Delivering Mental Health Care Virtually During the COVID-19 Pandemic: Qualitative Evaluation of Provider Experiences in a Scaled Context.
Virtual care delivery within mental health has increased rapidly during the COVID-19 pandemic. Understanding facilitators and challenges to adoption and perceptions of the quality of virtual care when delivered at scale can inform service planning postpandemic. We sought to understand consistent facilitators and persistent challenges to adoption of virtual care and perceived impact on quality of care in an initial pilot phase prior to the pandemic and then during scaled use during the pandemic in the mental health department of an ambulatory care hospital. This study took place at Women's College Hospital, an academic ambulatory hospital located in Toronto, Canada. We utilized a multimethods approach to collect quantitative data through aggregate utilization data of phone, video, and in-person visits prior to and during COVID-19 lockdown measures and through a provider experience survey administered to mental health providers (n=30). Qualitative data were collected through open-ended questions on provider experience surveys, focus groups (n=4) with mental health providers, and interviews with clinical administrative and implementation hospital staff (n=3). Utilization data demonstrated slower uptake of video visits at launch and prior to COVID-19 lockdown measures in Ontario (pre-March 2020) and subsequent increased uptake of phone and video visits during COVID-19 lockdown measures (post-March 2020). Mental health providers and clinic staff highlighted barriers and facilitators to adoption of virtual care at the operational, behavioral, cultural, and system/policy levels such as required changes in workflows and scheduling, increased provider effort, provider and staff acceptance, and billing codes for physician providers. Much of the described provider experiences focused on perceived impact on quality of mental health care delivery, including perceptions on providing appropriate and patient-centered care, virtual care effectiveness, and equitable access to care for patients. Continued efforts to enhance suggested facilitators, reduce persistent challenges, and address provider concerns about care quality based on these findings can enable a hybrid model of patient-centered and appropriate care to emerge in the future, with options for in-person, video, and phone visits being used to meet patient and clinical needs as required.


Oceanic protists with different forms of acquired phototrophy display contrasting biogeographies and abundance.
This first comprehensive analysis of the global biogeography of marine protistan plankton with acquired phototrophy shows these mixotrophic organisms to be ubiquitous and abundant; however, their biogeography differs markedly between different functional groups. These mixotrophs, lacking a constitutive capacity for photosynthesis (i.e. non-constitutive mixotrophs, NCMs), acquire their phototrophic potential through either integration of prey-plastids or through endosymbiotic associations with photosynthetic microbes. Analysis of field data reveals that 40-60% of plankton traditionally labelled as (non-phototrophic) microzooplankton are actually NCMs, employing acquired phototrophy in addition to phagotrophy. Specialist NCMs acquire chloroplasts or endosymbionts from specific prey, while generalist NCMs obtain chloroplasts from a variety of prey. These contrasting functional types of NCMs exhibit distinct seasonal and spatial global distribution patterns. Mixotrophs reliant on 'stolen' chloroplasts, controlled by prey diversity and abundance, dominate in high-biomass areas. Mixotrophs harbouring intact symbionts are present in all waters and dominate particularly in oligotrophic open ocean systems. The contrasting temporal and spatial patterns of distribution of different mixotroph functional types across the oceanic provinces, as revealed in this study, challenges traditional interpretations of marine food web structures. Mixotrophs with acquired phototrophy (NCMs) warrant greater recognition in marine research.


A Customized Human Mitochondrial DNA Database (hMITO DB v1.0) for Rapid Sequence Analysis, Haplotyping and Geo-Mapping.
The field of mitochondrial genomics has advanced rapidly and has revolutionized disciplines such as molecular anthropology, population genetics, and medical genetics/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated mitogenome database and an efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found to be consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient, and accurate means of sequence analysis for translational mitogenomics.


Perceptions of emerging tobacco products and nicotine replacement therapy among pregnant women and women planning a pregnancy.
The increasing availability of emerging non-combusted tobacco products (snus, dissolvables, and electronic nicotine delivery systems or ENDS) may have implications for pregnant women and women of reproductive age. We conducted 15 focus groups to explore how women perceive emerging non-combusted tobacco products and nicotine replacement therapy (NRT) in general, and during pregnancy. Sessions were held in 2013 in four U.S. cities. Participants were 18-40 years old and were pregnant smokers, pregnant quitters, or smokers planning a pregnancy. Responses were coded and analyzed to identify key themes using NVivo 10.0 qualitative software (QSR). Several themes emerged from focus groups. Participants generally found snus unappealing, but viewed dissolvables as a discreet and stigma-free way to use tobacco during pregnancy. Participants perceived NRT as ineffective and having undesired side effects. ENDS were thought to offer advantages over cigarettes, including use in smoke-free areas, lower cost, appealing flavors, and fewer health effects, and were seen by some as a potential quit aid. Some participants, however, worried that the lack of natural stopping point could lead to excessive use. Many participants felt that the use of any tobacco or NRT product is harmful during pregnancy. Women seeking to reduce health risks or stigma related to smoking during pregnancy may perceive advantages of using some emerging products over cigarettes. These findings can inform future public health efforts to reduce risks associated with tobacco product use among women of reproductive age.


Accelerated long-term forgetting in children with temporal lobe epilepsy.
Adults with temporal lobe epilepsy (TLE) have been found to have accelerated long-term forgetting, but this phenomenon has not yet been investigated in children. Although deficits in recall of materials after short (20- to 30-minute) delays have been shown to slowly emerge from childhood to adolescence in patients with TLE, it is unknown whether such a trend will also be found in recall of materials after long delays. This study examined the presence of accelerated long-term forgetting in children with TLE and how it relates to chronological age. Twenty-three children with TLE and 58 healthy controls of similar age, sex distribution and socioeconomic status completed a battery of neuropsychological tests, including standardised tests of story recall and design location, as well as two experimental tests requiring the learning of words and design locations to a criterion, both of which assessed recall after short (30-min) and long (7-day) delays. Word recall at the 7-day delay (relative to the 30-min recall) was significantly poorer in the TLE group, compared to the control group. The TLE group also exhibited worse 30-min recall performance on a standardised test of story recall. Individual patient analyses revealed dissociation between performance on the experimental and standardised verbal memory tests; children who were impaired on the experimental test (7-day delay) were not impaired on the standardised test (30-min delay). Compared to controls, patients with a left-hemisphere seizure focus recalled fewer words at short and long delays while patients with an abnormal hippocampus recalled fewer words at the long delay. No between-group differences were found with respect to the design location task. Age negatively correlated with the recall of words after short- and long-term delays within the TLE group, where older age was associated with worse memory. This association was not present in the control group. To our knowledge, this is the first study to show evidence of accelerated long-term forgetting in children with TLE, which could not be explained by poor performance on standardised memory tests. Additionally, these results suggest that the developmental trajectory of long-term memory in children with TLE is similar to that of short-term memory: deficits emerge gradually, therefore older children are more likely to present with long-term memory deficits.


Design Strategies and Applications of Biomaterials and Devices for Hernia Repair.
Hernia repair is one of the most commonly performed surgical procedures worldwide, with a multi-billion dollar global market. Implant design remains a critical challenge for the successful repair and prevention of recurrent hernias, and despite significant progress, there is no ideal mesh for every surgery. This review summarizes the evolution of prostheses design toward successful hernia repair beginning with a description of the anatomy of the disease and the classifications of hernias. Next, the major milestones in implant design are discussed. Commonly encountered complications and strategies to minimize these adverse effects are described, followed by a thorough description of the implant characteristics necessary for successful repair. Finally, available implants are categorized and their advantages and limitations elucidated, including non-absorbable and absorbable (synthetic and biologically derived) prostheses, composite prostheses, and coated prostheses. This review not only summarizes the state of the art in hernia repair, but also suggests future research directions toward improved hernia repair utilizing novel materials and fabrication methods.


Conversion of amino-terephthalonitriles to multi-substituted single benzene fluorophores with utility in bioimaging.
Substitution of two fluorine atoms of the tetrafluoroterephthalonitrile (TFTN) ring (ortho to each other) by amine nucleophiles through SNAr chemistry is achievable. However, tri- and tetra-substitution towards multi-substituted single benzene fluorophores (SBFs) is harder due to increased electron richness of the TFTN moiety. Tertiary amine donors promote the molecule towards such multi-substitution guided by the steric obstruction to intramolecular charge transfer to the TFTN ring. Contrarily, secondary amine substituents with better lone pair donation to the TFTN ring cannot induce the SNAr pathway and instead promote hydrolysis of the nitrile groups of the TFTN moiety. Theoretical investigations have helped unearth the reasons for this observed difference in chemical reactivities and also explain the differences in the emission spectra. Finally, the success of the synthetic method towards multi-substitution is showcased through creation of a highly lipophilic SBF bearing an octyl unit and demonstrating its utility in in vitro cellular imaging.


Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis.
The oxidative damage of the retinal pigment epithelium (RPE) is the early event that underlies the pathogenesis of maculopathies. Numerous studies have shown that punicalagin (PUN), a polyphenol present in pomegranate, can protect several cell types from oxidative stress. Our study aims to establish if PUN protects RPE from UV radiation-induced oxidative damage. We used an experimental model which involves the use of a human-RPE cell line (ARPE-19) exposed to UV-A radiation for 1, 3, and 5 hours. ARPE-19 cells were pre-treated with PUN (24 h) followed by UV-A irradiation; controls were treated identically, except for UV-A. Effects of pre-treatment with PUN on cell viability, intracellular reactive oxygen species ROS levels, modulation of Nrf2 and its antioxidant target genes, and finally apoptosis were examined. We found that pre‑treatment with PUN: (1) antagonized the decrease in cell viability and reduced high levels of ROS associated with UV-A-induced oxidative stress; (2) activated Nrf2 signaling pathway by promoting Nrf2 nuclear translocation and upregulating its downstream antioxidant target genes (HO-1 and NQO1); (3) induced an anti-apoptotic effect by decreasing Bax/Bcl-2 ratio. These findings provide the first evidence that PUN can prevent UV-A-induced oxidative damage in RPE, offering itself as a possible antioxidant agent capable of contrasting degenerative eye diseases.


Extension of fourier transform vibrational circular dichroism into the near-infrared region: continuous spectral coverage from 800 to 10 000 cm(-1).
We report the first vibrational circular dichroism (VCD) spectra with continuous coverage from 800 cm(-1) in the mid-infrared (MIR) region to 10 000 cm(-1) in the near-infrared (NIR) region. This coverage is illustrated with MIR and NIR absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), alpha-pinene, and camphor that serve as calibration samples over this entire region. Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD spectrometers were equipped with appropriate light sources, optics, and detectors, and were modified for dual-polarization-modulation (DPM) operation. The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT) detectors, as well as InGaAs and Germanium (Ge) detectors operating at room temperature, permitted collection of the desired absorbance and VCD spectra across the range of vibrational fundamental, combination band, and overtone frequencies. The spectra of DDM and alpha-pinene were measured as neat liquids and recorded for both enantiomers in the various spectral regions. Spectra for camphor were all measured in CCl(4) solution at a concentration of 0.6 M, except for the carbonyl-stretching region, where a more dilute concentration was used. The typical anisotropy ratios (g) of the three molecules were estimated with respect to their strongest VCD bands in each spectral region. It was found that for all three molecules in the spectral regions above 2000 cm(-1), anisotropy ratios are approximately the same order (10(-5)) of magnitude. However, in the MIR region, the typical anisotropy ratios are significantly different for the three molecules. This study demonstrates that with modern FT-VCD spectrometers modified for DPM operation, VCD spectra can be measured continuously across a wide spectral range from the MIR to nearly the visible region with an unsurpassed combination of signal-to-noise ratio and spectral resolution.


Cytologic and immunophenotypic features of CD34+ stem cells in body cavity fluids.
The possibility of leakage of CD34+ bone marrow stem cells from the peripheral blood into the coelomic cavity and the capability of coelomic fluid factors to induce their non-hematogenous differentiation were examined by immunocytochemistry (ICC). Body cavity fluid smears from 12 and 18 patients with and without cancer, respectively, were processed for double immunoperoxidase or double fluorescent ICC methods using antibodies against CD34, CD14, CD16, CD68, AE1/AE3, epidermal growth factor receptor (EGFR), D2-40, and CA125. Heavily irritated exudative fluid from 6 patients with or without cancer contained a few small round cells positive for CD34. Some of them co-expressed myeloid or monocytic markers such as CD14, CD68 or CD16. Some of the CD34+ cells also co-expressed AE1/AE3 or EGFR. In addition, D2-40 and CA125 were also demonstrated though the expression of the latter was quite sporadic. These findings support the concept that CD34+ stem cells can be released into irritated body cavity fluid and the possibility of subsequent differentiation to a non-hematogenous lineage under the influence of local humoral factors, in agreement with our previous in vitro experiments. The possibility of such a phenomenon should be kept in mind when body cavity fluid specimens are analyzed by ICC for diagnostic purposes.


In-line multipoint near-infrared spectroscopy for moisture content quantification during freeze-drying.
During the past decade, near-infrared (NIR) spectroscopy has been applied for in-line moisture content quantification during a freeze-drying process. However, NIR has been used as a single-vial technique and thus is not representative of the entire batch. This has been considered as one of the main barriers for NIR spectroscopy becoming widely used in process analytical technology (PAT) for freeze-drying. Clearly it would be essential to monitor samples that reliably represent the whole batch. The present study evaluated multipoint NIR spectroscopy for in-line moisture content quantification during a freeze-drying process. Aqueous sucrose solutions were used as model formulations. NIR data was calibrated to predict the moisture content using partial least-squares (PLS) regression with Karl Fischer titration being used as a reference method. PLS calibrations resulted in root-mean-square error of prediction (RMSEP) values lower than 0.13%. Three noncontact, diffuse reflectance NIR probe heads were positioned on the freeze-dryer shelf to measure the moisture content in a noninvasive manner, through the side of the glass vials. The results showed that the detection of unequal sublimation rates within a freeze-dryer shelf was possible with the multipoint NIR system in use. Furthermore, in-line moisture content quantification was reliable especially toward the end of the process. These findings indicate that the use of multipoint NIR spectroscopy can achieve representative quantification of moisture content and hence a drying end point determination to a desired residual moisture level.


Diagnostic accuracy of immunological methods in patients with tuberculous pleural effusion from Venezuela.
In recent years, better diagnostics for tuberculosis (TB) has received increasing attention, especially the diagnosis of tuberculous pleural effusion, which is difficult and at present the main tool in TPE diagnostic is pleural effusion smear and culture, but unfortunately, sensitivities are low, therefore better TPE diagnostic tools are needed. The aim of this study was to find a diagnostic algorithm to assess the progress in TPE diagnostic at the Hospital Vargas de Caracas, that permits identification of the majority of patients, at a satisfactory cost-benefit ratio, evaluating the levels of IFN-gamma and IL-12p40 in pleural effusion and serum, as well as the antibody reactivity in order to compare it with microbiological tests. A total of 60 individuals with pleural effusion were studied; 20 patients with tuberculous pleural effusion (TPE) formed the patient group and 40 patients with non-tuberculous pleural effusion (NTPE) formed the control group. The levels of IFN-gamma and IL-12p40 in effusion and serum and class and subclasses of IgG reactivity to Mycobacterium tuberculosis antigens were measured by ELISA. The utility of these methods for diagnosis of TPE was evaluated using receiver operating characteristic (ROC) curve analysis. The results of the 11 immunological methods evaluated showed that the anti-PPD IgG2 method was able to reach the highest specificity of 95% (CI: 88.3-101.8), positive predictive value (PPV) = 75 (at 30% sensitivity); while that the overall sensitivity of methods was between 95% and 30%, of these, two methods reached higher sensitivities; increased levels of pleural IFN-gamma, with a sensitivity of 95% (CI: 85.5-104.5) with the highest negative predictive value (NPV) = 97, (at 82.5% specificity), followed by decreased levels of serum IL-12p40 with a sensitivity of 95% (CI: 85.5-104.5), NPV = 95.2 (at 50% specificity). In contrast, microbiological methods showed that smear had a sensitivity of only 20%, while smear plus culture had, a sensitivity of 70%. Considering that TPE represents approximately 15 percent of all the TB clinically diagnosed at the Hospital Vargas de Caracas, in those patients with preliminary microbiology negativity in the effusion, the combined analysis of pleural IFN-gamma and anti-PPD IgG2 could represent a fast and effective diagnostic algorithm for improving the diagnosis previous to obtain culture results. In this way treatment against TB could be initiated or the need to cytological and pleural biopsy could be considered.


A fabric-dependent fracture criterion for bone.
A fracture criterion for bone tissue is proposed. Bone material is considered to be anisotropic and its properties are described by invoking the concept of directional variation of porosity. The fracture criterion is expressed as a scalar-valued function of the stress tensor and it incorporates an orientation-dependent distribution of compressive/tensile strength. The proposed mathematical framework is applied to a numerical analysis of fracture in the proximal femur due to a fall from standing height. The risk of fracture is assessed in the context of two different porosity distributions, simulating a healthy and an osteoporotic bone.


A critical appraisal of treatment decisions in multiple sclerosis--old versus new.
Interferon β and glatiramer acetate have been available for the treatment of multiple sclerosis (MS) for over a decade and their efficacy and safety are well established. These agents have detectable effects on the immune system, but have not been associated with a breakdown of immune surveillance. Novel MS therapies have been approved, or are awaiting approval, that differ from established immunotherapies with regard to their mechanisms of action, modes of administration, adverse-effect profiles and, possibly, the clinical and paraclinical benefits that they may provide for patients. Neurologists will soon be required to make complex treatment decisions with their patients on the basis of very limited clinical data and evidence. Under these circumstances, optimal assessment of risks and benefits will be challenging. In this Review, the anticipated benefits of novel therapies, including reduction in disease activity, possible prevention of disability, and improvement in quality of life, are outlined. In addition, the current acceptance of potential risks--including serious or even life-threatening adverse effects, the likelihood of which may rise with increased cumulative exposure to a particular agent--by patients with MS will be reviewed.


Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight.
Acanthosis nigricans (AN) is associated with obesity and type 2 diabetes, where insulin resistance (IR) is considered a predisposing factor. IR can also affect patients with type 1 diabetes (T1D). We evaluated the prevalence of AN in patients with T1D compared to subjects with obesity in order to define the interplay between IR and excess weight. We considered 138 pediatric patients who presented with T1D and 162 with obesity. As controls, 100 healthy normal-weight subjects were included. A physical examination with the detection of AN and biochemical assessments was performed. IR was calculated by using the homeostasis model assessment for IR in patients with obesity and the estimated glucose disposal rate in T1D. The AN prevalence was higher in T1D and obese subjects compared with controls in whom AN was not detected (p = 0.02 and p < 0.001, respectively). A greater number of AN cases were observed in subjects with obesity compared with T1D (p < 0.001). Patients with AN were older than subjects without AN (p = 0.005), and they had higher body mass index (BMI) values, waist circumference (WC), fasting triglycerides and blood pressure (all p < 0.001). Thirty-five patients with AN exhibited IR with an association between AN presence and IR in patients with obesity (p < 0.001). In T1D, there was an association between AN and being overweight/obese (p = 0.02), independently of IR. AN is a dermatological condition associated with obesity. In T1D, the presence of AN was significantly associated with overweight status or obesity but not IR. The presence of AN in the absence of IR supports the interplay role between impaired insulin signaling, IR and excess weight in the pathogenic mechanism.


DSSR: an integrated software tool for dissecting the spatial structure of RNA.
Insight into the three-dimensional architecture of RNA is essential for understanding its cellular functions. However, even the classic transfer RNA structure contains features that are overlooked by existing bioinformatics tools. Here we present DSSR (Dissecting the Spatial Structure of RNA), an integrated and automated tool for analyzing and annotating RNA tertiary structures. The software identifies canonical and noncanonical base pairs, including those with modified nucleotides, in any tautomeric or protonation state. DSSR detects higher-order coplanar base associations, termed multiplets. It finds arrays of stacked pairs, classifies them by base-pair identity and backbone connectivity, and distinguishes a stem of covalently connected canonical pairs from a helix of stacked pairs of arbitrary type/linkage. DSSR identifies coaxial stacking of multiple stems within a single helix and lists isolated canonical pairs that lie outside of a stem. The program characterizes 'closed' loops of various types (hairpin, bulge, internal, and junction loops) and pseudoknots of arbitrary complexity. Notably, DSSR employs isolated pairs and the ends of stems, whether pseudoknotted or not, to define junction loops. This new, inclusive definition provides a novel perspective on the spatial organization of RNA. Tests on all nucleic acid structures in the Protein Data Bank confirm the efficiency and robustness of the software, and applications to representative RNA molecules illustrate its unique features. DSSR and related materials are freely available at http://x3dna.org/.


Assortative mating in poison-dart frogs based on an ecologically important trait.
The origin of new species can be influenced by both deterministic and stochastic factors. Mate choice and natural selection may be important deterministic causes of speciation (as opposed to the essentially stochastic factors of geographic isolation and genetic drift). Theoretical models predict that speciation is more likely when mate choice depends on an ecologically important trait that is subject to divergent natural selection, although many authors have considered such mating/ecology pleiotropy, or "magic-traits" to be unlikely. However, phenotypic signals are important in both mate choice and ecological processes such as avoiding predation. In chemically defended species, it may be that the phenotypic characteristics influencing mate choice are the same signals being used to transmit a warning to potential predators, although few studies have demonstrated this in wild populations. We tested for assortative mating between two color morphs of the Strawberry Poison-Dart Frog, Dendrobates pumilio, a group with striking geographic variation in aposematic color patterns. We found that females significantly prefer individuals of their own morph under two different light treatments, indicating strong assortative mating based on multiple coloration cues that are also important ecological signals. This study provides a rare example of one phenotypic trait affecting both ecological viability and nonrandom mating, indicating that mating/ecology pleiotropy is plausible in wild populations, particularly for organisms that are aposematically colored and visually orienting.


Behaviour disturbance and mental handicap: typology and longitudinal trends.
Behaviour disturbance was investigated in mentally handicapped adults who were living in hospital or at home. The first part of the study describes an empirically derived typology of disturbed behaviour patterns and gives the details of a scale by means of which behaviour disturbance can be quantified along six dimensions: aggression, mood disturbance, communicativeness, antisocial conduct, idiosyncratic mannerisms, and self-injury. The second part of the study used the scale in a longitudinal study of behavioural disturbance. Different forms of disturbed behaviour exhibited different kinds of longitudinal stability, and the long-term changes in one aspect of disturbance depended on subjects' other disturbance scores.


Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery.
To compare the effectiveness of plasma-derived human thrombin and bovine thrombin for achieving hemostasis during surgery. Adults (N = 305) with > or = 1 mild or moderate bleeding site not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgical procedures at multiple study centers were randomized to human (n = 153) or bovine (n = 152) thrombin, applied topically with an absorbable gelatin sponge. Bleeding was assessed 3, 6, and 10 min post-application. Other evaluations included laboratory assessments, vital signs, blood loss, blood transfusions, time in specialty-care units, procedure duration, and length of hospital stay. Blood samples for antibody assessment were collected at baseline and postoperative week 5. The proportion of patients achieving hemostasis within 10 min (primary outcome) was equivalent for human and bovine thrombin (97.4 vs. 97.4%, respectively; ratio, 1.00; 95% CI, 0.96-1.05). The proportions of patients achieving hemostasis at 6 min (94.8 vs. 92.8%) and 3 min (73.2 vs. 72.4%) were also equivalent. No clinically meaningful differences were noted for other variables. The products had similar adverse event profiles. More patients (12.7%) who received bovine thrombin demonstrated seroconversion for > or = 1 of the 4 antibodies assayed than patients who received human thrombin (3.3%). No patients in the human thrombin group developed seroconversion for anti-human thrombin or anti-human factor V/Va antibodies. Limitations of this study include the lack of a placebo-control group, the potential for inter-surgeon variability, and the fact that antibody assessment was not evaluable in all patients. Plasma-derived human thrombin and bovine thrombin were equivalent in achieving hemostasis within 10, 6, and 3 min and had comparable safety profiles. None of the patients receiving human thrombin developed seroconversion for antibodies to any of the human antigens.


HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.
To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.


Application of multicriteria decision making methods to compression ignition engine efficiency and gaseous, particulate, and greenhouse gas emissions.
Compression ignition (CI) engine design is subject to many constraints, which present a multicriteria optimization problem that the engine researcher must solve. In particular, the modern CI engine must not only be efficient but must also deliver low gaseous, particulate, and life cycle greenhouse gas emissions so that its impact on urban air quality, human health, and global warming is minimized. Consequently, this study undertakes a multicriteria analysis, which seeks to identify alternative fuels, injection technologies, and combustion strategies that could potentially satisfy these CI engine design constraints. Three data sets are analyzed with the Preference Ranking Organization Method for Enrichment Evaluations and Geometrical Analysis for Interactive Aid (PROMETHEE-GAIA) algorithm to explore the impact of (1) an ethanol fumigation system, (2) alternative fuels (20% biodiesel and synthetic diesel) and alternative injection technologies (mechanical direct injection and common rail injection), and (3) various biodiesel fuels made from 3 feedstocks (i.e., soy, tallow, and canola) tested at several blend percentages (20-100%) on the resulting emissions and efficiency profile of the various test engines. The results show that moderate ethanol substitutions (~20% by energy) at moderate load, high percentage soy blends (60-100%), and alternative fuels (biodiesel and synthetic diesel) provide an efficiency and emissions profile that yields the most "preferred" solutions to this multicriteria engine design problem. Further research is, however, required to reduce reactive oxygen species (ROS) emissions with alternative fuels and to deliver technologies that do not significantly reduce the median diameter of particle emissions.


Hyperpyrexia in children: clinical implications.
A prospective study was done to determine the incidence of serious illness in children under two years of age with hyperpyrexia (temperature of 41.1 degrees C [106 degrees F] or greater). Nineteen children were seen and followed in the emergency department of Oklahoma Children's Memorial Hospital over a one-year period. The final clinical diagnoses included acute otitis media, pneumonia, acute gastroenteritis, roseola, and cellulitis of the leg. In the entire group there was no meningitis or subsequent death. One child was hospitalized. The statistical analysis (binomial test at the 0.05 level) confirms that the incidence of serious illness manifested only by high fever is no higher than 0.15. The mere presence of very high fever does not necessarily indicate a serious illness. Laboratory and other diagnostic work-up and hospitalization should be based on clinical evaluations, rather than done routinely.


Widespread diversity deficits of coral reef sharks and rays.
A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities.


Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose.
Mutations of the rearranged during transfection (RET) kinase are frequently reported in cancer, which make it as an attractive therapeutic target. Herein, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wild-type (wt) RET and RETV804M, which is a resistant mutant for several FDA-approved inhibitors. The X-ray structure of a representative inhibitor with RET revealed that the compound binds in a unique pose that bifurcates beneath the P-loop and confirmed the compound as a type I inhibitor. Through the structure-activity relationship (SAR) study, compound 20 was identified as a lead compound, showing potent inhibition of both RET and RETV804M. Additionally, compound 20 displayed potent antiproliferative activity of CCDC6-RET-driven LC-2/ad cells. Analysis of RET phosphorylation indicated that biological activity was mediated by RET inhibition. Collectively, N-trisubstituted pyrimidine derivatives could serve as scaffolds for the discovery and development of potent inhibitors of type I RET and its gatekeeper mutant for the treatment of RET-driven cancers.


'YourTube' the role of different diets in gastrostomy-fed children: Baseline findings from a prospective cohort study.
To assess the risks, benefits, and resource implications of home-blended food for children with gastrostomy tubes compared with a formula diet. This prospective cohort study of children (aged 0-18 years) collected baseline data on gastrointestinal symptoms, nutritional intake, anthropometric outcomes, parent and child quality of life, and resource use. A propensity score-weighted generalized linear mixed model was used to compare children receiving a home-blended versus formula diet. Baseline data were obtained for 180 children (2019-2021; 107 males, 73 females; mean age 9 years 7 months [SD 4 years 5 months]). Children receiving a home-blended diet (n = 104) had similar diagnoses and age but more lived in areas of lower deprivation and parental education was higher compared to the parents of children receiving a formula diet (n = 76). Children receiving home-blended diets had significantly better gastrointestinal scores than those receiving formula diets (B = 13.8, p < 0.001). The number of gut infections and tube blockages were similar between the two groups but with fewer stoma site infections in the group receiving home-blended food. Children receiving a home-blended diet had more fibre in their diet compared to children receiving a formula diet. Home-blended diets should be seen as a safe option for children who are gastrostomy-fed unless clinically contraindicated. Equality of access to home-blended diets for children with gastrostomy should be assessed by local clinical teams.


Fast-learning adaptive-subspace self-organizing map: an application to saliency-based invariant image feature construction.
The adaptive-subspace self-organizing map (ASSOM) is useful for invariant feature generation and visualization. However, the learning procedure of the ASSOM is slow. In this paper, two fast implementations of the ASSOM are proposed to boost ASSOM learning based on insightful discussions of the basis rotation operator of ASSOM. We investigate the objective function approximately maximized by the classical rotation operator. We then explore a sequence of two schemes to apply the proposed ASSOM implementations to saliency-based invariant feature construction for image classification. In the first scheme, a cumulative activity map computed from a single ASSOM is used as descriptor of the input image. In the second scheme, we use one ASSOM for each image category and a joint cumulative activity map is calculated as the descriptor. Both schemes are evaluated on a subset of the Corel photo database with ten classes. The multi-ASSOM scheme is favored. It is also applied to adult image filtering and shows promising results.


Male genitoplasty for 46 XX congenital adrenal hyperplasia patients presenting late and reared as males.
To evaluate the clinical profile and management of 46 XX Congenital Adrenal Hyperplasia (CAH) patients presenting with severe virilization and assigned a male gender. Of 173 children diagnosed with CAH at the Pediatric Intersex Clinic since 1980, seven children with CAH presented late with severe virilization and were reared as males. All of them were assigned the male sex with removal of the female adnexa. Six were treated with male genitoplasty. Appropriate hormonal supplementation was offered after puberty. The mean age at presentation was 14.2 years (7 - 21). Six patients had presented after puberty, only one at seven years of age. Staged male genitoplasty comprising of chordee correction, male urethroplasty, and bilateral testicular prosthesis was performed. The female adnexa (uterus, ovaries, most of the upper vagina, and the fallopian tubes) were removed. The mental makeup was masculine in six and bigender in one. Bilateral mastectomy was performed at puberty in all. Hormonal treatment comprised of glucocorticoids and testosterone. Six patients were comfortable with the outcome of the masculinizing genitoplasty. One had a short-sized phallus. One had repeated attacks of urinary tract infection arising from the retained lower vaginal pouch. Social adjustments were good in all, except in one who had a bigender mental makeup. CAH patients with severe virilization presenting late and reared as males are extremely rare. However, the assigned gender can be retained adequately as males, meeting the socioeconomic compulsions of the society. The results are satisfactory following appropriate surgical procedures and hormonal supplementation.


Zinc oxide nanocrystals as a nanoantibiotic and osteoinductive agent.
In this paper we aim to analyse the behaviour of ZnO nanocrystals (ZnO NCs), prepared with a new synthetic approach and not embedded in any composite matrix, for bone implant applications in vitro. In particular, we have developed a novel, fast and reproducible microwave-assisted synthesis, to obtain highly-crystalline, round-shaped ZnO NCs of 20 nm in diameter as an extremely-stable colloidal solution in ethanol. The nanocrystals were also partially chemically functionalized by anchoring amino-propyl groups to the ZnO surface (ZnO-NH2 NCs). Thus, the role of both ZnO NC concentration and surface chemistry were tested in terms of biocompatibility towards pre-osteoblast cells, promotion of cell proliferation and differentiation, and also in terms of antimicrobial activity against Gram positive and negative bacteria, such as Escherichia coli and Staphylococcus aureus, respectively. The results suggest that ZnO-NH2 NCs is the most promising candidate to solve infectious disease in bone implants and at the same time promote bone tissue proliferation, even at high concentrations. Although further investigations are needed to clarify the mechanism underlying the inhibition of biofilm formation and to investigate the role of the ZnO-NH2 NCs in in vivo assays, we demonstrated that fine and reproducible control over the chemical and structural parameters in ZnO nanomaterials can open up new horizons in the use of functionalized ZnO NCs as a highly biocompatible and osteoinductive nanoantibiotic agent for bone tissue engineering.


Moderate Reverberation Does Not Increase Subjective Fatigue, Subjective Listening Effort, or Behavioral Listening Effort in School-Aged Children.
Background noise and reverberation levels in typical classrooms have negative effects on speech recognition, but their effects on listening effort and fatigue are less well understood. Based on the Framework for Understanding Effortful Listening, noise and reverberation would be expected to increase both listening effort and fatigue. However, previous investigations of the effects of reverberation for adults have resulted in mixed findings. Some discrepancies in the literature might be accounted for by methodological differences; behavioral and subjective indices of listening effort do not often align in adults. The effects of sustained listening on self-reported fatigue in school-aged children are also not well understood. The purposes of this project were to (1) evaluate the effects of noise and reverberation on listening effort in school-aged children using behavioral and subjective measures, (2) compare subjective and behavioral indices of listening effort, and (3) evaluate the effects of reverberation on self-reported fatigue. Twenty typically developing children (10-17 years old) participated. Participants completed dual-task testing in two rooms that varied in terms of reverberation, an audiometric sound booth and a moderately reverberant room. In each room, testing was completed in quiet and in two levels of background noise. Participants provided subjective ratings of listening effort after completing the dual-task in each listening condition. Subjective ratings of fatigue were completed before and after testing in each level of reverberation. Results revealed background noise, not reverberation, increased behavioral and subjective listening effort. Subjective ratings of perceived performance, ease of listening, and desire to control the listening situation revealed a similar pattern of results as word recognition performance, making them poor candidates for providing an indication of behavioral listening effort. However, ratings of time perception were moderately correlated with behavioral listening effort. Finally, sustained listening for approximately 25 min increased self-reported fatigue, although changes in fatigue were comparable in low and moderately reverberant environments. In total, these data offer no evidence that a moderate level of reverberation increases listening effort or fatigue, but the data do support the reduction of background noise in classrooms.


Stirred anaerobic sequencing batch reactor containing immobilized biomass: a behavior study when submitted to different fill times.
The effect of the filling stage on the behavior of a mechanically stirred anaerobic sequencing batch reactor containing biomass immobilized on 1 cm polyurethane foam cubes was investigated. The reactor was made of acrylic with a capacity of 6.3 L, treating per cycle 2.5 L synthetic low-strength wastewater with a concentration of 500 mgCOD/L, at 30+/-1 degrees C. Eight-hour cycles (tC) and agitation of 500 rpm were utilized. At the beginning of each cycle 60% of the wastewater volume was treated, sufficient to completely cover the bed. The remaining volume was added at different fill times (tF) of 10, 120, 240, 260 and 480 min. The results obtained showed that ratios of tF/tC < or = 0.5 enabled organic matter removal higher than 75% and 70% for filtered and non-filtered samples, respectively. Ratios of tF/tC > 0.5, despite operation stability, resulted in loss of efficiency and formation of viscous material, similar to extra-cellular polymeric substances.


