenopausal women with hormone-sensitive breast cancer. However, in the treatment of postmenopausal women with advanced disease, the third-generation aromatase inhibitor anastrozole ('Arimidex') has been shown to be at least as effective as tamoxifen, and to be more effective than tamoxifen in patients with estrogen receptor-positive disease. Furthermore, anastrozole is well tolerated and is associated with fewer adverse reactions (such as thromboembolic events, vaginal bleeding, and endometrial cancer) compared with tamoxifen. A change in clinical practice has now emerged for the first-line treatment of postmenopausal advanced disease in patients, with tamoxifen becoming the second- or third-line choice for many clinicians. These data have raised questions about the optimal adjuvant treatment for postmenopausal women with early breast cancer. The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial has compared the efficacy and safety of tamoxifen and anastrozole in the adjuvant treatment of postmenopausal women with early breast cancer. At 3 years' follow-up in the overall population, anastrozole demonstrated a significant benefit compared with tamoxifen for disease-free survival (DFS) (89.4% vs. 87.4%; p = 0.013), time to recurrence (hazard ratio = 0.79; p = 0.008), and contralateral breast cancers (odds ratio = 0.42; 95% confidence interval: 0.22-0.79; p = 0.007). Anastrozole produced improvements in quality of life similar to tamoxifen and was better tolerated for a number of predefined adverse events. Of course, a large body of evidence is available regarding the safety profile of tamoxifen and some feel that more data are needed from the ATAC trial to demonstrate that the early advantages of anastrozole over tamoxifen can be maintained in the longer term. However, a follow-up analysis at 47 months has confirmed that the tolerability profile and the absolute benefit of anastrozole were maintained over the extended follow-up period, demonstrating that the benefits of anastrozole are likely to be maintained over the long term. This review assesses these and other data from the ATAC trial and presents the arguments for and against whether 3 years' follow-up is sufficient to inform a change in clinical practice for the adjuvant treatment of postmenopausal women with early breast cancer.


[Experimental study of the reliability of end to end arterial microanastomosis].
Since 1978 (Lauritzen), several experimental and clinical procedures of end-in-end vascular microanastomosis have been described, including that proposed by Wang (1986) in which the tubulisation is accompanied by a counter-incision of the recipient vessel. Our experimental study was designed to assess the reliability of this procedure, to quantify it in relation to the diameter of the artery and direction of flow and to verify the existence of absence of any particular intraluminal histological phenomena. 42 Wistar rats were operated under general anaesthesia. 42 microanastomoses were performed: 15 carotid and 15 femoral in the direction of arterial blood flow, and 15 carotid anastomoses in the opposite direction to flow. The 15 carotid anastomoses performed in the direction of flow were all patent at each of the postoperative examinations (D0, D + 15, D + 90). Patency decreased in the anastomoses performed in the opposite direction to blood flow (10 out of 15 carotid anastomoses were patent) and as a function of the arterial diamenter (5 out of 12 femoral anastomoses were patent). Horizontal and transverse histological sections performed on the 15th and 90th days demonstrated continuity of the intimal endothelial lining and thickening of the adventitia of the two internalised and recipient walls in every case. In practice, although this experimental study demonstrates the clinical reliability of this internalised microanastomosis procedure in rat carotid arteries, the other results and the anatomo-clinical discrepancy do not justify its clinical use in all circumstances, particularly in the opposite direction to blood flow and in arteries with a diameter less than or equal to 1 mm.


Macrophage type 2 differentiation in a patient with laryngeal squamous cell carcinoma and metastatic prostate adenocarcinoma to the cervical lymph nodes.
The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes. We report a 59-year-old male with recurrent T4 squamous cell carcinoma (SCC) of the larynx with synchronous prostate adenocarcinoma confined to the prostate and regional pelvic lymph nodes, without metastatic disease. The patient underwent salvage total laryngectomy and bilateral neck dissection with final pathology revealing a recurrent moderately differentiated SCC involving the larynx as well as prostate cancer in draining level 4 cervical lymph nodes bilaterally. CD163 staining was performed on the primary tumor, a negative draining lymph node, and a level four lymph node with a focus of metastatic prostate cancer and compared to benign controls. The negative draining lymph node demonstrated a large CD163 population of cells as did the interface of the focus of prostate cancer and surrounding lymph node. CD163 levels were markedly increased in this patient compared to benign lymph node controls. The macrophage differentiation at the primary tumor in the larynx was strongly CD163 positive supporting an immune permissive environment for tumor growth and metastasis. We describe a unique case of solitary metastatic prostate cancer to cervical lymph nodes in the setting of a laryngeal cancer. These observations suggest that SCC-derived factors drive a tumor-supportive environment in draining lymph nodes dominated by an overwhelming number of CD163+, M2 macrophages. Lymph nodes that are 'primed' by SCC differentiation to M2 phenotype may be at higher risk of harboring metastases.


Effect of Solvent on Convectively Driven Silica Particle Assembly: Decoupling Surface Tension, Viscosity, and Evaporation Rate.
The process of convectively self-assembling particles in films suffers from low reproducibility due to its high dependency on particle concentration, as well as a variety of interactions and physical parameters. Inhomogeneities in flow rates and instabilities at the air-liquid interface are mostly responsible for reproducibility issues. These problems are aggravated by adding multiple components to the dispersion, such as binary solvent mixtures or surfactant/polymer additives, both common approaches to control stick-slip behavior. When an additive is used, not only does it change the surface tension, but also the viscosity and the evaporation rate. Worse yet, gradients in these three properties can form, which then lead to Marangoni currents. Here, we use a series of alcohols to study the role of viscosity independently of other solvent properties, to show its impact on stick-slip behavior and interband distances. We show that mixtures of glycerol and alcohol or poly(acrylic acid) and alcohol lead to more complex patterning. Marangoni currents are not always observed in co-solvent systems, being dependent on the rate of solvent evaporation. To produce homogeneous particle assemblies and control stick-slip behavior, gradients must be avoided, and the surface tension and viscosity need both be carefully controlled.


Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta.
This study tested whether sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase regulates the ability of endothelin receptor antagonist to inhibit the endothelin-1 constriction. The endothelin A receptor antagonist BQ-123 (1 microM) completely relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta. Challenge with cyclopiazonic acid (10 microM), a sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase inhibitor, during the plateau of endothelin-1 constriction enhanced the constriction by approximately 30%. BQ-123 relaxed the endothelin-1 plus cyclopiazonic acid constriction by only approximately 10%. In contrast, prazosin (1 microM), an alpha-adrenergic receptor antagonist, still completely relaxed the 0.3 muM phenylephrine constriction in the presence of cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid constriction by approximately 30%, whereas Ni(2+) and 2-aminoethoxydiphenyl borate, nonselective cation channel and store-operated channel blockers, respectively, completely relaxed the constriction. These results suggest that lowered sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase activity selectively decreases the ability of endothelin receptor antagonist to inhibit the endothelin A receptor. The decreased antagonism may be related to the opening of store-operated channels and subsequent greater internalization of endothelin A receptor.


Acute Phase Protein Lipocalin-2 Is Associated with Formalin-induced Nociception and Pathological Pain.
Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.


NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation.
The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain-like structure in the predicted NH2 terminus, and a "kelch motif" in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110(RB)) is found to be associated with the nuclear matrix and overexpression of p110(RB) induces neuronal differentiation, we investigated whether NRP/B is associated with p110(RB). Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110(RB) during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110(RB) and participates in the regulation of neuronal process formation.


Redox properties of nanostructured lanthanide-doped ceria spheres prepared by microwave assisted hydrothermal homogeneous co-precipitation.
In this work, nanostructured LnxCe(1-x)O2-δ (Ln: Gd and Pr; x = 0.1 and 0.2) spheres were synthesized by microwave assisted hydrothermal homogeneous co-precipitation and their properties were characterized by synchrotron radiation XRD, X-ray absorption near-edge spectroscopy (XANES) and scanning and high-resolution electron microscopy (SEM and HRTEM). In situ XRD and XANES experiments were carried out under reducing and oxidizing conditions in order to investigate the redox behaviour of these materials. The nanostructured mixed oxide spheres were found to have a cubic crystal structure (Fm3m space group). The spheres were composed of nanoparticles with an average crystallite size of about 10 nm. The Ln(0.1)Ce(0.9)O2-δ compositions exhibited the highest specific surface area (∼ 60 m(2) g(-1)). In situ XRD experiments showed an increase in lattice parameters upon reduction, which was attributed to the reduction of Ce(4+) and Pr(4+) cations to Ce(3+) and Pr(3+), which have larger radii, and to the associated increase in VO concentration. This increase in lattice parameters was considerably more pronounced for PrDC than GDC, and was explained by the considerably larger change in ionic radius for Pr upon reduction. XANES absorption experiments at the Ce and Pr L3-edge showed that the changes observed upon reduction of the Pr-containing samples resulted mostly from the formation of Pr(3+) rather than Ce(3+), and supported the previously reported proposal that Pr(3+) has a stabilizing effect on Ce(4+).


Investigation of angle-insensitive grating color filters at periods much smaller than the wavelength of incidence.
We designed and simulated one-dimensional (1D) and two-dimensional (2D) reflective grating color filters inside the aluminized polyethylene (PE) film. The filters have several advantages: high angle insensitivity (up to 45° for the 1D filter, 40° for the 2D filter), high reflectance at non-resonant wavelengths, deep resonance dips, and a large color gamut. Both structures are characterized by with their grating periods being much smaller than the wavelength of incidence. A grating modal analysis was utilized to reveal the physical mechanism behind such structures that exhibit angle-insensitive spectral responses which are favored in the fields of color display and packaging.


Efficient multitasking: parallel versus serial processing of multiple tasks.
In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling.


A Poorly Differentiated Malignant Neoplasm Lacking Lung Markers Harbors an EML4-ALK Rearrangement and Responds to Crizotinib.
Suspected metastatic site lesions that are poorly differentiated present a diagnostic challenge when morphologic and immunohistochemical profiling cannot establish the primary tumor site. Here we present a patient diagnosed with both a malignant neoplasm in the lung and a right upper extremity (RUE) neoplasm of unclear histogenetic origin. Immunohistochemical staining performed on the latter specimen was inconclusive in determining the site of origin. Although the lung biopsy sample was insufficient for molecular testing, hybrid capture-based comprehensive genomic profiling (FoundationOne) identified an EML4-ALK rearrangement in the RUE lesion. Crizotinib treatment resulted in a major response in both the RUE and the lung lesions. This report illustrates the utility of comprehensive genomic profiling employed at the initial presentation of an unknown primary malignant neoplasm, which resulted in the front-line use of targeted therapy and a significant and sustained antitumor response.


Has the prevalence of invalidating musculoskeletal pain changed over the last 15 years (1993-2006)? A Spanish population-based survey.
The aim of the current study was to estimate the prevalence and time trend of invalidating musculoskeletal pain in the Spanish population and its association with socio-demographic factors, lifestyle habits, self-reported health status, and comorbidity with other diseases analyzing data from 1993-2006 Spanish National Health Surveys (SNHS). We analyzed individualized data taken from the SNHS conducted in 1993 (n = 20,707), 2001 (n = 21,058), 2003 (n = 21,650) and 2006 (n = 29,478). Invalidating musculoskeletal pain was defined as pain suffered from the preceding 2 weeks that decreased main working activity or free-time activity by at least half a day. We analyzed socio-demographic characteristics, self-perceived health status, lifestyle habits, and comorbid conditions using multivariate logistic regression models. Overall, the prevalence of invalidating musculoskeletal pain in Spanish adults was 6.1% (95% CI, 5.7-6.4) in 1993, 7.3% (95% CI, 6.9-7.7) in 2001, 5.5% (95% CI, 5.1-5.9) in 2003 and 6.4% (95% CI 6-6.8) in 2006. The prevalence of invalidating musculoskeletal pain among women was almost twice that of men in every year (P < .05). The multivariate analysis showed that occupational status (unemployed), sleep <8 hours/day and having any accident in the preceding year were significantly associated in both gender with a higher likelihood of suffering from invalidating musculoskeletal pain among Spanish adults. Within men, other predictors of invalidating musculoskeletal pain were to be married and lower educational level, whereas in women were age of 45-64 years old (OR 1.89, 95% CI 1.32-2.7), obesity (OR 1.23, 95% CI 1.06-1.42), a sedentary lifestyle (OR 1.23, 95% CI 1.06-1.42), and presence of comorbid chronic diseases (OR 1.32, 95% CI 1.14-1.53). Further, worse self-reported health status was also related to a greater prevalence of invalidating musculoskeletal pain (OR 6.88, 95% 5.62-8.40 men, OR 7.24, 95% 6.11-8.57 women). Finally, we found that the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001 for both men (OR 1.31, 95% 1.08-1.58) and women (OR 1.19, 95% 1.03-1.39) with no significant increase from the remaining surveys. Our results suggest that invalidating musculoskeletal pain deserves an increased awareness among health professionals. More educational programs which address postural hygiene, physical exercise, and how to prevent obesity and sedentary lifestyle habits should be provided by Public Health Services. This population-based study indicates that invalidating musculoskeletal pain that reduces main working activity is a public health problem in Spain. The prevalence of invalidating musculoskeletal pain was higher in women than in men and associated to lower income, poor sleeping, worse self-reported health status, and other comorbid conditions. Further, the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001, but remained stable from the last years (2001 to 2006).


Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker revealed from buccal swab analysis.
Mitochondrial function studies in autism spectrum disorders (ASD) have detected skeletal muscle mitochondrial enzyme deficiencies in respiratory complex (RC) activities. As a muscle biopsy is expensive and invasive, we assessed RC-I and RC-IV activities in buccal swabs. 92 children with ASD and 68 controls were studied with immunocapture for RC-I and microspectrophotometry for RC-IV. Significant RC activity deficiencies were found in 39 (42%) ASD patients (p < 0.01) and more prevalent in more severe cases. Aberrant RC overactivity was seen in 9 children. RC-I/RC-IV activity ratio was significantly increased in 64% of the entire ASD cohort including 76% of those more severely affected (p < 0.05). Buccal swab analysis revealed extensive RC abnormalities in ASD providing a noninvasive biomarker to assess mitochondrial function in ASD patients.


Bisphenol A Diglycidyl Ether-Primary Amine Cooligomer-poly(ε-caprolactone) Networks: Synthesis and Characterization.
In this work, the preparation and systematic investigation of cross-linked polyurethane-epoxy (PU-EP) polymer systems are reported. The PU-EP polymers were prepared using a reaction of isocyanate (NCO)-terminated PU-prepolymer with diglycidyl ether of bisphenol A (DGEBA)-amine cooligomer. The oligomerization of DGEBA was carried out by adding furfurylamine (FA) or ethanolamine (EA), resulting in DGEBA-amine cooligomers. For the synthesis of NCO-terminated PU-prepolymer, poly(ε-caprolactone)diol (PCD) (Mn = 2 kg/mol) and 1,6-hexamethylene diisocyanate (HDI) were used. The cross-linking was achieved by adding DGEBA-amine cooligomer to PU-prepolymer, in which the obtained urethane bonds, due to the presence of free hydroxil groups in the activated DGEBA, served as netpoints. During cross-linking, ethanolamine provides an additional free hydroxyl group for the formation of a new urethane bond, while furfurylamine can serve as a thermoreversible coupling element (e.g., Diels-Alder adduct). The PU-EP networks were characterized using attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), dynamical mechanical analysis (DMA) and scanning electron microscopy (SEM). The DMA curves of some PU-EPs (depending on the compositions and the synthetic method) revealed a plateau-like region above the melting temperature (Tm) of PCD, confirming the presence of a cross-linked structure. This property resulted in a shape memory (SM) behavior for these samples, which can be fine-tuned in the presence of furfurylamine through the formation of additional thermoreversible bonds (e.g., Diels-Alder adduct).


Small-angle neutron scattering study of structural changes in temperature sensitive microgel colloids.
The structure of temperature-sensitive poly(N-isopropylacrylamide) microgels in dilute suspension was investigated by means of small-angle neutron scattering. A direct modeling expression for the scattering intensity distribution was derived which describes very well the experimental data at all temperatures over an extensive q range. The overall particle form as well as the internal structure of the microgel network is described by the model. The influence of temperature, cross-linking density, and particle size on the structure was revealed by radial density profiles and clearly showed that the segment density in the swollen state is not homogeneous, but gradually decays at the surface. The density profile reveals a box profile only when the particles are collapsed at elevated temperatures. An increase of the cross-linking density resulted in both an increase of the polymer volume fraction in the inner region of the particle and a reduction of the smearing of the surface. The polymer volume fraction inside the colloid decreased with increasing particle size. The structural changes are in good agreement with the kinetics of the emulsion copolymerization used to prepare the microgel colloids.


Embryonal rhabdomyosarcoma of the chest wall: a case report and review of the literature.
Embryonal rhabdomyosarcoma is a soft-tissue sarcoma which has a predilection for the head and neck area, genitourinary tract and the extremities. We report a rare case of embryonal rhabdomyosarcoma of the chest wall in an 8-year-old girl, presenting as a destructive tumor in the rib and clinically and radiologically mimicking Ewing's sarcoma. Histopathological examination showed a small round cell tumor. Immunohistochemically, the positivity for muscle markers desmin and myogenin in the tumor cells proved to be useful for making a definitive diagnosis of embryonal rhabdomyosarcoma. Cytogenetic analysis revealed a high level of aneuploidy in the tumor cells, with double-minutes and additional chromosomal structural aberrations. The patient is responding well to chemotherapy.


Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.
Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.


A mouse stromal response to tumor invasion predicts prostate and breast cancer patient survival.
Primary and metastatic tumor growth induces host tissue responses that are believed to support tumor progression. Understanding the molecular changes within the tumor microenvironment during tumor progression may therefore be relevant not only for discovering potential therapeutic targets, but also for identifying putative molecular signatures that may improve tumor classification and predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, we performed cDNA microarray analysis of laser-microdissected stromal cells derived from prostate intraepithelial neoplasia (PIN) and invasive cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes identified in the stromal reaction to tumor progression in this mouse model were observed to be expressed in several human cancers, and to cluster prostate and breast cancer patients into groups with statistically different clinical outcomes. Univariate Cox analysis showed that overexpression of these genes is associated with shorter survival and recurrence-free periods. Taken together, our observations provide evidence that the expression signature of the stromal response to tumor invasion in a mouse tumor model can be used to probe human cancer, and to provide a powerful prognostic indicator for some of the most frequent human malignancies.


