Rapidly assessing the risks of infectious diseases to wildlife species.
Predicting the likelihood of rare events is increasingly demanded by risk managers. A key challenge is dealing with different types of uncertainty, including epistemic uncertainties (lack of knowledge), stochasticity (inherent randomness) and natural variation. One potentially catastrophic event which is impacted by high levels of all three of these uncertainty types is the transmission of livestock pathogens to wildlife, particularly for endangered species. There is often a lack of basic information, e.g. about a given pathogen's presence in local livestock populations or the susceptibility of a given wildlife species to infection by the pathogen. We adapted the OIE (World Organisation for Animal Health) risk assessment framework to rapidly assess and prioritize the risks of livestock pathogens for wildlife, taking account of epistemic uncertainties, stochasticity, seasonal movement of animals and interaction between different species at different spatial and temporal scales. We demonstrate the approach using the endangered saiga antelope (Saiga tatarica tatarica) as a case study. We conclude that, in general, transmission events are likely to be rare and limited to small geographical areas; however, their impact could be high. Brucella spp. and foot-and-mouth disease virus are among those most likely to be transmitted from livestock to the Betpak-Dala saiga population.


Alternative Retirement Paths and Cognitive Performance: Exploring the Role of Preretirement Job Complexity.
Recent research suggests that working longer may be protective of cognitive functioning in later life, especially for workers in low complexity jobs. As postretirement work becomes increasingly popular, it is important to understand how various retirement pathways influence cognitive function. The present study examines cognitive changes as a function of job complexity in the context of different types of retirement transitions. We use data from the Health and Retirement Study (HRS) to examine change in cognitive function for workers who have held low, moderate, and high complexity jobs and move through distinct retirement pathways-retiring and returning to work, partial retirement-compared with those who fully retire or remain full-time workers. Inverse probability weighted regression adjustment (a propensity score method) is used to adjust for selection effects. There are systematic variations in the relationships between work and cognitive performance as a function of job complexity and retirement pathways. All retirement pathways were associated with accelerated cognitive decline for workers in low complexity jobs. In contrast, for high complexity workers retirement was not associated with accelerated cognitive decline and retiring and returning to work was associated with modest improvement in cognitive functioning. Both policy makers and individuals are beginning to embrace longer working lives which offer variety of potential benefits. Our findings suggest that continued full-time work also may be protective for cognitive health in workers who hold low complexity jobs.


Random neural networks with multiple classes of signals.
By extending the pulsed recurrent random neural network (RNN) discussed in Gelenbe (1989, 1990, 1991), we propose a recurrent random neural network model in which each neuron processes several distinctly characterized streams of "signals" or data. The idea that neurons may be able to distinguish between the pulses they receive and use them in a distinct manner is biologically plausible. In engineering applications, the need to process different streams of information simultaneously is commonplace (e.g., in image processing, sensor fusion, or parallel processing systems). In the model we propose, each distinct stream is a class of signals in the form of spikes. Signals may arrive to a neuron from either the outside world (exogenous signals) or other neurons (endogenous signals). As a function of the signals it has received, a neuron can fire and then send signals of some class to another neuron or to the outside world. We show that the multiple signal class random model with exponential interfiring times, Poisson external signal arrivals, and Markovian signal movements between neurons has product form; this implies that the distribution of its state (i.e., the probability that each neuron of the network is excited) can be computed simply from the solution of a system of 2Cn simultaneous nonlinear equations where C is the number of signal classes and n is the number of neurons. Here we derive the stationary solution for the multiple class model and establish necessary and sufficient conditions for the existence of the stationary solution. The recurrent random neural network model with multiple classes has already been successfully applied to image texture generation (Atalay & Gelenbe, 1992), where multiple signal classes are used to model different colors in the image.


Ursolic acid induces cell cycle arrest and apoptosis of gallbladder carcinoma cells.
Ursolic acid (UA), a plant extract used in traditional Chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. In the present study, we evaluated the anti-tumoral properties of UA against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro. The anti-tumor activity of UA against GBC-SD and SGC-996 cells was assessed using MTT and colony formation assays. An annexin V/PI double-staining assay was used to detect cell apoptosis. Cell cycle changes were detected using flow cytometry. Rhodamine 123 staining was used to assess the mitochondrial membrane potential (ΔΨm) and validate UA's ability to induce apoptosis in both cell lines. The effectiveness of UA in gallbladder cancer was further verified in vivo by establishing a xenograft GBC model in nude mice. Finally, the expression levels of cell cycle- and apoptosis-related proteins were analyzed by western blotting. Our results suggest that UA can significantly inhibit the growth of gallbladder cancer cells. MTT and colony formation assays indicated dose-dependent decreases in cell proliferation. S-phase arrest was observed in both cell lines after treatment with UA. Annexin V/PI staining suggested that UA induced both early and late phases of apoptosis. UA also decreased ΔΨm and altered the expression of molecules regulating the cell cycle and apoptosis. In vivo study showed intraperitoneally injection of UA can significantly inhibited the growth of xenograft tumor in nude mice and the inhibition efficiency is dose related. Activation of caspase-3,-9 and PARP indicated that mitochondrial pathways may be involved in UA-induced apoptosis. Taken together, these results suggest that UA exhibits significant anti-tumor effects by suppressing cell proliferation, promoting apoptosis and inducing 7cell cycle arrest both in vitro and in vivo. It may be a potential agent for treating gallbladder cancer.


Optical chirality sensing using macrocycles, synthetic and supramolecular oligomers/polymers, and nanoparticle based sensors.
Optical sensors that respond to enantiomeric excess of chiral analytes are highly demanded in chirality related research fields and demonstrate their potential in many applications, for example, screening of asymmetric reaction products. Most sensors developed so far are small molecules. This Tutorial Review covers recent advances in chirality sensing systems that are different from the traditional small molecule-based sensors, by using macrocycles, synthetic oligomers/polymers, supramolecular polymers and nanoparticles as the sensors, in which supramolecular interactions operate.


The effects of alcohol on the emotional displays of Whites in interracial groups.
Discomfort during interracial interactions is common among Whites in the U.S. and is linked to avoidance of interracial encounters. While the negative consequences of interracial discomfort are well-documented, understanding of its causes is still incomplete. Alcohol consumption has been shown to decrease negative emotions caused by self-presentational concern but increase negative emotions associated with racial prejudice. Using novel behavioral-expressive measures of emotion, we examined the impact of alcohol on displays of discomfort among 92 White individuals interacting in all-White or interracial groups. We used the Facial Action Coding System and comprehensive content-free speech analyses to examine affective and behavioral dynamics during these 36-min exchanges (7.9 million frames of video data). Among Whites consuming nonalcoholic beverages, those assigned to interracial groups evidenced more facial and speech displays of discomfort than those in all-White groups. In contrast, among intoxicated Whites there were no differences in displays of discomfort between interracial and all-White groups. Results highlight the central role of self-presentational concerns in interracial discomfort and offer new directions for applying theory and methods from emotion science to the examination of intergroup relations.


Finite element analysis of effect of prosthesis height, angle of force application, and implant offset on supporting bone.
This finite element analysis was conducted to determine the magnitude of stress in the supporting bone when implants were arranged in either a straight-line or an offset configuration. In addition, the effects of axial and nonaxial loading and changes in prosthesis height were assessed. An 8-node hexahedral solid-element 3-dimensional finite element analysis model of the mandible was created using PATRAN software. Three titanium endosseous implants were placed in the model 7 mm apart. The center implant was placed on the line from the centers of the terminal implants (no offset), 1.5 mm lateral to this line (1.5-mm offset), or 3.0 mm lateral to this line (3.0-mm offset). Forces of 200 N were applied to a point corresponding to the center of the middle implant when the implants were in a straight-line configuration. Forces were applied in a straight vertical direction or in 15-degree increments to the vertical to a maximum of 60 degrees. Simulated type IV gold prostheses were made to simulate heights of 6 and 12 mm. The least stress in the supporting bone was found with vertical loading of the no-offset implants with the 6-mm prosthesis (3.12 MPa) followed by the same alignment with the 12-mm prosthesis (3.86 MPa). Changing the angle of force application by 15 degrees resulted in increased stress to the underlying bone, and the creation of an offset did not fully compensate for this increased stress. In contrast to previous studies, this study examined 3 elements not previously studied together in a single finite element analysis, using the maximum offset defined by normal anatomic contours of mandibular premolar and molar teeth, thereby describing the relative importance of clinically relevant methods for stress reduction. Vertical loading of an implant-supported prosthesis produced the lowest stress to the supporting bone. Changes in the angle of force application resulted in greater stress to supporting bone. Reduction in prosthesis height or use of an offset implant location for the middle implant reduced stress, but the reduction did not compensate for the increase found with off-axis loading.