Immunolocalization of natriuretic peptides and their receptors in goat (Capra hircus) heart.
Natriuretic peptides are structurally similar, but genetically distinct, hormones that participate in cardiovascular homeostasis by regulating blood and extracellular fluid volume and blood pressure. We investigated the distribution of natriuretic peptides and their receptors in goat (Capra hircus) heart tissue using the peroxidase-anti-peroxidase (PAP) immunohistochemical method. Strong staining of atrial natriuretic peptide (ANP) was observed in atrial cardiomyocytes, while strong staining for brain natriuretic peptide (BNP) was observed in ventricular cardiomyocytes. Slightly stronger cytoplasmic C-type natriuretic peptide (CNP) immunostaining was detected in the ventricles compared to the atria. Natriuretic peptide receptor-A (NPR-A) immunoreactivity was more prominent in the atria, while natriuretic peptide receptor-B (NPR-B) immunoreactivity was stronger in the ventricles. Cytoplasmic natriuretic peptide receptor-C (NPR-C) immunoreactivity was observed in both the atria and ventricles, although staining was more prominent in the ventricles. ANP immunoreactivity ranged from weak to strong in endothelial and vascular smooth muscle cells. Endothelial cells exhibited moderate to strong BNP immunoreactivity, while vascular smooth cells displayed weak to strong staining. Endothelial cells exhibited weak to strong cytoplasmic CNP immunoreactivity. Vascular smooth muscle cells were labeled moderately to strongly for CNP. Weak to strong cytoplasmic NPR-A immunoreactivity was found in the endothelial cells and vascular smooth muscle cells stained weakly to moderately for NPR-A. Endothelial and vascular smooth cells exhibited weak to strong cytoplasmic NPR-B immunoreactivity. Moderate to strong NPR-C immunoreactivity was observed in the endothelial and smooth muscle cells. Small gender differences in the immunohistochemical distribution of natriuretic peptides and receptors were observed. Our findings suggest that endothelial cells, vascular smooth cells and cardiomyocytes express both natriuretic peptides and their receptors.


Significance of chromogranin A and synaptophysin in medullary thyroid carcinoma.
Medullary thyroid carcinoma (MTC) is a relatively rare thyroid carcinoma of C-cell deviation and produces and secrete calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, both CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in both sporadic and inheritable cases and the hallmark of inheritable cases in multiple endocrine neoplasm 2 (NEN2) is MTC. MEN2 cases represent 30% of MTCs through germline RET protooncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% of cases of solitary tumor and occur in older ages. CgA and synaptophysin (SPY) are the two, most widely used and reliable immunohistochemical markers for neuroendocrine tumors including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small, microscopic lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤ 0.3 cm) were lesser immunostained for CgA and SPY, despite strong staining for CT, compared to the larger (≥ 0.5cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesion (≤ 0.5 cm) and larger tumors (≥ 1.0cm). One small sporadic tumor (0.5 x 0.3 cm) was strongly and weakly, patchy (about 10% of tumor tissue) stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely, stronger stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent aggressive immunohistochemical markers for MTCs.


Designing a Tangible User Interface (TUI) for the Elderly Based on Their Motivations and Game Elements.
The elderly population has grown significantly in recent years, requiring strategies focused on promoting active aging to improve health and well-being. It may be achieved in many ways, including using technology for this population. We propose an interactive system for older adults based on a tangible user interface. A group of 10 experts conducted a heuristic evaluation of a system of this type utilizing a questionnaire and obtaining satisfactory results. This study evaluated the older adult population's fun and pervasive game experience. The results will provide a basis for continuing to build this interactive system to promote active aging in older adults, either at the cognitive or physical level, depending on the applied approach.


Stop Codon Polymorphisms in the Human SLC9A1 Gene Disrupt or Compromise Na+/H+ Exchanger Function.
The NHE1 isoform of the mammalian Na+/H+ exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in mammalian cells by removing one intracellular proton in exchange for one extracellular sodium. Deletion of the NHE1 gene (SLC9A1) affects the growth and motor ability of mice and humans but mutations and polymorphisms of the gene are only beginning to be characterized. NHE1 has a cytosolic C-terminal regulatory tail of approximately 315 amino acids and a 500 amino acid membrane domain. We examined the functional effects of three human stop codon mutations at amino acids 321, 449 and 735 in comparison with a mutant that had a shortened tail region (543 stop codon). The short mutants, 321, 449 and 543 stop codon mutant proteins, lost NHE1 activity and expression, and did not target to the plasma membrane. Protein for these short mutants was more rapidly degraded than the wild type and 735 ending proteins. The 735 terminating mutant, with the membrane domain and much of the cytosolic tail, had reduced protein expression and activity. The results demonstrate that early stop codon polymorphisms have significant and deleterious effects on the activity of the SLC9A1 protein product. The 735-NHE1 mutant, without the last 80 amino acids, had more minor defects. Surprisingly, retention of a proximal 43 amino acids adjacent to the membrane domain did little to maintain NHE1 expression, targeting and activity.


[Disseminated carcinoma of the prostate: monotherapy or complete androgenic blockade?].
To review the different modalities of hormonal therapy in the treatment of prostatic cancer and to analyze the results achieved by monotherapy and total androgen blockade. The results of different studies published in the literature are reviewed, with special reference to the results of the more important randomized studies. Hormone suppression achieves a response rate of more than 75% and is therefore a valid alternative in the management of metastatic cancer of the prostate. Monotherapy and total androgen blockade have similar survival rates and disease free intervals. However, the results according to prognostic groups are significantly better for those treated with total androgen blockade and has less severe disease, suggesting early treatment.


Trimma irinae, (Pisces; Gobioidei) a new species of gobiid fish from Milne Bay Province, Papua New Guinea.
A new species of Trimma, T. irinae, is described from 65 m off Lawadi, Milne Bay Province, Papua New Guinea. This colourful new species has red-orange spots on the head and anterior trunk, with a yellow to orange body posteriorly. The first dorsal fin has two dark basal spots, and the elongated section of the second dorsal spine is bright white to pale blue in life. There are 8-9 scales in the predorsal midline, usually cycloid scales present along the upper border of the opercle in up to three horizontal rows, no cheek scales, and the middle 9-11 rays of the pectoral fin are branched. The fifth pelvic fin ray branches once dichotomously and is 52-64% the length of the fourth ray, and the basal membrane connecting the inner margins of the fifth pelvic fins rays is less than 15% the length of the fifth ray.


Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion.
The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and color-coded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion.


Ranking the community psychology research output of institutions and authors: A new system of evaluating the field.
There have been multiple efforts to evaluate the contributions of the field of Community Psychology, and one of the more popular methods has involved gathering citations and articles published in Community Psychology journals. In recent years, several sites have gathered citation analysis and article publication rates so that it is now relatively easy to summarize settings and scholar rankings. In the current study, articles published in the two major journals of the field of Community Psychology over the past five decades were evaluated for these publications and citations. Findings indicated that several of the settings with highest publication and citation rates have not developed Community Psychology graduate programs, thus indicating that many publishing authors are in settings without formal graduate programs in Community Psychology. The benefits and limitations of this method of ranking programs and individuals are reviewed.


Bioinspired Hierarchical Multi-Protective Membrane for Extreme Environments via Co-Electrospinning-Electrospray Strategy.
Extreme environments can cause severe harm to human health, and even threaten life safety. Lightweight, breathable clothing with multi-protective functions would be of great application value. However, integrating multi-protective functions into nanofibers in a facile way remains a great challenge. Here, a one-step co-electrospinning-electrospray strategy is developed to fabricate a superhydrophobic multi-protective membrane (S-MPM). The water contact angle of S-MPM can reach up to 164.3°. More importantly, S-MPM can resist the skin temperature drop (11.2 °C) or increase (17.2 °C) caused by 0 °C cold or 70 °C hot compared with pure electrospun membrane. In the cold climate (-5 °C), the anti-icing time of the S-MPM is extended by 2.52 times, while the deicing time is only 1.45 s due to the great photothermal effect. In a fire disaster situation, the total heat release and peak heat release rate values of flame retarded S-MPM drop sharply by 24.2% and 69.3%, respectively. The S-MPM will serve as the last line of defense for the human body and has the potential to trigger a revolution in the practical application of next-generation functional clothing.


[Kidney and iodinated and gadolinium-based contrast agents].
In patients with renal failure, iodinated contrast agents may cause acute deterioration of the renal function and gadolinium-based contrast agents (GBCAs) may cause nephrogenic systemic fibrosis (NSF). The administration of a contrast agent must thus be reviewed for each patient and evaluation of renal function is paramount even though its estimation using formulas derived from the creatinine level may fluctuate. For iodinated contrast agents, contrast induced nephropathy is reduced by hydratation, preferably intravenous, when the GFR is less than 60 ml/min. The risk for intravenous injections is less than the risk for arterial injections, and the GFR threshold may be reduced to 45 ml/min. For gadolinium-based contrast agents, patients at risk for NSF are those with end-stage renal disease and patients undergoing dialysis. In such cases, the injection of a gadolinium-based contrast agent is only considered after a risk-benefit analysis has been completed, an alternate linear or macrocyclic agent issued and the dose limited to 0,1 mmol Gd/kg. Recently, recommendations from US and European agencies have converged. to be familiar with the risk factors of CIN with iodinated contrast agents; to be familiar with hydration procedures for patients at risk of CIN; to be familiar with the diagnostic criteria of NSF; to be familiar with the classification of GBCA with regards to the risk of NSF; to be familiar with the contraindications of the different groups of GBCA.


Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior-posterior neural pattern.
Neural tissue in developing Xenopus embryos is induced by signals from the dorsal mesoderm. Induction of anterior neural tissue could be mediated by noggin, a secreted polypeptide found in dorsal mesoderm. We show that bFGF, a known mesoderm inducer of blastula staged ectoderm, induces neural tissue from gastrula stage ectoderm. The type of neural tissue induced by bFGF from stage 10.25 ectoderm is posterior, as marked by Hox B9 expression. When bFGF and noggin are combined on early gastrula stage ectoderm, a more complete neural pattern is generated and no mesodermal tissue is detected. Explants treated with noggin and bFGF elongate and display distinct anterior and posterior ends marked by otx2 and Hox B9 expression, respectively. Furthermore, treatment of early gastrula ectoderm with noggin and bFGF results in the induction of En-2, a marker of the midbrain-hindbrain junction and Krox 20, a marker of the third and fifth rhombomeres of the hindbrain. Neither of these genes is induced by noggin alone or bFGF alone at this stage, suggesting a synergy in anterior-posterior neural patterning. The response of later gastrula (stage 11-12) ectoderm to bFGF changes so that Krox 20 and En-2 are induced by bFGF alone, while induction of more posterior tissue marked by Hox B9 is eliminated. The dose of bFGF affects the amount of neural tissue induced, but has little effect on the anterior-posterior character, rather the age of the ectoderm treated is the determinant of the response. Thus, an FGF signal may account for posterior neural induction, and anterior-posterior neural patterning could be partly explained by the actions of noggin and FGF, together with the changing response of the ectoderm to these factors.


Effective interactions between a pair of particles modified with tethered chains.
Using molecular dynamics, we evaluate the potential of mean force for two models of hybrid nanoparticles, namely, for the models with fixed and movable chain ligands. We also investigate the structure of segments of chains around nanoparticles and its change when one nanoparticle approaches the other. In the case of an isolated particle, we also employ a density functional theory to compute the segment density profiles. Moreover, to determine the structure of segments around a core, we have employed the concept of the so-called mass dipoles.


Recurrent mammary gland contractions induced by a low tonic release of oxytocin in rats.
In urethane-anaesthetized lactating rats, intramammary pressure occasionally displayed recurrent variations or oscillations having a slow rise time, low amplitude, long duration and a periodicity of 1-4 min. These oscillations differed from changes in intramammary pressure characteristic of reflex milk ejections induced by suckling, and were also observed in unsuckled rats. They were suppressed by lesions of the pituitary stalk or by stimulating the septum, a structure that inhibits the activity of the magnocellular system. They could be induced by long-term low frequency stimulation of the pituitary stalk, lesions of the septum or long-term infusions of oxytocin at a low rate of 0.05-0.3 mu./min. We suggest that the recurrent oscillations in intramammary pressure constitute a particular mode of response of the mammary gland to a tonic release of oxytocin resulting from a moderate but sustained increase in the basal level of electrical activity of the oxytocin-secreting neurones.


Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair.
The biological half-life (t1/2) of methylmercury (MeHg) shows considerable individual variability (t1/2 < 30 to > 120 days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25-35 years) and child (4 - 6 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1/2 of 46.9, 38.9, and 31.5 days and steady-state blood MeHg of 2.6, 2.6, and 2.3 µg/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7 µg/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.


DELIVER: A Safety Study of a Dapivirine Vaginal Ring and Oral PrEP for the Prevention of HIV During Pregnancy.
Pregnancy represents a period of high HIV acquisition risk. Safety data for the monthly dapivirine vaginal ring (DVR) during pregnancy are limited. Here, we report data from the first 2 cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). MTN-042 is being conducted in 3 cohorts beginning with later gestational ages when risks of drug exposure are less. Eligible pregnant individuals aged 18-40 years in Malawi, South Africa, Uganda, and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants in cohort 1 initiated product use between 36 weeks 0 days (36 0/7 weeks) and 37 6/7 weeks gestation; participants in cohort 2 initiated product use between 30 0/7 and 35 6/7 weeks gestation. All participants continued product use until delivery or 41 6/7 weeks gestation. Pregnancy outcomes and complications were assessed and summarized using descriptive statistics and compared with local background rates obtained through a separate chart review. One-hundred and fifty participants were enrolled into cohort 1 with 101 randomized to DVR and 49 to TDF/FTC. One-hundred and fifty-seven participants were enrolled into cohort 2 with 106 randomized to DVR and 51 to TDF/FTC. In both cohorts, pregnancy complications were rare and similar to local background rates. In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC were used in the third trimester of pregnancy, suggesting a favorable safety profile for both prevention products.


Ultrasonic wave measurement by differential interferometry.
The theory and performance of a two beam differential interferometer for measurement of both surface and bulk waves are described. The system is insensitive to small errors (<1 mm) in focus or in specimen flatness. Both amplitude and phase measurements are demonstrated. The system has been absolutely calibrated and can detect 6 x 10(-4)-A surface wave displacements on glass.


Treating a 20 mm Hg gradient alleviates myocardial hypertrophy in experimental aortic coarctation.
Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG. Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at 32 weeks by magnetic resonance imaging using a spoiled cine GRE sequence (TR/TE/FA 8/2.9/20), 14 × 14-cm FOV, and 3-mm slice thickness. Images (20 frames/cycle) were acquired in 6-8 short axis views from the apex to the mitral valve annulus. LV volume, ejection fraction (EF), and mass were quantified. LV mass was elevated for CoA (5.2 ± 0.55 g) versus control (3.6 ± 0.16 g) and corrected (4.0 ± 0.44 g) rabbits, resulting in increased LV mass/volume ratio for CoA rabbits. A trend toward increased EF and stroke volume was observed but did not reach significance. Elevated EF by volumetric analysis in CoA rabbits was supported by concomitant increases in total aortic flow by phase-contrast magnetic resonance imaging. The indices quantified trended toward a persistent hyperdynamic LV despite correction, but differences were not statistically significant versus control rabbits. These findings suggest the current putative 20 mm Hg BPG for treatment may be reasonable from the LV's perspective.


Molecular evolution of the hemagglutinin and neuraminidase genes of pandemic (H1N1) 2009 influenza viruses in Sendai, Japan, during 2009-2011.
Analyzing the evolutionary pattern of the influenza A(H1N1)pdm09 strain in different regions is important for understanding its diversification. We therefore conducted this study to elucidate the genetic variability and molecular evolution of the influenza A(H1N1)pdm09 strains that circulated during the 2009-2010 and 2010-2011 influenza seasons in Sendai, Japan. Nasopharyngeal swab specimens were collected from patients with influenza-like illnesses who visited outpatient clinics in Sendai City, Japan, from September 2009 to April 2011. A total of 75 isolates were selected from September 2009 to April 2011 to analyze the genetic changes in the entire hemagglutinin 1 (HA1) segment of the HA gene and the neuraminidase (NA) gene based on sequence analysis. Bayesian coalescent Markov chain Monte Carlo analyses of HA1 and NA gene sequences were performed for further analysis. High sequence identities were observed for HA1 and NA in influenza A(H1N1)pdm09, displaying 99.06 and 99.33 % nucleotide identities, respectively, with the A(H1N1)pdm09 vaccine strain A/California/07/2009. The substitution rates of nucleotides for HA1 in the 2009-2010 and 2010-2011 were 1.5 × 10-3 and 1.6 × 10-3 substitutions per site per year, respectively. Phylogenetic tree analysis demonstrated that Sendai isolates were clustered into global clade 7, which is characterized by an S203T mutation in the HA1 gene. Moreover, two distinct circulation clusters were present in the 2010-2011 season. Mutations were present in antigenic or receptor-binding domains of the HA1 segment, including A141V, S143G, S183P, S185T, and S203T. The Bayesian skyline plot model illustrated a steady rate for the maintenance of genetic diversity, followed by a slight increase in the later part of the 2010-2011 season. Selection analysis revealed that the HA1 (position 197) and NA (position 46) sites were under positive selection; however, no known mutation conferring resistance to NA inhibitors such as H275Y was observed. The effect on control of the influenza A(H1N1)pdm09 virus, including vaccine strain selection, requires continuous monitoring of the strain by genetic surveillance.


Calcium signalling remodelling and disease.
A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.


