Limitations of functionally determined joint centers for the analysis of athletic human movement: a case study of the upper limb.
Much research is ongoing into improving the accuracy of functional algorithms to determine joint centers (JC), but there has been limited testing using human movement data. This paper is in three parts: Part 1, errors in determining JCs from real human movement data using the SCoRE method; Part 2, variability of marker combinations during a punch; Part 3, variability in the JC due to reconstruction. Results indicate determining the JC of the shoulder or elbow with a triad of markers per segment with an accuracy greater than 20 mm is unlikely. Part 2 suggests conducting a pilot study with abundant markers to obtain triads, which are most stable due to differences of 300-400% in variability between triads. Variability due to the choice of reference frame for reconstruction during the punch ranged from 2.5 to 13.8 mm for the shoulder and 1.5 to 21.1 mm for the elbow. It would appear more pertinent to enhance the practical methods in situ than to further improve theoretical accuracy of functional methods.


Telerehabilitation Use With Spinal Cord Injury: Occupational Therapists' Perspective.
Telerehabilitation provides people with spinal cord injury (SCI) an alternative mode of accessing specialized health care. Further research on occupational therapy practitioners' perspectives of telerehabilitation may provide additional evidence for clinical practice implementation. To explore urban occupational therapists' perspectives on the benefits of and barriers to telerehabilitation use with SCI. A qualitative study design using a demographic questionnaire and a single, individual semistructured interview. Thematic analyses included member checking, constant comparative analysis, triangulation, and self-description and self-reflexivity. Residential and community settings. Six occupational therapists with a range of experience in SCI rehabilitation were recruited using purposeful sampling. Six participants were interviewed, and four primary themes emerged: (1) communication, (2) personal factors, (3) benefits, and (4) barriers. Telerehabilitation offers numerous potential benefits for SCI intervention. This study provides an understanding of practitioner concerns and potential barriers to use. The results indicate that a hybrid model incorporating both in-person and distance-based treatment is likely optimal. What This Article Adds: Our results provide information that addresses practitioner concerns and recommendations for the use of telerehabilitation with people with SCI. As practitioner concerns are identified and addressed, telerehabilitation may increase in the U.S. health care system, potentially facilitating an alternative treatment delivery method for underserved populations.


Nursing student medication errors: a snapshot view from a school of nursing's quality and safety officer.
Medication errors are one of the most common types of errors in the health care arena. For more than a decade, health care providers have been challenged to improve patient safety outcomes, including medication administration issues. Nurse educators are challenged to provide didactic content and clinical experiences that will ensure students gain the knowledge necessary to administer medications in a safe manner. The aim of this article is to discuss nursing student medication errors identified at a university school of nursing, looking to categorize the errors into three areas: administration rights, system issues, and knowledge and understanding. Introducing nursing students to a reporting system early in their educational process can lead to increased transparency in error reporting and increased patient safety.


Evolution at a different pace: distinctive phylogenetic patterns of cone snails from two ancient oceanic archipelagos.
Ancient oceanic archipelagos of similar geological age are expected to accrue comparable numbers of endemic lineages with identical life history strategies, especially if the islands exhibit analogous habitats. We tested this hypothesis using marine snails of the genus Conus from the Atlantic archipelagos of Cape Verde and Canary Islands. Together with Azores and Madeira, these archipelagos comprise the Macaronesia biogeographic region and differ remarkably in the diversity of this group. More than 50 endemic Conus species have been described from Cape Verde, whereas prior to this study, only two nonendemic species, including a putative species complex, were thought to occur in the Canary Islands. We combined molecular phylogenetic data and geometric morphometrics with bathymetric and paleoclimatic reconstructions to understand the contrasting diversification patterns found in these regions. Our results suggest that species diversity is even lower than previously thought in the Canary Islands, with the putative species complex corresponding to a single species, Conus guanche. One explanation for the enormous disparity in Conus diversity is that the amount of available habitat may differ, or may have differed in the past due to eustatic (global) sea level changes. Historical bathymetric data, however, indicated that sea level fluctuations since the Miocene have had a similar impact on the available habitat area in both Cape Verde and Canary archipelagos and therefore do not explain this disparity. We suggest that recurrent gene flow between the Canary Islands and West Africa, habitat losses due to intense volcanic activity in combination with unsuccessful colonization of new Conus species from more diverse regions, were all determinant in shaping diversity patterns within the Canarian archipelago. Worldwide Conus species diversity follows the well-established pattern of latitudinal increase of species richness from the poles towards the tropics. However, the eastern Atlantic revealed a striking pattern with two main peaks of Conus species richness in the subtropical area and decreasing diversities toward the tropical western African coast. A Random Forests model using 12 oceanographic variables suggested that sea surface temperature is the main determinant of Conus diversity either at continental scales (eastern Atlantic coast) or in a broader context (worldwide). Other factors such as availability of suitable habitat and reduced salinity due to the influx of large rivers in the tropical area also play an important role in shaping Conus diversity patterns in the western coast of Africa.


Mapping of the ocean surface wind by ocean acoustic interferometers.
Measurements of marine surface winds are crucial to understanding mechanical and thermodynamic forces on the ocean. Satellite measurements of surface winds provide global coverage but are problematic at high wind speeds. Acoustic techniques of wind speed retrieval, and even for tracking hurricanes, have been suggested as an alternative since wind is a strong source of ambient noise in the ocean. Such approaches involve near-local measurements with bottom-mounted hydrophones located close to the area of interest. This paper suggests a complementary approach: measuring directivity of low-frequency ambient noise in the horizontal plane. These measurements would employ long vertical line arrays (VLAs) spanning a significant portion of the ocean waveguide. Two VLAs separated by a distance of some tens of kilometers and coherently measuring acoustic pressure form a single ocean interferometer. By sampling the area of interest from different perspectives with at least two interferometers, marine surface winds might be mapped over horizontal scales of the order of 1000 km with about 10 km resolution (more specifically, the 10 km resolution here means that contribution from the basis functions representing surface wind field with the scale of spatial variations of the order of 10 km can be resolved; independent retrieval of the wind within 10(4) cells of a corresponding grid is hardly possible). An averaging time required to overcome statistical variability in the noise field is estimated to be about 3 h. Numerical simulations of propagation conditions typical for the North Atlantic Ocean are presented.


Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin.
The processes by which ErbB-3, an inactive tyrosine kinase, exerts its biological effects are poorly understood. Using the yeast two-hybrid system, we have isolated an ErbB-3 binding protein (Ebp1) that interacts with the juxtamembrane domain of ErbB-3. This protein is identical to that predicted to be encoded for by the human PA2G4 gene. Ebp1 is the human homologue of a previously identified cell cycle-regulated mouse protein p38-2G4. Two transcripts of ebp1 mRNA (1.7 and 2.2 kb) were detected in several normal human organs. The interaction of Ebp1 with ErbB-3 was examined in vitro and in vivo. The first 15 amino acids of the juxtamembrane domain of ErbB-3 were essential for Ebp1 binding in vitro. Treatment of AU565 cells with the ErbB-3 ligand heregulin resulted in dissociation of Ebp1 from ErbB-3. Ebp1 translocated from the cytoplasm into the nucleus following heregulin stimulation. These findings suggest that Ebp1 may be a downstream member of an ErbB-3-regulated signal transduction pathway.


The neuropathic pain triad: neurons, immune cells and glia.
Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced nociceptive thresholds so that normally innocuous stimuli produce pain. The development of neuropathic pain involves not only neuronal pathways, but also Schwann cells, satellite cells in the dorsal root ganglia, components of the peripheral immune system, spinal microglia and astrocytes. As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain.