Recovery of nitrogen pools and processes in degraded riparian zones in the southern appalachians.
Establishment of riparian buffers is an effective method for reducing nutrient input to streams. However, the underlying biogeochemical processes are not fully understood. The objective of this 4-yr study was to examine the effects of riparian zone restoration on soil N cycling mechanisms in a mountain pasture previously degraded by cattle. Soil inorganic N pools, fluxes, and transformation mechanisms were compared across the following experimental treatments: (i) a restored area with vegetation regrowth; (ii) a degraded riparian area with simulated effects of continued grazing by compaction, vegetation removal, and nutrient addition (+N); and (iii) a degraded riparian area with simulated compaction and vegetation removal only (-N). Soil solution NO(3)(-) concentrations and fluxes of inorganic N in overland flow were >90% lower in the restored treatment relative to the degraded (+N) treatment. Soil solution NO(3)(-) concentrations decreased more rapidly in the restored treatment relative to the degraded (-N) following cattle (Bos taurus) exclusion. Mineralization and nitrification rates in the restored treatment were similar to the degraded (-N) treatment and, on average, 75% lower than in the degraded (+N) treatment. Nitrogen trace gas fluxes indicated that restoration increased the relative importance of denitrification, relative to nitrification, as a pathway by which N is diverted from the receiving stream to the atmosphere. Changes in soil nutrient cycling mechanisms following restoration of the degraded riparian zone were primarily driven by cessation of N inputs. The recovery rate, however, was influenced by the rate of vegetation regrowth.


DNA recovery after sequential processing of latent fingerprints on copy paper.
Forensic examiners must determine whether both latent fingerprint development and DNA profiling can be performed on the same area of an evidence item and, if only one is possible, which examination offers the best chance for identification. Latent fingerprints can be enhanced by targeting different components of fingerprint residues with sequential chemical treatments. This study investigated the effects of single-reagent and sequential latent fingerprint development processes on downstream DNA analysis to determine the point at which latent fingerprint development should be stopped to allow for DNA recovery. Latent fingerprints deposited on copy paper by one donor were developed using three sequential processes: 1,8-diazafluoren-9-one (DFO) → ninhydrin → physical developer (PD); 1,2-indanedione-zinc (IND-Zn) → ninhydrin → PD; and IND-Zn → ninhydrin → Oil Red O (ORO) → PD. Samples were examined after the addition of each chemical treatment. DNA was collected with cotton swabs, extracted, quantified, and amplified. DNA yields, peak heights, number of alleles obtained, and percentage of DNA profiles eligible for CODIS upload were examined. DNA profiles were obtained with varying degrees of success, depending on the number and type of treatments used for latent fingerprint development. The treatments that were found to be the least harmful to downstream DNA analysis were IND-Zn and IND-Zn/laser, and the most detrimental treatments were DFO, DFO/laser, and PD. In general, as the number of treatments increase, the opportunities for DNA loss or damage also increase, and it is preferable to use fewer treatments when developing latent fingerprints prior to downstream DNA processing.


The validity of physical therapy assessment of low back pain via telerehabilitation in a clinical setting.
Back pain is a common and disabling condition for people in rural and remote areas. In these areas, access to rehabilitation services is limited by service availability. Telerehabilitation is suggested as a solution for providing physical therapy services; however, the validity of clinical assessment is largely unproven. The aim of this study was to establish the validity of clinically pragmatic remote assessment of spinal posture, active movements of the lumbar spine, and the passive straight leg raise (SLR) test. Face-to-face physical therapist assessment was compared with telerehabilitation assessment of spinal posture, active movements of the lumbar spine, and the SLR test. Twenty-six participants recruited from a rural population with current or recent low back pain (LBP) were assessed by a face-to-face physical therapist and a remote physical therapist. Pain, disability, and clinical measurements were assessed. Outcomes were compared to establish agreement. High levels of agreement were found with detecting pain with specific lumbar movements, eliciting symptoms, and sensitizing the SLR test. Moderate agreement occurred with identifying the worst lumbar spine movement direction, SLR range of motion, and active lumbar spine range of motion. Poor agreement occurred with postural analysis and identifying reasons for limitations to lumbar movements. Conducted in a rural clinical setting, this study validates elements of the physical assessment of the lumbar spine and identifies technical and clinical issues to be addressed by future research. Important components of the standard musculoskeletal assessment of LBP are valid via telerehabilitation in a clinical setting.


The geriatric long-stay hospital patient: a Canadian case study.
This article examines the use of acute beds by the elderly in Manitoba over the five-year period, 1972--1976. The analysis reveals that transfers of long-stay (greater than 90 day) elderly to long-term care facilities took longer in 1976 than in 1972 despite major provincial initiatives which included construction of additional long-term treatment beds, expansion of home care resources, and extension of universal insurance coverage to long-term institutional and home care. Analyses of means to reduce long hospital stays prior to transfer suggests that building more long-term beds may be the least desirable policy alternative.


Acute effects of air pollutants on spontaneous pregnancy loss: a case-crossover study.
To investigate the relationship between acute exposure to air pollutants and spontaneous pregnancy loss. Case-crossover study from 2007 to 2015. An academic emergency department in the Wasatch Front area of Utah. A total of 1,398 women who experienced spontaneous pregnancy loss events. None. Odds of spontaneous pregnancy loss. We found that a 10-ppb increase in 7-day average levels of nitrogen dioxide was associated with a 16% increase in the odds of spontaneous pregnancy loss (odds ratio [OR] = 1.16; 95% confidence interval [CI] 1.01-1.33; P=.04). A 10-μg/m3 increase in 3-day and 7-day averages of fine particulate matter were associated with increased risk of spontaneous pregnancy loss, but the associations did not reach statistical significance (OR3-day average = 1.09; 95% CI 0.99-1.20; P=.05) (OR7-day average = 1.11; 95% CI 0.99-1.24; P=.06). We found no evidence of increased risk for any other metrics of nitrogen dioxide or fine particulate matter or any metric for ozone. We found that short-term exposure to elevated levels of air pollutants was associated with higher risk for spontaneous pregnancy loss.


Aspects of native proteins are retained in vacuum.
It is now well established that protein complexes can be maintained in the gas phase, under the reduced pressure conditions experienced within mass spectrometers. This remains an intriguing phenomenon, given the importance placed on water molecules in stabilizing protein structure. As a consequence, the overall structure of protein molecules and their complexes in the gas phase continues to stimulate much research. The eventual outcomes of this research will not only increase the number of applications of mass spectrometry to structural biology, but will also enhance our understanding of the interactions important for maintaining protein complexes in the absence of bulk solvent.


Infection in experimental hip arthroplasties.
The relationship between the route of inoculation, the dose of inoculum and the development of infection after prosthetic replacement has been determined in an animal model. The rabbit hip served as the model and a Staphylococcus aureus isolated from an infected human hip arthroplasty was introduced using different protocols. The 50% infective dose (ID50) was determined for comparative purposes. Contamination of the wound site with only a few bacteria was likely to result in infection. It was considerably more difficult to induce infection when the operation was performed without inserting the prosthesis, which suggests that the implant inhibits the body's mechanism for dealing with the insult. It was difficult to produce infection by inoculating the organisms into the bloodstream: if this inoculation was delayed till three weeks after operation the animals were often grossly septicaemic by the time the arthroplasty was infected. The results emphasise the importance of minimising intra-operative contamination and the efficacy of antibiotic cover.


Water translocation between ramets of strawberry during soil drying and its effects on photosynthetic performance.
To explore the mechanisms underlying water regulation in clonal plants and its effects on carbon assimilation under water stress, we studied the responses of water status, gas exchange and abscisic acid (ABA) contents to water stress in leaves of pairs of strawberry ramets that consist of mother and daughter ramets. There was a greater decrease in photosynthetic rates (P(n)) and stomatal conductance (G(s)) in the disconnected mother ramets than the connected mother ramets upon exposure to water stress, indicating that water stress in mother ramets was alleviated by water translocation from the well-watered daughter ramets. Conversely, the connected mother ramets displayed enhanced symptoms of water stress when the connected daughter ramets were exposed to water deficit. The mother ramets had lower water potential (psi(w)) due to their stronger osmotic adjustment than in well-watered daughter ramets; this resulted in water flow from the connected daughter ramets to mother ramets, thus alleviating water stress of mother ramets. During soil drying, there was a striking increase in ABA concentrations in leaves of the disconnected mother ramets, whereas leaf bulk ABA was much lower in the connected and water-stressed mother ramets than that in the drought-affected mother ramets in the disconnected group. In this study, though G(s) was linearly correlated with leaf bulk ABA and psi(w), G(s) in water-stressed mother ramets in disconnected group exhibited less sensitivity to the variation in leaf bulk ABA and psi(w) than that in connected and water-stressed mother ramets. Taken together, these results indicate that: (1) the flux of water translocation between the connected ramets is determined by a water potential gradient; (2) water translocation between connected ramets helps to keep sensitivity of G(s) to ABA and psi(w) in drought-affected ramets, thereby benefit to effectively maintain the homeostasis of leaf water status and (3) the improvements in P(n) in water-stressed ramets due to water translocation from well-watered ramets suggest the advantages of physiological integration in clonal plants in environments with heterogeneous water distribution.