Advanced electron microscopy characterization of nanostructured heterogeneous catalysts.
Heterogeneous catalysis is one of the oldest nanosciences. Although model catalysts can be designed, synthesized, and, to a certain degree, characterized, industrial heterogeneous catalysts are often chemically and physically complex systems that have been developed through many years of catalytic art, technology, and science. The preparation of commercial catalysts is generally not well controlled and is often based on accumulated experiences. Catalyst characterization is thus critical to developing new catalysts with better activity, selectivity, and/or stability. Advanced electron microscopy, among many characterization techniques, can provide useful information for the fundamental understanding of heterogeneous catalysis and for guiding the development of industrial catalysts. In this article, we discuss the recent developments in applying advanced electron microscopy techniques to characterizing model and industrial heterogeneous catalysts. The importance of understanding the catalyst nanostructure and the challenges and opportunities of advanced electron microscopy in developing nanostructured catalysts are also discussed.


Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia.
Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia. In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis. Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site. The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects. The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia. These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia. The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM.


Purification and Characterization of Biofilm-Associated EPS Exopolysaccharides from ESKAPE Organisms and Other Pathogens.
In bacterial biofilms, high molecular weight, secreted exopolysaccharides can serve as a scaffold to which additional carbohydrates, proteins, lipids, and nucleic acids adhere, forming the matrix of the developing biofilm. Here we report methods to extract and purify high molecular weight (>15 kDa) exopolysaccharides from biofilms of eight human pathogens, including species of Staphylcococcus, Klebsiella, Acinetobacter, Pseudomonas, and a toxigenic strain of Escherichia coli O157:H7. Glycosyl composition analysis indicated a high total mannose content across all strains with P. aeruginosa and A. baumannii exopolysaccharides comprised of 80-90% mannose, K. pneumoniae and S. epidermidis strains containing 40-50% mannose, and E. coli with ∼10% mannose. Galactose and glucose were also present in all eight strains, usually as the second and third most abundant carbohydrates. N-acetyl-glucosamine and galacturonic acid were found in 6 of 8 strains, while arabinose, fucose, rhamnose, and xylose were found in 5 of 8 strains. For linkage analysis, 33 distinct residue-linkage combinations were detected with the most abundant being mannose-linked moieties, in line with the composition analysis. The exopolysaccharides of two P. aeruginosa strains analyzed were consistent with the Psl carbohydrate, but not Pel or alginate. The S. epidermidis strain had a composition rich in mannose and glucose, which is consistent with the previously described slime associated antigen (SAA) and the extracellular slime substance (ESS), respectively, but no polysaccharide intracellular adhesion (PIA) was detected. The high molecular weight exopolysaccharides from E. coli, K. pneumoniae, and A. baumannii appear to be novel, based on composition and/or ratio analysis of carbohydrates.


Stakeholder perspectives towards the use of toxicants for managing wild pigs.
Wild pigs (Sus scrofa) are one of the most detrimental invasive mammals in the US. Lack of adequate population control has allowed pigs to become established across the landscape, causing significant ecological and economic damage. Given the need for additional tools for reducing wild pig populations, two toxicants, warfarin and sodium nitrite, are at the forefront of the discussion regarding future wild pig management. However, no research has examined stakeholders' perspectives towards the use of toxicants in wild pig management. Given the lack of knowledge, our goal was to determine stakeholders' perspectives towards the legal use of toxicants for managing wild pigs. We surveyed 1822 individuals from three stakeholder groups (hunters, farmers, and forestland owners) across Alabama during February 2018 using an online survey following the Tailored Design Method. All three stakeholder groups were generally supportive of toxicant use, though their views differed slightly by group. Furthermore, all stakeholder groups were supportive of toxicant purchasing and use regulations, while accidental water contamination, human health impact, and incorrect usage of a toxicant were stakeholders' greatest concerns. These results indicate that these groups would likely be in support of using toxicants for wild pig management in Alabama and could be a model for other states or locations. Consequently, these results have direct implications for shaping policy and possible use of toxicants as a future wild pig management tool.


Stroke prevention care delivery: predictors of risk factor management outcomes.
Internationally, the development and implementation of stroke care guidelines have resulted in the evolution of stroke prevention outpatient clinics designed to accelerate patient access to treatment and behavioral risk reduction following transient ischemic attack or stroke. To examine the extent to which selected demographic, social-psychological, physiological, and adherence characteristics predicted achievement of blood pressure and glucose targets in a group of patients referred to a Canadian stroke prevention clinic with confirmed transient ischemic attack (TIA) or stroke and hypertension and/or diabetes. A total of 313, English speaking, adult patients who were referred from family or emergency department physicians to a stroke prevention clinic provided demographic data and received social-psychological screening testing at intake. Of these, 93 participants who met criteria of confirmed TIA or stroke plus hypertension and/or diabetes were identified as the study group. Seventy-seven of study group participants completed a 6-month follow-up. Admission screening tests included the Modified and Mini-Mental State Examinations, Trail Making Test, Clock Drawing Test, a medication self-efficacy scale, the Lubben Social Network Scale and the Geriatric Depression Scale. Family physician follow-up was ascertained 4-8 weeks after intake. At approximately 6 months after the initial screening measures, 77 study group participants completed additional measures of adherence, blood pressure and/or glycated hemoglobin. Transient ischemic attack was confirmed in 58% and stroke in 42% of the study group. Mean age was 69 years (SD=11); 53% were male; 97% had hypertension; and 25% were diabetic; some had both. Twenty-three percent were not followed-up by family practitioners. At 6-month follow-up, 97% reported ≥80% adherence to medication; only 57% met treatment targets. A logistic regression analysis identified three independent predictors of achieving blood pressure and/or glucose targets: self-efficacy expectations (OR, 1.61; 95% CI, 1.03-2.54; p=0.04), Mini-Mental State (OR, 1.28; 95% CI, 1.06-1.54; p=0.009); and self-reported adherence (OR, 1.14; 95% CI, 1.01-1.29; p=0.03). Three simple screening measures identified patients at increased risk of not achieving clinical risk factor management targets.


Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children.
Community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is an established pathogen in several areas of the United States, but experience with clindamycin for the treatment of invasive MRSA infections is limited. We compared the outcome of therapy for MRSA with that of methicillin-susceptible (MSSA) invasive infections in children treated with clindamycin, vancomycin or beta-lactam antibiotics. The demographics, hospital course and outcome of children at Texas Children's Hospital between February and November 2000 and between August 2001 and August 2002 with invasive S. aureus infections were reviewed from medical records in this retrospective study. CA-MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused invasive infections in 46 and 53 children, respectively. The median ages (range) of the children were: MRSA, 3.5 years (2 months to 18.6 years); MSSA, 4.8 years (3 months to 19.8 years). The sites of infection for MRSA vs. MSSA isolates, respectively, were: bacteremia, 3 vs. 6; osteomyelitis, 14 vs. 14; septic arthritis, 5 vs. 7; pneumonia, 11 vs. 3; lymphadenitis, 7 vs. 14; other, 5 vs. 8. Among MRSA patients 39 (20 received clindamycin only, 18 had vancomycin initially and 8 were treated with a beta-lactam initially) received clindamycin and 6 received vancomycin as primary therapy. Among MSSA patients, clindamycin, nafcillin or other beta-lactam antibiotics were used in 24, 18 and 9, respectively. The median number of febrile days was 3 (0 to 14) and 2 (0 to 6) for MRSA and MSSA patients, respectively (P = 0.07). The median number of days with positive blood cultures was 2 for the MRSA (n = 16) and 1 for the MSSA (n = 18) patients (P = 0.04). Clindamycin was effective in treating children with invasive infections caused by susceptible CA-MRSA isolates.


Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses.
Seasonal variation of relapses in multiple sclerosis (MS) suggests that season-dependent factors, such as ambient air pollution, may trigger them. However, only few studies have considered possible role of air pollutants as relapse's risk factor. We investigated the effect of particulate matter of aerodynamic diameter smaller than 10µm (PM10) on MS relapses. In total, 536 relapsing MS patients from Strasbourg city (France) were included, accounting for 2052 relapses over 2000-2009 period. A case-crossover design was used with cases defined as the days of relapse and controls being selected in the same patient at plus and minus 35 days. Different lags from 0 to 30 days were considered. Conditional logistic regressions, adjusted on meteorological parameters, school and public holidays, were used and exposure was considered first as a quantitative variable and second, as a binary variable. The natural logarithm of the average PM10 concentration lagged from 1 to 3 days before relapse onset was significantly associated with relapse risk (OR =1.40 [95% confidence interval 1.08-1.81]) in cold season. Consistent results were observed when considering PM10 as a binary variable, even if not significant. With an appropriate study design and robust ascertainment of neurological events and exposure, the present study highlights the effect of PM10 on the risk of relapse in MS patients, probably through oxidative stress mechanisms.