Airway smooth muscle shortening in excised canine lung lobes.
To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)


High rates of nitrogen cycling in volcanic soils from Chilean grasslands.
There are over one million hectares of pasture in Chile, and 80% and 50% of the country's milk and meat comes from 72% of this area, situated in the lake region of southern Chile. The soils are volcanic and a major characteristic is that they have very high organic matter (OM) contents with the potential to support plant growth with only moderate levels of added nitrogen (N). To understand better the potential fertility of these soils in order to maximise production and minimise losses of N, we undertook studies using the stable isotope of N ((15)N) to resolve the rates of the main internal N cycling processes in three soils representing the two main volcanic soil types: Osorno and Chiloé (Andisol) and Cudico (Ultisol). We also assessed the longer-term potential of these soils to sustain N release using anaerobic incubation. Gross rates (µg N g(-1) day(-1)) of mineralisation were 27.9, 27.1 and 15.5 and rates of immobilisation were 5.9, 12.0 and 6.3 for Osorno, Chiloé and Cudico, respectively, implying high rates of net mineralisation in these soils. This was confirmed by anaerobic incubation which gave potential seasonal net mineralisation indices of 1225, 1059 and 450 kg N ha(-1) in the top 10 cm soil layers of the three soils. However, plant production may still benefit from added N, as the release of N from organic sources may not be closely synchronised with crop demand. The low rates of nitrification that we found with these acidic soils suggest that the more mobile N (viz. nitrate-N) would be in limited supply and plants would have to compete for the less mobile ammonium-N with the soil microbial biomass. Nitrogen was mineralised in appreciable amounts even down to 60 cm depth, so that leaching could become significant, particularly if the soils were limed, which could enhance nitrification and N mobility through the soil profile.


Induction and evolution of cytomegalovirus-specific CD4+ T cell clonotypes in rhesus macaques.
CMV infection induces robust CD4+ T cell responses in immunocompetent hosts that orchestrate immune control of viral replication, dissemination, and disease. In this study, we characterized the clonotypic composition of CD4+ T cell populations specific for rhesus CMV (RhCMV) in chronically infected adult rhesus macaques (RM) and in juvenile RM undergoing primary RhCMV infection and subsequent secondary challenge with RhCMV. In adult RM with established chronic infection, RhCMV-specific CD4+ T cell populations exhibited stable, pauciclonal structures with skewed hierarchies dominated by two or three clonotypes. During primary infection, in contrast, the initial RhCMV-specific CD4+ T cell populations were highly polyclonal and progressive evolution to the chronic pattern manifest in adults occurred over the ensuing 2-3 years. Clear patterns of clonal succession were observed during this maturation process, such that clonotypes present in the acute phase were largely replaced over time. However, rechallenge with RhCMV expanded virus-specific CD4+ T cell clonotypes identified solely during acute infection. These findings indicate that, during persistent viral infection, substantial selection pressures and ongoing clonotype recruitment shape the specific CD4+ T cell repertoire and that rapidly exhausted or superseded clonotypes often remain within the memory T cell pool.


Noise Control Capability of Structurally Integrated Resonator Arrays in a Foam-Treated Cylinder.
Corrugated-core sandwich structures with integrated acoustic resonator arrays have been of recent interest for launch vehicle noise control applications. Previous tests and analyses have demonstrated the ability of this concept to increase sound absorption and reduce sound transmission at low frequencies. However, commercial aircraft manufacturers often require fibrous or foam blanket treatments for broadband noise control and thermal insulation. Consequently, it is of interest to further explore the noise control benefit and trade-offs of structurally integrated resonators when combined with various degrees of blanket noise treatment in an aircraft-representative cylindrical fuselage system. In this study, numerical models were developed to predict the effect of broadband and multi-tone structurally integrated resonator arrays on the interior noise level of cylindrical vibroacoustic systems. Foam layers with a range of thicknesses were applied near the inside surface of the cylinder to represent different degrees of conventional blanket treatments. Excitations including point force as well as harmonic and random fluctuating pressure fields were considered. The results suggest that structurally integrated resonators can be tuned to address a variety of noise control requirements and effectively used in conjunction with foam blanket noise treatments, but their relative benefit is reduced when thicker foam treatments are used.


Survived so what? Identifying priorities for research with children and families post-paediatric intensive care unit.
The involvement of patients and the public in the development, implementation and evaluation of health care services and research is recognized to have tangible benefits in relation to effectiveness and credibility. However, despite >96% of children and young people surviving critical illness or injury, there is a paucity of published reports demonstrating their contribution to informing the priorities for aftercare services and outcomes research. We aimed to identify the service and research priorities for Paediatric Intensive Care Unit survivors with children and young people, their families and other stakeholders. We conducted a face-to-face, multiple-stakeholder consultation event, held in the Midlands (UK), to provide opportunities for experiences, views and priorities to be elicited. Data were gathered using write/draw and tell and focus group approaches. An inductive content analytical approach was used to categorize and conceptualize feedback. A total of 26 individuals attended the consultation exercise, including children and young people who were critical care survivors; their siblings; parents and carers; health professionals; academics; commissioners; and service managers. Consultation findings indicated that future services, interventions and research must be holistic and family-centred. Children and young people advisors reported priorities that focused on longer-term outcomes, whereas adult advisors identified priorities that mapped against the pathways of care. Specific priorities included developing and testing interventions that address unmet communication and information needs. Furthermore, initiatives to optimize the lives and longer-term functional and psycho-social outcomes of Paediatric Intensive Care Unit survivors were identified. This consultation exercise provides further evidence of the value of meaningful patient and public involvement in identifying the priorities for research and services for Paediatric Intensive Care Unit survivors and illuminates differences in proposed priorities between children, young people and adult advisors.


Health workforce demography: a framework to improve understanding of the health workforce and support achievement of the Sustainable Development Goals.
The ambition of universal health coverage entails estimation of the number, type and distribution of health workers required to meet the population need for health services. The demography of the population, including anticipated or estimated changes, is a factor in determining the 'universal' needs for health and well-being. Demography is concerned with the size, breakdown, age and gender structure and dynamics of a population. The same science, and its robust methodologies, is equally applicable to the demography of the health workforce itself. For example, a large percentage of the workforce close to retirement will impact availability, a geographically mobile workforce has implications for health coverage, and gender distribution in occupations may have implications for workforce acceptability and equity of opportunity. In a world with an overall shortage of health workers, and the expectation of increasing need as a result of both population growth in the global south and population ageing in the global north, studying and understanding demographic characteristics of the workforce can help with future planning. This paper discusses the dimensions of health worker demography and considers how demographic tools and techniques can be applied to the analysis of the health labour market. A conceptual framework is introduced as a step towards the application of demographic principles and techniques to health workforce analysis and planning exercises as countries work towards universal health coverage, the reduction of inequities and national development targets. Some illustrative data from Nepal and Finland are shown to illustrate the potential of this framework as a simple and effective contribution to health workforce planning.


Evaluation of reference values of standard semen parameters in fertile Egyptian men.
The reference values of human semen, published in the WHO's latest edition in 2010, were lower than those previously reported. The objective of this study was to evaluate reference values of standard semen parameters in fertile Egyptian men. This cross-sectional study included 240 fertile men. Men were considered fertile when their wives had recent spontaneous pregnancies with time to pregnancy (TTP) ≤12 months. The mean age of fertile men was 33.8 ± 0.5 years (range 20-55 years). The 5th percentiles (95% confidence interval) of macroscopic semen parameters were 1.5 ml for volume and 7.2 for pH. The 5th percentiles of microscopic parameters were 15 million/ml for sperm concentration, 30 million per ejaculate for total sperm count, 50% for total motility, 40% for progressive motility, 62% for vitality, 4% for normal sperm forms and 0.1 million/ml for seminal leucocyte counts. In conclusion, fertile Egyptian men had higher reference values of sperm total motility, progressive motility and vitality, and lower reference values for total sperm counts as compared to those determined by the latest edition of the WHO laboratory manual in 2010. Other semen parameters were identical to those defined by the WHO 2010 manual.


Evaluation of near infrared fluorescent labeling of monoclonal antibodies as a tool for tissue distribution.
The pharmacokinetic (PK) behavior of monoclonal antibodies (mAbs) is influenced by target-mediated drug disposition, off-target effects, antidrug antibody-mediated clearance, and interaction with fragment-crystallizable domain (Fc) receptors such as neonatal Fc receptor. All of these interactions hold the potential to impact mAb biodistribution. Near infrared (NIR) fluorescent probes offer an approach complementary to radionuclides to characterize drug disposition. Notably, the use of FDA-approved IRDye800 (IR800; LI-COR, Lincoln, NE) as a protein-labeling agent in preclinical work holds the potential for quantitative tissue analysis. Here, we tested the utility of the IR800 dye as a quantitative mAb tracer during pharmacokinetic analysis in both plasma and tissues using a model mouse monoclonal IgG1 (8C2) labeled with ≤1.5 molecules of IR800. The plasma PK parameters derived from a mixture of IR800-8C2 and 8C2 dosed intravenously to C57BL/6 mice at 8 mg/kg exhibited a large discrepancy in exposure depending on the method of quantitation [CLplasma = 8.4 ml/d per kilogram (NIR fluorescence detection) versus 2.5 ml/d per kilogram (enzyme-linked immunosorbent assay)]. The disagreement between measurements suggests that the PK of 8C2 is altered by addition of the IR800 dye. Additionally, direct fluorescence analysis of homogenized tissues revealed several large differences in IR800-8C2 tissue uptake when compared with a previously published study using [(125)I]8C2, most notably an over 4-fold increase in liver concentration. Finally, the utility of IR800 in combination with whole body imaging was examined by comparison of IR800-8C2 levels observed in animal sagittal cross-sections to those measured in homogenized tissues. Our results represent the first PK analysis in both mouse plasma and tissues of an IR800-mAb conjugate and suggest that mAb disposition is significantly altered by IR800 conjugation to 8C2.


