Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.
Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.


Why do nations matter? The struggle for belonging and security in an uncertain world.
This paper explores the reasons why national forms of identification and organization (might) matter in the contemporary era. In contrast to the majority of macro-sociological work dealing with this topic, I develop an analytical framework that draws together recent research on everyday nationalism with micro-sociological and psychological studies pointing to the importance of routine practices, institutional arrangements and symbolic systems in contributing to a relatively settled sense of identity, place and community. The second part of the paper focuses on the hierarchies of belonging that operate within a given national setting. Of particular interest is the largely taken-for-granted status of the ethnic majority and the degree to which it underpins claims to belonging and entitlement that are used to secure key allocative and authoritative resources.


Generation and analysis of Siah2 mutant mice.
Siah proteins function as E3 ubiquitin ligase enzymes to target the degradation of diverse protein substrates. To characterize the physiological roles of Siah2, we have generated and analyzed Siah2 mutant mice. In contrast to Siah1a knockout mice, which are growth retarded and exhibit defects in spermatogenesis, Siah2 mutant mice are fertile and largely phenotypically normal. While previous studies implicate Siah2 in the regulation of TRAF2, Vav1, OBF-1, and DCC, we find that a variety of responses mediated by these proteins are unaffected by loss of Siah2. However, we have identified an expansion of myeloid progenitor cells in the bone marrow of Siah2 mutant mice. Consistent with this, we show that Siah2 mutant bone marrow produces more osteoclasts in vitro than wild-type bone marrow. The observation that combined Siah2 and Siah1a mutation causes embryonic and neonatal lethality demonstrates that the highly homologous Siah proteins have partially overlapping functions in vivo.


Mydriatic effects using low concentrations of phenylephrine hydrochloride.
The dose response relationship of different concentrations of phenylephrine with and without prior application of topical anesthetic was measured to determine the minimum concentration which produced maximum mydriasis. As little as 0.125% phenylephrine caused mydriasis in some subjects and maximum mydriasis was achieved with 2%. Concentrations greater than 2% produced very little additional mydriasis. A therapeutically effective dose could be as low as 1% with prior installation of a topical anesthetic.


Laparoendoscopic single-site adrenalectomy versus conventional laparoscopic adrenalectomy: a comparison of surgical outcomes and an analysis of a single surgeon's learning curve.
Conventional laparoscopic adrenalectomy (LA) is the gold standard procedure for benign adrenal tumors. Laparoendoscopic single-site adrenalectomy (LESS-A) has been developed as an extension of standard laparoscopic minimally invasive procedures. This retrospective study compared the first experience of one surgeon with 70 LESS-A to 140 LA cases with respect to evaluating the influence of the inexperience on surgical outcomes and to assess this surgeon's learning curve for LESS-A. Age, gender, BMI, percentage of patients with prior abdominal surgery, tumor laterality, and tumor size were all comparable between the two groups. There were no statistically significant differences in any surgical outcomes, including mean operative time, pneumoperitoneum time, estimated blood loss, transfusion requirements, hemoglobin decrease at postoperative day 1, analgesic requirements, postoperative day of oral intake, conversion rate, or morbidity between the two groups. The one exception was hospital stay. There were no mortalities or reoperations in either group. The morbidity rates in the LESS-A group and LA group were 4.2 and 6.4%, respectively (p = 0.528). LESS-A appears to have a steep learning curve and the operative time of the initial 70 cases decreased markedly and remained stable when the experience level exceeded 12 cases. There was no morbidity or conversion in these first 12 LESS-A cases. Multiple regression analysis revealed that surgeon experience (p = 0.008) and tumor size (p = 0.001) were independent predictors of prolonged operative time. Surgical outcomes of LESS-A were equivalent to those of LA without compromising safety. The introduction of LESS-A at our hospital was smooth and safe. While the indication for LESS-A has been controversial, LESS-A was a useful procedure, especially for cases in which cosmesis is of paramount importance.


Cloning, characterisation and bacterial expression of full length cDNA for the mouse liver microsomal glutathione S-transferase.
We have isolated a cDNA encoding full length microsomal glutathione S-transferase (MGST) from mouse liver. The cDNA was isolated by RT-PCR using primers designed from published cDNA sequence of rat MGST with the addition of 5' Nde-1 and 3' HindIII sites, and cloned into bacterial expression vector pSP19T7LT. Deduced amino acid sequence (155 amino acids, calculated mol.mass 17512 Dalton) confirmed the identity of microsomal GST from mouse liver which has sequence homology with that of rat and human liver MGST1. Recombinant GST cDNA (Genbank accession # 159050) was expressed in BL21(DE3) in the presence of 1 mM IPTG at 30 degrees C. The expressed GST protein was found to be localised in the bacterial membrane as determined by measuring catalytic activity using CDNB and cumene hydroperoxide substrates, SDS-PAGE and Western blot analysis. We have demonstrated the cloning and expression of full length cDNA for MGST from mouse liver and have characterised the functionally active product as MGST protein. These results should facilitate studies on the role of MGST in the regulation of chemical carcinogenesis and in the prevention of oxidative stress caused by endogenous and exogenous chemicals.


Inula Viscosa Extract Inhibits Growth of Colorectal Cancer Cells in vitro and in vivo Through Induction of Apoptosis.
Colorectal cancer (CRC) is the second most common cancer in females and the third in males worldwide. Conventional therapy of CRC is limited by severe side effects and by the development of resistance. Therefore, additional therapies are needed in order to combat the problem of selectivity and drug resistance in CRC patients. Inula viscosa (IV) is a well-known medicinal perennial herb in traditional medicine. It is used for different therapeutic purposes, such as; topical anti-inflammatic, diuretic, hemostatic, antiseptic, antiphlogistic, and in the treatment of diabetes. Several studies attempted to reveal the anti-cancer activity of different extracts prepared by different organic solvents from different parts of the IV plant. The aim of the present study is to examine the potential beneficial effects of IV leaf aqueous extract on the growth of colon cancer cells in vitro and in vivo. The results indicated that exposure of colorectal cancer cells to IV extract, significantly reduced cell viability in a dose and time dependent manner. Moreover, treatment of cells with 300 μg/ml of IV extract induced apoptosis, as it was detected by Annexin V/FITC/PI, TUNEL assay, and the activation of caspases. In vivo studies revealed that treatment with 150 or 300 mg/kg IV extract inhibited tumor growth in mice transplanted with MC38 cells. Tumors' weight and volume were significantly (P < 0.001) reduced when compared to untreated-control group. Staining of the paraffin section of tumors revealed that IV treatment inhibited cell proliferation and induced apoptosis. Additionally, no side effects such as; weight loss, behavior changes, ruffled fur or changes in kidney, and liver functions were observed. These results may indicate that active doses of IV extract are not toxic. Further studies are needed in order to identify the structure of the active compounds. Results from this study may contribute to the development of new and efficient strategies for treatment of human colon cancer.


Socioeconomic Status, Waist-to-Hip Ratio, and Short-Term Heart Rate Variability in Cambodians with Type 2 Diabetes.
Diabetes, adiposity, and socioeconomic status (SES) are all associated with decreased heart rate variability (HRV), a marker of autonomic function predictive of mortality. Cambodians have high rates of diabetes and low SES. How these factors interact to explain HRV has not been examined. The aims of this study were to investigate associations among waist-to-hip ratio, socioeconomic status, and HRV among Cambodians with diabetes. Sixty patients with type 2 diabetes for ≥1 year, not taking insulin, aged 35-80 years were recruited from the Cambodian Diabetes Association. The 2010 Ministry of Health survey regarding household conditions was used to measure SES. Waist-to-hip ratio was measured two times and averaged. For HRV, beat-to-beat intervals were recorded on ambulatory ECG recorders, and short-term HRV was calculated in the time domain and in the frequency domain using spectral analysis. Cross-sectional data were analyzed using a series of multiple linear regressions using SPSS v21. Participants were of mean age of 56 years old, 60 % female, with National Glycohemoglobin Standardization Program (NGSP) HbA1c mean = 8.4. Participants were poor (e.g., 18 % did not have flush toilets), had high waist-to-hip ratios (mean = 0.91), and had HRV values below published norms. In linear regression, there was a significant interaction between waist-to-hip ratio and SES explaining HRV in the time domain (standard deviation of the R-R interval (SDNN), beta = .33, t = 2.61, p < .05) and the frequency domain (log transformed very low frequency (Ln VLF), LF, and total power; all p < .05). Among those with lower SES only, higher waist-to-hip ratio was associated with lower HRV. Findings remained significant after controlling for age, sex, and HbA1c. Central adiposity shows a stronger deleterious association with autonomic tone among individuals with more adverse social conditions.


Communicating about obesity and weight-related topics with children with a physical disability and their families: spina bifida as an example.
The purpose of this study was to explore the experiences of children with spina bifida (SB), their families and healthcare professionals (HCPs) when discussing weight-related topics. In-depth qualitative interviews were conducted with HCPs from Canadian outpatient SB clinics (n = 13), children aged 6-18 years with SB (n = 17) and their parents (n = 20). Data were analyzed using a phenomenological approach within an interpretative paradigm. Many HCPs were not confident talking about weight, concerned that they would damage relationships with children and families. Parents wanted routine weight surveillance, but were worried about their children's self-esteem if their weight was discussed. They wanted HCPs to acknowledge the challenges of weight management in children with a physical disability and provide specialized solutions. Children wanted a positively framed and tailored approach to weight discussions, although this had generally not been their experience. Stakeholders describe therapeutic relationships that are currently disconnected around the issue of weight and obesity. However, children, parents and HCPs all believed that discussing this topic was critical. Positively framed, strengths-based and tailored approaches to weight-related discussions are warranted. Implications for Rehabilitation Rates of overweight and obesity in children and youth with physical disabilities are substantially higher than their typically developing peers. Healthcare professionals, children with physical disabilities and families often find weight-related discussions challenging and disconnected. Weight-related discussions should be tailored to the child and family's circumstances and priorities. Positively framed and strengths-based approaches to weight-related discussions are warranted.


