Detection of peripheral nerve pathology: comparison of ultrasound and MRI.
To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions.


Assessing the internal and external validity of mobile health physical activity promotion interventions: a systematic literature review using the RE-AIM framework.
Mobile health (mHealth) interventions are effective in promoting physical activity (PA); however, the degree to which external validity indicators are reported is unclear. The purpose of this systematic review was to use the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to determine the extent to which mHealth intervention research for promoting PA reports on factors that inform generalizability across settings and populations and to provide recommendations for investigators planning to conduct this type of research. Twenty articles reflecting 15 trials published between 2000 and 2012 were identified through a systematic review process (ie, queries of three online databases and reference lists of eligible articles) and met inclusion criteria (ie, implementation of mobile technologies, target physical activity, and provide original data). Two researchers coded each article using a validated RE-AIM data extraction tool (reach, efficacy/effectiveness, adoption, implementation, maintenance). Two members of the study team independently abstracted information from each article (inter-rater reliability >90%) and group meetings were used to gain consensus on discrepancies. The majority of studies were randomized controlled trials (n=14). The average reporting across RE-AIM indicators varied by dimension (reach=53.3%, 2.67/5; effectiveness/efficacy=60.0%, 2.4/4; adoption=11.1%, 0.7/6; implementation=24.4%, 0.7/3; maintenance=0%, 0/3). While most studies described changes in the primary outcome (effectiveness), few addressed the representativeness of participants (reach) or settings (adoption) and few reported on issues related to maintenance and degree of implementation fidelity. This review suggests that more focus is needed on research designs that highlight and report on both internal and external validity indicators. Specific recommendations are provided to encourage future mHealth interventionists and investigators to report on representativeness, settings, delivery agents for planned interventions, the extent to which protocol is delivered as intended, and maintenance of effects at the individual or organizational level.


Urban-Rural Differences in Older Adult Depression: A Systematic Review and Meta-analysis of Comparative Studies.
Depression among older adults (aged 60 years or older) is a problem that could be exacerbated by global trends in urbanization and population aging. The study purpose was to assess whether urban, relative to rural, residence is associated with depression among older adults and whether associations differ in countries with developed versus developing economies. In 2017, the authors identified and extracted information from comparative studies of urban-rural depression prevalence among older adults. Studies were identified in PubMed, PsychINFO, and Web of Science and limited to English language articles published after 1985. Eighteen studies met inclusion criteria. Random effects meta-analysis was conducted to produce weighted pooled ORs estimating the association between urban-rural residence and depression for all study participants (N=31,598) and sub-analyses were conducted for developed (n=12,728) and developing (n=18,870) countries. Depression prevalence was significantly higher among urban residents in ten studies and significantly higher among rural residents in three studies (all three conducted in China). Associations between urban-rural residence and depression generally remained significant after adjusting for covariates. In developed countries, the odds of depression were significantly higher among urban than rural residents (pooled OR=1.44, 95% CI=1.10, 1.88). However, in developing countries, this association was not observed (pooled OR=0.91, 95% CI=0.46, 1.77). Converging trends of urbanization and population aging could increase the global burden of depression among older adults. The pathways through which urban-rural residence influences depression risk among older adults might differ by country context. Future research should focus on measuring variation in these contexts.


Pertussis vaccination in child care workers: room for improvement in coverage, policy and practice.
The "Staying Healthy in Child Care" Australian guidelines provide for illness and disease exclusions and encourage vaccination of staff in child care settings, however these requirements are not subject to accreditation and licensing, and their level of implementation is unknown. This study aimed to describe pertussis vaccination coverage in child care workers in a regional area of northern NSW during 2010; review current staff pertussis vaccination practices; and explore barriers to vaccination. A cross sectional survey of all child care centre directors in the Hunter New England (HNE) area of northern NSW was conducted in 2010 using a computer assisted telephone interviewing service. Ninety-eight percent (319/325) of child care centres identified within the HNE area participated in the survey. Thirty-five percent (113/319) of centres indicated that they had policies concerning respiratory illness in staff members. Sixty-three percent (202/319) of centres indicated that they kept a record of staff vaccination, however, of the 170 centre's who indicated they updated their records, 74% (125/170) only updated records if a staff member notified them. Of centres with records, 58% indicated that fewer than half of their staff were vaccinated. Many childcare workers have not had a recent pertussis immunisation. This potentially places young children at risk at an age when they are most vulnerable to severe disease. With increasing use of child care, national accreditation and licensing requirements need to monitor the implementation of policies on child care worker vaccination. Higher levels of vaccination would assist in reducing the risk of pertussis cases and subsequent outbreaks in child care centres.


A general approach to the isolation of cell cycle-regulated genes in the budding yeast, Saccharomyces cerevisiae.
We describe a general approach to the isolation of cell cycle-dependently regulated transcripts in Saccharomyces cerevisiae. This approach is based on the physical identification of cell cycle-regulated transcripts by Northern hybridization using as probes yeast DNA isolated from an ordered S. cerevisiae genomic library. The purpose of this is twofold; first, to assess the importance of transcriptional regulation in cell cycle control; and second, to identify novel genes that may have important roles in the eukaryotic cell cycle. We report the isolation of two previously uncharacterized genes that are transcribed at points in the cell cycle to which specific transcriptional activation has not been assigned: namely, mitosis and early G1 phase. It is argued that these transcripts serve as important landmarks for cell cycle events that are not readily distinguished by either morphological or cytological criteria. The cell cycle-dependent transcription of the RNR1 and CLN1 genes is also described and the implications for cell cycle control, in G1, are discussed with reference to these two genes.


The effect of long-term weight-loss intervention strategies on the dynamics of pancreatic-fat and morphology: An MRI RCT study.
The ability to mobilize pancreatic-fat and the meaning of decreased fat in the pancreas remain controversial. We followed the dynamics of pancreatic-fat and its morphology during various long weight-loss induced lifestyle-interventions. In isolated workplace with monitored/provided lunch, we randomly assigned healthy persons with abdominal obesity or dyslipidemia for one of two 18-month equal-caloric diets: low-fat (LF) or Mediterranean/low-carbohydrate (Med/LC, with provided 1oz walnuts/day), with or without added moderate exercise (supervised gym membership). We used magnetic-resonance-imaging to quantify pancreatic-fat and morphology. At baseline, 277 eligible participants (mean age = 48 years; 88% men; pancreatic-fat = 17.4 ± 5.1%) had higher pancreatic-fat in men (17.7 ± 4.9% vs 14.9 ± 5.5% in women; p = 0.004). Following 18-month intervention (adherence = 86.3%) and moderate weight-loss (mean = -3.0 ± 5.5 kg), pancreatic-fat decreased moderately but significantly (-0.26 ± 2.18% units; p = 0.049). Med/LC diet induced a greater decrease in pancreatic-fat compared to LF (p = 0.043), and the combination of Med/LC diet + exercise exhibited the highest reduction (-0.69% units) as compared to LF diet without exercise (+0.12%units; p = 0.027 between groups). In multivariate regression models, after further adjusted for visceral adipose-tissue (ΔVAT), pancreatic-fat loss associated with both decreases in pancreatic-morphology ratio (perimeter divided by area; beta = 0.361; p < 0.001) and superficial-subcutaneous adipose-tissue loss (beta = 0.242; p = 0.001), but not with changes in intrahepatic-fat (beta = -0.034; p = 0.638). Pancreatic-fat loss associated with increased intake of polyunsaturated-fat (beta = -0.137; p = 0.032), as with improved high-density lipoprotein-cholesterol (HDL; beta = -0.156; p = 0.023) and triglycerides/HDL ratio (beta = 0.162; p = 0.015), independently of ΔVAT, but not with glycemic-control parameters (e.g. HbA1c, HOMA-IR and HOMA-beta; p > 0.2 for all). Pancreatic-fat loss is mainly associated with improved lipid, rather than glycemic profiles. Med/LC diet, mostly with exercise, may benefit pancreatic-fat loss. Pancreatic-morphology could serve as a biomarker of pancreatic-fat state. (ClinicalTrials.gov identifier: NCT01530724).


Press-fit condylar design total knee arthroplasty. Fourteen to seventeen-year follow-up.
The Press-Fit Condylar total knee arthroplasty implant design has been used by many orthopaedic surgeons over the last twenty years. The design has survived with relatively minor modifications and remains a popular implant system today. The present study represents the fourteen to seventeen-year results for our patients who were described in our previous report on the eight to ten-year results. The senior author performed 160 consecutive total knee arthroplasties with use of the Press-Fit Condylar cruciate-retaining device in 134 patients between 1986 and 1989. The mean age of the patients at the time of the index procedure was 70.5 years. Follow-up data were available for sixty-three of sixty-four surviving knees. Surviving patients were followed for a mean of 15.8 years. The knees were evaluated on the basis of Knee Society function and clinical scores, radiographs, and survivorship analysis. The mean Knee Society function score was 65, and the mean clinical score was 89. The overall survival rate of the knee was 91.5% with revision for any reason as the end point and 97.2% with aseptic loosening as the end point. The rate of revision of the tibial insert because of wear-related aseptic loosening was 2.5%. We found no relationship between revision and the shelf life or method of sterilization of the polyethylene insert. Radiolucent lines were present in 62% (twenty-one) of thirty-four knees; all radiolucent lines were nonprogressive. None of the implants were loose according to the criteria of the Knee Society. This long-term analysis indicates that the Press-Fit Condylar total knee implant is a successful implant system with excellent longevity.