Serological testing in small vessel vasculitis.
Serological analysis has a central role in the diagnostic work-up of patients with suspected small vessel vasculitis, both for establishing a specific diagnosis and for the monitoring of response to therapy. Autoantibodies can be detected in all forms of primary small vessel vasculitis as well as in the most common forms of secondary vasculitis. For primary vasculitis the most important serological test is for ANCA. ANCA can be found in 75-95% of patients with pauci-immune small vessel vasculitis leading to this subgroup of vasculitides being named ANCA associated vasculitis. ANCA levels often follow this disease course, but the value of serial ANCA testing is controversial. Other important autoantibodies in primary small vessel vasculitis are anti-glomerular basement membrane antibodies, anti-C1q, anti-galactose deficient IgA and cryoglobulins. A wide variety of systemic inflammatory diseases and infections can be complicated by small vessel vasculitis and detected by serological testing. Important examples are SLE, rheumatoid arthritis, Hepatitis C and HIV.


ADVANCING TRANSFUSION MEDICINE IN SEA TURTLES: OPTIMIZATION OF A CROSS-MATCHING PROTOCOL.
Whole blood transfusions are an essential treatment modality during rehabilitation of stranded sea turtles, however, standardized protocols for transfusions are not available in reptile medicine. The objective of this study was to optimize a cross-matching protocol for sea turtle blood transfusions. Fresh venous blood samples from 15 turtles (n = 14 green turtles, Chelonia mydas [Cm]; n = 1 loggerhead sea turtle, Caretta caretta [Cc]) were tested using a temperature-appropriate (i.e., reflecting body temperature), time-sensitive protocol in 26 reactions using two procedures for cross-match evaluation at 30 and 60 min at ambient air and water bath temperature. There were no significant differences between both protocols at 30- and 60-min incubation times or between microscopic evaluations at 2 or 5 min. The major cross-match identified 7/22 incompatible Cm-Cm reactions as observed by microscopic erythrocyte agglutination. Minor cross-matches resulted in 6/22 incompatible Cm-Cm reactions. About half of all Cm-Cm reactions (12/22) were compatible by major and minor cross-match. All Cc-Cm reactions (4/4) were incompatible. A higher than expected proportion of incompatible Cm cross-matching reactions suggests preexisting antibodies to nonself erythrocyte antigens in this species, or other factors promoting erythrocyte aggregation or agglutination. Preliminary data across Cm and Cc suggests cross-species incompatibility. These results indicate that sea turtles may react to donor erythrocytes even at the first transfusion. Concurrent major and minor cross-matching using the proposed protocol at 30-min incubation at room temperature should be considered a necessary and effective way to test for patient and donor incompatibilities in sea turtles.


Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China.
New rationally designed i,i+7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. The antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication (IC50) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the IC50s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.


Aortic coarctation with hypoplastic arch in neonates: a spectrum of anatomic lesions requiring different surgical options.
Hypoplasia of the transverse aortic arch is frequently associated with isthmic coarctation in many patients referred for operation in early infancy, and the surgical technique should be adjusted to suit each type of anatomic lesion. Referring to the anatomic description of hypoplastic aortic arch reported by Moulaert and associates, between January 1988 and July 1991 we operated on 32 consecutive infants (< or = 3 months old) using a surgical approach based on the echocardiographic and angiographic findings; 20 patients (62%) were younger than 2 weeks of age and 20 patients (62%) had associated intracardiac lesions. According to the location, extension, and size of the hypoplasia of the aortic arch, we had three groups of patients: in group 1 (21 patients) we performed resection and extended end-to-end anastomosis, as previously described in 1985; in group 2 (5 patients) we performed resection, posterior end-to-end anastomosis, and anterior subclavian flap enlargement; and in group 3 (6 patients) we performed direct side-to-end anastomosis between ascending and descending aorta through a median sternotomy. One patient died during the postoperative course in group 3. With a mean follow-up time of 26 months we had 4 cases (13%) of "residual" or "recurrent" coarctation in group 1, successfully repaired at 2 months of age by an anterior approach in 2 patients and by percutaneous angioplasty in the others. In conclusion, hypoplastic aortic arch in neonates represents a common difficulty, and optimal reconstruction of the entire aortic arch is mandatory to reduce operative mortality and incidence of recoarctation, especially when there are complex associated intracardiac lesions or left ventricular dysfunction.


[Protein changes of the erythrocyte membrane during blood preservation].
The present study was conducted on erythrocytes banked in ACD-AG medium for 1, 21, or 42 days at 4 degrees C. Erythrocyte membrane proteins were analysed by means of SDS-polyacrylamide gel electrophoresis in relation to the action of beta-mercaptoethanol. Under banking conditions proteins of the erythrocyte membrane formed 380 000--420 000 daltons aggregates, presumably heterodimers of spectrin I and II, and very high molecular weight aggregates (MG > 600 000 daltons). Part of the aggregated proteins were cross-linked by disulfide bridges, which are subject of the reduction by beta-mercaptoethanol. The nonreducible components were considered an irreversible alteration of the erythrocyte membrane. Many samples of banked erythrocytes exhibited an increase of protein band II.3 (MG = 185 000 daltons) and band IV.2 (MG = 72 000 daltons). The amount of protein band VI (GAPDH) was shown to depend on both banking time and conditions of haemolysis. A modified hypotonic haemolysis with an additional intermediate alkaline incubation of ghosts resulted in a considerable decline of protein band VI of banked erythrocytes. Substraterich incubation of banked erythrocytes, which raised the ATP level well above normal, could only partially restore the membrane bound portion of protein band VI.