Military sexual trauma among US servicewomen during deployment: a qualitative study.
We explored qualitatively US servicewomen's experiences with and perceptions of military sexual trauma (MST), reporting, and related services. From May 2011 to January 2012, we conducted 22 telephone interviews with US servicewomen deployed overseas between 2002 and 2011. We analyzed data thematically with modified grounded theory methods. Factors identified as contributing to MST included deployment dynamics, military culture, and lack of consequences for perpetrators. Participants attributed low MST reporting to negative reactions and blame from peers and supervisors, concerns about confidentiality, and stigma. Unit cohesion was cited as both a facilitator and a barrier to reporting. Availability and awareness of MST services during deployment varied. Barriers to care seeking were similar to reporting barriers and included confidentiality concerns and stigma. We identified several avenues to address MST, including strengthening consequences for perpetrators. We identified barriers to MST reporting and services. Better understanding of these issues will allow policymakers to improve MST prevention and services.


Therapeutic bronchoscopy in broncholithiasis.
Bronchoscopy is considered the most important diagnostic test for broncholithiasis. However, its role in the treatment of broncholithiasis in a large group of patients has not been studied. To evaluate the therapeutic role of bronchoscopy, we retrospectively reviewed the clinical data of patients with broncholithiasis who also underwent bronchoscopy at Mayo Clinic. Bronchoscopy revealed 127 broncholiths (free or partly eroded calcified material in the airway lumen) in 95 patients (49 men and 46 women) evaluated between 1954 and 1994. Bronchoscopic removal of 71 (56%) broncholiths was attempted in 48 patients (50.5%) during 61 bronchoscopy sessions. Forty-eight of the broncholiths selected for removal were partly eroding into the tracheobronchial lumen and 23 were free. Forty-eight percent (23 of 48) of the partly eroding broncholiths were successfully removed bronchoscopically, with a greater percentage removed with the rigid bronchoscope (67%) than with the flexible bronchoscope (30%). All free broncholiths were completely extracted regardless of the type of bronchoscope used. Complications occurred in only two patients (4% of the bronchoscopic broncholithectomy group), both with partially eroded broncholiths, and consisted of hemorrhage in one patient requiring thoracotomy and acute dyspnea in another patient, caused by a loose broncholith lodged in the trachea. We conclude that flexible and/or rigid bronchoscopic extraction of partly eroded or free broncholiths in the tracheobronchial tree can be considered safe and effective.


Packaging cordycepin phycocyanin micelles for the inhibition of brain cancer.
Cordycepin has been successfully used as a natural anti-cancer drug, but it is rapidly metabolized in vivo. Nanoencapsulation is thus a promising method to improve its bioavailability. In this study, we adopted a green synthesis process to develop novel self-assembling phycocyanin-dextran-cordycepin (Phy-Dex-Cord) micelles for efficient cordycepin encapsulation and delivery. We first used the Maillard reaction method to graft dextran onto phycocyanin, forming a phycocyanin-dextran complex. Through the self-assembly of the cordycepin parcel to the phycocyanin-dextran complex, the micelles were formed. Their physical and chemical properties and characterization results showed that Phy-Dex-Cord micelles have a spherical shape and consistent size distribution of about 60 nm. In addition, anti-cancer activities in vitro and in vivo revealed that the Phy-Dex-Cord micelles have a comparable or even stronger inhibitory effect against C6 cells than do free cordycepin and free phycocyanin and no side effects.


Potential use of a baculovirus-expressed dengue-4 E protein as a diagnostic antigen in regions endemic for dengue and Japanese encephalitis.
Truncated dengue-4 E protein was produced as a fusion protein in insect cells using a baculovirus expression vector to examine its usefulness as a diagnostic antigen. A peroxidase-anti-peroxidase (PAP) staining method was used to examine the immunoreactivity of the antigenic determinants in recombinant virus-infected Sf-9 cells with human sera obtained from dengue (DEN) and Japanese encephalitis (JE) endemic areas (41 sera from DEN patients and 39 sera from JE patients or individuals with high JE-antibody titers). The expressed E protein, in which one-third of the carboxy-terminal end was deleted, reacted with sera from DEN patients, but it failed to react or responded only faintly with sera from JE patients. The antibody titers obtained by the staining method correlated with those obtained by enzyme-linked immunosorbent assay (ELISA) (r = 0.64, P less than 0.01). Calculation of the ratio (R) of the titer obtained by the PAP staining method to the ELISA titer can clearly differentiate DEN antibody from JE antibody (high R values in DEN sera and low R values in JE sera). The recombinant protein would be especially useful for diagnostic purposes in regions where DEN and JE viruses co-circulate.


Mining residue contacts in proteins using local structure predictions.
In this paper we develop data mining techniques to predict 3D contact potentials among protein residues (or amino acids) based on the hierarchical nucleation-propagation model of protein folding. We apply a hybrid approach, using a hidden Markov model to extract folding initiation sites, and then apply association mining to discover contact potentials. The new hybrid approach achieves accuracy results better than those reported previously.


Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 1 liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays - impact of 3-epi-25-hydroxyvitamin D3 on assay performance.
An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays used for the determination of serum total 25-hydroxyvitamin D (25(OH)D), which is the sum of 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3). A set of 50 single-donor samples was assigned target values for concentrations of 25(OH)D2, 25(OH)D3, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) using isotope dilution liquid chromatography - tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 1 includes results from 14 laboratories using 14 custom LC-MS/MS assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 53% of the LC-MS/MS assays met the VDSP criterion of mean % bias ≤ |±5%|. For the LC-MS/MS assays not meeting the ≤ |±5%| criterion, four assays had mean % bias of between 12 and 21%. Based on multivariable regression analysis using the concentrations of the four individual vitamin D metabolites in the 50 single-donor samples, the performance of several LC-MS/MS assays was found to be influenced by the presence of 3-epi-25(OH)D3. The results of this interlaboratory study represent the most comprehensive comparison of LC-MS/MS assay performance for serum total 25(OH)D and document the significant impact of the lack of separation of 3-epi-25(OH)D3 and 25(OH)D3 on assay performance, particularly with regard to mean % bias.


Identification of a tooth-like foreign body in swine sausage.
A tooth-like foreign body (FB) was found inside a sausage bread. Analysis aimed to investigate whether the FB was a tooth and its origin. The FB was measured, weighed, photographed, and radiographed. Macroscopic findings were suggestive of an anterior tooth. Histological slides of undecalcified cross-sections of the FB and samples of human and swine teeth were prepared. Histological features of the FB (in light microscopy, 125× magnification) were discrepant from human tissues. Compared histological analysis displayed majority of features consistent with a hypsodont swine tooth, probably a canine. Cellularized cementum in crown region, adjacent to the enamel, and shape of the cementocytes were the main criteria excluding the possibility of human origin of the FB. Scanning electronic microscopy and energy-dispersive spectroscopy were not performed because of fewer features to be analyzed and FB size. It was concluded that the FB may have been incorporated during meat grinding of the sausage.


Effects of early life exposure to traffic-related air pollution on brain development in juvenile Sprague-Dawley rats.
Epidemiological studies link traffic-related air pollution (TRAP) to increased risk for various neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship between TRAP and adverse neurodevelopmental outcomes. Moreover, much of the preclinical literature reports effects of concentrated ambient particles or diesel exhaust that do not recapitulate the complexity of real-world TRAP exposures. To assess the developmental neurotoxicity of more realistic TRAP exposures, we exposed male and female rats during gestation and early postnatal development to TRAP drawn directly from a traffic tunnel in Northern California and delivered to animals in real-time. We compared NDD-relevant neuropathological outcomes at postnatal days 51-55 in TRAP-exposed animals versus control subjects exposed to filtered air. As indicated by immunohistochemical analyses, TRAP significantly increased microglial infiltration in the CA1 hippocampus, but decreased astrogliosis in the dentate gyrus. TRAP exposure had no persistent effect on pro-inflammatory cytokine levels in the male or female brain, but did significantly elevate the anti-inflammatory cytokine IL-10 in females. In male rats, TRAP significantly increased hippocampal neurogenesis, while in females, TRAP increased granule cell layer width. TRAP had no effect on apoptosis in either sex. Magnetic resonance imaging revealed that TRAP-exposed females, but not males, also exhibited decreased lateral ventricular volume, which was correlated with increased granule cell layer width in the hippocampus in females. Collectively, these data indicate that exposure to real-world levels of TRAP during gestation and early postnatal development modulate neurodevelopment, corroborating epidemiological evidence of an association between TRAP exposure and increased risk of NDDs.


Low energy density diets are associated with favorable nutrient intake profile and adequacy in free-living elderly men and women.
Nutrient adequacy in the diet is of paramount importance to physical and mental health. The aim of this study was to characterize the dietary pattern associated with a low energy density diet and determine its nutrient adequacy in elderly men and women. The subjects were men (n = 1150) and women (n = 1094) >65 y, examined in 2 population-based cross-sectional surveys (2000 and 2005) in northeast Spain (Girona). Dietary data were recorded using a 165-item FFQ. Reduced rank regression (RRR) analysis was used to identify an energy density-associated dietary pattern. A nutrient adequacy score (NAS) and Mediterranean diet score (MDS) were computed to estimate the association of diet adequacy with energy density. The RRR-derived factor (dietary pattern) predicted 75.4% of the variance in energy density of the diet. Vegetables, fruits, legumes, cooked potatoes, and low-fat milk and yogurt were key to the low energy density of the diet. Higher proportions of men and women consuming low energy density diets met dietary recommendations for total fat, saturated fat, cholesterol, total fiber, vitamin C, vitamin E, thiamin, riboflavin, vitamin B-6, folate, calcium, and magnesium than their peers on high energy density diets. Multivariate linear regression analysis revealed an inverse association (P < 0.001) of the NAS and MDS with energy density and energy density-related patterns. A low energy density diet has a higher capacity to prevent nutrient deficiency, despite lower energy content, than a high energy density diet in the elderly population studied.


