Conjugating Micropatches to Living Cells Through Membrane Intercalation.
Existing clinical cell therapies, which rely on the use of biological functionalities of living cells, can be further enhanced by conjugating functional particles to the cells to form cell-particle complexes. Disk-shaped microparticles produced by the top-down microfabrication approach possess unique advantages for this application. However, none of the current mechanisms for conjugating the microfabricated microparticles to the cells are principally applicable to all types of cells with therapeutic potentials. On the other hand, membrane intercalation is a well-established mechanism for attaching fluorescent molecules to living cells or for immobilizing cells on a solid surface. This paper reports a study on conjugating disk-shaped microparticles, referred to as micropatches, to living cells through membrane intercalation for the first time. The procedure for producing the cell-micropatch complexes features an unprecedented integration of microcontact printing of micropatches, end-grafting of linear molecules of octadecyl chain and poly(ethylene glycol) to the printed micropatches, and use of gelatin as a temperature-sensitive sacrificial layer to allow the formation and subsequent release of the cell-micropatch complexes. Complexes composed of mouse neuroblastoma cells were found to be stable in vitro, and the micropatch-bound cells were viable, proliferative, and differentiable. Moreover, complexes composed of four other types of cells were produced. The membrane-intercalation mechanism and the corresponding fabrication technique developed in this study are potentially applicable to a wide range of therapeutic cells and thus promise to be useful for developing new cell therapies enhanced by the disk-shaped microparticles.


Identification of key pinch forces required to complete functional tasks.
Reconstructive hand surgeries restore key pinch to individuals with pinch force deficits caused by tetraplegia. Data that define the magnitudes of force necessary to complete functional key pinch tasks are limited. This study aims to establish target pinch forces for completing selected tasks that represent a range of useful functional activities. A robot arm instrumented with a force sensor completed the tasks and simultaneously measured the forces applied to the task objects. Lateral pinch force requirements were calculated from these measured object forces. Pinch force requirements ranged from 1.4 N to push a button on a remote to 31.4 N to insert a plug into an outlet. Of the tasks studied, 9 of 12 required less than 10.5 N. These pinch force requirements, when compared to pinch forces produced by 14 individuals with spinal cord injuries (with and without surgical reconstruction of pinch), accurately predicted success or failure in 81% of subject trials. The prediction errors indicate a need to measure other factors such as pinch opening, force location, force direction, and proximal joint control.


B-scan ultrasonography following open globe repair.
To examine the accuracy and predictive ability of B-scan ultrasonography in the post-repair assessment of an open globe injury. In all, 965 open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1 January 2000 and 1 June 2010 were retrospectively reviewed. A total of 427 ultrasound reports on 210 patients were analyzed. Ultrasound reports were examined for the following characteristics: vitreous hemorrhage, vitreous tag, retinal tear, RD (including subcategories total RD, partial RD, closed funnel RD, open funnel RD, and chronic RD), vitreous traction, vitreous debris, serous choroidal detachment, hemorrhagic choroidal detachment, kissing choroidal detachment, dislocated crystalline lens, dislocated intraocular lens (IOL), disrupted crystalline lens, intraocular foreign body (IOFB), intraocular air, irregular posterior globe contour, disorganized posterior intraocular contents, posterior vitreous detachment, choroidal vs retinal detachment, vitreal membranes, and choroidal thickening. The main outcome measure was visual outcome at final follow-up. Among 427 B-scan reports, there were a total of 57 retinal detachments, 19 retinal tears, 18 vitreous traction, 59 serous choroidal detachments, 47 hemorrhagic choroidal detachments, and 10 kissing choroidal detachments. Of patients with multiple studies, 26% developed retinal detachments or retinal tears on subsequent scans. Ultrasound had 100% positive predictive value for diagnosing retinal detachment and IOFB. The diagnoses of retinal detachment, disorganized posterior contents, hemorrhagic choroidal detachment, kissing choroidal detachment, and irregular posterior contour were associated with worse visual acuity at final follow-up. Disorganized posterior contents correlated with particularly poor outcomes. B-scan ultrasonography is a proven, cost-effective imaging modality in the management of an open globe injury. This tool can offer both diagnostic and prognostic information, useful for both surgical planning and further medical management.


Family factors associated with physical activity in children with intellectual disability: A systematic review.
This systematic review aimed to explore the influence of family factors on physical activity in children with intellectual disability. How and what family factors that specifically influence physical activity has not been compiled and reviewed previously. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was performed for articles published in English and Chinese without any year limits in six databases. Ten studies met the eligibility criteria and were included in the review. All studies were qualitatively integrated to identify and compare positive and negative family factors. A total of 1135 participants, of which 497 were children with intellectual disability while the other 638 participants were family members (parents, siblings and caregivers). The family factors of 6 themes and 18 sub-themes (10 positive, 7 negative and 1 inconclusive factors) were extracted. Overall, these results highlight the importance of encouragement, support and involvement by family members, concurrently it points out that parental psychological factors, socioeconomic status, responsibilities and electronic devices could both promote and hinder engagement in physical activity for children with intellectual disability. The findings accentuate the role of the family unit in helping determine the activity levels of children with intellectual disability. Future studies should include a wider range of participants and be longitudinal in nature, utilizing more accurate monitoring tools.


Cone-Traced Supersampling with Subpixel Edge Reconstruction.
While signed distance fields (SDFs) in theory offer infinite level of detail, they are typically rendered using the sphere tracing algorithm at finite resolutions, which causes the common rasterized image synthesis problem of aliasing. Most existing optimized antialiasing solutions rely on polygon mesh representations; SDF-based geometry can only be directly antialiased with the computationally expensive supersampling or with post-processing filters that may produce undesirable blurriness and ghosting. In this work, we present cone-traced supersampling (CTSS), an efficient and robust spatial antialiasing solution that naturally complements the sphere tracing algorithm, does not require casting additional rays per pixel or offline prefiltering, and can be easily implemented in existing real-time SDF renderers. CTSS performs supersampling along the traced ray near surfaces with partial visibility - object contours - identified by evaluating cone intersections within a pixel's view frustum. We further introduce subpixel edge reconstruction (SER), a technique that extends CTSS to locate and resolve complex pixels with geometric edges in relatively flat regions, which are otherwise undetected by cone intersections. Our combined solution relies on a specialized sampling strategy to minimize the number of shading computations and correlates sample visibility to aggregate the samples. With comparable antialiasing quality at significantly lower computational cost, CTSS is a reliable practical alternative to conventional supersampling.


The Impact of a Violent Physical Assault on a Registered Nurse: Her Healing Journey and Return to Work.
Healthcare practitioners are at an increased risk for workplace violence. What happens to a practitioner after a devastating physical assault from a patient in the workplace? This case report describes the impact of a violent assault on a registered nurse and her healing journey and return to the workplace. The Department of Veteran Affairs/Department of Defense "Clinical Practice Guidelines for Posttraumatic Stress Disorder" outline three categories of risk factors that are associated with the development of posttraumatic stress disorder: pretraumatic factors, peritraumatic or trauma-related factors, and posttraumatic factors. Each of these risk factors can contribute to the likelihood of an individual developing posttraumatic stress disorder after a traumatic incident and will be used to frame the discussion of this case. The registered nurse gave her full and informed consent for the author to tell her story.


Cytotype Affects the Capability of the Whitefly Bemisia tabaci MED Species To Feed and Oviposit on an Unfavorable Host Plant.
The acquisition of nutritional obligate primary endosymbionts (P-symbionts) allowed phloemo-phageous insects to feed on plant sap and thus colonize novel ecological niches. P-symbionts often coexist with facultative secondary endosymbionts (S-symbionts), which may also influence their hosts' niche utilization ability. The whitefly Bemisia tabaci is a highly diversified species complex harboring, in addition to the P-symbiont "Candidatus Portiera aleyrodidarum," seven S-symbionts whose roles remain poorly understood. Here, we compare the phenotypic and metabolic responses of three B. tabaci lines differing in their S-symbiont community, reared on three different host plants, hibiscus, tobacco, or lantana, and address whether and how S-symbionts influence insect capacity to feed and produce offspring on those plants. We first show that hibiscus, tobacco, and lantana differ in their free amino acid composition. Insects' performance, as well as free amino acid profile and symbiotic load, were shown to be plant dependent, suggesting a critical role for the plant nutritional properties. Insect fecundity was significantly lower on lantana, indicating that it is the least favorable plant. Remarkably, insects reared on this plant show a specific amino acid profile and a higher symbiont density compared to the two other plants. In addition, this plant was the only one for which fecundity differences were observed between lines. Using genetically homogeneous hybrids, we demonstrate that cytotype (mitochondria and symbionts), and not genotype, is a major determinant of females' fecundity and amino acid profile on lantana. As cytotypes differ in their S-symbiont community, we propose that these symbionts may mediate their hosts' suitable plant range. IMPORTANCE Microbial symbionts are universal in eukaryotes, and it is now recognized that symbiotic associations represent major evolutionary driving forces. However, the extent to which symbionts contribute to their hosts' ecological adaptation and subsequent diversification is far from being fully elucidated. The whitefly Bemisia tabaci is a sap feeder associated with multiple coinfecting intracellular facultative symbionts. Here, we show that plant species simultaneously affect whiteflies' performance, amino acid profile, and symbiotic density, which could be partially explained by differences in plant nutritional properties. We also demonstrate that, on lantana, the least favorable plant used in our study, whiteflies' performance is determined by their cytotype. We propose that the host plant utilization in B. tabaci is influenced by its facultative symbiont community composition, possibly through its impact on the host dietary requirements. Altogether, our data provide new insights into the impact of intracellular microorganisms on their animal hosts' ecological niche range and diversification.