DNA polymerases alpha and beta are required for DNA repair in an efficient nuclear extract from Xenopus oocytes.
Xenopus oocytes and an oocyte nuclear extract efficiently repair the bulky DNA lesions cyclobutane pyrimidine dimers,(6-4) photoproducts, and N-acetoxy-2-aminofluorene (AAF) adducts by an excision repair mechanism. Nearly all (>95%) of the input damaged DNA was repaired within 5 h in both injected cells and extracts with no significant incorporation of label into control undamaged DNA. Remarkably, more than 10(10) cyclobutane pyrimidine dimers or(6-4) photoproducts are repaired/nuclei. The extracts are free from nuclease activity, and repair is independent of exogenous light. Both the high efficiency and DNA polymerase requirements of this system appear to be different from extracts derived from human cells. We demonstrated a requirement for DNA polymerases alpha and beta in repair of both photoproducts and AAF by inhibiting repair with several independent antibodies specific to either DNA polymerases alpha or beta and then restoring repair by adding the appropriate purified polymerase. Repair is inhibited by aphidicolin at concentrations specific for blocking DNA polymerase alpha and dideoxynucleotide triphosphates at concentrations specific for inhibiting DNA polymerase beta.


Knockdown of the cell cycle inhibitor p21 enhances cartilage formation by induced pluripotent stem cells.
The limited regenerative capacity of articular cartilage contributes to progressive joint dysfunction associated with cartilage injury or osteoarthritis. Cartilage tissue engineering seeks to provide a biological substitute for repairing damaged or diseased cartilage, but requires a cell source with the capacity for extensive expansion without loss of chondrogenic potential. In this study, we hypothesized that decreased expression of the cell cycle inhibitor p21 would enhance the proliferative and chondrogenic potential of differentiated induced pluripotent stem cells (iPSCs). Murine iPSCs were directed to differentiate toward the chondrogenic lineage with an established protocol and then engineered to express a short hairpin RNA (shRNA) to reduce the expression of p21. Cells expressing the p21 shRNA demonstrated higher proliferative potential during monolayer expansion and increased synthesis of glycosaminoglycans (GAGs) in pellet cultures. Furthermore, these cells could be expanded ∼150-fold over three additional passages without a reduction in the subsequent production of GAGs, while control cells showed reduced potential for GAG synthesis with three additional passages. In pellets from extensively passaged cells, knockdown of p21 attenuated the sharp decrease in cell number that occurred in control cells, and immunohistochemical analysis showed that p21 knockdown limited the production of type I and type X collagen while maintaining synthesis of cartilage-specific type II collagen. These findings suggest that manipulating the cell cycle can augment the monolayer expansion and preserve the chondrogenic capacity of differentiated iPSCs, providing a strategy for enhancing iPSC-based cartilage tissue engineering.


The crowded sea: incorporating multiple marine activities in conservation plans can significantly alter spatial priorities.
Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic considerations within a country's territorial waters.


Radionuclide spatial distribution and dose deposition for in vitro assessments of 212 Pb-αVCAM-1 targeted alpha therapy.
Targeted alpha therapy (TAT) takes advantage of the short-range and high-linear energy transfer of α-particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α-emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α-emitting 212 Pb coupled to an anti-VCAM-1 antibody (212 Pb-αVCAM-1) and its evolution over time in the context of in vitro irradiations. Two experimental setups were implemented without cells to measure α-particle count rates and energy spectra in culture medium containing 15 kBq of 212 Pb-α-VCAM-1. Silicon detectors were placed above and below cell culture dishes for 20 h. One of the dishes had a 2.5-µm-thick mylar-base allowing easy detection of the α-particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modeled and α-energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212 Pb-αVCAM-1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments. Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212 Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations. This study demonstrated that accurate dosimetry of α-emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods.


Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1β- and IL-6-Related Impairment of Bone Marrow Function.
Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI. BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony-forming cell colony maximum in the BM of patients with AMI (estimate±SE, -0.13±0.05; P=0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony-forming cell colony outgrowth in the presence of exogenous IL-1β or IL-6 (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein correlated positively with BM-derived colony-forming unit-endothelial colony maximum (estimate±SE, 0.01±0.002; P<0.001), multipotent mesenchymal stromal cell colony maximum (estimate±SE, 0.01±0.002; P=0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P<0.001). Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684060.


The risk of bladder calculi in patients with spinal cord injuries.
A nonconcurrent prospective study of bladder calculi included 500 persons treated at the University of Alabama in Birmingham Spinal Cord Injury Care System between 1973 and 1981. Risk factors suspected of contributing to the development of bladder calculi were identified. Logistic regression analysis was used to estimate each risk factor's adjusted odds ratio and to develop a predictive model for bladder stone formation. Bladder calculi were most likely to develop within one year of injury. Patients developing bladder calculi prior to first definitive discharge were most likely to be white and have neurologically complete lesions and Klebsiella infections at admission. Patients developing bladder stones within two years of hospital discharge were most likely to be young and white and have indwelling urethral catheters and either Proteus or multiple-organism infections at discharge. The predictive model was 82% sensitive and 83% specific when applied to a validation sample of patients.


Normalized real-time PCR for diagnosis of H. pylori infection.
There is increasing interest in the use of quantitative PCR (q-PCR) for diagnosis of H. pylori infection. However, the assay remains largely unstandardized, making comparison between studies unreliable. The objective of this study was to assess accuracy of a normalized q-PCR assay for diagnosis of the infection. Seventy-six fresh gastric biopsy specimens were collected from patients undergoing upper gastrointestinal tract endoscopy and examined by rapid urease test (RUT), culture, and a commercial TaqMan q-PCR assay targeting the ureA gene. Counts obtained from the latter assay were normalized to the human ACTB gene. A subject was considered to be infected if two or more assays were positive. The detection rates were 42.1%, 52.6%, and 78.9% by culture, RUT and q-PCR, respectively. Bacterial density ranged 0.005 to 4800 bacteria per 100 human cells. Because q-PCR showed low initial specificity (45.7%), the cutoff value for the assay was recalculated as 1 bacterium per 100 human cells, using ROC curve analysis. Accordingly, the sensitivities and specificities were 79.5% and 97.3%, respectively, for culture; 94.9% and 91.9%, respectively, for RUT; and 94.9% and 94.6%, respectively, for q-PCR. By gold standard, 39 of the dyspeptic patients (51.3%) were found to be infected. With the identified cutoff value, the q-PCR assay diagnosed H. pylori infection with an accuracy slightly superior to that of RUT. However, the possibility that low counts detected only by q-PCR represent true infections warrants further investigation. Normalization of bacterial counts for standardization of q-PCR H. pylori assays is recommended.


Complete genome sequence of Calditerrivibrio nitroreducens type strain (Yu37-1).
Calditerrivibrio nitroreducens Iino et al. 2008 is the type species of the genus Calditerrivibrio. The species is of interest because of its important role in the nitrate cycle as nitrate reducer and for its isolated phylogenetic position in the Tree of Life. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the third complete genome sequence of a member of the family Deferribacteraceae. The 2,216,552 bp long genome with its 2,128 protein-coding and 50 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.


Posttranscriptional modulation of cytokine production in T cells for the regulation of excessive inflammation by TFL.
Posttranscriptional machinery regulates inflammation and is associated with autoimmunity as well as tumorigenesis in collaboration with transcription factors. We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL(-/-) mice in which TFL(-/-) lymphocytes proliferated more rapidly than TFL(+/+) upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-α, and IL-17a by 3' untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL(-/-) mice demonstrated persistent severe paralysis. CNS-infiltrated CD4(+) T cells in TFL(-/-) mice contained a higher proportion of Th17 cells than did those in TFL(+/+) mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL(-/-) cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell-mediated autoimmune diseases.


Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients.
Large artery damage is a major contributory factor to cardiovascular morbidity and mortality of patients with hypertension. Pulse wave velocity (PWV), a classic evaluation of arterial distensibility, has never been ascertained as a cardiovascular risk marker. To determine the factors influencing aortic PWV and the potential predictor role of this measurement, we studied a cohort of 710 patients with essential hypertension. Atherosclerosis alterations (AA) were defined on the basis of clinical events. Calculation of cardiovascular risks, by use of Framingham equations, was performed in subjects without AA. PWV was higher in the presence of AA (14.9+/-4.0 versus 12.4+/-2.6 m/s, P<0.0001), even after adjustments on confounding factors and was the first determinant (P<0.0001) of the extent of atherosclerosis assessed as the sum of the atherosclerotic sites. In patients without AA, all cardiovascular risks increased constantly with PWV. Furthermore, at a given age, aortic PWV was the best predictor of cardiovascular mortality. The odds ratio of being in a high cardiovascular mortality risk group (>5% for 10 years) for patients in the upper quartile of PWV was 7.1 (95% confidence intervals 4.5 to 11.3). The presence of a PWV >13 m/s, taken alone, appeared as a strong predictor of cardiovascular mortality with high performance values. This study shows that aortic PWV is strongly associated with the presence and extent of atherosclerosis and constitutes a forceful marker and predictor of cardiovascular risk in hypertensive patients.


