Insights into the "isolation" of the Basques: mtDNA lineages from the historical site of Aldaieta (6th-7th centuries AD).
We analyzed the hypervariable region I (HVR-I) sequence variability of the mitochondrial DNA (mtDNA) of individuals buried at Aldaieta (6th-7th centuries AD) in order to find out more about the biosocial implications of this cemetery. The results, fully authenticated by means of diverse criteria (analysis of duplicates, replication in an independent laboratory, quantification of target DNA, and sequencing and cloning of polymerase chain reaction products), suggest that Aldaieta largely consists of autochthonous individuals who shared common funereal customs with the late Ancient North Pyrenean cemeteries of Western Europe (the Reihengräberfelder), a cultural influence possibly accompanied by a certain genetic flow. Furthermore, the distribution of mtDNA lineages in the cemetery highlighted the existence of a significant number of family relationships, supporting the belief that it was a stable settlement and not a group that had haphazardly settled in the area. Finally, this paper stresses the importance of ancient DNA data for reconstructing the biological history of human populations, rendering it possible to verify certain hypotheses based solely on current population data. The presence at Aldaieta of an mtDNA lineage originating in Northwest Africa testifies to the existence of contact between the Iberian Peninsula and Northwest Africa prior to the Moorish occupation. Both this latter discovery and the high frequency of haplogroup J at the Aldaieta cemetery raise questions about the generally accepted belief that, since ancient times, the influence of other human groups has been very scarce in the Basque Country.


Genetic transformation of 9 in vitro clones of Alnus and Betula by Agrobacterium tumefaciens.
Crown gall tumorigenesis, integration and expression of T-DNA encoded genes from Agrobacterium tumefaciens were investigated in 9 clones of Alnus glutinosa, A. incana and Betula papyrifera. Tumor formation on in vitro shoots was frequent in all clones with strain Ach5 and present in 8 clones with strain C58. Tumors excised from shoots were selected for autotrophic growth in vitro and axenic cultures were established. Octopine or nopaline, respective of the strain type used for inoculation, was detected in tumorous cultures. Southern blot analyses demonstrated T-DNA integration by hybridization of DNA from tumors with tmr and nos gene probes. One clone of B. papyrifera produced tumors with a morphogenic character, unusual in calli of this species, generating viable shoots which did not synthesize opine.


Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States)
Recent experimental studies have suggested that isoflavones (such as genistein and daidzein) found in some soy products may reduce the risk of cancer. The purpose of this study was to evaluate the relationship between soy milk, a beverage containing isoflavones, and prostate cancer incidence. A prospective study with 225 incident cases of prostate cancer in 12,395 California Seventh-Day Adventist men who in 1976 stated how often they drank soy milk. Frequent consumption (more than once a day) of soy milk was associated with 70 per cent reduction of the risk of prostate cancer (relative risk = 0.3, 95 percent confidence interval 0.1-1.0, p-value for linear trend = 0.03). The association was upheld when extensive adjustments were performed. Our study suggests that men with high consumption of soy milk are at reduced risk of prostate cancer. Possible associations between soy bean products, isoflavones and prostate cancer risk should be further investigated.


In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses.
Suspensions of herpes simplex virus types 1 and 2, cytomegalovirus, and parainfluenzavirus type 2 were inactivated within 24 h when treated at 37 degrees C with 1 mg (5.05 mM) of copper-catalyzed sodium ascorbate per ml. The infectivity titer of respiratory syncytial virus was reduced substantially after 24 h but required 48 h for inactivation. Under these conditions, inactivation of these viruses was also successfully achieved with 5.68 mM catalyzed ascorbic acid. Copper (Cu2+), when added with the ascorbate solution at 5 micrograms/ml (0.022 mM), exhibited a catalytic effect on the inactivation of these viruses. The rate of inactivation was affected by the incubation temperature, time of exposure, and the virus concentration. Ascorbate concentrations as high as 10 mg/ml (50.5 mM) demonstrated only a minimum increase in effect on viral inactivation. The loss of infectivity did not alter either the hemagglutination or complement fixation qualities of the antigens.


Does anti-Müllerian hormone predict menopause in the general population? Results of a prospective ongoing cohort study.
Do ovarian reserve tests (ORTs) predict age at natural menopause (ANM) in a cohort of healthy women with a regular menstrual cycle? Of the ORTs researched, anti-Müllerian hormone (AMH) alone predicts age at menopause. However, its predictive value decreased with increasing age of the woman, prediction intervals were broad and extreme ages at menopause could not be predicted. A fixed interval is hypothesized to exist between ANM and age at loss of natural fertility. Therefore, if it is possible to predict ANM, one could identify women destined for early menopause and thus at higher risk for age-related subfertility. Of ORTs researched in the prediction of ANM, AMH is the most promising one. A long-term, extended follow-up study was conducted, results of the first follow-up round were previously published. Two hundred and sixty-five normo-ovulatory women (21-46 years) were included between 1992 and 2001, 49 women (18.5%) could not be reached in the current follow-up round. Two hundred and sixty-five healthy normo-ovulatory women were included, recruited in an Academic hospital. We measured baseline AMH, follicle-stimulating hormone and the antral follicle count (AFC). At follow-up (2009 and 2013), menopausal status was determined via questionnaires. Cox regression analysis calculated time to menopause (TTM) using age and ORT. A check of (non-) proportionality of the predictive effect of AMH was performed. A Weibull survival model was used in order to predict individual ANM. In total, 155 women were available for analyses. Eighty-one women (37.5%) had become post-menopausal during follow-up. Univariable Cox regression analysis demonstrated age and ORTs to be significantly correlated with TTM. Multivariable Cox regression analysis, adjusting for baseline age and smoking; however, demonstrated AMH alone to be an independent predictor of TTM (Hazard Ratio 0.70, 95% Confidence Interval 0.56-0.86, P-value <0.001). A (non-)proportionality analysis of AMH over time demonstrated AMH's predictive effect to decline over time. The observed predictive effect of AMH became less strong with increasing age of the woman. Individual AMH-based age at menopause predictions did not cover the full range of menopausal ages, but did reduce the variation around the predicted ANM from 20 to 10.1 years. Age-specific AMH levels are predictive for ANM. Unlike in our previous publication however, a declining AMH effect with increasing age was observed. This declining AMH effect is in line with recent long-term follow-up data published by others. Moreover, the accompanying predictive inaccuracy observed in individual age at menopause predictions based on AMH, makes this marker currently unsuitable for use in clinical practice. No external funds were used for this study. M.D., M.J.C.E, S.L.B., G.J.S. and I.A.J.R. have nothing to declare. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, MSD, Organon, Serono and Schering Plough. F.J.M.B. receives monetary compensation: member of the external advisory board for Merck Serono, the Netherlands; consultancy work for Gedeon Richter, Belgium; educational activities for Ferring BV, the Netherlands; strategic cooperation with Roche on automated AMH assay development.


Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors.
Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny.


Hollow-fiber delivery of high-power pulsed Nd:YAG laser light.
We propose hollow fibers for delivery of high-peak-power pulsed Nd:YAG laser light. Hollow fibers with an internal polymer layer were fabricated by a liquid-phase coating technique. We reduced the losses of the fibers in the near-infrared region by producing a silver film that was very smooth owing to use of an ultrasonic wave for mixing of the silver and the reducer solutions in the silver-plating process. The straight losses of the 1-m-long polymer-coated fibers were 0.3 dB for the 700-mum bore size and 0.1 dB for the 1000-mum bore fiber.


Antimicrobial Activity of Cinnamaldehyde on Streptococcus mutans Biofilms.
Streptococcus mutans is considered the most relevant bacteria in the transition of non-pathogenic commensal oral microbiota to biofilms which contribute to the dental caries process. The present study aimed to evaluate the antimicrobial activity of a natural plant product, cinnamaldehyde against S. mutans biofilms. Minimum inhibitory concentrations (MIC), minimal bactericidal concentration (MBC), and growth curves were determined to assess its antimicrobial effect against planktonic S. mutans. The biofilm biomass and metabolism with different concentrations of cinnamaldehyde and different incubation time points were assessed using the crystal violet and MTT assays. The biofilms were visualized using confocal laser scanning microscopy (CLSM). Bacterial cell surface hydrophobicity, aggregation, acid production, and acid tolerance were evaluated after cinnamaldehyde treatment. The gene expression of virulence-related factors (gtfB, gtfC, gtfD, gbpB, comDE, vicR, ciaH, ldh and relA) was investigated by real-time PCR. The MIC and MBC of cinnamaldehyde against planktonic S. mutans were 1000 and 2000 μg/mL, respectively. The results showed that cinnamaldehyde can decrease biofilm biomass and metabolism at sub-MIC concentrations. CLSM images revealed that the biofilm-covered surface areas decreased with increasing concentrations of cinnamaldehyde. Cinnamaldehyde increased cell surface hydrophobicity, reduced S. mutans aggregation, inhibited acid production, and acid tolerance. Genes expressions in the biofilms were down-regulated in the presence of cinnamaldehyde. Therefore, our data demonstrated that cinnamaldehyde at sub-MIC level suppressed the microbial activity on S. mutans biofilm by modulating hydrophobicity, aggregation, acid production, acid tolerance, and virulence gene expression.