A computer-controlled infrared eclipse telescope.
An f/8, chopped, dual beam, gyroscopically pointed telescope has been constructed for use in obtaining infrared (7-13 micro) observations of the spectrum of the thermal emission of the solar corona. The instrument employs a scanning Michelson interferometer with germanium beam splitter and a germanium bolometer operated at 2 K. A small general purpose digital computer is used for experiment control and data processing. The computer, using reference signals from the chopper, controls the position of the moving interferometer mirror (through a stepper motor), and the operation of an A/D converter enabling rapid measurements of the bolometer output to be made. Synchronous detection, necessary to minimize sky background radiation, is accomplished within the computer. The resulting interferograms are stored on magnetic tape for future processing and displayed on an x-y recorder. A fourier transformed spectrum may be generated on operator request in nearly real time.


Pulse-preserving broadband visible supercontinuum generation in all-normal dispersion tapered suspended-core optical fibers.
Recently, coherent pulse-preserving and octave-spanning supercontinuum (SC) generation was theoretically predicted and experimentally shown in photonic crystal fibers (PCFs) with all-normal dispersion behavior. Since this behavior is due only to the all-normal dispersion profile and not to the photonic crystal cladding, other all-normal optical waveguides exhibit these properties as well. We extend this concept to suspended-core fibers and optical nanofibers and show experimental demonstrations of this way of SC generation. We show that optical suspended-core fibers and optical nanofibers of appropriate dimensions exhibit all-normal dispersion and address octave-spanning single pulse SC generation in the visible (VIS) and ultra violet (UV) wavelength range. In addition, we discuss the feasibility of fiber taper transitions for suitable input coupling schemes in sub-micron diameter fibers and show the importance of short adiabatic transition profiles for utilizing high-energy pulses to obtain maximum spectral broadening. They are essential for coherent broadband UV SC generation in optical nanofibers.


Supervision of psychosocial skills in genetic counseling.
Little has been written about how genetic counseling supervisors can help students develop psychosocial skills in their clinical rotations. The authors describe several approaches supervisors can use, ranging from preventive measures (e.g., normalizing anxiety), to skill-enhancing interventions (e.g., modeling and thinking aloud), to more direct approaches (e.g., immediacy, confrontation) that may be necessary for students who are reluctant, or even resistant, to using psychosocial skills with their clients.


Two-field surface pattern control via marginally stable magnetorheological elastomers.
The stability and post-bifurcation of a non-linear magnetoelastic film/substrate block is experimentally exploited to obtain active control of surface roughness. The non-intuitive interplay between magnetic field and elastic deformation owes to material and geometry selection, namely a ferromagnetic particle composite film bonded on a compliant passive foundation. Cooperation of the two otherwise independent loading mechanisms-mechanical pre-compression and magnetic field-allows one to bring the structure near a marginally stable state and then destabilize it with either magnetic or mechanical fields. We demonstrate for the first time that the critical magnetic field is a decreasing function of pre-compression and vice versa. The experimental results are then probed successfully with full-field finite element simulations at large strains and magnetic fields. The magnetoelastic coupling allows for reversible on/off control of surface wrinkling under adjustable critical magnetic and mechanical fields, thus this study constitutes a first step towards realistic active haptic and morphing devices.


Functional brain mapping of the relaxation response and meditation.
Meditation is a conscious mental process that induces a set of integrated physiologic changes termed the relaxation response. Functional magnetic resonance imaging (fMRI) was used to identify and characterize the brain regions that are active during a simple form of meditation. Significant (p<10(-7)) signal increases were observed in the group-averaged data in the dorsolateral prefrontal and parietal cortices, hippocampus/parahippocampus, temporal lobe, pregenual anterior cingulate cortex, striatum, and pre- and post-central gyri during meditation. Global fMRI signal decreases were also noted, although these were probably secondary to cardiorespiratory changes that often accompany meditation. The results indicate that the practice of meditation activates neural structures involved in attention and control of the autonomic nervous system.


Genome-wide associations for milk production and somatic cell score in Holstein-Friesian cattle in Ireland.
Contemporary dairy breeding goals have broadened to include, along with milk production traits, a number of non-production-related traits in an effort to improve the overall functionality of the dairy cow. Increased indirect selection for resistance to mastitis, one of the most important production-related diseases in the dairy sector, via selection for reduced somatic cell count has been part of these broadened goals. A number of genome-wide association studies have identified genetic variants associated with milk production traits and mastitis resistance, however the majority of these studies have been based on animals which were predominantly kept in confinement and fed a concentrate-based diet (i.e. high-input production systems). This genome-wide association study aims to detect associations using genotypic and phenotypic data from Irish Holstein-Friesian cattle fed predominantly grazed grass in a pasture-based production system (low-input). Significant associations were detected for milk yield, fat yield, protein yield, fat percentage, protein percentage and somatic cell score using separate single-locus, frequentist and multi-locus, Bayesian approaches. These associations were detected using two separate populations of Holstein-Friesian sires and cows. In total, 1,529 and 37 associations were detected in the sires using a single SNP regression and a Bayesian method, respectively. There were 103 associations in common between the sires and cows across all the traits. As well as detecting associations within known QTL regions, a number of novel associations were detected; the most notable of these was a region of chromosome 13 associated with milk yield in the population of Holstein-Friesian sires. A total of 276 of novel SNPs were detected in the sires using a single SNP regression approach. Although obvious candidate genes may not be initially forthcoming, this study provides a preliminary framework upon which to identify the causal mechanisms underlying the various milk production traits and somatic cell score. Consequently this will deepen our understanding of how these traits are expressed.


The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis.
RBM and DAZ/SPGY are two families of genes located on the Y chromosome that encode proteins containing RNA-binding motifs, and both have been described as candidate human spermatogenesis genes. Transmission of deletions from father to son has been observed in the case of DAZ, but neither gene family has been shown to be essential for spermatogenesis in human males. The DAZ/SPGY genes are particularly amenable to a knockout approach, as they are found on the Y chromosome in Old World primates and apes, but in other mammals, they are represented only by an autosomal gene, DAZLA, which is also present in Old World primates and apes. It has also been shown that a Dazla homologue is essential for spermatogenesis in Drosophila. Here we show that Dazla protein is cytoplasmic in male and female germ cells, unlike the nuclear RBM protein. Disruption of the Dazla gene leads to loss of germ cells and complete absence of gamete production, demonstrating that Dazla is essential for the differentiation of germ cells.


Mouse models for mitochondrial disease.
Mutations in mitochondrial genes encoded by both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes have been implicated in a wide range of neuromuscular diseases. MtDNA base substitution and rearrangement mutations generally inactivate one or more tRNA or rRNA genes and can cause myopathy, cardiomyopathy, cataracts, growth retardation, diabetes, etc. nDNA mutations can cause Leigh syndrome, cardiomyopathy, and nephropathy, due to defects in oxidative phosphorylation (OXPHOS) enzyme complexes; cartilage-hair hypoplasia (CHH) and mtDNA depletion syndrome, through defects in mitochondrial nucleic acid metabolism; and ophthalmoplegia with multiple mtDNA deletions, caused by adenine nucleotide translocator-1 (ANT1) mutations. Mouse models have been prepared that recapitulate a number of these diseases. The mtDNA 16S rRNA chloramphenicol (CAP) resistance mutation was introduced into the mouse female germline and caused cataracts and rod and cone abnormalities in chimeras and neonatal lethal myopathy and cardiomyopathy in mutant animals. A mtDNA deletion was introduced into the mouse germline and caused myopathy, cardiomyopathy, and nephropathy. Conditional inactivation of the nDNA mitochondrial transcription factor (Tfam) gene in the heart resulted in neonatal lethal cardiomyopathy, while its inactivation in the pancreatic beta-cells caused diabetes. The ATP/ADP ratio was implicated in mitochondrial diabetes through transgenic modification of the beta-cell ATP-sensitive K(+) channel (K(ATP)). Mutational inactivation of the mouse Ant1 gene resulted in myopathy, cardiomyopathy, and multiple mtDNA deletions in association with elevated reactive oxygen species (ROS) production. Inactivation of uncoupler proteins (Ucp) 1-3 revealed that mitochondrial Delta Psi regulated ROS production. The role of mitochondrial ROS toxicity in disease and aging was confirmed by inactivating glutathione peroxidase (GPx1), resulting in growth retardation, and by total and partial inactivation of Mn superoxide dismutase (MnSOD; Sod2), resulting in neonatal lethal dilated cardiomyopathy and accelerated apoptosis in aging, respectively. The importance of mitochondrial ROS in degenerative diseases and aging was confirmed by treating Sod2 -/- mice and C. elegans with catalytic antioxidant drugs.


Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury.
Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target.


mTOR: more targets of resveratrol?
Resveratrol (RSV) is a natural polyphenol produced by plants and is proposed to have multiple beneficial effects on health. In recent years, the interest in this molecule has increased nearly exponentially following the major findings that RSV (I) is chemo-preventive in some cancer models, (II) is cardio-protective and (III) has positive effects on metabolism in mammals and increases lifespan in lower organisms. Mechanistic target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. As a part of the mTORC1 and mTORC2 complexes, the mTOR kinase plays a key role in several pathways involved in cancer and metabolic diseases. Recent studies suggest that modulation of the mTOR signalling pathway could play an important role in mediating the beneficial effects of RSV. Therefore, this review summarises the current findings regarding RSV and its inhibition/activation of the proteins in the mTOR pathway, and thereby propose the proteins of the mTOR cascade to be primary targets for RSV. RSV affects many different targets related to mTOR, and it is not clear which is most relevant. However, most frequently, RSV is found to inhibit the activity of the mTOR pathway proteins, and to activate AMPK and LKB1, which can suppress mTOR signalling. Thus, it appears that RSV plays a role in modulation of proteins of the mTOR pathway although more research is still needed to fully understand the interaction.


Associations of Social Isolation with Anxiety and Depression During the Early COVID-19 Pandemic: A Survey of Older Adults in London, UK.
The COVID-19 pandemic is imposing a profound negative impact on the health and wellbeing of societies and individuals, worldwide. One concern is the effect of social isolation as a result of social distancing on the mental health of vulnerable populations, including older people. Within six weeks of lockdown, we initiated the CHARIOT COVID-19 Rapid Response Study, a bespoke survey of cognitively healthy older people living in London, to investigate the impact of COVID-19 and associated social isolation on mental and physical wellbeing. The sample was drawn from CHARIOT, a register of people over 50 who have consented to be contacted for aging related research. A total of 7,127 men and women (mean age=70.7 [SD=7.4]) participated in the baseline survey, May-July 2020. Participants were asked about changes to the 14 components of the Hospital Anxiety Depression scale (HADS) after lockdown was introduced in the UK, on 23rd March. A total of 12.8% of participants reported feeling worse on the depression components of HADS (7.8% men and 17.3% women) and 12.3% reported feeling worse on the anxiety components (7.8% men and 16.5% women). Fewer participants reported feeling improved (1.5% for depression and 4.9% for anxiety). Women, younger participants, those single/widowed/divorced, reporting poor sleep, feelings of loneliness and who reported living alone were more likely to indicate feeling worse on both the depression and/or anxiety components of the HADS. There was a significant negative association between subjective loneliness and worsened components of both depression (OR 17.24, 95% CI 13.20, 22.50) and anxiety (OR 10.85, 95% CI 8.39, 14.03). Results may inform targeted interventions and help guide policy recommendations in reducing the effects of social isolation related to the pandemic, and beyond, on the mental health of older people.


Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation.
For a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1-ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.


Metformin-Loaded Hyaluronic Acid Nanostructure for Oral Delivery.
The objective of this study was to develop a nanodelivery system containing a mucoadhesive polymer hyaluronic acid (HA) for oral delivery. Metformin was used as a model drug. Blank and drug-loaded HA nanostructures were prepared by precipitation method and characterized for particle size (PS), zeta potential (ZP), physical stability (over 65 days), surface morphology, moisture content, and physical state of the drug in the nanostructures. The cytotoxicity and hemolysis potential of the delivery system was assessed in Caco-2 cells and whole human blood, respectively. The in vitro release of metformin and its uptake in Caco-2 cells was evaluated using high-performance liquid chromatography. Ex vivo permeability of metformin was measured through goat intestinal membrane. The nanoparticles were physically stable and neutrally charged with an average PS of 114.53 ± 12.01 nm. This nanodelivery system existed as nanofibers containing metformin in a crystalline state. This delivery system released the drug rapidly with > 50% of metformin released within 1 h. Cellular uptake studies on Caco-2 cells indicated higher uptake of metformin from nanoparticle as compared to metformin in solution, up to first 45 min. Ex vivo permeability studies on the other hand showed a higher metformin permeability from solution relative to that from nanoparticles through the goat intestinal membrane. Metformin nanoparticles were non-toxic at therapeutic concentrations in Caco-2 cells and showed no hemolytic effect to RBCs. This study indicates the preparation, characterization, as well as the potential use of HA nanostructures for oral delivery.


A spatial light modulator based on fused-silica plates for adaptive feedback control of intense femtosecond laser pulses.
A novel spatial light modulator (SLM) made of an array of fused-silica plates was developed for the purpose of feedback control for intense femtosecond laser pulses over a wide spectral range. Dispersion compensation for 20-fs pulses from a Ti:sapphire oscillator was successfully demonstrated using the SLM with an adaptive feedback control system. The SLM was also applied to the output pulses from a Ti:sapphire amplifier for compensation of material.


Salmonella cholerasuis bacteremia and mycotic aneurysm of abdominal aorta--report of five cases.
From August 1986 to October 1987, there were 5 cases of primary mycotic aneurysm of the lower abdominal aorta in Chang Gung Memorial Hospital at Kaoshiung. All patients were proved to have Salmonella cholerasuis (Sal. chol.) septicemia by blood culture. The ages ranged from 60 to 80 years old, the mean age was 71.6 years old. The male to female ratio was 4 to 1, 3 patients had diabetes mellitus (DM) and 3 had hypertension. The duration of symptoms lasted from 1 week to 2 months before diagnosis. Clinically, all patients had sepsis with fever, chills, leucocytosis, and complained of pain in the lower abdomen (80%), at flank (20%) or low back (20%). Abdominal tenderness was present in 3 (60%). Two patients underwent surgery, 1 expired during the operation, the other expired 1 month after operation because of retroperitoneal abscess and sepsis. Three were discharged in septic shock and expired within 1 day. The mortality rate was 100%. The diagnosis of complicated aneurysm of the lower abdominal aorta was established in all by computed tomography (CT). In conclusion, when there are clinical manifestations of sepsis, positive blood culture for Sal. chol., and pain or tenderness in the lower abdomen, flank area or back, one should consider the possibility of mycotic aneurysm of the lower abdominal aorta. Although the prognosis is poor, early surgical intervention may improve the outcome. And the diagnosis is best established by CT.


Creative or created: using anecdotes to investigate animal cognition.
In non-human animals, creative behaviour occurs spontaneously only at low frequencies, so is typically missed by standardised observational methods. Experimental approaches have tended to rely overly on paradigms from child development or adult human cognition, which may be inappropriate for species that inhabit very different perceptual worlds and possess quite different motor capacities than humans. The analysis of anecdotes offers a solution to this impasse, provided certain conditions are met. To be reliable, anecdotes must be recorded immediately after observation, and only the records of scientists experienced with the species and the individuals concerned should be used. Even then, interpretation of a single record is always ambiguous, and analysis is feasible only when collation of multiple records shows that a behaviour pattern occurs repeatedly under similar circumstances. This approach has been used successfully to study a number of creative capacities of animals: the distribution, nature and neural correlates of deception across the primate order; the occurrence of teaching in animals; and the neural correlates of several aptitudes--in birds, foraging innovation, and in primates, innovation, social learning and tool-use. Drawing on these approaches, we describe the use of this method to investigate a new problem, the cognition of the African elephant, a species whose sheer size and evolutionary distance from humans renders the conventional methods of comparative psychology of little use. The aim is both to chart the creative cognitive capacities of this species, and to devise appropriate experimental methods to confirm and extend previous findings.