Effects of piceatannol and pterostilbene against β-amyloid-induced apoptosis on the PI3K/Akt/Bad signaling pathway in PC12 cells.
Neuron apoptosis induced by β-amyloid (Aβ) is an important precipitating factor in the pathogenesis of Alzheimer's disease (AD). In the present study, the effects of piceatannol (PT) and pterostilbene (PS) against Aβ-induced apoptosis in PC12 cells were evaluated. PT and PS both showed observable anti-apoptosis activity. Increased cell viability, decreased apoptosis rate and declining intracellular ROS were observed after PT and PS treatment. For the signaling pathway, PT significantly promoted phosphorylation of Akt and Bad, further suppressed Bcl-2/Bax expression and inhibited cleavage of caspase-9, caspase-3 and PARP. PS promoted phosphorylation of Akt without affecting the other factors. The experimental results, for the first time, unambiguously suggested that PT showed a comprehensive protective effect against Aβ-induced apoptosis in PC12 cells via a novel PI3K/Akt/Bad signaling pathway and downstream mitochondria-mediated and caspase-dependent signaling pathway. Unlike PT, PS inhibited apoptosis against Aβ through a different PI3K/Akt signaling pathway in which the downstream targets need to be further investigated. The results also provide the basis for dietary intervention involved in the prevention and adjunctive therapy of AD.


Mutual energy transfer luminescent properties in novel CsGd(MoO4)2:Yb3+,Er3+/Ho3+ phosphors for solid-state lighting and solar cells.
In this work, we prepared a novel kind of Yb3+,Er3+/Ho3+ co-doped CsGd(MoO4)2 phosphors with a different structure from the reported ALn(MoO4)2 (A = Li, Na or K; Ln = La, Gd or Y) compounds using a high-temperature solid-state reaction method. X-ray diffraction showed that the as-prepared samples had a pure phase. Based on the efficient energy transfer from Yb3+ to Er3+/Ho3+, the up-conversion (UC) luminescence of the optimal CsGd(MoO4)2:0.30Yb3+,0.02Er3+ sample showed intensely green light with dominant emission peaks at 528 and 550 nm corresponding to Er3+ transitions 2H11/2 → 4I15/2 and 4S3/2 → 4I15/2, respectively, as well as a weak emission peak originating from 4F9/2 → 4I15/2 at 671 nm, under 975 nm laser excitation. The CsGd(MoO4)2:Yb3+,Ho3+ samples mainly displayed two emission bands around 540 and 660 nm together with a negligible one at 755 nm, which corresponded to Ho3+ transitions 4F4,5F2 → 5I8, 5F5 → 5I8 and 4F4,5F2 → 5I7, respectively, under 975 nm laser excitation. With increasing Yb3+ concentration in CsGd(MoO4)2:Yb3+,Ho3+ phosphors, the emission color could be tuned from orange red to light yellow due to the large energy gap between levels 4F4,5F2 and 5F5. In addition, the CsGd(MoO4)2:Yb3+,Er3+ showed green light under 376 nm UV irradiation similar to that upon 975 nm laser excitation. However, the emissions for CsGd(MoO4)2:Yb3+,Ho3+ samples under 358 nm UV or 449 nm blue excitation showed dominant emission peaks at 540 nm and weak 660 nm and 752 nm peaks, which were a bit different from those under 975 nm excitation. Interestingly, we observed efficient energy transfer phenomena (possible quantum cutting) from Er3+/Ho3+ to Yb3+ and a Yb3+-O2- charge transfer (CT) transition in the molybdates, which was deduced from the visible and near-infrared emission spectra and the decrease of the Er3+/Ho3+ luminescent lifetimes with increasing Yb3+ concentration in the CsGd(MoO4)2:Yb3+,Er3+/Ho3+ samples. The luminescence properties of these phosphors suggest their potential possibility for applications in solid-state lighting and displays as well as in c-Si solar energy conversion systems.


An event driven hybrid identity management approach to privacy enhanced e-health.
Credential-based authorization offers interesting advantages for ubiquitous scenarios involving limited devices such as sensors and personal mobile equipment: the verification can be done locally; it offers a more reduced computational cost than its competitors for issuing, storing, and verification; and it naturally supports rights delegation. The main drawback is the revocation of rights. Revocation requires handling potentially large revocation lists, or using protocols to check the revocation status, bringing extra communication costs not acceptable for sensors and other limited devices. Moreover, the effective revocation consent--considered as a privacy rule in sensitive scenarios--has not been fully addressed. This paper proposes an event-based mechanism empowering a new concept, the sleepyhead credentials, which allows to substitute time constraints and explicit revocation by activating and deactivating authorization rights according to events. Our approach is to integrate this concept in IdM systems in a hybrid model supporting delegation, which can be an interesting alternative for scenarios where revocation of consent and user privacy are critical. The delegation includes a SAML compliant protocol, which we have validated through a proof-of-concept implementation. This article also explains the mathematical model describing the event-based model and offers estimations of the overhead introduced by the system. The paper focus on health care scenarios, where we show the flexibility of the proposed event-based user consent revocation mechanism.


Structure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase.
Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogues that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 μM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, respectively. Finally, crystallographic studies showed the molecular basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer.


An Acquisition Method for Visible and Near Infrared Images from Single CMYG Color Filter Array-Based Sensor.
Near-infrared (NIR) images are very useful in many image processing applications, including banknote recognition, vein detection, and surveillance, to name a few. To acquire the NIR image together with visible range signals, an imaging device should be able to simultaneously capture NIR and visible range images. An implementation of such a system having separate sensors for NIR and visible light has practical shortcomings due to its size and hardware cost. To overcome this, a single sensor-based acquisition method is investigated in this paper. The proposed imaging system is equipped with a conventional color filter array of cyan, magenta, yellow, and green, and achieves signal separation by applying a proposed separation matrix which is derived by mathematical modeling of the signal acquisition structure. The elements of the separation matrix are calculated through color space conversion and experimental data. Subsequently, an additional denoising process is implemented to enhance the quality of the separated images. Experimental results show that the proposed method successfully separates the acquired mixed image of visible and near-infrared signals into individual red, green, and blue (RGB) and NIR images. The separation performance of the proposed method is compared to that of related work in terms of the average peak-signal-to-noise-ratio (PSNR) and color distance. The proposed method attains average PSNR value of 37.04 and 33.29 dB, respectively for the separated RGB and NIR images, which is respectively 6.72 and 2.55 dB higher than the work used for comparison.


Post-hoc analysis showing better clinical response with the loading dose of certolizumab pegol in Japanese patients with active rheumatoid arthritis.
To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.


Concept of a multichannel spin-resolving electron analyzer based on Mott scattering.
The concept of a multichannel electron spin detector based on optical imaging principles and Mott scattering (iMott) is presented. A multichannel electron image produced by a standard angle-resolving (photo) electron analyzer or microscope is re-imaged by an electrostatic lens at an accelerating voltage of 40 kV onto the Au target. Quasi-elastic electrons bearing spin asymmetry of the Mott scattering are imaged by magnetic lenses onto position-sensitive electron CCDs whose differential signals yield the multichannel spin asymmetry image. Fundamental advantages of this concept include acceptance of inherently divergent electron sources from the electron analyzer or microscope focal plane as well as small aberrations achieved by virtue of high accelerating voltages, as demonstrated by extensive ray-tracing analysis. The efficiency gain compared with the single-channel Mott detector can be a factor of more than 10(4) which opens new prospects of spin-resolved spectroscopies in application not only to standard bulk and surface systems (Rashba effect, topological insulators, etc.) but also to buried heterostructures. The simultaneous spin detection combined with fast CCD readout enables efficient use of the iMott detectors at X-ray free-electron laser facilities.


Cytotoxicity, mutagenicity, oxidative stress and mitochondrial impairment in human hepatoma (HepG2) cells exposed to copper oxide, copper-iron oxide and carbon nanoparticles.
The increasing application of nanomaterials in various fields such as drug delivery, cosmetics, disease detection, cancer treatment, food preservation etc. has resulted in high levels of engineered nanoparticles in the environment, thus leading to higher possibility of direct or indirect interactions between these particles and biological systems. In this study, the toxic effects of three commercially available nanomaterials; copper oxide nanoparticles, copper-iron oxide nanopowders and carbon nanopowders were determined in the human hepatoma HepG2 cells using various toxicological assays which are indicative of cytotoxicity (MTT and neutral red assays), mutagenicity (cytokinesis-block micronucleus assay), oxidative stress (total reactive oxygen species and superoxide anion production) and mitochondrial impairment (cellular oxygen consumption). There was increased cytotoxicity, mutagenicity, and mitochondrial impairment in the cells treated with higher concentrations of the nanomaterials, especially the copper oxide nanoparticles. The fold production of reactive oxygen species was similar at the concentrations tested in this study but longer exposure duration resulted in production of more superoxide anions. The results of this study showed that copper oxide nanoparticles are highly toxic to the human HepG2 cells, thus implying that the liver is a target organ in human for copper oxide nanoparticles toxicity.


Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.
The lin-12 gene of C. elegans and the Notch gene of D. melanogaster encode structurally related transmembrane proteins that mediate intercellular signaling. We show that truncated forms of these proteins consisting of only the intracellular domains cause cell fate transformations associated with constitutive activity in their respective organisms. This activity does not depend on endogenous gene function. Our results indicate that the intracellular domains of Lin-12 and Notch have intrinsic activity and that the principal role of the extracellular domains in the intact proteins is to regulate this activity. Our results also suggest that equivalent truncated forms of lin-12/Notch family members in vertebrates, including known oncogenes, are similarly active.


Self-stigma of people with schizophrenia as predictor of their adherence to psychosocial treatment.
Treatment non-adherence has frequently been noticed among people with schizophrenia. Self-stigma towards one's mental illness is believed to be a contributing factor undermining adherence. This study aimed at obtaining empirical support regarding the relationship between psychosocial treatment adherence and self-stigma. Other significant predictors of adherence to psychosocial interventions were to be identified. Eighty-six people with DSM IV diagnoses of schizophrenia were recruited from psychiatric hospitals and community settings in Hong Kong. Their level of stigma, self-esteem, self-efficacy, insight, psychosocial treatment adherence and demographic data were collected. Multiple regression was used to investigate the adjusted relationship between psychosocial treatment adherence and the selected independent variables. Higher level of self-stigma, poorer current insight on the social consequences of having mental illness, and living with others were found to be significant predictors of poor psychosocial treatment attendance. Better self-esteem and current insight about the negative social consequences were significant predictors of better psychosocial treatment participation. Self-stigma and self-esteem exhibited the strongest contributions to psychosocial treatment adherence. Self-stigmatization is associated with the level of treatment adherence among people with schizophrenia, and its negative effect was found to intensify along the self-stigmatization process. Further studies to enhance understanding of self-stigma and improve treatment adherence are suggested.


Androgen regulates the sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord that mediates male sexual function.
A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate male sexual reflexes such as erection and ejaculation. Because these reflexes are androgen dependent, we asked whether manipulating levels of androgen in adult rats would affect GRP expression in this spinal center. We found that castration resulted, 28 d later, in a profound decrease in the expression of GRP in the spinal cord, as reflected in immunocytochemistry and competitive ELISA for the protein as well as real-time quantitative PCR for the transcript. These effects were prevented if the castrates were treated with testosterone propionate. Genetically male (XY) rats with the dysfunctional testicular feminization allele for the androgen receptor (AR) displayed GRP mRNA and protein levels in the spinal cord similar to those of females, indicating that androgen normally maintains the system through AR. We saw no effect of castration or the testicular feminization allele on expression of the receptor for GRP in the spinal cord, but castration did reduce expression of AR transcripts within the spinal cord as revealed by real-time quantitative PCR and Western blots. Taken together, these results suggest that androgen signaling plays a pivotal role in the regulation of GRP expression in male lumbar spinal cord. A greater understanding of how androgen modulates the spinal GRP system might lead to new therapeutic approaches to male sexual dysfunction.


SU-E-J-67: A Potential New Technique to Measure Respiratory Tidal Volume Using Optical Surface Imaging: A Geometric and Deformable Phantom Study.
To develop a new method for accurate measurement of dynamic respiratory tidal volume, we investigate the feasibility of measuring torso volume change using optical surface imaging (OSI). Based on a validated volume conservation theory, the tidal volume is equal to the volume change of the torso during quiet respiration (Li et al, PMB, 54:1693, 2009). A clinical OSI system was employed to acquire surface images of seven geometric phantoms and two 'deformable' torso phantoms. The mesh surface images were converted into contours for volume calculation using a treatment planning system. For geometric phantoms, their volumes under the incomplete surface images were calculated with aid of their symmetry. The results were compared with theoretical calculation and water containment experiments. For deformable torso phantoms, we created volume-controlled deformation stages by placing deformable PlayDoh (DPD) materials on top of rigid Rando/Thorax phantoms, mimicking respiration-induced torso surface elevation and volume change. The volume difference under the surfaces with and without the DPD padding was calculated with aid of a common posterior line to enclose the region of interest. Three different volumes of DPD padding (>500cc) were mounted on the torso phantoms and CT scanned for volume measurements. For geometric phantoms, the OSI measured volume had accuracy (±1s) of 0.0%±1.6% (vs. geometric volume calculation) and 0.6%±3.8% (vs. water containment experiment). For deformable torso phantoms, the volume change was measured using OSI with an accuracy of 1.5%±2.5% against the measured volume using CT imaging. Linear regression showed a one-to-one relationship between the OSI volumes and CT volumes with a slope of 1.003 (r2=0.999). The optical surface imaging system can accurately measure the volume of geometric phantoms and the volume change of deformable torso phantoms. The accuracy is about 3% against standard volume measurement methods. Further study on human subjects is under investigation. Memorial Sloan-Kettering Cancer Center has a reserach agreement with Vision RT, Inc.


Antioxidant activity, antitumor effect, and antiaging property of proanthocyanidins extracted from Kunlun Chrysanthemum flowers.
The objective of the present study was to evaluate the antioxidant activity, antitumor effect, and antiaging property of proanthocyanidins from Kunlun Chrysanthemum flowers (PKCF) grown in Xinjiang. In vitro antioxidant experiments results showed that the total antioxidant activity and the scavenging capacity of hydroxyl radicals ((•)OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) radicals increased in a concentration-dependent manner and were stronger than those of vitamin C. To investigate the antioxidant activity of PKCF in vivo, we used serum, liver, and kidney from mouse for the measurement of superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (T-AOC). Results indicated that PKCF had antioxidative effect in vivo which significantly improved the activity of SOD and T-AOC and decreased MDA content. To investigate the antitumor activity of PKCF, we used H22 cells, HeLa cells, and Eca-109 cells with Vero cells as control. Inhibition ratio and IC50 values were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; PKCF showed great inhibitory activity on H22 cells and HeLa cells. We also used fruit flies as a model for analyzing the anti-aging property of PKCF. Results showed that PKCF has antiaging effect on Drosophila. Results of the present study demonstrated that PKCF could be a promising agent that may find applications in health care, medicine, and cosmetics.


Mouse Hepatomas with Ha-ras and B-raf Mutations Differ in Mitogen-Activated Protein Kinase Signaling and Response to Constitutive Androstane Receptor Activation.
Nuclear receptors mediate the hepatic induction of drug-metabolizing enzymes by xenobiotics. Not much is known about enzyme induction in liver tumors. Here, we treated tumor-bearing mice with phenobarbital, an activator of the constitutive androstane receptor (CAR), to analyze the response of chemically induced Ha-ras- and B-raf-mutated mouse liver adenoma to CAR activation in vivo. Both tumor subpopulations possess almost identical gene expression profiles. CAR target gene induction in the tumors was studied at the mRNA and protein levels, and a reverse-phase protein microarray approach was chosen to characterize important signaling cascades. CAR target gene induction was pronounced in B-raf-mutated but not in Ha-ras-mutated tumors. Phosphoproteomic profiling revealed that phosphorylation-activated extracellular signal-regulated kinase (ERK) 1/2 was more abundant in Ha-ras-mutated than in B-raf-mutated tumors. ERK activation in tumor tissue was negatively correlated with CAR target induction. ERK activation is known to inhibit CAR-dependent transcription. In summary, profound differences exist between the two closely related tumor subpopulations with respect to the activation of mitogenic signaling cascades, and these dissimilarities might explain the differences in xenobiotic induction of CAR target genes.


Surveillance of spontaneous breast cancer metastasis by TRAIL-expressing CD34⁺ cells in a xenograft model.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), delivered as a membrane-bound molecule expressed on the surface of adenovirus-transduced CD34(+) cells (CD34-TRAIL(+)), was analyzed for its apoptotic activity in vitro on 12 breast cancer cell lines representing estrogen receptor-positive, HER2(+) and triple-negative (TN) subtypes and for its effect on tumor growth, vascularization, necrosis, and lung metastasis incidence in NOD/SCID mice xenografted with the TN breast cancer line MDA-MB-231. Mesenchymal TN cell lines, which are the richest in putative tumor stem cells among the different breast cancer cell subtypes, were the most susceptible to apoptosis induced by CD34-TRAIL(+) cells. Indeed, tumor cell "stemness", assessed based on the proportion of CD44(+)/CD24(-/low) cells, was significantly correlated with susceptibility to TRAIL. Moreover, in vitro cytotoxicity experiments showed that CD34-TRAIL(+) cells selectively targeted CD44(+)/CD24(-/low) cells. Although in vivo treatment with CD34-TRAIL(+) cells did not lead to tumor growth inhibition, treated mice revealed significantly larger areas of necrosis associated with damage of tumor vasculature than did control mice. Moreover, lungs from MDA-MD-231 tumor-bearing mice were completely free of metastases at 12 days after the last injection of CD34-TRAIL(+) cells, whereas metastases were present in all control mouse lungs. An anti-metastatic effect of CD34-TRAIL(+) cells was also observed in a model of experimental lung metastases. The correlation between in vitro susceptibility to membrane-bound TRAIL and tumor stem cell content, together with CD34-TRAIL(+) cell-induced inhibition of the metastatic process, points to the selective targeting of cancer stem cells by CD34-armed cells and the potential value of such cells in eradicating tumor stem cells before the onset of overt metastases.


