Individual and temporal variation in habitat association of an alien carnivore at its invasion front.
Gathering information on how invasive species utilize the habitat is important, in order to better aim actions to reduce their negative impact. We studied habitat use and selection of 55 GPS-marked raccoon dogs (30 males, 25 females) at their invasion front in Northern Sweden, with particular focus on differences between males and females, between movement states, and between seasons and times of the day. Daily movement pattern was used to classify GPS-locations into dispersing and settled. We focused on both anthropogenic and natural landscape characteristics. Since we did not have any a priori knowledge about the spatial scale of raccoon dog habitat selection, we first assessed how landscape characteristics of random points changed with distance from the GPS-location they were paired to. Because changes in habitat use became less pronounced at approximately 5 km for all variables, we focused on habitat use at two spatial scales: fine (500 m) and coarse (5 km). Habitat selection was strongest at the coarse scale, and reflected the results found for habitat use. Raccoon dogs selected agricultural areas and wetlands, lower altitudes, and shallow slopes, and avoided forests, open natural areas, and areas close to water and roads. There were no differences in habitat selection between males and females, or between movement states. This lack of sexual segregation increases the probability of encountering potential mates during dispersal, and therefore the likelihood for reproduction in new areas. The seasonal and diurnal pattern of habitat use may provide guidance for where and when to aim management efforts.


Multiple-, but not single-, dose of parecoxib reduces shoulder pain after gynecologic laparoscopy.
The aim of this study was to investigate effect of single- and multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy. 126 patients requiring elective gynecologic laparoscopy were randomly allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at 30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and normal saline at the corresponding time points; Group C (control): receiving normal saline at the same three time points. The shoulder pain was evaluated, both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of shoulder pain on patients' recovery (activity, mood, walking and sleep) was also evaluated. Meanwhile, rescue analgesics and complications were recorded. The overall incidence of shoulder pain in group M (37.5%) was lower than that in group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single-dose regimen (61.0%) showed no significant reduction (difference with control=-0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the maximal intensity of shoulder pain and the impact for activity and mood in comparison to the control. Multiple-dose of parecoxib decreased the consumption of rescue analgesics. The complications were similar among all groups and no severe complications were observed. Multiple-, but not single-, dose of parecoxib may attenuate the incidence and intensity of shoulder pain and thereby improve patients' quality of recovery following gynecologic laparoscopy.


Micronutrients in paediatric Intestinal Failure Patients receiving home parenteral nutrition.
Children with intestinal failure (IF) receive parental nutrition to ensure adequate growth and development. The aim of this study was to assess micronutrient status in paediatric IF patients receiving home parenteral nutrition (HPN) in comparison to a group of healthy children. An observational cross-sectional study was performed at Oslo University Hospital and at the Department of Nutrition, University of Oslo from January to September 2017. All children with IF, aged two to 18 years, were invited to participate. A reference group of healthy children was recruited through social media advertisement. Dietary intake was assessed by a four-day food record, and enteral and parenteral provision was recorded. Blood samples were analysed for vitamins, minerals and haematology to assess iron status. Two spot urine samples from each subject were analysed for iodine concentration (UIC) and creatinine. Nineteen children with IF and 50 healthy children were included. The mean age of the participants was 10.0 years. IF-patients received a median of 76% of their estimated energy requirements from parenteral nutrition (PN). Recommended intake (RI) for iodine from the diet was reached by 16% of IF patients and 28% of healthy children. In the IF group there was a significant positive correlation between UIC and the percentage of iodine intake from oral diet and enteral nutrition support (r = 0.57, p = 0.03). Although the IF patients had a median parenteral iodine supply of more than twice the ESPGHAN recommendation, the median UIC was 89 μg/L indicating insufficient iodine status. This may suggest that the ESPGHAN recommendation for iodine in paediatric parenteral nutrition is too low. The healthy children had sufficient iodine status according to the median UIC (133 μg/L). IF patients had significantly lower total provision of iron compared to the healthy children, 4,9 vs 8,4 mg/day (p = 0.01) with 21% of IF patients and 28% of healthy children reaching RI for iron. The prevalence of anaemia was higher in IF patients than in the healthy children (40 vs.10%, p = 0.016). The study indicates an insufficient iodine and iron status among paediatric IF patients. Iodine status was associated with enteral provision and patients had insufficient status even if they received the ESPGHAN recommendation of iodine. Clinical Trials AEV2017/1. 2016/391/REK sør-øst B.


Hydrothermal synthesis, electronic structure and tunable luminescence of single-phase Ca5(PO4)3F:Tb3+,Eu3+ microrods.
Uniform and well-crystallized calcium fluorapatite [Ca5(PO4)3F, FAP] microrods have been successfully synthesized by a facile one-step hydrothermal synthesis method using sodium citrate as the crystal modifier. X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), photoluminescence (PL), photoluminescent excitation spectra (PLE) and decay studies were employed to characterize the samples. The electronic structure and orbital population of FAP were also determined by means of density functional theory calculations. Under ultraviolet irradiation, the FAP:Tb(3+),Eu(3+) samples exhibit a blue-light emission of the host matrix, as well as the typical green emission band of the Tb(3+) ions, and a red-light emission of Eu(3+). The highly intense red emission bands of the Eu(3+) ions were attributed to the effective energy transfer from the Tb(3+) to Eu(3+) ions, which has been justified through the luminescence spectra and the fluorescence decay dynamics. The luminescence colors of FAP:Tb(3+),Eu(3+) microrods can be easily tuned by changing the concentration of Eu(3+) ions. The results reveal that the combination of the self-activated luminescence and rare earth-doping emission in FAP:Tb(3+),Eu(3+) microrods could result in tunable emission in a large color gamut, which can be used as a potential candidate for white-light-emitting diodes and other display devices.


Dancing disclinations in confined active nematics.
The spontaneous emergence of collective flows is a generic property of active fluids and often leads to chaotic flow patterns characterised by swirls, jets, and topological disclinations in their orientation field. However, the ability to achieve structured flows and ordered disclinations is of particular importance in the design and control of active systems. By confining an active nematic fluid within a channel, we find a regular motion of disclinations, in conjunction with a well defined and dynamic vortex lattice. As pairs of moving disclinations travel through the channel, they continually exchange partners producing a dynamic ordered state, reminiscent of Ceilidh dancing. We anticipate that this biomimetic ability to self-assemble organised topological disclinations and dynamically structured flow fields in engineered geometries will pave the road towards establishing new active topological microfluidic devices.


Evidence against a role for platelet-activating factor in hypoxic pulmonary vasoconstriction in the rat.
1. The effect of two structurally different platelet-activating factor (PAF) receptor antagonists, WEB 2086((3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]- treazolo-[4,3-alpha][1,4]-diazepine-2-yl]-1-(morpholinyl)-1- propanone)) and BN 52021, on hypoxic pulmonary vasoconstriction (HPV) was studied using an isolated rat lung preparation perfused with blood. 2. In lungs treated with WEB 2086 there was a dose-dependent attenuation of HPV, with complete abolition of HPV at the maximum dose. 3. Low doses of WEB 2086 caused only slight diminution of the pressor response to angiotensin II, although higher doses caused increasing attenuation of the angiotensin pressor response. 4. BN 52021 did not affect HPV. 5. Injection of PAF caused an increase in pulmonary artery pressure of 145%, a response abolished by pretreatment of the lungs with either WEB 2086 or BN 52021. 6. These results suggest that PAF does not mediate HPV in the rat.


T2-weighted 3D fMRI using S2-SSFP at 7 tesla.
In this study, the sensitivity of the S(2)-steady-state free precession (SSFP) signal for functional MRI at 7 T was investigated. In order to achieve the necessary temporal resolution, a three-dimensional acquisition scheme with acceleration along two spatial axes was employed. Activation maps based on S(2)-steady-state free precession data showed similar spatial localization of activation and sensitivity as spin-echo echo-planar imaging (SE-EPI), but data can be acquired with substantially lower power deposition. The functional sensitivity estimated by the average z-values was not significantly different for SE-EPI compared to the S(2)-signal but was slightly lower for the S(2)-signal (6.74 +/- 0.32 for the TR = 15 ms protocol and 7.51 +/- 0.78 for the TR = 27 ms protocol) compared to SE-EPI (7.49 +/- 1.44 and 8.05 +/- 1.67) using the same activated voxels, respectively. The relative signal changes in these voxels upon activation were slightly lower for SE-EPI (2.37% +/- 0.18%) compared to the TR = 15 ms S(2)-SSFP protocol (2.75% +/- 0.53%) and significantly lower than the TR = 27 ms protocol (5.38% +/- 1.28%), in line with simulations results. The large relative signal change for the long TR SSFP protocol can be explained by contributions from multiple coherence pathways and the low intrinsic intensity of the S(2) signal. In conclusion, whole-brain T(2)-weighted functional MRI with negligible image distortion at 7 T is feasible using the S(2)-SSFP sequence and partially parallel imaging.