Hemifield-specific Correlations between Cue-related Blood Oxygen Level Dependent Activity in Bilateral Nodes of the Dorsal Attention Network and Attentional Benefits in a Spatial Orienting Paradigm.
The dorsal attention network (DAN) is known to be involved in shifts of spatial attention or in orienting. However, the involvement of each hemisphere in shifts to either hemifield is still a matter of debate. In this study, interindividual hemifield-specific attentional benefits in RTs were correlated with cue-related BOLD responses specific to directive cues in the left and right frontal and posterior nodes of the DAN, measured in a Spatial Orienting Paradigm. The pattern of correlations was analyzed with respect to its fit with three existing hypotheses of spatial attention control: the contralateral, right dominance, and hybrid hypotheses. Results showed that activation in frontal and parietal nodes of the DAN could explain a significant proportion of the interindividual variance in attentional benefits. Although we found that benefits in the right hemifield correlated with cue-related activity in the left, as well as the right, DAN and that the pattern of correlations fit best with the right dominance hypothesis, there were no significant correlations between left benefits and activation in the right (as well as left) DAN, which precludes the conclusion that our data support the right dominance hypothesis and might instead point toward a potential qualitative difference between leftward and rightward shifts of attention. In conclusion, this study demonstrates that behavioral effects of orienting can be linked to activation changes in the DAN, and it raises new questions with respect to the involvement of the frontal and parietal nodes in each hemisphere in hemifield-specific orienting.


Mammalian derived lipocalin and secretoglobin respiratory allergens strongly bind ligands with potentially immune modulating properties.
Allergens from furry animals frequently cause sensitization and respiratory allergic diseases. Most relevant mammalian respiratory allergens belong either to the protein family of lipocalins or secretoglobins. Their mechanism of sensitization remains largely unresolved. Mammalian lipocalin and secretoglobin allergens are associated with a function in chemical communication that involves abundant secretion into the environment, high stability and the ability to transport small volatile compounds. These properties are likely to contribute concomitantly to their allergenic potential. In this study, we aim to further elucidate the physiological function of lipocalin and secretoglobin allergens and link it to their sensitizing capacity, by analyzing their ligand-binding characteristics. We produced eight major mammalian respiratory allergens from four pet species in E.coli and compared their ligand-binding affinities to forty-nine ligands of different chemical classes by using a fluorescence-quenching assay. Furthermore, we solved the crystal-structure of the major guinea pig allergen Cav p 1, a typical lipocalin. Recombinant lipocalin and secretoglobin allergens are of high thermal stability with melting temperatures ranging from 65 to 90°C and strongly bind ligands with dissociation constants in the low micromolar range, particularly fatty acids, fatty alcohols and the terpene alcohol farnesol, that are associated with potential semiochemical and/or immune-modulating functions. Through the systematic screening of respiratory mammalian lipocalin and secretoglobin allergens with a large panel of potential ligands, we observed that total amino acid composition, as well as cavity shape and volume direct affinities to ligands of different chemical classes. Therefore, we were able to categorize lipocalin allergens over their ligand-binding profile into three sub-groups of a lipocalin clade that is associated with functions in chemical communication, thus strengthening the function of major mammalian respiratory allergens as semiochemical carriers. The promiscuous binding capability of hydrophobic ligands from environmental sources warrants further investigation regarding their impact on a molecule's allergenicity.


Association of body size measurements and mammographic density in Korean women: the Healthy Twin study.
Both greater body size and higher mammographic density seem to be associated with a risk of breast cancer. To understand a mechanism through which body size confers a higher risk of breast cancer, associations between mammographic measures and various measures of body size were examined. Study subjects were 730 Korean women selected from the Healthy Twin study. Body size measurements were completed according to standard protocol. Mammographic density was measured from digital mammograms using a computer-assisted method from which the total area and the dense area of the breast were calculated, and nondense area and percent of dense area were straightforwardly derived. Linear mixed models considering familial correlations were used for analyses. Total and nondense areas were positively associated with current body mass index (BMI), BMI at 35 years, total fat percent, waist circumference, and waist-hip ratio, whereas percent dense area was inversely associated with these characteristics in both premenopausal and postmenopausal women. Height was not associated with any mammographic measure. Total and nondense areas had strong positive genetic correlations with current BMI, total fat percent, waist circumference, and waist-hip ratio, whereas percent dense area had strong inverse genetic correlations with these body size measurements. Mammographic density and obesity are inversely associated with each other possibly from common genetic influences that have opposite effects on mammographic density and obesity in Korean women. The association between obesity and breast cancer does not seem to be mediated through mammographic density.


Separation of closely related peptide substrates of human proteinases by micellar electrokinetic chromatography with anionic and nonionic surfactants.
In order to use micellar electrokinetic chromatography to determine the proteolytic activity of different proteinases simultaneously present in physiological fluids, the technique must be able to separate mixtures of substrates with closely related structures. In an attempt to determine the best electrophoretic conditions for resolving six p-nitroanilide peptides used as synthetic substrates of the elastolytic enzymes (human neutrophil elastase, cathepsin G, Pseudomonas aeruginosa elastase) most commonly involved in pulmonary diseases, we investigated the efficiency of ionic and nonionic surfactants in achieving the separation of this complex mixture. The results presented here show that, of all the electrophoretic systems tested, 30 mM sodium tetraborate, pH 9.3, containing 25 mM Brij 35 as micellar agent offered the best performance; the separation efficiency of peptides is greater than that obtained with other reagents and all peaks are baseline resolved and unambiguously identifiable. Analysis of the micelle-solute interaction with the surfactants investigated allowed better definition of the mechanism involved in the distribution of these peptides to the micelles and identification of some structural features that determined the magnitude of the micelle peptide complex formation.


Changed women: the long-term impact of vaginal mesh complications.
The aim of this study was to describe how women experience vaginal mesh complications after optimized tertiary care level treatment. We conducted telephone interviews in 2012 with women at least 6 months after presentation to our tertiary care clinic between 2006 and 2011 for complications related to vaginal mesh and transcribed verbatim responses to 2 open-ended questions about their experiences surrounding vaginal mesh complications. We analyzed data using qualitative description with low-inference interpretation in a team-based setting followed by consensus meetings to arrive at descriptive trajectories of their experiences. Of 111 women, we successfully contacted 88, and 84 agreed to the interview. The mean duration from index mesh surgery to interview was 4.5 years, and the mean duration from presentation to our clinic for complications to the interview was 2.3 years. The effects of mesh complications caused both physical and emotional pain, in addition to the discomfort of the original pelvic floor dysfunction. The women's experiences followed 1 of 3 recovery trajectories. In "cascading health problems," the women experienced a spiral of health problems, anxiety, and desperation. In "settling for a new normal," the women who once considered themselves healthy now believed that they are unhealthy and worked to adjust to their degraded health status. In "returning to health," the women described a return to health. The women still symptomatic discharged from tertiary care clinic expressed hopelessness and abandonment. Concomitant with ongoing research to improve the safety of vaginal mesh procedures, there must be dedicated efforts to develop and study a range of therapies for holistically treating women with mesh complications.


Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect.
To assess the efficacy and safety of avocado/soybean unsaponifiables (ASU) in the treatment of patients with symptomatic osteoarthritis (OA) of the knee or hip, as well as the potential residual effects of ASU after stopping treatment, to determine whether ASU might be a symptomatic slow-acting drug for the treatment of OA. One hundred sixty-four patients with regular, painful, primary OA of the knee (n = 114) or hip (n = 50) entered a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial with a 6-month treatment period and a 2-month posttreatment followup. A 15-day washout period for nonsteroidal antiinflammatory drugs (NSAIDs) preceded the study. Efficacy was judged according to 1) Lequesne's functional index (LFI) and 2) pain on Huskisson's visual analog scale (VAS; 100-mm scale), intake of NSAIDs/analgesics, and overall disability score (by 100-mm VAS). Eighty-five patients received ASU; 79 received placebo. One hundred forty-four patients were evaluable at month 6 (75 taking ASU; 69 taking placebo). The mean +/- SEM LFI score decreased from 9.7 +/- 0.3 to 6.8 +/- 0.4 in the ASU group and from 9.4 +/- 0.3 to 8.9 +/- 0.4 in the placebo group (P < 0.001 for intergroup difference at month 6). Pain decreased from 56.1 +/- 1.6 mm to 35.3 +/- 2.3 in the ASU group and from 56.1 +/- 1.8 mm to 45.7 +/- 2.6 in the placebo group (P = 0.003 at month 6). NSAID consumption was slightly lower in the ASU group. Fewer patients in the ASU group required NSAIDs (48%, versus 63% in the placebo group; P = 0.054). The success rate was 39% in the ASU group and 18% in the placebo group. Overall functional disability was significantly reduced in the ASU group. Improvement appeared more marked in patients with hip OA. A residual effect was observed at month 8. Tolerance was good to excellent for most patients. ASU treatment showed significant symptomatic efficacy over placebo in the treatment of OA, acting from month 2 and showing a persistent effect after the end of treatment.


Characterizing the performance and outcomes of obesity surgery in California.
Between 1991 and 2000, the prevalence of obesity increased 65 per cent. As a result, increasing research is being directed at gastric bypass (GB) surgery, an operation that appears to achieve long-term weight reduction. Despite the rapid proliferation of this surgery, the quality of care at a population level is largely unknown. This study examines longitudinal trends in quality and identifies significant predictors of adverse outcomes. Using the California inpatient discharge database, all GB operations from 1996 to 2000 were identified. Demographic, comorbidity, complication, and volume data were obtained. Complications were defined as life-threatening cardiac, respiratory, or medical (renal failure or shock) events. Comorbidity was graded on a modified Charlson score. Annual hospital volume was categorized into four groups: < 50, 50-99, 100-199, and 200+ cases. Based on these data, we calculated longitudinal trends in complication rate and performed logistic regression to identify predictors of complications. A total of 16,232 patients were included. The average age was 41 years; 84 per cent were female, and 83.5 per cent were white. The complication rate was 10.4 per cent. Between 1996 and 2000, rates of cardiac and respiratory complications decreased while rates of medical complications remained unchanged. Complications were more likely in men [odd ratio (OR) = 1.69 compared to women] and in patients with comorbidities (OR = 1.60 for each additional comorbid disease). Furthermore, when examining the effect of volume, patients at very low (< 50) and low (50-99) volume hospitals were much more likely to have complications (OR = 2.72 and 2.70, respectively) compared to patients at high-volume hospitals (200+), even after controlling for differences in case-mix. The quality of care for obesity surgery has improved between 1996 and 2000. Despite operating on patients with more comorbidity, rates of cardiac and respiratory complications have decreased. Furthermore, this study identifies three independent predictors of complications: gender, comorbidity, and hospital volume. These findings are important initial steps toward improving quality in obesity surgery.