A meta-analysis of context integration deficits across the schizotypy spectrum using AX-CPT and DPX tasks.
Schizotypy and schizophrenia involve disrupted context integration (CI), the ability to assimilate internal and external information into coherent mental representations. Research has primarily examined patients with schizophrenia, with fewer studies assessing CI in schizotypy-spectrum groups. The literature shows overall CI deficits, but mixed results for specific performance patterns and associations with clinical symptoms. Furthermore, conclusions are limited by small samples and heterogeneity across studies. To examine CI deficits across the schizotypy spectrum using AX-Continuous Performance Task (CPT) and Dot Pattern Expectancy task (DPX) performance. Systematic review involved searching 4 databases and 12 journals, examining key references, and contacting 227 researchers for published and unpublished data. Search terms included AX-CPT/DPX/dot pattern expectancy task/CNTRACs/context* integration/context* processing and schizo*/prodromal/high risk/psychosis; context* and ultra high risk. Independent data from studies with diagnostically or psychometrically assessed schizotypy-spectrum groups and AX-CPT/DPX tasks with 10+ trials and 60+% AX trials were included. Articles were independently coded by two authors using predefined coding schemes with good agreement. Meta-analyses pooled outcomes using random-effects models. Forty-one studies met inclusion criteria. CI impairment was present across the schizotypy spectrum. CI deficits in schizophrenia were substantial and associated with disorganized and negative symptoms. Outcomes were comparable between patients with chronic and first-episode schizophrenia. At-risk groups demonstrated moderate CI impairment. Results were robust across task parameters and there was no evidence that reporting biases grossly impacted outcomes. Findings lend support to theories suggesting that CI is a stable vulnerability factor for schizophrenia. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Intracellular diversity of the V4 and V9 regions of the 18S rRNA in marine protists (radiolarians) assessed by high-throughput sequencing.
Metabarcoding is a powerful tool for exploring microbial diversity in the environment, but its accurate interpretation is impeded by diverse technical (e.g. PCR and sequencing errors) and biological biases (e.g. intra-individual polymorphism) that remain poorly understood. To help interpret environmental metabarcoding datasets, we investigated the intracellular diversity of the V4 and V9 regions of the 18S rRNA gene from Acantharia and Nassellaria (radiolarians) using 454 pyrosequencing. Individual cells of radiolarians were isolated, and PCRs were performed with generalist primers to amplify the V4 and V9 regions. Different denoising procedures were employed to filter the pyrosequenced raw amplicons (Acacia, AmpliconNoise, Linkage method). For each of the six isolated cells, an average of 541 V4 and 562 V9 amplicons assigned to radiolarians were obtained, from which one numerically dominant sequence and several minor variants were found. At the 97% identity, a diversity metrics commonly used in environmental surveys, up to 5 distinct OTUs were detected in a single cell. However, most amplicons grouped within a single OTU whereas other OTUs contained very few amplicons. Different analytical methods provided evidence that most minor variants forming different OTUs correspond to PCR and sequencing artifacts. Duplicate PCR and sequencing from the same DNA extract of a single cell had only 9 to 16% of unique amplicons in common, and alignment visualization of V4 and V9 amplicons showed that most minor variants contained substitutions in highly-conserved regions. We conclude that intracellular variability of the 18S rRNA in radiolarians is very limited despite its multi-copy nature and the existence of multiple nuclei in these protists. Our study recommends some technical guidelines to conservatively discard artificial amplicons from metabarcoding datasets, and thus properly assess the diversity and richness of protists in the environment.


Fatal necrotic enteritis associated with Clostridium perfringens in wild crows (Corvus macrorhynchos).
Sporadic outbreaks of fatal enteritis occurred among free-living wild crows ('large billed' or 'wok' crow; Corvus macrorhynchos) in an open-air park in Japan in 2002. Eight crows were found dead during February, followed by two more in September, and five of the eight were examined histopathologically. At necropsy, all cases showed a markedly dilated small intestine, especially the jejunum and ileum, with large amounts of gas, and dark red to greenish-brown soft content. The necrotic intestinal wall was markedly thickened with multifocal haemorrhages. All cases had multifocal white foci in the liver, and four cases showed marked splenomegaly. Histologically, there was severe necrotic enteritis characterized by extensive mucosal necrosis and multifocal haemorrhages, as well as inflammatory cell infiltrations. A prominent pseudo-membrane formation was noted in the affected intestine. Severe adhesive peritonitis was also observed in three cases. Gram-positive bacilli were present in large numbers in the lumen, and in and around necrotic lesions in the affected intestine. The bacilli were positive for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were also positive for C. perfringens type A using the immunofluorescence method. C. perfringens was isolated by anaerobic culture from the intestinal contents. The present enteritis was thought to be induced by proliferated C. perfringens in the intestine, and to be the cause of death.


Spine radiosurgery for spinal cord compression: the radiation oncologist's perspective.
Metastatic spinal cord compression (MSCC) is a common problem afflicting cancer patients. It affects 5-14% of all patients with cancer, and more than 20,000 cases are diagnosed annually in the United States (1-3). Once diagnosed, it is considered to be a medical emergency, and immediate intervention is required with high-dose corticosteroids and radiotherapy (RT), with or without decompressive surgery. Without therapy, MSCC is a source of significant morbidity and mortality, causing pain, paralysis, incontinence, and an overall decline in quality of life. Even with aggressive therapy, results can often be unsatisfactory. Although most patients will die of their underlying cancer within the first year of the diagnosis of MSCC, up to one-third will survive beyond one year (4-5). Therefore, optimal therapy is required to maintain quality of life.


Te-containing carbon dots for fluorescence imaging of superoxide anion in mice during acute strenuous exercise or emotional changes.
Acute strenuous exercise and emotional changes are closely related to important aspects of human health. The superoxide anion (O2˙-), as one of the primary reactive oxygen species (ROS), is intimately associated with major diseases. However, there is no relevant in vivo research for directly indicating the link between O2˙- level and acute physical exercise or emotional changes. Hence, we constructed three fluorescent probes for the detection of O2˙-, including a Te-containing molecular probe and Se- and Te-containing CDs, and evaluated their properties such as selectivity, sensitivity, instantaneity and dynamic response to O2˙-. Through performance comparisons, we found that the Te-containing CDs exhibited reversibility, instantaneity and the highest sensitivity (LOD ∼ 8.0 pM), under guarantees of specific recognition of O2˙-, which ensure they are suitable for tracing native level changes in O2˙- within living systems. The probe was applied for monitoring the levels of O2˙- in mice under the state of intense exercise, irritability and mild depression, which led to the levels of O2˙- significantly increasing compared to the normal condition. Furthermore, we used the Te-containing CDs for real-time and dynamic imaging of O2˙- fluxes in the brain of mild depression mice and witnessed a positive correlation between O2˙- levels and depression. This work provides a new strategy for studying the relationship between acute exercise or emotional changes and diseases at the level of ROS.


Outcome of 24 years national surveillance in different hereditary colorectal cancer subgroups leading to more individualised surveillance.
Individuals with hereditary non-polyposis colorectal cancer (HNPCC) have a high risk of colorectal cancer (CRC). The benefits of colonic surveillance in Lynch syndrome and Amsterdam-positive (familial CRC type X familial colorectal cancer type X (FCCTX)) families are clear; only the interval between colonoscopies is debated. The potential benefits for families not fulfilling the Amsterdam criteria are uncertain. The aim of this study was to compare the outcome of colonic surveillance in different hereditary subgroups and to evaluate the surveillance programmes. A prospective, observational study on the outcome of colonic surveillance in different hereditary subgroups based on 24 years of surveillance data from the national Danish HNPCC register. We analysed 13 444 surveillance sessions, including 8768 incidence sessions and 20 450 years of follow-up. CRC was more incident in the Lynch subgroup (2.0%) than in any other subgroup (0.0-0.4%, p<0.0001), but the incidence of advanced adenoma did not differ between the Lynch (3.6%) and non-Lynch (2.3-3.9%, p=0.28) subgroups. Non-Lynch Amsterdam-positive and Amsterdam-negative families were similar in their CRC (0.1-0.4%, p=0.072), advanced adenoma (2.3-3.3%, p=0.32) and simple adenoma (8.4-9.9%, p=0.43) incidence. In moderate-risk families, no CRC and only one advanced adenoma was found. The risk of CRC in Lynch families is considerable, despite biannual surveillance. We suggest less frequent and more individualised surveillance in non-Lynch families. Individuals from families with a strong history of CRC could be offered 5-year surveillance colonoscopies (unless findings at the preceding surveillance session indicate shorter interval) and individuals from moderate-risk families could be handled with the population-based screening programme for CRC after an initial surveillance colonoscopy.