Intracellular pH and bicarbonate concentration as determined in biopsy samples from the quadriceps muscle of man at rest.
1. A method for measuring intracellular pH and bicarbonate concentration of human muscle is described. 2. Muscle biopsies from the quadriceps muscle of 13 healthy subjects at rest were analysed for acid-labile carbon dioxide and volume of extra- and intra-cellular water. Extracellular water volume was estimated from the chloride content and intracellular water volume from the potassium content, or alternatively derived from the sample weight. 3. The measured total carbon dioxide content in muscle was 9-84+/-1-39 mmol/kg. 4. Assuming a normal membrane potential (88 mV) and PCO2 of muscle equal to venous blood, calculated intracellular pH was 7-00+/-0-06 and intracellular bicarbonate concentration was 10-2+/-1-2 mmol/l of water.


A characterization of scale invariant responses in enzymatic networks.
An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of three-node enzymatic networks (and sufficient for any number of nodes). Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions.


Using teledentistry in clinical practice as an enabler to improve access to clinical care: A qualitative systematic review.
Background Access to dental care is important for overall health, but can remain problematic for those in rural or isolated locations. It can be difficult to encourage clinicians to choose or continue a rural health career. Teledentistry is showing some promise as a strategy to support rural, isolated and new health care workers. This study aims to explore the quantitative and qualitative framework associated with teledentistry in an effort to uncover the interaction of multiple influences on its delivery and sustainability. Methods A systematic search of the literature was undertaken and studies were included if they evaluated consultative teledentistry, reports on implementation of teledentistry in practice or attitudes to teledentistry. Studies were evaluated qualitatively. Results Thirty-nine studies were included focusing on the accuracy, effectiveness or description a teledentistry project in practice. Five main themes were identified in the qualitative analysis: (1) using information and communication technology (ICT), (2) regulatory and system improvements, (3) accuracy of teledentistry, (4) effectiveness, including increasing access to clinical services, efficiencies and acceptability, and (5) building and increasing clinical capacity of the dental workforce. Conclusion Teledentistry provides a viable option for remote screening, diagnosis, consultation, treatment planning and mentoring in the field of dentistry. Rapidly developing information and communication technologies have increasingly shown improving cost effectiveness, accuracy and efficient remote assistance for clinicians. There is high acceptability for teledentistry amongst clinicians and patients alike. Remuneration of advising clinicians is critical to sustainability.


Expression and characterization of transforming growth factor alpha precursor protein in transfected mammalian cells.
Analysis of a cDNA clone derived from retrovirus-transformed rat fibroblasts has recently suggested that the mature 50-amino-acid form of transforming growth factor alpha (TGF alpha) is derived from a 159-amino-acid transmembrane precursor by proteolytic cleavage. To understand the processing of the TGF alpha precursor molecule in more detail, we have expressed this protein in baby hamster kidney (BHK) fibroblasts under control of the metal-ion-inducible metallothionein promoter and characterized the expressed precursor with site-specific antipeptide antibodies. One of the BHK transfectants, termed 5:2, expressed the TGF alpha mRNA in a cadmium- and zinc-inducible manner. The TGF alpha precursor protein was detected by immunoprecipitation analysis of radiolabeled cell cultures. In the induced 5:2 cells, a polypeptide of Mr 13,000 to 17,000 was readily identified by peptide antisera made to three different regions of the TGF alpha precursor protein. No such protein species were observed in BHK cells treated with cadmium and zinc or in uninduced 5:2 cells. However, two cell lines known to produce TGF alpha naturally, Leydig testicular tumor cells and Snyder-Theilan feline sarcoma virus-transformed Fisher rat embryo fibroblasts, possessed detectable levels of immunologically related Mr 13,000 to 17,000 proteins. Cell fractionation studies indicate that the Mr 13,000 to 17,000 species expressed in induced 5:2 cells is membrane associated, consistent with predictions based on the cDNA sequence of the TGF alpha precursor. Media conditioned by induced 5:2 cells contained epidermal growth factor receptor-competing activity, which, upon size fractionation, was similar in size to the mature processed form of TGF alpha. These data show that these nontransformed BHK cells possess the ability to process the TGF alpha precursor molecule into its native form.


Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy.
Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the suppressed phosphorylation of PKB/Akt via feedback inhibition by mTORC1 and subsequent increased expression of the E3 ubiquitin ligases MuRF1 and atrogin-1/MAFbx. In contrast, expression of both E3 ligases was not increased in soleus muscle suggesting the presence of compensatory mechanisms in this muscle. Our study shows that the mTORC1- and the PKB/Akt-FoxO pathways are tightly interconnected and differentially regulated depending on the muscle type. These results indicate that long-term activation of the mTORC1 signaling axis is not a therapeutic option to promote muscle growth because of its strong feedback induction of the E3 ubiquitin ligases involved in protein degradation.


FACKEL is a sterol C-14 reductase required for organized cell division and expansion in Arabidopsis embryogenesis.
In flowering plants, the developing embryo consists of growing populations of cells whose fates are determined in a position-dependent manner to form the adult organism. Mutations in the FACKEL (FK) gene affect body organization of the Arabidopsis seedling. We report that FK is required for cell division and expansion and is involved in proper organization of the embryo. We isolated FK by positional cloning. Expression analysis in embryos revealed that FK mRNA becomes localized to meristematic zones. FK encodes a predicted integral membrane protein related to the vertebrate lamin B receptor and sterol reductases across species, including yeast sterol C-14 reductase ERG24. We provide functional evidence that FK encodes a sterol C-14 reductase by complementation of erg24. GC/MS analysis confirmed that fk mutations lead to accumulation of intermediates in the biosynthetic pathway preceding the C-14 reductase step. Although fk represents a sterol biosynthetic mutant, the phenotype was not rescued by feeding with brassinosteroids (BRs), the only plant sterol signaling molecules known so far. We propose that synthesis of sterol signals in addition to BRs is important in mediating regulated cell growth and organization during embryonic development. Our results indicate a novel role for sterols in the embryogenesis of plants.


Reduced seroconversion to measles in infants given vitamin A with measles vaccination.
Administration of 100,000 IU vitamin A at the time of measles immunisation is currently recommended for infants in developing countries. However, the safety and value of giving vitamin A, a potent immune enhancer, with live measles virus vaccines are unknown. We conducted a randomised, double-blind, placebo-controlled clinical trial in Indonesia to evaluate the effect of simultaneous vitamin A supplementation on the immune response to measles immunisation at six months of age. 336 infants received either vitamin A (100,000 IU) or placebo when immunised with standard-titre Schwarz measles vaccine. 82% of infants seroconverted to measles. In a multiple logistic regression model adjusting for maternal antibody titres, vitamin A supplementation was associated with a lower likelihood of seroconversion to measles (odds ratio 0.40, 95% CI 0.19-0.88), and girls were less likely to seroconvert than boys (0.34, 0.15-0.76). Immunisation with standard-titre Schwarz vaccine at six months of age in this study population is characterised by high seroconversion rates. However, simultaneous high-dose vitamin A may interfere with seroconversion to live measles vaccine in infants with maternal antibody.


The transitioning experiences of internationally-educated nurses into a Canadian health care system: A focused ethnography.
Beyond well-documented credentialing issues, internationally-educated nurses (IENs) may need considerable support in transitioning into new social and health care environments. This study was undertaken to gain an understanding of transitioning experiences of IENs upon relocation to Canada, while creating policy and practice recommendations applicable globally for improving the quality of transitioning and the retention of IENs. A focused ethnography of newly-recruited IENs was conducted, using individual semi-structured interviews at both one-to-three months (Phase 1) and nine-to-twelve months post-relocation (Phase 2). A purposive sample of IENs was recruited during their orientation at a local college, to a health authority within western Canada which had recruited them for employment throughout the region. The interviews were recorded and transcribed, and data was managed using qualitative analytical software. Data analysis was informed by Roper and Shapira's framework for focused ethnography. Twenty three IENs consented to participate in 31 interviews. All IENs which indicated interest during their orientation sessions consented to the interviews, yet 14 did not complete the Phase 2 interview due to reorganization of health services and relocation. The ethno-culturally diverse group had an average age of 36.4 years, were primarily educated to first degree level or higher, and were largely (under) employed as "Graduate Nurses". Many IENs reported negative experiences related to their work contract and overall support upon arrival. There were striking differences in nursing practice and some experiences of perceived discrimination. The primary area of discontentment was the apparent communication breakdown at the recruitment stage with subsequent discrepancy in expected professional role and financial reimbursement. Explicit and clear communication is needed between employers and recruitment agencies to avoid employment contract misunderstandings and to enable clear interpretation of the credentialing processes. Pre-arrival orientation of IENs including health care communications should be encouraged and supported by the recruiting institution. Moreover, employers should provide more structured and comprehensive workplace orientation to IENs with consistent preceptorship. Similar to findings of many other studies, diversity should be valued and incorporated into the professional culture by nurse managers.