Feeding rates of a mammalian browser confirm the predictions of a 'foodscape' model of its habitat.
Adequate nutrition is a fundamental requirement for the maintenance and growth of populations, but complex interactions between nutrients and plant toxins make it difficult to link variation in plant quality to the ecology of wild herbivores. We asked whether a 'foodscape' model of habitat that uses near-infrared spectroscopy to describe the palatability of individual trees in the landscape, predicted the foraging decisions of a mammalian browser, the koala (Phascolarctos cinereus). Specifically, we considered four behavioural decision points at which nutritional quality may influence an animal's decision. These were: which tree to enter, whether to feed from that tree, when to stop eating, and how long to remain in that tree. There were trends for koalas to feed in eucalypt trees that were more palatable than unvisited neighbouring conspecific trees, and than trees that they visited but did not eat. Koalas ate longer meals in more palatable trees, and stayed longer and spent more time feeding per visit to these trees. Using more traditional chemical analyses, we identified that an interaction between the concentrations of formylated phloroglucinol compounds (a group of plant secondary metabolites) and available N (an integrated measure of tannins, digestibility and N) influenced feeding. The study shows that foodscape models that combine spatial information with integrated measures of food quality are a powerful tool to predict the feeding behaviour of herbivores in a landscape.


Origin of Outstanding Phase and Moisture Stability in a Na3P1-xAsxS4 Superionic Conductor.
Sodium ion (Na) solid-state electrolytes (SSEs) are critical to address notorious safety issues associated with liquid electrolytes used in the current Na ion batteries. Fulfilling multiple innovations is a grand challenge but is imperative for advanced Na ion SSEs, such as a combination of high ionic conductivity and excellent chemical stability. Here, our first-principles and phonon calculations reveal that Na3P1-xAsxS4 (0 ≤ x ≤ 1) is a solid-state superionic conductor stabilized at 0 K by zero-point vibrational energy and at finite temperatures by vibrational and configurational entropies. Especially, our integrated first-principles and experimental approach indicates that Na3P1-xAsxS4 is dry-air stable. Additionally, the alloying element arsenic greatly enhances the moisture (i.e., H2O) stability of Na3P1-xAsxS4 by shifting the reaction products from the easy-forming oxysulfides (such as Na3POS3 and Na3PO2S2 with H2S release) to the difficult-forming hydrates (such as Na3P1-xAsxS4·nH2O with n = 8 and/or 9) due mainly to a weaker As-O affinity compared to that of P-O. The present work demonstrates that alloying is able to achieve multiple innovations for solid-state electrolytes, such as a desirable superionic conductor with not only a high ionic conductivity (for example, 1.46 mS/cm at room temperature achieved in Na3P0.62As0.38S4) but also an excellent chemical stability with respect to temperature, composition, and moisture.


Setaria viridis: a model for C4 photosynthesis.
C(4) photosynthesis drives productivity in several major food crops and bioenergy grasses, including maize (Zea mays), sugarcane (Saccharum officinarum), sorghum (Sorghum bicolor), Miscanthus x giganteus, and switchgrass (Panicum virgatum). Gains in productivity associated with C(4) photosynthesis include improved water and nitrogen use efficiencies. Thus, engineering C(4) traits into C(3) crops is an attractive target for crop improvement. However, the lack of a small, rapid cycling genetic model system to study C(4) photosynthesis has limited progress in dissecting the regulatory networks underlying the C(4) syndrome. Setaria viridis is a member of the Panicoideae clade and is a close relative of several major feed, fuel, and bioenergy grasses. It is a true diploid with a relatively small genome of ~510 Mb. Its short stature, simple growth requirements, and rapid life cycle will greatly facilitate genetic studies of the C(4) grasses. Importantly, S. viridis uses an NADP-malic enzyme subtype C(4) photosynthetic system to fix carbon and therefore is a potentially powerful model system for dissecting C(4) photosynthesis. Here, we summarize some of the recent advances that promise greatly to accelerate the use of S. viridis as a genetic system. These include our recent successful efforts at regenerating plants from seed callus, establishing a transient transformation system, and developing stable transformation.


Transcriptional regulation of the novel monoamine oxidase renalase: Crucial roles of transcription factors Sp1, STAT3, and ZBP89.
Renalase, a novel monoamine oxidase, is emerging as an important regulator of cardiovascular, metabolic, and renal diseases. However, the mechanism of transcriptional regulation of this enzyme remains largely unknown. We undertook a systematic analysis of the renalase gene to identify regulatory promoter elements and transcription factors. Computational analysis coupled with transfection of human renalase promoter/luciferase reporter plasmids (5'-promoter-deletion constructs) into various cell types (HEK-293, IMR32, and HepG2) identified two crucial promoter domains at base pairs -485 to -399 and -252 to -150. Electrophoretic mobility shift assays using renalase promoter oligonucleotides with and without potential binding sites for transcription factors Sp1, STAT3, and ZBP89 displayed formation of specific complexes with HEK-293 nuclear proteins. Consistently, overexpression of Sp1, STAT3, and ZBP89 augmented renalase promoter activity; additionally, siRNA-mediated downregulation of Sp1, STAT3, and ZBP89 reduced the level of endogenous renalase transcription as well as the transfected renalase promoter activity. In addition, chromatin immunoprecipitation assays showed in vivo interactions of these transcription factors with renalase promoter. Interestingly, renalase promoter activity was augmented by nicotine and catecholamines; while Sp1 and STAT3 synergistically activated the nicotine-induced effect, Sp1 appeared to enhance epinephrine-evoked renalase transcription. Moreover, renalase transcript levels in mouse models of human essential hypertension were concomitantly associated with endogenous STAT3 and ZBP89 levels, suggesting crucial roles for these transcription factors in regulating renalase gene expression in cardiovascular pathological conditions.


A study of LiF GR-200 for radiotherapy mailed dosimetry.
A study of the measurement performance of LiF GR-200 for radiotherapy mailed dosimetry is presented. The study was carried out in the practical working conditions of a mailed system where a lengthy delay between dosimeter preparation and the final readout can occur. Prompt and delayed TL measurements were employed to determine, among other characteristics, the reusability and the stability during storage at room temperature. From the results obtained it can be concluded that GR-200, although producing dose results adequate for mailed dosimetry, does not improve the performance attainable with LiF TLD-100.


Surface defect analysis on formed chalcogenide glass Ge22Se58As20 lenses after the molding process.
Chalcogenide glass (ChG) is increasingly used in infrared optical systems owing to its excellent infrared optical properties and scalable production using precision glass molding (PGM). However, surface scratches affected by the molding temperature and microdimples on the lens surface caused by gas release seriously impair the quality of the formed lens. To reduce these surface defects when molding Ge22Se58As20 ChG, the temperature effect must be studied, and the gas generation must be minimized, while the gas escape must be maximized. In this work, we studied the effect of temperature on the surface defects. Additionally, we studied the influences of the roughness and curvature of the contact surfaces, as well as the pressing force on the formation of the microdimples. It was found that the molding temperature should be approximately 30°C higher than the softening temperature (Ts) to avoid surface scratches. The gas generation could be inhibited by increasing the pressing force and decreasing the roughness of the mold surface, and finally, increasing the curvature difference between the mold and glass preform surfaces improved the gas escape.


Frozen motion: how cryo-EM changes the way we look at ABC transporters.
ATP-binding cassette (ABC) transporters are widely present molecular machines that transfer substrates across the cell membrane. ABC transporters are involved in numerous physiological processes and are often clinical targets. Structural biology is fundamental to obtain the molecular details underlying ABC transporter function and suggest approaches to modulate it. Until recently, X-ray crystallography has been the only method capable of providing high-resolution structures of ABC transporters. However, modern cryo-electron microscopy (cryo-EM) opens entirely new ways of studying these dynamic membrane proteins. Cryo-EM enables analyses of targets that resist X-ray crystallography, challenging multicomponent complexes, and the exploration of conformational dynamics. These unique capacities have turned cryo-EM into the dominant technique for structural studies of membrane proteins, including ABC transporters.


Membrane activity of the phospholipase C-delta1 pleckstrin homology (PH) domain.
PH-PLCdelta1 [the PH domain (pleckstrin homology domain) of PLCdelta1 (phospholipase C-delta1)] is among the best-characterized phosphoinositide-binding domains. PH-PLCdelta1 binds with high specificity to the headgroup of PtdIns(4,5)P2, but little is known about its interfacial properties. In the present study, we show that PH-PLCdelta1 is also membrane-active and can insert significantly into PtdIns(4,5)P2-containing monolayers at physiological (bilayer-equivalent) surface pressures. However, this membrane activity appears to involve interactions distinct from those that target PH-PLCdelta1 to the PtdIns(4,5)P2 headgroup. Whereas the majority of PtdIns(4,5)P2-bound PH-PLCdelta1 can be displaced by adding excess of soluble headgroup [Ins(1,4,5)P3], membrane activity of PH-PLCdelta1 cannot. PH-PLCdelta1 differs from other phosphoinositide-binding domains in that its membrane insertion does not require that the phosphoinositide-binding site be occupied. Significant monolayer insertion remains when the phosphoinositide-binding site is mutated, and PH-PLCdelta1 can insert into monolayers that contain no PtdIns(4,5)P2 at all. Our results suggest a model in which reversible membrane binding of PH-PLCdelta1, mediated by PtdIns(4,5)P2 or other acidic phospholipids, occurs without membrane insertion. Accumulation of the PH domain at the membrane surface enhances the efficiency of insertion, but does not significantly affect its extent, whereas the presence of phosphatidylethanolamine and cholesterol in the lipid mixture promotes the extent of insertion. This is the first report of membrane activity in an isolated PH domain and has implications for understanding the membrane targeting by this common type of domain.