DDT, epigenetic harm, and transgenerational environmental justice.
Although the environmentally harmful effects of widespread dichlorodiphenyltrichloroethane (DDT) use became well-known following Rachel Carson's Silent Spring (1962), its human health effects have more recently become clearer. A ban on the use of DDT has been in place for over 30 years, but recently DDT has been used for malaria control in areas such as Africa. Recent work shows that DDT has transgenerational effects in progeny and generations never directly exposed to DDT. These effects have health implications for individuals who are not able to have any voice in the decision to use the pesticide. The transgenerational effects of DDT are considered in light of some widely accepted ethical principles. We argue that this reframes the decision to use DDT, requiring us to incorporate new considerations, and new kinds of decision making, into the deliberative process that determines its ongoing use. Ethical considerations for intergenerational environmental justice are presented that include concern and respect for autonomy, nonmaleficence, and justice. Here, we offer a characterization of the kinds of ethical considerations that must be taken into account in any satisfactory decisions to use DDT.


The safety of aeroplane travel in patients with symptomatic carotid occlusion.
Patients with carotid stenosis or occlusion may be at increased risk for stroke during air travel. Records from the Carotid Occlusion Surgery Study (COSS), a randomised trial of surgical revascularisation for complete carotid artery occlusion and haemodynamic ischaemia, were examined for evidence of stroke related to air travel. COSS subjects who travelled by aeroplane to a regional Positron Emission Tomography (PET) centre for a screening of cerebrovascular haemodynamic evaluation were identified. Maximum altitude and total flight time were estimated based on the distance between origin and destination. Ischaemic events were determined by a structured telephone interview within 24 h of travel. Patient demographics, comorbidities, oxygen extraction fraction (OEF) data and 24 h interview responses were recorded. Seventy-seven patients with symptomatic carotid occlusion travelled by aeroplane to a single PET centre (174 flights). Fifty-two (67.5%) were men and 25 (32.5%) were women. The average age was 58.7±1.4 years. Twenty-seven patients (35.1%) demonstrated evidence of ipsilateral haemodynamic cerebral ischaemia as measured by PET OEF, while 50 (64.9%) had normal OEF. Patients flew an average distance of 418.9±25.9 miles for 107.1±4.7 min per trip. No patient reported symptoms of a transient ischaemic attack or stroke during or within 24 h after aeroplane travel (95% CI 0% to 2.0%). The risk of stroke as a consequence of air travel is low, even in a cohort of patients at high risk for future stroke owing to haemodynamic impairment. These patients with symptomatic carotid occlusion should not be discouraged from air travel.


Effect of the genetic background on the phenotype of mouse mutations.
An increasing number of scientific articles report that the phenotype of a given single gene mutation in mice is modulated by the genetic background of the inbred strain in which the mutation is maintained. This effect is attributable to so-called modifier genes, which act in combination with the causative gene. The modulation of the phenotype can be major, as exemplified in the case of several mouse models of polycystic kidney disease. Because of the existence of inbred strains and the possibility of developing congenic strains, the effect of the genetic background can be analyzed in mice, including the identification of major modifier genes. Furthermore, by transferring a given mutation into different genetic backgrounds, mouse models can be manipulated with the aim of more accurately mimicking specific features of human diseases.


Establishment of a European-type strain of Echinococcus multilocularis in Canadian wildlife.
In 2009, a haplotype closely related to European strains of Echinococcus multilocularis was detected in a dog from the Quesnel region of British Columbia, Canada. We now report the establishment of this same haplotype in 7 coyotes (Canis latrans) trapped within 40 km of Quesnel, BC. In addition, 3 coyotes and 1 red fox (Vulpes vulpes) harboured adult cestodes morphologically compatible with that of E. multilocularis (overall prevalence 33% in 33 carnivores). None of 156 potential intermediate hosts, including 131 representatives of two highly suitable rodent species, Peromyscus maniculatus and Microtus pennsylvanicus, trapped from a region 120-210 km south of Quesnel were infected. This report confirms the establishment and local transmission of a European-type strain of E. multilocularis (the causative agent of human alveolar hydatid disease), in wildlife in a forested region of North America where this cestode had not been previously detected, with significance for public and animal health.


One-stage versus two-stage exchange arthroplasty for infected total knee arthroplasty: a systematic review.
Infection complicating total knee arthroplasty (TKA) has serious implications. Traditionally the debate on whether one- or two-stage exchange arthroplasty is the optimum management of infected TKA has favoured two-stage procedures; however, a paradigm shift in opinion is emerging. This study aimed to establish whether current evidence supports one-stage revision for managing infected TKA based on reinfection rates and functional outcomes post-surgery. MEDLINE/PubMed and CENTRAL databases were reviewed for studies that compared one- and two-stage exchange arthroplasty TKA in more than ten patients with a minimum 2-year follow-up. From an initial sample of 796, five cohort studies with a total of 231 patients (46 single-stage/185 two-stage; median patient age 66 years, range 61-71 years) met inclusion criteria. Overall, there were no significant differences in risk of reinfection following one- or two-stage exchange arthroplasty (OR -0.06, 95 % confidence interval -0.13, 0.01). Subgroup analysis revealed that in studies published since 2000, one-stage procedures have a significantly lower reinfection rate. One study investigated functional outcomes and reported that one-stage surgery was associated with superior functional outcomes. Scarcity of data, inconsistent study designs, surgical technique and antibiotic regime disparities limit recommendations that can be made. Recent studies suggest one-stage exchange arthroplasty may provide superior outcomes, including lower reinfection rates and superior function, in select patients. Clinically, for some patients, one-stage exchange arthroplasty may represent optimum treatment; however, patient selection criteria and key components of surgical and post-operative anti-microbial management remain to be defined. III.


The positive predictive value of myocardial perfusion imaging in screening patients for suspected coronary artery disease.
In patients with known or suspected coronary artery disease, diagnosis and risk stratification can be aided by non-invasive tests for myocardial ischaemia. The main indications for the use of radionuclide perfusion imaging (sestamibi) rather than exercise electrocardiography include complete left bundle branch block, inconclusive stress electrocardiography and an inability to exercise. The published data on myocardial perfusion imaging is limited to eight studies of only 628 patients with widely varying ranges of sensitivities and specificities and the major problem being the bias created when patients with positive test results are referred far more frequently for coronary angiography than those with negative results. Furthermore, certain categories of patients are postulated to have a high number of false positives, especially obese patients and women, but this hypothesis has not been tested. A retrospective descriptional study on patients with positive sestamibi scans, who had coronary angiography within six months of each other, was performed. The study population consisted of 132 patients, 53.8% of whom were male and 44.7% had a body mass index of less than 28. The overall positive predictive value of the sestamibi scan in predicting significant coronary angiographic stenosis was 63.6%. This value increased significantly to 80.3% in males (p = 0.000). The positive predictive value did not differ in the different age categories, nor did it change with the different indications for sestamibi scanning. The sestamibi scan remains a useful screening test for coronary artery disease in patients who are exercise intolerant or those with inconclusive stress electrocardiography. The test is highly predictive in males rather than females.


Practice parameters for the medical therapy of obstructive sleep apnea.
Therapies for obstructive sleep apnea other than positive airway pressure, oral appliances, and surgical modifications of the upper airway are reviewed in this practice parameter. Several of these therapies such as weight loss and positional therapy hold some promise. Others, such as serotonergic agents, may gain credibility in the future but lack well-designed clinical trials. No practice parameters could be developed for a number of possible therapeutic modalities that had little or no evidence-based data on which to form a conclusion. The role of an organized, targeted weight-loss program either as a single therapy or as a supplement to PAP needs to be clarified. Although bariatric surgery is increasingly performed for refractory medically complicated obesity, its long-term effectiveness in treatment of obstructive sleep apnea in morbidly obese patients is not yet demonstrated. Positional therapy, or methods for preventing sleep in the supine position, has probably been underutilized due to lack of easily measured predictive factors and randomized controlled trials.


Creatine supplementation with specific view to exercise/sports performance: an update.
Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly).


No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women.
In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.