Multi-omics analysis provides insight to the Ignicoccus hospitalis-Nanoarchaeum equitans association.
Studies of interspecies interactions are inherently difficult due to the complex mechanisms which enable these relationships. A model system for studying interspecies interactions is the marine hyperthermophiles Ignicoccus hospitalis and Nanoarchaeum equitans. Recent independently-conducted 'omics' analyses have generated insights into the molecular factors modulating this association. However, significant questions remain about the nature of the interactions between these archaea. We jointly analyzed multiple levels of omics datasets obtained from published, independent transcriptomics, proteomics, and metabolomics analyses. DAVID identified functionally-related groups enriched when I. hospitalis is grown alone or in co-culture with N. equitans. Enriched molecular pathways were subsequently visualized using interaction maps generated using STRING. Key findings of our multi-level omics analysis indicated that I. hospitalis provides precursors to N. equitans for energy metabolism. Analysis indicated an overall reduction in diversity of metabolic precursors in the I. hospitalis-N. equitans co-culture, which has been connected to the differential use of ribosomal subunits and was previously unnoticed. We also identified differences in precursors linked to amino acid metabolism, NADH metabolism, and carbon fixation, providing new insights into the metabolic adaptions of I. hospitalis enabling the growth of N. equitans. This multi-omics analysis builds upon previously identified cellular patterns while offering new insights into mechanisms that enable the I. hospitalis-N. equitans association. Our study applies statistical and visualization techniques to a mixed-source omics dataset to yield a more global insight into a complex system, that was not readily discernable from separate omics studies.


Preserving sequence annotations across reference sequences.
Matching and comparing sequence annotations of different reference sequences is vital to genomics research, yet many annotation formats do not specify the reference sequence types or versions used. This makes the integration of annotations from different sources difficult and error prone. As part of our effort to create linked data for interoperable sequence annotations, we present an RDF data model for sequence annotation using the ontological framework established by the OBO Foundry ontologies and the Basic Formal Ontology (BFO). We defined reference sequences as the common domain of integration for sequence annotations, and identified three semantic relationships between sequence annotations. In doing so, we created the Reference Sequence Annotation to compensate for gaps in the SO and in its mapping to BFO, particularly for annotations that refer to versions of consensus reference sequences. Moreover, we present three integration models for sequence annotations using different reference assemblies. We demonstrated a working example of a sequence annotation instance, and how this instance can be linked to other annotations on different reference sequences. Sequence annotations in this format are semantically rich and can be integrated easily with different assemblies. We also identify other challenges of modeling reference sequences with the BFO.


Fast retrieval of electronic messages that contain mistyped words or spelling errors.
This paper presents an index structure for retrieving electronic messages that contain mistyped words or spelling errors. Given a query string (e.g., a search key), we want to find those messages that approximately contain the query, i.e., certain inserts, deletes and mismatches are allowed when matching the query with a word (or phrase) in the messages. Our approach is to store the messages sequentially in a database and hash their "fingerprints" into a number of "fingerprint files." When the query is given, its fingerprints are also hashed into the files and a histogram of votes is constructed on the messages. We derive a lower bound, based on which one can prune a large number of nonqualifying messages (i.e., those whose votes are below the lower bound) during searching. The paper presents some experimental results, which demonstrate the effectiveness of the index structure and the lower bound.


Technical and clinical view on ambulatory assessment in Parkinson's disease.
With the progress of technologies of recent years, methods have become available that use wearable sensors and ambulatory systems to measure aspects of--particular axial--motor function. As Parkinson's disease (PD) can be considered a model disorder for motor impairment, a significant number of studies have already been performed with these patients using such techniques. In general, motion sensors such as accelerometers and gyroscopes are used, in combination with lightweight electronics that do not interfere with normal human motion. A fundamental advantage in comparison with usual clinical assessment is that these sensors allow a more quantitative, objective, and reliable evaluation of symptoms; they have also significant advantages compared to in-lab technologies (e.g., optoelectronic motion capture) as they allow long-term monitoring under real-life conditions. In addition, based on recent findings particularly from studies using functional imaging, we learned that non-motor symptoms, specifically cognitive aspects, may be at least indirectly assessable. It is hypothesized that ambulatory quantitative assessment strategies will allow users, clinicians, and scientists in the future to gain more quantitative, unobtrusive, and everyday relevant data out of their clinical evaluation and can also be designed as pervasive (everywhere) and intensive (anytime) tools for ambulatory assessment and even rehabilitation of motor and (partly) non-motor symptoms in PD.


Development of fluorescence in situ hybridization (FISH) probes to detect and enumerate Gambierdiscus species.
Ciguatera poisoning (CP) is a syndrome caused by the bioaccumulation of lipophilic ciguatoxins in coral reef fish and invertebrates, and their subsequent consumption by humans. These phycotoxins are produced by Gambierdiscus spp., tropical epiphytic dinoflagellates that live on a variety of macrophytes, as well as on dead corals and sand. Recent taxonomic studies have identified novel diversity within the Gambierdiscus genus, with at least 18 species and several sub-groups now identified, many of which co-occur and differ significantly in toxicity. The ability to accurately and quickly distinguish Gambierdiscus species in field samples and determine community composition and abundance is central to assessing CP risk, yet most Gambierdiscus species are indistinguishable using light microscopy, and other enumeration methods are semi-quantitative. In order to investigate the spatial and temporal dynamics of Gambierdiscus species and community toxicity, new tools for species identification and enumeration in field samples are needed. Here, fluorescence in situ hybridization (FISH) probes were designed for seven species commonly found in the Caribbean Sea and Pacific Ocean, permitting their enumeration in field samples using epifluorescence microscopy. This technique enables the assessment of community composition and accurate determination of cell abundances of individual species. Molecular probes detecting G. australes, G. belizeanus, G. caribaeus, G. carolinianus, G. carpenteri, and the G. silvae/G. polynesiensis clade were designed using alignments of large subunit ribosomal RNA (rRNA) sequences. These probes were tested for specificity and cross-reactivity through experiments in which field samples were spiked with known concentrations of Gambierdiscus cultures, and analyzed to confirm that Gambierdiscus can be successfully detected and enumerated by FISH in the presence of detritus and other organisms. These probes were then used to characterize Gambierdiscus community structure in field samples collected from the Florida Keys and Hawai'i, USA. The probes revealed the co-occurrence of multiple species at each location. Time-series FISH analyses of samples collected from the Florida Keys quantified seasonal shifts in community composition as well as fluctuations in overall Gambierdiscus cell abundance. Application of species-specific FISH probes provides a powerful new tool to those seeking to target individual Gambierdiscus species, including significant toxin-producers, in field populations. Moving forward, analysis of Gambierdiscus community composition across multiple environments and over time will also allow species dynamics to be linked to environmental parameters, improving our ability to understand and manage the current and changing risks of CP worldwide.


Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee.
Dimethyl sulphoxide and methylsulfonylmethane are two related nutritional supplements used for symptomatic relief of osteoarthritis (OA). We conducted a meta-analysis to evaluate their efficacy in reducing pain associated with OA. Randomized or quasi-randomized controlled trials (RCTs), identified by systematic electronic searches, citation tracking and searches of clinical trial registries, assessing these supplements in osteoarthritis of any joint were considered for inclusion. Meta-analysis, based on difference in mean pain related outcomes between treatment and comparator groups, was carried out based on a random effect model. Seven potential trials were identified of which three RCTs, two DMSO and one MSM (total N = 326 patients) were eligible for inclusion. All three trials were considered high methodological quality. A significant degree of heterogeneity (χ(2) = 6.28, P = .043) was revealed. Two studies demonstrated statistically significant (but not clinically relevant) reduction in pain compared with controls; with one showing no group difference. The meta-analysis confirmed a non significant reduction of pain on visual analogue scale of 6.34 mm (SE = 3.49, 95% CI, -0.49, 13.17). The overall effect size of 1.82 was neither statistically nor clinically significant. Current evidence suggests DMSO and MSM are not clinically effective in the reduction of pain in the treatment of OA. No definitive conclusions can currently be drawn from the data due to the mixed findings and the use of inadequate dosing periods.


Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism.
Glutamate receptor interacting protein 1 (GRIP1) is a neuronal scaffolding protein that interacts directly with the C termini of glutamate receptors 2/3 (GluA2/3) via its PDZ domains 4 to 6 (PDZ4-6). We found an association (P<0.05) of a SNP within the PDZ4-6 genomic region with autism by genotyping autistic patients (n=480) and matched controls (n=480). Parallel sequencing identified five rare missense variants within or near PDZ4-6 only in the autism cohort, resulting in a higher cumulative mutation load (P=0.032). Two variants correlated with a more severe deficit in reciprocal social interaction in affected sibling pairs from proband families. These variants were associated with altered interactions with GluA2/3 and faster recycling and increased surface distribution of GluA2 in neurons, suggesting gain-of-function because GRIP1/2 deficiency showed opposite phenotypes. Grip1/2 knockout mice exhibited increased sociability and impaired prepulse inhibition. These results support a role for GRIP in social behavior and implicate GRIP1 variants in modulating autistic phenotype.