The design, construction, and operation of a whole-body inhalation chamber for use in avian toxicity studies.
Environmental risk assessments are broadening to include evaluations of avian species exposed to gaseous and particulate materials (Mineau, 2002b; Irvine, 2004; Carmalt, 2005). Since the avian respiratory tract is fundamentally different from the respiratory tract of rodents, the effects of gaseous materials on birds cannot validly be extrapolated from data derived from rodent exposure studies (Briant & Driver, 1992; Brown et al., 1997). To address the lack of avian-specific lowest observable effect levels used to calculate reference concentrations for airborne pollutants, a system was designed to facilitate research on inhalation toxicology in small birds. Birds have long been used as early indicators of poor air quality (Brown et al., 1997), and various chambers have been designed for head only exposures of larger birds (Briant & Driver, 1992). Smaller birds with short tracheal lengths and hooked beaks however require less restrictive exposure apparatus, thus warranting the proposed design. The chamber described in this article was designed to accommodate a small falcon, the American kestrel, a species frequently used in toxicological risk assessments (Wiemeyer & Lincer, 1987a; Smits & Bortolotti, 2001; Bortolotti et al., 2003; Fisher et al., 2006). To accomplish this, a 41-L closed inhalation system capable of exposing 12 adult American kestrels was constructed primarily of galvanized steel, polyvinyl chloride, and copper tubing. Humidified air was passed over the birds and subsequently decontaminated by an activated carbon filter and released to a HEPA filtration system. The proposed inhalation chamber was successfully used in 2005 and 2006 to expose a total of 55 male American kestrels to benzene and toluene. Measurements of various biochemical endpoints associated with benzene and toluene toxicity allowed us to study the effects of airborne pollutants on small nondomesticated birds in a controlled laboratory setting.


Do Standard Bibliometric Measures Correlate with Academic Rank of Full-Time Pediatric Dentistry Faculty Members?
The aim of this cross-sectional study was to assess the relationship between quantitative measures of research productivity and academic rank for full-time pediatric dentistry faculty members in accredited U.S. and Canadian residency programs. For each pediatric dentist in the study group, academic rank and bibliometric factors derived from publicly available databases were recorded. Academic ranks were lecturer/instructor, assistant professor, associate professor, and professor. Bibliometric factors were mean total number of publications, mean total number of citations, maximum number of citations for a single work, and h-index (a measure of the impact of publications, determined by total number of publications h that had at least h citations each). The study sample was comprised of 267 pediatric dentists: 4% were lecturers/instructors, 44% were assistant professors, 30% were associate professors, and 22% were professors. The mean number of publications for the sample was 15.4±27.8. The mean number of citations was 218.4±482.0. The mean h-index was 4.9±6.6. The h-index was strongly correlated with academic rank (r=0.60, p=0.001). For this sample, an h-index of ≥3 was identified as a threshold for promotion to associate professor, and an h-index of ≥6 was identified as a threshold for promotion to professor. The h-index was strongly correlated with the academic rank of these pediatric dental faculty members, suggesting that this index may be considered a measure for promotion, along with a faculty member's quality and quantity of research, teaching, service, and clinical activities.


Surface-enhanced nitrate photolysis on ice.
Heterogeneous nitrate photolysis is the trigger for many chemical processes occurring in the polar boundary layer and is widely believed to occur in a quasi-liquid layer (QLL) at the surface of ice. The dipole-forbidden character of the electronic transition relevant to boundary layer atmospheric chemistry and the small photolysis/photoproduct yields in ice (and in water) may confer a significant enhancement and interfacial specificity to this important photochemical reaction at the surface of ice. Using amorphous solid water films at cryogenic temperatures as models for the disordered interstitial air-ice interface within the snowpack suppresses the diffusive uptake kinetics, thereby prolonging the residence time of nitrate anions at the surface of ice. This approach allows their slow heterogeneous photolysis kinetics to be studied, providing the first direct evidence that nitrates adsorbed onto the first molecular layer at the surface of ice are photolyzed more effectively than those dissolved within the bulk. Vibrational spectroscopy allows the ∼3-fold enhancement in photolysis rates to be correlated with the nitrates' distorted intramolecular geometry, thereby hinting at the role played by the greater chemical heterogeneity in their solvation environment at the surface of ice than that in the bulk. A simple 1D kinetic model suggests (1) that a 3(6)-fold enhancement in photolysis rate for nitrates adsorbed onto the ice surface could increase the photochemical NO2 emissions from a 5(8) nm thick photochemically active interfacial layer by 30(60)%, and (2) that 25(40)% of the NO2 photochemical emissions to the snowpack interstitial air are released from the topmost molecularly thin surface layer on ice. These findings may provide a new paradigm for heterogeneous (photo)chemistry at temperatures below those required for a QLL to form at the ice surface.


Perceptions of distance education among nursing faculty members in North America.
A strategy to increase access to nursing education, train nurses for practice, and prepare future nurse educators is distance education. Faculty member shortages are cited as the main reason for not accepting qualified applicants. Faculty members are the core of nursing education. In order to address nursing faculty members' concerns regarding distance education and to assist in faculty member recruitment, retention, growth, and development in order to improve and enhance the quality of distance education, one must answer the question: What are nursing faculty members' perceptions of distance education in nursing? Utilizing a number of databases to locate research specific to this topic, this article provides an integrative review of the nursing literature to ascertain the faculty members' perspective of distance education. The research was analyzed, findings summarized, and limitations mentioned. Utilizing a brief supplementary review of the literature, the implications, recommendations, and need for future research are discussed.


Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.
The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the proband's phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. Zebrafish in vivo complementation studies of the latter transcript demonstrated a loss of function effect. Finally, we conducted post-hoc trio-based whole exome sequencing studies to (a) test the possibility of other causal loci in the proband and (b) explain the Mendelian error of segregation for the IFT140 mutation. We show that the proband harbors a chromosome 16 maternal heterodisomy, with segmental isodisomy at 16p13, likely due to a meiosis I error in the maternal gamete. Using clinical phenotyping combined with research-based genetic and functional studies, we have characterized a recurrent IFT140 mutation in the proband; together, these data are consistent with MZSDS. Additionally, we report a rare instance of a uniparental isodisomy unmasking a deleterious mutation to cause a ciliary disorder.


Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis.
Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial. To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach. Ovid Medline, PsycINFO, Embase databases. We selected placebo-controlled, double-blind, randomized clinical trials assessing the efficacy of dietary interventions in ASD published from database inception through September 2017. Outcome variables were subsumed under 4 clinical domains and 17 symptoms and/or functions groups. Hedges' adjusted g values were used as estimates of the effect size of each dietary intervention relative to placebo. In this meta-analysis, we examined 27 double-blind, randomized clinical trials, including 1028 patients with ASD: 542 in the intervention arms and 486 in the placebo arms. Participant-weighted average age was 7.1 years. Participant-weighted average intervention duration was 10.6 weeks. Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains. Effect sizes were small (mean Hedges' g for significant analyses was 0.31), with low statistical heterogeneity and low risk of publication bias. Methodologic heterogeneity among the studies in terms of the intervention, clinical measures and outcomes, and sample characteristics. This meta-analysis does not support nonspecific dietary interventions as treatment of ASD but suggests a potential role for some specific dietary interventions in the management of some symptoms, functions, and clinical domains in patients with ASD.


[Patterns of mercury release from amalgam fillings into the oral cavity].
Seventy-five subjects aged 20 to 57 with 1 to 15 fillings of silver amalgam were examined. The level of mercury vapors in the oral cavity was assessed using an AGP-01 device and the method developed by the authors. Emission of mercury vapors in the oral cavity increased with the number of fillings. The concentration of mercury in the oral cavity depends largely on the number of silver amalgam fillings and less so on these fillings' length of service.


Words in melody: an H(2)15O PET study of brain activation during singing and speaking.
We used H(2)15O PET to characterize the interaction of words and melody by comparing brain activity measured while subjects spoke or sang the words to a familiar song. Relative increases in activity during speaking vs singing were observed in the left hemisphere, in classical perisylvian language areas including the posterior superior temporal gyrus, supramarginal gyrus, and frontal operculum, as well as in Rolandic cortices and putamen. Relative increases in activity during singing were observed in the right hemisphere: these were maximal in the right anterior superior temporal gyrus and contiguous portions of the insula; relative increases associated with singing were also detected in the right anterior middle temporal gyrus and superior temporal sulcus, medial and dorsolateral prefrontal cortices, mesial temporal cortices and cerebellum, as well as in Rolandic cortices and nucleus accumbens. These results indicate that the production of words in song is associated with activation of regions within right hemisphere areas that are not mirror-image homologues of left hemisphere perisylvian language areas, and suggest that multiple neural networks may be involved in different aspects of singing. Right hemisphere mechanisms may support the fluency-evoking effects of singing in neurological disorders such as stuttering or aphasia.