Differential roles for frontal eye fields (FEFs) and intraparietal sulcus (IPS) in visual working memory and visual attention.
Cortical activity was measured with functional magnetic resonance imaging to probe the involvement of the superior precentral sulcus (including putative human frontal eye fields, FEFs) and the intraparietal sulcus (IPS) in visual short-term memory and visual attention. In two experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. An earlier study (S. Offen, D. Schluppeck, & D. J. Heeger, 2009) had found a dissociation in early visual cortex that suggested different computational mechanisms underlying the two processes. In contrast, the results reported here show that the patterns of activation in prefrontal and parietal cortex were different from one another but were similar for the two tasks. In particular, the FEF showed evidence for sustained delay period activity for both the working memory and the attention task, while the IPS did not show evidence for sustained delay period activity for either task. The results imply differential roles for the FEF and IPS in these tasks; the results also suggest that feedback of sustained activity from frontal cortex to visual cortex might be gated by task demands.


Acute pulmonary hypertension and right ventricular failure in adult respiratory distress syndrome.
The severity of acute pulmonary hypertension (APHT) in acute respiratory distress syndrome was examined in 20 patients. All patients had significant APHT (mean pressure 40.6 +/- 6.3 mmHg) on admission to the intensive care unit. There was evidence of right ventricular (RV) failure, with a right ventricular stroke work index (RVSWI) of 9.20 +/- 3.3 g.m/m2 and a central venous pressure of 18.0 +/- 4.0 mmHg. The RV afterload, i.e. pulmonary artery elastance (Ea = stroke volume/peak pulmonary artery pressure), was raised. Stroke volume could not be predicted from Ea or RVSWI alone, but regression analysis indicated that the ratio of RVSWI/Ea (i.e. ventriculo-arterial coupling) could account for 88% of the stroke volume.


Vasopressin-mediated enhancement of adrenergic vasoconstriction involves both the tyrosine kinase and the protein kinase C pathways.
Vasopressin is frequently used to treat catecholamine-resistant vasodilatory shock. It enhances the vasoconstrictor effects of catecholamines at concentrations of vasopressin that have none or only minimal intrinsic pressor effects. However, the vascular mechanisms underlying this combined pharmacological approach have not been fully elucidated. We used isometric tension measurements in vascular rings to investigate potential cellular mechanisms. Vascular rings (0.2 mm diameter) were harvested from the superior mesenteric artery of Wistar rats (2 to 4 months of age). Dose-response relationships were derived for vasopressin (VP) and norepinephrine (NE), in the absence and presence of a subpressor dose of VP (10(-9) M). The contribution of tyrosine kinase (TK), the TK pathway proteins SRC and PYK2, as well as protein kinase C (PKC) were determined by measuring the modulating influence of specific inhibitors on the pressor response to NE (10(-5) M) alone and the augmented pressor response to VP (10(-9) M). VP (10(-9) M) had only minimal pressor effect alone (10% of maximal response), but significantly increased the E(max) response to NE (587.8 ± 40.7 vs 331.2 ± 10.4 mg). TK inhibition completely abolished the pressor response to NE (100% vs 1.0% 0.5%) and the augmented VP response alone (100% vs 2.0% ± 1.01%). Both responses were significantly, but equally, decreased by SRC inhibition (63% ± 4.0% and 69% 1.0%). In contrast, inhibition of the TK molecule PYK2 with salicylate had differential inhibitory effects on the vasoconstrictor responses. Salicylate caused a greater inhibition of VP-induced augmented NE response in comparison with NE alone (62.1% ± 7% and 15% ± 2%). Inhibition of either the µ or γ PKC isoform significantly decreased both responses, but the magnitude of the inhibition was significantly different for each isoform. Inhibition of the γ PKC isoform significantly decreased the vasoconstriction responses to both NE and VP plus NE (82.9 ± 3.9 vs 32.8 ± 3.8). Inhibition of the µ PKC isoform significantly decreased both responses and completely abolished the VP-augmented response to NE. These data are consistent with a central role for TK in mediating both the NE response and the VP-augmented response. Moreover, PYK2 and the µ and γ isoforms of PKC seem to play a preferential role in mediating the augmented VP response. The apparent divergent roles of these pathways in mediating NE- versus VP-augmented pressor responses could potentially lead to new targeted therapies in catecholamine-resistant shock.


[Women who are left behind: the impact of international migration on the process of seeking health care].
To analyze how women who are left behind seek care in communities with a high migration index. This is a cross-sectional study which used a qualitative approach. Sixty in-depth interviews were conducted between October 2004 and May 2005 with female partners of migrants in two communities (urban / rural) from a region in central Mexico with high migration to the United States. Migration determines two forms of familial reorganization: one in which female partners of migrants reintegrate with their families; and one in which they remain on their own. Women who reintegrate with their families receive more support, but are also subjected to more control, rendering them with less capability to seek care, particularly related to sexual and reproductive health. Women who remain on their own have less support but have more control and capacity to seek care, with privacy and independence. The familial reorganization influences timely health care-seeking behaviour of female partners of migrants. The situations identified can function as obstacles or facilitators to mobilize healthcare resources.


2D/3D perovskite hybrids as moisture-tolerant and efficient light absorbers for solar cells.
The lifetime and power conversion efficiency are the key issues for the commercialization of perovskite solar cells (PSCs). In this paper, the development of 2D/3D perovskite hybrids (CA2PbI4/MAPbIxCl3-x) was firstly demonstrated to be a reliable method to combine their advantages, and provided a new concept for achieving both stable and efficient PSCs through the hybridization of perovskites. 2D/3D perovskite hybrids afforded significantly-improved moisture stability of films and devices without encapsulation in a high humidity of 63 ± 5%, as compared with the 3D perovskite (MAPbIxCl3-x). The 2D/3D perovskite-hybrid film did not undergo any degradation after 40 days, while the 3D perovskite decomposed completely under the same conditions after 8 days. The 2D/3D perovskite-hybrid device maintained 54% of the original efficiency after 220 hours, whereas the 3D perovskite device lost all the efficiency within only 50 hours. Moreover, the 2D/3D perovskite hybrid achieved comparable device performances (PCE: 13.86%) to the 3D perovskite (PCE: 13.12%) after the optimization of device fabrication conditions.


Inhibition of hydroid aging in Campanularia flexuosa.
Hydranths of the colonial marine hydroid Campanularia flexuosa (phylum Cnidaria, class Hydrozoa, order Calyptoblastea) have a mean life span of approximately 7 days in intact colonies in culture. Hydranths then regress and are absorbed, and their cellular materials are utilized by the colony for continued growth. Hydranth life spans can be extended to 20 days in isolated hydranths if, repeatedly, the pedicel is damaged by pinching and is allowed to partially regen-erate. This suggests that tissue damage and reorganization function to maintain the hydranth.


Free-Ranging Pig and Wild Boar Interactions in an Endemic Area of African Swine Fever.
African swine fever virus (ASFV) is spreading throughout Eurasia and there is no vaccine nor treatment available, so the control is based on the implementation of strict sanitary measures. These measures include depopulation of infected and in-contact animals and export restrictions, which can lead to important economic losses, making currently African swine fever (ASF) the greatest threat to the global swine industry. ASF has been endemic on the island of Sardinia since 1978, the longest persistence of anywhere in Eurasia. In Sardinia, eradication programs have failed, in large part due to the lack of farm professionalism, the high density of wild boar and the presence of non-registered domestic pigs (free-ranging pigs). In order to clarify how the virus is transmitted from domestic to wild swine, we examined the interaction between free-ranging pigs and wild boar in an ASF-endemic area of Sardinia. To this end, a field study was carried out on direct and indirect interactions, using monitoring by camera trapping in different areas and risk points. Critical time windows (CTWs) for the virus to survive in the environment (long window) and remain infectious (short window) were estimated, and based on these, the number of indirect interactions were determined. Free-ranging pigs indirectly interacted often with wild boar (long window = 6.47 interactions/day, short window = 1.31 interactions/day) and these interactions (long window) were mainly at water sources. They also directly interacted 0.37 times per day, especially between 14:00 and 21:00 h, which is much higher than for other interspecific interactions observed in Mediterranean scenarios. The highly frequent interactions at this interspecific interface may help explain the more than four-decade-long endemicity of ASF on the island. Supporting that free-ranging pigs can act as a bridge to transmit ASFV between wild boar and registered domestic pigs. This study contributes broadly to improving the knowledge on the estimation of frequencies of direct and indirect interactions between wild and free-ranging domestic swine. As well as supporting the importance of the analysis of interspecific interactions in shared infectious diseases, especially for guiding disease management. Finally, this work illustrates the power of the camera-trapping method for analyzing interspecific interfaces.