Production and characterization of monoclonal antibodies to the sperm acrosome stabilizing factor (ASF): utilization for purification and molecular analysis of ASF.
Utilizing hybridoma technology and highly purified acrosome stabilizing factor (ASF), six monoclonal antibodies (mAbs) specific for ASF were produced and characterized. Specificity and binding properties of each clone were examined by immunoperoxidase labeling of electrophoretic blots of rabbit serum, seminal plasma, cauda epididymal fluid and vasectomized seminal plasma separated on native and sodium dodecyl sulfate (SDS)-polyacrylamide gels. All mAbs recognize ASF in seminal plasma and cauda epididymal fluid but do not bind components in serum or vasectomized seminal plasma. Purification of ASF by affinity chromatography utilizing the mAbs, has shortened the 6-day isolation procedure for ASF used previously to less than 2 h and has increased the yield from 2 micrograms to 300 micrograms of ASF obtained per ml of seminal plasma. Three mAbs were used in conjunction with Cleveland digest with Staphylococcus aureus V8 protease, SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoperoxidase labeling of Western Blots, to identify peptides containing specific determinants recognized by each mAb. At least five separate determinants were recognized by the six mAbs. The sensitivity of the Western blotting technique in conjunction with the specificity of the mAbs was exploited to detect polymeric forms of ASF in seminal plasma and cauda epididymal fluid. ASF is shown to be a 360-kd dimer consisting of two identical 180-kd monomers. Tools are now available to develop sensitive qualitative and quantitative assays for ASF, thus providing rapid, extremely sensitive methods for evaluating experiments designed to probe the molecular mechanism of capacitation.


Two new species of Atlantoscia Ferrara Taiti, 1981 (Isopoda: Oniscidea: Philosciidae) from southern Brazil described in the light of integrative taxonomy.
The use of molecular data in association with classical taxonomy has helped to alleviate the taxonomic impediment through the discovery, delimitation and description of new species. Terrestrial isopods are the largest suborder of Isopoda; however, there are very few active taxonomists in this group and a representative part of the terrestrial isopods world diversity remains unexplored. The genus Atlantoscia comprises five species in which diagnostic characters are few and show subtle differences among the species. The objective of this study was to delimit and describe two new species of the genus Atlantoscia from southern Brazil by using traditional taxonomy coupled with genetic information. Specimens were analyzed morphologically and by the aid of two molecular markers, mitochondrial COI and nuclear 18S rRNA. The validity of the new species Atlantoscia antennamaculata sp. nov. and Atlantoscia australis sp. nov. was corroborated, unambiguously, by morphological approach, phylogenetic analysis and species delimitation methods. Our study reinforces the fact that, despite the undeniable importance of comparative morphology in species discovery, new methods and data, particularly molecular ones, are becoming prominent and an integrative part of the taxonomy practice.


BAMBI: A new method for automated assessment of bidirectional early-life interaction between maternal behavior and pup vocalization in mouse dam-pup dyads.
Vital early-life dyadic interaction in mice requires a pup to signal its needs adequately, and a dam to recognize and respond to the pup's cues accurately and timely. Previous research might have missed important biological and/or environmental elements of this complex bidirectional interaction, because it often focused on one dyadic member only. In laboratory rodents, the Pup Retrieval Test (PRT) is the leading procedure to assess pup-directed maternal care. The present study describes BAMBI (Bidirectional Automated Mother-pup Behavioral Interaction test), a novel automated PRT methodology based on synchronous video recording of maternal behavior and audio recording of pup vocalizations, which allows to assess bidirectional dam-pup dyadic interaction. We were able to estimate pup retrieval and pup vocalization parameters accurately in 156 pups from 29 dams on postnatal days (PND) 5, 7, 9, 11, and 13. Moreover, we showed an association between number of emitted USVs and retrieval success, indicating dyadic interdependency and bidirectionality. BAMBI is a promising new automated home-cage behavioral method that can be applied to both basic and preclinical studies investigating complex phenotypes related to early-life social development.


A world of inflammation: the need for ecological solutions that co-benefit people, place and planet.
The ecology of the early environment - including microbial diversity, nutrition, nature, social interactions and the totality of exposures in the wider "exposome" - have life-long implications for all aspects of health and resilience. In particular, the emergence of "microbiome science" provides new evidence for vital relationships between biodiversity and health at every level. New perspectives of ecological interdependence connect personal and planetary health; the human health crisis cannot be separated from the social, political and economic "ecosystems" otherwise driving dysbiosis (from its etymological root, "life in distress") at every level. Adverse changes in macroscale ecology - of food systems, lifestyle behaviours, socioeconomic disadvantage and environmental degradation - all impact the microbial systems sitting at the foundations of all ecosystems. In particular, changes in the function and composition of the human-associated microbiome have been implicated in the mounting global burden of noncommunicable diseases (NCDs), exacerbating inflammation and metabolic dysregulation through multiple pathways across the lifespan. This "dysbiotic drift" (adverse shifts in ecology at all scales) underscores the need for ecological approaches aimed at restoring symbiosis, balance and mutualism. While there is promise with supplement-based strategies (e.g. probiotics, prebiotics), it is essential to focus on upstream factors implicated in dysbiosis, including the health of wider environments, lifestyle, nature relatedness, and the social policies and practices which can facilitate or inhibit dysbiotic drift. This also calls for ambitious integrative approaches which not only define these interconnections, but also capitalize on them to create novel, collaborative and mutualistic solutions to our vast interdependent global challenges.


Isolation and characterization of ubiquinol oxidase complexes from Paracoccus denitrificans cells cultured under various limiting growth conditions in the chemostat.
To obtain more information about the composition of the respiratory chain under different growth conditions and about the regulation of electron-transfer to several oxidases and reductases, ubiquinol oxidase complexes were partially purified from membranes of Paracoccus denitrificans cells grown in carbon-source-limited aerobic, nitrate-limited anaerobic and oxygen-limited chemostat cultures. The isolated enzymes consisted of cytochromes bc1, c552 and aa3. In comparison with the aerobic ubiquinol oxidase complex, the oxygen- and nitrate-limited ones contained, respectively, less and far less of the cytochrome aa3 subunits and the anaerobic complex also contained lower amounts of cytochrome c552. In addition, extra haem-containing polypeptides were present with apparent Mr of 14,000, 30,000 and 45,000, the former one only in the anaerobic and the latter two in both the anaerobic and oxygen-limited preparations. This is the first report describing four different membrane-bound c-type cytochromes. The potentiometric and spectral characteristics of the redox components in membrane particles and isolated ubiquinol oxidase fractions were determined by combined potentiometric analysis and spectrum deconvolution. Membranes of nitrate- and oxygen-limited cells contained extra high-potential cytochrome b in comparison with the membranes of aerobically grown cells. No difference was detected between the three isolated ubiquinol oxidase complexes. Aberrances with already published values of redox potentials are discussed.