Association of Socioeconomic Status with Chronic Graft-versus-Host Disease Outcomes.
Chronic graft-versus host disease (GVHD) is a chronic and disabling complication after hematopoietic cell transplantation (HCT). It is important to understand the association of socioeconomic status (SES) with health outcomes in patients with chronic GVHD because of the impaired physical health and dependence on intensive and prolonged health care utilization needs in these patients. We evaluated the association of SES with survival and quality of life (QOL) in a cohort of 421 patients with chronic GVHD enrolled on the Chronic GVHD Consortium Improving Outcomes Assessment study. Income, education, marital status, and work status were analyzed to determine the associations with patient-reported outcomes at the time of enrollment, nonrelapse mortality (NRM), and overall mortality. Higher income (P = .004), ability to work (P < .001), and having a partner (P = .021) were associated with better mean Lee chronic GVHD symptom scores. Higher income (P = .048), educational level (P = .044), and ability to work (P < .001) also were significantly associated with better QOL and improved activity. In multivariable models, higher income and ability to return to work were both significantly associated with better chronic GVHD Lee symptom scores, but income was not associated with activity level, QOL, or physical/mental functioning. The inability to return to work (hazard ratio, 1.82; P = .019) was associated with worse overall mortality, whereas none of the SES indicators were associated with NRM. Income, race, and education did not have statistically significant associations with survival. In summary, we did not observe an association between SES variables and survival or NRM in patients with chronic GVHD, although we found some association with patient-reported outcomes, such as symptom burden. Higher income status was associated with less severe chronic GVHD symptoms. More research is needed to understand the psychosocial, biological, and environmental factors that mediate this association of SES with major HCT outcomes.


15-Meth-oxy-14,15-di-hydro-andranginine.
The title polycyclic alkaloid, C22H26N2O3, an indole derivative obtained from Melodinus yunnanensis, comprises three chiral C atoms and crystallizes as a racemate. Its seven-membered heterocyclic ring has a twisted conformation, with the N atom within the plane of the indole moiety and with two adjacent C atoms deviating in opposite directions from its plane by 0.756 (3) (methyl-ene C) and -0.802 (3) Å (methine C). In the crystal, pairs of N-H⋯O hydrogen bonds connect the mol-ecules into centrosymmetric dimers.


[Heart rate variability in the prognosis of tilt-testing results].
Study aim was assessment of dynamics of spectral parameters of heart rate variability (HRV) during the Westminster and Italian protocols of tilt-test (TT). We included in this study 114 patients with recurrent vasovagal syncope (VVS). Basing on TT results we distinguished 4 groups of patients: with positive result of the Westminster protocol (WPTT) (group 1, n=30); with negative result of WPTT (group 2, n=23); with positive result of the Italian protocol (IPTT) (group 3, n=44); with negative result of IPTT (group 4, n=11). Control group comprised 14 healthy persons without history of syncope. Spectral parameters of HRV were analyzed in 3 five minutes intervals (before TT in horizontal position, during first and last 5 minutes of orthostasis). Structure of vasovagal responses was similar for all TT protocols used. In lying position in patients of groups 1-3 lower values of LF1 and LF1/HF1 were registered, as well as high values of HF1 compared with the control group and patients with negative results of IPTT. Initial stage of TT in patients with positive result of WPTT (group 1) was characterized by almost twofold increase of LF values (n.u.) and decrease of HF parameters (n.u.) compared with other patients. In the group 1 during the second period.


Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion.
The possibility that triacylglycerol (TAG) synthesis occurs on both aspects of the endoplasmic-reticular membrane during the process of incorporation of TAG into secreted very-low-density lipoprotein (VLDL) [Zammit (1996) Biochem. J. 314, 1-14] was investigated by measuring the latency of diacylglycerol acyltransferase (DGAT) in microsomal fractions obtained from rat liver homogenates. Permeabilization of microsomes with taurocholate resulted in the doubling of the activity, indicating that DGAT activities of approximately equal magnitude occur on either aspect of the microsomal membrane. The taurocholate concentrations required for exposure of the latent activity of DGAT were identical with those that resulted in the exposure of marker enzymes for the lumen of the endoplasmic reticulum. Fractionation of the microsomes into smooth and rough populations indicated that the distribution of overt and latent DGAT activities was the same throughout. The possibility that taurocholate effects may result from non-specific activation of the overt enzyme was excluded by employing the channel-forming peptide alamethicin to effect permeabilization, and by varying the mode of delivery of diacylglycerol substrate to the microsomal membranes. Permeabilization using alamethicin gave a slightly higher latent/overt ratio for DGAT. The possible roles of overt and latent DGAT activities in the synthesis and secretion of TAG by the liver are discussed.


Lung Cancer Screening Using Clinical Photon-Counting Detector Computed Tomography and Energy-Integrating-Detector Computed Tomography: A Prospective Patient Study.
To evaluate the diagnostic quality of photon-counting detector (PCD) computed tomography (CT) in patients undergoing lung cancer screening compared with conventional energy-integrating detector (EID) CT in a prospective multireader study. Patients undergoing lung cancer screening with conventional EID-CT were prospectively enrolled and scanned on a PCD-CT system using similar automatic exposure control settings and reconstruction kernels. Three thoracic radiologists blinded to CT system compared PCD-CT and EID-CT images and scored examinations using a 5-point Likert comparison score (-2 [left image is worse] to +2 [left image is better]) for artifacts, sharpness, image noise, diagnostic image quality, emphysema visualization, and lung nodule evaluation focusing on the border. Post hoc correction of Likert scores was performed such that they reflected PCD-CT performance in comparison to EID-CT. A nonreader radiologist measured objective image noise. Thirty-three patients (mean, 66.9 ± 5.6 years; 11 female; body mass index; 30.1 ± 5.1 kg/m 2 ) were enrolled. Mean volume CT dose index for PCD-CT was lower (0.61 ± 0.21 vs 0.73 ± 0.22; P < 0.001). Pooled reader results showed significant differences between imaging modalities for all comparative rankings ( P < 0.001), with PCD-CT favored for sharpness, image noise, image quality, and emphysema visualization and lung nodule border, but not artifacts. Photon-counting detector CT had significantly lower image noise (74.4 ± 10.5 HU vs 80.1 ± 8.6 HU; P = 0.048). Photon-counting detector CT with similar acquisition and reconstruction settings demonstrated improved image quality and less noise despite lower radiation dose, with improved ability to depict pulmonary emphysema and lung nodule borders compared with EID-CT at low-dose lung cancer CT screening.


The diagnosis of drug allergies. Utilizing in vitro mast cell test and IgE inhibition test.
With the ever-increasing use of pharmaceuticals and the relatively high risk of developing drug allergies, particularly for patients in hospitals and for ambulatory patients with a history of drug allergy, the need to develop in vitro assays for drug allergy is great. In the early 1970's a mast cell technique was developed for diagnosis of drug allergies. A PRIST inhibition assay has also recently been developed to detect IgE antibodies to drug allergens. This test has also been referred to as the Total IgE Inhibition Test by Specific Drug Allergen, and is a variant of the in vitro RAST Test. In vitro mast cell and IgE inhibition tests are applied for identification of drug and chemical allergens and for their cautious clinical trial to prevent future drug and chemical reactions. Over the last eight years, over 1,300 patients were examined utilizing the mast cell technique. Over 100 drugs were tested, with penicillin, barbiturates, "caine" derivatives and sulfonamides most frequently employed. Of 270 patients with well-defined drug reactions, 190 (70 per cent) gave a positive response to the mast cell test. Eighty-five per cent of sera tested with Type I reactions gave a mast cell response. Of these, a group of 30 patients was studied with PRIST inhibition as well. Procedures for comparative testing of necessary drugs and/or chemicals in cases of high anaphylaxis risk of reaction in the clinical setting, hospital or office are included in the study as well as individual case reports. Mast cell assay coupled with IgE inhibition has been successfully used to diagnose drug and chemical allergic reactions. The incidence of positivity is high when the offending drug causes a Type I allergic reaction. The cases reported indicate that both the Mast Cell and the PRIST inhibition assays are useful for diagnosing and setting the clinical treatment and clinical course of the patient. The mast cell assay would be potentially employed for patient use in hospitals where the incidence of drug allergy is highest and for occupational health in the chemical industry. The greatest potential would be in outpatient care applied to patients with multiple drug allergies in the selection of safe drugs (test negative by both methods, and other clinical studies) for future drug usage.


[SURPS French version validation in a Quebec adolescent population].
The Substance Use Risk Profile Scale (SURPS) has been developed to screen personality risk factors for substance abuse. This scale assesses 4 high-risk personality traits using a 23-item, self-report questionnaire. SURPS helps guiding targeted approaches to prevention of substance abuse and misuse. It has been validated in the United Kingdom, English Canada, Sri Lanka, and China. This study aims to validate this scale in a sample of French-speaking adolescents from Quebec as well as its sensitivity in a clinical sample of adolescents. Two hundred two 15-year-old youths from a community sample completed a French version of SURPS as well as other measures of personality and substance use. This study reports the internal consistency and concurrent validity of the scale, as well as a factor analysis of items. Further, 40 youths (mean age 15.7 years) from a clinical population completed SURPS and their scores were compared with those of the community sample. SURPS French translation has good internal consistency and demonstrated a 4-factor structure very similar to the original scale. The 4 subscales show good concurrent validity, and 3 of the subscales were found to correlate with measures of substance use. Finally, 95% of the clinical sample was identified at high risk for substance misuse according to SURPS cut-off scores. SURPS French translation seems to be a valid and sensitive scale that can be used in a French-speaking adolescent population from Quebec.