Patient perception of pain care in hospitals in the United States.
Assessment of patients' perception of pain control in hospitals in the United States. Limited data are available regarding the quality of pain care in the hospitalized patient. This is particularly valid for data that allow for comparison of pain outcomes from one hospital to another. Such data are critical for numerous reasons, including allowing patients and policy-makers to make data-driven decisions, and to guide hospitals in their efforts to improve pain care. The Hospital Quality Alliance was recently created by federal policy makers and private organizations in conjunction with the Centers for Medicare and Medicare Services to conduct patient surveys to evaluate their experience including pain control during their hospitalization. In March 2008, the results of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was released for review for health care providers and researchers. This survey includes a battery of questions for patients upon discharge from the hospital including pain-related questions and patient satisfaction that provide valuable data regarding pain care nationwide. This study will review the results from the pain questions from this available data set and evaluate the performance of these hospitals in pain care in relationship to patient satisfaction. Furthermore, this analysis will be providing valuable information on how hospital size, geographic location and practice setting may play a role in pain care in US hospitals. The data indicates that 63% of patients gave a high rating of global satisfaction for their care, and that an additional 26% of patients felt that they had a moderate level of global satisfaction with the global quality of their care. When correlated to satisfaction with pain control, the relationship with global satisfaction and "always" receiving good pain control was highly correlated (r >0.84). In respect to the other HCAHPS components, we found that the patient and health care staff relationship with the patient is also highly correlated with pain relief (r >0.85). The patients' reported level of pain relief was significantly different based upon hospital ownership, with government owned hospitals receiving the highest pain relief, followed by nonprofit hospitals, and lastly proprietary hospitals. Hospital care acuity also had an impact on the patient's perception of their pain care; patients cared for in acute care hospitals had lower levels of satisfaction than critical access hospitals. The results of this study are a representation of the experiences of patients in US hospitals with regard to pain care specifically and the need for improved methods of treating and evaluating pain care. This study provides the evidence needed for hospitals to make pain care a priority in to achieve patient satisfaction throughout the duration of their hospitalization. Furthermore, future research should be developed to make strategies for institutions and policy-makers to improve and optimize patient satisfaction with pain care.


Achieving biopolymer synergy in systems chemistry.
Synthetic and materials chemistry initiatives have enabled the translation of the macromolecular functions of biology into synthetic frameworks. These explorations into alternative chemistries of life attempt to capture the versatile functionality and adaptability of biopolymers in new orthogonal scaffolds. Information storage and transfer, however, so beautifully represented in the central dogma of biology, require multiple components functioning synergistically. Over a single decade, the emerging field of systems chemistry has begun to catalyze the construction of mutualistic biopolymer networks, and this review begins with the foundational small-molecule-based dynamic chemical networks and peptide amyloid-based dynamic physical networks on which this effort builds. The approach both contextualizes the versatile approaches that have been developed to enrich chemical information in synthetic networks and highlights the properties of amyloids as potential alternative genetic elements. The successful integration of both chemical and physical networks through β-sheet assisted replication processes further informs the synergistic potential of these networks. Inspired by the cooperative synergies of nucleic acids and proteins in biology, synthetic nucleic-acid-peptide chimeras are now being explored to extend their informational content. With our growing range of synthetic capabilities, structural analyses, and simulation technologies, this foundation is radically extending the structural space that might cross the Darwinian threshold for the origins of life as well as creating an array of alternative systems capable of achieving the progressive growth of novel informational materials.


Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging.
Prominent immune alterations associated with aging include the loss of naïve T-cell numbers, diversity and function. While genetic contributors and mechanistic details in the aging process have been addressed in multiple studies, the role of environmental agents in immune aging remains incompletely understood. From the standpoint of environmental infectious agents, latent cytomegalovirus (CMV) infection has been associated with an immune risk profile in the elderly humans, yet the cause-effect relationship of this association remains unclear. Here we present direct experimental evidence that mouse CMV (MCMV) infection results in select T-cell subset changes associated with immune aging, namely the increase of relative and absolute counts of CD8 T-cells in the blood, with a decreased representation of the naïve and the increased representation of the effector memory blood CD8 T-cells. Moreover, MCMV infection resulted in significantly weaker CD8 responses to superinfection with Influenza, Human Herpes Virus I or West-Nile-Virus, even 16 months following MCMV infection. These irreversible losses in T-cell function could not be observed in uninfected or in vaccinia virus-infected controls and were not due to the immune-evasive action of MCMV genes. Rather, the CD8 activation in draining lymph nodes upon viral challenge was decreased in MCMV infected mice and the immune response correlated directly to the frequency of the naïve and inversely to that of the effector cells in the blood CD8 pool. Therefore, latent MCMV infection resulted in pronounced changes of the T-cell compartment consistent with impaired naïve T-cell function.


The effect of minimal dietary changes with raisins in NAFLD patients with non-significant fibrosis: a randomized controlled intervention.
Aiming at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis, 55 patients with NAFLD were enrolled in a randomized controlled clinical trial. Patients were assigned into two isocaloric dietary treatment groups for 24 weeks: (a) nutritional counseling (Control arm, N = 27), (b) nutritional counseling with currants included (two fruit servings, 36 g per day), substituting snacks of similar caloric content (Currant arm, N = 28). Clinical tests, anthropometrics, inflammatory and oxidative stress markers were conducted pre- and post-intervention. A total of 50 patients completed the trial. Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels, these being significantly decreased only in Currant patients. Body weight, BMI, HbA1c, CRP and EUS values decreased in both arms, differences being insignificant between the two arms post-intervention. Participants in the Currant arm had significantly reduced total body fat, WC and trunk fat. Ultrasound scanning improved significantly in patients snacking currants daily. Also, volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids. Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this. Post-intervention, the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm. Conclusively, minimal modifications in snacking choices, such as the inclusion of dried grapes in diet, are beneficial in NAFLD patients with non-significant fibrosis.


Influence of an innovative and promising gas clarification process on the quality of stored extra virgin olive oils.
Filtration of extra virgin olive oil is a process that may improve preservation of the quality during storage. In the current study, different aliquots of extra virgin olive oils were subjected to filtration with a traditional filter press or an innovative patented alternative process of clarification by insufflating inert gas such as nitrogen and argon; all treated samples and, as control unfiltered ones, were stored for one year to evaluate the effects of these technologies on the quality of oil during shelf-life. Basic quality indexes, diglycerides, phenolics and volatiles, as well as the sensory characteristics of samples, were determined at 4 month intervals during storage. According to the volatile compounds, phenolics and sensory analysis, the novel technique had a beneficial effect on the storage of extra virgin olive oils; accordingly, this process could be exploited by the olive oil industry.


Optical transmission properties of Pentelic and Paros marble.
Ancient Greek and Roman sources report that the statue of Zeus in Olympia had a head, and in particular eyes, similar to the description of Zeus by Homer, so we think that the statue was visible to the human eye. Since the temple was 12 m high, and had a small door and no windows, the illumination of the statue by conventional media is questionable. The aim of this paper is to characterize the optical transmission of Paros and Pentelic marble to demonstrate that it was possible to have the Zeus temple illuminated through the roof marble tiles. Spectral absolute transmittance measurements were taken in samples with different thicknesses using a calibrated spectrophotometer, as well as total transmittance measurements using a luxmeter. The results show that both types of marble transmit light and that Pentelic marble has a higher transmittance in the visible range than Paros marble in some cases and hence could have been one reason, among others, to change the type of marble in the roof in antiquity.


Laboratory Evaluation of Femtosecond Laser Lamellar Cuts in Gamma-Irradiated Corneas.
To evaluate the stromal interface quality after femtosecond laser full lamellar cuts in gamma-irradiated corneas (VisionGraft sterile cornea) and to determine the limits of the cut depth using the VisionGraft as donor corneas for laser-assisted lamellar anterior keratoplasty. Fourteen VisionGraft corneas underwent full lamellar cuts using the femtosecond laser. The percent cut depth was 17% to 21% (100 μm, n = 2), 31% to 35% (n = 3), 38% to 40% (n = 3), 45% to 48% (n = 3), and 50% (n = 3) of the total stromal thickness (not including the epithelium). The cap and stromal bed surfaces were imaged with a scanning electron microscope. The quality of cut surfaces was graded by 2 masked observers based on two indices: ridge and roughness. Ridge grading indicated macroscopic irregularity. Roughness grading indicated microscopic irregularity. The grading was done on a subjective integer scale of 1 to 5 (1 = best and 5 = worst), which was used in a previous study of cut quality in fresh corneas. The ridge grading ranged from 1.5 for the shallowest cut to 2.2 for the deepest cut and weakly (r = 0.279) but significantly (P = 0.037) correlated with the percent cut depth. The roughness grading ranged from 2.63 to 2.56 and showed no trend with the percent cut depth (r = 0.006, P = 0.968). Compared with previously published results of fresh corneas, in which ridge grading exceeded 3 for cuts deeper than 31%, cut quality was better for the VisionGraft. Even at depths up to 48% of the total stromal thickness, ridge grading was not worse than shallow cuts. Thus, gamma-irradiated corneas could provide a smoother interface than do fresh eye bank corneas for laser-assisted lamellar anterior keratoplasty.