Keloidal Kaposi's sarcoma: report of three patients.
Kaposi's sarcoma is a unique neoplasm which has emerged as an important element of AIDS in homosexuals but not in others at high risk for AIDS. The biology of this important tumor may be related to cytokines secreted by HIV-infected cells and/or by Kaposi's sarcoma cells themselves. We report 3 patients with multiple keloid-like tumors. These lesions proved to be Kaposi's sarcoma histologically, yet with a unique keloidal component. This variant has not been described previously. It is possible that cytokines that stimulate Kaposi's sarcoma cell growth may also stimulate proliferation of local fibroblasts to produce this variant.


Functional interaction of plasminogen activator inhibitor type 1 (PAI-1) and heparin.
Plasminogen activator inhibitor type 1 (PAI-1), the fast-acting inhibitor of tissue-type plasminogen activator (t-PA) and urokinase (u-PA), is a member of the serpin superfamily of proteins. Both in plasma and in the growth substratum of cultured endothelial cells, PAI-1 is associated with its binding protein vitronectin, resulting in a stabilization of active PAI-1. Recently, it has been demonstrated that the PAI-1-binding site on vitronectin is adjacent to a heparin-binding site (Preissner et al., 1990). Furthermore, it can be deduced that the amino acid residues, proposed to mediate heparin binding in the serpins antithrombin III and heparin cofactor II, are conserved in PAI-1. Consequently, here we have investigated whether PAI-1 also interacts with heparin. At pH 7.4, PAI-1 quantitatively binds to heparin-Sepharose and can be eluted with increasing [NaCl]. Binding of PAI-1 to heparin-Sepharose can be efficiently competed with heparin in solution (IC50, 7 microM). In the presence of heparin, the protease specificity of PAI-1 toward thrombin is substantially increased. This is shown by (i) quenching of thrombin activity of PAI-1 in the presence of heparin and (ii) induction of the formation of SDS-stable complexes between thrombin and PAI-1 by heparin. In a dose response curve, both effects reached a maximum at approximately 1 unit/mL and then diminished again upon further increasing the heparin concentration, strongly suggesting a template mechanism as an explanation for the observed effect. In contrast to vitronectin, heparin does not stabilize the active conformation of PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Survey nonresponse among informal caregivers: effects on the presence and magnitude of associations with caregiver burden and satisfaction.
Informal caregiving is becoming more relevant with current trends such as population ageing. However, little is known about nonconsent and nonresponse bias in caregiving research. We investigated nonconsent and nonresponse bias in a sample of informal caregivers who participated in the LifeLines Cohort Study, and were invited for participation in an additional caregiving study. We compared socio-demographic characteristics, caregiver health, caregiving situation, and caregiver outcomes of nonconsent and consent caregivers, and nonresponse and response caregivers, on LifeLines data, by using Chi-square tests, Independent Sample T-tests, and Mann-Whitney tests. Furthermore, we examined the influence of nonconsent and nonresponse on the presence and magnitude of the associations between caregiver characteristics and two commonly used caregiving outcomes (caregiver burden and satisfaction). We conducted multinomial logistic regression analyses, including interaction terms with nonconsent and nonresponse. Within a subcohort of 8443 caregivers, aged >18 years, 5095 caregivers (60 %) gave consent for participation in the caregiving study. Within the subgroup of 2002 caregivers who received the questionnaire, 965 (48 %) responded. Caregivers who were highly involved in caregiving (i.e. high time investment, high caregiver burden), gave more commonly consent to participate, and responded more often to the questionnaire. Nonconsent and nonresponse influenced the associations between caregiver characteristics and caregiver burden for only a few characteristics, mainly indicating the level of caregiving involvement (e.g. time investment, caregiving duration). Especially for caregiver burden, these indicators were stronger for consent and response caregivers than for nonconsent and nonresponse caregivers. Our findings are important for caregiving research, as they emphasized that participation might not be evenly distributed among caregivers, and that the possibility of nonconsent and nonresponse bias should be considered.


Increased frequencies of circulating and tumor-resident Vδ1+ T cells in patients with diffuse large B-cell lymphoma.
Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1+ T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1+ T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1+ T cells of patients or HSs mostly exhibited a naïve phenotype, the majority of tumor Vδ1+ T cells showed a central memory phenotype. Resident or circulating γδ T cells from patients were not functionally impaired since they produced high levels of IFN-γ. Collectively, our findings are in favor of γδ T cell activation in tumors and open new perspectives for their modulation in DLBCL immunotherapy.


Ultrasound can improve the accuracy of the 2010 American College of Rheumatology/European League against rheumatism classification criteria for rheumatoid arthritis to predict the requirement for methotrexate treatment.
The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) refer to a possible use of ultrasound "for confirmation of the clinical findings." We undertook this study to determine the optimized definition of ultrasound-detected synovitis for the 2010 ACR/EULAR criteria and to assess the impact of its use on the accuracy of RA classification. One hundred nine patients with musculoskeletal symptoms for ≤3 years were enrolled in the study. Patients underwent clinical, laboratory, radiographic, and comprehensive ultrasonographic assessments at baseline and received routine management from expert rheumatologists who were blinded to the ultrasound findings. Sensitivity and specificity of the 2010 ACR/EULAR criteria using different definitions of synovitis to identify patients who developed a disease requiring methotrexate (MTX) treatment within 1 year were 58.5% and 79.4%, respectively, for clinical synovitis (tenderness or swelling), 78.0% and 79.4%, respectively, for ultrasound-detected synovitis with a gray-scale (GS) imaging score≥1 (GS≥1 ultrasound synovitis), and 56.1% and 93.7%, respectively, for GS≥2 ultrasound synovitis or a synovial power Doppler (PD) signal score≥1 (GS≥2/PD≥1 ultrasound synovitis). Receiver operating characteristic curve analysis for the criteria scores revealed the largest area under the curve with GS≥2/PD≥1 ultrasound synovitis. Ultrasound assessment improves the accuracy of the 2010 ACR/EULAR criteria for identifying patients with a disease requiring MTX treatment. Our data provide preliminary but vital information for the methodology to confirm the presence of synovitis using ultrasound in the 2010 ACR/EULAR criteria.