Sickness presenteeism in Spanish-born and immigrant workers in Spain.
Previous studies have shown that immigrant workers face relatively worse working and employment conditions, as well as lower rates of sickness absence than native-born workers. This study aims to assess rates of sickness presenteeism in a sample of Spanish-born and foreign-born workers according to different characteristics. A cross-sectional survey was conducted amongst a convenience sample of workers (Spanish-born and foreign-born), living in four Spanish cities: Barcelona, Huelva, Madrid and Valencia (2008-2009). Sickness presenteeism information was collected through two items in the questionnaire ("Have you had health problems in the last year?" and "Have you ever had to miss work for any health problem?") and was defined as worker who had a health problem (answered yes, first item) and had not missed work (answered no, second item). For the analysis, the sample of 2,059 workers (1,617 foreign-born) who answered yes to health problems was included. After descriptives, logistic regressions were used to establish the association between origin country and sickness presenteeism (adjusted odds ratios aOR; 95% confidence interval 95%CI). Analyses were stratified per time spent in Spain among foreign-born workers. All of the results refer to the comparison between foreign-born and Spanish-born workers as a whole, and in some categories relating to personal and occupational conditions. Foreign-born workers were more likely to report sickness presenteeism compared with their Spanish-born counterparts, especially those living in Spain for under 2 years [Prevalence: 42% in Spanish-born and 56.3% in Foreign-born; aOR 1.77 95%CI 1.24-2.53]. In case of foreign-born workers (with time in Spain < 2 years), men [aOR 2.31 95%CI 1.40-3.80], those with university studies [aOR 3.01 95%CI 1.04-8.69], temporary contracts [aOR 2.26 95%CI 1.29-3.98] and salaries between 751-1,200€ per month [aOR 1.74 95% CI 1.04-2.92] were more likely to report sickness presenteeism. Also, recent immigrants with good self-perceived health and good mental health were more likely to report presenteeism than Spanish-born workers with the same good health indicators. Immigrant workers report more sickness presenteeism than their Spanish-born counterparts. These results could be related to precarious work and employment conditions of immigrants. Immigrant workers should benefit from the same standards of social security, and of health and safety in the workplace that are enjoyed by Spanish workers.


National Partnership for Maternal Safety: Consensus Bundle on Obstetric Hemorrhage.
Hemorrhage is the most frequent cause of severe maternal morbidity and preventable maternal mortality and therefore is an ideal topic for the initial national maternity patient safety bundle. These safety bundles outline critical clinical practices that should be implemented in every maternity unit. They are developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. The safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and System Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. References contain sample resources and "Potential Best Practices" to assist with implementation.


Preventing alternans-induced spiral wave breakup in cardiac tissue: an ion-channel-based approach.
The detailed processes involved in spiral wave breakup, believed to be one major mechanism by which tachycardia evolves into fibrillation, are still poorly understood. This has rendered difficult the proper design of an efficient and practical control stimulus protocol to eliminate such events. In order to gain new insights into the underlying electrophysiological and dynamical mechanisms of breakup, we applied linear perturbation theory to a steadily rotating spiral wave in two spatial dimensions. The tissue was composed of cells modeled using the Fenton-Karma equations whose parameters were chosen to emphasize alternans as a primary mechanism for breakup. Along with one meandering mode, not just one but several unstable alternans modes were found with differing growth rates, frequencies, and spatial structures. As the conductance of the fast inward current was increased, the instability of the modes increased, consistent with increased meandering and propensity for spiral breakup in simulations. We also explored a promising new approach, based on the theory, for the design of an energy efficient electrical stimulus protocol to control spiral wave breakup. The novelty lies in addressing the problem directly at the ion channel level and taking advantage of the inherent two dimensional nature of the rotating wave. With the help of the eigenmode method, we were able to calculate the exact timing and amplitude of the stimulus, and locate it optimally to maximize efficiency. The analysis led to a special-case example that demonstrated that a single, properly timed stimulus can have a global effect, suppressing all growing alternans modes over the entire tissue, thus inhibiting spiral wave breakup.


Effect of Centella asiatica on cognition and oxidative stress in an intracerebroventricular streptozotocin model of Alzheimer's disease in rats.
1. Centella asiatica, an Indian medicinal plant, has been described as possessing central nervous system activity, such as improving intelligence. In addition, we have demonstrated that C. asiatica has cognitive-enhancing and anti-oxidant properties in normal rats. Oxidative stress or an impaired endogenous anti-oxidant mechanism is an important factor that has been implicated in Alzheimer's disease (AD) and cognitive deficits seen in the elderly. 2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has been likened to sporadic AD in humans and the cognitive impairment is associated with free radical generation in this model. Therefore, in the present study, the effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days) was evaluated in i.c.v. STZ-induced cognitive impairment and oxidative stress in rats. 3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance and elevated plus-maze paradigms on the days 13, 14 and 21. Rats were killed on the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA), glutathione, superoxide dismutase and catalase) in the whole brain upon completion of the behavioural task. 4. Rats treated with C. asiatica showed a dose-dependent increase in cognitive behaviour in both paradigms. A significant decrease in MDA and an increase in glutathione and catalase levels were observed only in rats treated with 200 and 300 mg/kg C. asiatica. 5. The present findings indicate that an aqueous extract of C. asiatica is effective in preventing the cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in rats.


A plasmonic random composite with atypical refractive index.
We present a material composite consisting of randomly oriented elements governed by non-resonant interactions. By exploiting near-field plasmonic interaction in a dense ensemble of subwavelength-sized dielectric and metallic particles, we reveal that the group refractive index of the composite can be increased to be larger than the effective refractive indices of constituent metallic and dielectric parent composites. These findings introduce a new class of engineered photonic materials having customizable and atypical optical constants.


Anti-inflammatory diet and inflammatory bowel disease: what clinicians and patients should know?
Current treatment for inflammatory bowel disease (IBD) includes the application of anti-inflammatory agents for the induction and remission of IBD. However, prolonged use of anti-inflammatory agents can exert adverse effects on patients. Recently, formulated dietary approach in treating IBD patients is utilized to improve clinical activity scores. An alteration of gastrointestinal microbiota through dietary therapy was found to reduce IBD and is recognized as a promising therapeutic strategy for IBD. One of the recommended formulated diets is an anti-inflammatory diet (AID) that restricts the intake of carbohydrates with modified fatty acids. This diet also contains probiotics and prebiotics that can promote balanced intestinal microbiota composition. However, scientific evidences are limited to support this specific dietary regime in maintaining the remission and prevention relapse of IBD. Therefore, this review aimed to summarize available data from various studies to evaluate the AID diet effectiveness which will be useful for clinicians to manage their IBD patients by application of improved dietary therapy.


Valuing the benefits of improved marine environmental quality under multiple stressors.
Many marine ecosystems are under increasing pressure from multiple stressors. In the Baltic Sea, these stressors include oil and chemical spills from shipping, nutrient run-off from land and the introduction of non-indigenous species. All of these pressures have been growing over recent years. Increasing pressures lead to reductions in environmental quality, which produce negative effects on human well-being. In this paper, the choice experiment method is used to estimate the benefits to people in Estonia resulting from reductions in pressure from multiple stressors in the Baltic Sea. The main results show that, firstly, respondents have a positive, statistically-significant willingness to pay to reduce each of the three stressors analysed. Secondly, the average willingness to pay for the improvement in the quality of all Estonian marine waters to achieve Good Environmental Status is around 65 euro per household per year, with a 95% confidence interval of 48-77 euro. Thirdly, the greatest share of value of this total economic benefit is derived from the willingness to pay for reductions in the risk of large scale oil and chemical spills.


Antagonizing the αv β3 integrin inhibits angiogenesis and impairs woven but not lamellar bone formation induced by mechanical loading.
Angiogenesis and osteogenesis are critically linked, although the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. αv β3 integrin-targeted nanoparticles or vehicle was injected intravenously after mechanical loading. β3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF-loaded limbs was increased compared with non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF- and LBF-loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that αv β3 integrin-mediated angiogenesis is critical for recovering fracture resistance after bone injury but is not required for bone modeling after modest mechanical strain. © 2014 American Society for Bone and Mineral Research.


Effects of anti-inflammatory drugs on fever and neutrophilia induced by Clostridium difficile toxin B.
This study investigated the ability of Clostridium difficile toxin B, isolated from the VPI 10463 strain, to induce fever and neutrophilia in rats. Intravenous injection of toxin B (0.005-0.5 mug/kg) evoked a dose-dependent increase in body temperature. The febrile response to 0.5 mug/kg of the toxin started in 2.5 h, peaked at 5 h, and subsided fully within 24 h. Toxin B also induced a dosedependent neutrophilia. Pretreatment with indomethacin (2 mg/kg, i.p.) did not affect the neutrophilia induced by toxin B, but significantly reduced the febrile response measured 4 to 8 h after toxin B injection. Dexamethasone (0.5 mg/ kg) also markedly diminished the febrile response induced by toxin B. These results show that Clostridium difficile toxin B induced a febrile response susceptible to inhibition by dexamethasone and indomethacin. Furthermore, they suggest that prostaglandins are not involved in the neutrophilia caused by this toxin.


A comparison of mail, telephone, and home interview strategies for household health surveys.
The method of data collection in household health surveys can be a major determinant of cost and data quality. A survey strategy can comprise mail, telephone, or home interview methods, individually or in combination to follow up non-respondents. The purpose of this study in Montreal was to compare cost and data quality of various strategies. Strategies which began with mail or telephone contact, followed by the two other methods, provided response rates as high as a home interview strategy (all between 80 and 90 per cent), for one-half the cost of home interviews when used as the sole method. The telephone response rate was higher than the mail response rate. Comparing different follow-up approaches to strategies beginning with mail or telephone, it proved less costly, and equally effective, to use home interviewing as a last resort for persistent non-respondents. Validity of response (comparing individual responses with records of a government health insurance data bank) and willingness to answer sensitive questions were greatest in mail strategy.


