Estimating the contribution of HIV-infected adults to household pneumococcal transmission in South Africa, 2016-2018: A hidden Markov modelling study.
Human immunodeficiency virus (HIV) infected adults are at a higher risk of pneumococcal colonisation and disease, even while receiving antiretroviral therapy (ART). To help evaluate potential indirect effects of vaccination of HIV-infected adults, we assessed whether HIV-infected adults disproportionately contribute to household transmission of pneumococci. We constructed a hidden Markov model to capture the dynamics of pneumococcal carriage acquisition and clearance observed during a longitudinal household-based nasopharyngeal swabbing study, while accounting for sample misclassifications. Households were followed-up twice weekly for approximately 10 months each year during a three-year study period for nasopharyngeal carriage detection via real-time PCR. We estimated the effect of participant's age, HIV status, presence of a HIV-infected adult within the household and other covariates on pneumococcal acquisition and clearance probabilities. Of 1,684 individuals enrolled, 279 (16.6%) were younger children (<5 years-old) of whom 4 (1.5%) were HIV-infected and 726 (43.1%) were adults (≥18 years-old) of whom 214 (30.4%) were HIV-infected, most (173, 81.2%) with high CD4+ count. The observed range of pneumococcal carriage prevalence across visits was substantially higher in younger children (56.9-80.5%) than older children (5-17 years-old) (31.7-50.0%) or adults (11.5-23.5%). We estimate that 14.4% (95% Confidence Interval [CI]: 13.7-15.0) of pneumococcal-negative swabs were false negatives. Daily carriage acquisition probabilities among HIV-uninfected younger children were similar in households with and without HIV-infected adults (hazard ratio: 0.95, 95%CI: 0.91-1.01). Longer average carriage duration (11.4 days, 95%CI: 10.2-12.8 vs 6.0 days, 95%CI: 5.6-6.3) and higher median carriage density (622 genome equivalents per millilitre, 95%CI: 507-714 vs 389, 95%CI: 311.1-435.5) were estimated in HIV-infected vs HIV-uninfected adults. The use of ART and antibiotics substantially reduced carriage duration in all age groups, and acquisition rates increased with household size. Although South African HIV-infected adults on ART have longer carriage duration and density than their HIV-uninfected counterparts, they show similar patterns of pneumococcal acquisition and onward transmission.


Factors Influencing Telehealth Service Use and Health Outcomes in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis: Cross-Sectional Study.
Several studies have demonstrated the efficacy and user acceptance of telehealth in managing patients with chronic conditions, including continuous ambulatory peritoneal dialysis (CAPD). However, the rates of telehealth service use in various patient groups have been low and have declined over time, which may affect important health outcomes. Telehealth service use in patients undergoing CAPD has been recognized as a key challenge that needs to be examined further. This study aimed to explore the rates of telehealth service use over 4 months, identify factors influencing its use, and examine the relationship between telehealth service use and health outcomes in Thai people undergoing CAPD. This cross-sectional study, which was a part of a pragmatic randomized controlled trial study, was conducted at a dialysis center in Bangkok, Thailand. The study included patients who were undergoing CAPD. These patients were randomly enrolled in the intervention group to receive telehealth service and additional standard care for 4 months. Data were collected using self-reported questionnaires, including a demographic form, Functional, Communicative, and Critical Health Literacy Scale, Perceived Usefulness Questionnaire, Brief Illness Perception Questionnaire, Patient-Doctor Relationship Questionnaire, and Kidney Disease Quality of Life 36 Questionnaire. Additionally, Google Analytics was used to obtain data on the actual use of the telehealth service. These data were analyzed using descriptive statistics, repeated-measures ANOVA, and regression analyses. A total of 159 patients were included in this study. The mean rate of telehealth service use throughout the period of 4 months was 62.06 (SD 49.71) times. The rate of telehealth service use was the highest in the first month (mean 23.48, SD 16.28 times) and the lowest in the third month (mean 11.09, SD 11.48 times). Independent variables explained 27.6% of the sample variances in telehealth service use. Older age (β=.221; P=.002), higher perceived usefulness (β=.414; P<.001), unemployment (β=-.155; P=.03), and positive illness perception (β=-.205; P=.004) were associated with a significantly higher rate of telehealth service use. Regarding the relationship between telehealth service use and health outcomes, higher rates of telehealth service use were linked to better quality of life (β=.241; P=.002) and lower peritonitis (odds ratio 0.980, 95% CI 0.962-0.997; P=.03). This study provides valuable insights into factors impacting telehealth service use, which in turn affect health outcomes in patients undergoing CAPD.


Food Allergy from Infancy Through Adulthood.
Food allergies are the result of immune responses that cause adverse reactions to foods. Immune responses to foods may produce a spectrum of symptoms and disorders, including acute allergic reactions and anaphylaxis, food protein-induced allergic proctocolitis, food protein-induced enterocolitis syndrome, food-dependent, exercise-induced anaphylaxis, and oral allergy syndrome (pollen-food allergy syndrome). Food-allergic responses also contribute to chronic inflammatory disorders such as eosinophilic esophagitis and atopic dermatitis. Although food allergy affects people from infancy through adulthood, there are allergic features that differ according to age (ie, presentation, triggers, and natural course) and have important implications for diagnosis, prognosis, and management. New food allergies can develop at any age, and we propose similarities in the etiology of de novo food allergy whether in infancy or adulthood. The approach to managing food allergy changes dramatically over the life course, and physicians and patients must respond accordingly to optimize care. Food allergy therapies are emerging, and the efficacy and safety of these interventions could differ by age group of those treated. In this review, we highlight interesting observations on the etiology and characteristics of food allergy presenting at different ages and discuss clinical management as it relates to life stage.


Early impact of COVID-19 on transplant center practices and policies in the United States.
COVID-19 is a novel, rapidly changing pandemic: consequently, evidence-based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center-level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID-19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID-19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID-19. Shortage of COVID-19 tests was reported by 42.5%. Respondents reported a total of 148 COVID-19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center-level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence-based practices.


Nuclear binding of oestradiol-17beta and induction of protein synthesis in the rat uterus during postnatal development.
1. The uterine response to a single injection of oestradiol-17beta during postnatal development of the rat was studied with respect to (i) nuclear binding of oestradiol-17beta; (ii) induction of the synthesis of a specific cytoplasmic protein (;induced protein' of Gorski); (iii) rate of incorporation of (3)H-labelled amino acids into total protein and into nuclear acid-soluble and acid-insoluble protein; and (iv) rate of [(3)H]thymidine incorporation into DNA. 2. Specific nuclear binding of oestradiol-17beta could be demonstrated even at birth. Administration of oestradiol-17beta in vivo caused a significant increase in the number of nuclear binding sites in rats aged 10 days or older. 3. A rapid method is described for the detection of the ;induced protein', based on cellulose acetate electrophoresis. Induction of this protein could be demonstrated at the age of 10, 15 and 20 days, but not in 5-day-old rats. 4. In 20-day-old rats the rate of (3)H-labelled amino acid incorporation into protein increased by 3h after oestradiol administration. Incorporation into the different protein fractions reached peak values asynchronously: at 3-4h for acid-insoluble nuclear protein, at 6h for total protein and at about 12h for acid-soluble protein. 5. Treatment with oestradiol failed to stimulate amino acid incorporation into protein in 5- or 10-day-old rats; at the age of 15 to 30 days the hormone caused a significant increase in incorporation into total protein and into both types of nuclear protein. 6. Since the capacity for nuclear binding of oestradiol and for synthesis of the induced protein is demonstrable in the rat uterus before it acquires the ability to respond to the hormone with enhanced general protein synthesis and DNA synthesis, it appears that nuclear binding and the synthesis of the induced protein may be necessary but not sufficient conditions for the trophic action of oestradiol.


Carbon coated core-shell multifunctional fluorescent SPIONs.
Due to their unique magnetic properties, multiple surface functionality and biocompatibility, superparamagnetic iron oxide nanoparticles (SPIONs) show very promising characteristics as magnetic resonance (MR) contrast agents in biomedical applications. However, a lack of fluorescence makes SPIONs inappropriate for multimodal bioimaging. SPIONs surface functionalized by either organic fluorescent molecules or semiconductor quantum dots (QDs) have been reported as bioimaging probes but subsequent deterioration of the fluorescent dyes due to low photostability and quick photobleaching limits their long term practical application. In addition, QDs are found to be toxic in nature. Here, we present a novel one step method to synthesize non-toxic carbon coated highly photostable core-shell magnetic and fluorescent SPIONs with long-lasting fluorescence alongside a superior magnetic resonance (MR) imaging ability. Apart from the highly comparable superparamagnetic properties of the SPIONs, the optical response of the material is much better than commonly used Rhodamine or cyanine dyes.


The validity and reliability of computer-aided semen analyzers in performing semen analysis: a systematic review.
Computer-aided sperm analyzers (CASA) are currently used worldwide for semen analysis. However, there are doubts about their reliability to fully substitute the human operator. Therefore, this study aimed to systematically review the current literature comparing results from semen evaluation by both CASA-based and manual approaches. A systematic screening of the literature was performed based on the PRISMA guidelines and by searching on PubMed, Scopus, and Embase databases. A total of 14 studies were included. Our results showed a high degree of correlation for sperm concentration and motility when analysis was performed either manually or by using a CASA system. However, CASA results showed increased variability in low (<15 million/mL) and high (>60 million/mL) concentration specimens, while sperm motility assessment was inaccurate in samples with higher concentration or in the presence of non-sperm cells and debris. Morphology results showed the highest level of difference, due to the high amount of heterogeneity seen between the shapes of the spermatozoa either in one sample or across multiple samples from the same subject. Overall, our study suggests CASA systems as a valid alternative for the evaluation of semen parameters in clinical practice, especially for sperm concentration and motility. However, further technological improvements are required before these devices can one day completely replace the human operator. Artificial intelligence-based CASA devices promise to offer higher efficiency of the analysis and improve the reliability of results.