Development of the Thirst Discomfort Scale: A Validity and Reliability Study.
Thirst is a sensation associated with a dry mouth and the desire or craving to drink water. Surgical patients are among those hospitalized individuals who are at high risk of developing both osmotic and hypovolemic thirst. To develop a new measurement tool for evaluating the thirst-related discomfort of surgical patients and to assess its validity and reliability. The study population consisted of patients admitted to the surgical clinics of a research hospital in Turkey between January and March 2022. The new measurement tool was developed in several stages: a pilot implementation phase with 51 patients and the main implementation phase with 198 patients. Data were collected by means of face-to-face interviews with patients. Exploratory factor and confirmatory factor analyses were performed using IBM SPSS Statistics, version 22, and IBM SPSS Amos. The final Thirst Discomfort Scale consisted of 12 items in 3 subdimensions. The Cronbach α values of the scale subdimensions ranged from 0.787 to 0.848, and the Cronbach α value for the scale as a whole was 0.886. The scale explained 66.237% of the total variance of the data. The Thirst Discomfort Scale consisting of 12 items and 3 subdimensions is a valid and reliable measurement tool for evaluating thirst-related discomfort of surgical patients.


Combat foot and ankle trauma.
Injury to the lower extremity is common in the current conflicts, often severely affecting the foot and ankle. Secondary to continued surgical advances, many lower extremities are able to undergo limb salvage procedures. However, scoring systems still do not reliably predict which patient will be best served with an amputation or limb salvage. Because of this, limb salvage should be attempted whenever possible, awaiting definitive treatment at a later time. Treatment begins at the time and location of injury with aggressive debridement, with reduction and external fixation of fractures when possible. Serial debridements are often necessary until the traumatic wounds are ready for coverage or closure. Forefoot injuries are treated with varying techniques depending on the location of the injury. Amputation of toes and/or flap coverage is often necessary secondary to tenuous soft tissues. Midfoot injury patterns are complex, possibly requiring arthrodesis, antibiotic spacers, soft tissue coverage, and thin-wire ring external fixation. Hindfoot or calcaneal injuries are often the most difficult to treat, requiring extraordinary efforts to salvage a viable limb. Early reduction of the remaining fragments and percutaneous fixation are often followed by arthrodesis of the subtalar joint. Fractures of the calcaneus requiring free soft tissue coverage frequently lead to amputation. Blast injuries to the lower extremity are severe injuries. They are frequently associated with fractures to multiple levels. Early elective amputation at the level V treatment center is frequently performed. When limb salvage is performed, basic principles must be followed to optimize treatment.


Lightweight and efficient microwave absorbing materials based on walnut shell-derived nano-porous carbon.
Lightweight microwave absorbing materials have drawn tremendous attention. Herein, nano-porous biomass carbon materials have been prepared by carbonization with a subsequent potassium hydroxide activation of walnut shells and the microwave absorption properties have also been investigated. The obtained samples have large specific surface areas with numerous micropores and nanopores. The sample activated at 600 °C with a specific surface area of 736.2 m2 g-1 exhibits the most enhanced microwave absorption performance. It has the maximum reflection loss of -42.4 dB at 8.88 GHz and the effective absorption bandwidth (reflection loss below -10 dB) is 1.76 GHz (from 8.08 GHz to 9.84 GHz), corresponding to a thickness of 2 mm. Additionally, the effective absorption bandwidth can reach 2.24 GHz (from 10.48 GHz to 12.72 GHz) when the absorber thickness is 1.5 mm. Three-dimensional porous architecture, interfacial polarization relaxation loss, and the dipolar relaxation loss make a great contribution to the excellent microwave absorption performance. In contrast, the non-activated sample with lower specific surface area (435.3 m2 g-1) has poor microwave absorption performance due to a poor dielectric loss capacity. This comparison highlights the role of micropores and nanopores in improving the dielectric loss property of porous carbon materials. To sum up, porous biomass carbon has great potential to become lightweight microwave absorbers. Moreover, KOH is an efficient activation agent in the fabrication of carbonaceous materials.


Synthetic Approach To Determine the Effect of Nuclear Spin Distance on Electronic Spin Decoherence.
Nuclear-electronic interactions are a fundamental phenomenon which impacts fields from magnetic resonance imaging to quantum information processing (QIP). The realization of QIP would transform diverse areas of research including accurate simulation of quantum dynamics and cryptography. One promising candidate for the smallest unit of QIP, a qubit, is electronic spin. Electronic spins in molecules offer significant advantages with regard to QIP, and for the emerging field of quantum sensing. Yet relative to other qubit candidates, they possess shorter superposition lifetimes, known as coherence times or T2, due to interactions with nuclear spins in the local environment. Designing complexes with sufficiently long values of T2 requires an understanding of precisely how the position of nuclear spins relative to the electronic spin center affects decoherence. Herein, we report the first synthetic study of the relationship between nuclear spin-electron spin distance and decoherence. Through the synthesis of four vanadyl complexes, (Ph4P)2[VO(C3H6S2)2] (1), (Ph4P)2[VO(C5H6S4)2] (2), (Ph4P)2[VO(C7H6S6)2] (3), and (Ph4P)2[VO(C9H6S8)2] (4), we are able to synthetically place a spin-laden propyl moiety at well-defined distances from an electronic spin center by employing a spin-free carbon-sulfur scaffold. We interrogate this series of molecules with pulsed electron paramagnetic resonance (EPR) spectroscopy to determine their coherence times. Our studies demonstrate a sharp jump in T2 when the average V-H distance is decreased from 6.6(6) to 4.0(4) Å, indicating that spin-active nuclei sufficiently close to the electronic spin center do not contribute to decoherence. These results illustrate the power of synthetic chemistry in elucidating the fundamental mechanisms underlying electronic polarization transfer and provide vital principles for the rational design of long-coherence electronic qubits.


Constitutive androstane receptor 1 is constitutively bound to chromatin and 'primed' for transactivation in hepatocytes.
The constitutive androstane receptor (CAR) is a xenobiotic sensor expressed in hepatocytes that activates genes involved in drug metabolism, lipid homeostasis, and cell proliferation. Much progress has been made in understanding the mechanism of activation of human CAR by drugs and xenobiotics. However, many aspects of the activation pathway remain to be elucidated. In this report, we have used viral constructs to express human CAR, its splice variants, and mutant CAR forms in hepatocytes from Car-/- mice in vitro and in vivo. We demonstrate CAR expression rescued the ability of Car-/- hepatocytes to respond to a wide range of CAR activators including phenobarbital. Additionally, two major splice isoforms of human CAR, CAR2 and CAR3, were inactive with almost all the agents tested. In contrast to the current model of CAR activation, ectopic CAR1 is constitutively localized in the nucleus and is loaded onto Cyp2b10 gene in the absence of an inducing agent. In studies to elucidate the role of threonine T38 in CAR regulation, we found that the T38D mutant was inactive even in the presence of CAR activators. However, the T38A mutant was activated by CAR inducers, showing that T38 is not essential for CAR activation. Also, using the inhibitor erlotinib, we could not confirm a role for the epidermal growth factor receptor in CAR regulation. Our data suggest that CAR is constitutively bound to gene regulatory regions and is regulated by exogenous agents through a mechanism which involves protein phosphorylation in the nucleus.


Autoimmune encephalitis -- new awareness, challenging questions.
The field of autoimmune encephalopathies has expanded rapidly in the last few years. It is now well-established that a substantial proportion of encephalitides are associated with autoantibodies directed against the extracellular domains of cell-surface proteins which are critical in the regulation of neuronal excitability. These include LGI1, CASPR2, contactin-2 (VGKC-complex antibodies), and the NMDA, AMPA, and GABA(B) receptors. The clinical importance of these conditions lies in their frequent immunotherapy-response and, less commonly, their association with distinctive tumors. Studies which have examined cohorts of patients defined by these serum antibodies have identified a number of clinical features that have helped understand the core phenotypes of these conditions. In addition, sensitive antibody assays have allowed the expansion of the phenotypes to include a minority of patients with isolated epilepsies or psychoses. There is also evidence that autoimmune encephalitis may progress to adult-onset hippocampal sclerosis. Clinical, and accumulating scientific, data strongly suggest direct pathogenicity of these autoantibodies. The generation of the autoantibody, in some patients, can be explained by the presence of tumors which express their antigenic target. Serum antibody levels are higher than their levels in CSF in the vast majority of cases. However, the majority of patients do not harbor a tumor and the etiology of the disease in these patients is less clear. Below, we suggest models for the etiology and pathogenic mechanisms of these autoantibodies by incorporating concepts such as serum generation of the autoantibodies, the blood-brain barrier, intrathecal antibody production, and prodromal infections.


Defining the relationship between Plasmodium vivax parasite rate and clinical disease.
Though essential to the development and evaluation of national malaria control programmes, precise enumeration of the clinical illness burden of malaria in endemic countries remains challenging where local surveillance systems are incomplete. Strategies to infer annual incidence rates from parasite prevalence survey compilations have proven effective in the specific case of Plasmodium falciparum, but have yet to be developed for Plasmodium vivax. Moreover, defining the relationship between P. vivax prevalence and clinical incidence may also allow levels of endemicity to be inferred for areas where the information balance is reversed, that is, incident case numbers are more widely gathered than parasite surveys; both applications ultimately facilitating cartographic estimates of P. vivax transmission intensity and its ensuring disease burden. A search for active case detection surveys was conducted and the recorded incidence values were matched to local, contemporary parasite rate measures and classified to geographic zones of differing relapse phenotypes. A hierarchical Bayesian model was fitted to these data to quantify the relationship between prevalence and incidence while accounting for variation among relapse zones. The model, fitted with 176 concurrently measured P. vivax incidence and prevalence records, was a linear regression of the logarithm of incidence against the logarithm of age-standardized prevalence. Specific relationships for the six relapse zones where data were available were drawn, as well as a pooled overall relationship. The slope of the curves varied among relapse zones; zones with short predicted time to relapse had steeper slopes than those observed to contain long-latency relapse phenotypes. The fitted relationships, along with appropriate uncertainty metrics, allow for estimates of clinical incidence of known confidence to be made from wherever P. vivax prevalence data are available. This is a prerequisite for cartographic-based inferences about the global burden of morbidity due to P. vivax, which will be used to inform control efforts.


Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma.
Bisphosphonates are effective in the prevention and treatment of bone disease in multiple myeloma (MM). Osteonecrosis of the jaw is Increasingly recognized as a serious complication of long-term bisphosphonate therapy. Issues such as the choice of bisphosphonate and duration of therapy have become the subject of intense debate given patient safety concerns. We reviewed available data concerning the use of bisphosphonates in MM. Guidelines for the use of bisphosphonates in MM were developed by a multidisciplinary panel consisting of hematologists, dental specialists, and nurses specializing in the treatment of MM. We conclude that intravenous pamidronate and intravenous zoledronic acid are equally effective and superior to placebo in reducing skeletal complications. Pamidronate is favored over zoledronic acid until more data are available on the risk of complications (osteonecrosis of the jaw). We recommend discontinuing bisphosphonates after 2 years of therapy for patients who achieve complete response and/or plateau phase. For patients whose disease is active, who have not achieved a response, or who have threatening bone disease beyond 2 years, therapy can be decreased to every 3 months. These guidelines were developed in the Interest of patient safety and will be reexamined as new data emerge regarding risks and benefits.


Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy.
High-density lipoprotein (HDL)-raising therapies are currently under intense evaluation, but the effects of HDL may be highly heterogeneous. We therefore compared the endothelial effects of HDL from healthy subjects and from patients with type 2 diabetes mellitus and low HDL (meeting the criteria for metabolic syndrome), who are frequently considered for HDL-raising therapies. Moreover, in diabetic patients, we examined the impact of extended-release (ER) niacin therapy on the endothelial effects of HDL. HDL was isolated from healthy subjects (n=10) and patients with type 2 diabetes (n=33) by sequential ultracentrifugation. Effects of HDL on endothelial nitric oxide and superoxide production were characterized by electron spin resonance spectroscopy analysis. Effects of HDL on endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair were examined. Patients with diabetes were randomized to a 3-month therapy with ER niacin (1500 mg/d) or placebo, and endothelial effects of HDL were characterized. HDL from healthy subjects stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair. In contrast, these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients, which suggests markedly impaired endothelial-protective properties of HDL. ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide, to reduce superoxide production, and to promote endothelial progenitor cell-mediated endothelial repair. Further measurements suggested increased lipid oxidation of HDL in diabetic patients, and a reduction after ER niacin therapy. HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important. clinicaltrials.gov. Identifier: NCT00346970.


Health-related quality of life in older depressed psychogeriatric patients: one year follow-up.
Knowledge about long-term change in health related quality of life (HQoL) among older adults after hospitalization for treatment of depression has clinical relevance. The aim was firstly to describe the change of HQoL one year after admission for treatment of depression, secondly to explore if improved HQoL was associated with remission of depression at follow-up and lastly to study how HQoL in patients with remission from depression were compared to a reference group of older persons without depression. This study had the one year follow-up information of 108 older patients (≥60 years), all hospitalized for depression at baseline, and a reference sample of 106 community-living older adults (≥60 years) without depression. HQoL was measured using the EuroQol Group's EQ-5D Index and a visual analog scale (EQ-VAS). Depression and remission were diagnosed according to ICD-10. Socio-demographic variables (age, gender, and education), depressive symptom score (Montgomery-Aasberg Depression Rating Scale), cognitive functioning (Mini Mental State Examination scale), instrumental activities of daily living (the Lawton and Brody's Instrumental Activities of Daily Living Scale), and poor general physical health (General Medical Health Rating) were included as covariates. HQoL had improved at follow-up for the total group of depressed patients, as indicated by better scores on the EQ-5D Index and EQ-VAS. In the multivariate linear regression model, improved EQ-5D Index and EQ-VAS was significantly better in those with remission of depression and those with better baseline physical health. In adjusted analyses, the HQoL in patients with remission from depression at follow-up did not differ from the HQoL in a reference group without depression. Older hospital patients with depression who experienced remission one year after admission gained HQoL and their HQoL was comparable with the HQoL in a reference group of older adults without depression when adjusting for differences in socio-demographics and health conditions.


The substitutability of cigarettes and food: A behavioral economic comparison in normal weight and overweight or obese smokers.
Obesity and cigarette smoking contribute to a multitude of preventable deaths in the United States and eating and smoking behavior may influence each other. The field of behavioral economics integrates principles from psychology and economics and permits systematic examination of how commodities interrelate with one another. Using this framework, the current study evaluated the effects of rising food and cigarette prices on consumption to investigate their substitutability and their relationship to BMI and associated variables. Behavioral economics categorizes commodities as substitutable when the consumption of one increases as a function of a price increase in the other. Smokers (N = 86) completed a 2-part hypothetical task in which money was allocated to purchase cigarettes and fast-food-style reinforcers (e.g., hamburgers, ice cream) at various prices. Results indicated that food and cigarettes were not substitutes for one another (cross-price elasticity coefficients < .20). Food purchases were independent of cigarette price, whereas cigarette purchases decreased as food price rose. Cross-price elasticity coefficients were significantly associated with confidence in one's ability to control weight without smoking (rs = -.23 and .29), but not BMI (rs = .04 and .04) or postcessation weight concerns (rs = -.05 and .12). Perceived ability to manage weight without cigarettes may influence who substitutes food for cigarettes when quitting. In addition, given observed decreases in purchases of both commodities as food prices increased, these findings imply that greater taxation of fast-food-style reinforcers could potentially reduce consumption of these foods and also cigarettes among smokers. (PsycINFO Database Record


Induction of a Th1 response from Th2-polarized T cells by activated dendritic cells: dependence on TCR:peptide-MHC interaction, ICAM-1, IL-12, and IFN-gamma.
Dendritic cells (DC) are important regulators of T cell immunity. The degree of stimulation, the pattern of costimulatory molecules expressed, and the cytokines secreted by DC dictate the nature of the effector and memory cells generated, particularly with respect to their Th1 or Th2 phenotypes. In this study, we demonstrate that the addition of activated DC to spleen cultures containing established Th2-polarized CD4(+) T cells was sufficient to suppress Th2 and induce Th1 cytokines in a recall response, a phenomenon referred to as phenotype reversal. The ability of activated DC to induce phenotype reversal displayed exquisite Ag specificity. The DC activator B7-DC cross-linking Ab (XAb) was >10,000-fold more efficient at inducing phenotype reversal than the TLR agonists CpG-oligodeoxynucleotide and Gardiquimod. Characterization of the mechanisms governing phenotype reversal revealed the requirement for cognate interaction between the TCR:peptide-MHC complex, the expression of the costimulation/adhesion molecule ICAM-1, and secretion of IL-12 and IFN-gamma by the activated DC. The requirement for the costimulation/adhesion molecule SLAM (signaling lymphocytic activation molecule) was found to be quantitative. Thus, activation of DC, particularly by crosslinking B7-DC, can modulate well-established Th2 T cell responses in an Ag-specific manner. Because the regulation of mouse and human DC by B7-DC XAb overlaps in several significant ways, immune modulation with B7-DC XAb is a potential strategy for treating Th2-mediated diseases.


Energy expenditure in people with motor-complete paraplegia.
The present descriptive clinical and laboratory study is cross-sectional in design. The primary aim is to describe and compare resting energy expenditure (REE) and energy expenditure (EE) during different standardized sedentary, non-exercise and exercise activities in people with motor-complete paraplegia (Th7 to Th12.). A secondary aim was to compare men and women. Thirty-eight adults (10 women) with SCI, T7-T12 AIS A-B, were recruited. All the data were collected through indirect calorimetry. REE was measured in supine for 30 min after 8 h of overnight fasting. Activity energy expenditure (AEE) for activities was measured for seven minutes during sedentary, non-exercise physical activity (NEPA) and exercise activities. AEE increased four to eight times when engaging in NEPA compared to that in sedentary activities. Men had significantly higher resting oxygen uptake compared to women, 0.19 vs 0.15 l min-1 (P=0.005), REE per 24 h, 1286 vs 1030 kcal (P=0.003) and EE during weight-bearing activities. However, these became nonsignificant after adjustment for body weight and speed of movement, with a mean resting oxygen uptake of 2.47 ml O2 per kg min-1 for the whole group (women 2.43 and men 2.57 ml O2 kg-1 min-1, P=0.49). NEPA increases AEE up to eight times compared to sedentary activities. Gender differences in oxygen uptake during both rest and weight-bearing activities were diminished after adjustment for body weight. The mean resting oxygen uptake for the whole group was 2.47 ml O2 kg-1 min-1. These results highlight the importance, especially of NEPA, for increasing total daily EE in the target population.