Increased degradation in rat liver induced by antilipolytic agents: a model for studying autophagy and protein degradation in liver?
A dramatic increase in the plasma glucagon/insulin ratio can be induced by treating fasted rats with antilipolytic drugs (e.g., with 3,5-dimethylpyrazole, 12 mg/kg body wt). These hormone changes are the physiologically appropriate response to a rapid decrease in free fatty acids and glucose plasma levels. Under this experimental condition, many vacuolated lysosomes can be observed at the electron microscopic level as early as 30 min and autophagic vacuoles are detectable in the liver cells 1 hr after the administration of the drug. By 1 hr and 45 min, vacuoles often contain recognizable peroxisomes. At the biochemical level, liver proteolysis in vitro is increased significantly. Very interestingly, changes in peroxisomal (but not mitochondrial or reticulum or cytosolic) enzyme activities are detected that are preventable by the administration of glutamine (i.e., of an inhibitor of proteolysis in vivo) but not by an isocaloric amount of glycine or alanine. It is concluded that the administration of antilipolytic agents to fasted animals may provide a convenient (i.e., an inexpensive, highly reproducible and timable) physiologic model to study hormone-induced autophagy in liver cells.


Developing a typology of patient-generated behavioral goals for cognitive behavioral therapy for chronic pain (CBT-CP): classification and predicting outcomes.
Patient-generated treatment goals describe what patients value, yet the content of these goals, and the relationship among goal types, goal accomplishment, and treatment outcomes has received little examination. We used inductive sorting to categorize patient-generated goals made by 147 adults receiving cognitive-behavioral therapy for chronic pain. The resulting goal categories were: Physical Activity (29.0%), Functional Status (24.6%), Wellness (16.3%), Recreational Activities (11.3%), House/Yard Work (9.7%), Socializing (7.1%), and Work/School (2.0%). Next, we examined associations between number of goals by category, goal accomplishment, and clinically meaningful improvements in pain-related interference, pain intensity and depressive symptoms. Improvement in all outcome domains was related to goal accomplishment. Additionally, depressive symptoms were related to number of Physical Activity, House/Yard Work, Recreational Activities, and Wellness goals, whereas improved pain-intensity was significantly related to House/Yard Work. Classifying patient-generated goals facilitates investigation of the relationships among goal type, goal accomplishment and treatment outcomes.


[Carotinoid deposits in the retina].
In this case report a 55-year-old Turkish patient with polymorphous light eruption, who has been treated with high doses of beta-carotene and canthaxanthin for more than 6 years is described. The examination of the fundus showed dense, glistening bright yellow crystalline deposits around the maculae. The only functional impairment that could be detected was a slight decrease in visual acuity and dark adaptation.


HLA-E regulatory and coding region variability and haplotypes in a Brazilian population sample.
The HLA-E gene is characterized by low but wide expression on different tissues. HLA-E is considered a conserved gene, being one of the least polymorphic class I HLA genes. The HLA-E molecule interacts with Natural Killer cell receptors and T lymphocytes receptors, and might activate or inhibit immune responses depending on the peptide associated with HLA-E and with which receptors HLA-E interacts to. Variable sites within the HLA-E regulatory and coding segments may influence the gene function by modifying its expression pattern or encoded molecule, thus, influencing its interaction with receptors and the peptide. Here we propose an approach to evaluate the gene structure, haplotype pattern and the complete HLA-E variability, including regulatory (promoter and 3'UTR) and coding segments (with introns), by using massively parallel sequencing. We investigated the variability of 420 samples from a very admixed population such as Brazilians by using this approach. Considering a segment of about 7kb, 63 variable sites were detected, arranged into 75 extended haplotypes. We detected 37 different promoter sequences (but few frequent ones), 27 different coding sequences (15 representing new HLA-E alleles) and 12 haplotypes at the 3'UTR segment, two of them presenting a summed frequency of 90%. Despite the number of coding alleles, they encode mainly two different full-length molecules, known as E*01:01 and E*01:03, which corresponds to about 90% of all. In addition, differently from what has been previously observed for other non classical HLA genes, the relationship among the HLA-E promoter, coding and 3'UTR haplotypes is not straightforward because the same promoter and 3'UTR haplotypes were many times associated with different HLA-E coding haplotypes. This data reinforces the presence of only two main full-length HLA-E molecules encoded by the many HLA-E alleles detected in our population sample. In addition, this data does indicate that the distal HLA-E promoter is by far the most variable segment. Further analyses involving the binding of transcription factors and non-coding RNAs, as well as the HLA-E expression in different tissues, are necessary to evaluate whether these variable sites at regulatory segments (or even at the coding sequence) may influence the gene expression profile.


Phototherapeutic keratectomy for granular and lattice corneal dystrophies at 1.5 to 4 years.
The capability of the 193-nm excimer laser to ablate the cornea and to remove opacities and various other corneal diseases in a procedure called phototherapeutic keratectomy (PTK) has been demonstrated. In this study we evaluated the long-term results of PTK for treatment of granular and lattice corneal dystrophies. Four eyes with granular or lattice corneal dystrophy were treated with a mean follow-up of 47.8 months (range, 36 to 58 months). Focal ablations of the central cornea with an ablation zone of 5.5 to 6.0 mm were performed. Ablation depth was 110 microns in three eyes and 140 microns in one eye. Removal of corneal opacities allowed for improvement in corrected visual acuity in all patients. Mean corneal thickness in the area of pathology decreased from 0.583 mm before surgery to 0.449 mm after surgery. Spherical equivalent of the manifest refraction measurements increased by a mean of +5.09 D. There were no major complications, but all patients developed slight haze. There was a hyperopic shift in three eyes. Our long-term results suggest that PTK is a safe and effective alternative to penetrating and lamellar keratoplasty in patients with granular or lattice corneal dystrophies.


Responsiveness of the coronary revascularisation outcome questionnaire compared with the SF-36 and Seattle Angina Questionnaire.
We describe a comparison of the responsiveness of three validated instruments when used with patients undergoing coronary bypass surgery (CABG) and angioplasty (PTCA). Patients were randomly selected to receive the Coronary Revascularisation Outcome Questionnaire (CROQ), and either the Seattle Angina Questionnaire (SAQ), or the SF-36 before and 3 months after coronary revascularisation. At total of 199 patients (127 CABG, 72 PTCA) completed the CROQ; 55/72 CABG and 34/38 PTCA patients also completed the SAQ or SF-36, respectively. Effect sizes and standardised response means were calculated as change over the 3-month period for scales measuring similar constructs on each instrument. We used bootstrap estimation to derive 95% confidence intervals for differences in the responsiveness indices. For CABG, the CROQ demonstrated significantly greater change in psychosocial functioning than the SF-36, but less than the SAQ. For PTCA, the CROQ showed greater change for symptoms than the SAQ, but the SAQ was more responsive in terms of physical functioning; and the CROQ showed significantly greater change than the SF-36 for psychosocial functioning. There were no other significant differences between similar scales on the three instruments. In conclusion, the CROQ was as responsive as the disease-specific SAQ and more responsive than the generic SF-36.


Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance.
A key tool of cancer therapy has been targeted inhibition of oncogene-addicted pathways. However, efficacy has been limited by progressive emergence of resistance as transformed cells adapt. Here, we use Drosophila to dissect response to targeted therapies. Treatment with a range of kinase inhibitors led to hyperactivation of overall cellular networks, resulting in emergent resistance and expression of stem cell markers, including Sox2. Genetic and drug screens revealed that inhibitors of histone deacetylases, proteasome, and Hsp90 family of proteins restrained this network hyperactivation. These "network brake" cocktails, used as adjuncts, prevented emergent resistance and promoted cell death at subtherapeutic doses. Our results highlight a general response of cells, transformed and normal, to targeted therapies that leads to resistance and toxicity. Pairing targeted therapeutics with subtherapeutic doses of broad-acting "network brake" drugs may provide a means of extending therapeutic utility while reducing whole body toxicity.Significance: These findings with a strong therapeutic potential provide an innovative approach of identifying effective combination treatments for cancer. Cancer Res; 78(15); 4344-59. ©2018 AACR.


Family environment and cognitive abilities in girls with fragile-X syndrome.
There remains some variance in cognitive ability that is unexplained in children with fragile-X syndrome (FXS). Studies in typically developing children suggest that family environment might be one contributor to this unexplained variance. However, the effect of family environment in relation to cognition in atypical children with FXS has been relatively unexplored to date. The present authors examined the putative genetic and environmental factors associated with cognition in a group of age-matched children consisting of 26 females with FXS and 31 typically developing children. All subjects were administered the Wechsler Intelligence Scale for Children-Revised; and the subjects' parents were administered the Wechsler Adult Intelligence Scale-Revised, and completed the Hollingshead Index of Social Status and the Moos & Moos Family Environment Scale. Using a multiple regression analytic strategy, the present authors found that family environment contributed significantly to cognitive abilities in typically developing girls, but did not have a unique contribution to cognitive abilities in girls with FXS. There was a suggestion that, for girls with FXS, socio-economic status, a measure of sociocultural environment, was correlated with IQ. The present study provides a basis for future research on the environmental contributions to cognitive abilities, particularly work related to verbal cognition.


Melatonin receptors and signal transduction mechanisms.
The ovine pars tuberalis (PT) still offers the best model for the study of signal transduction pathways regulated by the melatonin receptor. From the evidence accumulated so far, it seems likely that the cAMP signal transduction pathway will be a major effector of a stimulatory signal to the PT which can be regulated by melatonin. Thus a principal action of melatonin in the PT may be the repression of biochemical processes driven by cAMP. However, through the phenomenon of sensitization, melatonin may also act to amplify a stimulatory input to the cAMP signal transduction pathway in the PT. These events are mediated via the melatonin receptor, which is itself a target for regulation by the melatonin signal. Studies using the PT have identified several signalling pathways that may serve to positively or negatively regulate the expression of the melatonin receptor. These and other studies in the PT have alluded to cAMP-independent pathways regulated by the melatonin receptor.