Propofol Modulates Early Memory Consolidation in Humans.
Maintenance of memory across time is crucial for adaptive behavior. Current theories posit that the underlying consolidation process depends on stabilization of synapses and reorganization of interactions between hippocampus and neocortex. However, the temporal properties of hippocampal-neocortical network reconfiguration during consolidation are still a matter of debate. Translational research on this issue is challenged by the paucity of techniques to transiently interfere with memory in the healthy human brain. Here, we report a neuro-pharmacological approach with the GABAAergic anesthetic propofol and a memory task sensitive to hippocampal dysfunction. Patients undergoing minor surgery learned word lists before injection of an anesthetic dose of propofol. Results show that administration of the drug shortly after learning (∼13 min) impairs recall after awakening but spares recognition. By contrast, later administration (∼105 min) has no effect. These findings suggest significant changes in memory networks very early after learning that are decisive for later recall. Propofol general anesthesia provides an experimental tool to modulate the first steps of hippocampus-mediated memory consolidation in humans.


Allele mining for stress tolerance genes in Oryza species and related germplasm.
Allele mining exploits the deoxyribonucleic acid (DNA) sequence of one genotype to isolate useful alleles from related genotypes. The international project to sequence the genome of Oryza sativa L cv. Nipponbare will make allele mining possible for all genes of rice and possibly related cereals. We used a rice calmodulin gene, a rice gene encoding a late embryogenesis-associated protein, and salt-inducible rice gene to optimize the polymerase chain reaction (PCR) for allele mining of stress tolerance genes on identified accessions of rice and related germplasm. Two sets of PCR primers were designed for each gene. Primers based on the 5' and 3' untranslated region of genes were found to be sufficiently conserved so as to be effective over the entire range of germplasm in rice for which the concept of allelism is applicable. However, the primers based on the adjacent amino (N) and carboxy (C) termini amplify additional loci.


Survival after partial breast brachytherapy in elderly patients with nonmetastatic breast cancer.
Despite growing utilization of accelerated partial breast irradiation using brachytherapy (APBI-Brachy) for elderly breast cancer patients, there are limited data from randomized Phase III trials to support its routine use. This study uses population-based data to examine whether APBI-Brachy results in comparable survival rates compared with whole breast irradiation (WBI). A sample of 29,647 female patients diagnosed with nonmetastatic breast cancer in 2002-2007 treated with breast-conserving surgery and radiotherapy was identified in the Surveillance, Epidemiology, and End Results Program-Medicare data set. Log-rank tests, Cox proportional hazards models, instrumental variable analysis, and subgroup analysis were used to study the comparative effectiveness of APBI-Brachy and WBI. During a median followup of 3.6 and 4.8 years, 123 (7.7%) and 3438 (13.6%) patients died after APBI-Brachy and WBI, respectively. Recurrence-free survival (p = 0.9711) and overall survival rates (p = 0.0551) did not differ significantly between the two radiation modalities. After accounting for tumor characteristics, patient characteristics, community factors, and comorbidities, the recurrence-free survival (hazard ratio, 1.05; 95% confidence interval, 0.90-1.23; p = 0.5125) and overall survival (hazard ratio, 0.87; 95% confidence interval, 0.72-1.04; p = 0.1332) rates were still not significantly different between patients treated with APBI-Brachy and WBI. Partial breast brachytherapy and WBI resulted in similar recurrence-free and overall survival rates in this cohort of elderly breast cancer patients, even after adjustment for the more favorable characteristics of patients in the former group. These findings will need to be confirmed by the randomized trials comparing these modalities.


Cardiolipin inhibitor ameliorates the non-alcoholic steatohepatitis through suppressing NLRP3 inflammasome activation.
Non-alcoholic fatty liver disease (NAFLD) has been proven to be the most common liver disease in the world, which is a sterile liver disease and is characterized by chronic hepatic steatosis and inflammation. The first step of the spectrum of the disease is the non-alcoholic fatty liver (NAFL). Based on hepatocellular necrosis and inflammation, NAFL will progress to non-alcoholic steatohepatitis (NASH), which may have the potential to progress cirrhosis, and even hepatocellular carcinoma (HCC) in a few years. Kupffer cells (KCs) are liver-resident macrophages and have been proven to play a crucial role in NAFLD development. Cardiolipin is reported to be effective to trigger the activation of NLRP3 inflammasome through a ROS-independent signaling pathway. However, the exact mechanism of NLRP3 inflammasome activated by cardiolipin in KCs is still unclear. To make clear of the specific mechanism mentioned above, we firstly used a MCD-induced NASH mice model to demonstrate that CLS1 suppression reduced hepatic steatosis and inflammation. Secondly, the results of IHC staining indicated that the expressions of CLS1 and NLRP3 in liver tissues were significantly upregulated in the NASH group compared to the ND group. On the contrary, CLS1 inhibition significantly downregulated NLRP3 expression in liver tissues, which indicated that CLS1 probably regulated the level of NLRP3 expression. Furthermore, we demonstrated that CLS1 suppression significantly ameliorated the liver function and decreased the TG level, and interleukin-1β (IL-1β) and IL-18 were markedly reduced upon CLS1 inhibition. In this work, we reported that cardiolipin is involved in the development of NASH, and the suppression of the cardiolipin synthesis by shRNA-CLS1 could ameliorate the hepatic pathogenic manifestations, as well as the serum inflammatory biomarkers. We further showed that the protein expressions of CLS1, NLRP3, ASC, and Caspase-1 were all upregulated in the NASH liver tissues and palmitic stimulated KCs. Our study showed that the upregulation of NLRP3 inflammasome activated by cardiolipin is crucial in NASH pathogenesis, which might provide a novel potential role of cardiolipin blockade in the treatment of NASH.


Femoral neuropathy: A clinical and electrodiagnostic review.
Femoral neuropathies can cause severe, prolonged debility, yet there have been few clinical and electrodiagnostic (EDx) studies addressing this condition. The aim of this study was to better understand the etiologies, EDx features, and clinical course of femoral neuropathy. We identified patients evaluated at Mayo Clinic Rochester between January 1, 1999 and July 31, 2019, with possible new femoral neuropathy ascertained via International Classification of Diseases-versions 9 and 10 diagnosis codes presenting within 6 months of symptom onset. A retrospective review of 1084 records was performed and we ultimately identified 159 patients with isolated femoral neuropathy for inclusion. The most common femoral neuropathy etiologies were compressive (40%), perioperative stretch (35%), and inflammatory (6%). Presenting symptoms included weakness (96%), sensory loss (73%), and pain (53%). Presenting motor physical exam findings demonstrated moderate weakness (34%) or no activation (25%) of knee extension and mild (32%) or moderate (35%) weakness of hip flexion. Seventy-two percent of patients underwent EDx testing, including 22 with femoral motor nerve conduction studies. Treatment often involved physical therapy (89%) and was otherwise etiology-specific. In patients with follow-up data available (n = 154), 83% had subjective clinical improvement at follow-up with a mean time to initial improvement of 3.3 months and mean time to recovery at final follow-up of 14.8 months. Only 48% of patients had nearly complete or complete recovery. In our cohort, the most common etiologies of femoral neuropathy were compression or perioperative stretch with high initial morbidity. Although motor recovery is common, improvement is often prolonged and incomplete.


Climate, food, density and wildlife population growth rate.
1. The aim of this study was to derive and evaluate a priori models of the relationship between annual instantaneous population growth rate (r) and climate. These were derived from the numerical response of annual r and food, and the effect of climate on a parameter in the numerical response. The goodness of fit of a range of such deductive models to data on annual r of Soay sheep and red deer were evaluated using information-theoretic (AICc-based) analyses. 2. The analysis for sheep annual r showed negative effects of abundance and negative effects of the interaction of abundance and climate, measured as March rainfall (and winter NAO) in the best fitting models. The analysis for deer annual r showed a negative effect of deer abundance and a positive effect of climate measured as March rainfall (but a negative effect of winter NAO), but no interaction of abundance and climate in the best fitting models. 3. There was most support in the analysis of sheep dynamics for the ratio numerical response and the assumption that parameter J (equilibrium food per animal) was influenced by climate. In the analysis of deer dynamics there was most support for the numerical responses assuming effects of food and density (Ivlev and density, food and density, and additive responses) and slightly less support for the ratio numerical response. The evaluation of such models would be aided by the collection of and incorporation of food data into the analyses.


A ribosome-inactivating protein in a Drosophila defensive symbiont.
Vertically transmitted symbionts that protect their hosts against parasites and pathogens are well known from insects, yet the underlying mechanisms of symbiont-mediated defense are largely unclear. A striking example of an ecologically important defensive symbiosis involves the woodland fly Drosophila neotestacea, which is protected by the bacterial endosymbiont Spiroplasma when parasitized by the nematode Howardula aoronymphium. The benefit of this defense strategy has led to the rapid spread of Spiroplasma throughout the range of D. neotestacea, although the molecular basis for this protection has been unresolved. Here, we show that Spiroplasma encodes a ribosome-inactivating protein (RIP) related to Shiga-like toxins from enterohemorrhagic Escherichia coli and that Howardula ribosomal RNA (rRNA) is depurinated during Spiroplasma-mediated protection of D. neotestacea. First, we show that recombinant Spiroplasma RIP catalyzes depurination of 28S rRNAs in a cell-free assay, as well as Howardula rRNA in vitro at the canonical RIP target site within the α-sarcin/ricin loop (SRL) of 28S rRNA. We then show that Howardula parasites in Spiroplasma-infected flies show a strong signal of rRNA depurination consistent with RIP-dependent modification and large decreases in the proportion of 28S rRNA intact at the α-sarcin/ricin loop. Notably, host 28S rRNA is largely unaffected, suggesting targeted specificity. Collectively, our study identifies a novel RIP in an insect defensive symbiont and suggests an underlying RIP-dependent mechanism in Spiroplasma-mediated defense.