Inactivation of the open reading frame slr0399 in Synechocystis sp. PCC 6803 functionally complements mutations near the Q(A) niche of photosystem II. A possible role of Slr0399 as a chaperone for quinone binding.
The Synechocystis sp. PCC 6803 triple mutant D2R8 with V247M/A249T/M329I mutations in the D2 subunit of the photosystem II is impaired in Q(A) function, has an apparently mobile Q(A), and is unable to grow photoautotrophically. Several photoautotrophic pseudorevertants of this mutant have been isolated, each of which retained the original psbDI mutations of D2R8. Using a newly developed mapping technique, the site of the secondary mutations has been located in the open reading frame slr0399. Two different nucleotide substitutions and a deletion of about 60% of slr0399 were each shown to restore photoautotrophy in different pseudorevertants of the mutant D2R8, suggesting that inactivation of Slr0399 leads to photoautotrophic growth in D2R8. Indeed, a targeted deletion of slr0399 restores photoautotrophy in D2R8 and in other psbDI mutants impaired in Q(A) function. Slr0399 is similar to the hypothetical protein Ycf39, which is encoded in the cyanelle genome of Cyanophora paradoxa; in the chloroplast genomes of diatoms, dinoflagellates, and red algae; and in the nuclear genome of Arabidopsis thaliana. Slr0399 and Ycf39 have a NAD(P)H binding motif near their N terminus and have some similarity to isoflavone reductase-like proteins and to a subunit of the eukaryotic NADH dehydrogenase complex I. Deletion of slr0399 in wild type Synechocystis sp. PCC 6803 has no significant phenotypic effects other than a decrease in thermotolerance under both photoautotrophic and photomixotrophic conditions. We suggest that Slr0399 is a chaperone-like protein that aids in, but is not essential for, quinone insertion and protein folding around Q(A) in photosystem II. Moreover, as the effects of Slr0399 are not limited to photosystem II, this protein may also be involved in assembly of quinones in other photosynthetic and respiratory complexes.


Lens thickness in western Nigeria. A comparative ultrasonic study in Negros and Danes.
A comparative ultrasonic, oculometric study was performed in negroes, West Nigeria (151 persons) and in caucasians, Denmark (88 persons). The negros have thinner lenses than caucasians, and overall ethnic difference of 0.12 mm was found. Male negroes have longer vitreous and axial lengths than male caucasians (VB 0.56 mm, AxL 0.30 mm).


Properties of alpha-crystallin bound to lens membrane: probing organization at the membrane surface.
Alpha crystallin, one of the three major soluble proteins of the eye lens, appears to be a natural extrinsic protein of lens plasma membrane. Membrane-immobilized alpha-crystallin could provide a template for the increased association of protein with lens membrane seen in aging and cataracts. Alpha-crystallin binds to lens membrane through both a high-affinity saturable and low-affinity nonsaturable process. The organization of alpha-crystallin at the membrane surface was proved by the examination of various chemical reactivities and a functional property of the membrane bound protein. The carboxyl-terminal domain of membrane bound alpha-crystallin appeared to be as readily cleaved by mild trypsinolysis as that of the soluble protein and the cleaved protein remained bound to the membrane. The immobilized protein was more extensively crosslinked by a bifunctional primary amine-reactive agent than the soluble protein. No evidence for crosslinking to membrane intrinsic protein was obtained. Like soluble alpha-crystallin, the membrane bound protein displayed chaperone-like activity, a property dependent upon quaternary structure. These findings were interpreted to indicate that alpha-crystallin binds to lens membrane as an aggregate with only a fraction of each aggregate in direct contact with the membrane's hydrophobic surface. It is suggested that the nonsaturable binding reflects low affinity association of soluble alpha-crystallin with a layer of membrane-immobilised protein.


Congenital insensitivity to pain: report of two cases.
Congenital indifference or insensitivity to pain (CIP) is a rare syndrome. It mimics a number of other syndromes categorized under peripheral sensory neuropathies, often making early diagnosis difficult. Two cases from the middle east are presented, highlighting possible diagnostic, and management difficulties.


Predicting Performance on the National Athletic Trainers' Association Board of Certification Examination From Grade Point Average and Number of Clinical Hours.
OBJECTIVE: To determine whether grade point average, hours of clinical education, or both are significant predictors of performance on the National Athletic Trainers' Association Board of Certification examination and whether curriculum and internship candidates' scores on the certification examination can be differentially predicted. DESIGN AND SETTING: Data collection forms and consent forms were mailed to the subjects to collect data for predictor variables. Subject scores on the certification examination were obtained from Columbia Assessment Services. SUBJECTS: A total of 270 first-time candidates for the April and June 1998 certification examinations. MEASUREMENTS: Grade point average, number of clinical hours completed, sex, route to certification eligibility (curriculum or internship), scores on each section of the certification examination, and pass/fail criteria for each section. RESULTS: We found no significant difference between the scores of men and women on any section of the examination. Scores for curriculum and internship candidates differed significantly on the written and practical sections of the examination but not on the simulation section. Grade point average was a significant predictor of scores on each section of the examination and the examination as a whole. Clinical hours completed did not add a significant increment for any section but did add a significant increment for the examination overall. Although no significant difference was noted between curriculum and internship candidates in predicting scores on sections of the examination, a significant difference by route was found in predicting whether candidates would pass the examination as a whole (P =.047). Proportion of variance accounted for was less than R(2) = 0.0723 for any section of the examination and R(2) = 0.057 for the examination as a whole. CONCLUSIONS: Potential predictors of performance on the certification examination can be useful to athletic training educators in assisting students. These findings must be used cautiously because of the low proportion of explained variance. Low R(2) values suggest that the largest contributors to performance on the examination were not identified in this study. Although the results of this study support the decision to discontinue the internship route to certification, continued research focusing on identification and investigation of the constructs that contribute to examination success is needed.


Antagonistic interactions peak at intermediate genetic distance in clinical and laboratory strains of Pseudomonas aeruginosa.
Bacteria excrete costly toxins to defend their ecological niche. The evolution of such antagonistic interactions between individuals is expected to depend on both the social environment and the strength of resource competition. Antagonism is expected to be weak among highly similar genotypes because most individuals are immune to antagonistic agents and among dissimilar genotypes because these are unlikely to be competing for the same resources and antagonism should not yield much benefit. The strength of antagonism is therefore expected to peak at intermediate genetic distance. We studied the ability of laboratory strains of Pseudomonas aeruginosa to prevent growth of 55 different clinical P. aeruginosa isolates derived from cystic fibrosis patients. Genetic distance was determined using genetic fingerprints. We found that the strength of antagonism was maximal among genotypes of intermediate genetic distance and we show that genetic distance and resource use are linked. Our results suggest that the importance of social interactions like antagonism may be modulated by the strength of resource competition.


Contribution of the C-terminal regions of promyelocytic leukemia protein (PML) isoforms II and V to PML nuclear body formation.
Promyelocytic leukemia protein (PML) nuclear bodies are dynamic and heterogeneous nuclear protein complexes implicated in various important functions, most notably tumor suppression. PML is the structural component of PML nuclear bodies and has several nuclear splice isoforms that share a common N-terminal region but differ in their C termini. Previous studies have suggested that the coiled-coil motif within the N-terminal region is sufficient for PML nuclear body formation by mediating homo/multi-dimerization of PML molecules. However, it has not been investigated whether any of the C-terminal variants of PML may contribute to PML body assembly. Here we report that the unique C-terminal domains of PML-II and PML-V can target to PML-NBs independent of their N-terminal region. Strikingly, both domains can form nuclear bodies in the absence of endogenous PML. The C-terminal domain of PML-II interacts transiently with unknown binding sites at PML nuclear bodies, whereas the C-terminal domain of PML-V exhibits hyperstable binding to PML bodies via homo-dimerization. This strong interaction is mediated by a putative α-helix in the C terminus of PML-V. Moreover, nuclear bodies assembled from the C-terminal domain of PML-V also recruit additional PML body components, including Daxx and Sp100. These observations establish the C-terminal domain of PML-V as an additional important contributor to the assembly mechanism(s) of PML bodies.


Slice thickness in the assessment of medial and lateral tibial cartilage volume and accuracy for the measurement of change in a longitudinal study.
The optimal magnetic resonance image (MRI) slice thickness required to assess cartilage volume accurately and efficiently in cross-sectional and longitudinal studies is unknown. We compared cartilage volume measured from MRI of the knees using different slice thicknesses (1.5 to 7.5 mm) and assessed longitudinal change. A total of 123 subjects with osteoarthritis had baseline and followup MRI on their symptomatic knee at 2 years. Medial and lateral tibial cartilage volumes were calculated using increasing slice thickness by extracting each second, third, fourth, or fifth slice area to calculate total volume, which was compared to the "gold standard" volume calculated from the original 1.5 mm slices. There was little difference in the average medial and lateral tibial cartilage volume observed as the slice thickness increased from 1.5 to 7.5 mm; medial tibial cartilage volume ranged from 1750 microl to 1787 microl and lateral tibial cartilage volume ranged from 1949 microl to 2007 microl. There was also little absolute difference in the average change in medial and lateral tibial cartilage volume measured over 2 years. However, with increasing slice thickness, there was a decreased correlation between the tibial cartilage volume change calculated from the increased slice thickness, with the lowest correlation being 0.77 (p < 0.001) when the lateral cartilage volume calculated from the 7.5 mm slice was compared to the 1.5 mm slices. Increasing slice thickness may provide sufficiently accurate measurement of tibial cartilage volume and change over time in some studies. This would result in reduction in MRI scanning and postimaging processing time, which has the potential of increasing the feasibility of this technique.