Assessing anticoagulation knowledge in patients new to warfarin therapy.
Warfarin is highly efficacious for the treatment and prevention of thromboembolic disorders. However, anticoagulation control has been a long-standing challenge, as patients' lack of knowledge of warfarin therapy is a predictor of nonadherence and compromised patient safety. To ascertain whether hospitalized patients newly initiated on warfarin are provided adequate anticoagulation education during hospitalization, as measured at discharge, as well as determine whether there is a difference in the knowledge obtained by patients educated via a structured program versus those counseled by "usual care." A prospective evaluation of warfarin education of inpatients new to warfarin therapy was performed at Bassett Medical Center, Cooperstown, NY. Patients who were admitted to the hospital and receiving warfarin for any given diagnosis, were >18 years of age and able to give informed consent, and spoke English were recruited. Patients with dementia or cognitive impairment, those who were pregnant, or those who had previously been on warfarin therapy were excluded. Recruited patients received warfarin education in the form of a structured program provided by a pharmacist or counseling by usual care during hospitalization. Prior to discharge, the Oral Anticoagulation Knowledge (OAK) test, a prevalidated tool used to measure warfarin knowledge, was administered to evaluate outcomes. Further warfarin education was provided posttest if necessary. The intervention group (n = 20) scored significantly higher on the OAK test than the usual care group (n = 20): 74% versus 55%, respectively (p = 0.004). This preliminary study demonstrated that there is a large amount of variability regarding patient knowledge of warfarin on discharge from an inpatient facility. A formalized inpatient warfarin education program may empower patients to achieve a larger degree of initial warfarin knowledge than those educated by usual care. Previous studies have demonstrated that this may improve adherence and subsequently increase long-term safety associated with oral anticoagulation. Larger, prospective, randomized studies are necessary to further evaluate patient education and safety outcomes.


Determinants of O6-alkylguanine-DNA alkyltransferase activity in human colon cancer.
The DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) repairs cytotoxic DNA O6-alkylguanine adducts induced by the nitrosoureas, triazines, and tetrazines. In this study, we determined whether there was a relationship between alkyltransferase activity in colon cancer and that of adjacent normal mucosa, and whether there were demographic patient characteristics which correlated with alkyltransferase expression in either tissue. Alkyltransferase activity and expression of the alkyltransferase gene, MGMT, were measured in 49 paired primary colon cancer samples and adjacent normal appearing mucosa. Alkyltransferase activity was found in all samples. The mean activity was higher in the tumor than the mucosa (r = 0.374, P < 0. 01), although the low correlation coefficient suggested that multiple factors influence the alkyltransferase activity. MGMT mRNA could also be detected in all samples and was highly correlated with alkyltransferase activity (r = 0.64, P < 0.001). No correlation was found between alkyltransferase activity and age, or gender of the patient, or location of the tumor, although activity tended to be higher in patients with lower stage disease. Thus, alkyltransferase activity is present in most, if not all, colon cancer samples, suggesting that it could play an important role in chemotherapeutic resistance of human colon cancer. Patients with colon cancer would appear to be prime candidates for studies utilizing O6-benzylguanine to deplete alkyltransferase prior to therapy with a nitrosourea, triazine, or tetrazine.


Potentiation of radiation effects on two murine tumors by lonidamine.
Lonidamine is a potent inhibitor of spermatogenesis and a hyperthermic sensitizer. The principal established locus of biochemical action of lonidamine is a selective inhibitory effect of the energy metabolism either in NAD-linked reactions in germ cell mitochondria, as well as the glycolytic metabolism of a variety of tumor cell lines by means of inhibition of mitochondrially bound hexokinase. We carried out in vivo tumor experiments to determine whether lonidamine when combined with radiation could potentiate the cytotoxic effects of radiation on two murine tumors. The combined effects of single acute lonidamine (100 mg/kg) and single dose X-irradiation were evaluated on the transplanted methylcholanthrene-induced fibrosarcoma in BALB/c mice and on the radiation-induced fibrosarcoma in C3H/He mice. The radiosensitizing effect by lonidamine was maximal when lonidamine was administered immediately prior to or after X-irradiation. The dose modifying factor of lonidamine is estimated to be 1.36 for methylcholanthrene-induced fibrosarcoma tumors and 1.25 for radiation-induced fibrosarcoma tumors. There was no disproportionately enhanced skin reaction following the combined treatments. The present results of the potentiating effects of radiation may be attributed, in part, to the findings of cell culture studies that lonidamine is a potent inhibitor of repair of potentially lethal damage.


Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass.
Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein.


Enhancing rehabilitation and functional recovery after brain and spinal cord trauma with electrical neuromodulation.
This review discusses recent advances in the rehabilitation of motor deficits after traumatic brain injury (TBI) and spinal cord injury (SCI) using neuromodulatory techniques. Neurorehabilitation is currently the only treatment option for long-term improvement of motor functions that can be offered to patients with TBI or SCI. Major advances have been made in recent years in both preclinical and clinical rehabilitation. Activity-dependent plasticity of neuronal connections and circuits is considered key for successful recovery of motor functions, and great therapeutic potential is attributed to the combination of high-intensity training with electrical neuromodulation. First clinical case reports have demonstrated that repetitive training enabled or enhanced by electrical spinal cord stimulation can yield substantial improvements in motor function. Described achievements include regaining of overground walking capacity, independent standing and stepping, and improved pinch strength that recovered even years after injury. Promising treatment options have emerged from research in recent years using neurostimulation to enable or enhance intense training. However, characterizing long-term benefits and side-effects in clinical trials and identifying patient subsets who can benefit are crucial. Regaining lost motor function remains challenging.


Backcross analysis of genes linked to autoantibody production in New Zealand White mice.
F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice are genetically predisposed to develop a lupus-like autoimmune disease characterized by IgG autoantibody production and an immune complex glomerulonephritis. Genes from both parental strains contribute to autoimmunity in the F1 animal. NZW mice produce mostly non-pathogenic autoantibodies to ssDNA and histones as their major autoimmune trait. We studied the genetics of this trait in order to gain insight into the NZW contribution to F1 disease. Genome-wide mapping of (NZW x BALB/c)F1 x NZW backcross mice showed that four NZW non-MHC loci on chromosomes 1, 11, 16, and 19 were linked with IgG autoantibody production. Another NZW locus on chromosome 14 appeared to be selectively linked with IgG anti-histone Abs. In this backcross, contributions from the nonautoimmune BALB/c strain were also apparent. Heterozygosity for the BALB/c MHC (H2d) was linked with IgG autoantibody production. This influence of H2d is therefore similar to that seen in (NZW x NZB)F1 mice, in which heterozygosity for H2d enhances autoantibody production and disease. Surprisingly, two non-MHC BALB/c loci were linked with IgM autoantibody levels, whereas no NZW loci had such an effect. Neither of these two loci have been previously linked with autoimmunity in lupus-prone mice. These data show that autoantibody production in NZW mice is a polygenic trait that is influenced by contributions from MHC and non-MHC genes. The results also support the hypothesis that NZW genes act to class-switch the autoantibody response, an effect that appears to contribute to disease in (NZB x NZW)F1 mice.


Crystal structure of the lytic CHAP(K) domain of the endolysin LysK from Staphylococcus aureus bacteriophage K.
Bacteriophages encode endolysins to lyse their host cell and allow escape of their progeny. Endolysins are also active against Gram-positive bacteria when applied from the outside and are thus attractive anti-bacterial agents. LysK, an endolysin from staphylococcal phage K, contains an N-terminal cysteine-histidine dependent amido-hydrolase/peptidase domain (CHAP(K)), a central amidase domain and a C-terminal SH3b cell wall-binding domain. CHAP(K) cleaves bacterial peptidoglycan between the tetra-peptide stem and the penta-glycine bridge. The CHAP(K) domain of LysK was crystallized and high-resolution diffraction data was collected both from a native protein crystal and a methylmercury chloride derivatized crystal. The anomalous signal contained in the derivative data allowed the location of heavy atom sites and phase determination. The resulting structures were completed, refined and analyzed. The presence of calcium and zinc ions in the structure was confirmed by X-ray fluorescence emission spectroscopy. Zymogram analysis was performed on the enzyme and selected site-directed mutants. The structure of CHAP(K) revealed a papain-like topology with a hydrophobic cleft, where the catalytic triad is located. Ordered buffer molecules present in this groove may mimic the peptidoglycan substrate. When compared to previously solved CHAP domains, CHAP(K) contains an additional lobe in its N-terminal domain, with a structural calcium ion, coordinated by residues Asp45, Asp47, Tyr49, His51 and Asp56. The presence of a zinc ion in the active site was also apparent, coordinated by the catalytic residue Cys54 and a possible substrate analogue. Site-directed mutagenesis was used to demonstrate that residues involved in calcium binding and of the proposed active site were important for enzyme activity. The high-resolution structure of the CHAP(K) domain of LysK was determined, suggesting the location of the active site, the substrate-binding groove and revealing the presence of a structurally important calcium ion. A zinc ion was found more loosely bound. Based on the structure, we propose a possible reaction mechanism. Future studies will be aimed at co-crystallizing CHAP(K) with substrate analogues and elucidating its role in the complete LysK protein. This, in turn, may lead to the design of site-directed mutants with altered activity or substrate specificity.