Characterization of AfaE adhesins produced by extraintestinal and intestinal human Escherichia coli isolates: PCR assays for detection of Afa adhesins that do or do not recognize Dr blood group antigens.
Operons of the afa family are expressed by pathogenic Escherichia coli strains associated with intestinal and extraintestinal infections in humans and animals. The recently demonstrated heterogeneity of these operons (L. Lalioui, M. Jouve, P. Gounon, and C. Le Bouguénec, Infect. Immun. 67:5048-5059, 1999) was used to develop a new PCR assay for detecting all the operons of the afa family with a single genetic tool. This PCR approach was validated by investigating three collections of human E. coli isolates originating from the stools of infants with diarrhea (88 strains), the urine of patients with pyelonephritis (97 strains), and the blood of cancer patients (115 strains). The results obtained with this single test and those previously obtained with several PCR assays were closely correlated. The AfaE adhesins encoded by the afa operons are variable, particularly with respect to the primary sequence encoded by the afaE gene. The receptor binding specificities have not been determined for all of these adhesins; some recognize the Dr blood group antigen (Afa/Dr(+) adhesins) on the human decay-accelerating factor (DAF) as a receptor, and others (Afa/Dr(-) adhesins) do not. Thus, the afa operons detected in this study were characterized by subtyping the afaE gene using specific PCRs. In addition, the DAF-binding capacities of as-yet-uncharacterized AfaE adhesins were tested by various cellular approaches. The afaE8 subtype (Afa/Dr(-) adhesin) was found to predominate in afa-positive isolates from sepsis patients (75%); it was frequent in afa-positive pyelonephritis E. coli (55.5%) and absent from diarrhea-associated strains. In contrast, Afa/Dr(+) strains (regardless of the afaE subtype) were associated with both diarrhea (100%) and extraintestinal infections (44 and 25% in afa-positive pyelonephritis and sepsis strains, respectively). These data suggest that there is an association between the subtype of AfaE adhesin and the physiological site of the infection caused by afa-positive strains.


In vitro antifungal activity of the fourth generation fluoroquinolones against Candida isolates from human ocular infections.
To evaluate and compare the in vitro antifungal activity of moxifloxacin and gatifloxacin against Candida species isolated from ocular infections. Tube microdilutions test was used to determine antifungal activity of the agents for 21 Candida isolates and one quality control strain. Drugs evaluated included topical preparations of fluoroquinolones (FQs), moxifloxacin (Vigamox), and gatifloxacin (Zymar). Serial dilutions of moxifloxacin (0.5%, 0.25%, 0.125%) and gatifloxacin (0.3%, 0.15%, 0.075%) were prepared for the microtube dilutions test. Aliquots (0.01 ul) were plated onto Sabouraud agar and colonies were counted. Both drugs undiluted inhibited greater than 95% of growth at 24 hrs. There was no significant difference between moxifloxacin and gatifloxacin at undiluted concentrations (p = 1.00); however, the mean number of colony forming units in gatifloxacin group was significantly less than that of moxifloxacin at diluted concentrations of the drugs (p < 0.05). Current commercial topical preparations of moxifloxacin and gatifloxacin demonstrated a definite in vitro antifungal activity against ocular Candida species; however, clinical efficacy of these agents remains unproven. The greater inhibition of growth of organisms with gatifloxacin compared to moxifloxacin is possibly because of the presence of BAK in Zymar.


Cortical activity is more stable when sensory stimuli are consciously perceived.
According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial--the pattern of activity must be relatively stable. Stability is characteristic of decision states in recurrent attractor networks, and its possible relevance to conscious perception has been suggested by theorists. However, it is difficult to measure on the within-trial time scales and broadly distributed spatial scales relevant to perception. We recorded simultaneous magneto- and electroencephalography (MEG and EEG) data while subjects observed threshold-level visual stimuli. Pattern-similarity analyses applied to the data from MEG gradiometers uncovered a pronounced decrease in variability across trials after stimulus onset, consistent with previous single-unit data. This was followed by a significant divergence in variability depending upon subjective report (seen/unseen), with seen trials exhibiting less variability. Applying the same analysis across time, within trial, we found that the latter effect coincided in time with a difference in the stability of the pattern of activity. Stability alone could be used to classify data from individual trials as "seen" or "unseen." The same metric applied to EEG data from patients with disorders of consciousness exposed to auditory stimuli diverged parametrically according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results. Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision.


Primary Care Outcomes Questionnaire: psychometric testing of a new instrument.
Patients attend primary care for many reasons and to achieve a range of possible outcomes. There is currently no Patient Reported Outcome Measure (PROM) designed to capture these diverse outcomes, and trials of interventions in primary care may thus fail to detect beneficial effects. This study describes the psychometric testing of the Primary Care Outcomes Questionnaire (PCOQ), which was designed to capture a broad range of outcomes relevant to primary care. Questionnaires were administered in primary care in South West England. Patients completed the PCOQ in GP waiting rooms before a consultation, and a second questionnaire, including the PCOQ and seven comparator PROMs, after 1 week. Psychometric testing included exploratory factor analysis on the PCOQ, internal consistency, correlation coefficients between domain scores and comparator measures, and repeated measures effect sizes indicating change across 1 week. In total, 602 patients completed the PCOQ at baseline, and 264 (44%) returned the follow-up questionnaire. Exploratory factor analysis suggested four dimensions underlying the PCOQ items: health and wellbeing, health knowledge and self-care, confidence in health provision, and confidence in health plan. Each dimension was internally consistent and correlated as expected with comparator PROMs, providing evidence of construct validity. Patients reporting an improvement in their main problem exhibited small to moderate improvements in relevant domain scores on the PCOQ. The PCOQ was acceptable, feasible, showed strong psychometric properties, and was responsive to change. It is a promising new tool for assessment of outcomes of primary care interventions from a patient perspective.


Carbonic anhydrase IX (CA9) modulates tumor-associated cell migration and invasion.
Expression of carbonic anhydrase IX (CA9) was shown to be strongly involved in high incidences of metastasis and poor prognosis in various human tumors. In this study, we investigated the possible role for CA9 in tumor metastases in vitro, using a gene transfection tool in the human cervical carcinoma cell line C33A. Gene expression profiling of CA9-transfected cells (C33A/CA9) and vector-transfected cells (C33A/Mock) was investigated by DNA microarray. The biological functions of differentially expressed genes between the C33A/CA9 and C33A/Mock cells included cell growth, regulation of cell-cell and cell-extracellular matrix adhesion and cytoskeletal organization. Immunofluorescent stain and Matrigel culture showed cytoskeletal remodeling, disassembled focal adhesion, weakened cell-cell adhesion and increased motility in C33A/CA9 cells. These invasive and metastatic phenotypes were associated with Rho-GTPase-related epithelial-mesenchymal transition. Inhibition of the Rho/Rho kinase pathway by a ROCK inhibitor (Y27632) and si-Rho (short interference RNA against RhoA) showed that Rho-GTPase signaling was involved in cellular morphologic and migratory changes. The effect of CA9 on Rho-GTPase signaling was also confirmed by silencing CA9 expression. Our results suggest that CA9 overexpression induces weakening of cell adhesions and augmented cell motility by aberrant Rho-GTPase signal transduction. Our study shows an underlying mechanism of CA9-related enhanced metastatic potential of tumor cells.


Harnessing interactive technologies to improve health outcomes in juvenile idiopathic arthritis.
Children and adolescents with Juvenile Idiopathic Arthritis (JIA) typically have reduced physical activity level and impaired aerobic and anaerobic exercise capacity when compared to their non-JIA counterparts. Low intensity exercise regimens appear to be safe in children with JIA and may results in improvements in overall physical function. Poor adherence to paediatric rheumatology treatment may lead to negative clinical outcomes and possibly increased disease activity. This includes symptoms such as pain, fatigue, quality of life, longer term outcomes including joint damage, as well as increase of healthcare associated costs. Low adherence to medications such as methotrexate and biological-drugs remains a significant issue for paediatric rheumatologists, with alarming reports that less than half of the children with JIA are compliant to drug-therapy. The recent advances in interactive technology resulting in a variety of wearable user-friendly smart devices may become a key solution to address important questions in JIA clinical management. Fully understanding the impact that arthritis and treatment complications have upon individual children and their families has long been a challenge for clinicians. Modern interactive technologies can be customised and accessed directly in the hands or wrists of children with JIA. These secured networks could be accessible 'live' at anytime and anywhere by the child, parents and clinicians. Multidisciplinary teams in paediatric rheumatology may benefit from adopting these technologies to better understand domains such as patient biological parameters, symptoms progression, adherence to drug-therapy, quality of life, and participation in physical activities. Most importantly the use of smart devices technologies may also facilitate more timely clinical decisions, improve self-management and parents awareness in the progression of their child's disease. Paediatric rheumatology research could also benefit from the use of these smart devices, as they would allow real-time access to meaningful data to thoroughly understand the disease-patterns of JIA, such as pain and physical activity outcomes. Data collection that typically occurs once every 1 or 3 months in the clinical setting could instead be gathered every week, day, minute or virtually live online. Arguably, few limitations in wearing such interactive technologies still exist and require further developments. Finally, by embracing and adapting these new and now highly accessible interactive technologies, clinical management and research in paediatric rheumatology may be greatly advanced.