Impact of low-dose computed tomography for lung cancer screening on lung cancer surgical volume: The urgent need in health workforce education and training.
This study aimed to investigate the time trend variation in the surgical volume and prognostic outcome of patients with lung cancer after the gradual prolonged implementation of a low-dose computed tomography (LDCT) lung cancer screening program.Using the hospital-based cancer registry data on number of patients with lung cancer and deaths from 2008 to 2017, we conducted a retrospective study using a hospital-based cohort to investigate the relationship between changes in lung cancer surgical volume, the proportion of lung-sparing surgery, and prolonged prognostic outcomes after the gradual implementation of the LDCT lung cancer screening program in recent years.From 2008 to 2017, 3251 patients were diagnosed with lung cancer according to the hospital-based cancer registry. The 5-year mortality rate decreased gradually from 83.54% to 69.44% between 2008 and 2017. The volume of total lung cancer surgical procedures and proportion of lung-sparing surgery performed gradually increased significantly from 2008 to 2017, especially from 2014 to 2017 after implementation of a large volume of LDCT lung cancer screening examinations. In conclusion, our real-world data suggest that there will be an increase in cases of operable early-stage lung cancers, which in turn will increase the surgical volume and proportion of lung-sparing surgery, after the gradual implementation of the LDCT lung cancer screening program in recent years. These findings suggest the importance of a successful national policy regarding LDCT screening programs, regulation of shortage of thoracic surgeons, thoracic radiologist workforce training positions, and education programs.


Assessment of glomerular filtration rate by means of the three-compartment closed model after a single intravenous injection.
The two-compartment open model is currently used to assess glomerular filtration rate (GFR) with multiple blood samples. Numerous limited sampling models have been developed to reduce the number of blood samples. In the present study, the three-compartment closed model was used to assess GFR after a single intravenous injection. The three-compartment closed model includes blood, peripheral and urine compartments, thus the samples in urine can be used to estimate parts of pharmacokinetic parameters, thus to reduce the number of blood samples. Theoretically, the three-compartment closed model can assess GFR with one blood sample at any sampling time and three urine samples at any three sampling times.


SERS and DFT study of p-hydroxybenzoic acid adsorbed on colloidal silver particles.
In this study, normal Raman spectra of p—hydroxybenzoic acid (PHBA) powder and its surface—enhanced Raman scattering (SERS) spectra in silver colloidal solutions were measured under near infrared excitation conditions. In theoretical calculation, two models of PHBA adsorbed on the surfaces of silver nanoparticles were established. The Raman frequencies of these two models using density functional theory (DFT) method were calculated, and compared with the experimental results. It was found that the calculated Raman frequencies were in good agreement with experimental values, which indicates that there are two enhanced mechanism physical (electromagnetic, EM) enhancement and chemical (charge—transfer, CT) enhancement, in silver colloidal solutions regarding SERS effect. Furthermore, from high—quality SERS spectrum of PHBA obtained in silver colloids, we inferred that PHBA molecules in silver colloids adsorb onto the metal surfaces through carboxyl at a perpendicular orientation. The combination of SERS spectra and DFT calculation is thus useful for studies of the adsorption—orientation of a molecule on a metal colloid.


IBIS: an inverse geometry Brillouin inelastic neutron spectrometer for the SNS.
The high power target station at the Spallation Neutron Source (SNS) currently has about 20 completed neutron scattering instruments. With a broad coverage of the momentum transfer (Q)-energy (E) space, these instruments serve an extensive user community. In an effort to further expand the scientific capabilities of the SNS instrument suites, we propose a low background, inverse geometry Brillouin inelastic spectrometer for the SNS which will expand the Q-E coverage of the current instrument suite and facilitate the study of inelastic and quasi-elastic scatterings at low Q values. The possible location for the proposed instrument is either beamline 8 which views the decoupled water moderator, or beamline 14A, which views a cold, coupled super critical hydrogen moderator. The instrument parameters, optimizations, and performances at these two beamline locations are discussed.


Dietary fatty acid modulation of events associated with mouse skin tumor promotion.
Increasing levels of dietary corn oil have been correlated with inhibition of 12-O-tetradecanoylphorbol-13-acetate-(TPA) promoted skin tumorigenesis in mice (Leyton et al. Cancer Res. 51, 907-915, 1991). This study was undertaken to assess the effects of dietary corn oil on several events associated with tumor promotion. Three semipurified diets containing 15% (wt/wt) total fat with increasing levels of linoleate (0.8%, 4.5%, and 8.4%) supplied by corn oil were fed to mice for at least four weeks. Although incorporation of linoleate into epidermal phosphatidylcholine increased with increasing amounts of dietary corn oil, the elongated desaturated product of linoleate, arachidonate, was similar or decreased slightly in mice fed the three diets. Minimal activity of delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleate to arachidonic acid, was found in the epidermis compared with the liver, suggesting that linoleate is not converted to arachidonic acid in the skin. Subcellular distribution of protein kinase C was altered in mice fed 0.8% linoleate, where 69% of protein kinase C activity was in the cytosol compared with 78% and 74% for groups fed 4.5% and 8.4% linoleate, respectively. Activation of partially purified protein kinase C isolated from mouse epidermis by linoleate was significantly lower (p < 0.01) than that isolated by arachidonic acid. TPA-induced vascular permeability was significantly greater (p < 0.05), whereas hyperplasia 48 hours after TPA treatment was significantly lower, in mice fed the 8.4% linoleate diet. However, TPA induction of ornithine decarboxylase activity did not appear to be significantly modified by dietary linoleate. These data suggest that cellular processes associated with carcinogenesis are affected by the level of dietary linoleate.


Indication of varicocelectomy in the era of assisted reproductive technology: prediction of treatment outcome by noninvasive diagnostic methods.
Of 103 patients who underwent varicocelectomies, 87 underwent all the diagnostic methods: color Doppler ultrasonography (DOP), scrotal deep body temperature (DBT), and scrotal scintigraphy (SSG). Total motile sperm (TM) was calculated. The positivities of DOP, DBT, and SSG were 67, 51, and 90%, respectively. In the patients <30 years old, TM increased in the DBT-positive group. In older patients, positive for DBT indicated poor improvement of TM, whereas positive for DOP indicated better response in the group. Patients older than 30 years and positive for DBT, but not DOP, should be counseled directly to receive intrauterine insemination or in vitro fertilization/intracytoplasmic sperm injection.