Appropriate aims: setting boundaries for reprogenetic technology.
Not too long ago, ten fingers and ten toes defined a successful birth. Not too far from now, ten fingers and ten toes will be just the beginning. Parents always hope for a healthy baby, and medical advances continue to help secure the fulfillment of this hope. But reprogenetics, a new combination of technology and science that allows us to choose the genes, and thus the traits, of the children we create, is raising new questions about what it means to have a healthy baby.


Trabecular meshwork glycosaminoglycans in human and cynomolgus monkey eye.
The glycosaminoglycans (GAGs) extractable from the trabecular meshworks (TM) of human and non-human primate eye have been analyzed by sequential enzymatic degradation and cellulose acetate electrophoresis. For comparison, similar extracts of the cornea, sclera, iris, and ciliary body have also been analyzed. The distribution of glycosaminoglycans in human and in cynomolgus monkey TMs are similar, although not identical. The human TM contains hyaluronic acid (HA), chondroitin-4-sulfate and/or 6-sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS), heparan sulfate (HS), and an unidentified band of Alcian Blue staining material, which is resistant to the enzymes that we used. Based upon quantitation of the Alcian Blue staining intensities of extracted GAGs, which have been corrected by a relative dye-binding factor, the GAGs of the human TM include: 29.0% HA, 14.1% CS, 21.5% DS, 20.3% KS, and 15.0% HS. The cynomolgus monkey trabecular GAGs include: 12.8% HA, 14.3% CS, 15.2% DS, 42.1% KS, and 15.6% HS.


Ffz1, a new transporter specific for fructose from Zygosaccharomyces bailii.
The basis of fructophily in the yeast Zygosaccharomyces bailii has been shown to reside in the performance of transport systems for hexoses. In this study, a gene encoding a fructose-specific transporter was characterized. The strategy involved the functional complementation of a Saccharomyces cerevisiae strain that does not take up hexoses (hxt-null strain). This strain was transformed with a genomic library of Z. bailii. One transformant capable of growing on fructose, but not on glucose, was obtained. This transformant did not transport d-[(14)C]glucose, and the kinetic parameters for d-[(14)C]fructose were V(max)=3.3 mmol h(-1) g(-1) and K(m)=80.4 mM. As in the original strain of Z. bailii, fructose uptake was not inhibited by the presence of other hexoses or uranyl. The plasmid responsible for the observed phenotype was found to carry an ORF encoding a 616 amino acid protein with the characteristics of a membrane transporter, which was designated FFZ1 (fructose facilitator Zygosaccharomyces). The impairment in function observed in an S. cerevisiae transformant expressing a truncated Ffz1 protein lacking 67 amino acids at the C-terminus suggests an important role for this terminal part in the proper structure of the transporter.


A Case of Rhabdomyolysis Caused by Blood Flow-Restricted Resistance Training.
Blood flow-restricted resistance (BFRR) training is effective as a means to improve muscle strength and size while enduring less mechanical stress. It is generally safe but can have adverse effects. We present a case of an active duty Soldier who developed rhabdomyolysis as a result of a single course of BFRR training. He was presented to the emergency department with bilateral lower extremity pain, was admitted for electrolyte monitoring and rehydration, and had an uncomplicated hospital course and full recovery. This is an increasingly common mode of rehabilitation in the military, and practitioners and providers should be aware of it and its possible adverse effects.


Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells.
Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81(-/-) knockout), weakened (Egr3(-/-) knockout), or strengthened (mlcNT3(+/-) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells.


Evolutionary toggling of Vpx/Vpr specificity results in divergent recognition of the restriction factor SAMHD1.
SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts.


Development of a 3D Underground Cadastral System with Indoor Mapping for As-Built BIM: The Case Study of Gangnam Subway Station in Korea.
The cadastral system provides land ownership information by registering and representing land boundaries on a map. The current cadastral system in Korea, however, focuses mainly on the management of 2D land-surface boundaries. It is not yet possible to provide efficient or reliable land administration, as this 2D system cannot support or manage land information on 3D properties (including architectures and civil infrastructures) for both above-ground and underground facilities. A geometrical model of the 3D parcel, therefore, is required for registration of 3D properties. This paper, considering the role of the cadastral system, proposes a framework for a 3D underground cadastral system that can register various types of 3D underground properties using indoor mapping for as-built Building Information Modeling (BIM). The implementation consists of four phases: (1) geometric modeling of a real underground infrastructure using terrestrial laser scanning data; (2) implementation of as-built BIM based on geometric modeling results; (3) accuracy assessment for created as-built BIM using reference points acquired by total station; and (4) creation of three types of 3D underground cadastral map to represent underground properties. The experimental results, based on indoor mapping for as-built BIM, show that the proposed framework for a 3D underground cadastral system is able to register the rights, responsibilities, and restrictions corresponding to the 3D underground properties. In this way, clearly identifying the underground physical situation enables more reliable and effective decision-making in all aspects of the national land administration system.


Landau-Zener sweeps and sudden quenches in coupled Bose-Hubbard chains.
We simulate numerically the dynamics of strongly correlated bosons in a two-leg ladder subject to a time-dependent energy bias between the two chains. When all atoms are initially in the leg with higher energy, we find a drastic reduction of the interchain particle transfer for slow linear sweeps, in quantitative agreement with recent experiments. This effect is preceded by a rapid broadening of the quasimomentum distribution of atoms, signaling the presence of a bath of low-energy excitations in the chains. We further investigate the scenario of quantum quenches to fixed values of the energy bias. We find that for a large enough density the momentum distribution relaxes to that of an equilibrium thermal state with the same energy.


New species of Homidia (Collembola, Entomobryidae) from eastern China with description of the first instar larvae.
Morphology of the first instar larvae of Collembola has considerably taxonomical and phylogenetic significance. We describe the first instar larvae for the first time in Homidia. External morphology of first instar larvae and adults of Homidia jordanai sp. n. is described based on observations under light and scanning electron microscopes. Most organs of adults bear considerably more setae than the first instar larvae; in addition, first instar larval Homidia lack labial seta R, seta on tenaculum, mucronal spine, and dental spines. The new species is characterized by weakly pigmented body, long antennae subequal to body in length, 1+1 inner macrochaetae on Abd. III, few inner macrochaetae on posterior Abd. IV, and spiny and short seta pi on dental base. Differences between new species and other two similar ones, taxonomical significance of the first instar larvae and the position of Homidia are also discussed.


The method of contact angle measurements and estimation of work of adhesion in bioleaching of metals.
In this paper, we present our method for the measurement of contact angles on the surface of minerals during the bioleaching process because the standard deviation obtained in our measurements achieved unexpectedly low error. Construction of a goniometer connected with a specially prepared computer program allowed us to repeat measurements several times over a short time course, yielding excellent results.After defining points on the outline of the image of a drop and its baseline as well of the first approximation of the outline of the drop, an iterative process is initiated that is aimed at fitting the model of the drop and baseline. In turn, after defining the medium for which measurements were made, the work of adhesion is determined according to Young-Dupré equation. Calculations were made with the use of two methods named the L-M and L-Q methods.


Advantages and disadvantages of peripherally inserted central venous catheters (PICC) compared to other central venous lines: a systematic review of the literature.
The use of central venous lines carries a significant risk for serious complications and high economic costs. Lately, the peripherally inserted central venous catheter (PICC) has gained in popularity due to presumed advantages over other central venous lines. The aim of this systematic literature review was to identify scientific evidence justifying the use of PICC. The literature review was performed according to the principles of Cochrane Collaboration. The electronic literature search included common databases up to March 2011. Only those studies rated as high or moderate quality were used for grading of evidence and conclusions. The search resulted in 827 abstracts, 48 articles were read in full text, and 11 met the inclusion criteria. None of the articles was classified as high quality and two had moderate quality. The results of these two studies indicate that PICC increases the risk for deep venous thrombosis (DVT), but decreases the risk for catheter occlusion. The quality of scientific evidence behind these conclusions, however, was limited. Due to the lack of studies with sufficiently high quality, questions such as early complications, patient satisfaction and costs could not be answered. We conclude that although PICCs are frequently used in oncology, scientific evidence supporting any advantage or disadvantage of PICC when comparing PICC with traditional central venous lines is limited, apart from a tendency towards increased risk for DVT and a decreased risk for catheter occlusion with PICC.


Deciphering bacterial epigenomes using modern sequencing technologies.
Prokaryotic DNA contains three types of methylation: N6-methyladenine, N4-methylcytosine and 5-methylcytosine. The lack of tools to analyse the frequency and distribution of methylated residues in bacterial genomes has prevented a full understanding of their functions. Now, advances in DNA sequencing technology, including single-molecule, real-time sequencing and nanopore-based sequencing, have provided new opportunities for systematic detection of all three forms of methylated DNA at a genome-wide scale and offer unprecedented opportunities for achieving a more complete understanding of bacterial epigenomes. Indeed, as the number of mapped bacterial methylomes approaches 2,000, increasing evidence supports roles for methylation in regulation of gene expression, virulence and pathogen-host interactions.