Evaluation of a pushrim-activated, power-assisted wheelchair.
To evaluate a novel pushrim-activated, power-assisted wheelchair (PAPAW) for compliance with wheelchair standards, metabolic energy cost during propulsion, and ergonomics during selected activities of daily living (ADLs). A 3-phase study, the second and third of which were repeated-measures designs. A rehabilitation engineering center within a Veterans Affairs medical center. Eleven full-time, community-dwelling, manual wheelchair users (4 women, 6 men) with spinal cord injuries or multiple sclerosis. Phase 1: Compliance testing, with a test dummy, in accordance with the wheelchair standards of the American National Standards Institute and the Rehabilitation Engineering and Assistive Technology Society of North America. Phase 2: Metabolic energy consumption testing-at 2 speeds and 3 resistance levels-in subjects' manual wheelchair and the PAPAW. Phase 3: Evaluation of ability to perform ADLs and ergonomics of the PAPAW compared with the subjects personal wheelchair. Phase 1: The PAPAW's static stability, static strength, impact strength, fatigue strength, environmental response, obstacle climbing ability, range, maximum speed, and braking distance. Phase 2: Subjects' oxygen consumption per minute, minute ventilation, and heart rate during different speeds and workloads with a PAPAW and their own wheelchairs. Phase 3: Subject ratings of perceived comfort and basic ergonomics while performing selected ADLs. Completion time, stroke frequency, and heart rate during each ADL. Phase 1: The PAPAW was found to be in compliance with wheelchair standards. Phase 2: With the PAPAW, the user had a significantly lower oxygen consumption (&Vdot;O(2)mL/min: p <.0001; &Vdot;O(2)mL/kg x min: p <.0001) and heart rate (p <.0001) when compared with a manual wheelchair at different speeds. Phase 3: The PAPAW had a significantly higher mean ergonomic evaluation (p <.01) than the subjects' personal wheelchairs. The results of comparing the ratings of the car transfer between the PAPAW and the subjects' personal wheelchair showed a significant difference in the task of taking the wheels off (p <.001) and putting the wheels back on (p =.001), with the PAPAW receiving lower ratings. This study indicated that the PAPAW is compliant with wheelchair standards, reduces the energy demand placed on the user during propulsion, and that subjects rated its ergonomics favorably when compared with their personal wheelchair. PAPAWs may provide manual wheelchairs with a less physiologically stressful means of mobility with few adaptations to the vehicle or home environment.


Magnetic resonance angiography in children with sickle cell disease and abnormal transcranial Doppler ultrasonography findings enrolled in the STOP study.
The stroke prevention study in sickle cell disease (STOP) demonstrated a 90% reduction in stroke risk with transfusion among patients with time-averaged mean cerebral blood velocity (TAMV) of 200 cm/s or more as measured by transcranial Doppler (TCD). In STOP, 232 brain magnetic resonance angiograms (MRAs) were performed on 100 patients, 47 in the transfusion arm and 53 in the standard care arm. Baseline MRA findings were interpreted as normal in 75 patients and as indicating mild stenosis in 4 patients and severe stenosis in 21 patients. Among 35 patients who underwent magnetic resonance angiography within 30 days of random assignment, the TAMV was significantly higher in 7 patients with severe stenosis compared with 28 patients with normal MRA findings or mild stenosis (276.7 +/- 34 vs 215 +/- 15.6 cm/s; P<.001). In the standard care arm, 4 of 13 patients with abnormal MRA findings had strokes compared with 5 of 40 patients with normal MRA findings (P=.03). In this arm, TAMV became normal (less than 170 cm/s) or conditional (170-199 cm/s) in 26 of 38 patients with normal or mildly abnormal baseline MRA but remained abnormal in 8 of 10 patients with severely abnormal baseline MRA. These results suggest that TCD often detects flow abnormalities indicative of stroke risk before MRA lesions become evident. Furthermore, patients with abnormal MRA findings and higher TCD velocities are at higher risk for stroke, and their cerebral TAMVs are unlikely to decrease without transfusion.


Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial.
Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at ɑ 0.025). Both per-protocol and intention-to-treat analyses will be performed. This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly. Dutch Trial Register, NTR6128 . Registered on 20 December 2016.


Blockade of B7-H1 suppresses the development of chronic intestinal inflammation.
A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested that its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation and cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 and B7-DC interaction in the development of colitis. We first examined the expression profiles of PD-1 and its ligands in both human inflammatory bowel disease and a murine chronic colitis model induced by adoptive transfer of CD4(+)CD45RB(high) T cells to SCID mice. Second, we assessed the therapeutic potential of neutralizing anti-B7-H1 and/or B7-DC mAbs using this colitis model. We found significantly increased expression of PD-1 on T cells and of B7-H1 on T, B, and macrophage/DCs in inflamed colon from both inflammatory bowel disease patients and colitic mice. Unexpectedly, the administration of anti-B7-H1, but not anti-B7-DC, mAb after transfer of CD4(+)CD45RB(high) T cells suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced the production of IFN-gamma, IL-2, and TNF-alpha, but not IL-4 or IL-10, by lamina propria CD4(+) T cells. These data suggest that the interaction of PD-1/B7-H1, but not PD-1/B7-DC, might be involved in intestinal mucosal inflammation and also show a possible role of interaction between B7-H1 and an as yet unidentified receptor for B7-H1 in inducing T cell activation.


Uvulopalatopharyngoplasty versus sequential uvulopalatoplasty for surgical treatment of snoring.
Military personnel serving on active duty suffering from loud, bothersome snoring often require surgical treatment. This elective treatment should not disrupt the command and should have minimal impact on military readiness. Major drawbacks of the standard procedure, uvulopalatopharyngoplasty, include postoperative pain requiring convalescent leave, postoperative bleeding, and velopharyngeal incompetence. In addition, the surgery consumes limited operating room time for what many consider elective surgery. Sequential uvulopalatoplasty was developed as an alternative. This is performed with a carbon dioxide laser under local anesthesia in a clinic setting, but it requires cumbersome laser precautions and expensive laser equipment. Standard electrocautery can be used instead of a laser for this procedure. This avoids additional expense, special precautions, and equipment but is equally safe and effective. We compare time lost from work, duration and level of pain experienced, number of days until regular diet resumed, and effectiveness between uvulopalatopharyngoplasty and sequential uvulopalatoplasty. We found sequential uvulopalatoplasty to have less impact on military readiness while being as effective as uvulopalatopharyngoplasty for snoring. This makes it an ideal treatment modality for patients desiring surgical correction of snoring.


Life and Limb In-Flight Surgical Intervention: Fifteen Years of Experience by Joint Medical Augmentation Unit Surgical Resuscitation Teams.
Expedient resuscitation and emergent damage control interventions remain critical tools of modern combat casualty care. Although fortunately rare, the requirement for life and limb salvaging surgical intervention prior to arrival at traditional deployed medical treatment facilities may be required for the care of select casualties. The optimal employment of a surgical resuscitation team (SRT) may afford life and limb salvage in these unique situations. Fifteen years of after-action reports (AARs) from a highly specialized SRTs were reviewed. Patient demographics, specific details of encounter, team role, advanced emergent life and limb interventions, and outcomes were analyzed. Data from 317 casualties (312 human, five canines) over 15 years were reviewed. Among human casualties, 20 had no signs of life at intercept, with only one (5%) surviving to reach a Military Treatment Facility (MTF). Among the 292 casualties with signs of life at intercept, SRTs were employed in a variety of roles, including MTF augmentation (48.6%), as a transport capability from other aeromedical platforms, critical care transport (CCT) between MTFs (27.7%), or as an in-flight damage control capability directly to point of injury (POI) (18.2%). In the context of these roles, the SRT performed in-flight life and limb preserving surgery for nine patients. Procedures performed included resuscitative thoracotomy (7/9; 77.8%), damage control laparotomy (1/9; 11.1%) and extremity fasciotomy for acute lower extremity compartment syndrome (1/11; 11%). Survival following in-flight resuscitative thoracotomy was 33% (1/3) when signs of life (SOL) were absent at intercept and 75% (3/4) among patients who lost SOL during transport. In-flight surgery by a specifically trained and experienced SRT can salvage life and limb for casualties of major combat injury. Additional research is required to determine optimal SRT utilization in present and future conflicts.


Mechanisms associated with maternal adverse childhood experiences on offspring's mental health in Nairobi informal settlements: a mediational model testing approach.
Adverse childhood experiences (ACEs) is a significant public health and social welfare problem in low-and middle income countries (LMICs). However, most ACEs research is based on developed countries, and little is known about mechanisms of early ACEs on adulthood health and offspring's wellbeing for populations in LMICs. This area is needed to guide social welfare policy and intervention service planning. This study addresses these research gaps by examining patterns of ACEs and understanding the role of ACEs on adulthood health (i.e., physical, mental health, experience of underage pregnancy) and offspring's mental health in Kenya. The study was guided by an Integrated Family Stress and Adverse Childhood Experiences Mediation Framework. Three hundred ninety four mothers from two informal communities in Kariobangi and Kangemi in Nairobi were included in this study. The Adverse Childhood Experiences International Questionnaire (ACE-IQ), the Kessler Psychological Distress Scale (K10), Overall Health and Quality of Life items, and Child Behavior Checklist were used to study research questions. Data was gathered through a one-time interview with mothers. Structural Equational Modeling (SEM) was applied for mediational mechanism testing. Among 13 ACE areas, most mothers experienced multiple adversity during their childhood (Mean (SD) = 4.93 (2.52)), with household member treated violently (75%) as the most common ACE. SEM results showedthat all domains of ACEs were associated with some aspects of maternal health, and all three domains of maternal health (maternal mental health, physical health, and adolescent pregnancy) were significantly associated with development of offspring's mental health problems. ACEs are highly prevalent in Kenyan informal settlements. Consistent with cross cultural literature on family stress model, maternal ACEs are robust predictors for poor child mental health. Preventive interventions for child mental health need to address maternal adverse childhood traumatic experiences as well as their current health in order to effectively promote child mental health.


Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer.
Altered epigenetic mechanisms, similar to gene mutations, contribute to the pathogenesis and molecular heterogeneity of neoplasms, including colorectal cancer (CRC). Enhancer of zeste 2 (EZH2) is a histone methyltransferase, which is involved in epigenetic gene silencing and is aberrantly expressed in CRC. Therefore, the identification of the genes regulated by EZH2 in CRC is important to improve current understanding of its role in cancer epigenetics. The present study used chromatin immunoprecipitation (ChIP) followed by deep sequencing to assess genome-wide EZH2‑DNA interactions in healthy or CRC mucosa samples. In total, 86.9/61.6 and 92.5/62.6 million tags were sequenced/mapped in healthy and CRC mucosa samples, respectively. The EZH2-binding densities were correlated with transcriptomic datasets and this demonstrated that the claudin-23 (CLDN23) gene, which encodes a component of cell-cell adhesion structures, was occupied by EZH2 and significantly silenced in CRC tissue. The measurement of DNA methylation at the CLDN23 promoter using pyrosequencing excluded the possibility that silencing of this gene in CRC patient samples was a result of DNA hypermethylation. Following treatment of the Colo205 and HT-29 CRC cell lines, with the EZH2 inhibitor, GSK126, the level of histone H3 lysine 27 trimethylation (H3K27me3) was reduced and the mRNA and protein expression levels of CLDN23 were increased. ChIP analysis confirmed that the level of H3K27m3 along the CLDN23 gene was decreased in the GSK126-treated cell lines. Furthermore, ChIP analysis of these samples detected histone H3 lysine 4 trimethylation (H3K4me3) at the CLDN23 promoter, demonstrating that the balance between H3K27me3 and H3K4me3 may underlie the regulation of the expression of CLDN23. The present study demonstrated an epigenetic link between the activity of the EZH2 methyltransferase at the CLDN23 locus and the expression of CLDN23 in CRC tissue.


Expansion and diversification of the SET domain gene family following whole-genome duplications in Populus trichocarpa.
Histone lysine methylation modifies chromatin structure and regulates eukaryotic gene transcription and a variety of developmental and physiological processes. SET domain proteins are lysine methyltransferases containing the evolutionarily-conserved SET domain, which is known to be the catalytic domain. We identified 59 SET genes in the Populus genome. Phylogenetic analyses of 106 SET genes from Populus and Arabidopsis supported the clustering of SET genes into six distinct subfamilies and identified 19 duplicated gene pairs in Populus. The chromosome locations of these gene pairs and the distribution of synonymous substitution rates showed that the expansion of the SET gene family might be caused by large-scale duplications in Populus. Comparison of gene structures and domain architectures of each duplicate pair indicated that divergence took place at the 3'- and 5'-terminal transcribed regions and at the N- and C-termini of the predicted proteins, respectively. Expression profile analysis of Populus SET genes suggested that most Populus SET genes were expressed widely, many with the highest expression in young leaves. In particular, the expression profiles of 12 of the 19 duplicated gene pairs fell into two types of expression patterns. The 19 duplicated SET genes could have originated from whole genome duplication events. The differences in SET gene structure, domain architecture, and expression profiles in various tissues of Populus suggest that members of the SET gene family have a variety of developmental and physiological functions. Our study provides clues about the evolution of epigenetic regulation of chromatin structure and gene expression.


Advances in membrane materials: desalination membranes based on directly copolymerized disulfonated poly(arylene ether sulfone) random copolymers.
The water and salt transport properties of chlorine tolerant disulfonated poly(arylene ether sulfone) (BPS) copolymers have been characterized. Cast BPS membranes of both salt form and acid form with sulfonation levels from 20% to 40% were investigated. Water permeability of BPS films increases more than one order of magnitude as sulfonation level increases from 20% to 40%, while the salt permeability of the corresponding membranes increases two orders of magnitude. Moderate salt rejection (98.2%) was achieved by a BPS salt form membrane with a sulfonation level of 20%.


Mucormycosis in a patient with low risk myelodysplasia treated with anti-TNF-alpha.
Accelerated programmed cell death or apoptosis appears to play an important role in the pathogenesis of myelodysplasia. As overexpression of TNF-alpha has been described to induce cell death in myelodysplasia, treatment with anti-TNF-alpha is currently being explored. Caution is needed because of an increased risk of opportunistic infection during anti-TNF-alpha treatment. We here describe a patient who was treated with anti-TNF-alpha for low risk myelodysplasia and died of invasive mucormycosis.


Preharvest aflatoxin contamination: effect of moisture and substrate variation in developing cottonseed and corn kernels.
Variations in moisture and substrate in preharvest corn kernels and cottonseed were linked with the ability of Aspergillus parasiticus to infect the seed and produce aflatoxin. Osmotic pressures and moisture content (MC) levels of developing starch-rich corn kernels and lipid-rich cottonseed were determined. For in vivo studies, corn kernels and cottonseed were inoculated with A. parasiticus conidia and retained on plants through maturation. For in vitro studies, samples of corn kernels and cottonseed were collected at various stages, sterilized, inoculated, incubated for 2 weeks, and assayed for toxin. Aflatoxin levels were highest in corn kernels inoculated at 28 days postflowering (52% MC) in both the in vivo and in vitro tests. Toxin concentrations in cottonseed were greatest with inoculation at 35 days postflowering (70% MC) in seed retained on the plant, but toxin accumulation continued to increase with the maturity of the seed inoculated in cottonseed used in the in vitro trials. Moisture and substrate conditions in the midrange of seed development provided optimum conditions for fungal development and toxin production in seed retained on the plant.


Evidence of light-dependent magnetic compass orientation in urodele amphibian larvae.
Experiments were conducted to investigate whether larval palmate newts undertake orientation toward or away from the home shoreline (y-axis orientation) using the geomagnetic field to steer the most direct route, and if they accomplish this task through a light-dependent magnetoreception mechanism similar to that found in anuran tadpoles and adult newts. Larval palmate newts trained and then tested under full-spectrum light showed bimodal magnetic compass orientation that coincided with the magnetic direction of the trained y-axis. In contrast, larvae trained under long-wavelength (≥500nm) light and then tested under full-spectrum light displayed bimodal orientation perpendicular to the trained y-axis direction. These results offer evidence for the use of magnetic compass cues in orienting urodele amphibian larvae, and provide additional support for the light-dependent magnetoreception mechanism since they are in complete agreement with earlier studies showing that the observed 90° shift in the direction of magnetic compass orientation under long-wavelength light (≥500nm) is due to a direct effect of light on the underlying magnetoreception mechanism. This study is the first to provide evidence of a light-dependent magnetic compass in larval urodeles.


ASPIRE-2-PREVENT: a survey of lifestyle, risk factor management and cardioprotective medication in patients with coronary heart disease and people at high risk of developing cardiovascular disease in the UK.
To determine in patients with coronary heart disease (CHD) and people at high risk of developing cardiovascular disease (CVD) whether the Joint British Societies' guidelines on CVD prevention (JBS2) are followed in everyday clinical practice. A cross-sectional survey was undertaken of medical records and patient interviews and examinations at least 6 months after the recruiting event or diagnosis using standardised instruments and a central laboratory for measurement of lipids and glucose. The ASPIRE-2-PREVENT survey was undertaken in 19 randomly selected hospitals and 19 randomly selected general practices in 12 geographical regions in England, Northern Ireland, Wales and Scotland. In hospitals, 1474 consecutive patients with CHD were identified and 676 (25.6% women) were interviewed. In general practice, 943 people at high CVD risk were identified and 446 (46.5% women) were interviewed. The prevalence of risk factors in patients with CHD and high-risk individuals was, respectively: smoking 14.1%, 13.3%; obesity 38%, 50.2%; not reaching physical activity target 83.3%, 85.4%; blood pressure ≥130/80 mm Hg (patients with CHD and self-reported diabetes) or ≥140/85 mm Hg (high-risk individuals) 46.9%, 51.3%; total cholesterol ≥4 mmol/l 52.6%, 78.7%; and diabetes 17.8%, 43.8%. The potential among patients with CHD and individuals at high risk of developing CVD in the UK to achieve the JBS2 lifestyle and risk factor targets is considerable. CVD prevention needs a comprehensive multidisciplinary approach, addressing all aspects of lifestyle and risk factor management. The challenge is to engage and motivate cardiologists, physicians and other health professionals to routinely practice high quality preventive cardiology in a healthcare system which must invest in prevention.


Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency.
The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci) provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST) and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu's inbred populations. Inbreeding values (FIS) show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE) or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates is required if discernible levels of co-ancestry exist. In the reference group, optimum assignment accuracy was achievable achieved through a combination of different markers by ranking the heterozygosity, FST and allelic number of close lineage populations.


The CATCH Kids Club: a pilot after-school study for improving elementary students' nutrition and physical activity.
Although many school-based diet and physical activity interventions have been designed and evaluated, relatively few have been tested for the after-school setting. After-school day-care programmes at either elementary schools or private locations provide a ready-made opportunity for health programmes that may be difficult to incorporate into an already-full school day. The purpose of this paper is to report on a pilot study of an after-school adaptation of the CATCH (Coordinated Approach To Child Health) elementary school programme called the CATCH Kids Club (CKC). The CKC was pilot-tested and formatively evaluated in 16 Texas after-school programmes: eight in El Paso and eight in Austin (four intervention and four reference sites each). Evaluation consisted of direct observation of moderate to vigorous physical activity during play time, self-reported food intake and physical activity, and focus group interviews with after-school programme staff. Students responded well to the physical activity and snack components and were less interested in the five-module education component. Routine staff training was a key variable in achieving proper implementation; the ideal would be a full day with repeated follow-up model teaching visits. Staff turnover was a logistic issue, as was programme leader readiness and interest in conducting the programme. Strong and significant effects were observed for the physical activity but not for the education component. The results of the physical education component suggest it is feasible, effective and ready for larger-scale evaluation or dissemination.