Lives, liberty, and seat belts in Britain: lessons for the United States.
By the end of this decade virtually all fifty U.S. state legislatures will have debated, and many will have adopted, mandatory seat belt legislation. While the debate in the United States has just begun, one can anticipate and preview the issues, arguments, and results by examining the British debate over, and experience with, a mandatory seat belt law. From this cross-national perspective, this article examines the practical, philosophical, and preventive health care dimensions and implications of this debate. Based upon personal interviews and the Parliamentary record, the author traces the background of the issue, and the major arguments for and against mandating seat belt use. Particular emphasis is placed upon the libertarian objections to such legislation, and how some British Conservatives were able to reconcile their philosophical beliefs with public safety needs. The article concludes by suggesting some lessons which U.S. proponents of mandatory seat belt legislation might learn from the British experience.


A therapeutic DNA vaccination strategy for autoimmunity and transplantation.
De novo autoimmunity induced by an allograft may play a significant role in chronic organ rejection, which remains a major barrier to successful transplantation. Accordingly, immunization with non-polymorphic antigens found in both donor allograft and recipient would be an attractive means to prevent long-term graft rejection, because it would rely on recipient mechanisms of immune homeostasis and could minimize the need to identify appropriate donor polymorphic antigens for induction of graft tolerance. Here we show that intradermal injection of plasmid DNA encoding glutamic acid decarboxylase (GAD) polypeptide, which is synthesized in both pancreatic islet and skin tissue, ameliorated new-onset type 1 diabetes in NOD mice and increased skin allograft survival in a BALB/c-C57BL/6 model system in a donor-specific manner. Successful therapy of autoimmune diabetes required CpG-methylation of plasmid DNA and co-delivery of a cDNA coding for the pro-apoptotic BAX protein, which was shown previously to induce Foxp3(+) regulatory T cells in NOD mice. In contrast, significantly increased skin allograft survival after immunization of recipient only required CpG-methylation of plasmid DNA coding for GAD alone. Injection of unmethylated plasmid DNA coding for BAX alone near the allograft also promoted graft survival, but induced a pro-inflammatory response to self-antigens. Our results reveal a promising potential for autoimmunity-targeting DNA vaccination to be applied to transplantation.


Developing and validating the Arabic version of the Diabetes Quality of Life questionnaire.
The Diabetes Quality of Life (DQoL) questionnaire has been used frequently among people with diabetes. To develop and validate a revised Arabic version of the DQoL questionnaire for patients in Jordan with type 2 diabetes. We recruited patients with type 2 diabetes from 3 public health clinics in Jordan. The original DQoL questionnaire was translated to Arabic and then back-translated by a different translator, and the 2 versions were compared. Prior to circulating the final version of the questionnaire, a cognitive validity test was applied to ensure that all the questions were clear. The final Arabic version of the DQoL questionnaire, along with a questionnaire that included demographic and other health-related questions, were circulated to the participants. The questionnaire data were analysed using exploratory factor analysis and confirmatory factor analysis after excluding duplicated questions and questions that included > 10% missing data. Cronbach's α was also conducted to confirm internal consistency. Analysis validated an Arabic version of DQoL questionnaire that included 29 items divided into 3 factors: worries, impact and satisfaction. Different variables were associated with DQoL scores including insulin administration, low income status, marital status, and presence of diabetic complications. We validated an Arabic tool that can be used to evaluate QoL among Arabic-speaking patients with type 2 diabetes.


SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.
The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes.


[The left atrial-femoral bypass in operations on the descending aorta].
Fifteen patients were operated on for aortic aneurysms and were fitted with prostheses of the thoracoabdominal portion of the aorta in March 1997-February 1999. The operations were performed under conditions of a left atrial-femoral bypass with a centrifuge pump with a working heart. The patients were divided into 2 groups. In group 1 (10 pts), standard extracorporeal shunting and Cell-Saver were used, in group 2 (5 pts) the extracorporeal contour included an original system for rapid collection and return of autoblood. A left-atrial bypass prevented ischemia of the organs of the abdominal cavity and lower part of the body. Incorporation of a system for rapid collection and return of autoblood into the extracorporeal contour maintained stable hemodynamics, decreased heparin dose, preserved autoblood, and decreased the amount of transfused donor blood and its components.


Immune responses to the hepatitis C virus NS4A protein are profoundly influenced by the combination of the viral genotype and the host major histocompatibility complex.
The interaction between the host major histocompatibility complex (MHC) and the genotype of the hepatitis C virus (HCV) was analysed using synthetic full-length non-structural (NS) 4A proteins, residues 1658-1712, of genotypes 1b, 2b, 3a, 4a and 5a. Human and murine antibodies specific for the five NS4A genotypes analysed focused on residues 1688-1707. In immunized B10 H-2 congenic mice, the H-2d, H-2f and H-2s haplotypes were good responders to NS4A, irrespective of the viral genotype. In contrast, the H-2k haplotype was a low or non-responder to all NS4A genotypes, except for genotype 2b. Also, H-2f- and H-2s-restricted NS4A genotype 1b-specific T-cells focused on residues 1670-1679 and 1683-1692, respectively, whereas H-2k-restricted NS4A genotype 2b-specific T-cells focused on the carboxy terminus. Interestingly, H-2f-restricted genotype 1b-specific T-cells did not cross-react with T-cell site analogues of seven other genotypes, whereas the H-2s-restricted, genotype 1b-specific T-cells cross-reacted with genotypes 1a, 4a and 5a. Thus the combination of viral genotype and host MHC profoundly influences the ability to mount an HCV NS4A-specific immune response.


Canine dirofilariosis in two cities of southeastern Spain.
Several cases of human subcutaneous/ocular dirofilariosis caused by Dirofilaria repens from an area in the southeastern Spain where previous epidemiological studies have shown a very low prevalence of this species in dogs, have been studied in our laboratory. Since the prevalence of this species in dogs did not correspond to the incidence of human cases in the zone studied, a preliminary epidemiological survey was carried out on 114 dog blood samples from two kennels and one veterinary clinic. Knott, polymerase chain reaction (PCR) with specific primers for Dirofilaria immitis and D. repens, and ELISA with adult E/S D. immitis and adult somatic D. repens antigens for the detection of specific IgG, were used. Fifty-three out of the 114 samples analyzed were positive for Knott and/or PCR to D. immitis or to D. repens. D. repens was the species with the highest prevalence, 84.6 and 37.1%, respectively, in each kennel. IgG antibodies against D. immitis and D. repens, were detected in 11 samples which gave negative results to both Knott and PCR. These results demonstrate a very high prevalence of D. repens that could be associated with the increasing incidence of human subcutaneous/ocular cases recently detected in this zone.


LED power consumption in joint illumination and communication system.
This paper addresses the power penalty in an illumination LED caused by visible light communication (VLC). This study models the extra power consumption of the LED by taking into account the convex relation between the dissipated electrical power versus the LED current on one hand and the concave relation between the output luminous flux versus the current on the other hand. The ratio of the output luminous flux to input electrical power, which is known the LED luminous efficacy, is analyzed considering various recombination mechanisms and their dependency on current and temperature. As examples, the rapid light fluctuations induced by Pulse Amplitude Modulation (PAM) and orthogonal frequency division multiplexing (OFDM) are analyzed for joint illumination and communication (JIC) systems. Due to the signal modulation, there is a decrease in the output light of LED. Nevertheless, the total power offered to LED is larger than without modulation and thus extra heating occurs. Moreover, particularly when burst transmission is used in communication networks, visible flicker may occur.


Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up.
The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence, where initial multidrug resistance (MDR) among adult TB cases was 1.1% during 1992-1993. To determine the long-term prevalence of TB infection and disease in children in household contact with adults with MDR pulmonary TB, and to establish the efficacy of chemoprophylaxis in preventing disease in these children. Children <5 years old in contact with 73 MDR TB adults were evaluated. Disease was treated by prescribing at least 2 drugs to which the adult's strain was susceptible. The remaining children were classified as infected or noninfected and received chemoprophylaxis according to the index's strain susceptibility or were followed up and treated when indicated. All were followed up for 30 months. At the initial evaluation 125 children were seen, median age 27.5 months. Of these, 119 were followed up. Fourteen (12%) had disease, 61 (51%) were infected only, and 44 (37%) were noninfected. By 30-month follow-up, 29 (24%) had developed disease and 64 (54%) were infected only. Four adult-child pair Mycobacterium tuberculosis isolates were compared by DNA fingerprinting; 3 were identical. All children who developed TB disease were clinically cured. Two (5%) of 41 children who received appropriate chemoprophylaxis and 13 (20%) of 64 who did not, developed TB during follow-up (odds ratio: 4.97). The study confirms MDR TB transmission to childhood contacts. Seventy-eight percent of children were infected or developed disease. Appropriate chemoprophylaxis may prevent disease in these children.


Serum levels of DHEAS in gynecologic endocrinopathy and infertility.
Serum dehydroepiandrosterone sulfate (DHEAS) was measured in 32 infertility patients who were found to be ovulatory, in 37 women with oligomenorrhea, and in 52 hirsute patients under basal conditions. It was also measured in conjunction with adrenocorticotropic hormone (ACTH) stimulation and dexamethasone suppression in 10 of the hirsute women. Serum DHEAS levels were elevated in only 19% of the infertile women with regular ovulation, in 34% of the oligomenorrheic patients, and in 60% of the hirsute women. Of the C-19 steroids (androgens) measured in the 52 hirsute women, ie, total and unbound serum testosterone (T), androstenedione (A), and DHEAS, unbound serum T was most frequently elevated. Eighty-two percent of the hirsute women had either an elevated serum DHEAS level or an increased unbound T level, suggesting 1) that elevations in unbound serum T may be associated with or result from increased serum DHEAS levels and 2) that only a minority of women with so-called idiopathic hirsutism do not have demonstrable androgen excess. Three of 10 hirsute women with elevated serum DHEAS levels had an increased ACTH-induced rise in DHEAS. Dexamethasone given as a single daily dose of 0.5 mg at bedtime resulted in a marked decrease in serum DHEAS in all of the 10 hirsute patients tested within 2 weeks of therapy. Thus, serum DHEAS is a clinically useful indication of adrenal C-19 steroid secretion. When combined with clinical and other hormonal evaluations, its measurement adds an important dimension to the study of gynecologic endocrinology and infertility.