Implications of all-or-none synaptic transmission and short-term depression beyond vesicle depletion: a computational study.
The all-or-none character of transmission at central synapses is commonly viewed as evidence that only one vesicle can be released per action potential at a single release site. This interpretation is still a matter of debate; its resolution is important for our understanding of the nature of quantal response. In this work we explore observable consequences of the univesicular release hypothesis by studying a stochastic model of synaptic transmission. We investigated several alternative mechanisms for the all-or-none response: (1) the univesicular release constraint realized through lateral inhibition across presynaptic membrane, (2) the constraint of a single releasable vesicle per active zone, and (3) the postsynaptic receptor saturation. We show that both the univesicular release constraint and the postsynaptic receptor saturation lead to a limited amount of depression by vesicle depletion, so that depletion alone cannot account for the strong paired-pulse depression observed at some cortical synapses. Although depression can be rapid if there is only one releasable vesicle per active zone, this scenario leads to a limit on the transmission probability. We evaluate additional mechanisms beyond vesicle depletion, and our results suggest that the strong paired-pulse depression may be a result of activity-dependent inactivation of the exocytosis machinery. Furthermore, we found that the statistical analysis of release events, in response to a long stimulus train, might allow one to distinguish experimentally between univesicular and multivesicular release scenarios. We show that without the univesicular release constraint, the temporal correlation between release events is always negative, whereas it is typically positive with such a constraint if the vesicle fusion probability is sufficiently large.


Isolation and culture of larval cells from C. elegans.
Cell culture is an essential tool to study cell function. In C. elegans the ability to isolate and culture cells has been limited to embryonically derived cells. However, cells or blastomeres isolated from mixed stage embryos terminally differentiate within 24 hours of culture, thus precluding post-embryonic stage cell culture. We have developed an efficient and technically simple method for large-scale isolation and primary culture of larval-stage cells. We have optimized the treatment to maximize cell number and minimize cell death for each of the four larval stages. We obtained up to 7.8×10(4) cells per microliter of packed larvae, and up to 97% of adherent cells isolated by this method were viable for at least 16 hours. Cultured larval cells showed stage-specific increases in both cell size and multinuclearity and expressed lineage- and cell type-specific reporters. The majority (81%) of larval cells isolated by our method were muscle cells that exhibited stage-specific phenotypes. L1 muscle cells developed 1 to 2 wide cytoplasmic processes, while L4 muscle cells developed 4 to 14 processes of various thicknesses. L4 muscle cells developed bands of myosin heavy chain A thick filaments at the cell center and spontaneously contracted ex vivo. Neurons constituted less than 10% of the isolated cells and the majority of neurons developed one or more long, microtubule-rich protrusions that terminated in actin-rich growth cones. In addition to cells such as muscle and neuron that are high abundance in vivo, we were also able to isolate M-lineage cells that constitute less than 0.2% of cells in vivo. Our novel method of cell isolation extends C. elegans cell culture to larval developmental stages, and allows use of the wealth of cell culture tools, such as cell sorting, electrophysiology, co-culture, and high-resolution imaging of subcellular dynamics, in investigation of post-embryonic development and physiology.


In search of a selective therapy of viral infections.
This article is meant as an introductory chapter to the special issue of Antiviral Research on "Twenty-five years of antiretroviral drug development: progress and prospects", commemorating the first description of azidothymidine (AZT) as an antiretroviral agent. This has prompted me to highlight some of the hallmarks that played an important role in my own search of a selective therapy of viral infections: i.e., the induction of interferon by double-stranded RNA [such as poly(I).poly(C)], allowing the cloning and expression of beta-interferon; the discovery of the reverse transcriptase (RT) (and HIV as a retrovirus depending for its replication on RT), allowing the identification and development of a wide variety of RT inhibitors, nowadays used for the treatment of AIDS; the specificity of herpesvirus inhibitors such as acyclovir and BVDU, in the treatment of HSV and VZV infections; the role of acyclic nucleoside phosphonates (tenofovir, adefovir and cidofovir) in the treatment of HIV, HBV and DNA virus infections; and that of the NNRTIs (leading from TIBO to rilpivirine) as an essential part of the current anti-HIV drug cocktails. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010.


Contextual alignment of cognitive and neural dynamics.
Effective real-world communication requires the alignment of multiple individuals to a common perspective or mental framework. To study how this alignment occurs at the level of the brain, we measured BOLD response during fMRI while participants (n = 24) listened to a series of vignettes either in the presence or absence of a valid contextual cue. The valid contextual cue was necessary to understand the information in each vignette. We then examined where and to what extent the shared valid context led to greater intersubject similarity of neural processing. Regions of the default mode network including posterior cingulate cortex and medial pFC became more aligned when participants shared a valid contextual framework, whereas other regions, including primary sensory cortices, responded to the stimuli reliably regardless of contextual factors. Taken in conjunction with previous research, the present results suggest that default mode regions help the brain to organize incoming verbal information in the context of previous knowledge.


Intraspecific phylogeography of Lasmigona subviridis (Bivalvia: Unionidae): conservation implications of range discontinuity.
A nucleotide sequence analysis of the first internal transcribed spacer region (ITS-1) between the 5.8S and 18S ribosomal DNA genes (640 bp) and cytochrome c oxidase subunit I (COI) of mitochondrial DNA (mtDNA) (576 bp) was conducted for the freshwater bivalve Lasmigona subviridis and three congeners to determine the utility of these regions in identifying phylogeographic and phylogenetic structure. Sequence analysis of the ITS-1 region indicated a zone of discontinuity in the genetic population structure between a group of L. subviridis populations inhabiting the Susquehanna and Potomac Rivers and more southern populations. Moreover, haplotype patterns resulting from variation in the COI region suggested an absence of gene exchange between tributaries within two different river drainages, as well as between adjacent rivers systems. The authors recommend that the northern and southern populations, which are reproductively isolated and constitute evolutionarily significant lineages, be managed as separate conservation units. Results from the COI region suggest that, in some cases, unionid relocations should be avoided between tributaries of the same drainage because these populations may have been reproductively isolated for thousands of generations. Therefore, unionid bivalves distributed among discontinuous habitats (e.g. Atlantic slope drainages) potentially should be considered evolutionarily distinct. The DNA sequence divergences observed in the nuclear and mtDNA regions among the Lasmigona species were congruent, although the level of divergence in the COI region was up to three times greater. The genus Lasmigona, as represented by the four species surveyed in this study, may not be monophyletic.


The current situation and needs of rare disease registries in Europe.
Registries are considered key instruments for developing rare disease (RD) clinical research, enhancing patient care and health planning, and improving social, economic and quality-of-life outcomes. Indeed, it is usually the case that no single institution, and in many cases no single country, has sufficient data to provide results that can be applied broadly to clinical and translational research. However, the fragmentation and heterogeneity of the registries, which are often the result of spontaneous initiatives, limit the general applicability of their observations. An inquiry has been carried out by the EPIRARE, a European Union (EU)-funded project ('Building Consensus and Synergies for the EU Registration of Rare Disease Patients') aiming at paving the way to the creation of a European Platform for RD Registries, by means of an on-line questionnaire among European RD registries on their main activities and needs, the way they deal with methodological, technical and regulatory issues and the way they find resources to carry on their activities. In spite of the heterogeneity of the European registries, some elements of relevance for an action to improve the situation of patient registries in the EU are apparent. The needs more frequently indicated by registry holders were financial support, motivation of data providers, data quality assessment, improvement of communication and visibility, and extension of collaborations. Moreover, the registry holders were in favor of a common EU platform providing services for RD registries. It appears that the current situation of the European registries provides the transition towards a more uniform, higher quality and better coordinated approach.


Arthroscopy-Assisted Corrective Osteotomy, Reduction, Internal Fixation and Strut Allograft Augmentation for Tibial Plateau Malunion or Nonunion.
The purpose of this study was to present the results of arthroscopy-assisted corrective osteotomy (AACO), reduction, internal fixation, and strut allograft augmentation for tibial plateau malunion or nonunion. Fifty-eight patients, mean age 49 ± 11.9 years old, with tibial plateau malunion (n = 44) or nonunion (n = 14), were included in this study. There were 19 Schatzker type II fractures (32.7%), 2 type III fractures (3.4%), 7 type IV fractures (12%), 20 type V fractures (34.5%), and 10 type VI fractures (17.2%). The mean follow-up period was 46.2 ± 17.6 months. Clinical and radiologic outcomes were scored by the Rasmussen system. Articular depression was measured from computed tomography. Secondary osteoarthritis was diagnosed when radiographs showed a narrowed joint space in the injured knee at follow-up. Mean clinical score improved from 15.4 ± 3.9 (pre-revision) to 23.2 ± 4.5 (post-revision). Mean radiologic score improved from 7.7 ± 2.5 (pre-revision) to 12.0 ± 3.9 (post-revision). Fifty-six fractures achieved successful union. The average union time was 19.6 ± 7.5 weeks. Post-revision, 81% had good or excellent clinical results and 62% had good or excellent radiological results. Secondary osteoarthritis (OA) was noted in 91% of all injured knees, where 25.8% were mild OA, 25.8 % were moderate OA, and 38% were severe OA. There were 6 cases of deep infection (10.3%) and 1 case of wound edge necrosis (1.7%). Five cases were converted to total knee replacement after the index surgery with an average period of 13.5 months (range 8-24 months). Arthroscopy-assisted corrective osteotomy, reduction, internal fixation, and strut allograft augmentation can restore tibial plateau malunion/nonunion with well-documented radiographic healing and good clinical outcomes.