Viral receptors on isolated murine and human ependymal cells.
Viruses that infect ependyma cause ependymitis in humans and hydrocephalus in experimental animals. We report that reovirus type 1 (which induces hydrocephalus in mice) binds to the surface of isolated human and murine ciliated ependymal cells. With the use of recombinant viral clones, the binding property was mapped to the type 1 viral hemagglutinin, which also determines in vivo the affinity of reovirus type 1 for ependyma. Mumps virus, measles virus, parainfluenza type 3, and herpes simplex virus type 1 bind to murine ependyma cells, whereas reovirus type 3, herpes simplex virus type 2, and poliovirus type 2 do not.


Bird species migration ratio in East Asia, Australia, and surrounding islands.
Bird migration and its relationship with the contemporary environment have attracted long-term discussion. We calculated the avian migration ratio (the proportion of breeding species that migrate) in the areas from 70°E to 180°E and examined its relationship with the annual ranges of ambient temperature, primary productivity (estimated by the Enhanced Vegetation Index), and precipitation, along with island isolation and elevational range. The avian migration ratio increased with increasing latitude in general but varied greatly between the two hemispheres. Additionally, it showed minimal differences between continents and islands. Our analyses revealed that the seasonality of ambient temperature, which represents the energy expenditure of birds, is the dominant factor in determining bird species migration. Seasonality in primary productivity and other environmental factors play an indirect or limited role in bird species migration. The lower avian migration ratio in the Southern Hemisphere can be attributed to its paleogeographical isolation, stable paleoclimate, and warm contemporary environment. Under current trends of global warming, our findings should lead to further studies of the impact of warming on bird migration.


Effects of orthopaedic immobilization of the right lower limb on driving performance: an experimental study during simulated driving by healthy volunteers.
The effects of immobilization of the right lower limb on driving performance are unknown. Therefore, clinicians and legislators cannot put forth recommendations for road safety for patients requiring such immobilization. The objective of the present study was to evaluate the effect of two orthopaedic immobilization devices on the braking performances of healthy volunteers under simulated driving conditions. The braking performances of forty-eight healthy volunteers were evaluated under three conditions: wearing a running shoe, wearing a walking cast, and wearing an Aircast Walker on the right lower limb. A computerized driving simulator was used to measure the maximum force applied on the brake pedal during braking as well as the braking reaction time and the total braking time during emergency braking with and without a distractor. The mean braking forces applied with the shoe, the walking cast, and the Aircast Walker were 293.8, 275.4, and 287.2 lb (133.3, 124.9, and 130.3 kg), respectively. The value with the walking cast was significantly lower than that with the shoe or Aircast Walker (p < 0.0001); there was no difference between the shoe and the Aircast Walker. The adjusted mean braking reaction times during emergency braking without a distractor were 0.580 second (shoe), 0.609 second (cast), and 0.619 second (Aircast Walker). The value with the running shoe was significantly lower than that with either type of immobilization (p < or = 0.0001). With a distractor, the mean braking reaction time was shorter with the running shoe than it was with either form of immobilization (p < or = 0.0001); the mean time was also shorter with the walking cast than it was with the Aircast Walker (p = 0.003). During both emergency braking tasks (with and without a distractor), the mean total braking time was shorter with the shoe than it was with either type of immobilization (p < 0.0001). With a distractor, the adjusted mean total braking time was shorter with the walking cast than it was with the Aircast Walker (p = 0.035). Immobilization of the right lower limb affects the braking force as well as the braking reaction time and total braking time during emergency braking by healthy volunteers. While these changes are significant, their impact on the ability to drive safely during emergency braking situations is questionable. Future research into the impact of such immobilization on the emergency braking performances of patients is warranted to confirm these observations.


181,450 children with disabilities in New York State.
2000 Census data on the number of children with disabilities in New York State are presented on a county-by-county basis. There are numerous difficulties associated with the delivery of dental care to these youngsters with special needs. Nevertheless, if all dentists were willing to help, each practitioner would need to care for about one dozen of these youngsters.


DPDPE-UK14,304 synergy is retained in mu opioid receptor knockout mice.
When agonists to alpha(2)adrenergic receptor (AR) and delta opioid receptor (DOR) are co-administered, they act synergistically to inhibit nociceptive elicited behavior. Some previous studies of synergism have used the DOR-selective agonist [D-Pen(2),D-Pen(5)]-enkehphalin (DPDPE), however, DPDPE has been shown to be less potent in mu opioid receptor-knockout (MOR-KO) mice. It is possible, therefore, that MOR contributes to the synergism of DPDPE with the alpha(2)AR agonists. We compared the interactions of spinally administered DPDPE with an alpha(2)AR-adrenergic agonist in MOR-KO and MOR-wildtype (WT) mice. In these mice, morphine is ineffective and the potency of spinally administered DOR agonists, deltorphin II (DELT II) and DPDPE decreased 16- and 250-fold, respectively. Antagonism studies using the MOR-selective antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP) and the DOR-selective antagonist, naltrindole HCl (naltrindole) demonstrated that while DOR mediates DPDPE-induced antinociception in MOR-KO, both MOR and DOR participate in DPDPE antinociception in WT mice, suggesting that DPDPE is less selective for DOR than previously observed in binding studies when given in vivo. The potency of the alpha(2)AR agonist UK14,304 was equivalent in WT and MOR-KO, demonstrating that the loss of opioid-mediated antinociception in the MOR-KO was not due to generalized impairment of antinociceptive processing. Interestingly, isobolographic analysis showed that, despite substantial loss of DPDPE potency in MOR-KO, DPDPE-UK14,304 synergism is fully retained. Collectively, these experiments demonstrate that although MOR participates in DELT II- and DPDPE-mediated spinal antinociception, DOR independently participates in synergistic antinociception with alpha(2)AR. Resolution of the roles of the opioid receptor subtypes in opioid agonist-induced effects may require comparison of the effects of multiple selective agonists in knockout animals.


Variation in resting strategies across trophic levels and habitats in mammals.
Mammals must carefully balance rest with other behaviors that influence fitness (e.g., foraging, finding a mate) while minimizing predation risk. However, factors influencing resting strategies and the degree to which resting strategies are driven by the activities of predators and/or prey remain largely unknown. Our goal was to examine how mammalian resting strategies varied with trophic level, body mass, and habitat. We reviewed findings from 127 publications and classified the resting strategies of terrestrial and aquatic mammalian species into three categories: social (e.g., resting in groups), temporal (e.g., resting during the day), or spatial (e.g., resting in burrows). Temporal strategies were most common (54% of cases), but the prevalence of strategies varied with body mass and among trophic levels. Specifically, lower trophic levels and smaller species such as rodents and lagomorphs used more spatial and social resting strategies, whereas top predators and larger species used mostly temporal resting strategies. Resting strategies also varied among habitat types (e.g., rainforest vs. grassland), but this was primarily because closely related species shared both habitats and resting strategies. Human presence also affected resting strategies at all trophic levels but most strongly influenced top predators through shifts in rest timing. Human-induced behavioral changes in rest patterns cascade to modify behaviors across multiple trophic levels. These findings advance our fundamental understanding of natural history and ecology in wild animals and provide a roadmap for future comparative studies.


Monitoring the formation and decay of transient photosensitized intermediates using pump-probe UV resonance Raman spectroscopy. I: Self-modeling curve resolution.
Resolution of transient excited-state Raman scattering from ground-state and solvent bands is a challenging spectroscopic measurement since excited-state spectral features are often of low intensity, overlapping the dominant ground-state and solvent bands. The Raman spectra of these intermediates can be resolved, however, by acquiring time-resolved data and using multidimensional data analysis methods. In the absence of a physical model describing the kinetic behavior of a reaction, resolution of the pure-component spectra from these data can be accomplished using self-modeling curve resolution, a factor analysis technique that relies on the correlation in the data along a changing composition dimension to resolve the component spectra. A two-laser UV pump-probe resonance-enhanced Raman instrument was utilized to monitor the kinetics of amine quenching of excited-triplet states of benzophenone. The formation and decay of transient intermediates were monitored over time, from 15 ns to 100 micros. Factor analysis of the time-resolved spectral data identified three significant components in the data. The time-resolved intensities at each Raman wavenumber shift were projected onto the three significant eigenvectors, and least-squares criteria were developed to find the common plane in the space of the eigenvectors that includes the observed data. Within that plane, the three pure-component spectra were resolved using geometric criteria of convex hull analysis. The resolved spectra were found to arise from benzophenone excited-triplet states, diphenylketyl radicals, and the solvent and ground-state benzophenone.