Investigating the interaction of direct and indirect relation on memory judgments and retrieval.
This study examined the interactive relationship between two measures of association (direct and indirect associations) when predicting relatedness judgments and cued-recall performance. Participants were recruited from Amazon's Mechanical Turk and were given word pairs of varying relatedness to judge for their semantic, thematic, and associative strength. After completing a distractor task, participants then completed a cued-recall task. First, we sought to expand previous work on judgments of associative memory to include semantic- and thematic-based judgments (judgments of relatedness), while also replicating bias and sensitivity findings. Next, we tested for an interaction between direct and indirect association when predicting participant judgments while also expanding upon previous work by examining that interaction when predicting recall. The interaction between direct and indirect association was significant for both judgments and recall. For low indirect association, direct association was the primary predictor of both judgment strength and recall proportions. However, this trend reversed for high indirect association, as higher levels of indirect relation decreased the effectiveness of direct relation as a predictor. Overall, our findings indicate the degree to which the processing of similarity information impacts cognitive processes such as retrieval and item judgments, while also parsing apart the underlying, interactive relationship that exists between the norms used to represent concept information.


Increased Risk of Postoperative Complications After Total Knee Arthroplasty in Patients With Previous Patellectomy.
Few studies have reported the results of total knee arthroplasty (TKA) in patients with previous patellectomy. The purpose of this study was to assess the risk of complications and survivorship of primary TKA in patients who previously had a patellectomy in comparison to those undergoing TKA with patellar resurfacing. This was a historical cohort study and comprised 134 knees with previous patellectomy in a cohort of 17,946 primary TKA procedures at a single institution between 1985 and 2010. Multivariable Cox regression analyses were used to estimate the risk of complications and revisions in patients with previous patellectomy. When compared to TKA with patellar resurfacing, the risk of complications (hazards ratio: 1.38, 95% confidence interval: 1.05, 1.81) was significantly higher in post-patellectomy knees, but there was no difference in the risk of revisions (hazards ratio: 1.32, 95% confidence interval: 0.80, 2.18). There was no significant difference between the posterior-stabilized and cruciate-retaining designs in terms of both complications and revisions (P > .05). The most common complications in post-patellectomy knees were instability, delayed healing, and infection. TKA patients with previous patellectomy have a higher risk of complications but not a higher risk of revisions.


Application of dual carbon-bromine isotope analysis for investigating abiotic transformations of tribromoneopentyl alcohol (TBNPA).
Many of polybrominated organic compounds, used as flame retardant additives, belong to the group of persistent organic pollutants. Compound-specific isotope analysis is one of the potential analytical tools for investigating their fate in the environment. However, the isotope effects associated with transformations of brominated organic compounds are still poorly explored. In the present study, we investigated carbon and bromine isotope fractionation during degradation of tribromoneopentyl alcohol (TBNPA), one of the widely used flame retardant additives, in three different chemical processes: transformation in aqueous alkaline solution (pH 8); reductive dehalogenation by zero-valent iron nanoparticles (nZVI) in anoxic conditions; oxidative degradation by H2O2 in the presence of CuO nanoparticles (nCuO). Two-dimensional carbon-bromine isotope plots (δ(13)C/Δ(81)Br) for each reaction gave different process-dependent isotope slopes (Λ(C/Br)): 25.2 ± 2.5 for alkaline hydrolysis (pH 8); 3.8 ± 0.5 for debromination in the presence of nZVI in anoxic conditions; ∞ in the case of catalytic oxidation by H2O2 with nCuO. The obtained isotope effects for both elements were generally in agreement with the values expected for the suggested reaction mechanisms. The results of the present study support further applications of dual carbon-bromine isotope analysis as a tool for identification of reaction pathway during transformations of brominated organic compounds in the environment.


A review of Alcoholics Anonymous/ Narcotics Anonymous programs for teens.
The investigation of the applicability of Alcoholics Anonymous/Narcotics Anonymous (AA/NA) for teens has only been a subject of empirical research investigation since the early 1990s. In the present review, the author describes teen involvement in AA/NA programming, provides an exhaustive review of the outcomes of 19 studies that used an AA/NA model as part of their formal teen substance abuse treatment programs, and provides data on the effects of AA/NA attendance on abstinence at follow-up, on which youth tend to become involved in AA/NA, and on mediation of the benefits of AA/NA participation. In addition, the author suggests the reasons for somewhat limited participation by teens in more informal, community-based 12-step meetings, and makes suggestions for maximizing participation at meetings in the community. The author concludes that AA/ NA participation is a valuable modality of substance abuse treatment for teens and that much can be done to increase teen participation, though more research is needed.


Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair.
The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda.


[Quantitative measurements of regional extra-vascular lung water in dogs using positron emission tomography].
A new method for quantifying regional variations in extravascular lung water (rELW) has been developed. The positron source 15O (T1/2 = 2.0 min.) was provided as H215O 'on line' by constant intravenous injection. Tomographic images (PET) of the water distribution were obtained during equilibrium. The distribution of blood volume was obtained by marking erythrocytes (carboxyhaemoglobin) using a bolus inhalation [C-11)-CO; T1/2 = 20.4 min). Absorption is calculated from transmission tomography. The rELW is defined as: total lung water minus intravascular space. The method was carried out in five intubated and anaesthetised dogs before and after induction of pulmonary oedema with oleic acid (0.06 ml./kg.). Mean ELW (PET) rose from 0.13 +/- 0.02 g./cm.3 to 0.24 +/- 0.04 g./cm.3. There was good correlation with a simultaneously performed thermo-dye method (7.1 +/- 1.3 ml./kg. KG to 13.3 +/- 1.9 ml./kg. KG; r = 0.94). Gravimetric estimations resulted in 13.7 +/- 2.6 ml./kg. KG. The development and distribution of the pulmonary oedema was non-homogeneous and varied regionally.


Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository.
To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-β2 -glycoprotein I [anti-β2 GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). The 804 aPL-positive patients assessed in the present study had a mean age of 45 ± 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-β2 GPI only. Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.


Translating Science into Survival: Report on the Inaugural International Cancer Immunotherapy Conference.
The inaugural International Cancer Immunotherapy Conference, cohosted by the Cancer Research Institute (CRI), the American Association for Cancer Research (AACR), the Association for Cancer Immunotherapy (CIMT), and the European Academy of Tumor Immunology (EATI), was held in New York City on September 16–19, 2015. The conference brought together nearly 1,400 scientists, clinicians, regulators, patient advocates, and other stakeholders to discuss the latest scientific developments in cancer immunology and immunotherapy, as well as the regulatory hurdles facing new drug development. This conference report summarizes the main themes that emerged during the 4-day meeting.


High Mobility Group Box 1 Promotes Aortic Calcification in Chronic Kidney Disease via the Wnt/β-Catenin Pathway.
Vascular calcification (VC) is common in chronic kidney disease (CKD), where cardiovascular mortality remains the leading cause of death. Here, we examined the role of high-mobility group box1 (HMGB1), a nuclear DNA-binding protein involved in inflammation, in aortic calcification and renal dysfunction induced by high phosphate in a mouse model of CKD induced by 5/6 nephrectomy. HMGB1 and kidney function markers were measured by ELISA in the serum of CKD patients and in CKD mice. Sections of the aortas of mice were analyzed by immunofluorescence and Alizarin red staining, and protein lysates were generated to analyze the expression of related proteins in response to silencing of HMGB1 or β-catenin by western blotting. Our results showed that serum HMGB1 levels were significantly higher in CKD patients than in healthy controls and related to disease stage. High phosphate promoted the translocation of HMGB1 from the nucleus to the cytosol and aortic calcification in CKD mice in vivo, whereas HMGB1 knockdown ameliorated part of renal and vascular function. β-catenin silencing reversed high phosphate-induced calcification and restored renal marker levels. Taken together, our results suggest that HMGB1 is involved in VC associated with CKD via a mechanism involving the β-catenin.


Validation of monoclonal antibody F99/97.6.1 for immunohistochemical staining of brain and tonsil in mule deer (Odocoileus hemionus) with chronic wasting disease.
A new monoclonal antibody (MAb), F99/97.6.1, that has been used to demonstrate scrapie-associated prion protein PrP(Sc) in brain and lymphoid tissues of domestic sheep with scrapie was used in an immunohistochemistry assay for diagnosis of chronic wasting disease (CWD) in mule deer (Odocoileus hemionus). The MAb F99/97.6.1 immunohistochemistry assay was evaluated in brain and tonsil tissue from 100 mule deer that had spongiform encephalopathy compatible with CWD and from 1,050 mule deer outside the CWD-endemic area. This MAb demonstrated abnormal protease-resistant prion protein (PrP(res)) in brains of all of the 100 mule deer and in 99 of the 100 tonsil samples. No immunostaining was seen in samples collected from deer outside the endemic area. MAb F99/97.6.1 demonstrated excellent properties for detection of PrP(res) in fresh, frozen, or mildly to moderately autolytic samples of brain and tonsil. This immunohistochemistry assay is a sensitive, specific, readily standardized diagnostic test for CWD in deer.


Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.
A low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population. We compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol. Of the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003). These data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non-lipid-related cardiovascular risk factors.


Homoeobox gene Hox-1.5 expression in mouse embryos: earliest detection by in situ hybridization is during gastrulation.
We showed earlier (Gaunt, Miller, Powell & Duboule, 1986) that the mouse homoeobox gene Hox-1.5 is expressed in posterior ectoderm and mesoderm of 7 1/2- and 7 3/4-day embryos, and in the 9 1/2-day nervous system posterior to a discrete boundary within the hindbrain. In further in situ hybridization experiments, it is now shown that restriction of Hox-1.5 expression to the posterior regions of the embryo can be detected at stages of development between 7 1/2 and 9 1/2 days. During this period, the intensity of transcription in presomitic and somitic mesoderm declines relative to that in the overlying neural ectoderm, and the transcription boundary within the presumptive hindbrain region sharpens. Hox-1.5 expression posterior to the hindbrain boundary is detected in the 10 1/2- and 12 1/2-day embryo, but this is no longer found in newborn mice. Embryos of ages 3 1/2, 6 1/2 and 7 1/4 days showed no evidence of Hox-1.5 transcripts. It is concluded that embryos undergoing gastrulation (at 7 1/2 days) are the earliest stage at which Hox-1.5 transcripts can be detected by the in situ hybridization technique. In discussion, it is shown how this lies within the period of development during which tissues become determined along the anteroposterior axis of the mouse. Since there may be anterior-to-posterior variation in the time of determination along the body axis, it is suggested that homoeobox genes expressed more posteriorly, such as Hox-3 (Awgulewitsch et al. 1986), might start expression at times later in development.


Expression and characterization of the catalytic domains of soluble guanylate cyclase: interaction with the heme domain.
The catalytic domains (alpha(cat) and beta(cat)) of alpha1beta1 soluble guanylate cyclase (sGC) were expressed in Escherichia coli and purified to homogeneity. alpha(cat), beta(cat), and the alpha(cat)beta(cat) heterodimeric complex were characterized by analytical gel filtration and circular dichroism spectroscopy, and activity was assessed in the absence and presence of two different N-terminal regulatory heme-binding domain constructs. Alpha(cat) and beta(cat) were inactive separately, but together the domains exhibited guanylate cyclase activity. Analysis by gel filtration chromatography demonstrated that each of the approximately 25-kDa domains form homodimers. Heterodimers were formed when alpha(cat) and beta(cat) were combined. Results from circular dichroism spectroscopy indicated that no major structural changes occur upon heterodimer formation. Like the full-length enzyme, the alpha(cat)beta(cat) complex was more active in the presence of Mn(2+) as compared to the physiological cofactor Mg(2+), although the magnitude of the difference was much larger for the catalytic domains than for the full-length enzyme. The K(M) for Mn(2+)-GTP was measured to be 85 +/- 18 microM, and in the presence of Mn(2+)-GTP, the K(D) for the alpha(cat)beta(cat) complex was 450 +/- 70 nM. The N-terminal heme-bound regulatory domain of the beta1 subunit of sGC inhibited the activity of the alpha(cat)beta(cat) complex in trans, suggesting a domain-scale mechanism of regulation by NO. A model in which binding of NO to sGC causes relief of an autoinhibitory interaction between the regulatory heme-binding domain and the catalytic domains of sGC is proposed.


International initiative for a curated SDHB variant database improving the diagnosis of hereditary paraganglioma and pheochromocytoma.
SDHB is one of the major genes predisposing to paraganglioma/pheochromocytoma (PPGL). Identifying pathogenic SDHB variants in patients with PPGL is essential to the management of patients and relatives due to the increased risk of recurrences, metastases and the emergence of non-PPGL tumours. In this context, the 'NGS and PPGL (NGSnPPGL) Study Group' initiated an international effort to collect, annotate and classify SDHB variants and to provide an accurate, expert-curated and freely available SDHB variant database. A total of 223 distinct SDHB variants from 737 patients were collected worldwide. Using multiple criteria, each variant was first classified according to a 5-tier grouping based on American College of Medical Genetics and NGSnPPGL standardised recommendations and was then manually reviewed by a panel of experts in the field. This multistep process resulted in 23 benign/likely benign, 149 pathogenic/likely pathogenic variants and 51 variants of unknown significance (VUS). Expert curation reduced by half the number of variants initially classified as VUS. Variant classifications are publicly accessible via the Leiden Open Variation Database system (https://databases.lovd.nl/shared/genes/SDHB). This international initiative by a panel of experts allowed us to establish a consensus classification for 223 SDHB variants that should be used as a routine tool by geneticists in charge of PPGL laboratory diagnosis. This accurate classification of SDHB genetic variants will help to clarify the diagnosis of hereditary PPGL and to improve the clinical care of patients and relatives with PPGL.


The elusive premenstrual syndrome.
Premenstrual syndrome (PMS) is a condition that is widespread and has been talked about for almost 60 years, yet today there is no consistent method used to diagnose PMS; there is no well-supported etiology; and there is no noninvasive and low-risk proven treatment for the condition. This paper reviews current ideas about diagnosis, etiology, and treatment and makes recommendations for ways a clinician might safely help women with PMS.


Health education theory: an application to the process of patient-provider communication.
Although the medical visit is widely acknowledged as an important event presenting unique opportunities for the modification of health beliefs and behaviors, health education theory has provided few explanatory mechanisms for understanding its communication process. The purpose of this paper is to explore a theoretical model loosely derived from social exchange and reciprocity theory for viewing the dynamics and consequences of patient-provider interaction during the medical encounter. We have elaborated this notion of reciprocity to suggest that provider behaviors within both the technical and socioemotional realm inspire parallel patient behaviors. For instance, a physician who is very informative may expect a patient to remember his instructions and comply with his recommendations. Further, a physician who is warm and friendly will inspire parallel patient attitudes in the socioemotional domain, such as friendliness and satisfaction. However, we believe that the reciprocity principle is only partially operative between domains. While an informative physician may be perceived as concerned and caring, merely being nice or caring, in the absence of indications of task performance (such as information giving), does not supply the evidence on competence that patients need to decide to attend to information or adhere to a therapeutic regimen. Our theory of reciprocal exchange in the medical visit is consistent with a consumerist perspective of patient-provider relations and with the activated patient philosophy of health education.


Spatial distribution of lamin A and B1 in the K562 cell nuclear matrix stabilized with metal ions.
When the nucleus is stripped of most DNA, RNA, and soluble proteins, a structure remains that has been referred to as the nuclear matrix, which acts as a framework to determine the higher order of chromatin organization. However, there is always uncertainty as to whether or not the nuclear matrix, isolated in vitro, could really represent a skeleton of the nucleus in vivo. In fact, the only nuclear framework of which the existence is universally accepted is the nuclear lamina, a continuous thin layer that underlies the inner nuclear membrane and is mainly composed of three related proteins: lamins A, B, and C. Nevertheless, a number of recent investigations performed on different cell types have suggested that nuclear lamins are also present within the nucleoplasm and could be important constituents of the nuclear matrix. In most cell types investigated, the nuclear matrix does not spontaneously resist the extraction steps, but must rather be stabilized before the application of extracting agents. In this investigation, by immunochemical and morphological analysis, we studied the effect of stabilization with different divalent cations (Zn(2+), Cu(2+), Cd(2+)) on the distribution of lamin A and B1 in the nuclear matrix obtained from K562 human erythroleukemia cells. In intact cells, antibodies to both lamin A and B1 mainly stained the nuclear periphery, although some immunoreactivity was detected in the nuclear interior. The fluorescent lamin A pattern detected in Cu(2+)- and Cd(2+)-stabilized nuclei was markedly modified, whereas Zn(2+)-incubated nuclei showed an unaltered pattern of lamin A distribution. By contrast, the distribution of lamin B1 in isolated nuclei was not modified by the stabilizing cations. When chromatin was removed by nuclease digestion and extraction with solutions of high ionic strength, a previously masked immunoreactivity for lamin A, but not for lamin B1, became evident in the internal part of the residual structures representing the nuclear matrix. Our results indicate that when metal ions are used as stabilizing agents for the recovery of the nuclear matrix, the distribution of both lamin A and lamin B1 in the final structures, corresponds to the pattern we have very recently reported using different extraction procedures. This observation strengthen the concept that intranuclear lamins may act as structural components of the nuclear matrix.