Lower fitness levels, higher fat-to-lean mass ratios, and lower cardiorespiratory endurance are more likely to affect the body mass index of Saudi children and adolescents.
Several studies suggest that health-related physical fitness may play a prominent role in preventing obesity in children and adolescents. The present study examined fitness levels using five components of health-related fitness in Saudi students aged 10-17 years (fat-to-lean mass ratio, cardiorespiratory endurance, upper body strength and endurance, abdominal muscle strength and endurance, and flexibility). Subsequently, the association between BMI and a health-related fitness index (HR-PFI) based on the five fitness components was investigated. The study was conducted on 1,291 students with a mean age of 12.95 ± 1.72 years. Participants included 1,030 boys aged 12.80 ± 1.79 years, with 479 young boys (11.24 ± 0.81b years), and 551 adolescents (14.16 ± 1.21 years). Moreover, the study examined 261 girls averaging 13.54 ± 1.2 years old, with 66 young girls (11.92 ± 0.27 years), and 195 teenage girls (14.09 ± 0.85 years). Each participant's health-related fitness level was assessed by the following tests: Bioelectrical Impedance Analyzer (BIA) for body composition, one-mile run/walk test for cardiorespiratory endurance, curl-up test for abdominal muscle strength and endurance (AMSE), push-up test for upper body strength and endurance (UBSE), and back-saver sit-and-reach test for flexibility. The overall prevalence of overweight and obesity was 10.4 and 24.7% in boys and 10 and 8.4% in girls, respectively. The mean Z-scores of performances decreased from the underweight to the obese groups. BMI was positively associated with the ratio of fat mass to lean mass and negatively associated with cardiorespiratory endurance in the overall group of participants as well as in the subgroups by sex and age categories. BMI was also negatively associated with flexibility and HR-PFI in the total group, UBSE, AMSE, and HR-PFI in prepubertal boys, and UBSE in prepubertal girls. The coefficient of determination values was 0.65 in the total group, 0.72 in prepubertal boys, 0.863 in adolescent boys, 0.956 in prepubertal girls, and 0.818 in adolescent girls. Overall health-related physical fitness, fat-to-lean mass ratio, and cardiorespiratory endurance are the factors that most affect BMI in Saudi students aged 10 to 17.


Metastasizing neuroblastomas in mice transgenic for simian virus 40 large T (SV40T) under the olfactory marker protein gene promoter.
The olfactory marker protein (OMP) is a M(r) 19,000 polypeptide originally considered a selective marker for differentiated olfactory receptor neurons. In an attempt to induce neoplastic proliferation in the olfactory cells, we made mice transgenic for the simian virus 40 large T-antigen gene linked to the OMP gene promoter. Four independent lines of transgenic mice were established. Despite a high expression of the transgene in the olfactory receptor neurons, no evidence of tumor growth was observed. Instead, starting from an age of 4 months, animals of all four lines presented with highly metastatic tumors originating in the adrenal medullas or sympathetic ganglia. The histological, ultrastructural, and immunohistochemical features of the tumors were identical to those of human infant neuroblastoma. Five independent neuroblastoma cell lines were established from tumors of different transgenic animals. All cell lines constitutively express the endogenous OMP gene. The transgene product, simian virus 40 large T-antigen, associates with the product of the anti-oncogene p53 in these cell lines. This transgene system not only offers a biologically faithful model for investigations on the pathogenesis of neuroblastoma, the most common solid neoplasia of infancy, it also raises intriguing questions about the role of the OMP gene for the differentiation of the sympathetic neurons.


A collaborative approach to advance student research at the University of Southern California.
The continued advancement of oral health and science relies upon the cultivation of a student's interest in research. The Student Research Group at the Ostrow School of Dentistry of the University of Southern California is working to increase student involvement in research and develop future academic leaders. This study aims to, through student surveys, quantitatively evaluate students' involvement in research, students' interest in participating in research and to identify specific barriers students feel challenge their ability to participate in research.


Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol.
Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points. A proteomic analysis was carried out by nanoLC-MS/MS in raft and non-raft fractions from MGCs after treatment with 24S-OHC (10μM). The expression of structural and functional proteins was further analyzed by Western-blotting, as well as the levels of GM3 ganglioside by LC-MS. Cholesterol, sphingomyelin, saturated fatty acids and ganglioside GM3 are enriched in the rafts fractions in MGCs. Caveolin-1, flotillin-1, connexin-30 and -43 are localized in the MGCs rafts. Proteins implicated in adhesion or oxidative stress pathways in raft fractions were up and down-regulated by the treatment. Our data showed that 24S-OHC induced early changes in protein distribution in raft microdomains; however, further studies are needed to better characterize the surrounded mechanisms.


Misdiagnosis of cervical ectopic pregnancy.
To determine the presenting symptoms as well as the frequency and reasons for the delayed diagnosis of cervical ectopic pregnancy (CEP) in order to increase detection and prevent treatment delay. Retrospective case series of 15 women treated for CEP from January 1997 through December 2008 at a university teaching hospital. Fifteen patients were treated for CEP during the study period. Eight patients presented to the emergency department, of which 6 (75%) were initially misdiagnosed. The most common misdiagnosis was threatened miscarriage (n = 5). All patients with accurately diagnosed CEP presented with heavy vaginal bleeding; those misdiagnosed reported mild to moderate vaginal bleeding. Three of six patients misdiagnosed did not have an ultrasound performed upon presentation, and three patients had an ultrasound report not suggestive of CEP. CEP was diagnosed on follow-up ultrasound, delaying treatment 1-4 days. Misdiagnosis of CEP upon initial presentation is a common occurrence. Transvaginal ultrasound performed by a qualified practitioner may increase detection and prevent treatment delay.


Advances in industrial microbiome based on microbial consortium for biorefinery.
One of the important targets of industrial biotechnology is using cheap biomass resources. The traditional strategy is microbial fermentations with single strain. However, cheap biomass normally contains so complex compositions and impurities that it is very difficult for single microorganism to utilize availably. In order to completely utilize the substrates and produce multiple products in one process, industrial microbiome based on microbial consortium draws more and more attention. In this review, we first briefly described some examples of existing industrial bioprocesses involving microbial consortia. Comparison of 1,3-propanediol production by mixed and pure cultures were then introduced, and interaction relationships between cells in microbial consortium were summarized. Finally, the outlook on how to design and apply microbial consortium in the future was also proposed.