Quantifying the contribution of gluconeogenesis to glucose production in fasted human subjects using stable isotopes.
The contribution of gluconeogenesis to glucose production is estimated from the enrichment of the H bound to C-5 of glucose relative to either that bound to C-2 of glucose or the enrichment in body water on ingesting 2H2O in the fasted state. Contributions of all gluconeogenic substrates are included in the estimate and the limitation of an uncertain precursor enrichment removed. The half-life of 2H2O in body water precludes a repeat study for many weeks. Glycogen cycling could result in underestimation, but there is evidence that glycogen cycling does not occur in liver in the fasted state. Gluconeogenesis has been estimated by mass-isotopomer-distribution analyses, usually by administering 13C-labelled glycerol. Underestimates emphasize the major limitation of the method, i.e. the need to assume a single enrichment of the precursor pool. Estimates of gluconeogenesis from isotopomer distribution in arterial-blood glucose and lactate on infusing [U-13C6] glucose are unreliable, as a proportion of the glucose is formed from glycerol and from amino acids not converted to glucose via pyruvate. Loss of label in the Krebs cycle and relying on enrichment of arterial-blood lactate as a measure of hepatic pyruvate further add to the uncertainty. Estimates of the rate of gluconeogenesis by NMR are obtained by subtraction of the rate of glycogenolysis determined by NMR from the rate of glucose production. Estimates are then the mean rate for the period over which glycogen contents are measured. Technical considerations can limit the accuracy of analyses and result in overestimates.


Reconstructing Neanderthal diet: The case for carbohydrates.
Evidence for plants rarely survives on Paleolithic sites, while animal bones and biomolecular analyses suggest animal produce was important to hominin populations, leading to the perspective that Neanderthals had a very-high-protein diet. But although individual and short-term survival is possible on a relatively low-carbohydrate diet, populations are unlikely to have thrived and reproduced without plants and the carbohydrates they provide. Today, nutritional guidelines recommend that around half the diet should be carbohydrate, while low intake is considered to compromise physical performance and successful reproduction. This is likely to have been the same for Paleolithic populations, highlighting an anomaly in that the basic physiological recommendations do not match the extensive archaeological evidence. Neanderthals had large, energy-expensive brains and led physically active lifestyles, suggesting that for optimal health they would have required high amounts of carbohydrates. To address this anomaly, we begin by outlining the essential role of carbohydrates in the human reproduction cycle and the brain and the effects on physical performance. We then evaluate the evidence for resource availability and the archaeological evidence for Neanderthal diet and investigate three ways that the anomaly between the archaeological evidence and the hypothetical dietary requirements might be explained. First, Neanderthals may have had an as yet unidentified genetic adaptation to an alternative physiological method to spare blood glucose and glycogen reserves for essential purposes. Second, they may have existed on a less-than-optimum diet and survived rather than thrived. Third, the methods used in dietary reconstruction could mask a complex combination of dietary plant and animal proportions. We end by proposing that analyses of Paleolithic diet and subsistence strategies need to be grounded in the minimum recommendations throughout the life course and that this provides a context for interpretation of the archaeological evidence from the behavioral and environmental perspectives.


SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases.
Members of the DEAD/H box-containing helicase superfamily include proteins essential to genome replication, repair, and expression. We report here the cloning and initial characterization of a novel human member of this protein family, designated hHel1 (human helicase 1), now designated SMARCAD1 by HUGO. This DEAD/H box-containing molecule has seven highly conserved sequence regions that allow us to place it in the SNF2 family of the helicase superfamily. Uniquely, though, hHel1 contains two DEAD/H box motifs, a property not reported to be shared by any other SNF2 family members. This defines a new subfamily consisting of hHel1 and its homologues. In addition to these DEAD/H box/ATP-binding motifs, hHel1 has a putative nuclear localization signal and several regions that may mediate protein-protein interactions. Expression analysis indicates that hHel1 transcripts are ubiquitous, with particularly high levels in endocrine tissue. We have mapped the gene for hHel1 to human chromosome 4q22-q23; this region is rich in breakpoints and deletion mutants of genes involved in several human diseases, notably soft tissue leiomyosarcoma, hepatocellular carcinoma, and hematologic malignancies. Our observation that human Hel1 gene overexpression is present in an E1A-expressing cell line with increased capacity for gene reactivation events by genomic rearrangement suggests that human Hel1 may play a role in genetic instability development.


Protein kinase A-mediated gating of neuregulin-dependent ErbB2-ErbB3 activation underlies the synergistic action of cAMP on Schwann cell proliferation.
In Schwann cells (SCs), cyclic adenosine monophosphate (cAMP) enhances the action of neuregulin, the most potent known mitogen for SCs, by synergistically increasing the activation of two crucial signaling pathways: ERK and Akt. However, the underlying mechanism of cross-talk between neuregulin and cAMP signaling remains mostly undefined. Here, we report that the activation of protein kinase A (PKA), but not that of exchange protein activated by cAMP (EPAC), enhances S-phase entry of SCs by synergistically enhancing the ligand-dependent tyrosine phosphorylation/activation of the neuregulin co-receptor, ErbB2-ErbB3. The role of PKA in neuregulin-ErbB signaling was confirmed using PKA inhibitors, pathway-selective cAMP analogs, and natural ligands stimulating PKA activity in SCs, such as adenosine and epinephrine. Two basic observations defined the synergistic action of PKA as "gating" for neuregulin-ErbB signaling: 1) the activation of PKA was not sufficient to induce S-phase entry or the activation of either ErbB2 or ErbB3; and 2) the presence of neuregulin was strictly required to ignite ErbB activation and thereby ERK and Akt signaling. However, PKA directly phosphorylated ErbB2 on Thr-686, a highly conserved intracellular regulatory site that was required for the PKA-mediated synergistic enhancement of neuregulin-induced ErbB2-ErbB3 activation and proliferation in SCs. The gating action of PKA on neuregulin-induced ErbB2-ErbB3 activation has important biological significance, because it insures signal amplification into the ERK and Akt pathways without compromising either the neuregulin dependence or the high specificity of ErbB signaling pathways.


Neoplasms in domestic animals: a review of experimental and spontaneous carcinogenesis.
Clues to environmental and host factors in human oncogenesis are derived from clinical or epidemiologic studies; additional evidence is provided by animal experimentation. Induced tumors in animals are useful because of their reproducibility and predictability, allowing detailed study of specific carcinogens or carcinogenic influences. Spontaneously or naturally occurring tumors in domestic animals are of particular interest for comparative studies - these tumors occur in heterogenous outbred populations of animal closely sharing man's environment; their cause is generally unknown; many tumors occur in numbers suitable for detailed investigations; and tumors generally occur in aged animals, thus facilitating study of chronic processes associated with carcinogenesis in nature.


Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases.
Geldanamycin (GM) is a natural antibiotic that binds Hsp90 and induces the degradation of receptor tyrosine kinases, steroid receptors, and Raf. It is a potent inhibitor of cancer cells that overexpress HER-kinases, but its effects on other important proteins may cause significant toxicity and limit its clinical use. We report the synthesis and identification of a GM dimer, GMD-4c, which had selective activity against HER-kinases. Selectivity was a function of linker length and required two intact GM moieties. GMD-4c is a potent inducer of G1 block and apoptosis of breast cancer cell lines that overexpress HER2, but does not appreciably inhibit the growth of 32D cells that lack HER-kinases. GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases.


Large-sized rare tree species contribute disproportionately to functional diversity in resource acquisition in African tropical forest.
Increasing evidence is available for a positive effect of biodiversity on ecosystem productivity and standing biomass, also in highly diverse systems as tropical forests. Biodiversity conservation could therefore be a critical aspect of climate mitigation policies. There is, however, limited understanding of the role of individual species for this relationship, which could aid in focusing conservation efforts and forest management planning. This study characterizes the functional specialization and redundancy for 95% of all tree species (basal area weighted percentage) in a diverse tropical forest in the central Congo Basin and relates this to species' abundance, contribution to aboveground carbon, and maximum size. Functional characterization is based on a set of traits related to resource acquisition (wood density, specific leaf area, leaf carbon, nitrogen and phosphorus content, and leaf stable carbon isotope composition). We show that within both mixed and monodominant tropical forest ecosystems, the highest functional specialization and lowest functional redundancy are solely found in rare tree species and significantly more in rare species holding large-sized individuals. Rare species cover the entire range of low and high functional redundancy, contributing both unique and redundant functions. Loss of species supporting functional redundancy could be buffered by other species in the community, including more abundant species. This is not the case for species supporting high functional specialization and low functional redundancy, which would need specific conservation attention. In terms of tropical forest management planning, we argue that specific conservation of large-sized trees is imperative for long-term maintenance of ecosystem functioning.


Healthcare and Behavior Changes for Adults With Down Syndrome 1-Year Into COVID-19.
Individuals with Down syndrome (DS) have been disproportionately harmed by the COVID-19 pandemic and may have been more likely to have sacrificed opportunity and activity to avoid potential exposures. Our objective was to describe the experience one to one and half years into the COVID-19 pandemic for adults with DS, as reported by their caregivers in an online survey conducted between April 2021 and September of 2021. In our sample of 438 adults with DS, caregivers reported that adults with DS lost activities, struggled with employment, had negative behavioral changes, lost skills, and developed more mental health conditions. For adults with DS, one in five caregivers reported less healthcare usage, one in four reported delayed routine care, and 86.5% reported lost activities. As the pandemic continues, targeted support for adults with DS is needed to prevent further skill loss and mental health conditions.