Factors in the fracture microenvironment induce primary osteoblast angiogenic cytokine production.
Neoangiogenesis is essential for successful wound repair. Platelets are among the earliest cells recruited to a site of skeletal injury and are thought to provide numerous factors critical to successful repair. The release of platelet-derived growth factor (PDGF) after skeletal injury increases osteoblast proliferation, chemotaxis, and collagen synthesis; however, its angiogenic effect on osteoblast biology remains unknown. The purpose of this study was to investigate the effect of recombinant human (rh)PDGF-BB on the synthesis of vascular endothelial growth factor (VEGF) by primary neonatal rat calvarial osteoblasts. Furthermore, the authors investigated whether PDGF works in concert with hypoxia, another component of the fracture microenvironment, to additively or synergistically induce VEGF production. Osteoblast cultures were stimulated with varying concentrations of rhPDGF-BB (1, 10, 50, and 100 ng/ml) in normoxic and hypoxic (<1% oxygen) conditions for 0, 3, 6, 12, and 24 hours, and VEGF gene expression was analyzed by Northern blot analysis. To determine whether rhPDGF-BB-induced VEGF messenger RNA (mRNA) expression was transcriptionally mediated or required de novo protein synthesis, transcription, and translation, studies were performed using actinomycin D and cycloheximide, respectively. Treatment with 50 ng/ml rhPDGF-BB resulted in a 2.4-fold increase in VEGF mRNA expression after 3 hours. Interestingly, rhPDGF-BB and hypoxia seemed to have an additive effect, resulting in a 3.7-fold increase in VEGF mRNA expression after 6 hours in primary neonatal rat calvarial osteoblasts. Furthermore, by using actinomycin D and cycloheximide, the authors demonstrated that the rhPDGF-BB-induced VEGF mRNA expression was transcriptionally mediate and not dependent on de novo protein synthesis. These data demonstrate that rhPDGF-BB transcriptionally increases osteoblasts VEGF mRNA expression in vitro. Furthermore, the semiquantitative results suggest that rhPDGF-BB and hypoxia act additively to increase VEGF mRNA expression. It is postulated that similar mechanisms may occur in vivo, at a site of skeletal injury, to induce neoangiogenesis and promote fracture repair.


Trampoline Park Injury Trends.
Trampolines are an important cause of childhood injury and focus of injury prevention. Understanding and prevention of trampoline park injury is constrained by inadequate exposure data to estimate the at-risk population. This study aimed to measure trampoline park injury incidence and time trends using industry data. Cross-sectional study to retrospectively analyze reported injuries and exposure in 18 trampoline parks operating in Australia and the Middle East, from 2017 to 2019. Exposure was derived from ticket sales and expressed as jumper hours. Exposure-adjusted incidence was measured using marginalized 0-inflated Poisson modeling and time trends using Joinpoint regression. There were 13 256 injured trampoline park users reported from 8 387 178 jumper hours; 11% sustained significant injury. Overall, trampoline park injuries occurred at a rate of 1.14 injuries per 1000 jumper hours (95% confidence intervals 1.00 to 1.28), with rates highest for high-performance (2.11/1000 jumper hours, 1.66 to 2.56) and inflatable bag or foam pit (1.91/1000 jumper hours, 1.35 to 2.50) jumping. Significant injuries occurred at a rate of 0.11 injuries per 1000 jumper hours (0.10 to 0.13), with rates highest for high-performance (0.29/1000 jumper hours, 0.23 to 0.36), and parkour (0.22/1000 jumper hours, 0.15 to 0.28) jumping. Overall, injury rates decreased by 0.72%/month (-1.05 to -0.40) over the study period. Trampoline park injuries occur in important numbers with sometimes serious consequences. However, within these safety standard-compliant parks, exposure-adjusted estimates show injuries to be uncommon and injury rates to be declining. Further reductions are required, especially severe injuries, and this study can enhance injury prevention initiatives.


Rating of four different foods in women with hyperemesis gravidarum: a randomised controlled trial.
To evaluate four foods in women with hyperemesis gravidarum (HG) on their agreeability and tolerability. Prospective, randomised, within-subject cross-over trial. Single-centre, tertiary, university hospital in Malaysia. 72 women within 24-hour of first admission for HG who were 18 years or above, with confirmed clinical pregnancy of less than 16 weeks' gestation were recruited and analysed. Women unable to consume food due to extreme symptoms, known taste or swallowing disorder were excluded. Each participant chewed and swallowed a small piece of apple, watermelon, cream cracker and white bread in random order and was observed for 10 min after each tasting followed by a 2 min washout for mouth rinsing and data collection. Primary outcome was food agreeability scored after 10 min using an 11-point 0-10 Visual Numerical Rating Scale (VNRS). Nausea was scored at baseline (prior to tasting) and 2 and 10 min using an 11-point VNRS. Intolerant responses of gagging, heaving and vomiting were recorded. On agreeability scoring, apple (mean±SD 7.2±2.4) ranked highest followed by watermelon (7.0±2.7) and crackers (6.5±2.6), with white bread ranked lowest (6.0±2.7); Kruskal-Wallis H test, p=0.019. Apple had the lowest mean nausea score and mean rank score, while white bread had the highest at both 2 and 10 min; the Kruskal-Wallis H test showed a significant difference only at 10 min (p=0.019) but not at 2 min (p=0.29) in the ranking analyses. The intolerant (gagged, heaved or vomited) response rates within the 10 min study period were apple 3/72 (4%), watermelon 7/72 (10%), crackers 8/72 (11%) and white bread 12/72 (17%): χ2 test for trend p=0.02. Sweet apple had the highest agreeability score, the lowest nausea severity and intolerance-emesis response rate when tasted by women with HG. White bread consistently performed worst.


Phase I and pharmacokinetic study of amrubicin, a synthetic 9-aminoanthracycline, in patients with refractory or relapsed lung cancer.
Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses. Neutropenia was the major toxicity (grade 4, 67%). The MTD was 40 mg/m(2), with the specific dose-limiting toxicities being grade 4 neutropenia persisting for >4 days, febrile neutropenia, or grade 3 arrhythmia in the three patients treated at this dose. A patient with non-small-cell lung cancer showed a partial response, and ten individuals experienced a stable disease. The area under the plasma concentration versus time curve (AUC) for amrubicin and that for amrubicinol increased with amrubicin dose. The amrubicin AUC was significantly correlated with the amrubicinol AUC. The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks.


Abnormal N400 word repetition effects in fragile X-associated tremor/ataxia syndrome.
Fragile X-associated tremor/ataxia syndrome, a neurodegenerative disorder associated with premutation alleles (55-200 CGG repeats) of the FMR1 gene, affects many carriers in late-life. Patients with fragile X-associated tremor/ataxia syndrome typically have cerebellar ataxia, intranuclear inclusions in neurons and astrocytes, as well as cognitive impairment. Dementia can also be present with cognitive deficits that are as severe as in Alzheimer's disease, however frontosubcortical type impairment is more pronounced in fragile X-associated tremor/ataxia syndrome. We sought to characterize the P600 and N400 word repetition effects in patients with fragile X-associated tremor/ataxia syndrome, using an event-related potential word repetition paradigm with demonstrated sensitivity to very early Alzheimer's disease. We hypothesized that the fragile X-associated tremor/ataxia syndrome-affected participants with poor declarative verbal memory would have pronounced abnormalities in the P600 repetition effect. In the event-related potential experiment, subjects performed a category decision task whilst an electroencephalogram was recorded. Auditory category statements were each followed by an associated visual target word (50% 'congruous' category exemplars, 50% 'incongruous' nouns). Two-thirds of the stimuli (category statement-target word pairs) were repeated, either at short-lag (approximately 10-40 s) or long-lag (approximately 100-140 s). The N400 and P600 amplitude data were submitted to split-plot analyses of variance. These analyses of variance showed a highly significant reduction of the N400 repetition effect (F = 22.5, P < 0.001), but not of the P600 repetition effect, in mild fragile X-associated tremor/ataxia syndrome (n = 32, mean age = 68.7, mean Mini-Mental State Examination score = 26.8). Patients with fragile X-associated tremor/ataxia syndrome had significantly smaller late positive amplitude (550-800 ms post-stimulus onset) to congruous words (P = 0.04 for group effect). Reduced P600 repetition effect amplitude was associated with poorer recall within fragile X-associated tremor/ataxia syndrome patients (r = 0.66) and across all subjects (r = 0.52). Larger P600 amplitude to new congruous words also correlated significantly with higher free recall scores (r = 0.37, P < 0.01) across all subjects. We found a correlation between the amplitude of late positivity and CGG repeat length in those with fragile X-associated tremor/ataxia syndrome (r = 0.47, P = 0.006). Higher levels of FMR1 mRNA were associated with smaller N400s to incongruous words and larger positive amplitudes (between 300 and 500 ms) to congruous words. In conclusion, event-related potential word repetition effects appear sensitive to the cognitive dysfunction present in patients with mild fragile X-associated tremor/ataxia syndrome. Their more severe reduction in N400 repetition effect, than P600, is in contrast to the reverse pattern reported in amnestic mild cognitive impairment and incipient Alzheimer's disease (Olichney et al., 2008).


Economic value of dengue vaccine in Thailand.
With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.


Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.
Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous, SCAR, Neuroglian and Synaptobrevin, and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained.