Evaluation of hand asymmetry in relation to hand preference.
We evaluated the asymmetric hand measurements in right- and left-handed individuals. 343 men and 290 women aged 18-42 years (22.11 +/- 2.07) participated in the study. There were no statistically significant differences when right-left differences in hand length, third finger length, palmar length, and the digit index value were evaluated according to hand preference and sex. Statistically significant differences were found for right-left differences in hand width, hand-shape index, and the palmar length/width according to hand preference. The strong left-handers, weak left-handers, and ambidextrous individuals in the study group all exhibited asymmetry favoring the left and were considered together. Similarly, the strong and weak right-handers exhibited asymmetry favoring the right hand and were considered together. The difference between these two groups was significant. When the data were evaluated according to sex, significant differences were found between the subgroups. In particular, right-left differences in the hand-shape index and palmar length/width values of the strong left-handers, weak left-handers, and ambidextrous individuals were found to be statistically significant according to sex; in contrast, the strong and weak right-handers showed no significant differences according to sex. These results suggest a relation of hand asymmetry to hand preference in a Turkish population.


Rotary nickel-titanium GT and ProTaper files for root canal shaping by novice operators: a radiographic and micro-computed tomography evaluation.
The purpose of this study was to assess canal preparation outcomes in vitro by novice clinicians after standardized teaching sessions. All students received a training session. In experiment 1, twenty canals of mandibular molars were prepared with GT and ProTaper rotaries by 10 students. Standardized radiographs were exposed before and after canal preparation, and canal curvature was measured; canals were assessed for patency and preparation time. In experiment 2, mandibular molars (20 canals) were submitted to microcomputed tomography before and after canal preparation with ProTaper and GT rotaries by 2 dental students. Canals were metrically assessed for changes (volume, surface, cross-sectional shape, transportation) during canal preparation by using software. In experiment 1, canal curvature decreased by 7.6 degrees and 7.8 degrees for GT and ProTaper preparations; there were no broken instruments, and 2 canals lost patency. The time for GT preparation was longer than for ProTaper (29.7 +/- 6.8 vs 19.4 +/- 8.1 minutes, P <.05). In experiment 2, canal volumes and surface areas increased (P < .001), and prepared canals were rounder in cross-section and more tapered. Mean canal transportation ranged between 0.14 +/- 0.05 mm and 0.23 +/- 0.09 mm for apical and coronal canal thirds. There were no significant differences between the instruments or the operators regarding center of mass shifts; qualitative and quantitative data for canal transportation were similar to earlier studies with experienced operators. Both rotary instruments performed adequately with inexperienced operators who received a brief structured training session.


A catecholaminergic sensory neuron phenotype in cranial derivatives of the neural crest: regulation by cell aggregation and nerve growth factor.
Tyrosine hydroxylase (TH) is transiently detectable in cells distributed throughout cranial sensory ganglia during early stages of gangliogenesis [embryonic day (E) 10.5-15.5]. Although TH cells appear in embryonic ganglia of both neural crest and placode origin, mature cranial sensory neurons that express catecholaminergic properties are restricted to placode derivatives. The mechanism(s) underlying the loss of TH expression in crest-derived sensory ganglia is unknown, and the present study was undertaken to define the temporal regulation of this phenotype. Our data indicate that transient TH cells belong to a large subset of primary sensory neurons that exhibit the capability to express TH throughout development. The lack of TH expression after E15.5 appears to be due to modulation of this catecholaminergic potential. The phenotype reappears, however, when E16.5 and older ganglia are dissociated in culture into single cells, suggesting that factors associated with cell aggregation modulate TH expression. In support of this hypothesis, sensory neurons grown at high cell density exhibit lower levels of TH expression than low-density cultures. The decrease in TH levels seen at high density was associated with changes in sensory neuron morphology that are characteristic of ganglion cell maturation in vivo; therefore, modulation of TH expression may be only one facet of a more general program of sensory neuron differentiation associated with cell aggregation in developing ganglia. In contrast to the effects of cell aggregation, treatment with NGF increased the proportion of TH cells in dissociate cultures of E14.5 and E16.5 cranial sensory ganglia. Our findings indicate that sensory transmitter phenotype may be modulated by multiple factors during gangliogenesis, including cellular interactions intrinsic to the developing ganglionic microenvironment.


Holocene deglaciation of Marie Byrd Land, West Antarctica.
Surface exposure ages of glacial deposits in the Ford Ranges of western Marie Byrd Land indicate continuous thinning of the West Antarctic Ice Sheet by more than 700 meters near the coast throughout the past 10,000 years. Deglaciation lagged the disappearance of ice sheets in the Northern Hemisphere by thousands of years and may still be under way. These results provide further evidence that parts of the West Antarctic Ice Sheet are on a long-term trajectory of decline. West Antarctic melting contributed water to the oceans in the late Holocene and may continue to do so in the future.


The coexistence of neuropathic pain, sleep, and psychiatric disorders: a novel treatment approach.
The diagnosis and treatment of neuropathic pain may be complicated by comorbid conditions such as sleep disturbances, depression, and anxiety. The interrelationship between the index neuropathic pain state and these comorbidities is complex: comorbid conditions exacerbate pain, and in turn, pain exacerbates the comorbid conditions. Because comorbidities can negatively impact response to pain treatment, healthcare providers should assess comorbidities as part of the diagnostic work-up, and management strategies should be designed to treat the whole patient, not just the pain. Theoretically, therapies that not only reduce pain, but also improve sleep and reduce anxiety and depression can provide multiple benefits without the risk of increased side effects inherent in combination therapy. Anticonvulsants and antidepressants have demonstrated efficacy in improving neuropathic pain and positively impacting comorbid sleep and mood disturbances. Novel anticonvulsants that can address one or more comorbidities in addition to pain may represent viable treatment options for patients with neuropathic pain.


X-Ray scattering and physicochemical studies of trialkylamine/carboxylic acid mixtures: nanoscale structure in pseudoprotic ionic liquids and related solutions.
We report the results of X-ray scattering, physical, and spectroscopic measurements on a series of water-saturated trialkylamine/carboxylic acid mixtures. The results demonstrate the existence of well-defined nanoscale structures in bulk liquid mixtures at specific acid : amine ratios. These structures are analogous to those observed in ionic liquids but are driven by the formation of a hydrogen-bonded network rather than via inter-ion Coulomb forces. The results of the physical components of this study are closely analogous to prior observations on anhydrous, low molecular weight acid/amine mixtures, but this is to our knowledge the first time these observations have been augmented by the use of X-ray scattering. The results therefore bridge the gap between early work on amine/acid mixtures and recent studies of protic and pseudoprotic ionic liquids.


Unprecedented magnetic behaviour in lanthanide-based ionic liquids.
Ionic liquids containing lanthanide halide anions give the opportunity to investigate magnetic behaviour in non-ordered systems. Reported herein is the synthesis and characterization of ionic liquids containing a series of lanthanide halide anions, with the resulting materials displaying unusual behaviour below 50 K. Specifically, the ionic liquid structural glass formation appears to drive magnetic behaviour due to cluster formation of the anions during rapid cooling. This system presents a possible probe to study the dynamics of glass forming materials.