Heterogeneity in 14-year Dementia Incidence Between Asian American Subgroups.
Asian Americans are a rapidly growing and diverse population. Prior research on dementia among Asian Americans focused on Japanese Americans or Asian Americans overall, although marked differences in cardiometabolic conditions between subgroups have been documented. We compared dementia incidence among 4 Asian American subgroups (n=8384 Chinese; n=4478 Japanese; n=6210 Filipino; n=197 South Asian) and whites (n=206,490) who were Kaiser Permanente Northern California members aged 64 years and above with no dementia diagnoses as of January 1, 2000. Dementia diagnoses were collected from medical records January 1, 2000 to December 31, 2013. Baseline medical utilization and comorbidities (diabetes, depression, hypertension, stroke, cardiovascular disease) were abstracted from medical records January 1, 1996 to December 31, 1999. We calculated age-standardized dementia incidence rates and Cox models adjusted for age, sex, medical utilization, and comorbidities. Mean baseline age was 71.7 years; mean follow-up was 9.6 years. Age-standardized dementia incidence rates were higher among whites than "All Asian-Americans" or any subgroup. Compared with Chinese (13.7/1000 person-years), dementia incidence was slightly higher among Japanese [14.8/1000 person-years; covariate-adjusted hazard ratio (adjusted-HR)=1.08; 95% confidence interval (CI), 0.99-1.18] and Filipinos (17.3/1000 person-years; adjusted-HR=1.20; 95% CI, 1.11-1.31), and lower among South Asians (12.1/1000 person-years; adjusted-HR=0.81; 95% CI, 0.53-1.25). Future studies are needed to understand how immigration history, social, environmental, and genetic factors contribute to dementia risk in the growing and diverse Asian American population.


Pneumococcal vaccination coverage and vaccination-related factors among older adults in Japan: LIFE Study.
To investigate individual and environmental vaccination-related factors among the older adults in Japan, using administrative data. We conducted a cohort study and included people who reached the relevant age (≥65 years) for routine pneumococcal vaccination of older adults between April 2015 and March 2020. Monthly data of residents in the two municipalities from April 2014 to March 2020 and vaccination records from April 2015 to March 2020 were used. We defined five cohorts according to the year in which routine vaccinations were available. Each cohort was followed for a total of two years, with the first year being the "baseline period" and second year being the "vaccine follow-up period." Pneumococcal vaccination data was extracted from vaccination records at "first dose." Age, sex, socioeconomic status, comorbidities, hospital visit history, hospitalization history, Specific Health Check-ups participation, and information on contracted hospitals for pneumococcal vaccination were used as covariates. A multivariate logistic regression model was used to investigate the relationship between pneumococcal vaccination and vaccination-related factors. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. Analysis included 17,991 patients. Vaccination coverage was 33.6 % for all subjects. Multivariate analysis found the following as significant vaccination-related factors: female (OR: 1.18, 95 % CI: 1.11-1.26), not low income (1.76, 1.17-2.76), hospital visits: ≥once/month (1.27, 1.19-1.35), and Specific Health Check-ups participation (2.10, 1.95-2.27). No significant results were found for hospitals that contracted pneumococcal vaccination. Individual factors, such as sex and Specific Health Check-ups participation, were found to be important factors affecting pneumococcal vaccination among older adults in Japan. Environmental factors, such as the characteristics of residential areas, should be evaluated in further investigations.


Does blood type affect the COVID-19 infection pattern?
Among the many aspects that characterize the COVID-19 pandemic, two seem particularly challenging to understand: i) the great geographical differences in the degree of virus contagiousness and lethality that were found in the different phases of the epidemic progression, and, ii) the potential role of the infected people's blood type in both the virus infectivity and the progression of the disease. A recent hypothesis could shed some light on both aspects. Specifically, it has been proposed that, in the subject-to-subject transfer, SARS-CoV-2 conserves on its capsid the erythrocytes' antigens of the source subject. Thus these conserved antigens can potentially cause an immune reaction in a receiving subject that has previously acquired specific antibodies for the source subject antigens. This hypothesis implies a blood type-dependent infection rate. The strong geographical dependence of the blood type distribution could be, therefore, one of the factors at the origin of the observed heterogeneity in the epidemics spread. Here, we present an epidemiological deterministic model where the infection rules based on blood types are taken into account, and we compare our model outcomes with the exiting worldwide infection progression data. We found an overall good agreement, which strengthens the hypothesis that blood types do play a role in the COVID-19 infection.


Palliative radiotherapy knowledge among community family physicians and nurses.
Primary care physicians and nurses care for patients with advanced cancer and need to be aware of the role for palliative radiotherapy (PR). We surveyed 250 family physicians, family medicine residents, and nurses attending oncology educational symposia to determine their knowledge of PR. The survey response rate was 59%, and most respondents (77%) were involved with the care of cancer patients. Many (58%) thought that their knowledge of PR was insufficient for their needs. Although bone metastasis and spinal cord compression were frequently recognized indications for PR, only 50% of other assessed indications for PR were correctly identified. Almost all respondents stated that they wanted to learn more about PR. More education regarding PR is required for primary care physicians and nurses caring for cancer patients.


Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag.
Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene.


Design and verification of a high-gradient and high-power 2nd harmonic cavity for the China Spallation Neutron Source upgrade project.
Here, we report our recent progress in the design, fluid thermodynamics simulation, and high-power test of the2nd harmonic cavity for the China Spallation Neutron Source Phase II. A high-performance and large-size magnetic alloy (MA) core was developed as the load material for the radiofrequency cavity to achieve a high gradient of 40 kV/m. The water-cooling structure and cooling efficiency were studied and improved through numerical analysis and thermal experiments. The long-term stability of the cavity, especially the waterproofness of the MA cores with high heat load, was verified by high power tests.


Linezolid in the treatment of multidrug-resistant tuberculosis.
Linezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in animal studies. Several small case series suggest that linezolid is poorly tolerated because of the side effects of anemia/thrombocytopenia and peripheral neuropathy. To characterize our clinical experience with linezolid, the California Department of Public Health Tuberculosis Control Branch's Multidrug-Resistant Tuberculosis (MDR-TB) Service reviewed cases in which the MDR-TB treatment regimens included linezolid therapy. Record review was performed for 30 patients treated with linezolid as part of an MDR-TB regimen. Data were collected on clinical and microbiological characteristics, linezolid tolerability, and treatment outcomes. The dosage of linezolid was 600 mg daily. Vitamin B6 at a dosage of 50-100 mg daily was used to mitigate hematologic toxicity. During 2003-2007, 30 patients received linezolid for the treatment of MDR-TB. Patients had isolates resistant to a median of 5 drugs (range, 2-13 drugs). Of the 30 cases, 29 (97%) were pulmonary; of these 29, 21 (72%) had positive results of acid-fast bacilli smear, and 16 (55%) were cavitary. Culture conversion occurred in all pulmonary cases at a median of 7 weeks. At data censure (31 December 2008), 22 (73%) of 30 patients had successfully completed treatment. Five continued to receive treatment. There were no deaths. Three patients had a poor outcome, including 2 defaults and 1 treatment failure. Side effects occurred in 9 patients, including peripheral and optic neuropathy, anemia/thrombocytopenia, rash, and diarrhea. However, only 3 patients stopped linezolid treatment because of side effects. Linezolid was well tolerated, had low rates of discontinuation, and may have efficacy in the treatment of MDR-TB.


Spatial and temporal organization of the binocular input to frog optic tectum.
Single-unit recordings in the frog's optic tectum have demonstrated the existence of a systematic spatial separation between the direct contralateral and indirect ipsilateral excitatory receptive fields. Marked differences in this spatial organization were found between paralyzed and anesthesized animals. Significant latency differences were found between sustained (class I/II) and transient (class III) contralateral fibers. Corresponding latency differences were also seen in ipsilaterally driven responses. It is suggested that there may be at least two different classes of ipsilateral fibers. The existence of binocular interaction at the level of the afferent terminal arborizations was investigated, utilizing temporally asynchronous dichoptic stimulation. No such phenomena were seen in curarized animals. These findings are discussed in terms of possible velocity and direction sensitivity mechanisms.


Serum C-Reactive Protein and Max Polyp Diameter Are Useful Markers of Complications of Small-Intestinal Polypectomy.
BACKGROUND This study aimed to identify the risk factors of complications after small-intestinal polypectomy by single-balloon enteroscopy (SBE), and to assess the value of serum C-reactive protein (CRP) and the max polyp diameter (Dmax) in predicting postoperative complications of small-intestinal polypectomy. MATERIAL AND METHODS Between April 2017 and April 2018, clinical data from 37 patients who underwent small-intestinal polypectomy were retrospectively analyzed. RESULTS Thirty-seven small-intestinal polypectomy procedures (18 oral and 19 anal) were carried out in 37 patients (M: F 20: 17; age 35.6±13.0 years). A total of 1081 small-intestine polyps were removed. Three patients (8.1%) had bleeding and 3 patients (8.1%) had perforation after small-intestinal polypectomy. Based on multivariate logistic analysis, CRP [1.104 (95% CI 1.022-1.191)] was the only risk factor for complications among the patients. According to the area under the receiver operating characteristic (AUROC) curve, CRP (27.5 mg/L), Dmax (3.5 cm), and the combination of CRP + Dmax appear to be predictive factors for complications after small-intestinal polypectomy. CONCLUSIONS SBE is an effective endoscopic tool for patients with small-intestinal polyps. CRP, Dmax, and the combination of CRP+Dmax may be potential predictors of complications from small-intestinal polypectomy.