Who Knew? Hospice Is a Business. What that Means for All of Us.
A seasoned gerontologist whose work has explored end-of-life care, I thought I knew what I was getting into when I undertook care for my brother Jim. In April 2014, Jim, whose health was then declining rapidly due to liver cancer, moved from his apartment in Minneapolis to my house in Santa Monica. Jim had come for a liver transplant evaluation at the University of California, Los Angeles (UCLA). When the UCLA team declined to list him-his cancer was just too widespread-Jim elected to stay with my family and me, enrolling in hospice. I did my homework when shopping for a hospice provider. Colleagues in the field gave me referrals. I googled their recommendations and read the reviews. I interviewed admissions counselors. When Jim signed the admission papers, I was confident that we were in good hands with the agency we selected. For the most part, we were. Hospice is widely considered an effective program. Studies show that it prevents pain and suffering among dying patients and increases satisfaction with care. Although other health care programs are regularly pilloried in the press, hospice programs are often lauded. Indeed, they sometimes appear so mission driven that one might mistake them for charities. They are not. Whether for-profit or not-for-profit enterprises, they are businesses-and concerned about their bottom line. Through Jim's story and mine, this article highlights the implications of this business orientation for patients and providers. Methods for evaluating hospice programs nationally are critiqued. Finally, recommendations for improving the business of hospice care are offered.


In Situ, Atomic-Resolution Observation of Lithiation and Sodiation of WS2 Nanoflakes: Implications for Lithium-Ion and Sodium-Ion Batteries.
WS2 nanoflakes have great potential as electrode materials of lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) because of their unique 2D structure, which facilitates the reversible intercalation and extraction of alkali metal ions. However, a fundamental understanding of the electrochemical lithiation/sodiation dynamics of WS2 nanoflakes especially at the nanoscale level, remains elusive. Here, by combining battery electrochemical measurements, density functional theory calculations, and in situ transmission electron microscopy, the electrochemical-reaction kinetics and mechanism for both lithiation and sodiation of WS2 nanoflakes are investigated at the atomic scale. It is found that compared to LIBs, SIBs exhibit a higher reversible sodium (Na) storage capacity and superior cyclability. For sodiation, the volume change due to ion intercalation is smaller than that in lithiation. Also, sodiated WS2 maintains its layered structure after the intercalation process, and the reduced metal nanoparticles after conversion in sodiation are well-dispersed and aligned forming a pattern similar to the layered structure. Overall, this work shows a direct interconnection between the reaction dynamics of lithiated/sodiated WS2 nanoflakes and their electrochemical performance, which sheds light on the rational optimization and development of advanced WS2 -based electrodes.


Comparative analysis of nephrolithiasis in otherwise healthy versus medically complex gastrostomy fed children.
The purpose was to compare nephrolithiasis in healthy versus medically complex gastrostomy fed children. Children with nephrolithiasis with and without gastrostomy were identified by database searches from 1999 to 2009. Gastrostomy fed stone formers (GSF) were compared to an age-matched cohort of non-gastrostomy-fed stone formers (NGSF) for demographic and clinical data. 16 neurologically impaired GSF (10M:6F), mean age 10.4 years (range 1.7-17.5 years), were compared to 32 matched neurologically intact NGSF. Compared to NGSF, GSF had significantly higher urine pH (6.93 vs 6.23, p = 0.001) and larger stones (14.5 vs 6.9 mm, p = 0.02) more commonly composed of calcium phosphate (7/11, 64% vs 3/28, 11%, p = 0.002). 15/16 (94%) of GSF were immobile while 0% of NGSF were immobile. GSF had lower l-spine bone density Z-scores (-3.02 vs -1, p = 0.002) but an equal rate of hypercalciuria (2/7, 29% vs 7/24, 29%, p = NS). Contributing lithogenic factors in 8/16 (50%) GSF included urinary tract infection (UTI) (5), lithogenic medications (2), and xanthinuria (1). Stone disease in GSF is multifactorial, and half of our study group had an identifiable risk factor for nephrolithiasis. A recurring pattern of alkaline urine and calcium phosphate stone formation was evident. GSF did not have higher rates of hypercalciuria despite chronic immobilization and markedly lower bone density. An awareness of the potential risk factors identified is mandatory for this vulnerable population.


[Surgical treatment of a pectus excavatum deformity].
The results of treatment of 114 patients, suffering pectus excavatum deformity (PED), in 42 of whom Marfan syndrome was diagnosed, were analyzed. Parasternal chondrotomy of a deformed cartilaginous parts of the ribs with subsequent fixation of their sternal ends towards sternum was used for the symmetric correction. The asymmetric PED correction on a convex side was performed similarly and on a concave one a mobilization effect was achieved, using a multiple notches putting on a cartilaginous parts of the deformed ribs. Good result in the treatment of a symmetric PED was achieved in 52 (81.2%) patients and satisfactory one--in 12 (18.7%), and in asymmetric PED--in 31 (62%) and 16 (32%) accordingly, poor result was noted in 3 (6%) patients. A sufficient efficacy of method of the deformity correction was confirmed by the analysis made on the applied surgical treatment results.


Embolization of Large and Giant Posterior Fossa Hemangioblastomas: The Experience of a Single Tertiary Care Center.
Background Hemangioblastomas pose an inherent surgical risk due to the potential for high intraoperative blood loss, especially in larger tumors. One approach to minimize this risk is to use preoperative embolization. Herein, we present our institutional experience treating large and giant cerebellar hemangioblastomas. Methods We performed a retrospective chart review of 19 patients with cerebellar hemangioblastomas that had a maximal diameter of >3 cm. We performed a literature review and included individual patient-level data that met our >3 cm diameter cerebellar hemangioblastoma inclusion criteria. Results Our cohort consisted of 19 patients that received a total of 20 resections for their cerebellar hemangioblastomas. Preoperative embolization was utilized in eight cases (38.1%). One patient experienced transient neurological complications after embolization (12.5%). Tumors of patients in the embolization group had larger median total, solid, and cystic volumes and were more likely to involve the cerebellopontine angle than those in the non-embolized group. Compared with non-embolized patients, embolized patients had less decrease in their hemoglobin, lower volumes of estimated blood loss, reduced rates of postoperative complications and permanent deficits, and greater instances of neurological improvement. The larger cohort (obtained from the combining our cohort with patients identified during a literature review) consisted of 99 patients with 39 receiving preoperative embolization. Conclusion It is important to examine individual patient characteristics when determining eligibility for preoperative embolization. However, improvements in endovascular techniques have made preoperative embolization a safe and effective procedure with minimal risks that can be performed in many patients.


Validation and comparison of 15-D and EQ-5D-5L instruments in a Spanish Parkinson's disease population sample.
To contribute to the ongoing discussion on the choice of a preference-based health-related quality of life (HRQoL) instrument to be used in cost-effectiveness analysis by studying and comparing the validity, sensitivity and relative efficiency of 15-D and EuroQol 5D 5L (EQ-5D-5L) in a Spanish Parkinson's disease (PD) population sample. One hundred and thirty-three volunteers were asked to complete an interview using 15-D and EQ-5D-5L. Spearman's rank correlation coefficient (r) was used to test the convergent validity of these instruments with specific PD measures. Sensitivity and efficiency were compared using receiver operating characteristic (ROC) curves and relative efficiency statistic, respectively. A strong correlation (r > 0.65; p < 0.001) was found between both 15-D and EQ-5D-5L utilities with the summary score of the PDQ-8, and a strong correlation (r > 0.50; p < 0.001) was found between 15-D and EQ-5D-5L utilities with the EQ-VAS. The areas under the ROC of both instruments all exceeded 0.5 (p < 0.001). The 15-D instrument was 4.1-29.8 % less efficient at detecting differences between patients with optimal HRQoL, while this instrument was 11 % more efficient at detecting differences between patients at mild and moderate to strong severity of the PD symptoms. 15-D and EQ-5D-5L are showed to be valid and sensitivity generic HRQoL measures in Spanish PD patients with both instruments showing similar HRQoL dimension coverage and ceiling/floor effects. The 15-D has better efficiency and greater sensitivity to detect clinical changes in PD severity of the symptoms meanwhile the EQ-5D-5L is better to detect clinical HRQoL changes. Additionally, the EQ-5D-5L questionnaire requires less time than 15-D to be administered, and it might be more appropriate for studies conducted in Spain, since a country-specific "value set" is available for this instrument and not for the 15-D.


[Treatment of patients with cholelithiasis and concomitant gastritis using sodium-calcium sulfate mineral water].
Choledocholithiasis (CDL) is known to be associated with gastric problems, such as disturbances of secretory function of the stomach. A frequent occurrence in this pathological condition is chronic gastritis with atrophy of gastric mucosa. It was shown that consumption of Uvinskaya mineral water during the period preceding calculi formation has beneficial therapeutic effect not only on the gallbladder function but also on both the morphological structure of the stomach and the secretory function of its mucous membrane.