Detection of GB virus C RNA by GBV-C LCx and two PCR assays with primers from the 5' non-coding and NS5B region.
The objective of this study was to compare the sensitivity of three different reverse transcriptase-polymerase chain reaction (RT-PCR) based tests, for detection of GB virus C (GBV-C) RNA. One commercial and two 'in house' RT-PCR assays were employed in the testing of serum samples from 114 chronic hepatitis C infected individuals. A part of the 5' non-coding region (5'NCR) of the GBV-C genome was amplified by the GBV-C LCx assay (Abbott) and one of the 'in house' RT-PCR tests. In the other 'in house' RT-PCR a segment of the NS5B region was amplified. The 'in house' assays included the use of internal controls that were co-amplified with use of the same outer PCR primers as the virus targets. The GBV-C LCx from Abbott and 5'NCR 'in house' PCR tests detected 28 and 27 GBV-C positive individuals, respectively. The sample positive only in the LCx test was confirmed by the 'in house' 5'NCR RT PCR using an increased virus input. In comparison, the NS5B 'in house' PCR test detected 24 of the GBV-C positive samples. One sample showed no amplification of internal controls/virus target in the 5'NCR 'in house' PCR and another samples was amplification negative in the NS5B PCR. The PCR assays with primers from the 5'NCR of the virus genome e.g. the GBV-C LCx, were more sensitive compared with RT-PCR using primers from the NS5B region. The GBV-C LCx seemed to be the most sensitive and robust assay. Internal controls included in the 'in house' assays identified two samples with failure of the amplification.


Radioimmunoscintigraphy and biodistribution of technetium-99m-labeled monoclonal antibody U36 in patients with head and neck cancer.
So far, mAb E48 is the most promising antibody described for specific targeting of head and neck squamous cell carcinoma (HNSCC) in patients. On the basis of its more homogeneous reactivity pattern on HNSCC, the novel mAb U36 may be even better suited for targeting. In this study the biodistribution of mAb U36 was evaluated by radioimmunoscintigraphy (RIS) and biopsy measurements in 10 patients who were suspected of having neck lymph node metastases from a histologically proven HNSCC and who had been scheduled to undergo resection of the primary tumor and neck dissection. Patients received 1.8-53.0 mg mAb U36 IgG labeled with 756 +/- 95 MBq technetium-99m i.v. Preoperatively, palpation, computerized tomography, magnetic resonance imaging, and RIS were performed. RIS images included planar and single-photon emission computerized tomography images of the head and neck and planar images of the whole body. The diagnostic findings were recorded per side as well as per lymph node level of the neck and compared to the histopathological outcome. Radioactivity in blood samples and biopsies from the surgical specimens were measured. All 10 primary tumors were visualized by RIS. All diagnostic modalities were correct in 7 of 14 tumor-involved lymph node levels. The missed lymph node metastases comprised micrometastases, small tumor-involved nodes (<9 mm), and tumor-involved nodes with much necrosis, keratin, or fibrin. There were no false-positive observations with mAb U36. Besides activity uptake in tumor tissue, only a slight accumulation of activity was observed in the mouth, lungs, liver, spleen, kidneys, and scrotal area. Biopsies from the surgical specimen showed a high tumor uptake of 20.4 +/- 12.4% of the injected dose/kg (range, 8.0-43.0% of injected dose/kg), 44 h postinjection. An increase in the mAb dose did not influence uptake of activity in tumor tissue. The mean tumor:nontumor ratio at this time point was 2.3 for mucosa, 2.8 for blood, 3.0 for bone marrow aspirate, 12.9 for fat, and 13.0 for muscle tissue. The present clinical study shows that technetium-99m-labeled U36 IgG accumulates selectively and to a high level in HNSCC. The tumor-targeting results for U36 IgG are comparable to those previously described for E48 IgG. On the basis of the results of ongoing biodistribution studies in which both mAbs E48 and U36, labeled with different iodine isotopes, are simultaneously evaluated for tumor uptake and retention in HNSCC patients, one of these mAbs will be selected for future adjuvant radioimmunotherapy trials.


Onset and rate of cognitive change before dementia diagnosis: findings from two Swedish population-based longitudinal studies.
We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.


Chemokine antagonism in chronic hepatitis C virus infection.
Immune responses to hepatitis C virus (HCV) fail to clear the virus in most individuals. Why patients who are less likely to clear HCV infection have high plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells to sites of infection, has long been unclear. In this issue of the JCI, Casrouge and colleagues shed light on this paradox by showing that CXCL10 in the plasma of many HCV patients is enzymatically processed to produce a CXCL10 receptor antagonist. These findings introduce a role for chemokine antagonism during HCV infection and unveil new avenues for improved HCV diagnosis and therapy.


Comparison of serum estradiol to urinary estrone conjugates in the rhesus macaque (Macaca mulatta).
Paired urine and serum samples were collected daily during fourteen nonconceptive (7 females) and ten conceptive (9 females) ovarian cycles from a total of 12 female rhesus monkeys (Macaca mulatta). Daily urine samples were analyzed for concentrations of estrone conjugates (Ei Conj). Serum samples were evaluated for concentrations of estradiol (E2) and progesterone (P) by radioimmunoassay (RIA), and bioactive luteinizing hormone (bLH) and monkey chorionic gonadotropin (mCG) were analyzed by a mouse Leydig cell bioassay. Linear correlation (r) between urinary E1 Conj and serum E2 (r range = -0.176-0.948) during nonconceptive cycles aligned by the preovulatory E1 Conj peak (Day 0) improved when daily hormone values were realigned to account for an approximately 24-h delay in the excretion of hormonal metabolites in urine (r range = 0.465-0.967). Similarly, correlation between urinary E1 Conj and serum E2 during conceptive cycles aligned by Day 0 (r range = 0.300-0.824) improved when values were offset by 24 h (r range = 0.408-0.876). When conceptive cycles were compared to nonconceptive cycles, serum P levels were significantly elevated over nonconceptive levels by Day +12 (p less than 0.001), and urinary E1 Conj levels by Day +13 (p less than 0.02), whereas serum E2 and bLH were both significantly elevated by Day +14 (p less than 0.0006 and p less than 0.01, respectively). In both nonconceptive and conceptive cycles, urinary E1 Conj paralleled serum E2 and demonstrated incremental increases above baseline levels, which were greater than for serum E2.


Revisiting the intersection of amyloid, pathologically modified tau and iron in Alzheimer's disease from a ferroptosis perspective.
The complexity of Alzheimer's disease (AD) complicates the search for effective treatments. While the key roles of pathologically modified proteins has occupied a central role in hypotheses of the pathophysiology, less attention has been paid to the potential role for transition metals overload, subsequent oxidative stress, and tissue injury. The association of transition metals, the major focus heretofore iron and amyloid, the same can now be said for the likely pathogenic microtubular associated tau (MAPT). This review discusses the interplay between iron, pathologically modified tau and oxidative stress, and connects many related discoveries. Basic principles of the transition to pathological MAPT are discussed. Iron, its homeostatic mechanisms, the recently described phenomenon of ferroptosis and purported, although still controversial roles in AD are reviewed as well as considerations to overcome existing hurdles of iron-targeted therapeutic avenues that have been attempted in AD. We summarize the involvement of multiple pathological pathways at different disease stages of disease progression that supports the potential for a combinatorial treatment strategy targeting multiple factors.


Evidence based outcomes of the American Society of Breast Surgeons Nipple Sparing Mastectomy Registry.
The American Society of Breast Surgeons (ASBrS) Nipple Sparing Mastectomy Registry (NSMR) is a prospective, non-randomized, IRB approved, multi-institutional registry. The purpose of this Registry is to provide a large, prospective, non-randomized database of patient characteristics, tumor characteristics, surgical technique, and outcome (both aesthetic and oncologic) of the nipple sparing mastectomy (NSM). Data is entered into the ASBrS NSMR, housed within the Mastery of Surgery Program, after patients consent to participation. Each investigator routinely offers NSM in their practice has obtained IRB approval and completed forms of agreement to participate in the ASBrS NSMR. This data set represents a total of 1,935 NSMs performed on 1,170 patients by 98 investigators from 70 institutions/sites. Of the 1,935 NSMs: 833 were performed for an indication of cancer [594 invasive carcinoma and 239 for ductal carcinoma in situ (DCIS)] and 1,102 were prophylactic. Of the 1,170 total patients, 352 underwent a unilateral and 818 underwent a bilateral NSM. Recurrence at a mean follow-up of 31 months/median follow-up of 27 months, with a range of 9.7 to 58.3 months since surgery was 1.4% with no recurrences at the nipple or nipple areola complex (NAC). Cancer occurrence (0.3%) also did not involve the nipple/NAC. Overall patient satisfaction of excellent/good: 94.9% and overall cosmesis (surgeon rated) of excellent/good was 96.4%. Overall infection rates included flap infection of 4.4%, NAC complication rate of 4.5% (defined as necrosis/other or ischemia/epidermolysis requiring surgery), and a 10% rate of NAC epidermolysis with full recovery. NSMs were performed on breasts with a variety of sizes and degrees of ptosis, via multiple incisions, dissection and reconstruction techniques with low complication rates and high patient satisfaction and surgeon rated cosmesis.