Placebo control groups in randomized treatment trials: a statistician's perspective.
Because a statistical tie between standard treatment and an innovation is uninterpretable, most trials intended to demonstrate efficacy of innovations in psychopharmacology employ a placebo control group, despite the existence of standard medications for many disorders. In this review I consider the statistical issues that inform the ethics of the decision to use a placebo condition and make the following points: 1) the investigator is relying on the assumption that the effects of delayed standard treatment are neither long-lasting nor harmful; 2) the usual practice of truncating follow-up when a patient ceases to adhere to a study treatment makes it difficult to empirically test that assumption; 3) placebo control trials often suffer from methodological weaknesses (including nonrandom truncation) that reduce their inferential power; 4) these subtleties place a substantial burden on the informed consent process; 5) alternative designs are available but not well explored, due to the dominant role of "regulatory" trial methodology; and 6) researchers should consider other goals besides helping to introduce another treatment that improves on placebos but not the standard treatment.


CT of primary cystic pancreatic neoplasms: can CT be used for patient triage and treatment?
The purpose of this study was to determine whether CT can be used to distinguish serous cystadenomas from mucinous cystadenomas or cystadenocarcinomas of the pancreas and play an enhanced role in patient triage and treatment. A blinded retrospective analysis of CT scans from 50 patients with pathologically proven primary cystic pancreatic neoplasms was performed independently by three radiologists. Using classic CT criteria as reported in the literature, each tumor was categorized as definitely serous, mucinous, or indeterminate. Tumor location, size, presence of calcification, and size of largest cyst were recorded. Data for each reviewer were analyzed independently. Consensus data were then subjected to multivariate logistic regression analysis. The ability of our reviewers to diagnose serous neoplasms ranged from 23% to 41%. Eight mucinous neoplasms were mistaken for serous tumors by two of the three reviewers. When consensus between at least two of the three reviewers was used for diagnosis, 27% of serous neoplasms were correctly diagnosed and all of the mucinous tumors were correctly identified as uncertain or mucinous, yielding the same clinical end point. For multivariate logistic regression analysis, a cyst smaller than 2 cm had a statistically significant association (p = 0.005) with serous tumors, and the presence of peripheral tumoral calcification had a statistically significant association (p = 0.01) with mucinous tumors. There is significant variability in the CT appearance of serous and mucinous neoplasms of the pancreas, making CT an insensitive tool for differentiating these tumors. All tumors with peripheral calcifications were identified as mucinous neoplasms.


Toward new perspectives on the interaction of iron and sulfur metabolism in plants.
The deficiency of nutrients has been extensively investigated because of its impact on plant growth and yield. So far, the effects of a combined nutrient limitation have rarely been analyzed, although such situations are likely to occur in agroecosystems. Iron (Fe) is a prerequisite for many essential cellular functions. Its availability is easily becoming limiting for plant growth and thus higher plants have evolved different strategies to cope with Fe deficiency. Sulfur (S) is an essential macro-nutrient and the responses triggered by shortage situations have been well characterized. The interaction between these two nutrients is less investigated but might be of particular importance because most of the metabolically active Fe is bound to S in Fe-S clusters. The biosynthesis of Fe-S clusters requires the provision of reduced S and chelated Fe in a defined stoichiometric ratio, strongly suggesting coordination between the metabolisms of the two nutrients. Here the available information on interactions between Fe and S nutritional status is evaluated. Experiments with Arabidopsis thaliana and crop plants indicate a co-regulation and point to a possible role of Fe-S cluster synthesis or abundance in the Fe/S network.


Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions.
Familial pulmonary arterial hypertension (PAH) is associated with mutations in bone morphogenetic protein type II receptor (BMPR2). Many of these mutations occur in the BMPR2 tail domain, leaving the SMAD functions intact. To determine the in vivo consequences of BMPR2 tail domain mutation, we created a smooth muscle-specific doxycycline-inducible BMPR2 mutation with an arginine to termination mutation at amino acid 899. When these SM22-rtTA x TetO(7)-BMPR2(R899X) mice had transgene induced for 9 wk, starting at 4 wk of age, they universally developed pulmonary vascular pruning as assessed by fluorescent microangiography. Approximately one-third of the time, the induced animals developed elevated right ventricular systolic pressures (RVSP), associated with extensive pruning, muscularization of small pulmonary vessels, and development of large structural pulmonary vascular changes. These lesions included large numbers of macrophages and T cells in their adventitial compartment as well as CD133-positive cells in the lumen. Small vessels filled with CD45-positive and sometimes CD3-positive cells were a common feature in all SM22-rtTA x TetO(7)-BMPR2(R899X) mice. Gene array experiments show changes in stress response, muscle organization and function, proliferation, and apoptosis and developmental pathways before RVSP increases. Our results show that the primary phenotypic result of BMPR2 tail domain mutation in smooth muscle is pulmonary vascular pruning leading to elevated RVSP, associated with early dysregulation in multiple pathways with clear relevance to PAH. This model should be useful to the research community in examining early molecular and physical events in the development of PAH and as a platform to validate potential treatments.


Genetic evolution of T-cell resistance in the course of melanoma progression.
CD8(+) T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell-stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alterations affecting the tumor-T-cell interaction. Metastases Ma-Mel-48a and Ma-Mel-48b, in contrast with Ma-Mel-48c, were infiltrated by T cells. The T-cell-stimulatory capacity was found to be strong for Ma-Mel-48a, lower for Ma-Mel-48b, and completely abrogated for Ma-Mel-48c cells. The latter proved to be HLA class I-negative due to an inactivating mutation in one allele of the beta-2-microglobulin (B2M) gene and concomitant loss of the other allele by a deletion on chromosome 15q. The same deletion was already present in Ma-Mel-48a and Ma-Mel-48b cells, pointing to an early acquired genetic event predisposing to development of β2m deficiency. Notably, the same chronology of genetic alterations was also observed in a second β2m-deficient melanoma model. Our study reveals a progressive loss in melanoma immunogenicity during the course of metastatic disease. The genetic evolvement of T-cell resistance suggests screening tumors for genetic alterations affecting immunogenicity could be clinically relevant in terms of predicting patient responses to T-cell-based immunotherapy.


Synergistic induction of HL60 cell differentiation by ketoconazole and 1-desoxy analogues of vitamin D3.
The goal of differentiation therapy is to induce cancer cells to stop proliferating and to express characteristics of normal cells. Vitamin D analogues, such as the deltanoids, are being evaluated as differentiation agents in the treatment of several human cancers (e.g., myeloid leukemias); however, these compounds have a tendency to produce hypercalcemia in patients receiving therapy. A combination of a differentiation-inducing deltanoid with a compound that blocks entry of calcium into cells (e.g., ketoconazole) may offer a new approach to differentiation therapy and address the problem of hypercalcemia. We investigated whether various ketoconazole-deltanoid combinations would alter cellular differentiation or intracellular calcium homeostasis in comparison with deltanoids used alone. Cultured human leukemia HL60 cells were treated with ketoconazole-deltanoid combinations. Markers of differentiation (expression of CD11b and CD14 antigens and of non-specific esterase) were measured by flow cytometry and cytochemistry; cell cycle distribution was measured by flow cytometry of propidium iodide-stained cells. Expression of differentiation-related genes was assessed by northern blotting and immunoblotting, and changes in intracellular calcium homeostasis were monitored by fluorescence analysis of fura-2-containing cells. Ketoconazole strongly potentiated the differentiating activity of the deltanoids, which exhibited low potency when used alone. Ketoconazole-deltanoid combinations had little effect on HL60 cell-cycle distribution, although the cells did stop proliferating and they differentiated. Ketoconazole-deltanoid combinations produced only minor changes in intracellular calcium homeostasis compared with changes produced by 1,25-dihydroxyvitamin D3, either alone or in combination with ketoconazole. These results suggest that ketoconazole may be useful in combination with vitamin D analogues in the differentiation therapy for myeloid leukemias.


Homocysteine and human reproduction.
Homocysteine is an amino acid that is capable of disturbing the proper growth of cells. Hyperhomocysteinemia can lead to a non-closure of the neural tube. The underlying basis is a derangement of homocysteine metabolism due to a missense mutation of the MTHFR enzyme that has to catalyze the folate metabolic cycle furnishing sufficient methyl groups for DNA and tRNA synthesis. Folate can overcome the dysfunction of the mutation and the decreased activity of the thermolabile MTHFR. Homocysteine is also recognized as an independent risk factor for obstetrical vascular disease that can manifest itself in maternal veins (thrombosis), arteries (preeclampsia) or spiral arteries supplying the placenta (placental abruption). Low vitamin status (folic acid, vitamin B6 and B12), hyperhomocysteinemia, the MTHFR gene mutation C677T, and thrombotic factors like Protein C, Protein S. antithrombin III, factor V Leiden and Activated Protein C, are alone or in combination high risk factors for obstetrical vascular disease. Their values can be modulated by B-vitamin status and could be able to prevent disease from occurring or recurring. Placebo-randomized trials have been done in neural tube defects but are urgently needed in the vascular area. The common denominator of the effect of homocysteine on the embryo and the blood vessels (endothelium) could be sited in the process of proliferation of cells that need proper methyl groups for proper function.