Identification of Actinomyces denticolens as a cause of a soft tissue abscess in a horse.
A 6-year-old Arabian mare had a 4-week history of a subcutaneous mass (15 × 15 cm) at the base of the neck, cranial and distal to the prescapular lymph node on the right side. The mass was solid and painful on deep palpation. Ultrasonographic examination showed a soft-tissue abscess. Purulent aspirate was submitted for bacterial culture, which showed a moderate growth of an Actinomyces species. 16S rRNA gene sequencing was performed for definitive identification. Gene sequencing demonstrated close nucleotide homology with A. denticolens. Prolonged therapeutic management resulted in resolution of the abscess with a small scar. Speciation of actinomycetes is not a routine diagnostic procedure and 16S rRNA gene sequencing to identify A. denticolens as a cause of soft-tissue abscessation in horses in Australia has not been previously described. Practitioners should include this bacterial species in their differential diagnosis, particularly if abscesses do not respond to drainage and lavage alone.


Expression of the efflux pump genes cmeB, cmeF and the porin gene porA in multiple-antibiotic-resistant Campylobacter jejuni.
In Escherichia coli, increased expression of efflux pumps and/or decreased expression of porins can confer multiple antibiotic resistance (MAR), causing resistance to at least three unrelated classes of antibiotics, detergents and dyes. It was hypothesized that in Campylobacter jejuni, the efflux systems CmeABC, CmeDEF and the major outer membrane porin protein, MOMP (encoded by porA) could confer MAR. The expression of cmeB, cmeF and porA in 32 MAR C. jejuni isolated from humans or poultry was determined by comparative (C)-reverse transcriptase (RT)-PCR and denaturing DHPLC. A further 13 ethidium bromide-resistant isolates and three control strains were also investigated. Accumulation of ciprofloxacin+/-carbonyl cyanide-m-chlorophenyl hydrazone (CCCP) was also determined for all strains. Although resistance to ethidium bromide has been associated with MAR, expression of all three genes was similar in the ethidium bromide-resistant isolates. These data indicate that CmeB, CmeF and MOMP play no role in resistance to this agent in C. jejuni. Six MAR isolates over-expressed cmeB, 3/32 over-expressed cmeB and cmeF. No isolates over-expressed cmeF alone. Expression of porA was similar in all isolates. All nine isolates that over-expressed cmeB contained a mutation in cmeR, substituting glycine 86 with alanine. All cmeB over-expressing isolates also accumulated low concentrations of ciprofloxacin, which were restored to wild-type levels in the presence of CCCP. These data indicate that over-expression of cmeB is associated with MAR in isolates of C. jejuni. However, as cmeB was over-expressed by only one-third (9/32) of MAR isolates, these data also indicate other mechanisms of MAR in C. jejuni.


Cathepsin B acts as a dominant execution protease in tumor cell apoptosis induced by tumor necrosis factor.
Death receptors can trigger cell demise dependent or independent of caspases. In WEHI-S fibrosarcoma cells, tumor necrosis factor (TNF) induced an increase in cytosolic cathepsin B activity followed by death with apoptotic features. Surprisingly, this process was enhanced by low, but effectively inhibiting, concentrations of pan-caspase inhibitors. Contrary to caspase inhibitors, a panel of pharmacological cathepsin B inhibitors, the endogenous cathepsin inhibitor cystatin A as well as antisense-mediated depletion of cathepsin B rescued WEHI-S cells from apoptosis triggered by TNF or TNF-related apoptosis-inducing ligand. Thus, cathepsin B can take over the role of the dominant execution protease in death receptor-induced apoptosis. The conservation of this alternative execution pathway was further examined in other tumor cell lines. Here, cathepsin B acted as an essential downstream mediator of TNF-triggered and caspase-initiated apoptosis cascade, whereas apoptosis of primary cells was only minimally dependent on cathepsin B. These data imply that cathepsin B, which is commonly overexpressed in human primary tumors, may have two opposing roles in malignancy, reducing it by its proapoptotic features and enhancing it by its known facilitation of invasion.


Temporal effects of cyclic stretching on distribution and gene expression of integrin and cytoskeleton by ligament fibroblasts in vitro.
Cyclic stretching is pivotal to maintenance of the ligaments. However, it is still not clear when ligament fibroblasts switch on expression of genes related to the mechanotransduction pathway in response to cyclic stretching. This in vitro study investigated, using ligament fibroblasts, the time-dependent changes in distribution and gene expression of beta1 integrin, the cytoskeleton, and collagens after the application of 6% cyclic stretching at a frequency of 0.1 Hz for 3 hr on silicon membranes. We carried out confocal laser scanning microscopy to demonstrate changes in distribution of these components as well as quantitative real-time RT-PCR to quantify levels of these gene expression both during application of cyclic stretching and at 0, 2, 6, 12, and 18 hr after the termination of stretching. Control (unstretched) cells were used at each time point. Within 1 hr of the application of stretching, the fibroblasts and their actin stress fibers became aligned in a direction perpendicular to the major axis of stretch, whereas control (unstretched) cells were randomly distributed. In response to cyclic stretching, upregulation of actin at the mRNA level was first observed within 1 hr after the onset of stretching, while upregulation of beta1 integrin and type I and type III collagens was observed between 2 and 12 hr after the termination of stretching. These results indicate that the fibroblasts quickly modify their morphology in response to cyclic stretching, and subsequently they upregulate the expression of genes related to the mechanotransduction pathway mainly during the resting period after the termination of stretching.


Attitudes towards bipolar disorder and predictive genetic testing among patients and providers.
Attitudes about bipolar disorder (manic depressive disorder) and genetic testing were investigated. Three groups of subjects were surveyed including members of a manic depressive support group, medical students, and psychiatry residents. The questionnaire was intended to elicit impressions and attitudes about bipolar disorder (BP) from mental health consumers and health care providers with varying levels of personal and professional familiarity with the disorder. Attitudes towards prenatal testing and pregnancy termination were also assessed. The intention hypothetically to terminate a pregnancy was influenced by the likelihood of developing BP a well as the projected course and severity of illness. Nearly half of the total sample would terminate pregnancy if the fetus were definitely to develop an unspecified form of bipolar disorder. Presumed severity of illness was also found to be a modifying factor in the decision, with a low percentage of subjects electing to terminate for a mild course of bipolar disorder and a majority opting for termination in the case of an extremely severe presentation. Support group members were the least likely to terminate a hypothetical pregnancy in the case of a positive prenatal test and were the most likely to desire childhood testing in the absence of preventive or treatment options. The possible implications of these findings, as well as avenues of future research, are discussed.


The murine p75 TNF receptor promoter region: DNA sequence and characterization of a cis-acting silencer.
The promoter region of the murine p75 TNF receptor (TNF-R) was isolated from a mouse genomic DNA cosmid library. The promoter region is devoid of TATA box and has the characteristics of a house keeping gene since it contains multiple SP1 binding sites. Its mRNA has different initiation sites in different lymphoid cell lines. This promoter confers transcriptional activity to heterologous reporter genes. Deletion analysis showed that there is a silencer element located upstream from position -841. This inhibitory sequence is active both in fibroblasts and T-cell lines transiently or permanently transfected. A fragment from -929 to -841 is capable of transferring this 'silencer' activity to the early SV40 promoter. This activity could be blocked in trans- when a plasmid containing the same sequence was co-transfected with the reporter plasmid indicating that a protein binds to this region of the promoter.


Facile preparation of tissue engineering scaffolds with pore size gradients using the muesli effect and their application to cell spheroid encapsulation.
Porous biodegradable scaffolds have many applications in bioengineering, ranging from cell culture and transplantation, to support structures, to induce blood vessel and tissue formation in vivo. While numerous strategies have been developed for the manufacture of porous scaffolds, it remains challenging to control the spatial organization of the pores. In this study, we introduce the use of the granular convection effect, also known as the muesli or brazil nut effect, to rapidly engineer particulate templates with a vertical size gradient. These templates can then be used to prepare scaffolds with pore size gradients. To demonstrate this approach, we prepared templates with particle size gradients, which were then infused with a prepolymer solution consisting of the pentaerythritol ethoxylate (polyol), sebacoyl chloride (acid chloride), and poly(caprolactone). Following curing, the template was dissolved to yield biodegradable polyester-ether scaffolds with pore size gradients that could be tuned depending on the size range of the particulates used. The application of these scaffolds was demonstrated using pancreatic islets, which were loaded via centrifugation and retained within the scaffold's pores without a decrease in viability. The proposed strategy provides a facile approach to prepare templates with spatially organized pores that could potentially be used for cell transplantation, or guided tissue formation.