Responses of seagrass to anthropogenic and natural disturbances do not equally translate to its consumers.
Coastal communities are under threat from many and often co-occurring local (e.g., pollution, eutrophication) and global stressors (e.g., climate change), yet understanding the interactive and cumulative impacts of multiple stressors in ecosystem function is far from being accomplished. Ecological redundancy may be key for ecosystem resilience, but there are still many gaps in our understanding of interspecific differences within a functional group, particularly regarding response diversity, that is, whether members of a functional group respond equally or differently to anthropogenic stressors. Herbivores are critical in determining plant community structure and the transfer of energy up the food web. Human disturbances may alter the ecological role of herbivory by modifying the defense strategies of plants and thus the feeding patterns and performance of herbivores. We conducted a suite of experiments to examine the independent and interactive effects of anthropogenic (nutrient and CO2 additions) and natural (simulated herbivory) disturbances on a seagrass and its interaction with two common generalist consumers to understand how multiple disturbances can impact both a foundation species and a key ecological function (herbivory) and to assess the potential existence of response diversity to anthropogenic and natural changes in these systems. While all three disturbances modified seagrass defense traits, there were contrasting responses of herbivores to such plant changes. Both CO2 and nutrient additions influenced herbivore feeding behavior, yet while sea urchins preferred nutrient-enriched seagrass tissue (regardless of other experimental treatments), isopods were deterred by these same plant tissues. In contrast, carbon enrichment deterred sea urchins and attracted isopods, while simulated herbivory only influenced isopod feeding choice. These contrasting responses of herbivores to disturbance-induced changes in seagrass help to better understand the ecological functioning of seagrass ecosystems in the face of human disturbances and may have important implications regarding the resilience and conservation of these threatened ecosystems.


Laparoscopic adjustable gastric banding for morbidly obese adolescents affects android fat loss, resolution of comorbidities, and improved metabolic status.
The distribution of weight loss and its impact on metabolic health has not been documented for laparoscopic adjustable gastric banding (LAGB) in the adolescent population. We hypothesized that LAGB in obese adolescents would result in loss of android fat mass, resolution of comorbidities, and improvement in metabolic status. Adolescents ages 14 to 17 who met criteria for bariatric surgery were enrolled in our FDA-approved LAGB trial. Demographic data, body mass index, body composition and bone density, laboratory evaluations, and comorbid conditions were assessed pre- and postoperatively. Forty-five patients had complete 1-year followup and 41 patients had complete 2-year followup. Mean preoperative weight was 299 + or - 57 lb and body mass index was 48 + or - 6.4 kg/m(2). The percent excess weight losses at 6 months, 1 year, and 2 years were 31 + or - 16, 46 + or - 21, and 47 + or - 22, respectively. At 1-year followup, patients after LAGB had a significant decrease in their total and android fat mass. In addition, 47 of 85 identified comorbidities (55%) were completely resolved and 25 (29%) were improved in comparison with baseline. Improvements in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, fasting insulin, triglycerides, and high density lipoprotein, were also seen. The percent excess weight loss after LAGB in morbidly obese adolescents is approximately 45% at 1- and 2-year followup, with the majority of weight loss consisting of android fat mass. Resolution or improvement of comorbidities is seen, and improved metabolic status, as demonstrated by liver function tests, lipid levels, and measures of glucose homeostasis, may be expected. These data support LAGB as an appropriate surgical option for morbidly obese adolescents.


New spectroscopic and electrochemical insights on a class I superoxide reductase: evidence for an intramolecular electron-transfer pathway.
SORs (superoxide reductases) are enzymes involved in bacterial resistance to reactive oxygen species, catalysing the reduction of superoxide anions to hydrogen peroxide. So far three structural classes have been identified. Class I enzymes have two iron-centre-containing domains. Most studies have focused on the catalytic iron site (centre II), yet the role of centre I is poorly understood. The possible roles of this iron site were approached by an integrated study using both classical and fast kinetic measurements, as well as direct electrochemistry. A new heterometallic form of the protein with a zinc-substituted centre I, maintaining the iron active-site centre II, was obtained, resulting in a stable derivative useful for comparison with the native all-iron from. Second-order rate constants for the electron transfer between reduced rubredoxin and the different SOR forms were determined to be 2.8 × 10⁷ M⁻¹ · s⁻¹ and 1.3 × 10⁶ M⁻¹ · s⁻¹ for SORFe(IIII)-Fe(II) and for SORFe(IIII)-Fe(III) forms respectively, and 3.2 × 10⁶ M⁻¹ · s⁻¹ for the SORZn(II)-Fe(III) form. The results obtained seem to indicate that centre I transfers electrons from the putative physiological donor rubredoxin to the catalytic active iron site (intramolecular process). In addition, electrochemical results show that conformational changes are associated with the redox state of centre I, which may enable a faster catalytic response towards superoxide anion. The apparent rate constants calculated for the SOR-mediated electron transfer also support this observation.


An Appraisal of the Clinical Features of Pediatric Enteric Fever: Systematic Review and Meta-analysis of the Age-Stratified Disease Occurrence.
Children bear a substantial proportion of the enteric fever disease burden in endemic areas. Controversy persists regarding which age groups are most affected, leading to uncertainty about optimal intervention strategies. We performed a systematic review and meta-analysis of studies in Asia and Africa to compare the relative proportion of children with enteric fever in the age groups <5 years, 5-9 years, and 10-14 years. Overall, studies conducted in Africa showed a relatively smaller occurrence of disease in the youngest age group, whereas in Asia the picture was more mixed with a very large degree of heterogeneity in estimates. The clinical features of enteric fever reviewed here differ between younger and older children and adults, likely leading to further uncertainty over disease burden. It is evident from our review that preschool children and infants also contribute a significant proportion of disease burden but have not been adequately targeted via vaccination programs, which have been focusing primarily on school-based vaccination campaigns.


Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: a systematic review, statistical modelling and survey.
The National Institute for Health and Care Excellence recommends the use of generic preference-based measures (GPBMs) of health for its Health Technology Assessments (HTAs). However, these data may not be available or appropriate for all health conditions. To determine whether GPBMs are appropriate for some key conditions and to explore alternative methods of utility estimation when data from GPBMs are unavailable or inappropriate. The project was conducted in three stages: (1) A systematic review of the psychometric properties of three commonly used GPBMs [EQ-5D, SF-6D and Health Utilities Index Mark 3 (HUI3)] in four broadly defined conditions: visual impairment, hearing impairment, cancer and skin conditions. (2) Potential modelling approaches to 'map' EQ-5D values from condition-specific and clinical measures of health [European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy - General Scale (FACT-G)] are compared for predictive ability and goodness of fit using two separate data sets. (3) Three potential extensions to the EQ-5D are developed as 'bolt-on' items relating to hearing, tiredness and vision. They are valued using the time trade-off method. A second valuation study is conducted to fully value the EQ-5D with and without the vision bolt-on item in an additional sample of 300 people. The valuation surveys were conducted using face-to-face interviews in the respondents' homes. Two representative samples of the UK general population from Yorkshire (n=600). None. Comparisons of EQ-5D, SF-6D and HUI3 in four conditions with various generic and condition-specific measures. Mapping functions were estimated between EORTC QLQ-C30 and FACT-G with EQ-5D. Three bolt-ons to the EQ-5D were developed: EQ + hearing/vision/tiredness. A full valuation study was conducted for the EQ + vision. (1) EQ-5D was valid and responsive for skin conditions and most cancers; in vision, its performance varied according to aetiology; and performance was poor for hearing impairments. The HUI3 performed well for hearing and vision disorders. It also performed well in cancers although evidence was limited and there was no evidence in skin conditions. There were limited data for SF-6D in all four conditions and limited evidence on reliability of all instruments. (2) Mapping algorithms were estimated to predict EQ-5D values from alternative cancer-specific measures of health. Response mapping using all the domain scores was the best performing model for the EORTC QLQ-C30. In an exploratory analysis, a limited dependent variable mixture model performed better than an equivalent linear model. In the full analysis for the FACT-G, linear regression using ordinary least squares gave the best predictions followed by the tobit model. (3) The exploratory valuation study found that bolt-on items for vision, hearing and tiredness had a significant impact on values of the health states, but the direction and magnitude of differences depended on the severity of the health state. The vision bolt-on item had a statistically significant impact on EQ-5D health state values and a full valuation model was estimated. EQ-5D performs well in studies of cancer and skin conditions. Mapping techniques provide a solution to predict EQ-5D values where EQ-5D has not been administered. For conditions where EQ-5D was found to be inappropriate, including some vision disorders and for hearing, bolt-ons provide a promising solution. More primary research into the psychometric properties of the generic preference-based measures is required, particularly in cancer and for the assessment of reliability. Further research is needed for the development and valuation of bolt-ons to EQ-5D. This project was funded by the UK Medical Research Council (MRC) as part of the MRC-NIHR methodology research programme (reference G0901486) and will be published in full in Health Technology Assessment; Vol. 18, No. 9. See the NIHR Journals Library website for further project information.


Avian influenza shedding patterns in waterfowl: implications for surveillance, environmental transmission, and disease spread.
Despite the recognized importance of fecal/oral transmission of low pathogenic avian influenza (LPAI) via contaminated wetlands, little is known about the length, quantity, or route of AI virus shed by wild waterfowl. We used published laboratory challenge studies to evaluate the length and quantity of low pathogenic (LP) and highly pathogenic (HP) virus shed via oral and cloacal routes by AI-infected ducks and geese, and how these factors might influence AI epidemiology and virus detection. We used survival analysis to estimate the duration of infection (from virus inoculation to the last day virus was shed) and nonlinear models to evaluate temporal patterns in virus shedding. We found higher mean virus titer and longer median infectious period for LPAI-infected ducks (10-11.5 days in oral and cloacal swabs) than HPAI-infected ducks (5 days) and geese (7.5 days). Based on the median bird infectious dose, we found that environmental contamination is two times higher for LPAI- than HPAI-infectious ducks, which implies that susceptible birds may have a higher probability of infection during LPAI than HPAI outbreaks. Less environmental contamination during the course of infection and previously documented shorter environmental persistence for HPAI than LPAI suggest that the environment is a less favorable reservoir for HPAI. The longer infectious period, higher virus titers, and subclinical infections with LPAI viruses favor the spread of these viruses by migratory birds in comparison to HPAI. Given the lack of detection of HPAI viruses through worldwide surveillance, we suggest monitoring for AI should aim at improving our understanding of AI dynamics (in particular, the role of the environment and immunity) using long-term comprehensive live bird, serologic, and environmental sampling at targeted areas. Our findings on LPAI and HPAI shedding patterns over time provide essential information to parameterize environmental transmission and virus spread in predictive epizootiologic models of disease risks.