[Frequency and type of offences committed by men with severe mental disorders by age of antisocial behaviors onset].
There are important differences in frequency and type of offence committed by individuals with severe mental disorders (SMD), depending on whether their antisocial behaviors began at an early age or as adults. However, individuals having shown early antisocial behaviors do not form an homogenous group. This study's objective is to test if the antisocial behaviors earliness could explain this heterogeneity. 137 men with SMD under 3 separate legal status were recruited. They were distributed in 3 groups according to the antisocial behaviors earliness. The participants in the childhood group commit more violent offences and more of them present a substance use disorder compared with those in the adult group. A more frequent alcohol use disorder separates the youth group from the adult group. There is no significant difference between the childhood and the youth group, but there are more reported offences in the childhood group. Our results suggest that the age of antisocial behaviors onset should be considered in evaluating risk and managing individuals with SMD.


UXT interacts with the transcriptional repressor protein EVI1 and suppresses cell transformation.
The EVI1 transcriptional repressor is critical to the normal development of a variety of tissues and participates in the progression of acute myeloid leukaemias. The repressor domain (Rp) was used to screen an adult human kidney yeast two-hybrid library and a novel binding partner designated ubiquitously expressed transcript (UXT) was isolated. Enforced expression of UXT in Evi1-expressing Rat1 fibroblasts suppresses cell transformation and UXT may therefore be a negative regulator of Evi1 biological activity. The Rp-binding site for UXT was determined and non-UXT-binding Evi1 mutants (Evi1Delta706-707) were developed which retain the ability to bind the corepressor mCtBP2. Evi1Delta706-707 transforms Rat1 fibroblasts, showing that the interaction is not essential for Evi1-mediated cell transformation. However, Evi1Delta706-707 produces an increased proportion of large colonies relative to wild-type, showing that endogenous UXT has an inhibitory effect on Evi1 biological activity. Exogenous UXT still suppresses Evi1Delta706-707-mediated cell transformation, indicating that it inhibits cell proliferation and/or survival by both Evi1-dependent and Evi1-independent mechanisms. These observations are consistent with the growth-suppressive function attributed to UXT in human prostate cancer. Our results show that UXT suppresses cell transformation and might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like Evi1.


Identification and functional analysis of healing regulators in Drosophila.
Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response.


Predicting adult offending behavior for individuals who experienced a traumatic brain injury during childhood.
To examine whether individuals who experienced a childhood traumatic brain injury (TBI) are at increased risk for subsequent offending behavior, to identify the emotional characteristics of adults who experienced childhood TBI, and to examine whether these predict offending behavior. Individuals from the Canterbury region who had experienced a childhood (<18 years of age) injury event and were now 18 years or older and more than 5 years postinjury (between 18 and 30 years of age). Three groups were formed: (1) moderate/severe TBI (n = 62); (2) mild TBI (n = 58); and (3) fracture control group (n = 38). University of Canterbury. A semistructured interview assessed lifetime involvement in offending behavior; the Emotional Behavior Scale measured internalizing and externalizing behaviors, including malevolent aggression, social anxiety, and social self-esteem. Compared with controls, there was an increased risk of offending behavior (mild TBI: odds ratio = 8.7; moderate/severe TBI odds ratio = 20.4). Binary logistic regression analysis revealed that the strongest predictors of offending behavior were TBI status, higher levels of malevolent aggression, and age at injury. Individuals who experienced childhood TBI are at increased risk of offending behavior. Emotional behavior measures were useful predictors of offending behavior, offering opportunity for intervention.


Comparison of arterial pressure cardiac output monitoring with transpulmonary thermodilution in septic patients.
The measurement of cardiac output in critically ill patients is complicated by rapid pathophysiological changes. The aim of this study was to compare the recently developed Arterial Pressure Cardiac Output algorithm (APCO) with transpulmonary thermodilution (TDCO). Clinical and hemodynamic parameters were tested for their impact on the measurements. Twenty septic patients were examined. Cardiac output measurements were performed simultaneously on 3 consecutive days. The data were evaluated using regression analysis and the Bland Altman approach. Bland Altman analysis presented a bias of 0.72 L/min and limits of agreement of 2.16 to 3.61 L/min for TDCO vs. APCO. Statistically significant covariables in the regression analysis were systemic vascular resistance (p<0.001), mean arterial pressure (p<0.001), cardiac function index (p=0.01), global end-diastolic index (p=0.02) and stroke volume index (p=0.005). Multiple linear regression analysis showed the residual percentage error decreased from 49.1% to 21.5%. The APCO algorithm provides a broad range of hemodynamic measurements with a minimally invasive approach and simple access to the patient's hemodynamic state. However, an underestimation at high cardiac output and an overestimation at low cardiac output relative to transpulmonary thermodilution were observed in septic patients. Therefore, the APCO algorithm in its current state cannot be substituted for transpulmonary thermodilution.


Community-university Research Liaisons: Translating the Languages of Research and Culture.
This article describes the experiences of six individuals employed as community-university research liaisons in a grant-funded centre for health disparities research. The liaisons were located in Native American communities and bridged the communities and the university, providing information between these groups, expanding understanding and knowledge of how research can address health disparities, and assisting in the development and ongoing work of partnerships using CBPR approaches. While tribal communities within the state may face similar health disparities, the approach to solving these disparities must be based on an understanding of the context and environment of the specific tribal community. In this paper, the tribal liaisons share their stories of negotiating and navigating their unique positions. Suggestions for utilizing tribal community-university positions to support community and partnership development are offered.


Genomic repertoires of DNA-binding transcription factors across the tree of life.
Sequence-specific transcription factors (TFs) are important to genetic regulation in all organisms because they recognize and directly bind to regulatory regions on DNA. Here, we survey and summarize the TF resources available. We outline the organisms for which TF annotation is provided, and discuss the criteria and methods used to annotate TFs by different databases. By using genomic TF repertoires from ∼700 genomes across the tree of life, covering Bacteria, Archaea and Eukaryota, we review TF abundance with respect to the number of genes, as well as their structural complexity in diverse lineages. While typical eukaryotic TFs are longer than the average eukaryotic proteins, the inverse is true for prokaryotes. Only in eukaryotes does the same family of DNA-binding domain (DBD) occur multiple times within one polypeptide chain. This potentially increases the length and diversity of DNA-recognition sequence by reusing DBDs from the same family. We examined the increase in TF abundance with the number of genes in genomes, using the largest set of prokaryotic and eukaryotic genomes to date. As pointed out before, prokaryotic TFs increase faster than linearly. We further observe a similar relationship in eukaryotic genomes with a slower increase in TFs.


Synthesis of oligomeric 4-(glycosyloxy)benzoate macrocyclic glycosides.
Clemoarmanoside A and Clemahexapetoside A, two novel cyclic dimers of 4-(glycosyloxy)benzoates containing the unusual d-allopyranose as one of the sugar units, were synthesized for the first time. The convenient synthetic approach was adapted to the assembly of the symmetrical trimeric, tetrameric, and pentameric congeners. The synthesis clarified the discrepancy in the NMR data reported for the natural products. X-ray diffraction analysis of Clemahexapetoside A revealed that it adopted an armchair conformation with two carbohydrate rings as the arms and two aromatic rings as the back and seat, respectively.


Reducing hypertensive cardiovascular disease risk of African Americans with diet: focus on the facts.
Hypertension is more common and more severe in African Americans than in other population groups in the United States, placing them at increased risk of cardiovascular disease, stroke, and end-stage renal disease. Whereas past efforts to reduce blood pressure (BP) via the diet centered on manipulating isolated nutrients, there are now conclusive data demonstrating that it is not single dietary components but the overall dietary pattern that has the greatest influence on BP. A nutritionally complete diet rich in fruits, vegetables, and low-fat dairy foods has been clearly proven to significantly lower BP in all population groups. This diet, commonly referred to as the Dietary Approaches to Stop Hypertension (DASH) diet, has been tested in randomized, controlled trials emphasizing African American populations and documented the greatest beneficial effects in hypertensive African Americans. Improving diet quality has been shown to be simply implemented without adverse effects such as symptoms of lactose maldigestion. It is also known to beneficially affect other cardiovascular risk factors and is in keeping with dietary recommendations for prevention of some cancers and osteoporosis. This paper reviews the current data relating dietary patterns to BP control, and advocates dietary recommendations that can accomplish their intended objective of enhancing the health of Americans by promoting safe, feasible, and proven-effective means of doing so. In the case of hypertension prevention and treatment, and thus the reduction of cardiovascular disease risk, overall diet quality should be the primary focus of nutritional recommendations.


Drug evaluation: Deferitrin for iron overload disorders.
Deferitrin (GT-56-252) is the first drug in a class of desferrithiocin-derived hexadentate iron chelators. Genzyme Corp is developing this compound as an oral drug for the treatment of severe iron overload in people who require repeated erythrocyte transfusion for management of chronic anemia such as beta-thalassemia major. In phase I clinical trials in adults with beta-thalassemia, deferitrin promoted iron excretion in a dose-related manner and was well tolerated as both a liquid and capsule in fed and fasted states. There were no serious adverse events or significant laboratory abnormalities. The author concludes that deferitrin may be useful as chelation monotherapy or as part of combination or doublet chelation therapy for the treatment of severe iron overload in patients with beta-thalassemia major if its favorable pharmacokinetic profile, efficacy, safety and tolerability are confirmed in more extensive clinical trials. A phase I/II clinical trial that began in September 2003 has reportedly completed recruitment.


Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance.
Autoimmune diseases appeared frequently in adults in the prostate and stomach of C3.129 mice after thymectomy on day 3 (Tx-3) without any additional treatment. Lesions of both organs could be completely prevented by a single i.p. injection of spleen cells from syngeneic adult mouse on day 4. For prevention of prostatis, the most effective cell source was normal males (4 X 10(6); normal females or Orx-0 males were less effective as the cell source, and higher doses of cells (4 X 10(7)) were needed. In contrast, spleen cells (4 X 10(6)) from these three donors had equivalent capacity for the prevention of gastritis. Similar autoimmune prostatis developed at very high frequency when spleen cells (4 X 10(6)) from normal females or Orx-0 males, but not from normal males, were injected i.p. into C3.129 nu/nu mice at 4 d. However, no sign of prostatis was found in nu/+ recipients. Injection of a larger dose (4 X 10(7)) from the same donors was not effective for induction of prostatis. Gastritis could not be induced in nu/nu mice by this procedure. Injection of spleen cells from Tx-3 males or females was effective for induction of both prostatis and gastritis in nu/nu recipients. It was also shown that a T cell population (Thy-1.2+, Ig-) had the capacity to prevent and to induce autoimmune diseases. These results together strongly suggest a role for active tissue-specific suppressor T cells in self tolerance, and elimination of such T cell populations causes autoimmunity.


Multi-person feature fusion transfer learning-based convolutional neural network for SSVEP-based collaborative BCI.
The conventional single-person brain-computer interface (BCI) systems have some intrinsic deficiencies such as low signal-to-noise ratio, distinct individual differences, and volatile experimental effect. To solve these problems, a centralized steady-state visually evoked potential collaborative BCI system (SSVEP-cBCI), which characterizes multi-person electroencephalography (EEG) feature fusion was constructed in this paper. Furthermore, three different feature fusion methods compatible with this new system were developed and applied to EEG classification, and a comparative analysis of their classification accuracy was performed with transfer learning-based convolutional neural network (TL-CNN) approach. An EEG-based SSVEP-cBCI system was set up to merge different individuals' EEG features stimulated by the instructions for the same task, and three feature fusion methods were adopted, namely parallel connection, serial connection, and multi-person averaging. The fused features were then input into CNN for classification. Additionally, transfer learning (TL) was applied first to a Tsinghua University (THU) benchmark dataset, and then to a collected dataset, so as to meet the CNN training requirement with a much smaller size of collected dataset and increase the classification accuracy. Ten subjects were recruited for data collection, and both datasets were used to gauge the three fusion algorithms' performance. The results predicted by TL-CNN approach in single-person mode and in multi-person mode with the three feature fusion methods were compared. The experimental results show that each multi-person mode is superior to single-person mode. Within the 3 s time window, the classification accuracy of the single-person CNN is only 90.6%, while the same measure of the two-person parallel connection fusion method can reach 96.6%, achieving better classification effect. The results show that the three multi-person feature fusion methods and the deep learning classification algorithm based on TL-CNN can effectively improve the SSVEP-cBCI classification performance. The feature fusion method of multi -person parallel feature connection achieves better classification results. Different feature fusion methods can be selected in different application scenarios to further optimize cBCI.


Clinical relevance of apolipoprotein E genotyping based on a family history of Alzheimer's disease.
Having a family history of Alzheimer' s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE ε-2 (p=0.034) as well as APOE ε-4 (p=0.038) were found between study participants with (n=67) and without (n=470) a family history of AD. LDL cholesterol levels were inversely associated with physical activity in the study group with a positive family history of AD (p<0.001) but not in those with a negative family history of AD (p=0.257). Similar to its existing use in the diagnosis of monogenic dyslipidemias such as familial hypercholesterolemia, clinical inquiry regarding family history was identified as an important determinant of eligibility for APOE genotyping performed in the context of chronic disease risk management. To our knowledge, this is the first study to demonstrate the modulating influence of AD family history on expression of a dyslipidemic phenotype associated with the APOE ε-4 allele. Our findings provide the scientific rationale supporting a novel clinical application for APOE genotyping as a means of identifying a genetic subgroup of dyslipidemic patients set to derive the greatest benefit from early lifestyle-based interventions aimed at decreasing cumulative risk for cardiovascular disease and prevention of AD later in life.


Erectile dysfunction in heart failure patients: a critical reappraisal.
Heart failure (HF) is a complex clinical syndrome with a constantly increasing incidence and prevalence in western countries. Total absence of sexual activity is registered in 30% of HF patients. Moreover, HF-induced reduction in exercise tolerance, side effects of HF medications and the coexistence of shared risk factors between HF and sexual dysfunction may further aggravate the sexual health of HF patients. The purpose of this review is to examine the pathophysiological mechanisms behind the association of erectile dysfunction (ED) and HF, the potential therapeutic approaches and the eventual indications for sexual activity in HF patients. Medline and Cochrane Library search was performed from January 1970 through October 2012 to retrieve relevant papers outlining the association between ED and HF. Many evidences have outlined a tight association between ED and HF pathophysiological standpoint. Shared risk factors, common pathogenic traits and epidemiologic association represent some of the links between these conditions. Erectile dysfunction has been recognized as an earlier predictor of cardiovascular events; moreover, HF itself may cause and/or worsen ED because of its particular feature and co-morbidities. Furthermore, some cardiovascular drugs may contribute to impaired erectile function. In stable patients with stable HF, sexual activity is generally not contraindicated but it should be encouraged, as a form of moderate-intensity physical exertion. An effective treatment of ED in HF patients should be founded on the correction of reversible risk factors, on the choice of cardiovascular drugs with the lowest effect upon patient's erectile function, and on the use of phosphodiesterase-5-inhibitors. Physicians should be aware of the close relation between HF and ED and of the related clinical and therapeutic implications, in order to improve patients quality of life and clinical outcome.


Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA mutations.
The value of allogeneic hematopoietic cell transplantation (alloHCT) as postremission treatment is not well defined for patients with intermediate-risk acute myeloid leukemia (AML) without FLT3-ITD, biallelic CEBPA-, or NPM1 mutations (here referred to as NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML) in first complete remission (CR1). We addressed this question using data from two prospective randomized controlled trials on intensive induction- and risk-stratified postremission therapy. The NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML subgroup comprised 497 patients, aged 18-60 years. In donor versus no-donor analyses, patients with a matched related donor had a longer relapse-free survival (HR 0.5; 95% CI 0.3-0.9, P = 0.02) and a trend toward better overall survival (HR 0.6, 95% CI 0.3-1.1, P = 0.08) compared with patients who received postremission chemotherapy. Notably, only 58% of patients in the donor group were transplanted in CR1. We therefore complemented the donor versus no-donor analysis with multivariable Cox regression analyses, where alloHCT was tested as a time-dependent covariate: overall survival (HR 0.58, 95% CI 0.37-0.9, P = 0.02) and relapse-free survival (HR 0.51, 95% CI 0.34-0.76; P = 0.001) for patients who received alloHCT compared with chemotherapy in CR1 were significantly longer. Outside clinical trials, alloHCT should be the preferred postremission treatment of patients with intermediate risk NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML in CR1. NCT00180115, NCT00180102.


A single Mediterranean, possibly Jewish, origin for the Val59Gly CDKN2A mutation in four melanoma-prone families.
We have screened for CDKN2A germline mutations in 49 Jewish families with two or more cases of melanoma. The Val59Gly mutation, one of the three different alterations identified among these families, was also detected independently in two kindreds from France and one from Spain. The impact of the Val59Gly substitution on the function of the cyclin-dependent kinase inhibitor p16(INK4a), a product of the CDKN2A gene, was assessed by protein-protein interaction and cell proliferation assays and related to potential structural alterations predicted by molecular modeling. Seven microsatellite markers in the vicinity of the CDKN2A gene were used to determine whether the mutation in these families is identical by descent, or represents a mutational hotspot in the CDKN2A gene. Our results show that the Val59Gly substitution impairs p16(INK4a) function, and this dysfunction is consistent with structural predictions. All melanoma-affected individuals tested in the families under study harbor this mutation. Interestingly, the Israeli pedigree includes an affected individual who is homozygous for the Val59Gly mutation. A common haplotype of microsatellite markers has been demonstrated for mutation carriers in all four pedigrees. The Israeli pedigree and one of the French melanoma families are of Moroccan and Tunisian Jewish descent, respectively, and the other families originate from regions of France and Spain close to the Pyrenees. We conclude that the Val59Gly mutation is a major contributor to melanoma risk in the families under study and that it may derive from a single ancestral founder of Mediterranean (possibly Jewish) origin.


MitoTracker Green labeling of mitochondrial proteins and their subsequent analysis by capillary electrophoresis with laser-induced fluorescence detection.
MitoTracker Green (MTG) is a mitochondrial-selective fluorescent label commonly used in confocal microscopy and flow cytometry. It is expected that this dye selectively accumulates in the mitochondrial matrix where it covalently binds to mitochondrial proteins by reacting with free thiol groups of cysteine residues. Here we demonstrate that MTG can be used as a protein labeling reagent that is compatible with a subsequent analysis by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). Although the MTG-labeled proteins and MTG do not seem to electrophoretically separate, an enhancement in fluorescence intensity of the product indicates that only proteins with free thiol groups are capable of reacting with MTG. In addition we propose that MTG is a partially selective label towards some mitochondrial proteins. This selectivity stems from the high MTG concentration in the mitochondrial matrix that favors alkylation of the available thiol groups in this subcellular compartment. To that effect we treated mitochondria-enriched fractions that had been prepared by differential centrifugation of an NS-1 cell lysate. This fraction was solubilized with an SDS-containing buffer and analyzed by CE-LIF. The presence of a band with fluorescence stronger than MTG alone also indicated the presence of an MTG-protein product. Confirming that MTG is labeling mitochondrial proteins was done by treating the solubilized mitochondrial fraction with 5-furoylquinoline-3-carboxaldehyde (FQ), a fluorogenic reagent that reacts with primary amino groups, and analysis by CE-LIF using two separate detection channels: 520 nm for MTG-labeled species and 635 nm for FQ-labeled species. In addition, these results indicate that MTG labels only a subset of proteins in the mitochondria-enriched fraction.


Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons.
Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms of post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution of these molecules in resting and potassium chloride depolarized human neuroblasts, and found both selective enrichment and depletion in neurites. Depolarization was associated with a neurite-restricted decrease in miRNA expression; a subset of these molecules was recovered from the depolarization medium in nuclease resistant extracellular exosomes. These vesicles were enriched with primate specific miRNA and the synaptic-plasticity-associated protein MAP1b. These findings further support a role for miRNA as neural plasticity regulators, as they are compartmentalized in neurons and undergo activity-associated redistribution or release into the extracellular matrix.


Molecular genetics of H.
Formal genetics of ABO, H-h and Se-se systems illustrate that these three systems are genetically independent Population analysis of phenotypes and family segregation of the ABH related genetic markers Inactivating mutations of FUT1 and FUT2 are compatible with a structural gene model assuming that FUT1 and FUT2 genes encode for two distinct enzymes, one encoding for the H antigen expressed in red cells (FUT1) and the other encoding for the H gene expressed in saliva (FUT2) Most inactivating mutations of FUT1 and FUT2 genes are located in the coding region of the genes and are nonprevalent sporadic mutations of relative recent appearance.


Sedimentation Field-Flow Fractionation: A Diagnostic Tool for Rapid Antimicrobial Susceptibility Testing.
Conventional antimicrobial susceptibility testing (AST) methods require 24-48 h to provide results, creating the need for a probabilistic antibiotic therapy that increases the risk of antibiotic resistance emergence. Consequently, the development of rapid AST methods has become a priority. Over the past decades, sedimentation field-flow fractionation (SdFFF) has demonstrated high sensitivity in early monitoring of induced biological events in eukaryotic cell populations. This proof-of-concept study aimed at investigating SdFFF for the rapid assessment of bacterial susceptibility to antibiotics. Three bacterial species were included (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) with two panels of antibiotics tailored to each bacterial species. The results demonstrate that SdFFF, when used in "Hyperlayer" elution mode, enables monitoring of antibiotic-induced morphological changes. The percentage variation of the retention factor (PΔR) was used to quantify the biological effect of antibiotics on bacteria with the establishment of a threshold value of 16.8% to differentiate susceptible and resistant strains. The results obtained with SdFFF were compared to that of the AST reference method, and a categorical agreement of 100% was observed. Overall, this study demonstrates the potential of SdFFF as a rapid method for the determination of antibiotic susceptibility or resistance since it is able to provide results within a shorter time frame than that needed for conventional methods (3-4 h vs 16-24 h, respectively), enabling earlier targeted antibiotic therapy. Further research and validation are necessary to establish the effectiveness and reliability of SdFFF in clinical settings.


Microendoscopic decompression for cervical spondylotic myelopathy.
Cervical spondylotic myelopathy (CSM) is a common cervical degenerative disease that affects the elderly population. Spinal cord decompression is achieved through various anterior and posterior approaches including anterior cervical decompression and fusion, laminectomy, laminoplasty, and combined approaches. The authors describe another option, minimally invasive endoscopically assisted decompression of stenosis (MEDS), which obviates the need for muscle dissection and disruption of the posterior tension band, a cause of postlaminectomy kyphosis. The authors conducted a retrospective study of 10 patients with CSM who underwent MEDS from January 2002 through July 2012. Data were collected on demographics, preoperative and postoperative Nurick scores, postoperative Odom scores, and preoperative and postoperative Cobb angles. The mean patient age (± SD) was 67 ± 7.7 years; 8 patients were male. The average number of disc levels operated on was 2.2 (range 1-4). The mean Nurick score was 1.6 ± 0.7 preoperatively and improved to 0.3 ± 0.7 postoperatively (p < 0.0005). The postoperative Odom scores indicated excellent outcomes for 4 patients, good for 3, fair for 2, and poor for 1. The average preoperative focal Cobb angle at the disc levels operated on was -0.43º ± 1.9º. The average Cobb angle at the last follow-up visit was 0.25° ± 1.6° (p = 0.6). The average follow-up time was 18.9 ± 32.1 months. There were no intraoperative or postoperative complications. For selected patients with CSM, whose pathologic changes are primarily posterior and who have acceptable preoperative lordosis, MEDS is an alternative to open laminectomy and laminoplasty.


The Relationship Between Resilience and Internet Addiction: A Multiple Mediation Model Through Peer Relationship and Depression.
Heavy use of the Internet may lead to profound academic problems in elementary students, such as poor grades, academic probation, and even expulsion from school. It is of great concern that Internet addiction problems in elementary school students have increased sharply in recent years. In this study, 58,756 elementary school students from the Henan province of China completed four questionnaires to explore the mechanisms of Internet addiction. The results showed that resilience was negatively correlated with Internet addiction. There were three mediational paths in the model: (a) the mediational path through peer relationship with an effect size of 50.0 percent, (b) the mediational path through depression with an effect size of 15.6 percent, (c) the mediational path through peer relationship and depression with an effect size of 13.7 percent. The total mediational effect size was 79.27 percent. The effect size through peer relationship was the strongest among the three mediation paths. The current findings suggest that resilience is a predictor of Internet addiction. Improving children's resilience (such as toughness, emotional control, and problem solving) can be an effective way to reduce Internet addiction behavior. The current findings provide useful information for early detection and intervention for Internet addiction.


Assessing the potential of fish cell lines as tools for the cytotoxicity testing of estuarine sediment aqueous elutriates.
In the present study, we assess the potential of fish cell lines (CHSE, EPC and RTG-2) to be used as screening tools for the ecotoxicological assessment of estuarine sediments. The processing of sediment to a form suitable for in vitro exposure is an inherent problem when using cell cultures. The approach employed in this study was to prepare aqueous elutriate extracts from whole sediments, which were subsequently used to reconstitute powdered media. This procedure allowed the exposure of cell cultures to concentrations of up to and including 100% of the original aqueous sample. Cytotoxicity was assessed using multiple endpoint measurements. Cell viability was quantified using the neutral red and alamar blue colorimetric assays, which specifically assess lysosomal and mitochondrial function, respectively. In addition, the total protein content of the cells was measured using the coomassie blue assay. Initial tests were conducted to ensure that any resultant cytotoxicity was due to sample contaminants and not osmotic stress. In addition, elutriate samples were spiked with a model toxicant to verify the ability of the cell lines to detect and respond to bioavailable contaminants. Chemical analyses were conducted on sediments from all sampling sites to assist in interpreting any observed cytotoxicity. A differential response was observed for the cytotoxicity assays following exposure treatments, which emphasises the importance of employing multiple endpoints for the determination of toxicity. Of the three cell lines utilised in this study, RTG-2 cells were the most suitable for the testing of estuarine aqueous elutriate samples on the basis of tolerance to osmolality effects. Slight toxicity was observed following exposure to the aqueous elutriates tested in this study using RTG-2 cells and the alamar blue assay. In order to fully evaluate the overall sensitivity of this cell line, further research is warranted using an extensive range of test sites incorporating more polluted sediments.


Approaches and landings at wrong airports: analysis of 54 incidents and 11 accidents, 1981-2004.
Inadvertent approaches and landings at airports other than the intended destination are instances of pilot disorientation. The circumstances that lead to such navigational errors point toward preventive measures. The objective was to gain insight into the circumstances of a wrong airport approach or landing as well as the moment at which the navigation error became apparent to the pilot. Accident reports published by the National Safety Transportation Board for the period 1981 through 2004 were studied in combination with Federal Aviation Administration incident reports of the same period. In the studied period there were 54 incidents and 11 accidents. There were 15 pilots who tried to avoid a landing, which in 5 cases led to an accident. All other pilots made a full-stop landing at the wrong airport. Damage to the aircraft was significantly more likely during night flights and in flights with a student or pilot with a private pilot license. Corrective measures during the landing procedure, such as a go-around or a touch-and-go landing, accounted for 42% of the accidents. Eighty percent of the cases were reported in the first 12 yr of the studied period and 20% in the last 12 yr. A further implementation of GPS receivers in all aircraft could further reduce the number of incidents and accidents. Pilots need to be made aware of the dangers of a visual approach after an IFR flight without following an airport identification procedure. Recommendations include a comparison of airports in the vicinity of a destination airport and the use of GPS to assist in an identification procedure.


Boradeption: a new procedure for transferring water-insoluble agents across cell membranes.
A new process has been developed which is called "Boradeption" to signify boronic acid--dependent phase transfer of water-insoluble agents. Highly fluorescent boronic acid dervatives, FluoroBoras, are solubilized with a physiologically compatible carrier buffer containing a receptor group for boronate adduct formation. The system can be used to stain living cells. In another variation of the Boradeption concept, an insoluble reporter molecule containing a boronate receptor is solubilized with a carrier buffer containing a boronic acid functional group. The boronate-receptor complexes, which are in dynamic equilibrium, can be designed as vital stains and reagents for a variety of biological and medical applications.