Distribution of Pathogenic Vibrio Species in the Coastal Seawater of South Korea (2017-2018).
Pathogenic Vibrio species are widely distributed in warm estuarine and coastal environments, and can infect humans through the consumption of raw or mishandled contaminated seafood and seawater. For this reason, the distribution of these bacteria in South Korea was investigated. Seawater samples were collected from 145 coastal area points in the aquatic environment in which Vibrio species live. Environmental data (i.e., water temperature, salinity, turbidity, and atmospheric temperature) was collected which may help predict the distribution of the species (data not shown). Seawater samples were filtered, and incubated overnight in alkaline peptone water, at 37°C. Using species-specific polymerase chain reaction methods, screening tests were performed for the hlyA, ctxA, vvhA, and tlh genes. Clones of pathogenic Vibrio species were isolated using 3 selective plating media. In 2017, total seawater isolation rates for Vibrio vulnificus, Vibrio cholerae (non-pathogenic, non-O1, non-O139 serogroups), and Vibrio parahaemolyticus were 15.82%, 13.18%, 65.80%, respectively. However, in 2018 isolation rates for each were 21.81%, 19.40%, and 70.05%, respectively. The isolation rates of pathogenic Vibrio species positively correlated with the temperature of seawater and atmosphere, but negatively correlated with salinity and turbidity. From 2017 to 2018, the most frequent seawater-isolated Vibrio species were V. parahaemolyticus (68.10 %), V. vulnificus (16.54%), and non-toxigenic V. cholerae (19.58%). Comprehensive monitoring, prevention, and control efforts are needed to protect the public from pathogenic Vibrio species.


Leadership Pathways in Academic Family Medicine: Focus on Underrepresented Minorities and Women.
Leadership positions in academic medicine lack racial and gender diversity. In 2016, the Council of Academic Family Medicine (CAFM) established a Leadership Development Task Force to specifically address the lack of diversity among leadership in academic family medicine, particularly for underrepresented minorities and women. The task force was formed in August 2016 with members from each of the CAFM organizations representing diversity of race, gender, and academic position. The group met from August 2016 to December 2017. The task force reviewed available leadership development programming, and through consensus identified common pathways toward key leadership positions in academic family medicine-department chairs, program directors, medical student education directors, and research directors. consensus development: The task force developed a model that describes possible pathways to several leadership positions within academic family medicine. Additionally, we identified the intentional use of a multidimensional mentoring team as critically important for successfully navigating the path to leadership. There are ample opportunities available for leadership development both within family medicine organizations and outside. That said, individuals may require assistance in identifying and accessing appropriate opportunities. The path to leadership is not linear and leaders will likely hold more than one position in each of the domains of family medicine. Development as a leader is greatly enhanced by forming a multidimensional team of mentors.


Searching for line active molecules on biphasic lipid monolayers.
In membranes with phase coexistence, line tension appears as an important parameter for the determination of the amount of domains, as well as their size and their shape, thus defining the membrane texture. Different molecules have been proposed as "linactants" (i.e. molecules that reduce the line tension, thereby modulating the membrane texture). In this work, we explore the efficiency of different molecules as linactants in monolayers with two coexisting phases of different thicknesses. We tested the linactant ability of a molecule with chains of different saturation degrees, another molecule with different chain lengths and a bulky molecule. In this way, we show in the same system the effect of molecules with chains of different rigidities, with an intrinsic thickness mismatch and with a bulky moiety, thereby analyzing different hypotheses of how a molecule may change the line tension in a monolayer system. Both lipids with different hydrocarbon chains did not act as linactants, while only one of the bulky molecules tested decreased the line tension in the monolayer studied. We conclude that there are no universal rules for the structure of a molecule that enable us to predict that it will behave as a linactant and thus, designing linactants appears to be a difficult task and a challenge for future studies. Furthermore, in regard to the membrane texture, there was no direct influence of the line tension in the distribution of domain sizes.


A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation.
Clinical studies have revealed that social support improves the outcome of cancer patients, whereas epidemiologic studies suggest that social isolation increases the risk of death associated with several chronic diseases. However, the precise molecular consequences of an unfavorable social environment have not been defined. To do so, robust, reproducible preclinical models are needed to study the mechanisms whereby an adverse environment affects gene expression and cancer biology. Because random assignment of inbred laboratory mice to well-defined social environments allows accurate and repeated measurements of behavioral and endocrine parameters, transgenic mice provide a preclinical framework with which to begin to determine gene-environment mechanisms. In this study, we found that female C3(1)/SV40 T-antigen mice deprived of social interaction from weaning exhibited increased expression of genes encoding key metabolic pathway enzymes in the premalignant mammary gland. Chronic social isolation was associated with up-regulated lipid synthesis and glycolytic pathway gene expression-both pathways are known to contribute to increased breast cancer growth. Consistent with the expression of metabolic genes in premalignant mammary tissue, isolated mice subsequently developed a significantly larger mammary gland tumors burden compared with group-housed mice. Endocrine evaluation confirmed that isolated mice developed a heightened corticosterone stress response compared with group-housed mice. Together, these transdisciplinary studies show for the first time that an adverse social environment is associated with altered mammary gland gene expression and tumor growth. Moreover, the identification of specific alterations in metabolic pathways gene expression favoring tumor growth suggests potential molecular biomarkers and/or targets (e.g., fatty acid synthesis) for preventive intervention in breast cancer.


Molecular progress on the mapping and cloning of functional genes for blast disease in rice (Oryza sativa L.): current status and future considerations.
Rice blast disease, which is caused by the fungal pathogen Magnaporthe oryzae, is a recurring problem in all rice-growing regions of the world. The use of resistance (R) genes in rice improvement breeding programmes has been considered to be one of the best options for crop protection and blast management. Alternatively, quantitative resistance conferred by quantitative trait loci (QTLs) is also a valuable resource for the improvement of rice disease resistance. In the past, intensive efforts have been made to identify major R-genes as well as QTLs for blast disease using molecular techniques. A review of bibliographic references shows over 100 blast resistance genes and a larger number of QTLs (∼500) that were mapped to the rice genome. Of the blast resistance genes, identified in different genotypes of rice, ∼22 have been cloned and characterized at the molecular level. In this review, we have summarized the reported rice blast resistance genes and QTLs for utilization in future molecular breeding programmes to introgress high-degree resistance or to pyramid R-genes in commercial cultivars that are susceptible to M. oryzae. The goal of this review is to provide an overview of the significant studies in order to update our understanding of the molecular progress on rice and M. oryzae. This information will assist rice breeders to improve the resistance to rice blast using marker-assisted selection which continues to be a priority for rice-breeding programmes.


Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations.
Pre-implantation embryo development in mammals begins at fertilization with the migration and fusion of the maternal and paternal pro-nuclei, followed by the degradation of inherited factors involved in germ cell specification and the activation of embryonic genes required for subsequent cell divisions, compaction, and blastulation. The majority of studies on early embryogenesis have been conducted in the mouse or non-mammalian species, often requiring extrapolation of the findings to human development. Given both conserved similarities and species-specific differences, however, even comparison between closely related mammalian species may be challenging as certain aspects, including susceptibility to chromosomal aberrations, varies considerably across mammals. Moreover, most human embryo studies are limited to patient samples obtained from in vitro fertilization (IVF) clinics and donated for research, which are generally of poorer quality and produced with germ cells that may be sub-optimal. Recent technical advances in genetic, epigenetic, chromosomal, and time-lapse imaging analyses of high quality whole human embryos have greatly improved our understanding of early human embryogenesis, particularly at the single embryo and cell level. This review summarizes the major characteristics of mammalian pre-implantation development from a chromosomal perspective, in addition to discussing the technological achievements that have recently been developed to obtain this data. We also discuss potential translation to clinical applications in reproductive medicine and conclude by examining the broader implications of these findings for the evolution of mammalian species and cancer pathology in somatic cells.


Ocular transfer of retinal glial cells transduced ex vivo with adenovirus expressing viral IL-10 or CTLA4-Ig inhibits experimental autoimmune uveoretinitis.
Gene transfer using immunomodulatory molecules is a promising tool for in vivo regulation of immune responses. Experimental autoimmune uveitis (EAU), which serves as a model for human ocular inflammation, is induced by systemic immunization with autoantigens, but its expression is restricted to the eye. Previously, we reported protection of rodents against EAU by intravenous or/and periocular injection of vIL-10-expressing adenovirus. Here, the expression of vIL-10 was targeted into the rat Lewis eye, by intravitreal injection of either the free virus or ex vivo transfected retinal Müller glial cells (RMG-vIL-10). As shown using GFP-expressing adenovirus, a longer expression of transgene was observed in the eye after transfer of transfected syngeneic RMG cells than was seen after injection of free virus. Intravitreal injection of RMG-vIL-10 led to significant decrease in ocular pathological manifestations, compared to control RMG cells. This was observed when cells were injected simultaneously with autoantigen, but also after a delayed administration of transfected cells. Finally, injection of RMG cells transfected with adenovirus expressing CTLA4 had a strongly protective effect. In conclusion, inhibition of antigen presentation at the site of expression of the autoimmune disorders represents an attractive alternative to treat ocular inflammation, and the transfer of ex vivo genetically modified cells provides a promising method to target the factor of interest into the eye.