Ischaemic and haemorrhagic stroke in the dog.
Cerebrovascular disease results from any pathological process of the blood vessels supplying the brain. Stroke, characterised by its abrupt onset, is the third leading cause of death in humans. This rare condition in dogs is increasingly being recognised with the advent of advanced diagnostic imaging. Magnetic resonance imaging (MRI) is the first choice diagnostic tool for stroke, particularly using diffusion-weighted images and magnetic resonance angiography for ischaemic stroke and gradient echo sequences for haemorrhagic stroke. An underlying cause is not always identified in either humans or dogs. Underlying conditions that may be associated with canine stroke include hypothyroidism, neoplasia, sepsis, hypertension, parasites, vascular malformation and coagulopathy. Treatment is mainly supportive and recovery often occurs within a few weeks. The prognosis is usually good if no underlying disease is found.


Albumin precursor and Hsp70 modulate corneal wound healing in an organ culture model.
In order to investigate the role of albumin precursor and Hsp70 in corneal wound healing, we have analyzed the distribution of these proteins in wounded and non-wounded corneas of rabbits and the effects of topical applications of anti-albumin precursor and anti-Hsp70 antibodies on wound healing. Anti-albumin precursor and anti-Hsp70 antibodies were topically applied in healing corneal epithelium of rabbit eyes in organ culture. Corneas were allowed to heal in vitro for up to 120 h in serum-free medium with 5 and 10 μg/ml or without (migrating control) anti-albumin precursor/ or anti-Hsp70 antibodies. Fibronectin (Fb) (5 μg/ml) was used as a positive control. Immunofluorescence labelling was used to detect proteins in corneal epithelium at various time intervals following an epithelial defect. Delay in wound healing (p<0.005) was observed with 10 μg/ml anti-albumin antibody labelling. A similar pattern was observed when anti-fibronectin antibody (5 μg/ml) alone and in combination with anti-albumin (10 μg/ml) was ectopically added with wound closure occurring at 120 h. However with anti-Hsp70 antibody (5 μg/ml) slightly delayed (p<0.005) wound closure was observed at 96 h and considerable retardation >120 h with 10 μg/ml. Additionally, immunofluoresence showed a strong co-localization of Hsp70 and albumin precursor during the active phase of wound healing. The presence of albumin precursor and Hsp70 in the epithelial compartment of the cornea indicates a role for these proteins in modulating cell behavior such as epithelial growth, adhesion or regeneration, thus contributing to corneal epithelial wound healing.


[Chronic splenic abscess : a case report].
A 16-year-old girl had had a splenic abscess for approximately 20 months with minimal symptoms and signs. Progressive elevation of the left hemidiaphragm could be traced on chest radiographs from 20 months before admission, and was shown on ultrasonography, radionuclide scintigraphy and computed tomography to be secondary to massive splenomegaly. The presence of splenic abscesses was confirmed by laparotomy and she was cured by splenectomy. The nonspecific clinical presentation and potential high mortality of this condition are stressed, and the role of diagnostic aids is discussed. Ultrasonography is a good screening procedure in terms of cost and speed, but splenic scintigraphy is more sensitive. Computed tomography is the most sensitive and specific non-invasive procedure for the diagnosis of splenic abscesses.


Strategy for degradomic-peptidomic analysis of human blood plasma.
Herein we describe a strategy for degradomic-peptidomic analyses. The human blood peptidome was isolated through application of AC/SEC, which enriched its components by >300-fold. The isolated peptidome components were separated by long column HRLC providing a peak capacity of approximately 300 for species having MWs of up to 20 kDa. The separated species were identified by the FT MS/MS-UStags sequencing method. We identified >200 peptidome components that originated from 29 protein substrates from the blood plasma of a single healthy person. The peptidome peptides identified had MWs range of 0.5-14 kDa and identifications were achieved with extremely low (near zero) false discovery rates through searching the IPI human protein database (approximately 70,000 entries). Some of the peptidome peptides identified have mutations and modifications such as acetylation, acetylhexosamine, amidation, cysteinylation, didehydro, oxidation, and pyro-glu. The capabilities described enable the global analysis of the peptidome peptides to identify degradome targets such as degradome proteases, proteases inhibitors, and other relevant substrates, the cleavage specificities for the degradation of individual substrates, as well as a potential basis for using the various extents of substrate degradation for diagnostic purposes.


Evidence for struvite in poultry litter: effect of storage and drying.
The use of spectroscopic techniques (especially phosphorus-31 nuclear magnetic resonance [(31)P-NMR] and X-ray absorption near edge structure spectroscopy) has recently advanced the analysis of the speciation of P in poultry litter (PL) and greatly enhanced our understanding of changes in P pools in PL that receive alum (aluminum sulfate) to reduce water-soluble P and control ammonia emissions from poultry houses. Questions remain concerning changes of P species during long-term storage, drying, or after application of PL to cropland or for other uses, such as turfgrass. In this study, we investigated a set of six PL samples (of which three were alum-amended and three were unamended) that had been characterized previously. The P speciation was analyzed using solid-state (31)P-NMR spectroscopy, and the mineralogy was analyzed by powder X-ray diffraction (XRD) after storing the samples moist and dried for up to 5 yr under controlled conditions. The magnesium ammonium phosphate mineral struvite was identified in all but one PL samples. Struvite concentrations were generally lower in dried samples (< or = 14%) than in samples stored moist (23 and 26%). The moist samples also had higher concentrations of phosphate bound to aluminum hydroxides. Solid-state NMR spectroscopy was in general more sensitive than XRD in detecting and quantifying P species. Although phosphate associated with calcium and aluminum made up a large proportion of P species, they were not detected by XRD.


Self-Healing of a Confined Phase Change Memory Device with a Metallic Surfactant Layer.
Understanding and possibly recovering from the failure mechanisms of phase change memories (PCMs) are critical to improving their cycle life. Extensive electrical testing and postfailure electron microscopy analysis have shown that stuck-set failure can be recovered. Here, self-healing of novel confined PCM devices is directly shown by controlling the electromigration of the phase change material at the nanoscale. In contrast to the current mushroom PCM, the confined PCM has a metallic surfactant layer, which enables effective Joule heating to control the phase change material even in the presence of a large void. In situ transmission electron microscope movies show that the voltage polarity controls the direction of electromigration of the phase change material, which can be used to fill nanoscale voids that form during programing. Surprisingly, a single voltage pulse can induce dramatic migration of antimony (Sb) due to high current density in the PCM device. Based on the finding, self-healing of a large void inside a confined PCM device with a metallic liner is demonstrated for the first time.


Full-wave electromagentic analysis of a plasmonic nanoparticle separated from a plasmonic film by a thin spacer layer.
This paper presents a theoretical analysis of the electromagnetic response of a plasmonic nanoparticle-spacer-plasmonic film system. The physical system consists of a spherical nanoparticle of a plasmonic material such as gold or silver over a plasmonic metal film and separated from the same by a dielectric spacer material. This paper presents a complete analytical solution of the Maxwell's equations, to determine the optical fields near the gold nanoparticle. It was found that the electromagnetic fields in between the plasmonic nanoparticle and the plasmonic film are extremely sensitive to the spacing between the nanoparticle and the film. This could enable the use of such a system for various sensing applications. The non-local nature of the plasmonic medium was also included in our analysis and it's effect on the resonances of the system was studied. The analytical solution was compared with an independent numerical method, the Finite Difference Time Domain (FDTD) method, to demonstrate the accuracy of the solution.


Subintimal angioplasty is superior to SilverHawk atherectomy for the treatment of occlusive lesions of the lower extremities.
To evaluate the outcomes of atherectomy versus subintimal angioplasty (SIA) in patients with lower extremity arterial occlusive disease. From September 2005 through July 2006, 27 patients (17 women; mean age 65 years, range 37-85) underwent atherectomy of 46 lesions (11 TASC C/D occlusions) with the SilverHawk device. Results were compared to 67 patients (34 men; mean age 69 years, range 46-92) undergoing SIA for 67 lower extremity arterial occlusions from July 1999 through June 2004. Technical success in the atherectomy cohort was 100%. In the 11 patients with occlusions, symptoms improved in 10 and worsened in 1, but 9 (82.0%) of the 11 patients required reintervention, and 8 (72.7%) patients with occlusive lesions re-occluded. Endovascular reintervention was required to maintain primary patency in only 2 (12.5%) of 16 patients treated for stenotic lesions. At 1 year, the assisted primary patency was 37.7% in the atherectomy group. In the 11 patients with occlusive lesions, the patency rates were 36.8% and 12.3% at 6 and 9 months, respectively, versus 100% and 83.3% at the same time intervals in patients with stenotic lesions. SIA was technically successful in 56 (83.6%) of 67 occlusions. The assisted primary patency and limb salvage rates of the entire group (intention-to-treat) at 12 and 24 months were 59.2% and 45.0%, respectively, while the assisted primary patency of the 56 technically successful SIAs at 12 and 24 months were 70.7% and 53.8%, respectively. Limb salvage for the entire group (intention-to-treat) was 90.6% and 87.9% at 12 and 24 months, respectively. Atherectomy may yield acceptable primary patency and limb salvage in patients with stenotic lesions. Many of the patients treated for occlusive lesions require reintervention. Based on patency and limb salvage, SIA appears superior to atherectomy for the treatment of lower extremity occlusive disease.