Mapping the rectum: spatial analysis of transanal endoscopic microsurgical outcomes using GIS technology.
Transanal endoscopic microsurgery (TEM) is a technically challenging procedure hindered by rectal anatomic constraints. To study the relationship of lesion position with performance of TEM, a novel approach of spatial analysis using Geographic Information Systems (GIS) was developed. A retrospective review was conducted on 144 consecutive TEMs, analyzing clinical, pathologic, and positional characteristics. Two- and three-dimensional maps of rectal topology were developed. GIS was used for spatial analysis, accounting for regional position and clustering of lesions. Lesions were located at a mean distance of 9.3 +/- 4.9 (SD) cm from the dentate line, with an average size of 3.1 +/- 1.4 cm. Proximal regions were associated with prolonged operative time. Regions between the rectosigmoid junction and the peritoneal reflection were associated with peritoneal breach. In spatial regression analysis, regional characteristics that were significantly associated with operative time included distance, presence of cancers, and positive margins; peritoneal breach was significantly associated with lesion size and location; conversions were associated with distance (P < 0.05). Specific knowledge of lesion size and location in the context of anatomic relationships is important for optimizing operative intervention. GIS provides a valuable tool in organizing spatial information and can be extended into clinical research topics involving the distinction of anatomic relationships.


Changing expectations concerning life-extending treatment: the relevance of opportunity cost.
Rising public expectations and health care costs along with demographic ageing raise questions about whether individuals should consider the drain on community resources when deciding whether to have expensive, life-extending medical interventions towards the end of their lifespan. All respondents (n = 208) in this novel, policy-capturing study were prepared to nominate an age along their life trajectory where they would likely decline a life-extending medical intervention indicating a "sense of limits" or "reasonableness" associated with the concept of a natural lifespan. The results showed that individuals altered end-of-life decisions in circumstances of higher opportunity cost and competing need but their propensity to do so was affected by their age, gender, and their expectations of medical progress. Other within-person factors (type of scarcity, treatment side effects, and health at diagnosis) affected the age one would decline a medical intervention in the face of a life threatening illness. Between-person predictors of this age included subjective life expectancy and attitude to health spending. The results suggest possibilities for building on this sense of reasonableness in public discussions of the opportunity cost of current health care resource allocation and by having physicians consider appropriate ways of presenting cost of treatment in end-of life contexts.


The Spleen as a Target to Characterize Immunomodulatory Effects of Down-Stream Processed Cyberlindnera jadinii Yeasts in Atlantic Salmon Exposed to a Dietary Soybean Meal Challenge.
Aquaculture feeds have changed dramatically from being largely based on fishmeal (FM) towards increased use of plant protein sources, which could impact the fish's immune response. In order to characterize immunomodulatory properties of novel functional ingredients, this study used four diets, one based on FM, a challenging diet with 40% soybean meal (SBM), and two diets containing 40% SBM with 5% of Cyberlindnera jadinii yeast exposed to different down-stream processing conditions: heat-inactivated (ICJ) or autolysation (ACJ). The immunomodulatory effects of the diets were analyzed in the spleen of Atlantic salmon after 37 days of feeding, using a transcriptomic evaluation by RNA sequencing (RNA-seq) and the detection of specific immunological markers at the protein level through indirect Enzyme-linked Immunosorbent Assay (indirect ELISA). The results showed that SBM (compared to FM) induced a down-regulation of pathways related to ion binding and transport, along with an increase at the protein level of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). On the other hand, while ICJ (compared to FM-group) maintain the inflammatory response associated with SBM, with higher levels of TNFα and IFNγ, and with an upregulation of creatine kinase activity and phosphagen metabolic process, the inclusion of ACJ was able to modulate the response of Atlantic salmon compared to fish fed the SBM-diet by the activation of biological pathways related to endocytosis, Pattern recognition receptor (PPRs)-signal transduction and transporter activity. In addition, ACJ was also able to control the pro-inflammatory profile of SBM, increasing Interleukin 10 (IL-10) levels and decreasing TNFα production, triggering an immune response similar to that of fish fed an FM-based diet. Finally, we suggest that the spleen is a good candidate to characterize the immunomodulatory effects of functional ingredients in Atlantic salmon. Moreover, the inclusion of ACJ in fish diets, with the ability to control inflammatory processes, could be considered in the formulation of sustainable salmon feed.


Micropuncture of Bowman's Space in Mice Facilitated by 2 Photon Microscopy.
Renal micropuncture and renal 2-photon imaging are seminal techniques in renal physiology. However, micropuncture is limited by dependence on conventional microscopy to surface nephron features, and 2-photon studies are limited in that interventions can only be assessed at the organ, rather than the nephron level. In particular, micropuncture studies of the glomeruli of mice have been challenged by the paucity of surface glomeruli in mice. To address this limitation in order to pursue studies of aspirate from Bowman's space in mouse physiologic models, we developed 2-photon glomerular micropuncture. We present a novel surgical preparation that allows lateral access to the kidney while preserving the required vertical imaging column for 2-photon microscopy. Administration of high molecular weight fluorescein isothiocyanate (FITC)-dextran is used to render the renal vasculature and therefore glomeruli visible for 2-photon imaging. A quantum dot-coated pipette is then introduced under stereotactic guidance to a glomerulus selected from the several to many which may be visualized within the imaging window. In this protocol, we provide details of the preparation, materials, and methods necessary to carry out the procedure. This technique facilitates previously-impossible physiologic study of the kidney, including recovery of filtrate from Bowman's space and all segments of the nephron within the imaging depth limit, about 100 µm below the renal capsule. Pressure, charge and flow may all be measured using the introduced pipette. Here, we provide representative data from liquid chromatography/mass spectrometry performed on aspirate from Bowman's space. We expect this technique to have wide applicability in renal physiologic investigation.


The relationship between the serum levels of ferritin and the radiological brain injury indices in patients with spontaneous intracerebral hemorrhage.
Preclinical studies show that iron plays a key role in mediating neuronal injury. This study was performed in order to identify the relationship between the serum level of ferritin and severity of the brain injury which occur after an Intracerebral hemorrhage (ICH). This was a cross sectional descriptive - analytic study, which was conducted on those patients who had suffered from an ICH and had attended Poursina Hospital. The Serum levels of ferritin were measured at admittance. A Cranial CT scan was performed at admission and also 72 hr afterward. Hematoma and edema surrounding the hematoma volumes were also measured at entrance and 72 hr afterward. Data analysis was carried out by a descriptive - analytic statistics approach and calculated later on by the Spss-20 software. In this investigation, 63 patients were studied, from which 34 (54%) were male and 29 (46%) female. The average age of the patients was 69.7± 11.9 (Min 43 and Max 94 years old). A significant relationship was observed between the level of ferritin and the edema volume surrounding the hematoma at first and next 72 hr after the patients were admitted. These results delineated the effective role of iron on the edema volume elevation. More studies are essentially urged to ascertain the clinical evaluation of the curing effect of iron chelators in those patients who suffer from ICH.


Predictors of outcome after 6 and 12 months following anthroposophic therapy for adult outpatients with chronic disease: a secondary analysis from a prospective observational study.
Anthroposophic medicine is a physician-provided complementary therapy system involving counselling, artistic and physical therapies, and special medications. The purpose of this analysis was to identify predictors of symptom improvement in patients receiving anthroposophic treatment for chronic diseases. 913 adult outpatients from Germany participated in a prospective cohort study. Patients were starting anthroposophic treatment for mental (30.4% of patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%), genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic indications. Stepwise multiple linear regression analysis was performed with the improvement of Symptom Score (patients' assessment, 0: not present, 10: worst possible) after 6 and 12 months as dependent variables. 61 independent variables pertaining to socio-demographics, life style, disease status, co-morbidity, health status (SF-36), depression, and therapy factors were analysed. Compared to baseline, Symptom Score improved by average 2.53 points (95% confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement after six months was baseline Symptom Score, which alone accounted for 25% of the variance (total model 32%). Improvement after six months was also positively predicted by better physical function, better general health, shorter disease duration, higher education level, a diagnosis of respiratory disorders, and by a higher therapy goal documented by the physician at baseline; and negatively predicted by the number of physiotherapy sessions in the pre-study year and by a diagnosis of genitourinary disorders. Seven of these nine variables (not the two diagnoses) also predicted improvement after 12 months. When repeating the 0-6 month analysis on two random subsamples of the original sample, three variables (baseline Symptom Score, physical function, general health) remained significant predictors in both analyses, and three further variables (education level, respiratory disorders, therapy goal) were significant in one analysis. In adult outpatients receiving anthroposophic treatment for chronic diseases, symptom improvement after 6 and 12 months was predicted by baseline symptoms, health status, disease duration, education, and therapy goal. Other variables were not associated with the outcome. This secondary predictor analysis of data from a pre-post study does not allow for causal conclusions; the results are hypothesis generating and need verification in subsequent studies.