The effect of intense interval exercise on iron status parameters in trained men.
Iron and iron-binding proteins play a critical role in the physiology of many human systems, including the immune system. Intense interval exercise in trained men (mean [SD] age = 31.5 [4.5] yr; VO2max = 64.3 [3.8] ml.kg-1.min-1) is associated with significant modulation of iron status parameters. The concentration of red blood cells, hemoglobin, and transferrin all increased significantly immediately post-test (P < 0.01), increases which can largely be attributed to hemoconcentration. Serum iron was elevated by approximately 25% both immediately and 1 h post-test (P < 0.08). Maximum post-test serum iron values (either immediately or 1 h post-test) were significantly elevated with respect to rest (P < 0.01). Transferrin concentration was also significantly elevated at 24 h post-test (P < 0.05). Transferrin saturation was not significantly altered by this protocol (P > 0.10). Despite a trend toward elevation at 24 h post-test, ferritin concentration was not significantly different from the resting value at any sampling point. Intense interval exercise appears to be associated with significant modulation of iron status, the biological importance of which remains to be determined.


Equatorial currents in the Western Indian ocean.
Measurements were made in the equatorial Indian Ocean during spring and summer 1979 from the Somali coast to 62 degrees E in the interior of the western basin. The detailed vertical profiles of horizontal current show that the energetic dominance throughout the region of variability was on vertical scales of several hundreds of meters, confined to within a few degrees of the equator, as observed in 1976. The near-surface equatorial circulation responded directly to variations in the wind field, and satellite-tracked drifter buoys showed the equatorial surface jet extending across the width of the ocean. This eastward flow is generated by the eastward winds that appear in the interval between the northeast and southwest monsoons. The zonal velocity fluctuations extended in a consistent pattern over the observation region. The time and meridional scales of the variability were similar to those observed in 1976, suggesting that the velocity field is dominated by long-term, equatorially trapped motions with long zonal scales.


The circadian timing system: making sense of day/night gene expression.
The circadian time-keeping system ensures predictive adaptation of individuals to the reproducible 24-h day/night alternations of our planet by generating the 24-h (circadian) rhythms found in hormone release and cardiovascular, biophysical and behavioral functions, and others. In mammals, the master clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. The molecular events determining the functional oscillation of the SCN neurons with a period of 24-h involve recurrent expression of several clock proteins that interact in complex transcription/translation feedback loops. In mammals, a glutamatergic monosynaptic pathway originating from the retina regulaltes the clock gene expression pattern in the SCN neurons, synchronizing them to the light:dark cycle. The emerging concept is that neural/humoral output signals from the SCN impinge upon peripheral clocks located in other areas of the brain, heart, lung, gastrointestinal tract, liver, kidney, fibroblasts, and most of the cell phenotypes, resulting in overt circadian rhythms in integrated physiological functions. Here we review the impact of day/night alternation on integrated physiology; the molecular mechanisms and input/output signaling pathways involved in SCN circadian function; the current concept of peripheral clocks; and the potential role of melatonin as a circadian neuroendocrine transducer.


Nonmechanical bifocal zoom telescope.
We report on a novel zoom lens with no moving parts in the form of a switchable Galilean telescope. This zoom telescope consists of two flat liquid-crystal diffractive lenses with apertures of 10mm that can each take on the focal lengths of -50 and +100cm, with a spacing of 50cm and, hence, a zoom ratio of 4x. The lenses are driven using a low-voltage ac source with 1.6V and exhibit millisecond switching times. The spectral characteristic of this diffractive zoom system is evaluated for light sources of various bandwidths. Potential applications for this technology include a zoom lens with no moving parts for camera phones and medical imaging devices.


A mathematical model predicting the coculture dynamics of endothelial and mesenchymal stem cells for tissue regeneration.
In most tissue engineering applications, understanding the factors affecting the growth dynamics of coculture systems is crucial for directing the population toward a desirable regenerative process. Yet, no comprehensive analysis method exists to quantify coculture population dynamics, let alone, a unifying model addressing the "environmental" factors influencing cell growth, all together. Here we suggest a modification of the Lotka-Volterra model to analyze the population dynamics of cocultured cells and predict their growth profiles for tissue engineering applications. This model, commonly used to describe the population dynamics of a prey and predator sharing a closed ecological niche, was found to fit our empirical data on cocultures of endothelial cells (ECs) and mesenchymal stem cells (MSCs) that have been widely investigated for their regenerative potential. Applying this model to cocultures of this sort allows us to quantify the effect that culturing conditions have on the way cell growth is affected by the same cells or by the other cells in the coculture. We found that in most cases, EC growth was inhibited by the same cells but promoted by MSCs. The principles resulting from this analysis can be used in various applications to guide the population toward a desired direction while shedding new light on the fundamental interactions between ECs and MSCs. Similar results were also demonstrated on complex substrates made from decellularized porcine cardiac extracellular matrix, where growth occurred only after coculturing ECs and MSCs together. Finally, this unique implementation of the Lotka-Volterra model may also be regarded as a roadmap for using such models with other potentially regenerative cocultures in various applications.


Global and relationship-specific perceptions of support and the development of postpartum depressive symptomatology.
A lack of social support has consistently been demonstrated to be an important modifiable risk factor for postpartum depression. As such, a greater understanding of specific support variables may assist health professionals in the development of effective preventive interventions. The purpose of this paper was two-fold: (1) to determine if women discriminated between global and relationship-specific perceptions of support, and (2) to examine the influence of global and relationship-specific perceptions of support in the immediate postpartum period on the development of depressive symptomatology at 8 weeks postpartum. As part of a longitudinal study, a diverse sample of 594 mothers completed questionnaires that included the Edinburgh Postnatal Depression Scale (EPDS) and global and relationship-specific (e.g., partner, mother, and other women with children) measures of support. Mothers clearly discriminated between global and relationship-specific perceptions of support and those with depressive symptomatology at 8 weeks had significantly lower perceptions of both global and relationship-specific support at 1-week postpartum. Using discriminant function analysis, four variables, reliable reliance from partner, nurturance from partner, attachment to other women with children, and EPDS score at 1-week postpartum, differentiated between mothers who experienced depressive symptomatology at 8 weeks and those who did not. Relationship-specific interventions may be beneficial if they include strategies that target a positive partner relationship through preceptions of reliable alliance and feeling needed and provide opportunites for interaction with other mothers. Maternal mood at 1 week postpartum was the largest predictor of depressive symptomatology at 8 weeks.


Taurocholate-stimulated leukotriene C4 biosynthesis and leukotriene C4-stimulated choleresis in isolated rat liver.
Cysteinyl-containing leukotrienes seem to exert a cholestatic effect. However, leukotriene inhibitors were found to reduce bile salt efflux in isolated rat hepatocytes, suggesting a role for leukotrienes in bile flow formation. In the isolated rat liver, the effects of two different concentrations of leukotriene C4 on bile flow and bile salt excretion are analyzed, as well as the possible effect of taurocholate on the hepatic production of cysteinyl-containing leukotrienes. Leukotriene C4 (0.25 fmol) increased bile salt excretion (+22.2%; P < 0.05), whereas a much higher dose (0.25 x 10(6) fmol) showed the known cholestatic effect, reducing bile salt excretion (-25.9%; P < 0.01). These dose-dependent biphasic effects were specific because they could be prevented by the simultaneous administration of cysteinyl-containing leukotriene antagonists. On the other hand, taurocholate administration induced a dose-dependent increase in biliary excretion of cysteinyl-containing leukotrienes. Furthermore, taurocholate increased messenger RNA levels of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Taurocholate increase of hepatocyte intracellular calcium was not significant, suggesting that taurocholate effects are not mediated by stimulation of calcium metabolism. These results constitute evidence for the existence of a positive feedback mechanism by which bile salts stimulate the synthesis of leukotrienes that, in turn, stimulate bile salt excretion.


Postoperative outcomes in oesophagectomy with trainee involvement.
The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery.