Pressure-induced non-innocence in bis(1,2-dionedioximato)Pt(ii) complexes: an experimental and theoretical study of their insulator-metal transitions.
Bis(1,2-dionedioximato) complexes of Pt(ii) are known for their propensity to form linear chains of metal complexes in the solid state, and under the application of pressure members of the family display interesting optical and conductive properties. Two examples, Pt(bqd)2 and Pt(dmg)2, are known to undergo insulator-to-metal-to-insulator transitions, with the metallic state reached at 0.8-1.4 GPa and 5 GPa, respectively. Previous interpretations of these materials' behaviour focused on the role of the filled dz2 and vacant p orbitals on platinum, with little consideration to the role of the ligand. Here, the pressure-structural behaviour of Pt(bqd)2 is investigated through single crystal X-ray diffraction, the first such study on this material. The difference in conductive behaviour under pressure between Pt(bqd)2 and Pt(dmg)2 is then interpreted through a combination of experimental and computational methods, including conductivity measurements under high pressure and electronic structure calculations. Our computational work reveals the significant contribution from ligand low-lying vacant π-orbitals to the frontier orbitals and bands in these complexes, and provides an explanation for the experimentally observed re-entrant insulator-to-metal-to-insulator transitions, and the differences in behaviour between the two compounds.


What Spirituality Means for Patients and Families in Health Care.
This research focuses on the spiritual care experiences of patients and families at a hospital in Australia. Twenty-four patients and 10 family members were interviewed. Results indicate the importance of relatedness: being treated as a person, reminded of your capabilities and conversations about what matters. Maintaining contact with friends and family, sustaining religious and spiritual practices, music therapy and pet therapy were also significant and contact with the natural world and shared activities. The results indicate the importance of spirituality offered through pastoral care, and that all those involved in health care can contribute to the spiritually nurturing environment that reinforces healing.


Vitamin D plasma binding protein. Turnover and fate in the rabbit.
The metabolic disposition of the plasma binding protein (DBP) for vitamin D and its metabolites was studied in adult rabbits. Apo-DBP was purified from rabbit plasma and enzymatically labeled with radioiodine. The radioiodine-labeled protein retained its ability to bind vitamin D sterols and its physicochemical properties. When 125I-labeled DBP and 131I-labeled rabbit albumin were simultaneously injected intravenously, the 125I was cleared from plasma at a faster rate (t 1/2 = 1.7 d) than 131I (t 1/2 = 5 d) and 125I was present in excess of 131I in kidney, liver, skeletal muscle, heart, lung, intestine, testis, and bone 1 h after injection. In contrast to DBP, 25(OH)D3 was cleared more slowly (t 1/2 = 10.7 d). Compared to albumin, DBP radioactivity appeared earlier and in greater quantity in the urine of catheterized rabbits. Gel filtration analyses of plasma revealed most of the 125I to elute in the position of DBP, with only small amounts in the less than 1,000-dalton region. In contrast, almost all of the urine 125I eluted in this small molecular weight fraction. The molar ratio of DBP to 25(OH)D3 in normal rabbit plasma was 138/1. The extravascular pool of DBP was calculated to be 1.5-2.4 times larger than the intravascular DBP pool, and the molar replacement rate of DBP was 1,350-fold higher than that of 25(OH)D3. The plasma disappearance curves of holo-DBP, prepared either by saturating with 25(OH)D3 or by covalently linking 3 beta-bromoacetoxy-25(OH)D3, were very similar to that of apo-DBP. Neuraminidase treatment of DBP did not alter its plasma survival. These studies indicate that DBP or DBP-25(OH)D3 complex is removed from plasma by a variety of tissues, that the DBP moiety is degraded during this process, and that a significant recirculation of 25(OH)D3 probably occurs. The molar excess of DBP to 25(OH)D3 in plasma, and the relatively rapid turnover of DBP indicate that a high capacity, high affinity, and dynamic transport mechanism for vitamin D sterols exists in rabbit plasma.


Leaner and greener analysis of cannabinoids.
There is an explosion in the number of labs analyzing cannabinoids in marijuana (Cannabis sativa L., Cannabaceae) but existing methods are inefficient, require expert analysts, and use large volumes of potentially environmentally damaging solvents. The objective of this work was to develop and validate an accurate method for analyzing cannabinoids in cannabis raw materials and finished products that is more efficient and uses fewer toxic solvents. An HPLC-DAD method was developed for eight cannabinoids in cannabis flowers and oils using a statistically guided optimization plan based on the principles of green chemistry. A single-laboratory validation determined the linearity, selectivity, accuracy, repeatability, intermediate precision, limit of detection, and limit of quantitation of the method. Amounts of individual cannabinoids above the limit of quantitation in the flowers ranged from 0.02 to 14.9% w/w, with repeatability ranging from 0.78 to 10.08% relative standard deviation. The intermediate precision determined using HorRat ratios ranged from 0.3 to 2.0. The LOQs for individual cannabinoids in flowers ranged from 0.02 to 0.17% w/w. This is a significant improvement over previous methods and is suitable for a wide range of applications including regulatory compliance, clinical studies, direct patient medical services, and commercial suppliers.


Comparative Study between the Efficacy of Fentanyl, Antihistamines, and Dexmedetomidine in Suppressing Photic Sneeze Reflex during Peribulbar Block.
The photic sneeze reflex (autosomal dominant) is a condition that causes sneezing in response to numerous stimuli, such as looking at bright lights or periocular (surrounding the eyeball) injection. Unexpected or sudden sneezing during injection can be a dangerous side effect in periocular injection, in which abrupt head movement may cause globe injury. We intended to evaluate the efficacy of adding fentanyl, dexmedetomidine, and antihistamines on the incidence of the sneeze reflex associated with propofol sedation during periocular local anesthesia injections. Our study was a randomized, prospective, double-blinded and controlled clinical study. This study was conducted in Ain Shams and Fayoum university hospitals at the ophthalmic surgery department. After obtaining approval from our universities ethical committee and written informed valid consents from the patients, 90 patients were included in this study. The study population included patients of both sex, ASA grade 1 and 2, in the age ranging from 18-65 years. Patients were scheduled for cataract extraction surgeries and received peribulbar block. Then patients were randomly divided into three groups (30 patients each) using a computer- generated table of random numbers. Patients were preoxygenated with supplemental oxygen by nasal cannula, all 90 patients received intravenous propofol 1mg.kg- 1 bolus for sedation and were randomized to receive adjunctive drug 2 to 4 minutes prior to propofol injection: 30 patients received intravenous fentanyl 1 μmg.kg-1 (Group F), 30 patients received dexmedetomidine 1μmg.kg-1 (Group D), and 30 patients received antihistamine (pheniramine 22.75 mg) (Group H). The same local anesthetic admixture, consisting of 5 mL 2% lidocaine with 90 IU hyaluronidase, combined with 5 mL 0.5% plain bupivacaine in a 10-mL syringe at room temperature was administered to all patients using peribulbar block technique. A masked observer (surgeon or anesthesia assistant) recorded whether the patient had a sneezing event. Continuous cardiorespiratory monitoring was performed intraoperatively. Intraoperative and postoperative medication side effects were recorded including bradycardia (HR <55 beats/min), hypotension (MAP <50 mmHg sustained for >10 min), oxygen desaturation (SpO2<90%), nausea, vomiting and prolonged sedation using Ramsay Sedation Score (RSS). Student's t-test and Chi-square test were used for analysis. The demographic data of the three study groups revealed non-significant differences between the three study groups as regards age, sex distribution, and the duration of surgery. No patient was excluded after inclusion to the study. All patients were able to complete the entire study and their data were included in the final analysis. Five events of sneezing had occurred in 90 patients. Two in (D) group and three in (H) group with is no statistically significant difference between the three groups as regard sneezing. Bradycardia, hypotension and sedation had occurred significantly in group (D) compared to group (F) and group (D). No patient suffered from nausea, vomiting or oxygen desaturation in all studied groups. No statistically significant difference as regards patient satisfaction between the three studied groups. Fentanyl, dexmedetomidine and antihistamines with propofol sedation suppress photic sneeze reflex during peribulbar block.


The CARAMAL study could not assess the effectiveness of rectal artesunate in treating suspected severe malaria.
CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that "pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival". We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.


The significance of degenerate processes to enantioselective olefin metathesis reactions promoted by stereogenic-at-Mo complexes.
The present study provides spectroscopic and experimental evidence demonstrating that degenerate metathesis is critical to the effectiveness of this emerging class of chiral catalysts. Isolation and X-ray characterization of both diastereomeric complexes, as well as an examination of the reactivity and enantioselectivity patterns exhibited by such initiating neophylidenes in promoting ring-closing metathesis processes, are disclosed. Only when sufficient amounts of ethylene are generated and inversion at Mo through degenerate processes occurs at a sufficiently rapid rate is high enantioselectivity achieved, irrespective of the stereochemical identity of the initiating alkylidene (Curtin-Hammett kinetics). With diastereomeric metal complexes that undergo rapid interconversion, stereomutation at the metal center becomes inconsequential, and stereoselective synthesis of a chiral catalyst is not required.