Attitudes, Knowledge, Use, and Recommendation of Complementary and Alternative Medicine by Health Professionals in Western Mexico.
The use of complementary and alternative medicine (CAM) has increased in many countries, and this has altered the knowledge, attitudes, and treatment recommendations of health professionals in regard to CAM. Considering Mexican health professionals׳ lack of knowledge of CAM, in this report we surveyed 100 biomedical researchers and Ph.D. students and 107 specialized physicians and residents of a medical specialty in Guadalajara, México (Western Mexico) with a questionnaire to address their attitudes, knowledge, use, and recommendation of CAM. We observed that significantly more researchers had ever used CAM than physicians (83% vs. 69.2%, P = .023) and that only 36.4% of physicians had ever recommended CAM. Female researchers tended to have ever used CAM more than male researchers, but CAM use did not differ between genders in the physician group or by age in either group. Homeopathy, herbal medicine, and massage therapy were the most commonly used CAMs in both the groups. Physicians more frequently recommended homeopathy, massage therapy, and yoga to their patients than other forms of CAM, and physicians had the highest perception of safety and had taken the most courses in homeopathy. All CAMs were perceived to have high efficacy (>60%) in both the groups. The attitude questionnaire reported favorable attitudes toward CAM in both the groups. We observed a high rate of Mexican health professionals that had ever used CAM, and they had mainly used homeopathy, massage therapy, and herbal medicine. However, the recommendation rate of CAM by Mexican physicians was significantly lower than that in other countries, which is probably due to the lack of CAM training in most Mexican medical schools.


Medicare Advantage: what explains its robust health?
The Medicare Advantage (MA) program continues to grow and thrive, despite plan payment cuts imposed through the Affordable Care Act. What explains this surprising outcome (one that is strikingly different than the experience of MA plans in the late 1990s, when payment cuts led to dramatic shrinkage in enrollment and curtailment of plans)? This analysis argues that a combination of factors, including the way payment cuts were imposed, the plan offerings, the characteristics of beneficiaries, and the way they make choices together explain the program's current health. Understanding these factors is important for MA, Medicare, and, more generally, for participants in new payment models.


A life cycle database for parasitic acanthocephalans, cestodes, and nematodes.
Parasitologists have worked out many complex life cycles over the last ~150 yr, yet there have been few efforts to synthesize this information to facilitate comparisons among taxa. Most existing host-parasite databases focus on particular host taxa, do not distinguish final from intermediate hosts, and lack parasite life-history information. We summarized the known life cycles of trophically transmitted parasitic acanthocephalans, cestodes, and nematodes. For 973 parasite species, we gathered information from the literature on the hosts infected at each stage of the parasite life cycle (8,510 host-parasite species associations), what parasite stage is in each host, and whether parasites need to infect certain hosts to complete the life cycle. We also collected life-history data for these parasites at each life cycle stage, including 2,313 development time measurements and 7,660 body size measurements. The result is the most comprehensive data summary available for these parasite taxa. In addition to identifying gaps in our knowledge of parasite life cycles, these data can be used to test hypotheses about life cycle evolution, host specificity, parasite life-history strategies, and the roles of parasites in food webs.


Novel sol-gel fabrication of Yb3+/Tm3+ co-doped β-NaYF4 thin films and investigation of their upconversion properties.
An innovative sol-gel process, using a mixture of Na(hfa)·tetraglyme and RE(hfa)3·diglyme (RE = Y, Yb, Tm) complexes, has been optimized to produce upconverting β-NaYF4:Yb3+/Tm3+ thin films. The X-ray diffraction (XRD) analysis confirms that the new sol-gel preparation route yields reproducibly and selectively the hexagonal Na(Y1.5Na0.5)F6 structure (β-NaYF4) without any impurity phases, since no peaks of the cubic NaYF4, YOF, Y2O3 or NaF phases were observed. This final goal has been achieved through an accurate optimization of the operative parameters such as the molar ratio of the precursor mixture, the aging time of the sol, the spin coating procedure and the annealing temperature. Field-emission scanning electron microscopy (FE-SEM) images indicate that the morphology of the surfaces, grain dimensions and thickness are strongly related to the processing parameters, with the hexagonal phase films having a very uniform morphology. Energy dispersive X-ray (EDX) analyses established the film composition in terms of dopant ions, which are responsible for the upconverting properties of the material. Luminescence measurements under laser excitation at 980 nm confirmed the promising upconversion properties of the β-NaYF4:Yb3+/Tm3+ films.


Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2.
Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappaB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.


Family History, Tobacco Smoking, and Risk of Ischemic Stroke.
Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.


Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.
Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications. ACTRN12617000520336; Pre-results.


Analysis of multiple genetic loci reveals MPDZ-NF1B rs1324183 as a putative genetic marker for keratoconus.
To investigate the associations between 16 single-nucleotide polymorphisms (SNPs) in 14 genetic loci and keratoconus in an independent Chinese cohort. This cross-sectional, case-control association study included a Chinese cohort of 133 patients with keratoconus and 371 control subjects. In a recent meta-analysis study, we identified association of 16 SNPs in 14 gene loci with keratoconus. In this study, we genotyped these 16 SNPs in all the patients and controls and analysed their association with keratoconus, its clinical severities and progression profiles. We also analysed the genotype-phenotype correlation between individual SNPs and steep keratometry, flat keratometry (Kf), average keratometry (Avg K) and best-fit sphere diameter (BFS) of the anterior and posterior corneal surface. Among the 16 selected SNPs, rs1324183 in the MPDZ-NF1B locus showed a significant association with keratoconus (OR=2.22; 95% CI 1.42 to 3.45, p=4.30×10-4), especially severe keratoconus (OR=5.10, 95% CI 1.63 to 15.93, p=0.005). The rs1324183 A allele was positively associated with anterior Kf (p=0.008), anterior Avg K (p=0.017), posterior Kf (p=0.01) and negatively associated with apex pachymetry (p=0.007) and anterior BFS (p=0.023) in keratoconus. The other 15 SNPs had no significant association with keratoconus or genotype-phenotype correlations. This study confirmed the association of SNP rs1324183 in MPDZ-NF1B with keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention.


Experimental protection of two-qubit quantum gates against environmental noise by dynamical decoupling.
Hybrid systems consisting of different types of qubits are promising for building quantum computers if they combine useful properties of their constituent qubits. However, they also pose additional challenges if one type of qubits is more susceptible to environmental noise than the others. Dynamical decoupling can help to protect such systems by reducing the decoherence due to the environmental noise, but the protection must be designed such that it does not interfere with the control fields driving the logical operations. Here, we test such a protection scheme on a quantum register consisting of the electronic and nuclear spins of a nitrogen-vacancy center in diamond. The results show that processing is compatible with protection: The dephasing time was extended almost to the limit given by the longitudinal relaxation time of the electron spin.


Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial.
To determine the effectiveness and safety of moderate whole-body hypothermia in newborns with hypoxic-ischemic encephalopathy born in hospitals with and without newborn intensive care facilities or complicated hypothermia equipment. Multicenter, international, randomized controlled trial. Neonatal intensive care units in Australia, New Zealand, Canada, and the United States (N = 28) from February 2001 through July 2007. Newborns of 35 weeks' gestation or more, with indicators of peripartum hypoxia-ischemia and moderate to severe clinical encephalopathy, randomly allocated to hypothermia (n = 110) or standard care (n = 111). Whole-body hypothermia to 33.5°C for 72 hours or standard care (37°C). Infants who received hypothermia were treated at ambient environmental temperature by turning off the radiant warmer and then applying refrigerated gel packs to maintain rectal temperature at 33°C to 34°C. Death or major sensorineural disability at 2 years of age. Therapeutic hypothermia reduced the risk of death or major sensorineural disability at 2 years of age: 55 of 107 infants (51.4%) in the hypothermia group and 67 of 101 infants (66.3%) in the control group died or had a major sensorineural disability at 2 years (risk ratio, 0.77 [95% confidence interval, 0.62-0.98]; P = .03). The mortality rate decreased, and the survival rate free of any sensorineural disability increased. Adverse effects of hypothermia were minimal. Whole-body hypothermia is effective and appears to be safe when commenced within 6 hours of birth at the hospital of birth in term and near-term newborns with hypoxic-ischemic encephalopathy. This simple method of hypothermia could be used within strict protocols with appropriate training on correct diagnosis and application of hypothermia in nontertiary neonatal settings while awaiting retrieval and transport to the regional neonatal intensive care unit. anzctr.org.au Identifier: ACTRN12606000036516.


Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis dysfunction.
The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning.


Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies.
Marrow mesenchymal cells (MSCs) contain stem cells and possess the ability to regenerate bone, cartilage, and fibrous tissues. Here, we applied this regenerative ability to intervertebral disc regeneration therapy in an attempt to develop a new spinal surgery technique. We analyzed the regenerative restoration ability of autologous MSCs in the markedly degenerated intervertebral discs. Fusion for lumbar intervertebral disc instability improves lumbago. However, fused intervertebral discs lack the natural and physiologic functions of intervertebral discs. If intervertebral discs can be regenerated and repaired, then damage to adjacent intervertebral discs can be avoided. We verified the regenerative ability of MSCs by animal studies, and for the first time, performed therapeutic intervertebral disc regeneration therapy in patients and obtained favorable findings. Subjects were 2 women aged 70 and 67 years; both patients had lumbago, leg pain, and numbness. Myelography and magnetic resonance imaging showed lumbar spinal canal stenosis, and radiograph confirmed the vacuum phenomenon with instability. From the ilium of each patient, marrow fluid was collected, and MSCs were cultured using the medium containing autogenous serum. In surgery, fenestration was performed on the stenosed spinal canal and then pieces of collagen sponge containing autologous MSCs were grafted percutaneously to degenerated intervertebral discs. At 2 years after surgery, radiograph and computed tomography showed improvements in the vacuum phenomenon in both patients. On T2-weighted magnetic resonance imaging, signal intensity of intervertebral discs with cell grafts was high, thus indicating high moisture contents. Roentgenkymography showed that lumbar disc instability improved. Symptom was alleviated in both patients. The intervertebral disc regeneration therapy using MSC brought about favorable results in these 2 cases. It seems to be a promising minimally invasive treatment.


Simulation-Based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM)-A Prospective Single-Arm Multicenter Trial.
Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2-3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the "door-to-needle" time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three "STREAM multipliers" from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2-3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings. Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.


Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry.
Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100,000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (<70 years) and 79% for older (>80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.


Patients' expectations of osteopathic care: a qualitative study.
Research has shown that patients' expectations of health care and health-care practitioners are complex and may have a significant impact on outcomes of care. Little is known about the expectations of osteopathic patients. To explore osteopathic patients' expectations of private sector care. Focus groups and individual interviews with purposively selected patients; this was the qualitative phase of a mixed methods study, the final phase being a patient survey. A total of 34 adult patients currently attending for treatment at private osteopathic practices across the United Kingdom. Focus group discussions and individual interviews around expectations before, during and after osteopathic care. Thematic analysis of text data to identify topics raised by patients and to group these into broad themes. Many components of expectation were identified. A preliminary conceptual framework describing the way the therapeutic encounter is approached in osteopathy comprised five themes: individual agency, professional expertise, customer experience, therapeutic process and interpersonal relationship. The components of expectation identified in this phase of the study provided potential question topics for the survey questionnaire in the subsequent phase of the investigation. The model developed in this study may add a new perspective to existing evidence on expectations. Further research is recommended to test the findings both within private practice and the National Health Service.


Cryotherapy reduces muscle hypertonia, but does not affect lower limb strength or gait kinematics post-stroke: a randomized controlled crossover study.
Based on the premise that spasticity might affect gait post-stroke, cryotherapy is among the techniques used to temporarily reduce spasticity in neurological patients. This effective technique would enhance muscle performance, and ultimately, functional training, such as walking. However, understanding whether a decrease in spasticity level, if any, would lead to improving muscle performance and gait parameters is not based on evidence and needs to be clarified. to investigate the immediate effects of cryotherapy, applied to spastic plantarflexor muscles of subjects post-stroke, on tonus level, torque generation capacity of plantarflexors and dorsiflexors, and angular/spatiotemporal gait parameters. Sixteen chronic hemiparetic subjects participated in this randomized controlled crossover study. Cryotherapy (ice pack) or Control (room temperature sand pack) were applied to the calf muscles of the paretic limb. The measurements taken (before and immediately after intervention) were: 1) Tonus according to the Modified Ashworth Scale; 2) Torque assessments were performed using an isokinetic dynamometer; and 3) Spatiotemporal and angular kinematics of the hip, knee, and ankle (flexion/extension), obtained using a tridimensional movement analysis system (Qualisys). Cryotherapy decreased plantarflexor tonus but did not change muscle torque generation capacity and did not affect spatiotemporal or angular parameters during gait compared to control application. These findings contribute to the evidence-based approach to clinical rehabilitation post-stroke. The findings of this study suggest that cryotherapy applied to the calf muscles of subjects with chronic hemiparesis reduces muscle hypertonia but does not improve dorsiflexors and plantarflexors performance and gait parameters.


CD8+ T-cell recognition of human cytomegalovirus latency-associated determinant pUL138.
Recent studies have shown that long-term persistence of human cytomegalovirus (HCMV) in mononuclear cells of myeloid lineage is dependent on the UL138 open reading frame, which promotes latent infection. Although T-cell recognition of protein antigens from all stages of lytic HCMV infection is well established, it is not clear whether proteins expressed during latent HCMV infection can also be recognized. This study conducted an analysis of T-cell response towards proteins associated with HCMV latency. Ex vivo analysis of T cells from healthy virus carriers revealed a dominant CD8(+) T-cell response to the latency-associated pUL138 protein, which recognized a non-canonical 13 aa epitope in association with HLA-B*3501. These pUL138-specific T cells displayed a range of memory phenotypes that were in general less differentiated than that previously described in T cells specific for HCMV lytic antigens. Antigen-presentation assays revealed that endogenous pUL138 could be presented efficiently by HCMV-infected cells. However, T-cell recognition of pUL138 was dependent on newly synthesized protein, with little presentation from stable, long-lived protein. These data demonstrate that T cells targeting latency-associated protein products exist, although HCMV may limit the presentation of latent proteins, thereby restricting T-cell recognition of latently infected cells.


Aber-OWL: a framework for ontology-based data access in biology.
Many ontologies have been developed in biology and these ontologies increasingly contain large volumes of formalized knowledge commonly expressed in the Web Ontology Language (OWL). Computational access to the knowledge contained within these ontologies relies on the use of automated reasoning. We have developed the Aber-OWL infrastructure that provides reasoning services for bio-ontologies. Aber-OWL consists of an ontology repository, a set of web services and web interfaces that enable ontology-based semantic access to biological data and literature. Aber-OWL is freely available at http://aber-owl.net . Aber-OWL provides a framework for automatically accessing information that is annotated with ontologies or contains terms used to label classes in ontologies. When using Aber-OWL, access to ontologies and data annotated with them is not merely based on class names or identifiers but rather on the knowledge the ontologies contain and the inferences that can be drawn from it.


Effect of curcumin on galactose-induced cataractogenesis in rats.
Curcumin, the active principle of turmeric, has been shown to have both antioxidant and hypoglycemic activity in vitro and in vivo. The purpose of this study was to investigate the effect of curcumin on the onset and maturation of galactose induced cataract. Sprague-Dawley rats (21 days old) were divided into 5 groups. The control group (A) received an AIN-93 diet, the galactose group (B) received 30% galactose in the diet, the test groups (C and D) received the B group diet plus 0.002% and 0.01% curcumin respectively, and group (E) received the control diet plus 0.01% curcumin, all for a period of 4 weeks. Cataract progression due to galactose feeding was monitored by slit lamp microscope and classified into 4 stages. At the end of the experiment biochemical parameters such as lipid peroxidation, aldose reductase (AR), sorbitol dehydrogenase (SDH), reduced glutathione, protein content, and protein carbonyls were measured in the lens. Advanced glycated end products (AGE) and protein oxidation were measured by AGE and tryptophon fluorescence respectively. Crystallin profile was analyzed by size exclusion chromatography (HPLC). Slit lamp microscope observations indicated that curcumin at 0.002% (group C) delayed the onset and maturation of cataract. In contrast even though there was a slight delay in the onset of cataract at the 0.01% level (group D), maturation of cataract was faster when compared to group B. Biochemical analysis showed that curcumin at the 0.002% level appeared to exert antioxidant and antiglycating effects, as it inhibited lipid peroxidation, AGE-fluorescence, and protein aggregation. Though the reasons for faster onset and maturation of cataract in group D rats was not clear, the data suggested that under hyperglycemic conditions higher levels of curcumin (0.01%) in the diet may increase oxidative stress, AGE formation, and protein aggregation. However, feeding of curcumin to normal rats up to a 0.01% level did not result in any changes in lens morphology or biochemical parameters. These results suggest that curcumin is effective against galactose-induced cataract only at very low amounts (0.002%) in the diet. On the other hand at and above a 0.01% level curcumin seems to not be beneficial under hyperglycemic conditions, at least with the model of galactose-cataract.