Building our youth for the future.
Adolescents and young adults are at increased risk for HIV due to the many developmental, psychological, social, and structural transitions that converge in this period of the lifespan. In addition, adolescent deaths resulting from HIV continue to rise despite declines in other age groups. There are also young key populations (YKPs) that bear disproportionate burdens of HIV and are the most vulnerable, including young men who have sex with men (MSM), transgender youth, young people who inject drugs, and adolescent and young adult sex workers. As a society, we must do more to stop new HIV infections and untimely HIV-related deaths through both primary and secondary prevention and better management approaches. Using an interwoven prevention and treatment cascade approach, the starting point for all interventions must be HIV counselling and testing. Subsequent interventions for both HIV-negative and HIV-positive youth must be "adolescent-centred," occur within the socio-ecological context of young people and take advantage of the innovations and technologies that youth have easily incorporated into their daily lives. In order to achieve the global goals of zero infections, zero discrimination and zero deaths, a sustained focus on HIV research, policy and advocacy for YKPs must occur.


Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions.
Adaptive optics-optical coherence tomography (AO-OCT) permits improved imaging of microscopic retinal structures by combining the high lateral resolution of AO with the high axial resolution of OCT, resulting in the narrowest three-dimensional (3D) point-spread function (PSF) of all in vivo retinal imaging techniques. Owing to the high volumetric resolution of AO-OCT systems, it is now possible, for the first time, to acquire images of 3D cellular structures in the living retina. Thus, with AO-OCT, those retinal structures that are not visible with AO or OCT alone (e.g., bundles of retinal nerve fiber layers, 3D mosaic of photoreceptors, 3D structure of microvasculature, and detailed structure of retinal disruptions) can be visualized. Our current AO-OCT instrumentation uses spectrometer-based Fourier-domain OCT technology and two-deformable-mirror-based AO wavefront correction. We describe image processing methods that help to remove motion artifacts observed in volumetric data, followed by innovative data visualization techniques [including two-dimensional (2D) and 3D representations]. Finally, examples of microscopic retinal structures that are acquired with the University of California Davis AO-OCT system are presented.


The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers.
The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes. Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity. Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed.


EVpedia: A community web resource for prokaryotic and eukaryotic extracellular vesicles research.
For cell-to-cell communication, all living cells including archaea, bacteria, and eukaryotes secrete nano-sized membrane vesicles into the extracellular space. These extracellular vesicles harbor specific subsets of proteins, mRNAs, miRNAs, lipids, and metabolites that represent their cellular status. These vesicle-specific cargos are considered as novel diagnostic biomarkers as well as therapeutic targets. With the advancement in high-throughput technologies on multiomics studies and improvements in bioinformatics approaches, a huge number of vesicular proteins, mRNAs, miRNAs, lipids, and metabolites have been identified, and our understanding of these complex extracellular organelles has considerably increased during these past years. In this review, we highlight EVpedia (http://evpedia.info), a community web portal for systematic analyses of prokaryotic and eukaryotic extracellular vesicles research.


A pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa.
Low dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50-150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical benefit in terms of improvement in oxygenation at day 3 following LDRT and the ability to avoid mechanical ventilation at day 7 post LDRT. Patients with both polymerase chain reaction (PCR) and high-resolution computer tomogram (HRCT) confirmed severe COVID-19 pneumonia, not improving on conventional therapy including Dexamethasone and with increasing oxygen requirement were enrolled in the study. Patients on mechanical ventilation were excluded. Eligible patients received a single 100cGy fraction to the whole lung. In the absence of any dose limiting toxicity the study proposed to treat a total of 10 patients. The primary endpoints were to assess the safety/feasibility, and toxicity within the first 24 hours post LDRT. The secondary endpoints were to assess efficacy of LDRT at Day 3, 7, 14 and 28 post LDRT. Ten patients were treated with LDRT. All (100%) of patients were able to complete LDRT without treatment related SAE within the first 24 hours post treatment. None of the patients treated with LDRT experienced any acute toxicity as defined by change in clinical and respiratory status at 24hr following LDRT. Majority (90%) of patients avoided mechanical ventilation within 7 days of LDRT. Four patients (40%) demonstrated at least 25% improvement in oxygen requirements within 3 days. Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). Median time to discharge (n = 6) was 16.5 days and median time to death (n = 4) was 11.0 days. Patients who ultimately died showed elevated inflammatory markers including Ferritin, CRP and D-dimers as compared to those who were discharged alive. LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.


IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis.
Periodontal disease is the most frequent cause of tooth loss in humans and is the most prevalent disease associated with bone loss, including osteoporosis. Periodontal destruction is initiated by bacteria that colonize the tooth surface, leading to inflammation and bone resorption. To assess the roles of IL-1 and TNF in this process, studies were conducted in a Macaca fascicularis primate model of experimental periodontitis. Function-blocking soluble receptors to IL-1 and TNF were applied by local injection to sites with induced periodontal destruction and compared with similar sites injected with vehicle alone. The results indicate that injection of soluble receptors to IL-1 and TNF inhibited by approximately 80% the recruitment of inflammatory cells in close proximity to bone. The formation of osteoclasts was reduced by 67% at the experimental sites compared with that at the control sites, and the amount of bone loss was reduced by 60%. All results were statistically significant (p < 0.01). These findings indicate that a significant component of the pathologic process of periodontitis is due to IL-1/TNF activity, since inhibiting IL-1/TNF reduces both inflammatory cell recruitment and bone loss. The data also suggest that inflammation associated with gingivitis is actively protective, since blocking further up-regulation of the host response with IL-1/TNF inhibitors does not cause periodontal damage. Furthermore, these results coupled with recent evidence that IL-1 and TNF participate in endocrine-associated osteoporosis suggest that multiple pathologies involving excessive loss of bone may operate through a common mechanism involving IL-1 and/or TNF.


An argument for the universal prophylaxis of hepatitis B infection in patients receiving rituximab: a 7-year institutional experience of hepatitis screening.
Reactivation of hepatitis B virus (HBV) replication in patients receiving rituximab is well described. Current international guidelines recommend HBV screening prior to the commencement of immunosuppressive therapy. However, adherence to such protocols has not previously been studied. We therefore audited screening practices and clinical outcomes in patients prescribed rituximab since its introduction in a large metropolitan health service. All patients receiving rituximab over an 88-month period were identified via pharmacy records. Medical records and laboratory results were reviewed to determine the timing and type of hepatitis screening. HBV flares were identified and correlated with clinical outcomes and any screening or prophylaxis given. Rituximab was given to 355 patients over 88 months (average age, 61 years; 51% male, 48% born overseas); 83% received rituximab for treatment of a hematological malignancy. HBV screening occurred in 31% of patients and, of these, 66% had pre-emptive screening. Five patients given cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab experienced HBV flares. Four died from viral reactivation. None received antiviral prophylaxis. Hepatitis screening rates in patients receiving rituximab in this study were lower than recommended in clinical guidelines. The identification of five patients with clinically important flares and four deaths in this group highlight the critical need to identify at-risk patients and provide timely prophylactic antiviral therapy to prevent serious morbidity and mortality. Even those with evidence of HBV seroconversion are at risk for fatal flares without active prophylactic antiviral therapy.


A simple optical model to estimate suspended particulate matter in Yellow River Estuary.
Distribution of the suspended particulate matter (SPM) concentration is a key issue for analyzing the deposition and erosion variety of the estuary and evaluating the material fluxes from river to sea. Satellite remote sensing is a useful tool to investigate the spatial variation of SPM concentration in estuarial zones. However, algorithm developments and validations of the SPM concentrations in Yellow River Estuary (YRE) have been seldom performed before and therefore our knowledge on the quality of retrieval of SPM concentration is poor. In this study, we developed a new simple optical model to estimate SPM concentration in YRE by specifying the optimal wavelength ratios (600-710 nm)/ (530-590 nm) based on observations of 5 cruises during 2004 and 2011. The simple optical model was attentively calibrated and the optimal band ratios were selected for application to multiple sensors, 678/551 for the Moderate Resolution Imaging Spectroradiometer (MODIS), 705/560 for the Medium Resolution Imaging Spectrometer (MERIS) and 680/555 for the Geostationary Ocean Color Imager (GOCI). With the simple optical model, the relative percentage difference and the mean absolute error were 35.4% and 15.6 gm(-3) respectively for MODIS, 42.2% and 16.3 gm(-3) for MERIS, and 34.2% and 14.7 gm(-3) for GOCI, based on an independent validation data set. Our results showed a good precision of estimation for SPM concentration using the new simple optical model, contrasting with the poor estimations derived from existing empirical models. Providing an available atmospheric correction scheme for satellite imagery, our simple model could be used for quantitative monitoring of SPM concentrations in YRE.