Seroprevalence of Toxoplasma gondii in bred cynomolgus monkeys ( Macaca fascicularis ) in China.
Little is known of the seroprevalence of Toxoplasma gondii in bred cynomolgus monkeys ( Macaca fascicularis ) in China. In the present survey, 240 serum samples of cynomolgus monkeys from 4 nonhuman primate centers in Guangxi Zhuang Nationality Autonomous Region (GX), and 120 serum samples from 2 nonhuman primate centers in Guangdong Province (GD) were obtained, and the modified agglutination test (MAT) was performed to assay for anti- T. gondii antibodies. Antibodies to T. gondii (MAT titer of 1:16 or higher) were found in 0 of 120 (0/120) samples in GD, and 5 (2.1%) of 240 sera with titers of 1:16 in 1, 1:64 or higher in 4 in primate centers from GX. The total prevalence of T. gondii in bred cynomolgus monkeys was 1.4% (5/360, MAT titer > or = 1:16) in southern China according to our investigation. To our knowledge, this is the first seropositive report in China on the prevalence of anti- T. gondii antibodies in bred cynomolgus monkeys using MAT.


Reduction of exposure to plasticizers in stored red blood cell units.
Plastic can be toxic and hazardous to an organism's health, but it is being widely used in our daily lives. Di-2-ethylhexyl-phthalate is the most common plasticizer in medical devices made of polyvinylchloride and is commonly found in soft bags storing red blood cell units. Di-2-ethylhexyl-phthalate and its degradation product mono-2-ethylhexyl-phthalate can migrate into human body fluids, for example, blood and tissues. The aim of the study was to assess the concentration of plasticizers in red blood cell units according to storage time and after mechanical rinsing using a cell salvage device. Levels of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate were analysed in 50 unwashed red blood cell units using liquid chromatography coupled with tandem mass spectrometry. In addition, phthalate concentrations were measured before and after mechanical rinsing in six more washed red blood cell units with storage times ranging between 36 and 56 days. A linear regression model was determined by the daily increase of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate in the stored red blood cell units subject to their storage time (range = 4-38 days), and the effect of mechanical rinsing on their phthalate concentration was calculated. A linear correlation was found between storage time of unwashed red blood cell units and the concentration of di-2-ethylhexyl-phthalate (p < 0.001) or mono-2-ethylhexyl-phthalate (p < 0.001). Stored red blood cell units older than 14 days had significantly higher concentrations of both contaminants than red blood cell units of shorter storage time (p < 0.001). Mechanical rinsing in washed red blood cell units attained a reduction in the di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate concentration by a median of 53% (range = 18-68%; p = 0.031) and 87% (range = 68-96%; p = 0.031), respectively. Leaching of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate into red blood cell units depends on the duration of storage time. Plasticizers can be significantly reduced by mechanical rinsing using cell salvage devices, and thus, red blood cell units can be regenerated with respect to chemical contamination.


Combining ChIP-chip and expression profiling to model the MoCRZ1 mediated circuit for Ca/calcineurin signaling in the rice blast fungus.
Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen.


Boosting Understanding and Identification of Scientific Consensus Can Help to Correct False Beliefs.
Some people hold beliefs that are opposed to overwhelming scientific evidence. Such misperceptions can be harmful to both personal and societal well-being. Communicating scientific consensus has been found to be effective in eliciting scientifically accurate beliefs, but it is unclear whether it is also effective in correcting false beliefs. Here, we show that a strategy that boosts people's understanding of and ability to identify scientific consensus can help to correct misperceptions. In three experiments with more than 1,500 U.S. adults who held false beliefs, participants first learned the value of scientific consensus and how to identify it. Subsequently, they read a news article with information about a scientific consensus opposing their beliefs. We found strong evidence that in the domain of genetically engineered food, this two-step communication strategy was more successful in correcting misperceptions than merely communicating scientific consensus. The data suggest that the current approach may not work for misperceptions about climate change.


An overview of intravascular ultrasound.
Intravascular ultrasound is a new technique based on the use of high-frequency transducers mounted in or on flexible catheters which can be inserted into arteries or veins. Although this technique is extremely promising for the evaluation or guidance of intravascular interventions, this application has yet to be proven conclusively. Intravascular ultrasound is already established as a research technique, especially for the evaluation of details of lesion size, morphology, or the results of interventions. Catheters can be divided into two principles of operation, mechanical or electronic. The mechanical systems can be further subdivided according whether the core, rotating element is fixed relative to the outside sheath, or can be moved. Interpretation of images requires knowledge of the histology of the arterial wall, as well as of the physics of ultrasound at high frequencies. Studies are now underway to assess the contribution of intravascular ultrasound to prognosis and outcome in interventional procedures.


Antileukemic activity of Flt3 ligand in murine leukemia.
Flt3-ligand (Flt3-L) is an early acting costimulatory cytokine that has been shown to possess antitumor properties in murine solid tumor models. Flt3-L is a trans-membrane protein (tm) but can be proteolytically cleaved to a soluble form, which is also biologically active. In this study, the antitumor effect of both soluble and tmFlt3-L was evaluated in a mouse leukemia model. To mimic the multiorgan involvement characteristic of human leukemia, a factor-dependent cell line FDC.P1 was made leukemogenic by transfection with the human BCR/ABL gene. The resulting cell line, AW, expresses BCR/ABL RNA and protein. It maintains a similar in vitro growth rate as the parent cell line, but unlike the parent cell line, AW cells are factor independent and tumorigenic. Growth of FDC.P1 and AW cells are unaffected by the addition of soluble human Flt3-L to the culture medium. Also, AW growth is unaltered after transduction with a retroviral vector expressing the tm isoform of human Flt3-L (AW/tmFlt3-L). When 10(5) AW cells were i.v. injected into syngeneic DBA/2 mice, fatal leukemia developed in nine of nine (100%) mice within 4-6 weeks with involvement of the blood, bone marrow, spleen, and thymus. Systematic administration of soluble human Flt3-L (500 microg/kg/day) for 10 days protected mice from leukemia, with 11 of 17 mice tumor free at week 8 (64.7%) The tm isoform of Flt3-L also was protective. When 10(4) AW/tmFlt3-L cells were injected i.v. into mice, only 35.7% (5 of 14) developed leukemia versus 100% in control groups. Adoptive transfer of immunity was also demonstrated; T cells obtained from tumor-free animals conferred protection to 87% (seven of eight) naive mice challenged with AW cells. These results demonstrate that both soluble and membrane-bound human Flt3-L has antitumor activity in this leukemia model.


Multibody modeling of the cervical spine in the simulation of flexion-extension after disc arthroplasty.
This paper presents a three-dimensional (3D) multibody model of the cervical spine implanted with an artificial disc. The model was used to predict prosthesis placement influence on the resulting cervical kinematics in a series of patients. The vertebral tract modeled was the C2-C7, and the vertebral geometries were reconstructed from computed tomography (CT) images. The model was used to simulate the flexion-extension motion of the cervical spine in 10 patients implanted with the Prestige commercial disc prosthesis at a single level. For each patient, a geometrical model of the prosthesis was scaled and included in the multibody model to match the size and positioning of the actual prosthesis, as assessed on post-operative radiographs. Simulations of complete flexion-extension were carried out for each patient, and the main parameters relevant to the motion of the vertebral bodies were calculated and compared to data measured from dynamic post-operative radiographs. At the implanted level, the simulated ranges of motion generally agreed with the measured ones, with an average deviation <2 degrees. In addition, the simulated relative angles between vertebral bodies agreed with the measured ones, with minor average differ-ences of 1.2, 1.8 and 2.1 degrees in full flexion, neutral alignment and full extension, respectively. The cervical kinematics after prosthesis placement was influenced both by the design of the artificial joint and by surgical positioning. Therefore, the model presented can be used both to support pre-operative planning for disc arthroplasty and in the optimization of new prostheses design.


[Erotic hallucinations associated with the use of propofol].
A 42-year-old woman underwent outpatient surgery to remove vocal cord polyps. She had a history of depressive syndrome and had previously undergone surgery without complications. Before surgery she received 3.5 mg of midazolam orally. General anesthesia was provided with propofol: one initial bolus of 1 mg/kg followed by an infusion of 6 mg/kg/h. Surgery was uneventful. Upon arrival in the postanesthetic recovery ward, the patient, greatly agitated, accused the orderlies pushing the gurney of forcing her to touch his genitals. Twenty-four hours after surgery she did not remember the incident. Since 1987 various cases of postoperative sexual hallucination have been associated with the use of propofol. Usually the patients are women undergoing minor gynecological procedures and involve male health-care providers in the surgical area. The incidents are characteristically followed by amnesia. This clinical picture has also been described for midazolam and nitrous oxide, but the frequency is higher for propofol owing to its pharmacodynamic and pharmacokinetic properties (rapidly recovered awareness and lowering of inhibition). Given the legal implications, the presence of someone of the same sex as the patient is recommended when the patient awakens.


[Abnormal hypothalamic-hypophyseal regulation as a new endocrine sign in the testicular feminisation syndrome (author's transl)].
In a 38-year-old woman with the testicular feminisation syndrome (TFS) there were increased serum levels of LH and FSH, despite normal testosterone levels, ranging from 808 to 1330 ng/dl. The patient exhibited complete end-organ resistance to androgens, as well as decreased free testosterone fraction of 1.5 percent. On stimulation with LH-RH there was enhanced LH reaction to 15 ng/ml, while FSH levels remained unchanged. Fluoxymesterone did not suppress LH and testosterone, as it did in normal controls. But the functional Leydig-cell reserve could be normally stimulated with HCG. Our results apparently confirm the suspected reduction in sensitivity of the hypothalamic-pituitary axis to androgens and suggest that this plays an important part in the pathogenesis of TES.