Exploring adaptations to the modified shuttle walking test.
The 10 m modified shuttle walking test (MSWT) is recommended to determine the functional capacity in older individuals and for patients entering cardiac rehabilitation. Participants are required to negotiate around cones set 1 m from the end markers. However, consistent comments indicate that for some individuals manoeuvring around the cones can be quite difficult. Therefore, the objective of this study was to explore differences within and between non-cardiac and postmyocardial infarction (MI) males during MSWT with and without the cones. Comparative study. 20 post-MI (64.8±6.6, range 51-74 years) and 20 non-cardiac male controls (64.1±5.7, range 52-74 years) participated. Participants performed MSWT with and without cones. Throughout, the participants expired air, and the heart rate (bpm) (HR) and ratings of perceived exertion (RPE) were measured. Participant protocol preference was recorded verbatim. One-way analysis of variance found no significant difference in VO2 peak (cones 20.4±5.1 vs no-cones 21.9±4.8 ml/kg/min, p=0.197) or distance ambulated (cones 631.8±132.9 m vs no-cones 662.4±164.1 m, p=0.371) between protocols or groups. Analysis comparing lines of regression showed a significant trajectory difference in VO2 (ml/kg/min) (p<0.01) between protocols with higher HR (p<0.01) and respiratory exchange ratio (RER, p<0.001) values during cones. RPEs were higher for post-MIs versus controls during both protocols (p<0.05). Post-MIs taking β-blockers produce significantly lower HR values. The χ(2) analysis found no significant difference in protocol preference (no-cones: all n=25, 63%; post-MIs n=13, 65%; and controls n=12, 60%). Post-MIs found both protocols subjectively harder than controls with no significant difference in the VO2 peak. However, both groups worked at a lesser percentage of their anaerobic threshold during no-cones protocol as indicated by lower RER values. Importantly, for the post-MIs, this would reduce their risk of functional impairment. Therefore, though more research is required, indicators at present are more favourable for the use of the no-cones with post-MIs.


Somatostatin type-2 receptor activation inhibits glutamate release and prevents status epilepticus.
Newer therapies are needed for the treatment of status epilepticus (SE) refractory to benzodiazepines. Enhanced glutamatergic neurotransmission leads to SE, and AMPA receptors are modified during SE. Reducing glutamate release during SE is a potential approach to terminate SE. The neuropeptide somatostatin (SST) is proposed to diminish presynaptic glutamate release by activating SST type-2 receptors (SST2R). SST exerts an anticonvulsant action in some experimental models of seizures. Here, we investigated the mechanism of action of SST on excitatory synaptic transmission at the Schaffer collateral-CA1 synapses and the ability of SST to treat SE in rats using patch-clamp electrophysiology and video-EEG monitoring of seizures. SST reduced action potential-dependent EPSCs (sEPSCs) at Schaffer collateral-CA1 synapses at concentrations up to 1μM; higher concentrations had no effect or increased the sEPSC frequency. SST also prevented paired-pulse facilitation of evoked EPSCs and did not alter action-potential-independent miniature EPSCs (mEPSCs). The effect of SST on EPSCs was inhibited by the SST2R antagonist cyanamid-154806 and was mimicked by the SST2R agonists, octreotide and lanreotide. Both SST and octreotide reduced the firing rate of CA1 pyramidal neurons. Intraventricular administration of SST, within a range of doses, either prevented or attenuated pilocarpine-induced SE or delayed the median time to the first grade 5 seizure by 11min. Similarly, octreotide or lanreotide prevented or attenuated SE in more than 65% of animals. Compared to the pilocarpine model, octreotide was highly potent in preventing or attenuating continuous hippocampal stimulation-induced SE in all animals within 60min of SE onset. Our results demonstrate that SST, through the activation of SST2Rs, diminishes presynaptic glutamate release and attenuates SE.


Contribution of smoking-attributable mortality to life expectancy differences by marital status among Finnish men and women, 1971-2010.
Smoking is known to vary by marital status, but little is known about its contribution to marital status differences in longevity. We examined the changing contribution of smoking to mortality differences between married and never married, divorced or widowed Finnish men and women aged 50 years and above in 1971-2010. The data sets cover all persons permanently living in Finland in the census years 1970, 1975 through 2000 and 2005 with a five-year mortality follow-up. Smoking-attributable mortality was estimated using an indirect method that uses lung cancer mortality as an indicator for the impact of smoking on mortality from all other causes. Life expectancy differences between the married and the other marital status groups increased rapidly over the 40-year study period because of the particularly rapid decline in mortality among married individuals. In 1971-1975 37-48% of life expectancy differences between married and divorced or widowed men were attributable to smoking, and this contribution declined to 11-18% by 2006-2010. Among women, in 1971-1975 up to 16% of life expectancy differences by marital status were due to smoking, and the contribution of smoking increased over time to 10-29% in 2006-2010. In recent decades smoking has left large but decreasing imprints on marital status differences in longevity between married and previously married men, and small but increasing imprints on these differences among women. Over time the contribution of other factors, such as increasing material disadvantage or alcohol use, may have increased.


Spatial extrapolation of soil characteristics using whole-soil particle size distributions.
Soils support ecosystem functions such as plant growth and water quality because of certain physical, chemical, and biological properties. These properties have been studied at different spatial scales, including point scales to satisfy basic research needs, and regional scales to satisfy monitoring needs. Recently, soil property data for the entire USA have become available in the State Soil Geographic Data Base (STATSGO), which is appropriate for regional-scale research. We analyzed and created models of STATSGO data in this study to serve as a research tool, for example, for linking the soil to regional water quality monitoring data in our companion paper. Map units in STATSGO define geographic land areas by soil characteristics (SCs) of similar soil series. We selected 27 SCs that influenced water properties (in varying degrees), aggregated the layer and component SCs to map unit SCs, and used SCs to calculate relationships among map units. The relationships were defined by equations of conditional mean for the qth SC (SCq), while using the remaining 26 SCs as predictors. The relative standard errors for 22 of the 27 SCs were less than 10%, and less than 22% for the remaining five. We conclude that spatial extrapolation of SCs is feasible and the procedures are a first step toward extrapolating information across a region using SC-water property relationships. Although our procedure is for regional scale monitoring, it is also applicable to finer spatial scales commensurate with available soil data.


Two novel Zn-MOFs: structures and characterization.
Two novel three-dimensional Zn-MOFs (zinc metal-organic frameworks), Zn(5)(μ(3)-OH)(BTC)(3)(Phen)(4)·5H(2)O (denoted as HUT-11) and Zn(4)(μ(4)-O)(BTC)(2)(Phen)(2)·4H(2)O (denoted as HUT-12), have been synthesized by metal-ligand-directed assembly under hydrothermal conditions. Here, BTC and Phen are denoted as 1,3,5-benzenetricarboxylate and phenanthroline. HUT-11 contains two kinds of secondary building units (SBUs), Zn(3)(μ(3)-OH)(COO)(5) clusters and Zn(2)(COO)(4) clusters. This material exhibits a new three-dimensional (3,4,5)-connected topology with the Schläfli symbol (4·6·8)(2)(4·8(2))(4·6(4)·8(5))(4(2)·6(2)·8(2)). Two perpendicular planes cross at five coordinated Zn1-Zn3-Zn5 nodes, giving a new three-dimensional network. HUT-12 is composed of Zn(4)(μ(4)-O)(COO)(6) clusters as the secondary building units and displays a two-dimensional (3,6)-connected TiS(2) related net topology with the Schläfli symbol (4(2)·6)(4(4)·6(2)·8(8)·10). Both MOFs show blue light emission and a high thermal stability above 673 K.


MAPK Pathway under Chronic Copper Excess in Green Macroalgae (Chlorophyta): Involvement in the Regulation of Detoxification Mechanisms.
Following the physiological complementary/parallel Celis-Plá et al., by inhibiting extracellular signal regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and cytokinin specific binding protein (p38), we assessed the role of the mitogen-activated protein kinases (MAPK) pathway in detoxification responses mediated by chronic copper (10 µM) in U. compressa. Parameters were taken at 6, 24, and 48 h, and 6 days (d). H2O2 and lipid peroxidation under copper and inhibition of ERK, JNK, or p38 alone increased but recovered by the sixth day. By blocking two or more MAPKs under copper, H2O2 and lipid peroxidation decayed even below controls. Inhibition of more than one MAPK (at 6 d) caused a decrease in total glutathione (reduced glutathione (GSH) + oxidised glutathione (GSSG)) and ascorbate (reduced ascorbate (ASC) + dehydroascorbate (DHA)), although in the latter it did not occur when the whole MAPK was blocked. Catalase (CAT), superoxide dismutase (SOD), thioredoxin (TRX) ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), and glutathione synthase (GS), were downregulated when blocking more than one MAPK pathway. When one MAPK pathway was blocked under copper, a recovery and even enhancement of detoxification mechanisms was observed, likely due to crosstalk within the MAPKs and/or other signalling processes. In contrast, when more than one MAPK pathway were blocked under copper, impairment of detoxification defences occurred, demonstrating that MAPKs were key signalling mechanisms for detoxification in macroalgae.


Reversible leukoencephalopathy associated with graft-versus-host disease: MR findings.
Ten weeks after undergoing bone marrow transplantation for metastatic lymphoma of the parotid gland, a 9-year-old girl became disoriented and had tremor and myoclonus in the context of graft-versus-host disease (GVHD). MR images showed abnormal signal primarily within the brain stem and deep white matter, which resolved almost completely after treatment. The findings are consistent with brain involvement by GVHD.