C-MAC videolaryngoscope versus Macintosh laryngoscope for tracheal intubation: A systematic review and meta-analysis with trial sequential analysis.
The C-MAC laryngoscope (C-MAC) is a videolaryngoscope that uses a modified Macintosh blade. Although several anecdotal reports exist, it remains unclear whether the C-MAC is superior to the Macintosh laryngoscope for tracheal intubation in the adult population. Systematic review, meta-analysis. Operating room, intensive care unit. For inclusion in our analysis, studies had to be prospective randomised trials which compared the C-MAC with the Macintosh laryngoscope for tracheal intubation in the adult population. Data on success rates, intubation time, glottic visualisation and incidence of external laryngeal manipulations (ELM) during tracheal intubation were extracted from the identified studies. In subgroup analysis, we separated those parameters to assess the influence of the airway condition (normal or difficult) and laryngoscopists (novice or experienced). We conducted a trial sequential analysis (TSA). Sixteen articles with 18 trials met the inclusion criteria. The C-MAC provided better glottic visualisation compared to the Macintosh (RR, 1.08; 95% CI, 1.03-1.14). TSA corrected the CI to 1.01-1.19; thus, total sample size reached the required information size (RIS). Success rates and intubation time did not differ significantly between the laryngoscopes. TSA showed that total sample size reached the RIS for success rates. The TSA Z curve surpassed the futility boundary. The C-MAC required less ELM compared to the Macintosh (RR, 0.83; 95% CI, 0.72-0.96). TSA corrected the CI to 0.67-1.03; 52.3% of the RIS was achieved. In difficult airways, the C-MAC showed superior success rates, glottic visualisation, and less ELM compared to the Macintosh. Among experienced laryngoscopists, the C-MAC offered better glottic visualisation with less ELM than the Macintosh. The C-MAC provided better glottic visualisation and less ELM (GRADE: Very Low or Moderate), with improved success rates, glottic visualisation, and less ELM in difficult airways.


The SF-36 in multiple sclerosis: why basic assumptions must be tested.
To evaluate, in people with multiple sclerosis, two psychometric assumptions that must be satisfied for valid use of the medical outcomes study 36-item short form health survey (SF-36): the data are of high quality and, it is legitimate to generate scores for eight scales and two summary measures using the standard algorithms. SF-36 data from 438 people representing the full range of multiple sclerosis were examined (mean age 48; 70% women). Data quality (per cent missing data and computable scale and summary scores) were determined, six scaling criteria were tested to determine the legitimacy of generating the eight SF-36 scale scores using Likert's method of summed ratings, and two scaling criteria were tested to determine the appropriateness of the standard SF-36 algorithms for weighting scale scores to generate two summary measures. Data quality was excellent except in the most disabled subgroup where missing responses reached a maximum of 16.5% and summary scores could only be computed for 72%. There was clear support for the generation of SF-36 scale scores. Item response distributions were symmetric, item mean scores and variances were equivalent, corrected item-total correlations were high (range 0.46-0.85) and similar, and definite scaling success rates exceeded 96%. Nevertheless, there were notable floor or ceiling effects in four of the eight scales. Assumptions for generating two SF-36 summary measures were only partially satisfied. Although principal components analysis suggested a two component model, these components explained less than 60% of the total variance in SF-36 scales, and less than 75% of the variance in five of the eight scales. Moreover, scale to component correlations did not support the use of scale weights derived from United States population data. When using the SF-36 as a health measure in multiple sclerosis summary scores should be reported with caution.


Decreased cortical gyrification in major depressive disorder.
Early neurodevelopmental deviations, such as abnormal cortical folding patterns, are candidate biomarkers of major depressive disorder (MDD). We aimed to investigate the association of MDD with the local gyrification index (LGI) in each cortical region at the whole-brain level, and the association of the LGI with clinical characteristics of MDD. We obtained T1-weighted images from 234 patients with MDD and 215 healthy controls (HCs). The LGI values from 66 cortical regions in the bilateral hemispheres were automatically calculated according to the Desikan-Killiany atlas. We compared the LGI values between the MDD and HC groups using analysis of covariance, including age, sex, and years of education as covariates. The association between the clinical characteristics and LGI values was investigated in the MDD group. Compared with HCs, patients with MDD showed significantly decreased LGI values in the cortical regions, including the bilateral ventrolateral and dorsolateral prefrontal cortices, medial and lateral orbitofrontal cortices, insula, right rostral anterior cingulate cortex, and several temporal and parietal regions, with the largest effect size in the left pars triangularis (Cohen's f2 = 0.361; p = 1.78 × 10-13). Regarding the association of clinical characteristics with LGIs within the MDD group, recurrence and longer illness duration were associated with increased gyrification in several occipital and temporal regions, which showed no significant difference in LGIs between the MDD and HC groups. These findings suggest that the LGI may be a relatively stable neuroimaging marker associated with MDD predisposition.


Influence of galvanic vestibular stimulation on egocentric and object-based mental transformations.
The vestibular system analyses angular and linear accelerations of the head that are important information for perceiving the location of one's own body in space. Vestibular stimulation and in particular galvanic vestibular stimulation (GVS) that allow a systematic modification of vestibular signals has so far mainly been used to investigate vestibular influence on sensori-motor integration in eye movements and postural control. Comparatively, only a few behavioural and imaging studies have investigated how cognition of space and body may depend on vestibular processing. This study was designed to differentiate the influence of left versus right anodal GVS compared to sham stimulation on object-based versus egocentric mental transformations. While GVS was applied, subjects made left-right judgments about pictures of a plant or a human body presented at different orientations in the roll plane. All subjects reported illusory sensations of body self-motion and/or visual field motion during GVS. Response times in the mental transformation task were increased during right but not left anodal GVS for the more difficult stimuli and the larger angles of rotation. Post-hoc analyses suggested that the interfering effect of right anodal GVS was only present in subjects who reported having imagined turning themselves to solve the mental transformation task (egocentric transformation) as compared to those subjects having imagined turning the picture in space (object-based mental transformation). We suggest that this effect relies on shared functional and cortical mechanisms in the posterior parietal cortex associated with both right anodal GVS and mental imagery.


Clinical applications of coenzyme Q10.
Coenzyme Q10 (CoQ10) or ubiquinone was known for its key role in mitochondrial bioenergetics as electron and proton carrier; later studies demonstrated its presence in other cellular membranes and in blood plasma, and extensively investigated its antioxidant role. These two functions constitute the basis for supporting the clinical indication of CoQ10. Furthermore, recent data indicate that CoQ10 affects expression of genes involved in human cell signalling, metabolism and transport and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, ageing-related oxidative stress and carcinogenesis processes, and also a secondary effect of statin treatment. Many neurodegenerative disorders, diabetes, cancer, fibromyalgia, muscular and cardiovascular diseases have been associated with low CoQ10 levels. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral CoQ10 treatment is a frequent mitochondrial energizer and antioxidant strategy in many diseases that may provide a significant symptomatic benefit.


Short report: Rosette formation in Plasmodium ovale infection.
Red blood cells infected by mature stages of Plasmodium ovale obtained from a 56-year-old Thai patient formed rosettes readily with uninfected erythrocytes. Ex vivo, the ring stage-infected erythrocytes matured well under the in vitro conditions used for P. falciparum culture, and the infected erythrocytes formed rosettes when the parasites became mature trophozoites. These rosettes were stable and remained intact until completion of schizogony. Plasmodium ovale rosettes were similar to those formed by P. falciparum- and P. vivax-infected erythrocytes. Rosette formation appears to be a common property of three species of human plasmodia.


Usefulness of argon plasma coagulation for superficial esophageal squamous cell neoplasia in patients at high risk or with limited endoscopic resectability.
Endoscopic resection is the standard treatment for superficial esophageal squamous-cell neoplasia (SESCN). However, we encounter patients in whom endoscopic resection is difficult to perform. We retrospectively studied the usefulness of argon plasma coagulation (APC) in patients with SESCN. The study comprised 45 patients with SESCN (81 lesions) who underwent APC in our hospital from March 1999 through August 2016. Clinicopathological characteristics, treatment time, the presence or absence of metastasis and recurrence, adverse events, and outcomes were studied. The median follow-up was 40 months. The median age was 70 years. The tumor diameter was 10 mm or longer in 48 lesions and less than 10 mm in 33 lesions. The median treatment time was 22 minutes. The reasons for selecting APC were as follows: technical difficulty caused by the presence of metachronous multiple lesions in the radiation field after chemoradiotherapy or close proximity to the ulcer scar remaining after endoscopic treatment in 49 lesions (60.4%), and the presence of underlying diseases in 26 lesions (32.0%). Adverse events occurred in 2 patients (4.4%) who had hypoxemia due to over-sedation. Two lesions (2.5%) recurred locally but could be locally controlled by additional APC. No patient had metastasis or recurrence or died of esophageal neoplasia. The 3-year overall survival rate was 87.0%, and the 3-year recurrence-free survival rate was 97.2%. APC can be a useful treatment option for SESCN in patients with a limited life expectancy, poor performance status, or technical difficulty in resection of superficial neoplasms.